Combination therapy with relugolix (Orgovyx, Relumina), a gonadotropin-releasing hormone antagonist, significantly reduced the pain of uterine fibroids, an undertreated aspect of this disease.

In pooled results from the multicenter randomized placebo-controlled LIBERTY 1 and 2 trials, relugolix combination therapy (CT) with the progestin norethindrone (Aygestin, Camila) markedly decreased both menstrual and nonmenstrual fibroid pain, as well as heavy bleeding and other symptoms of leiomyomas. This hormone-dependent condition occurs in 70%-80% of premenopausal women.

“Historically, studies of uterine fibroids have not asked about pain, so one of strengths of these studies is that they asked women to rate their pain and found a substantial proportion listed pain as a symptom,” lead author Elizabeth A. Stewart, MD, director of reproductive endocrinology at the Mayo Clinic in Rochester, Minn., said in an interview.

The combination was effective against all categories of leiomyoma symptoms, she said, and adverse events were few.

Bleeding has been the main focus of studies of leiomyoma therapies, while chronic pain has been largely neglected, said James H. Segars Jr., MD, director of the division of reproductive science and women’s health research at Johns Hopkins Medicine in Baltimore, who was not involved in the studies. Across both of the LIBERTY trials, involving 509 women randomized during the period April 2017 to December 2018, more than half overall (54.4%) met their pain reduction goals in a subpopulation analysis. Pain reduction was a secondary outcome of the trials, with bleeding reduction the primary endpoint. Other fibroid symptoms are abdominal bloating and pressure.

“The consistent and significant reduction in measures of pain with relugolix-CT observed in the LIBERTY program is clinically meaningful, patient-relevant, and together with an improvement of heavy menstrual bleeding and other uterine leiomyoma–associated symptoms, is likely to have a substantial effect on the life of women with symptomatic uterine leiomyomas,” Dr. Stewart and colleagues wrote. Their report was published online in Obstetrics & Gynecology.

Dr. Segars concurred. “This study is important because sometimes the only fibroid symptom women have is pain. If we ignore that, we miss a lot of women who have pain but no bleeding.”
 

The study

The premenopausal participants had a mean age of just over 42 years (range, 18-50) and were enrolled from North and South America, Europe, and Africa. All reported leiomyoma-associated heavy menstrual bleeding of 80 mL or greater per cycle for two cycles, or 160 mL or greater during one cycle.

In both arms, the mean body mass index was 32 kg/m², while menstrual blood loss volume was 245.4 (± 186.4) mL in the relugolix-CT and 207.4 (± 114.3) mL in the placebo group.

Pain was a frequent symptom, with approximately 70% in the intervention group and 74% in the placebo group reporting fibroid pain at baseline.

Women were randomized 1:1:1 to receive:

• Relugolix-CT (relugolix 40 mg, estradiol 1 mg, norethindrone acetate 0.5 mg)
• Delayed relugolix-CT (relugolix 40 mg monotherapy followed by relugolix-CT, each for 12 weeks)
• Placebo, taken orally once daily for 24 weeks

The therapy was well tolerated and adverse events were low.

The subpopulation analysis found that over the study period, the proportion of women achieving minimal to no pain (level 0 to 1) during the last 35 days of treatment was notably higher in the relugolix-CT arm than in the placebo arm: 45.2% (95% confidence interval [CI], 36.4%-54.3%) versus 13.9% (95% CI, 8.8%-20.5%) in the placebo group (nominal P = .001).

Moreover, the proportions of women with minimal to no pain during both menstrual days and nonmenstrual days were significantly higher with relugolix-CT: 65.0% (95% CI, 55.6%-73.5%) and 44.6% (95% CI, 32.3%-7.5%), respectively, compared with placebo: 19.3% (95% CI 13.2%–26.7%, nominal P = 001), and 21.6% (95% CI, 12.9%-32.7%, nominal P = 004), respectively.

Studies of relugolix monotherapy in Japanese women with uterine leiomyomas have demonstrated reductions in pain.

“Significantly, this combination therapy allows women to be treated over 2 years and to take the oral tablet themselves, unlike Lupron [leuprolide], which is injected and can only be taken for a couple of months because of bone loss,” Dr. Segars said. And the add-back component of combination therapy prevents the adverse symptoms of a hypoestrogenic state.

“The pain of fibroids is chronic, and the longer treatment allows time for the pain fibers to revert to a normal state,” he explained. “The pain pathways get etched into the nerves and it takes time to revert.”

He noted that the LIBERTY trials showed a slight downward trend in pain continuing after 24 weeks of treatment. Other studies of similar hormonal treatments have shown a reduction in the size of fibroids, which can be as large as a tennis ball.

As in endometriosis, leiomyomas are associated with elevated circulating cytokines and a systemic proinflammatory state. In endometriosis, this milieu is linked to the risk of inflammatory arthritis, fibromyalgia, lupus, and cardiovascular disease, Dr. Segars said. “If we did a deeper dive, we might find the same associations for fibroids.” Apart from chronic depression and fatigue, fibroids are linked to downstream pregnancy complications and poor outcomes such as miscarriage and preterm birth, he said.

“There remains a high unmet need for effective treatments, especially nonsurgical interventions, for women with uterine leiomyomas,” the authors wrote. Dr. Stewart added that “it would be helpful to learn more about how relugolix and other drugs in its class work in fibroids. No category of symptoms has been unresponsive to these medications – they are powerful drugs to help women with uterine fibroids.” She noted that relugolix-CT has already been approved outside the United States for symptoms beyond heavy menstrual bleeding.

Future research should focus on developing a therapy that does not interfere with fertility, Dr. Segars said. “We need a treatment that will allow women to get pregnant on it.”

Myovant Sciences GmbH sponsored LIBERTY 1 and 2 and oversaw all aspects of the studies. Dr. Stewart has provided consulting services to Myovant, Bayer, AbbVie, and ObsEva. She has received royalties from UpToDate and fees from Med Learning Group, Med-IQ, Medscape, Peer View, and PER, as well as honoraria from the American College of Obstetricians and Gynecologists and Massachusetts Medical Society. She holds a patent for methods and compounds for treatment of abnormal uterine bleeding. Dr. Segars has consulted for Bayer and Organon. Several coauthors reported similar financial relationships with private-sector entities and two coauthors are employees of Myovant.

Combination therapy with relugolix (Orgovyx, Relumina), a gonadotropin-releasing hormone antagonist, significantly reduced the pain of uterine fibroids, an undertreated aspect of this disease.

In pooled results from the multicenter randomized placebo-controlled LIBERTY 1 and 2 trials, relugolix combination therapy (CT) with the progestin norethindrone (Aygestin, Camila) markedly decreased both menstrual and nonmenstrual fibroid pain, as well as heavy bleeding and other symptoms of leiomyomas. This hormone-dependent condition occurs in 70%-80% of premenopausal women.

“Historically, studies of uterine fibroids have not asked about pain, so one of strengths of these studies is that they asked women to rate their pain and found a substantial proportion listed pain as a symptom,” lead author Elizabeth A. Stewart, MD, director of reproductive endocrinology at the Mayo Clinic in Rochester, Minn., said in an interview.

The combination was effective against all categories of leiomyoma symptoms, she said, and adverse events were few.

Bleeding has been the main focus of studies of leiomyoma therapies, while chronic pain has been largely neglected, said James H. Segars Jr., MD, director of the division of reproductive science and women’s health research at Johns Hopkins Medicine in Baltimore, who was not involved in the studies. Across both of the LIBERTY trials, involving 509 women randomized during the period April 2017 to December 2018, more than half overall (54.4%) met their pain reduction goals in a subpopulation analysis. Pain reduction was a secondary outcome of the trials, with bleeding reduction the primary endpoint. Other fibroid symptoms are abdominal bloating and pressure.

“The consistent and significant reduction in measures of pain with relugolix-CT observed in the LIBERTY program is clinically meaningful, patient-relevant, and together with an improvement of heavy menstrual bleeding and other uterine leiomyoma–associated symptoms, is likely to have a substantial effect on the life of women with symptomatic uterine leiomyomas,” Dr. Stewart and colleagues wrote. Their report was published online in Obstetrics & Gynecology.

Dr. Segars concurred. “This study is important because sometimes the only fibroid symptom women have is pain. If we ignore that, we miss a lot of women who have pain but no bleeding.”
 

The study

The premenopausal participants had a mean age of just over 42 years (range, 18-50) and were enrolled from North and South America, Europe, and Africa. All reported leiomyoma-associated heavy menstrual bleeding of 80 mL or greater per cycle for two cycles, or 160 mL or greater during one cycle.

In both arms, the mean body mass index was 32 kg/m², while menstrual blood loss volume was 245.4 (± 186.4) mL in the relugolix-CT and 207.4 (± 114.3) mL in the placebo group.

Pain was a frequent symptom, with approximately 70% in the intervention group and 74% in the placebo group reporting fibroid pain at baseline.

Women were randomized 1:1:1 to receive:

• Relugolix-CT (relugolix 40 mg, estradiol 1 mg, norethindrone acetate 0.5 mg)
• Delayed relugolix-CT (relugolix 40 mg monotherapy followed by relugolix-CT, each for 12 weeks)
• Placebo, taken orally once daily for 24 weeks

The therapy was well tolerated and adverse events were low.

The subpopulation analysis found that over the study period, the proportion of women achieving minimal to no pain (level 0 to 1) during the last 35 days of treatment was notably higher in the relugolix-CT arm than in the placebo arm: 45.2% (95% confidence interval [CI], 36.4%-54.3%) versus 13.9% (95% CI, 8.8%-20.5%) in the placebo group (nominal P = .001).

Moreover, the proportions of women with minimal to no pain during both menstrual days and nonmenstrual days were significantly higher with relugolix-CT: 65.0% (95% CI, 55.6%-73.5%) and 44.6% (95% CI, 32.3%-7.5%), respectively, compared with placebo: 19.3% (95% CI 13.2%–26.7%, nominal P = 001), and 21.6% (95% CI, 12.9%-32.7%, nominal P = 004), respectively.

Studies of relugolix monotherapy in Japanese women with uterine leiomyomas have demonstrated reductions in pain.

“Significantly, this combination therapy allows women to be treated over 2 years and to take the oral tablet themselves, unlike Lupron [leuprolide], which is injected and can only be taken for a couple of months because of bone loss,” Dr. Segars said. And the add-back component of combination therapy prevents the adverse symptoms of a hypoestrogenic state.

“The pain of fibroids is chronic, and the longer treatment allows time for the pain fibers to revert to a normal state,” he explained. “The pain pathways get etched into the nerves and it takes time to revert.”

He noted that the LIBERTY trials showed a slight downward trend in pain continuing after 24 weeks of treatment. Other studies of similar hormonal treatments have shown a reduction in the size of fibroids, which can be as large as a tennis ball.

As in endometriosis, leiomyomas are associated with elevated circulating cytokines and a systemic proinflammatory state. In endometriosis, this milieu is linked to the risk of inflammatory arthritis, fibromyalgia, lupus, and cardiovascular disease, Dr. Segars said. “If we did a deeper dive, we might find the same associations for fibroids.” Apart from chronic depression and fatigue, fibroids are linked to downstream pregnancy complications and poor outcomes such as miscarriage and preterm birth, he said.

“There remains a high unmet need for effective treatments, especially nonsurgical interventions, for women with uterine leiomyomas,” the authors wrote. Dr. Stewart added that “it would be helpful to learn more about how relugolix and other drugs in its class work in fibroids. No category of symptoms has been unresponsive to these medications – they are powerful drugs to help women with uterine fibroids.” She noted that relugolix-CT has already been approved outside the United States for symptoms beyond heavy menstrual bleeding.

Future research should focus on developing a therapy that does not interfere with fertility, Dr. Segars said. “We need a treatment that will allow women to get pregnant on it.”

Myovant Sciences GmbH sponsored LIBERTY 1 and 2 and oversaw all aspects of the studies. Dr. Stewart has provided consulting services to Myovant, Bayer, AbbVie, and ObsEva. She has received royalties from UpToDate and fees from Med Learning Group, Med-IQ, Medscape, Peer View, and PER, as well as honoraria from the American College of Obstetricians and Gynecologists and Massachusetts Medical Society. She holds a patent for methods and compounds for treatment of abnormal uterine bleeding. Dr. Segars has consulted for Bayer and Organon. Several coauthors reported similar financial relationships with private-sector entities and two coauthors are employees of Myovant.

Combination therapy with relugolix (Orgovyx, Relumina), a gonadotropin-releasing hormone antagonist, significantly reduced the pain of uterine fibroids, an undertreated aspect of this disease.

In pooled results from the multicenter randomized placebo-controlled LIBERTY 1 and 2 trials, relugolix combination therapy (CT) with the progestin norethindrone (Aygestin, Camila) markedly decreased both menstrual and nonmenstrual fibroid pain, as well as heavy bleeding and other symptoms of leiomyomas. This hormone-dependent condition occurs in 70%-80% of premenopausal women.

“Historically, studies of uterine fibroids have not asked about pain, so one of strengths of these studies is that they asked women to rate their pain and found a substantial proportion listed pain as a symptom,” lead author Elizabeth A. Stewart, MD, director of reproductive endocrinology at the Mayo Clinic in Rochester, Minn., said in an interview.

The combination was effective against all categories of leiomyoma symptoms, she said, and adverse events were few.

Bleeding has been the main focus of studies of leiomyoma therapies, while chronic pain has been largely neglected, said James H. Segars Jr., MD, director of the division of reproductive science and women’s health research at Johns Hopkins Medicine in Baltimore, who was not involved in the studies. Across both of the LIBERTY trials, involving 509 women randomized during the period April 2017 to December 2018, more than half overall (54.4%) met their pain reduction goals in a subpopulation analysis. Pain reduction was a secondary outcome of the trials, with bleeding reduction the primary endpoint. Other fibroid symptoms are abdominal bloating and pressure.

“The consistent and significant reduction in measures of pain with relugolix-CT observed in the LIBERTY program is clinically meaningful, patient-relevant, and together with an improvement of heavy menstrual bleeding and other uterine leiomyoma–associated symptoms, is likely to have a substantial effect on the life of women with symptomatic uterine leiomyomas,” Dr. Stewart and colleagues wrote. Their report was published online in Obstetrics & Gynecology.

Dr. Segars concurred. “This study is important because sometimes the only fibroid symptom women have is pain. If we ignore that, we miss a lot of women who have pain but no bleeding.”
 

The study

The premenopausal participants had a mean age of just over 42 years (range, 18-50) and were enrolled from North and South America, Europe, and Africa. All reported leiomyoma-associated heavy menstrual bleeding of 80 mL or greater per cycle for two cycles, or 160 mL or greater during one cycle.

In both arms, the mean body mass index was 32 kg/m², while menstrual blood loss volume was 245.4 (± 186.4) mL in the relugolix-CT and 207.4 (± 114.3) mL in the placebo group.

Pain was a frequent symptom, with approximately 70% in the intervention group and 74% in the placebo group reporting fibroid pain at baseline.

Women were randomized 1:1:1 to receive:

• Relugolix-CT (relugolix 40 mg, estradiol 1 mg, norethindrone acetate 0.5 mg)
• Delayed relugolix-CT (relugolix 40 mg monotherapy followed by relugolix-CT, each for 12 weeks)
• Placebo, taken orally once daily for 24 weeks

The therapy was well tolerated and adverse events were low.

The subpopulation analysis found that over the study period, the proportion of women achieving minimal to no pain (level 0 to 1) during the last 35 days of treatment was notably higher in the relugolix-CT arm than in the placebo arm: 45.2% (95% confidence interval [CI], 36.4%-54.3%) versus 13.9% (95% CI, 8.8%-20.5%) in the placebo group (nominal P = .001).

Moreover, the proportions of women with minimal to no pain during both menstrual days and nonmenstrual days were significantly higher with relugolix-CT: 65.0% (95% CI, 55.6%-73.5%) and 44.6% (95% CI, 32.3%-7.5%), respectively, compared with placebo: 19.3% (95% CI 13.2%–26.7%, nominal P = 001), and 21.6% (95% CI, 12.9%-32.7%, nominal P = 004), respectively.

Studies of relugolix monotherapy in Japanese women with uterine leiomyomas have demonstrated reductions in pain.

“Significantly, this combination therapy allows women to be treated over 2 years and to take the oral tablet themselves, unlike Lupron [leuprolide], which is injected and can only be taken for a couple of months because of bone loss,” Dr. Segars said. And the add-back component of combination therapy prevents the adverse symptoms of a hypoestrogenic state.

“The pain of fibroids is chronic, and the longer treatment allows time for the pain fibers to revert to a normal state,” he explained. “The pain pathways get etched into the nerves and it takes time to revert.”

He noted that the LIBERTY trials showed a slight downward trend in pain continuing after 24 weeks of treatment. Other studies of similar hormonal treatments have shown a reduction in the size of fibroids, which can be as large as a tennis ball.

