The American College of Surgeons (ACS) Foundation Board of Directors will present the 2016 Distinguished Philanthropist Award to Mary H. McGrath, MD, MPH, FACS, professor of surgery, University of California, San Francisco (UCSF), at its annual Donor Recognition Luncheon Monday, October 17, at Clinical Congress 2016 in Washington, DC. Dr. McGrath will be recognized for her generous contributions to the College, her service to the larger philanthropic community, her long-standing record of ACS volunteerism, and a career-long dedication to the quality of surgical patient care.

A graduate of St. Louis University School of Medicine, MO (1970), she completed her general surgery residency at the University of Colorado Medical Center, Denver (1976), trained in plastic surgery at the Yale University School of Medicine (1976–1978), New Haven, CT, and completed a fellowship in hand surgery at the University of Connecticut, Storrs, and Yale University (1978).

Contributions to the profession

Since then, Dr. McGrath has made outstanding clinical and academic contributions to the field of plastic surgery, especially in the areas of breast and hand surgery, wound healing, introduction of new technology, and workforce issues. Her career as an academic surgeon started at Yale in 1978 with a position as assistant professor of surgery in the school of medicine’s division of plastic and reconstructive surgery.

In 1980, she became assistant professor of surgery, division of plastic and reconstructive surgery, Columbia University College of Physicians and Surgeons, New York, NY. In 1984, she moved to the George Washington University Medical Center, Washington, DC, where she began as chief, division of plastic and reconstructive surgery, and director, residency training program, and ultimately, ascended to professor of surgery. She has held her current position at UCSF since 2003.

A Fellow of the College since 1983, Dr. McGrath has provided exceptional service to the ACS and has served for 25 years in leadership roles, including First Vice-President (2007–2008); Vice-Chair, Board of Regents (2005–2006); member, Executive Committee, Board of Regents (2002–2006); Regent (1997–2006); and Chair, Committee on Ethics (2003–2006).

She served on the Board of Governors Executive Committee and as a Governor-at-Large representing the District of Columbia and is a member of the ACS Foundation Board. In 2009, the ACS appointed her to serve on the Board of Commissioners of The Joint Commission; she is currently serving her third term in this capacity. For this remarkable service, Dr. McGrath received the College’s higher honor, the Distinguished Service Award, in 2011.

Generous philanthropist

As an ACS donor since 1994, Dr. McGrath’s generous philanthropy has elevated her to the Fellows Leadership Society Legacy Circle, one of the top giving tiers that ACS Foundation donors may achieve. Remarking on her reasons for supporting the ACS, she said, “The surgical profession and other surgeons have enabled me to be personally and financially successful, for which I am tremendously grateful. I encourage other Fellows to consider making their own contributions and join the community of colleagues planning to see surgery survive successfully in the future.”

The American College of Surgeons (ACS) Foundation Board of Directors will present the 2016 Distinguished Philanthropist Award to Mary H. McGrath, MD, MPH, FACS, professor of surgery, University of California, San Francisco (UCSF), at its annual Donor Recognition Luncheon Monday, October 17, at Clinical Congress 2016 in Washington, DC. Dr. McGrath will be recognized for her generous contributions to the College, her service to the larger philanthropic community, her long-standing record of ACS volunteerism, and a career-long dedication to the quality of surgical patient care.

A graduate of St. Louis University School of Medicine, MO (1970), she completed her general surgery residency at the University of Colorado Medical Center, Denver (1976), trained in plastic surgery at the Yale University School of Medicine (1976–1978), New Haven, CT, and completed a fellowship in hand surgery at the University of Connecticut, Storrs, and Yale University (1978).

Contributions to the profession

Since then, Dr. McGrath has made outstanding clinical and academic contributions to the field of plastic surgery, especially in the areas of breast and hand surgery, wound healing, introduction of new technology, and workforce issues. Her career as an academic surgeon started at Yale in 1978 with a position as assistant professor of surgery in the school of medicine’s division of plastic and reconstructive surgery.

In 1980, she became assistant professor of surgery, division of plastic and reconstructive surgery, Columbia University College of Physicians and Surgeons, New York, NY. In 1984, she moved to the George Washington University Medical Center, Washington, DC, where she began as chief, division of plastic and reconstructive surgery, and director, residency training program, and ultimately, ascended to professor of surgery. She has held her current position at UCSF since 2003.

A Fellow of the College since 1983, Dr. McGrath has provided exceptional service to the ACS and has served for 25 years in leadership roles, including First Vice-President (2007–2008); Vice-Chair, Board of Regents (2005–2006); member, Executive Committee, Board of Regents (2002–2006); Regent (1997–2006); and Chair, Committee on Ethics (2003–2006).

She served on the Board of Governors Executive Committee and as a Governor-at-Large representing the District of Columbia and is a member of the ACS Foundation Board. In 2009, the ACS appointed her to serve on the Board of Commissioners of The Joint Commission; she is currently serving her third term in this capacity. For this remarkable service, Dr. McGrath received the College’s higher honor, the Distinguished Service Award, in 2011.

Generous philanthropist

As an ACS donor since 1994, Dr. McGrath’s generous philanthropy has elevated her to the Fellows Leadership Society Legacy Circle, one of the top giving tiers that ACS Foundation donors may achieve. Remarking on her reasons for supporting the ACS, she said, “The surgical profession and other surgeons have enabled me to be personally and financially successful, for which I am tremendously grateful. I encourage other Fellows to consider making their own contributions and join the community of colleagues planning to see surgery survive successfully in the future.”

The American College of Surgeons (ACS) Foundation Board of Directors will present the 2016 Distinguished Philanthropist Award to Mary H. McGrath, MD, MPH, FACS, professor of surgery, University of California, San Francisco (UCSF), at its annual Donor Recognition Luncheon Monday, October 17, at Clinical Congress 2016 in Washington, DC. Dr. McGrath will be recognized for her generous contributions to the College, her service to the larger philanthropic community, her long-standing record of ACS volunteerism, and a career-long dedication to the quality of surgical patient care.

A graduate of St. Louis University School of Medicine, MO (1970), she completed her general surgery residency at the University of Colorado Medical Center, Denver (1976), trained in plastic surgery at the Yale University School of Medicine (1976–1978), New Haven, CT, and completed a fellowship in hand surgery at the University of Connecticut, Storrs, and Yale University (1978).

Contributions to the profession

Since then, Dr. McGrath has made outstanding clinical and academic contributions to the field of plastic surgery, especially in the areas of breast and hand surgery, wound healing, introduction of new technology, and workforce issues. Her career as an academic surgeon started at Yale in 1978 with a position as assistant professor of surgery in the school of medicine’s division of plastic and reconstructive surgery.

In 1980, she became assistant professor of surgery, division of plastic and reconstructive surgery, Columbia University College of Physicians and Surgeons, New York, NY. In 1984, she moved to the George Washington University Medical Center, Washington, DC, where she began as chief, division of plastic and reconstructive surgery, and director, residency training program, and ultimately, ascended to professor of surgery. She has held her current position at UCSF since 2003.

A Fellow of the College since 1983, Dr. McGrath has provided exceptional service to the ACS and has served for 25 years in leadership roles, including First Vice-President (2007–2008); Vice-Chair, Board of Regents (2005–2006); member, Executive Committee, Board of Regents (2002–2006); Regent (1997–2006); and Chair, Committee on Ethics (2003–2006).

She served on the Board of Governors Executive Committee and as a Governor-at-Large representing the District of Columbia and is a member of the ACS Foundation Board. In 2009, the ACS appointed her to serve on the Board of Commissioners of The Joint Commission; she is currently serving her third term in this capacity. For this remarkable service, Dr. McGrath received the College’s higher honor, the Distinguished Service Award, in 2011.

Generous philanthropist

As an ACS donor since 1994, Dr. McGrath’s generous philanthropy has elevated her to the Fellows Leadership Society Legacy Circle, one of the top giving tiers that ACS Foundation donors may achieve. Remarking on her reasons for supporting the ACS, she said, “The surgical profession and other surgeons have enabled me to be personally and financially successful, for which I am tremendously grateful. I encourage other Fellows to consider making their own contributions and join the community of colleagues planning to see surgery survive successfully in the future.”

