Key clinical point: In patients with prostate cancer undergoing active surveillance (AS), Gleason grade group (GG) 2 compared with GG1 at diagnosis was associated with a higher definitive treatment rate.

Major finding: There was no significant difference in the 5-year reclassification rates in patients with GG2 vs GG1 disease (30% vs 37%; P = .11). A higher proportion of patients with GG2 disease received treatment at 5 years (58% vs 34%; P < .001).

Study details: A prospective multicenter Canary PASS cohort study of 1,728 patients undergoing AS.

Disclosures: This work was supported by Canary Foundation and Institute for Prostate Cancer Research. The authors reported no conflict of interests.

Source: Malaret AJW et al. J Urol. 2021 Dec 2. doi: 10.1097/JU.0000000000002354.

Key clinical point: In patients with prostate cancer undergoing active surveillance (AS), Gleason grade group (GG) 2 compared with GG1 at diagnosis was associated with a higher definitive treatment rate.

Major finding: There was no significant difference in the 5-year reclassification rates in patients with GG2 vs GG1 disease (30% vs 37%; P = .11). A higher proportion of patients with GG2 disease received treatment at 5 years (58% vs 34%; P < .001).

Study details: A prospective multicenter Canary PASS cohort study of 1,728 patients undergoing AS.

Disclosures: This work was supported by Canary Foundation and Institute for Prostate Cancer Research. The authors reported no conflict of interests.

Source: Malaret AJW et al. J Urol. 2021 Dec 2. doi: 10.1097/JU.0000000000002354.

Key clinical point: In patients with prostate cancer undergoing active surveillance (AS), Gleason grade group (GG) 2 compared with GG1 at diagnosis was associated with a higher definitive treatment rate.

Major finding: There was no significant difference in the 5-year reclassification rates in patients with GG2 vs GG1 disease (30% vs 37%; P = .11). A higher proportion of patients with GG2 disease received treatment at 5 years (58% vs 34%; P < .001).

Study details: A prospective multicenter Canary PASS cohort study of 1,728 patients undergoing AS.

Disclosures: This work was supported by Canary Foundation and Institute for Prostate Cancer Research. The authors reported no conflict of interests.

Source: Malaret AJW et al. J Urol. 2021 Dec 2. doi: 10.1097/JU.0000000000002354.

Key clinical point: A significant patient- and surgeon-level variation in sexual function recovery is seen over 2 years after radical prostatectomy.

Major finding: At 24-month follow-up, 24% of patients recovered sexual function. Across 12 surgeons, patients achieving sexual function recovery ranged from 3% to 44%. At the surgeon level, the Pearson correlation coefficient between case volume and mean Expanded Prostate Cancer Index Composite-26 sexual domain score was 0.08 (95% CI, −0.52 to 0.62). The Spearman correlation coefficient between case volume and the proportion of patients achieving sexual function recovery was −0.16 (95% CI, −0.67 to 0.46).

Study details: A prospective cohort of 1,426 patients with prostate cancer who underwent radical prostatectomy between May 2014 and August 2019.

Disclosures: This work was supported by Blue Cross Blue Shield of Michigan and National Institutes of Health. The authors received financial/nonfinancial support and/or served as journal editors without compensation outside this work.

Source: Agochukwu-Mmonu N et al. JAMA Surg. 2021 Dec 1. doi: 10.1001/jamasurg.2021.6215.

Key clinical point: A significant patient- and surgeon-level variation in sexual function recovery is seen over 2 years after radical prostatectomy.

Major finding: At 24-month follow-up, 24% of patients recovered sexual function. Across 12 surgeons, patients achieving sexual function recovery ranged from 3% to 44%. At the surgeon level, the Pearson correlation coefficient between case volume and mean Expanded Prostate Cancer Index Composite-26 sexual domain score was 0.08 (95% CI, −0.52 to 0.62). The Spearman correlation coefficient between case volume and the proportion of patients achieving sexual function recovery was −0.16 (95% CI, −0.67 to 0.46).

Study details: A prospective cohort of 1,426 patients with prostate cancer who underwent radical prostatectomy between May 2014 and August 2019.

Disclosures: This work was supported by Blue Cross Blue Shield of Michigan and National Institutes of Health. The authors received financial/nonfinancial support and/or served as journal editors without compensation outside this work.

Source: Agochukwu-Mmonu N et al. JAMA Surg. 2021 Dec 1. doi: 10.1001/jamasurg.2021.6215.

Key clinical point: A significant patient- and surgeon-level variation in sexual function recovery is seen over 2 years after radical prostatectomy.

Major finding: At 24-month follow-up, 24% of patients recovered sexual function. Across 12 surgeons, patients achieving sexual function recovery ranged from 3% to 44%. At the surgeon level, the Pearson correlation coefficient between case volume and mean Expanded Prostate Cancer Index Composite-26 sexual domain score was 0.08 (95% CI, −0.52 to 0.62). The Spearman correlation coefficient between case volume and the proportion of patients achieving sexual function recovery was −0.16 (95% CI, −0.67 to 0.46).

Study details: A prospective cohort of 1,426 patients with prostate cancer who underwent radical prostatectomy between May 2014 and August 2019.

Disclosures: This work was supported by Blue Cross Blue Shield of Michigan and National Institutes of Health. The authors received financial/nonfinancial support and/or served as journal editors without compensation outside this work.

Source: Agochukwu-Mmonu N et al. JAMA Surg. 2021 Dec 1. doi: 10.1001/jamasurg.2021.6215.

Key clinical point: Treatment-related regret is common in patients with clinically localized prostate cancer. Patients undergoing surgery reported a significantly higher regret vs those undergoing radiotherapy or active surveillance.

Major finding: Overall treatment-related regret at 5 years was 13%. Treatment-related regret with surgery, radiotherapy, and active surveillance was 16%, 11%, and 7%, respectively. Patients who underwent surgery had a higher likelihood of regret than those who underwent active surveillance (adjusted odds ratio [aOR], 2.40; P < .001) or radiotherapy (aOR, 1.57; P = .01).

Study details: An observational study of 2,072 patients with clinically localized prostate cancer between 2011 and 2012.

Disclosures: This work was supported by Patient-Centered Outcomes Research Institute, Agency for Healthcare Research and Quality, and National Cancer Institute. The authors reported receiving personal fees and grants outside this work.

Source: Wallis CJD et al. JAMA Oncol. 2021 Nov 18. doi: 10.1001/jamaoncol.2021.5160.

Key clinical point: Treatment-related regret is common in patients with clinically localized prostate cancer. Patients undergoing surgery reported a significantly higher regret vs those undergoing radiotherapy or active surveillance.

Major finding: Overall treatment-related regret at 5 years was 13%. Treatment-related regret with surgery, radiotherapy, and active surveillance was 16%, 11%, and 7%, respectively. Patients who underwent surgery had a higher likelihood of regret than those who underwent active surveillance (adjusted odds ratio [aOR], 2.40; P < .001) or radiotherapy (aOR, 1.57; P = .01).

Study details: An observational study of 2,072 patients with clinically localized prostate cancer between 2011 and 2012.

Disclosures: This work was supported by Patient-Centered Outcomes Research Institute, Agency for Healthcare Research and Quality, and National Cancer Institute. The authors reported receiving personal fees and grants outside this work.

Source: Wallis CJD et al. JAMA Oncol. 2021 Nov 18. doi: 10.1001/jamaoncol.2021.5160.

Key clinical point: Treatment-related regret is common in patients with clinically localized prostate cancer. Patients undergoing surgery reported a significantly higher regret vs those undergoing radiotherapy or active surveillance.

Major finding: Overall treatment-related regret at 5 years was 13%. Treatment-related regret with surgery, radiotherapy, and active surveillance was 16%, 11%, and 7%, respectively. Patients who underwent surgery had a higher likelihood of regret than those who underwent active surveillance (adjusted odds ratio [aOR], 2.40; P < .001) or radiotherapy (aOR, 1.57; P = .01).

Study details: An observational study of 2,072 patients with clinically localized prostate cancer between 2011 and 2012.

Disclosures: This work was supported by Patient-Centered Outcomes Research Institute, Agency for Healthcare Research and Quality, and National Cancer Institute. The authors reported receiving personal fees and grants outside this work.

Source: Wallis CJD et al. JAMA Oncol. 2021 Nov 18. doi: 10.1001/jamaoncol.2021.5160.

Key clinical point: Nivolumab plus docetaxel shows good response in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC).

Major finding: The confirmed overall response rate was 40%. The median time to objective response was 2 months, and the median response duration was 7 months. The confirmed prostate-specific antigen (PSA) 50-response rate (50% or higher decline in PSA) was 46.9%.

Study details: A phase 2, nonrandomized CheckMate 9KD trial of 84 patients with chemotherapy-naive mCRPC who received androgen deprivation therapy and ≤2 prior novel hormonal therapies and were treated with nivolumab and docetaxel with prednisone followed by nivolumab maintenance for ≤2 years.

Disclosures: This work was supported by Bristol Myers Squibb (BMS). The authors reported receiving consulting/advisory/speaker fees, travel accommodations, expenses, honoraria, and research funding from various sources. Some authors were employed by/owned stocks in BMS.

Source: Fizazi K et al. Eur J Cancer. 2021 Nov 18. doi: 10.1016/j.ejca.2021.09.043.

Key clinical point: Nivolumab plus docetaxel shows good response in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC).

Major finding: The confirmed overall response rate was 40%. The median time to objective response was 2 months, and the median response duration was 7 months. The confirmed prostate-specific antigen (PSA) 50-response rate (50% or higher decline in PSA) was 46.9%.

Study details: A phase 2, nonrandomized CheckMate 9KD trial of 84 patients with chemotherapy-naive mCRPC who received androgen deprivation therapy and ≤2 prior novel hormonal therapies and were treated with nivolumab and docetaxel with prednisone followed by nivolumab maintenance for ≤2 years.

Disclosures: This work was supported by Bristol Myers Squibb (BMS). The authors reported receiving consulting/advisory/speaker fees, travel accommodations, expenses, honoraria, and research funding from various sources. Some authors were employed by/owned stocks in BMS.

Source: Fizazi K et al. Eur J Cancer. 2021 Nov 18. doi: 10.1016/j.ejca.2021.09.043.

Key clinical point: Nivolumab plus docetaxel shows good response in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC).

Major finding: The confirmed overall response rate was 40%. The median time to objective response was 2 months, and the median response duration was 7 months. The confirmed prostate-specific antigen (PSA) 50-response rate (50% or higher decline in PSA) was 46.9%.

Study details: A phase 2, nonrandomized CheckMate 9KD trial of 84 patients with chemotherapy-naive mCRPC who received androgen deprivation therapy and ≤2 prior novel hormonal therapies and were treated with nivolumab and docetaxel with prednisone followed by nivolumab maintenance for ≤2 years.

Disclosures: This work was supported by Bristol Myers Squibb (BMS). The authors reported receiving consulting/advisory/speaker fees, travel accommodations, expenses, honoraria, and research funding from various sources. Some authors were employed by/owned stocks in BMS.

Source: Fizazi K et al. Eur J Cancer. 2021 Nov 18. doi: 10.1016/j.ejca.2021.09.043.

