Evidence-based prescribing of opioids after laparotomy: A quality-improvement initiative in gynecologic oncology.

Introduction: Across specialties, surgeons over-prescribe opioids to patients after surgery. We aimed to develop and implement an evidence-based calculator to inform post-discharge opioid prescription size for gynecologic oncology patients after laparotomy. Methods: In 2021, open surgical gynecologic oncology patients were called 2-4 weeks after surgery to ask about their home opioid use. This data was used to develop a calculator for post-discharge opioid prescription size using two factors: 1) age of the patient, 2) oral morphine equivalents (OME) used by patients the day before hospital discharge. The calculator was implemented on the inpatient service from 8/21/22 and patients were contacted 2-4 weeks after surgery to again assess their opioid use at home. Results: Data from 95 surveys were used to develop the opioid prescription size calculator and are compared to 95 post-intervention surveys. There was no difference pre- to post-intervention in demographic data, surgical procedure, or immediate postoperative recovery. The median opioid prescription size decreased from 150 to 37.5 OME (p < 0.01) and self-reported use of opioids at home decreased from 22.5 to 7.5 OME (p = 0.05). The refill rate did not differ (12.6 % pre- and 11.6 % post-intervention, p = 0.82). The surplus of opioids our patients reported having at home decreased from 1264 doses of 5 mg oxycodone tabs in the pre-intervention cohort, to 490 doses in the post-intervention cohort, a 61 % reduction. Conclusions: An evidence-based approach for prescribing opioids to patients after laparotomy decreased the surplus of opioids we introduced into our patients' communities without impacting refill rates.

Incorporating low haemoglobin into a risk prediction model for conversion in minimally invasive gynaecologic oncology surgeries.

BACKGROUND: A well-known complication of laparoscopic management of gynaecologic masses and cancers is the need to perform an intraoperative conversion to laparotomy. The purpose of this study was to identify novel patient risk factors for conversion from minimally invasive to open surgeries for gynaecologic oncology operations. METHODS: This was a retrospective cohort study of 1356 patients ≥18 years of age who underwent surgeries for gynaecologic masses or malignancies between February 2015 and May 2020 at a single academic medical centre. Multivariable logistic regression was used to study the effects of older age, higher body mass index (BMI), higher American Society of Anaesthesiologist (ASA) physical status, and lower preoperative haemoglobin (Hb) on odds of converting from minimally invasive to open surgery. Receiver operating characteristic (ROC) curve analysis assessed the discriminatory ability of a risk prediction model for conversion. RESULTS: A total of 704 planned minimally invasive surgeries were included with an overall conversion rate of 6.1% (43/704). Preoperative Hb was lowest for conversion cases, compared to minimally invasive and open cases (11.6 ± 1.9 vs 12.8 ± 1.5 vs 11.8 ± 1.9 g/dL, p<.001). Patients with preoperative Hb <10 g/dL had an adjusted odds ratio (OR) of 3.94 (CI: 1.65-9.41, p=.002) for conversion while patients with BMI ≥30 kg/m2 had an adjusted OR of 2.86 (CI: 1.50-5.46, p=.001) for conversion. ROC curve analysis using predictive variables of age >50 years, BMI ≥30 kg/m2, ASA physical status >2, and preoperative haemoglobin <10 g/dL resulted in an area under the ROC curve of 0.71. Patients with 2 or more risk factors were at highest risk of requiring an intraoperative conversion (12.0%). CONCLUSIONS: Lower preoperative haemoglobin is a novel risk factor for conversion from minimally invasive to open gynaecologic oncology surgeries and stratifying patients based on conversion risk may be helpful for preoperative planning.

Minimally invasive surgery for management of gynaecologic masses (masses that affect the female reproductive organs) is often preferred over more invasive surgery, because it involves smaller surgical incisions and can have overall better recovery time. However, one unwanted complication of minimally invasive surgery is the need to unexpectedly convert the surgery to an open surgery, which entails a larger incision and is a higher risk procedure. In our study, we aimed to find patient characteristics that are associated with higher risk of converting a minimally invasive surgery to an open surgery. Our study identified that lower levels of preoperative haemoglobin, the protein that carries oxygen within red blood cells, is correlated with higher risk for conversion. This new risk factor was used with other known risk factors, including having higher age, higher body mass index, and higher baseline medical complexity to create a model to help surgical teams identify high risk patients for conversion. This model may be useful for surgical planning before and during the operation to improve patient outcomes.

