AVAHO

Patients with newly diagnosed multiple myeloma have similar outcomes whether they receive carfilzomib once or twice a week, according to a pooled analysis of trial data.

Courtesy Wikimedia Commons/KGH/Creative Commons License

Researchers found no significant difference in safety, progression-free survival (PFS), or overall survival (OS) whether patients received carfilzomib at 70 mg/m² once a week or 36 mg/m² twice a week.

Sara Bringhen, MD, PhD, of University of Turin, Italy, and her colleagues conducted this analysis and detailed the results in Haematologica.

The researchers pooled data from a phase 1/2 trial (NCT01857115) and a phase 2 trial (NCT01346787), both enrolling transplant-ineligible patients with newly diagnosed multiple myeloma.

In both studies, induction consisted of nine 4-week cycles of carfilzomib (given once or twice weekly), cyclophosphamide (300 mg on days 1, 8, and 15), and dexamethasone (40 mg on days 1, 8, 15, and 22). After induction, patients received carfilzomib maintenance (at either dose) until progression or intolerable toxicity.

jensmith@mdedge.com

SOURCE: Bringhen S et al. Haematologica. 2019 Feb 7. doi: 10.3324/haematol.2018.208272.

Patients with newly diagnosed multiple myeloma have similar outcomes whether they receive carfilzomib once or twice a week, according to a pooled analysis of trial data.

Courtesy Wikimedia Commons/KGH/Creative Commons License

Researchers found no significant difference in safety, progression-free survival (PFS), or overall survival (OS) whether patients received carfilzomib at 70 mg/m² once a week or 36 mg/m² twice a week.

Sara Bringhen, MD, PhD, of University of Turin, Italy, and her colleagues conducted this analysis and detailed the results in Haematologica.

The researchers pooled data from a phase 1/2 trial (NCT01857115) and a phase 2 trial (NCT01346787), both enrolling transplant-ineligible patients with newly diagnosed multiple myeloma.

In both studies, induction consisted of nine 4-week cycles of carfilzomib (given once or twice weekly), cyclophosphamide (300 mg on days 1, 8, and 15), and dexamethasone (40 mg on days 1, 8, 15, and 22). After induction, patients received carfilzomib maintenance (at either dose) until progression or intolerable toxicity.

jensmith@mdedge.com

SOURCE: Bringhen S et al. Haematologica. 2019 Feb 7. doi: 10.3324/haematol.2018.208272.

Patients with newly diagnosed multiple myeloma have similar outcomes whether they receive carfilzomib once or twice a week, according to a pooled analysis of trial data.

Courtesy Wikimedia Commons/KGH/Creative Commons License

Researchers found no significant difference in safety, progression-free survival (PFS), or overall survival (OS) whether patients received carfilzomib at 70 mg/m² once a week or 36 mg/m² twice a week.

Sara Bringhen, MD, PhD, of University of Turin, Italy, and her colleagues conducted this analysis and detailed the results in Haematologica.

The researchers pooled data from a phase 1/2 trial (NCT01857115) and a phase 2 trial (NCT01346787), both enrolling transplant-ineligible patients with newly diagnosed multiple myeloma.

In both studies, induction consisted of nine 4-week cycles of carfilzomib (given once or twice weekly), cyclophosphamide (300 mg on days 1, 8, and 15), and dexamethasone (40 mg on days 1, 8, 15, and 22). After induction, patients received carfilzomib maintenance (at either dose) until progression or intolerable toxicity.

jensmith@mdedge.com

SOURCE: Bringhen S et al. Haematologica. 2019 Feb 7. doi: 10.3324/haematol.2018.208272.

For patients with diffuse large B-cell lymphoma (DLBCL) who need allogeneic hematopoietic cell transplantation (allo-HCT), a haploidentical family member could be a viable donor, according to a retrospective study of 1,438 patients.

Nephron/Wikimedia Commons/CC BY-SA 3.0

When combined with nonmyeloablative/reduced intensity conditioning (NMC/RIC) and posttransplant cyclophosphamide (PTCy), patients treated with haploidentical HCT (haplo-HCT) had outcomes similar to those seen in patients with matched donors, reported Peter Dreger, MD, of the University of Heidelberg (Germany) and his colleagues.

“Using well-matched sibling donors (MSDs) or unrelated donors (MUDs), allo-HCT can result in sustained disease control in 30% to 45% of patients with DLBCL who have early disease recurrence after standard chemoimmunotherapy or have failed auto-HCT [autologous HCT],” the investigators wrote in Blood Advances. “However, the search for a well-matched unrelated donor could be time-consuming and unsuccessful in up to 50% of the patients in need.”

But the present findings suggest that haplo-HCT may one day improve these odds by providing a larger pool of potential donors.

The patients in the study were divided into four treatment groups: haplo-HCT (n = 132), MSD (n = 525), MUD with T-cell depletion (n = 403), and MUD without T-cell depletion (n = 378). For graft-versus-host disease (GVHD) prophylaxis, patients in the haplo-HCT group received PTCy, with or without a calcineurin inhibitor and mycophenolate mofetil, whereas all patients with matched donors received a calcineurin inhibitor. T-cell depletion was accomplished by in vivo antithymocyte globulin and alemtuzumab.

The primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), progression/relapse, and nonrelapse mortality (NRM).

After a median follow-up of 4.1 years, all groups had similar outcomes, without statistical differences in multivariable analysis.

In the haplo-HCT group, the 3-year OS rate was 46%, the NRM rate was 22%, the PFS rate was 38%, and the relapse/progression rate was 41%.

Of note, patients receiving haplo-HCT did have a lower cumulative incidence of chronic GVHD, at 15% after 1 year and 18% after 2 years. These rates were significantly lower than the other groups’ 1- and 2-year GVHD rates, which were as follows: MSD, 41% and 48%; MUD with T-cell depletion, 23% and 27%; and MUD without T-cell depletion, 48% and 57%.

The investigators noted that these disparities may actually be caused by the use of bone marrow grafts in the haplo-HCT group instead of peripheral blood grafts, which were used in most of the patients in the other groups.

Overall, the findings were encouraging, but the investigators cautioned that “additional studies are needed before haploidentical donors can be considered as equivalent to well-matched related or unrelated donors in patients with DLBCL.”

The study was funded by the Center for International Blood & Marrow Transplant Research (CIBMTR) and the European Society for Blood and Marrow Transplantation. CIBMTR is supported by grants from the U.S. government and the pharmaceutical industry. The authors reported having no competing financial interests.

SOURCE: Dreger P et al. Blood Adv. 2019 Feb 12;3(3):360-9.

For patients with diffuse large B-cell lymphoma (DLBCL) who need allogeneic hematopoietic cell transplantation (allo-HCT), a haploidentical family member could be a viable donor, according to a retrospective study of 1,438 patients.

Nephron/Wikimedia Commons/CC BY-SA 3.0

When combined with nonmyeloablative/reduced intensity conditioning (NMC/RIC) and posttransplant cyclophosphamide (PTCy), patients treated with haploidentical HCT (haplo-HCT) had outcomes similar to those seen in patients with matched donors, reported Peter Dreger, MD, of the University of Heidelberg (Germany) and his colleagues.

“Using well-matched sibling donors (MSDs) or unrelated donors (MUDs), allo-HCT can result in sustained disease control in 30% to 45% of patients with DLBCL who have early disease recurrence after standard chemoimmunotherapy or have failed auto-HCT [autologous HCT],” the investigators wrote in Blood Advances. “However, the search for a well-matched unrelated donor could be time-consuming and unsuccessful in up to 50% of the patients in need.”

But the present findings suggest that haplo-HCT may one day improve these odds by providing a larger pool of potential donors.

The patients in the study were divided into four treatment groups: haplo-HCT (n = 132), MSD (n = 525), MUD with T-cell depletion (n = 403), and MUD without T-cell depletion (n = 378). For graft-versus-host disease (GVHD) prophylaxis, patients in the haplo-HCT group received PTCy, with or without a calcineurin inhibitor and mycophenolate mofetil, whereas all patients with matched donors received a calcineurin inhibitor. T-cell depletion was accomplished by in vivo antithymocyte globulin and alemtuzumab.

The primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), progression/relapse, and nonrelapse mortality (NRM).

After a median follow-up of 4.1 years, all groups had similar outcomes, without statistical differences in multivariable analysis.

In the haplo-HCT group, the 3-year OS rate was 46%, the NRM rate was 22%, the PFS rate was 38%, and the relapse/progression rate was 41%.

Of note, patients receiving haplo-HCT did have a lower cumulative incidence of chronic GVHD, at 15% after 1 year and 18% after 2 years. These rates were significantly lower than the other groups’ 1- and 2-year GVHD rates, which were as follows: MSD, 41% and 48%; MUD with T-cell depletion, 23% and 27%; and MUD without T-cell depletion, 48% and 57%.

The investigators noted that these disparities may actually be caused by the use of bone marrow grafts in the haplo-HCT group instead of peripheral blood grafts, which were used in most of the patients in the other groups.

Overall, the findings were encouraging, but the investigators cautioned that “additional studies are needed before haploidentical donors can be considered as equivalent to well-matched related or unrelated donors in patients with DLBCL.”

The study was funded by the Center for International Blood & Marrow Transplant Research (CIBMTR) and the European Society for Blood and Marrow Transplantation. CIBMTR is supported by grants from the U.S. government and the pharmaceutical industry. The authors reported having no competing financial interests.

SOURCE: Dreger P et al. Blood Adv. 2019 Feb 12;3(3):360-9.

For patients with diffuse large B-cell lymphoma (DLBCL) who need allogeneic hematopoietic cell transplantation (allo-HCT), a haploidentical family member could be a viable donor, according to a retrospective study of 1,438 patients.

Nephron/Wikimedia Commons/CC BY-SA 3.0

When combined with nonmyeloablative/reduced intensity conditioning (NMC/RIC) and posttransplant cyclophosphamide (PTCy), patients treated with haploidentical HCT (haplo-HCT) had outcomes similar to those seen in patients with matched donors, reported Peter Dreger, MD, of the University of Heidelberg (Germany) and his colleagues.

“Using well-matched sibling donors (MSDs) or unrelated donors (MUDs), allo-HCT can result in sustained disease control in 30% to 45% of patients with DLBCL who have early disease recurrence after standard chemoimmunotherapy or have failed auto-HCT [autologous HCT],” the investigators wrote in Blood Advances. “However, the search for a well-matched unrelated donor could be time-consuming and unsuccessful in up to 50% of the patients in need.”

But the present findings suggest that haplo-HCT may one day improve these odds by providing a larger pool of potential donors.

