Jennifer Kelly Shepphird

Results from a large, multinational phase III trial showed that consolidation chemotherapy with docetaxel and cisplatin after concurrent chemoradiation with the same agents failed to improve progression-free survival in patients with locally advanced non–small cell lung cancer (NSCLC), according to a report published online in the Journal of Clinical Oncology.

After a median follow up of 50.7 months, progression-free survival (PFS) for the arm that received consolidation chemotherapy (CC) was 8.1 months, compared with 9.1 months for the arm that did not receive CC (hazard ratio, 0.91; 95% confidence interval, 0.73-1.12; P = .36). Median overall survival (OS) was also similar between groups: 20.6 vs. 21.8 months, respectively (P = .44).

Among patients assigned to the CC arm, only 42.1% received all three planned cycles, 54.1% completed at least two cycles, and 31.6% did not receive any CC.

“The major obstacle in this trial was that many patients could not complete the three planned cycles of CC,” wrote Dr. Jin Seok Ahn of the Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, and colleagues. A large proportion of patients failed to start CC because of disease progression or death, and many patients had incomplete recovery from the adverse effects of concurrent chemoradiation. “A full-dose doublet regimen of CC in our trial might have further reduced the rate of completing the three planned cycles of CC,” the investigators noted (J. Clin. Onc. 2015 July 6 [doi:10.1200/JCO.2014.60.0130]).

The randomized phase III trial included 420 patients with inoperable stage IIIA or IIIB non–small cell lung cancer, enrolled from 31 centers in Korea, China, and Taiwan from 2005 to 2011.

Patients older than 60 years, who had similar baseline characteristics to younger patients, experienced significant benefit from CC (HR 0.72), for reasons that remain unexplained.

An exploratory biomarker study indicated the expression of ERCC1 and class III beta-tubulin was not correlated with PFS or OS.

The study was supported in part by Sanofi-Aventis Korea. Dr. Jin Seok Ahn reported financial ties to Eli Lilly, Pfizer, and Roche. Several of his coauthors reported ties to industry sources.

Results from a large, multinational phase III trial showed that consolidation chemotherapy with docetaxel and cisplatin after concurrent chemoradiation with the same agents failed to improve progression-free survival in patients with locally advanced non–small cell lung cancer (NSCLC), according to a report published online in the Journal of Clinical Oncology.

After a median follow up of 50.7 months, progression-free survival (PFS) for the arm that received consolidation chemotherapy (CC) was 8.1 months, compared with 9.1 months for the arm that did not receive CC (hazard ratio, 0.91; 95% confidence interval, 0.73-1.12; P = .36). Median overall survival (OS) was also similar between groups: 20.6 vs. 21.8 months, respectively (P = .44).

Among patients assigned to the CC arm, only 42.1% received all three planned cycles, 54.1% completed at least two cycles, and 31.6% did not receive any CC.

“The major obstacle in this trial was that many patients could not complete the three planned cycles of CC,” wrote Dr. Jin Seok Ahn of the Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, and colleagues. A large proportion of patients failed to start CC because of disease progression or death, and many patients had incomplete recovery from the adverse effects of concurrent chemoradiation. “A full-dose doublet regimen of CC in our trial might have further reduced the rate of completing the three planned cycles of CC,” the investigators noted (J. Clin. Onc. 2015 July 6 [doi:10.1200/JCO.2014.60.0130]).

The randomized phase III trial included 420 patients with inoperable stage IIIA or IIIB non–small cell lung cancer, enrolled from 31 centers in Korea, China, and Taiwan from 2005 to 2011.

Patients older than 60 years, who had similar baseline characteristics to younger patients, experienced significant benefit from CC (HR 0.72), for reasons that remain unexplained.

An exploratory biomarker study indicated the expression of ERCC1 and class III beta-tubulin was not correlated with PFS or OS.

The study was supported in part by Sanofi-Aventis Korea. Dr. Jin Seok Ahn reported financial ties to Eli Lilly, Pfizer, and Roche. Several of his coauthors reported ties to industry sources.

Results from a large, multinational phase III trial showed that consolidation chemotherapy with docetaxel and cisplatin after concurrent chemoradiation with the same agents failed to improve progression-free survival in patients with locally advanced non–small cell lung cancer (NSCLC), according to a report published online in the Journal of Clinical Oncology.

After a median follow up of 50.7 months, progression-free survival (PFS) for the arm that received consolidation chemotherapy (CC) was 8.1 months, compared with 9.1 months for the arm that did not receive CC (hazard ratio, 0.91; 95% confidence interval, 0.73-1.12; P = .36). Median overall survival (OS) was also similar between groups: 20.6 vs. 21.8 months, respectively (P = .44).

Among patients assigned to the CC arm, only 42.1% received all three planned cycles, 54.1% completed at least two cycles, and 31.6% did not receive any CC.

“The major obstacle in this trial was that many patients could not complete the three planned cycles of CC,” wrote Dr. Jin Seok Ahn of the Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, and colleagues. A large proportion of patients failed to start CC because of disease progression or death, and many patients had incomplete recovery from the adverse effects of concurrent chemoradiation. “A full-dose doublet regimen of CC in our trial might have further reduced the rate of completing the three planned cycles of CC,” the investigators noted (J. Clin. Onc. 2015 July 6 [doi:10.1200/JCO.2014.60.0130]).

The randomized phase III trial included 420 patients with inoperable stage IIIA or IIIB non–small cell lung cancer, enrolled from 31 centers in Korea, China, and Taiwan from 2005 to 2011.

Patients older than 60 years, who had similar baseline characteristics to younger patients, experienced significant benefit from CC (HR 0.72), for reasons that remain unexplained.

An exploratory biomarker study indicated the expression of ERCC1 and class III beta-tubulin was not correlated with PFS or OS.

The study was supported in part by Sanofi-Aventis Korea. Dr. Jin Seok Ahn reported financial ties to Eli Lilly, Pfizer, and Roche. Several of his coauthors reported ties to industry sources.

Patients with newly diagnosed multiple myeloma or smoldering multiple myeloma experienced good responses and few severe adverse events from carfilzomib-lenalidomide-dexamethasone with lenalidomide extension (CRd-R), according to a report published online in JAMA Oncology.

The regimen was not associated with peripheral neuropathy of grade 3 or above, and both groups had high rates of minimal residual disease negativity, which has been shown to be associated with improved progression-free survival and overall survival in newly diagnosed patients treated with CRd.

Wikimedia This file is licensed under the Creative Commons Attribution-Share Alike 3.0 Unported license.

However, the three tools used for measuring patient response differed in their abilities to detect minimal residual disease, the researchers reported.