Exploring the relationship between language, postoperative pain, and opioid use.

BACKGROUND: Racial and ethnic disparities in pain management are well documented. Differences in pain assessment and management by language have not been studied in the postoperative setting in gynecologic surgery. OBJECTIVE: This study aimed to investigate the association between language and immediate postoperative pain management by comparing pain assessments and perioperative opioid use in non-English speakers and English speakers. STUDY DESIGN: This was a retrospective cohort study comparing perioperative outcomes between non-English-speaking patients and English-speaking patients who had undergone a gynecologic oncology open surgery between July 2012 and December 2020. The primary language was extracted from the electronic medical record. Opioid use is expressed in oral morphine equivalents. Proportions are compared using chi-square tests, and mean values are compared using 2-sample t tests. Although interpreter services are widely available in our institution, the use of interpreters for any given inpatient-provider interaction is not documented. RESULTS: Between 2012 and 2020, 1203 gynecologic oncology patients underwent open surgery, of whom 181 (15.1%) were non-English speakers and 1018 (84.9%) were English speakers. There was no difference between the 2 cohorts concerning body mass index, surgical risk score, or preoperative opioid use. Compared with the English-speaking group, the non-English-speaking group was younger (57 vs 54 years old, respectively; P<.01) and had lower rates of depression (26% vs 14%, respectively; P<.01) and chronic pain (13% vs 6%, respectively; P<.01). Although non-English-speaking patients had higher rates of hysterectomy than English-speaking patients (80% vs 72%, respectively; P=.03), there was no difference in the rates of bowel resections, adnexal surgeries, lengths of surgery, intraoperative oral morphine equivalents administered, blood loss, use of opioid-sparing modalities, lengths of hospital stay, or intensive care unit admissions. In the postoperative period, compared with English-speaking patients, non-English-speaking patients received fewer oral morphine equivalents per day (31.7 vs 43.9 oral morphine equivalents, respectively; P<.01) and had their pain assessed less frequently (7.7 vs 8.8 checks per day, respectively; P<.01) postoperatively. English-speaking patients received a median of 19.5 more units of oral morphine equivalents daily in the hospital and 205.1 more units of oral morphine equivalents at the time of discharge (P=.02 and P=.04, respectively) than non-English-speaking patients. When controlling for differences between groups and several factors that may influence oral morphine equivalent use, English-speaking patients received a median of 15.9 more units of oral morphine equivalents daily in the hospital cohort and similar oral morphine equivalents at the time of discharge compared with non-English-speaking patients. CONCLUSION: Patients who do not speak English may be at risk of undertreated pain in the immediate postoperative setting. Language barrier, frequency of pain assessments, and provider bias may perpetuate disparity in pain management. Based on this study's findings, we advocate for the use of regular verbal pain assessments with language-concordant staff or medical interpreters for all postoperative patients.

Roadmap to safety: a single center study of evidence-informed approach to placenta accreta spectrum.