The patients in the study were divided into four treatment groups: haplo-HCT (n = 132), MSD (n = 525), MUD with T-cell depletion (n = 403), and MUD without T-cell depletion (n = 378). For graft-versus-host disease (GVHD) prophylaxis, patients in the haplo-HCT group received PTCy, with or without a calcineurin inhibitor and mycophenolate mofetil, whereas all patients with matched donors received a calcineurin inhibitor. T-cell depletion was accomplished by in vivo antithymocyte globulin and alemtuzumab.

The primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), progression/relapse, and nonrelapse mortality (NRM).

After a median follow-up of 4.1 years, all groups had similar outcomes, without statistical differences in multivariable analysis.

In the haplo-HCT group, the 3-year OS rate was 46%, the NRM rate was 22%, the PFS rate was 38%, and the relapse/progression rate was 41%.

Of note, patients receiving haplo-HCT did have a lower cumulative incidence of chronic GVHD, at 15% after 1 year and 18% after 2 years. These rates were significantly lower than the other groups’ 1- and 2-year GVHD rates, which were as follows: MSD, 41% and 48%; MUD with T-cell depletion, 23% and 27%; and MUD without T-cell depletion, 48% and 57%.

The investigators noted that these disparities may actually be caused by the use of bone marrow grafts in the haplo-HCT group instead of peripheral blood grafts, which were used in most of the patients in the other groups.

Overall, the findings were encouraging, but the investigators cautioned that “additional studies are needed before haploidentical donors can be considered as equivalent to well-matched related or unrelated donors in patients with DLBCL.”

The study was funded by the Center for International Blood & Marrow Transplant Research (CIBMTR) and the European Society for Blood and Marrow Transplantation. CIBMTR is supported by grants from the U.S. government and the pharmaceutical industry. The authors reported having no competing financial interests.

SOURCE: Dreger P et al. Blood Adv. 2019 Feb 12;3(3):360-9.

SAN FRANCISCO – When used as first-line therapy for renal cell carcinoma (RCC), the combination of avelumab and axitinib has better efficacy than does single-agent sunitinib, which is the current standard of care, across a wide range of patients, subgroup analyses of the JAVELIN Renal 101 trial have shown. Results were reported at the 2019 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

Previous research had shown that avelumab (Bavencio), an immune checkpoint inhibitor targeting programmed death-ligand 1 (PD-L1), is active when used alone for advanced RCC, noted lead investigator Toni K. Choueiri, MD, director of the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute, Boston. And axitinib (Inlyta), a vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor, is approved for use in the second line. In an early-phase trial among patients being treated in the first line, a combination of the two drugs led to an impressive 58% objective response rate (ORR) and had a favorable safety profile (Lancet Oncol. 2018 Apr;19(4):451-60).

JAVELIN Renal 101 (NCT02684006), a phase 3 randomized, controlled trial, enrolled 886 patients with treatment-naive advanced RCC having a clear cell component regardless of their tumor’s PD-L1 status. They were randomized to the combination of avelumab/axitinib or to the VEGF tyrosine kinase inhibitor sunitinib (Sutent) alone.

Full trial results, published during the symposium in the New England Journal of Medicine (2019 Feb 16. doi: 10.1056/NEJMoa1816047), showed significant progression-free and overall survival benefits of avelumab/axitinib over sunitinib in the 63.2% of patients with PD-L1–positive tumors – the trial’s primary endpoints – as well as a progression-free survival benefit in the entire trial population.

In the subgroup analyses reported at the symposium, the combination reduced risk of progression or death by roughly 20%-50% across patients having different statuses in regard to International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group, Memorial Sloan Kettering Cancer Center (MSKCC) risk group, and tumor PD-L1, as well as other characteristics. Findings were similar for ORR, with the combination roughly doubling to quadrupling the odds of response, irrespective of patient and disease characteristics.

“The progression-free survival and response rate benefit was observed in all patients, regardless of PD-L1 status, regardless of prognostic risk group. At this time, the study continues to follow up for overall survival,” Dr. Choueiri commented. Taken together, “the results do support avelumab plus axitinib as a new first-line standard of care for patients with advanced RCC.”

When it comes to selecting among the three combinations above, “I don’t think PD-L1 expression is going to help us at all,” she said. In contrast, IMDC risk category is likely still helpful because, in CheckMate 214, there was no progression-free or overall survival benefit of ipilimumab/nivolumab in patients with favorable-risk disease.

Differences in rates of discontinuation of all treatment because of treatment-related adverse events are hard to assess because CheckMate 214 had restrictions on allowing patients in the combination group to receive single-agent nivolumab, according to Dr. Wood. Financial costs are a major consideration, but so are time and staffing costs: Compared with single-agent sunitinib, the combinations as much as triple physician visits, nurse visits, infusions, and unscheduled visits.

SOURCE: Choueiri TK et al. GUCS 2019, Abstract 544.

SAN FRANCISCO – When used as first-line therapy for renal cell carcinoma (RCC), the combination of avelumab and axitinib has better efficacy than does single-agent sunitinib, which is the current standard of care, across a wide range of patients, subgroup analyses of the JAVELIN Renal 101 trial have shown. Results were reported at the 2019 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

Previous research had shown that avelumab (Bavencio), an immune checkpoint inhibitor targeting programmed death-ligand 1 (PD-L1), is active when used alone for advanced RCC, noted lead investigator Toni K. Choueiri, MD, director of the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute, Boston. And axitinib (Inlyta), a vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor, is approved for use in the second line. In an early-phase trial among patients being treated in the first line, a combination of the two drugs led to an impressive 58% objective response rate (ORR) and had a favorable safety profile (Lancet Oncol. 2018 Apr;19(4):451-60).

JAVELIN Renal 101 (NCT02684006), a phase 3 randomized, controlled trial, enrolled 886 patients with treatment-naive advanced RCC having a clear cell component regardless of their tumor’s PD-L1 status. They were randomized to the combination of avelumab/axitinib or to the VEGF tyrosine kinase inhibitor sunitinib (Sutent) alone.

Full trial results, published during the symposium in the New England Journal of Medicine (2019 Feb 16. doi: 10.1056/NEJMoa1816047), showed significant progression-free and overall survival benefits of avelumab/axitinib over sunitinib in the 63.2% of patients with PD-L1–positive tumors – the trial’s primary endpoints – as well as a progression-free survival benefit in the entire trial population.

In the subgroup analyses reported at the symposium, the combination reduced risk of progression or death by roughly 20%-50% across patients having different statuses in regard to International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group, Memorial Sloan Kettering Cancer Center (MSKCC) risk group, and tumor PD-L1, as well as other characteristics. Findings were similar for ORR, with the combination roughly doubling to quadrupling the odds of response, irrespective of patient and disease characteristics.

“The progression-free survival and response rate benefit was observed in all patients, regardless of PD-L1 status, regardless of prognostic risk group. At this time, the study continues to follow up for overall survival,” Dr. Choueiri commented. Taken together, “the results do support avelumab plus axitinib as a new first-line standard of care for patients with advanced RCC.”

When it comes to selecting among the three combinations above, “I don’t think PD-L1 expression is going to help us at all,” she said. In contrast, IMDC risk category is likely still helpful because, in CheckMate 214, there was no progression-free or overall survival benefit of ipilimumab/nivolumab in patients with favorable-risk disease.

Differences in rates of discontinuation of all treatment because of treatment-related adverse events are hard to assess because CheckMate 214 had restrictions on allowing patients in the combination group to receive single-agent nivolumab, according to Dr. Wood. Financial costs are a major consideration, but so are time and staffing costs: Compared with single-agent sunitinib, the combinations as much as triple physician visits, nurse visits, infusions, and unscheduled visits.

SOURCE: Choueiri TK et al. GUCS 2019, Abstract 544.

SAN FRANCISCO – When used as first-line therapy for renal cell carcinoma (RCC), the combination of avelumab and axitinib has better efficacy than does single-agent sunitinib, which is the current standard of care, across a wide range of patients, subgroup analyses of the JAVELIN Renal 101 trial have shown. Results were reported at the 2019 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

Previous research had shown that avelumab (Bavencio), an immune checkpoint inhibitor targeting programmed death-ligand 1 (PD-L1), is active when used alone for advanced RCC, noted lead investigator Toni K. Choueiri, MD, director of the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute, Boston. And axitinib (Inlyta), a vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor, is approved for use in the second line. In an early-phase trial among patients being treated in the first line, a combination of the two drugs led to an impressive 58% objective response rate (ORR) and had a favorable safety profile (Lancet Oncol. 2018 Apr;19(4):451-60).

JAVELIN Renal 101 (NCT02684006), a phase 3 randomized, controlled trial, enrolled 886 patients with treatment-naive advanced RCC having a clear cell component regardless of their tumor’s PD-L1 status. They were randomized to the combination of avelumab/axitinib or to the VEGF tyrosine kinase inhibitor sunitinib (Sutent) alone.

Full trial results, published during the symposium in the New England Journal of Medicine (2019 Feb 16. doi: 10.1056/NEJMoa1816047), showed significant progression-free and overall survival benefits of avelumab/axitinib over sunitinib in the 63.2% of patients with PD-L1–positive tumors – the trial’s primary endpoints – as well as a progression-free survival benefit in the entire trial population.

In the subgroup analyses reported at the symposium, the combination reduced risk of progression or death by roughly 20%-50% across patients having different statuses in regard to International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group, Memorial Sloan Kettering Cancer Center (MSKCC) risk group, and tumor PD-L1, as well as other characteristics. Findings were similar for ORR, with the combination roughly doubling to quadrupling the odds of response, irrespective of patient and disease characteristics.

“The progression-free survival and response rate benefit was observed in all patients, regardless of PD-L1 status, regardless of prognostic risk group. At this time, the study continues to follow up for overall survival,” Dr. Choueiri commented. Taken together, “the results do support avelumab plus axitinib as a new first-line standard of care for patients with advanced RCC.”

When it comes to selecting among the three combinations above, “I don’t think PD-L1 expression is going to help us at all,” she said. In contrast, IMDC risk category is likely still helpful because, in CheckMate 214, there was no progression-free or overall survival benefit of ipilimumab/nivolumab in patients with favorable-risk disease.

Differences in rates of discontinuation of all treatment because of treatment-related adverse events are hard to assess because CheckMate 214 had restrictions on allowing patients in the combination group to receive single-agent nivolumab, according to Dr. Wood. Financial costs are a major consideration, but so are time and staffing costs: Compared with single-agent sunitinib, the combinations as much as triple physician visits, nurse visits, infusions, and unscheduled visits.