Use of vascular lasers in the Medicare population is increasing, primarily among dermatologists. In addition, as a proportion of Medicare charges submitted that were reimbursed, the highest reimbursements were for dermatologists and those in the Western geographic region.

Those are among the key findings from an analysis that aimed to characterize trends in use and reimbursement patterns of vascular lasers in the Medicare-insured population.

“There are several modalities for vascular laser treatment, including the pulse dye laser, the frequency doubled KTP laser, and others,” presenting author Partik Singh, MD, MBA, said during a virtual abstract session at the annual meeting of the American Society for Dermatologic Surgery. “Laser treatment of vascular lesions may sometimes be covered by insurance, depending on the indication, but little is known about how and which clinicians are taking advantage of this covered treatment.”

Dr. Singh, a 2nd-year dermatology resident at the University of Rochester Medical Center, and coauthor Mara Weinstein Velez, MD, extracted data from the 2012-2018 Medicare Public Use File, which includes 100% fee-for-service, non–Medicare Advantage claims based on CPT codes, yet no information on patient data, clinical context, or indications. Outcomes of interest were total vascular laser claims per year, annual vascular laser claims per clinician, annual clinicians using vascular lasers, accepted reimbursements defined by the allowed charge or the submitted charge to Medicare, and clinical specialties and geographic location.

The researchers found that more than half of clinicians who used vascular lasers during the study period were dermatologists (55%), followed by general surgeons (6%), family practice/internal medicine physicians (5% each) and various others. Use of vascular lasers among all clinicians increased 10.5% annually during the study period, from 3,786 to 6,883, and was most pronounced among dermatologists, whose use increased 18.4% annually, from 1,878 to 5,182. “Nondermatologists did not have a big change in their overall utilization rate, but they did have a steady utilization of vascular lasers, roughly at almost 2,000 claims per year,” Dr. Singh said.

The researchers also observed that the use of vascular lasers on a per-clinician basis increased 7.4% annually among all clinicians during the study period, from 77.3 to 118.7. This was mostly driven by dermatologists, whose per-clinician use increased 10.4% annually, from 81.7 to 148.7. Use by nondermatologists remained about stable, with just a 0.1% increase annually, from 73.4 to 74. In addition, the number of clinicians who billed for vascular laser procedures increased 2.9% annually between 2012 and 2018, from 49 to 58. This growth was driven mostly by dermatologists, who increased their billing for vascular laser procedures by 7.2% annually, from 23 to 35 clinicians.

In other findings, dermatologists were reimbursed at 68.3% of submitted charges, compared with 59.3% of charges submitted by other clinicians (P = .0001), and reimbursement rates were greatest in the Western geographic region of the United States vs. the Northeast, Midwest, and Southern regions (73.1% vs. 50.2%, 65.4%, and 55.3%, respectively; P < .0001).

“Use of vascular lasers is increasing primarily among dermatologists, though there is steady use of these procedures by nondermatologists,” Dr. Singh concluded. “Medicare charges were more often fully reimbursed when billed by dermatologists and those in the Western U.S., perhaps suggesting a better familiarity with appropriate indications and better administrative resources for coverage of vascular laser procedures.”

After the meeting, Dr. Singh acknowledged certain limitations of the analysis, including the fact that it “was limited only to Medicare Part B fee-for-service claims, not including Medicare Advantage,” he told this news organization. “Our conclusions do not necessarily hold true for Medicaid or commercial insurers, for instance. Moreover, this dataset doesn’t provide patient-specific information, such as the indication for the procedure. Further studies are needed to characterize utilization of various lasers in not only Medicare beneficiaries, but also those with Medicaid, private insurance, and patients paying out-of-pocket. Additionally, study is also needed to explain why these differences in reimbursement hold true.”

The researchers reported having no relevant financial disclosures.

[email protected]

Use of vascular lasers in the Medicare population is increasing, primarily among dermatologists. In addition, as a proportion of Medicare charges submitted that were reimbursed, the highest reimbursements were for dermatologists and those in the Western geographic region.

Those are among the key findings from an analysis that aimed to characterize trends in use and reimbursement patterns of vascular lasers in the Medicare-insured population.

“There are several modalities for vascular laser treatment, including the pulse dye laser, the frequency doubled KTP laser, and others,” presenting author Partik Singh, MD, MBA, said during a virtual abstract session at the annual meeting of the American Society for Dermatologic Surgery. “Laser treatment of vascular lesions may sometimes be covered by insurance, depending on the indication, but little is known about how and which clinicians are taking advantage of this covered treatment.”

Dr. Singh, a 2nd-year dermatology resident at the University of Rochester Medical Center, and coauthor Mara Weinstein Velez, MD, extracted data from the 2012-2018 Medicare Public Use File, which includes 100% fee-for-service, non–Medicare Advantage claims based on CPT codes, yet no information on patient data, clinical context, or indications. Outcomes of interest were total vascular laser claims per year, annual vascular laser claims per clinician, annual clinicians using vascular lasers, accepted reimbursements defined by the allowed charge or the submitted charge to Medicare, and clinical specialties and geographic location.

The researchers found that more than half of clinicians who used vascular lasers during the study period were dermatologists (55%), followed by general surgeons (6%), family practice/internal medicine physicians (5% each) and various others. Use of vascular lasers among all clinicians increased 10.5% annually during the study period, from 3,786 to 6,883, and was most pronounced among dermatologists, whose use increased 18.4% annually, from 1,878 to 5,182. “Nondermatologists did not have a big change in their overall utilization rate, but they did have a steady utilization of vascular lasers, roughly at almost 2,000 claims per year,” Dr. Singh said.

The researchers also observed that the use of vascular lasers on a per-clinician basis increased 7.4% annually among all clinicians during the study period, from 77.3 to 118.7. This was mostly driven by dermatologists, whose per-clinician use increased 10.4% annually, from 81.7 to 148.7. Use by nondermatologists remained about stable, with just a 0.1% increase annually, from 73.4 to 74. In addition, the number of clinicians who billed for vascular laser procedures increased 2.9% annually between 2012 and 2018, from 49 to 58. This growth was driven mostly by dermatologists, who increased their billing for vascular laser procedures by 7.2% annually, from 23 to 35 clinicians.

In other findings, dermatologists were reimbursed at 68.3% of submitted charges, compared with 59.3% of charges submitted by other clinicians (P = .0001), and reimbursement rates were greatest in the Western geographic region of the United States vs. the Northeast, Midwest, and Southern regions (73.1% vs. 50.2%, 65.4%, and 55.3%, respectively; P < .0001).

“Use of vascular lasers is increasing primarily among dermatologists, though there is steady use of these procedures by nondermatologists,” Dr. Singh concluded. “Medicare charges were more often fully reimbursed when billed by dermatologists and those in the Western U.S., perhaps suggesting a better familiarity with appropriate indications and better administrative resources for coverage of vascular laser procedures.”

After the meeting, Dr. Singh acknowledged certain limitations of the analysis, including the fact that it “was limited only to Medicare Part B fee-for-service claims, not including Medicare Advantage,” he told this news organization. “Our conclusions do not necessarily hold true for Medicaid or commercial insurers, for instance. Moreover, this dataset doesn’t provide patient-specific information, such as the indication for the procedure. Further studies are needed to characterize utilization of various lasers in not only Medicare beneficiaries, but also those with Medicaid, private insurance, and patients paying out-of-pocket. Additionally, study is also needed to explain why these differences in reimbursement hold true.”

The researchers reported having no relevant financial disclosures.

[email protected]

Use of vascular lasers in the Medicare population is increasing, primarily among dermatologists. In addition, as a proportion of Medicare charges submitted that were reimbursed, the highest reimbursements were for dermatologists and those in the Western geographic region.

Those are among the key findings from an analysis that aimed to characterize trends in use and reimbursement patterns of vascular lasers in the Medicare-insured population.

“There are several modalities for vascular laser treatment, including the pulse dye laser, the frequency doubled KTP laser, and others,” presenting author Partik Singh, MD, MBA, said during a virtual abstract session at the annual meeting of the American Society for Dermatologic Surgery. “Laser treatment of vascular lesions may sometimes be covered by insurance, depending on the indication, but little is known about how and which clinicians are taking advantage of this covered treatment.”

Dr. Singh, a 2nd-year dermatology resident at the University of Rochester Medical Center, and coauthor Mara Weinstein Velez, MD, extracted data from the 2012-2018 Medicare Public Use File, which includes 100% fee-for-service, non–Medicare Advantage claims based on CPT codes, yet no information on patient data, clinical context, or indications. Outcomes of interest were total vascular laser claims per year, annual vascular laser claims per clinician, annual clinicians using vascular lasers, accepted reimbursements defined by the allowed charge or the submitted charge to Medicare, and clinical specialties and geographic location.

The researchers found that more than half of clinicians who used vascular lasers during the study period were dermatologists (55%), followed by general surgeons (6%), family practice/internal medicine physicians (5% each) and various others. Use of vascular lasers among all clinicians increased 10.5% annually during the study period, from 3,786 to 6,883, and was most pronounced among dermatologists, whose use increased 18.4% annually, from 1,878 to 5,182. “Nondermatologists did not have a big change in their overall utilization rate, but they did have a steady utilization of vascular lasers, roughly at almost 2,000 claims per year,” Dr. Singh said.

The researchers also observed that the use of vascular lasers on a per-clinician basis increased 7.4% annually among all clinicians during the study period, from 77.3 to 118.7. This was mostly driven by dermatologists, whose per-clinician use increased 10.4% annually, from 81.7 to 148.7. Use by nondermatologists remained about stable, with just a 0.1% increase annually, from 73.4 to 74. In addition, the number of clinicians who billed for vascular laser procedures increased 2.9% annually between 2012 and 2018, from 49 to 58. This growth was driven mostly by dermatologists, who increased their billing for vascular laser procedures by 7.2% annually, from 23 to 35 clinicians.

In other findings, dermatologists were reimbursed at 68.3% of submitted charges, compared with 59.3% of charges submitted by other clinicians (P = .0001), and reimbursement rates were greatest in the Western geographic region of the United States vs. the Northeast, Midwest, and Southern regions (73.1% vs. 50.2%, 65.4%, and 55.3%, respectively; P < .0001).

“Use of vascular lasers is increasing primarily among dermatologists, though there is steady use of these procedures by nondermatologists,” Dr. Singh concluded. “Medicare charges were more often fully reimbursed when billed by dermatologists and those in the Western U.S., perhaps suggesting a better familiarity with appropriate indications and better administrative resources for coverage of vascular laser procedures.”

After the meeting, Dr. Singh acknowledged certain limitations of the analysis, including the fact that it “was limited only to Medicare Part B fee-for-service claims, not including Medicare Advantage,” he told this news organization. “Our conclusions do not necessarily hold true for Medicaid or commercial insurers, for instance. Moreover, this dataset doesn’t provide patient-specific information, such as the indication for the procedure. Further studies are needed to characterize utilization of various lasers in not only Medicare beneficiaries, but also those with Medicaid, private insurance, and patients paying out-of-pocket. Additionally, study is also needed to explain why these differences in reimbursement hold true.”

The researchers reported having no relevant financial disclosures.