As in endometriosis, leiomyomas are associated with elevated circulating cytokines and a systemic proinflammatory state. In endometriosis, this milieu is linked to the risk of inflammatory arthritis, fibromyalgia, lupus, and cardiovascular disease, Dr. Segars said. “If we did a deeper dive, we might find the same associations for fibroids.” Apart from chronic depression and fatigue, fibroids are linked to downstream pregnancy complications and poor outcomes such as miscarriage and preterm birth, he said.

“There remains a high unmet need for effective treatments, especially nonsurgical interventions, for women with uterine leiomyomas,” the authors wrote. Dr. Stewart added that “it would be helpful to learn more about how relugolix and other drugs in its class work in fibroids. No category of symptoms has been unresponsive to these medications – they are powerful drugs to help women with uterine fibroids.” She noted that relugolix-CT has already been approved outside the United States for symptoms beyond heavy menstrual bleeding.

Future research should focus on developing a therapy that does not interfere with fertility, Dr. Segars said. “We need a treatment that will allow women to get pregnant on it.”

Myovant Sciences GmbH sponsored LIBERTY 1 and 2 and oversaw all aspects of the studies. Dr. Stewart has provided consulting services to Myovant, Bayer, AbbVie, and ObsEva. She has received royalties from UpToDate and fees from Med Learning Group, Med-IQ, Medscape, Peer View, and PER, as well as honoraria from the American College of Obstetricians and Gynecologists and Massachusetts Medical Society. She holds a patent for methods and compounds for treatment of abnormal uterine bleeding. Dr. Segars has consulted for Bayer and Organon. Several coauthors reported similar financial relationships with private-sector entities and two coauthors are employees of Myovant.

A study presented at ESMO Breast Cancer 2022 documents a “significant long-term benefit” among women with breast cancer who were treated with tamoxifen.

The study was a secondary analysis of women with estrogen receptor (ER)-positive HER2-negative breast cancer who were treated between 1976 and 1996 in Sweden.

“Our findings suggest a significant long-term tamoxifen treatment benefit among patients with larger tumors, lymph node-negative tumors, PR-positive tumors, and Ki-67 low tumors,” according to Huma Dar, a doctoral candidate at Karolinska Institute, Stockholm, who authored the study.

The analysis found that patients with tumor size T1c, grade 2, lymph node-negative, PR-positive, and Ki-67-low tumors significantly benefited from treatment with tamoxifen for 20 years. And, for patients with tumor size T2-3, benefited significantly after 10 years of treatment with tamoxifen.

It is known that breast cancer patients with ER-positive tumors have a greater risk of distant recurrence – cancer spreading to tissues and organs far from the original tumor site. The selective estrogen receptor modulator tamoxifen, when used as an adjuvant therapy, has been shown to reduce the risk of tumor recurrence and increase survival in patients with ER-positive breast cancer, but not all patients benefit from this therapy.

To examine the long-term benefit of tamoxifen, Ms. Dar and colleagues analyzed data from randomized clinical trials of tamoxifen that took place in Stockholm between 1976 and 1997. The study included 1,242 patients with ER-positive/HER2-negative breast cancer and included a 20-year follow-up. Researchers looked at the relationship between tumor characteristics – including size, grade, lymph node status, the presence of progesterone receptor (PR), and levels of Ki-67, a protein linked with cell proliferation – and patient outcomes. 

In a related study published last year in JAMA Network Open, Ms. Dar and colleagues examined the long-term effects of tamoxifen in patients with low risk, postmenopausal, and lymph-node negative cancer. They found that patients with larger tumors, lower tumor grade and PR-positive tumors appeared to significantly benefit from tamoxifen treatment for up to 25 years. The team has since extended that work by looking at pre- and postmenopausal as well as low- and high-risk patients, Ms. Dar said. 

“We believe that our findings together with other study findings are important to understand the lifetime risk for patients diagnosed with breast cancer,” Ms. Dar said. “One potential clinical implication is related to tamoxifen benefit, which in our study we don’t see for patients with the smallest tumors.” She said that more studies are needed to confirm this result.

A limitation of this study is that clinical recommendations for disease management and treatment have changed since the initiation of the clinical trials. “The STO-trials were performed before aromatase inhibitors or ovarian function suppression became one of the recommended treatment options for ER-positive breast cancer, and when the duration of tamoxifen therapy was shorter than current recommendations,” Ms. Dar said.

The study was funded by the Swedish Research Council, Swedish Research Council for Health, Working life and Welfare, The Gösta Milton Donation Fund, and Swedish Cancer Society. The authors had no relevant disclosures.

A study presented at ESMO Breast Cancer 2022 documents a “significant long-term benefit” among women with breast cancer who were treated with tamoxifen.

The study was a secondary analysis of women with estrogen receptor (ER)-positive HER2-negative breast cancer who were treated between 1976 and 1996 in Sweden.

“Our findings suggest a significant long-term tamoxifen treatment benefit among patients with larger tumors, lymph node-negative tumors, PR-positive tumors, and Ki-67 low tumors,” according to Huma Dar, a doctoral candidate at Karolinska Institute, Stockholm, who authored the study.

The analysis found that patients with tumor size T1c, grade 2, lymph node-negative, PR-positive, and Ki-67-low tumors significantly benefited from treatment with tamoxifen for 20 years. And, for patients with tumor size T2-3, benefited significantly after 10 years of treatment with tamoxifen.

It is known that breast cancer patients with ER-positive tumors have a greater risk of distant recurrence – cancer spreading to tissues and organs far from the original tumor site. The selective estrogen receptor modulator tamoxifen, when used as an adjuvant therapy, has been shown to reduce the risk of tumor recurrence and increase survival in patients with ER-positive breast cancer, but not all patients benefit from this therapy.

To examine the long-term benefit of tamoxifen, Ms. Dar and colleagues analyzed data from randomized clinical trials of tamoxifen that took place in Stockholm between 1976 and 1997. The study included 1,242 patients with ER-positive/HER2-negative breast cancer and included a 20-year follow-up. Researchers looked at the relationship between tumor characteristics – including size, grade, lymph node status, the presence of progesterone receptor (PR), and levels of Ki-67, a protein linked with cell proliferation – and patient outcomes. 

In a related study published last year in JAMA Network Open, Ms. Dar and colleagues examined the long-term effects of tamoxifen in patients with low risk, postmenopausal, and lymph-node negative cancer. They found that patients with larger tumors, lower tumor grade and PR-positive tumors appeared to significantly benefit from tamoxifen treatment for up to 25 years. The team has since extended that work by looking at pre- and postmenopausal as well as low- and high-risk patients, Ms. Dar said. 

“We believe that our findings together with other study findings are important to understand the lifetime risk for patients diagnosed with breast cancer,” Ms. Dar said. “One potential clinical implication is related to tamoxifen benefit, which in our study we don’t see for patients with the smallest tumors.” She said that more studies are needed to confirm this result.

A limitation of this study is that clinical recommendations for disease management and treatment have changed since the initiation of the clinical trials. “The STO-trials were performed before aromatase inhibitors or ovarian function suppression became one of the recommended treatment options for ER-positive breast cancer, and when the duration of tamoxifen therapy was shorter than current recommendations,” Ms. Dar said.

The study was funded by the Swedish Research Council, Swedish Research Council for Health, Working life and Welfare, The Gösta Milton Donation Fund, and Swedish Cancer Society. The authors had no relevant disclosures.

A study presented at ESMO Breast Cancer 2022 documents a “significant long-term benefit” among women with breast cancer who were treated with tamoxifen.

The study was a secondary analysis of women with estrogen receptor (ER)-positive HER2-negative breast cancer who were treated between 1976 and 1996 in Sweden.

“Our findings suggest a significant long-term tamoxifen treatment benefit among patients with larger tumors, lymph node-negative tumors, PR-positive tumors, and Ki-67 low tumors,” according to Huma Dar, a doctoral candidate at Karolinska Institute, Stockholm, who authored the study.

The analysis found that patients with tumor size T1c, grade 2, lymph node-negative, PR-positive, and Ki-67-low tumors significantly benefited from treatment with tamoxifen for 20 years. And, for patients with tumor size T2-3, benefited significantly after 10 years of treatment with tamoxifen.

It is known that breast cancer patients with ER-positive tumors have a greater risk of distant recurrence – cancer spreading to tissues and organs far from the original tumor site. The selective estrogen receptor modulator tamoxifen, when used as an adjuvant therapy, has been shown to reduce the risk of tumor recurrence and increase survival in patients with ER-positive breast cancer, but not all patients benefit from this therapy.

To examine the long-term benefit of tamoxifen, Ms. Dar and colleagues analyzed data from randomized clinical trials of tamoxifen that took place in Stockholm between 1976 and 1997. The study included 1,242 patients with ER-positive/HER2-negative breast cancer and included a 20-year follow-up. Researchers looked at the relationship between tumor characteristics – including size, grade, lymph node status, the presence of progesterone receptor (PR), and levels of Ki-67, a protein linked with cell proliferation – and patient outcomes. 

In a related study published last year in JAMA Network Open, Ms. Dar and colleagues examined the long-term effects of tamoxifen in patients with low risk, postmenopausal, and lymph-node negative cancer. They found that patients with larger tumors, lower tumor grade and PR-positive tumors appeared to significantly benefit from tamoxifen treatment for up to 25 years. The team has since extended that work by looking at pre- and postmenopausal as well as low- and high-risk patients, Ms. Dar said. 

“We believe that our findings together with other study findings are important to understand the lifetime risk for patients diagnosed with breast cancer,” Ms. Dar said. “One potential clinical implication is related to tamoxifen benefit, which in our study we don’t see for patients with the smallest tumors.” She said that more studies are needed to confirm this result.

A limitation of this study is that clinical recommendations for disease management and treatment have changed since the initiation of the clinical trials. “The STO-trials were performed before aromatase inhibitors or ovarian function suppression became one of the recommended treatment options for ER-positive breast cancer, and when the duration of tamoxifen therapy was shorter than current recommendations,” Ms. Dar said.

The study was funded by the Swedish Research Council, Swedish Research Council for Health, Working life and Welfare, The Gösta Milton Donation Fund, and Swedish Cancer Society. The authors had no relevant disclosures.

BOSTON – As a former active-duty cavalry officer in the U.S. Army who served a 15-month tour in Iraq in 2003, Adam C. Byrd, MD, isn’t easily rattled.

On any given day, as the only dermatologist in his hometown of Louisville, Miss., which has a population of about 6,500, he sees 35-40 patients who present with conditions ranging from an infantile hemangioma to dermatomyositis and porphyria cutanea tarda. Being the go-to specialist for hundreds of miles with no on-site lab and no immediate personal access to Mohs surgeons and other subspecialists might unnerve some dermatologists, but not him.

Courtesy Dr. Adam Byrd

“They’re a text message away, but they’re not in my office,” he said during a session on rural dermatology at the annual meeting of the American Academy of Dermatology. “I don’t have a mid-level practitioner, either. It’s just me and the residents, so it can be somewhat isolating. But in a rural area, you’re doing your patients a disservice if you can’t handle broad-spectrum medical dermatology. I consider myself a family dermatologist; I do a little bit of everything.” This includes prescribing treatments ranging from methotrexate for psoriasis, psoriatic arthritis, eczema, and other conditions; cyclosporine and azathioprine for pediatric eczema; propranolol for infantile hemangiomas; to IV infusions for dermatomyositis; phlebotomy for porphyria cutanea tarda; and biologics.

With no on-site pathology lab, Dr. Byrd sends specimens twice a week to the University of Mississippi Medical Center in Jackson via FedEx to be read. “I have to wait 3 days for results instead of 2,” he said. At the end of each workday, he personally carries microbiology samples to Winston Medical Center in Louisville – the area’s only hospital and where he was born – for processing.

After completing a 5-year integrated internal medicine-dermatology residency at the University of Minnesota in 2016, Dr. Byrd worked with Robert T. Brodell, MD, who chairs the department of dermatology at UMMC, and other university officials to open a satellite clinic in Louisville, where he provides full-spectrum skin care for Northern Mississippians. The clinic, located about 95 miles from UMMC’s “mothership” in Jackson, has become a vital training ground for the university, which created the only rural-specific dermatology residency of the 142 accredited dermatology programs in the United States. Of the three to four residents accepted per year, one is a rural track resident who spends 3-month–long rotations at rural clinic sites such as Dr. Byrd’s during each of the 3 years of general dermatology training, and the remaining 9 months of each year alongside their non–rural track coresidents.

Courtesy Dr. Adam Byrd

One of the program’s rural track residents, Joshua R. Ortego, MD, worked in Dr. Byrd’s clinic during PGY-2. “It’s unique for one attending and one resident to work together for 3 months straight,” said Dr. Ortego, who grew up in Bay St. Louis on the Gulf Coast of Mississippi, which has a population of about 9,200. “Dr. Byrd learns our weaknesses and knows our strengths and areas for improvement. You get close. And there’s continuity; you see some patients back. With all the shuffling in the traditional dermatology residency model, sometimes you’re not seeing patients for follow-up appointments. But here you do.”

Rural dermatology track residents who rotate through Dr. Byrd’s Louisville clinic spend each Monday at the main campus in Jackson for a continuity clinic and didactics with non–rural track residents, “which allows for collegiality,” Dr. Ortego said. “My coresidents are like family; it would be hard to spend 3 months or even a year away from family like that.” The department foots the cost of lodging in a Louisville hotel 4 nights per week during these 3 months of training.

Dr. Ortego said that he performed a far greater number of procedures during PGY-2, compared with the averages performed in UMMC’s general dermatology rotation: 75 excisions (vs. 17), 71 repairs (vs. 15), and 23 excisions on the face or scalp (vs. none). He also cared for patients who presented with advanced disease because of access issues, and others with rare conditions. For example, in one afternoon clinic he and Dr. Byrd saw two patients with porphyria cutanea tarda, and one case each of dermatomyositis, bullous pemphigoid, and pyoderma gangrenosum. “We have an autoimmune blistering disease clinic in Jackson, but patients don’t want to drive there,” he said.

Courtesy Dr. Adam Byrd

Then there are the perks that come with practicing in a rural area, including ready access to hiking, fishing, hunting, and spending time with family and friends. “Rural residents should be comfortable with the lifestyle,” he said. “Some cities don’t have the same amenities as San Francisco or Boston, but not everyone requires that. They just love where they’re from.”

The residency’s structure is designed to address the dire shortage of rural-based dermatologists in the United States. A study published in 2018 found that the difference in dermatologist density between metropolitan and rural counties in the United States increased from 3.41 per 100,000 people (3.47 vs. 0.065 per 100,000 people) in 1995 to 4.03 per 100, 000 people (4.11 vs. 0.085 per 100,000 people in 2013; P = .053). That’s about 40 times the number of dermatologists in metro areas, compared with rural areas.

Residents enrolled in UMMC’s rural dermatology track are expected to serve at least 3 years at a rural location upon graduation at a site mutually agreed upon by the resident and the UMMC. Dr. Ortego plans to practice in Bay St. Louis after completing his residency. “The idea is that you’re happy, that you’re in your hometown,” he said.

According to Dr. Byrd, the 3-year commitment brings job security to rural track residents in their preferred location while meeting the demands of an underserved population. “We are still tweaking this,” he said of the residency track, which includes plans to establish more satellite clinics in other areas of rural Mississippi. “Our department chair does not have 100% control over hiring and office expansion. We are subject to the Mississippi Institutions of Higher Learning, which is a branch of the state government. This has to be addressed at the council of chairs and university chancellor level and even state government. It can be done, but you really must be dedicated.”

Meanwhile, the effect that dermatologists like Dr. Byrd have on citizens of his area of rural Mississippi is palpable. Many refuse to travel outside of Louisville city limits to see a specialist, so when surgery for a suspicious lesion is indicated, they tell him, “You’re going to do it, or it’s not going to get done,” said Dr. Byrd, who continues to serve in the Mississippi Army National Guard as a field surgeon. “I don’t say ‘no’ a whole lot.” He refers patients to Mohs micrographic surgery colleagues in Jackson daily and is transparent with patients who hesitate to elect Mohs surgery. “I’ll say, ‘I can do the job, but there’s a higher risk of positive margins, and a Mohs surgeon could do a much better job.’”

He acknowledged that rural dermatology “isn’t for everyone. It requires a physician that has a good training foundation in medical and surgical dermatology, someone with a ‘can do’ attitude and a healthy level of confidence. I try to do the best for my patients. It’s endearing when they trust you.”

Mary Logue, MD, who practices dermatology in Minot, N.D., finds the structure of UMMC’s rural dermatology track inspiring. Upon completing her dermatology residency at the University of New Mexico, where she remains on the volunteer faculty, she had hoped to return to serve the community of Gallup, N.M., and help bridge the gap in dermatology health care access for residents of rural New Mexico, especially those on Native American reservations. That opportunity never transpired, but Dr. Logue was able to pursue her passion for rural medicine in North Dakota.

“It is my hope that more programs will implement a similar structure to UMMC’s rural dermatology track and get more dermatologists practicing in rural areas,” Dr. Logue told this news organization. “They have developed a very practical and financially sustainable model, which I think every state could benefit from.”