SOURCE: Choueiri TK et al. GUCS 2019, Abstract 544.

In this episode, Daniel G. Haller, MD, of the University of Pennsylvania joins David H. Henry, MD, to talk about the best ways to read and review scientific literature.
And Ilana Yurkiewicz, MD, talks about chaos and opportunity. Dr. Yurkiewicz is a fellow in hematology and oncology at Stanford (Calif.) University and is also a columnist for Hematology News. More from Dr. Yurkiewicz here.

Subscribe to Blood & Cancer here:

Apple Podcasts
Google Podcasts

Show notes
By Hitomi Hosoya, MD, PhD,
Resident in the department of internal medicine, University of Pennsylvania Health System

- If you are a peer reviewer of a manuscript submitted to a journal, you should be unbiased, consistent, constructive, and focused on the research. COPE guideline is a good resource.

- If you are a reader of a published article, it is important to ensure that the abstract has the same conclusion as the body of the article. 

- If you are a clinical practitioner and wondering how to apply findings of published data, the editorial section is a good source.

- If you are a trainee and wondering how to stay up-to-date, Oxford Textbook of Oncology or ASCO University are recommended.

Reference:

https://publicationethics.org/resources/guidelines-new/cope-ethical-guidelines-peer-reviewers

In this episode, Daniel G. Haller, MD, of the University of Pennsylvania joins David H. Henry, MD, to talk about the best ways to read and review scientific literature.
And Ilana Yurkiewicz, MD, talks about chaos and opportunity. Dr. Yurkiewicz is a fellow in hematology and oncology at Stanford (Calif.) University and is also a columnist for Hematology News. More from Dr. Yurkiewicz here.

Subscribe to Blood & Cancer here:

Apple Podcasts
Google Podcasts

Show notes
By Hitomi Hosoya, MD, PhD,
Resident in the department of internal medicine, University of Pennsylvania Health System

- If you are a peer reviewer of a manuscript submitted to a journal, you should be unbiased, consistent, constructive, and focused on the research. COPE guideline is a good resource.

- If you are a reader of a published article, it is important to ensure that the abstract has the same conclusion as the body of the article. 

- If you are a clinical practitioner and wondering how to apply findings of published data, the editorial section is a good source.

- If you are a trainee and wondering how to stay up-to-date, Oxford Textbook of Oncology or ASCO University are recommended.

Reference:

https://publicationethics.org/resources/guidelines-new/cope-ethical-guidelines-peer-reviewers

In this episode, Daniel G. Haller, MD, of the University of Pennsylvania joins David H. Henry, MD, to talk about the best ways to read and review scientific literature.
And Ilana Yurkiewicz, MD, talks about chaos and opportunity. Dr. Yurkiewicz is a fellow in hematology and oncology at Stanford (Calif.) University and is also a columnist for Hematology News. More from Dr. Yurkiewicz here.

Subscribe to Blood & Cancer here:

Apple Podcasts
Google Podcasts

Show notes
By Hitomi Hosoya, MD, PhD,
Resident in the department of internal medicine, University of Pennsylvania Health System

- If you are a peer reviewer of a manuscript submitted to a journal, you should be unbiased, consistent, constructive, and focused on the research. COPE guideline is a good resource.

- If you are a reader of a published article, it is important to ensure that the abstract has the same conclusion as the body of the article. 

- If you are a clinical practitioner and wondering how to apply findings of published data, the editorial section is a good source.

- If you are a trainee and wondering how to stay up-to-date, Oxford Textbook of Oncology or ASCO University are recommended.

Reference:

https://publicationethics.org/resources/guidelines-new/cope-ethical-guidelines-peer-reviewers

While treatment with rivaroxaban did not significantly reduce venous thromboembolism incidence in high-risk ambulatory patients with cancer over the entire course of a 180-day intervention period (6.0% vs. 8.8% in controls; hazard ratio, 0.66; 95% confidence interval, 0.40-1.09), it did reduce major bleeding incidence while patients were on treatment (2.0% vs. 6.4%; HR, 0.40; 95% CI, 0.20 0.80), according to results from the multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3b CASSINI trial published in the New England Journal of Medicine (2019 Feb 20. doi: 10.1056/NEJMoa1814630).

We reported this story at the annual meeting of the American Society of Hematology before it was published in the journal. Find our coverage at the link below.

lfranki@mdedge.com

While treatment with rivaroxaban did not significantly reduce venous thromboembolism incidence in high-risk ambulatory patients with cancer over the entire course of a 180-day intervention period (6.0% vs. 8.8% in controls; hazard ratio, 0.66; 95% confidence interval, 0.40-1.09), it did reduce major bleeding incidence while patients were on treatment (2.0% vs. 6.4%; HR, 0.40; 95% CI, 0.20 0.80), according to results from the multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3b CASSINI trial published in the New England Journal of Medicine (2019 Feb 20. doi: 10.1056/NEJMoa1814630).

We reported this story at the annual meeting of the American Society of Hematology before it was published in the journal. Find our coverage at the link below.

lfranki@mdedge.com

While treatment with rivaroxaban did not significantly reduce venous thromboembolism incidence in high-risk ambulatory patients with cancer over the entire course of a 180-day intervention period (6.0% vs. 8.8% in controls; hazard ratio, 0.66; 95% confidence interval, 0.40-1.09), it did reduce major bleeding incidence while patients were on treatment (2.0% vs. 6.4%; HR, 0.40; 95% CI, 0.20 0.80), according to results from the multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3b CASSINI trial published in the New England Journal of Medicine (2019 Feb 20. doi: 10.1056/NEJMoa1814630).

We reported this story at the annual meeting of the American Society of Hematology before it was published in the journal. Find our coverage at the link below.

lfranki@mdedge.com

Researchers say they have characterized a subtype of diffuse large B-cell lymphoma (DLBCL) with distinct molecular features and poor prognosis.

Patients with this subtype, dubbed “molecular high-grade” (MHG) DLBCL, were more likely to have germinal center B-cell-like (GCB) DLBCL, MYC rearrangements, and double-hit lymphoma.

When compared to other DLBCL patients, those with MHG DLBCL had inferior progression-free and overall survival.

Chulin Sha, PhD, of the University of Leeds (England), and colleagues reported these findings in the Journal of Clinical Oncology. The findings were published alongside a related editorial and a similar study from another group.

Dr. Sha and colleagues began their study by applying a previously developed gene expression classifier (Genome Med. 2015 Jul 1;7[1]:64) to 928 DLBCL patients enrolled in the REMoDL-B trial. REMoDL-B was designed to compare rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) to R-CHOP plus bortezomib (Hematol Oncol. 2017;35:130-1).

Dr. Sha and colleagues looked for somatic mutations in 400 REMoDL-B patient samples that were sequenced for a 70-gene panel.

The team also tested 360 samples for MYC, BCL2, and BCL6 chromosomal rearrangements using fluorescent in situ hybridization, and they tested 355 samples for MYC and BCL2 protein expression with immunohistochemistry.

Characteristics of MHG DLBCL

The researchers identified 83 REMoDL-B patients as having MHG DLBCL (9%). Most of the MHG patients had GCB DLBCL (90%), 48.6% had MYC rearrangements, and 36.1% had double-hit lymphoma.

Patients with MHG DLBCL had higher International Prognostic Index scores (P = .004), greater tumor bulk (P = .007), higher disease stage (P = .06), and higher lactate dehydrogenase levels (P less than .001) than patients with non-MHG DLBCL.

Although most MHG patients had GCB DLBCL, the researchers found key differences between patients with MHG DLBCL and non-MHG GCB DLBCL. MHG patients were significantly more likely than patients with non-MHG GCB DLBCL to have mutations in KMT2D, BCL2, MYC, and DDX3X. Additionally, some genes frequently mutated in GCB DLBCL — such as B2M, SGK1, and NFKBIA — were rare in MHG DLBCL.

Dr. Sha and colleagues also compared the MHG patients to 70 patients with Burkitt lymphoma (BL) who had been analyzed in a previous study (Genome Med. 2015 Jul 1;7[1]:64).

The researchers found that BL has more upregulated genes than GCB (2,483 genes) and MHG DLBCL (1,784 genes), and MHG DLBCL has more upregulated genes than GCB DLBCL (382 genes). The team observed a similar pattern with downregulated genes and said this suggests “MHG is an intermediate group but closer to GCB than to BL.”

• 37% for MHG patients
• 78% for patients with GCB DLBCL
• 64% for patients with activated B-cell like (ABC) DLBCL
• 65% for patients with unclassified DLBCL.

Among patients who received bortezomib plus R-CHOP, there was a trend toward improved PFS for patients with MHG DLBCL (58%; P = .08).

Validation cohort

Dr. Sha and colleagues validated their initial findings using RNA sequencing data from another group of DLBCL patients (Cell. 2017 Oct 5;171[2]:481-94.e15). This data set included 624 patients who received rituximab-based therapy.

Seventy-two patients in this group had MHG DLBCL (11.5%), and most MHG patients had GCB DLBCL (82%).

The researchers said the MHG group in this cohort “showed similar associations with clinical variables” and a “similar mutation spectrum” as the MHG group in the REMoDL-B cohort. Additionally, MHG patients in the validation cohort had inferior overall survival (P less than .001) compared to patients with non-MHG GCB DLBCL.

Dr. Sha and colleagues said the poor prognosis in MHG patients in both cohorts suggests a need for different treatment approaches in this group.

In the related editorial, Wing C. Chan, MD, of City of Hope Medical Center in Duarte, Calif., echoed that sentiment and said it will be important to include patients with high-risk DLBCL in clinical trials.

“Their tumors should be comprehensively characterize[d] for correlative analysis to determine the molecular lesions that underlie their biology and response to treatment,” Dr. Chan wrote.

Dr. Chan disclosed a patent for a diagnostic algorithm on GCB/ABC-type DLBCL and a patent on a diagnostic algorithm for peripheral T-cell lymphoma.

Dr. Sha and colleagues disclosed relationships with a range of pharmaceutical companies. The team’s research was supported by a grant from Bloodwise.

The REMoDL-B trial was endorsed by Cancer Research UK and was funded by Janssen-Cillag.

jensmith@mdedge.com

SOURCES: Sha C et al. J Clin Oncol. 2019 Jan 20;37(3):202-12. doi: 10.1200/JCO.18.01314; Chan WC. J Clin Oncol. 2019 Jan 20;37(3):175-7. doi: 10.1200/JCO.18.01910; Ennishi D et al. J Clin Oncol. 2019 Jan 20;37(3):190-201. doi: 10.1200/JCO.18.01583

Researchers say they have characterized a subtype of diffuse large B-cell lymphoma (DLBCL) with distinct molecular features and poor prognosis.