[email protected]

New results from the phase 3 RxPONDER trial add to mounting evidence that most postmenopausal women with early-stage breast cancer derive no added benefits from chemotherapy and can be effectively treated with endocrine therapy alone.

The study, published in The New England Journal of Medicine, conversely shows that premenopausal women do benefit from adjuvant chemotherapy, theorized by many to largely be the result of chemotherapy-induced ovarian function suppression.

The RxPONDER trial results are in line with those from the practice-changing TAILORx trial and underscore that “postmenopausal women with 1 to 3 positive nodes and [a recurrence score] of 0 to 25 can likely safely forgo adjuvant chemotherapy without compromising invasive disease-free survival,” first author Kevin Kalinsky, MD, of the Winship Cancer Institute at Emory University, Atlanta, told this news organization. “This will save tens of thousands of women the time, expense, and potentially harmful side effects that can be associated with chemotherapy infusions.”

However, the authors note, “premenopausal women with 1-3 positive lymph nodes had a significant benefit from chemotherapy.”

The study, conducted by the Southwest Oncology Group (SWOG) Cancer Research Network, involved 5,018 women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer with one to three positive axillary lymph nodes – a breast cancer profile that represents approximately 20% of cases in the U.S.

All women had recurrence scores on the 100-point 21-gene breast cancer assay (Oncotype Dx) under 25, which is considered the lowest risk of recurrence. Patients were randomized to treatment with endocrine therapy only (n = 2,507) or chemotherapy followed by endocrine therapy (n = 2,511).

After a median follow-up of 5.3 years, women treated with adjunctive chemotherapy plus endocrine therapy exhibited no significant improvements in invasive disease-free survival compared to those who received endocrine therapy alone.

A prespecified analysis stratifying women by menopausal status underscored those results among postmenopausal women. In this cohort, researchers reported invasive disease-free survival was 91.9% in the endocrine-only group and 91.3% in the chemotherapy group (HR, 1.02; P = .89), indicating no benefit of the adjunctive chemotherapy.

However, among premenopausal women, the invasive disease-free survival rate was significantly higher with the addition of chemotherapy – 89.0% with endocrine-only therapy and 93.9% with both therapies (HR, 0.60; P = .002). Increases in distant relapse-free survival observed in the dual-therapy group similarly favored adding chemotherapy (HR, 0.58; P = .009).

Even when the authors further stratified the women into recurrence scores of 0 to 13 or 14 to 25, the results remained consistent. Postmenopausal women in each of the recurrence score groups continued to show no difference in invasive disease recurrence, new primary cancer, or death from chemotherapy (HR, 1.01 for each score group). Conversely, premenopausal women showed significant improvements in those outcomes when chemotherapy was added to endocrine therapy.

To what degree were the effects observed in premenopausal women the result of chemotherapy-induced ovarian suppression?

“I think it’s fair to say it’s the most interesting question right now in early-stage breast cancer for ER-positive tumors,” Harold Burstein, MD, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, said during a debate at the recent San Antonio Breast Cancer Symposium.

According to Sibylle Loibl, MD, PhD, when it comes to the use of chemotherapy, “age matters.”

“I strongly believe the biology of tumors is different in younger women with HR-positive/HER2-negative breast cancer,” Dr. Loibl, an associate professor at the University of Frankfurt, said during the debate. “It’s a different disease and the effects of chemotherapy are different.”

In young women, chemotherapy has “a direct cytotoxic effect, which cannot be neglected, and an endocrine effect on ovarian function suppression,” Dr. Loibl added. “I think both are needed in young premenopausal patients.”

According to the RxPONDER authors, “whether a chemotherapy benefit in premenopausal women is due to both direct cytocidal effects and treatment-induced menopause remains unclear,” but they noted that “it is possible that the contribution of these mechanisms may vary according to age.”

Further complicating matters, Dr. Loibl added, is that age appears to be poorly represented in genetic diagnostic tools.

“I think the gene expression profiles we are currently using as standard diagnostic tools do not capture the right biology for our premenopausal patients,” she said. “We have to keep in mind that these tests were designed and validated in postmenopausal patients and were only retrospectively used in premenopausal patients.”

The study was funded by the National Cancer Institute and others. Dr. Loibl has received honoraria from Prime and Chugai and numerous institutional research grants.

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

New results from the phase 3 RxPONDER trial add to mounting evidence that most postmenopausal women with early-stage breast cancer derive no added benefits from chemotherapy and can be effectively treated with endocrine therapy alone.

The study, published in The New England Journal of Medicine, conversely shows that premenopausal women do benefit from adjuvant chemotherapy, theorized by many to largely be the result of chemotherapy-induced ovarian function suppression.

The RxPONDER trial results are in line with those from the practice-changing TAILORx trial and underscore that “postmenopausal women with 1 to 3 positive nodes and [a recurrence score] of 0 to 25 can likely safely forgo adjuvant chemotherapy without compromising invasive disease-free survival,” first author Kevin Kalinsky, MD, of the Winship Cancer Institute at Emory University, Atlanta, told this news organization. “This will save tens of thousands of women the time, expense, and potentially harmful side effects that can be associated with chemotherapy infusions.”

However, the authors note, “premenopausal women with 1-3 positive lymph nodes had a significant benefit from chemotherapy.”

The study, conducted by the Southwest Oncology Group (SWOG) Cancer Research Network, involved 5,018 women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer with one to three positive axillary lymph nodes – a breast cancer profile that represents approximately 20% of cases in the U.S.

All women had recurrence scores on the 100-point 21-gene breast cancer assay (Oncotype Dx) under 25, which is considered the lowest risk of recurrence. Patients were randomized to treatment with endocrine therapy only (n = 2,507) or chemotherapy followed by endocrine therapy (n = 2,511).

After a median follow-up of 5.3 years, women treated with adjunctive chemotherapy plus endocrine therapy exhibited no significant improvements in invasive disease-free survival compared to those who received endocrine therapy alone.

A prespecified analysis stratifying women by menopausal status underscored those results among postmenopausal women. In this cohort, researchers reported invasive disease-free survival was 91.9% in the endocrine-only group and 91.3% in the chemotherapy group (HR, 1.02; P = .89), indicating no benefit of the adjunctive chemotherapy.

However, among premenopausal women, the invasive disease-free survival rate was significantly higher with the addition of chemotherapy – 89.0% with endocrine-only therapy and 93.9% with both therapies (HR, 0.60; P = .002). Increases in distant relapse-free survival observed in the dual-therapy group similarly favored adding chemotherapy (HR, 0.58; P = .009).

Even when the authors further stratified the women into recurrence scores of 0 to 13 or 14 to 25, the results remained consistent. Postmenopausal women in each of the recurrence score groups continued to show no difference in invasive disease recurrence, new primary cancer, or death from chemotherapy (HR, 1.01 for each score group). Conversely, premenopausal women showed significant improvements in those outcomes when chemotherapy was added to endocrine therapy.

To what degree were the effects observed in premenopausal women the result of chemotherapy-induced ovarian suppression?

“I think it’s fair to say it’s the most interesting question right now in early-stage breast cancer for ER-positive tumors,” Harold Burstein, MD, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, said during a debate at the recent San Antonio Breast Cancer Symposium.

According to Sibylle Loibl, MD, PhD, when it comes to the use of chemotherapy, “age matters.”

“I strongly believe the biology of tumors is different in younger women with HR-positive/HER2-negative breast cancer,” Dr. Loibl, an associate professor at the University of Frankfurt, said during the debate. “It’s a different disease and the effects of chemotherapy are different.”

In young women, chemotherapy has “a direct cytotoxic effect, which cannot be neglected, and an endocrine effect on ovarian function suppression,” Dr. Loibl added. “I think both are needed in young premenopausal patients.”

According to the RxPONDER authors, “whether a chemotherapy benefit in premenopausal women is due to both direct cytocidal effects and treatment-induced menopause remains unclear,” but they noted that “it is possible that the contribution of these mechanisms may vary according to age.”

Further complicating matters, Dr. Loibl added, is that age appears to be poorly represented in genetic diagnostic tools.

“I think the gene expression profiles we are currently using as standard diagnostic tools do not capture the right biology for our premenopausal patients,” she said. “We have to keep in mind that these tests were designed and validated in postmenopausal patients and were only retrospectively used in premenopausal patients.”

The study was funded by the National Cancer Institute and others. Dr. Loibl has received honoraria from Prime and Chugai and numerous institutional research grants.

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

New results from the phase 3 RxPONDER trial add to mounting evidence that most postmenopausal women with early-stage breast cancer derive no added benefits from chemotherapy and can be effectively treated with endocrine therapy alone.

The study, published in The New England Journal of Medicine, conversely shows that premenopausal women do benefit from adjuvant chemotherapy, theorized by many to largely be the result of chemotherapy-induced ovarian function suppression.

The RxPONDER trial results are in line with those from the practice-changing TAILORx trial and underscore that “postmenopausal women with 1 to 3 positive nodes and [a recurrence score] of 0 to 25 can likely safely forgo adjuvant chemotherapy without compromising invasive disease-free survival,” first author Kevin Kalinsky, MD, of the Winship Cancer Institute at Emory University, Atlanta, told this news organization. “This will save tens of thousands of women the time, expense, and potentially harmful side effects that can be associated with chemotherapy infusions.”

However, the authors note, “premenopausal women with 1-3 positive lymph nodes had a significant benefit from chemotherapy.”

The study, conducted by the Southwest Oncology Group (SWOG) Cancer Research Network, involved 5,018 women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer with one to three positive axillary lymph nodes – a breast cancer profile that represents approximately 20% of cases in the U.S.

All women had recurrence scores on the 100-point 21-gene breast cancer assay (Oncotype Dx) under 25, which is considered the lowest risk of recurrence. Patients were randomized to treatment with endocrine therapy only (n = 2,507) or chemotherapy followed by endocrine therapy (n = 2,511).

After a median follow-up of 5.3 years, women treated with adjunctive chemotherapy plus endocrine therapy exhibited no significant improvements in invasive disease-free survival compared to those who received endocrine therapy alone.

A prespecified analysis stratifying women by menopausal status underscored those results among postmenopausal women. In this cohort, researchers reported invasive disease-free survival was 91.9% in the endocrine-only group and 91.3% in the chemotherapy group (HR, 1.02; P = .89), indicating no benefit of the adjunctive chemotherapy.

However, among premenopausal women, the invasive disease-free survival rate was significantly higher with the addition of chemotherapy – 89.0% with endocrine-only therapy and 93.9% with both therapies (HR, 0.60; P = .002). Increases in distant relapse-free survival observed in the dual-therapy group similarly favored adding chemotherapy (HR, 0.58; P = .009).

Even when the authors further stratified the women into recurrence scores of 0 to 13 or 14 to 25, the results remained consistent. Postmenopausal women in each of the recurrence score groups continued to show no difference in invasive disease recurrence, new primary cancer, or death from chemotherapy (HR, 1.01 for each score group). Conversely, premenopausal women showed significant improvements in those outcomes when chemotherapy was added to endocrine therapy.

To what degree were the effects observed in premenopausal women the result of chemotherapy-induced ovarian suppression?

“I think it’s fair to say it’s the most interesting question right now in early-stage breast cancer for ER-positive tumors,” Harold Burstein, MD, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, said during a debate at the recent San Antonio Breast Cancer Symposium.

