Cancer

Clinicians are not following guidelines that recommend a de-escalation in surveillance for patients with low-risk non–muscle-invasive bladder cancer (NMIBC), a new study concludes.  

These cancers are associated with low rates of recurrence, progression, and bladder cancer–specific death, so current clinical practice guidelines recommend against frequent monitoring and testing.

However, the study authors found that patients with a low grade Ta NMIBC diagnosis underwent a median of three cystoscopies per year, and many also received a median of two imagine scans (CT or MRI) as well as 2-3 urine-based tests.

“These data suggest a need for ongoing efforts to limit overuse of treatment and surveillance, which may in turn mitigate associated increases in the costs of care,” write the authors, led by Kelly K. Bree, MD, from the department of urology, University of Texas MD Anderson Cancer Center, Houston. Bladder cancer has the highest lifetime treatment cost of all malignancies, they point out.

The study was published online in JAMA Network Open.
 

Higher value and more evidence-based

The impact of increased surveillance of this patient cohort has broad implications for patients and the health care system in general, say experts writing in an accompanying editorial.

“It has been well established that workup for NMIBC can have negative consequences for the physical and psychological health of patients,” note Grayden S. Cook, BS, and Jeffrey M. Howard, MD, PhD, both from University of Texas Southwestern Medical Center, Dallas.

“Many of these patients undergo frequent CT imaging of the urinary tract, which carries a high dose of radiation as well as the potential for financial toxic effects (that is, detrimental consequences to the patient because of health care costs),” they write.

Additionally, patient distress is a factor, as they may experience preprocedural anxiety, physical discomfort during procedures, and worry about disease progression, they point out.

“The impact of these patterns is substantial and may have negative consequences for both patients and the health care system,” they conclude. “Thus, it is imperative to move forward with initiatives that provide higher value and are more evidence-based and patient-centered.”
 

Study finds frequent surveillance

The American Urological Association (AUA)/Society of Urologic Oncologists (SUO), the European Association of Urology, and the International Bladder Cancer Group have made an effort to de-escalate surveillance and treatment for patients with low-grade Ta disease, while at the same time maintaining appropriate surveillance for high-grade aggressive disease.

However, the new study found that in practice, such patients undergo frequent testing.

The study involved 13,054 patients with low-grade Ta NMIBC. Most of the participants were male (73.5%), with a median age of 76 years, and had no or few comorbidities (71.2%).

Most patients had undergone cystoscopy, and rates increased over time: from 79.3% of patients in 2004 to 81.5% of patients in 2013 (P = .007). Patients underwent a median of 3.0 cystoscopies per year following their diagnosis, and upper-tract imaging was performed in most patients.

The use of kidney ultrasonography also rose from 19% of patients in 2004 to 23.2% in 2013, as did retrograde pyelography (20.9% in 2004 vs. 24.2% in 2013). Conversely, the use of intravenous pyelography declined (from 14.5% in 2004 to 1.7% in 2012), but there was an increase in CT and MRI in all years except 2010 (from 30.4% of patients in 2004 to 47% of patients in 2013; P < .001). The rate of urine-based testing also significantly increased during the study period (from 44.8% in 2004 to 54.9% in 2013; P < .001), with patients undergoing between two to three tests per year.

Adherence to current guidelines remained similar during the study time frame. For example, 55.2% of patients received two cystoscopies per year in 2004-2008, compared with 53.8% in 2009-2013 (P = .11), suggesting that there was an overuse of all surveillance testing modalities.

As for treatment, 17.2% received intravesical immunotherapy with bacillus Calmette-Guérin, 6.1% were treated with intravesical chemotherapy (excluding receipt of a single perioperative dose). Disease recurrence within this cohort was 1.7%, and only 0.4% experienced disease progression.

When looking at the cost, the total median expenditures at 1 year after diagnosis increased by 60% during the study period, from $34,792 in 2004 to $53,986 in 2013. Higher costs were seen among patients who experienced a recurrence versus no recurrence ($76,669 vs. $53,909).

The study was supported by a grant from the U.S. Department of Defense Peer Reviewed Cancer Research Program. Several of the authors have disclosed relationships with industry, as noted in the original article. Editorialists Mr. Cook and Dr. Howard have disclosed no relevant financial relationships.

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

Clinicians are not following guidelines that recommend a de-escalation in surveillance for patients with low-risk non–muscle-invasive bladder cancer (NMIBC), a new study concludes.  

These cancers are associated with low rates of recurrence, progression, and bladder cancer–specific death, so current clinical practice guidelines recommend against frequent monitoring and testing.

However, the study authors found that patients with a low grade Ta NMIBC diagnosis underwent a median of three cystoscopies per year, and many also received a median of two imagine scans (CT or MRI) as well as 2-3 urine-based tests.

“These data suggest a need for ongoing efforts to limit overuse of treatment and surveillance, which may in turn mitigate associated increases in the costs of care,” write the authors, led by Kelly K. Bree, MD, from the department of urology, University of Texas MD Anderson Cancer Center, Houston. Bladder cancer has the highest lifetime treatment cost of all malignancies, they point out.

The study was published online in JAMA Network Open.
 

Higher value and more evidence-based

The impact of increased surveillance of this patient cohort has broad implications for patients and the health care system in general, say experts writing in an accompanying editorial.

“It has been well established that workup for NMIBC can have negative consequences for the physical and psychological health of patients,” note Grayden S. Cook, BS, and Jeffrey M. Howard, MD, PhD, both from University of Texas Southwestern Medical Center, Dallas.

“Many of these patients undergo frequent CT imaging of the urinary tract, which carries a high dose of radiation as well as the potential for financial toxic effects (that is, detrimental consequences to the patient because of health care costs),” they write.

Additionally, patient distress is a factor, as they may experience preprocedural anxiety, physical discomfort during procedures, and worry about disease progression, they point out.

“The impact of these patterns is substantial and may have negative consequences for both patients and the health care system,” they conclude. “Thus, it is imperative to move forward with initiatives that provide higher value and are more evidence-based and patient-centered.”
 

Study finds frequent surveillance

The American Urological Association (AUA)/Society of Urologic Oncologists (SUO), the European Association of Urology, and the International Bladder Cancer Group have made an effort to de-escalate surveillance and treatment for patients with low-grade Ta disease, while at the same time maintaining appropriate surveillance for high-grade aggressive disease.

However, the new study found that in practice, such patients undergo frequent testing.

The study involved 13,054 patients with low-grade Ta NMIBC. Most of the participants were male (73.5%), with a median age of 76 years, and had no or few comorbidities (71.2%).

Most patients had undergone cystoscopy, and rates increased over time: from 79.3% of patients in 2004 to 81.5% of patients in 2013 (P = .007). Patients underwent a median of 3.0 cystoscopies per year following their diagnosis, and upper-tract imaging was performed in most patients.

The use of kidney ultrasonography also rose from 19% of patients in 2004 to 23.2% in 2013, as did retrograde pyelography (20.9% in 2004 vs. 24.2% in 2013). Conversely, the use of intravenous pyelography declined (from 14.5% in 2004 to 1.7% in 2012), but there was an increase in CT and MRI in all years except 2010 (from 30.4% of patients in 2004 to 47% of patients in 2013; P < .001). The rate of urine-based testing also significantly increased during the study period (from 44.8% in 2004 to 54.9% in 2013; P < .001), with patients undergoing between two to three tests per year.

Adherence to current guidelines remained similar during the study time frame. For example, 55.2% of patients received two cystoscopies per year in 2004-2008, compared with 53.8% in 2009-2013 (P = .11), suggesting that there was an overuse of all surveillance testing modalities.

As for treatment, 17.2% received intravesical immunotherapy with bacillus Calmette-Guérin, 6.1% were treated with intravesical chemotherapy (excluding receipt of a single perioperative dose). Disease recurrence within this cohort was 1.7%, and only 0.4% experienced disease progression.

When looking at the cost, the total median expenditures at 1 year after diagnosis increased by 60% during the study period, from $34,792 in 2004 to $53,986 in 2013. Higher costs were seen among patients who experienced a recurrence versus no recurrence ($76,669 vs. $53,909).

The study was supported by a grant from the U.S. Department of Defense Peer Reviewed Cancer Research Program. Several of the authors have disclosed relationships with industry, as noted in the original article. Editorialists Mr. Cook and Dr. Howard have disclosed no relevant financial relationships.

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

Clinicians are not following guidelines that recommend a de-escalation in surveillance for patients with low-risk non–muscle-invasive bladder cancer (NMIBC), a new study concludes.  

These cancers are associated with low rates of recurrence, progression, and bladder cancer–specific death, so current clinical practice guidelines recommend against frequent monitoring and testing.

However, the study authors found that patients with a low grade Ta NMIBC diagnosis underwent a median of three cystoscopies per year, and many also received a median of two imagine scans (CT or MRI) as well as 2-3 urine-based tests.

“These data suggest a need for ongoing efforts to limit overuse of treatment and surveillance, which may in turn mitigate associated increases in the costs of care,” write the authors, led by Kelly K. Bree, MD, from the department of urology, University of Texas MD Anderson Cancer Center, Houston. Bladder cancer has the highest lifetime treatment cost of all malignancies, they point out.

The study was published online in JAMA Network Open.
 

Higher value and more evidence-based

The impact of increased surveillance of this patient cohort has broad implications for patients and the health care system in general, say experts writing in an accompanying editorial.

“It has been well established that workup for NMIBC can have negative consequences for the physical and psychological health of patients,” note Grayden S. Cook, BS, and Jeffrey M. Howard, MD, PhD, both from University of Texas Southwestern Medical Center, Dallas.

“Many of these patients undergo frequent CT imaging of the urinary tract, which carries a high dose of radiation as well as the potential for financial toxic effects (that is, detrimental consequences to the patient because of health care costs),” they write.

Additionally, patient distress is a factor, as they may experience preprocedural anxiety, physical discomfort during procedures, and worry about disease progression, they point out.

“The impact of these patterns is substantial and may have negative consequences for both patients and the health care system,” they conclude. “Thus, it is imperative to move forward with initiatives that provide higher value and are more evidence-based and patient-centered.”
 

Study finds frequent surveillance

The American Urological Association (AUA)/Society of Urologic Oncologists (SUO), the European Association of Urology, and the International Bladder Cancer Group have made an effort to de-escalate surveillance and treatment for patients with low-grade Ta disease, while at the same time maintaining appropriate surveillance for high-grade aggressive disease.

However, the new study found that in practice, such patients undergo frequent testing.

The study involved 13,054 patients with low-grade Ta NMIBC. Most of the participants were male (73.5%), with a median age of 76 years, and had no or few comorbidities (71.2%).

Most patients had undergone cystoscopy, and rates increased over time: from 79.3% of patients in 2004 to 81.5% of patients in 2013 (P = .007). Patients underwent a median of 3.0 cystoscopies per year following their diagnosis, and upper-tract imaging was performed in most patients.

The use of kidney ultrasonography also rose from 19% of patients in 2004 to 23.2% in 2013, as did retrograde pyelography (20.9% in 2004 vs. 24.2% in 2013). Conversely, the use of intravenous pyelography declined (from 14.5% in 2004 to 1.7% in 2012), but there was an increase in CT and MRI in all years except 2010 (from 30.4% of patients in 2004 to 47% of patients in 2013; P < .001). The rate of urine-based testing also significantly increased during the study period (from 44.8% in 2004 to 54.9% in 2013; P < .001), with patients undergoing between two to three tests per year.

Adherence to current guidelines remained similar during the study time frame. For example, 55.2% of patients received two cystoscopies per year in 2004-2008, compared with 53.8% in 2009-2013 (P = .11), suggesting that there was an overuse of all surveillance testing modalities.

As for treatment, 17.2% received intravesical immunotherapy with bacillus Calmette-Guérin, 6.1% were treated with intravesical chemotherapy (excluding receipt of a single perioperative dose). Disease recurrence within this cohort was 1.7%, and only 0.4% experienced disease progression.

