SEATTLE – Disease anatomy is the main determinant of subsequent quality of life (QOL) in patients with locally recurrent rectal cancer at both base line and in the long term, according to findings presented at the annual Society of Surgical Oncology Cancer Symposium.

Posterior recurrences were associated with the worst QOL scores and the most severe pain.

Recurrent rectal cancer is a morbid disease state, leading to pain and disability. “Patients experience a multitude of symptoms, including disability as a result of tumor growth in a confined space in the pelvis and invasion of adjacent organs as well as complications from surgery and neoadjuvant treatment,” said lead author Dr. Tarik Sammour of the University of Texas MD Anderson Cancer Center in Houston.

He noted, however, that “it is not all doom and gloom.” Survival outcomes have been improving in this population, with the median 5-year survival now approaching 40%-50%.

“Decade by decade, the 5-year survival outcomes are increasing,” explained Dr. Sammour.

Increasing survival also begs the question: “Are we helping patients or affording them the option of living longer with pain and disability? In other words, we need to measure patient-centered outcomes,” he said.

Data for recurrent rectal cancer are very limited, particularly when it comes to measuring patient outcomes. Most studies have been retrospective in design, making it difficult to gauge symptoms and quality of life.

The majority of studies also have focused on surgery, have short follow-up times, and may be missing data.

“Very few measure baseline quality of life, so it makes it difficult to measure trajectories,” Dr. Sammour said. “So overall we don’t know very much about the quality of life of these patients, so we thought to remedy that with a prospective study.”

Dr. Sammour and his colleagues examined the longitudinal trajectory of cancer survivorship in recurrent rectal cancer over a 7-year period. A total of 104 patients diagnosed with recurrent rectal cancer were enrolled between 2008 and 2015, and they prospectively self reported QOL using the validated EORTC QLQ-C30 and EORTC QLQ-CR29. Pain was measured by the Brief Pain Inventory.

Symptoms were measured at baseline and then every 6 months for 5 years or until death.

Within this cohort, 73 (70.2%) patients were amenable to salvage surgery with curative intent. A variety of types of surgery were performed, and R0 resection was achieved in 75% of cases.

The 30-day complication rate was 49% (21% with grade 3/4), and 5-year disease-free survival was 40%. There was no immediate mortality from the surgery.

When looking at differences between patients who underwent surgery and those who didn’t, there was a significant difference in the location of the disease. The nonsurgical group was more likely to have posterior recurrences (26%) than was the surgical group (19%).

“This makes sense since these are more difficult to achieve a R0 result with, so it may be less likely that they were offered the procedure,” Dr. Sammour said.

There was also a significant difference in estimated 5-year survival. Overall survival was 7.7% in the nonsurgical group vs. 50.9% in the surgical group (P less than .0001), and cancer-specific survival was 11.5% vs. 59.6% (P less than .0001).

As for pain and QOL scores, there were no differences between groups at baseline.

“So when they arrived at clinic they had roughly equivalent quality of life,” he said.

At follow-up, male patients were more likely to experience severe pain, but “we felt it was due to the anatomical location. Men have a narrower pelvis and don’t have the luxury of a uterus to protect the genitourinary organs,” he explained. “We suspect this may have played a role in the severity of their pain.”

Patients with posterior recurrences also had worse pain, and this was true for both surgical and nonsurgical patients.

The only determinant for QOL in those who underwent surgery was a positive margin (global health score 70.4 for negative margin and 61.9 for positive margins [P = .024]), but otherwise there were no differences by type of surgery or postoperative complications.

At a median follow-up of 33 months, patients who underwent surgery showed gradual sustained improvement in QOL but not pain scores.

“We were encouraged to see improvement,” concluded Dr. Sammour. “Surgery does improve quality of life in resectable cases.”

No funding source was disclosed. Dr. Sammour and his coauthors had no disclosures.

SEATTLE – Disease anatomy is the main determinant of subsequent quality of life (QOL) in patients with locally recurrent rectal cancer at both base line and in the long term, according to findings presented at the annual Society of Surgical Oncology Cancer Symposium.

Posterior recurrences were associated with the worst QOL scores and the most severe pain.

Recurrent rectal cancer is a morbid disease state, leading to pain and disability. “Patients experience a multitude of symptoms, including disability as a result of tumor growth in a confined space in the pelvis and invasion of adjacent organs as well as complications from surgery and neoadjuvant treatment,” said lead author Dr. Tarik Sammour of the University of Texas MD Anderson Cancer Center in Houston.

He noted, however, that “it is not all doom and gloom.” Survival outcomes have been improving in this population, with the median 5-year survival now approaching 40%-50%.

“Decade by decade, the 5-year survival outcomes are increasing,” explained Dr. Sammour.

Increasing survival also begs the question: “Are we helping patients or affording them the option of living longer with pain and disability? In other words, we need to measure patient-centered outcomes,” he said.

Data for recurrent rectal cancer are very limited, particularly when it comes to measuring patient outcomes. Most studies have been retrospective in design, making it difficult to gauge symptoms and quality of life.

The majority of studies also have focused on surgery, have short follow-up times, and may be missing data.

“Very few measure baseline quality of life, so it makes it difficult to measure trajectories,” Dr. Sammour said. “So overall we don’t know very much about the quality of life of these patients, so we thought to remedy that with a prospective study.”

Dr. Sammour and his colleagues examined the longitudinal trajectory of cancer survivorship in recurrent rectal cancer over a 7-year period. A total of 104 patients diagnosed with recurrent rectal cancer were enrolled between 2008 and 2015, and they prospectively self reported QOL using the validated EORTC QLQ-C30 and EORTC QLQ-CR29. Pain was measured by the Brief Pain Inventory.

Symptoms were measured at baseline and then every 6 months for 5 years or until death.

Within this cohort, 73 (70.2%) patients were amenable to salvage surgery with curative intent. A variety of types of surgery were performed, and R0 resection was achieved in 75% of cases.

The 30-day complication rate was 49% (21% with grade 3/4), and 5-year disease-free survival was 40%. There was no immediate mortality from the surgery.

When looking at differences between patients who underwent surgery and those who didn’t, there was a significant difference in the location of the disease. The nonsurgical group was more likely to have posterior recurrences (26%) than was the surgical group (19%).

“This makes sense since these are more difficult to achieve a R0 result with, so it may be less likely that they were offered the procedure,” Dr. Sammour said.

There was also a significant difference in estimated 5-year survival. Overall survival was 7.7% in the nonsurgical group vs. 50.9% in the surgical group (P less than .0001), and cancer-specific survival was 11.5% vs. 59.6% (P less than .0001).

As for pain and QOL scores, there were no differences between groups at baseline.

“So when they arrived at clinic they had roughly equivalent quality of life,” he said.

At follow-up, male patients were more likely to experience severe pain, but “we felt it was due to the anatomical location. Men have a narrower pelvis and don’t have the luxury of a uterus to protect the genitourinary organs,” he explained. “We suspect this may have played a role in the severity of their pain.”

Patients with posterior recurrences also had worse pain, and this was true for both surgical and nonsurgical patients.

The only determinant for QOL in those who underwent surgery was a positive margin (global health score 70.4 for negative margin and 61.9 for positive margins [P = .024]), but otherwise there were no differences by type of surgery or postoperative complications.

At a median follow-up of 33 months, patients who underwent surgery showed gradual sustained improvement in QOL but not pain scores.

“We were encouraged to see improvement,” concluded Dr. Sammour. “Surgery does improve quality of life in resectable cases.”

No funding source was disclosed. Dr. Sammour and his coauthors had no disclosures.

SEATTLE – Disease anatomy is the main determinant of subsequent quality of life (QOL) in patients with locally recurrent rectal cancer at both base line and in the long term, according to findings presented at the annual Society of Surgical Oncology Cancer Symposium.

Posterior recurrences were associated with the worst QOL scores and the most severe pain.

Recurrent rectal cancer is a morbid disease state, leading to pain and disability. “Patients experience a multitude of symptoms, including disability as a result of tumor growth in a confined space in the pelvis and invasion of adjacent organs as well as complications from surgery and neoadjuvant treatment,” said lead author Dr. Tarik Sammour of the University of Texas MD Anderson Cancer Center in Houston.

He noted, however, that “it is not all doom and gloom.” Survival outcomes have been improving in this population, with the median 5-year survival now approaching 40%-50%.

“Decade by decade, the 5-year survival outcomes are increasing,” explained Dr. Sammour.

Increasing survival also begs the question: “Are we helping patients or affording them the option of living longer with pain and disability? In other words, we need to measure patient-centered outcomes,” he said.

Data for recurrent rectal cancer are very limited, particularly when it comes to measuring patient outcomes. Most studies have been retrospective in design, making it difficult to gauge symptoms and quality of life.

The majority of studies also have focused on surgery, have short follow-up times, and may be missing data.

“Very few measure baseline quality of life, so it makes it difficult to measure trajectories,” Dr. Sammour said. “So overall we don’t know very much about the quality of life of these patients, so we thought to remedy that with a prospective study.”

Dr. Sammour and his colleagues examined the longitudinal trajectory of cancer survivorship in recurrent rectal cancer over a 7-year period. A total of 104 patients diagnosed with recurrent rectal cancer were enrolled between 2008 and 2015, and they prospectively self reported QOL using the validated EORTC QLQ-C30 and EORTC QLQ-CR29. Pain was measured by the Brief Pain Inventory.

Symptoms were measured at baseline and then every 6 months for 5 years or until death.

Within this cohort, 73 (70.2%) patients were amenable to salvage surgery with curative intent. A variety of types of surgery were performed, and R0 resection was achieved in 75% of cases.

The 30-day complication rate was 49% (21% with grade 3/4), and 5-year disease-free survival was 40%. There was no immediate mortality from the surgery.

When looking at differences between patients who underwent surgery and those who didn’t, there was a significant difference in the location of the disease. The nonsurgical group was more likely to have posterior recurrences (26%) than was the surgical group (19%).