According to Sibylle Loibl, MD, PhD, when it comes to the use of chemotherapy, “age matters.”

“I strongly believe the biology of tumors is different in younger women with HR-positive/HER2-negative breast cancer,” Dr. Loibl, an associate professor at the University of Frankfurt, said during the debate. “It’s a different disease and the effects of chemotherapy are different.”

In young women, chemotherapy has “a direct cytotoxic effect, which cannot be neglected, and an endocrine effect on ovarian function suppression,” Dr. Loibl added. “I think both are needed in young premenopausal patients.”

According to the RxPONDER authors, “whether a chemotherapy benefit in premenopausal women is due to both direct cytocidal effects and treatment-induced menopause remains unclear,” but they noted that “it is possible that the contribution of these mechanisms may vary according to age.”

Further complicating matters, Dr. Loibl added, is that age appears to be poorly represented in genetic diagnostic tools.

“I think the gene expression profiles we are currently using as standard diagnostic tools do not capture the right biology for our premenopausal patients,” she said. “We have to keep in mind that these tests were designed and validated in postmenopausal patients and were only retrospectively used in premenopausal patients.”

The study was funded by the National Cancer Institute and others. Dr. Loibl has received honoraria from Prime and Chugai and numerous institutional research grants.

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

Advances in technology and genomics have given rise to many issues, such as the extent to which genetic and lifestyle factors contribute to the individual-level risk for coronary artery disease, and the extent one’s genetic risk can be offset by a healthy lifestyle.

Mount Sinai Heart/CCA 3.0

Over the years, Valentin Fuster, MD, PhD, director of Mount Sinai Heart and physician-in-chief at the Mount Sinai Hospital, both in New York, has focused much of his research on this topic. At the virtual ACC Latin America 2021 conference, the cardiologist spoke about his hypotheses and findings during his opening plenary on imaging genomics, an emerging field that is rapidly identifying genes that influence the brain, cognition, and risk for disease.

Dr. Fuster discussed his research (J Am Coll Cardiol. 2021;77:2777-91; J Am Coll Cardiol. 2020;75:1617-27; J Am Coll Cardiol. 2019;73:1371-82; J Am Coll Cardiol. 2017;70:2979-91; Circulation. 2015;131:2104-13) and spoke about his innovative program that looks at cardiovascular health in people from young children to senior citizens. The work has been a process of learning and discovery. “We’re beginning to understand how the disease can develop earlier and how we can prevent it from getting worse. There’s nothing more beneficial than beginning to see how the disease starts in the arteries – something that we’re able to do with imaging technologies that, in the next 2 years, will be available worldwide.” And “by using imaging biomarkers in conjunction with genomic biomarkers, we’re beginning to get an idea earlier on as to whether the person is at risk.”

We need to be talking more about health and healthy arteries and trying to come up with epistemologies that are more modern, Dr. Fuster said. “To be able to see who we actually are is fascinating, and all of this is completely new” with imaging genomics.

Developing cardiovascular disease can be identified in people aged 40-60 years when seven risk factors – obesity, metabolic syndrome, blood pressure, diabetes, smoking, sedentary lifestyle, and poor nutrition” – are grouped together, he explained. In their 2015 study, Dr. Fuster and colleagues explored, using high-quality three-dimensional ultrasonography, five areas of the body – right and left carotids, aorta, and right and left iliofemorals – in more than 4,000 people with no history of cardiovascular disease.

“The first thing I want to point out is that the disease originates in a territory that is not commonly evaluated. And we had no idea. We only learned about this development through imaging tests, assessing plaques. The disease starts in the femoral artery and, in fact, it starts with an inflammatory process – seen at autopsy – that can lead to fibrosis and, in later years, can form lipid-rich vulnerable plaque,” he said.

His work has shown an increase in disease progression in groups of people who have been monitored for 20 years. What is most interesting is the way lesions are silent and evolve as the years go by.

“Atherosclerosis appears as a silent phenomenon initially and worsens in the presence of risk factors that trigger its progression,” he said.

But can subclinical disease be identified in people who have few or no risk factors? “What we call normal is not, in fact, normal,” said Dr. Fuster. To not have subclinical disease, LDL cholesterol needs to be 70 mg/dL and hemoglobin A1c needs to be 5%-6%, according to a 2020 study by Dr. Fuster and colleagues.

“The fact that we’re seeing people with no apparent risk factors develop atherosclerosis is the reason what we consider normal is not,” he said. It is necessary to take into account what happened in the first 40 years of these individuals’ lives, he added.

Dr. Fuster presented findings on 6,000 people aged 60-100 years underwent three-dimensional ultrasonography and were monitored for 12 years. The data have yet to be published, but they indicate that, with this disease, more than just risk factors are at play; atherosclerosis is related to what happens early on in one’s life.

In their 2016 study of more than 55,000 participants, Dr. Fuster and associates quantified the genetic risk for coronary artery disease with a polygenic risk score derived from an analysis of up to 50 genetic polymorphisms that had been associated with coronary artery disease in previous studies. On the basis of this score, the participants were divided into subgroups by genetic risk: low, intermediate, and high. Genetic and lifestyle factors were independently associated with susceptibility to coronary artery disease. For participants at high genetic risk, a favorable lifestyle was associated with a relative risk for coronary artery disease nearly 50% lower than an unfavorable lifestyle.

The risk factors cause the bone marrow to be activated and, when this happens, an inflammatory process occurs in the arteries. This activation is a defense mechanism designed to help monocytes heal the arteries. “When we’re dealing with a disease in the arteries, inflammation starts in the bone marrow, where cholesterol is deposited, and there are macrophages that, because there’s too much to clean up and they can’t keep up, will actually kill themselves. When that happens, they will release substances that will damage the arteries,” Dr. Fuster reported.

In elderly people, risk factors have an impact not only on the great vessels, they can also lead to cerebral small vessel disease.

“The problem is that, before, we didn’t have the technology to make this observation. And this is something critical with respect to late-onset dementia,” he said, citing a 2016 study on Alzheimer’s disease. Even if risk factors are increasing, the person will not necessarily develop the disease, but there is a greater chance that they will.
 

Education

Playful activities have a major impact in childhood. With this in mind, Dr. Fuster instituted a 6-month, 60-hour educational program for children aged 3-6 years. The approach was aimed at teaching children about healthy eating habits and how the human body works. “Children are able to absorb everything we say, but then at age 10, it all goes away,” he said. With another intervention that involved the same children, he showed that the benefits were greater than those seen in the first intervention.

“Our hypothesis is that, regardless of age, any program that has to do with prevention needs to be repeated,” Dr. Fuster said. “Repetition will bring more benefits every x years. That’s what we’re learning.

“We learned that when these children go home, they tell their parents what to do. The program had a greater impact on the children than their parents. So we need to use repetition in prevention efforts directed at young children. And we need to remember that the later we start this kind of work, the less impact it will have. The sooner things start, the greater the benefit and the lower the cost,” he concluded.

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

Advances in technology and genomics have given rise to many issues, such as the extent to which genetic and lifestyle factors contribute to the individual-level risk for coronary artery disease, and the extent one’s genetic risk can be offset by a healthy lifestyle.

Mount Sinai Heart/CCA 3.0

Over the years, Valentin Fuster, MD, PhD, director of Mount Sinai Heart and physician-in-chief at the Mount Sinai Hospital, both in New York, has focused much of his research on this topic. At the virtual ACC Latin America 2021 conference, the cardiologist spoke about his hypotheses and findings during his opening plenary on imaging genomics, an emerging field that is rapidly identifying genes that influence the brain, cognition, and risk for disease.

Dr. Fuster discussed his research (J Am Coll Cardiol. 2021;77:2777-91; J Am Coll Cardiol. 2020;75:1617-27; J Am Coll Cardiol. 2019;73:1371-82; J Am Coll Cardiol. 2017;70:2979-91; Circulation. 2015;131:2104-13) and spoke about his innovative program that looks at cardiovascular health in people from young children to senior citizens. The work has been a process of learning and discovery. “We’re beginning to understand how the disease can develop earlier and how we can prevent it from getting worse. There’s nothing more beneficial than beginning to see how the disease starts in the arteries – something that we’re able to do with imaging technologies that, in the next 2 years, will be available worldwide.” And “by using imaging biomarkers in conjunction with genomic biomarkers, we’re beginning to get an idea earlier on as to whether the person is at risk.”

We need to be talking more about health and healthy arteries and trying to come up with epistemologies that are more modern, Dr. Fuster said. “To be able to see who we actually are is fascinating, and all of this is completely new” with imaging genomics.

Developing cardiovascular disease can be identified in people aged 40-60 years when seven risk factors – obesity, metabolic syndrome, blood pressure, diabetes, smoking, sedentary lifestyle, and poor nutrition” – are grouped together, he explained. In their 2015 study, Dr. Fuster and colleagues explored, using high-quality three-dimensional ultrasonography, five areas of the body – right and left carotids, aorta, and right and left iliofemorals – in more than 4,000 people with no history of cardiovascular disease.

“The first thing I want to point out is that the disease originates in a territory that is not commonly evaluated. And we had no idea. We only learned about this development through imaging tests, assessing plaques. The disease starts in the femoral artery and, in fact, it starts with an inflammatory process – seen at autopsy – that can lead to fibrosis and, in later years, can form lipid-rich vulnerable plaque,” he said.

His work has shown an increase in disease progression in groups of people who have been monitored for 20 years. What is most interesting is the way lesions are silent and evolve as the years go by.

“Atherosclerosis appears as a silent phenomenon initially and worsens in the presence of risk factors that trigger its progression,” he said.

But can subclinical disease be identified in people who have few or no risk factors? “What we call normal is not, in fact, normal,” said Dr. Fuster. To not have subclinical disease, LDL cholesterol needs to be 70 mg/dL and hemoglobin A1c needs to be 5%-6%, according to a 2020 study by Dr. Fuster and colleagues.

“The fact that we’re seeing people with no apparent risk factors develop atherosclerosis is the reason what we consider normal is not,” he said. It is necessary to take into account what happened in the first 40 years of these individuals’ lives, he added.

Dr. Fuster presented findings on 6,000 people aged 60-100 years underwent three-dimensional ultrasonography and were monitored for 12 years. The data have yet to be published, but they indicate that, with this disease, more than just risk factors are at play; atherosclerosis is related to what happens early on in one’s life.

In their 2016 study of more than 55,000 participants, Dr. Fuster and associates quantified the genetic risk for coronary artery disease with a polygenic risk score derived from an analysis of up to 50 genetic polymorphisms that had been associated with coronary artery disease in previous studies. On the basis of this score, the participants were divided into subgroups by genetic risk: low, intermediate, and high. Genetic and lifestyle factors were independently associated with susceptibility to coronary artery disease. For participants at high genetic risk, a favorable lifestyle was associated with a relative risk for coronary artery disease nearly 50% lower than an unfavorable lifestyle.