Objective: To assess the impact of an evidence-informed protocol for management of placenta accreta spectrum (PAS). Methods: This was a retrospective cohort study of patients who underwent cesarean hysterectomy (c-hyst) for suspected PAS from 2012 to 2022 at a single tertiary care center. Perioperative outcomes were compared pre- and post-implementation of a standardized Multidisciplinary Approach to the Placenta Service (MAPS) protocol, which incorporates evidence-informed perioperative interventions including preoperative imaging and group case review. Intraoperatively, the MAPS protocol includes placement of ureteral stents, possible placental mapping with ultrasound, and uterine artery embolization by interventional radiology. Patients suspected to have PAS on prenatal imaging who underwent c-hyst were included in the analysis. Primary outcomes were intraoperative complications and postoperative complications. Secondary outcomes were blood loss, need for ICU, and length of stay. Proportions were compared using Fisher's exact test, and continuous variables were compared used t-tests and Mood's Median test. Results: There were no differences in baseline demographics between the pre- (n = 38) and post-MAPS (n = 34) groups. The pre-MAPS group had more placenta previa (95% pre- vs. 74% post-MAPS, p = 0.013) and prior cesarean sections (2 prior pre- vs. 1 prior post-MAPS, p = 0.012). The post-MAPS group had more severe pathology (PAS Grade 3 8% pre- vs. 47% post-MAPS, p = 0.001). There were fewer intraoperative complications (39% pre- vs.3% post-MAPS, p < 0.001), postoperative complications (32% pre- vs.12% post-MAPS, p = 0.043), hemorrhages >1l (95% pre- vs.65% post-MAPS, p = 0.001), ICU admissions (59% pre- vs.35% post-MAPS, p = 0.04) and shorter hospital stays (10 days pre- vs.7 days post-MAPS, p = 0.02) in the post-MAPS compared to pre-MAPS patients. Neonatal length of stay was 8 days longer in the post-MAPS group (9 days pre- vs. 17 days post-MAPS, p = 0.03). Subgroup analyses demonstrated that ureteral stent placement and uterine artery embolization (UAE) may be important steps to reduce complications and ICU admissions. When comparing just those who underwent UAE, patients in the post-MAPS group experienced fewer hemorrhages greater five liters (EBL >5l 43% pre- vs.4% post-MAPS, p = 0.007). Conclusion: An evidence-informed approach to management of PAS was associated with decreased complication rate, EBL >1l, ICU admission and length of hospitalization, particularly for patients with severe pathology.

Impact of abnormal uterine bleeding care in premenopausal patients prior to endometrial malignancy diagnosis.

Background: Literature evaluating the management of abnormal uterine bleeding in premenopausal patients prior to endometrial malignancy diagnosis is lacking. Objective: To evaluate predictors and consequences of inadequate evaluation and management of abnormal uterine bleeding and time to endometrial sampling in premenopausal patients prior to endometrial malignancy diagnosis.Study Design.This was a retrospective cohort study of premenopausal individuals with endometrioid endometrial cancer or atypical hyperplasia at a single institution from 2015 to 2020.. Complete noninvasive management encompassed pelvic exam, ultrasound, and progestin treatment before or in conjunction with the endometrial sampling of diagnosis. Multivariable logistic and ordinal odds models were used to evaluate predictors and outcomes. Results: 152 subjects were included, 80.3 % with cancer and 19.7 % with atypical hyperplasia. The majority of patients had anovulatory bleeding, obesityand recent health care. Only 20.4 % had complete nonvinvasive management, and only 12.5 % had complete noninvasive management or endometrial sampling within 2 months of presentation with abnormal bleeding. Class III obesity reduced the likelihood of complete assessment and increased time to sampling, while age 45 and up and parity reduced time to sampling. Most patients had partial workup but no progestin treatment and long intervals before endometrial sampling after presentation to a provider with abnormal bleeding. Incomplete workup correlated to worse cancer grade and stage. Conclusion: Despite high clinical risk and health care contact, most patients had insufficient gynecologic management preceding a diagnosis of endometrial malignancy. Inadequate care correlated to worse oncologic outcomes and demonstrates missed opportunities for early detection and prevention of endometrial cancer.

Same day service: A genetic testing station model to improve germline genetic testing in patients with ovarian cancer.

OBJECTIVE: Genetic testing for ovarian cancer (OC) patients is essential to consideration of PARP inhibitor therapy. To improve access, we piloted a Genetic Testing Station (GTS) allowing patients to have a same-day genetic testing visit facilitated by Genetic Counselor Assistants (GCAs) under the supervision of Genetic Counselors (GCs). METHODS: The GTS was implemented December 2018 and operated through February 2020. Gynecologic Oncologists offered ovarian cancer patients a same-day GTS visit with a GCA. The patient received education via videos designed by GCs and then provided consent, a brief family history, and a sample for a standardized 133-gene panel. Results were provided by a GC. Patients were retrospectively identified by querying the medical record for OC patients seen 12 months prior to and 18 months after GTS implementation. RESULTS: A total of 482 patients pre-GTS were compared to 625 patients post-GTS. Genetic testing increased from 68.5% to 75.4% (p = 0.012) after implementation, primarily in patients with epithelial histologies (80% vs 89% in pre-GTS vs post-GTS, p = 0.005). Time from referral for genetic testing to obtaining results was evaluated in the post-GTS cohort, comparing patients who had traditional counseling to those who utilized the GTS. Time to obtaining results was 21 days in the GTS group (95% CI [10, 34]) compared to 56 days (95% CI [41,76]) in the traditional genetic counseling group. CONCLUSIONS: The GTS reduces barriers to care and facilitates discussion of precision treatment within a timely fashion while optimizing GC clinic time. Access improvement remains integral to improving uptake of genetic testing.

