Diseases Involving the Lung Peribronchovascular Region: A CT Imaging Pathologic Classification.

TOPIC IMPORTANCE: Chest CT imaging holds a major role in the diagnosis of lung diseases, many of which affect the peribronchovascular region. Identification and categorization of peribronchovascular abnormalities on CT imaging can assist in formulating a differential diagnosis and directing further diagnostic evaluation. REVIEW FINDINGS: The peribronchovascular region of the lung encompasses the pulmonary arteries, airways, and lung interstitium. Understanding disease processes associated with structures of the peribronchovascular region and their appearances on CT imaging aids in prompt diagnosis. This article reviews current knowledge in anatomic and pathologic features of the lung interstitium composed of intercommunicating prelymphatic spaces, lymphatics, collagen bundles, lymph nodes, and bronchial arteries; diffuse lung diseases that present in a peribronchovascular distribution; and an approach to classifying diseases according to patterns of imaging presentations. Lung peribronchovascular diseases can appear on CT imaging as diffuse thickening, fibrosis, masses or masslike consolidation, ground-glass or air space consolidation, and cysts, acknowledging some disease may have multiple presentations. SUMMARY: A category approach to peribronchovascular diseases on CT imaging can be integrated with clinical features as part of a multidisciplinary approach for disease diagnosis.

Health-related quality of life in patients with newly diagnosed advanced ovarian cancer treated with niraparib vs placebo: Results from the phase 3 randomized PRIMA/ENGOT-OV26/GOG-3012 trial.

OBJECTIVE: To assess patient-reported health-related quality of life (HRQoL) in patients with ovarian cancer (OC) who received niraparib as first-line maintenance therapy. METHODS: PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) enrolled patients with newly diagnosed advanced OC who responded to first-line platinum-based chemotherapy. Patients were randomized (2:1) to niraparib or placebo once daily in 28-day cycles until disease progression, intolerable toxicity, or death. HRQoL was assessed as a prespecified secondary end point using patient-reported responses to the European Organisation for Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C30), the EORTC QLQ Ovarian Cancer Module (EORTC QLQ-OV28), the Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI), and EQ-5D-5L questionnaires. Assessments were collected at baseline and every 8 weeks (±7 days) for 56 weeks, beginning on cycle 1/day 1, then every 12 weeks (±7 days) thereafter while the patient received study treatment. RESULTS: Among trial participants (niraparib, n = 487; placebo, n = 246), PRO adherence exceeded 80% for all instruments across all cycles. Patients reported no decline over time in HRQoL measured via EORTC QLQ-C30 Global Health Status/QoL and FOSI overall scores. Scores for abdominal/gastrointestinal symptoms (EORTC QLQ-OV28) and nausea and vomiting, appetite loss, and constipation (EORTC QLQ-C30) were higher (worse symptoms) in niraparib-treated patients than placebo-treated patients; except for constipation, these differences resolved over time. Patients did not self-report any worsening from baseline of fatigue, headache, insomnia, or abdominal pain on questionnaires. CONCLUSIONS: Despite some early, largely transient increases in gastrointestinal symptoms, patients with OC treated with niraparib first-line maintenance therapy reported no worsening in overall HRQoL.

Internal iliac artery aneurysm masquerading as a sciatic nerve schwannoma: illustrative case.

BACKGROUND: Schwannomas are common peripheral nerve sheath tumors. Imaging techniques such as magnetic resonance imaging (MRI) and computed tomography (CT) can help to distinguish schwannomas from other types of lesions. However, there have been several reported cases describing the misdiagnosis of aneurysms as schwannomas. OBSERVATIONS: A 70-year-old male with ongoing pain despite spinal fusion surgery underwent MRI. A lesion was noted along the left sciatic nerve, which was believed to be a sciatic nerve schwannoma. During the surgery for planned neurolysis and tumor resection, the lesion was noted to be pulsatile. Electromyography mapping and intraoperative ultrasound confirmed vascular pulsations and turbulent flow within the aneurysm, so the surgery was aborted. A formal CT angiogram revealed the lesion to be an internal iliac artery (IIA) branch aneurysm. The patient underwent coil embolization with complete obliteration of the aneurysm. LESSONS: The authors report the first case of an IIA aneurysm misdiagnosed as a sciatic nerve schwannoma. Surgeons should be aware of this potential misdiagnosis and potentially use other imaging modalities to confirm the lesion before proceeding with surgery.

Temporal Trends and Contemporary Regional Variation in Management of Patients Undergoing Carotid Endarterectomy.