Patients with this subtype, dubbed “molecular high-grade” (MHG) DLBCL, were more likely to have germinal center B-cell-like (GCB) DLBCL, MYC rearrangements, and double-hit lymphoma.

When compared to other DLBCL patients, those with MHG DLBCL had inferior progression-free and overall survival.

Chulin Sha, PhD, of the University of Leeds (England), and colleagues reported these findings in the Journal of Clinical Oncology. The findings were published alongside a related editorial and a similar study from another group.

Dr. Sha and colleagues began their study by applying a previously developed gene expression classifier (Genome Med. 2015 Jul 1;7[1]:64) to 928 DLBCL patients enrolled in the REMoDL-B trial. REMoDL-B was designed to compare rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) to R-CHOP plus bortezomib (Hematol Oncol. 2017;35:130-1).

Dr. Sha and colleagues looked for somatic mutations in 400 REMoDL-B patient samples that were sequenced for a 70-gene panel.

The team also tested 360 samples for MYC, BCL2, and BCL6 chromosomal rearrangements using fluorescent in situ hybridization, and they tested 355 samples for MYC and BCL2 protein expression with immunohistochemistry.

Characteristics of MHG DLBCL

The researchers identified 83 REMoDL-B patients as having MHG DLBCL (9%). Most of the MHG patients had GCB DLBCL (90%), 48.6% had MYC rearrangements, and 36.1% had double-hit lymphoma.

Patients with MHG DLBCL had higher International Prognostic Index scores (P = .004), greater tumor bulk (P = .007), higher disease stage (P = .06), and higher lactate dehydrogenase levels (P less than .001) than patients with non-MHG DLBCL.

Although most MHG patients had GCB DLBCL, the researchers found key differences between patients with MHG DLBCL and non-MHG GCB DLBCL. MHG patients were significantly more likely than patients with non-MHG GCB DLBCL to have mutations in KMT2D, BCL2, MYC, and DDX3X. Additionally, some genes frequently mutated in GCB DLBCL — such as B2M, SGK1, and NFKBIA — were rare in MHG DLBCL.

Dr. Sha and colleagues also compared the MHG patients to 70 patients with Burkitt lymphoma (BL) who had been analyzed in a previous study (Genome Med. 2015 Jul 1;7[1]:64).

The researchers found that BL has more upregulated genes than GCB (2,483 genes) and MHG DLBCL (1,784 genes), and MHG DLBCL has more upregulated genes than GCB DLBCL (382 genes). The team observed a similar pattern with downregulated genes and said this suggests “MHG is an intermediate group but closer to GCB than to BL.”

• 37% for MHG patients
• 78% for patients with GCB DLBCL
• 64% for patients with activated B-cell like (ABC) DLBCL
• 65% for patients with unclassified DLBCL.

Among patients who received bortezomib plus R-CHOP, there was a trend toward improved PFS for patients with MHG DLBCL (58%; P = .08).

Validation cohort

Dr. Sha and colleagues validated their initial findings using RNA sequencing data from another group of DLBCL patients (Cell. 2017 Oct 5;171[2]:481-94.e15). This data set included 624 patients who received rituximab-based therapy.

Seventy-two patients in this group had MHG DLBCL (11.5%), and most MHG patients had GCB DLBCL (82%).

The researchers said the MHG group in this cohort “showed similar associations with clinical variables” and a “similar mutation spectrum” as the MHG group in the REMoDL-B cohort. Additionally, MHG patients in the validation cohort had inferior overall survival (P less than .001) compared to patients with non-MHG GCB DLBCL.

Dr. Sha and colleagues said the poor prognosis in MHG patients in both cohorts suggests a need for different treatment approaches in this group.

In the related editorial, Wing C. Chan, MD, of City of Hope Medical Center in Duarte, Calif., echoed that sentiment and said it will be important to include patients with high-risk DLBCL in clinical trials.

“Their tumors should be comprehensively characterize[d] for correlative analysis to determine the molecular lesions that underlie their biology and response to treatment,” Dr. Chan wrote.

Dr. Chan disclosed a patent for a diagnostic algorithm on GCB/ABC-type DLBCL and a patent on a diagnostic algorithm for peripheral T-cell lymphoma.

Dr. Sha and colleagues disclosed relationships with a range of pharmaceutical companies. The team’s research was supported by a grant from Bloodwise.

The REMoDL-B trial was endorsed by Cancer Research UK and was funded by Janssen-Cillag.

jensmith@mdedge.com

SOURCES: Sha C et al. J Clin Oncol. 2019 Jan 20;37(3):202-12. doi: 10.1200/JCO.18.01314; Chan WC. J Clin Oncol. 2019 Jan 20;37(3):175-7. doi: 10.1200/JCO.18.01910; Ennishi D et al. J Clin Oncol. 2019 Jan 20;37(3):190-201. doi: 10.1200/JCO.18.01583

Researchers say they have characterized a subtype of diffuse large B-cell lymphoma (DLBCL) with distinct molecular features and poor prognosis.

Patients with this subtype, dubbed “molecular high-grade” (MHG) DLBCL, were more likely to have germinal center B-cell-like (GCB) DLBCL, MYC rearrangements, and double-hit lymphoma.

When compared to other DLBCL patients, those with MHG DLBCL had inferior progression-free and overall survival.

Chulin Sha, PhD, of the University of Leeds (England), and colleagues reported these findings in the Journal of Clinical Oncology. The findings were published alongside a related editorial and a similar study from another group.

Dr. Sha and colleagues began their study by applying a previously developed gene expression classifier (Genome Med. 2015 Jul 1;7[1]:64) to 928 DLBCL patients enrolled in the REMoDL-B trial. REMoDL-B was designed to compare rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) to R-CHOP plus bortezomib (Hematol Oncol. 2017;35:130-1).

Dr. Sha and colleagues looked for somatic mutations in 400 REMoDL-B patient samples that were sequenced for a 70-gene panel.

The team also tested 360 samples for MYC, BCL2, and BCL6 chromosomal rearrangements using fluorescent in situ hybridization, and they tested 355 samples for MYC and BCL2 protein expression with immunohistochemistry.

Characteristics of MHG DLBCL

The researchers identified 83 REMoDL-B patients as having MHG DLBCL (9%). Most of the MHG patients had GCB DLBCL (90%), 48.6% had MYC rearrangements, and 36.1% had double-hit lymphoma.

Patients with MHG DLBCL had higher International Prognostic Index scores (P = .004), greater tumor bulk (P = .007), higher disease stage (P = .06), and higher lactate dehydrogenase levels (P less than .001) than patients with non-MHG DLBCL.

Although most MHG patients had GCB DLBCL, the researchers found key differences between patients with MHG DLBCL and non-MHG GCB DLBCL. MHG patients were significantly more likely than patients with non-MHG GCB DLBCL to have mutations in KMT2D, BCL2, MYC, and DDX3X. Additionally, some genes frequently mutated in GCB DLBCL — such as B2M, SGK1, and NFKBIA — were rare in MHG DLBCL.

Dr. Sha and colleagues also compared the MHG patients to 70 patients with Burkitt lymphoma (BL) who had been analyzed in a previous study (Genome Med. 2015 Jul 1;7[1]:64).

The researchers found that BL has more upregulated genes than GCB (2,483 genes) and MHG DLBCL (1,784 genes), and MHG DLBCL has more upregulated genes than GCB DLBCL (382 genes). The team observed a similar pattern with downregulated genes and said this suggests “MHG is an intermediate group but closer to GCB than to BL.”

• 37% for MHG patients
• 78% for patients with GCB DLBCL
• 64% for patients with activated B-cell like (ABC) DLBCL
• 65% for patients with unclassified DLBCL.

Among patients who received bortezomib plus R-CHOP, there was a trend toward improved PFS for patients with MHG DLBCL (58%; P = .08).

Validation cohort

Dr. Sha and colleagues validated their initial findings using RNA sequencing data from another group of DLBCL patients (Cell. 2017 Oct 5;171[2]:481-94.e15). This data set included 624 patients who received rituximab-based therapy.

Seventy-two patients in this group had MHG DLBCL (11.5%), and most MHG patients had GCB DLBCL (82%).

The researchers said the MHG group in this cohort “showed similar associations with clinical variables” and a “similar mutation spectrum” as the MHG group in the REMoDL-B cohort. Additionally, MHG patients in the validation cohort had inferior overall survival (P less than .001) compared to patients with non-MHG GCB DLBCL.

Dr. Sha and colleagues said the poor prognosis in MHG patients in both cohorts suggests a need for different treatment approaches in this group.

In the related editorial, Wing C. Chan, MD, of City of Hope Medical Center in Duarte, Calif., echoed that sentiment and said it will be important to include patients with high-risk DLBCL in clinical trials.

“Their tumors should be comprehensively characterize[d] for correlative analysis to determine the molecular lesions that underlie their biology and response to treatment,” Dr. Chan wrote.

Dr. Chan disclosed a patent for a diagnostic algorithm on GCB/ABC-type DLBCL and a patent on a diagnostic algorithm for peripheral T-cell lymphoma.

Dr. Sha and colleagues disclosed relationships with a range of pharmaceutical companies. The team’s research was supported by a grant from Bloodwise.

The REMoDL-B trial was endorsed by Cancer Research UK and was funded by Janssen-Cillag.

jensmith@mdedge.com

SOURCES: Sha C et al. J Clin Oncol. 2019 Jan 20;37(3):202-12. doi: 10.1200/JCO.18.01314; Chan WC. J Clin Oncol. 2019 Jan 20;37(3):175-7. doi: 10.1200/JCO.18.01910; Ennishi D et al. J Clin Oncol. 2019 Jan 20;37(3):190-201. doi: 10.1200/JCO.18.01583

LONDON – A concerted effort is needed by everyone to address gender inequality in science and medicine, a group of prominent female physicians and thought-leaders said at a recent event hosted by The Lancet.

Sara Freeman/MDedge News

“Gender equality is everyone’s business,” Sarah Hawkes, MBBS, PhD, a professor of global public health at University College London (England), said at the event.

“We’re not talking about women taking over the shop, but women being given an equal opportunity to run the shop. It doesn’t matter where we place ourselves on the gender spectrum as far as advancing equality in science is concerned. What matters is that we all, irrespective of gender, call ourselves feminists.”

For years, women have been “underrepresented in positions of power and leadership, undervalued, and experience discrimination and gender-based violence in scientific and health disciplines across the world,” according to an editorial in the British-based journal (Lancet. 2019;393:493). Such inequalities are compounded and hard to separate from other inequalities, including ethnicity, disability, class, geography, and sexuality.