Identification of distinct symptom profiles in patients with gynecologic cancers using a pre-specified symptom cluster.

PURPOSE: Pain, fatigue, sleep disturbance, and depression are four of the most common symptoms in patients with gynecologic cancer. The purposes were to identify subgroups of patients with distinct co-occurring pain, fatigue, sleep disturbance, and depression profiles (i.e., pre-specified symptom cluster) in a sample of patients with gynecologic cancer receiving chemotherapy and assess for differences in demographic and clinical characteristics, as well as the severity of other common symptoms and QOL outcomes among these subgroups. METHODS: Patients completed symptom questionnaires prior to their second or third cycle of chemotherapy. Latent profile analysis was used to identify subgroups of patients using the pre-specified symptom cluster. Parametric and nonparametric tests were used to evaluate for differences between the subgroups. RESULTS: In the sample of 233 patients, two distinct latent classes were identified (i.e., low (64.8%) and high (35.2%)) indicating lower and higher levels of symptom burden. Patients in high class were younger, had child care responsibilities, were unemployed, and had a lower annual income. In addition, these women had a higher body mass index, a higher comorbidity burden, and a lower functional status. Patients in the high class reported higher levels of anxiety, as well as lower levels of energy and cognitive function and poorer quality of life scores. CONCLUSIONS: This study identified a number of modifiable and non-modifiable risk factors associated with membership in the high class. Clinicians can use this information to refer patients to dieticians and physical therapists for tailored interventions.

Changes in Bone Density in Carriers of BRCA1 and BRCA2 Pathogenic Variants After Salpingo-Oophorectomy.

OBJECTIVE: To evaluate the effect of risk-reducing salpingo-oophorectomy (RRSO) on change in bone mineral density (BMD) in women aged 34-50 years with pathogenic variants in BRCA1 or BRCA2 ( BRCA1 /2). METHODS: The PROSper (Prospective Research of Outcomes after Salpingo-oophorectomy) study is a prospective cohort of women aged 34-50 years with BRCA1 or two germline pathogenic variants that compares health outcomes after RRSO to a non-RRSO control group with ovarian conservation. Women aged 34-50 years, who were planning either RRSO or ovarian conservation, were enrolled for 3 years of follow-up. Spine and total hip BMD were measured by dual-energy X-ray absorptiometry (DXA) scans obtained at baseline before RRSO or at the time of enrollment for the non-RRSO group, and then at 1 and 3 years of study follow-up. Differences in BMD between the RRSO and non-RRSO groups, as well as the association between hormone use and BMD, were determined by using mixed effects multivariable linear regression models. RESULTS: Of 100 PROSper participants, 91 obtained DXA scans (RRSO group: 40; non-RRSO group: 51). Overall, total spine, and hip BMD decreased significantly from baseline to 12 months after RRSO (estimated percent change -3.78%, 95% CI -6.13% to -1.43% for total spine; -2.96%, 95% CI -4.79% to -1.14% for total hip) and at 36 months (estimated percent change -5.71%, 95% CI -8.64% to -2.77% for total spine; -5.19%, 95% CI -7.50% to -2.87% for total hip. In contrast, total spine and hip BMD were not significantly different from baseline for the non-RRSO group. The differences in mean percent change in BMD from baseline between the RRSO and non-RRSO groups were statistically significant at both 12 and 36 months for spine BMD (12-month difference -4.49%, 95% CI -7.67% to -1.31%; 36-month difference -7.06%, 95% CI -11.01% to -3.11%) and at 36 months for total hip BMD (12-month difference -1.83%, 95% CI -4.23% to 0.56%; 36-month difference -5.14%, 95% CI -8.11% to -2.16%). Across the study periods, hormone use was associated with significantly less bone loss at both the spine and hip within the RRSO group compared with no hormone use ( P <.001 at both 12 months and 36 months) but did not completely prevent bone loss (estimated percent change from baseline at 36 months -2.79%, 95% CI -5.08% to -0.51% for total spine BMD; -3.93%, 95% CI -7.27% to -0.59% for total hip BMD). CONCLUSION: Women with pathogenic variants in BRCA1 /2 who undergo RRSO before the age of 50 years have greater bone loss after surgery that is clinically significant when compared with those who retain their ovaries. Hormone use mitigates, but does not eliminate, bone loss after RRSO. These results suggest that women who undergo RRSO may benefit from routine screening for BMD changes to identify opportunities for prevention and treatment of bone loss. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT01948609.