INTRODUCTION: The purpose of this study is to investigate regional variation and temporal trends in seven quality metrics amongst CEA patients: discharge on antiplatelet after CEA; discharge on statin after CEA; protamine administration during CEA; patch placement at conventional CEA site; continued statin usage at the time of most recent follow-up; continued antiplatelet usage at the time of most recent follow-up; and smoking cessation at the time of long term follow up. METHODS: There are 19 de-identified regions within the VQI database in the United States. Patients were placed into one of three temporal eras based on the time of their CEA: 2003-2008; 2009-2015; and 2016-2022. We first investigated temporal trends across the seven quality metrics for all regions combined on a national basis. The percentage of patients in each time era with the presence/absence of each metric was identified. Chi-squared testing was performed to confirm statistical significance of the differences across eras. Next, analysis was performed within each region and within each time metric. We separated out the 2016-2022 patients within each region to serve as the status of each metric application in the most modern era. We then compared the frequency of metric non-adherence in each region utilizing Chi-squared testing. RESULTS: There was statistically significant improvement in achievement of all seven metrics between the initial 2003-2008 era and the modern 2016-2022 era. The most marked change in practice pattern was noted for lack of protamine usage at surgery (decreased from 48.7% to 25.9%), discharge home postoperatively without statin (decreased from 50.6% to 15.3%), and lack of statin usage confirmed at time of most recent long term follow up (decreased from 24% to 8.9%). Significant regional variation exists across all metrics (P < .01 for all). Lack of patch placement at the time of conventional endarterectomy ranges from 1.9% to 17.8% across regions in the modern era. Lack of protamine utilization ranges from 10.8% to 49.7%. Lack of antiplatelet and statin at the time of discharge varies from 5.5% to 8.2% and 4.8% to 14.4% respectively. Adherence to the various measures at the time of most recent follow up are more tightly aligned across regions with ranges of: 5.3% to 7.5% for lack of antiplatelet usage; 6.6% to 11.7% lack of statin utilization; and 13.3 to 15.4% for persistent smoking. CONCLUSIONS: Prior studies and societal initiatives on CEA documenting the beneficial effects of patch angioplasty, protamine use at surgery, smoking cessation, antiplatelet utilization and statin compliance have positively impacted adherence to these measures over time. In the modern 2016-2022 era the widest regional variation is noted in patch placement, protamine utilization and discharge medications allowing individual geographic areas to identify areas for potential improvement via internal VQI administrative feedback.

Carboplatin dosing in the treatment of ovarian cancer: An NRG oncology group study.

OBJECTIVE: To determine the effects of using National Comprehensive Cancer Network (NCCN) guidelines to estimate renal function on carboplatin dosing and explore adverse effects associated with a more accurate estimation of lower creatinine clearance (CrCl). METHODS: Retrospective data were obtained for 3830 of 4312 patients treated on GOG182 (NCT00011986)-a phase III trial of platinum-based chemotherapy for advanced-stage ovarian cancer. Carboplatin dose per patient on GOG182 was determined using the Jelliffe formula. We recalculated CrCl to determine dosing using Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault (with/without NCCN recommended modifications) formulas. Associations between baseline CrCl and toxicity were described using the area under the receiver operating characteristic curve (AUC). Sensitivity and positive predictive values described the model's ability to discriminate between subjects with/without the adverse event. RESULTS: AUC statistics (range, 0.52-0.64) showed log(CrClJelliffe) was not a good predictor of grade ≥3 adverse events (anemia, thrombocytopenia, febrile neutropenia, auditory, renal, metabolic, neurologic). Of 3830 patients, 628 (16%) had CrCl <60 mL/min. Positive predictive values for adverse events ranged from 1.8%-15%. Using the Cockcroft-Gault, Cockcroft-Gault with NCCN modifications, and MDRD (instead of Jelliffe) formulas to estimate renal function resulted in a >10% decrease in carboplatin dosing in 16%, 32%, and 5.2% of patients, respectively, and a >10% increase in carboplatin dosing in 41%, 9.6% and 12% of patients, respectively. CONCLUSION: The formula used to estimate CrCl affects carboplatin dosing. Estimated CrCl <60 mL/min (by Jelliffe) did not accurately predict adverse events. Efforts continue to better predict renal function. Endorsing National Cancer Institute initiatives to broaden study eligibility, our data do not support a minimum threshold CrCl <60 mL/min as an exclusion criterion from clinical trials.

The effect of older age on treatment outcomes in women with advanced ovarian cancer receiving chemotherapy: An NRG-Oncology/Gynecologic Oncology Group (GOG-0182-ICON5) ancillary study.