Despite efforts to readdress the predominantly male culture of medicine, the problem of gender inequality remains “stubbornly persistent,” the editorial said.

“We have spent years being told that the problem lies with us as individuals and that we just need to be better, stronger, more vocal, as women,” Dr. Hawkes observed. “But what really needs to happen is for change to happen in places that hold power.” She further argued: “We don’t need any more individual change; we need organizational and institutional norm change.”

Gender inequality has a long history, and not just in medicine, said British journalist Caroline Criado-Perez OBE, who gave a keynote speech. Ms. Criado-Perez, who is a well-respected feminist campaigner, noted that the world was largely “modeled to fit men.” From architecture to transport, and even crash-test dummies, everything was largely modeled on, or to accommodate, the male rather than the female body.

“I don’t need to tell you that women are 50% more likely to be misdiagnosed following a heart attack” than men. There is no more urgent need to challenge gender inequality than in medicine, Women are dying because of the gender data gap in medicine,” she asserted. “In medical research, in medical education, in medical practice, it needs to be closed as a matter of urgency.”

Original data published in the Advancing Women in Science, Medicine and Global Health special edition of The Lancet found that only 31% of biomedical research papers published in 2016 reported outcomes for both men and women (Lancet. 2019;393:550-9). Reporting of sex differences was somewhat better in clinical or public health-related research papers, at 67% and 69%, respectively. Sex-differences were more likely to be reported if a woman was one of the key authors, Cassidy R. Sugimoto, PhD, associate professor of informatics at Indiana University in Bloomington, and associates, observed in their paper.

That said, women often have to fight to be included as an author on a paper, even when they have done the majority of the work, the event participants highlighted. Women were still less likely than men to be named as the first or last author on a paper, as well as be less likely to receive research funding to enable them to do the work in the first place (Lancet. 2018;393:531-40).

“Was it really you?” was a question sometimes asked of a woman named as a lead or first author, noted Sonia Gandhi, MD, PhD, group leader of the Neurodegeneration Biology Laboratory at the Francis Crick Institute in Cambridge (England). Women network differently to men, Dr. Gandhi observed, and not necessarily in networks that forward careers. Women were also often questioned about their productivity, and regardless of any training on unconscious bias, women were still at a disadvantage if they took a career break to have children.

Female representation is so important, said F. Gigi Osler, MD, head of otolaryngology-head and neck surgery at St. Boniface Hospital in Winnipeg. Dr. Osler is the 2018-2019 president of the Canadian Medical Association, the eighth woman to hold this prestigious position in the organization’s 151 years of operation. She also happens to be the first female surgeon and the first woman of color in the role. “When I stepped into the presidency last August, I thought very long and very hard about how I was going to use my voice and this platform,” Dr. Osler said. “It became very clear to me after I started how important representation was. I can’t tell you how many women, young women, and women of color...have come up to me to say, ‘I’m so excited to have you in this position. I’ve never seen someone who looks like me in that type of leadership position,’ ” she observed.

“As leaders, I think we can advocate for structures and processes,” Dr. Osler added, “I think we set the culture.” Leaders have the responsibility for creating and nurturing and fostering a professional, respectful, and inclusive environment, she said.

“We need more strong leaders, we need more diversity in leadership.” Dr. Osler was keen to point out that greater diversity does not mean only women, but other groups as well. “Look around the room. Who is not here? How can I make it easier for them to get here?”

Another strong female role model at the event was Dame Sally Davies, the Chief Medical Officer for England, a hematologist by training. Not only is she the first female in that role, she will also become the first female Master of Trinity College Cambridge starting in October 2019, a role dominated by men for more than 500 years.

All people, women and men, need to be given fair opportunity, Dame Sally said. Addressing structural issues can help, she said. “We need role models, mentors, and champions,” she said, noting that there were differences between the three. “Mentors give you advice, they get to know you, and they help you think through your issue. Champions may not have time for that, but they know you are good,” and they are putting you forward for opportunities.

“If the system isn’t right, or we are treated badly, we need to call it out,” Dame Sally said. “I do think that we often let things pass that we shouldn’t.” A classic situation is where a woman may suggest something at a meeting and it is ignored, but when a man says the same thing it is taken on board. That kind of behavior needs to stop and be addressed when it happens, by everyone at the table, she said.

Dr. Hawkes observed in her summing up of the day: “Throughout the history of health, change comes about not just through action at the top, but also from action from the bottom up.” She added: “The question is how do we make that change happen?” That’s where the next phase of research needs to take place, she suggested, “we need to actually see, in a very evidence-informed way, what actually works to make and sustain change.”

No financial disclosures were reported by any of the speakers quoted.

SOURCE: Lancet. 2019;393:493–610, e6-e28

LONDON – A concerted effort is needed by everyone to address gender inequality in science and medicine, a group of prominent female physicians and thought-leaders said at a recent event hosted by The Lancet.

Sara Freeman/MDedge News

“Gender equality is everyone’s business,” Sarah Hawkes, MBBS, PhD, a professor of global public health at University College London (England), said at the event.

“We’re not talking about women taking over the shop, but women being given an equal opportunity to run the shop. It doesn’t matter where we place ourselves on the gender spectrum as far as advancing equality in science is concerned. What matters is that we all, irrespective of gender, call ourselves feminists.”

For years, women have been “underrepresented in positions of power and leadership, undervalued, and experience discrimination and gender-based violence in scientific and health disciplines across the world,” according to an editorial in the British-based journal (Lancet. 2019;393:493). Such inequalities are compounded and hard to separate from other inequalities, including ethnicity, disability, class, geography, and sexuality.

Despite efforts to readdress the predominantly male culture of medicine, the problem of gender inequality remains “stubbornly persistent,” the editorial said.

“We have spent years being told that the problem lies with us as individuals and that we just need to be better, stronger, more vocal, as women,” Dr. Hawkes observed. “But what really needs to happen is for change to happen in places that hold power.” She further argued: “We don’t need any more individual change; we need organizational and institutional norm change.”

Gender inequality has a long history, and not just in medicine, said British journalist Caroline Criado-Perez OBE, who gave a keynote speech. Ms. Criado-Perez, who is a well-respected feminist campaigner, noted that the world was largely “modeled to fit men.” From architecture to transport, and even crash-test dummies, everything was largely modeled on, or to accommodate, the male rather than the female body.

“I don’t need to tell you that women are 50% more likely to be misdiagnosed following a heart attack” than men. There is no more urgent need to challenge gender inequality than in medicine, Women are dying because of the gender data gap in medicine,” she asserted. “In medical research, in medical education, in medical practice, it needs to be closed as a matter of urgency.”

Original data published in the Advancing Women in Science, Medicine and Global Health special edition of The Lancet found that only 31% of biomedical research papers published in 2016 reported outcomes for both men and women (Lancet. 2019;393:550-9). Reporting of sex differences was somewhat better in clinical or public health-related research papers, at 67% and 69%, respectively. Sex-differences were more likely to be reported if a woman was one of the key authors, Cassidy R. Sugimoto, PhD, associate professor of informatics at Indiana University in Bloomington, and associates, observed in their paper.

That said, women often have to fight to be included as an author on a paper, even when they have done the majority of the work, the event participants highlighted. Women were still less likely than men to be named as the first or last author on a paper, as well as be less likely to receive research funding to enable them to do the work in the first place (Lancet. 2018;393:531-40).

“Was it really you?” was a question sometimes asked of a woman named as a lead or first author, noted Sonia Gandhi, MD, PhD, group leader of the Neurodegeneration Biology Laboratory at the Francis Crick Institute in Cambridge (England). Women network differently to men, Dr. Gandhi observed, and not necessarily in networks that forward careers. Women were also often questioned about their productivity, and regardless of any training on unconscious bias, women were still at a disadvantage if they took a career break to have children.

Female representation is so important, said F. Gigi Osler, MD, head of otolaryngology-head and neck surgery at St. Boniface Hospital in Winnipeg. Dr. Osler is the 2018-2019 president of the Canadian Medical Association, the eighth woman to hold this prestigious position in the organization’s 151 years of operation. She also happens to be the first female surgeon and the first woman of color in the role. “When I stepped into the presidency last August, I thought very long and very hard about how I was going to use my voice and this platform,” Dr. Osler said. “It became very clear to me after I started how important representation was. I can’t tell you how many women, young women, and women of color...have come up to me to say, ‘I’m so excited to have you in this position. I’ve never seen someone who looks like me in that type of leadership position,’ ” she observed.

“As leaders, I think we can advocate for structures and processes,” Dr. Osler added, “I think we set the culture.” Leaders have the responsibility for creating and nurturing and fostering a professional, respectful, and inclusive environment, she said.

“We need more strong leaders, we need more diversity in leadership.” Dr. Osler was keen to point out that greater diversity does not mean only women, but other groups as well. “Look around the room. Who is not here? How can I make it easier for them to get here?”

Another strong female role model at the event was Dame Sally Davies, the Chief Medical Officer for England, a hematologist by training. Not only is she the first female in that role, she will also become the first female Master of Trinity College Cambridge starting in October 2019, a role dominated by men for more than 500 years.

All people, women and men, need to be given fair opportunity, Dame Sally said. Addressing structural issues can help, she said. “We need role models, mentors, and champions,” she said, noting that there were differences between the three. “Mentors give you advice, they get to know you, and they help you think through your issue. Champions may not have time for that, but they know you are good,” and they are putting you forward for opportunities.

“If the system isn’t right, or we are treated badly, we need to call it out,” Dame Sally said. “I do think that we often let things pass that we shouldn’t.” A classic situation is where a woman may suggest something at a meeting and it is ignored, but when a man says the same thing it is taken on board. That kind of behavior needs to stop and be addressed when it happens, by everyone at the table, she said.

Dr. Hawkes observed in her summing up of the day: “Throughout the history of health, change comes about not just through action at the top, but also from action from the bottom up.” She added: “The question is how do we make that change happen?” That’s where the next phase of research needs to take place, she suggested, “we need to actually see, in a very evidence-informed way, what actually works to make and sustain change.”

No financial disclosures were reported by any of the speakers quoted.

SOURCE: Lancet. 2019;393:493–610, e6-e28

LONDON – A concerted effort is needed by everyone to address gender inequality in science and medicine, a group of prominent female physicians and thought-leaders said at a recent event hosted by The Lancet.

Sara Freeman/MDedge News

“Gender equality is everyone’s business,” Sarah Hawkes, MBBS, PhD, a professor of global public health at University College London (England), said at the event.