“This makes sense since these are more difficult to achieve a R0 result with, so it may be less likely that they were offered the procedure,” Dr. Sammour said.

There was also a significant difference in estimated 5-year survival. Overall survival was 7.7% in the nonsurgical group vs. 50.9% in the surgical group (P less than .0001), and cancer-specific survival was 11.5% vs. 59.6% (P less than .0001).

As for pain and QOL scores, there were no differences between groups at baseline.

“So when they arrived at clinic they had roughly equivalent quality of life,” he said.

At follow-up, male patients were more likely to experience severe pain, but “we felt it was due to the anatomical location. Men have a narrower pelvis and don’t have the luxury of a uterus to protect the genitourinary organs,” he explained. “We suspect this may have played a role in the severity of their pain.”

Patients with posterior recurrences also had worse pain, and this was true for both surgical and nonsurgical patients.

The only determinant for QOL in those who underwent surgery was a positive margin (global health score 70.4 for negative margin and 61.9 for positive margins [P = .024]), but otherwise there were no differences by type of surgery or postoperative complications.

At a median follow-up of 33 months, patients who underwent surgery showed gradual sustained improvement in QOL but not pain scores.

“We were encouraged to see improvement,” concluded Dr. Sammour. “Surgery does improve quality of life in resectable cases.”

No funding source was disclosed. Dr. Sammour and his coauthors had no disclosures.

ORLANDO – A guideline published late last year for the diagnostic work-up of myeloproliferative neoplasms and for the management of myelofibrosis in particular is just the first in a series of National Comprehensive Cancer Network guidelines on this “family of myeloid neoplasms,” according to the guideline panel chair, Ruben A. Mesa, MD.

The myeloproliferative neoplasm (MPN) guideline panel first worked to develop a framework based on existing understanding of the MPNs. Members consulted with two other panels working in the area of chronic myeloid diseases, including chronic myeloid leukemia and myelodysplastic syndrome.

Sharon Worcester/Frontline Medical News

[email protected]

ORLANDO – A guideline published late last year for the diagnostic work-up of myeloproliferative neoplasms and for the management of myelofibrosis in particular is just the first in a series of National Comprehensive Cancer Network guidelines on this “family of myeloid neoplasms,” according to the guideline panel chair, Ruben A. Mesa, MD.

The myeloproliferative neoplasm (MPN) guideline panel first worked to develop a framework based on existing understanding of the MPNs. Members consulted with two other panels working in the area of chronic myeloid diseases, including chronic myeloid leukemia and myelodysplastic syndrome.

Sharon Worcester/Frontline Medical News

[email protected]

ORLANDO – A guideline published late last year for the diagnostic work-up of myeloproliferative neoplasms and for the management of myelofibrosis in particular is just the first in a series of National Comprehensive Cancer Network guidelines on this “family of myeloid neoplasms,” according to the guideline panel chair, Ruben A. Mesa, MD.

The myeloproliferative neoplasm (MPN) guideline panel first worked to develop a framework based on existing understanding of the MPNs. Members consulted with two other panels working in the area of chronic myeloid diseases, including chronic myeloid leukemia and myelodysplastic syndrome.

Sharon Worcester/Frontline Medical News

[email protected]

Antihemophilic factor

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for nonacog beta pegol (N9-GP, Refixia®).

N9-GP is an extended half-life factor IX molecule intended for replacement therapy in patients with hemophilia B.

The CHMP has recommended N9-GP for use as prophylaxis, for on-demand treatment of bleeding, and for control of bleeding related to surgical procedures in adolescents (older than 12 years of age) and adults with hemophilia B.

The CHMP’s opinion has been forwarded to the European Commission, which will decide whether or not to grant marketing authorization for N9-GP. The product is being developed by Novo Nordisk.

Trial results

The CHMP’s recommendation for N9-GP is based on results from the paradigm™ clinical trials. Results from the paradigm 4 trial were published in Thrombosis Research in May 2016.

Paradigm 4 was an extension trial enrolling patients who had participated in a pair of phase 3 trials known as paradigm 2 and paradigm 3.

In paradigm 2, researchers assessed N9-GP as treatment and prophylaxis in previously treated patients with hemophilia B. In paradigm 3, researchers assessed N9-GP in hemophilia B patients undergoing surgical procedures.

Paradigm 4 included 71 patients (ages 13 to 70) who continued to receive N9-GP as on-demand treatment (40 IU/kg for mild/moderate bleeds and 80 IU/kg for severe bleeds) or prophylaxis (10 IU/kg or 40 IU/kg once-weekly). Sixty-five patients completed treatment.

Safety

None of the patients developed factor IX inhibitors. Two patients had transient binding antibodies to N9-GP, but there was no sign that these antibodies had an inhibitory effect.

Four patients developed anti-CHO antibodies, but only 2 of these patients were still positive for these antibodies at the end of the trial.

There were a total of 155 adverse events. However, only 4 of these (in 3 patients) were considered possibly or probably related to N9-GP.

These events consisted of an injection site rash in 1 patient, 2 overdoses in 1 patient, and neutropenia in 1 patient. The rash and neutropenia resolved, and the patient who overdosed recovered without complications.

Efficacy

The researchers said the success rate for the treatment of reported bleeds was 94.6%. Most bleeds (87.9%) were resolved with a single injection of N9-GP, but 9.2% required 2 injections, and 2.9% required 3 or 4 injections.

The median annualized bleeding rate for patients on prophylaxis was 1.05 (interquartile range [IQR], 0.00–2.20) overall. It was 1.36 (IQR, 0.00-2.23) for the 10 IU/kg arm and 1.00 (IQR, 0.00-2.03) for the 40 IU/kg arm.

There were 14 patients on prophylaxis who underwent 23 minor surgical procedures.

The hemostatic response was considered “excellent” (better than expected/predicted for the procedure in question) in 19 procedures and “good” (as expected) in 2 procedures. In the remaining 2 procedures, hemostatic responses were not determined.

Antihemophilic factor

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for nonacog beta pegol (N9-GP, Refixia®).

N9-GP is an extended half-life factor IX molecule intended for replacement therapy in patients with hemophilia B.

The CHMP has recommended N9-GP for use as prophylaxis, for on-demand treatment of bleeding, and for control of bleeding related to surgical procedures in adolescents (older than 12 years of age) and adults with hemophilia B.

The CHMP’s opinion has been forwarded to the European Commission, which will decide whether or not to grant marketing authorization for N9-GP. The product is being developed by Novo Nordisk.

Trial results

The CHMP’s recommendation for N9-GP is based on results from the paradigm™ clinical trials. Results from the paradigm 4 trial were published in Thrombosis Research in May 2016.

Paradigm 4 was an extension trial enrolling patients who had participated in a pair of phase 3 trials known as paradigm 2 and paradigm 3.

In paradigm 2, researchers assessed N9-GP as treatment and prophylaxis in previously treated patients with hemophilia B. In paradigm 3, researchers assessed N9-GP in hemophilia B patients undergoing surgical procedures.

Paradigm 4 included 71 patients (ages 13 to 70) who continued to receive N9-GP as on-demand treatment (40 IU/kg for mild/moderate bleeds and 80 IU/kg for severe bleeds) or prophylaxis (10 IU/kg or 40 IU/kg once-weekly). Sixty-five patients completed treatment.

Safety

None of the patients developed factor IX inhibitors. Two patients had transient binding antibodies to N9-GP, but there was no sign that these antibodies had an inhibitory effect.

Four patients developed anti-CHO antibodies, but only 2 of these patients were still positive for these antibodies at the end of the trial.

There were a total of 155 adverse events. However, only 4 of these (in 3 patients) were considered possibly or probably related to N9-GP.

These events consisted of an injection site rash in 1 patient, 2 overdoses in 1 patient, and neutropenia in 1 patient. The rash and neutropenia resolved, and the patient who overdosed recovered without complications.

Efficacy

The researchers said the success rate for the treatment of reported bleeds was 94.6%. Most bleeds (87.9%) were resolved with a single injection of N9-GP, but 9.2% required 2 injections, and 2.9% required 3 or 4 injections.

The median annualized bleeding rate for patients on prophylaxis was 1.05 (interquartile range [IQR], 0.00–2.20) overall. It was 1.36 (IQR, 0.00-2.23) for the 10 IU/kg arm and 1.00 (IQR, 0.00-2.03) for the 40 IU/kg arm.

There were 14 patients on prophylaxis who underwent 23 minor surgical procedures.

The hemostatic response was considered “excellent” (better than expected/predicted for the procedure in question) in 19 procedures and “good” (as expected) in 2 procedures. In the remaining 2 procedures, hemostatic responses were not determined.

Antihemophilic factor

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for nonacog beta pegol (N9-GP, Refixia®).

N9-GP is an extended half-life factor IX molecule intended for replacement therapy in patients with hemophilia B.

The CHMP has recommended N9-GP for use as prophylaxis, for on-demand treatment of bleeding, and for control of bleeding related to surgical procedures in adolescents (older than 12 years of age) and adults with hemophilia B.

The CHMP’s opinion has been forwarded to the European Commission, which will decide whether or not to grant marketing authorization for N9-GP. The product is being developed by Novo Nordisk.

Trial results

The CHMP’s recommendation for N9-GP is based on results from the paradigm™ clinical trials. Results from the paradigm 4 trial were published in Thrombosis Research in May 2016.

Paradigm 4 was an extension trial enrolling patients who had participated in a pair of phase 3 trials known as paradigm 2 and paradigm 3.

In paradigm 2, researchers assessed N9-GP as treatment and prophylaxis in previously treated patients with hemophilia B. In paradigm 3, researchers assessed N9-GP in hemophilia B patients undergoing surgical procedures.

Paradigm 4 included 71 patients (ages 13 to 70) who continued to receive N9-GP as on-demand treatment (40 IU/kg for mild/moderate bleeds and 80 IU/kg for severe bleeds) or prophylaxis (10 IU/kg or 40 IU/kg once-weekly). Sixty-five patients completed treatment.

