In April 2018, the US Food and Drug Administration expanded the approval of the combination of nivolumab and ipilimumab into a new indication, following a previous approval in patients with metastatic melanoma. The double immune checkpoint inhibitor combination was approved on the basis of the phase 3 CheckMate-214 study for the treatment of patients with intermediate- or poor-risk, previously untreated advanced renal cell carcinoma (RCC).¹

Nivolumab monotherapy is already approved in the second-line setting for the treatment of advanced RCC, and the demonstration of significantly improved overall survival (OS) in this study suggests that the combination should supplant sunitinib in the front-line setting in the treatment of this type of cancer.

A total of 1,096 patients at 175 sites in 28 countries were randomized 1:1 to receive nivolumab (3 mg/kg) and ipilimumab (1 mg/kg) intravenously every 3 weeks for 4 doses in an induction phase, followed by nivolumab monotherapy (3 mg/kg) every 2 weeks in a maintenance phase or sunitinib (50 mg) orally daily for 4 weeks of each 6-week cycle.

Eligible patients were 18 years or older, had previously untreated advanced RCC with a clear-cell component, had measurable disease according to Response Evaluation Criteria in Solid Tumors (version 1.1), and had a Karnofsky performance status of at least 70 (on a scale from 0 to 100, with lower scores indicating greater disability). Patients with central nervous system metastases or autoimmune disease who were being treated with glucocorticoids and immunosuppressants were excluded from the study.

Around three-quarters of patients with advanced RCC have intermediate- or poor-risk disease and experience worse outcomes than patients with favorable-risk disease. Patients in CheckMate-214 were stratified according to International Metastatic Renal Cell Carcinoma Database Consortium risk score as favorable (score of 0), intermediate (score of 1 or 2) or poor risk (score of 3-6), according to the number of risk factors present.

Risk factors included a Karnofsky performance score of 70, time from initial diagnosis to randomization of <1 year, a hemoglobin level below the lower limit of normal, a corrected serum calcium concentration of >10 mg/dL, or an absolute neutrophil count or platelet count above the upper limit of normal. Patients were also stratified according to geographic region (United States versus Canada and Europe versus the rest of the world).

The coprimary endpoints were objective response rate (ORR), progression-free survival (PFS), and OS in a subset of 847 intermediate- and poor-risk patients. Over a median follow-up of 25.2 months, there was a statistically significant improvement in OS and ORR in patients treated with nivolumab and ipilimumab (mPFS not reached; ORR, 41.6%), compared with sunitinib (OS, 25.9 months; ORR, 26.5%), with P <.001 for both. The immunotherapy combination was favored across subgroups.

The most common adverse events (AEs) in patients treated with nivolumab and ipilimumab included fatigue, rash, diarrhea, musculoskeletal pain, pruritus, nausea, cough, pyrexia, arthralgia, and decreased appetite. The combination was associated with fewer grade 3/4 AEs (63% vs 46% for sunitinib), but a higher rate of treatment discontinuations because of AEs (31% vs 21%, respectively). There were 8 deaths in the combination arm, and 4 in the sunitinib arm that were reported to be treatment related.²

The warnings and precautions related to nivolumab–ipilimumab combination therapy outlined in the prescribing information include mostly immune-mediated AEs, such as immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, skin adverse reactions, and encephalitis. There are also warnings relating to the risk of infusion reactions and the potential for embryofetal toxicity.

Patients should be monitored for hyperglycemia and for changes in liver, thyroid, renal, and neurologic function. Treatment with nivolumab and ipilimumab should be withheld for moderate and permanently discontinued for severe or life-threatening immune-mediated pneumonitis, colitis, and hepatitis, as well as transaminase or total bilirubin elevation. It should also be withheld for moderate or severe hypophysitis and serum creatinine elevation, moderate adrenal insufficiency and severe hyperglycemia, and permanently discontinued for life-threatening hypophysitis and serum creatinine elevation, severe or life-threatening adrenal insufficiency, and life-threatening hyperglycemia.

New-onset moderate to severe neurologic signs or symptoms warrant treatment being withheld, and immune-mediated encephalitis should lead to treatment discontinuation. For mild or moderate infusion reactions, the infusion rate can be slowed or interrupted, and infusions should be discontinued in the event of severe or life-threatening infusion reactions. Patients should be advised of the potential for fetal harm and the need for effective contraception during and after treatment. Ipilimumab and nivolumab are marketed as Yervoy and Opdivo, respectively, by Bristol-Myers Squibb.^3,4

In April 2018, the US Food and Drug Administration expanded the approval of the combination of nivolumab and ipilimumab into a new indication, following a previous approval in patients with metastatic melanoma. The double immune checkpoint inhibitor combination was approved on the basis of the phase 3 CheckMate-214 study for the treatment of patients with intermediate- or poor-risk, previously untreated advanced renal cell carcinoma (RCC).¹

Nivolumab monotherapy is already approved in the second-line setting for the treatment of advanced RCC, and the demonstration of significantly improved overall survival (OS) in this study suggests that the combination should supplant sunitinib in the front-line setting in the treatment of this type of cancer.

A total of 1,096 patients at 175 sites in 28 countries were randomized 1:1 to receive nivolumab (3 mg/kg) and ipilimumab (1 mg/kg) intravenously every 3 weeks for 4 doses in an induction phase, followed by nivolumab monotherapy (3 mg/kg) every 2 weeks in a maintenance phase or sunitinib (50 mg) orally daily for 4 weeks of each 6-week cycle.

Eligible patients were 18 years or older, had previously untreated advanced RCC with a clear-cell component, had measurable disease according to Response Evaluation Criteria in Solid Tumors (version 1.1), and had a Karnofsky performance status of at least 70 (on a scale from 0 to 100, with lower scores indicating greater disability). Patients with central nervous system metastases or autoimmune disease who were being treated with glucocorticoids and immunosuppressants were excluded from the study.

Around three-quarters of patients with advanced RCC have intermediate- or poor-risk disease and experience worse outcomes than patients with favorable-risk disease. Patients in CheckMate-214 were stratified according to International Metastatic Renal Cell Carcinoma Database Consortium risk score as favorable (score of 0), intermediate (score of 1 or 2) or poor risk (score of 3-6), according to the number of risk factors present.

Risk factors included a Karnofsky performance score of 70, time from initial diagnosis to randomization of <1 year, a hemoglobin level below the lower limit of normal, a corrected serum calcium concentration of >10 mg/dL, or an absolute neutrophil count or platelet count above the upper limit of normal. Patients were also stratified according to geographic region (United States versus Canada and Europe versus the rest of the world).

The coprimary endpoints were objective response rate (ORR), progression-free survival (PFS), and OS in a subset of 847 intermediate- and poor-risk patients. Over a median follow-up of 25.2 months, there was a statistically significant improvement in OS and ORR in patients treated with nivolumab and ipilimumab (mPFS not reached; ORR, 41.6%), compared with sunitinib (OS, 25.9 months; ORR, 26.5%), with P <.001 for both. The immunotherapy combination was favored across subgroups.

The most common adverse events (AEs) in patients treated with nivolumab and ipilimumab included fatigue, rash, diarrhea, musculoskeletal pain, pruritus, nausea, cough, pyrexia, arthralgia, and decreased appetite. The combination was associated with fewer grade 3/4 AEs (63% vs 46% for sunitinib), but a higher rate of treatment discontinuations because of AEs (31% vs 21%, respectively). There were 8 deaths in the combination arm, and 4 in the sunitinib arm that were reported to be treatment related.²

The warnings and precautions related to nivolumab–ipilimumab combination therapy outlined in the prescribing information include mostly immune-mediated AEs, such as immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, skin adverse reactions, and encephalitis. There are also warnings relating to the risk of infusion reactions and the potential for embryofetal toxicity.

Patients should be monitored for hyperglycemia and for changes in liver, thyroid, renal, and neurologic function. Treatment with nivolumab and ipilimumab should be withheld for moderate and permanently discontinued for severe or life-threatening immune-mediated pneumonitis, colitis, and hepatitis, as well as transaminase or total bilirubin elevation. It should also be withheld for moderate or severe hypophysitis and serum creatinine elevation, moderate adrenal insufficiency and severe hyperglycemia, and permanently discontinued for life-threatening hypophysitis and serum creatinine elevation, severe or life-threatening adrenal insufficiency, and life-threatening hyperglycemia.

New-onset moderate to severe neurologic signs or symptoms warrant treatment being withheld, and immune-mediated encephalitis should lead to treatment discontinuation. For mild or moderate infusion reactions, the infusion rate can be slowed or interrupted, and infusions should be discontinued in the event of severe or life-threatening infusion reactions. Patients should be advised of the potential for fetal harm and the need for effective contraception during and after treatment. Ipilimumab and nivolumab are marketed as Yervoy and Opdivo, respectively, by Bristol-Myers Squibb.^3,4

In April 2018, the US Food and Drug Administration expanded the approval of the combination of nivolumab and ipilimumab into a new indication, following a previous approval in patients with metastatic melanoma. The double immune checkpoint inhibitor combination was approved on the basis of the phase 3 CheckMate-214 study for the treatment of patients with intermediate- or poor-risk, previously untreated advanced renal cell carcinoma (RCC).¹

Nivolumab monotherapy is already approved in the second-line setting for the treatment of advanced RCC, and the demonstration of significantly improved overall survival (OS) in this study suggests that the combination should supplant sunitinib in the front-line setting in the treatment of this type of cancer.

A total of 1,096 patients at 175 sites in 28 countries were randomized 1:1 to receive nivolumab (3 mg/kg) and ipilimumab (1 mg/kg) intravenously every 3 weeks for 4 doses in an induction phase, followed by nivolumab monotherapy (3 mg/kg) every 2 weeks in a maintenance phase or sunitinib (50 mg) orally daily for 4 weeks of each 6-week cycle.

Eligible patients were 18 years or older, had previously untreated advanced RCC with a clear-cell component, had measurable disease according to Response Evaluation Criteria in Solid Tumors (version 1.1), and had a Karnofsky performance status of at least 70 (on a scale from 0 to 100, with lower scores indicating greater disability). Patients with central nervous system metastases or autoimmune disease who were being treated with glucocorticoids and immunosuppressants were excluded from the study.

Around three-quarters of patients with advanced RCC have intermediate- or poor-risk disease and experience worse outcomes than patients with favorable-risk disease. Patients in CheckMate-214 were stratified according to International Metastatic Renal Cell Carcinoma Database Consortium risk score as favorable (score of 0), intermediate (score of 1 or 2) or poor risk (score of 3-6), according to the number of risk factors present.

Risk factors included a Karnofsky performance score of 70, time from initial diagnosis to randomization of <1 year, a hemoglobin level below the lower limit of normal, a corrected serum calcium concentration of >10 mg/dL, or an absolute neutrophil count or platelet count above the upper limit of normal. Patients were also stratified according to geographic region (United States versus Canada and Europe versus the rest of the world).

The coprimary endpoints were objective response rate (ORR), progression-free survival (PFS), and OS in a subset of 847 intermediate- and poor-risk patients. Over a median follow-up of 25.2 months, there was a statistically significant improvement in OS and ORR in patients treated with nivolumab and ipilimumab (mPFS not reached; ORR, 41.6%), compared with sunitinib (OS, 25.9 months; ORR, 26.5%), with P <.001 for both. The immunotherapy combination was favored across subgroups.