Associations Between Distinct State Anxiety Profiles, Exposure to Stressful Life Events, Resilience, and Coping in Patients with Gynecologic Cancers Receiving Chemotherapy.

OBJECTIVES: In a sample of patients with gynecologic cancers who are receiving chemotherapy, subgroups of patients with distinct state anxiety profiles were identified, and differences among the subgroups in demographic and clinical characteristics, stress, exposure to stressful life events, resilience, and coping behaviors were evaluated. DATA SOURCES: Patients (n = 230) completed questionnaires six times over two chemotherapy cycles. State anxiety was measured using the Spielberger State Anxiety Inventory. Subgroups of patients with distinct state anxiety profiles were identified using latent profile analysis. Differences among the classes were assessed using parametric and nonparametric tests. CONCLUSION: Three distinct state anxiety profiles were identified: low (55.2%), moderate (38.3%), and very high (6.5%). Compared with the low class, persons in the other two classes had lower functional status, more comorbidities, higher perceived stress, and lower resilience and were more likely to report a history of depression and to use disengagement coping strategies. Compared with the low class, the very high class was more likely to report childcare responsibilities; have a history of lung disease, stomach disease, or low back pain; have experienced physical neglect, serious money problems, a serious disaster, or foster care; or were a caregiver for someone with a severe disability. IMPLICATIONS FOR NURSING PRACTICE: Nearly 45% of patients reported clinically meaningful levels of state anxiety that persisted over two cycles of chemotherapy. Experiences with a variety of stressors may be risk factors for higher levels of anxiety during chemotherapy. Clinicians need to perform comprehensive social histories and assess for anxiety in patients receiving chemotherapy.

The past, present, and future of opioid prescribing: Perioperative opioid use in gynecologic oncology patients after laparotomy at a single institution from 2012 to 2021.

Objective: To describe the evolution of perioperative opioid management in gynecologic oncology patients after open surgeries and determine current opioid over-prescription rates. Methods: Part one of this two-part study was a retrospective chart review of adult patients who underwent laparotomy by a gynecologic oncologist from July 1, 2012 to June 30, 2021, comparing changes in clinical characteristics, pain management and discharge opioid prescription sizes between fiscal year 2012 (FY2012) and 2020 (FY2020). In part two, we prospectively surveyed patients after laparotomy in 2021 to determine opioid use after hospital discharge. Results: 1187 patients were included in the chart review. Demographic and surgical characteristics remained stable from FY2012 to FY2020 with differences notable for increased rates of interval cytoreductive surgeries for advanced ovarian cancer and decreased rates of full lymph node dissection. Median inpatient opioid use decreased by 62 % from FY2012 to FY2020. Median discharge opioid prescription size was 675 oral morphine equivalents (OME) per patient in FY2012 and decreased by 77.7 % to 150 OME in FY2020. Of 95 surveyed patients in 2021, median self-reported opioid use after discharge was 22.5 OME. Patients had an excess of opioids equivalent to 1331 doses of 5-milligram oxycodone tablets per 100 patients. Conclusion: Inpatient opioid use in our gynecologic oncology open surgical patients and post-discharge opioid prescription size significantly decreased over the last decade. Despite this progress, our current prescribing patterns continue to significantly overestimate patients' actual opioid use after hospital discharge. Individualized point of care tools are needed to determine an appropriate opioid prescription size.

Efficacy and safety of rucaparib treatment in patients with BRCA-mutated, relapsed ovarian cancer: final results from Study 10.