Safety

None of the patients developed factor IX inhibitors. Two patients had transient binding antibodies to N9-GP, but there was no sign that these antibodies had an inhibitory effect.

Four patients developed anti-CHO antibodies, but only 2 of these patients were still positive for these antibodies at the end of the trial.

There were a total of 155 adverse events. However, only 4 of these (in 3 patients) were considered possibly or probably related to N9-GP.

These events consisted of an injection site rash in 1 patient, 2 overdoses in 1 patient, and neutropenia in 1 patient. The rash and neutropenia resolved, and the patient who overdosed recovered without complications.

Efficacy

The researchers said the success rate for the treatment of reported bleeds was 94.6%. Most bleeds (87.9%) were resolved with a single injection of N9-GP, but 9.2% required 2 injections, and 2.9% required 3 or 4 injections.

The median annualized bleeding rate for patients on prophylaxis was 1.05 (interquartile range [IQR], 0.00–2.20) overall. It was 1.36 (IQR, 0.00-2.23) for the 10 IU/kg arm and 1.00 (IQR, 0.00-2.03) for the 40 IU/kg arm.

There were 14 patients on prophylaxis who underwent 23 minor surgical procedures.

The hemostatic response was considered “excellent” (better than expected/predicted for the procedure in question) in 19 procedures and “good” (as expected) in 2 procedures. In the remaining 2 procedures, hemostatic responses were not determined.

NATIONAL HARBOR, MD. – Surgical resection to the point of no residual macroscopic disease significantly improved survival among patients with low-grade serous ovarian carcinoma, based on the findings of a large multicenter retrospective cohort study.

Adjuvant platinum-based therapy, however, did not appear to boost survival in the analysis, Tamayaa May, MD, MSc, said at the annual meeting of the Society of Gynecologic Oncology. “Genotyping and targeted sequencing of low-grade serous ovarian carcinoma often identifies actionable mutations, and treatment with MEK-based combination therapy might be a viable therapeutic strategy in patients with KRAS or NRAS mutations,” added Dr. May of Princess Margaret Cancer Center at the University of Toronto. She and her associates plan to examine more subgroups to determine if genomic alterations predict systemic response, she said.

NATIONAL HARBOR, MD. – Surgical resection to the point of no residual macroscopic disease significantly improved survival among patients with low-grade serous ovarian carcinoma, based on the findings of a large multicenter retrospective cohort study.

Adjuvant platinum-based therapy, however, did not appear to boost survival in the analysis, Tamayaa May, MD, MSc, said at the annual meeting of the Society of Gynecologic Oncology. “Genotyping and targeted sequencing of low-grade serous ovarian carcinoma often identifies actionable mutations, and treatment with MEK-based combination therapy might be a viable therapeutic strategy in patients with KRAS or NRAS mutations,” added Dr. May of Princess Margaret Cancer Center at the University of Toronto. She and her associates plan to examine more subgroups to determine if genomic alterations predict systemic response, she said.

NATIONAL HARBOR, MD. – Surgical resection to the point of no residual macroscopic disease significantly improved survival among patients with low-grade serous ovarian carcinoma, based on the findings of a large multicenter retrospective cohort study.

Adjuvant platinum-based therapy, however, did not appear to boost survival in the analysis, Tamayaa May, MD, MSc, said at the annual meeting of the Society of Gynecologic Oncology. “Genotyping and targeted sequencing of low-grade serous ovarian carcinoma often identifies actionable mutations, and treatment with MEK-based combination therapy might be a viable therapeutic strategy in patients with KRAS or NRAS mutations,” added Dr. May of Princess Margaret Cancer Center at the University of Toronto. She and her associates plan to examine more subgroups to determine if genomic alterations predict systemic response, she said.

NATIONAL HARBOR, MD. – Combining a liquid-based Pap smear and cell-free DNA plasma testing can boost the sensitivity of screening for primary ovarian tumors, based on the results of a prospective study of 201 patients.

The approach, however, was most sensitive when women already had late-stage disease, Amanda Nickles Fader, MD, said at the annual meeting of the Society of Gynecologic Oncology. Nonetheless, she called combined Pap and plasma testing “a promising step toward a broadly applicable screening methodology for the early detection of ovarian cancer.”

Ovarian cancer is a “legal malignancy,” and detecting it at “earlier, more curable stages is a clinical imperative,” said Dr. Fader of the Johns Hopkins Kelly Gynecologic Oncology Service in Baltimore, Md.

Routine screening with ultrasound or the CA-125 test has not been shown to reduce deaths from ovarian cancer and can lead to unnecessary diagnostic surgeries. Therefore, population-based screening is not recommended by the U.S. Preventive Services Task Force, the American Cancer Society, the American Congress of Obstetricians and Gynecologists, or the National Comprehensive Cancer Network, Dr. Fader noted.

This paradigm, however, is starting to change with the advent of DNA-based tests for ovarian cancer, including the PapGene test and assays for circulating DNA released by apoptotic tumor cells (ctDNA), Dr. Fader said. In a previous pilot study, Pap testing identified oncogenic driver mutations in 41% of primary ovarian tumors. In another study, polymerase chain reaction (PCR) testing detected ctDNA in more than 75% of metastatic solid tumors.

Might combining Pap and plasma testing for ctDNA further boost sensitivity? To test this idea, Dr. Fader and her associates performed liquid-based Pap tests and collected plasma from patients just before they underwent surgery for primary ovarian cancer.

They purified DNA from the Pap tests and used a Safe SeqS assay to amplify for 18 genes with known driver mutations in ovarian cancer: AKT1, APC, BRAF, CDKN2A, CTNNB1, EGFR, FBXW7, FGFR2, KRAS, MAPK1, NRAS, PIK3CA, PIK3R1, POLE, PPP2R1A, PTEN, RN F43, and TP53. Plasma DNA was purified and amplified for 16 genes of interest: AKT1, APC, BRAF, CDKN2A, CTNNB1, EGFR, FBXW7, FGFR2, GNAS, HRAS, KRAS, NRAS, PIK3CA, PPP2R1A, PTEN, and TP53. Tests were considered positive if they identified at least one driver mutation.

By itself, the Pap test identified only 34% of cases of stage I or stage II ovarian cancer and only 37% of cases of stage III/IV cancers, for an overall sensitivity of 36%, Dr. Fader reported. Likewise, ctDNA plasma testing yielded sensitivity values of 34% in stage I/II disease and 54% in stage III/IV disease. But combining these assays yielded sensitivities of 64% for stage I/II ovarian cancer and 97% for stage III/IV cancer, for an overall sensitivity of 76%.

Driver mutations most often involved the TP53 gene, followed by PIK3CA and CDKN2A. Rarer mutations included those of PTEN, KRAS, NRAS, APC, POLE, and PPP2RIA, Dr. Fader said. Study participants were 20-79 years old, with a median age of 61, and about 70% had stage III or stage IV disease. Nearly three-quarters of tumors were serous adenocarcinomas, of which 65% were high grade. Other tumors were mucinous (10%), clear cell (5%), germ cell (3%), carcinosarcomas (2%), or sex cord stromal (1%).

There was less detection of early-stage disease in this study, even though the investigators used a sensitive test that identified relatively rare driver mutations, Dr. Fader said. So far, ctDNA testing seems to be more effective for detecting metastatic ovarian cancer, she said. Future studies should further refine DNA detection by adding Tao Brush testing and should evaluate Pap and plasma testing in a larger cohort of women with early-stage ovarian cancer or precursor lesions, including carriers of BRCA mutations, she added.

Dr. Fader did not acknowledge external funding sources. She reported having no conflicts of interest.

NATIONAL HARBOR, MD. – Combining a liquid-based Pap smear and cell-free DNA plasma testing can boost the sensitivity of screening for primary ovarian tumors, based on the results of a prospective study of 201 patients.

The approach, however, was most sensitive when women already had late-stage disease, Amanda Nickles Fader, MD, said at the annual meeting of the Society of Gynecologic Oncology. Nonetheless, she called combined Pap and plasma testing “a promising step toward a broadly applicable screening methodology for the early detection of ovarian cancer.”

Ovarian cancer is a “legal malignancy,” and detecting it at “earlier, more curable stages is a clinical imperative,” said Dr. Fader of the Johns Hopkins Kelly Gynecologic Oncology Service in Baltimore, Md.

Routine screening with ultrasound or the CA-125 test has not been shown to reduce deaths from ovarian cancer and can lead to unnecessary diagnostic surgeries. Therefore, population-based screening is not recommended by the U.S. Preventive Services Task Force, the American Cancer Society, the American Congress of Obstetricians and Gynecologists, or the National Comprehensive Cancer Network, Dr. Fader noted.

This paradigm, however, is starting to change with the advent of DNA-based tests for ovarian cancer, including the PapGene test and assays for circulating DNA released by apoptotic tumor cells (ctDNA), Dr. Fader said. In a previous pilot study, Pap testing identified oncogenic driver mutations in 41% of primary ovarian tumors. In another study, polymerase chain reaction (PCR) testing detected ctDNA in more than 75% of metastatic solid tumors.

Might combining Pap and plasma testing for ctDNA further boost sensitivity? To test this idea, Dr. Fader and her associates performed liquid-based Pap tests and collected plasma from patients just before they underwent surgery for primary ovarian cancer.

They purified DNA from the Pap tests and used a Safe SeqS assay to amplify for 18 genes with known driver mutations in ovarian cancer: AKT1, APC, BRAF, CDKN2A, CTNNB1, EGFR, FBXW7, FGFR2, KRAS, MAPK1, NRAS, PIK3CA, PIK3R1, POLE, PPP2R1A, PTEN, RN F43, and TP53. Plasma DNA was purified and amplified for 16 genes of interest: AKT1, APC, BRAF, CDKN2A, CTNNB1, EGFR, FBXW7, FGFR2, GNAS, HRAS, KRAS, NRAS, PIK3CA, PPP2R1A, PTEN, and TP53. Tests were considered positive if they identified at least one driver mutation.