OBJECTIVE: To assess the effect of age on overall survival (OS) in women with ovarian cancer receiving chemotherapy. Secondary objectives were to describe the effect of age on treatment compliance, toxicities, progression free survival (PFS), time from surgery to chemotherapy, and rates of optimal cytoreduction. METHODS: Women enrolled in GOG 0182-ICON5 with stage III or IV epithelial ovarian cancer (EOC) who underwent surgery and chemotherapy between 2001 and 2004 were included. Patients were divided into ages <70 and ≥ 70 years. Baseline characteristics, treatment compliance, toxicities, and clinical outcomes were compared. RESULTS: We included a total of 3686 patients, with 620 patients (16.8%) ≥ 70 years. OS was 37.2 months in older compared to 45.0 months in younger patients (HR 1.21, 95% CI, 1.09-1.34, p < 0.001). Older patients had an increased risk of cancer-specific-death (HR 1.16, 95% CI, 1.04-1.29) as well as non-cancer related deaths (HR 2.78, 95% CI, 2.00-3.87). Median PFS was 15.1 months in older compared to 16.0 months in younger patients (HR 1.10, 95% CI, 1.00-1.20, p = 0.056). In the carboplatin/paclitaxel arm, older patients were just as likely to complete therapy and more likely to develop grade ≥ 2 peripheral neuropathy (35.7 vs 19.7%, p < 0.001). Risk of other toxicities remained equal between groups. CONCLUSIONS: In women with advanced EOC receiving chemotherapy, age ≥ 70 was associated with shorter OS and cancer specific survival. Older patients receiving carboplatin and paclitaxel reported higher rates of grade ≥ 2 neuropathy but were not more likely to suffer from other chemotherapy related toxicities. Clintrials.gov: NCT00011986.

Crohn's disease phenotype analysis with iodine density from dual-energy CT enterography.

PURPOSE: To compare dual-source dual-energy CT enterography (dsDECTE) obtained iodine density (I) (mg/mL) and I normalized to the aorta (I%) with Crohn's disease (CD) phenotypes defined by the SAR-AGA small bowel CD consensus statement. METHODS: Fifty CD patients (31 male, 19 female; mean [SD] age: 50.4 [15.2] years) who underwent dsDECTE were retrospectively identified. Two abdominal radiologists assigned CD phenotypes: no active inflammation (group-2), active inflammation without (group-3) or with luminal narrowing (group-4), stricture with active inflammation (group-5), stricture without active inflammation (group-1), and penetrating disease (group-6). Semiautomatic prototype software was used to determine the median I and I% of CD-affected small bowel mucosa for each patient. The means of the I and I% medians were compared among 4 groups ("1 + 2", "3 + 4", "5", "6") using one-way ANOVA (significance level 0.05 for each outcome) for each outcome individually followed by Tukey's range test for pairwise comparisons with adjusted p-values (overall alpha = 0.05). RESULTS: Mean [SD] I was 2.14 [1.07] mg/mL for groups 1 + 2 (n = 16), 3.54 [1.71] mg/mL for groups 3 + 4 (n = 15), 5.5 [3.27] mg/mL for group- "5" (n = 9), and 3.36 [1.43] mg/mL for group-"6" (n = 10) (ANOVA p = .001; group "1 + 2" versus "5" adj-p = .0005). Mean [SD] I% was 21.2 [6.13]% for groups 1 + 2, 39.47 [9.71]% for groups 3 + 4, 40.98 [11.76]% for group-5, and 35.01 [7.58]% for group-6 (ANOVA p < .0001; groups "1 + 2" versus "3 + 4" adj-p < .0001, group "1 + 2" versus "5" adj-p < .0001, and groups "1 + 2" versus "6" adj-p = .002). CONCLUSION: Iodine density obtained from dsDECTE significantly differed among CD phenotypes defined by SAR-AGA, with I (mg/mL) increasing with phenotype severity and decreasing for penetrating disease. I and I% can be used to phenotype CD.

Lifestyle intervention in ovarian cancer enhanced survival (LIVES) study (NRG/GOG0225): Recruitment, retention and baseline characteristics of a randomized trial of diet and physical activity in ovarian cancer survivors.

OBJECTIVE: The Lifestyle Intervention for oVarian cancer Enhanced Survival (LIVES) is a national study of a combined diet and physical activity intervention for stage II-IV ovarian cancer survival, an under-represented cancer in lifestyle behavioral intervention research. Here, we present the data on recruitment, retention, and baseline demographic, clinical and lifestyle behavior characteristics of the LIVES study participants. METHODS: The LIVES study (NRG Oncology/GOG 0225) is a Phase III diet plus physical activity intervention trial testing the hypothesis that ovarian cancer survivors in the lifestyle intervention will demonstrate better progression-free survival than those in the control condition. Study interventions were delivered via centralized telephone-based health coaching. Baseline descriptive statistics were computed for demographic, clinical, and lifestyle behavior characteristics. RESULTS: The LIVES study exceeded its recruitment goals, enrolling 1205 ovarian cancer survivors from 195 NRG/NCORP-affiliated oncology practices across 49 states from 2012 to 2018. The mean age of enrollees was 59.6 years; the majority (69.4%) with stage III disease; 89% White, 5.5% Hispanic; 64% overweight/obese. Baseline self-reported diet showed a mean daily intake of 6.6 servings of fruit and vegetables, 62.7 fat grams, and 21.7 g of fiber. Physical activity averaged 13.0 MET-hours/week of moderate to vigorous physical activity; 50.9 h/week of sedentary time. Retention rates exceeded 88%. CONCLUSION: The LIVES study demonstrates efficiency in recruiting and retaining ovarian cancer survivors in a 24-month study of diet and physical activity intervention with a primary endpoint of progression free survival that will be reported. TRIAL REGISTRATION: ClinicalTrials.govNCT00719303.