The most common adverse events (AEs) in patients treated with nivolumab and ipilimumab included fatigue, rash, diarrhea, musculoskeletal pain, pruritus, nausea, cough, pyrexia, arthralgia, and decreased appetite. The combination was associated with fewer grade 3/4 AEs (63% vs 46% for sunitinib), but a higher rate of treatment discontinuations because of AEs (31% vs 21%, respectively). There were 8 deaths in the combination arm, and 4 in the sunitinib arm that were reported to be treatment related.²

The warnings and precautions related to nivolumab–ipilimumab combination therapy outlined in the prescribing information include mostly immune-mediated AEs, such as immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, skin adverse reactions, and encephalitis. There are also warnings relating to the risk of infusion reactions and the potential for embryofetal toxicity.

Patients should be monitored for hyperglycemia and for changes in liver, thyroid, renal, and neurologic function. Treatment with nivolumab and ipilimumab should be withheld for moderate and permanently discontinued for severe or life-threatening immune-mediated pneumonitis, colitis, and hepatitis, as well as transaminase or total bilirubin elevation. It should also be withheld for moderate or severe hypophysitis and serum creatinine elevation, moderate adrenal insufficiency and severe hyperglycemia, and permanently discontinued for life-threatening hypophysitis and serum creatinine elevation, severe or life-threatening adrenal insufficiency, and life-threatening hyperglycemia.

New-onset moderate to severe neurologic signs or symptoms warrant treatment being withheld, and immune-mediated encephalitis should lead to treatment discontinuation. For mild or moderate infusion reactions, the infusion rate can be slowed or interrupted, and infusions should be discontinued in the event of severe or life-threatening infusion reactions. Patients should be advised of the potential for fetal harm and the need for effective contraception during and after treatment. Ipilimumab and nivolumab are marketed as Yervoy and Opdivo, respectively, by Bristol-Myers Squibb.^3,4

BOSTON – Hemithyroidectomy rates increased following the 2015 release of clinical practice guidelines that position the procedure as equivalent to total thyroidectomy, an analysis of U.S. hospital data shows.

Andrew Bowser/MDedge News

Patients undergoing hemithyroidectomy had fewer complications and shorter length of stay versus patients who received a bilateral procedure, with no corresponding increase in completion thyroidectomy, according to results of the retrospective analysis reported here at the annual clinical congress of the American College of Surgeons.

“We think this suggests that surgeons might be changing their practice at these hospitals, at least in part in response to the guidelines,” investigator Timothy M. Ullmann, MD, endocrine oncology research fellow in the department of surgery at New York Presbyterian Hospital–Weill Cornell Medical Center, New York.

Dr. Ullmann and colleagues queried the American College of Surgeons National Surgical Quality Improvement Program database for the 2014-2016 period to illustrate operative trends before and after release of the 2015 guidelines from the American Thyroid Association guidelines. They looked at a total of 26,562 procedures done before the guidelines were release, and 7,422 done after.

The rate of hemithyroidectomy increased from 15.6% before guidelines to 18.3% afterward (P less than .001), according to Dr. Ullmann. By contrast, the rates of completion thyroidectomy were 7.8% for the pre-guidelines period and 7.4% post-guidelines (P = .19).

Andrew Bowser/MDedge News

The increase was gradual throughout the 2014-2016 period, though it was especially steep after the guideline introduction, according to co-investigator Toni Beninato, MD, of Weill Cornell Medicine.

“While we can’t say that the guidelines directly caused an increase, it’s a pretty good association,” Dr. Beninato said in a press conference. “I think going forward, we would expect this to continue to increase, because the vast majority of patients with thyroid cancer probably fit criteria to have a hemithyroidectomy rather than a total thyroidectomy.”

Patients treated by otolaryngologists were more likely to undergo hemithyroidectomies versus those treated by general surgeons, multivariate analysis of this data set suggested (odds ratio, 1.13, P less than .001). On the other hand, Hispanic patients and those with a higher operative risk classification were less likely to undergo a unilateral procedure.

Complications were less likely in the hemithyroidectomy patients, according to investigators. There were significantly fewer superficial surgical site infections, at 0.2% versus 0.4% for total thyroidectomy, and operative time was 91.6 minutes versus 141.1 minutes.

Hemithyroidectomy patients were less likely to be reintubated after surgery, had a shorter length of stay, and were more likely to be managed on an outpatient basis, they added at the press conference.

Prior ATA guidelines, in place since 2009, called for near-total or total thyroidectomy for cancers that were at least 1 cm in size in patients with no contraindications to the procedure. The 2015 update says the initial surgical procedure could also be a unilateral procedure, or lobectomy, in cancers greater than 1 cm, or smaller than 4 cm with no extrathyroidal extension.

Dr. Ullmann and Dr. Beninato had no relevant financial relationships with commercial interests pertaining to the content of their presentation.

SOURCE: Ullmann TM et al. Abstract SF121 presented at the American College of Surgeons Clinical Congress.

BOSTON – Hemithyroidectomy rates increased following the 2015 release of clinical practice guidelines that position the procedure as equivalent to total thyroidectomy, an analysis of U.S. hospital data shows.

Andrew Bowser/MDedge News

Patients undergoing hemithyroidectomy had fewer complications and shorter length of stay versus patients who received a bilateral procedure, with no corresponding increase in completion thyroidectomy, according to results of the retrospective analysis reported here at the annual clinical congress of the American College of Surgeons.

“We think this suggests that surgeons might be changing their practice at these hospitals, at least in part in response to the guidelines,” investigator Timothy M. Ullmann, MD, endocrine oncology research fellow in the department of surgery at New York Presbyterian Hospital–Weill Cornell Medical Center, New York.

Dr. Ullmann and colleagues queried the American College of Surgeons National Surgical Quality Improvement Program database for the 2014-2016 period to illustrate operative trends before and after release of the 2015 guidelines from the American Thyroid Association guidelines. They looked at a total of 26,562 procedures done before the guidelines were release, and 7,422 done after.

The rate of hemithyroidectomy increased from 15.6% before guidelines to 18.3% afterward (P less than .001), according to Dr. Ullmann. By contrast, the rates of completion thyroidectomy were 7.8% for the pre-guidelines period and 7.4% post-guidelines (P = .19).

Andrew Bowser/MDedge News

The increase was gradual throughout the 2014-2016 period, though it was especially steep after the guideline introduction, according to co-investigator Toni Beninato, MD, of Weill Cornell Medicine.

“While we can’t say that the guidelines directly caused an increase, it’s a pretty good association,” Dr. Beninato said in a press conference. “I think going forward, we would expect this to continue to increase, because the vast majority of patients with thyroid cancer probably fit criteria to have a hemithyroidectomy rather than a total thyroidectomy.”

Patients treated by otolaryngologists were more likely to undergo hemithyroidectomies versus those treated by general surgeons, multivariate analysis of this data set suggested (odds ratio, 1.13, P less than .001). On the other hand, Hispanic patients and those with a higher operative risk classification were less likely to undergo a unilateral procedure.

Complications were less likely in the hemithyroidectomy patients, according to investigators. There were significantly fewer superficial surgical site infections, at 0.2% versus 0.4% for total thyroidectomy, and operative time was 91.6 minutes versus 141.1 minutes.

Hemithyroidectomy patients were less likely to be reintubated after surgery, had a shorter length of stay, and were more likely to be managed on an outpatient basis, they added at the press conference.

Prior ATA guidelines, in place since 2009, called for near-total or total thyroidectomy for cancers that were at least 1 cm in size in patients with no contraindications to the procedure. The 2015 update says the initial surgical procedure could also be a unilateral procedure, or lobectomy, in cancers greater than 1 cm, or smaller than 4 cm with no extrathyroidal extension.

Dr. Ullmann and Dr. Beninato had no relevant financial relationships with commercial interests pertaining to the content of their presentation.

SOURCE: Ullmann TM et al. Abstract SF121 presented at the American College of Surgeons Clinical Congress.

BOSTON – Hemithyroidectomy rates increased following the 2015 release of clinical practice guidelines that position the procedure as equivalent to total thyroidectomy, an analysis of U.S. hospital data shows.

Andrew Bowser/MDedge News

Patients undergoing hemithyroidectomy had fewer complications and shorter length of stay versus patients who received a bilateral procedure, with no corresponding increase in completion thyroidectomy, according to results of the retrospective analysis reported here at the annual clinical congress of the American College of Surgeons.

“We think this suggests that surgeons might be changing their practice at these hospitals, at least in part in response to the guidelines,” investigator Timothy M. Ullmann, MD, endocrine oncology research fellow in the department of surgery at New York Presbyterian Hospital–Weill Cornell Medical Center, New York.

Dr. Ullmann and colleagues queried the American College of Surgeons National Surgical Quality Improvement Program database for the 2014-2016 period to illustrate operative trends before and after release of the 2015 guidelines from the American Thyroid Association guidelines. They looked at a total of 26,562 procedures done before the guidelines were release, and 7,422 done after.

The rate of hemithyroidectomy increased from 15.6% before guidelines to 18.3% afterward (P less than .001), according to Dr. Ullmann. By contrast, the rates of completion thyroidectomy were 7.8% for the pre-guidelines period and 7.4% post-guidelines (P = .19).

Andrew Bowser/MDedge News

The increase was gradual throughout the 2014-2016 period, though it was especially steep after the guideline introduction, according to co-investigator Toni Beninato, MD, of Weill Cornell Medicine.

“While we can’t say that the guidelines directly caused an increase, it’s a pretty good association,” Dr. Beninato said in a press conference. “I think going forward, we would expect this to continue to increase, because the vast majority of patients with thyroid cancer probably fit criteria to have a hemithyroidectomy rather than a total thyroidectomy.”

Patients treated by otolaryngologists were more likely to undergo hemithyroidectomies versus those treated by general surgeons, multivariate analysis of this data set suggested (odds ratio, 1.13, P less than .001). On the other hand, Hispanic patients and those with a higher operative risk classification were less likely to undergo a unilateral procedure.

Complications were less likely in the hemithyroidectomy patients, according to investigators. There were significantly fewer superficial surgical site infections, at 0.2% versus 0.4% for total thyroidectomy, and operative time was 91.6 minutes versus 141.1 minutes.

Hemithyroidectomy patients were less likely to be reintubated after surgery, had a shorter length of stay, and were more likely to be managed on an outpatient basis, they added at the press conference.

Prior ATA guidelines, in place since 2009, called for near-total or total thyroidectomy for cancers that were at least 1 cm in size in patients with no contraindications to the procedure. The 2015 update says the initial surgical procedure could also be a unilateral procedure, or lobectomy, in cancers greater than 1 cm, or smaller than 4 cm with no extrathyroidal extension.

Dr. Ullmann and Dr. Beninato had no relevant financial relationships with commercial interests pertaining to the content of their presentation.

SOURCE: Ullmann TM et al. Abstract SF121 presented at the American College of Surgeons Clinical Congress.

BOSTON – A survey of U.S. humanitarian surgical non-governmental organizations (NGOs) revealed a range of practices and suggests that a best-practices guide would be beneficial in helping them adhere more closely to standard protocols.

While most NGOs follow guideline-based practices, some deviations from standard of care do occur. Deviations occurred most often in the areas of preoperative workup, operative technique, and pain management, according to survey results presented at the annual clinical congress of the American College of Surgeons.

Consensus guidelines specific to the NGO sector would be used by the great majority of NGOs surveyed, reported Peter F. Johnston, MD, a general surgery resident and the Ben Rush Global Surgery Fellow at Rutgers New Jersey Medical School.

“There is a lot of heterogeneity in the sector, based on the different organizations doing general surgery and organizations doing plastics,” Dr. Johnston said in an interview. “What we think we can do in terms of low-hanging fruit is come up with guidelines for things like perioperative antibiotics that are pretty much common to all types of surgeries.”