By itself, the Pap test identified only 34% of cases of stage I or stage II ovarian cancer and only 37% of cases of stage III/IV cancers, for an overall sensitivity of 36%, Dr. Fader reported. Likewise, ctDNA plasma testing yielded sensitivity values of 34% in stage I/II disease and 54% in stage III/IV disease. But combining these assays yielded sensitivities of 64% for stage I/II ovarian cancer and 97% for stage III/IV cancer, for an overall sensitivity of 76%.

Driver mutations most often involved the TP53 gene, followed by PIK3CA and CDKN2A. Rarer mutations included those of PTEN, KRAS, NRAS, APC, POLE, and PPP2RIA, Dr. Fader said. Study participants were 20-79 years old, with a median age of 61, and about 70% had stage III or stage IV disease. Nearly three-quarters of tumors were serous adenocarcinomas, of which 65% were high grade. Other tumors were mucinous (10%), clear cell (5%), germ cell (3%), carcinosarcomas (2%), or sex cord stromal (1%).

There was less detection of early-stage disease in this study, even though the investigators used a sensitive test that identified relatively rare driver mutations, Dr. Fader said. So far, ctDNA testing seems to be more effective for detecting metastatic ovarian cancer, she said. Future studies should further refine DNA detection by adding Tao Brush testing and should evaluate Pap and plasma testing in a larger cohort of women with early-stage ovarian cancer or precursor lesions, including carriers of BRCA mutations, she added.

Dr. Fader did not acknowledge external funding sources. She reported having no conflicts of interest.

NATIONAL HARBOR, MD. – Combining a liquid-based Pap smear and cell-free DNA plasma testing can boost the sensitivity of screening for primary ovarian tumors, based on the results of a prospective study of 201 patients.

The approach, however, was most sensitive when women already had late-stage disease, Amanda Nickles Fader, MD, said at the annual meeting of the Society of Gynecologic Oncology. Nonetheless, she called combined Pap and plasma testing “a promising step toward a broadly applicable screening methodology for the early detection of ovarian cancer.”

Ovarian cancer is a “legal malignancy,” and detecting it at “earlier, more curable stages is a clinical imperative,” said Dr. Fader of the Johns Hopkins Kelly Gynecologic Oncology Service in Baltimore, Md.

Routine screening with ultrasound or the CA-125 test has not been shown to reduce deaths from ovarian cancer and can lead to unnecessary diagnostic surgeries. Therefore, population-based screening is not recommended by the U.S. Preventive Services Task Force, the American Cancer Society, the American Congress of Obstetricians and Gynecologists, or the National Comprehensive Cancer Network, Dr. Fader noted.

This paradigm, however, is starting to change with the advent of DNA-based tests for ovarian cancer, including the PapGene test and assays for circulating DNA released by apoptotic tumor cells (ctDNA), Dr. Fader said. In a previous pilot study, Pap testing identified oncogenic driver mutations in 41% of primary ovarian tumors. In another study, polymerase chain reaction (PCR) testing detected ctDNA in more than 75% of metastatic solid tumors.

Might combining Pap and plasma testing for ctDNA further boost sensitivity? To test this idea, Dr. Fader and her associates performed liquid-based Pap tests and collected plasma from patients just before they underwent surgery for primary ovarian cancer.

They purified DNA from the Pap tests and used a Safe SeqS assay to amplify for 18 genes with known driver mutations in ovarian cancer: AKT1, APC, BRAF, CDKN2A, CTNNB1, EGFR, FBXW7, FGFR2, KRAS, MAPK1, NRAS, PIK3CA, PIK3R1, POLE, PPP2R1A, PTEN, RN F43, and TP53. Plasma DNA was purified and amplified for 16 genes of interest: AKT1, APC, BRAF, CDKN2A, CTNNB1, EGFR, FBXW7, FGFR2, GNAS, HRAS, KRAS, NRAS, PIK3CA, PPP2R1A, PTEN, and TP53. Tests were considered positive if they identified at least one driver mutation.

By itself, the Pap test identified only 34% of cases of stage I or stage II ovarian cancer and only 37% of cases of stage III/IV cancers, for an overall sensitivity of 36%, Dr. Fader reported. Likewise, ctDNA plasma testing yielded sensitivity values of 34% in stage I/II disease and 54% in stage III/IV disease. But combining these assays yielded sensitivities of 64% for stage I/II ovarian cancer and 97% for stage III/IV cancer, for an overall sensitivity of 76%.

Driver mutations most often involved the TP53 gene, followed by PIK3CA and CDKN2A. Rarer mutations included those of PTEN, KRAS, NRAS, APC, POLE, and PPP2RIA, Dr. Fader said. Study participants were 20-79 years old, with a median age of 61, and about 70% had stage III or stage IV disease. Nearly three-quarters of tumors were serous adenocarcinomas, of which 65% were high grade. Other tumors were mucinous (10%), clear cell (5%), germ cell (3%), carcinosarcomas (2%), or sex cord stromal (1%).

There was less detection of early-stage disease in this study, even though the investigators used a sensitive test that identified relatively rare driver mutations, Dr. Fader said. So far, ctDNA testing seems to be more effective for detecting metastatic ovarian cancer, she said. Future studies should further refine DNA detection by adding Tao Brush testing and should evaluate Pap and plasma testing in a larger cohort of women with early-stage ovarian cancer or precursor lesions, including carriers of BRCA mutations, she added.

Dr. Fader did not acknowledge external funding sources. She reported having no conflicts of interest.

Evaluate bone health no longer than 6 months after onset of functional hypothalamic amenorrhea (FHA), according to new guidance on its diagnosis and management.

The preferred measure of bone mineral density (BMD) is dual-energy x-ray absorptiometry (DXA), guidance lead author Catherine M. Gordon, MD, of Cincinnati Children’s Hospital Medical Center noted in an interview.

“Our group has tried to raise awareness with our guideline about bone health,” said Dr. Gordon. “Bone is unfortunately detrimentally affected in adolescents and adult women with FHA, [so] our guideline now formally recommends bone density screening after 6 months of amenorrhea.”

Among the available therapies to preserve or restore bone density is short-term use of transdermal E2 therapy, with cyclic oral progestin, only after conventional intervention with nurtritional and exercise modification has been attempted for a “reasonable” amount of time but menstrual cycles have not yet been reestablished. Bisphosphonates, denosumab, testosterone, and leptin also can be used to improve bone mineral density (BMD), with recombinant parathyroid hormone 1-34 (rPTH) recommended in rare cases of extremely low BMD.

“Patients should not use oral contraceptives as a way to induce menstruation or improve BMD,” she said.

“We anticipate that some clinicians will be surprised to see that combined oral contraceptive pills do not provide bone protection for patients with FHA,” Dr. Gordon explained. “Our guideline reviews data on this point, which led to our recommendation that short-term transdermal estrogen may be helpful in restoring menses for select patients with longstanding amenorrhea despite efforts to correct their ‘energy deficit.’ ”

Clinicians also should be aware that FHA can mask the signs and symptoms of polycystic ovary syndrome in some young women. It’s therefore important for providers to understand that a patient could carry both diagnoses: Such patients should have a baseline BMD measurement taken, along with “clinical monitoring for hyper-response in those treated with exogenous gonadotropins for infertility,” according to the guidelines.

In general, “FHA is a ‘diagnosis of exclusion,’ meaning that underlying anatomic or organic pathologies must first be ruled out. It is important to consider other etiologies first before the amenorrhea is attributed to inadequate intake, overexercise, or stress,” Dr. Gordon said.

According to the guidelines, patients should only undergo evaluation for FHA if menstrual cycle interval exceeds 45 days on a consistent basis, or if they present with amenorrhea for at least 3 months. Patients with suspected FHA should be screened for psychological stressors that could be inducing anovulation.

When trying to make a diagnosis of FHA, providers should be “obtaining a detailed personal history with a focus on diet; eating disorders; exercise and athletic training; attitudes, such as perfectionism and high need for social approval; ambitions and expectations for self and others; weight fluctuations; sleep patterns; stressors; mood; menstrual pattern; fractures; and substance abuse,” the guidelines state.

Family histories also should be evaluated, and patients should undergo a full physical. Once a diagnosis of FHA is made, however, clinicians should help educate patients about different menstrual cycles while letting women know that an irregular cycle does not necessarily prevent them from conceiving.

The most important aspect of managing FHA is to take a multidiscipinary approach, according to Dr. Gordon and her colleagues (J Clin Endocrinol Metab. May 2017;102[5]:1-27).

“We emphasize that the mainstay of therapy for these adolescents and women is close attention to nutrition, exercise, and alleviating stressors through psychological support, best achieved through a multidisciplinary team,” Dr. Gordon stated.

Any patient diagnosed with FHA who also develops severe bradycardia, hypotension, orthostasis, or electrolyte imbalance should be treated as an inpatient. Energy imbalances can affect the hypothalamic-pituitary-ovarian (HPO) axis function, so correcting that should be considered a priority.

Adolescents and women for whom pregnancy has been excluded are recommended to undergo a progestin challenge, which should indicate chronic estrogen exposure via induced withdrawal bleeding. A brain MRI also can be conducted if the patient complains about chronic headaches, vomiting, or problems with vision or thirst.

FHA patients who wish to conceive have a number of options outlined by the guidelines. Pulsatile gonadotropin-releasing hormone (GnRH) should be the first treatment, followed by gonadotropin therapy, which must be administered as carefully as possible. Clomiphene citrate also can be used in certain situations, and cognitive behavior therapy is also a viable option, although the guidelines note that only one relatively small study offered any evidence of its efficacy. Kisspeptin and leptin should not be used as a treatment for infertility under any circumstances.

These guidelines were created in conjunction with the American Society for Reproductive Medicine, the European Society of Endocrinology, and the Pediatric Endocrine Society. An evidence-based approach was undertaken by a panel of eight experts, a methodologist, and a medical writer.