The Convocation Ceremony on Sunday, October 16, which officially will open the American College of Surgeons (ACS) Clinical Congress 2016, confers Fellowship upon surgeons who meet ACS requirements and provide optimal care to their patients. ACS Officers will be installed at the ceremony, and 2016−2017 ACS President Courtney M. Townsend, Jr., MD, FACS, will deliver the Presidential Address. The ceremony also will include recognition of the Honorary Fellows as well as presentation of the Distinguished Service Award, the Mary Edwards Walker Inspiring Women in Surgery Award, and the Scientific Forum Award. In addition, this year’s Convocation Ceremony will recognize the 25- and 50-year Initiate classes from 1966 and 1991. The first Convocation Ceremony took place on November 13, 1913, at the Congress Hotel in Chicago, IL. The inaugural class of 1,059 surgeons represented the U.S. and Canada and included 6 female surgeons. Clinical Congress participants are encouraged to attend this year’s ceremony to welcome the 2016 class of 1,823 Initiates. Visit the ACS website at https://www.facs.org/member-services/initiates for more information on the ceremony and additional benefits that new initiates will receive.

The Convocation Ceremony on Sunday, October 16, which officially will open the American College of Surgeons (ACS) Clinical Congress 2016, confers Fellowship upon surgeons who meet ACS requirements and provide optimal care to their patients. ACS Officers will be installed at the ceremony, and 2016−2017 ACS President Courtney M. Townsend, Jr., MD, FACS, will deliver the Presidential Address. The ceremony also will include recognition of the Honorary Fellows as well as presentation of the Distinguished Service Award, the Mary Edwards Walker Inspiring Women in Surgery Award, and the Scientific Forum Award. In addition, this year’s Convocation Ceremony will recognize the 25- and 50-year Initiate classes from 1966 and 1991. The first Convocation Ceremony took place on November 13, 1913, at the Congress Hotel in Chicago, IL. The inaugural class of 1,059 surgeons represented the U.S. and Canada and included 6 female surgeons. Clinical Congress participants are encouraged to attend this year’s ceremony to welcome the 2016 class of 1,823 Initiates. Visit the ACS website at https://www.facs.org/member-services/initiates for more information on the ceremony and additional benefits that new initiates will receive.

The Convocation Ceremony on Sunday, October 16, which officially will open the American College of Surgeons (ACS) Clinical Congress 2016, confers Fellowship upon surgeons who meet ACS requirements and provide optimal care to their patients. ACS Officers will be installed at the ceremony, and 2016−2017 ACS President Courtney M. Townsend, Jr., MD, FACS, will deliver the Presidential Address. The ceremony also will include recognition of the Honorary Fellows as well as presentation of the Distinguished Service Award, the Mary Edwards Walker Inspiring Women in Surgery Award, and the Scientific Forum Award. In addition, this year’s Convocation Ceremony will recognize the 25- and 50-year Initiate classes from 1966 and 1991. The first Convocation Ceremony took place on November 13, 1913, at the Congress Hotel in Chicago, IL. The inaugural class of 1,059 surgeons represented the U.S. and Canada and included 6 female surgeons. Clinical Congress participants are encouraged to attend this year’s ceremony to welcome the 2016 class of 1,823 Initiates. Visit the ACS website at https://www.facs.org/member-services/initiates for more information on the ceremony and additional benefits that new initiates will receive.

American College of Surgeons (ACS) Clinical Congress 2016 attendees should plan to stay in Washington, DC, through the evening of Wednesday, October 19, to participate in the ACS Taste of the City. Join this fun event, 5:00–7:00 pm in Hall D of the Walter E. Washington Convention Center and enjoy Washington, DC’s diverse dining and cultural scene. Enjoy live music and networking with ACS leaders, staff, friends, and colleagues. The event is free to all attendees and their families. Plan to move seamlessly from Wednesday’s educational sessions to the ACS Taste of the City. The hotel shuttle bus schedule will be extended to accommodate attendees and their family members. Casual dress is encouraged. Visit the ACS website at https://www.facs.org/clincon2016/about/events/engagement for more information on this event.

American College of Surgeons (ACS) Clinical Congress 2016 attendees should plan to stay in Washington, DC, through the evening of Wednesday, October 19, to participate in the ACS Taste of the City. Join this fun event, 5:00–7:00 pm in Hall D of the Walter E. Washington Convention Center and enjoy Washington, DC’s diverse dining and cultural scene. Enjoy live music and networking with ACS leaders, staff, friends, and colleagues. The event is free to all attendees and their families. Plan to move seamlessly from Wednesday’s educational sessions to the ACS Taste of the City. The hotel shuttle bus schedule will be extended to accommodate attendees and their family members. Casual dress is encouraged. Visit the ACS website at https://www.facs.org/clincon2016/about/events/engagement for more information on this event.

American College of Surgeons (ACS) Clinical Congress 2016 attendees should plan to stay in Washington, DC, through the evening of Wednesday, October 19, to participate in the ACS Taste of the City. Join this fun event, 5:00–7:00 pm in Hall D of the Walter E. Washington Convention Center and enjoy Washington, DC’s diverse dining and cultural scene. Enjoy live music and networking with ACS leaders, staff, friends, and colleagues. The event is free to all attendees and their families. Plan to move seamlessly from Wednesday’s educational sessions to the ACS Taste of the City. The hotel shuttle bus schedule will be extended to accommodate attendees and their family members. Casual dress is encouraged. Visit the ACS website at https://www.facs.org/clincon2016/about/events/engagement for more information on this event.

The American College of Surgeons (ACS) Women in Surgery Committee (WiSC) will sponsor several activities at Clinical Congress 2016. The WiSC will present the inaugural Mary Edwards Walker Inspiring Women in Surgery Award to Mary Maniscalco-Theberge, MD, FACS, department of surgery, National Naval Medical Center, Bethesda, MD, during Convocation 6:00−8:00 pm October 16 at the Walter E. Washington Convention Center, Hall D. Alexa I. Canady, MD, FACS, will present the Olga M. Jonasson Lecture, The Journey: Becoming a Neurosurgeon and Back Again, 2:30–3:00 pm, October 18 in the convention center, Room 145. Check the Program Book or meeting app for details. View a complete list of Women in Surgery Committee–sponsored events at Clinical Congress on the ACS website at https://www.facs.org/about-acs/governance/acs-committees/women-in-surgery-committee/activities.

The American College of Surgeons (ACS) Women in Surgery Committee (WiSC) will sponsor several activities at Clinical Congress 2016. The WiSC will present the inaugural Mary Edwards Walker Inspiring Women in Surgery Award to Mary Maniscalco-Theberge, MD, FACS, department of surgery, National Naval Medical Center, Bethesda, MD, during Convocation 6:00−8:00 pm October 16 at the Walter E. Washington Convention Center, Hall D. Alexa I. Canady, MD, FACS, will present the Olga M. Jonasson Lecture, The Journey: Becoming a Neurosurgeon and Back Again, 2:30–3:00 pm, October 18 in the convention center, Room 145. Check the Program Book or meeting app for details. View a complete list of Women in Surgery Committee–sponsored events at Clinical Congress on the ACS website at https://www.facs.org/about-acs/governance/acs-committees/women-in-surgery-committee/activities.

The American College of Surgeons (ACS) Women in Surgery Committee (WiSC) will sponsor several activities at Clinical Congress 2016. The WiSC will present the inaugural Mary Edwards Walker Inspiring Women in Surgery Award to Mary Maniscalco-Theberge, MD, FACS, department of surgery, National Naval Medical Center, Bethesda, MD, during Convocation 6:00−8:00 pm October 16 at the Walter E. Washington Convention Center, Hall D. Alexa I. Canady, MD, FACS, will present the Olga M. Jonasson Lecture, The Journey: Becoming a Neurosurgeon and Back Again, 2:30–3:00 pm, October 18 in the convention center, Room 145. Check the Program Book or meeting app for details. View a complete list of Women in Surgery Committee–sponsored events at Clinical Congress on the ACS website at https://www.facs.org/about-acs/governance/acs-committees/women-in-surgery-committee/activities.

History buffs attending the American College of Surgeons (ACS) Clinical Congress 2016, October 16−20, in Washington, DC, should plan to participate in several events sponsored by the College’s Surgical History Group (SHG). Stop by the Archives booth in the ACS Resource Center of the Walter E. Washington Convention Center, and pick up this year’s premium, a packet of baseball-sized cards commemorating the first four ACS Presidents. Start collecting the first cards in this annual series. John A. Weigelt, MD, FACS, Milt & Lidy Lunda/Charles Aprahamian Professor of Trauma Surgery; professor and chief, division of trauma and critical care; and associate dean for quality, Medical College of Wisconsin, Milwaukee, and the 2015 recipient of the ACS Distinguished Service Award, will present a history of the Surgical Education and Self-Assessment Program at the Surgical History Group breakfast session, 7:00-8:00 am, Tuesday, October 18 in Room 204BC of the convention center. Attendees should plan to visit the more than 20 History of Surgery Posters, and attend the Panel Session, Three Pioneering African American Surgeons. Check the Program Book or meeting app for details, and find additional information about other SHG-sponsored events on the ACS website at https://www.facs.org/about-acs/archives/shg-events.