“Given the high degree of CR [complete response] rates achievable by three-drug combination regimens, there is an increased need for clinical trials to detect MRD [minimal residual disease] beyond traditional methods and characterize optimal MRD technique,” wrote Dr. Neha Korde of the myeloma service at Memorial Sloan Kettering Cancer Center, New York, and colleagues.

The researchers used three measures to assess minimal residual disease: multiparametric flow cytometry, next-generation sequencing, and fluorodeoxyglucose positron-emission tomography/computed tomography.

Based on multiparametric flow cytometry, minimal residual disease was not detected in 62% (28/45) of the patients with newly diagnosed disease and in 92% (11/12) of those with smoldering multiple myeloma, (JAMA Oncol. 2015 July 2 [doi:10.1001/jamaoncol.2015.2010]). Based on flow cytometry, 98% negativity for minimal residual disease was seen in patients with at least nCR. Based on next-generation sequencing, an additional 30% of patients were positive for minimal residual disease, highlighting the potential increased sensitivity of that assay, the researcher said.

In patients with newly diagnosed disease, 98% achieved at least a partial response, 89% had at least a very good partial response, 62% had at least a near complete response, and 56% had at least a complete response or a stringent complete response. Responses improved with more therapy; the median time to CR was 5 (2-17) cycles, and six patients reached CR during the lenalidomide extension. The median duration of response was not reached.

All of the patients with high-risk smoldering multiple myeloma achieved at least a complete response, with median time of 6 (2-20) cycles to CR.

In a 2-year study, 45 patients with newly diagnosed multiple myeloma received a treatment regimen that included eight 28-day cycles of CRd, followed by 24 cycles of lenalidomide extended dosing for those with stable disease. Promising early results led to a pilot study with the same regimen in 12 patients with high-risk SMM, a condition that leads to symptomatic disease within a median of 2 years.

None of the patients with newly diagnosed multiple myeloma had peripheral neuropathy of grade 3 or above, the primary endpoint. Grade 1 peripheral neuropathy affected 33% of patients, and grade 2 was experienced by 9%. Lymphopenia and electrolyte or metabolism abnormalities were the most common adverse events. Grade 3 or 4 cardiac events included two patients with congestive heart failure and three patients with hypertension.

Patients with smoldering multiple myeloma had similar rates of adverse events.

Patients with newly diagnosed multiple myeloma or smoldering multiple myeloma experienced good responses and few severe adverse events from carfilzomib-lenalidomide-dexamethasone with lenalidomide extension (CRd-R), according to a report published online in JAMA Oncology.

The regimen was not associated with peripheral neuropathy of grade 3 or above, and both groups had high rates of minimal residual disease negativity, which has been shown to be associated with improved progression-free survival and overall survival in newly diagnosed patients treated with CRd.

Wikimedia This file is licensed under the Creative Commons Attribution-Share Alike 3.0 Unported license.

However, the three tools used for measuring patient response differed in their abilities to detect minimal residual disease, the researchers reported.

“Given the high degree of CR [complete response] rates achievable by three-drug combination regimens, there is an increased need for clinical trials to detect MRD [minimal residual disease] beyond traditional methods and characterize optimal MRD technique,” wrote Dr. Neha Korde of the myeloma service at Memorial Sloan Kettering Cancer Center, New York, and colleagues.

The researchers used three measures to assess minimal residual disease: multiparametric flow cytometry, next-generation sequencing, and fluorodeoxyglucose positron-emission tomography/computed tomography.

Based on multiparametric flow cytometry, minimal residual disease was not detected in 62% (28/45) of the patients with newly diagnosed disease and in 92% (11/12) of those with smoldering multiple myeloma, (JAMA Oncol. 2015 July 2 [doi:10.1001/jamaoncol.2015.2010]). Based on flow cytometry, 98% negativity for minimal residual disease was seen in patients with at least nCR. Based on next-generation sequencing, an additional 30% of patients were positive for minimal residual disease, highlighting the potential increased sensitivity of that assay, the researcher said.

In patients with newly diagnosed disease, 98% achieved at least a partial response, 89% had at least a very good partial response, 62% had at least a near complete response, and 56% had at least a complete response or a stringent complete response. Responses improved with more therapy; the median time to CR was 5 (2-17) cycles, and six patients reached CR during the lenalidomide extension. The median duration of response was not reached.

All of the patients with high-risk smoldering multiple myeloma achieved at least a complete response, with median time of 6 (2-20) cycles to CR.

In a 2-year study, 45 patients with newly diagnosed multiple myeloma received a treatment regimen that included eight 28-day cycles of CRd, followed by 24 cycles of lenalidomide extended dosing for those with stable disease. Promising early results led to a pilot study with the same regimen in 12 patients with high-risk SMM, a condition that leads to symptomatic disease within a median of 2 years.

None of the patients with newly diagnosed multiple myeloma had peripheral neuropathy of grade 3 or above, the primary endpoint. Grade 1 peripheral neuropathy affected 33% of patients, and grade 2 was experienced by 9%. Lymphopenia and electrolyte or metabolism abnormalities were the most common adverse events. Grade 3 or 4 cardiac events included two patients with congestive heart failure and three patients with hypertension.

Patients with smoldering multiple myeloma had similar rates of adverse events.

Patients with newly diagnosed multiple myeloma or smoldering multiple myeloma experienced good responses and few severe adverse events from carfilzomib-lenalidomide-dexamethasone with lenalidomide extension (CRd-R), according to a report published online in JAMA Oncology.

The regimen was not associated with peripheral neuropathy of grade 3 or above, and both groups had high rates of minimal residual disease negativity, which has been shown to be associated with improved progression-free survival and overall survival in newly diagnosed patients treated with CRd.

Wikimedia This file is licensed under the Creative Commons Attribution-Share Alike 3.0 Unported license.

However, the three tools used for measuring patient response differed in their abilities to detect minimal residual disease, the researchers reported.

“Given the high degree of CR [complete response] rates achievable by three-drug combination regimens, there is an increased need for clinical trials to detect MRD [minimal residual disease] beyond traditional methods and characterize optimal MRD technique,” wrote Dr. Neha Korde of the myeloma service at Memorial Sloan Kettering Cancer Center, New York, and colleagues.

The researchers used three measures to assess minimal residual disease: multiparametric flow cytometry, next-generation sequencing, and fluorodeoxyglucose positron-emission tomography/computed tomography.

Based on multiparametric flow cytometry, minimal residual disease was not detected in 62% (28/45) of the patients with newly diagnosed disease and in 92% (11/12) of those with smoldering multiple myeloma, (JAMA Oncol. 2015 July 2 [doi:10.1001/jamaoncol.2015.2010]). Based on flow cytometry, 98% negativity for minimal residual disease was seen in patients with at least nCR. Based on next-generation sequencing, an additional 30% of patients were positive for minimal residual disease, highlighting the potential increased sensitivity of that assay, the researcher said.