When looking at the cost, the total median expenditures at 1 year after diagnosis increased by 60% during the study period, from $34,792 in 2004 to $53,986 in 2013. Higher costs were seen among patients who experienced a recurrence versus no recurrence ($76,669 vs. $53,909).

The study was supported by a grant from the U.S. Department of Defense Peer Reviewed Cancer Research Program. Several of the authors have disclosed relationships with industry, as noted in the original article. Editorialists Mr. Cook and Dr. Howard have disclosed no relevant financial relationships.

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

BOSTON – Although skin biopsy remains the gold standard for diagnosing early-stage melanoma, advances in genetic expression profiling are helping dermatologists provide a nuanced approach to managing suspicious lesions.

One such test, the Pigmented Lesional Assay (PLA) uses adhesive patches applied to lesions of concern at the bedside to extract RNA from the stratum corneum to help determine the risk for melanoma.

At the annual meeting of the American Academy of Dermatology, Caroline C. Kim, MD, director of melanoma and pigmented lesion clinics at Newton Wellesley Dermatology, Wellesley Hills, Mass., and Tufts Medical Center, Boston, spoke about the PLA, which uses genetic expression profiling to measure the expression level of specific genes that are associated with melanoma: PRAME (preferentially expressed antigen in melanoma) and LINC00518 (LINC). There are four possible results of the test: Aberrant expression of both LINC and PRAME (high risk); aberrant expression of a single gene (moderate risk); aberrant expression of neither gene (low risk); or inconclusive.

Validation data have shown a sensitivity of 91% and a specificity of 69% for the PLA, with a 99% negative predictive value; so a lesion that tested negative by PLA has a less than 1% chance of being melanoma. In addition, a study published in 2020 found that the addition of TERT (telomerase reverse transcriptase) mutation analyses increased the sensitivity of the PLA to 97%.

While the high negative predictive value is helpful to consider in clinical scenarios to rule-out melanoma for borderline lesions, one must consider the positive predictive value as well and how this may impact clinical care, Dr. Kim said. In a study examining outcomes of 381 lesions, 51 were PLA positive (single or double) and were biopsied, of which 19 (37%) revealed a melanoma diagnosis. In a large U.S. registry study of 3,418 lesions, 324 lesions that were PLA double positive were biopsied, with 18.7% revealing a melanoma diagnosis.

“No test is perfect, and this applies to PLA, even if you get a double-positive or double-negative test result,” Dr. Kim said. “You want to make sure that patients are aware of false positives and negatives. However, PLA could be an additional piece of data to inform your decision to proceed with biopsy on select borderline suspicious pigmented lesions. More studies are needed to better understand the approach to single- and double-positive PLA results.”

The PLA kit contains adhesive patches and supplies and a FedEx envelope for return to DermTech, the test’s manufacturer, for processing. The patches can be applied to lesions at least 4 mm in diameter; multiple kits are recommended for those greater than 16 mm in diameter. The test is not validated for lesions located on mucous membranes, palms, soles, nails, or on ulcerated or bleeding lesions, nor for those that have been previously biopsied. It is also not validated for use in pediatric patients or in those with skin types IV or higher. Results are returned in 2-3 days. If insurance does not cover the test, the cost to the patient is approximately $50 per lesion or a maximum of $150, according to Dr. Kim.
 

Use in clinical practice

In Dr. Kim’s clinical experience, the PLA can be considered for suspicious pigmented lesions on cosmetically sensitive areas and for suspicious lesions in areas difficult to biopsy or excise. For example, she discussed the case of a 72-year-old woman with a family history of melanoma, who presented to her clinic with a longstanding pigmented lesion on her right upper and lower eyelids that had previously been treated with laser. She had undergone multiple prior biopsies over 12 years, which caused mild to moderate atypical melanocytic proliferation. The PLA result was double negative for PRAME and LINC in her upper and lower eyelid, “which provided reassurance to the patient,” Dr. Kim said. The patient continues to be followed closely for any clinical changes.

Another patient, a 67-year-old woman, was referred to Dr. Kim from out of state for a teledermatology visit early in the COVID-19 pandemic. The patient had a lesion on her right calf that was hard, raised, and pink, did not resemble other lesions on her body, and had been present for a few weeks. “Her husband had recently passed away from brain cancer and she was very concerned about melanoma,” Dr. Kim recalled. “She lived alone, and the adult son was with her during the teledermatology call to assist. The patient asked about the PLA test, and given her difficulty going to a medical office at the time, we agreed to help her with this test.” The patient and her son arranged another teledermatology visit with Dr. Kim after receiving the kit in the mail from DermTech, and Dr. Kim coached them on how to properly administer the test. The results came back as PRAME negative and LINC positive. A biopsy with a local provider was recommended and the pathology results showed an inflamed seborrheic keratosis.

“This case exemplifies a false-positive result. We should be sure to make patients aware of this possibility,” Dr. Kim said.

Incorporating PLA into clinical practice requires certain workflow considerations, with paperwork to fill out in addition to performing the adhesive test, collection of insurance information, mailing the kit via FedEx, retrieving the results, and following up with the patient, said Dr. Kim. “For select borderline pigmented lesions, I discuss the rationale of the test with patients, the possibility of false-positive and false-negative results and the need to return for a biopsy when there is positive result. Clinical follow-up is recommended for negative results. There is also the possibility of charge to the patient if the test is not covered by their insurance.”
 

Skin biopsy still the gold standard

Despite the availability of the PLA as an assessment tool, Dr. Kim emphasized that skin biopsy remains the gold standard for diagnosing melanoma. “Future prospective randomized clinical trials are needed to examine the role of genetic expression profiling in staging and managing patients,” she said.

In 2019, she and her colleagues surveyed 42 pigmented lesion experts in the United States about why they ordered one of three molecular tests on the market or not and how results affected patient treatment. The proportion of clinicians who ordered the tests ranged from 21% to 29%. The top 2 reasons respondents chose for not ordering the PLA test specifically were: “Feel that further validation studies are necessary” (20%) and “do not feel it would be useful in my practice” (18%).

Results of a larger follow-up survey on usage patterns of PLA of both pigmented lesion experts and general clinicians on this topic are expected to be published shortly.

Dr. Kim reported having no disclosures related to her presentation.

BOSTON – Although skin biopsy remains the gold standard for diagnosing early-stage melanoma, advances in genetic expression profiling are helping dermatologists provide a nuanced approach to managing suspicious lesions.

One such test, the Pigmented Lesional Assay (PLA) uses adhesive patches applied to lesions of concern at the bedside to extract RNA from the stratum corneum to help determine the risk for melanoma.

At the annual meeting of the American Academy of Dermatology, Caroline C. Kim, MD, director of melanoma and pigmented lesion clinics at Newton Wellesley Dermatology, Wellesley Hills, Mass., and Tufts Medical Center, Boston, spoke about the PLA, which uses genetic expression profiling to measure the expression level of specific genes that are associated with melanoma: PRAME (preferentially expressed antigen in melanoma) and LINC00518 (LINC). There are four possible results of the test: Aberrant expression of both LINC and PRAME (high risk); aberrant expression of a single gene (moderate risk); aberrant expression of neither gene (low risk); or inconclusive.

Validation data have shown a sensitivity of 91% and a specificity of 69% for the PLA, with a 99% negative predictive value; so a lesion that tested negative by PLA has a less than 1% chance of being melanoma. In addition, a study published in 2020 found that the addition of TERT (telomerase reverse transcriptase) mutation analyses increased the sensitivity of the PLA to 97%.

While the high negative predictive value is helpful to consider in clinical scenarios to rule-out melanoma for borderline lesions, one must consider the positive predictive value as well and how this may impact clinical care, Dr. Kim said. In a study examining outcomes of 381 lesions, 51 were PLA positive (single or double) and were biopsied, of which 19 (37%) revealed a melanoma diagnosis. In a large U.S. registry study of 3,418 lesions, 324 lesions that were PLA double positive were biopsied, with 18.7% revealing a melanoma diagnosis.

“No test is perfect, and this applies to PLA, even if you get a double-positive or double-negative test result,” Dr. Kim said. “You want to make sure that patients are aware of false positives and negatives. However, PLA could be an additional piece of data to inform your decision to proceed with biopsy on select borderline suspicious pigmented lesions. More studies are needed to better understand the approach to single- and double-positive PLA results.”

The PLA kit contains adhesive patches and supplies and a FedEx envelope for return to DermTech, the test’s manufacturer, for processing. The patches can be applied to lesions at least 4 mm in diameter; multiple kits are recommended for those greater than 16 mm in diameter. The test is not validated for lesions located on mucous membranes, palms, soles, nails, or on ulcerated or bleeding lesions, nor for those that have been previously biopsied. It is also not validated for use in pediatric patients or in those with skin types IV or higher. Results are returned in 2-3 days. If insurance does not cover the test, the cost to the patient is approximately $50 per lesion or a maximum of $150, according to Dr. Kim.
 

Use in clinical practice

In Dr. Kim’s clinical experience, the PLA can be considered for suspicious pigmented lesions on cosmetically sensitive areas and for suspicious lesions in areas difficult to biopsy or excise. For example, she discussed the case of a 72-year-old woman with a family history of melanoma, who presented to her clinic with a longstanding pigmented lesion on her right upper and lower eyelids that had previously been treated with laser. She had undergone multiple prior biopsies over 12 years, which caused mild to moderate atypical melanocytic proliferation. The PLA result was double negative for PRAME and LINC in her upper and lower eyelid, “which provided reassurance to the patient,” Dr. Kim said. The patient continues to be followed closely for any clinical changes.

Another patient, a 67-year-old woman, was referred to Dr. Kim from out of state for a teledermatology visit early in the COVID-19 pandemic. The patient had a lesion on her right calf that was hard, raised, and pink, did not resemble other lesions on her body, and had been present for a few weeks. “Her husband had recently passed away from brain cancer and she was very concerned about melanoma,” Dr. Kim recalled. “She lived alone, and the adult son was with her during the teledermatology call to assist. The patient asked about the PLA test, and given her difficulty going to a medical office at the time, we agreed to help her with this test.” The patient and her son arranged another teledermatology visit with Dr. Kim after receiving the kit in the mail from DermTech, and Dr. Kim coached them on how to properly administer the test. The results came back as PRAME negative and LINC positive. A biopsy with a local provider was recommended and the pathology results showed an inflamed seborrheic keratosis.

“This case exemplifies a false-positive result. We should be sure to make patients aware of this possibility,” Dr. Kim said.

Incorporating PLA into clinical practice requires certain workflow considerations, with paperwork to fill out in addition to performing the adhesive test, collection of insurance information, mailing the kit via FedEx, retrieving the results, and following up with the patient, said Dr. Kim. “For select borderline pigmented lesions, I discuss the rationale of the test with patients, the possibility of false-positive and false-negative results and the need to return for a biopsy when there is positive result. Clinical follow-up is recommended for negative results. There is also the possibility of charge to the patient if the test is not covered by their insurance.”
 

Skin biopsy still the gold standard

Despite the availability of the PLA as an assessment tool, Dr. Kim emphasized that skin biopsy remains the gold standard for diagnosing melanoma. “Future prospective randomized clinical trials are needed to examine the role of genetic expression profiling in staging and managing patients,” she said.

In 2019, she and her colleagues surveyed 42 pigmented lesion experts in the United States about why they ordered one of three molecular tests on the market or not and how results affected patient treatment. The proportion of clinicians who ordered the tests ranged from 21% to 29%. The top 2 reasons respondents chose for not ordering the PLA test specifically were: “Feel that further validation studies are necessary” (20%) and “do not feel it would be useful in my practice” (18%).

Results of a larger follow-up survey on usage patterns of PLA of both pigmented lesion experts and general clinicians on this topic are expected to be published shortly.