The risk factors cause the bone marrow to be activated and, when this happens, an inflammatory process occurs in the arteries. This activation is a defense mechanism designed to help monocytes heal the arteries. “When we’re dealing with a disease in the arteries, inflammation starts in the bone marrow, where cholesterol is deposited, and there are macrophages that, because there’s too much to clean up and they can’t keep up, will actually kill themselves. When that happens, they will release substances that will damage the arteries,” Dr. Fuster reported.

In elderly people, risk factors have an impact not only on the great vessels, they can also lead to cerebral small vessel disease.

“The problem is that, before, we didn’t have the technology to make this observation. And this is something critical with respect to late-onset dementia,” he said, citing a 2016 study on Alzheimer’s disease. Even if risk factors are increasing, the person will not necessarily develop the disease, but there is a greater chance that they will.
 

Education

Playful activities have a major impact in childhood. With this in mind, Dr. Fuster instituted a 6-month, 60-hour educational program for children aged 3-6 years. The approach was aimed at teaching children about healthy eating habits and how the human body works. “Children are able to absorb everything we say, but then at age 10, it all goes away,” he said. With another intervention that involved the same children, he showed that the benefits were greater than those seen in the first intervention.

“Our hypothesis is that, regardless of age, any program that has to do with prevention needs to be repeated,” Dr. Fuster said. “Repetition will bring more benefits every x years. That’s what we’re learning.

“We learned that when these children go home, they tell their parents what to do. The program had a greater impact on the children than their parents. So we need to use repetition in prevention efforts directed at young children. And we need to remember that the later we start this kind of work, the less impact it will have. The sooner things start, the greater the benefit and the lower the cost,” he concluded.

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

Advances in technology and genomics have given rise to many issues, such as the extent to which genetic and lifestyle factors contribute to the individual-level risk for coronary artery disease, and the extent one’s genetic risk can be offset by a healthy lifestyle.

Mount Sinai Heart/CCA 3.0

Over the years, Valentin Fuster, MD, PhD, director of Mount Sinai Heart and physician-in-chief at the Mount Sinai Hospital, both in New York, has focused much of his research on this topic. At the virtual ACC Latin America 2021 conference, the cardiologist spoke about his hypotheses and findings during his opening plenary on imaging genomics, an emerging field that is rapidly identifying genes that influence the brain, cognition, and risk for disease.

Dr. Fuster discussed his research (J Am Coll Cardiol. 2021;77:2777-91; J Am Coll Cardiol. 2020;75:1617-27; J Am Coll Cardiol. 2019;73:1371-82; J Am Coll Cardiol. 2017;70:2979-91; Circulation. 2015;131:2104-13) and spoke about his innovative program that looks at cardiovascular health in people from young children to senior citizens. The work has been a process of learning and discovery. “We’re beginning to understand how the disease can develop earlier and how we can prevent it from getting worse. There’s nothing more beneficial than beginning to see how the disease starts in the arteries – something that we’re able to do with imaging technologies that, in the next 2 years, will be available worldwide.” And “by using imaging biomarkers in conjunction with genomic biomarkers, we’re beginning to get an idea earlier on as to whether the person is at risk.”

We need to be talking more about health and healthy arteries and trying to come up with epistemologies that are more modern, Dr. Fuster said. “To be able to see who we actually are is fascinating, and all of this is completely new” with imaging genomics.

Developing cardiovascular disease can be identified in people aged 40-60 years when seven risk factors – obesity, metabolic syndrome, blood pressure, diabetes, smoking, sedentary lifestyle, and poor nutrition” – are grouped together, he explained. In their 2015 study, Dr. Fuster and colleagues explored, using high-quality three-dimensional ultrasonography, five areas of the body – right and left carotids, aorta, and right and left iliofemorals – in more than 4,000 people with no history of cardiovascular disease.

“The first thing I want to point out is that the disease originates in a territory that is not commonly evaluated. And we had no idea. We only learned about this development through imaging tests, assessing plaques. The disease starts in the femoral artery and, in fact, it starts with an inflammatory process – seen at autopsy – that can lead to fibrosis and, in later years, can form lipid-rich vulnerable plaque,” he said.

His work has shown an increase in disease progression in groups of people who have been monitored for 20 years. What is most interesting is the way lesions are silent and evolve as the years go by.

“Atherosclerosis appears as a silent phenomenon initially and worsens in the presence of risk factors that trigger its progression,” he said.

But can subclinical disease be identified in people who have few or no risk factors? “What we call normal is not, in fact, normal,” said Dr. Fuster. To not have subclinical disease, LDL cholesterol needs to be 70 mg/dL and hemoglobin A1c needs to be 5%-6%, according to a 2020 study by Dr. Fuster and colleagues.

“The fact that we’re seeing people with no apparent risk factors develop atherosclerosis is the reason what we consider normal is not,” he said. It is necessary to take into account what happened in the first 40 years of these individuals’ lives, he added.

Dr. Fuster presented findings on 6,000 people aged 60-100 years underwent three-dimensional ultrasonography and were monitored for 12 years. The data have yet to be published, but they indicate that, with this disease, more than just risk factors are at play; atherosclerosis is related to what happens early on in one’s life.

In their 2016 study of more than 55,000 participants, Dr. Fuster and associates quantified the genetic risk for coronary artery disease with a polygenic risk score derived from an analysis of up to 50 genetic polymorphisms that had been associated with coronary artery disease in previous studies. On the basis of this score, the participants were divided into subgroups by genetic risk: low, intermediate, and high. Genetic and lifestyle factors were independently associated with susceptibility to coronary artery disease. For participants at high genetic risk, a favorable lifestyle was associated with a relative risk for coronary artery disease nearly 50% lower than an unfavorable lifestyle.

The risk factors cause the bone marrow to be activated and, when this happens, an inflammatory process occurs in the arteries. This activation is a defense mechanism designed to help monocytes heal the arteries. “When we’re dealing with a disease in the arteries, inflammation starts in the bone marrow, where cholesterol is deposited, and there are macrophages that, because there’s too much to clean up and they can’t keep up, will actually kill themselves. When that happens, they will release substances that will damage the arteries,” Dr. Fuster reported.

In elderly people, risk factors have an impact not only on the great vessels, they can also lead to cerebral small vessel disease.

“The problem is that, before, we didn’t have the technology to make this observation. And this is something critical with respect to late-onset dementia,” he said, citing a 2016 study on Alzheimer’s disease. Even if risk factors are increasing, the person will not necessarily develop the disease, but there is a greater chance that they will.
 

Education

Playful activities have a major impact in childhood. With this in mind, Dr. Fuster instituted a 6-month, 60-hour educational program for children aged 3-6 years. The approach was aimed at teaching children about healthy eating habits and how the human body works. “Children are able to absorb everything we say, but then at age 10, it all goes away,” he said. With another intervention that involved the same children, he showed that the benefits were greater than those seen in the first intervention.

“Our hypothesis is that, regardless of age, any program that has to do with prevention needs to be repeated,” Dr. Fuster said. “Repetition will bring more benefits every x years. That’s what we’re learning.

“We learned that when these children go home, they tell their parents what to do. The program had a greater impact on the children than their parents. So we need to use repetition in prevention efforts directed at young children. And we need to remember that the later we start this kind of work, the less impact it will have. The sooner things start, the greater the benefit and the lower the cost,” he concluded.

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

Gastroenterology centers with higher adenoma detection rates (ADR) with the use of flexible sigmoidoscopy (FS) had a lower long-term colorectal cancer incidence and lower CRC mortality among its patients, according to a new study.

Detection and removal of polyps during colonoscopy screening is vital to the prevention of CRC, and previous research has shown that centers with higher detection rates are associated with lower rates of CRC diagnosis within 3-5 years after a negative screen.

In Clinical Gastroenterology and Hepatology, researchers led by Amanda J. Cross, PhD, a professor of cancer epidemiology at Imperial College London, published an analysis of the UK Flexible Sigmoidoscopy Screening Trial, which found that FS screening between the ages 55 and 64 led to a 35% reduction of CRC incidence and a 41% reduction in CRC over a mean follow-up 17.1 years. The screening program had no apparent effect on incidence and mortality of proximal cancers. The researchers speculated that this was because few patients underwent proximal examination during follow-up colonoscopy.

“Considering only 5% of participants were referred for follow-up colonoscopy and 4% were referred for surveillance, we conclude that the improved detection of adenomas at FS has a measurable impact on long-term distal CRC outcomes, even when there is infrequent colonoscopy use. It is possible that high detectors also were more adept at polypectomy than intermediate or low detectors, and achieved more complete resection of detected lesions,” the authors wrote.

The researchers analyzed data from 38,550 patients who underwent screening at 14 U.K. hospitals, between 1994 and 1999. A single endoscopist was responsible for nearly all FS screens performed at each participating hospital.

The mean patient age was 60 years, and 49% were male. The researchers calculated ADRs for each center using the percentage of patients who had at least one adenoma detected during screening, which included any distal adenomas discovered during follow-up colonoscopy.

The ADR overall was 12%. The researchers used multivariate logistic regression to rank individual centers as having high (15%; five centers), intermediate (12%; four centers), or low (9%; four centers) detection rates.

There was a strong association between detection rates of small adenomas and a center’s ADR (P < .001), but not for large or advanced adenomas. In the high-detector group, 6.2% of patients screened were referred to colonoscopy versus 4.5% in the intermediate group and 4.5% in the low group. About half of colonoscopies were conducted by the same endoscopist who performed FS.

During follow-up, the distal CRC incidence was 1.5% in the high ADR group, 1.4% in the intermediate group, and 1.7% in the low group, and mortality rates were 0.4%, 0.4%, and 0.5%, respectively.

Compared with unscreened controls, risk of distal CRC was lowest among individuals who underwent screening in the high ADR group (hazard ratio, 0.34; 95% confidence interval, 0.27-0.42), followed by the intermediate group (HR, 0.46; 95% CI, 0.36-0.59), and the low ADR group (HR, 0.55; 95% CI, 0.44-0.68; P < .05 for all).

Compared with unscreened controls, CRC mortality was lower among individuals who underwent screening in the high ADR group (HR, 0.22; 95% CI, 0.13-0.37), followed by the intermediate group (HR, 0.30; 95% CI, 0.17-0.55), and the low ADR group (HR, 0.54; 95% CI, 0.34-0.86; P < .05 for between group differences).

All-site CRC incidence followed similar trends, with the lowest risks in the high ADR group (HR, 0.58; 95% CI, 0.50-0.67), followed by intermediate ADR (HR, 0.65; 95% CI, 0.55-0.77) and low ADR groups (HR, 0.72; 95% CI, 0.61-0.85; between group differences not statistically significant).

All-site CRC mortality was lowest in the high ADR group (HR, 0.52; 95% CI, 0.39-0.69), followed by the intermediate group (HR, 0.53; 95% CI, 0.38-0.73), and the low ADR group (HR, 0.68; 95% CI, 0.51-0.92; between-group differences not statistically significant).

The number needed to screen (NNS) to prevent one CRC diagnosis was 78 in the high ADR group (95% CI, 61-106), 103 in the intermediate group (95% CI, 74-171), and 125 in the low ADR group (95% CI, 82-256). The NNS to prevent one CRC death was 226 (95% CI, 159-387), 247 (95% CI, 165-490), and 349 respectively (95% CI, 192-1,904).