She added that the UMMC “has found a way to bring dermatology to disadvantaged rural communities while also addressing the problem of underrepresented minorities in medicine. Medical students of color and medical students from rural communities are the least represented groups in dermatology, but the most likely to return to their communities to practice. Every day I see patients with adverse dermatologic outcomes as a direct result of lack of access to a dermatologist. This is happening across the country, which is why the efforts of UMMC Dermatology and their department chair, Dr. Brodell, are so important.”

BOSTON – As a former active-duty cavalry officer in the U.S. Army who served a 15-month tour in Iraq in 2003, Adam C. Byrd, MD, isn’t easily rattled.

On any given day, as the only dermatologist in his hometown of Louisville, Miss., which has a population of about 6,500, he sees 35-40 patients who present with conditions ranging from an infantile hemangioma to dermatomyositis and porphyria cutanea tarda. Being the go-to specialist for hundreds of miles with no on-site lab and no immediate personal access to Mohs surgeons and other subspecialists might unnerve some dermatologists, but not him.

Courtesy Dr. Adam Byrd

“They’re a text message away, but they’re not in my office,” he said during a session on rural dermatology at the annual meeting of the American Academy of Dermatology. “I don’t have a mid-level practitioner, either. It’s just me and the residents, so it can be somewhat isolating. But in a rural area, you’re doing your patients a disservice if you can’t handle broad-spectrum medical dermatology. I consider myself a family dermatologist; I do a little bit of everything.” This includes prescribing treatments ranging from methotrexate for psoriasis, psoriatic arthritis, eczema, and other conditions; cyclosporine and azathioprine for pediatric eczema; propranolol for infantile hemangiomas; to IV infusions for dermatomyositis; phlebotomy for porphyria cutanea tarda; and biologics.

With no on-site pathology lab, Dr. Byrd sends specimens twice a week to the University of Mississippi Medical Center in Jackson via FedEx to be read. “I have to wait 3 days for results instead of 2,” he said. At the end of each workday, he personally carries microbiology samples to Winston Medical Center in Louisville – the area’s only hospital and where he was born – for processing.

After completing a 5-year integrated internal medicine-dermatology residency at the University of Minnesota in 2016, Dr. Byrd worked with Robert T. Brodell, MD, who chairs the department of dermatology at UMMC, and other university officials to open a satellite clinic in Louisville, where he provides full-spectrum skin care for Northern Mississippians. The clinic, located about 95 miles from UMMC’s “mothership” in Jackson, has become a vital training ground for the university, which created the only rural-specific dermatology residency of the 142 accredited dermatology programs in the United States. Of the three to four residents accepted per year, one is a rural track resident who spends 3-month–long rotations at rural clinic sites such as Dr. Byrd’s during each of the 3 years of general dermatology training, and the remaining 9 months of each year alongside their non–rural track coresidents.

Courtesy Dr. Adam Byrd

One of the program’s rural track residents, Joshua R. Ortego, MD, worked in Dr. Byrd’s clinic during PGY-2. “It’s unique for one attending and one resident to work together for 3 months straight,” said Dr. Ortego, who grew up in Bay St. Louis on the Gulf Coast of Mississippi, which has a population of about 9,200. “Dr. Byrd learns our weaknesses and knows our strengths and areas for improvement. You get close. And there’s continuity; you see some patients back. With all the shuffling in the traditional dermatology residency model, sometimes you’re not seeing patients for follow-up appointments. But here you do.”

Rural dermatology track residents who rotate through Dr. Byrd’s Louisville clinic spend each Monday at the main campus in Jackson for a continuity clinic and didactics with non–rural track residents, “which allows for collegiality,” Dr. Ortego said. “My coresidents are like family; it would be hard to spend 3 months or even a year away from family like that.” The department foots the cost of lodging in a Louisville hotel 4 nights per week during these 3 months of training.

Dr. Ortego said that he performed a far greater number of procedures during PGY-2, compared with the averages performed in UMMC’s general dermatology rotation: 75 excisions (vs. 17), 71 repairs (vs. 15), and 23 excisions on the face or scalp (vs. none). He also cared for patients who presented with advanced disease because of access issues, and others with rare conditions. For example, in one afternoon clinic he and Dr. Byrd saw two patients with porphyria cutanea tarda, and one case each of dermatomyositis, bullous pemphigoid, and pyoderma gangrenosum. “We have an autoimmune blistering disease clinic in Jackson, but patients don’t want to drive there,” he said.

Courtesy Dr. Adam Byrd

Then there are the perks that come with practicing in a rural area, including ready access to hiking, fishing, hunting, and spending time with family and friends. “Rural residents should be comfortable with the lifestyle,” he said. “Some cities don’t have the same amenities as San Francisco or Boston, but not everyone requires that. They just love where they’re from.”

The residency’s structure is designed to address the dire shortage of rural-based dermatologists in the United States. A study published in 2018 found that the difference in dermatologist density between metropolitan and rural counties in the United States increased from 3.41 per 100,000 people (3.47 vs. 0.065 per 100,000 people) in 1995 to 4.03 per 100, 000 people (4.11 vs. 0.085 per 100,000 people in 2013; P = .053). That’s about 40 times the number of dermatologists in metro areas, compared with rural areas.

Residents enrolled in UMMC’s rural dermatology track are expected to serve at least 3 years at a rural location upon graduation at a site mutually agreed upon by the resident and the UMMC. Dr. Ortego plans to practice in Bay St. Louis after completing his residency. “The idea is that you’re happy, that you’re in your hometown,” he said.

According to Dr. Byrd, the 3-year commitment brings job security to rural track residents in their preferred location while meeting the demands of an underserved population. “We are still tweaking this,” he said of the residency track, which includes plans to establish more satellite clinics in other areas of rural Mississippi. “Our department chair does not have 100% control over hiring and office expansion. We are subject to the Mississippi Institutions of Higher Learning, which is a branch of the state government. This has to be addressed at the council of chairs and university chancellor level and even state government. It can be done, but you really must be dedicated.”

Meanwhile, the effect that dermatologists like Dr. Byrd have on citizens of his area of rural Mississippi is palpable. Many refuse to travel outside of Louisville city limits to see a specialist, so when surgery for a suspicious lesion is indicated, they tell him, “You’re going to do it, or it’s not going to get done,” said Dr. Byrd, who continues to serve in the Mississippi Army National Guard as a field surgeon. “I don’t say ‘no’ a whole lot.” He refers patients to Mohs micrographic surgery colleagues in Jackson daily and is transparent with patients who hesitate to elect Mohs surgery. “I’ll say, ‘I can do the job, but there’s a higher risk of positive margins, and a Mohs surgeon could do a much better job.’”

He acknowledged that rural dermatology “isn’t for everyone. It requires a physician that has a good training foundation in medical and surgical dermatology, someone with a ‘can do’ attitude and a healthy level of confidence. I try to do the best for my patients. It’s endearing when they trust you.”

Mary Logue, MD, who practices dermatology in Minot, N.D., finds the structure of UMMC’s rural dermatology track inspiring. Upon completing her dermatology residency at the University of New Mexico, where she remains on the volunteer faculty, she had hoped to return to serve the community of Gallup, N.M., and help bridge the gap in dermatology health care access for residents of rural New Mexico, especially those on Native American reservations. That opportunity never transpired, but Dr. Logue was able to pursue her passion for rural medicine in North Dakota.

“It is my hope that more programs will implement a similar structure to UMMC’s rural dermatology track and get more dermatologists practicing in rural areas,” Dr. Logue told this news organization. “They have developed a very practical and financially sustainable model, which I think every state could benefit from.”

She added that the UMMC “has found a way to bring dermatology to disadvantaged rural communities while also addressing the problem of underrepresented minorities in medicine. Medical students of color and medical students from rural communities are the least represented groups in dermatology, but the most likely to return to their communities to practice. Every day I see patients with adverse dermatologic outcomes as a direct result of lack of access to a dermatologist. This is happening across the country, which is why the efforts of UMMC Dermatology and their department chair, Dr. Brodell, are so important.”

BOSTON – As a former active-duty cavalry officer in the U.S. Army who served a 15-month tour in Iraq in 2003, Adam C. Byrd, MD, isn’t easily rattled.

On any given day, as the only dermatologist in his hometown of Louisville, Miss., which has a population of about 6,500, he sees 35-40 patients who present with conditions ranging from an infantile hemangioma to dermatomyositis and porphyria cutanea tarda. Being the go-to specialist for hundreds of miles with no on-site lab and no immediate personal access to Mohs surgeons and other subspecialists might unnerve some dermatologists, but not him.

Courtesy Dr. Adam Byrd

“They’re a text message away, but they’re not in my office,” he said during a session on rural dermatology at the annual meeting of the American Academy of Dermatology. “I don’t have a mid-level practitioner, either. It’s just me and the residents, so it can be somewhat isolating. But in a rural area, you’re doing your patients a disservice if you can’t handle broad-spectrum medical dermatology. I consider myself a family dermatologist; I do a little bit of everything.” This includes prescribing treatments ranging from methotrexate for psoriasis, psoriatic arthritis, eczema, and other conditions; cyclosporine and azathioprine for pediatric eczema; propranolol for infantile hemangiomas; to IV infusions for dermatomyositis; phlebotomy for porphyria cutanea tarda; and biologics.

With no on-site pathology lab, Dr. Byrd sends specimens twice a week to the University of Mississippi Medical Center in Jackson via FedEx to be read. “I have to wait 3 days for results instead of 2,” he said. At the end of each workday, he personally carries microbiology samples to Winston Medical Center in Louisville – the area’s only hospital and where he was born – for processing.

After completing a 5-year integrated internal medicine-dermatology residency at the University of Minnesota in 2016, Dr. Byrd worked with Robert T. Brodell, MD, who chairs the department of dermatology at UMMC, and other university officials to open a satellite clinic in Louisville, where he provides full-spectrum skin care for Northern Mississippians. The clinic, located about 95 miles from UMMC’s “mothership” in Jackson, has become a vital training ground for the university, which created the only rural-specific dermatology residency of the 142 accredited dermatology programs in the United States. Of the three to four residents accepted per year, one is a rural track resident who spends 3-month–long rotations at rural clinic sites such as Dr. Byrd’s during each of the 3 years of general dermatology training, and the remaining 9 months of each year alongside their non–rural track coresidents.

Courtesy Dr. Adam Byrd

One of the program’s rural track residents, Joshua R. Ortego, MD, worked in Dr. Byrd’s clinic during PGY-2. “It’s unique for one attending and one resident to work together for 3 months straight,” said Dr. Ortego, who grew up in Bay St. Louis on the Gulf Coast of Mississippi, which has a population of about 9,200. “Dr. Byrd learns our weaknesses and knows our strengths and areas for improvement. You get close. And there’s continuity; you see some patients back. With all the shuffling in the traditional dermatology residency model, sometimes you’re not seeing patients for follow-up appointments. But here you do.”

Rural dermatology track residents who rotate through Dr. Byrd’s Louisville clinic spend each Monday at the main campus in Jackson for a continuity clinic and didactics with non–rural track residents, “which allows for collegiality,” Dr. Ortego said. “My coresidents are like family; it would be hard to spend 3 months or even a year away from family like that.” The department foots the cost of lodging in a Louisville hotel 4 nights per week during these 3 months of training.

Dr. Ortego said that he performed a far greater number of procedures during PGY-2, compared with the averages performed in UMMC’s general dermatology rotation: 75 excisions (vs. 17), 71 repairs (vs. 15), and 23 excisions on the face or scalp (vs. none). He also cared for patients who presented with advanced disease because of access issues, and others with rare conditions. For example, in one afternoon clinic he and Dr. Byrd saw two patients with porphyria cutanea tarda, and one case each of dermatomyositis, bullous pemphigoid, and pyoderma gangrenosum. “We have an autoimmune blistering disease clinic in Jackson, but patients don’t want to drive there,” he said.

Courtesy Dr. Adam Byrd

Then there are the perks that come with practicing in a rural area, including ready access to hiking, fishing, hunting, and spending time with family and friends. “Rural residents should be comfortable with the lifestyle,” he said. “Some cities don’t have the same amenities as San Francisco or Boston, but not everyone requires that. They just love where they’re from.”

The residency’s structure is designed to address the dire shortage of rural-based dermatologists in the United States. A study published in 2018 found that the difference in dermatologist density between metropolitan and rural counties in the United States increased from 3.41 per 100,000 people (3.47 vs. 0.065 per 100,000 people) in 1995 to 4.03 per 100, 000 people (4.11 vs. 0.085 per 100,000 people in 2013; P = .053). That’s about 40 times the number of dermatologists in metro areas, compared with rural areas.

Residents enrolled in UMMC’s rural dermatology track are expected to serve at least 3 years at a rural location upon graduation at a site mutually agreed upon by the resident and the UMMC. Dr. Ortego plans to practice in Bay St. Louis after completing his residency. “The idea is that you’re happy, that you’re in your hometown,” he said.

According to Dr. Byrd, the 3-year commitment brings job security to rural track residents in their preferred location while meeting the demands of an underserved population. “We are still tweaking this,” he said of the residency track, which includes plans to establish more satellite clinics in other areas of rural Mississippi. “Our department chair does not have 100% control over hiring and office expansion. We are subject to the Mississippi Institutions of Higher Learning, which is a branch of the state government. This has to be addressed at the council of chairs and university chancellor level and even state government. It can be done, but you really must be dedicated.”

Meanwhile, the effect that dermatologists like Dr. Byrd have on citizens of his area of rural Mississippi is palpable. Many refuse to travel outside of Louisville city limits to see a specialist, so when surgery for a suspicious lesion is indicated, they tell him, “You’re going to do it, or it’s not going to get done,” said Dr. Byrd, who continues to serve in the Mississippi Army National Guard as a field surgeon. “I don’t say ‘no’ a whole lot.” He refers patients to Mohs micrographic surgery colleagues in Jackson daily and is transparent with patients who hesitate to elect Mohs surgery. “I’ll say, ‘I can do the job, but there’s a higher risk of positive margins, and a Mohs surgeon could do a much better job.’”

He acknowledged that rural dermatology “isn’t for everyone. It requires a physician that has a good training foundation in medical and surgical dermatology, someone with a ‘can do’ attitude and a healthy level of confidence. I try to do the best for my patients. It’s endearing when they trust you.”

Mary Logue, MD, who practices dermatology in Minot, N.D., finds the structure of UMMC’s rural dermatology track inspiring. Upon completing her dermatology residency at the University of New Mexico, where she remains on the volunteer faculty, she had hoped to return to serve the community of Gallup, N.M., and help bridge the gap in dermatology health care access for residents of rural New Mexico, especially those on Native American reservations. That opportunity never transpired, but Dr. Logue was able to pursue her passion for rural medicine in North Dakota.

“It is my hope that more programs will implement a similar structure to UMMC’s rural dermatology track and get more dermatologists practicing in rural areas,” Dr. Logue told this news organization. “They have developed a very practical and financially sustainable model, which I think every state could benefit from.”

She added that the UMMC “has found a way to bring dermatology to disadvantaged rural communities while also addressing the problem of underrepresented minorities in medicine. Medical students of color and medical students from rural communities are the least represented groups in dermatology, but the most likely to return to their communities to practice. Every day I see patients with adverse dermatologic outcomes as a direct result of lack of access to a dermatologist. This is happening across the country, which is why the efforts of UMMC Dermatology and their department chair, Dr. Brodell, are so important.”

Women with ductal carcinoma in situ (DCIS) breast cancer are generally uninformed about their diagnosis and are making uninformed treatment decisions, according to results of a study presented this month at ESMO Breast Cancer 2022, an annual meeting of the European Society for Medical Oncology.

The standard of care for women diagnosed with DCIS includes surgery with or without radiotherapy – even low-risk patients who are increasingly being steered toward active surveillance with annual mammograms. But few patients understand their diagnosis well enough to make informed decisions about treatment, according to a study led by Ellen Engelhardt, PhD, a postdoctoral fellow at The Netherlands Cancer Institute, Amsterdam.

“You’re not able to really have an informed preference until you understand the choices,” she said.

Dr. Engelhardt and colleagues surveyed 200 patients (mean age 59 years) from the LORD study, which is currently underway at The Netherlands Cancer Institute. The women were asked to complete a survey before treatment decisions were made. Their objective was to determine how knowledgeable patients were about DCIS. They found that only 34% of women answered four out of seven questions correctly: 19% of patients believed that DCIS could metastasize to organs other than the breast; 31% did not realize DCIS could progress to invasive breast cancer if left untreated; 79% thought DCIS could always be seen on mammograms; and, 93% said that progression could always be detected before it becomes “too extensive.” Knowledge of DCIS was found not to be associated with patient education level.

Susie X. Sun, MD, FACS, a breast surgeon at the University of Texas MD Anderson Cancer Center, Houston, said the findings clearly highlight a disconnect in communication between doctor and patient.