The survey conducted by Dr. Johnston and colleagues is one of the first to characterize the clinical practices of U.S. humanitarian organizations that provide general or subspecialty care through short-term surgical missions. It was completed by representatives of 30 of 83 organizations (36%) that were contacted.

Of respondents, 20% said their organizations deviated from standard U.S. practice often or very often, Dr. Johnston said in his presentation. The respondents mentioned deviation from standard practice in pain management (18%), preoperative workup (16%), and operative technique (16%).

Only about one-third of respondents said they believed those deviations impacted patient outcomes, the results show.

In all, 67% of respondents adhered to at least four protocol-driven practices. Those NGOs that adhered most closely to standard protocol tended to be older, more established organizations, compared with those less protocolized organizations, according to Dr. Johnston (age of organization 22 vs. 14 years, P < .05).

“It makes sense... from my own experience of going back to the same countries,” said Dr. Johnston, who has participated in missions in countries including Ghana, Sierra Leone, and Peru. “As an organization, and even within different countries, the process gets smoother as you keep working at it.”

A total of 85% of respondents expressed interest in best-practice guidelines to guide short-term surgical missions, according to the survey data.

Dr. Johnston reported no conflicts of interest related to his presentation.
 

SOURCE: Johnston P, et al. Abstract SF121 presented at the American College of Surgeons Clinical Congress.

BOSTON – A survey of U.S. humanitarian surgical non-governmental organizations (NGOs) revealed a range of practices and suggests that a best-practices guide would be beneficial in helping them adhere more closely to standard protocols.

While most NGOs follow guideline-based practices, some deviations from standard of care do occur. Deviations occurred most often in the areas of preoperative workup, operative technique, and pain management, according to survey results presented at the annual clinical congress of the American College of Surgeons.

Consensus guidelines specific to the NGO sector would be used by the great majority of NGOs surveyed, reported Peter F. Johnston, MD, a general surgery resident and the Ben Rush Global Surgery Fellow at Rutgers New Jersey Medical School.

“There is a lot of heterogeneity in the sector, based on the different organizations doing general surgery and organizations doing plastics,” Dr. Johnston said in an interview. “What we think we can do in terms of low-hanging fruit is come up with guidelines for things like perioperative antibiotics that are pretty much common to all types of surgeries.”

The survey conducted by Dr. Johnston and colleagues is one of the first to characterize the clinical practices of U.S. humanitarian organizations that provide general or subspecialty care through short-term surgical missions. It was completed by representatives of 30 of 83 organizations (36%) that were contacted.

Of respondents, 20% said their organizations deviated from standard U.S. practice often or very often, Dr. Johnston said in his presentation. The respondents mentioned deviation from standard practice in pain management (18%), preoperative workup (16%), and operative technique (16%).

Only about one-third of respondents said they believed those deviations impacted patient outcomes, the results show.

In all, 67% of respondents adhered to at least four protocol-driven practices. Those NGOs that adhered most closely to standard protocol tended to be older, more established organizations, compared with those less protocolized organizations, according to Dr. Johnston (age of organization 22 vs. 14 years, P < .05).

“It makes sense... from my own experience of going back to the same countries,” said Dr. Johnston, who has participated in missions in countries including Ghana, Sierra Leone, and Peru. “As an organization, and even within different countries, the process gets smoother as you keep working at it.”

A total of 85% of respondents expressed interest in best-practice guidelines to guide short-term surgical missions, according to the survey data.

Dr. Johnston reported no conflicts of interest related to his presentation.
 

SOURCE: Johnston P, et al. Abstract SF121 presented at the American College of Surgeons Clinical Congress.

BOSTON – A survey of U.S. humanitarian surgical non-governmental organizations (NGOs) revealed a range of practices and suggests that a best-practices guide would be beneficial in helping them adhere more closely to standard protocols.

While most NGOs follow guideline-based practices, some deviations from standard of care do occur. Deviations occurred most often in the areas of preoperative workup, operative technique, and pain management, according to survey results presented at the annual clinical congress of the American College of Surgeons.

Consensus guidelines specific to the NGO sector would be used by the great majority of NGOs surveyed, reported Peter F. Johnston, MD, a general surgery resident and the Ben Rush Global Surgery Fellow at Rutgers New Jersey Medical School.

“There is a lot of heterogeneity in the sector, based on the different organizations doing general surgery and organizations doing plastics,” Dr. Johnston said in an interview. “What we think we can do in terms of low-hanging fruit is come up with guidelines for things like perioperative antibiotics that are pretty much common to all types of surgeries.”

The survey conducted by Dr. Johnston and colleagues is one of the first to characterize the clinical practices of U.S. humanitarian organizations that provide general or subspecialty care through short-term surgical missions. It was completed by representatives of 30 of 83 organizations (36%) that were contacted.

Of respondents, 20% said their organizations deviated from standard U.S. practice often or very often, Dr. Johnston said in his presentation. The respondents mentioned deviation from standard practice in pain management (18%), preoperative workup (16%), and operative technique (16%).

Only about one-third of respondents said they believed those deviations impacted patient outcomes, the results show.

In all, 67% of respondents adhered to at least four protocol-driven practices. Those NGOs that adhered most closely to standard protocol tended to be older, more established organizations, compared with those less protocolized organizations, according to Dr. Johnston (age of organization 22 vs. 14 years, P < .05).

“It makes sense... from my own experience of going back to the same countries,” said Dr. Johnston, who has participated in missions in countries including Ghana, Sierra Leone, and Peru. “As an organization, and even within different countries, the process gets smoother as you keep working at it.”

A total of 85% of respondents expressed interest in best-practice guidelines to guide short-term surgical missions, according to the survey data.

Dr. Johnston reported no conflicts of interest related to his presentation.
 

SOURCE: Johnston P, et al. Abstract SF121 presented at the American College of Surgeons Clinical Congress.

ATLANTA – Statin use among a cohort of veterans with traumatic spinal cord injury reduced all-cause mortality, results from a novel observational study showed.

“This is the first clinical study to show that administration of statins irrespective of the lipid levels reduces all-cause mortality, not just cardiovascular mortality,” lead study author Meheroz H. Rabadi, MD, said in an interview in advance of the annual meeting of the American Neurological Association. “This clinical study confirms the impression of several prior studies in animal models with spinal cord injury, which have shown the anti-inflammatory and neuro-protective effects of statins.”

To determine whether statin use in a cohort of patients with traumatic spinal cord injuries (SCI) reduced overall and cause-specific mortality, Dr. Rabadi and his colleagues retrospectively reviewed the medical charts and death records of 163 individuals with SCI who were treated at the Oklahoma City Veterans Administration Medical Center Spinal Cord Injury & Disease, Multiple Sclerosis, and ALS Program, an outpatient clinic, from 2000 to 2014. They collected data on statin use, duration of statin use, and intensity of statin therapy, as well as cause-specific mortality.

Of the 163 subjects studied, 75 (46%) had taken statins for an average of 5.7 years, and had greater cardiovascular risk burdens than those who had not taken statins. The mortality rate for patients on statins, however, was 33.8-49.9 per 1,000 person-years, compared with 47.4-66.8 deaths per 1,000 person-years among those who had not taken statins. Kaplan-Meier survival curves showed a significant difference between the two groups (P less than .0052). Within the statin group, neither duration nor average intensity of statin therapy affected mortality.

“We were surprised to note statins reduced pneumonia-related mortality in patients with SCI,” Dr. Rabadi said. “Since our publication there have been several publications, including a meta-analysis of statins reducing community-acquired pneumonia-related mortality and reducing the need for mechanical ventilation or ICU admission (see CHEST 2015;148:523-32, Clin Med (Lond) 2017;17(5):403-7, and Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2018;40(1):30-40). Another surprise was neither the intensity, duration, or types of statin affected the result.”

He acknowledged certain limitations of the analysis, including its retrospective design, its relatively small sample size, and the fact that most of the subjects were non-Hispanic white men. “Routine prescription of statins in any dose in patients with SCI – even if the lipid profile is normal – is more beneficial than detrimental over the long haul,” concluded Dr. Rabadi, who also directs the Oklahoma VAMC Stroke Program. “Nearly all our patients with SCI continue to be on varying doses of statins.”

Dr. Rabadi reported having no financial disclosures.

[email protected]

SOURCE: Ann Neurol. 2018;84[S22]:S127. Abstract S302.


 

ATLANTA – Statin use among a cohort of veterans with traumatic spinal cord injury reduced all-cause mortality, results from a novel observational study showed.

“This is the first clinical study to show that administration of statins irrespective of the lipid levels reduces all-cause mortality, not just cardiovascular mortality,” lead study author Meheroz H. Rabadi, MD, said in an interview in advance of the annual meeting of the American Neurological Association. “This clinical study confirms the impression of several prior studies in animal models with spinal cord injury, which have shown the anti-inflammatory and neuro-protective effects of statins.”

To determine whether statin use in a cohort of patients with traumatic spinal cord injuries (SCI) reduced overall and cause-specific mortality, Dr. Rabadi and his colleagues retrospectively reviewed the medical charts and death records of 163 individuals with SCI who were treated at the Oklahoma City Veterans Administration Medical Center Spinal Cord Injury & Disease, Multiple Sclerosis, and ALS Program, an outpatient clinic, from 2000 to 2014. They collected data on statin use, duration of statin use, and intensity of statin therapy, as well as cause-specific mortality.

Of the 163 subjects studied, 75 (46%) had taken statins for an average of 5.7 years, and had greater cardiovascular risk burdens than those who had not taken statins. The mortality rate for patients on statins, however, was 33.8-49.9 per 1,000 person-years, compared with 47.4-66.8 deaths per 1,000 person-years among those who had not taken statins. Kaplan-Meier survival curves showed a significant difference between the two groups (P less than .0052). Within the statin group, neither duration nor average intensity of statin therapy affected mortality.

“We were surprised to note statins reduced pneumonia-related mortality in patients with SCI,” Dr. Rabadi said. “Since our publication there have been several publications, including a meta-analysis of statins reducing community-acquired pneumonia-related mortality and reducing the need for mechanical ventilation or ICU admission (see CHEST 2015;148:523-32, Clin Med (Lond) 2017;17(5):403-7, and Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2018;40(1):30-40). Another surprise was neither the intensity, duration, or types of statin affected the result.”

He acknowledged certain limitations of the analysis, including its retrospective design, its relatively small sample size, and the fact that most of the subjects were non-Hispanic white men. “Routine prescription of statins in any dose in patients with SCI – even if the lipid profile is normal – is more beneficial than detrimental over the long haul,” concluded Dr. Rabadi, who also directs the Oklahoma VAMC Stroke Program. “Nearly all our patients with SCI continue to be on varying doses of statins.”

Dr. Rabadi reported having no financial disclosures.

[email protected]

SOURCE: Ann Neurol. 2018;84[S22]:S127. Abstract S302.


 

ATLANTA – Statin use among a cohort of veterans with traumatic spinal cord injury reduced all-cause mortality, results from a novel observational study showed.

“This is the first clinical study to show that administration of statins irrespective of the lipid levels reduces all-cause mortality, not just cardiovascular mortality,” lead study author Meheroz H. Rabadi, MD, said in an interview in advance of the annual meeting of the American Neurological Association. “This clinical study confirms the impression of several prior studies in animal models with spinal cord injury, which have shown the anti-inflammatory and neuro-protective effects of statins.”