History buffs attending the American College of Surgeons (ACS) Clinical Congress 2016, October 16−20, in Washington, DC, should plan to participate in several events sponsored by the College’s Surgical History Group (SHG). Stop by the Archives booth in the ACS Resource Center of the Walter E. Washington Convention Center, and pick up this year’s premium, a packet of baseball-sized cards commemorating the first four ACS Presidents. Start collecting the first cards in this annual series. John A. Weigelt, MD, FACS, Milt & Lidy Lunda/Charles Aprahamian Professor of Trauma Surgery; professor and chief, division of trauma and critical care; and associate dean for quality, Medical College of Wisconsin, Milwaukee, and the 2015 recipient of the ACS Distinguished Service Award, will present a history of the Surgical Education and Self-Assessment Program at the Surgical History Group breakfast session, 7:00-8:00 am, Tuesday, October 18 in Room 204BC of the convention center. Attendees should plan to visit the more than 20 History of Surgery Posters, and attend the Panel Session, Three Pioneering African American Surgeons. Check the Program Book or meeting app for details, and find additional information about other SHG-sponsored events on the ACS website at https://www.facs.org/about-acs/archives/shg-events.

History buffs attending the American College of Surgeons (ACS) Clinical Congress 2016, October 16−20, in Washington, DC, should plan to participate in several events sponsored by the College’s Surgical History Group (SHG). Stop by the Archives booth in the ACS Resource Center of the Walter E. Washington Convention Center, and pick up this year’s premium, a packet of baseball-sized cards commemorating the first four ACS Presidents. Start collecting the first cards in this annual series. John A. Weigelt, MD, FACS, Milt & Lidy Lunda/Charles Aprahamian Professor of Trauma Surgery; professor and chief, division of trauma and critical care; and associate dean for quality, Medical College of Wisconsin, Milwaukee, and the 2015 recipient of the ACS Distinguished Service Award, will present a history of the Surgical Education and Self-Assessment Program at the Surgical History Group breakfast session, 7:00-8:00 am, Tuesday, October 18 in Room 204BC of the convention center. Attendees should plan to visit the more than 20 History of Surgery Posters, and attend the Panel Session, Three Pioneering African American Surgeons. Check the Program Book or meeting app for details, and find additional information about other SHG-sponsored events on the ACS website at https://www.facs.org/about-acs/archives/shg-events.

The American College of Surgeons Surgical Research Committee is accepting applications until February 24 for the 2017 Joan L. and Julius H. Jacobson II Promising Investigator Award. This award recognizes outstanding surgeons engaged in research, advancing the art and science of surgery, and demonstrating early promise of significant contributions to the practice of surgery and the safety of surgical patients.

This award is intended for surgeons who are at the “tipping point” of their research careers with a track record indicative of early promise and potential. Well-established surgeon-scientists are ineligible for the award.

For details on award criteria and nomination procedures, visit the Jacobson Promising Investigator Award website at https://www.facs.org/quality-programs/about/cqi/Jacobson.

The American College of Surgeons Surgical Research Committee is accepting applications until February 24 for the 2017 Joan L. and Julius H. Jacobson II Promising Investigator Award. This award recognizes outstanding surgeons engaged in research, advancing the art and science of surgery, and demonstrating early promise of significant contributions to the practice of surgery and the safety of surgical patients.

This award is intended for surgeons who are at the “tipping point” of their research careers with a track record indicative of early promise and potential. Well-established surgeon-scientists are ineligible for the award.

For details on award criteria and nomination procedures, visit the Jacobson Promising Investigator Award website at https://www.facs.org/quality-programs/about/cqi/Jacobson.

The American College of Surgeons Surgical Research Committee is accepting applications until February 24 for the 2017 Joan L. and Julius H. Jacobson II Promising Investigator Award. This award recognizes outstanding surgeons engaged in research, advancing the art and science of surgery, and demonstrating early promise of significant contributions to the practice of surgery and the safety of surgical patients.

This award is intended for surgeons who are at the “tipping point” of their research careers with a track record indicative of early promise and potential. Well-established surgeon-scientists are ineligible for the award.

For details on award criteria and nomination procedures, visit the Jacobson Promising Investigator Award website at https://www.facs.org/quality-programs/about/cqi/Jacobson.

BOSTON – For patients with resected brain metastases, stereotactic radiosurgery offers survival comparable with what’s seen with whole-brain radiotherapy, but with better quality of life and more effective preservation of cognitive function, investigators reported.

In the phase III N107C trial, there was no difference in overall survival between patients who were randomly assigned to undergo stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT), but patients who underwent WBRT had a twofold greater decline in cognitive function, compared with patients who underwent SRS, Paul D. Brown, MD, a radiation oncologist at the Mayo Clinic in Rochester, Minn., reported at the annual meeting of the American Society for Radiation Oncology.

In a similar prospective, randomized study, Anita Mahajan, MD, and colleagues from the University of Texas MD Anderson Cancer Center in Houston compared postoperative SRS after complete resection with observation alone in 128 patients, and found that although there was no difference in either distant brain metastases or overall survival, SRS was associated with significant improvements in local control.

“I think that going forward with the next patient I see with this scenario, I’m going to be a bit better informed and be able to inform my patient better of the trade-offs involved with regards to the decision of SRS vs. whole-brain radiotherapy,” commented George Rodrigues, MD, from the London (Ontario) Health Sciences Center in Canada. Dr. Rodrigues moderated a briefing during which Dr. Brown and Dr. Mahajan presented their data.

WBRT has been the standard of care for improving local control following surgical resection of brain metastases, but it does not offer a survival benefit and comes at a significant cost in side effects, including alopecia, fatigue, erythema, and, most distressing to patients, significant decline in cognitive function.

The precision of radiosurgery, on the other hand, allows the radiation dose to be concentrated on the surgical bed, limiting exposure of surrounding tissues and structures. For this reason, many centers have begun to adopt SRS for patients with resected brain metastases, but there is not level I evidence to back it up, Dr. Brown said.

WBRT vs. SRS

To rectify this situation, Dr. Brown and his colleagues at the Mayo Clinic and 47 other institutions conducted a clinical trial in 194 patients with one to four brain metastases.

Following surgical resection, the patients were stratified by age, duration of extracranial disease control, number of preoperative metastases, histology, maximum diameter of the resection cavity, and institution, and then randomly assigned to undergo either WBRT or SRS.

Patients were assessed for cognitive function (a coprimary endpoint with overall survival) at baseline and approximately every 3 months thereafter for up to 24 months. Other assessments included MRI scans, and FACT-Br (Functional Assessment of Cancer Therapy-Brain), a quality-of-life instrument.

After a median follow-up of 18.7 months, there was no difference in median overall survival, which was 11.5 months for WBRT and 11.8 months for SRS.

There was, however, a significant difference in cognitive deterioration–free survival, which was 2.8 months for WBRT vs. 3.3 months for SRS. The hazard ratio for WBRT was 2.05 (P = .0001). Cognitive deterioration–free survival rates at 6 months were 5.4% and 22.9%, respectively (P = .0012).

The declines in cognitive function were accounted for by significant differences in the Hopkins Verbal Learning Test (HVLT) domains of total and delayed recall and in the Trail Making Test (Part A).

Overall brain disease control was significantly better with WBRT than with SRS at 3 months (P = .003) and at 6 and 12 months (P less than .001 for each time point).

Surgical bed control was similar between the treatment groups at 6 and 12 months, but was significantly better with WBRT at 12 months, with surgical bed relapse occurring in 21.8% and 44.4% of patients, respectively.

Patients treated with SRS reported significantly better physical well being at 3 and 6 months (P = .002 and .014, respectively). There were 18 grade 3 or greater radiation-related adverse events among patients treated with WBRT, compared with 7 among patients treated with SRS.

SRS vs. observation

In the MD Anderson study, 45% of patients who underwent observation alone had local control of disease at 12 months, compared with 72% treated with SRS. The hazard ratio for SRS was 0.46 (P = .01). The median time to local recurrence was 7.6 months among patients on observation only, but no time point was reached for SRS-treated patients.

The evidence from the two trials suggests that “radiosurgery is a, but not the, standard of care following resection for brain metastasis,” said Vinai Gondi, MD, of the Northwestern Medicine Cancer Center in Warrenville, Ill., the invited discussant.

“While the MD Anderson trial clearly demonstrated that radiosurgery reduces the risk of surgical bed relapse, the N107C trial demonstrated a 44% risk of surgical bed relapse, a rate that is arguably too high in regards to the long survival of resected brain metastasis patients, and it also challenges and risks the resection of surgical bed relapse following radiosurgery,” he said.