Dr. Kim reported having no disclosures related to her presentation.

BOSTON – Although skin biopsy remains the gold standard for diagnosing early-stage melanoma, advances in genetic expression profiling are helping dermatologists provide a nuanced approach to managing suspicious lesions.

One such test, the Pigmented Lesional Assay (PLA) uses adhesive patches applied to lesions of concern at the bedside to extract RNA from the stratum corneum to help determine the risk for melanoma.

At the annual meeting of the American Academy of Dermatology, Caroline C. Kim, MD, director of melanoma and pigmented lesion clinics at Newton Wellesley Dermatology, Wellesley Hills, Mass., and Tufts Medical Center, Boston, spoke about the PLA, which uses genetic expression profiling to measure the expression level of specific genes that are associated with melanoma: PRAME (preferentially expressed antigen in melanoma) and LINC00518 (LINC). There are four possible results of the test: Aberrant expression of both LINC and PRAME (high risk); aberrant expression of a single gene (moderate risk); aberrant expression of neither gene (low risk); or inconclusive.

Validation data have shown a sensitivity of 91% and a specificity of 69% for the PLA, with a 99% negative predictive value; so a lesion that tested negative by PLA has a less than 1% chance of being melanoma. In addition, a study published in 2020 found that the addition of TERT (telomerase reverse transcriptase) mutation analyses increased the sensitivity of the PLA to 97%.

While the high negative predictive value is helpful to consider in clinical scenarios to rule-out melanoma for borderline lesions, one must consider the positive predictive value as well and how this may impact clinical care, Dr. Kim said. In a study examining outcomes of 381 lesions, 51 were PLA positive (single or double) and were biopsied, of which 19 (37%) revealed a melanoma diagnosis. In a large U.S. registry study of 3,418 lesions, 324 lesions that were PLA double positive were biopsied, with 18.7% revealing a melanoma diagnosis.

“No test is perfect, and this applies to PLA, even if you get a double-positive or double-negative test result,” Dr. Kim said. “You want to make sure that patients are aware of false positives and negatives. However, PLA could be an additional piece of data to inform your decision to proceed with biopsy on select borderline suspicious pigmented lesions. More studies are needed to better understand the approach to single- and double-positive PLA results.”

The PLA kit contains adhesive patches and supplies and a FedEx envelope for return to DermTech, the test’s manufacturer, for processing. The patches can be applied to lesions at least 4 mm in diameter; multiple kits are recommended for those greater than 16 mm in diameter. The test is not validated for lesions located on mucous membranes, palms, soles, nails, or on ulcerated or bleeding lesions, nor for those that have been previously biopsied. It is also not validated for use in pediatric patients or in those with skin types IV or higher. Results are returned in 2-3 days. If insurance does not cover the test, the cost to the patient is approximately $50 per lesion or a maximum of $150, according to Dr. Kim.
 

Use in clinical practice

In Dr. Kim’s clinical experience, the PLA can be considered for suspicious pigmented lesions on cosmetically sensitive areas and for suspicious lesions in areas difficult to biopsy or excise. For example, she discussed the case of a 72-year-old woman with a family history of melanoma, who presented to her clinic with a longstanding pigmented lesion on her right upper and lower eyelids that had previously been treated with laser. She had undergone multiple prior biopsies over 12 years, which caused mild to moderate atypical melanocytic proliferation. The PLA result was double negative for PRAME and LINC in her upper and lower eyelid, “which provided reassurance to the patient,” Dr. Kim said. The patient continues to be followed closely for any clinical changes.

Another patient, a 67-year-old woman, was referred to Dr. Kim from out of state for a teledermatology visit early in the COVID-19 pandemic. The patient had a lesion on her right calf that was hard, raised, and pink, did not resemble other lesions on her body, and had been present for a few weeks. “Her husband had recently passed away from brain cancer and she was very concerned about melanoma,” Dr. Kim recalled. “She lived alone, and the adult son was with her during the teledermatology call to assist. The patient asked about the PLA test, and given her difficulty going to a medical office at the time, we agreed to help her with this test.” The patient and her son arranged another teledermatology visit with Dr. Kim after receiving the kit in the mail from DermTech, and Dr. Kim coached them on how to properly administer the test. The results came back as PRAME negative and LINC positive. A biopsy with a local provider was recommended and the pathology results showed an inflamed seborrheic keratosis.

“This case exemplifies a false-positive result. We should be sure to make patients aware of this possibility,” Dr. Kim said.

Incorporating PLA into clinical practice requires certain workflow considerations, with paperwork to fill out in addition to performing the adhesive test, collection of insurance information, mailing the kit via FedEx, retrieving the results, and following up with the patient, said Dr. Kim. “For select borderline pigmented lesions, I discuss the rationale of the test with patients, the possibility of false-positive and false-negative results and the need to return for a biopsy when there is positive result. Clinical follow-up is recommended for negative results. There is also the possibility of charge to the patient if the test is not covered by their insurance.”
 

Skin biopsy still the gold standard

Despite the availability of the PLA as an assessment tool, Dr. Kim emphasized that skin biopsy remains the gold standard for diagnosing melanoma. “Future prospective randomized clinical trials are needed to examine the role of genetic expression profiling in staging and managing patients,” she said.

In 2019, she and her colleagues surveyed 42 pigmented lesion experts in the United States about why they ordered one of three molecular tests on the market or not and how results affected patient treatment. The proportion of clinicians who ordered the tests ranged from 21% to 29%. The top 2 reasons respondents chose for not ordering the PLA test specifically were: “Feel that further validation studies are necessary” (20%) and “do not feel it would be useful in my practice” (18%).

Results of a larger follow-up survey on usage patterns of PLA of both pigmented lesion experts and general clinicians on this topic are expected to be published shortly.

Dr. Kim reported having no disclosures related to her presentation.

In recent years, patients with advanced lung cancer have benefited from the advent of immune therapies and genotype-directed therapies –both of which have led to improved survival rates. But what will lung cancer look like in 2030?

Pasi A. Janne, MD, PhD, of the Dana-Farber Cancer Institute, Boston, hopes to see improved access to tumor and blood-based genotyping.

Dr. Janne, who serves as director of the Lowe Center for Thoracic Oncology at Dana-Farber, gave a keynote presentation at the 2022 European Lung Cancer Congress, where he highlighted the need to broaden the scope of targeted therapies, make “great drugs work even better,” improve the ability to treat patients based on risk level, and expand the use of targeted therapies in the adjuvant and neoadjuvant setting to make significant progress in the treatment lung cancer treatment in coming years.

Genotyping is underutilized, he said. A 2019 multicenter study reported at the annual meeting of the American Society of Clinical Oncology showed that only 54% of 1,203 patients underwent testing for EGFR mutations, 22% were tested for EGFR, ALK, ROS1, and BRAF mutations, and only 7% were tested for all biomarkers recommended by National Comprehensive Cancer Network guidelines at the time.

That study also showed that only 45% of patients received biomarker-driven treatment, even when driver mutations were detected.

“Immunotherapy was often prescribed instead of targeted therapy, even when molecular results were available,” Dr. Janne said.

Another study, reported at the 2021 ASCO annual meeting, showed some improvement in testing rates, but still, only 37% of patients were tested for all biomarkers as recommended.

Racial disparities in testing have also been observed. Bruno and colleagues found that any next-generation sequencing was performed in 50.1% of White patients, compared with 39.8% of black patients, and NGS prior to first-line therapy was performed in 35.5% and 25.8%, respectively.

The study, also reported at ASCO in 2021, showed that trial participation was observed among 3.9% of White patients and 1.9% of Black patients.

“The studies really highlight the need for increased testing rates and appropriate utilization of testing results to deliver optimal care to our patients with advanced lung cancer. We have a long way to go. To live the promise and appreciate the promise of precision therapy ... we need to be able to offer this testing to all of our patients with lung cancer,” he said.

Dr. Janne reported relationships with numerous pharmaceutical companies, including consulting, research support and stock ownership. He also receives postmarketing royalties from Dana-Farber Cancer Institute–owned intellectual property on EGFR mutations.

In recent years, patients with advanced lung cancer have benefited from the advent of immune therapies and genotype-directed therapies –both of which have led to improved survival rates. But what will lung cancer look like in 2030?

Pasi A. Janne, MD, PhD, of the Dana-Farber Cancer Institute, Boston, hopes to see improved access to tumor and blood-based genotyping.

Dr. Janne, who serves as director of the Lowe Center for Thoracic Oncology at Dana-Farber, gave a keynote presentation at the 2022 European Lung Cancer Congress, where he highlighted the need to broaden the scope of targeted therapies, make “great drugs work even better,” improve the ability to treat patients based on risk level, and expand the use of targeted therapies in the adjuvant and neoadjuvant setting to make significant progress in the treatment lung cancer treatment in coming years.

Genotyping is underutilized, he said. A 2019 multicenter study reported at the annual meeting of the American Society of Clinical Oncology showed that only 54% of 1,203 patients underwent testing for EGFR mutations, 22% were tested for EGFR, ALK, ROS1, and BRAF mutations, and only 7% were tested for all biomarkers recommended by National Comprehensive Cancer Network guidelines at the time.

That study also showed that only 45% of patients received biomarker-driven treatment, even when driver mutations were detected.

“Immunotherapy was often prescribed instead of targeted therapy, even when molecular results were available,” Dr. Janne said.

Another study, reported at the 2021 ASCO annual meeting, showed some improvement in testing rates, but still, only 37% of patients were tested for all biomarkers as recommended.

Racial disparities in testing have also been observed. Bruno and colleagues found that any next-generation sequencing was performed in 50.1% of White patients, compared with 39.8% of black patients, and NGS prior to first-line therapy was performed in 35.5% and 25.8%, respectively.

The study, also reported at ASCO in 2021, showed that trial participation was observed among 3.9% of White patients and 1.9% of Black patients.

“The studies really highlight the need for increased testing rates and appropriate utilization of testing results to deliver optimal care to our patients with advanced lung cancer. We have a long way to go. To live the promise and appreciate the promise of precision therapy ... we need to be able to offer this testing to all of our patients with lung cancer,” he said.

Dr. Janne reported relationships with numerous pharmaceutical companies, including consulting, research support and stock ownership. He also receives postmarketing royalties from Dana-Farber Cancer Institute–owned intellectual property on EGFR mutations.

In recent years, patients with advanced lung cancer have benefited from the advent of immune therapies and genotype-directed therapies –both of which have led to improved survival rates. But what will lung cancer look like in 2030?

Pasi A. Janne, MD, PhD, of the Dana-Farber Cancer Institute, Boston, hopes to see improved access to tumor and blood-based genotyping.

Dr. Janne, who serves as director of the Lowe Center for Thoracic Oncology at Dana-Farber, gave a keynote presentation at the 2022 European Lung Cancer Congress, where he highlighted the need to broaden the scope of targeted therapies, make “great drugs work even better,” improve the ability to treat patients based on risk level, and expand the use of targeted therapies in the adjuvant and neoadjuvant setting to make significant progress in the treatment lung cancer treatment in coming years.

Genotyping is underutilized, he said. A 2019 multicenter study reported at the annual meeting of the American Society of Clinical Oncology showed that only 54% of 1,203 patients underwent testing for EGFR mutations, 22% were tested for EGFR, ALK, ROS1, and BRAF mutations, and only 7% were tested for all biomarkers recommended by National Comprehensive Cancer Network guidelines at the time.

That study also showed that only 45% of patients received biomarker-driven treatment, even when driver mutations were detected.

“Immunotherapy was often prescribed instead of targeted therapy, even when molecular results were available,” Dr. Janne said.

Another study, reported at the 2021 ASCO annual meeting, showed some improvement in testing rates, but still, only 37% of patients were tested for all biomarkers as recommended.

Racial disparities in testing have also been observed. Bruno and colleagues found that any next-generation sequencing was performed in 50.1% of White patients, compared with 39.8% of black patients, and NGS prior to first-line therapy was performed in 35.5% and 25.8%, respectively.