BACKGROUND: Study 10, a four-part Phase 1/2 study, evaluated oral rucaparib monotherapy in patients with advanced solid tumours. Here we report the final efficacy and safety results in heavily pretreated patients with ovarian cancer who received rucaparib in Study 10 Parts 2A and 2B. METHODS: Parts 2A and 2B (Phase 2 portions) enrolled patients with relapsed, high-grade, platinum-sensitive or platinum-resistant, BRCA-mutated ovarian cancer who had received 2-4 (Part 2A) or 3-4 (Part 2B) prior chemotherapies. Patients received oral rucaparib 600 mg twice daily (starting dose). The primary endpoint was the investigator-assessed objective response rate (ORR) by RECIST v1.1. RESULTS: Fifty-four patients were enrolled: 42 in Part 2A (all had platinum-sensitive disease) and 12 in Part 2B (4 with platinum-sensitive disease; 8 with platinum-resistant disease). ORR was 59.3% (95% CI 45.0-72.4%). The median time to onset of the most common nonhaematological treatment-emergent adverse events (TEAEs) was typically early (<56 days) and was later for haematological TEAEs (53-84 days). The median duration of grade ≥3 TEAEs was ≤13 days. CONCLUSIONS: In patients with relapsed, platinum-sensitive or platinum-resistant germline BRCA-mutant high-grade ovarian cancer who had received ≥2 prior chemotherapies, rucaparib had robust antitumour activity with a safety profile consistent with prior reports. CLINICAL TRIAL REGISTRATION: NCT01482715.

NCCN Guidelines® Insights: Ovarian Cancer, Version 3.2022.

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with less than half of patients living >5 years following diagnosis. The NCCN Guidelines for Ovarian Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with ovarian, fallopian tube, and primary peritoneal cancers. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised guidance on alternative chemotherapy regimens for patients with advanced age and/or comorbidities, a new algorithm for recurrent low-grade serous carcinoma based on developing research and novel therapeutic agents, and updated language regarding tumor molecular analysis applications in ovarian cancer.

The role of adjuvant radiation therapy in older patients with node-positive vulvar cancer: A national cancer database analysis.

OBJECTIVE: We sought to evaluate whether the survival benefit of adjuvant radiotherapy in patients with node-positive vulvar cancer is maintained in older patients, who comprise a large subgroup of patients with vulvar cancer. METHODS: The National Cancer Database (NCDB) was queried for patients aged 65 years or older, who were diagnosed with vulvar squamous cell carcinoma from 2004 to 2017 and underwent surgery with confirmed node-positive disease. Statistical analysis was performed with propensity-score matching, chi-square test, log-rank test, Kaplan-Meier, and multivariable Cox proportional regression. RESULTS: A total of 2396 patients were analyzed, and 1517 (63.3%) received adjuvant radiotherapy. Median follow-up was 73 months. Median age at diagnosis was 77 years (range 65-90). In the propensity score-matched cohort, five-year overall survival (OS) was 29%. Five-year OS was 33% in patients who received surgery followed by adjuvant radiotherapy and 26% in patients who received surgery alone (p < 0.0001). Multivariable analysis continued to demonstrate a survival benefit associated with the addition of adjuvant radiotherapy (OR 0.77 [95% CI 0.69-00.87], p < 0.001). Adjuvant radiotherapy was associated with improved OS among patients aged 65-84 (5-year OS 35% vs 29%, p = 0.0004), but not in patients aged 85 years and older (5-year OS 20% vs 19%, p = 0.32). CONCLUSION: This NCDB study suggests that in older patients with node-positive vulvar cancer, radiotherapy continues to be a vital component of multimodality therapy. However, a comprehensive and geriatrics-specific approach is crucial for treating older adults with node-positive vulvar cancer, as the benefit of adjuvant radiotherapy may be compromised by treatment-related morbidity/toxicity.

Homologous Recombination Deficiency and Ovarian Cancer Treatment Decisions: Practical Implications for Pathologists for Tumor Typing and Reporting.