“I was surprised, because this clearly demonstrates there is a disconnect between what patients are being told by their providers and what is being perceived. It really shows us that we need to do a better job of making sure that our patients understand the information they’re given,” she said.

Dr. Sun, who was not involved in the study, said that DCIS needs to be explained well to patients. When they receive a diagnosis, often all they hear is, “I have breast cancer. It is really important for us to stress to patients how DCIS is different from invasive breast cancer,” she said.

The “Management of Low-risk (grade I and II) DCIS (LORD)” study is one of three studies comparing active surveillance to surgery (with or without radiotherapy).

A limitation of the study presented at ESMO Breast Cancer is that it remains unclear why patients answered questions incorrectly. Was information never communicated to them? Or, did they mishear or misunderstand the doctor? In future studies, Dr. Engelhardt and her colleagues plan to record and analyze audio tapes of consultations to determine where the communication disconnect lies.

Dr. Engelhardt did not disclose any conflicts associated with this work.

Women with ductal carcinoma in situ (DCIS) breast cancer are generally uninformed about their diagnosis and are making uninformed treatment decisions, according to results of a study presented this month at ESMO Breast Cancer 2022, an annual meeting of the European Society for Medical Oncology.

The standard of care for women diagnosed with DCIS includes surgery with or without radiotherapy – even low-risk patients who are increasingly being steered toward active surveillance with annual mammograms. But few patients understand their diagnosis well enough to make informed decisions about treatment, according to a study led by Ellen Engelhardt, PhD, a postdoctoral fellow at The Netherlands Cancer Institute, Amsterdam.

“You’re not able to really have an informed preference until you understand the choices,” she said.

Dr. Engelhardt and colleagues surveyed 200 patients (mean age 59 years) from the LORD study, which is currently underway at The Netherlands Cancer Institute. The women were asked to complete a survey before treatment decisions were made. Their objective was to determine how knowledgeable patients were about DCIS. They found that only 34% of women answered four out of seven questions correctly: 19% of patients believed that DCIS could metastasize to organs other than the breast; 31% did not realize DCIS could progress to invasive breast cancer if left untreated; 79% thought DCIS could always be seen on mammograms; and, 93% said that progression could always be detected before it becomes “too extensive.” Knowledge of DCIS was found not to be associated with patient education level.

Susie X. Sun, MD, FACS, a breast surgeon at the University of Texas MD Anderson Cancer Center, Houston, said the findings clearly highlight a disconnect in communication between doctor and patient.

“I was surprised, because this clearly demonstrates there is a disconnect between what patients are being told by their providers and what is being perceived. It really shows us that we need to do a better job of making sure that our patients understand the information they’re given,” she said.

Dr. Sun, who was not involved in the study, said that DCIS needs to be explained well to patients. When they receive a diagnosis, often all they hear is, “I have breast cancer. It is really important for us to stress to patients how DCIS is different from invasive breast cancer,” she said.

The “Management of Low-risk (grade I and II) DCIS (LORD)” study is one of three studies comparing active surveillance to surgery (with or without radiotherapy).

A limitation of the study presented at ESMO Breast Cancer is that it remains unclear why patients answered questions incorrectly. Was information never communicated to them? Or, did they mishear or misunderstand the doctor? In future studies, Dr. Engelhardt and her colleagues plan to record and analyze audio tapes of consultations to determine where the communication disconnect lies.

Dr. Engelhardt did not disclose any conflicts associated with this work.

Women with ductal carcinoma in situ (DCIS) breast cancer are generally uninformed about their diagnosis and are making uninformed treatment decisions, according to results of a study presented this month at ESMO Breast Cancer 2022, an annual meeting of the European Society for Medical Oncology.

The standard of care for women diagnosed with DCIS includes surgery with or without radiotherapy – even low-risk patients who are increasingly being steered toward active surveillance with annual mammograms. But few patients understand their diagnosis well enough to make informed decisions about treatment, according to a study led by Ellen Engelhardt, PhD, a postdoctoral fellow at The Netherlands Cancer Institute, Amsterdam.

“You’re not able to really have an informed preference until you understand the choices,” she said.

Dr. Engelhardt and colleagues surveyed 200 patients (mean age 59 years) from the LORD study, which is currently underway at The Netherlands Cancer Institute. The women were asked to complete a survey before treatment decisions were made. Their objective was to determine how knowledgeable patients were about DCIS. They found that only 34% of women answered four out of seven questions correctly: 19% of patients believed that DCIS could metastasize to organs other than the breast; 31% did not realize DCIS could progress to invasive breast cancer if left untreated; 79% thought DCIS could always be seen on mammograms; and, 93% said that progression could always be detected before it becomes “too extensive.” Knowledge of DCIS was found not to be associated with patient education level.

Susie X. Sun, MD, FACS, a breast surgeon at the University of Texas MD Anderson Cancer Center, Houston, said the findings clearly highlight a disconnect in communication between doctor and patient.

“I was surprised, because this clearly demonstrates there is a disconnect between what patients are being told by their providers and what is being perceived. It really shows us that we need to do a better job of making sure that our patients understand the information they’re given,” she said.

Dr. Sun, who was not involved in the study, said that DCIS needs to be explained well to patients. When they receive a diagnosis, often all they hear is, “I have breast cancer. It is really important for us to stress to patients how DCIS is different from invasive breast cancer,” she said.

The “Management of Low-risk (grade I and II) DCIS (LORD)” study is one of three studies comparing active surveillance to surgery (with or without radiotherapy).

A limitation of the study presented at ESMO Breast Cancer is that it remains unclear why patients answered questions incorrectly. Was information never communicated to them? Or, did they mishear or misunderstand the doctor? In future studies, Dr. Engelhardt and her colleagues plan to record and analyze audio tapes of consultations to determine where the communication disconnect lies.

Dr. Engelhardt did not disclose any conflicts associated with this work.

Reducing the frequency of routine blood monitoring for methotrexate in patients with rheumatoid arthritis during the COVID-19 pandemic was associated with no adverse outcomes for patients, British researchers have found.

Similar laboratory results were recorded in patients who were switched from testing once per month to once every 3 or 5 months, Natasha Wood, a general practice trainee at North Devon District Hospital in Barnstaple, England, reported at the annual meeting of the British Society for Rheumatology.

sshepard/iStock

“Less frequent monitoring did not result in patient harm,” she said.

“There’s an increasing evidence base; we wonder whether now’s the time to reconsider our DMARD-monitoring strategy,” Ms. Wood said.
 

Changes in monitoring because of pandemic

Methotrexate monitoring is important to minimize the risk of harm to patients, and it is recommended that standard laboratory tests, such as a complete blood count, creatinine, and liver enzymes are measured regularly. Indeed, both the BSR and the American College of Rheumatology have specific recommendations on the monitoring of methotrexate and other conventional synthetic disease-modifying antirheumatic drugs (csDMARDS).

“The BSR used to advise for monthly blood tests in patients taking methotrexate,” Ms. Wood said, but the BSR moved to recommend testing patients on a stable dose every 3 months in 2017.

“Things of course changed again rapidly with COVID, with the BSR quickly updating their guidelines advising for less frequent monitoring in this patient group,” Ms. Wood said.

As a result, the North Devon Clinical Commissioning Group, which covers the hospital where Ms. Wood works, agreed to allow testing every 6 months for patients on a stable methotrexate dose. “This was across specialties, so not just rheumatology, but dermatology and gastroenterology as well,” she said.

“This provided us with a really exciting and unique opportunity to look at this patient group and see what happened,” Ms. Wood explained.

Effect of less frequent monitoring

At the meeting, Ms. Wood presented the results of an audit of 854 patients found via a search of hospital pathology records who were stable on methotrexate monotherapy for at least 12 months.

Two subanalyses were performed: One looked at patients who had changed from blood testing once every month to once every 3 months (n = 229) and the other looking at a group of 120 patients who had gone from testing once every 3 months to approximately every 5 months.

The mean age of patients was 67 for monthly testing, 69 for testing every 3 months, and 66 for testing about every 5 months, with around two-thirds of patients being of female sex.

A comparison of the number of blood tests performed to the end of April 2020 with the number performed to the end of April 2021 showed that there had mainly been a shift from testing once per month to once every 3 months, with some patients being tested in line with the revised BSR guidelines at around 5 months.

“Interestingly, a third of this group had no changed monitoring frequency despite the change in guidelines,” Ms. Wood said.

“Prepandemic, most patients [were] having monthly bloods despite BSR advice from 2017, and despite the pandemic with the updated shared care guidelines,” patients were still having blood drawn every 3 months, Ms. Wood noted. This perhaps needs further investigation and consideration to understand why recommended changes to the frequency of testing are not being adhered to.

The overall distribution of laboratory findings was similar among those who went from testing once per month to once every 3 months and from every 3 months to every 5 months. This included the distribution of neutrophils, whole blood counts, and alanine aminotransferase. There were some changes for platelets, mean cell volume, and the estimated glomerular filtration rate, but these were not clinically significant.

“Abnormal blood results aren’t common in stable methotrexate monotherapy patients,” Ms. Wood reported. “Where abnormalities did occur, it was in the context of patients being concurrently unwell and symptomatic.”
 

Time for patient-initiated testing?

There are several advantages of less frequent methotrexate monitoring, Ms. Wood said. One is the practicalities of getting to and from appointments, particularly in remote locations, such as where she works.

In addition to reducing workloads and pressure on already busy hospitals and primary care, this could have a huge environmental impact, she suggested.

Moreover, “moderate-quality evidence” supports the current monitoring frequency recommendation.

“We know that our numbers are small – we’re a small center – but our findings are consistent with much larger studies across the U.K.,” Ms. Wood said.

“We wonder whether there’s the possibility of moving towards annual monitoring with good safety netting and patient education for additional blood tests if they are unwell,” she said, adding that “now may be the time for patient-initiated methotrexate monitoring.”

Ms. Wood disclosed Janssen sponsorship for attending the BSR 2022 annual meeting.

Reducing the frequency of routine blood monitoring for methotrexate in patients with rheumatoid arthritis during the COVID-19 pandemic was associated with no adverse outcomes for patients, British researchers have found.

Similar laboratory results were recorded in patients who were switched from testing once per month to once every 3 or 5 months, Natasha Wood, a general practice trainee at North Devon District Hospital in Barnstaple, England, reported at the annual meeting of the British Society for Rheumatology.

sshepard/iStock

“Less frequent monitoring did not result in patient harm,” she said.

“There’s an increasing evidence base; we wonder whether now’s the time to reconsider our DMARD-monitoring strategy,” Ms. Wood said.
 

Changes in monitoring because of pandemic

Methotrexate monitoring is important to minimize the risk of harm to patients, and it is recommended that standard laboratory tests, such as a complete blood count, creatinine, and liver enzymes are measured regularly. Indeed, both the BSR and the American College of Rheumatology have specific recommendations on the monitoring of methotrexate and other conventional synthetic disease-modifying antirheumatic drugs (csDMARDS).

“The BSR used to advise for monthly blood tests in patients taking methotrexate,” Ms. Wood said, but the BSR moved to recommend testing patients on a stable dose every 3 months in 2017.

“Things of course changed again rapidly with COVID, with the BSR quickly updating their guidelines advising for less frequent monitoring in this patient group,” Ms. Wood said.

As a result, the North Devon Clinical Commissioning Group, which covers the hospital where Ms. Wood works, agreed to allow testing every 6 months for patients on a stable methotrexate dose. “This was across specialties, so not just rheumatology, but dermatology and gastroenterology as well,” she said.

“This provided us with a really exciting and unique opportunity to look at this patient group and see what happened,” Ms. Wood explained.

Effect of less frequent monitoring

At the meeting, Ms. Wood presented the results of an audit of 854 patients found via a search of hospital pathology records who were stable on methotrexate monotherapy for at least 12 months.

Two subanalyses were performed: One looked at patients who had changed from blood testing once every month to once every 3 months (n = 229) and the other looking at a group of 120 patients who had gone from testing once every 3 months to approximately every 5 months.

The mean age of patients was 67 for monthly testing, 69 for testing every 3 months, and 66 for testing about every 5 months, with around two-thirds of patients being of female sex.

A comparison of the number of blood tests performed to the end of April 2020 with the number performed to the end of April 2021 showed that there had mainly been a shift from testing once per month to once every 3 months, with some patients being tested in line with the revised BSR guidelines at around 5 months.

“Interestingly, a third of this group had no changed monitoring frequency despite the change in guidelines,” Ms. Wood said.

“Prepandemic, most patients [were] having monthly bloods despite BSR advice from 2017, and despite the pandemic with the updated shared care guidelines,” patients were still having blood drawn every 3 months, Ms. Wood noted. This perhaps needs further investigation and consideration to understand why recommended changes to the frequency of testing are not being adhered to.

The overall distribution of laboratory findings was similar among those who went from testing once per month to once every 3 months and from every 3 months to every 5 months. This included the distribution of neutrophils, whole blood counts, and alanine aminotransferase. There were some changes for platelets, mean cell volume, and the estimated glomerular filtration rate, but these were not clinically significant.

“Abnormal blood results aren’t common in stable methotrexate monotherapy patients,” Ms. Wood reported. “Where abnormalities did occur, it was in the context of patients being concurrently unwell and symptomatic.”
 

Time for patient-initiated testing?

There are several advantages of less frequent methotrexate monitoring, Ms. Wood said. One is the practicalities of getting to and from appointments, particularly in remote locations, such as where she works.

In addition to reducing workloads and pressure on already busy hospitals and primary care, this could have a huge environmental impact, she suggested.

Moreover, “moderate-quality evidence” supports the current monitoring frequency recommendation.

“We know that our numbers are small – we’re a small center – but our findings are consistent with much larger studies across the U.K.,” Ms. Wood said.

“We wonder whether there’s the possibility of moving towards annual monitoring with good safety netting and patient education for additional blood tests if they are unwell,” she said, adding that “now may be the time for patient-initiated methotrexate monitoring.”

Ms. Wood disclosed Janssen sponsorship for attending the BSR 2022 annual meeting.

Reducing the frequency of routine blood monitoring for methotrexate in patients with rheumatoid arthritis during the COVID-19 pandemic was associated with no adverse outcomes for patients, British researchers have found.

Similar laboratory results were recorded in patients who were switched from testing once per month to once every 3 or 5 months, Natasha Wood, a general practice trainee at North Devon District Hospital in Barnstaple, England, reported at the annual meeting of the British Society for Rheumatology.

sshepard/iStock

“Less frequent monitoring did not result in patient harm,” she said.

“There’s an increasing evidence base; we wonder whether now’s the time to reconsider our DMARD-monitoring strategy,” Ms. Wood said.
 

Changes in monitoring because of pandemic

Methotrexate monitoring is important to minimize the risk of harm to patients, and it is recommended that standard laboratory tests, such as a complete blood count, creatinine, and liver enzymes are measured regularly. Indeed, both the BSR and the American College of Rheumatology have specific recommendations on the monitoring of methotrexate and other conventional synthetic disease-modifying antirheumatic drugs (csDMARDS).

“The BSR used to advise for monthly blood tests in patients taking methotrexate,” Ms. Wood said, but the BSR moved to recommend testing patients on a stable dose every 3 months in 2017.

“Things of course changed again rapidly with COVID, with the BSR quickly updating their guidelines advising for less frequent monitoring in this patient group,” Ms. Wood said.

As a result, the North Devon Clinical Commissioning Group, which covers the hospital where Ms. Wood works, agreed to allow testing every 6 months for patients on a stable methotrexate dose. “This was across specialties, so not just rheumatology, but dermatology and gastroenterology as well,” she said.

“This provided us with a really exciting and unique opportunity to look at this patient group and see what happened,” Ms. Wood explained.

Effect of less frequent monitoring

At the meeting, Ms. Wood presented the results of an audit of 854 patients found via a search of hospital pathology records who were stable on methotrexate monotherapy for at least 12 months.

Two subanalyses were performed: One looked at patients who had changed from blood testing once every month to once every 3 months (n = 229) and the other looking at a group of 120 patients who had gone from testing once every 3 months to approximately every 5 months.

The mean age of patients was 67 for monthly testing, 69 for testing every 3 months, and 66 for testing about every 5 months, with around two-thirds of patients being of female sex.

A comparison of the number of blood tests performed to the end of April 2020 with the number performed to the end of April 2021 showed that there had mainly been a shift from testing once per month to once every 3 months, with some patients being tested in line with the revised BSR guidelines at around 5 months.

“Interestingly, a third of this group had no changed monitoring frequency despite the change in guidelines,” Ms. Wood said.

“Prepandemic, most patients [were] having monthly bloods despite BSR advice from 2017, and despite the pandemic with the updated shared care guidelines,” patients were still having blood drawn every 3 months, Ms. Wood noted. This perhaps needs further investigation and consideration to understand why recommended changes to the frequency of testing are not being adhered to.

The overall distribution of laboratory findings was similar among those who went from testing once per month to once every 3 months and from every 3 months to every 5 months. This included the distribution of neutrophils, whole blood counts, and alanine aminotransferase. There were some changes for platelets, mean cell volume, and the estimated glomerular filtration rate, but these were not clinically significant.