“There is currently a lack of consistency in clinical practice regarding the evaluation for patients with FHA,” said Dr. Gordon. “Our guideline attempts to clarify for clinicians what the appropriate general, endocrine, and imaging work-up would entail.”

The creation of these guidelines was funded by the Endocrine Society.

[email protected]

Evaluate bone health no longer than 6 months after onset of functional hypothalamic amenorrhea (FHA), according to new guidance on its diagnosis and management.

The preferred measure of bone mineral density (BMD) is dual-energy x-ray absorptiometry (DXA), guidance lead author Catherine M. Gordon, MD, of Cincinnati Children’s Hospital Medical Center noted in an interview.

“Our group has tried to raise awareness with our guideline about bone health,” said Dr. Gordon. “Bone is unfortunately detrimentally affected in adolescents and adult women with FHA, [so] our guideline now formally recommends bone density screening after 6 months of amenorrhea.”

Among the available therapies to preserve or restore bone density is short-term use of transdermal E2 therapy, with cyclic oral progestin, only after conventional intervention with nurtritional and exercise modification has been attempted for a “reasonable” amount of time but menstrual cycles have not yet been reestablished. Bisphosphonates, denosumab, testosterone, and leptin also can be used to improve bone mineral density (BMD), with recombinant parathyroid hormone 1-34 (rPTH) recommended in rare cases of extremely low BMD.

“Patients should not use oral contraceptives as a way to induce menstruation or improve BMD,” she said.

“We anticipate that some clinicians will be surprised to see that combined oral contraceptive pills do not provide bone protection for patients with FHA,” Dr. Gordon explained. “Our guideline reviews data on this point, which led to our recommendation that short-term transdermal estrogen may be helpful in restoring menses for select patients with longstanding amenorrhea despite efforts to correct their ‘energy deficit.’ ”

Clinicians also should be aware that FHA can mask the signs and symptoms of polycystic ovary syndrome in some young women. It’s therefore important for providers to understand that a patient could carry both diagnoses: Such patients should have a baseline BMD measurement taken, along with “clinical monitoring for hyper-response in those treated with exogenous gonadotropins for infertility,” according to the guidelines.

In general, “FHA is a ‘diagnosis of exclusion,’ meaning that underlying anatomic or organic pathologies must first be ruled out. It is important to consider other etiologies first before the amenorrhea is attributed to inadequate intake, overexercise, or stress,” Dr. Gordon said.

According to the guidelines, patients should only undergo evaluation for FHA if menstrual cycle interval exceeds 45 days on a consistent basis, or if they present with amenorrhea for at least 3 months. Patients with suspected FHA should be screened for psychological stressors that could be inducing anovulation.

When trying to make a diagnosis of FHA, providers should be “obtaining a detailed personal history with a focus on diet; eating disorders; exercise and athletic training; attitudes, such as perfectionism and high need for social approval; ambitions and expectations for self and others; weight fluctuations; sleep patterns; stressors; mood; menstrual pattern; fractures; and substance abuse,” the guidelines state.

Family histories also should be evaluated, and patients should undergo a full physical. Once a diagnosis of FHA is made, however, clinicians should help educate patients about different menstrual cycles while letting women know that an irregular cycle does not necessarily prevent them from conceiving.

The most important aspect of managing FHA is to take a multidiscipinary approach, according to Dr. Gordon and her colleagues (J Clin Endocrinol Metab. May 2017;102[5]:1-27).

“We emphasize that the mainstay of therapy for these adolescents and women is close attention to nutrition, exercise, and alleviating stressors through psychological support, best achieved through a multidisciplinary team,” Dr. Gordon stated.

Any patient diagnosed with FHA who also develops severe bradycardia, hypotension, orthostasis, or electrolyte imbalance should be treated as an inpatient. Energy imbalances can affect the hypothalamic-pituitary-ovarian (HPO) axis function, so correcting that should be considered a priority.

Adolescents and women for whom pregnancy has been excluded are recommended to undergo a progestin challenge, which should indicate chronic estrogen exposure via induced withdrawal bleeding. A brain MRI also can be conducted if the patient complains about chronic headaches, vomiting, or problems with vision or thirst.

FHA patients who wish to conceive have a number of options outlined by the guidelines. Pulsatile gonadotropin-releasing hormone (GnRH) should be the first treatment, followed by gonadotropin therapy, which must be administered as carefully as possible. Clomiphene citrate also can be used in certain situations, and cognitive behavior therapy is also a viable option, although the guidelines note that only one relatively small study offered any evidence of its efficacy. Kisspeptin and leptin should not be used as a treatment for infertility under any circumstances.

These guidelines were created in conjunction with the American Society for Reproductive Medicine, the European Society of Endocrinology, and the Pediatric Endocrine Society. An evidence-based approach was undertaken by a panel of eight experts, a methodologist, and a medical writer.

“There is currently a lack of consistency in clinical practice regarding the evaluation for patients with FHA,” said Dr. Gordon. “Our guideline attempts to clarify for clinicians what the appropriate general, endocrine, and imaging work-up would entail.”

The creation of these guidelines was funded by the Endocrine Society.

[email protected]

Evaluate bone health no longer than 6 months after onset of functional hypothalamic amenorrhea (FHA), according to new guidance on its diagnosis and management.

The preferred measure of bone mineral density (BMD) is dual-energy x-ray absorptiometry (DXA), guidance lead author Catherine M. Gordon, MD, of Cincinnati Children’s Hospital Medical Center noted in an interview.

“Our group has tried to raise awareness with our guideline about bone health,” said Dr. Gordon. “Bone is unfortunately detrimentally affected in adolescents and adult women with FHA, [so] our guideline now formally recommends bone density screening after 6 months of amenorrhea.”

Among the available therapies to preserve or restore bone density is short-term use of transdermal E2 therapy, with cyclic oral progestin, only after conventional intervention with nurtritional and exercise modification has been attempted for a “reasonable” amount of time but menstrual cycles have not yet been reestablished. Bisphosphonates, denosumab, testosterone, and leptin also can be used to improve bone mineral density (BMD), with recombinant parathyroid hormone 1-34 (rPTH) recommended in rare cases of extremely low BMD.

“Patients should not use oral contraceptives as a way to induce menstruation or improve BMD,” she said.

“We anticipate that some clinicians will be surprised to see that combined oral contraceptive pills do not provide bone protection for patients with FHA,” Dr. Gordon explained. “Our guideline reviews data on this point, which led to our recommendation that short-term transdermal estrogen may be helpful in restoring menses for select patients with longstanding amenorrhea despite efforts to correct their ‘energy deficit.’ ”

Clinicians also should be aware that FHA can mask the signs and symptoms of polycystic ovary syndrome in some young women. It’s therefore important for providers to understand that a patient could carry both diagnoses: Such patients should have a baseline BMD measurement taken, along with “clinical monitoring for hyper-response in those treated with exogenous gonadotropins for infertility,” according to the guidelines.

In general, “FHA is a ‘diagnosis of exclusion,’ meaning that underlying anatomic or organic pathologies must first be ruled out. It is important to consider other etiologies first before the amenorrhea is attributed to inadequate intake, overexercise, or stress,” Dr. Gordon said.

According to the guidelines, patients should only undergo evaluation for FHA if menstrual cycle interval exceeds 45 days on a consistent basis, or if they present with amenorrhea for at least 3 months. Patients with suspected FHA should be screened for psychological stressors that could be inducing anovulation.

When trying to make a diagnosis of FHA, providers should be “obtaining a detailed personal history with a focus on diet; eating disorders; exercise and athletic training; attitudes, such as perfectionism and high need for social approval; ambitions and expectations for self and others; weight fluctuations; sleep patterns; stressors; mood; menstrual pattern; fractures; and substance abuse,” the guidelines state.

Family histories also should be evaluated, and patients should undergo a full physical. Once a diagnosis of FHA is made, however, clinicians should help educate patients about different menstrual cycles while letting women know that an irregular cycle does not necessarily prevent them from conceiving.

The most important aspect of managing FHA is to take a multidiscipinary approach, according to Dr. Gordon and her colleagues (J Clin Endocrinol Metab. May 2017;102[5]:1-27).

“We emphasize that the mainstay of therapy for these adolescents and women is close attention to nutrition, exercise, and alleviating stressors through psychological support, best achieved through a multidisciplinary team,” Dr. Gordon stated.

Any patient diagnosed with FHA who also develops severe bradycardia, hypotension, orthostasis, or electrolyte imbalance should be treated as an inpatient. Energy imbalances can affect the hypothalamic-pituitary-ovarian (HPO) axis function, so correcting that should be considered a priority.

Adolescents and women for whom pregnancy has been excluded are recommended to undergo a progestin challenge, which should indicate chronic estrogen exposure via induced withdrawal bleeding. A brain MRI also can be conducted if the patient complains about chronic headaches, vomiting, or problems with vision or thirst.

FHA patients who wish to conceive have a number of options outlined by the guidelines. Pulsatile gonadotropin-releasing hormone (GnRH) should be the first treatment, followed by gonadotropin therapy, which must be administered as carefully as possible. Clomiphene citrate also can be used in certain situations, and cognitive behavior therapy is also a viable option, although the guidelines note that only one relatively small study offered any evidence of its efficacy. Kisspeptin and leptin should not be used as a treatment for infertility under any circumstances.

These guidelines were created in conjunction with the American Society for Reproductive Medicine, the European Society of Endocrinology, and the Pediatric Endocrine Society. An evidence-based approach was undertaken by a panel of eight experts, a methodologist, and a medical writer.

“There is currently a lack of consistency in clinical practice regarding the evaluation for patients with FHA,” said Dr. Gordon. “Our guideline attempts to clarify for clinicians what the appropriate general, endocrine, and imaging work-up would entail.”

The creation of these guidelines was funded by the Endocrine Society.

[email protected]

NATIONAL HARBOR, MD. – The folate-binding protein vaccine E39+GM-CSF was well tolerated and exhibited a statistically significant, dose-dependent effect on recurrence and disease-free survival among patients with remitted primary ovarian or endometrial cancer, according to the results of a small prospective controlled phase I/IIa trial.