Clinical testing for homologous repair (HR) deficiency (HRD) in ovarian cancers has emerged as a means to tailor the use of poly(ADP-ribose)polymerase (PARP) inhibitor therapy to the patients most likely to respond. The currently available HRD tests evaluate tumor tissue for genomic evidence of impairment of the HR pathway of DNA damage repair, which, if present, renders the tumor vulnerable to PARP inhibitors in conjunction with platinum chemotherapy. Germline or somatic mutation of BRCA1/2 is a major contributor HRD. Thus, tubo-ovarian/peritoneal high-grade serous carcinoma (HGSC) is enriched by HRD. After highlighting the general concepts underlying HRD testing and PARP inhibitor therapy, this review discusses practical roles for pathologists to maximize the opportunities for eligible patients with ovarian cancer to benefit from HRD testing, chiefly by applying contemporary diagnostic criteria for ovarian cancer tumor typing and navigating through potential pitfalls of tumor types that may mimic HGSC but are unlikely to harbor HRD.

Better late than never: Brachytherapy is more important than timing in treatment of locally advanced cervical cancer.

PURPOSE: To evaluate the utilization of brachytherapy and duration of treatment on overall survival for locally advanced cervical cancer. METHODS: The National Cancer Database (NCDB) was queried to identify stage II-IVA cervical cancer patients diagnosed in the United States between 2004 and 2015 who were treated with definitive chemoradiation therapy. We defined standard of care (SOC) treatment as receiving external beam radiation therapy (EBRT) and concurrent chemotherapy, brachytherapy (BT), and completing treatment within 8 weeks, and compared SOC treatment to non-SOC. The primary outcome was overall survival (OS). We also evaluated the effect of sociodemographic and clinical variables on receiving SOC. RESULTS: We identified 10,172 women with locally advanced cervical cancer primarily treated with chemotherapy and concurrent EBRT of which 6047 (59.4%) patients received brachytherapy, and only 2978 (29.3%) completed treatment within 8 weeks (SOC). Receipt of SOC was associated with significantly improved overall survival (median OS 131.0 mos vs 95.5 mos, 78.1 mos, 49.2 mos; p < 0.0001). Furthemore, in patients whose treatment extended beyond 8 weeks, brachytherapy was still associated with an improved survival (median OS 95.5 vs 49.2 mos, p < 0.0001). More advanced stage, Non-Hispanic Black race, lower income, lack of insurance or government insurance, less education, and rural residence were associated with decreased likelihood of receiving SOC. CONCLUSIONS: Completing standard of care concurrent chemoradiation therapy and brachytherapy in the recommended 8 weeks was associated with a superior overall survival. Patients who received brachytherapy boost show superior survival to patients receiving EBRT alone, regardless of treatment duration. Disparities in care for vulnerable populations highlight the challenges and importance of care coordination for patients with cervical cancer.

Stability of Symptom Clusters in Patients With Gynecologic Cancer Receiving Chemotherapy.

BACKGROUND: Patients with gynecologic cancer undergoing chemotherapy experience multiple co-occurring symptoms. Understanding how symptom clusters change over time is essential to the development of interventions that target multiple co-occurring symptoms. OBJECTIVE: The aim of this study was to assess the relative stability of symptom clusters across a chemotherapy cycle in patients with gynecologic cancer. METHODS: This is a longitudinal, descriptive study. Eligible patients (n = 232) were English-speaking adults (≥18 years old) with gynecologic cancer. Data were collected in the week before patients' second or third cycle of chemotherapy (T1) and at 1 (T2) and 2 (T3) weeks after chemotherapy. Three dimensions of the symptom experience (occurrence, severity, and distress) were assessed using a modified version of the Memorial Symptom Assessment Scale. Symptom clusters for each dimension and time point were identified through exploratory factor analysis. RESULTS: A 5-factor solution was selected for each exploratory factor analysis. Hormonal, respiratory, and weight change clusters were identified across all dimensions and time points. A psychological symptom cluster was identified at T1 for occurrence and severity and at T2 and T3 for all 3 dimensions. A gastrointestinal symptom cluster was identified at T1 for occurrence and at T2 and T3 for all 3 dimensions. The hormonal, respiratory, psychological, and weight change symptom clusters exhibited common symptoms across dimensions and time points. CONCLUSIONS: Hormonal, respiratory, weight change, and psychological symptom clusters are relatively stable across a cycle of chemotherapy in patients with gynecologic cancer. IMPLICATIONS FOR PRACTICE: Clinicians need to assess patients for multiple co-occurring symptoms and initiate multimodal interventions.