“We’re not talking about women taking over the shop, but women being given an equal opportunity to run the shop. It doesn’t matter where we place ourselves on the gender spectrum as far as advancing equality in science is concerned. What matters is that we all, irrespective of gender, call ourselves feminists.”

For years, women have been “underrepresented in positions of power and leadership, undervalued, and experience discrimination and gender-based violence in scientific and health disciplines across the world,” according to an editorial in the British-based journal (Lancet. 2019;393:493). Such inequalities are compounded and hard to separate from other inequalities, including ethnicity, disability, class, geography, and sexuality.

Despite efforts to readdress the predominantly male culture of medicine, the problem of gender inequality remains “stubbornly persistent,” the editorial said.

“We have spent years being told that the problem lies with us as individuals and that we just need to be better, stronger, more vocal, as women,” Dr. Hawkes observed. “But what really needs to happen is for change to happen in places that hold power.” She further argued: “We don’t need any more individual change; we need organizational and institutional norm change.”

Gender inequality has a long history, and not just in medicine, said British journalist Caroline Criado-Perez OBE, who gave a keynote speech. Ms. Criado-Perez, who is a well-respected feminist campaigner, noted that the world was largely “modeled to fit men.” From architecture to transport, and even crash-test dummies, everything was largely modeled on, or to accommodate, the male rather than the female body.

“I don’t need to tell you that women are 50% more likely to be misdiagnosed following a heart attack” than men. There is no more urgent need to challenge gender inequality than in medicine, Women are dying because of the gender data gap in medicine,” she asserted. “In medical research, in medical education, in medical practice, it needs to be closed as a matter of urgency.”

Original data published in the Advancing Women in Science, Medicine and Global Health special edition of The Lancet found that only 31% of biomedical research papers published in 2016 reported outcomes for both men and women (Lancet. 2019;393:550-9). Reporting of sex differences was somewhat better in clinical or public health-related research papers, at 67% and 69%, respectively. Sex-differences were more likely to be reported if a woman was one of the key authors, Cassidy R. Sugimoto, PhD, associate professor of informatics at Indiana University in Bloomington, and associates, observed in their paper.

That said, women often have to fight to be included as an author on a paper, even when they have done the majority of the work, the event participants highlighted. Women were still less likely than men to be named as the first or last author on a paper, as well as be less likely to receive research funding to enable them to do the work in the first place (Lancet. 2018;393:531-40).

“Was it really you?” was a question sometimes asked of a woman named as a lead or first author, noted Sonia Gandhi, MD, PhD, group leader of the Neurodegeneration Biology Laboratory at the Francis Crick Institute in Cambridge (England). Women network differently to men, Dr. Gandhi observed, and not necessarily in networks that forward careers. Women were also often questioned about their productivity, and regardless of any training on unconscious bias, women were still at a disadvantage if they took a career break to have children.

Female representation is so important, said F. Gigi Osler, MD, head of otolaryngology-head and neck surgery at St. Boniface Hospital in Winnipeg. Dr. Osler is the 2018-2019 president of the Canadian Medical Association, the eighth woman to hold this prestigious position in the organization’s 151 years of operation. She also happens to be the first female surgeon and the first woman of color in the role. “When I stepped into the presidency last August, I thought very long and very hard about how I was going to use my voice and this platform,” Dr. Osler said. “It became very clear to me after I started how important representation was. I can’t tell you how many women, young women, and women of color...have come up to me to say, ‘I’m so excited to have you in this position. I’ve never seen someone who looks like me in that type of leadership position,’ ” she observed.

“As leaders, I think we can advocate for structures and processes,” Dr. Osler added, “I think we set the culture.” Leaders have the responsibility for creating and nurturing and fostering a professional, respectful, and inclusive environment, she said.

“We need more strong leaders, we need more diversity in leadership.” Dr. Osler was keen to point out that greater diversity does not mean only women, but other groups as well. “Look around the room. Who is not here? How can I make it easier for them to get here?”

Another strong female role model at the event was Dame Sally Davies, the Chief Medical Officer for England, a hematologist by training. Not only is she the first female in that role, she will also become the first female Master of Trinity College Cambridge starting in October 2019, a role dominated by men for more than 500 years.

All people, women and men, need to be given fair opportunity, Dame Sally said. Addressing structural issues can help, she said. “We need role models, mentors, and champions,” she said, noting that there were differences between the three. “Mentors give you advice, they get to know you, and they help you think through your issue. Champions may not have time for that, but they know you are good,” and they are putting you forward for opportunities.

“If the system isn’t right, or we are treated badly, we need to call it out,” Dame Sally said. “I do think that we often let things pass that we shouldn’t.” A classic situation is where a woman may suggest something at a meeting and it is ignored, but when a man says the same thing it is taken on board. That kind of behavior needs to stop and be addressed when it happens, by everyone at the table, she said.

Dr. Hawkes observed in her summing up of the day: “Throughout the history of health, change comes about not just through action at the top, but also from action from the bottom up.” She added: “The question is how do we make that change happen?” That’s where the next phase of research needs to take place, she suggested, “we need to actually see, in a very evidence-informed way, what actually works to make and sustain change.”

No financial disclosures were reported by any of the speakers quoted.

SOURCE: Lancet. 2019;393:493–610, e6-e28

One chimeric antigen receptor (CAR) T-cell therapy may appear better than another, but confounding factors make it difficult to compare these therapies effectively, according to a review published in the Journal of Clinical Oncology.

Caron A. Jacobson, MD, of the Dana-Farber Cancer Institute in Boston, reviewed results from three trials of CAR T-cell therapies in patients with B-cell non-Hodgkin lymphoma (B-NHL).

She noted that cross-trial comparisons are always limited, but such comparisons of CAR T-cell therapies are hindered by several confounding factors.

Dr. Jacobson said differences in manufacturing procedures and turnaround time, differences in patient eligibility and management, and the complexity of CAR T-cell therapies make it difficult to compare results from three CAR-T trials in B-NHL:

• The ZUMA-1 trial (NCT02348216) of axicabtagene ciloleucel (axi-cel, Yescarta)
• The JULIET trial (NCT02445248) of tisagenlecleucel (t-cel, Kymriah)
• The TRANSCEND-NHL-001 trial (NCT02631044) of lisocabtagene maraleucel (liso-cel, JCAR017).

Looking at response rates alone, axi-cel appears the most promising. The overall response rate (ORR) was 82% with axi-cel, 75% with liso-cel, and 52% with t-cel.

When considering cytokine release syndrome (CRS), liso-cel appears the safest. The rate of CRS was 93% with axi-cel (13% grade 3 or higher), 58% with t-cel (22% grade 3 or higher), and 39% with liso-cel (1% grade 3 or higher).

However, as Dr. Jacobson pointed out, it’s impossible to know if these differences in efficacy and toxicity are “statistically meaningful.”

jensmith@mdedge.com

SOURCE: Jacobson CA. J Clin Oncol. 2019 Feb 1;37(4):328-35. doi: 10.1200/JCO.18.01457

One chimeric antigen receptor (CAR) T-cell therapy may appear better than another, but confounding factors make it difficult to compare these therapies effectively, according to a review published in the Journal of Clinical Oncology.

Caron A. Jacobson, MD, of the Dana-Farber Cancer Institute in Boston, reviewed results from three trials of CAR T-cell therapies in patients with B-cell non-Hodgkin lymphoma (B-NHL).

She noted that cross-trial comparisons are always limited, but such comparisons of CAR T-cell therapies are hindered by several confounding factors.

Dr. Jacobson said differences in manufacturing procedures and turnaround time, differences in patient eligibility and management, and the complexity of CAR T-cell therapies make it difficult to compare results from three CAR-T trials in B-NHL:

• The ZUMA-1 trial (NCT02348216) of axicabtagene ciloleucel (axi-cel, Yescarta)
• The JULIET trial (NCT02445248) of tisagenlecleucel (t-cel, Kymriah)
• The TRANSCEND-NHL-001 trial (NCT02631044) of lisocabtagene maraleucel (liso-cel, JCAR017).

Looking at response rates alone, axi-cel appears the most promising. The overall response rate (ORR) was 82% with axi-cel, 75% with liso-cel, and 52% with t-cel.

When considering cytokine release syndrome (CRS), liso-cel appears the safest. The rate of CRS was 93% with axi-cel (13% grade 3 or higher), 58% with t-cel (22% grade 3 or higher), and 39% with liso-cel (1% grade 3 or higher).

However, as Dr. Jacobson pointed out, it’s impossible to know if these differences in efficacy and toxicity are “statistically meaningful.”

jensmith@mdedge.com

SOURCE: Jacobson CA. J Clin Oncol. 2019 Feb 1;37(4):328-35. doi: 10.1200/JCO.18.01457

One chimeric antigen receptor (CAR) T-cell therapy may appear better than another, but confounding factors make it difficult to compare these therapies effectively, according to a review published in the Journal of Clinical Oncology.

Caron A. Jacobson, MD, of the Dana-Farber Cancer Institute in Boston, reviewed results from three trials of CAR T-cell therapies in patients with B-cell non-Hodgkin lymphoma (B-NHL).

She noted that cross-trial comparisons are always limited, but such comparisons of CAR T-cell therapies are hindered by several confounding factors.

Dr. Jacobson said differences in manufacturing procedures and turnaround time, differences in patient eligibility and management, and the complexity of CAR T-cell therapies make it difficult to compare results from three CAR-T trials in B-NHL:

• The ZUMA-1 trial (NCT02348216) of axicabtagene ciloleucel (axi-cel, Yescarta)
• The JULIET trial (NCT02445248) of tisagenlecleucel (t-cel, Kymriah)
• The TRANSCEND-NHL-001 trial (NCT02631044) of lisocabtagene maraleucel (liso-cel, JCAR017).

Looking at response rates alone, axi-cel appears the most promising. The overall response rate (ORR) was 82% with axi-cel, 75% with liso-cel, and 52% with t-cel.

When considering cytokine release syndrome (CRS), liso-cel appears the safest. The rate of CRS was 93% with axi-cel (13% grade 3 or higher), 58% with t-cel (22% grade 3 or higher), and 39% with liso-cel (1% grade 3 or higher).

However, as Dr. Jacobson pointed out, it’s impossible to know if these differences in efficacy and toxicity are “statistically meaningful.”

jensmith@mdedge.com

SOURCE: Jacobson CA. J Clin Oncol. 2019 Feb 1;37(4):328-35. doi: 10.1200/JCO.18.01457

In 2017, the National Academy of Medicine recognized the urgent need to address burnout, wellness, and resilience in physicians. A consortium was subsequently put together comprising many cosponsoring organizations, including the Accreditation Council for Graduate Medical Education (ACGME), and the American Board of Medical Specialties (ABMS). One of many outputs of this consortium was a discussion paper, “A Journey to Construct an All-Encompassing Conceptual Model of Factors Affecting Clinician Well-Being and Resilience.”