After a median follow-up of 12 months, cancer recurred in 41% of all vaccine recipients and 55% of controls (P = .41), G. Larry Maxwell, MD, reported at the annual meeting of the Society of Gynecologic Oncology. However, cancer recurred in only 13% of patients who received the highest (1,000 mcg) dose of peptide in the vaccine (P = .01 compared with the control group). A closer look showed that this survival benefit was limited to patients with primary disease, indicating that this vaccine has potential as an adjuvant to standard therapy for primary endometrial or ovarian cancer, he added.

Mortality from these cancers continues to rise in the United States despite conventional treatment with chemotherapy and radiation, noted Dr. Maxwell, who is chairman of the department of obstetrics and gynecology of Inova Fairfax Hospital in Annandale, Va.

“Targeted therapies have been evaluated, but durable response remains limited. Novel agents are needed,” he emphasized. He and his coinvestigators have focused on folate-binding protein, which is overexpressed by 20- to 80-fold in endometrial and ovarian tumors, compared with healthy tissue. To develop the vaccine, they combined E39, an immunogenic peptide of folate receptor 1 that amplifies the lymphocytic tumor response, with the immune adjuvant, granulocyte macrophage-colony stimulating factor (GM-CSF).

The trial included 51 patients, of whom 40 had primary ovarian or endometrial cancer and 11 had recurrent cancer. The 29 patients who were HLA-A2 positive were allocated to the vaccine group, receiving six intradermal inoculations of either 100-mcg, 500-mcg, or 1,000-mcg E39 plus 250-mcg GM-CSF, spaced by 21-28 days. Fifteen of these patients received 1,000-mcg E39, while 14 received 500- or 100-mcg doses. The treatment group also received two booster vaccines spaced 6 months apart. The 22 HLA-A2–negative patients were followed as controls. The intervention and control groups resembled each other clinically and demographically, Dr. Maxwell said.

Estimated rates of 2-year disease-free survival were 77% for patients in the 1,000 mcg–dose group, 44% for controls (P = .05), and 23% for patients who received less than 1,000 mcg vaccine (P = .005). Adverse events mainly included grade 1 or grade 2 myalgias, headaches, or reactions at the vaccination site. Mild adverse events were significantly more common at the 1,000-mcg E39 dose than at lower doses (P = .04). There was one grade 3 toxicity, and no grade 4 or 5 adverse events.

Delayed-type hypersensitivity reactions were more pronounced after vaccination, compared with baseline (5.7 ± 1.5 mm versus 10.3 ± 3.0 mm; P = .06), particularly in the 1,000-mcg group (3.8 ± 2.0 mm vs. 9.5 ± 3.5 mm, P = .03), Dr. Maxwell reported. Among patients whose cancer did not recur, delayed-type hypersensitivity was markedly higher after vaccination than at baseline (P = .06). “Our functional immunologic data show that vaccination is associated with delayed type hypersensitivity, but more important, it is associated with clinical outcome,” Dr. Maxwell said.

Low levels of folate-binding protein expression correlated with better disease-free survival, he also reported. “Possibly, this is because high levels of expression are associated with disease aggressiveness, which may outpace the immune response,” he said.

A phase Ib trial of the E39 folate-binding protein peptide vaccine is underway. Dr. Maxwell did not cite external funding sources and reported having no conflicts of interest.

NATIONAL HARBOR, MD. – The folate-binding protein vaccine E39+GM-CSF was well tolerated and exhibited a statistically significant, dose-dependent effect on recurrence and disease-free survival among patients with remitted primary ovarian or endometrial cancer, according to the results of a small prospective controlled phase I/IIa trial.

After a median follow-up of 12 months, cancer recurred in 41% of all vaccine recipients and 55% of controls (P = .41), G. Larry Maxwell, MD, reported at the annual meeting of the Society of Gynecologic Oncology. However, cancer recurred in only 13% of patients who received the highest (1,000 mcg) dose of peptide in the vaccine (P = .01 compared with the control group). A closer look showed that this survival benefit was limited to patients with primary disease, indicating that this vaccine has potential as an adjuvant to standard therapy for primary endometrial or ovarian cancer, he added.

Mortality from these cancers continues to rise in the United States despite conventional treatment with chemotherapy and radiation, noted Dr. Maxwell, who is chairman of the department of obstetrics and gynecology of Inova Fairfax Hospital in Annandale, Va.

“Targeted therapies have been evaluated, but durable response remains limited. Novel agents are needed,” he emphasized. He and his coinvestigators have focused on folate-binding protein, which is overexpressed by 20- to 80-fold in endometrial and ovarian tumors, compared with healthy tissue. To develop the vaccine, they combined E39, an immunogenic peptide of folate receptor 1 that amplifies the lymphocytic tumor response, with the immune adjuvant, granulocyte macrophage-colony stimulating factor (GM-CSF).

The trial included 51 patients, of whom 40 had primary ovarian or endometrial cancer and 11 had recurrent cancer. The 29 patients who were HLA-A2 positive were allocated to the vaccine group, receiving six intradermal inoculations of either 100-mcg, 500-mcg, or 1,000-mcg E39 plus 250-mcg GM-CSF, spaced by 21-28 days. Fifteen of these patients received 1,000-mcg E39, while 14 received 500- or 100-mcg doses. The treatment group also received two booster vaccines spaced 6 months apart. The 22 HLA-A2–negative patients were followed as controls. The intervention and control groups resembled each other clinically and demographically, Dr. Maxwell said.

Estimated rates of 2-year disease-free survival were 77% for patients in the 1,000 mcg–dose group, 44% for controls (P = .05), and 23% for patients who received less than 1,000 mcg vaccine (P = .005). Adverse events mainly included grade 1 or grade 2 myalgias, headaches, or reactions at the vaccination site. Mild adverse events were significantly more common at the 1,000-mcg E39 dose than at lower doses (P = .04). There was one grade 3 toxicity, and no grade 4 or 5 adverse events.

Delayed-type hypersensitivity reactions were more pronounced after vaccination, compared with baseline (5.7 ± 1.5 mm versus 10.3 ± 3.0 mm; P = .06), particularly in the 1,000-mcg group (3.8 ± 2.0 mm vs. 9.5 ± 3.5 mm, P = .03), Dr. Maxwell reported. Among patients whose cancer did not recur, delayed-type hypersensitivity was markedly higher after vaccination than at baseline (P = .06). “Our functional immunologic data show that vaccination is associated with delayed type hypersensitivity, but more important, it is associated with clinical outcome,” Dr. Maxwell said.

Low levels of folate-binding protein expression correlated with better disease-free survival, he also reported. “Possibly, this is because high levels of expression are associated with disease aggressiveness, which may outpace the immune response,” he said.

A phase Ib trial of the E39 folate-binding protein peptide vaccine is underway. Dr. Maxwell did not cite external funding sources and reported having no conflicts of interest.

NATIONAL HARBOR, MD. – The folate-binding protein vaccine E39+GM-CSF was well tolerated and exhibited a statistically significant, dose-dependent effect on recurrence and disease-free survival among patients with remitted primary ovarian or endometrial cancer, according to the results of a small prospective controlled phase I/IIa trial.

After a median follow-up of 12 months, cancer recurred in 41% of all vaccine recipients and 55% of controls (P = .41), G. Larry Maxwell, MD, reported at the annual meeting of the Society of Gynecologic Oncology. However, cancer recurred in only 13% of patients who received the highest (1,000 mcg) dose of peptide in the vaccine (P = .01 compared with the control group). A closer look showed that this survival benefit was limited to patients with primary disease, indicating that this vaccine has potential as an adjuvant to standard therapy for primary endometrial or ovarian cancer, he added.

Mortality from these cancers continues to rise in the United States despite conventional treatment with chemotherapy and radiation, noted Dr. Maxwell, who is chairman of the department of obstetrics and gynecology of Inova Fairfax Hospital in Annandale, Va.

“Targeted therapies have been evaluated, but durable response remains limited. Novel agents are needed,” he emphasized. He and his coinvestigators have focused on folate-binding protein, which is overexpressed by 20- to 80-fold in endometrial and ovarian tumors, compared with healthy tissue. To develop the vaccine, they combined E39, an immunogenic peptide of folate receptor 1 that amplifies the lymphocytic tumor response, with the immune adjuvant, granulocyte macrophage-colony stimulating factor (GM-CSF).

The trial included 51 patients, of whom 40 had primary ovarian or endometrial cancer and 11 had recurrent cancer. The 29 patients who were HLA-A2 positive were allocated to the vaccine group, receiving six intradermal inoculations of either 100-mcg, 500-mcg, or 1,000-mcg E39 plus 250-mcg GM-CSF, spaced by 21-28 days. Fifteen of these patients received 1,000-mcg E39, while 14 received 500- or 100-mcg doses. The treatment group also received two booster vaccines spaced 6 months apart. The 22 HLA-A2–negative patients were followed as controls. The intervention and control groups resembled each other clinically and demographically, Dr. Maxwell said.

Estimated rates of 2-year disease-free survival were 77% for patients in the 1,000 mcg–dose group, 44% for controls (P = .05), and 23% for patients who received less than 1,000 mcg vaccine (P = .005). Adverse events mainly included grade 1 or grade 2 myalgias, headaches, or reactions at the vaccination site. Mild adverse events were significantly more common at the 1,000-mcg E39 dose than at lower doses (P = .04). There was one grade 3 toxicity, and no grade 4 or 5 adverse events.

Delayed-type hypersensitivity reactions were more pronounced after vaccination, compared with baseline (5.7 ± 1.5 mm versus 10.3 ± 3.0 mm; P = .06), particularly in the 1,000-mcg group (3.8 ± 2.0 mm vs. 9.5 ± 3.5 mm, P = .03), Dr. Maxwell reported. Among patients whose cancer did not recur, delayed-type hypersensitivity was markedly higher after vaccination than at baseline (P = .06). “Our functional immunologic data show that vaccination is associated with delayed type hypersensitivity, but more important, it is associated with clinical outcome,” Dr. Maxwell said.