In patients with newly diagnosed disease, 98% achieved at least a partial response, 89% had at least a very good partial response, 62% had at least a near complete response, and 56% had at least a complete response or a stringent complete response. Responses improved with more therapy; the median time to CR was 5 (2-17) cycles, and six patients reached CR during the lenalidomide extension. The median duration of response was not reached.

All of the patients with high-risk smoldering multiple myeloma achieved at least a complete response, with median time of 6 (2-20) cycles to CR.

In a 2-year study, 45 patients with newly diagnosed multiple myeloma received a treatment regimen that included eight 28-day cycles of CRd, followed by 24 cycles of lenalidomide extended dosing for those with stable disease. Promising early results led to a pilot study with the same regimen in 12 patients with high-risk SMM, a condition that leads to symptomatic disease within a median of 2 years.

None of the patients with newly diagnosed multiple myeloma had peripheral neuropathy of grade 3 or above, the primary endpoint. Grade 1 peripheral neuropathy affected 33% of patients, and grade 2 was experienced by 9%. Lymphopenia and electrolyte or metabolism abnormalities were the most common adverse events. Grade 3 or 4 cardiac events included two patients with congestive heart failure and three patients with hypertension.

Patients with smoldering multiple myeloma had similar rates of adverse events.

Urea cream is more effective at preventing hand-foot syndrome (HFS) than is a medical ointment high in antioxidants for patients receiving capecitabine, according to a randomized phase III study published online in the Journal of Clinical Oncology.

During a 6-week treatment period, 17 of 76 patients (22.4%) who used 10% urea cream experienced HFS, compared with 30 of 76 patients (39.5%) who used the new ointment Mapisal, which has been available on the German market since 2011 (odds ratio 2.37; 95% CI 1.14 to 4.84; P = .02). The distribution of HFS grades within the groups was similar, with the majority having grade 1 and about 6% experiencing grade 3 HFS. A secondary endpoint, time to develop HFS, was significantly longer in the urea cream group (J. Clin. Oncol. 2015 June 29 [doi:10.1200/JCO.2014.60.4587]).

The result was unexpected. Mapisal contains several antioxidants and oil extracts and exhibits a high radical protection factor, which was hypothesized to be of benefit due to a decline in antioxidative capacity of the skin in patients using capecitabine. “The most striking explanation for the observed ineffectiveness of Mapisal is that either the hypothesis – that is, that Mapisal’s crucial mode of action against HFS is to act as an antioxidant against free radicals – is incorrect, or that this is not the main mechanism of HFS development, at least in the case of capecitabine,” wrote Dr. Ralf-Dieter Hofheinz of University Hospital Mannheim, Germany, and colleagues.

Between 2012 and 2013, the study enrolled 160 patients with GI tumors or breast cancer who were being treated with capecitabine, and 152 were randomly assigned to receive prophylactic treatment with either Mapisal or 10% urea cream for a 6-week period. Aside from HFS, adverse events were similar between the groups. After the treatment period, skin-related quality of life was significantly lower in the Mapisal vs. urea group.

The results of this study, along with findings from a previous phase II study demonstrating activity of urea cream in patients treated with sorafenib, supports the idea that urea cream is an appropriate prophylaxis for HFS and a reasonable standard for future investigations, the researchers noted.

Urea cream is more effective at preventing hand-foot syndrome (HFS) than is a medical ointment high in antioxidants for patients receiving capecitabine, according to a randomized phase III study published online in the Journal of Clinical Oncology.

During a 6-week treatment period, 17 of 76 patients (22.4%) who used 10% urea cream experienced HFS, compared with 30 of 76 patients (39.5%) who used the new ointment Mapisal, which has been available on the German market since 2011 (odds ratio 2.37; 95% CI 1.14 to 4.84; P = .02). The distribution of HFS grades within the groups was similar, with the majority having grade 1 and about 6% experiencing grade 3 HFS. A secondary endpoint, time to develop HFS, was significantly longer in the urea cream group (J. Clin. Oncol. 2015 June 29 [doi:10.1200/JCO.2014.60.4587]).

The result was unexpected. Mapisal contains several antioxidants and oil extracts and exhibits a high radical protection factor, which was hypothesized to be of benefit due to a decline in antioxidative capacity of the skin in patients using capecitabine. “The most striking explanation for the observed ineffectiveness of Mapisal is that either the hypothesis – that is, that Mapisal’s crucial mode of action against HFS is to act as an antioxidant against free radicals – is incorrect, or that this is not the main mechanism of HFS development, at least in the case of capecitabine,” wrote Dr. Ralf-Dieter Hofheinz of University Hospital Mannheim, Germany, and colleagues.

Between 2012 and 2013, the study enrolled 160 patients with GI tumors or breast cancer who were being treated with capecitabine, and 152 were randomly assigned to receive prophylactic treatment with either Mapisal or 10% urea cream for a 6-week period. Aside from HFS, adverse events were similar between the groups. After the treatment period, skin-related quality of life was significantly lower in the Mapisal vs. urea group.

The results of this study, along with findings from a previous phase II study demonstrating activity of urea cream in patients treated with sorafenib, supports the idea that urea cream is an appropriate prophylaxis for HFS and a reasonable standard for future investigations, the researchers noted.

Urea cream is more effective at preventing hand-foot syndrome (HFS) than is a medical ointment high in antioxidants for patients receiving capecitabine, according to a randomized phase III study published online in the Journal of Clinical Oncology.

During a 6-week treatment period, 17 of 76 patients (22.4%) who used 10% urea cream experienced HFS, compared with 30 of 76 patients (39.5%) who used the new ointment Mapisal, which has been available on the German market since 2011 (odds ratio 2.37; 95% CI 1.14 to 4.84; P = .02). The distribution of HFS grades within the groups was similar, with the majority having grade 1 and about 6% experiencing grade 3 HFS. A secondary endpoint, time to develop HFS, was significantly longer in the urea cream group (J. Clin. Oncol. 2015 June 29 [doi:10.1200/JCO.2014.60.4587]).

The result was unexpected. Mapisal contains several antioxidants and oil extracts and exhibits a high radical protection factor, which was hypothesized to be of benefit due to a decline in antioxidative capacity of the skin in patients using capecitabine. “The most striking explanation for the observed ineffectiveness of Mapisal is that either the hypothesis – that is, that Mapisal’s crucial mode of action against HFS is to act as an antioxidant against free radicals – is incorrect, or that this is not the main mechanism of HFS development, at least in the case of capecitabine,” wrote Dr. Ralf-Dieter Hofheinz of University Hospital Mannheim, Germany, and colleagues.