To determine whether statin use in a cohort of patients with traumatic spinal cord injuries (SCI) reduced overall and cause-specific mortality, Dr. Rabadi and his colleagues retrospectively reviewed the medical charts and death records of 163 individuals with SCI who were treated at the Oklahoma City Veterans Administration Medical Center Spinal Cord Injury & Disease, Multiple Sclerosis, and ALS Program, an outpatient clinic, from 2000 to 2014. They collected data on statin use, duration of statin use, and intensity of statin therapy, as well as cause-specific mortality.

Of the 163 subjects studied, 75 (46%) had taken statins for an average of 5.7 years, and had greater cardiovascular risk burdens than those who had not taken statins. The mortality rate for patients on statins, however, was 33.8-49.9 per 1,000 person-years, compared with 47.4-66.8 deaths per 1,000 person-years among those who had not taken statins. Kaplan-Meier survival curves showed a significant difference between the two groups (P less than .0052). Within the statin group, neither duration nor average intensity of statin therapy affected mortality.

“We were surprised to note statins reduced pneumonia-related mortality in patients with SCI,” Dr. Rabadi said. “Since our publication there have been several publications, including a meta-analysis of statins reducing community-acquired pneumonia-related mortality and reducing the need for mechanical ventilation or ICU admission (see CHEST 2015;148:523-32, Clin Med (Lond) 2017;17(5):403-7, and Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2018;40(1):30-40). Another surprise was neither the intensity, duration, or types of statin affected the result.”

He acknowledged certain limitations of the analysis, including its retrospective design, its relatively small sample size, and the fact that most of the subjects were non-Hispanic white men. “Routine prescription of statins in any dose in patients with SCI – even if the lipid profile is normal – is more beneficial than detrimental over the long haul,” concluded Dr. Rabadi, who also directs the Oklahoma VAMC Stroke Program. “Nearly all our patients with SCI continue to be on varying doses of statins.”

Dr. Rabadi reported having no financial disclosures.

[email protected]

SOURCE: Ann Neurol. 2018;84[S22]:S127. Abstract S302.


 

BOSTON–Vitamin C, angiotensin-II, and methylene blue are emerging options on the cutting edge of refractory septic shock treatment that require more investigation, but nevertheless appear promising, Rishi Rattan, MD, said at the annual clinical congress of the American College of Surgeons.

Andrew Bowser/MDedge News

Trials evaluating vitamin C in this setting have demonstrated a large mortality impact with an absence of side effects, according to Dr. Rattan, a trauma and critical care surgeon with the Ryder Trauma Center at the University of Miami.

“It’s something that I have decided to start early adopting, and many of my colleagues at University of Miami do as well,” Dr. Rattan said in a panel session on updates in septic shock. “We’re anecdotally so far at least seeing good results and are going to be excited to see what these ongoing trials show.”

As an antioxidant, vitamin C has anti-inflammatory properties that may possibly attenuate the overly exuberant inflammatory response seen in septic shock, Dr. Rattan said in his presentation.

The limited clinical data for vitamin C in refractory shock include three studies, of which two are randomized controlled trials, comprising a total of 146 patients, he added.

“I will admit an N of 146 is hardly practice-changing for most people,” Dr. Rattan said. “There’s still a significant and sustained large mortality effect for the use of vitamin C, with nearly no adverse effects.”

Pooled analysis of all three studies revealed a marked reduction in mortality with the use of vitamin C (odds ratio, 0.17, 95% confidence interval 0.07–0.40; P less than .001), according to a meta-analysis recently just published in Critical Care that Dr. Rattan referenced in his presentation (Critical Care 2018;22:258, DOI:10.1186/s13054-018-2191-x).

When taken in recommended dosages, vitamin C given with corticosteroids and thiamine is without known side effects, researcher Paul E. Marik wrote earlier this year in an editorial in Pharmacology & Therapeutics (2018;189[9]:63-70, DOI:10.1016/j.pharmthera.2018.04.007) noted Dr. Rattan, who said he uses the intravenous vitamin C, thiamine, and hydrocortisone protocol previously reported by Dr. Marik and colleagues.

There are 13 ongoing trials, including some prospective blinded, randomized trials, looking at the role of vitamin C in refractory shock, he added.

Angiotensin-II is another intervention that may be promising in refractory septic shock, Dr. Rattan told attendees, pointing to the 2017 publication of the ATHOS-3 trial in the New England Journal of Medicine (2017; 377:419-430,DOI: 10.1056/NEJMoa1704154) showing that treatment increased blood pressure in patients with vasodilatory shock not responding to conventional vasopressors at high doses.

Likewise, methylene blue has shown promise in septic shock, at least in some limited clinical investigations and anecdotally in patients not improving despite standard interventions. “I’ve been able to have a couple patients walk out of the hospital with the use of methylene blue,” Dr. Rattan said. “Again, the plural of ‘anecdote’ is not ‘data,’ but it’s something to consider for the early adopters.”

Dr. Rattan had no disclosures related to his presentation.

BOSTON–Vitamin C, angiotensin-II, and methylene blue are emerging options on the cutting edge of refractory septic shock treatment that require more investigation, but nevertheless appear promising, Rishi Rattan, MD, said at the annual clinical congress of the American College of Surgeons.

Andrew Bowser/MDedge News

Trials evaluating vitamin C in this setting have demonstrated a large mortality impact with an absence of side effects, according to Dr. Rattan, a trauma and critical care surgeon with the Ryder Trauma Center at the University of Miami.

“It’s something that I have decided to start early adopting, and many of my colleagues at University of Miami do as well,” Dr. Rattan said in a panel session on updates in septic shock. “We’re anecdotally so far at least seeing good results and are going to be excited to see what these ongoing trials show.”

As an antioxidant, vitamin C has anti-inflammatory properties that may possibly attenuate the overly exuberant inflammatory response seen in septic shock, Dr. Rattan said in his presentation.

The limited clinical data for vitamin C in refractory shock include three studies, of which two are randomized controlled trials, comprising a total of 146 patients, he added.

“I will admit an N of 146 is hardly practice-changing for most people,” Dr. Rattan said. “There’s still a significant and sustained large mortality effect for the use of vitamin C, with nearly no adverse effects.”

Pooled analysis of all three studies revealed a marked reduction in mortality with the use of vitamin C (odds ratio, 0.17, 95% confidence interval 0.07–0.40; P less than .001), according to a meta-analysis recently just published in Critical Care that Dr. Rattan referenced in his presentation (Critical Care 2018;22:258, DOI:10.1186/s13054-018-2191-x).

When taken in recommended dosages, vitamin C given with corticosteroids and thiamine is without known side effects, researcher Paul E. Marik wrote earlier this year in an editorial in Pharmacology & Therapeutics (2018;189[9]:63-70, DOI:10.1016/j.pharmthera.2018.04.007) noted Dr. Rattan, who said he uses the intravenous vitamin C, thiamine, and hydrocortisone protocol previously reported by Dr. Marik and colleagues.

There are 13 ongoing trials, including some prospective blinded, randomized trials, looking at the role of vitamin C in refractory shock, he added.

Angiotensin-II is another intervention that may be promising in refractory septic shock, Dr. Rattan told attendees, pointing to the 2017 publication of the ATHOS-3 trial in the New England Journal of Medicine (2017; 377:419-430,DOI: 10.1056/NEJMoa1704154) showing that treatment increased blood pressure in patients with vasodilatory shock not responding to conventional vasopressors at high doses.

Likewise, methylene blue has shown promise in septic shock, at least in some limited clinical investigations and anecdotally in patients not improving despite standard interventions. “I’ve been able to have a couple patients walk out of the hospital with the use of methylene blue,” Dr. Rattan said. “Again, the plural of ‘anecdote’ is not ‘data,’ but it’s something to consider for the early adopters.”

Dr. Rattan had no disclosures related to his presentation.

BOSTON–Vitamin C, angiotensin-II, and methylene blue are emerging options on the cutting edge of refractory septic shock treatment that require more investigation, but nevertheless appear promising, Rishi Rattan, MD, said at the annual clinical congress of the American College of Surgeons.

Andrew Bowser/MDedge News

Trials evaluating vitamin C in this setting have demonstrated a large mortality impact with an absence of side effects, according to Dr. Rattan, a trauma and critical care surgeon with the Ryder Trauma Center at the University of Miami.

“It’s something that I have decided to start early adopting, and many of my colleagues at University of Miami do as well,” Dr. Rattan said in a panel session on updates in septic shock. “We’re anecdotally so far at least seeing good results and are going to be excited to see what these ongoing trials show.”

As an antioxidant, vitamin C has anti-inflammatory properties that may possibly attenuate the overly exuberant inflammatory response seen in septic shock, Dr. Rattan said in his presentation.

The limited clinical data for vitamin C in refractory shock include three studies, of which two are randomized controlled trials, comprising a total of 146 patients, he added.

“I will admit an N of 146 is hardly practice-changing for most people,” Dr. Rattan said. “There’s still a significant and sustained large mortality effect for the use of vitamin C, with nearly no adverse effects.”

Pooled analysis of all three studies revealed a marked reduction in mortality with the use of vitamin C (odds ratio, 0.17, 95% confidence interval 0.07–0.40; P less than .001), according to a meta-analysis recently just published in Critical Care that Dr. Rattan referenced in his presentation (Critical Care 2018;22:258, DOI:10.1186/s13054-018-2191-x).

When taken in recommended dosages, vitamin C given with corticosteroids and thiamine is without known side effects, researcher Paul E. Marik wrote earlier this year in an editorial in Pharmacology & Therapeutics (2018;189[9]:63-70, DOI:10.1016/j.pharmthera.2018.04.007) noted Dr. Rattan, who said he uses the intravenous vitamin C, thiamine, and hydrocortisone protocol previously reported by Dr. Marik and colleagues.

There are 13 ongoing trials, including some prospective blinded, randomized trials, looking at the role of vitamin C in refractory shock, he added.

Angiotensin-II is another intervention that may be promising in refractory septic shock, Dr. Rattan told attendees, pointing to the 2017 publication of the ATHOS-3 trial in the New England Journal of Medicine (2017; 377:419-430,DOI: 10.1056/NEJMoa1704154) showing that treatment increased blood pressure in patients with vasodilatory shock not responding to conventional vasopressors at high doses.

Likewise, methylene blue has shown promise in septic shock, at least in some limited clinical investigations and anecdotally in patients not improving despite standard interventions. “I’ve been able to have a couple patients walk out of the hospital with the use of methylene blue,” Dr. Rattan said. “Again, the plural of ‘anecdote’ is not ‘data,’ but it’s something to consider for the early adopters.”

Dr. Rattan had no disclosures related to his presentation.

SEATTLE – Recent events have highlighted the issue of sexual assault in adolescents. But the onus still is on psychiatrists and other clinicians to ask patients whether they’ve ever been a victim of sexual assault or other kinds of trauma, according to an expert.

“It turns out that these experiences are common for kids, and they’re very correlated with the development of all kinds of psychiatric disorders. And if we ask, they will tell us. If we don’t ask they probably won’t,” said Lucy Berliner, director of the Harborview Center for Sexual Assault and Traumatic Stress, who discussed the epidemiology of sexual trauma in adolescents at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

A common misconception is that victims of sexual assault have endured multiple, chronic traumas. A more common scenario, however, is a single incident, much like the one described by Christine Blasey Ford, PhD, in her testimony before Congress, and clinicians should be more on the lookout for such cases. “I think those young people get a little bit lost,” Ms. Berliner said at the meeting.