Beyond Sedlis-A novel histology-specific nomogram for predicting cervical cancer recurrence risk: An NRG/GOG ancillary analysis.

PURPOSE: The Sedlis criteria define risk factors for recurrence warranting post-hysterectomy radiation for early-stage cervical cancer; however, these factors were defined for squamous cell carcinoma (SCC) at an estimated recurrence risk of ≥30%. Our study evaluates and compares risk factors for recurrence for cervical SCC compared with adenocarcinoma (AC) and develops histology-specific nomograms to estimate risk of recurrence and guide adjuvant treatment. METHODS: We performed an ancillary analysis of GOG 49, 92, and 141, and included stage I patients who were surgically managed and received no neoadjuvant/adjuvant therapy. Multivariable Cox proportional hazards models were used to evaluate independent risk factors for recurrence by histology and to generate prognostic histology-specific nomograms for 3-year recurrence risk. RESULTS: We identified 715 patients with SCC and 105 with AC; 20% with SCC and 17% with AC recurred. For SCC, lymphvascular space invasion (LVSI: HR 1.58, CI 1.12-2.22), tumor size (TS ≥4 cm: HR 2.67, CI 1.67-4.29), and depth of invasion (DOI; middle 1/3, HR 4.31, CI 1.81-10.26; deep 1/3, HR 7.05, CI 2.99-16.64) were associated with recurrence. For AC, only TS ≥4 cm, was associated with recurrence (HR 4.69, CI 1.25-17.63). For both histologies, there was an interaction effect between TS and LVSI. For those with SCC, DOI was most associated with recurrence (16% risk); for AC, TS conferred a 15% risk with negative LVSI versus a 25% risk with positive LVSI. CONCLUSIONS: Current treatment standards are based on the Sedlis criteria, specifically derived from data on SCC. However, risk factors for recurrence differ for squamous cell and adenocarcinoma of the cervix. Histology-specific nomograms accurately and linearly represent risk of recurrence for both SCC and AC tumors and may provide a more contemporary and tailored tool for clinicians to base adjuvant treatment recommendations to their patients with cervical cancer.

Circulating Tumor Cells In Advanced Cervical Cancer: NRG Oncology-Gynecologic Oncology Group Study 240 (NCT 00803062).

To isolate circulating tumor cells (CTC) from women with advanced cervical cancer and estimate the impact of CTCs and treatment on overall survival and progression-free survival (PFS). A total of 7.5 mL of whole blood was drawn pre-cycle 1 and 36 days post-cycle 1 from patients enrolled on Gynecologic Oncology Group 0240, the phase III randomized trial that led directly to regulatory approval of the antiangiogenesis drug, bevacizumab, in women with recurrent/metastatic cervical cancer. CTCs (defined as anti-cytokeratin+/anti-CD45- cells) were isolated from the buffy coat layer using an anti-EpCAM antibody-conjugated ferrofluid and rare earth magnet, and counted using a semiautomated fluorescence microscope. The median pre-cycle 1 CTC count was 7 CTCs/7.5 mL whole blood (range, 0-18) and, at 36 days posttreatment, was 4 (range, 0-17). The greater the declination in CTCs between time points studied, the lower the risk of death [HR, 0.87; 95% confidence interval (CI), 0.79-0.95)]. Among patients with high (≥ median) pretreatment CTCs, bevacizumab treatment was associated with a reduction in the hazard of death (HR, 0.57; 95% CI, 0.32-1.03) and PFS (HR, 0.59; 95% CI, 0.36-0.96). This effect was not observed with low (< median) CTCs. CTCs can be isolated from women with advanced cervical cancer and may have prognostic significance. A survival benefit conferred by bevacizumab among patients with high pretreatment CTCs may reflect increased tumor neovascularization and concomitant vulnerability to VEGF inhibition. These data support studying CTC capture as a potential predictive biomarker.

Long term survival outcomes of stage I mucinous ovarian cancer - A clinical calculator predictive of chemotherapy benefit.