Between 2012 and 2013, the study enrolled 160 patients with GI tumors or breast cancer who were being treated with capecitabine, and 152 were randomly assigned to receive prophylactic treatment with either Mapisal or 10% urea cream for a 6-week period. Aside from HFS, adverse events were similar between the groups. After the treatment period, skin-related quality of life was significantly lower in the Mapisal vs. urea group.

The results of this study, along with findings from a previous phase II study demonstrating activity of urea cream in patients treated with sorafenib, supports the idea that urea cream is an appropriate prophylaxis for HFS and a reasonable standard for future investigations, the researchers noted.

A cancer risk algorithm using serial measurements of serum cancer antigen 125 (CA-125) detected more cases of ovarian cancer than did a single-threshold rule, according to a large, prospective screening study published in the Journal of Clinical Oncology.

The findings “highlight the need to examine serial change in biomarker levels in the context of screening and early detection of cancer. Reliance on predefined single-threshold rules may result in biomarkers of value being discarded,” wrote Dr. Usha Menon, professor of gynecological cancer at University College London (J. Clin. Oncol. 2015 June 20 [doi:10.1200/JCO.2014.59.4945]).

The risk of ovarian cancer algorithm (ROCA) compares an individual’s CA-125 serial profile with that of cancer cases and healthy controls to estimate a risk for ovarian cancer. The United Kingdom Collaborative Trial of Ovarian Cancer Screening enrolled 202,638 women and randomly allocated about 50,000 to multimodal screening using CA-125 velocity measurements and ROCA. From 2002 to 2011, 296,911 incident screens were performed, which was a median 7 screens per participant.

Out of 155 women with invasive epithelial ovarian or tubal cancers (iEOC), ROCA detected 85.8%, whereas single measurements of CA-125 as thresholds 35, 30, and 22 U/mL would have identified 41.3%, 48.4%, and 66.5%, respectively. The ROCA had significantly larger area under the receiver operating curve (ROC) 0.915) than did single CA-125 measurements (0.915 vs. 0.869; P = .0027). Most of the screen-detected iEOCs (82.0%) were aggressive type II, contrary to concerns that screening identifies more indolent cancers.

Surgery as a result of positive screen results occurred in 640 women (0.2% of all screens) and of these, 154 (24.1%) had primary ovarian and/or tubal malignancies detected, representing a lower false-positive rate than other screening strategies.

The median time from annual screen to surgery was 20 weeks, but for women who had CA-125 in the normal range (and intermediate ROCA), the median time to surgery was 30 weeks, because of a requirement for repeat tests. Modifications to the screening strategy to decrease this time may be warranted given that this group had a higher proportion of stage I and II iEOCs compared with those who had intermediate ROCA coupled with above-normal CA-125, did not require more testing, and had a median time to surgery of 12 weeks.

A cancer risk algorithm using serial measurements of serum cancer antigen 125 (CA-125) detected more cases of ovarian cancer than did a single-threshold rule, according to a large, prospective screening study published in the Journal of Clinical Oncology.

The findings “highlight the need to examine serial change in biomarker levels in the context of screening and early detection of cancer. Reliance on predefined single-threshold rules may result in biomarkers of value being discarded,” wrote Dr. Usha Menon, professor of gynecological cancer at University College London (J. Clin. Oncol. 2015 June 20 [doi:10.1200/JCO.2014.59.4945]).

The risk of ovarian cancer algorithm (ROCA) compares an individual’s CA-125 serial profile with that of cancer cases and healthy controls to estimate a risk for ovarian cancer. The United Kingdom Collaborative Trial of Ovarian Cancer Screening enrolled 202,638 women and randomly allocated about 50,000 to multimodal screening using CA-125 velocity measurements and ROCA. From 2002 to 2011, 296,911 incident screens were performed, which was a median 7 screens per participant.

Out of 155 women with invasive epithelial ovarian or tubal cancers (iEOC), ROCA detected 85.8%, whereas single measurements of CA-125 as thresholds 35, 30, and 22 U/mL would have identified 41.3%, 48.4%, and 66.5%, respectively. The ROCA had significantly larger area under the receiver operating curve (ROC) 0.915) than did single CA-125 measurements (0.915 vs. 0.869; P = .0027). Most of the screen-detected iEOCs (82.0%) were aggressive type II, contrary to concerns that screening identifies more indolent cancers.

Surgery as a result of positive screen results occurred in 640 women (0.2% of all screens) and of these, 154 (24.1%) had primary ovarian and/or tubal malignancies detected, representing a lower false-positive rate than other screening strategies.

The median time from annual screen to surgery was 20 weeks, but for women who had CA-125 in the normal range (and intermediate ROCA), the median time to surgery was 30 weeks, because of a requirement for repeat tests. Modifications to the screening strategy to decrease this time may be warranted given that this group had a higher proportion of stage I and II iEOCs compared with those who had intermediate ROCA coupled with above-normal CA-125, did not require more testing, and had a median time to surgery of 12 weeks.

A cancer risk algorithm using serial measurements of serum cancer antigen 125 (CA-125) detected more cases of ovarian cancer than did a single-threshold rule, according to a large, prospective screening study published in the Journal of Clinical Oncology.

The findings “highlight the need to examine serial change in biomarker levels in the context of screening and early detection of cancer. Reliance on predefined single-threshold rules may result in biomarkers of value being discarded,” wrote Dr. Usha Menon, professor of gynecological cancer at University College London (J. Clin. Oncol. 2015 June 20 [doi:10.1200/JCO.2014.59.4945]).

The risk of ovarian cancer algorithm (ROCA) compares an individual’s CA-125 serial profile with that of cancer cases and healthy controls to estimate a risk for ovarian cancer. The United Kingdom Collaborative Trial of Ovarian Cancer Screening enrolled 202,638 women and randomly allocated about 50,000 to multimodal screening using CA-125 velocity measurements and ROCA. From 2002 to 2011, 296,911 incident screens were performed, which was a median 7 screens per participant.

Out of 155 women with invasive epithelial ovarian or tubal cancers (iEOC), ROCA detected 85.8%, whereas single measurements of CA-125 as thresholds 35, 30, and 22 U/mL would have identified 41.3%, 48.4%, and 66.5%, respectively. The ROCA had significantly larger area under the receiver operating curve (ROC) 0.915) than did single CA-125 measurements (0.915 vs. 0.869; P = .0027). Most of the screen-detected iEOCs (82.0%) were aggressive type II, contrary to concerns that screening identifies more indolent cancers.

Surgery as a result of positive screen results occurred in 640 women (0.2% of all screens) and of these, 154 (24.1%) had primary ovarian and/or tubal malignancies detected, representing a lower false-positive rate than other screening strategies.