A 2001 study of adolescents (aged 12-17) who reported and sought treatment for sexual assault in the Seattle area found that 54% of cases resulted from a single incident.

Unlike the incident described by Dr. Ford, coercion often was not physical. Fifty-two percent of the time, the adolescents experienced abuse by authority figures, such as an assault by a teacher or coach, or even someone who used social advantage such as being older or more popular. In 17% of the cases, the victim was drugged or unconscious. Physical restraint was reported in 20% of cases. Weapons were involved only 7% of the time.

Twenty-eight percent of the adolescents were victims of a teenager, compared with 54% who attributed the assault to an adult. Overall, 72% of the subjects presented at an emergency department rather than a counseling clinic, which suggests that screening in medical environments also is a key factor in identifying and responding to people who have been assaulted.

All study subjects were offered counseling, but the uptake was low: The median was 2 sessions.

“My guess is that in the beginning, a lot of people say, ‘I just want to put it behind me, or I want to try to figure it out myself,’ and it only comes around later, in mental health settings, where these kids are in there for some type of psychiatric disorder. And unless we ask, we’re not going to find out (about a previous assault), and we won’t be able to give them the help that would help them with this psychiatric disorder,” said Ms. Berliner, also a clinical associate professor at the University of Washington School of Social Work in Seattle.

Clinicians might not ask about these experiences, she said, because of fears of triggering raw emotions. But such fears are unfounded, she stated. “We need to get over ourselves,” Ms. Berliner said. “If we don’t create the opportunity, why would they tell us? And if they don’t want to tell us, they won’t. But you can’t traumatize a kid by talking about something that’s already actually happened to them.”

That point can even extend to the legal system. Also during the session, Emily Petersen, senior deputy prosecuting attorney in the Special Assault Unit in King County, Washington, emphasized that, in her experience, young people who are victims of sexual and other forms of assault are resilient – and they will not be traumatized by speaking with a prosecutor or to police about their experiences.

But the legal system cannot provide healing, she and Ms. Berliner noted. That must come from the victim’s support system. “These experiences don’t have to define victims of sexual assault as long as the adults in their lives are responding appropriately to them,” Ms. Petersen said.

Ms. Berliner and Ms. Petersen disclosed no conflicts of interest.

SEATTLE – Recent events have highlighted the issue of sexual assault in adolescents. But the onus still is on psychiatrists and other clinicians to ask patients whether they’ve ever been a victim of sexual assault or other kinds of trauma, according to an expert.

“It turns out that these experiences are common for kids, and they’re very correlated with the development of all kinds of psychiatric disorders. And if we ask, they will tell us. If we don’t ask they probably won’t,” said Lucy Berliner, director of the Harborview Center for Sexual Assault and Traumatic Stress, who discussed the epidemiology of sexual trauma in adolescents at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

A common misconception is that victims of sexual assault have endured multiple, chronic traumas. A more common scenario, however, is a single incident, much like the one described by Christine Blasey Ford, PhD, in her testimony before Congress, and clinicians should be more on the lookout for such cases. “I think those young people get a little bit lost,” Ms. Berliner said at the meeting.

A 2001 study of adolescents (aged 12-17) who reported and sought treatment for sexual assault in the Seattle area found that 54% of cases resulted from a single incident.

Unlike the incident described by Dr. Ford, coercion often was not physical. Fifty-two percent of the time, the adolescents experienced abuse by authority figures, such as an assault by a teacher or coach, or even someone who used social advantage such as being older or more popular. In 17% of the cases, the victim was drugged or unconscious. Physical restraint was reported in 20% of cases. Weapons were involved only 7% of the time.

Twenty-eight percent of the adolescents were victims of a teenager, compared with 54% who attributed the assault to an adult. Overall, 72% of the subjects presented at an emergency department rather than a counseling clinic, which suggests that screening in medical environments also is a key factor in identifying and responding to people who have been assaulted.

All study subjects were offered counseling, but the uptake was low: The median was 2 sessions.

“My guess is that in the beginning, a lot of people say, ‘I just want to put it behind me, or I want to try to figure it out myself,’ and it only comes around later, in mental health settings, where these kids are in there for some type of psychiatric disorder. And unless we ask, we’re not going to find out (about a previous assault), and we won’t be able to give them the help that would help them with this psychiatric disorder,” said Ms. Berliner, also a clinical associate professor at the University of Washington School of Social Work in Seattle.

Clinicians might not ask about these experiences, she said, because of fears of triggering raw emotions. But such fears are unfounded, she stated. “We need to get over ourselves,” Ms. Berliner said. “If we don’t create the opportunity, why would they tell us? And if they don’t want to tell us, they won’t. But you can’t traumatize a kid by talking about something that’s already actually happened to them.”

That point can even extend to the legal system. Also during the session, Emily Petersen, senior deputy prosecuting attorney in the Special Assault Unit in King County, Washington, emphasized that, in her experience, young people who are victims of sexual and other forms of assault are resilient – and they will not be traumatized by speaking with a prosecutor or to police about their experiences.

But the legal system cannot provide healing, she and Ms. Berliner noted. That must come from the victim’s support system. “These experiences don’t have to define victims of sexual assault as long as the adults in their lives are responding appropriately to them,” Ms. Petersen said.

Ms. Berliner and Ms. Petersen disclosed no conflicts of interest.

SEATTLE – Recent events have highlighted the issue of sexual assault in adolescents. But the onus still is on psychiatrists and other clinicians to ask patients whether they’ve ever been a victim of sexual assault or other kinds of trauma, according to an expert.

“It turns out that these experiences are common for kids, and they’re very correlated with the development of all kinds of psychiatric disorders. And if we ask, they will tell us. If we don’t ask they probably won’t,” said Lucy Berliner, director of the Harborview Center for Sexual Assault and Traumatic Stress, who discussed the epidemiology of sexual trauma in adolescents at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

A common misconception is that victims of sexual assault have endured multiple, chronic traumas. A more common scenario, however, is a single incident, much like the one described by Christine Blasey Ford, PhD, in her testimony before Congress, and clinicians should be more on the lookout for such cases. “I think those young people get a little bit lost,” Ms. Berliner said at the meeting.

A 2001 study of adolescents (aged 12-17) who reported and sought treatment for sexual assault in the Seattle area found that 54% of cases resulted from a single incident.

Unlike the incident described by Dr. Ford, coercion often was not physical. Fifty-two percent of the time, the adolescents experienced abuse by authority figures, such as an assault by a teacher or coach, or even someone who used social advantage such as being older or more popular. In 17% of the cases, the victim was drugged or unconscious. Physical restraint was reported in 20% of cases. Weapons were involved only 7% of the time.

Twenty-eight percent of the adolescents were victims of a teenager, compared with 54% who attributed the assault to an adult. Overall, 72% of the subjects presented at an emergency department rather than a counseling clinic, which suggests that screening in medical environments also is a key factor in identifying and responding to people who have been assaulted.

All study subjects were offered counseling, but the uptake was low: The median was 2 sessions.

“My guess is that in the beginning, a lot of people say, ‘I just want to put it behind me, or I want to try to figure it out myself,’ and it only comes around later, in mental health settings, where these kids are in there for some type of psychiatric disorder. And unless we ask, we’re not going to find out (about a previous assault), and we won’t be able to give them the help that would help them with this psychiatric disorder,” said Ms. Berliner, also a clinical associate professor at the University of Washington School of Social Work in Seattle.

Clinicians might not ask about these experiences, she said, because of fears of triggering raw emotions. But such fears are unfounded, she stated. “We need to get over ourselves,” Ms. Berliner said. “If we don’t create the opportunity, why would they tell us? And if they don’t want to tell us, they won’t. But you can’t traumatize a kid by talking about something that’s already actually happened to them.”

That point can even extend to the legal system. Also during the session, Emily Petersen, senior deputy prosecuting attorney in the Special Assault Unit in King County, Washington, emphasized that, in her experience, young people who are victims of sexual and other forms of assault are resilient – and they will not be traumatized by speaking with a prosecutor or to police about their experiences.

But the legal system cannot provide healing, she and Ms. Berliner noted. That must come from the victim’s support system. “These experiences don’t have to define victims of sexual assault as long as the adults in their lives are responding appropriately to them,” Ms. Petersen said.

Ms. Berliner and Ms. Petersen disclosed no conflicts of interest.

For patients with hemophilia and high-titer inhibitors, a new era of treatment has begun with the development of improved variants of traditional bypassing agents and novel, nonfactor-based, prophylactic agents, say authors of a recent review article.

©designer491/Thinkstock

“These new agents may transform the treatment of inhibitor patients and inhibitor-related bleeds, potentially decreasing morbidity and mortality and improving patients’ quality of life,” Amy D. Shapiro, MD, and coauthors wrote in the Journal of Thrombosis and Haemostasis.

Until recently, the only two bypassing agents available were activated prothrombin complex concentrates and recombinant factor VIIa, noted Dr. Shapiro, who is CEO and co-medical director of the Indiana Hemophilia and Thrombosis Center, Indianapolis, and her coauthors.

The first of the novel targeted agents, emicizumab, is a humanized, bispecific monoclonal antibody that was approved for prophylactic use in hemophilia A in the United States in November 2017.

Emicizumab could transform the treatment of patients with inhibitors, but it also requires reconsideration of how to treat breakthrough bleeds and eliminate the underlying inhibitor, the authors said.

In a phase 3 study, this biologic significantly decreased the annualized bleeding rate by 87% versus on-demand bypassing agent therapy, and by 79% versus a prophylactic bypassing agent regimen, they said, noting that 63% of patients had no bleeding events during the study.

Serious adverse events were seen in patients receiving emicizumab prophylaxis, including thrombosis in 2 out of 103 subjects and thrombotic microangiopathy in 3. In all cases, the patients were treating breakthrough bleeds with activated prothrombin complex concentrate, Dr. Shapiro and coauthors wrote.

Other novel agents in clinical development include fitusiran and tissue factor pathway inhibitors, which each target a different natural anticoagulant and could result in new prophylactic options, according to the study coauthors.

“The possibility of multiple therapeutic targets may allow for a highly personalized approach to prophylaxis therapy, with traditional bypassing agents providing options when breakthrough bleeds occur,” they wrote.

In the meantime, eptacog alfa is the “de facto standard” for recombinant factor VIIa, though a new variant under development, eptacog beta, has been accepted for regulatory review in the United States. In a phase 3 clinical trial, eptacog beta appeared to provide improved efficacy and decreased dosing requirements, possibly due to increased binding affinity to endothelial protein C receptor (EPCR), the authors said.

“The addition of improved rFVIIa variants with unique pharmacological and pharmacokinetic profiles will provide new tools to treat bleeding events in inhibitor patients,” Dr. Shapiro and her colleagues wrote.

The use of traditional bypassing agents is expected to decrease over time as new and improved therapeutics are developed. Traditional agents, however, will “remain a necessity” for breakthrough bleeds in hemophilia A patients with inhibitors, and until novel agents become available for hemophilia B, the authors said.

The review article was supported by an unrestricted educational grant from HEMA Biologics, LLC, which had no involvement or editorial control in research, writing or submission. Dr. Shapiro reported disclosures related to HEMA Biologics, Shire, Novo Nordisk, Kedrion Biopharma, Bioverativ, and Genentech.
 

SOURCE: Shapiro AD, et al. J Thromb Haemost. 2018 Sep 28.

For patients with hemophilia and high-titer inhibitors, a new era of treatment has begun with the development of improved variants of traditional bypassing agents and novel, nonfactor-based, prophylactic agents, say authors of a recent review article.