The study, also reported at ASCO in 2021, showed that trial participation was observed among 3.9% of White patients and 1.9% of Black patients.

“The studies really highlight the need for increased testing rates and appropriate utilization of testing results to deliver optimal care to our patients with advanced lung cancer. We have a long way to go. To live the promise and appreciate the promise of precision therapy ... we need to be able to offer this testing to all of our patients with lung cancer,” he said.

Dr. Janne reported relationships with numerous pharmaceutical companies, including consulting, research support and stock ownership. He also receives postmarketing royalties from Dana-Farber Cancer Institute–owned intellectual property on EGFR mutations.

Pathological response has emerged as a valuable endpoint and surrogate marker for overall survival in lung cancer studies, but much work remains to be done, said William D. Travis, MD, director of thoracic pathology at Memorial Sloan Kettering Cancer Center, New York.

In a keynote address at the 2022 European Lung Cancer Conference, Dr. Travis highlighted advances in the use of pathological response in this setting and outlined areas that need refinement. “Pathologic response after preoperative therapy is important because the extent of pathologic response strongly correlates with improved overall survival, and it is reflective of neoadjuvant therapy. The degree of response is associated with the degree of benefit in survival, and it’s being used as a surrogate for survival in phase 2 and 3 neoadjuvant clinical trials.”

In fact, multiple studies have demonstrated that non–small cell lung cancer patients with 10% or less viable residual tumor after treatment have improved overall survival and disease-free survival, compared with patients who have more residual tumor, he explained.

Recent studies have demonstrated the value of pathological response as an endpoint in the neoadjuvant therapy and molecular targeted therapy setting, he said, citing a study published in the Journal of Clinical Oncology that showed major pathological response rates of 14%-45% and pathological complete response rates up to 29% in patients treated with single-agent checkpoint inhibition.

In the CheckMate 816 trial, both major pathologic response and pathological complete response were significantly higher in patients treated with combination nivolumab and chemotherapy, compared with those treated with chemotherapy alone (37% vs. 8.9% and 24% vs. 2%, respectively).

“This high rate of responses with combined immunotherapy and chemotherapy is quite exciting,” he said.

Dr. Travis also stressed the importance of consulting the current International Association for the Study of Lung Cancer Recommendations for Pathologic Assessment of Lung Cancer Resection Specimens After Neoadjuvant Therapy.

He highlighted several key points regarding pathological response in lung cancer:

• Major pathological response (MPR) is calculated as the estimated size of viable tumor divided by the size of the tumor bed.
• Optimal cutoffs for determining MPR is currently 10%, but recent data suggest that in the conventional chemotherapy setting this may vary by tumor histology, with much higher cutoffs of about 65% for adenocarcinoma.
• Estimating the amount of viable tumor is “quite complicated and requires quite a number of steps,” and one the most important steps is “for the surgeon to the pathologist know that given specimen is from a patient who received neoadjuvant therapy.”
• Determining the border of the tumor bed can be challenging, therefore “resection specimens after neoadjuvant therapy should be sampled to optimize comprehensive gross and histologic assessment of the lung tumor bed for pathologic response ... as outlined in the guidelines.”
• The IASLC panel determined that having a single approach for estimating treatment effect would be best, despite the different therapy types and combinations used, but “it is recognized that there may be certain types of features that need to be addressed,” such as immune cell infiltrates in pats who received immunotherapy.
• The recommendations provide specific guidance for measuring tumor size for staging, including for special circumstances.

As for future direction, Dr. Travis said, “one question is how to assess treatment effect in lymph node samples.

“This is done for lymph nodes in breast cancer but not in lung cancer. We need system[s] for lung cancer.”

Good “infrastructure for pathology departments” is needed to support clinical trials, he said, noting that the team at Memorial Sloan Kettering Cancer Center includes physician assistants, tissue procurement staff, frozen section techs, research fellows, and research assistants.

Future work should also aim to standardize pathology assessment for clinical trials, improve the current recommendations, make use of new technology like artificial intelligence, optimize banking protocols and special techniques, and identify radiologic-pathological correlations, he said.

He added that “IASLC is promoting the design and implementation of an international database to collect uniformly clinical and pathologic information with the ultimate goal of fostering collaboration and to facilitate the identification of surrogate endpoints of long-term survival.”

Dr. Travis is a nonpaid pathology consultant for the LCMC3 and LCMC4 trials.

Pathological response has emerged as a valuable endpoint and surrogate marker for overall survival in lung cancer studies, but much work remains to be done, said William D. Travis, MD, director of thoracic pathology at Memorial Sloan Kettering Cancer Center, New York.

In a keynote address at the 2022 European Lung Cancer Conference, Dr. Travis highlighted advances in the use of pathological response in this setting and outlined areas that need refinement. “Pathologic response after preoperative therapy is important because the extent of pathologic response strongly correlates with improved overall survival, and it is reflective of neoadjuvant therapy. The degree of response is associated with the degree of benefit in survival, and it’s being used as a surrogate for survival in phase 2 and 3 neoadjuvant clinical trials.”

In fact, multiple studies have demonstrated that non–small cell lung cancer patients with 10% or less viable residual tumor after treatment have improved overall survival and disease-free survival, compared with patients who have more residual tumor, he explained.

Recent studies have demonstrated the value of pathological response as an endpoint in the neoadjuvant therapy and molecular targeted therapy setting, he said, citing a study published in the Journal of Clinical Oncology that showed major pathological response rates of 14%-45% and pathological complete response rates up to 29% in patients treated with single-agent checkpoint inhibition.

In the CheckMate 816 trial, both major pathologic response and pathological complete response were significantly higher in patients treated with combination nivolumab and chemotherapy, compared with those treated with chemotherapy alone (37% vs. 8.9% and 24% vs. 2%, respectively).

“This high rate of responses with combined immunotherapy and chemotherapy is quite exciting,” he said.

Dr. Travis also stressed the importance of consulting the current International Association for the Study of Lung Cancer Recommendations for Pathologic Assessment of Lung Cancer Resection Specimens After Neoadjuvant Therapy.

He highlighted several key points regarding pathological response in lung cancer:

• Major pathological response (MPR) is calculated as the estimated size of viable tumor divided by the size of the tumor bed.
• Optimal cutoffs for determining MPR is currently 10%, but recent data suggest that in the conventional chemotherapy setting this may vary by tumor histology, with much higher cutoffs of about 65% for adenocarcinoma.
• Estimating the amount of viable tumor is “quite complicated and requires quite a number of steps,” and one the most important steps is “for the surgeon to the pathologist know that given specimen is from a patient who received neoadjuvant therapy.”
• Determining the border of the tumor bed can be challenging, therefore “resection specimens after neoadjuvant therapy should be sampled to optimize comprehensive gross and histologic assessment of the lung tumor bed for pathologic response ... as outlined in the guidelines.”
• The IASLC panel determined that having a single approach for estimating treatment effect would be best, despite the different therapy types and combinations used, but “it is recognized that there may be certain types of features that need to be addressed,” such as immune cell infiltrates in pats who received immunotherapy.
• The recommendations provide specific guidance for measuring tumor size for staging, including for special circumstances.

As for future direction, Dr. Travis said, “one question is how to assess treatment effect in lymph node samples.

“This is done for lymph nodes in breast cancer but not in lung cancer. We need system[s] for lung cancer.”

Good “infrastructure for pathology departments” is needed to support clinical trials, he said, noting that the team at Memorial Sloan Kettering Cancer Center includes physician assistants, tissue procurement staff, frozen section techs, research fellows, and research assistants.

Future work should also aim to standardize pathology assessment for clinical trials, improve the current recommendations, make use of new technology like artificial intelligence, optimize banking protocols and special techniques, and identify radiologic-pathological correlations, he said.

He added that “IASLC is promoting the design and implementation of an international database to collect uniformly clinical and pathologic information with the ultimate goal of fostering collaboration and to facilitate the identification of surrogate endpoints of long-term survival.”

Dr. Travis is a nonpaid pathology consultant for the LCMC3 and LCMC4 trials.

Pathological response has emerged as a valuable endpoint and surrogate marker for overall survival in lung cancer studies, but much work remains to be done, said William D. Travis, MD, director of thoracic pathology at Memorial Sloan Kettering Cancer Center, New York.

In a keynote address at the 2022 European Lung Cancer Conference, Dr. Travis highlighted advances in the use of pathological response in this setting and outlined areas that need refinement. “Pathologic response after preoperative therapy is important because the extent of pathologic response strongly correlates with improved overall survival, and it is reflective of neoadjuvant therapy. The degree of response is associated with the degree of benefit in survival, and it’s being used as a surrogate for survival in phase 2 and 3 neoadjuvant clinical trials.”

In fact, multiple studies have demonstrated that non–small cell lung cancer patients with 10% or less viable residual tumor after treatment have improved overall survival and disease-free survival, compared with patients who have more residual tumor, he explained.

Recent studies have demonstrated the value of pathological response as an endpoint in the neoadjuvant therapy and molecular targeted therapy setting, he said, citing a study published in the Journal of Clinical Oncology that showed major pathological response rates of 14%-45% and pathological complete response rates up to 29% in patients treated with single-agent checkpoint inhibition.

In the CheckMate 816 trial, both major pathologic response and pathological complete response were significantly higher in patients treated with combination nivolumab and chemotherapy, compared with those treated with chemotherapy alone (37% vs. 8.9% and 24% vs. 2%, respectively).

“This high rate of responses with combined immunotherapy and chemotherapy is quite exciting,” he said.

Dr. Travis also stressed the importance of consulting the current International Association for the Study of Lung Cancer Recommendations for Pathologic Assessment of Lung Cancer Resection Specimens After Neoadjuvant Therapy.

He highlighted several key points regarding pathological response in lung cancer:

• Major pathological response (MPR) is calculated as the estimated size of viable tumor divided by the size of the tumor bed.
• Optimal cutoffs for determining MPR is currently 10%, but recent data suggest that in the conventional chemotherapy setting this may vary by tumor histology, with much higher cutoffs of about 65% for adenocarcinoma.
• Estimating the amount of viable tumor is “quite complicated and requires quite a number of steps,” and one the most important steps is “for the surgeon to the pathologist know that given specimen is from a patient who received neoadjuvant therapy.”
• Determining the border of the tumor bed can be challenging, therefore “resection specimens after neoadjuvant therapy should be sampled to optimize comprehensive gross and histologic assessment of the lung tumor bed for pathologic response ... as outlined in the guidelines.”
• The IASLC panel determined that having a single approach for estimating treatment effect would be best, despite the different therapy types and combinations used, but “it is recognized that there may be certain types of features that need to be addressed,” such as immune cell infiltrates in pats who received immunotherapy.
• The recommendations provide specific guidance for measuring tumor size for staging, including for special circumstances.

As for future direction, Dr. Travis said, “one question is how to assess treatment effect in lymph node samples.

“This is done for lymph nodes in breast cancer but not in lung cancer. We need system[s] for lung cancer.”

Good “infrastructure for pathology departments” is needed to support clinical trials, he said, noting that the team at Memorial Sloan Kettering Cancer Center includes physician assistants, tissue procurement staff, frozen section techs, research fellows, and research assistants.

Future work should also aim to standardize pathology assessment for clinical trials, improve the current recommendations, make use of new technology like artificial intelligence, optimize banking protocols and special techniques, and identify radiologic-pathological correlations, he said.

He added that “IASLC is promoting the design and implementation of an international database to collect uniformly clinical and pathologic information with the ultimate goal of fostering collaboration and to facilitate the identification of surrogate endpoints of long-term survival.”

Dr. Travis is a nonpaid pathology consultant for the LCMC3 and LCMC4 trials.

A new consensus statement from the American Head and Neck Society Endocrine Surgery Section and International Thyroid Oncology Group focuses on a definition of advanced thyroid cancer and outlines strategies for mutation testing and targeted treatment.