The median time from annual screen to surgery was 20 weeks, but for women who had CA-125 in the normal range (and intermediate ROCA), the median time to surgery was 30 weeks, because of a requirement for repeat tests. Modifications to the screening strategy to decrease this time may be warranted given that this group had a higher proportion of stage I and II iEOCs compared with those who had intermediate ROCA coupled with above-normal CA-125, did not require more testing, and had a median time to surgery of 12 weeks.

Subsequent to the 2012 U.S. Preventative Services Task Force recommendation discouraging prostate-specific antigen (PSA)-based screening, prostate cancer screening significantly declined among men age 50 years and older in the United States, according to a study published online in the Journal of Clinical Oncology.

Based on National Health Interview Surveys in 2005, 2010, and 2013, self-reported PSA-testing levels decreased most among men aged 50-59 years, from 33.2% in 2010 to 24.8% in 2013 (odds ratio, 0.66; P < .01). Declines from 2010 to 2013 were also observed among men aged 60-74 years (51.2%-43.6%; OR, 0.74; P < .01); and aged 75 and older (43.9%-37.1%, OR, 0.75; P = .03). Among men aged 40-49 years, the decline from 12.5% to 11.2% was not significant (Journ. Clin. Onc. 2015 June 8 [doi:10.1200/JCO.2015.61.6532]).

©alexdans/Thinkstock

The declines may reflect increased adherence by physicians to USPSTF guidelines; nevertheless, in 2013 approximately one-third of men aged 65 or older who had high risk for 9-year mortality (about 1.4 million individuals) were screened.

“Persistently elevated screening rates among men with limited remaining life expectancies are troubling and merit further interventions,” wrote Dr. Michael Drazer of the University of Chicago Medical Center and colleagues. “These may include increasing awareness of initiatives such as Choosing Wisely recommendations from the American Society of Clinical Oncology and recommendations from the American Geriatrics Society,” they wrote.

If these efforts prove unsuccessful, reducing or eliminating reimbursements for screening and interventions may be considered, the authors suggest.

A multivariate model identified factors that predict which men over age 65 are likely to be screened, and these are men who went to college, were married, consumed alcohol, and received a colonoscopy in the last 10 years. They found no significant predictors in the patient population for declines in screening from 2010 to 2013.

Several studies support the use of extended screening intervals (every 2-3 years) for patients at low risk for prostate cancer. Annual screening of men aged 55-67 years has been estimated to result in a 50% overdiagnosis rate.

Drs. Drazer and Huo reported having no financial disclosures. Dr. Eggener reported having consulting or advisory roles with Myriad Genetics, Medivation, Janssen Pharmaceuticals, Genomic Health, OPKO Diagnostics, and MDxHealth.

Subsequent to the 2012 U.S. Preventative Services Task Force recommendation discouraging prostate-specific antigen (PSA)-based screening, prostate cancer screening significantly declined among men age 50 years and older in the United States, according to a study published online in the Journal of Clinical Oncology.

Based on National Health Interview Surveys in 2005, 2010, and 2013, self-reported PSA-testing levels decreased most among men aged 50-59 years, from 33.2% in 2010 to 24.8% in 2013 (odds ratio, 0.66; P < .01). Declines from 2010 to 2013 were also observed among men aged 60-74 years (51.2%-43.6%; OR, 0.74; P < .01); and aged 75 and older (43.9%-37.1%, OR, 0.75; P = .03). Among men aged 40-49 years, the decline from 12.5% to 11.2% was not significant (Journ. Clin. Onc. 2015 June 8 [doi:10.1200/JCO.2015.61.6532]).

©alexdans/Thinkstock

The declines may reflect increased adherence by physicians to USPSTF guidelines; nevertheless, in 2013 approximately one-third of men aged 65 or older who had high risk for 9-year mortality (about 1.4 million individuals) were screened.

“Persistently elevated screening rates among men with limited remaining life expectancies are troubling and merit further interventions,” wrote Dr. Michael Drazer of the University of Chicago Medical Center and colleagues. “These may include increasing awareness of initiatives such as Choosing Wisely recommendations from the American Society of Clinical Oncology and recommendations from the American Geriatrics Society,” they wrote.

If these efforts prove unsuccessful, reducing or eliminating reimbursements for screening and interventions may be considered, the authors suggest.

A multivariate model identified factors that predict which men over age 65 are likely to be screened, and these are men who went to college, were married, consumed alcohol, and received a colonoscopy in the last 10 years. They found no significant predictors in the patient population for declines in screening from 2010 to 2013.

Several studies support the use of extended screening intervals (every 2-3 years) for patients at low risk for prostate cancer. Annual screening of men aged 55-67 years has been estimated to result in a 50% overdiagnosis rate.

Drs. Drazer and Huo reported having no financial disclosures. Dr. Eggener reported having consulting or advisory roles with Myriad Genetics, Medivation, Janssen Pharmaceuticals, Genomic Health, OPKO Diagnostics, and MDxHealth.

Subsequent to the 2012 U.S. Preventative Services Task Force recommendation discouraging prostate-specific antigen (PSA)-based screening, prostate cancer screening significantly declined among men age 50 years and older in the United States, according to a study published online in the Journal of Clinical Oncology.

Based on National Health Interview Surveys in 2005, 2010, and 2013, self-reported PSA-testing levels decreased most among men aged 50-59 years, from 33.2% in 2010 to 24.8% in 2013 (odds ratio, 0.66; P < .01). Declines from 2010 to 2013 were also observed among men aged 60-74 years (51.2%-43.6%; OR, 0.74; P < .01); and aged 75 and older (43.9%-37.1%, OR, 0.75; P = .03). Among men aged 40-49 years, the decline from 12.5% to 11.2% was not significant (Journ. Clin. Onc. 2015 June 8 [doi:10.1200/JCO.2015.61.6532]).

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The declines may reflect increased adherence by physicians to USPSTF guidelines; nevertheless, in 2013 approximately one-third of men aged 65 or older who had high risk for 9-year mortality (about 1.4 million individuals) were screened.

“Persistently elevated screening rates among men with limited remaining life expectancies are troubling and merit further interventions,” wrote Dr. Michael Drazer of the University of Chicago Medical Center and colleagues. “These may include increasing awareness of initiatives such as Choosing Wisely recommendations from the American Society of Clinical Oncology and recommendations from the American Geriatrics Society,” they wrote.

If these efforts prove unsuccessful, reducing or eliminating reimbursements for screening and interventions may be considered, the authors suggest.