Low levels of folate-binding protein expression correlated with better disease-free survival, he also reported. “Possibly, this is because high levels of expression are associated with disease aggressiveness, which may outpace the immune response,” he said.

A phase Ib trial of the E39 folate-binding protein peptide vaccine is underway. Dr. Maxwell did not cite external funding sources and reported having no conflicts of interest.

Photo courtesy of Merck

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for the anti-PD-1 therapy pembrolizumab (Keytruda) as a treatment for patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

The recommendation pertains specifically to adults with cHL who have failed autologous hematopoietic stem cell transplant (auto-HSCT) and treatment with brentuximab vedotin (BV) or adults with cHL who are transplant-ineligible and have failed treatment with BV.

The CHMP’s recommendation will be reviewed by the European Commission, which is expected to make a decision about the drug in the second quarter of 2017.

Pembrolizumab is already approved for use in the European Union as a treatment for melanoma and non-small-cell lung cancer.

The CHMP’s positive opinion of pembrolizumab for cHL was based on data from the KEYNOTE-087 and KEYNOTE-013 trials. Results from both trials were presented at ASH 2016 (abstract 1107 and abstract 1108).

KEYNOTE-087

KEYNOTE-087 is a phase 2 trial in which researchers evaluated pembrolizumab (a 200 mg fixed dose every 3 weeks) in patients with relapsed or refractory cHL across 3 cohorts:

• Cohort 1: Patients who progressed after auto-HSCT and subsequent treatment with BV
• Cohort 2: Patients who failed salvage chemotherapy, were ineligible for a transplant, and progressed after BV
• Cohort 3: Patients who progressed after auto-HSCT and did not receive BV after transplant.

Across all 210 enrolled patients, the overall response rate (ORR) was 69.0%, and the complete response (CR) rate was 22.4%.

In Cohort 1 (n=69), the ORR was 73.9%. The CR rate was 21.7%, the partial response (PR) rate was 52.2%, 15.9% of patients had stable disease (SD), and 7.2% progressed. In 82.2% of responders, the response lasted 6 months or more.

In Cohort 2 (n=81), the ORR was 64.2%. The CR rate was 24.7%, the PR rate was 39.5%, 12.3% of patients had SD, and 21.0% progressed. In 70.0% of responders, the response lasted 6 months or more.

In Cohort 3 (n=60), the ORR was 70.0%. Twenty percent of patients had a CR, 50.0% had a PR, 16.7% had SD, and 13.3% progressed. In 75.6% of responders, the response lasted 6 months or more.

Results also included an analysis of patients with primary refractory disease (n=73), which was defined as failure to achieve CR or PR with first-line treatment. In this patient population, the ORR was 79.5%.

An ORR of 67.8% was reported in patients who relapsed after 3 or more lines of prior therapy (99/146).

The most common treatment-related adverse events (AEs) were hypothyroidism (12.4%), pyrexia (10.5%), fatigue (9.0%), rash (7.6%), diarrhea (7.1%), headache (6.2%), nausea (5.7%), cough (5.7%), and neutropenia (5.2%).

The most common grade 3/4 treatment-related AEs were neutropenia (2.4%), diarrhea (1.0%), and dyspnea (1.0%). Immune-mediated AEs included pneumonitis (2.9%), hyperthyroidism (2.9%), colitis (1.0%), and myositis (1.0%).

There were 9 discontinuations because of treatment-related AEs and no treatment-related deaths.

KEYNOTE-013

KEYNOTE-013 is a phase 1b trial that has enrolled 31 patients with relapsed or refractory cHL who failed auto-HSCT and subsequent BV or who were transplant-ineligible.

Patients received pembrolizumab at 10 mg/kg every 2 weeks. The median duration of follow-up was 29 months.

The ORR was 58%. Nineteen percent of patients achieved a CR, 39% had a PR, and 23% had SD.

The median duration of response had not been reached at last follow-up (range, 0.0+ to 26.1+ months), and 70% of responding patients had a response lasting 12 months or more.

The median progression-free survival (PFS) was 11.4 months (range, 4.9-27.8 months). The six-month PFS rate was 66%, and the 12-month PFS rate was 48%.

The median overall survival was not reached. Six-month and 12-month overall survival rates were 100% and 87%, respectively.

The most common treatment-related AEs were diarrhea (19%), hypothyroidism (13%), pneumonitis (13%), nausea (13%), fatigue (10%), and dyspnea (10%).

The most common grade 3/4 treatment-related AEs were colitis (3%), axillary pain (3%), AST increase (3%), joint swelling (3%), nephrotic syndrome back pain (3%), and dyspnea (3%).

AEs leading to discontinuation were nephrotic syndrome (grade 3), interstitial lung disease (grade 2), and pneumonitis (grade 2). There were no treatment-related deaths.

Photo courtesy of Merck

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for the anti-PD-1 therapy pembrolizumab (Keytruda) as a treatment for patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

The recommendation pertains specifically to adults with cHL who have failed autologous hematopoietic stem cell transplant (auto-HSCT) and treatment with brentuximab vedotin (BV) or adults with cHL who are transplant-ineligible and have failed treatment with BV.

The CHMP’s recommendation will be reviewed by the European Commission, which is expected to make a decision about the drug in the second quarter of 2017.

Pembrolizumab is already approved for use in the European Union as a treatment for melanoma and non-small-cell lung cancer.

The CHMP’s positive opinion of pembrolizumab for cHL was based on data from the KEYNOTE-087 and KEYNOTE-013 trials. Results from both trials were presented at ASH 2016 (abstract 1107 and abstract 1108).

KEYNOTE-087

KEYNOTE-087 is a phase 2 trial in which researchers evaluated pembrolizumab (a 200 mg fixed dose every 3 weeks) in patients with relapsed or refractory cHL across 3 cohorts:

• Cohort 1: Patients who progressed after auto-HSCT and subsequent treatment with BV
• Cohort 2: Patients who failed salvage chemotherapy, were ineligible for a transplant, and progressed after BV
• Cohort 3: Patients who progressed after auto-HSCT and did not receive BV after transplant.

Across all 210 enrolled patients, the overall response rate (ORR) was 69.0%, and the complete response (CR) rate was 22.4%.

In Cohort 1 (n=69), the ORR was 73.9%. The CR rate was 21.7%, the partial response (PR) rate was 52.2%, 15.9% of patients had stable disease (SD), and 7.2% progressed. In 82.2% of responders, the response lasted 6 months or more.

In Cohort 2 (n=81), the ORR was 64.2%. The CR rate was 24.7%, the PR rate was 39.5%, 12.3% of patients had SD, and 21.0% progressed. In 70.0% of responders, the response lasted 6 months or more.

In Cohort 3 (n=60), the ORR was 70.0%. Twenty percent of patients had a CR, 50.0% had a PR, 16.7% had SD, and 13.3% progressed. In 75.6% of responders, the response lasted 6 months or more.

Results also included an analysis of patients with primary refractory disease (n=73), which was defined as failure to achieve CR or PR with first-line treatment. In this patient population, the ORR was 79.5%.

An ORR of 67.8% was reported in patients who relapsed after 3 or more lines of prior therapy (99/146).

The most common treatment-related adverse events (AEs) were hypothyroidism (12.4%), pyrexia (10.5%), fatigue (9.0%), rash (7.6%), diarrhea (7.1%), headache (6.2%), nausea (5.7%), cough (5.7%), and neutropenia (5.2%).

The most common grade 3/4 treatment-related AEs were neutropenia (2.4%), diarrhea (1.0%), and dyspnea (1.0%). Immune-mediated AEs included pneumonitis (2.9%), hyperthyroidism (2.9%), colitis (1.0%), and myositis (1.0%).

There were 9 discontinuations because of treatment-related AEs and no treatment-related deaths.

KEYNOTE-013

KEYNOTE-013 is a phase 1b trial that has enrolled 31 patients with relapsed or refractory cHL who failed auto-HSCT and subsequent BV or who were transplant-ineligible.

Patients received pembrolizumab at 10 mg/kg every 2 weeks. The median duration of follow-up was 29 months.

The ORR was 58%. Nineteen percent of patients achieved a CR, 39% had a PR, and 23% had SD.

The median duration of response had not been reached at last follow-up (range, 0.0+ to 26.1+ months), and 70% of responding patients had a response lasting 12 months or more.

The median progression-free survival (PFS) was 11.4 months (range, 4.9-27.8 months). The six-month PFS rate was 66%, and the 12-month PFS rate was 48%.

The median overall survival was not reached. Six-month and 12-month overall survival rates were 100% and 87%, respectively.

The most common treatment-related AEs were diarrhea (19%), hypothyroidism (13%), pneumonitis (13%), nausea (13%), fatigue (10%), and dyspnea (10%).

The most common grade 3/4 treatment-related AEs were colitis (3%), axillary pain (3%), AST increase (3%), joint swelling (3%), nephrotic syndrome back pain (3%), and dyspnea (3%).

AEs leading to discontinuation were nephrotic syndrome (grade 3), interstitial lung disease (grade 2), and pneumonitis (grade 2). There were no treatment-related deaths.

Photo courtesy of Merck

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for the anti-PD-1 therapy pembrolizumab (Keytruda) as a treatment for patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

The recommendation pertains specifically to adults with cHL who have failed autologous hematopoietic stem cell transplant (auto-HSCT) and treatment with brentuximab vedotin (BV) or adults with cHL who are transplant-ineligible and have failed treatment with BV.

The CHMP’s recommendation will be reviewed by the European Commission, which is expected to make a decision about the drug in the second quarter of 2017.

Pembrolizumab is already approved for use in the European Union as a treatment for melanoma and non-small-cell lung cancer.

The CHMP’s positive opinion of pembrolizumab for cHL was based on data from the KEYNOTE-087 and KEYNOTE-013 trials. Results from both trials were presented at ASH 2016 (abstract 1107 and abstract 1108).