Adavosertib with Chemotherapy in Patients with Primary Platinum-Resistant Ovarian, Fallopian Tube, or Peritoneal Cancer: An Open-Label, Four-Arm, Phase II Study.

PURPOSE: This study assessed the efficacy, safety, and pharmacokinetics of adavosertib in combination with four chemotherapy agents commonly used in patients with primary platinum-resistant ovarian cancer. PATIENTS AND METHODS: Women with histologically or cytologically confirmed epithelial ovarian, fallopian tube, or peritoneal cancer with measurable disease were enrolled between January 2015 and January 2018 in this open-label, four-arm, multicenter, phase II study. Patients received adavosertib (oral capsules, 2 days on/5 days off or 3 days on/4 days off) in six cohorts from 175 mg once daily to 225 mg twice daily combined with gemcitabine, paclitaxel, carboplatin, or pegylated liposomal doxorubicin. The primary outcome measurement was overall response rate. RESULTS: Three percent of patients (3/94) had confirmed complete response and 29% (27/94) had confirmed partial response. The response rate was highest with carboplatin plus weekly adavosertib, at 66.7%, with 100% disease control rate, and median progression-free survival of 12.0 months. The longest median duration of response was in the paclitaxel cohort (12.0 months). The most common grade ≥3 adverse events across all cohorts were neutropenia [45/94 (47.9%) patients], anemia [31/94 (33.0%)], thrombocytopenia [30/94 (31.9%)], and diarrhea and vomiting [10/94 (10.6%) each]. CONCLUSIONS: Adavosertib showed preliminary efficacy when combined with chemotherapy. The most promising treatment combination was adavosertib 225 mg twice daily on days 1-3, 8-10, and 15-17 plus carboplatin every 21 days. However, hematologic toxicity was more frequent than would be expected for carboplatin monotherapy, and the combination requires further study to optimize the dose, schedule, and supportive medications.

NCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 1.2021.

Identifying individuals with hereditary syndromes allows for timely cancer surveillance, opportunities for risk reduction, and syndrome-specific management. Establishing criteria for hereditary cancer risk assessment allows for the identification of individuals who are carriers of pathogenic genetic variants. The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal provides recommendations for the assessment and management of patients at risk for or diagnosed with high-risk colorectal cancer syndromes. The NCCN Genetic/Familial High-Risk Assessment: Colorectal panel meets annually to evaluate and update their recommendations based on their clinical expertise and new scientific data. These NCCN Guidelines Insights focus on familial adenomatous polyposis (FAP)/attenuated familial adenomatous polyposis (AFAP) syndrome and considerations for management of duodenal neoplasia.

Survival impact of bowel resection at the time of interval cytoreductive surgery for advanced ovarian cancer.

OBJECTIVES: To evaluate the impact of bowel resection at the time of interval cytoreductive surgery on survival. METHODS: We identified patients with advanced ovarian cancer who underwent neoadjuvant chemotherapy and interval cytoreductive surgery between 2008 and 2018 from a single-institution tumor registry. Kaplan-Meier survival analysis and Cox proportional hazards models were performed comparing patients who underwent bowel resection to those who did not. RESULTS: Of 158 patients, 43 (27%) underwent bowel resection. Rates of optimal (95%) and sub-optimal (5%) resection did not differ with bowel resection. Patients that required bowel resection had worse three-year survival (43% vs. 63%), even after adjusting for confounding variables of age, stage, number of neoadjuvant cycles, R0 resection, and ASA score (HR 2.27, p < 0.01). Adjusted progression-free survival did not differ between groups (HR 0.92, p = 0.72). Patients who underwent bowel resection were more likely to require blood transfusion (p < 0.01), and have a longer hospital stay (5 days vs 7.5 days, p < 0.01). CONCLUSIONS: Bowel resection at the time of interval cytoreduction confers a greater than 2-fold increased risk of mortality and does not impact progression-free survival. Long-term sequelae of the peri-operative morbidity of bowel resection may contribute to increased mortality, and bowel resection may be a surrogate for disease biology with poor prognosis.