A multivariate model identified factors that predict which men over age 65 are likely to be screened, and these are men who went to college, were married, consumed alcohol, and received a colonoscopy in the last 10 years. They found no significant predictors in the patient population for declines in screening from 2010 to 2013.

Several studies support the use of extended screening intervals (every 2-3 years) for patients at low risk for prostate cancer. Annual screening of men aged 55-67 years has been estimated to result in a 50% overdiagnosis rate.

Drs. Drazer and Huo reported having no financial disclosures. Dr. Eggener reported having consulting or advisory roles with Myriad Genetics, Medivation, Janssen Pharmaceuticals, Genomic Health, OPKO Diagnostics, and MDxHealth.

Treatment with the oncolytic immunotherapy talimogene laherparepvec (T-VEC) resulted in significantly longer rates of durable response and overall response, compared with subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF), according to results from the phase III OPTiM trial reported in the Journal of Clinical Oncology.

“To our knowledge, OPTiM is the first randomized, controlled, phase III study evaluating an oncolytic immunotherapy to demonstrate a therapeutic benefit in melanoma,” wrote Dr. Robert Andtbacka, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, and colleagues (J. Clin. Onc. 2015 May 26 [doi:10.1200/JCO.2014.58.3377]).

Patients who received T-VEC vs. subcutaneous GM-CSF had significantly improved rates of durable response, defined as responses lasting 6 months or more, (16.3% vs. 2.1%; P < .001), as well as improved overall response rates (26.4% vs. 5.7% ; P < .001). Complete responses were achieved in 10.8% of the T-VEC arm (32 patients) and < 1% (1 patient) in the GM-CSF arm. Median overall survival was 23.3 months for T-VEC and 18.9 months for GM-CSF (P = .051).

Differences in durable response rates and overall response rates between the T-VEC and GM-CSF arms were greater among patients with stage IIIb or IIIC (33% vs. 0%) and IVM1a disease (16% vs. 2%) than in patients with stage IVM1b (3% vs. 4%) or IVM1c disease (7% vs. 3%). This may be because of insufficient time for the immunotherapy to benefit patients with visceral disease, or because injection of T-VEC into dermal, subcutaneous, and nodal metastases may activate an immune response that preferentially targets metastases in similar anatomic sites.

Among patients in the T-VEC arm who achieved a response, 54% had disease progression prior to response. This pseudoprogression is consistent with other immunotherapies and illustrates the importance of continuing treatment in stable patients despite increasing lesions, the investigators noted.

Based on a modified herpes simplex virus type 1, T-VEC is an oncolytic virus designed to replicate in and lyse tumor cells while promoting an antitumor immune response.

Adverse events more frequently observed in the T-VEC group were flu-like symptoms, including chills, pyrexia, nausea, and fatigue. Incidence of grade 3 or 4 adverse events was 11% for T-VEC and 5% for GM-CSF. The tolerable safety profile of T-VEC is an important factor in considering combined immunotherapy approaches, wrote Dr. Robert Andtbacka and associates.

“The evidence of local and systemic immune responses with T-VEC supports combinations with other immunotherapies as a rational approach. A phase 1b/2 study of T-VEC and ipilimumab is evaluating the safety and efficacy of this combination,” they wrote.

Treatment with the oncolytic immunotherapy talimogene laherparepvec (T-VEC) resulted in significantly longer rates of durable response and overall response, compared with subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF), according to results from the phase III OPTiM trial reported in the Journal of Clinical Oncology.

“To our knowledge, OPTiM is the first randomized, controlled, phase III study evaluating an oncolytic immunotherapy to demonstrate a therapeutic benefit in melanoma,” wrote Dr. Robert Andtbacka, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, and colleagues (J. Clin. Onc. 2015 May 26 [doi:10.1200/JCO.2014.58.3377]).

Patients who received T-VEC vs. subcutaneous GM-CSF had significantly improved rates of durable response, defined as responses lasting 6 months or more, (16.3% vs. 2.1%; P < .001), as well as improved overall response rates (26.4% vs. 5.7% ; P < .001). Complete responses were achieved in 10.8% of the T-VEC arm (32 patients) and < 1% (1 patient) in the GM-CSF arm. Median overall survival was 23.3 months for T-VEC and 18.9 months for GM-CSF (P = .051).

Differences in durable response rates and overall response rates between the T-VEC and GM-CSF arms were greater among patients with stage IIIb or IIIC (33% vs. 0%) and IVM1a disease (16% vs. 2%) than in patients with stage IVM1b (3% vs. 4%) or IVM1c disease (7% vs. 3%). This may be because of insufficient time for the immunotherapy to benefit patients with visceral disease, or because injection of T-VEC into dermal, subcutaneous, and nodal metastases may activate an immune response that preferentially targets metastases in similar anatomic sites.

Among patients in the T-VEC arm who achieved a response, 54% had disease progression prior to response. This pseudoprogression is consistent with other immunotherapies and illustrates the importance of continuing treatment in stable patients despite increasing lesions, the investigators noted.

Based on a modified herpes simplex virus type 1, T-VEC is an oncolytic virus designed to replicate in and lyse tumor cells while promoting an antitumor immune response.

Adverse events more frequently observed in the T-VEC group were flu-like symptoms, including chills, pyrexia, nausea, and fatigue. Incidence of grade 3 or 4 adverse events was 11% for T-VEC and 5% for GM-CSF. The tolerable safety profile of T-VEC is an important factor in considering combined immunotherapy approaches, wrote Dr. Robert Andtbacka and associates.

“The evidence of local and systemic immune responses with T-VEC supports combinations with other immunotherapies as a rational approach. A phase 1b/2 study of T-VEC and ipilimumab is evaluating the safety and efficacy of this combination,” they wrote.

Treatment with the oncolytic immunotherapy talimogene laherparepvec (T-VEC) resulted in significantly longer rates of durable response and overall response, compared with subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF), according to results from the phase III OPTiM trial reported in the Journal of Clinical Oncology.

“To our knowledge, OPTiM is the first randomized, controlled, phase III study evaluating an oncolytic immunotherapy to demonstrate a therapeutic benefit in melanoma,” wrote Dr. Robert Andtbacka, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, and colleagues (J. Clin. Onc. 2015 May 26 [doi:10.1200/JCO.2014.58.3377]).

Patients who received T-VEC vs. subcutaneous GM-CSF had significantly improved rates of durable response, defined as responses lasting 6 months or more, (16.3% vs. 2.1%; P < .001), as well as improved overall response rates (26.4% vs. 5.7% ; P < .001). Complete responses were achieved in 10.8% of the T-VEC arm (32 patients) and < 1% (1 patient) in the GM-CSF arm. Median overall survival was 23.3 months for T-VEC and 18.9 months for GM-CSF (P = .051).