“Abnormal blood results aren’t common in stable methotrexate monotherapy patients,” Ms. Wood reported. “Where abnormalities did occur, it was in the context of patients being concurrently unwell and symptomatic.”
 

Time for patient-initiated testing?

There are several advantages of less frequent methotrexate monitoring, Ms. Wood said. One is the practicalities of getting to and from appointments, particularly in remote locations, such as where she works.

In addition to reducing workloads and pressure on already busy hospitals and primary care, this could have a huge environmental impact, she suggested.

Moreover, “moderate-quality evidence” supports the current monitoring frequency recommendation.

“We know that our numbers are small – we’re a small center – but our findings are consistent with much larger studies across the U.K.,” Ms. Wood said.

“We wonder whether there’s the possibility of moving towards annual monitoring with good safety netting and patient education for additional blood tests if they are unwell,” she said, adding that “now may be the time for patient-initiated methotrexate monitoring.”

Ms. Wood disclosed Janssen sponsorship for attending the BSR 2022 annual meeting.

New data present further evidence that SARS-CoV-2 infection can settle in the gastrointestinal (GI) tract and that it can persist long after the infection has cleared the lungs.

Infection of the GI tract may figure prominently in long COVID, the study authors suggest.

Led by Aravind Natarajan, PhD, with the departments of genetics and medicine at Stanford (Calif.) University, they analyzed fecal RNA shedding up to 10 months after a COVID-19 diagnosis in 673 stool samples from 113 patients with mild to moderate disease.

They found that in the week after diagnosis, COVID RNA remnants were present in the stool of approximately half (49.2%) of the patients. Seven months later, about 4% of them shed fecal viral RNA.

The authors note that there was no ongoing SARS-CoV-2 RNA shedding in respiratory samples of patients at the 4-month mark.

Using self-reported symptoms regularly collected by questionnaire, they also found a correlation of long-term fecal shedding of SARS-CoV-2 RNA with abdominal pain, nausea, and vomiting.

The findings were published online in Med.
 

Implications of long-term viral shedding

Previous studies have found SARS-CoV-2 RNA in respiratory and fecal samples and have documented viral replication in lung and intestinal tissue.

But before the current study, little had been known about long-term shedding, especially in those who have mild COVID. Most studies of viral shedding have been with severe COVID cases.

The authors note that most studies of this kind are cross-sectional. The few other longitudinal studies have focused on early time points just after diagnosis.

Senior author Ami S. Bhatt, MD, associate professor in the departments of medicine and hematology at Stanford, told this news organization that though the viral genetic material in the feces lingers, on the basis of available evidence, it is highly unlikely to be contagious in most cases.

She said that understanding the dynamics of fecal shedding of SARS-CoV-2 genetic material will help interpret wastewater-based studies that are trying to determine population prevalence of the virus.

“While we don’t know the exact clinical importance of the longer-term shedding of SARS-CoV-2 in individuals with COVID-19, some have speculated that those who have long-term shedding of SARS-CoV-2 may have ongoing infections that might benefit from treatment,” she said.

“Our data support the idea that the long-term GI-related symptoms in some people might be the consequence of an ongoing infection in the GI tract, even after the respiratory infection has cleared,” Dr. Bhatt said.

“Alternatively, the presence of ongoing viral genetic material in the gut might be a trigger for the immune system to continually be active against the virus, and our immune system reaction may be the reason for long-COVID type symptoms,” she added. “This area is ripe for additional studies.”

Dr. Bhatt and colleagues will continue studying viral shedding in fecal samples as part of the nationwide RECOVER Initiative.

When reached for comment, David A. Johnson, MD, professor of medicine and chief of gastroenterology, Eastern Virginia Medical School, Norfolk, said in an interview that previous studies have indicated that the virus may be detected in the stool for a month or more and for about 2 weeks on average. Whether the virus is infectious has been in question.

But it’s not so much that the virus is infectious in the GI tract and causing symptoms, he said. Rather, there are biomic changes related to COVID, including a loss of diversity in the gut bacteria, which disrupts the balance.

“This may actually in some way predispose some patients to impaired clearance of their symptoms,” Dr. Johnson explained. “There seems to be a growing recognition that this entity called long-haul COVID may be related to specific bacterial disruptions, and the more rapidly you can resolve these disruptions, the less likely you are to continue with long-haul symptoms.”

He said that among people who have mild COVID, the virus typically clears and gut bacteria return to normal. With severe or persistent illness, gut dysbiosis persists, he said.

“People need to be aware that the GI tract is involved in a sizable percent of patients with COVID,” Dr. Johnson said. “The GI-tract testing may reflect that the virus is there, but persistence of the detectable test positivity is very unlikely to reflect active virus.”

The authors note in this study that they collected only six samples from the participants over the 10-month period.

“Follow-up studies with more frequent sampling, especially in the first 2 months after diagnosis, may help build a more nuanced model of decline of fecal viral RNA concentration over time,” they write.

The study was supported by a Stanford ChemH-IMA grant, fellowships from the AACR and the National Science Foundation, and the National Institutes of Health. The authors and Dr. Johnson report no relevant financial relationships. Dr. Johnson is a regular contributor to Medscape.

A version of this article first appeared to Medscape.com.

New data present further evidence that SARS-CoV-2 infection can settle in the gastrointestinal (GI) tract and that it can persist long after the infection has cleared the lungs.

Infection of the GI tract may figure prominently in long COVID, the study authors suggest.

Led by Aravind Natarajan, PhD, with the departments of genetics and medicine at Stanford (Calif.) University, they analyzed fecal RNA shedding up to 10 months after a COVID-19 diagnosis in 673 stool samples from 113 patients with mild to moderate disease.

They found that in the week after diagnosis, COVID RNA remnants were present in the stool of approximately half (49.2%) of the patients. Seven months later, about 4% of them shed fecal viral RNA.

The authors note that there was no ongoing SARS-CoV-2 RNA shedding in respiratory samples of patients at the 4-month mark.

Using self-reported symptoms regularly collected by questionnaire, they also found a correlation of long-term fecal shedding of SARS-CoV-2 RNA with abdominal pain, nausea, and vomiting.

The findings were published online in Med.
 

Implications of long-term viral shedding

Previous studies have found SARS-CoV-2 RNA in respiratory and fecal samples and have documented viral replication in lung and intestinal tissue.

But before the current study, little had been known about long-term shedding, especially in those who have mild COVID. Most studies of viral shedding have been with severe COVID cases.

The authors note that most studies of this kind are cross-sectional. The few other longitudinal studies have focused on early time points just after diagnosis.

Senior author Ami S. Bhatt, MD, associate professor in the departments of medicine and hematology at Stanford, told this news organization that though the viral genetic material in the feces lingers, on the basis of available evidence, it is highly unlikely to be contagious in most cases.

She said that understanding the dynamics of fecal shedding of SARS-CoV-2 genetic material will help interpret wastewater-based studies that are trying to determine population prevalence of the virus.

“While we don’t know the exact clinical importance of the longer-term shedding of SARS-CoV-2 in individuals with COVID-19, some have speculated that those who have long-term shedding of SARS-CoV-2 may have ongoing infections that might benefit from treatment,” she said.

“Our data support the idea that the long-term GI-related symptoms in some people might be the consequence of an ongoing infection in the GI tract, even after the respiratory infection has cleared,” Dr. Bhatt said.

“Alternatively, the presence of ongoing viral genetic material in the gut might be a trigger for the immune system to continually be active against the virus, and our immune system reaction may be the reason for long-COVID type symptoms,” she added. “This area is ripe for additional studies.”

Dr. Bhatt and colleagues will continue studying viral shedding in fecal samples as part of the nationwide RECOVER Initiative.

When reached for comment, David A. Johnson, MD, professor of medicine and chief of gastroenterology, Eastern Virginia Medical School, Norfolk, said in an interview that previous studies have indicated that the virus may be detected in the stool for a month or more and for about 2 weeks on average. Whether the virus is infectious has been in question.

But it’s not so much that the virus is infectious in the GI tract and causing symptoms, he said. Rather, there are biomic changes related to COVID, including a loss of diversity in the gut bacteria, which disrupts the balance.

“This may actually in some way predispose some patients to impaired clearance of their symptoms,” Dr. Johnson explained. “There seems to be a growing recognition that this entity called long-haul COVID may be related to specific bacterial disruptions, and the more rapidly you can resolve these disruptions, the less likely you are to continue with long-haul symptoms.”

He said that among people who have mild COVID, the virus typically clears and gut bacteria return to normal. With severe or persistent illness, gut dysbiosis persists, he said.

“People need to be aware that the GI tract is involved in a sizable percent of patients with COVID,” Dr. Johnson said. “The GI-tract testing may reflect that the virus is there, but persistence of the detectable test positivity is very unlikely to reflect active virus.”

The authors note in this study that they collected only six samples from the participants over the 10-month period.

“Follow-up studies with more frequent sampling, especially in the first 2 months after diagnosis, may help build a more nuanced model of decline of fecal viral RNA concentration over time,” they write.

The study was supported by a Stanford ChemH-IMA grant, fellowships from the AACR and the National Science Foundation, and the National Institutes of Health. The authors and Dr. Johnson report no relevant financial relationships. Dr. Johnson is a regular contributor to Medscape.

A version of this article first appeared to Medscape.com.

New data present further evidence that SARS-CoV-2 infection can settle in the gastrointestinal (GI) tract and that it can persist long after the infection has cleared the lungs.

Infection of the GI tract may figure prominently in long COVID, the study authors suggest.

Led by Aravind Natarajan, PhD, with the departments of genetics and medicine at Stanford (Calif.) University, they analyzed fecal RNA shedding up to 10 months after a COVID-19 diagnosis in 673 stool samples from 113 patients with mild to moderate disease.

They found that in the week after diagnosis, COVID RNA remnants were present in the stool of approximately half (49.2%) of the patients. Seven months later, about 4% of them shed fecal viral RNA.

The authors note that there was no ongoing SARS-CoV-2 RNA shedding in respiratory samples of patients at the 4-month mark.

Using self-reported symptoms regularly collected by questionnaire, they also found a correlation of long-term fecal shedding of SARS-CoV-2 RNA with abdominal pain, nausea, and vomiting.

The findings were published online in Med.
 

Implications of long-term viral shedding

Previous studies have found SARS-CoV-2 RNA in respiratory and fecal samples and have documented viral replication in lung and intestinal tissue.

But before the current study, little had been known about long-term shedding, especially in those who have mild COVID. Most studies of viral shedding have been with severe COVID cases.

The authors note that most studies of this kind are cross-sectional. The few other longitudinal studies have focused on early time points just after diagnosis.

Senior author Ami S. Bhatt, MD, associate professor in the departments of medicine and hematology at Stanford, told this news organization that though the viral genetic material in the feces lingers, on the basis of available evidence, it is highly unlikely to be contagious in most cases.

She said that understanding the dynamics of fecal shedding of SARS-CoV-2 genetic material will help interpret wastewater-based studies that are trying to determine population prevalence of the virus.

“While we don’t know the exact clinical importance of the longer-term shedding of SARS-CoV-2 in individuals with COVID-19, some have speculated that those who have long-term shedding of SARS-CoV-2 may have ongoing infections that might benefit from treatment,” she said.

“Our data support the idea that the long-term GI-related symptoms in some people might be the consequence of an ongoing infection in the GI tract, even after the respiratory infection has cleared,” Dr. Bhatt said.

“Alternatively, the presence of ongoing viral genetic material in the gut might be a trigger for the immune system to continually be active against the virus, and our immune system reaction may be the reason for long-COVID type symptoms,” she added. “This area is ripe for additional studies.”

Dr. Bhatt and colleagues will continue studying viral shedding in fecal samples as part of the nationwide RECOVER Initiative.

When reached for comment, David A. Johnson, MD, professor of medicine and chief of gastroenterology, Eastern Virginia Medical School, Norfolk, said in an interview that previous studies have indicated that the virus may be detected in the stool for a month or more and for about 2 weeks on average. Whether the virus is infectious has been in question.

But it’s not so much that the virus is infectious in the GI tract and causing symptoms, he said. Rather, there are biomic changes related to COVID, including a loss of diversity in the gut bacteria, which disrupts the balance.

“This may actually in some way predispose some patients to impaired clearance of their symptoms,” Dr. Johnson explained. “There seems to be a growing recognition that this entity called long-haul COVID may be related to specific bacterial disruptions, and the more rapidly you can resolve these disruptions, the less likely you are to continue with long-haul symptoms.”

He said that among people who have mild COVID, the virus typically clears and gut bacteria return to normal. With severe or persistent illness, gut dysbiosis persists, he said.

“People need to be aware that the GI tract is involved in a sizable percent of patients with COVID,” Dr. Johnson said. “The GI-tract testing may reflect that the virus is there, but persistence of the detectable test positivity is very unlikely to reflect active virus.”

The authors note in this study that they collected only six samples from the participants over the 10-month period.

“Follow-up studies with more frequent sampling, especially in the first 2 months after diagnosis, may help build a more nuanced model of decline of fecal viral RNA concentration over time,” they write.

The study was supported by a Stanford ChemH-IMA grant, fellowships from the AACR and the National Science Foundation, and the National Institutes of Health. The authors and Dr. Johnson report no relevant financial relationships. Dr. Johnson is a regular contributor to Medscape.

A version of this article first appeared to Medscape.com.

The current sustained increase in COVID-19 has brought the total number of cases in children to over 13 million since the start of the pandemic, according to the American Academy of Pediatrics and the Children’s Hospital Association.

The latest weekly count – 62,467 reported for the week ending May 5 – was 17.4% higher than the previous week and marks four consecutive increases since early April, when cases dropped to their lowest point since last summer. The cumulative number of cases in children is 13,052,988, which accounts for 19.0% of all cases reported in the United States, the AAP and CHA said in their weekly COVID-19 report.

Other measures of incidence show the same steady rise. The rate of new admissions of children aged 0-17 with confirmed COVID-19, which had dipped as low as 0.13 per 100,000 population on April 11, was up to 0.19 per 100,000 on May 6, and the 7-day average for total admissions was 136 per day for May 1-7, compared with 118 for the last week of April, according to the Centers for Disease Control and Prevention.

At the state level, new admission rates for May 6 show wide variation, even regionally. Rhode Island came in with a 0.00 per 100,000 on that day, while Vermont recorded 0.88 admissions per 100,000, the highest of any state and lower only than the District of Columbia’s 1.23 per 100,000. Connecticut (0.45) and Massachusetts (0.33) also were in the highest group (see map), while Maine was in the lowest, CDC data show.

Nationally, emergency department visits also have been rising over the last month or so. Children aged 0-11 years, who were down to a 7-day average of 0.5% of ED visits with diagnosed COVID-19 in early April, saw that number rise to 1.4% on May 5. Children aged 12-15 years went from a rate of 0.3% in late March to the current 1.2%, as did 16- to 17-year-olds, the CDC said on its COVID Data Tracker.

The vaccination effort, meanwhile, continues to lose steam, at least among children who are currently eligible. Initial vaccinations in those aged 5-11 slipped to their lowest-ever 1-week total, 47,000 for April 28 to May 4, while children aged 16-17 continued a long-term slide that has the weekly count down to just 29,000, the AAP said in its weekly vaccination report.

Here’s how those latest recipients changed the populations of vaccinated children in the last week: 35.4% of all 5- to 11-year-olds had received at least one dose as of May 4, compared with 35.3% on April 27, with increases from 67.4% to 67.5% for 12- to 15-year-olds and 72.7% to 72.8% among those aged 16-17, the CDC reported.
 

The current sustained increase in COVID-19 has brought the total number of cases in children to over 13 million since the start of the pandemic, according to the American Academy of Pediatrics and the Children’s Hospital Association.

The latest weekly count – 62,467 reported for the week ending May 5 – was 17.4% higher than the previous week and marks four consecutive increases since early April, when cases dropped to their lowest point since last summer. The cumulative number of cases in children is 13,052,988, which accounts for 19.0% of all cases reported in the United States, the AAP and CHA said in their weekly COVID-19 report.

Other measures of incidence show the same steady rise. The rate of new admissions of children aged 0-17 with confirmed COVID-19, which had dipped as low as 0.13 per 100,000 population on April 11, was up to 0.19 per 100,000 on May 6, and the 7-day average for total admissions was 136 per day for May 1-7, compared with 118 for the last week of April, according to the Centers for Disease Control and Prevention.

At the state level, new admission rates for May 6 show wide variation, even regionally. Rhode Island came in with a 0.00 per 100,000 on that day, while Vermont recorded 0.88 admissions per 100,000, the highest of any state and lower only than the District of Columbia’s 1.23 per 100,000. Connecticut (0.45) and Massachusetts (0.33) also were in the highest group (see map), while Maine was in the lowest, CDC data show.