However, the researchers also pointed out that efforts to increase ADR could result in more complications, such as perforations or gastrointestinal bleeding, as well as more frequent diagnosis and recommended surveillance for diminutive adenomas.

The study is limited by the fact that endoscopists were either gastroenterologists or surgeons and the study population was made up of individuals who desired screening.

The UK Flexible Sigmoidoscopy Screening Trial was funded by the UK Medical Research Council and the National Institute for Health Research. The authors disclosed no conflicts of interest.

Gastroenterology centers with higher adenoma detection rates (ADR) with the use of flexible sigmoidoscopy (FS) had a lower long-term colorectal cancer incidence and lower CRC mortality among its patients, according to a new study.

Detection and removal of polyps during colonoscopy screening is vital to the prevention of CRC, and previous research has shown that centers with higher detection rates are associated with lower rates of CRC diagnosis within 3-5 years after a negative screen.

In Clinical Gastroenterology and Hepatology, researchers led by Amanda J. Cross, PhD, a professor of cancer epidemiology at Imperial College London, published an analysis of the UK Flexible Sigmoidoscopy Screening Trial, which found that FS screening between the ages 55 and 64 led to a 35% reduction of CRC incidence and a 41% reduction in CRC over a mean follow-up 17.1 years. The screening program had no apparent effect on incidence and mortality of proximal cancers. The researchers speculated that this was because few patients underwent proximal examination during follow-up colonoscopy.

“Considering only 5% of participants were referred for follow-up colonoscopy and 4% were referred for surveillance, we conclude that the improved detection of adenomas at FS has a measurable impact on long-term distal CRC outcomes, even when there is infrequent colonoscopy use. It is possible that high detectors also were more adept at polypectomy than intermediate or low detectors, and achieved more complete resection of detected lesions,” the authors wrote.

The researchers analyzed data from 38,550 patients who underwent screening at 14 U.K. hospitals, between 1994 and 1999. A single endoscopist was responsible for nearly all FS screens performed at each participating hospital.

The mean patient age was 60 years, and 49% were male. The researchers calculated ADRs for each center using the percentage of patients who had at least one adenoma detected during screening, which included any distal adenomas discovered during follow-up colonoscopy.

The ADR overall was 12%. The researchers used multivariate logistic regression to rank individual centers as having high (15%; five centers), intermediate (12%; four centers), or low (9%; four centers) detection rates.

There was a strong association between detection rates of small adenomas and a center’s ADR (P < .001), but not for large or advanced adenomas. In the high-detector group, 6.2% of patients screened were referred to colonoscopy versus 4.5% in the intermediate group and 4.5% in the low group. About half of colonoscopies were conducted by the same endoscopist who performed FS.

During follow-up, the distal CRC incidence was 1.5% in the high ADR group, 1.4% in the intermediate group, and 1.7% in the low group, and mortality rates were 0.4%, 0.4%, and 0.5%, respectively.

Compared with unscreened controls, risk of distal CRC was lowest among individuals who underwent screening in the high ADR group (hazard ratio, 0.34; 95% confidence interval, 0.27-0.42), followed by the intermediate group (HR, 0.46; 95% CI, 0.36-0.59), and the low ADR group (HR, 0.55; 95% CI, 0.44-0.68; P < .05 for all).

Compared with unscreened controls, CRC mortality was lower among individuals who underwent screening in the high ADR group (HR, 0.22; 95% CI, 0.13-0.37), followed by the intermediate group (HR, 0.30; 95% CI, 0.17-0.55), and the low ADR group (HR, 0.54; 95% CI, 0.34-0.86; P < .05 for between group differences).

All-site CRC incidence followed similar trends, with the lowest risks in the high ADR group (HR, 0.58; 95% CI, 0.50-0.67), followed by intermediate ADR (HR, 0.65; 95% CI, 0.55-0.77) and low ADR groups (HR, 0.72; 95% CI, 0.61-0.85; between group differences not statistically significant).

All-site CRC mortality was lowest in the high ADR group (HR, 0.52; 95% CI, 0.39-0.69), followed by the intermediate group (HR, 0.53; 95% CI, 0.38-0.73), and the low ADR group (HR, 0.68; 95% CI, 0.51-0.92; between-group differences not statistically significant).

The number needed to screen (NNS) to prevent one CRC diagnosis was 78 in the high ADR group (95% CI, 61-106), 103 in the intermediate group (95% CI, 74-171), and 125 in the low ADR group (95% CI, 82-256). The NNS to prevent one CRC death was 226 (95% CI, 159-387), 247 (95% CI, 165-490), and 349 respectively (95% CI, 192-1,904).

However, the researchers also pointed out that efforts to increase ADR could result in more complications, such as perforations or gastrointestinal bleeding, as well as more frequent diagnosis and recommended surveillance for diminutive adenomas.

The study is limited by the fact that endoscopists were either gastroenterologists or surgeons and the study population was made up of individuals who desired screening.

The UK Flexible Sigmoidoscopy Screening Trial was funded by the UK Medical Research Council and the National Institute for Health Research. The authors disclosed no conflicts of interest.

Gastroenterology centers with higher adenoma detection rates (ADR) with the use of flexible sigmoidoscopy (FS) had a lower long-term colorectal cancer incidence and lower CRC mortality among its patients, according to a new study.

Detection and removal of polyps during colonoscopy screening is vital to the prevention of CRC, and previous research has shown that centers with higher detection rates are associated with lower rates of CRC diagnosis within 3-5 years after a negative screen.

In Clinical Gastroenterology and Hepatology, researchers led by Amanda J. Cross, PhD, a professor of cancer epidemiology at Imperial College London, published an analysis of the UK Flexible Sigmoidoscopy Screening Trial, which found that FS screening between the ages 55 and 64 led to a 35% reduction of CRC incidence and a 41% reduction in CRC over a mean follow-up 17.1 years. The screening program had no apparent effect on incidence and mortality of proximal cancers. The researchers speculated that this was because few patients underwent proximal examination during follow-up colonoscopy.

“Considering only 5% of participants were referred for follow-up colonoscopy and 4% were referred for surveillance, we conclude that the improved detection of adenomas at FS has a measurable impact on long-term distal CRC outcomes, even when there is infrequent colonoscopy use. It is possible that high detectors also were more adept at polypectomy than intermediate or low detectors, and achieved more complete resection of detected lesions,” the authors wrote.

The researchers analyzed data from 38,550 patients who underwent screening at 14 U.K. hospitals, between 1994 and 1999. A single endoscopist was responsible for nearly all FS screens performed at each participating hospital.

The mean patient age was 60 years, and 49% were male. The researchers calculated ADRs for each center using the percentage of patients who had at least one adenoma detected during screening, which included any distal adenomas discovered during follow-up colonoscopy.

The ADR overall was 12%. The researchers used multivariate logistic regression to rank individual centers as having high (15%; five centers), intermediate (12%; four centers), or low (9%; four centers) detection rates.

There was a strong association between detection rates of small adenomas and a center’s ADR (P < .001), but not for large or advanced adenomas. In the high-detector group, 6.2% of patients screened were referred to colonoscopy versus 4.5% in the intermediate group and 4.5% in the low group. About half of colonoscopies were conducted by the same endoscopist who performed FS.

During follow-up, the distal CRC incidence was 1.5% in the high ADR group, 1.4% in the intermediate group, and 1.7% in the low group, and mortality rates were 0.4%, 0.4%, and 0.5%, respectively.

Compared with unscreened controls, risk of distal CRC was lowest among individuals who underwent screening in the high ADR group (hazard ratio, 0.34; 95% confidence interval, 0.27-0.42), followed by the intermediate group (HR, 0.46; 95% CI, 0.36-0.59), and the low ADR group (HR, 0.55; 95% CI, 0.44-0.68; P < .05 for all).

Compared with unscreened controls, CRC mortality was lower among individuals who underwent screening in the high ADR group (HR, 0.22; 95% CI, 0.13-0.37), followed by the intermediate group (HR, 0.30; 95% CI, 0.17-0.55), and the low ADR group (HR, 0.54; 95% CI, 0.34-0.86; P < .05 for between group differences).

All-site CRC incidence followed similar trends, with the lowest risks in the high ADR group (HR, 0.58; 95% CI, 0.50-0.67), followed by intermediate ADR (HR, 0.65; 95% CI, 0.55-0.77) and low ADR groups (HR, 0.72; 95% CI, 0.61-0.85; between group differences not statistically significant).

All-site CRC mortality was lowest in the high ADR group (HR, 0.52; 95% CI, 0.39-0.69), followed by the intermediate group (HR, 0.53; 95% CI, 0.38-0.73), and the low ADR group (HR, 0.68; 95% CI, 0.51-0.92; between-group differences not statistically significant).

The number needed to screen (NNS) to prevent one CRC diagnosis was 78 in the high ADR group (95% CI, 61-106), 103 in the intermediate group (95% CI, 74-171), and 125 in the low ADR group (95% CI, 82-256). The NNS to prevent one CRC death was 226 (95% CI, 159-387), 247 (95% CI, 165-490), and 349 respectively (95% CI, 192-1,904).

However, the researchers also pointed out that efforts to increase ADR could result in more complications, such as perforations or gastrointestinal bleeding, as well as more frequent diagnosis and recommended surveillance for diminutive adenomas.

The study is limited by the fact that endoscopists were either gastroenterologists or surgeons and the study population was made up of individuals who desired screening.

The UK Flexible Sigmoidoscopy Screening Trial was funded by the UK Medical Research Council and the National Institute for Health Research. The authors disclosed no conflicts of interest.

Remarkable results were reported at the annual meeting of the American Society of Hematology for the investigational drug fitusiran to prevent bleeding in hemophilia patients.

Fitusiran is a small interfering RNA molecule that blocks antithrombin production in liver cells. Instead of taking the traditional approach in hemophilia treatment of boosting the coagulation cascade by replacing what’s missing, the idea of fitusiran is to short circuit the body’s anticoagulation system by targeting antithrombin.

Patients in two trials presented at the meeting, ATLAS-A/B and ATLAS-INH, had about a 90% reduction in their annualized bleeding rates when treated with prophylactic fitusiran, with half or more having no bleeds that required treatment during the 9-month trials. The median annualized bleeding rate fell to 0, trial investigators reported at the meeting.

These findings held in both hemophilia A and B with and without inhibitors, which are antibodies formed against exogenous clotting factors, and on subanalysis of spontaneous and joint bleeding rates. Reduced bleeding was associated with substantial improvements in health-care related quality of life, particularly in the physical health domain.
 

A question about study design

An audience member at ASH noted that the trials didn’t compare fitusiran against prophylactic treatment, which is standard of care for hemophilia, but rather against episodic treatment – concentrated factors or bypassing agents in subjects with inhibitors – once subjects in the control groups started to bleed.

Still, the numbers reported in the studies “have never been achieved with standard prophylaxis in the past.” Furthermore, standard prophylaxis requires lifelong intravenous infusions, sometimes several a week, said lead ATLAS-A/B investigator Alok Srivastava, MD, a hematologist at the Christian Medical College in Vellore, India.