OBJECTIVES: To determine the long-term potential benefit of adjuvant chemotherapy in subgroups of high-risk stage I mucinous ovarian cancer patients using a predictive scoring algorithm. METHODS: Data were collected from the National Cancer Database from 2004 to 2014. Based on demographic and surgical characteristics, a novel 10-year survival prognostic scoring system was developed using Cox regression. RESULTS: There were 2041 eligible patients with stage I mucinous ovarian cancer including 1362 (67%) with stage IA/IB disease, 598 (29%) with stage IC disease, and 81 (4%) with stage I disease not otherwise specified. Median age was 52 with a range of 13-90 years old. 737 (36%) patients were treated with adjuvant chemotherapy. Adjuvant chemotherapy was more common in patients with stage IC relative to stage IA/IB disease (69% vs. 21%, P < 0.001) or with poorly-differentiated relative to well-differentiated tumors (69% vs. 23%, P < 0.001). Unadjusted 10-year survival was 81% relative to 79% for patients treated with vs. without chemotherapy, respectively (P = 0.46). Patients were predicted to exhibit a low- or a high-risk of death using a multivariate Cox regression model with age, stage, grade, lymphovascular space invasion and ascites. Risk of death without vs. with adjuvant chemotherapy was similar in low-risk patients (88% vs. 84%; HR = 0.80, 95%CI = 0.56-1.15, P = 0.23) and worse in high-risk patients (51% vs. 74%; HR = 1.58, 95%CI: 1.05-2.38, P = 0.03) with stage I mucinous ovarian cancer. CONCLUSIONS: A predictive scoring algorithm may provide prognostic information on long-term survival and identify high-risk stage I mucinous ovarian cancer patients who might achieve a survival benefit from adjuvant chemotherapy.

Balloon-Assisted Ultrasound-Guided Percutaneous Thrombin Injection of Iatrogenic Femoral Artery Pseudoaneurysms: A Case Report and Description of the Technique.

Ultrasound-guided thrombin injection (UGTI) has emerged as the first-line treatment for moderately sized or persistent pseudoaneurysms (PSAs). Although rare, the most feared complication of UGTI is arterial thrombosis or embolism during the off-label injection of thrombin causing acute limb ischemia requiring emergent surgical intervention. Higher thrombin volume, rapidity of injection, and wide or short-neck PSAs are all thought to increase the risk of arterial thrombosis or embolism during this procedure. For patients with unfavorable PSA anatomy who are high-risk surgical candidates due to their medical comorbidities or active critical illness, balloon-assisted thrombin injection (BATI) has been suggested as a means to potentially reduce the risk of thrombosis or distal embolization associated with UGTI. This minimally invasive technique also decreases the risk of groin wound dehiscence or infection associated with open repair, especially in patients who are morbidly obese or have had prior groin surgery. We report a patient with a complex femoral artery PSA after endovascular intervention who was successfully treated with BATI and describe the procedure in detail.

Single-Arm Phases 1 and 2 Trial of Niraparib in Combination With Pembrolizumab in Patients With Recurrent Platinum-Resistant Ovarian Carcinoma.

IMPORTANCE: Patients with recurrent ovarian carcinoma frequently develop resistance to platinum-based chemotherapy, at which time treatment options become limited. OBJECTIVE: To evaluate the poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor niraparib combined with pembrolizumab in patients with recurrent ovarian carcinoma. DESIGN, SETTING, AND PARTICIPANTS: The TOPACIO/KEYNOTE-162 (Niraparib in Combination With Pembrolizumab in Patients With Triple-Negative Breast Cancer or Ovarian Cancer) trial, an open-label, single-arm phases 1 and 2 study enrolled women with advanced or metastatic triple-negative breast cancer (TNBC) or recurrent ovarian carcinoma, irrespective of BRCA mutation status. Median follow-up was 12.4 months (range, 1.2 to ≥23.0 months). Data were collected from April 15, 2016, through September 4, 2018, with September 4, 2018, as a data cutoff, and analyzed from September 4, 2018, through January 30, 2019. INTERVENTIONS: The recommended phase 2 dose (RP2D) was 200 mg of oral niraparib once daily and 200 mg of intravenous pembrolizumab on day 1 of each 21-day cycle. MAIN OUTCOMES AND MEASURES: The primary objectives of phase 1 were to evaluate dose-limiting toxic effects and establish the RP2D and dosing schedule. The primary objective of phase 2 was to assess objective response rate (ORR; complete plus partial responses). Results from the phase 1 ovarian carcinoma and TNBC cohorts and phase 2 ovarian carcinoma cohort are reported. Because of the similarity in the phase 1 and 2 ovarian carcinoma populations, the data were pooled to perform an integrated efficacy analysis. RESULTS: Fourteen patients (9 with ovarian carcinoma and 5 with TNBC) in phase 1 and 53 patients with ovarian carcinoma in phase 2 were enrolled, for a pooled ovarian carcinoma cohort of 62 patients (median age, 60 years [range, 46-83 years]). In the integrated efficacy phases 1 and 2 ovarian carcinoma population (60 of 62 evaluable patients), ORR was 18% (90% CI, 11%-29%), with a disease control rate of 65% (90% CI, 54%-75%), including 3 (5%) with confirmed complete responses, 8 (13%) with confirmed partial responses, 28 (47%) with stable disease, and 20 (33%) with progressive disease. The ORRs were consistent across subgroups based on platinum-based chemotherapy sensitivity, previous bevacizumab treatment, or tumor BRCA or homologous recombination deficiency (HRD) biomarker status. Median duration of response was not reached (range, 4.2 to ≥14.5 months). At data cutoff, 2 patients with a response and 1 patient with stable disease continued to receive treatment. CONCLUSIONS AND RELEVANCE: Niraparib in combination with pembrolizumab is tolerable, with promising antitumor activity for patients with ovarian carcinoma who have limited treatment options regardless of platinum status, biomarker status, or prior treatment with bevacizumab. Responses in patients without tumor BRCA mutations or non-HRD cancers were higher than expected with either agent as monotherapy. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02657889.