Nationally, emergency department visits also have been rising over the last month or so. Children aged 0-11 years, who were down to a 7-day average of 0.5% of ED visits with diagnosed COVID-19 in early April, saw that number rise to 1.4% on May 5. Children aged 12-15 years went from a rate of 0.3% in late March to the current 1.2%, as did 16- to 17-year-olds, the CDC said on its COVID Data Tracker.

The vaccination effort, meanwhile, continues to lose steam, at least among children who are currently eligible. Initial vaccinations in those aged 5-11 slipped to their lowest-ever 1-week total, 47,000 for April 28 to May 4, while children aged 16-17 continued a long-term slide that has the weekly count down to just 29,000, the AAP said in its weekly vaccination report.

Here’s how those latest recipients changed the populations of vaccinated children in the last week: 35.4% of all 5- to 11-year-olds had received at least one dose as of May 4, compared with 35.3% on April 27, with increases from 67.4% to 67.5% for 12- to 15-year-olds and 72.7% to 72.8% among those aged 16-17, the CDC reported.
 

The current sustained increase in COVID-19 has brought the total number of cases in children to over 13 million since the start of the pandemic, according to the American Academy of Pediatrics and the Children’s Hospital Association.

The latest weekly count – 62,467 reported for the week ending May 5 – was 17.4% higher than the previous week and marks four consecutive increases since early April, when cases dropped to their lowest point since last summer. The cumulative number of cases in children is 13,052,988, which accounts for 19.0% of all cases reported in the United States, the AAP and CHA said in their weekly COVID-19 report.

Other measures of incidence show the same steady rise. The rate of new admissions of children aged 0-17 with confirmed COVID-19, which had dipped as low as 0.13 per 100,000 population on April 11, was up to 0.19 per 100,000 on May 6, and the 7-day average for total admissions was 136 per day for May 1-7, compared with 118 for the last week of April, according to the Centers for Disease Control and Prevention.

At the state level, new admission rates for May 6 show wide variation, even regionally. Rhode Island came in with a 0.00 per 100,000 on that day, while Vermont recorded 0.88 admissions per 100,000, the highest of any state and lower only than the District of Columbia’s 1.23 per 100,000. Connecticut (0.45) and Massachusetts (0.33) also were in the highest group (see map), while Maine was in the lowest, CDC data show.

Nationally, emergency department visits also have been rising over the last month or so. Children aged 0-11 years, who were down to a 7-day average of 0.5% of ED visits with diagnosed COVID-19 in early April, saw that number rise to 1.4% on May 5. Children aged 12-15 years went from a rate of 0.3% in late March to the current 1.2%, as did 16- to 17-year-olds, the CDC said on its COVID Data Tracker.

The vaccination effort, meanwhile, continues to lose steam, at least among children who are currently eligible. Initial vaccinations in those aged 5-11 slipped to their lowest-ever 1-week total, 47,000 for April 28 to May 4, while children aged 16-17 continued a long-term slide that has the weekly count down to just 29,000, the AAP said in its weekly vaccination report.

Here’s how those latest recipients changed the populations of vaccinated children in the last week: 35.4% of all 5- to 11-year-olds had received at least one dose as of May 4, compared with 35.3% on April 27, with increases from 67.4% to 67.5% for 12- to 15-year-olds and 72.7% to 72.8% among those aged 16-17, the CDC reported.
 

For nonpedunculated polyps measuring 3 mm or less, cold forceps polypectomy is noninferior to cold snare polypectomy and takes significantly less time, according to the results of the TINYPOLYP trial.

“In our trial, which is the largest to date evaluating complete resection of polyps ≤ 3 mm using cold forceps versus cold snare, we demonstrate that it is acceptable to remove ≤ 3 mm polyps with either cold snare or cold forceps,” lead author Mike Wei, MD, a gastroenterology and hepatology fellow at Stanford University, California, told this news organization.

“Cold forceps can oftentimes be the more efficient way to remove polyps compared to cold snare, and, as such, it was important to provide validation for this practice,” Dr. Wei said.

The study was published online in The American Journal of Gastroenterology.
 

Evaluating two techniques

Both the U.S. Multi-Society Task Force on Colorectal Cancer and the European Society of Gastrointestinal Endoscopy recommend that diminutive (< 5 mm) and small (6-9 mm) polyps be removed by cold snare polypectomy (CSP).

But whether CSP has a significant advantage over cold forceps polypectomy (CFP) for polyps ≤ 3 mm was unclear.

The TINYPOLYP trial enrolled 179 adults aged 18 years and older who underwent colonoscopy for any indication; colonoscopy was performed by four board-certified endoscopists who each had at least 4 years of experience after completing their fellowship.

A total of 279 nonpedunculated polyps ≤ 3 mm were identified; 138 were removed by CSP, and 141 were removed by CFP. Patient and procedure characteristics were similar in the two groups.

The polyps were similar in size in the CSP and CFP groups (2.5 and 2.6 mm, respectively), as was the distribution of polyps (33.3% and 26.2% in the ascending colon; 26.8% and 24.8% in the transverse colon). A higher proportion of tubular adenomas were removed by CSP than by CFP (79.7% vs. 66.0%).

CSP took significantly longer to perform than CFP (42.3 sec vs. 23.2 sec, P < .001). But with CFP, it was significantly more likely that polyps would need to be removed in more than one piece, compared with CSP (15.6% vs. 3.6%, P < .001).

Hemostatic clip was deployed for one polyp in the CFP group (0.7%); none were used in the CSP group, which was a nonsignificant difference.

There was also no significant difference in positive margins on biopsy (two cases in each group; 1.7%) or in the rate of complete resection (98.3% in both groups), demonstrating noninferiority of CFP, compared with CSP, the study team says.

There were no 30-day complications in either group, including perforation, postpolypectomy bleeding, and postpolypectomy syndrome, and no patient required management of postpolypectomy bleeding. No patient died within 30 days of colonoscopy.

On the basis of their results, Dr. Wei and colleagues say, “When an endoscopist encounters a diminutive polyp ≤ 3 mm, either a cold forceps or cold snare can be utilized during the procedure.”
 

Guidance for endoscopists

Reached for comment, Emre Gorgun, MD, in the department of colorectal surgery at the Cleveland Clinic, Ohio, said this is an “interesting” study that attempts to pinpoint the “best endoscopic management of tiny polyps.”

“From previously published, well-designed studies, we know that the cold snare technique works very well for polyps up to 10 mm. There have been more recent studies showing that the cold snare technique can be used even in larger polyps, 10-15 mm,” Dr. Gorgun said in an interview.

On the other hand, for polyps < 5 mm, “cold snare technique may take longer and may not provide any added benefits,” he noted. “It may be associated with higher cost due to utilizing more tools, as well as more procedure time and provider services.”

Dr. Gorgun said that the results of the TINYPOLYP study “can help endoscopists in decisionmaking when they come across polyps smaller than 5 mm.”

The study demonstrates that these tiny polyps can “certainly be destroyed/removed by the cold forceps approach,” he added.

The trial had no specific funding. Dr. Wei reports no relevant financial relationships. Dr. Gorgun is a consultant for Boston Scientific, Olympus, and Dilumen.

A version of this article first appeared on Medscape.com.

For nonpedunculated polyps measuring 3 mm or less, cold forceps polypectomy is noninferior to cold snare polypectomy and takes significantly less time, according to the results of the TINYPOLYP trial.

“In our trial, which is the largest to date evaluating complete resection of polyps ≤ 3 mm using cold forceps versus cold snare, we demonstrate that it is acceptable to remove ≤ 3 mm polyps with either cold snare or cold forceps,” lead author Mike Wei, MD, a gastroenterology and hepatology fellow at Stanford University, California, told this news organization.

“Cold forceps can oftentimes be the more efficient way to remove polyps compared to cold snare, and, as such, it was important to provide validation for this practice,” Dr. Wei said.

The study was published online in The American Journal of Gastroenterology.
 

Evaluating two techniques

Both the U.S. Multi-Society Task Force on Colorectal Cancer and the European Society of Gastrointestinal Endoscopy recommend that diminutive (< 5 mm) and small (6-9 mm) polyps be removed by cold snare polypectomy (CSP).

But whether CSP has a significant advantage over cold forceps polypectomy (CFP) for polyps ≤ 3 mm was unclear.

The TINYPOLYP trial enrolled 179 adults aged 18 years and older who underwent colonoscopy for any indication; colonoscopy was performed by four board-certified endoscopists who each had at least 4 years of experience after completing their fellowship.

A total of 279 nonpedunculated polyps ≤ 3 mm were identified; 138 were removed by CSP, and 141 were removed by CFP. Patient and procedure characteristics were similar in the two groups.

The polyps were similar in size in the CSP and CFP groups (2.5 and 2.6 mm, respectively), as was the distribution of polyps (33.3% and 26.2% in the ascending colon; 26.8% and 24.8% in the transverse colon). A higher proportion of tubular adenomas were removed by CSP than by CFP (79.7% vs. 66.0%).

CSP took significantly longer to perform than CFP (42.3 sec vs. 23.2 sec, P < .001). But with CFP, it was significantly more likely that polyps would need to be removed in more than one piece, compared with CSP (15.6% vs. 3.6%, P < .001).

Hemostatic clip was deployed for one polyp in the CFP group (0.7%); none were used in the CSP group, which was a nonsignificant difference.

There was also no significant difference in positive margins on biopsy (two cases in each group; 1.7%) or in the rate of complete resection (98.3% in both groups), demonstrating noninferiority of CFP, compared with CSP, the study team says.

There were no 30-day complications in either group, including perforation, postpolypectomy bleeding, and postpolypectomy syndrome, and no patient required management of postpolypectomy bleeding. No patient died within 30 days of colonoscopy.

On the basis of their results, Dr. Wei and colleagues say, “When an endoscopist encounters a diminutive polyp ≤ 3 mm, either a cold forceps or cold snare can be utilized during the procedure.”
 

Guidance for endoscopists

Reached for comment, Emre Gorgun, MD, in the department of colorectal surgery at the Cleveland Clinic, Ohio, said this is an “interesting” study that attempts to pinpoint the “best endoscopic management of tiny polyps.”

“From previously published, well-designed studies, we know that the cold snare technique works very well for polyps up to 10 mm. There have been more recent studies showing that the cold snare technique can be used even in larger polyps, 10-15 mm,” Dr. Gorgun said in an interview.

On the other hand, for polyps < 5 mm, “cold snare technique may take longer and may not provide any added benefits,” he noted. “It may be associated with higher cost due to utilizing more tools, as well as more procedure time and provider services.”

Dr. Gorgun said that the results of the TINYPOLYP study “can help endoscopists in decisionmaking when they come across polyps smaller than 5 mm.”

The study demonstrates that these tiny polyps can “certainly be destroyed/removed by the cold forceps approach,” he added.

The trial had no specific funding. Dr. Wei reports no relevant financial relationships. Dr. Gorgun is a consultant for Boston Scientific, Olympus, and Dilumen.

A version of this article first appeared on Medscape.com.

For nonpedunculated polyps measuring 3 mm or less, cold forceps polypectomy is noninferior to cold snare polypectomy and takes significantly less time, according to the results of the TINYPOLYP trial.

“In our trial, which is the largest to date evaluating complete resection of polyps ≤ 3 mm using cold forceps versus cold snare, we demonstrate that it is acceptable to remove ≤ 3 mm polyps with either cold snare or cold forceps,” lead author Mike Wei, MD, a gastroenterology and hepatology fellow at Stanford University, California, told this news organization.

“Cold forceps can oftentimes be the more efficient way to remove polyps compared to cold snare, and, as such, it was important to provide validation for this practice,” Dr. Wei said.

The study was published online in The American Journal of Gastroenterology.
 

Evaluating two techniques

Both the U.S. Multi-Society Task Force on Colorectal Cancer and the European Society of Gastrointestinal Endoscopy recommend that diminutive (< 5 mm) and small (6-9 mm) polyps be removed by cold snare polypectomy (CSP).

But whether CSP has a significant advantage over cold forceps polypectomy (CFP) for polyps ≤ 3 mm was unclear.

The TINYPOLYP trial enrolled 179 adults aged 18 years and older who underwent colonoscopy for any indication; colonoscopy was performed by four board-certified endoscopists who each had at least 4 years of experience after completing their fellowship.

A total of 279 nonpedunculated polyps ≤ 3 mm were identified; 138 were removed by CSP, and 141 were removed by CFP. Patient and procedure characteristics were similar in the two groups.

The polyps were similar in size in the CSP and CFP groups (2.5 and 2.6 mm, respectively), as was the distribution of polyps (33.3% and 26.2% in the ascending colon; 26.8% and 24.8% in the transverse colon). A higher proportion of tubular adenomas were removed by CSP than by CFP (79.7% vs. 66.0%).

CSP took significantly longer to perform than CFP (42.3 sec vs. 23.2 sec, P < .001). But with CFP, it was significantly more likely that polyps would need to be removed in more than one piece, compared with CSP (15.6% vs. 3.6%, P < .001).

Hemostatic clip was deployed for one polyp in the CFP group (0.7%); none were used in the CSP group, which was a nonsignificant difference.

There was also no significant difference in positive margins on biopsy (two cases in each group; 1.7%) or in the rate of complete resection (98.3% in both groups), demonstrating noninferiority of CFP, compared with CSP, the study team says.

There were no 30-day complications in either group, including perforation, postpolypectomy bleeding, and postpolypectomy syndrome, and no patient required management of postpolypectomy bleeding. No patient died within 30 days of colonoscopy.

On the basis of their results, Dr. Wei and colleagues say, “When an endoscopist encounters a diminutive polyp ≤ 3 mm, either a cold forceps or cold snare can be utilized during the procedure.”
 

Guidance for endoscopists

Reached for comment, Emre Gorgun, MD, in the department of colorectal surgery at the Cleveland Clinic, Ohio, said this is an “interesting” study that attempts to pinpoint the “best endoscopic management of tiny polyps.”

“From previously published, well-designed studies, we know that the cold snare technique works very well for polyps up to 10 mm. There have been more recent studies showing that the cold snare technique can be used even in larger polyps, 10-15 mm,” Dr. Gorgun said in an interview.

On the other hand, for polyps < 5 mm, “cold snare technique may take longer and may not provide any added benefits,” he noted. “It may be associated with higher cost due to utilizing more tools, as well as more procedure time and provider services.”

Dr. Gorgun said that the results of the TINYPOLYP study “can help endoscopists in decisionmaking when they come across polyps smaller than 5 mm.”

The study demonstrates that these tiny polyps can “certainly be destroyed/removed by the cold forceps approach,” he added.

The trial had no specific funding. Dr. Wei reports no relevant financial relationships. Dr. Gorgun is a consultant for Boston Scientific, Olympus, and Dilumen.

A version of this article first appeared on Medscape.com.

Eating disorders are among the most prevalent, disabling, and potentially fatal psychiatric illnesses, and the COVID-19 pandemic has exacerbated their burden, with a 15.3% increase in incidence in 2020 compared with previous years.¹ This increase was almost solely among adolescent girls with anorexia nervosa (AN), which is often insidious in onset and more difficult to treat as it advances. Adolescents with AN are most likely to present to their pediatricians, so awareness and early recognition of the symptoms is critical. Pediatricians are also an integral part of the treatment team in AN and can offer monitoring for serious complications, alongside valuable guidance to parents, who are central to treatment and the reestablishment of healthy eating habits in their children. Here we will review the epidemiology, diagnosis, and treatment of anorexia, with an emphasis on what pediatricians need to know to screen and to facilitate treatment.

Epidemiology

AN is marked by a fear of gaining weight or behaviors that interfere with weight gain and a self-evaluation unduly influenced by weight and body shape. Youth with AN often deny the seriousness of their malnutrition, although that is not required for diagnosis. AN can be of a restrictive or binge-purge subtype, and amenorrhea is no longer a requirement for diagnosis. There is not a specific weight or body mass index cutoff for the diagnosis, but the severity of AN is determined by the BMI percentile normed to age and sex. The average age of onset is 18, and the prepandemic prevalence of AN was about 1% of the population. It affects about 10 times as many females as males. It is quite rare prior to puberty, affecting about 0.01% of that age group. There is a heritable component, with a fivefold relative risk in youth with a parent with AN, and twin studies suggest heritability rates as high as 75%. Youth with rigid cognitive styles appear more vulnerable, as do those who participate in activities such as ballet, gymnastics, modeling, and wrestling because of the role of appearance and weight in performance. More than half of patients with AN will have another psychiatric illness, most commonly anxiety disorders, depression, or obsessive-compulsive disorder. AN becomes chronic in up to 15% of sufferers and the mortality rate is close to 10%, with approximately half dying from medical complications and half dying by suicide.

Screening

Parents and pediatricians are usually the first to notice that a child has started to lose weight or is falling off the growth curve. But weight changes usually emerge after feelings of preoccupation with weight, body shape, and body satisfaction. If parents report escalating pickiness around food, increased or compulsive exercise, persistent self-consciousness and self-criticism around weight and body shape, it is worth starting with screening questions.