Fitusiran was dosed in the studies as a once-a-month 80 mg subcutaneous injection, so is much less bothersome. Also, it seems likely that some patients will only need dosing every other month. Maker Sanofi Genzyme is exploring lower and less frequent dosing to reduce thrombotic event risks that emerged in earlier studies, said Steven Pipe, MD, a pediatric hematologist at the University of Michigan, Ann Arbor, and the senior investigator on ATLAS-A/B, which assessed fitusiran in patients without inhibitors.

Serious thrombotic events occurred in two fitusiran patients in the trials, one of which led to discontinuation.
 

No pricing information

Overall, “I think [fitusiran] is a tremendous leap forward” with “the opportunity to transform the day-to-day lives of patients,” particularly those with hemophilia B, who have limited treatment options, Dr. Pipe said.

If approved for the U.S. market, fitusiran will go up against the monoclonal antibody emicizumab (Hemlibra), a subcutaneous injection dosed weekly to monthly that mimics the function of factor VIII, so it’s approved only for hemophilia A with or without inhibitors.

Several audience members at ASH noted that a major consideration for fitusiran, if approved, will be its cost. There’s no pricing information yet, but annual list price for emicizumab is reported to be in the $500,000 range.

For hemophilia A, “it will come to what proves to be the most efficacious and safe, with also consideration given to pricing,” Nigel Key, MD, a hematologist at the University of North Carolina at Chapel Hill, said in a comment.
 

Trial details

In ATLAS-A/B, 80 male patients were randomized to prophylactic fitusiran once monthly and 40 to continue with clotting factors as needed for bleeding. Just over 20% had hemophilia B, the rest hemophilia A. The mean age was 34 years, and subjects had a mean of about 12 bleeds in the 6 months leading up to the study.

Half of the fitusiran group had no treated bleeds during the study period versus only 5% in the control arm.

The five treatment emergent serious adverse events in the fitusiran arm included cholelithiasis in two subjects, plus cholecystitis, lower respiratory tract infection, and asthma in one each. Two fitusiran patients discontinued treatment because of cholecystitis and increased alanine aminotransferase.

ATLAS-INH had the same study design, and investigated patients with inhibitors; again, just over 20% had hemophilia B, the rest A. Mean age was 28 years, and patients had a mean of about 13 bleeds over the 6 months before the study. A total of 38 subjects were randomized to fitusiran, and 19 to bypassing agents as needed.

Almost 66% of fitusiran patients had no treated bleeds versus about 5% in the control arm.

none provided

There “was far less bleeding both for hemophilia A and B. It’s definitely a clinically meaningful and important” effect, said ATLAS-INH lead investigator Guy Young, MD, director of the hemostasis and thrombosis program at Children’s Hospital Los Angeles.

He said the improved quality of life with fitusiran noted in both trials was “not surprising. If you only have to dose once a month subcutaneously, and you are not bleeding, of course your quality of life is going to improve.”

Both fitusiran thrombotic events occurred in ATLAS-INH. One patient developed deep vein thrombosis, subclavian vein thrombosis, and superficial thrombophlebitis but stayed in the study. Another discontinued after developing suspected spinal vessel thrombosis. Serious adverse events among five other subjects included acute cholecystitis and hematuria.

Fitusiran was associated with liver enzyme elevations in both trials, but they were generally mild to moderate.

The studies were funded by fitusiran maker Sanofi Genzyme. Several investigators were employees. Dr. Pipe is a consultant, Dr. Srivastava is a researcher and adviser, and Dr. Young is a speaker and consultant for the company and disclosed honoraria from it. Dr. Key had no relevant disclosures.

[email protected]

Remarkable results were reported at the annual meeting of the American Society of Hematology for the investigational drug fitusiran to prevent bleeding in hemophilia patients.

Fitusiran is a small interfering RNA molecule that blocks antithrombin production in liver cells. Instead of taking the traditional approach in hemophilia treatment of boosting the coagulation cascade by replacing what’s missing, the idea of fitusiran is to short circuit the body’s anticoagulation system by targeting antithrombin.

Patients in two trials presented at the meeting, ATLAS-A/B and ATLAS-INH, had about a 90% reduction in their annualized bleeding rates when treated with prophylactic fitusiran, with half or more having no bleeds that required treatment during the 9-month trials. The median annualized bleeding rate fell to 0, trial investigators reported at the meeting.

These findings held in both hemophilia A and B with and without inhibitors, which are antibodies formed against exogenous clotting factors, and on subanalysis of spontaneous and joint bleeding rates. Reduced bleeding was associated with substantial improvements in health-care related quality of life, particularly in the physical health domain.
 

A question about study design

An audience member at ASH noted that the trials didn’t compare fitusiran against prophylactic treatment, which is standard of care for hemophilia, but rather against episodic treatment – concentrated factors or bypassing agents in subjects with inhibitors – once subjects in the control groups started to bleed.

Still, the numbers reported in the studies “have never been achieved with standard prophylaxis in the past.” Furthermore, standard prophylaxis requires lifelong intravenous infusions, sometimes several a week, said lead ATLAS-A/B investigator Alok Srivastava, MD, a hematologist at the Christian Medical College in Vellore, India.

Fitusiran was dosed in the studies as a once-a-month 80 mg subcutaneous injection, so is much less bothersome. Also, it seems likely that some patients will only need dosing every other month. Maker Sanofi Genzyme is exploring lower and less frequent dosing to reduce thrombotic event risks that emerged in earlier studies, said Steven Pipe, MD, a pediatric hematologist at the University of Michigan, Ann Arbor, and the senior investigator on ATLAS-A/B, which assessed fitusiran in patients without inhibitors.

Serious thrombotic events occurred in two fitusiran patients in the trials, one of which led to discontinuation.
 

No pricing information

Overall, “I think [fitusiran] is a tremendous leap forward” with “the opportunity to transform the day-to-day lives of patients,” particularly those with hemophilia B, who have limited treatment options, Dr. Pipe said.

If approved for the U.S. market, fitusiran will go up against the monoclonal antibody emicizumab (Hemlibra), a subcutaneous injection dosed weekly to monthly that mimics the function of factor VIII, so it’s approved only for hemophilia A with or without inhibitors.

Several audience members at ASH noted that a major consideration for fitusiran, if approved, will be its cost. There’s no pricing information yet, but annual list price for emicizumab is reported to be in the $500,000 range.

For hemophilia A, “it will come to what proves to be the most efficacious and safe, with also consideration given to pricing,” Nigel Key, MD, a hematologist at the University of North Carolina at Chapel Hill, said in a comment.
 

Trial details

In ATLAS-A/B, 80 male patients were randomized to prophylactic fitusiran once monthly and 40 to continue with clotting factors as needed for bleeding. Just over 20% had hemophilia B, the rest hemophilia A. The mean age was 34 years, and subjects had a mean of about 12 bleeds in the 6 months leading up to the study.

Half of the fitusiran group had no treated bleeds during the study period versus only 5% in the control arm.

The five treatment emergent serious adverse events in the fitusiran arm included cholelithiasis in two subjects, plus cholecystitis, lower respiratory tract infection, and asthma in one each. Two fitusiran patients discontinued treatment because of cholecystitis and increased alanine aminotransferase.

ATLAS-INH had the same study design, and investigated patients with inhibitors; again, just over 20% had hemophilia B, the rest A. Mean age was 28 years, and patients had a mean of about 13 bleeds over the 6 months before the study. A total of 38 subjects were randomized to fitusiran, and 19 to bypassing agents as needed.

Almost 66% of fitusiran patients had no treated bleeds versus about 5% in the control arm.

none provided

There “was far less bleeding both for hemophilia A and B. It’s definitely a clinically meaningful and important” effect, said ATLAS-INH lead investigator Guy Young, MD, director of the hemostasis and thrombosis program at Children’s Hospital Los Angeles.

He said the improved quality of life with fitusiran noted in both trials was “not surprising. If you only have to dose once a month subcutaneously, and you are not bleeding, of course your quality of life is going to improve.”

Both fitusiran thrombotic events occurred in ATLAS-INH. One patient developed deep vein thrombosis, subclavian vein thrombosis, and superficial thrombophlebitis but stayed in the study. Another discontinued after developing suspected spinal vessel thrombosis. Serious adverse events among five other subjects included acute cholecystitis and hematuria.

Fitusiran was associated with liver enzyme elevations in both trials, but they were generally mild to moderate.

The studies were funded by fitusiran maker Sanofi Genzyme. Several investigators were employees. Dr. Pipe is a consultant, Dr. Srivastava is a researcher and adviser, and Dr. Young is a speaker and consultant for the company and disclosed honoraria from it. Dr. Key had no relevant disclosures.

[email protected]

Remarkable results were reported at the annual meeting of the American Society of Hematology for the investigational drug fitusiran to prevent bleeding in hemophilia patients.

Fitusiran is a small interfering RNA molecule that blocks antithrombin production in liver cells. Instead of taking the traditional approach in hemophilia treatment of boosting the coagulation cascade by replacing what’s missing, the idea of fitusiran is to short circuit the body’s anticoagulation system by targeting antithrombin.

Patients in two trials presented at the meeting, ATLAS-A/B and ATLAS-INH, had about a 90% reduction in their annualized bleeding rates when treated with prophylactic fitusiran, with half or more having no bleeds that required treatment during the 9-month trials. The median annualized bleeding rate fell to 0, trial investigators reported at the meeting.

These findings held in both hemophilia A and B with and without inhibitors, which are antibodies formed against exogenous clotting factors, and on subanalysis of spontaneous and joint bleeding rates. Reduced bleeding was associated with substantial improvements in health-care related quality of life, particularly in the physical health domain.
 

A question about study design

An audience member at ASH noted that the trials didn’t compare fitusiran against prophylactic treatment, which is standard of care for hemophilia, but rather against episodic treatment – concentrated factors or bypassing agents in subjects with inhibitors – once subjects in the control groups started to bleed.

Still, the numbers reported in the studies “have never been achieved with standard prophylaxis in the past.” Furthermore, standard prophylaxis requires lifelong intravenous infusions, sometimes several a week, said lead ATLAS-A/B investigator Alok Srivastava, MD, a hematologist at the Christian Medical College in Vellore, India.

Fitusiran was dosed in the studies as a once-a-month 80 mg subcutaneous injection, so is much less bothersome. Also, it seems likely that some patients will only need dosing every other month. Maker Sanofi Genzyme is exploring lower and less frequent dosing to reduce thrombotic event risks that emerged in earlier studies, said Steven Pipe, MD, a pediatric hematologist at the University of Michigan, Ann Arbor, and the senior investigator on ATLAS-A/B, which assessed fitusiran in patients without inhibitors.

Serious thrombotic events occurred in two fitusiran patients in the trials, one of which led to discontinuation.
 

No pricing information

Overall, “I think [fitusiran] is a tremendous leap forward” with “the opportunity to transform the day-to-day lives of patients,” particularly those with hemophilia B, who have limited treatment options, Dr. Pipe said.

If approved for the U.S. market, fitusiran will go up against the monoclonal antibody emicizumab (Hemlibra), a subcutaneous injection dosed weekly to monthly that mimics the function of factor VIII, so it’s approved only for hemophilia A with or without inhibitors.

Several audience members at ASH noted that a major consideration for fitusiran, if approved, will be its cost. There’s no pricing information yet, but annual list price for emicizumab is reported to be in the $500,000 range.