The N107C trial was sponsored by the National Cancer Institute and the Alliance for Clinical Trials in Oncology. The MD Anderson trial was funded by a Cancer Center Grant. Dr. Brown, Dr. Mahajan, and Dr. Rodrigues reported no conflicts of interest.

BOSTON – For patients with resected brain metastases, stereotactic radiosurgery offers survival comparable with what’s seen with whole-brain radiotherapy, but with better quality of life and more effective preservation of cognitive function, investigators reported.

In the phase III N107C trial, there was no difference in overall survival between patients who were randomly assigned to undergo stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT), but patients who underwent WBRT had a twofold greater decline in cognitive function, compared with patients who underwent SRS, Paul D. Brown, MD, a radiation oncologist at the Mayo Clinic in Rochester, Minn., reported at the annual meeting of the American Society for Radiation Oncology.

In a similar prospective, randomized study, Anita Mahajan, MD, and colleagues from the University of Texas MD Anderson Cancer Center in Houston compared postoperative SRS after complete resection with observation alone in 128 patients, and found that although there was no difference in either distant brain metastases or overall survival, SRS was associated with significant improvements in local control.

“I think that going forward with the next patient I see with this scenario, I’m going to be a bit better informed and be able to inform my patient better of the trade-offs involved with regards to the decision of SRS vs. whole-brain radiotherapy,” commented George Rodrigues, MD, from the London (Ontario) Health Sciences Center in Canada. Dr. Rodrigues moderated a briefing during which Dr. Brown and Dr. Mahajan presented their data.

WBRT has been the standard of care for improving local control following surgical resection of brain metastases, but it does not offer a survival benefit and comes at a significant cost in side effects, including alopecia, fatigue, erythema, and, most distressing to patients, significant decline in cognitive function.

The precision of radiosurgery, on the other hand, allows the radiation dose to be concentrated on the surgical bed, limiting exposure of surrounding tissues and structures. For this reason, many centers have begun to adopt SRS for patients with resected brain metastases, but there is not level I evidence to back it up, Dr. Brown said.

WBRT vs. SRS

To rectify this situation, Dr. Brown and his colleagues at the Mayo Clinic and 47 other institutions conducted a clinical trial in 194 patients with one to four brain metastases.

Following surgical resection, the patients were stratified by age, duration of extracranial disease control, number of preoperative metastases, histology, maximum diameter of the resection cavity, and institution, and then randomly assigned to undergo either WBRT or SRS.

Patients were assessed for cognitive function (a coprimary endpoint with overall survival) at baseline and approximately every 3 months thereafter for up to 24 months. Other assessments included MRI scans, and FACT-Br (Functional Assessment of Cancer Therapy-Brain), a quality-of-life instrument.

After a median follow-up of 18.7 months, there was no difference in median overall survival, which was 11.5 months for WBRT and 11.8 months for SRS.

There was, however, a significant difference in cognitive deterioration–free survival, which was 2.8 months for WBRT vs. 3.3 months for SRS. The hazard ratio for WBRT was 2.05 (P = .0001). Cognitive deterioration–free survival rates at 6 months were 5.4% and 22.9%, respectively (P = .0012).

The declines in cognitive function were accounted for by significant differences in the Hopkins Verbal Learning Test (HVLT) domains of total and delayed recall and in the Trail Making Test (Part A).

Overall brain disease control was significantly better with WBRT than with SRS at 3 months (P = .003) and at 6 and 12 months (P less than .001 for each time point).

Surgical bed control was similar between the treatment groups at 6 and 12 months, but was significantly better with WBRT at 12 months, with surgical bed relapse occurring in 21.8% and 44.4% of patients, respectively.

Patients treated with SRS reported significantly better physical well being at 3 and 6 months (P = .002 and .014, respectively). There were 18 grade 3 or greater radiation-related adverse events among patients treated with WBRT, compared with 7 among patients treated with SRS.

SRS vs. observation

In the MD Anderson study, 45% of patients who underwent observation alone had local control of disease at 12 months, compared with 72% treated with SRS. The hazard ratio for SRS was 0.46 (P = .01). The median time to local recurrence was 7.6 months among patients on observation only, but no time point was reached for SRS-treated patients.

The evidence from the two trials suggests that “radiosurgery is a, but not the, standard of care following resection for brain metastasis,” said Vinai Gondi, MD, of the Northwestern Medicine Cancer Center in Warrenville, Ill., the invited discussant.

“While the MD Anderson trial clearly demonstrated that radiosurgery reduces the risk of surgical bed relapse, the N107C trial demonstrated a 44% risk of surgical bed relapse, a rate that is arguably too high in regards to the long survival of resected brain metastasis patients, and it also challenges and risks the resection of surgical bed relapse following radiosurgery,” he said.

The N107C trial was sponsored by the National Cancer Institute and the Alliance for Clinical Trials in Oncology. The MD Anderson trial was funded by a Cancer Center Grant. Dr. Brown, Dr. Mahajan, and Dr. Rodrigues reported no conflicts of interest.

BOSTON – For patients with resected brain metastases, stereotactic radiosurgery offers survival comparable with what’s seen with whole-brain radiotherapy, but with better quality of life and more effective preservation of cognitive function, investigators reported.

In the phase III N107C trial, there was no difference in overall survival between patients who were randomly assigned to undergo stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT), but patients who underwent WBRT had a twofold greater decline in cognitive function, compared with patients who underwent SRS, Paul D. Brown, MD, a radiation oncologist at the Mayo Clinic in Rochester, Minn., reported at the annual meeting of the American Society for Radiation Oncology.

In a similar prospective, randomized study, Anita Mahajan, MD, and colleagues from the University of Texas MD Anderson Cancer Center in Houston compared postoperative SRS after complete resection with observation alone in 128 patients, and found that although there was no difference in either distant brain metastases or overall survival, SRS was associated with significant improvements in local control.

“I think that going forward with the next patient I see with this scenario, I’m going to be a bit better informed and be able to inform my patient better of the trade-offs involved with regards to the decision of SRS vs. whole-brain radiotherapy,” commented George Rodrigues, MD, from the London (Ontario) Health Sciences Center in Canada. Dr. Rodrigues moderated a briefing during which Dr. Brown and Dr. Mahajan presented their data.

WBRT has been the standard of care for improving local control following surgical resection of brain metastases, but it does not offer a survival benefit and comes at a significant cost in side effects, including alopecia, fatigue, erythema, and, most distressing to patients, significant decline in cognitive function.

The precision of radiosurgery, on the other hand, allows the radiation dose to be concentrated on the surgical bed, limiting exposure of surrounding tissues and structures. For this reason, many centers have begun to adopt SRS for patients with resected brain metastases, but there is not level I evidence to back it up, Dr. Brown said.

WBRT vs. SRS

To rectify this situation, Dr. Brown and his colleagues at the Mayo Clinic and 47 other institutions conducted a clinical trial in 194 patients with one to four brain metastases.

Following surgical resection, the patients were stratified by age, duration of extracranial disease control, number of preoperative metastases, histology, maximum diameter of the resection cavity, and institution, and then randomly assigned to undergo either WBRT or SRS.

Patients were assessed for cognitive function (a coprimary endpoint with overall survival) at baseline and approximately every 3 months thereafter for up to 24 months. Other assessments included MRI scans, and FACT-Br (Functional Assessment of Cancer Therapy-Brain), a quality-of-life instrument.

After a median follow-up of 18.7 months, there was no difference in median overall survival, which was 11.5 months for WBRT and 11.8 months for SRS.

There was, however, a significant difference in cognitive deterioration–free survival, which was 2.8 months for WBRT vs. 3.3 months for SRS. The hazard ratio for WBRT was 2.05 (P = .0001). Cognitive deterioration–free survival rates at 6 months were 5.4% and 22.9%, respectively (P = .0012).

The declines in cognitive function were accounted for by significant differences in the Hopkins Verbal Learning Test (HVLT) domains of total and delayed recall and in the Trail Making Test (Part A).

Overall brain disease control was significantly better with WBRT than with SRS at 3 months (P = .003) and at 6 and 12 months (P less than .001 for each time point).

Surgical bed control was similar between the treatment groups at 6 and 12 months, but was significantly better with WBRT at 12 months, with surgical bed relapse occurring in 21.8% and 44.4% of patients, respectively.

Patients treated with SRS reported significantly better physical well being at 3 and 6 months (P = .002 and .014, respectively). There were 18 grade 3 or greater radiation-related adverse events among patients treated with WBRT, compared with 7 among patients treated with SRS.

SRS vs. observation

In the MD Anderson study, 45% of patients who underwent observation alone had local control of disease at 12 months, compared with 72% treated with SRS. The hazard ratio for SRS was 0.46 (P = .01). The median time to local recurrence was 7.6 months among patients on observation only, but no time point was reached for SRS-treated patients.