If you notice preoccupation or anxiety around being weighed, even if the weight or growth curve are still normal, it is worthwhile to screen. Screening questions, such as the SCOFF questionnaire with five simple questions, can be very sensitive for both AN and bulimia nervosa.² There are also many validated screening instruments, such as the Eating Disorder Inventory or Eating Attitudes Test (for adolescents) and the Kids Eating Disorder Survey and the Child Eating Attitudes Test (for younger children), that are short self-reports that you can have your patients fill out when you have a higher index of suspicion. Weight loss or growth failure without a preoccupation around weight or appearance needs a thorough a medical workup, and could be a function of other psychiatric problems, such as depression.

If a child screens positive for an eating disorder, your full physical examination, growth curves, and longitudinal growth charts are critical for diagnosis. Percentile BMIs must be used, given the inaccuracy of standard BMI calculations in this age group. (Centers for Disease Control and Prevention age and sex growth charts include methods for this calculation). Laboratory assessment, including metabolic, kidney, pancreatic, and thyroid function, and an EKG can illuminate if there are consequences of restricting or purging. Of course, you want to evaluate for significant medical symptoms, including bradycardia, orthostasis, and hypokalemia. These medical symptoms are not limited to the severely underweight and merit referral to an emergency department and possible medical admission.

Then, a referral to a clinician who is expert in the assessment and treatment of eating disorders is needed. This may be a child psychiatrist, psychologist, or a colleague pediatrician with this specialization. It is also very important to begin the conversation with the family to introduce your concerns, describe what you have noticed, and discuss the need for further assessment and possibly treatment.

Treatment

Family-based therapy (FBT) is the first-line treatment of shorter-duration AN in children and adolescents. It focuses on the parents, helping them to calmly and effectively manage their child’s eating behaviors until their weight and behaviors have normalized. As a patient’s nutritional status improves, so does cognitive function, emotional flexibility, and mood. Individual therapy and psychopharmacologic treatment can be very effective for comorbid anxiety, mood, attentional, and thought disorders. Family-based work does include the child and is often done in group-based settings with clinicians from multiple disciplines. Dietitians provide education and guidance about healthy nutrition to the child and parents. Therapists may work with the child, parents, or full family to focus on behavior modification and managing distress. Most academic medical centers provide access to FBT, but there are many regions with no providers of this evidence-based treatment. One of the silver linings of the COVID-19 pandemic is that several online services have emerged offering FBT, working with families to manage mealtimes and treatment entirely at home.³ Pediatricians provide regular medical checks to measure progress and help with decisions about when it is safe to permit exercise or advance privileges and independence around eating. Some pediatricians have discovered a deep interest in this area of pediatrics and built their practices on it. Given the surge in prevalence of AN and the needs for adolescent mental health services, we hope more will do so.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

References

1. Taquet M et al. Br J Psychiatry. 2022;220:262-4.

2. Morgan JF et al. West J Med. 2000 Mar;172(3):164-5.

3. Matheson BE et al. Int J Eat Disord. 2020 Jul;53(7):1142-54.

Eating disorders are among the most prevalent, disabling, and potentially fatal psychiatric illnesses, and the COVID-19 pandemic has exacerbated their burden, with a 15.3% increase in incidence in 2020 compared with previous years.¹ This increase was almost solely among adolescent girls with anorexia nervosa (AN), which is often insidious in onset and more difficult to treat as it advances. Adolescents with AN are most likely to present to their pediatricians, so awareness and early recognition of the symptoms is critical. Pediatricians are also an integral part of the treatment team in AN and can offer monitoring for serious complications, alongside valuable guidance to parents, who are central to treatment and the reestablishment of healthy eating habits in their children. Here we will review the epidemiology, diagnosis, and treatment of anorexia, with an emphasis on what pediatricians need to know to screen and to facilitate treatment.

Epidemiology

AN is marked by a fear of gaining weight or behaviors that interfere with weight gain and a self-evaluation unduly influenced by weight and body shape. Youth with AN often deny the seriousness of their malnutrition, although that is not required for diagnosis. AN can be of a restrictive or binge-purge subtype, and amenorrhea is no longer a requirement for diagnosis. There is not a specific weight or body mass index cutoff for the diagnosis, but the severity of AN is determined by the BMI percentile normed to age and sex. The average age of onset is 18, and the prepandemic prevalence of AN was about 1% of the population. It affects about 10 times as many females as males. It is quite rare prior to puberty, affecting about 0.01% of that age group. There is a heritable component, with a fivefold relative risk in youth with a parent with AN, and twin studies suggest heritability rates as high as 75%. Youth with rigid cognitive styles appear more vulnerable, as do those who participate in activities such as ballet, gymnastics, modeling, and wrestling because of the role of appearance and weight in performance. More than half of patients with AN will have another psychiatric illness, most commonly anxiety disorders, depression, or obsessive-compulsive disorder. AN becomes chronic in up to 15% of sufferers and the mortality rate is close to 10%, with approximately half dying from medical complications and half dying by suicide.

Screening

Parents and pediatricians are usually the first to notice that a child has started to lose weight or is falling off the growth curve. But weight changes usually emerge after feelings of preoccupation with weight, body shape, and body satisfaction. If parents report escalating pickiness around food, increased or compulsive exercise, persistent self-consciousness and self-criticism around weight and body shape, it is worth starting with screening questions.

If you notice preoccupation or anxiety around being weighed, even if the weight or growth curve are still normal, it is worthwhile to screen. Screening questions, such as the SCOFF questionnaire with five simple questions, can be very sensitive for both AN and bulimia nervosa.² There are also many validated screening instruments, such as the Eating Disorder Inventory or Eating Attitudes Test (for adolescents) and the Kids Eating Disorder Survey and the Child Eating Attitudes Test (for younger children), that are short self-reports that you can have your patients fill out when you have a higher index of suspicion. Weight loss or growth failure without a preoccupation around weight or appearance needs a thorough a medical workup, and could be a function of other psychiatric problems, such as depression.

If a child screens positive for an eating disorder, your full physical examination, growth curves, and longitudinal growth charts are critical for diagnosis. Percentile BMIs must be used, given the inaccuracy of standard BMI calculations in this age group. (Centers for Disease Control and Prevention age and sex growth charts include methods for this calculation). Laboratory assessment, including metabolic, kidney, pancreatic, and thyroid function, and an EKG can illuminate if there are consequences of restricting or purging. Of course, you want to evaluate for significant medical symptoms, including bradycardia, orthostasis, and hypokalemia. These medical symptoms are not limited to the severely underweight and merit referral to an emergency department and possible medical admission.

Then, a referral to a clinician who is expert in the assessment and treatment of eating disorders is needed. This may be a child psychiatrist, psychologist, or a colleague pediatrician with this specialization. It is also very important to begin the conversation with the family to introduce your concerns, describe what you have noticed, and discuss the need for further assessment and possibly treatment.

Treatment

Family-based therapy (FBT) is the first-line treatment of shorter-duration AN in children and adolescents. It focuses on the parents, helping them to calmly and effectively manage their child’s eating behaviors until their weight and behaviors have normalized. As a patient’s nutritional status improves, so does cognitive function, emotional flexibility, and mood. Individual therapy and psychopharmacologic treatment can be very effective for comorbid anxiety, mood, attentional, and thought disorders. Family-based work does include the child and is often done in group-based settings with clinicians from multiple disciplines. Dietitians provide education and guidance about healthy nutrition to the child and parents. Therapists may work with the child, parents, or full family to focus on behavior modification and managing distress. Most academic medical centers provide access to FBT, but there are many regions with no providers of this evidence-based treatment. One of the silver linings of the COVID-19 pandemic is that several online services have emerged offering FBT, working with families to manage mealtimes and treatment entirely at home.³ Pediatricians provide regular medical checks to measure progress and help with decisions about when it is safe to permit exercise or advance privileges and independence around eating. Some pediatricians have discovered a deep interest in this area of pediatrics and built their practices on it. Given the surge in prevalence of AN and the needs for adolescent mental health services, we hope more will do so.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

References

1. Taquet M et al. Br J Psychiatry. 2022;220:262-4.

2. Morgan JF et al. West J Med. 2000 Mar;172(3):164-5.

3. Matheson BE et al. Int J Eat Disord. 2020 Jul;53(7):1142-54.

Eating disorders are among the most prevalent, disabling, and potentially fatal psychiatric illnesses, and the COVID-19 pandemic has exacerbated their burden, with a 15.3% increase in incidence in 2020 compared with previous years.¹ This increase was almost solely among adolescent girls with anorexia nervosa (AN), which is often insidious in onset and more difficult to treat as it advances. Adolescents with AN are most likely to present to their pediatricians, so awareness and early recognition of the symptoms is critical. Pediatricians are also an integral part of the treatment team in AN and can offer monitoring for serious complications, alongside valuable guidance to parents, who are central to treatment and the reestablishment of healthy eating habits in their children. Here we will review the epidemiology, diagnosis, and treatment of anorexia, with an emphasis on what pediatricians need to know to screen and to facilitate treatment.

Epidemiology

AN is marked by a fear of gaining weight or behaviors that interfere with weight gain and a self-evaluation unduly influenced by weight and body shape. Youth with AN often deny the seriousness of their malnutrition, although that is not required for diagnosis. AN can be of a restrictive or binge-purge subtype, and amenorrhea is no longer a requirement for diagnosis. There is not a specific weight or body mass index cutoff for the diagnosis, but the severity of AN is determined by the BMI percentile normed to age and sex. The average age of onset is 18, and the prepandemic prevalence of AN was about 1% of the population. It affects about 10 times as many females as males. It is quite rare prior to puberty, affecting about 0.01% of that age group. There is a heritable component, with a fivefold relative risk in youth with a parent with AN, and twin studies suggest heritability rates as high as 75%. Youth with rigid cognitive styles appear more vulnerable, as do those who participate in activities such as ballet, gymnastics, modeling, and wrestling because of the role of appearance and weight in performance. More than half of patients with AN will have another psychiatric illness, most commonly anxiety disorders, depression, or obsessive-compulsive disorder. AN becomes chronic in up to 15% of sufferers and the mortality rate is close to 10%, with approximately half dying from medical complications and half dying by suicide.

Screening

Parents and pediatricians are usually the first to notice that a child has started to lose weight or is falling off the growth curve. But weight changes usually emerge after feelings of preoccupation with weight, body shape, and body satisfaction. If parents report escalating pickiness around food, increased or compulsive exercise, persistent self-consciousness and self-criticism around weight and body shape, it is worth starting with screening questions.

If you notice preoccupation or anxiety around being weighed, even if the weight or growth curve are still normal, it is worthwhile to screen. Screening questions, such as the SCOFF questionnaire with five simple questions, can be very sensitive for both AN and bulimia nervosa.² There are also many validated screening instruments, such as the Eating Disorder Inventory or Eating Attitudes Test (for adolescents) and the Kids Eating Disorder Survey and the Child Eating Attitudes Test (for younger children), that are short self-reports that you can have your patients fill out when you have a higher index of suspicion. Weight loss or growth failure without a preoccupation around weight or appearance needs a thorough a medical workup, and could be a function of other psychiatric problems, such as depression.

If a child screens positive for an eating disorder, your full physical examination, growth curves, and longitudinal growth charts are critical for diagnosis. Percentile BMIs must be used, given the inaccuracy of standard BMI calculations in this age group. (Centers for Disease Control and Prevention age and sex growth charts include methods for this calculation). Laboratory assessment, including metabolic, kidney, pancreatic, and thyroid function, and an EKG can illuminate if there are consequences of restricting or purging. Of course, you want to evaluate for significant medical symptoms, including bradycardia, orthostasis, and hypokalemia. These medical symptoms are not limited to the severely underweight and merit referral to an emergency department and possible medical admission.

Then, a referral to a clinician who is expert in the assessment and treatment of eating disorders is needed. This may be a child psychiatrist, psychologist, or a colleague pediatrician with this specialization. It is also very important to begin the conversation with the family to introduce your concerns, describe what you have noticed, and discuss the need for further assessment and possibly treatment.

Treatment

Family-based therapy (FBT) is the first-line treatment of shorter-duration AN in children and adolescents. It focuses on the parents, helping them to calmly and effectively manage their child’s eating behaviors until their weight and behaviors have normalized. As a patient’s nutritional status improves, so does cognitive function, emotional flexibility, and mood. Individual therapy and psychopharmacologic treatment can be very effective for comorbid anxiety, mood, attentional, and thought disorders. Family-based work does include the child and is often done in group-based settings with clinicians from multiple disciplines. Dietitians provide education and guidance about healthy nutrition to the child and parents. Therapists may work with the child, parents, or full family to focus on behavior modification and managing distress. Most academic medical centers provide access to FBT, but there are many regions with no providers of this evidence-based treatment. One of the silver linings of the COVID-19 pandemic is that several online services have emerged offering FBT, working with families to manage mealtimes and treatment entirely at home.³ Pediatricians provide regular medical checks to measure progress and help with decisions about when it is safe to permit exercise or advance privileges and independence around eating. Some pediatricians have discovered a deep interest in this area of pediatrics and built their practices on it. Given the surge in prevalence of AN and the needs for adolescent mental health services, we hope more will do so.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

References

1. Taquet M et al. Br J Psychiatry. 2022;220:262-4.

2. Morgan JF et al. West J Med. 2000 Mar;172(3):164-5.

3. Matheson BE et al. Int J Eat Disord. 2020 Jul;53(7):1142-54.

Nasopharyngeal carcinoma (NPC) differs from other head and neck (H&N) cancers in its epidemiology and treatment. Unlike other H&N cancers, NPC has a distinct geographical distribution with a much higher incidence in endemic areas, such as southern China, than in areas where it is relatively uncommon, such as the United States.¹ The etiology of NPC varies based on the geographical distribution, with Epstein-Barr virus (EBV) thought to be the primary etiologic agent in endemic areas. On the other hand, in North America 2 additional subsets of NPC have been identified: human papillomavirus (HPV)–positive/EBV-negative and HPV-negative/EBV-negative.^2,3 NPC arises from the epithelial lining of the nasopharynx, often in the fossa of Rosenmuller, and is the most seen tumor in the nasopharynx.⁴ NPC is less surgically accessible than other H&N cancers, and surgery to the nasopharynx poses more risks given the proximity of critical surrounding structures. NPC is radiosensitive, and therefore radiotherapy (RT), in combination with chemotherapy for locally advanced tumors, has become the mainstay of treatment for nonmetastatic NPC.⁴

NPC often presents with an asymptomatic neck mass or with symptoms of epistaxis, nasal obstruction, and otitis media.⁵ Advanced cases of NPC can present with direct extension into the skull base, paranasal sinuses, and orbit, as well as involvement of cranial nerves. Radiation planning for tumors of the nasopharynx is complicated by the need to deliver an adequate dose to the tumor while limiting dose and toxicity to nearby critical structures such as the brainstem, optic chiasm, eyes, spinal cord (SC), temporal lobes, and cochleae. Achieving an adequate dose to nasopharyngeal primary tumors is especially complicated for T4 tumors invading the skull base with intracranial extension, in direct contact with these critical structures (Table 1).

Case Presentation

A 34-year-old male patient with no previous medical history presented to the emergency department with worsening diplopia, nasal obstruction, facial pain, and neck stiffness. The patient reported a 3 pack-year smoking history with recent smoking cessation. His physical examination was notable for a right abducens nerve palsy and an ulcerated nasopharyngeal mass on endoscopy.

Computed tomography (CT) scan revealed a 7-cm mass in the nasopharynx, eroding through the skull base with destruction and replacement of the clivus by tumor. Also noted was erosion of the petrous apices, carotid canals, sella turcica, dens, and the bilateral occipital condyles. There was intracranial extension with replacement of portions of the cavernous sinuses as well as mass effect on the prepontine cistern. Additional brain imaging studies, including magnetic resonance imaging (MRI) and positron emission tomography (PET) scans, were obtained for completion of the staging workup. The MRI correlated with the findings noted on CT and demonstrated involvement of Meckel cave, foramen ovale, foramen rotundum, Dorello canal, and the hypoglossal canals. No cervical lymphadenopathy or distant metastases were noted on imaging. Pathology from biopsy revealed poorly differentiated squamous cell carcinoma, EBV-negative, strongly p16-positive, HPV-16 positive, and P53-negative.

RT planning was complicated by the tumor’s contact with the brainstem and upper cervical SC, as well as proximity of the tumor to the optic apparatus. The patient underwent 2 replanning CT scans at 26 Gy and 44 Gy to evaluate for tumor shrinkage. These CT scans demonstrated shrinkage of the tumor away from critical neural structures, allowing the treatment volume to be reduced away from these structures in order to achieve required dose tolerances (brainstem < 54 Gy, optic nerves and chiasm < 50 Gy, SC < 45 Gy for this case). The replanning CT scan at 44 Gy, 5 weeks after treatment initiation, demonstrated that dramatic tumor shrinkage had occurred early in treatment, with separation of the remaining tumor from the area of the SC and brainstem with which it was initially in contact (Figure 1). This improvement allowed for shrinkage of the high-dose radiation field away from these critical neural structures.