Doug Brunk/MDedge News

The authors conceptually divided wellness and resilience drivers into external and individual factors. It turns out that a large portion of clinician well-being and resilience is related to individual factors that include personal factors, skills, and abilities. Taking personal responsibility and ownership of developing these individual factors is important, but many do not know where to begin.

My journey in this area began 5 years ago. This was a time when organizational resources were sparse and there was little local or national attention to addressing physician wellness. My life was horribly out of balance. While this should have been obvious, the “hit-on-the-head” moment was weighing myself one day and realizing that I was 30 pounds overweight. This was the ultimate sign to me that there was a problem because throughout my entire life, I was always very athletic, even during residency and fellowship training. I was using food as a reward system for several years which, in combination with a dramatic decrease in physical activity due to prioritizing everything related to work, led to this problem. A slowing metabolism that we all face as we age certainly accentuated it.

I was taking care of everybody else, but not myself. Many family members, friends, and even patients told me this over the years, which I conveniently ignored. For several years, my patients were asking me, “How are you doing?” at the end of their office visits. As a surgeon with a busy cancer practice, this should have been a signal for me – my cancer patients asking me how I am doing!

I started to think more about why this was happening. I realized that I was a victim of my own passions. In terms of my clinical practice, I cherished and absolutely loved every aspect of my practice and taking care of patients. I loved educating our next generation and thrived on conducting research, presenting at meetings, and publishing papers. And as I was accumulating more administrative roles and responsibilities at the department, hospital, and medical school levels, I realized I had a growing passion for administrative work. I found that the administrative work was uniquely challenging and allowed me to meaningfully serve others in a very special way.

In all of these areas for which I had a deep passion, I was committed to nothing short of excellence in everything I did. That is what I expected of myself. Self-compassion was almost absent. In addition, I have a people-pleasing personality and find it difficult to say no to people. As I have come to realize, this characteristic can be self-destructive.

I began to recognize that I fell into an acceptance (and almost expectation) that every 6-8 months I’d experience an episode of burnout that lasted 3-4 days. My burnout trigger was feeling a sense of helplessness. Everything seemed to come down all at once, and I felt helpless to dig out of it.

I realized I wanted to change, but I had no idea what resources were available or how to go about making a change. One day, I was talking to a colleague about these issues, and he asked, “Have you read the book, ‘Lone Survivor?’ ” I hadn’t heard of it, but I picked it up and started reading. Looking back, this was one of the most important decisions I made in my effort to help myself. “Lone Survivor” tells the the story of Marcus Luttrell, a retired U.S. Navy SEAL who received the Navy Cross for his actions facing Taliban fighters during Operation Red Wings.

When I finished reading this book, I realized that this was a remarkable story of resilience. The entirety of his story really connected with me. I then began to think there might be something I could learn from the Navy SEAL community that I could apply to my own civilian life.

Candidates who enter training for Navy SEALs are physically fit to succeed, but only approximately 20% make it through Basic Underwater Demolition/SEAL (BUD/S). Many drop out on request, largely because they don’t have the mental toughness and emotional resilience to tolerate intense stress continuously over a prolonged period of time. The ones who succeed have a deep meaning to their “Why” to become a SEAL.

I then learned about a retired Navy SEAL Commander, Mark Devine, who had a program intended to train civilians in physical fitness, mental toughness, emotional resilience, intuitional awareness, and spiritual consciousness in a manner similar to that of preparing prospective candidates for BUD/S training. The website stated that the defining attribute for enrollees was “a burning desire to better oneself.” I connected with that. After resolving my self-doubts and uncomfortable feelings about doing this, I signed up for the 3-day Fundamentals immersion program.

My 3 days with Coach Divine and his team were truly transformative. This was definitely not a “Navy SEAL Fantasy Camp,” and perhaps were the 3 most difficult days of my life in many regards.

When I got back from this program, I had a framework and toolbox for developing resilience to avoid burnout and improve my personal wellness. I immediately changed several things in my life, in an enduring way for the past 5 years. I started to train regularly. While I could not find a predictable time to do this during the week, I prioritized training during weekends. I improved my nutrition, stopped using food as a reward system, and started getting more sleep. Within 6 months after completing the program, I dropped the 30 pounds by being disciplined, not motivated, to make these changes. I also developed a morning ritual upon awakening. This consists of drinking a glass of water, doing box-breathing exercises, positive self-talk, thinking through my day, prioritizing what needs to be done, doing an ethos check-in to make sure that the priorities of the day correlate with my “Why,” engaging in further positive self-talk, and then engaging in positive visualization. I think this mindfulness activity has been critically important.

With the enduring changes I made, my regular schedule of burnout episodes every 6-8 months stopped, despite some very stressful events in my life. Go figure. My productivity was not affected, and my happiness was certainly improved. I had a definite sense that the changes I made were real and effective. One day a few years later while rounding with an intern, one of my patients said to the resident, “I remember Dr. Nussenbaum when he was fat.” The intern looked at me with a puzzled expression.

Based on my own journey, what advice can I give you to improve your own personal wellness and resilience? Most importantly, know your “Why” and your “3 Ps” (passion, purpose, and principles in life). What’s your personal ethos? Make sure that the job you do and the activities you perform tie into your ethos as much and as often as possible. Engage in mindfulness activities. There are many possibilities. For me, the mindfulness activity is my morning ritual. Talking about failures with trusted friends and colleagues rather than hiding them can also increase your resilience.

Developing and maintaining resilience is still an evolving and ongoing process for me. I consider this a lifelong learning process, rather than a one-time deal. Most difficult has been becoming disciplined and patient to learn new things and incorporate them into my life, and along the way becoming comfortable with being uncomfortable. And taking the necessary time to define a personal ethos, which took much longer than I thought it would.

I’ve continued to learn from several resources available from the Harvard Business Review, and from reading several widely available books. I have taken an academic approach to supplement what I learned from Coach Divine and his team, which is not surprising to those that know me well. Societies also now have many resources, such as The American Medical Association’s Burnout Tip-of-the Week, as one example.

One of the four guiding principles from the recent article, “Charter on Physician Well-Being,” states that physician well-being is a shared responsibility. It’s shared among the organizations we work in, society and its regulatory agencies, and individuals. It’s important to remind ourselves that taking individual responsibility for your wellness and developing resilience will still be a key component even as resources from our organizations and society continue to expand and become more available. Improving physician well-being needs to be a team sport.

Dr. Brian Nussenbaum is executive director of the American Board of Otolaryngology–Head and Neck Surgery. He lives in Houston. These remarks were adapted from a presentation that Dr. Nussenbaum gave at the Triological Society’s Combined Sections Meeting in Coronado, Calif., which was jointly sponsored by the Triological Society and the American College of Surgeons.

In 2017, the National Academy of Medicine recognized the urgent need to address burnout, wellness, and resilience in physicians. A consortium was subsequently put together comprising many cosponsoring organizations, including the Accreditation Council for Graduate Medical Education (ACGME), and the American Board of Medical Specialties (ABMS). One of many outputs of this consortium was a discussion paper, “A Journey to Construct an All-Encompassing Conceptual Model of Factors Affecting Clinician Well-Being and Resilience.”

Doug Brunk/MDedge News

The authors conceptually divided wellness and resilience drivers into external and individual factors. It turns out that a large portion of clinician well-being and resilience is related to individual factors that include personal factors, skills, and abilities. Taking personal responsibility and ownership of developing these individual factors is important, but many do not know where to begin.

My journey in this area began 5 years ago. This was a time when organizational resources were sparse and there was little local or national attention to addressing physician wellness. My life was horribly out of balance. While this should have been obvious, the “hit-on-the-head” moment was weighing myself one day and realizing that I was 30 pounds overweight. This was the ultimate sign to me that there was a problem because throughout my entire life, I was always very athletic, even during residency and fellowship training. I was using food as a reward system for several years which, in combination with a dramatic decrease in physical activity due to prioritizing everything related to work, led to this problem. A slowing metabolism that we all face as we age certainly accentuated it.

I was taking care of everybody else, but not myself. Many family members, friends, and even patients told me this over the years, which I conveniently ignored. For several years, my patients were asking me, “How are you doing?” at the end of their office visits. As a surgeon with a busy cancer practice, this should have been a signal for me – my cancer patients asking me how I am doing!

I started to think more about why this was happening. I realized that I was a victim of my own passions. In terms of my clinical practice, I cherished and absolutely loved every aspect of my practice and taking care of patients. I loved educating our next generation and thrived on conducting research, presenting at meetings, and publishing papers. And as I was accumulating more administrative roles and responsibilities at the department, hospital, and medical school levels, I realized I had a growing passion for administrative work. I found that the administrative work was uniquely challenging and allowed me to meaningfully serve others in a very special way.

In all of these areas for which I had a deep passion, I was committed to nothing short of excellence in everything I did. That is what I expected of myself. Self-compassion was almost absent. In addition, I have a people-pleasing personality and find it difficult to say no to people. As I have come to realize, this characteristic can be self-destructive.

I began to recognize that I fell into an acceptance (and almost expectation) that every 6-8 months I’d experience an episode of burnout that lasted 3-4 days. My burnout trigger was feeling a sense of helplessness. Everything seemed to come down all at once, and I felt helpless to dig out of it.

I realized I wanted to change, but I had no idea what resources were available or how to go about making a change. One day, I was talking to a colleague about these issues, and he asked, “Have you read the book, ‘Lone Survivor?’ ” I hadn’t heard of it, but I picked it up and started reading. Looking back, this was one of the most important decisions I made in my effort to help myself. “Lone Survivor” tells the the story of Marcus Luttrell, a retired U.S. Navy SEAL who received the Navy Cross for his actions facing Taliban fighters during Operation Red Wings.

When I finished reading this book, I realized that this was a remarkable story of resilience. The entirety of his story really connected with me. I then began to think there might be something I could learn from the Navy SEAL community that I could apply to my own civilian life.

Candidates who enter training for Navy SEALs are physically fit to succeed, but only approximately 20% make it through Basic Underwater Demolition/SEAL (BUD/S). Many drop out on request, largely because they don’t have the mental toughness and emotional resilience to tolerate intense stress continuously over a prolonged period of time. The ones who succeed have a deep meaning to their “Why” to become a SEAL.