The evidence from the two trials suggests that “radiosurgery is a, but not the, standard of care following resection for brain metastasis,” said Vinai Gondi, MD, of the Northwestern Medicine Cancer Center in Warrenville, Ill., the invited discussant.

“While the MD Anderson trial clearly demonstrated that radiosurgery reduces the risk of surgical bed relapse, the N107C trial demonstrated a 44% risk of surgical bed relapse, a rate that is arguably too high in regards to the long survival of resected brain metastasis patients, and it also challenges and risks the resection of surgical bed relapse following radiosurgery,” he said.

The N107C trial was sponsored by the National Cancer Institute and the Alliance for Clinical Trials in Oncology. The MD Anderson trial was funded by a Cancer Center Grant. Dr. Brown, Dr. Mahajan, and Dr. Rodrigues reported no conflicts of interest.

A great volume of HIV and AIDS research enters the medical literature every month. It’s difficult to monitor everything, so here’s a quick look at some notable news items and journal articles published over the past few weeks.

The frequency of safety monitoring for HIV pre-exposure prophylaxis (PrEP) might need to be different between age groups, according to a recent study, and pharmacological measures can monitor for toxic effects as well as adherence.

©alexskopje/ThinkStock.com

A European research group found a beneficial effect of starting antiretroviral therapy before adolescence in perinatally infected individuals, and starting young people on boosted protease inhibitors, to maximize treatment response during this transitional stage of development.

Chinese investigators found that an online social entrepreneurship testing (SET) model to promote HIV and syphilis self-testing among Chinese men who have sex with men was acceptable and feasible, and they say that the model adds a new testing platform to the current testing service system.

A review analysis found that dolutegravir 50 mg given once daily, combined with an active background drug, is a better choice than raltegravir- or efavirenz-based regimens for treatment of HIV-1 infection, in terms of both efficacy and safety.

A recent study found that HIV suppression restores lung mucosal HIV-specific CD4⁺ T-cell multifunctional immunity and CD4:CD8 balance, often resolving CD8⁺ alveolitis in active smokers.

A study in Clinical Infectious Diseases found that only the Framingham general cardiovascular Risk Score (FRS) accurately estimated the risk of cardiovascular disease risk events in HIV patients, while the American College of Cardiology/American Heart Association Pooled Cohort equations (PCE), and the Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) study equation underestimated risk.

A study in AIDS Care found a high burden of mental health disorders among harder-to-reach people living with HIV/AIDS (PHA), and suggests that PHA with at least one mental health disorder diagnosis are disproportionately affected by sexual violence and stigma.

Neurocognitive declines in HIV-positive patients may vary by domains of functioning and disparities may exist across subpopulations of the seropositive aging population, according to a recent study, and these challenges may exist even in those actively engaged in HIV care.

A high rate of recent HIV infection is potentially resulting in progressive deterioration of the overall HIV epidemic among men who have sex with men in China, according to a study in Infectious Diseases of Poverty. The authors said targeted interventions to address high-risk men who have sex with men including those having multiple partners, history of recreational drug use, and syphilis or HSV-2 infection are needed.

A recent study indicated that the variability in estimates of spontaneous viral clearance of hepatitis C virus infection – between HIV-positive men who have sex with men and people who inject drugs – suggests the impact of HIV coinfection and HCV reinfection.

A study published in the journal AIDS found that despite substantially higher CD4% at initiation of antiretroviral therapy, viral suppression was significantly slower among infants than older children.

Grip strength decline is accelerated in HIV-infected men, which may signal decreased life expectancy and lower quality of life with aging, according to an analysis by the Multicenter AIDS Cohort Study.

A study in HIV Medicine found that reference curves for CD4 T-cell count response aid the evaluation of the immune response in HIV-positive patients early after antiretroviral therapy initiation that leads to viral control.

According to WHO standards, Rwanda antenatal clinic HIV serosurveillance is ready to transition to prevention of mother to child transmission (PMTCT)-based serosurveillance.

Oxidized lipoproteins may contribute to persistent immune activation in HIV patients on antiretroviral therapy, a new study found.

A French study found that the rate of patients failing to return for the results of HIV, HBV, HCV, and syphilis testing is a problem, but the use of currently available technologies, such as phone texting, might be a partial solution in conjunction with rapid tests for diagnosis.

A 12-city U.S. research project on pre-exposure prophylaxis for HIV found that young men who have sex with men may need PrEP access in youth-friendly settings with tailored adherence support and potentially augmented visit schedules.

rpizzi@frontlinemedcom.com

On Twitter @richpizzi

A great volume of HIV and AIDS research enters the medical literature every month. It’s difficult to monitor everything, so here’s a quick look at some notable news items and journal articles published over the past few weeks.

The frequency of safety monitoring for HIV pre-exposure prophylaxis (PrEP) might need to be different between age groups, according to a recent study, and pharmacological measures can monitor for toxic effects as well as adherence.

©alexskopje/ThinkStock.com

A European research group found a beneficial effect of starting antiretroviral therapy before adolescence in perinatally infected individuals, and starting young people on boosted protease inhibitors, to maximize treatment response during this transitional stage of development.

Chinese investigators found that an online social entrepreneurship testing (SET) model to promote HIV and syphilis self-testing among Chinese men who have sex with men was acceptable and feasible, and they say that the model adds a new testing platform to the current testing service system.

A review analysis found that dolutegravir 50 mg given once daily, combined with an active background drug, is a better choice than raltegravir- or efavirenz-based regimens for treatment of HIV-1 infection, in terms of both efficacy and safety.

A recent study found that HIV suppression restores lung mucosal HIV-specific CD4⁺ T-cell multifunctional immunity and CD4:CD8 balance, often resolving CD8⁺ alveolitis in active smokers.

A study in Clinical Infectious Diseases found that only the Framingham general cardiovascular Risk Score (FRS) accurately estimated the risk of cardiovascular disease risk events in HIV patients, while the American College of Cardiology/American Heart Association Pooled Cohort equations (PCE), and the Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) study equation underestimated risk.

A study in AIDS Care found a high burden of mental health disorders among harder-to-reach people living with HIV/AIDS (PHA), and suggests that PHA with at least one mental health disorder diagnosis are disproportionately affected by sexual violence and stigma.

Neurocognitive declines in HIV-positive patients may vary by domains of functioning and disparities may exist across subpopulations of the seropositive aging population, according to a recent study, and these challenges may exist even in those actively engaged in HIV care.

A high rate of recent HIV infection is potentially resulting in progressive deterioration of the overall HIV epidemic among men who have sex with men in China, according to a study in Infectious Diseases of Poverty. The authors said targeted interventions to address high-risk men who have sex with men including those having multiple partners, history of recreational drug use, and syphilis or HSV-2 infection are needed.

A recent study indicated that the variability in estimates of spontaneous viral clearance of hepatitis C virus infection – between HIV-positive men who have sex with men and people who inject drugs – suggests the impact of HIV coinfection and HCV reinfection.

A study published in the journal AIDS found that despite substantially higher CD4% at initiation of antiretroviral therapy, viral suppression was significantly slower among infants than older children.

Grip strength decline is accelerated in HIV-infected men, which may signal decreased life expectancy and lower quality of life with aging, according to an analysis by the Multicenter AIDS Cohort Study.

A study in HIV Medicine found that reference curves for CD4 T-cell count response aid the evaluation of the immune response in HIV-positive patients early after antiretroviral therapy initiation that leads to viral control.

According to WHO standards, Rwanda antenatal clinic HIV serosurveillance is ready to transition to prevention of mother to child transmission (PMTCT)-based serosurveillance.

Oxidized lipoproteins may contribute to persistent immune activation in HIV patients on antiretroviral therapy, a new study found.

A French study found that the rate of patients failing to return for the results of HIV, HBV, HCV, and syphilis testing is a problem, but the use of currently available technologies, such as phone texting, might be a partial solution in conjunction with rapid tests for diagnosis.

A 12-city U.S. research project on pre-exposure prophylaxis for HIV found that young men who have sex with men may need PrEP access in youth-friendly settings with tailored adherence support and potentially augmented visit schedules.

rpizzi@frontlinemedcom.com

On Twitter @richpizzi

A great volume of HIV and AIDS research enters the medical literature every month. It’s difficult to monitor everything, so here’s a quick look at some notable news items and journal articles published over the past few weeks.

The frequency of safety monitoring for HIV pre-exposure prophylaxis (PrEP) might need to be different between age groups, according to a recent study, and pharmacological measures can monitor for toxic effects as well as adherence.