For hemophilia A, “it will come to what proves to be the most efficacious and safe, with also consideration given to pricing,” Nigel Key, MD, a hematologist at the University of North Carolina at Chapel Hill, said in a comment.
 

Trial details

In ATLAS-A/B, 80 male patients were randomized to prophylactic fitusiran once monthly and 40 to continue with clotting factors as needed for bleeding. Just over 20% had hemophilia B, the rest hemophilia A. The mean age was 34 years, and subjects had a mean of about 12 bleeds in the 6 months leading up to the study.

Half of the fitusiran group had no treated bleeds during the study period versus only 5% in the control arm.

The five treatment emergent serious adverse events in the fitusiran arm included cholelithiasis in two subjects, plus cholecystitis, lower respiratory tract infection, and asthma in one each. Two fitusiran patients discontinued treatment because of cholecystitis and increased alanine aminotransferase.

ATLAS-INH had the same study design, and investigated patients with inhibitors; again, just over 20% had hemophilia B, the rest A. Mean age was 28 years, and patients had a mean of about 13 bleeds over the 6 months before the study. A total of 38 subjects were randomized to fitusiran, and 19 to bypassing agents as needed.

Almost 66% of fitusiran patients had no treated bleeds versus about 5% in the control arm.

none provided

There “was far less bleeding both for hemophilia A and B. It’s definitely a clinically meaningful and important” effect, said ATLAS-INH lead investigator Guy Young, MD, director of the hemostasis and thrombosis program at Children’s Hospital Los Angeles.

He said the improved quality of life with fitusiran noted in both trials was “not surprising. If you only have to dose once a month subcutaneously, and you are not bleeding, of course your quality of life is going to improve.”

Both fitusiran thrombotic events occurred in ATLAS-INH. One patient developed deep vein thrombosis, subclavian vein thrombosis, and superficial thrombophlebitis but stayed in the study. Another discontinued after developing suspected spinal vessel thrombosis. Serious adverse events among five other subjects included acute cholecystitis and hematuria.

Fitusiran was associated with liver enzyme elevations in both trials, but they were generally mild to moderate.

The studies were funded by fitusiran maker Sanofi Genzyme. Several investigators were employees. Dr. Pipe is a consultant, Dr. Srivastava is a researcher and adviser, and Dr. Young is a speaker and consultant for the company and disclosed honoraria from it. Dr. Key had no relevant disclosures.

[email protected]

There is an increased incidence of locally staged Merkel cell carcinoma (MCC) among patients who live in rural areas of the United States, compared with those in urban and metropolitan areas, yet overall survival is worse in rural areas.

This paradox was discovered in an analysis of data from the Surveillance, Epidemiology, and End Results (SEER) Program that primary author Bryan T. Carroll, MD, PhD, and colleagues presented during a virtual abstract session at the annual meeting of the American Society for Dermatologic Surgery.

“MCC is a rare and aggressive neoplasm of the skin with high mortality,” said coauthor Emma Larson, MD, a dermatology clinical research fellow at University Hospitals of Cleveland. “Previous studies have demonstrated that MCC survival is lower in low–dermatologist density areas. Associations are difficult to characterize without historical staging data aggregated from large registries. We hypothesized that decreased MCC survival is associated with rural counties.”

The researchers used 18 registries from the November 2019 SEER database to retrospectively evaluate adults who were diagnosed with MCC between 2004 and 2015 as confirmed by positive histology. Study endpoints were SEER historic stage at diagnosis and 5-year survival. MCC cases were stratified by 2013 USDA urban-rural continuum codes, which defines metropolitan counties as those with a population of 1 million or more, urban counties as those with a population of less than 1 million, and rural counties as nonmetropolitan counties not adjacent to a metropolitan area.

A total of 6,291 cases with a mean age of 75 years were included in the final analysis: 3,750 from metro areas, 2,235 from urban areas, and 306 from rural areas. A higher proportion of MCC patients from rural areas were male (69% vs. 62% from metro areas and 64% from urban areas) and white (97% vs. 95% and 96%, respectively). “This may contribute to differences in MCC care,” Dr. Larson said. “However, we also found that there is an increased incidence of locally staged disease in rural areas (51%) than in metro (44%) or urban (45%) areas (P = .02). In addition, fewer lymph node surgeries were performed in rural (50%) and urban (51%) areas than in metro areas (45%; P = .01).”

Overall survival was worse among patients in rural areas (a mean of 34 months), compared with those in urban (a mean of 41 months) and metro areas (a mean of 47 months; P = .02). “This may be due to the fact that rural counties have the higher risk factors for MCC incidence and death, but when we account for the confounders, including sex, age, race, and MCC stage, we still found a difference in overall survival in rural counties, compared to metro and urban counties,” Dr. Larson said.

Dr. Carroll, an associate professor of dermatology at University Hospitals of Cleveland, characterized the finding as “not what you’d expect with a higher incidence of local disease. Therefore, there is the potential for mis-staging in rural counties, where we did see that the interrogation of lymph nodes was done less frequently than in urban centers, which were more aligned with National Comprehensive Cancer Network guidelines during this time period. Still, after correction, rural location is still associated with a higher MCC mortality. There is a need for us to further interrogate what the causes are for this disparity in care between rural and urban centers.”

The other study authors were Dustin DeMeo and Christian Scheufele, MD. The researchers reported having no relevant financial disclosures.

[email protected]

There is an increased incidence of locally staged Merkel cell carcinoma (MCC) among patients who live in rural areas of the United States, compared with those in urban and metropolitan areas, yet overall survival is worse in rural areas.

This paradox was discovered in an analysis of data from the Surveillance, Epidemiology, and End Results (SEER) Program that primary author Bryan T. Carroll, MD, PhD, and colleagues presented during a virtual abstract session at the annual meeting of the American Society for Dermatologic Surgery.

“MCC is a rare and aggressive neoplasm of the skin with high mortality,” said coauthor Emma Larson, MD, a dermatology clinical research fellow at University Hospitals of Cleveland. “Previous studies have demonstrated that MCC survival is lower in low–dermatologist density areas. Associations are difficult to characterize without historical staging data aggregated from large registries. We hypothesized that decreased MCC survival is associated with rural counties.”

The researchers used 18 registries from the November 2019 SEER database to retrospectively evaluate adults who were diagnosed with MCC between 2004 and 2015 as confirmed by positive histology. Study endpoints were SEER historic stage at diagnosis and 5-year survival. MCC cases were stratified by 2013 USDA urban-rural continuum codes, which defines metropolitan counties as those with a population of 1 million or more, urban counties as those with a population of less than 1 million, and rural counties as nonmetropolitan counties not adjacent to a metropolitan area.

A total of 6,291 cases with a mean age of 75 years were included in the final analysis: 3,750 from metro areas, 2,235 from urban areas, and 306 from rural areas. A higher proportion of MCC patients from rural areas were male (69% vs. 62% from metro areas and 64% from urban areas) and white (97% vs. 95% and 96%, respectively). “This may contribute to differences in MCC care,” Dr. Larson said. “However, we also found that there is an increased incidence of locally staged disease in rural areas (51%) than in metro (44%) or urban (45%) areas (P = .02). In addition, fewer lymph node surgeries were performed in rural (50%) and urban (51%) areas than in metro areas (45%; P = .01).”

Overall survival was worse among patients in rural areas (a mean of 34 months), compared with those in urban (a mean of 41 months) and metro areas (a mean of 47 months; P = .02). “This may be due to the fact that rural counties have the higher risk factors for MCC incidence and death, but when we account for the confounders, including sex, age, race, and MCC stage, we still found a difference in overall survival in rural counties, compared to metro and urban counties,” Dr. Larson said.

Dr. Carroll, an associate professor of dermatology at University Hospitals of Cleveland, characterized the finding as “not what you’d expect with a higher incidence of local disease. Therefore, there is the potential for mis-staging in rural counties, where we did see that the interrogation of lymph nodes was done less frequently than in urban centers, which were more aligned with National Comprehensive Cancer Network guidelines during this time period. Still, after correction, rural location is still associated with a higher MCC mortality. There is a need for us to further interrogate what the causes are for this disparity in care between rural and urban centers.”

The other study authors were Dustin DeMeo and Christian Scheufele, MD. The researchers reported having no relevant financial disclosures.

[email protected]

There is an increased incidence of locally staged Merkel cell carcinoma (MCC) among patients who live in rural areas of the United States, compared with those in urban and metropolitan areas, yet overall survival is worse in rural areas.

This paradox was discovered in an analysis of data from the Surveillance, Epidemiology, and End Results (SEER) Program that primary author Bryan T. Carroll, MD, PhD, and colleagues presented during a virtual abstract session at the annual meeting of the American Society for Dermatologic Surgery.

“MCC is a rare and aggressive neoplasm of the skin with high mortality,” said coauthor Emma Larson, MD, a dermatology clinical research fellow at University Hospitals of Cleveland. “Previous studies have demonstrated that MCC survival is lower in low–dermatologist density areas. Associations are difficult to characterize without historical staging data aggregated from large registries. We hypothesized that decreased MCC survival is associated with rural counties.”

The researchers used 18 registries from the November 2019 SEER database to retrospectively evaluate adults who were diagnosed with MCC between 2004 and 2015 as confirmed by positive histology. Study endpoints were SEER historic stage at diagnosis and 5-year survival. MCC cases were stratified by 2013 USDA urban-rural continuum codes, which defines metropolitan counties as those with a population of 1 million or more, urban counties as those with a population of less than 1 million, and rural counties as nonmetropolitan counties not adjacent to a metropolitan area.

A total of 6,291 cases with a mean age of 75 years were included in the final analysis: 3,750 from metro areas, 2,235 from urban areas, and 306 from rural areas. A higher proportion of MCC patients from rural areas were male (69% vs. 62% from metro areas and 64% from urban areas) and white (97% vs. 95% and 96%, respectively). “This may contribute to differences in MCC care,” Dr. Larson said. “However, we also found that there is an increased incidence of locally staged disease in rural areas (51%) than in metro (44%) or urban (45%) areas (P = .02). In addition, fewer lymph node surgeries were performed in rural (50%) and urban (51%) areas than in metro areas (45%; P = .01).”

Overall survival was worse among patients in rural areas (a mean of 34 months), compared with those in urban (a mean of 41 months) and metro areas (a mean of 47 months; P = .02). “This may be due to the fact that rural counties have the higher risk factors for MCC incidence and death, but when we account for the confounders, including sex, age, race, and MCC stage, we still found a difference in overall survival in rural counties, compared to metro and urban counties,” Dr. Larson said.

Dr. Carroll, an associate professor of dermatology at University Hospitals of Cleveland, characterized the finding as “not what you’d expect with a higher incidence of local disease. Therefore, there is the potential for mis-staging in rural counties, where we did see that the interrogation of lymph nodes was done less frequently than in urban centers, which were more aligned with National Comprehensive Cancer Network guidelines during this time period. Still, after correction, rural location is still associated with a higher MCC mortality. There is a need for us to further interrogate what the causes are for this disparity in care between rural and urban centers.”

The other study authors were Dustin DeMeo and Christian Scheufele, MD. The researchers reported having no relevant financial disclosures.

[email protected]