I then learned about a retired Navy SEAL Commander, Mark Devine, who had a program intended to train civilians in physical fitness, mental toughness, emotional resilience, intuitional awareness, and spiritual consciousness in a manner similar to that of preparing prospective candidates for BUD/S training. The website stated that the defining attribute for enrollees was “a burning desire to better oneself.” I connected with that. After resolving my self-doubts and uncomfortable feelings about doing this, I signed up for the 3-day Fundamentals immersion program.

My 3 days with Coach Divine and his team were truly transformative. This was definitely not a “Navy SEAL Fantasy Camp,” and perhaps were the 3 most difficult days of my life in many regards.

When I got back from this program, I had a framework and toolbox for developing resilience to avoid burnout and improve my personal wellness. I immediately changed several things in my life, in an enduring way for the past 5 years. I started to train regularly. While I could not find a predictable time to do this during the week, I prioritized training during weekends. I improved my nutrition, stopped using food as a reward system, and started getting more sleep. Within 6 months after completing the program, I dropped the 30 pounds by being disciplined, not motivated, to make these changes. I also developed a morning ritual upon awakening. This consists of drinking a glass of water, doing box-breathing exercises, positive self-talk, thinking through my day, prioritizing what needs to be done, doing an ethos check-in to make sure that the priorities of the day correlate with my “Why,” engaging in further positive self-talk, and then engaging in positive visualization. I think this mindfulness activity has been critically important.

With the enduring changes I made, my regular schedule of burnout episodes every 6-8 months stopped, despite some very stressful events in my life. Go figure. My productivity was not affected, and my happiness was certainly improved. I had a definite sense that the changes I made were real and effective. One day a few years later while rounding with an intern, one of my patients said to the resident, “I remember Dr. Nussenbaum when he was fat.” The intern looked at me with a puzzled expression.

Based on my own journey, what advice can I give you to improve your own personal wellness and resilience? Most importantly, know your “Why” and your “3 Ps” (passion, purpose, and principles in life). What’s your personal ethos? Make sure that the job you do and the activities you perform tie into your ethos as much and as often as possible. Engage in mindfulness activities. There are many possibilities. For me, the mindfulness activity is my morning ritual. Talking about failures with trusted friends and colleagues rather than hiding them can also increase your resilience.

Developing and maintaining resilience is still an evolving and ongoing process for me. I consider this a lifelong learning process, rather than a one-time deal. Most difficult has been becoming disciplined and patient to learn new things and incorporate them into my life, and along the way becoming comfortable with being uncomfortable. And taking the necessary time to define a personal ethos, which took much longer than I thought it would.

I’ve continued to learn from several resources available from the Harvard Business Review, and from reading several widely available books. I have taken an academic approach to supplement what I learned from Coach Divine and his team, which is not surprising to those that know me well. Societies also now have many resources, such as The American Medical Association’s Burnout Tip-of-the Week, as one example.

One of the four guiding principles from the recent article, “Charter on Physician Well-Being,” states that physician well-being is a shared responsibility. It’s shared among the organizations we work in, society and its regulatory agencies, and individuals. It’s important to remind ourselves that taking individual responsibility for your wellness and developing resilience will still be a key component even as resources from our organizations and society continue to expand and become more available. Improving physician well-being needs to be a team sport.

Dr. Brian Nussenbaum is executive director of the American Board of Otolaryngology–Head and Neck Surgery. He lives in Houston. These remarks were adapted from a presentation that Dr. Nussenbaum gave at the Triological Society’s Combined Sections Meeting in Coronado, Calif., which was jointly sponsored by the Triological Society and the American College of Surgeons.

In 2017, the National Academy of Medicine recognized the urgent need to address burnout, wellness, and resilience in physicians. A consortium was subsequently put together comprising many cosponsoring organizations, including the Accreditation Council for Graduate Medical Education (ACGME), and the American Board of Medical Specialties (ABMS). One of many outputs of this consortium was a discussion paper, “A Journey to Construct an All-Encompassing Conceptual Model of Factors Affecting Clinician Well-Being and Resilience.”

Doug Brunk/MDedge News

The authors conceptually divided wellness and resilience drivers into external and individual factors. It turns out that a large portion of clinician well-being and resilience is related to individual factors that include personal factors, skills, and abilities. Taking personal responsibility and ownership of developing these individual factors is important, but many do not know where to begin.

My journey in this area began 5 years ago. This was a time when organizational resources were sparse and there was little local or national attention to addressing physician wellness. My life was horribly out of balance. While this should have been obvious, the “hit-on-the-head” moment was weighing myself one day and realizing that I was 30 pounds overweight. This was the ultimate sign to me that there was a problem because throughout my entire life, I was always very athletic, even during residency and fellowship training. I was using food as a reward system for several years which, in combination with a dramatic decrease in physical activity due to prioritizing everything related to work, led to this problem. A slowing metabolism that we all face as we age certainly accentuated it.

I was taking care of everybody else, but not myself. Many family members, friends, and even patients told me this over the years, which I conveniently ignored. For several years, my patients were asking me, “How are you doing?” at the end of their office visits. As a surgeon with a busy cancer practice, this should have been a signal for me – my cancer patients asking me how I am doing!

I started to think more about why this was happening. I realized that I was a victim of my own passions. In terms of my clinical practice, I cherished and absolutely loved every aspect of my practice and taking care of patients. I loved educating our next generation and thrived on conducting research, presenting at meetings, and publishing papers. And as I was accumulating more administrative roles and responsibilities at the department, hospital, and medical school levels, I realized I had a growing passion for administrative work. I found that the administrative work was uniquely challenging and allowed me to meaningfully serve others in a very special way.

In all of these areas for which I had a deep passion, I was committed to nothing short of excellence in everything I did. That is what I expected of myself. Self-compassion was almost absent. In addition, I have a people-pleasing personality and find it difficult to say no to people. As I have come to realize, this characteristic can be self-destructive.

I began to recognize that I fell into an acceptance (and almost expectation) that every 6-8 months I’d experience an episode of burnout that lasted 3-4 days. My burnout trigger was feeling a sense of helplessness. Everything seemed to come down all at once, and I felt helpless to dig out of it.

I realized I wanted to change, but I had no idea what resources were available or how to go about making a change. One day, I was talking to a colleague about these issues, and he asked, “Have you read the book, ‘Lone Survivor?’ ” I hadn’t heard of it, but I picked it up and started reading. Looking back, this was one of the most important decisions I made in my effort to help myself. “Lone Survivor” tells the the story of Marcus Luttrell, a retired U.S. Navy SEAL who received the Navy Cross for his actions facing Taliban fighters during Operation Red Wings.

When I finished reading this book, I realized that this was a remarkable story of resilience. The entirety of his story really connected with me. I then began to think there might be something I could learn from the Navy SEAL community that I could apply to my own civilian life.

Candidates who enter training for Navy SEALs are physically fit to succeed, but only approximately 20% make it through Basic Underwater Demolition/SEAL (BUD/S). Many drop out on request, largely because they don’t have the mental toughness and emotional resilience to tolerate intense stress continuously over a prolonged period of time. The ones who succeed have a deep meaning to their “Why” to become a SEAL.

I then learned about a retired Navy SEAL Commander, Mark Devine, who had a program intended to train civilians in physical fitness, mental toughness, emotional resilience, intuitional awareness, and spiritual consciousness in a manner similar to that of preparing prospective candidates for BUD/S training. The website stated that the defining attribute for enrollees was “a burning desire to better oneself.” I connected with that. After resolving my self-doubts and uncomfortable feelings about doing this, I signed up for the 3-day Fundamentals immersion program.

My 3 days with Coach Divine and his team were truly transformative. This was definitely not a “Navy SEAL Fantasy Camp,” and perhaps were the 3 most difficult days of my life in many regards.

When I got back from this program, I had a framework and toolbox for developing resilience to avoid burnout and improve my personal wellness. I immediately changed several things in my life, in an enduring way for the past 5 years. I started to train regularly. While I could not find a predictable time to do this during the week, I prioritized training during weekends. I improved my nutrition, stopped using food as a reward system, and started getting more sleep. Within 6 months after completing the program, I dropped the 30 pounds by being disciplined, not motivated, to make these changes. I also developed a morning ritual upon awakening. This consists of drinking a glass of water, doing box-breathing exercises, positive self-talk, thinking through my day, prioritizing what needs to be done, doing an ethos check-in to make sure that the priorities of the day correlate with my “Why,” engaging in further positive self-talk, and then engaging in positive visualization. I think this mindfulness activity has been critically important.

With the enduring changes I made, my regular schedule of burnout episodes every 6-8 months stopped, despite some very stressful events in my life. Go figure. My productivity was not affected, and my happiness was certainly improved. I had a definite sense that the changes I made were real and effective. One day a few years later while rounding with an intern, one of my patients said to the resident, “I remember Dr. Nussenbaum when he was fat.” The intern looked at me with a puzzled expression.

Based on my own journey, what advice can I give you to improve your own personal wellness and resilience? Most importantly, know your “Why” and your “3 Ps” (passion, purpose, and principles in life). What’s your personal ethos? Make sure that the job you do and the activities you perform tie into your ethos as much and as often as possible. Engage in mindfulness activities. There are many possibilities. For me, the mindfulness activity is my morning ritual. Talking about failures with trusted friends and colleagues rather than hiding them can also increase your resilience.

Developing and maintaining resilience is still an evolving and ongoing process for me. I consider this a lifelong learning process, rather than a one-time deal. Most difficult has been becoming disciplined and patient to learn new things and incorporate them into my life, and along the way becoming comfortable with being uncomfortable. And taking the necessary time to define a personal ethos, which took much longer than I thought it would.

I’ve continued to learn from several resources available from the Harvard Business Review, and from reading several widely available books. I have taken an academic approach to supplement what I learned from Coach Divine and his team, which is not surprising to those that know me well. Societies also now have many resources, such as The American Medical Association’s Burnout Tip-of-the Week, as one example.

One of the four guiding principles from the recent article, “Charter on Physician Well-Being,” states that physician well-being is a shared responsibility. It’s shared among the organizations we work in, society and its regulatory agencies, and individuals. It’s important to remind ourselves that taking individual responsibility for your wellness and developing resilience will still be a key component even as resources from our organizations and society continue to expand and become more available. Improving physician well-being needs to be a team sport.

Dr. Brian Nussenbaum is executive director of the American Board of Otolaryngology–Head and Neck Surgery. He lives in Houston. These remarks were adapted from a presentation that Dr. Nussenbaum gave at the Triological Society’s Combined Sections Meeting in Coronado, Calif., which was jointly sponsored by the Triological Society and the American College of Surgeons.