Randomized Trial of Intravenous Versus Intraperitoneal Chemotherapy Plus Bevacizumab in Advanced Ovarian Carcinoma: An NRG Oncology/Gynecologic Oncology Group Study.

PURPOSE: To evaluate the impact of two different intraperitoneal (IP) chemotherapy regimens on progression-free survival (PFS) among women with newly diagnosed advanced ovarian carcinoma. METHODS: Eligible patients were randomly assigned to six cycles of IV paclitaxel 80 mg/m2 once per week with intravenous (IV) carboplatin area under the curve 6 (IV carboplatin) versus IV paclitaxel 80 mg/m2 once per week with IP carboplatin area under the curve 6 (IP carboplatin) versus once every 3 weeks IV paclitaxel 135 mg/m2 over 3 hours day 1, IP cisplatin 75 mg/m2 day 2, and IP paclitaxel 60 mg/m2 day 8 (IP cisplatin). All participants received bevacizumab 15 mg/kg IV every 3 weeks in cycles 2 to 22. RESULTS: A total of 1,560 participants were enrolled and had 84.8 months of follow-up. The median PFS duration was 24.9 months in the IV carboplatin arm, 27.4 months in the IP carboplatin arm, and 26.2 months in the IP cisplatin arm. For the subgroup of 1,380 patients with stage II/III and residual disease of 1 cm or less, median PFS was 26.9 (IV-carboplatin), 28.7 (IP-carboplatin), and 27.8 months (IP cisplatin), respectively. Median PFS for patients with stage II/III and no residual disease was 35.9, 38.8, and 35.5 months, respectively. Median overall survival for all enrolled was 75.5, 78.9, and 72.9 months, respectively, and median overall survival for stage II/III with no gross residual disease was 98.8 months, 104.8 months, and not reached. Mean patient-reported Functional Assessment of Cancer Therapy neurotoxicity scores (Gynecologic Oncology Group) were similar for all arms, but the mean Trial Outcome Index of the Functional Assessment of Cancer Therapy-Ovary scores during chemotherapy were statistically worse in the IP cisplatin arm. CONCLUSION: Compared with the IV carboplatin reference arm, the duration of PFS was not significantly increased with either IP regimen when combined with bevacizumab and was better tolerated than IP cisplatin.

Nomogram for Predicting Individual Survival After Recurrence of Advanced-Stage, High-Grade Ovarian Carcinoma.

OBJECTIVE: To analyze clinical prognostic factors for survival after recurrence of high-grade, advanced-stage ovarian-peritoneal-tubal carcinoma and to develop a nomogram to predict individual survival after recurrence. METHODS: We retrospectively analyzed patients treated in multicenter Gynecologic Oncology Group protocols for stage III and IV ovarian-peritoneal-tubal carcinoma who underwent primary debulking surgery, received chemotherapy with paclitaxel and a platinum compound, and subsequently developed recurrence. Prognostic factors affecting survival were identified and used to develop a nomogram, which was both internally and externally validated. RESULTS: There were 4,739 patients included in this analysis, of whom, 84% had stage III and 16% had stage IV ovarian carcinoma. At a median follow-up of 88.8 months (95% CI 86.2-92.0 months), the vast majority of patients (89.4%) had died. The median survival after recurrence was 21.4 months (95% CI 20.5-21.9 months). Time to recurrence after initial chemotherapy, clear cell or mucinous histology, performance status, stage IV disease, and age were significant variables used to develop a nomogram for survival after recurrence, which had a concordance index of 0.67. The time to recurrence alone accounted for 85% of the prognostic information. Similar results were found for patients who underwent second look laparotomy and had a complete pathologic response or received intraperitoneal chemotherapy. CONCLUSION: For individuals with advanced-stage ovarian carcinoma who recur after standard first-line therapy, estimated survivals after recurrence are closely related to the time to recurrence after chemotherapy and prognostic variables can be used to predict subsequent survival. CLINICAL TRIAL REGISTRATION: ClinialTrials.gov, NCT00002568, NCT00837993, NCT00002717, NCT01074398, and NCT00011986.