©designer491/Thinkstock

“These new agents may transform the treatment of inhibitor patients and inhibitor-related bleeds, potentially decreasing morbidity and mortality and improving patients’ quality of life,” Amy D. Shapiro, MD, and coauthors wrote in the Journal of Thrombosis and Haemostasis.

Until recently, the only two bypassing agents available were activated prothrombin complex concentrates and recombinant factor VIIa, noted Dr. Shapiro, who is CEO and co-medical director of the Indiana Hemophilia and Thrombosis Center, Indianapolis, and her coauthors.

The first of the novel targeted agents, emicizumab, is a humanized, bispecific monoclonal antibody that was approved for prophylactic use in hemophilia A in the United States in November 2017.

Emicizumab could transform the treatment of patients with inhibitors, but it also requires reconsideration of how to treat breakthrough bleeds and eliminate the underlying inhibitor, the authors said.

In a phase 3 study, this biologic significantly decreased the annualized bleeding rate by 87% versus on-demand bypassing agent therapy, and by 79% versus a prophylactic bypassing agent regimen, they said, noting that 63% of patients had no bleeding events during the study.

Serious adverse events were seen in patients receiving emicizumab prophylaxis, including thrombosis in 2 out of 103 subjects and thrombotic microangiopathy in 3. In all cases, the patients were treating breakthrough bleeds with activated prothrombin complex concentrate, Dr. Shapiro and coauthors wrote.

Other novel agents in clinical development include fitusiran and tissue factor pathway inhibitors, which each target a different natural anticoagulant and could result in new prophylactic options, according to the study coauthors.

“The possibility of multiple therapeutic targets may allow for a highly personalized approach to prophylaxis therapy, with traditional bypassing agents providing options when breakthrough bleeds occur,” they wrote.

In the meantime, eptacog alfa is the “de facto standard” for recombinant factor VIIa, though a new variant under development, eptacog beta, has been accepted for regulatory review in the United States. In a phase 3 clinical trial, eptacog beta appeared to provide improved efficacy and decreased dosing requirements, possibly due to increased binding affinity to endothelial protein C receptor (EPCR), the authors said.

“The addition of improved rFVIIa variants with unique pharmacological and pharmacokinetic profiles will provide new tools to treat bleeding events in inhibitor patients,” Dr. Shapiro and her colleagues wrote.

The use of traditional bypassing agents is expected to decrease over time as new and improved therapeutics are developed. Traditional agents, however, will “remain a necessity” for breakthrough bleeds in hemophilia A patients with inhibitors, and until novel agents become available for hemophilia B, the authors said.

The review article was supported by an unrestricted educational grant from HEMA Biologics, LLC, which had no involvement or editorial control in research, writing or submission. Dr. Shapiro reported disclosures related to HEMA Biologics, Shire, Novo Nordisk, Kedrion Biopharma, Bioverativ, and Genentech.
 

SOURCE: Shapiro AD, et al. J Thromb Haemost. 2018 Sep 28.

For patients with hemophilia and high-titer inhibitors, a new era of treatment has begun with the development of improved variants of traditional bypassing agents and novel, nonfactor-based, prophylactic agents, say authors of a recent review article.

©designer491/Thinkstock

“These new agents may transform the treatment of inhibitor patients and inhibitor-related bleeds, potentially decreasing morbidity and mortality and improving patients’ quality of life,” Amy D. Shapiro, MD, and coauthors wrote in the Journal of Thrombosis and Haemostasis.

Until recently, the only two bypassing agents available were activated prothrombin complex concentrates and recombinant factor VIIa, noted Dr. Shapiro, who is CEO and co-medical director of the Indiana Hemophilia and Thrombosis Center, Indianapolis, and her coauthors.

The first of the novel targeted agents, emicizumab, is a humanized, bispecific monoclonal antibody that was approved for prophylactic use in hemophilia A in the United States in November 2017.

Emicizumab could transform the treatment of patients with inhibitors, but it also requires reconsideration of how to treat breakthrough bleeds and eliminate the underlying inhibitor, the authors said.

In a phase 3 study, this biologic significantly decreased the annualized bleeding rate by 87% versus on-demand bypassing agent therapy, and by 79% versus a prophylactic bypassing agent regimen, they said, noting that 63% of patients had no bleeding events during the study.

Serious adverse events were seen in patients receiving emicizumab prophylaxis, including thrombosis in 2 out of 103 subjects and thrombotic microangiopathy in 3. In all cases, the patients were treating breakthrough bleeds with activated prothrombin complex concentrate, Dr. Shapiro and coauthors wrote.

Other novel agents in clinical development include fitusiran and tissue factor pathway inhibitors, which each target a different natural anticoagulant and could result in new prophylactic options, according to the study coauthors.

“The possibility of multiple therapeutic targets may allow for a highly personalized approach to prophylaxis therapy, with traditional bypassing agents providing options when breakthrough bleeds occur,” they wrote.

In the meantime, eptacog alfa is the “de facto standard” for recombinant factor VIIa, though a new variant under development, eptacog beta, has been accepted for regulatory review in the United States. In a phase 3 clinical trial, eptacog beta appeared to provide improved efficacy and decreased dosing requirements, possibly due to increased binding affinity to endothelial protein C receptor (EPCR), the authors said.

“The addition of improved rFVIIa variants with unique pharmacological and pharmacokinetic profiles will provide new tools to treat bleeding events in inhibitor patients,” Dr. Shapiro and her colleagues wrote.

The use of traditional bypassing agents is expected to decrease over time as new and improved therapeutics are developed. Traditional agents, however, will “remain a necessity” for breakthrough bleeds in hemophilia A patients with inhibitors, and until novel agents become available for hemophilia B, the authors said.

The review article was supported by an unrestricted educational grant from HEMA Biologics, LLC, which had no involvement or editorial control in research, writing or submission. Dr. Shapiro reported disclosures related to HEMA Biologics, Shire, Novo Nordisk, Kedrion Biopharma, Bioverativ, and Genentech.
 

SOURCE: Shapiro AD, et al. J Thromb Haemost. 2018 Sep 28.

The Food and Drug Administration has cleared Xyrem (sodium oxybate) oral solution to treat cataplexy and excessive daytime sleepiness in patients ages 7-17 with narcolepsy.

The central nervous system depressant previously had been approved to treat cataplexy in adults with narcolepsy.

The current approval was granted by the FDA under a Priority Review designation. Xyrem also received the FDA’s Orphan Drug designation, which is intended to encourage the development of drugs for rare diseases.

The agency noted in a press release, however, that the drug would continue to be available only through risk evaluation mitigation strategy (REMS) programs because of “the risk of serious outcomes resulting from inappropriate prescribing, misuse, abuse and diversion.” Xyrem either alone or in combination with other CNS depressants may be associated with reactions including seizure, respiratory depression, decreases in the level of consciousness, coma, and death, the FDA said.

The most common adverse reactions in pediatric patients were enuresis, nausea, headache, vomiting, weight decrease, decreased appetite, and dizziness.

For more information on prescribing Xyrem for pediatric patients, see the revised labeling information on the FDA website.

[email protected]

The Food and Drug Administration has cleared Xyrem (sodium oxybate) oral solution to treat cataplexy and excessive daytime sleepiness in patients ages 7-17 with narcolepsy.

The central nervous system depressant previously had been approved to treat cataplexy in adults with narcolepsy.

The current approval was granted by the FDA under a Priority Review designation. Xyrem also received the FDA’s Orphan Drug designation, which is intended to encourage the development of drugs for rare diseases.

The agency noted in a press release, however, that the drug would continue to be available only through risk evaluation mitigation strategy (REMS) programs because of “the risk of serious outcomes resulting from inappropriate prescribing, misuse, abuse and diversion.” Xyrem either alone or in combination with other CNS depressants may be associated with reactions including seizure, respiratory depression, decreases in the level of consciousness, coma, and death, the FDA said.

The most common adverse reactions in pediatric patients were enuresis, nausea, headache, vomiting, weight decrease, decreased appetite, and dizziness.

For more information on prescribing Xyrem for pediatric patients, see the revised labeling information on the FDA website.

[email protected]

The Food and Drug Administration has cleared Xyrem (sodium oxybate) oral solution to treat cataplexy and excessive daytime sleepiness in patients ages 7-17 with narcolepsy.

The central nervous system depressant previously had been approved to treat cataplexy in adults with narcolepsy.

The current approval was granted by the FDA under a Priority Review designation. Xyrem also received the FDA’s Orphan Drug designation, which is intended to encourage the development of drugs for rare diseases.

The agency noted in a press release, however, that the drug would continue to be available only through risk evaluation mitigation strategy (REMS) programs because of “the risk of serious outcomes resulting from inappropriate prescribing, misuse, abuse and diversion.” Xyrem either alone or in combination with other CNS depressants may be associated with reactions including seizure, respiratory depression, decreases in the level of consciousness, coma, and death, the FDA said.

The most common adverse reactions in pediatric patients were enuresis, nausea, headache, vomiting, weight decrease, decreased appetite, and dizziness.

For more information on prescribing Xyrem for pediatric patients, see the revised labeling information on the FDA website.

[email protected]

The practice of oncology and the science driving it have undergone substantial change in recent years, so it was particularly exciting when this year’s Nobel Prize for Physiology or Medicine was awarded to James Allison and Tasuko Honjo for their discovery that the body’s immune system can be harnessed to fight cancer. The advent of immunotherapy has expanded our therapeutic options, especially for patients whose previous treatments have failed, and in some patients, improvement in overall survival and safety profiles have been encouraging. But we still have a way to go with immunotherapies: not all patients respond to them and they are a costly therapeutic option. In addition, while chemotherapy supresses the immune system, immune-checkpoint inhibitors can hyperactivate it, and patients can experience serious immune-related adverse events that can result in life-threatening toxicities. Among the many things we grapple with in our daily practice is pairing these new and thrilling findings with our patients on a case-by-case basis to ensure the best-possible outcomes at every level – clinical, psychosocial, financial.

In recent years, we have seen an uptick in the number of FDA approvals, and as our therapeutic options have expanded, we have been able to refine and microtarget our treatment approaches, with encouraging clinical and quality-of-life outcomes. Our approach to practice has changed as well – our care is more patient focused, and we work more as part of a team, rather than individually, to ensure that our patients’ clinical and supportive needs are met. We hope our content reflects these shifts. For example, on page e188, Ibrahimi and colleagues looked at the time from admission to treatment initiation (TAT) in patients who were newly diagnosed with acute myeloid leukemia to see if it had an impact on overall survival (OS) and event-free survival. They obtained retrospective data over 5 years, focusing on patients with a TAT of 0-4 days and those with a TAT of >4 days, and found that the median OS in the 0-4 days group was almost double that of the <4 days group (1.3 years and 0.57 years, respectively). Median event-free survival for the groups was 1.21 years and 0.57 years, respectively. Moreover, that association remained significant in a multivariate analysis adjusting for age, white blood cell count, molecular risk group, and undergoing allogeneic stem cell transplant.
 

Marriage and survival

Does marital status have a prognostic bearing on outcomes in patients with cancer? Vyfhuis and colleagues addressed that question in their study of patients with stage III non–small-cell lung cancer (NSCLC) who had been treated uniformly with curative intent (p. e194). Specifically, they looked at OS and freedom from recurrence and they adjusted for patient-, disease-, and treatment-specific factors, as well as the interaction with racial, nutritional, and immunologic status.