©alexskopje/ThinkStock.com

A European research group found a beneficial effect of starting antiretroviral therapy before adolescence in perinatally infected individuals, and starting young people on boosted protease inhibitors, to maximize treatment response during this transitional stage of development.

Chinese investigators found that an online social entrepreneurship testing (SET) model to promote HIV and syphilis self-testing among Chinese men who have sex with men was acceptable and feasible, and they say that the model adds a new testing platform to the current testing service system.

A review analysis found that dolutegravir 50 mg given once daily, combined with an active background drug, is a better choice than raltegravir- or efavirenz-based regimens for treatment of HIV-1 infection, in terms of both efficacy and safety.

A recent study found that HIV suppression restores lung mucosal HIV-specific CD4⁺ T-cell multifunctional immunity and CD4:CD8 balance, often resolving CD8⁺ alveolitis in active smokers.

A study in Clinical Infectious Diseases found that only the Framingham general cardiovascular Risk Score (FRS) accurately estimated the risk of cardiovascular disease risk events in HIV patients, while the American College of Cardiology/American Heart Association Pooled Cohort equations (PCE), and the Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) study equation underestimated risk.

A study in AIDS Care found a high burden of mental health disorders among harder-to-reach people living with HIV/AIDS (PHA), and suggests that PHA with at least one mental health disorder diagnosis are disproportionately affected by sexual violence and stigma.

Neurocognitive declines in HIV-positive patients may vary by domains of functioning and disparities may exist across subpopulations of the seropositive aging population, according to a recent study, and these challenges may exist even in those actively engaged in HIV care.

A high rate of recent HIV infection is potentially resulting in progressive deterioration of the overall HIV epidemic among men who have sex with men in China, according to a study in Infectious Diseases of Poverty. The authors said targeted interventions to address high-risk men who have sex with men including those having multiple partners, history of recreational drug use, and syphilis or HSV-2 infection are needed.

A recent study indicated that the variability in estimates of spontaneous viral clearance of hepatitis C virus infection – between HIV-positive men who have sex with men and people who inject drugs – suggests the impact of HIV coinfection and HCV reinfection.

A study published in the journal AIDS found that despite substantially higher CD4% at initiation of antiretroviral therapy, viral suppression was significantly slower among infants than older children.

Grip strength decline is accelerated in HIV-infected men, which may signal decreased life expectancy and lower quality of life with aging, according to an analysis by the Multicenter AIDS Cohort Study.

A study in HIV Medicine found that reference curves for CD4 T-cell count response aid the evaluation of the immune response in HIV-positive patients early after antiretroviral therapy initiation that leads to viral control.

According to WHO standards, Rwanda antenatal clinic HIV serosurveillance is ready to transition to prevention of mother to child transmission (PMTCT)-based serosurveillance.

Oxidized lipoproteins may contribute to persistent immune activation in HIV patients on antiretroviral therapy, a new study found.

A French study found that the rate of patients failing to return for the results of HIV, HBV, HCV, and syphilis testing is a problem, but the use of currently available technologies, such as phone texting, might be a partial solution in conjunction with rapid tests for diagnosis.

A 12-city U.S. research project on pre-exposure prophylaxis for HIV found that young men who have sex with men may need PrEP access in youth-friendly settings with tailored adherence support and potentially augmented visit schedules.

rpizzi@frontlinemedcom.com

On Twitter @richpizzi

Pre-exposure prophylaxis (PrEP) therapy is safe for HIV-uninfected women breastfeeding their infants, according to a study in PLOS Medicine.

As PrEP becomes more widely used in heterosexual populations, an important consideration is its safety in infants who are breastfed by women taking the drugs, reported Kenneth Mugwanya, MBChB, PhD, of the University of Washington, Seattle, and his associates (PLOS Med. 2016 Sep 27. doi: 10.1371/journal.pmed.1002132).

oksun70/ThinkStock

The purpose of this small, prospective short-term trialwas to quantify drug levels in maternal blood samples, breast milk, and infant blood samples to begin to understand if PrEP is safe for use in pregnant or breastfeeding women at high risk for contracting HIV.

Antiretroviral PrEP with 300 mg tenofovir disoproxil fumarate and 200 mg emtricitabine was administered to 50 HIV-uninfected breastfeeding mothers through daily directly observed therapy for 10 consecutive days and then discontinued thereafter. All mothers were African and resided in Kenya or Uganda. Median maternal age was 25 years; 48% of infants were younger than 12 weeks and 52% were between 13 and 24 weeks of age. Across the study cohort, the median daily frequency of breastfeeding was 15 times.

Maternal blood and breast milk samples were collected and analyzed for drug concentrations at days 7 and 10 of the study. Peak concentration samples, collected 1-2 hours after PrEP administration, and trough concentration levels, collected 23-24 hours after PrEP dose, were collected on day 7 and day 10. Infant blood samples were collected only once, on day 7.

In maternal blood samples, tenofovir was detected at concentrations consistent with steady-state use (median peak concentration, 152.0 ng/mL). In breast milk, tenofovir was present in significantly lower concentrations (3.2 ng/mL). Emtricitabine was also detected at concentrations consistent with steady-state use in maternal blood samples (median peak concentration, 267.5 ng/mL); however, unlike tenofovir, emtricitabine concentration in breast milk was similar to peak plasma concentrations (212.5 ng/mL). Tenofovir was undetectable in 46 of 49 (94%) infant plasma samples. For the three infants with detectable tenofovir, the plasma concentrations were 0.9, 0.9, and 17.4 ng/mL, corresponding body weights were 6.4, 5.8, and 6.2 kg, and their maternal milk tenofovir concentrations were “modestly greater” than the median at 6.57, 3.64, and 4.05 ng/mL, respectively.

Emtricitabine, on the other hand, was detectable in 47 of 49 (96%) infant plasma samples with a median concentration of 13.2 ng/mL.

“The estimated daily tenofovir and emtricitabine doses ingested by the infant through breastfeeding were 12,500-fold and 200-fold, respectively, lower than the proposed daily pediatric dose for prophylaxis against vertical HIV acquisition. Thus, infants had low exposures to tenofovir and emtricitabine, which would not be expected to pose substantial safety risk to infants of mothers who use PrEP during breastfeeding,” Dr. Mugwanya and his associates wrote.

“These data provide evidence suggesting that this PrEP regimen can be safely used during breastfeeding, which is informative for clinical guidelines for women who are at substantial risk of HIV during pregnancy and the postpartum period,” the researchers concluded.

This study was funded by the Bill and Melinda Gates Foundation and the National Institutes of Health. The authors did not report disclosures.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig

Pre-exposure prophylaxis (PrEP) therapy is safe for HIV-uninfected women breastfeeding their infants, according to a study in PLOS Medicine.

As PrEP becomes more widely used in heterosexual populations, an important consideration is its safety in infants who are breastfed by women taking the drugs, reported Kenneth Mugwanya, MBChB, PhD, of the University of Washington, Seattle, and his associates (PLOS Med. 2016 Sep 27. doi: 10.1371/journal.pmed.1002132).

oksun70/ThinkStock

The purpose of this small, prospective short-term trialwas to quantify drug levels in maternal blood samples, breast milk, and infant blood samples to begin to understand if PrEP is safe for use in pregnant or breastfeeding women at high risk for contracting HIV.

Antiretroviral PrEP with 300 mg tenofovir disoproxil fumarate and 200 mg emtricitabine was administered to 50 HIV-uninfected breastfeeding mothers through daily directly observed therapy for 10 consecutive days and then discontinued thereafter. All mothers were African and resided in Kenya or Uganda. Median maternal age was 25 years; 48% of infants were younger than 12 weeks and 52% were between 13 and 24 weeks of age. Across the study cohort, the median daily frequency of breastfeeding was 15 times.

Maternal blood and breast milk samples were collected and analyzed for drug concentrations at days 7 and 10 of the study. Peak concentration samples, collected 1-2 hours after PrEP administration, and trough concentration levels, collected 23-24 hours after PrEP dose, were collected on day 7 and day 10. Infant blood samples were collected only once, on day 7.

In maternal blood samples, tenofovir was detected at concentrations consistent with steady-state use (median peak concentration, 152.0 ng/mL). In breast milk, tenofovir was present in significantly lower concentrations (3.2 ng/mL). Emtricitabine was also detected at concentrations consistent with steady-state use in maternal blood samples (median peak concentration, 267.5 ng/mL); however, unlike tenofovir, emtricitabine concentration in breast milk was similar to peak plasma concentrations (212.5 ng/mL). Tenofovir was undetectable in 46 of 49 (94%) infant plasma samples. For the three infants with detectable tenofovir, the plasma concentrations were 0.9, 0.9, and 17.4 ng/mL, corresponding body weights were 6.4, 5.8, and 6.2 kg, and their maternal milk tenofovir concentrations were “modestly greater” than the median at 6.57, 3.64, and 4.05 ng/mL, respectively.