A Review of Gynecologic Oncology in the Global Setting: Educating and Training the Next Generation of Women's Health Providers.

IMPORTANCE: Women in low- and middle-income countries (LMICs) are responsible for the stability of their families. Child survival is directly linked to the health and well-being of their mother. Cancer is the leading cause of morbidity and mortality worldwide, and the incidence and mortality for women from cancer are projected to increase over the coming decades. Gynecologic cancer outcomes are improved when women are cared for by a gynecologic oncologist; however, there are limited specialized providers in LMICs. Increasing interest and involvement from specialists in the United States will improve partnerships abroad and the care of women worldwide. OBJECTIVE: To summarize the importance of global gynecologic oncology care and the current data for US trainees in obstetrics and gynecology to participate in clinical and capacity-building opportunities. EVIDENCE ACQUISITION: We performed a PubMed literature search for articles pertaining to the topic of global health education in obstetrics and gynecology and gynecologic oncology specifically. RESULTS: Many obstetric and gynecologic residency programs offer international opportunities, but these are less than those in other specialties and are more frequently focused in obstetrics. Many gynecologic oncology fellowship programs offer international experiences for fellows; however, the time and resources required are limited. Several US and international programs are ongoing to improve capacity building for gynecologic oncology in LMICs with local trainees. CONCLUSIONS AND RELEVANCE: Training and care in gynecologic oncology care worldwide are improving through efforts at multiple levels. Continued efforts are needed to improve US trainee international education and experience.

Laparoscopic Peritoneal Dialysis Surgery is Safe and Effective in Patients with Prior Abdominal Surgery.

BACKGROUND: Despite the lower cost, improved early survival, and preservation of the remaining kidney function, peritoneal dialysis is used by only 8.8% of the dialysis population in the USA. Intraabdominal adhesions reported in 70-90% of patients with prior abdominal surgery (PAS) reduce the peritoneal surface area and may increase the intraoperative and postoperative morbidity. The objective of this study is to evaluate the outcomes of laparoscopic peritoneal dialysis (LPD) catheter placement in patients with and without PAS. METHODS: Patients who had LPD catheters placed between January 2014 and August 2016 were retrospectively reviewed. A Kaplan-Meier analysis was performed to assess the revision-free catheter survival (RFCS) and revision-assisted catheter survival (RACS) between the 2 groups. RESULTS: One hundred forty-two patients had had LPD catheter placed during the study time, 82 (58%) with PAS. Lysis of adhesions (LOA) was required in 26 patients (28%) with PAS. Demographics and comorbidities were similar, but more women had PAS (65% vs. 35%, P < 0.001). Seventeen patients (12%) required revision, with no difference between the 2 groups. Both RFCS and RACS were similar in patients without and with PAS (P = 0.38 and 0.98, respectively). RFCS was 73% vs. 64% at 1 year (no PAS versus PAS) and 62% vs. 51% at 2 years, whereas RACS was 84% vs. 77% at 1 year (no PAS versus PAS) and 69% vs. 68% at 2 years. Only 2 intraoperative complications occurred, namely a superficial liver injury and pelvic hematoma. Three complications (0.02%) occurred within 30 days, namely 1 peritonitis and 2 catheter malfunctions. Overall complication rate was 25%, predominantly poor drainage (17% and 22% for PAS and no PAS, respectively), and there were no differences between the subgroups. No deaths occurred within a year of surgery during the study follow-up. CONCLUSIONS: LPD and LOA can be performed safely in patients with multiple PAS. When possible, LPD catheters should be part of the vascular surgery training armamentarium and offered to patients with PAS.

Evaluation of a Streamlined Oncologist-Led BRCA Mutation Testing and Counseling Model for Patients With Ovarian Cancer.