In all, 52% of patients in the study were married, and were more likely to self-identify as white; live in areas with a higher household median income; undergo surgery; and have insurance, an ECOG of 0, and higher pretreatment albumin. The authors report that on multivariate analysis, marital status remained an independent predictor of survival and was associated with a 40% decreased risk of death, further stratifying outcomes beyond gender and stage grouping. Freedom from recurrence was comparable between the married and not-married patients. These findings suggest that in a cancer such as NSCLC, for which survival is modest despite therapeutic advances and which is associated with considerable treatment-related toxicities, marital status might be an independent predictor for survival. The authors suggest that marriage is likely a surrogate for better psychosocial support, and that the survival improvements might justify investment in supportive care interventional strategies to help advance overall outcomes.

Cancer in children and AYAs

Two articles in this issue examine cancers in pediatric patients and in adolescents and young adults (AYAs), and by doing so, demonstrate the importance of having evidence-based research findings to help us refine and deliver better-quality, patient-focused care. On page e217, Sharon Worcester documents the growing efforts by researchers and clinicians to understand and address the disparities in survival outcomes between AYAs with cancer and their pediatric and adult counterparts.

It has been known for a while that some cancers are more common among AYAs compared with the other 2 populations, and others are less common. More recent findings suggest that the biology and molecular make-up of AYA cancers might also be different and therefore necessitate different therapeutic protocols, and that the social and psychological needs unique to this population also require specifically tailored supportive care. What about treatment setting for AYAs with cancer – would outcomes be better in a pediatric or adult care center? There is evidence that the pediatric setting might have some advantage, but a recent study from Canada suggests that the cost of care in that setting might be higher. Despite these encouraging findings, there are very few trials designed specifically for the AYA cancer population, and the “pediatric-versus-adult” question also applies to AYA participation in trials. Worcester’s comprehensive article weaves together these issues and offers insights and useful explanations from a number of experts who study or care for AYAs with cancers.

Pediatric cancers are rare, representing just 1% of all new cancers diagnosed annually in the United States, but they are the second leading cause of death in children aged 1 to 14 years and therefore warrant attention, writes Jane de Lartigue in an article on page e210. She echoes Worcester’s point that better understanding of cancers in this younger population has brought to light their unique molecular drivers and challenged the assumption that drugs developed for adults can be used in children and young adults. Dr de Lartigue drills down into the science behind the unique biology and molecular aberrations in pediatric cancers and provides a useful list of ongoing clinical trials of targeted therapies in this population. She notes that because of their rarity, pediatric cancers are difficult to study and adequate enrollment in trials is challenging, although that is changing with researchers’ greater awareness of the uniqueness of these cancers and need for age-specific trials.

Also included in this issue are Community Translation articles on the approval of an immunotherapy combination – nivolumab plus ipilimumab – for the treatment of advanced RCC (p. e182), and for venetoclax as a therapy for patients with chronic lymphocytic leukemia, regardless of genotype (p. e185); and 2 Case Reports, one describing a diagnostic dilemma relating to a patient eventually diagnosed with primary renal synovial sarcoma (p. e202), and another detailing prolonged survival in a patient with adenocarcinoma of unknown primary who was treated with chemoradiotherapy (p. e206).

The practice of oncology and the science driving it have undergone substantial change in recent years, so it was particularly exciting when this year’s Nobel Prize for Physiology or Medicine was awarded to James Allison and Tasuko Honjo for their discovery that the body’s immune system can be harnessed to fight cancer. The advent of immunotherapy has expanded our therapeutic options, especially for patients whose previous treatments have failed, and in some patients, improvement in overall survival and safety profiles have been encouraging. But we still have a way to go with immunotherapies: not all patients respond to them and they are a costly therapeutic option. In addition, while chemotherapy supresses the immune system, immune-checkpoint inhibitors can hyperactivate it, and patients can experience serious immune-related adverse events that can result in life-threatening toxicities. Among the many things we grapple with in our daily practice is pairing these new and thrilling findings with our patients on a case-by-case basis to ensure the best-possible outcomes at every level – clinical, psychosocial, financial.

In recent years, we have seen an uptick in the number of FDA approvals, and as our therapeutic options have expanded, we have been able to refine and microtarget our treatment approaches, with encouraging clinical and quality-of-life outcomes. Our approach to practice has changed as well – our care is more patient focused, and we work more as part of a team, rather than individually, to ensure that our patients’ clinical and supportive needs are met. We hope our content reflects these shifts. For example, on page e188, Ibrahimi and colleagues looked at the time from admission to treatment initiation (TAT) in patients who were newly diagnosed with acute myeloid leukemia to see if it had an impact on overall survival (OS) and event-free survival. They obtained retrospective data over 5 years, focusing on patients with a TAT of 0-4 days and those with a TAT of >4 days, and found that the median OS in the 0-4 days group was almost double that of the <4 days group (1.3 years and 0.57 years, respectively). Median event-free survival for the groups was 1.21 years and 0.57 years, respectively. Moreover, that association remained significant in a multivariate analysis adjusting for age, white blood cell count, molecular risk group, and undergoing allogeneic stem cell transplant.
 

Marriage and survival

Does marital status have a prognostic bearing on outcomes in patients with cancer? Vyfhuis and colleagues addressed that question in their study of patients with stage III non–small-cell lung cancer (NSCLC) who had been treated uniformly with curative intent (p. e194). Specifically, they looked at OS and freedom from recurrence and they adjusted for patient-, disease-, and treatment-specific factors, as well as the interaction with racial, nutritional, and immunologic status.

In all, 52% of patients in the study were married, and were more likely to self-identify as white; live in areas with a higher household median income; undergo surgery; and have insurance, an ECOG of 0, and higher pretreatment albumin. The authors report that on multivariate analysis, marital status remained an independent predictor of survival and was associated with a 40% decreased risk of death, further stratifying outcomes beyond gender and stage grouping. Freedom from recurrence was comparable between the married and not-married patients. These findings suggest that in a cancer such as NSCLC, for which survival is modest despite therapeutic advances and which is associated with considerable treatment-related toxicities, marital status might be an independent predictor for survival. The authors suggest that marriage is likely a surrogate for better psychosocial support, and that the survival improvements might justify investment in supportive care interventional strategies to help advance overall outcomes.

Cancer in children and AYAs

Two articles in this issue examine cancers in pediatric patients and in adolescents and young adults (AYAs), and by doing so, demonstrate the importance of having evidence-based research findings to help us refine and deliver better-quality, patient-focused care. On page e217, Sharon Worcester documents the growing efforts by researchers and clinicians to understand and address the disparities in survival outcomes between AYAs with cancer and their pediatric and adult counterparts.

It has been known for a while that some cancers are more common among AYAs compared with the other 2 populations, and others are less common. More recent findings suggest that the biology and molecular make-up of AYA cancers might also be different and therefore necessitate different therapeutic protocols, and that the social and psychological needs unique to this population also require specifically tailored supportive care. What about treatment setting for AYAs with cancer – would outcomes be better in a pediatric or adult care center? There is evidence that the pediatric setting might have some advantage, but a recent study from Canada suggests that the cost of care in that setting might be higher. Despite these encouraging findings, there are very few trials designed specifically for the AYA cancer population, and the “pediatric-versus-adult” question also applies to AYA participation in trials. Worcester’s comprehensive article weaves together these issues and offers insights and useful explanations from a number of experts who study or care for AYAs with cancers.

Pediatric cancers are rare, representing just 1% of all new cancers diagnosed annually in the United States, but they are the second leading cause of death in children aged 1 to 14 years and therefore warrant attention, writes Jane de Lartigue in an article on page e210. She echoes Worcester’s point that better understanding of cancers in this younger population has brought to light their unique molecular drivers and challenged the assumption that drugs developed for adults can be used in children and young adults. Dr de Lartigue drills down into the science behind the unique biology and molecular aberrations in pediatric cancers and provides a useful list of ongoing clinical trials of targeted therapies in this population. She notes that because of their rarity, pediatric cancers are difficult to study and adequate enrollment in trials is challenging, although that is changing with researchers’ greater awareness of the uniqueness of these cancers and need for age-specific trials.

Also included in this issue are Community Translation articles on the approval of an immunotherapy combination – nivolumab plus ipilimumab – for the treatment of advanced RCC (p. e182), and for venetoclax as a therapy for patients with chronic lymphocytic leukemia, regardless of genotype (p. e185); and 2 Case Reports, one describing a diagnostic dilemma relating to a patient eventually diagnosed with primary renal synovial sarcoma (p. e202), and another detailing prolonged survival in a patient with adenocarcinoma of unknown primary who was treated with chemoradiotherapy (p. e206).

The practice of oncology and the science driving it have undergone substantial change in recent years, so it was particularly exciting when this year’s Nobel Prize for Physiology or Medicine was awarded to James Allison and Tasuko Honjo for their discovery that the body’s immune system can be harnessed to fight cancer. The advent of immunotherapy has expanded our therapeutic options, especially for patients whose previous treatments have failed, and in some patients, improvement in overall survival and safety profiles have been encouraging. But we still have a way to go with immunotherapies: not all patients respond to them and they are a costly therapeutic option. In addition, while chemotherapy supresses the immune system, immune-checkpoint inhibitors can hyperactivate it, and patients can experience serious immune-related adverse events that can result in life-threatening toxicities. Among the many things we grapple with in our daily practice is pairing these new and thrilling findings with our patients on a case-by-case basis to ensure the best-possible outcomes at every level – clinical, psychosocial, financial.

In recent years, we have seen an uptick in the number of FDA approvals, and as our therapeutic options have expanded, we have been able to refine and microtarget our treatment approaches, with encouraging clinical and quality-of-life outcomes. Our approach to practice has changed as well – our care is more patient focused, and we work more as part of a team, rather than individually, to ensure that our patients’ clinical and supportive needs are met. We hope our content reflects these shifts. For example, on page e188, Ibrahimi and colleagues looked at the time from admission to treatment initiation (TAT) in patients who were newly diagnosed with acute myeloid leukemia to see if it had an impact on overall survival (OS) and event-free survival. They obtained retrospective data over 5 years, focusing on patients with a TAT of 0-4 days and those with a TAT of >4 days, and found that the median OS in the 0-4 days group was almost double that of the <4 days group (1.3 years and 0.57 years, respectively). Median event-free survival for the groups was 1.21 years and 0.57 years, respectively. Moreover, that association remained significant in a multivariate analysis adjusting for age, white blood cell count, molecular risk group, and undergoing allogeneic stem cell transplant.
 

Marriage and survival

Does marital status have a prognostic bearing on outcomes in patients with cancer? Vyfhuis and colleagues addressed that question in their study of patients with stage III non–small-cell lung cancer (NSCLC) who had been treated uniformly with curative intent (p. e194). Specifically, they looked at OS and freedom from recurrence and they adjusted for patient-, disease-, and treatment-specific factors, as well as the interaction with racial, nutritional, and immunologic status.

In all, 52% of patients in the study were married, and were more likely to self-identify as white; live in areas with a higher household median income; undergo surgery; and have insurance, an ECOG of 0, and higher pretreatment albumin. The authors report that on multivariate analysis, marital status remained an independent predictor of survival and was associated with a 40% decreased risk of death, further stratifying outcomes beyond gender and stage grouping. Freedom from recurrence was comparable between the married and not-married patients. These findings suggest that in a cancer such as NSCLC, for which survival is modest despite therapeutic advances and which is associated with considerable treatment-related toxicities, marital status might be an independent predictor for survival. The authors suggest that marriage is likely a surrogate for better psychosocial support, and that the survival improvements might justify investment in supportive care interventional strategies to help advance overall outcomes.