Mutation testing should not be pursued if cancer burden and disease threat is low, since most thyroid cancers have a very good prognosis and are highly treatable. But 15% of differentiated thyroid cancer cases are locally advanced, and radioiodine refractory differentiated thyroid cancer has a 10-year survival below 50%.

More generally, advanced thyroid cancer has not been well defined clinically. Physicians with experience diagnosing advanced disease may recognize it, but there is no widely accepted definition. “This may be the first time that an expert group of physicians has attempted to define what advanced thyroid cancer is,” said David Shonka, MD, who is a coauthor of the consensus statement, which was published online in Head & Neck. He is an associate professor of otolaryngology/head and neck surgery at the University of Virginia, Charlottesville.

“All patients with advanced thyroid disease and most patients with incurable radioiodine refractory differentiated thyroid cancer should undergo somatic mutational testing,” the authors wrote. “Next-generation sequencing can reveal targetable mutations and potentially give patients affected by advanced thyroid carcinoma systemic treatment options that can prolong survival. These new innovative approaches are changing the landscape of clinical care for patients with advanced thyroid cancer.”

For differentiated thyroid cancer and medullary thyroid carcinoma, the authors created a definition that combines structural factors on imaging, along with surgical findings, and biochemical, histologic, and molecular factors. Anaplastic thyroid cancer should always be considered advanced, even after a complete resection and incidental pathological identification.

The statement also summarizes recent advances in thyroid cancer that have revealed molecular markers which contribute to oncogenesis. Initially, those approaches were applied to indeterminate fine needle biopsies to improve diagnosis. More recent studies used them to match patients to targeted therapies. There are Food and Drug Administration–approved therapies targeting the BRAF and RET mutations, but advanced thyroid cancer is also included in some “basket” trials that test targeted agents against driver mutations across multiple tumor types.

Radioiodine refractory differentiated thyroid cancer had few treatments as recently as 10 years ago. But recent research has shown that multikinase inhibitors improve outcomes, and a range of mutations have been found in this type of thyroid cancer, including BRAF V600E, RET, PIK3CA, and PTEN, and fusions involving RET, NTRK, and ALK. Other mutations have been linked to more aggressive disease. Efforts to personalize treatment also include microsatellite stability status, tumor mutational burden, and programmed death–ligand 1 status as indicators for immunotherapy. “With discovery of many other molecular targets, and emerging literature showcasing promise of matched targeted therapies, we recommend that all patients with advanced thyroid cancer have comprehensive genomic profiling on tumor tissue through (next generation sequencing),” the authors wrote.

These newer and novel therapies have presented physicians with options outside of surgery, chemotherapy, or radiotherapy, which have low efficacy against advanced thyroid cancer. “It is an area in which there has been substantial change. Even 5-7 years ago, patients with advanced thyroid cancer that was not responsive to radioactive iodine or surgery really didn’t have a lot of options. This is a really an exciting and growing field,” Dr. Shonka said.

He specifically cited anaplastic thyroid cancer, which like radioiodine refractory differentiated thyroid cancer has had few treatment options until recently. “Now, if you see a patient with anaplastic thyroid cancer, your knee-jerk reaction should be ‘let’s do molecular testing on this, this is definitely advanced disease.’ If they have a BRAF mutation, that’s targetable, and we can treat this patient with combination therapy that actually improves their survival. So, there’s some exciting stuff happening and probably more coming down the road as we develop new drugs that can target these mutations that we’re identifying.”

Dr. Shonka has no relevant financial disclosures.

A new consensus statement from the American Head and Neck Society Endocrine Surgery Section and International Thyroid Oncology Group focuses on a definition of advanced thyroid cancer and outlines strategies for mutation testing and targeted treatment.

Mutation testing should not be pursued if cancer burden and disease threat is low, since most thyroid cancers have a very good prognosis and are highly treatable. But 15% of differentiated thyroid cancer cases are locally advanced, and radioiodine refractory differentiated thyroid cancer has a 10-year survival below 50%.

More generally, advanced thyroid cancer has not been well defined clinically. Physicians with experience diagnosing advanced disease may recognize it, but there is no widely accepted definition. “This may be the first time that an expert group of physicians has attempted to define what advanced thyroid cancer is,” said David Shonka, MD, who is a coauthor of the consensus statement, which was published online in Head & Neck. He is an associate professor of otolaryngology/head and neck surgery at the University of Virginia, Charlottesville.

“All patients with advanced thyroid disease and most patients with incurable radioiodine refractory differentiated thyroid cancer should undergo somatic mutational testing,” the authors wrote. “Next-generation sequencing can reveal targetable mutations and potentially give patients affected by advanced thyroid carcinoma systemic treatment options that can prolong survival. These new innovative approaches are changing the landscape of clinical care for patients with advanced thyroid cancer.”

For differentiated thyroid cancer and medullary thyroid carcinoma, the authors created a definition that combines structural factors on imaging, along with surgical findings, and biochemical, histologic, and molecular factors. Anaplastic thyroid cancer should always be considered advanced, even after a complete resection and incidental pathological identification.

The statement also summarizes recent advances in thyroid cancer that have revealed molecular markers which contribute to oncogenesis. Initially, those approaches were applied to indeterminate fine needle biopsies to improve diagnosis. More recent studies used them to match patients to targeted therapies. There are Food and Drug Administration–approved therapies targeting the BRAF and RET mutations, but advanced thyroid cancer is also included in some “basket” trials that test targeted agents against driver mutations across multiple tumor types.

Radioiodine refractory differentiated thyroid cancer had few treatments as recently as 10 years ago. But recent research has shown that multikinase inhibitors improve outcomes, and a range of mutations have been found in this type of thyroid cancer, including BRAF V600E, RET, PIK3CA, and PTEN, and fusions involving RET, NTRK, and ALK. Other mutations have been linked to more aggressive disease. Efforts to personalize treatment also include microsatellite stability status, tumor mutational burden, and programmed death–ligand 1 status as indicators for immunotherapy. “With discovery of many other molecular targets, and emerging literature showcasing promise of matched targeted therapies, we recommend that all patients with advanced thyroid cancer have comprehensive genomic profiling on tumor tissue through (next generation sequencing),” the authors wrote.

These newer and novel therapies have presented physicians with options outside of surgery, chemotherapy, or radiotherapy, which have low efficacy against advanced thyroid cancer. “It is an area in which there has been substantial change. Even 5-7 years ago, patients with advanced thyroid cancer that was not responsive to radioactive iodine or surgery really didn’t have a lot of options. This is a really an exciting and growing field,” Dr. Shonka said.

He specifically cited anaplastic thyroid cancer, which like radioiodine refractory differentiated thyroid cancer has had few treatment options until recently. “Now, if you see a patient with anaplastic thyroid cancer, your knee-jerk reaction should be ‘let’s do molecular testing on this, this is definitely advanced disease.’ If they have a BRAF mutation, that’s targetable, and we can treat this patient with combination therapy that actually improves their survival. So, there’s some exciting stuff happening and probably more coming down the road as we develop new drugs that can target these mutations that we’re identifying.”

Dr. Shonka has no relevant financial disclosures.

A new consensus statement from the American Head and Neck Society Endocrine Surgery Section and International Thyroid Oncology Group focuses on a definition of advanced thyroid cancer and outlines strategies for mutation testing and targeted treatment.

Mutation testing should not be pursued if cancer burden and disease threat is low, since most thyroid cancers have a very good prognosis and are highly treatable. But 15% of differentiated thyroid cancer cases are locally advanced, and radioiodine refractory differentiated thyroid cancer has a 10-year survival below 50%.

More generally, advanced thyroid cancer has not been well defined clinically. Physicians with experience diagnosing advanced disease may recognize it, but there is no widely accepted definition. “This may be the first time that an expert group of physicians has attempted to define what advanced thyroid cancer is,” said David Shonka, MD, who is a coauthor of the consensus statement, which was published online in Head & Neck. He is an associate professor of otolaryngology/head and neck surgery at the University of Virginia, Charlottesville.

“All patients with advanced thyroid disease and most patients with incurable radioiodine refractory differentiated thyroid cancer should undergo somatic mutational testing,” the authors wrote. “Next-generation sequencing can reveal targetable mutations and potentially give patients affected by advanced thyroid carcinoma systemic treatment options that can prolong survival. These new innovative approaches are changing the landscape of clinical care for patients with advanced thyroid cancer.”

For differentiated thyroid cancer and medullary thyroid carcinoma, the authors created a definition that combines structural factors on imaging, along with surgical findings, and biochemical, histologic, and molecular factors. Anaplastic thyroid cancer should always be considered advanced, even after a complete resection and incidental pathological identification.

The statement also summarizes recent advances in thyroid cancer that have revealed molecular markers which contribute to oncogenesis. Initially, those approaches were applied to indeterminate fine needle biopsies to improve diagnosis. More recent studies used them to match patients to targeted therapies. There are Food and Drug Administration–approved therapies targeting the BRAF and RET mutations, but advanced thyroid cancer is also included in some “basket” trials that test targeted agents against driver mutations across multiple tumor types.

Radioiodine refractory differentiated thyroid cancer had few treatments as recently as 10 years ago. But recent research has shown that multikinase inhibitors improve outcomes, and a range of mutations have been found in this type of thyroid cancer, including BRAF V600E, RET, PIK3CA, and PTEN, and fusions involving RET, NTRK, and ALK. Other mutations have been linked to more aggressive disease. Efforts to personalize treatment also include microsatellite stability status, tumor mutational burden, and programmed death–ligand 1 status as indicators for immunotherapy. “With discovery of many other molecular targets, and emerging literature showcasing promise of matched targeted therapies, we recommend that all patients with advanced thyroid cancer have comprehensive genomic profiling on tumor tissue through (next generation sequencing),” the authors wrote.

These newer and novel therapies have presented physicians with options outside of surgery, chemotherapy, or radiotherapy, which have low efficacy against advanced thyroid cancer. “It is an area in which there has been substantial change. Even 5-7 years ago, patients with advanced thyroid cancer that was not responsive to radioactive iodine or surgery really didn’t have a lot of options. This is a really an exciting and growing field,” Dr. Shonka said.

He specifically cited anaplastic thyroid cancer, which like radioiodine refractory differentiated thyroid cancer has had few treatment options until recently. “Now, if you see a patient with anaplastic thyroid cancer, your knee-jerk reaction should be ‘let’s do molecular testing on this, this is definitely advanced disease.’ If they have a BRAF mutation, that’s targetable, and we can treat this patient with combination therapy that actually improves their survival. So, there’s some exciting stuff happening and probably more coming down the road as we develop new drugs that can target these mutations that we’re identifying.”

Dr. Shonka has no relevant financial disclosures.

A ketogenic diet fed to mice with epithelial ovarian cancer led to significantly increased tumor growth and gut microbiome alterations, according to study recently presented at the annual meeting of the Society of Gynecologic Oncology.

“The keto diet is very popular, especially among patients who believe it may treat cancer by starving tumors of the fuel they need to grow, altering the immune system, and other anticancer effects,” said study leader Mariam AlHilli, MD, of the Cleveland Clinic.

The findings are surprising because in other studies the high-fat, zero-carb ketogenic diet has demonstrated tumor-suppressing effects. It has been under study as a possible adjuvant therapy for other cancers, such as glioblastoma, colon cancer, prostate cancer, and pancreatic cancer.

“While we don’t know yet whether these findings extend to patients, the results in animals indicate that instead of being protective, the keto diet appears to promote ovarian cancer growth and progression,” Dr. AlHilli said. In the present study, tumor bearing mice were fed a keto diet consisting of 10% protein, 0% carbohydrates, and 90% fat, while the high-fat diet was 10% protein, 15% carbohydrates, and 75% fat. The control diet consisted of 10% protein, 77% carbohydrates, and 13% fat. Epithelial ovarian cancer tumor growth was monitored weekly.