Emtricitabine, on the other hand, was detectable in 47 of 49 (96%) infant plasma samples with a median concentration of 13.2 ng/mL.

“The estimated daily tenofovir and emtricitabine doses ingested by the infant through breastfeeding were 12,500-fold and 200-fold, respectively, lower than the proposed daily pediatric dose for prophylaxis against vertical HIV acquisition. Thus, infants had low exposures to tenofovir and emtricitabine, which would not be expected to pose substantial safety risk to infants of mothers who use PrEP during breastfeeding,” Dr. Mugwanya and his associates wrote.

“These data provide evidence suggesting that this PrEP regimen can be safely used during breastfeeding, which is informative for clinical guidelines for women who are at substantial risk of HIV during pregnancy and the postpartum period,” the researchers concluded.

This study was funded by the Bill and Melinda Gates Foundation and the National Institutes of Health. The authors did not report disclosures.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig

Pre-exposure prophylaxis (PrEP) therapy is safe for HIV-uninfected women breastfeeding their infants, according to a study in PLOS Medicine.

As PrEP becomes more widely used in heterosexual populations, an important consideration is its safety in infants who are breastfed by women taking the drugs, reported Kenneth Mugwanya, MBChB, PhD, of the University of Washington, Seattle, and his associates (PLOS Med. 2016 Sep 27. doi: 10.1371/journal.pmed.1002132).

oksun70/ThinkStock

The purpose of this small, prospective short-term trialwas to quantify drug levels in maternal blood samples, breast milk, and infant blood samples to begin to understand if PrEP is safe for use in pregnant or breastfeeding women at high risk for contracting HIV.

Antiretroviral PrEP with 300 mg tenofovir disoproxil fumarate and 200 mg emtricitabine was administered to 50 HIV-uninfected breastfeeding mothers through daily directly observed therapy for 10 consecutive days and then discontinued thereafter. All mothers were African and resided in Kenya or Uganda. Median maternal age was 25 years; 48% of infants were younger than 12 weeks and 52% were between 13 and 24 weeks of age. Across the study cohort, the median daily frequency of breastfeeding was 15 times.

Maternal blood and breast milk samples were collected and analyzed for drug concentrations at days 7 and 10 of the study. Peak concentration samples, collected 1-2 hours after PrEP administration, and trough concentration levels, collected 23-24 hours after PrEP dose, were collected on day 7 and day 10. Infant blood samples were collected only once, on day 7.

In maternal blood samples, tenofovir was detected at concentrations consistent with steady-state use (median peak concentration, 152.0 ng/mL). In breast milk, tenofovir was present in significantly lower concentrations (3.2 ng/mL). Emtricitabine was also detected at concentrations consistent with steady-state use in maternal blood samples (median peak concentration, 267.5 ng/mL); however, unlike tenofovir, emtricitabine concentration in breast milk was similar to peak plasma concentrations (212.5 ng/mL). Tenofovir was undetectable in 46 of 49 (94%) infant plasma samples. For the three infants with detectable tenofovir, the plasma concentrations were 0.9, 0.9, and 17.4 ng/mL, corresponding body weights were 6.4, 5.8, and 6.2 kg, and their maternal milk tenofovir concentrations were “modestly greater” than the median at 6.57, 3.64, and 4.05 ng/mL, respectively.

Emtricitabine, on the other hand, was detectable in 47 of 49 (96%) infant plasma samples with a median concentration of 13.2 ng/mL.

“The estimated daily tenofovir and emtricitabine doses ingested by the infant through breastfeeding were 12,500-fold and 200-fold, respectively, lower than the proposed daily pediatric dose for prophylaxis against vertical HIV acquisition. Thus, infants had low exposures to tenofovir and emtricitabine, which would not be expected to pose substantial safety risk to infants of mothers who use PrEP during breastfeeding,” Dr. Mugwanya and his associates wrote.

“These data provide evidence suggesting that this PrEP regimen can be safely used during breastfeeding, which is informative for clinical guidelines for women who are at substantial risk of HIV during pregnancy and the postpartum period,” the researchers concluded.

This study was funded by the Bill and Melinda Gates Foundation and the National Institutes of Health. The authors did not report disclosures.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig

ORLANDO – Transitioning patients with hemophilia from standard clotting factor concentrates to newer extended half-life products takes planning, education, and a little patience, but the payoff can be better hemostasis, a hemophilia treatment specialist said.

“Real-world experience shows us that you can maintain effective protection with less infusion with these new products, but we also know that each person should be evaluated individually when determining what their specific optimal treatment is,” said Jennifer Maahs, a hemophilia nurse practitioner at the Indiana Hemophilia and Thrombosis Center in Indianapolis.

Staff and patient education about the proper use of newer extended half-life (EHL) products is the key to success, she added in an oral session at the World Federation of Hemophilia World Congress.

The new EHL products allow for longer intervals between doses, especially with EHL recombinant factor IX used to treat hemophilia B. Prophylaxis with standard factor IX concentrates requires doses of 25-40 IU/kg twice weekly; in contrasts, EHL products can be given in various doses based on patient responses of either 50 IU/kg every 7 days, 100 IU/kg every 10 days, 25-40 IU/kg every 7 days, or 50-75 IU/kg every 14 days.

In general, the longer intervals between dosing occur in adults; young children tend to require more frequent dosing and have lower levels of factor recovery, she noted.

Extended Experience

Her center currently has more than 100 patients maintained on prolonged half-life factor VIII and factor IX products.

“We have really learned a lot of lessons along the way, and we have had to modify our approach based on these lessons,” she said. “Each patient situation is unique, and everything needs to be individualized.”

Staff review the published literature to educate themselves on the EHL products and prepare answers to expected questions from patients. Ms. Maahs suggested identifying key staff who are best equipped to answer specific questions.

“From a patient standpoint, we’ve developed a patient notification letter, so for any new product that comes out – for example a new factor VIII product – the notification gets sent out factor VIII patients, and we do that for every new product that comes out,” she said.

PK OK

Pharmacokinetic (PK) analyses may also be helpful in transitioning patients to EHL products.

To test patient responses to new products, her center tests patients for recovery from 15 minutes to 1 hour post-infusion, which will provide information about how the patient may respond to the product during a bleeding episode.

If the patient is on prophylaxis they will evaluate trough effectiveness to determine that patient’s responsiveness at the lowest level prior to the next infusion. Testing at other time points may be required based on the patient’s individual clinical history.

Center staff talk with each patient to discuss his needs and capabilities. If the patient is currently being managed with on-demand therapy, the talk may center on obstacles to utilization of prophylaxis and the patient’s desired infusion interval.

For patients currently on prophylaxis, they discuss the current regimen frequency and dose and assess how well it’s working. Staff members also provide information about alternative approaches to therapy, and ask patients specifically about their activity levels and dates of activity, compared with currently scheduled infusion days.

Patients are also educated about the reconstitution requirements for the new product, and are told to use up any remaining concentrates before switching over to the new product.

“As we move forward, within 2 to 4 weeks of starting a new therapy, we like to obtain a trough to see how their prophylaxis is working. At that time we ask how have you been doing on the new product, are you having any breakthrough bleeding, and how are you feeling about it,” Ms. Maahs said.

Weekly phone calls to the patient during the first month are also very helpful for reinforcing information about dosing regimens for bleeding episodes, reminding patients to call in if they experience a lead, and encouraging them to keep a treatment log. The phone call can also be helpful in identifying potential product-related reactions or other issues, she said.

‘Big impact’

“What’s the impact that we’ve seen? With factor IX, it has been really big. Previous on-demand patients have agreed that, ‘gosh, I’m infusing a couple of times a month anyway,’ so starting an every 14-day prophylactic regimen seems pretty reasonable,” she said.

“We’ve had infusion schedules in children change from twice weekly to once weekly and that has really decreased the burden of disease,” she added.

A few adults, however, have gone back to standard half-life products because of concerns that they would not be able to infuse when they thought they needed treatment, she noted.

The impact of the EHL factor VIII products has been smaller, although it has allowed slight increases in the dosing intervals (from every other day to every third day in children, for example), and has overall decreased the average number of monthly infusions from about 15 to about 10.

Some adolescents and young adults, who often have been on prophylaxis for all of their lives, have experienced absent or only minimal joint disease, and some have been able to extend their dosing intervals from every 4 to every 5 to 7 days, she said.

Ms. Maahs disclosed serving on advisory committees to Baxalta, Novo Nordisk, Biogen, Genentech, and CSL, and receiving honoraria related to those activities.