Cancer in children and AYAs

Two articles in this issue examine cancers in pediatric patients and in adolescents and young adults (AYAs), and by doing so, demonstrate the importance of having evidence-based research findings to help us refine and deliver better-quality, patient-focused care. On page e217, Sharon Worcester documents the growing efforts by researchers and clinicians to understand and address the disparities in survival outcomes between AYAs with cancer and their pediatric and adult counterparts.

It has been known for a while that some cancers are more common among AYAs compared with the other 2 populations, and others are less common. More recent findings suggest that the biology and molecular make-up of AYA cancers might also be different and therefore necessitate different therapeutic protocols, and that the social and psychological needs unique to this population also require specifically tailored supportive care. What about treatment setting for AYAs with cancer – would outcomes be better in a pediatric or adult care center? There is evidence that the pediatric setting might have some advantage, but a recent study from Canada suggests that the cost of care in that setting might be higher. Despite these encouraging findings, there are very few trials designed specifically for the AYA cancer population, and the “pediatric-versus-adult” question also applies to AYA participation in trials. Worcester’s comprehensive article weaves together these issues and offers insights and useful explanations from a number of experts who study or care for AYAs with cancers.

Pediatric cancers are rare, representing just 1% of all new cancers diagnosed annually in the United States, but they are the second leading cause of death in children aged 1 to 14 years and therefore warrant attention, writes Jane de Lartigue in an article on page e210. She echoes Worcester’s point that better understanding of cancers in this younger population has brought to light their unique molecular drivers and challenged the assumption that drugs developed for adults can be used in children and young adults. Dr de Lartigue drills down into the science behind the unique biology and molecular aberrations in pediatric cancers and provides a useful list of ongoing clinical trials of targeted therapies in this population. She notes that because of their rarity, pediatric cancers are difficult to study and adequate enrollment in trials is challenging, although that is changing with researchers’ greater awareness of the uniqueness of these cancers and need for age-specific trials.

Also included in this issue are Community Translation articles on the approval of an immunotherapy combination – nivolumab plus ipilimumab – for the treatment of advanced RCC (p. e182), and for venetoclax as a therapy for patients with chronic lymphocytic leukemia, regardless of genotype (p. e185); and 2 Case Reports, one describing a diagnostic dilemma relating to a patient eventually diagnosed with primary renal synovial sarcoma (p. e202), and another detailing prolonged survival in a patient with adenocarcinoma of unknown primary who was treated with chemoradiotherapy (p. e206).

Photo by Aaron Logan

Researchers have identified a promising therapeutic target for t(8;21) acute myeloid leukemia (AML), according to preclinical data published in Cancer Cell.

The fusion protein RUNX1/ETO drives t(8;21) AML by promoting cell-cycle progression.

Using an RNAi screen, the team recognized the cell-cycle regulator cyclin D2 (CCND2) as having critical involvement in RUNX1/ETO-driven leukemia propagation.

And when they knocked down CCND2 with palbociclib, a drug already approved for breast cancer, leukemic expansion of human AML cells and engraftment in murine models were significantly impaired.

"Our discovery that this treatment can be effective in AML is an important step towards a more effective and less toxic treatment for patients with this form of leukemia,” said study author Olaf Heidenreich, PhD, from the Wolfson Childhood Cancer Research Centre at Newcastle University in the U.K.

After identifying the fusion protein with the RNAi screen, the investigators determined that RUNX1/ETO regulates CCND2 transcription. They knocked down the fusion protein and found the expression of CCND2 was diminished in primary AML blasts. They therefore concluded that RUNX1/ETO maintains CCND2 expression.

The team then examined the significance of CCND2 in engraftment, proliferation, and clonal expansion of AML cells and its impact on the accumulation of cells in the G1 phase of the cell cycle. They found that depletion of CCND2 inhibited cell proliferation and clonogenic capacity and arrested the cell cycle in G0/G1 without increasing apoptosis.

They also confirmed that knockdown of RUNX1/ETO or CCND2 did not affect the expression of other D cyclins and G1 cyclin-dependent kinase (CDK)-CCND complexes, such as CDK4/6.

Next, they explored whether RUNX1/ETO-expressing cells were sensitive to the CDK4/6 inhibitor palbociclib. AML cells were highly sensitive to palbociclib and did not proliferate during drug exposure.

The researchers cultured cells from t(8;21)-positive and -negative AML patients and found palbociclib to cause a dose-dependent inhibition of proliferation of AML blasts.

They also tested palbociclib on a sample from a relapsed t(8;21) AML patient. The sample was highly sensitive to palbociclib, with a five-fold reduction in cell numbers using 300 nM of drug.

The investigators conducted in vivo experiments with palbociclib in mice transplanted with AML cells. Mice treated with palbociclib at doses of 100–150 mg/kg had a significantly longer survival than control mice.

Finally, the team examined whether interference with G1 CDK activity would create other vulnerabilities, such as activating KIT mutations, which are frequent secondary mutations found in t(8;21) AML.

They found that G1 CDK inhibition sensitized AML cells toward KIT inhibition, suggesting that “concurrent targeting of the two mutations may offer substantial therapeutic benefit.”

The team plans to conduct experiments that will refine the precise palbociclib dose in AML either as a single agent or in combination.

This study was supported by grants from Bloodwise, Children with Cancer, North of England Children’s Cancer Research Fund, Children's Cancer and Leukaemia Group, and a CRUK program grant in addition to an Aga Khan PhD studentship, a University Sains Malaysia PhD studentship, and an NC3R fellowship.

The authors had no competing interests to disclose. 

Photo by Aaron Logan

Researchers have identified a promising therapeutic target for t(8;21) acute myeloid leukemia (AML), according to preclinical data published in Cancer Cell.

The fusion protein RUNX1/ETO drives t(8;21) AML by promoting cell-cycle progression.

Using an RNAi screen, the team recognized the cell-cycle regulator cyclin D2 (CCND2) as having critical involvement in RUNX1/ETO-driven leukemia propagation.

And when they knocked down CCND2 with palbociclib, a drug already approved for breast cancer, leukemic expansion of human AML cells and engraftment in murine models were significantly impaired.

"Our discovery that this treatment can be effective in AML is an important step towards a more effective and less toxic treatment for patients with this form of leukemia,” said study author Olaf Heidenreich, PhD, from the Wolfson Childhood Cancer Research Centre at Newcastle University in the U.K.

After identifying the fusion protein with the RNAi screen, the investigators determined that RUNX1/ETO regulates CCND2 transcription. They knocked down the fusion protein and found the expression of CCND2 was diminished in primary AML blasts. They therefore concluded that RUNX1/ETO maintains CCND2 expression.

The team then examined the significance of CCND2 in engraftment, proliferation, and clonal expansion of AML cells and its impact on the accumulation of cells in the G1 phase of the cell cycle. They found that depletion of CCND2 inhibited cell proliferation and clonogenic capacity and arrested the cell cycle in G0/G1 without increasing apoptosis.

They also confirmed that knockdown of RUNX1/ETO or CCND2 did not affect the expression of other D cyclins and G1 cyclin-dependent kinase (CDK)-CCND complexes, such as CDK4/6.

Next, they explored whether RUNX1/ETO-expressing cells were sensitive to the CDK4/6 inhibitor palbociclib. AML cells were highly sensitive to palbociclib and did not proliferate during drug exposure.

The researchers cultured cells from t(8;21)-positive and -negative AML patients and found palbociclib to cause a dose-dependent inhibition of proliferation of AML blasts.

They also tested palbociclib on a sample from a relapsed t(8;21) AML patient. The sample was highly sensitive to palbociclib, with a five-fold reduction in cell numbers using 300 nM of drug.

The investigators conducted in vivo experiments with palbociclib in mice transplanted with AML cells. Mice treated with palbociclib at doses of 100–150 mg/kg had a significantly longer survival than control mice.

Finally, the team examined whether interference with G1 CDK activity would create other vulnerabilities, such as activating KIT mutations, which are frequent secondary mutations found in t(8;21) AML.

They found that G1 CDK inhibition sensitized AML cells toward KIT inhibition, suggesting that “concurrent targeting of the two mutations may offer substantial therapeutic benefit.”

The team plans to conduct experiments that will refine the precise palbociclib dose in AML either as a single agent or in combination.

This study was supported by grants from Bloodwise, Children with Cancer, North of England Children’s Cancer Research Fund, Children's Cancer and Leukaemia Group, and a CRUK program grant in addition to an Aga Khan PhD studentship, a University Sains Malaysia PhD studentship, and an NC3R fellowship.

The authors had no competing interests to disclose. 

Photo by Aaron Logan

Researchers have identified a promising therapeutic target for t(8;21) acute myeloid leukemia (AML), according to preclinical data published in Cancer Cell.

The fusion protein RUNX1/ETO drives t(8;21) AML by promoting cell-cycle progression.

Using an RNAi screen, the team recognized the cell-cycle regulator cyclin D2 (CCND2) as having critical involvement in RUNX1/ETO-driven leukemia propagation.

And when they knocked down CCND2 with palbociclib, a drug already approved for breast cancer, leukemic expansion of human AML cells and engraftment in murine models were significantly impaired.

"Our discovery that this treatment can be effective in AML is an important step towards a more effective and less toxic treatment for patients with this form of leukemia,” said study author Olaf Heidenreich, PhD, from the Wolfson Childhood Cancer Research Centre at Newcastle University in the U.K.

After identifying the fusion protein with the RNAi screen, the investigators determined that RUNX1/ETO regulates CCND2 transcription. They knocked down the fusion protein and found the expression of CCND2 was diminished in primary AML blasts. They therefore concluded that RUNX1/ETO maintains CCND2 expression.

The team then examined the significance of CCND2 in engraftment, proliferation, and clonal expansion of AML cells and its impact on the accumulation of cells in the G1 phase of the cell cycle. They found that depletion of CCND2 inhibited cell proliferation and clonogenic capacity and arrested the cell cycle in G0/G1 without increasing apoptosis.

They also confirmed that knockdown of RUNX1/ETO or CCND2 did not affect the expression of other D cyclins and G1 cyclin-dependent kinase (CDK)-CCND complexes, such as CDK4/6.

Next, they explored whether RUNX1/ETO-expressing cells were sensitive to the CDK4/6 inhibitor palbociclib. AML cells were highly sensitive to palbociclib and did not proliferate during drug exposure.

The researchers cultured cells from t(8;21)-positive and -negative AML patients and found palbociclib to cause a dose-dependent inhibition of proliferation of AML blasts.

They also tested palbociclib on a sample from a relapsed t(8;21) AML patient. The sample was highly sensitive to palbociclib, with a five-fold reduction in cell numbers using 300 nM of drug.

The investigators conducted in vivo experiments with palbociclib in mice transplanted with AML cells. Mice treated with palbociclib at doses of 100–150 mg/kg had a significantly longer survival than control mice.

Finally, the team examined whether interference with G1 CDK activity would create other vulnerabilities, such as activating KIT mutations, which are frequent secondary mutations found in t(8;21) AML.

They found that G1 CDK inhibition sensitized AML cells toward KIT inhibition, suggesting that “concurrent targeting of the two mutations may offer substantial therapeutic benefit.”

The team plans to conduct experiments that will refine the precise palbociclib dose in AML either as a single agent or in combination.

This study was supported by grants from Bloodwise, Children with Cancer, North of England Children’s Cancer Research Fund, Children's Cancer and Leukaemia Group, and a CRUK program grant in addition to an Aga Khan PhD studentship, a University Sains Malaysia PhD studentship, and an NC3R fellowship.

The authors had no competing interests to disclose.