Over the 6- to 10-week course of study, a 9.1-fold increase from baseline in tumor growth was observed in the keto diet-fed mice (n = 20). Among mice fed a high-fat diet (n = 20) that included some carbohydrates, tumor growth increased 2.0-fold from baseline, and among control group mice (n = 20) fed a low-fat, high carbohydrate diet, tumor growth increased 3.1-fold.

The investigators observed several hallmarks of tumor progression: tumor associated macrophages were enriched significantly, activated lymphoid cells (natural killer cells) were significantly reduced (P < .001), and M2:M1 polarization trended higher. Also, in keto diet–fed mice, gene set enrichment analysis revealed that epithelial ovarian cancer tumors had increased angiogenesis and inflammatory responses, enhanced epithelial-to-mesenchymal transition phenotype, and altered lipid metabolism. Compared with high-fat diet–fed mice, the keto-fed mice had increases in lipid catalytic activity and catabolism, as well as decreases in lipid synthesis.

“The tumor increase could be mediated by the gut microbiome or by gene alterations or by metabolite levels that influence tumor growth. It’s possible that each cancer type is different. The composition of the diet may be a factor, as well as how tumors metabolize fat and ketones,” Dr. AlHilli said.

The results need to be confirmed in preclinical animal studies and in additional models, she added.

The study was funded by a K12 Grant and internal funding from Cleveland Clinic. Dr. AlHilli declared no relevant disclosures.

A ketogenic diet fed to mice with epithelial ovarian cancer led to significantly increased tumor growth and gut microbiome alterations, according to study recently presented at the annual meeting of the Society of Gynecologic Oncology.

“The keto diet is very popular, especially among patients who believe it may treat cancer by starving tumors of the fuel they need to grow, altering the immune system, and other anticancer effects,” said study leader Mariam AlHilli, MD, of the Cleveland Clinic.

The findings are surprising because in other studies the high-fat, zero-carb ketogenic diet has demonstrated tumor-suppressing effects. It has been under study as a possible adjuvant therapy for other cancers, such as glioblastoma, colon cancer, prostate cancer, and pancreatic cancer.

“While we don’t know yet whether these findings extend to patients, the results in animals indicate that instead of being protective, the keto diet appears to promote ovarian cancer growth and progression,” Dr. AlHilli said. In the present study, tumor bearing mice were fed a keto diet consisting of 10% protein, 0% carbohydrates, and 90% fat, while the high-fat diet was 10% protein, 15% carbohydrates, and 75% fat. The control diet consisted of 10% protein, 77% carbohydrates, and 13% fat. Epithelial ovarian cancer tumor growth was monitored weekly.

Over the 6- to 10-week course of study, a 9.1-fold increase from baseline in tumor growth was observed in the keto diet-fed mice (n = 20). Among mice fed a high-fat diet (n = 20) that included some carbohydrates, tumor growth increased 2.0-fold from baseline, and among control group mice (n = 20) fed a low-fat, high carbohydrate diet, tumor growth increased 3.1-fold.

The investigators observed several hallmarks of tumor progression: tumor associated macrophages were enriched significantly, activated lymphoid cells (natural killer cells) were significantly reduced (P < .001), and M2:M1 polarization trended higher. Also, in keto diet–fed mice, gene set enrichment analysis revealed that epithelial ovarian cancer tumors had increased angiogenesis and inflammatory responses, enhanced epithelial-to-mesenchymal transition phenotype, and altered lipid metabolism. Compared with high-fat diet–fed mice, the keto-fed mice had increases in lipid catalytic activity and catabolism, as well as decreases in lipid synthesis.

“The tumor increase could be mediated by the gut microbiome or by gene alterations or by metabolite levels that influence tumor growth. It’s possible that each cancer type is different. The composition of the diet may be a factor, as well as how tumors metabolize fat and ketones,” Dr. AlHilli said.

The results need to be confirmed in preclinical animal studies and in additional models, she added.

The study was funded by a K12 Grant and internal funding from Cleveland Clinic. Dr. AlHilli declared no relevant disclosures.

A ketogenic diet fed to mice with epithelial ovarian cancer led to significantly increased tumor growth and gut microbiome alterations, according to study recently presented at the annual meeting of the Society of Gynecologic Oncology.

“The keto diet is very popular, especially among patients who believe it may treat cancer by starving tumors of the fuel they need to grow, altering the immune system, and other anticancer effects,” said study leader Mariam AlHilli, MD, of the Cleveland Clinic.

The findings are surprising because in other studies the high-fat, zero-carb ketogenic diet has demonstrated tumor-suppressing effects. It has been under study as a possible adjuvant therapy for other cancers, such as glioblastoma, colon cancer, prostate cancer, and pancreatic cancer.

“While we don’t know yet whether these findings extend to patients, the results in animals indicate that instead of being protective, the keto diet appears to promote ovarian cancer growth and progression,” Dr. AlHilli said. In the present study, tumor bearing mice were fed a keto diet consisting of 10% protein, 0% carbohydrates, and 90% fat, while the high-fat diet was 10% protein, 15% carbohydrates, and 75% fat. The control diet consisted of 10% protein, 77% carbohydrates, and 13% fat. Epithelial ovarian cancer tumor growth was monitored weekly.

Over the 6- to 10-week course of study, a 9.1-fold increase from baseline in tumor growth was observed in the keto diet-fed mice (n = 20). Among mice fed a high-fat diet (n = 20) that included some carbohydrates, tumor growth increased 2.0-fold from baseline, and among control group mice (n = 20) fed a low-fat, high carbohydrate diet, tumor growth increased 3.1-fold.

The investigators observed several hallmarks of tumor progression: tumor associated macrophages were enriched significantly, activated lymphoid cells (natural killer cells) were significantly reduced (P < .001), and M2:M1 polarization trended higher. Also, in keto diet–fed mice, gene set enrichment analysis revealed that epithelial ovarian cancer tumors had increased angiogenesis and inflammatory responses, enhanced epithelial-to-mesenchymal transition phenotype, and altered lipid metabolism. Compared with high-fat diet–fed mice, the keto-fed mice had increases in lipid catalytic activity and catabolism, as well as decreases in lipid synthesis.

“The tumor increase could be mediated by the gut microbiome or by gene alterations or by metabolite levels that influence tumor growth. It’s possible that each cancer type is different. The composition of the diet may be a factor, as well as how tumors metabolize fat and ketones,” Dr. AlHilli said.

The results need to be confirmed in preclinical animal studies and in additional models, she added.

The study was funded by a K12 Grant and internal funding from Cleveland Clinic. Dr. AlHilli declared no relevant disclosures.

An artificial intelligence (AI) model successfully predicted which high-grade serous ovarian cancer patients would have excellent responses to laparoscopic surgery. The model, using still-frame images from pretreatment laparoscopic surgical videos, had an overall accuracy rate of 93%, according to the pilot study’s first author, Deanna Glassman, MD, an oncologic fellow at the University of Texas MD Anderson Cancer Center, Houston.

Dr. Glassman described her research in a presentation given at the annual meeting of the Society of Gynecologic Oncology.

While the AI model successfully identified all excellent-response patients, it did classify about a third of patients with poor responses as excellent responses. The smaller number of images in the poor-response category, Dr. Glassman speculated, may explain the misclassification.

Researchers took 435 representative still-frame images from pretreatment laparoscopic surgical videos of 113 patients with pathologically proven high-grade serous ovarian cancer. Using 70% of the images to train the model, they used 10% for validation and 20% for the actual testing. They developed the AI model with images from four anatomical locations (diaphragm, omentum, peritoneum, and pelvis), training it using deep learning and neural networks to extract morphological disease patterns for correlation with either of two outcomes: excellent response or poor response. An excellent response was defined as progression-free survival of 12 months or more, and poor response as PFS of 6 months or less. In the retrospective study of images, after excluding 32 gray-zone patients, 75 patients (66%) had durable responses to therapy and 6 (5%) had poor responses.

The PFS was 19 months in the excellent-response group and 3 months in the poor-response group.

Clinicians have often observed differences in gross morphology within the single histologic diagnosis of high-grade serous ovarian cancer. The research intent was to determine if AI could detect these distinct morphological patterns in the still frame images taken at the time of laparoscopy, and correlate them with the eventual clinical outcomes. Dr. Glassman and colleagues are currently validating the model with a much larger cohort, and will look into clinical testing.

“The big-picture goal,” Dr. Glassman said in an interview, “would be to utilize the model to predict which patients would do well with traditional standard of care treatments and those who wouldn’t do well so that we can personalize the treatment plan for those patients with alternative agents and therapies.”

Once validated, the model could also be employed to identify patterns of disease in other gynecologic cancers or distinguish between viable and necrosed malignant tissue.

The study’s predominant limitation was the small sample size which is being addressed in a larger ongoing study.

Funding was provided by a T32 grant, MD Anderson Cancer Center Support Grant, MD Anderson Ovarian Cancer Moon Shot, SPORE in Ovarian Cancer, the American Cancer Society, and the Ovarian Cancer Research Alliance. Dr. Glassman declared no relevant financial relationships.

An artificial intelligence (AI) model successfully predicted which high-grade serous ovarian cancer patients would have excellent responses to laparoscopic surgery. The model, using still-frame images from pretreatment laparoscopic surgical videos, had an overall accuracy rate of 93%, according to the pilot study’s first author, Deanna Glassman, MD, an oncologic fellow at the University of Texas MD Anderson Cancer Center, Houston.

Dr. Glassman described her research in a presentation given at the annual meeting of the Society of Gynecologic Oncology.

While the AI model successfully identified all excellent-response patients, it did classify about a third of patients with poor responses as excellent responses. The smaller number of images in the poor-response category, Dr. Glassman speculated, may explain the misclassification.

Researchers took 435 representative still-frame images from pretreatment laparoscopic surgical videos of 113 patients with pathologically proven high-grade serous ovarian cancer. Using 70% of the images to train the model, they used 10% for validation and 20% for the actual testing. They developed the AI model with images from four anatomical locations (diaphragm, omentum, peritoneum, and pelvis), training it using deep learning and neural networks to extract morphological disease patterns for correlation with either of two outcomes: excellent response or poor response. An excellent response was defined as progression-free survival of 12 months or more, and poor response as PFS of 6 months or less. In the retrospective study of images, after excluding 32 gray-zone patients, 75 patients (66%) had durable responses to therapy and 6 (5%) had poor responses.

The PFS was 19 months in the excellent-response group and 3 months in the poor-response group.

Clinicians have often observed differences in gross morphology within the single histologic diagnosis of high-grade serous ovarian cancer. The research intent was to determine if AI could detect these distinct morphological patterns in the still frame images taken at the time of laparoscopy, and correlate them with the eventual clinical outcomes. Dr. Glassman and colleagues are currently validating the model with a much larger cohort, and will look into clinical testing.

“The big-picture goal,” Dr. Glassman said in an interview, “would be to utilize the model to predict which patients would do well with traditional standard of care treatments and those who wouldn’t do well so that we can personalize the treatment plan for those patients with alternative agents and therapies.”

Once validated, the model could also be employed to identify patterns of disease in other gynecologic cancers or distinguish between viable and necrosed malignant tissue.

The study’s predominant limitation was the small sample size which is being addressed in a larger ongoing study.

Funding was provided by a T32 grant, MD Anderson Cancer Center Support Grant, MD Anderson Ovarian Cancer Moon Shot, SPORE in Ovarian Cancer, the American Cancer Society, and the Ovarian Cancer Research Alliance. Dr. Glassman declared no relevant financial relationships.

An artificial intelligence (AI) model successfully predicted which high-grade serous ovarian cancer patients would have excellent responses to laparoscopic surgery. The model, using still-frame images from pretreatment laparoscopic surgical videos, had an overall accuracy rate of 93%, according to the pilot study’s first author, Deanna Glassman, MD, an oncologic fellow at the University of Texas MD Anderson Cancer Center, Houston.