Differences in durable response rates and overall response rates between the T-VEC and GM-CSF arms were greater among patients with stage IIIb or IIIC (33% vs. 0%) and IVM1a disease (16% vs. 2%) than in patients with stage IVM1b (3% vs. 4%) or IVM1c disease (7% vs. 3%). This may be because of insufficient time for the immunotherapy to benefit patients with visceral disease, or because injection of T-VEC into dermal, subcutaneous, and nodal metastases may activate an immune response that preferentially targets metastases in similar anatomic sites.

Among patients in the T-VEC arm who achieved a response, 54% had disease progression prior to response. This pseudoprogression is consistent with other immunotherapies and illustrates the importance of continuing treatment in stable patients despite increasing lesions, the investigators noted.

Based on a modified herpes simplex virus type 1, T-VEC is an oncolytic virus designed to replicate in and lyse tumor cells while promoting an antitumor immune response.

Adverse events more frequently observed in the T-VEC group were flu-like symptoms, including chills, pyrexia, nausea, and fatigue. Incidence of grade 3 or 4 adverse events was 11% for T-VEC and 5% for GM-CSF. The tolerable safety profile of T-VEC is an important factor in considering combined immunotherapy approaches, wrote Dr. Robert Andtbacka and associates.

“The evidence of local and systemic immune responses with T-VEC supports combinations with other immunotherapies as a rational approach. A phase 1b/2 study of T-VEC and ipilimumab is evaluating the safety and efficacy of this combination,” they wrote.

To identify patients at increased risk for certain types of cancer, ob.gyns. should perform and regularly update hereditary cancer risk assessments, according to a new recommendation from the American College of Obstetricians and Gynecologists.

Patients at increased risk for hereditary cancer syndromes should be referred to a cancer genetics specialist for further assessment and counseling, according to the opinion from ACOG’s Committee on Genetics (Obstet. Gynecol. 2015;125:1538-43).

Alexander Raths/Fotolia.com

Personal and family histories provide key information to determine the appropriateness of genetic counseling, which is distinct from genetic testing. Discussed in the counseling visit, the decision for genetic testing is based on family history, pedigree analysis, and, in some cases, pathology reports and confirmation of cancer deaths.

Patient intake forms are used in many office settings to gather relevant information. Online versions of intake forms, such as the Surgeon General’s “My Family Health Portrait,” can facilitate documentation of comprehensive histories. The American Society of Clinical Oncology also has identified some key elements of an adequate family history for assessing cancer risk, including first- and second-degree relatives, maternal and paternal sides, European Jewish ancestry, age of onset and type of cancer, and results of predisposition tests in any relative.

There are several indicators for the presence of hereditary cancer syndromes, including cancer diagnosed at an unusually young age, the presence of several different types of cancer, several close relatives with the same type of cancer, unusual presentation (such as breast cancer in a man), certain birth defects (such as skin growths or skeletal abnormalities associated with inherited cancer syndromes), and Ashkenazi Jewish ancestry.

The ACOG committee opinion identifies common hereditary cancer syndromes involved in gynecologic cancers, including hereditary breast and ovarian cancer syndrome and Lynch, Li-Fraumeni, Cowden, and Peutz-Jeghers syndromes.

Mutations in DNA repair genes BRCA1 and BRCA2 cause hereditary breast and ovarian cancer syndrome and account for 5%-15% of all breast and ovarian cancers in the United States. The carrier frequency in the general population is 1 in 500, but it is much higher (1 in 40) in the Ashkenazi Jewish population. Women with hereditary breast and ovarian cancer syndrome have a 65%-74% lifetime risk of breast cancer and 39%-46% (BRCA1) or 12%-20% (BRCA2) risk of ovarian cancer.

Also caused by DNA repair defects, Lynch syndrome, or hereditary nonpolyposis colorectal cancer, has a prevalence of 1 in 600 to 1 in 3,000. Individuals with Lynch syndrome have increased risk of colon (52%-82%), endometrial (25%-60%), and ovarian (4%-24%) cancers. Malignancies associated with Lynch syndrome include uterine, gastric, small bowel, hepatobiliary, breast, brain, and sebaceous skin cancers.

The presence of Li-Fraumeni syndrome increases the risk of osteosarcoma, breast cancer, colon cancer, adrenocortical carcinoma, leukemia and lymphoma, and brain cancer. Caused by mutations in the tumor suppressor gene TP53, individuals with the syndrome have a 90% risk of cancer by age 60 years. Patients diagnosed with a Li-Fraumeni syndrome–associated malignancy should be referred to a cancer genetics specialist for counseling, according to the committee opinion.

Individuals with the relatively rare (1 in 200,000) Cowden syndrome usually have pathognomonic skin lesions, including papillomatous papules on the face and mucous membranes, by age 30 years. The presence of Cowden syndrome increases the lifetime risk of breast cancer to 25%-50% and endometrial cancer to 5%-10%. Clinicians should consult frequently updated guidelines to determine which patients should be referred for genetic evaluation.

Mutations in serine/threonine kinase 11 cause Peutz-Jehgers syndrome. Two of the following three criteria characterize the syndrome: two or more hamartomatous polyps in the GI tract; mucocutaneous hyperpigmentation of the mouth, lips, nose, eyes, genitalia, or fingers; and a family history of Peutz-Jeghers syndrome. Women with Peutz-Jeghers syndrome have a 50% increased lifetime risk of breast cancer and increased risk of ovarian, uterine, and cervical cancer.

To identify patients at increased risk for certain types of cancer, ob.gyns. should perform and regularly update hereditary cancer risk assessments, according to a new recommendation from the American College of Obstetricians and Gynecologists.

Patients at increased risk for hereditary cancer syndromes should be referred to a cancer genetics specialist for further assessment and counseling, according to the opinion from ACOG’s Committee on Genetics (Obstet. Gynecol. 2015;125:1538-43).

Alexander Raths/Fotolia.com

Personal and family histories provide key information to determine the appropriateness of genetic counseling, which is distinct from genetic testing. Discussed in the counseling visit, the decision for genetic testing is based on family history, pedigree analysis, and, in some cases, pathology reports and confirmation of cancer deaths.

Patient intake forms are used in many office settings to gather relevant information. Online versions of intake forms, such as the Surgeon General’s “My Family Health Portrait,” can facilitate documentation of comprehensive histories. The American Society of Clinical Oncology also has identified some key elements of an adequate family history for assessing cancer risk, including first- and second-degree relatives, maternal and paternal sides, European Jewish ancestry, age of onset and type of cancer, and results of predisposition tests in any relative.