Purpose There is a growing demand for BRCA1/ 2 mutation ( BRCAm) testing in patients with ovarian cancer; however, the limited number of genetic counselors presents a potential barrier. To facilitate more widespread BRCAm testing in ovarian cancer, pretest counseling by the oncology team could shorten testing turnaround times and ease the pressure on genetic counselors. Patients and Methods The prospective, observational Evaluating a Streamlined Onco-genetic BRCA Testing and Counseling Model Among Patients With Ovarian Cancer (ENGAGE) study evaluated a streamlined, oncologist-led BRCAm testing pathway. The analysis population comprised 700 patients with ovarian cancer at 26 sites in the United States, Italy, and Spain. The primary objectives were to assess turnaround time and, using questionnaires, to evaluate stakeholder satisfaction (patients, oncologists, and geneticists or genetic counselors) with the oncologist-led BRCAm testing pathway. Results The median overall turnaround time was 9.1 weeks (range, 0.9 to 37.1 weeks), with median turnaround times in the United States, Italy, and Spain of 4.1 weeks (range, 0.9 to 37.1 weeks), 20.4 weeks (range, 2.9 to 35.4 weeks), and 12.0 weeks (range, 2.0 to 36.7 weeks), respectively. Patient satisfaction with the oncologist-led BRCAm testing pathway was high, with > 99% of patients expressing satisfaction with pre- and post- BRCAm test counseling. Oncologist satisfaction with the BRCAm testing pathway was also high, with > 80% agreeing that the process for performing BRCAm testing worked well and that counseling patients on BRCAm testing was an efficient use of their time. Oncologists expressed higher levels of satisfaction with the BRCAm testing pathway than did geneticists or genetic counselors. Conclusion The results of the ENGAGE study demonstrate that an oncologist-led BRCAm testing process is feasible in ovarian cancer. Development of local BRCAm testing guidelines similar to the one used in this study could allow faster treatment decisions and better use of resources in the management of patients with ovarian cancer.

Paclitaxel With and Without Pazopanib for Persistent or Recurrent Ovarian Cancer: A Randomized Clinical Trial.

IMPORTANCE: Ovarian cancer is the leading cause of gynecologic cancer deaths in the United States. Pazopanib is an oral, multitarget kinase inhibitor of vascular endothelial growth factor receptors 1, 2, and 3; platelet-derived growth factor receptors α and ß; and proto-oncogene receptor tyrosine kinase (c-KIT). OBJECTIVE: To estimate the progression-free survival (PFS) hazard ratio (HR) of weekly paclitaxel and pazopanib compared with weekly paclitaxel and placebo in women with recurrent ovarian cancer. Secondary objectives included frequency and severity of adverse events, proportion responding, and overall survival (OS) in each arm. Translational research objectives included exploring the association between possible biomarkers and single-nucleotide polymorphisms in vascular endothelial growth factor A, interleukin 8, and hypoxia-inducible factor 1α; and PFS, OS, and proportion responding. DESIGN, SETTING, AND PARTICIPANTS: A randomized, placebo-controlled, double-blind phase 2 study was conducted at 26 participating institutions. Patients were enrolled between December 12, 2011, and April 22, 2013. Data were frozen on August 11, 2014. Participants were patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with 1 to 3 prior regimens and performance status of 0 to 2. One hundred six patients enrolled; 100 were evaluable for toxic effects. INTERVENTIONS: All patients received paclitaxel 80 mg/m2 intravenously on days 1, 8, and 15 every 28 days and were randomized 1:1 to pazopanib 800 mg orally daily or placebo. MAIN OUTCOMES AND MEASURES: The primary end point was PFS. The study was designed to detect a 37.5% reduction in the hazard with 80% power (α = 10%). RESULTS: A total of 106 women (median age [range], 61 [35-87] years; 88 [83%] white) were enrolled. Study arms were well balanced for age, performance status, measurable disease, and prior bevacizumab. Proportion responding was 14 of 44 (31.8%) vs 10 of 44 (22.7%) for pazopanib plus paclitaxel vs paclitaxel alone. Median PFS was 7.5 vs 6.2 months for pazopanib plus paclitaxel vs paclitaxel alone, respectively (HR, 0.84; 90% CI, 0.57-1.22; P = .20). Median OS was 20.7 vs 23.3 months for pazopanib plus paclitaxel vs paclitaxel alone (HR, 1.04; 90% CI, 0.60-1.79; P = .90). Severe hypertension was more common on the pazopanib plus paclitaxel arm (relative risk, 12.0; 95% CI, 1.62-88.84). More patients discontinued treatment on the paclitaxel arm for disease progression (34 of 52 [65.4%] vs 17 of 54 [31.5%]), and more on the pazopanib plus paclitaxel arm for adverse events (20 of 54 [37%] vs 5 of 52 [9.6%]). No association was found between single-nucleotide polymorphisms (interleukin 8 and hypoxia-inducible factor 1α) and OS and proportion responding. Patients with VEGFA CC genotype may be more resistant to weekly paclitaxel than those with the AC or AA genotype, with 1 of 14 (7%), 3 of 15 (20%), and 4 of 8 (50%) responding, respectively. CONCLUSIONS AND RELEVANCE: The combination of pazopanib plus paclitaxel is not superior to paclitaxel in women with recurrent ovarian cancer. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01468909.