Dr. Glassman described her research in a presentation given at the annual meeting of the Society of Gynecologic Oncology.

While the AI model successfully identified all excellent-response patients, it did classify about a third of patients with poor responses as excellent responses. The smaller number of images in the poor-response category, Dr. Glassman speculated, may explain the misclassification.

Researchers took 435 representative still-frame images from pretreatment laparoscopic surgical videos of 113 patients with pathologically proven high-grade serous ovarian cancer. Using 70% of the images to train the model, they used 10% for validation and 20% for the actual testing. They developed the AI model with images from four anatomical locations (diaphragm, omentum, peritoneum, and pelvis), training it using deep learning and neural networks to extract morphological disease patterns for correlation with either of two outcomes: excellent response or poor response. An excellent response was defined as progression-free survival of 12 months or more, and poor response as PFS of 6 months or less. In the retrospective study of images, after excluding 32 gray-zone patients, 75 patients (66%) had durable responses to therapy and 6 (5%) had poor responses.

The PFS was 19 months in the excellent-response group and 3 months in the poor-response group.

Clinicians have often observed differences in gross morphology within the single histologic diagnosis of high-grade serous ovarian cancer. The research intent was to determine if AI could detect these distinct morphological patterns in the still frame images taken at the time of laparoscopy, and correlate them with the eventual clinical outcomes. Dr. Glassman and colleagues are currently validating the model with a much larger cohort, and will look into clinical testing.

“The big-picture goal,” Dr. Glassman said in an interview, “would be to utilize the model to predict which patients would do well with traditional standard of care treatments and those who wouldn’t do well so that we can personalize the treatment plan for those patients with alternative agents and therapies.”

Once validated, the model could also be employed to identify patterns of disease in other gynecologic cancers or distinguish between viable and necrosed malignant tissue.

The study’s predominant limitation was the small sample size which is being addressed in a larger ongoing study.

Funding was provided by a T32 grant, MD Anderson Cancer Center Support Grant, MD Anderson Ovarian Cancer Moon Shot, SPORE in Ovarian Cancer, the American Cancer Society, and the Ovarian Cancer Research Alliance. Dr. Glassman declared no relevant financial relationships.

A humanized mouse model suggests that head and neck cancer growth may stem from chronic stress. The study found that animals had immunophenotypic changes and a greater propensity towards tumor growth and metastasis.

It is not uncommon for low-income patients with head and neck cancer to present with more aggressive disease at diagnosis. Other studies have shown this may be caused by the lack of access to health care services or poor quality care. but the difference remains even after adjusting for these factors, according to researchers writing in Head and Neck.

Led by Heather A. Himburg, PhD, associate professor of radiation oncology with the Medical College of Wisconsin, Milwaukee, researchers conducted a study of head and neck cancer models in which tumor cells were implanted into a mouse with a humanized immune system.

Their theory was that psychosocial stress may contribute to the growth of head and neck tumors. The stress of poverty, social deprivation and social isolation can lead to the up-regulation of proinflammatory markers in circulating blood leukocytes, and this has been tied to worse outcomes in hematologic malignancies and breast cancer. Many such studies examined social adversity and found an association with greater tumor growth rates and treatment resistance.

Other researchers have used mouse models to study the phenomenon, but the results have been inconclusive. For example, some research linked the beta-adrenergic pathway to head and neck cancer, but clinical trials of beta-blockers showed no benefit, and even potential harm, for patients with head and neck cancers. Those results imply that this pathway does not drive tumor growth and metastasis in the presence of chronic stress.

Previous research used immunocompromised or nonhumanized mice. However, neither type of model reproduces the human tumor microenvironment, which may contribute to ensuing clinical failures. In the new study, researchers describe results from a preclinical model created using a human head and neck cancer xenograft in a mouse with a humanized immune system.
 

How the study was conducted

The animals were randomly assigned to normal housing of two or three animals from the same litter to a cage, or social isolation from littermates. There were five male and five female animals in each arm, and the animals were housed in their separate conditions for 4 weeks before tumor implantation.

The isolated animals experienced increased growth and metastasis of the xenografts, compared with controls. The results are consistent with findings in immunodeficient or syngeneic mice, but the humanized nature of the new model could lead to better translation of findings into clinical studies. “The humanized model system in this study demonstrated the presence of both human myeloid and lymphoid lineages as well as expression of at least 40 human cytokines. These data indicate that our model is likely to well-represent the human condition and better predict human clinical responses as compared to both immunodeficient and syngeneic models,” the authors wrote.

The researchers also found that chronic stress may act through an immunoregulatory effect, since there was greater human immune infiltrate into the tumors of stressed animals. Increased presence of regulatory components like myeloid-derived suppressor cells or regulatory T cells, or eroded function of tumor-infiltrating lymphocytes, might explain this finding. The researchers also identified a proinflammatory change in peripheral blood monocular cells in the stressed group. When they analyzed samples from patients who were low income earners of less than $45,000 in annual household income, they found a similar pattern. “This suggests that chronic socioeconomic stress may induce a similar proinflammatory immune state as our chronic stress model system,” the authors wrote.

Tumors were also different between the two groups of mice. Tumors in stressed animals had a higher percentage of cancer stem cells, which is associated with more aggressive tumors and worse disease-free survival. The researchers suggested that up-regulated levels of the chemokine SDF-1 seen in the stressed animals may be driving the higher proportion of stem cells through its effects on the CXCR4 receptor, which is expressed by stem cells in various organs and may cause migration, proliferation, and cell survival.

The study was funded by an endowment from Advancing a Healthier Wisconsin and a grant from the National Center for Advancing Translational Sciences. The authors reported no conflicts of interest.

A humanized mouse model suggests that head and neck cancer growth may stem from chronic stress. The study found that animals had immunophenotypic changes and a greater propensity towards tumor growth and metastasis.

It is not uncommon for low-income patients with head and neck cancer to present with more aggressive disease at diagnosis. Other studies have shown this may be caused by the lack of access to health care services or poor quality care. but the difference remains even after adjusting for these factors, according to researchers writing in Head and Neck.

Led by Heather A. Himburg, PhD, associate professor of radiation oncology with the Medical College of Wisconsin, Milwaukee, researchers conducted a study of head and neck cancer models in which tumor cells were implanted into a mouse with a humanized immune system.

Their theory was that psychosocial stress may contribute to the growth of head and neck tumors. The stress of poverty, social deprivation and social isolation can lead to the up-regulation of proinflammatory markers in circulating blood leukocytes, and this has been tied to worse outcomes in hematologic malignancies and breast cancer. Many such studies examined social adversity and found an association with greater tumor growth rates and treatment resistance.

Other researchers have used mouse models to study the phenomenon, but the results have been inconclusive. For example, some research linked the beta-adrenergic pathway to head and neck cancer, but clinical trials of beta-blockers showed no benefit, and even potential harm, for patients with head and neck cancers. Those results imply that this pathway does not drive tumor growth and metastasis in the presence of chronic stress.

Previous research used immunocompromised or nonhumanized mice. However, neither type of model reproduces the human tumor microenvironment, which may contribute to ensuing clinical failures. In the new study, researchers describe results from a preclinical model created using a human head and neck cancer xenograft in a mouse with a humanized immune system.
 

How the study was conducted

The animals were randomly assigned to normal housing of two or three animals from the same litter to a cage, or social isolation from littermates. There were five male and five female animals in each arm, and the animals were housed in their separate conditions for 4 weeks before tumor implantation.

The isolated animals experienced increased growth and metastasis of the xenografts, compared with controls. The results are consistent with findings in immunodeficient or syngeneic mice, but the humanized nature of the new model could lead to better translation of findings into clinical studies. “The humanized model system in this study demonstrated the presence of both human myeloid and lymphoid lineages as well as expression of at least 40 human cytokines. These data indicate that our model is likely to well-represent the human condition and better predict human clinical responses as compared to both immunodeficient and syngeneic models,” the authors wrote.

The researchers also found that chronic stress may act through an immunoregulatory effect, since there was greater human immune infiltrate into the tumors of stressed animals. Increased presence of regulatory components like myeloid-derived suppressor cells or regulatory T cells, or eroded function of tumor-infiltrating lymphocytes, might explain this finding. The researchers also identified a proinflammatory change in peripheral blood monocular cells in the stressed group. When they analyzed samples from patients who were low income earners of less than $45,000 in annual household income, they found a similar pattern. “This suggests that chronic socioeconomic stress may induce a similar proinflammatory immune state as our chronic stress model system,” the authors wrote.

Tumors were also different between the two groups of mice. Tumors in stressed animals had a higher percentage of cancer stem cells, which is associated with more aggressive tumors and worse disease-free survival. The researchers suggested that up-regulated levels of the chemokine SDF-1 seen in the stressed animals may be driving the higher proportion of stem cells through its effects on the CXCR4 receptor, which is expressed by stem cells in various organs and may cause migration, proliferation, and cell survival.

The study was funded by an endowment from Advancing a Healthier Wisconsin and a grant from the National Center for Advancing Translational Sciences. The authors reported no conflicts of interest.

A humanized mouse model suggests that head and neck cancer growth may stem from chronic stress. The study found that animals had immunophenotypic changes and a greater propensity towards tumor growth and metastasis.

It is not uncommon for low-income patients with head and neck cancer to present with more aggressive disease at diagnosis. Other studies have shown this may be caused by the lack of access to health care services or poor quality care. but the difference remains even after adjusting for these factors, according to researchers writing in Head and Neck.

Led by Heather A. Himburg, PhD, associate professor of radiation oncology with the Medical College of Wisconsin, Milwaukee, researchers conducted a study of head and neck cancer models in which tumor cells were implanted into a mouse with a humanized immune system.

Their theory was that psychosocial stress may contribute to the growth of head and neck tumors. The stress of poverty, social deprivation and social isolation can lead to the up-regulation of proinflammatory markers in circulating blood leukocytes, and this has been tied to worse outcomes in hematologic malignancies and breast cancer. Many such studies examined social adversity and found an association with greater tumor growth rates and treatment resistance.

Other researchers have used mouse models to study the phenomenon, but the results have been inconclusive. For example, some research linked the beta-adrenergic pathway to head and neck cancer, but clinical trials of beta-blockers showed no benefit, and even potential harm, for patients with head and neck cancers. Those results imply that this pathway does not drive tumor growth and metastasis in the presence of chronic stress.

Previous research used immunocompromised or nonhumanized mice. However, neither type of model reproduces the human tumor microenvironment, which may contribute to ensuing clinical failures. In the new study, researchers describe results from a preclinical model created using a human head and neck cancer xenograft in a mouse with a humanized immune system.
 

How the study was conducted

The animals were randomly assigned to normal housing of two or three animals from the same litter to a cage, or social isolation from littermates. There were five male and five female animals in each arm, and the animals were housed in their separate conditions for 4 weeks before tumor implantation.

The isolated animals experienced increased growth and metastasis of the xenografts, compared with controls. The results are consistent with findings in immunodeficient or syngeneic mice, but the humanized nature of the new model could lead to better translation of findings into clinical studies. “The humanized model system in this study demonstrated the presence of both human myeloid and lymphoid lineages as well as expression of at least 40 human cytokines. These data indicate that our model is likely to well-represent the human condition and better predict human clinical responses as compared to both immunodeficient and syngeneic models,” the authors wrote.

The researchers also found that chronic stress may act through an immunoregulatory effect, since there was greater human immune infiltrate into the tumors of stressed animals. Increased presence of regulatory components like myeloid-derived suppressor cells or regulatory T cells, or eroded function of tumor-infiltrating lymphocytes, might explain this finding. The researchers also identified a proinflammatory change in peripheral blood monocular cells in the stressed group. When they analyzed samples from patients who were low income earners of less than $45,000 in annual household income, they found a similar pattern. “This suggests that chronic socioeconomic stress may induce a similar proinflammatory immune state as our chronic stress model system,” the authors wrote.