KEYNOTE-087

KEYNOTE-087 is a phase 2 trial in which researchers evaluated pembrolizumab (a 200 mg fixed dose every 3 weeks) in patients with relapsed or refractory cHL across 3 cohorts:

• Cohort 1: Patients who progressed after auto-HSCT and subsequent treatment with BV
• Cohort 2: Patients who failed salvage chemotherapy, were ineligible for a transplant, and progressed after BV
• Cohort 3: Patients who progressed after auto-HSCT and did not receive BV after transplant.

Across all 210 enrolled patients, the overall response rate (ORR) was 69.0%, and the complete response (CR) rate was 22.4%.

In Cohort 1 (n=69), the ORR was 73.9%. The CR rate was 21.7%, the partial response (PR) rate was 52.2%, 15.9% of patients had stable disease (SD), and 7.2% progressed. In 82.2% of responders, the response lasted 6 months or more.

In Cohort 2 (n=81), the ORR was 64.2%. The CR rate was 24.7%, the PR rate was 39.5%, 12.3% of patients had SD, and 21.0% progressed. In 70.0% of responders, the response lasted 6 months or more.

In Cohort 3 (n=60), the ORR was 70.0%. Twenty percent of patients had a CR, 50.0% had a PR, 16.7% had SD, and 13.3% progressed. In 75.6% of responders, the response lasted 6 months or more.

Results also included an analysis of patients with primary refractory disease (n=73), which was defined as failure to achieve CR or PR with first-line treatment. In this patient population, the ORR was 79.5%.

An ORR of 67.8% was reported in patients who relapsed after 3 or more lines of prior therapy (99/146).

The most common treatment-related adverse events (AEs) were hypothyroidism (12.4%), pyrexia (10.5%), fatigue (9.0%), rash (7.6%), diarrhea (7.1%), headache (6.2%), nausea (5.7%), cough (5.7%), and neutropenia (5.2%).

The most common grade 3/4 treatment-related AEs were neutropenia (2.4%), diarrhea (1.0%), and dyspnea (1.0%). Immune-mediated AEs included pneumonitis (2.9%), hyperthyroidism (2.9%), colitis (1.0%), and myositis (1.0%).

There were 9 discontinuations because of treatment-related AEs and no treatment-related deaths.

KEYNOTE-013

KEYNOTE-013 is a phase 1b trial that has enrolled 31 patients with relapsed or refractory cHL who failed auto-HSCT and subsequent BV or who were transplant-ineligible.

Patients received pembrolizumab at 10 mg/kg every 2 weeks. The median duration of follow-up was 29 months.

The ORR was 58%. Nineteen percent of patients achieved a CR, 39% had a PR, and 23% had SD.

The median duration of response had not been reached at last follow-up (range, 0.0+ to 26.1+ months), and 70% of responding patients had a response lasting 12 months or more.

The median progression-free survival (PFS) was 11.4 months (range, 4.9-27.8 months). The six-month PFS rate was 66%, and the 12-month PFS rate was 48%.

The median overall survival was not reached. Six-month and 12-month overall survival rates were 100% and 87%, respectively.

The most common treatment-related AEs were diarrhea (19%), hypothyroidism (13%), pneumonitis (13%), nausea (13%), fatigue (10%), and dyspnea (10%).

The most common grade 3/4 treatment-related AEs were colitis (3%), axillary pain (3%), AST increase (3%), joint swelling (3%), nephrotic syndrome back pain (3%), and dyspnea (3%).

AEs leading to discontinuation were nephrotic syndrome (grade 3), interstitial lung disease (grade 2), and pneumonitis (grade 2). There were no treatment-related deaths.

CLINICAL QUESTION: Does perioperative statin use reduce 30-day mortality in noncardiac surgery?

BACKGROUND: Current perioperative guidelines focus on continuation of existing therapy in long-term statin users with weak recommendations of potential efficacy in reducing perioperative complications.

Statin exposure was associated with reduced 30-day all-cause mortality with a marginally favorable effect with longer-term statin use (6 months to 1 year before admission). For the secondary outcomes, there was significant risk reduction in cardiac, infectious, respiratory, and renal complications but no significant change in central nervous system or nonatherosclerotic thrombotic complications.

Statin exposure may be associated with adherence to medical treatment and follow-up thus causing a selection bias.

BOTTOM LINE: Perioperative statin use was associated with a reduction in 30-day mortality and other complications.

CITATIONS: London MJ, Schwartz GG, Hur K, Henderson WG. Association of perioperative statin use with mortality and morbidity after major noncardiac surgery. JAMA Intern Med. 2017 Feb 1;177(2):231-42.

Dr. Dietsche is a clinical instructor, Division of Hospital Medicine, University of Colorado School of Medicine, Aurora.

CLINICAL QUESTION: Does perioperative statin use reduce 30-day mortality in noncardiac surgery?

BACKGROUND: Current perioperative guidelines focus on continuation of existing therapy in long-term statin users with weak recommendations of potential efficacy in reducing perioperative complications.

Statin exposure was associated with reduced 30-day all-cause mortality with a marginally favorable effect with longer-term statin use (6 months to 1 year before admission). For the secondary outcomes, there was significant risk reduction in cardiac, infectious, respiratory, and renal complications but no significant change in central nervous system or nonatherosclerotic thrombotic complications.

Statin exposure may be associated with adherence to medical treatment and follow-up thus causing a selection bias.

BOTTOM LINE: Perioperative statin use was associated with a reduction in 30-day mortality and other complications.

CITATIONS: London MJ, Schwartz GG, Hur K, Henderson WG. Association of perioperative statin use with mortality and morbidity after major noncardiac surgery. JAMA Intern Med. 2017 Feb 1;177(2):231-42.

Dr. Dietsche is a clinical instructor, Division of Hospital Medicine, University of Colorado School of Medicine, Aurora.

CLINICAL QUESTION: Does perioperative statin use reduce 30-day mortality in noncardiac surgery?

BACKGROUND: Current perioperative guidelines focus on continuation of existing therapy in long-term statin users with weak recommendations of potential efficacy in reducing perioperative complications.

Statin exposure was associated with reduced 30-day all-cause mortality with a marginally favorable effect with longer-term statin use (6 months to 1 year before admission). For the secondary outcomes, there was significant risk reduction in cardiac, infectious, respiratory, and renal complications but no significant change in central nervous system or nonatherosclerotic thrombotic complications.

Statin exposure may be associated with adherence to medical treatment and follow-up thus causing a selection bias.

BOTTOM LINE: Perioperative statin use was associated with a reduction in 30-day mortality and other complications.

CITATIONS: London MJ, Schwartz GG, Hur K, Henderson WG. Association of perioperative statin use with mortality and morbidity after major noncardiac surgery. JAMA Intern Med. 2017 Feb 1;177(2):231-42.

Dr. Dietsche is a clinical instructor, Division of Hospital Medicine, University of Colorado School of Medicine, Aurora.

Clinical Question: Does physician sex affect hospitalized patient outcomes?

Background: Previous studies had suggested different practice patterns between male and female physicians in process measure of quality. No prior evaluation of patient outcomes examining those differences was studied in the past.

Also, 30-day readmission rate, after adjustment readmissions (from 1,540,797 hospitalizations) was 15.02% vs. 15.57% (adjusted risk difference, –0.55%; 95% confidence interval, –0.71% to 0.39%; P less than .001) showing that the care provided by a female physician can reduce one readmission when treating 182 patients.

Bottom line: Patients older than 65 years have lower 30-day mortality and readmission rates when receiving inpatient care from a female internist, compared with care by a male internist.

Citations: Tsugawa Y, Jena AB, Figueroa JF, et al. Comparison of hospital mortality and readmission rates for Medicare patients treated by male vs. female physicians. JAMA Intern Med. 2017 Feb;177(2):206-13.

Dr. Orjuela is assistant professor of neurology at the University of Colorado School of Medicine, Aurora.

Clinical Question: Does physician sex affect hospitalized patient outcomes?

Background: Previous studies had suggested different practice patterns between male and female physicians in process measure of quality. No prior evaluation of patient outcomes examining those differences was studied in the past.

Also, 30-day readmission rate, after adjustment readmissions (from 1,540,797 hospitalizations) was 15.02% vs. 15.57% (adjusted risk difference, –0.55%; 95% confidence interval, –0.71% to 0.39%; P less than .001) showing that the care provided by a female physician can reduce one readmission when treating 182 patients.

Bottom line: Patients older than 65 years have lower 30-day mortality and readmission rates when receiving inpatient care from a female internist, compared with care by a male internist.

Citations: Tsugawa Y, Jena AB, Figueroa JF, et al. Comparison of hospital mortality and readmission rates for Medicare patients treated by male vs. female physicians. JAMA Intern Med. 2017 Feb;177(2):206-13.

Dr. Orjuela is assistant professor of neurology at the University of Colorado School of Medicine, Aurora.

Clinical Question: Does physician sex affect hospitalized patient outcomes?

Background: Previous studies had suggested different practice patterns between male and female physicians in process measure of quality. No prior evaluation of patient outcomes examining those differences was studied in the past.

Also, 30-day readmission rate, after adjustment readmissions (from 1,540,797 hospitalizations) was 15.02% vs. 15.57% (adjusted risk difference, –0.55%; 95% confidence interval, –0.71% to 0.39%; P less than .001) showing that the care provided by a female physician can reduce one readmission when treating 182 patients.

Bottom line: Patients older than 65 years have lower 30-day mortality and readmission rates when receiving inpatient care from a female internist, compared with care by a male internist.

Citations: Tsugawa Y, Jena AB, Figueroa JF, et al. Comparison of hospital mortality and readmission rates for Medicare patients treated by male vs. female physicians. JAMA Intern Med. 2017 Feb;177(2):206-13.

Dr. Orjuela is assistant professor of neurology at the University of Colorado School of Medicine, Aurora.