Discussion

RT for NPC is complicated by the proximity of these tumors to critical surrounding neural structures. It is challenging to achieve the required dose constraints to surrounding neural tissues while delivering the usual 70-Gy dose to the gross tumor, especially when the tumor comes into direct contact with these structures.

This case provides an example of response-adapted RT using imaging during treatment to shrink the high-dose target as the tumor shrinks away from critical surrounding structures.⁷ This strategy permits delivery of the maximum dose to the tumor while minimizing radiation dose, and therefore risk of toxicity, to normal surrounding structures. While it is typical to deliver 70 Gy to the full extent of tumor involvement for H&N tumors, this was not possible in this case as the tumor was in contact with the brainstem and upper cervical SC. Delivering the full 70 Gy to these areas of tumor would have placed this patient at substantial risk of brainstem and/or SC toxicity. This report demonstrates that response-adapted RT with shrinking fields can allow for tumor control while avoiding toxicity to critical neural structures for cases of locally advanced NPC in which tumor is abutting these structures.

Bony regeneration of the skull base following RT has been reported in the literature, but in limited reviews. Early reports used plain radiography to follow changes. Unger and colleagues demonstrated the regeneration of bone using skull radiographs 4 to 6 months after completion of RT for NPC.⁸ More recent literature details the ability of bone to regenerate after RT based on CT findings. Fang and colleagues reported on 90 cases of NPC with skull base destruction, with 63% having bony regeneration on posttreatment CT.⁹ Most of the patients in Fang’s report had bony regeneration within 1 year of treatment, and in general, bony regeneration became more evident on imaging with longer follow-up. Of note, local control was significantly greater in patients with regeneration vs persistent destruction (77% vs 21%, P < .001). On multivariate analysis, complete tumor response was significantly associated with bony regeneration; other factors such as age, sex, radiation dose, and chemotherapy were not significantly associated with the likelihood of bony regeneration.

Our report details a nasopharyngeal tumor that destroyed the skull base with no intact bony barrier. In such cases, concern arises regarding craniospinal instability with tumor regression if there is not simultaneous bone regeneration. Tumor invasion of the skull base and C1-2 vertebral bodies and complications from treatment of such tumor extent can lead to symptoms of craniospinal instability, including pain, difficulty with neck range of motion, and loss of strength and sensation in the upper and lower extremities.¹⁰ A case report of a woman treated with chemoradiation for a plasmacytoma of the skull base detailed her posttreatment presentation with quadriparesis resulting from craniospinal instability after tumor regression.¹¹ Such instability is generally treated surgically, and during this woman’s surgery, there was an injury to the right vertebral artery, although this did not cause any additional neurologic deficits.

Conclusions

There is a paucity of literature on bony regeneration in patients with skull base destruction from advanced NPC, and in particular, the ability of skull base regeneration to occur during treatment simultaneous with tumor regression. Our patient had HPV-positive/EBV-negative NPC, but it is unclear how this subtype affected his prognosis. Factors such as tumor histology, radiosensitivity with rapid tumor regression, and young age may have all contributed to the rapidity of bone regeneration in our patient. This case report demonstrates that an impressive tumor response to chemoradiation with simultaneous bony regeneration is possible among patients presenting with tumor destruction of the skull base, precluding the need for neurosurgical intervention.

Nasopharyngeal carcinoma (NPC) differs from other head and neck (H&N) cancers in its epidemiology and treatment. Unlike other H&N cancers, NPC has a distinct geographical distribution with a much higher incidence in endemic areas, such as southern China, than in areas where it is relatively uncommon, such as the United States.¹ The etiology of NPC varies based on the geographical distribution, with Epstein-Barr virus (EBV) thought to be the primary etiologic agent in endemic areas. On the other hand, in North America 2 additional subsets of NPC have been identified: human papillomavirus (HPV)–positive/EBV-negative and HPV-negative/EBV-negative.^2,3 NPC arises from the epithelial lining of the nasopharynx, often in the fossa of Rosenmuller, and is the most seen tumor in the nasopharynx.⁴ NPC is less surgically accessible than other H&N cancers, and surgery to the nasopharynx poses more risks given the proximity of critical surrounding structures. NPC is radiosensitive, and therefore radiotherapy (RT), in combination with chemotherapy for locally advanced tumors, has become the mainstay of treatment for nonmetastatic NPC.⁴

NPC often presents with an asymptomatic neck mass or with symptoms of epistaxis, nasal obstruction, and otitis media.⁵ Advanced cases of NPC can present with direct extension into the skull base, paranasal sinuses, and orbit, as well as involvement of cranial nerves. Radiation planning for tumors of the nasopharynx is complicated by the need to deliver an adequate dose to the tumor while limiting dose and toxicity to nearby critical structures such as the brainstem, optic chiasm, eyes, spinal cord (SC), temporal lobes, and cochleae. Achieving an adequate dose to nasopharyngeal primary tumors is especially complicated for T4 tumors invading the skull base with intracranial extension, in direct contact with these critical structures (Table 1).

Case Presentation

A 34-year-old male patient with no previous medical history presented to the emergency department with worsening diplopia, nasal obstruction, facial pain, and neck stiffness. The patient reported a 3 pack-year smoking history with recent smoking cessation. His physical examination was notable for a right abducens nerve palsy and an ulcerated nasopharyngeal mass on endoscopy.

Computed tomography (CT) scan revealed a 7-cm mass in the nasopharynx, eroding through the skull base with destruction and replacement of the clivus by tumor. Also noted was erosion of the petrous apices, carotid canals, sella turcica, dens, and the bilateral occipital condyles. There was intracranial extension with replacement of portions of the cavernous sinuses as well as mass effect on the prepontine cistern. Additional brain imaging studies, including magnetic resonance imaging (MRI) and positron emission tomography (PET) scans, were obtained for completion of the staging workup. The MRI correlated with the findings noted on CT and demonstrated involvement of Meckel cave, foramen ovale, foramen rotundum, Dorello canal, and the hypoglossal canals. No cervical lymphadenopathy or distant metastases were noted on imaging. Pathology from biopsy revealed poorly differentiated squamous cell carcinoma, EBV-negative, strongly p16-positive, HPV-16 positive, and P53-negative.

RT planning was complicated by the tumor’s contact with the brainstem and upper cervical SC, as well as proximity of the tumor to the optic apparatus. The patient underwent 2 replanning CT scans at 26 Gy and 44 Gy to evaluate for tumor shrinkage. These CT scans demonstrated shrinkage of the tumor away from critical neural structures, allowing the treatment volume to be reduced away from these structures in order to achieve required dose tolerances (brainstem < 54 Gy, optic nerves and chiasm < 50 Gy, SC < 45 Gy for this case). The replanning CT scan at 44 Gy, 5 weeks after treatment initiation, demonstrated that dramatic tumor shrinkage had occurred early in treatment, with separation of the remaining tumor from the area of the SC and brainstem with which it was initially in contact (Figure 1). This improvement allowed for shrinkage of the high-dose radiation field away from these critical neural structures.

Discussion

RT for NPC is complicated by the proximity of these tumors to critical surrounding neural structures. It is challenging to achieve the required dose constraints to surrounding neural tissues while delivering the usual 70-Gy dose to the gross tumor, especially when the tumor comes into direct contact with these structures.

This case provides an example of response-adapted RT using imaging during treatment to shrink the high-dose target as the tumor shrinks away from critical surrounding structures.⁷ This strategy permits delivery of the maximum dose to the tumor while minimizing radiation dose, and therefore risk of toxicity, to normal surrounding structures. While it is typical to deliver 70 Gy to the full extent of tumor involvement for H&N tumors, this was not possible in this case as the tumor was in contact with the brainstem and upper cervical SC. Delivering the full 70 Gy to these areas of tumor would have placed this patient at substantial risk of brainstem and/or SC toxicity. This report demonstrates that response-adapted RT with shrinking fields can allow for tumor control while avoiding toxicity to critical neural structures for cases of locally advanced NPC in which tumor is abutting these structures.

Bony regeneration of the skull base following RT has been reported in the literature, but in limited reviews. Early reports used plain radiography to follow changes. Unger and colleagues demonstrated the regeneration of bone using skull radiographs 4 to 6 months after completion of RT for NPC.⁸ More recent literature details the ability of bone to regenerate after RT based on CT findings. Fang and colleagues reported on 90 cases of NPC with skull base destruction, with 63% having bony regeneration on posttreatment CT.⁹ Most of the patients in Fang’s report had bony regeneration within 1 year of treatment, and in general, bony regeneration became more evident on imaging with longer follow-up. Of note, local control was significantly greater in patients with regeneration vs persistent destruction (77% vs 21%, P < .001). On multivariate analysis, complete tumor response was significantly associated with bony regeneration; other factors such as age, sex, radiation dose, and chemotherapy were not significantly associated with the likelihood of bony regeneration.

Our report details a nasopharyngeal tumor that destroyed the skull base with no intact bony barrier. In such cases, concern arises regarding craniospinal instability with tumor regression if there is not simultaneous bone regeneration. Tumor invasion of the skull base and C1-2 vertebral bodies and complications from treatment of such tumor extent can lead to symptoms of craniospinal instability, including pain, difficulty with neck range of motion, and loss of strength and sensation in the upper and lower extremities.¹⁰ A case report of a woman treated with chemoradiation for a plasmacytoma of the skull base detailed her posttreatment presentation with quadriparesis resulting from craniospinal instability after tumor regression.¹¹ Such instability is generally treated surgically, and during this woman’s surgery, there was an injury to the right vertebral artery, although this did not cause any additional neurologic deficits.

Conclusions

There is a paucity of literature on bony regeneration in patients with skull base destruction from advanced NPC, and in particular, the ability of skull base regeneration to occur during treatment simultaneous with tumor regression. Our patient had HPV-positive/EBV-negative NPC, but it is unclear how this subtype affected his prognosis. Factors such as tumor histology, radiosensitivity with rapid tumor regression, and young age may have all contributed to the rapidity of bone regeneration in our patient. This case report demonstrates that an impressive tumor response to chemoradiation with simultaneous bony regeneration is possible among patients presenting with tumor destruction of the skull base, precluding the need for neurosurgical intervention.

Nasopharyngeal carcinoma (NPC) differs from other head and neck (H&N) cancers in its epidemiology and treatment. Unlike other H&N cancers, NPC has a distinct geographical distribution with a much higher incidence in endemic areas, such as southern China, than in areas where it is relatively uncommon, such as the United States.¹ The etiology of NPC varies based on the geographical distribution, with Epstein-Barr virus (EBV) thought to be the primary etiologic agent in endemic areas. On the other hand, in North America 2 additional subsets of NPC have been identified: human papillomavirus (HPV)–positive/EBV-negative and HPV-negative/EBV-negative.^2,3 NPC arises from the epithelial lining of the nasopharynx, often in the fossa of Rosenmuller, and is the most seen tumor in the nasopharynx.⁴ NPC is less surgically accessible than other H&N cancers, and surgery to the nasopharynx poses more risks given the proximity of critical surrounding structures. NPC is radiosensitive, and therefore radiotherapy (RT), in combination with chemotherapy for locally advanced tumors, has become the mainstay of treatment for nonmetastatic NPC.⁴

NPC often presents with an asymptomatic neck mass or with symptoms of epistaxis, nasal obstruction, and otitis media.⁵ Advanced cases of NPC can present with direct extension into the skull base, paranasal sinuses, and orbit, as well as involvement of cranial nerves. Radiation planning for tumors of the nasopharynx is complicated by the need to deliver an adequate dose to the tumor while limiting dose and toxicity to nearby critical structures such as the brainstem, optic chiasm, eyes, spinal cord (SC), temporal lobes, and cochleae. Achieving an adequate dose to nasopharyngeal primary tumors is especially complicated for T4 tumors invading the skull base with intracranial extension, in direct contact with these critical structures (Table 1).

Case Presentation

A 34-year-old male patient with no previous medical history presented to the emergency department with worsening diplopia, nasal obstruction, facial pain, and neck stiffness. The patient reported a 3 pack-year smoking history with recent smoking cessation. His physical examination was notable for a right abducens nerve palsy and an ulcerated nasopharyngeal mass on endoscopy.

Computed tomography (CT) scan revealed a 7-cm mass in the nasopharynx, eroding through the skull base with destruction and replacement of the clivus by tumor. Also noted was erosion of the petrous apices, carotid canals, sella turcica, dens, and the bilateral occipital condyles. There was intracranial extension with replacement of portions of the cavernous sinuses as well as mass effect on the prepontine cistern. Additional brain imaging studies, including magnetic resonance imaging (MRI) and positron emission tomography (PET) scans, were obtained for completion of the staging workup. The MRI correlated with the findings noted on CT and demonstrated involvement of Meckel cave, foramen ovale, foramen rotundum, Dorello canal, and the hypoglossal canals. No cervical lymphadenopathy or distant metastases were noted on imaging. Pathology from biopsy revealed poorly differentiated squamous cell carcinoma, EBV-negative, strongly p16-positive, HPV-16 positive, and P53-negative.

RT planning was complicated by the tumor’s contact with the brainstem and upper cervical SC, as well as proximity of the tumor to the optic apparatus. The patient underwent 2 replanning CT scans at 26 Gy and 44 Gy to evaluate for tumor shrinkage. These CT scans demonstrated shrinkage of the tumor away from critical neural structures, allowing the treatment volume to be reduced away from these structures in order to achieve required dose tolerances (brainstem < 54 Gy, optic nerves and chiasm < 50 Gy, SC < 45 Gy for this case). The replanning CT scan at 44 Gy, 5 weeks after treatment initiation, demonstrated that dramatic tumor shrinkage had occurred early in treatment, with separation of the remaining tumor from the area of the SC and brainstem with which it was initially in contact (Figure 1). This improvement allowed for shrinkage of the high-dose radiation field away from these critical neural structures.

Discussion

RT for NPC is complicated by the proximity of these tumors to critical surrounding neural structures. It is challenging to achieve the required dose constraints to surrounding neural tissues while delivering the usual 70-Gy dose to the gross tumor, especially when the tumor comes into direct contact with these structures.

This case provides an example of response-adapted RT using imaging during treatment to shrink the high-dose target as the tumor shrinks away from critical surrounding structures.⁷ This strategy permits delivery of the maximum dose to the tumor while minimizing radiation dose, and therefore risk of toxicity, to normal surrounding structures. While it is typical to deliver 70 Gy to the full extent of tumor involvement for H&N tumors, this was not possible in this case as the tumor was in contact with the brainstem and upper cervical SC. Delivering the full 70 Gy to these areas of tumor would have placed this patient at substantial risk of brainstem and/or SC toxicity. This report demonstrates that response-adapted RT with shrinking fields can allow for tumor control while avoiding toxicity to critical neural structures for cases of locally advanced NPC in which tumor is abutting these structures.

Bony regeneration of the skull base following RT has been reported in the literature, but in limited reviews. Early reports used plain radiography to follow changes. Unger and colleagues demonstrated the regeneration of bone using skull radiographs 4 to 6 months after completion of RT for NPC.⁸ More recent literature details the ability of bone to regenerate after RT based on CT findings. Fang and colleagues reported on 90 cases of NPC with skull base destruction, with 63% having bony regeneration on posttreatment CT.⁹ Most of the patients in Fang’s report had bony regeneration within 1 year of treatment, and in general, bony regeneration became more evident on imaging with longer follow-up. Of note, local control was significantly greater in patients with regeneration vs persistent destruction (77% vs 21%, P < .001). On multivariate analysis, complete tumor response was significantly associated with bony regeneration; other factors such as age, sex, radiation dose, and chemotherapy were not significantly associated with the likelihood of bony regeneration.

Our report details a nasopharyngeal tumor that destroyed the skull base with no intact bony barrier. In such cases, concern arises regarding craniospinal instability with tumor regression if there is not simultaneous bone regeneration. Tumor invasion of the skull base and C1-2 vertebral bodies and complications from treatment of such tumor extent can lead to symptoms of craniospinal instability, including pain, difficulty with neck range of motion, and loss of strength and sensation in the upper and lower extremities.¹⁰ A case report of a woman treated with chemoradiation for a plasmacytoma of the skull base detailed her posttreatment presentation with quadriparesis resulting from craniospinal instability after tumor regression.¹¹ Such instability is generally treated surgically, and during this woman’s surgery, there was an injury to the right vertebral artery, although this did not cause any additional neurologic deficits.

Conclusions

There is a paucity of literature on bony regeneration in patients with skull base destruction from advanced NPC, and in particular, the ability of skull base regeneration to occur during treatment simultaneous with tumor regression. Our patient had HPV-positive/EBV-negative NPC, but it is unclear how this subtype affected his prognosis. Factors such as tumor histology, radiosensitivity with rapid tumor regression, and young age may have all contributed to the rapidity of bone regeneration in our patient. This case report demonstrates that an impressive tumor response to chemoradiation with simultaneous bony regeneration is possible among patients presenting with tumor destruction of the skull base, precluding the need for neurosurgical intervention.