There are several indicators for the presence of hereditary cancer syndromes, including cancer diagnosed at an unusually young age, the presence of several different types of cancer, several close relatives with the same type of cancer, unusual presentation (such as breast cancer in a man), certain birth defects (such as skin growths or skeletal abnormalities associated with inherited cancer syndromes), and Ashkenazi Jewish ancestry.

The ACOG committee opinion identifies common hereditary cancer syndromes involved in gynecologic cancers, including hereditary breast and ovarian cancer syndrome and Lynch, Li-Fraumeni, Cowden, and Peutz-Jeghers syndromes.

Mutations in DNA repair genes BRCA1 and BRCA2 cause hereditary breast and ovarian cancer syndrome and account for 5%-15% of all breast and ovarian cancers in the United States. The carrier frequency in the general population is 1 in 500, but it is much higher (1 in 40) in the Ashkenazi Jewish population. Women with hereditary breast and ovarian cancer syndrome have a 65%-74% lifetime risk of breast cancer and 39%-46% (BRCA1) or 12%-20% (BRCA2) risk of ovarian cancer.

Also caused by DNA repair defects, Lynch syndrome, or hereditary nonpolyposis colorectal cancer, has a prevalence of 1 in 600 to 1 in 3,000. Individuals with Lynch syndrome have increased risk of colon (52%-82%), endometrial (25%-60%), and ovarian (4%-24%) cancers. Malignancies associated with Lynch syndrome include uterine, gastric, small bowel, hepatobiliary, breast, brain, and sebaceous skin cancers.

The presence of Li-Fraumeni syndrome increases the risk of osteosarcoma, breast cancer, colon cancer, adrenocortical carcinoma, leukemia and lymphoma, and brain cancer. Caused by mutations in the tumor suppressor gene TP53, individuals with the syndrome have a 90% risk of cancer by age 60 years. Patients diagnosed with a Li-Fraumeni syndrome–associated malignancy should be referred to a cancer genetics specialist for counseling, according to the committee opinion.

Individuals with the relatively rare (1 in 200,000) Cowden syndrome usually have pathognomonic skin lesions, including papillomatous papules on the face and mucous membranes, by age 30 years. The presence of Cowden syndrome increases the lifetime risk of breast cancer to 25%-50% and endometrial cancer to 5%-10%. Clinicians should consult frequently updated guidelines to determine which patients should be referred for genetic evaluation.

Mutations in serine/threonine kinase 11 cause Peutz-Jehgers syndrome. Two of the following three criteria characterize the syndrome: two or more hamartomatous polyps in the GI tract; mucocutaneous hyperpigmentation of the mouth, lips, nose, eyes, genitalia, or fingers; and a family history of Peutz-Jeghers syndrome. Women with Peutz-Jeghers syndrome have a 50% increased lifetime risk of breast cancer and increased risk of ovarian, uterine, and cervical cancer.

To identify patients at increased risk for certain types of cancer, ob.gyns. should perform and regularly update hereditary cancer risk assessments, according to a new recommendation from the American College of Obstetricians and Gynecologists.

Patients at increased risk for hereditary cancer syndromes should be referred to a cancer genetics specialist for further assessment and counseling, according to the opinion from ACOG’s Committee on Genetics (Obstet. Gynecol. 2015;125:1538-43).

Alexander Raths/Fotolia.com

Personal and family histories provide key information to determine the appropriateness of genetic counseling, which is distinct from genetic testing. Discussed in the counseling visit, the decision for genetic testing is based on family history, pedigree analysis, and, in some cases, pathology reports and confirmation of cancer deaths.

Patient intake forms are used in many office settings to gather relevant information. Online versions of intake forms, such as the Surgeon General’s “My Family Health Portrait,” can facilitate documentation of comprehensive histories. The American Society of Clinical Oncology also has identified some key elements of an adequate family history for assessing cancer risk, including first- and second-degree relatives, maternal and paternal sides, European Jewish ancestry, age of onset and type of cancer, and results of predisposition tests in any relative.

There are several indicators for the presence of hereditary cancer syndromes, including cancer diagnosed at an unusually young age, the presence of several different types of cancer, several close relatives with the same type of cancer, unusual presentation (such as breast cancer in a man), certain birth defects (such as skin growths or skeletal abnormalities associated with inherited cancer syndromes), and Ashkenazi Jewish ancestry.

The ACOG committee opinion identifies common hereditary cancer syndromes involved in gynecologic cancers, including hereditary breast and ovarian cancer syndrome and Lynch, Li-Fraumeni, Cowden, and Peutz-Jeghers syndromes.

Mutations in DNA repair genes BRCA1 and BRCA2 cause hereditary breast and ovarian cancer syndrome and account for 5%-15% of all breast and ovarian cancers in the United States. The carrier frequency in the general population is 1 in 500, but it is much higher (1 in 40) in the Ashkenazi Jewish population. Women with hereditary breast and ovarian cancer syndrome have a 65%-74% lifetime risk of breast cancer and 39%-46% (BRCA1) or 12%-20% (BRCA2) risk of ovarian cancer.

Also caused by DNA repair defects, Lynch syndrome, or hereditary nonpolyposis colorectal cancer, has a prevalence of 1 in 600 to 1 in 3,000. Individuals with Lynch syndrome have increased risk of colon (52%-82%), endometrial (25%-60%), and ovarian (4%-24%) cancers. Malignancies associated with Lynch syndrome include uterine, gastric, small bowel, hepatobiliary, breast, brain, and sebaceous skin cancers.

The presence of Li-Fraumeni syndrome increases the risk of osteosarcoma, breast cancer, colon cancer, adrenocortical carcinoma, leukemia and lymphoma, and brain cancer. Caused by mutations in the tumor suppressor gene TP53, individuals with the syndrome have a 90% risk of cancer by age 60 years. Patients diagnosed with a Li-Fraumeni syndrome–associated malignancy should be referred to a cancer genetics specialist for counseling, according to the committee opinion.

Individuals with the relatively rare (1 in 200,000) Cowden syndrome usually have pathognomonic skin lesions, including papillomatous papules on the face and mucous membranes, by age 30 years. The presence of Cowden syndrome increases the lifetime risk of breast cancer to 25%-50% and endometrial cancer to 5%-10%. Clinicians should consult frequently updated guidelines to determine which patients should be referred for genetic evaluation.

Mutations in serine/threonine kinase 11 cause Peutz-Jehgers syndrome. Two of the following three criteria characterize the syndrome: two or more hamartomatous polyps in the GI tract; mucocutaneous hyperpigmentation of the mouth, lips, nose, eyes, genitalia, or fingers; and a family history of Peutz-Jeghers syndrome. Women with Peutz-Jeghers syndrome have a 50% increased lifetime risk of breast cancer and increased risk of ovarian, uterine, and cervical cancer.