ORLANDO – Transitioning patients with hemophilia from standard clotting factor concentrates to newer extended half-life products takes planning, education, and a little patience, but the payoff can be better hemostasis, a hemophilia treatment specialist said.

“Real-world experience shows us that you can maintain effective protection with less infusion with these new products, but we also know that each person should be evaluated individually when determining what their specific optimal treatment is,” said Jennifer Maahs, a hemophilia nurse practitioner at the Indiana Hemophilia and Thrombosis Center in Indianapolis.

Staff and patient education about the proper use of newer extended half-life (EHL) products is the key to success, she added in an oral session at the World Federation of Hemophilia World Congress.

The new EHL products allow for longer intervals between doses, especially with EHL recombinant factor IX used to treat hemophilia B. Prophylaxis with standard factor IX concentrates requires doses of 25-40 IU/kg twice weekly; in contrasts, EHL products can be given in various doses based on patient responses of either 50 IU/kg every 7 days, 100 IU/kg every 10 days, 25-40 IU/kg every 7 days, or 50-75 IU/kg every 14 days.

In general, the longer intervals between dosing occur in adults; young children tend to require more frequent dosing and have lower levels of factor recovery, she noted.

Extended Experience

Her center currently has more than 100 patients maintained on prolonged half-life factor VIII and factor IX products.

“We have really learned a lot of lessons along the way, and we have had to modify our approach based on these lessons,” she said. “Each patient situation is unique, and everything needs to be individualized.”

Staff review the published literature to educate themselves on the EHL products and prepare answers to expected questions from patients. Ms. Maahs suggested identifying key staff who are best equipped to answer specific questions.

“From a patient standpoint, we’ve developed a patient notification letter, so for any new product that comes out – for example a new factor VIII product – the notification gets sent out factor VIII patients, and we do that for every new product that comes out,” she said.

PK OK

Pharmacokinetic (PK) analyses may also be helpful in transitioning patients to EHL products.

To test patient responses to new products, her center tests patients for recovery from 15 minutes to 1 hour post-infusion, which will provide information about how the patient may respond to the product during a bleeding episode.

If the patient is on prophylaxis they will evaluate trough effectiveness to determine that patient’s responsiveness at the lowest level prior to the next infusion. Testing at other time points may be required based on the patient’s individual clinical history.

Center staff talk with each patient to discuss his needs and capabilities. If the patient is currently being managed with on-demand therapy, the talk may center on obstacles to utilization of prophylaxis and the patient’s desired infusion interval.

For patients currently on prophylaxis, they discuss the current regimen frequency and dose and assess how well it’s working. Staff members also provide information about alternative approaches to therapy, and ask patients specifically about their activity levels and dates of activity, compared with currently scheduled infusion days.

Patients are also educated about the reconstitution requirements for the new product, and are told to use up any remaining concentrates before switching over to the new product.

“As we move forward, within 2 to 4 weeks of starting a new therapy, we like to obtain a trough to see how their prophylaxis is working. At that time we ask how have you been doing on the new product, are you having any breakthrough bleeding, and how are you feeling about it,” Ms. Maahs said.

Weekly phone calls to the patient during the first month are also very helpful for reinforcing information about dosing regimens for bleeding episodes, reminding patients to call in if they experience a lead, and encouraging them to keep a treatment log. The phone call can also be helpful in identifying potential product-related reactions or other issues, she said.

‘Big impact’

“What’s the impact that we’ve seen? With factor IX, it has been really big. Previous on-demand patients have agreed that, ‘gosh, I’m infusing a couple of times a month anyway,’ so starting an every 14-day prophylactic regimen seems pretty reasonable,” she said.

“We’ve had infusion schedules in children change from twice weekly to once weekly and that has really decreased the burden of disease,” she added.

A few adults, however, have gone back to standard half-life products because of concerns that they would not be able to infuse when they thought they needed treatment, she noted.

The impact of the EHL factor VIII products has been smaller, although it has allowed slight increases in the dosing intervals (from every other day to every third day in children, for example), and has overall decreased the average number of monthly infusions from about 15 to about 10.

Some adolescents and young adults, who often have been on prophylaxis for all of their lives, have experienced absent or only minimal joint disease, and some have been able to extend their dosing intervals from every 4 to every 5 to 7 days, she said.

Ms. Maahs disclosed serving on advisory committees to Baxalta, Novo Nordisk, Biogen, Genentech, and CSL, and receiving honoraria related to those activities.

ORLANDO – Transitioning patients with hemophilia from standard clotting factor concentrates to newer extended half-life products takes planning, education, and a little patience, but the payoff can be better hemostasis, a hemophilia treatment specialist said.

“Real-world experience shows us that you can maintain effective protection with less infusion with these new products, but we also know that each person should be evaluated individually when determining what their specific optimal treatment is,” said Jennifer Maahs, a hemophilia nurse practitioner at the Indiana Hemophilia and Thrombosis Center in Indianapolis.

Staff and patient education about the proper use of newer extended half-life (EHL) products is the key to success, she added in an oral session at the World Federation of Hemophilia World Congress.

The new EHL products allow for longer intervals between doses, especially with EHL recombinant factor IX used to treat hemophilia B. Prophylaxis with standard factor IX concentrates requires doses of 25-40 IU/kg twice weekly; in contrasts, EHL products can be given in various doses based on patient responses of either 50 IU/kg every 7 days, 100 IU/kg every 10 days, 25-40 IU/kg every 7 days, or 50-75 IU/kg every 14 days.

In general, the longer intervals between dosing occur in adults; young children tend to require more frequent dosing and have lower levels of factor recovery, she noted.

Extended Experience

Her center currently has more than 100 patients maintained on prolonged half-life factor VIII and factor IX products.

“We have really learned a lot of lessons along the way, and we have had to modify our approach based on these lessons,” she said. “Each patient situation is unique, and everything needs to be individualized.”

Staff review the published literature to educate themselves on the EHL products and prepare answers to expected questions from patients. Ms. Maahs suggested identifying key staff who are best equipped to answer specific questions.

“From a patient standpoint, we’ve developed a patient notification letter, so for any new product that comes out – for example a new factor VIII product – the notification gets sent out factor VIII patients, and we do that for every new product that comes out,” she said.

PK OK

Pharmacokinetic (PK) analyses may also be helpful in transitioning patients to EHL products.

To test patient responses to new products, her center tests patients for recovery from 15 minutes to 1 hour post-infusion, which will provide information about how the patient may respond to the product during a bleeding episode.

If the patient is on prophylaxis they will evaluate trough effectiveness to determine that patient’s responsiveness at the lowest level prior to the next infusion. Testing at other time points may be required based on the patient’s individual clinical history.

Center staff talk with each patient to discuss his needs and capabilities. If the patient is currently being managed with on-demand therapy, the talk may center on obstacles to utilization of prophylaxis and the patient’s desired infusion interval.

For patients currently on prophylaxis, they discuss the current regimen frequency and dose and assess how well it’s working. Staff members also provide information about alternative approaches to therapy, and ask patients specifically about their activity levels and dates of activity, compared with currently scheduled infusion days.

Patients are also educated about the reconstitution requirements for the new product, and are told to use up any remaining concentrates before switching over to the new product.

“As we move forward, within 2 to 4 weeks of starting a new therapy, we like to obtain a trough to see how their prophylaxis is working. At that time we ask how have you been doing on the new product, are you having any breakthrough bleeding, and how are you feeling about it,” Ms. Maahs said.

Weekly phone calls to the patient during the first month are also very helpful for reinforcing information about dosing regimens for bleeding episodes, reminding patients to call in if they experience a lead, and encouraging them to keep a treatment log. The phone call can also be helpful in identifying potential product-related reactions or other issues, she said.

‘Big impact’

“What’s the impact that we’ve seen? With factor IX, it has been really big. Previous on-demand patients have agreed that, ‘gosh, I’m infusing a couple of times a month anyway,’ so starting an every 14-day prophylactic regimen seems pretty reasonable,” she said.

“We’ve had infusion schedules in children change from twice weekly to once weekly and that has really decreased the burden of disease,” she added.

A few adults, however, have gone back to standard half-life products because of concerns that they would not be able to infuse when they thought they needed treatment, she noted.

The impact of the EHL factor VIII products has been smaller, although it has allowed slight increases in the dosing intervals (from every other day to every third day in children, for example), and has overall decreased the average number of monthly infusions from about 15 to about 10.

Some adolescents and young adults, who often have been on prophylaxis for all of their lives, have experienced absent or only minimal joint disease, and some have been able to extend their dosing intervals from every 4 to every 5 to 7 days, she said.

Ms. Maahs disclosed serving on advisory committees to Baxalta, Novo Nordisk, Biogen, Genentech, and CSL, and receiving honoraria related to those activities.