Tumors were also different between the two groups of mice. Tumors in stressed animals had a higher percentage of cancer stem cells, which is associated with more aggressive tumors and worse disease-free survival. The researchers suggested that up-regulated levels of the chemokine SDF-1 seen in the stressed animals may be driving the higher proportion of stem cells through its effects on the CXCR4 receptor, which is expressed by stem cells in various organs and may cause migration, proliferation, and cell survival.

The study was funded by an endowment from Advancing a Healthier Wisconsin and a grant from the National Center for Advancing Translational Sciences. The authors reported no conflicts of interest.

Even by cautious calculations, the worldwide incidence of cutaneous melanoma is high and predicted to rise sharply over the next 2 decades, cancer epidemiologists warn.

An estimated 325,000 people worldwide received a new diagnosis of cutaneous melanoma in 2020, and if present trends continue, the incidence of new cases is predicted to increase by about 50% in 2040, with melanoma deaths expected to rise by almost 70%, Melina Arnold, PhD, from the Cancer Surveillance Branch of the International Agency for Research on Cancer in Lyon, France, and colleagues reported.

“Melanoma is the most lethal form of skin cancer; this epidemiological assessment found a heavy public health and economic burden, and our projections suggest that it will remain so in the coming decades,” they wrote in a study published online in JAMA Dermatology.

In an accompanying editorial, Mavis Obeng-Kusi, MPharm and Ivo Abraham, PhD from the Center for Health Outcomes and PharmacoEconomic Research at the University of Arizona, Tucson, commented that the findings are “sobering,” but may substantially underestimate the gravity of the problem in low- and middle-income countries (LMIC).

“The study by Arnold et al. brings to the fore a public health concern that requires global attention and initiates conversations particularly related to LMIC settings, where the incidence and mortality of melanoma is thought to be minimal and for which preventive measures may be insufficient,” they wrote.

Down Under nations lead

Dr. Arnold and colleagues looked at data on age-standardized melanoma incidence and mortality rates per 100,000 person-years (PY) by country, each of 20 world regions as defined by the United Nations, and according to the UN’s four-tier Human Development Index, which stratifies countries into low-, medium-, high-, and very high–income categories.

As noted previously, the researchers estimated that there were 325,000 new melanoma cases worldwide in 2020 (174,000 cases in males and 151,000 in females). There were 57,000 estimated melanoma deaths the same year (32,000 in males and 25,000 in females.

The highest incidence rates were seen in Australia and New Zealand, at 42 per 100,000 PY among males and 31 per 100,000 PY in females, followed by Western Europe with 19 per 100,000 PY in both males and females, North America with 18 and 14 cases per 100,000 PY in males and females respectively, and Northern Europe, with 17 per 100,000 PY in males, and 18 per 100,000 PY in females.

In contrast, in most African and Asian countries melanoma was rare, with rates commonly less than 1 per 100,000 PY, the investigators noted.

The melanoma mortality rate was highest in New Zealand, at 5 per 100,000 PY. Mortality rates worldwide varied less widely than incidence rates. In most other regions of the world, mortality rates were “much lower,” ranging between 0.2-1.0 per 100,000 PY, they wrote.

The authors estimated that, if 2020 rates remain stable, the global burden from melanoma in 2040 will increase to approximately 510,000 new cases and 96,000 deaths.

Public health efforts needed

In their editorial, Ms. Obeng-Kusi and Dr. Abraham pointed out that the study was hampered by the limited availability of cancer data from LMICs, leading the authors to estimate incidence and mortality rates based on proxy data, such as statistical modeling or averaged rates from neighboring countries.

They emphasized the need for going beyond the statistics: “Specific to cutaneous melanoma data, what is most important globally, knowing the exact numbers of cases and deaths or understanding the order of magnitude of the present and future epidemiology? No doubt the latter. Melanoma can be treated more easily if caught at earlier stages.”

Projections such as those provided by Dr. Arnold and colleagues could help to raise awareness of the importance of decreasing exposure to UV radiation, which accounts for three-fourths of all incident melanomas, the editorialists said.

The study was funded in part by a grant to coauthor Anna E. Cust, PhD, MPH. Dr. Cust reported receiving a fellowship from the Australian National Health and Medical Research Council outside the submitted work. Dr. Arnold had no conflicts of interested to disclose. Dr. Abraham reported financial relationships with various entities. Ms. Obeng-Kusi had no disclosures.

Even by cautious calculations, the worldwide incidence of cutaneous melanoma is high and predicted to rise sharply over the next 2 decades, cancer epidemiologists warn.

An estimated 325,000 people worldwide received a new diagnosis of cutaneous melanoma in 2020, and if present trends continue, the incidence of new cases is predicted to increase by about 50% in 2040, with melanoma deaths expected to rise by almost 70%, Melina Arnold, PhD, from the Cancer Surveillance Branch of the International Agency for Research on Cancer in Lyon, France, and colleagues reported.

“Melanoma is the most lethal form of skin cancer; this epidemiological assessment found a heavy public health and economic burden, and our projections suggest that it will remain so in the coming decades,” they wrote in a study published online in JAMA Dermatology.

In an accompanying editorial, Mavis Obeng-Kusi, MPharm and Ivo Abraham, PhD from the Center for Health Outcomes and PharmacoEconomic Research at the University of Arizona, Tucson, commented that the findings are “sobering,” but may substantially underestimate the gravity of the problem in low- and middle-income countries (LMIC).

“The study by Arnold et al. brings to the fore a public health concern that requires global attention and initiates conversations particularly related to LMIC settings, where the incidence and mortality of melanoma is thought to be minimal and for which preventive measures may be insufficient,” they wrote.

Down Under nations lead

Dr. Arnold and colleagues looked at data on age-standardized melanoma incidence and mortality rates per 100,000 person-years (PY) by country, each of 20 world regions as defined by the United Nations, and according to the UN’s four-tier Human Development Index, which stratifies countries into low-, medium-, high-, and very high–income categories.

As noted previously, the researchers estimated that there were 325,000 new melanoma cases worldwide in 2020 (174,000 cases in males and 151,000 in females). There were 57,000 estimated melanoma deaths the same year (32,000 in males and 25,000 in females.

The highest incidence rates were seen in Australia and New Zealand, at 42 per 100,000 PY among males and 31 per 100,000 PY in females, followed by Western Europe with 19 per 100,000 PY in both males and females, North America with 18 and 14 cases per 100,000 PY in males and females respectively, and Northern Europe, with 17 per 100,000 PY in males, and 18 per 100,000 PY in females.

In contrast, in most African and Asian countries melanoma was rare, with rates commonly less than 1 per 100,000 PY, the investigators noted.

The melanoma mortality rate was highest in New Zealand, at 5 per 100,000 PY. Mortality rates worldwide varied less widely than incidence rates. In most other regions of the world, mortality rates were “much lower,” ranging between 0.2-1.0 per 100,000 PY, they wrote.

The authors estimated that, if 2020 rates remain stable, the global burden from melanoma in 2040 will increase to approximately 510,000 new cases and 96,000 deaths.

Public health efforts needed

In their editorial, Ms. Obeng-Kusi and Dr. Abraham pointed out that the study was hampered by the limited availability of cancer data from LMICs, leading the authors to estimate incidence and mortality rates based on proxy data, such as statistical modeling or averaged rates from neighboring countries.

They emphasized the need for going beyond the statistics: “Specific to cutaneous melanoma data, what is most important globally, knowing the exact numbers of cases and deaths or understanding the order of magnitude of the present and future epidemiology? No doubt the latter. Melanoma can be treated more easily if caught at earlier stages.”

Projections such as those provided by Dr. Arnold and colleagues could help to raise awareness of the importance of decreasing exposure to UV radiation, which accounts for three-fourths of all incident melanomas, the editorialists said.

The study was funded in part by a grant to coauthor Anna E. Cust, PhD, MPH. Dr. Cust reported receiving a fellowship from the Australian National Health and Medical Research Council outside the submitted work. Dr. Arnold had no conflicts of interested to disclose. Dr. Abraham reported financial relationships with various entities. Ms. Obeng-Kusi had no disclosures.

Even by cautious calculations, the worldwide incidence of cutaneous melanoma is high and predicted to rise sharply over the next 2 decades, cancer epidemiologists warn.

An estimated 325,000 people worldwide received a new diagnosis of cutaneous melanoma in 2020, and if present trends continue, the incidence of new cases is predicted to increase by about 50% in 2040, with melanoma deaths expected to rise by almost 70%, Melina Arnold, PhD, from the Cancer Surveillance Branch of the International Agency for Research on Cancer in Lyon, France, and colleagues reported.

“Melanoma is the most lethal form of skin cancer; this epidemiological assessment found a heavy public health and economic burden, and our projections suggest that it will remain so in the coming decades,” they wrote in a study published online in JAMA Dermatology.

In an accompanying editorial, Mavis Obeng-Kusi, MPharm and Ivo Abraham, PhD from the Center for Health Outcomes and PharmacoEconomic Research at the University of Arizona, Tucson, commented that the findings are “sobering,” but may substantially underestimate the gravity of the problem in low- and middle-income countries (LMIC).

“The study by Arnold et al. brings to the fore a public health concern that requires global attention and initiates conversations particularly related to LMIC settings, where the incidence and mortality of melanoma is thought to be minimal and for which preventive measures may be insufficient,” they wrote.

Down Under nations lead

Dr. Arnold and colleagues looked at data on age-standardized melanoma incidence and mortality rates per 100,000 person-years (PY) by country, each of 20 world regions as defined by the United Nations, and according to the UN’s four-tier Human Development Index, which stratifies countries into low-, medium-, high-, and very high–income categories.

As noted previously, the researchers estimated that there were 325,000 new melanoma cases worldwide in 2020 (174,000 cases in males and 151,000 in females). There were 57,000 estimated melanoma deaths the same year (32,000 in males and 25,000 in females.

The highest incidence rates were seen in Australia and New Zealand, at 42 per 100,000 PY among males and 31 per 100,000 PY in females, followed by Western Europe with 19 per 100,000 PY in both males and females, North America with 18 and 14 cases per 100,000 PY in males and females respectively, and Northern Europe, with 17 per 100,000 PY in males, and 18 per 100,000 PY in females.

In contrast, in most African and Asian countries melanoma was rare, with rates commonly less than 1 per 100,000 PY, the investigators noted.

The melanoma mortality rate was highest in New Zealand, at 5 per 100,000 PY. Mortality rates worldwide varied less widely than incidence rates. In most other regions of the world, mortality rates were “much lower,” ranging between 0.2-1.0 per 100,000 PY, they wrote.

The authors estimated that, if 2020 rates remain stable, the global burden from melanoma in 2040 will increase to approximately 510,000 new cases and 96,000 deaths.

Public health efforts needed

In their editorial, Ms. Obeng-Kusi and Dr. Abraham pointed out that the study was hampered by the limited availability of cancer data from LMICs, leading the authors to estimate incidence and mortality rates based on proxy data, such as statistical modeling or averaged rates from neighboring countries.

They emphasized the need for going beyond the statistics: “Specific to cutaneous melanoma data, what is most important globally, knowing the exact numbers of cases and deaths or understanding the order of magnitude of the present and future epidemiology? No doubt the latter. Melanoma can be treated more easily if caught at earlier stages.”

Projections such as those provided by Dr. Arnold and colleagues could help to raise awareness of the importance of decreasing exposure to UV radiation, which accounts for three-fourths of all incident melanomas, the editorialists said.

The study was funded in part by a grant to coauthor Anna E. Cust, PhD, MPH. Dr. Cust reported receiving a fellowship from the Australian National Health and Medical Research Council outside the submitted work. Dr. Arnold had no conflicts of interested to disclose. Dr. Abraham reported financial relationships with various entities. Ms. Obeng-Kusi had no disclosures.