NRG-CC004 ancillary data study-exploring the effect of bupropion on sexual desire in female cancer survivors with and without vulvovaginal symptoms.

BACKGROUND: Female cancer survivors often experience estrogen-deprivation symptoms, which may lead to decreases in sexual desire, vulvovaginal health (lubrication, dryness, discomfort), and sexual satisfaction. Interventions are needed to address these concerns. AIM: The objective of this secondary analysis was to determine if women with higher (better) scores on the Female Sexual Function Index (FSFI) lubrication and pain subscales reported higher desire scores based on treatment with bupropion vs placebo. METHODS: Participants were part of NRG Oncology's NRG-CC004 (NCT03180294), a randomized placebo-controlled clinical trial evaluating bupropion (150 vs 300 mg) to improve sexual desire in survivors of breast or gynecologic cancer. All participants with baseline data from the FSFI lubrication, pain, and desire subscales with 5- and/or 9-week data were analyzed. The FSFI subscale scores were correlated using Spearman correlation coefficients. Logistic regression was used to determine associations between FSFI desire and other FSFI subscales while accounting for treatment arm and other covariates. OUTCOMES: The primary outcome of NRG Oncology's NRG-CC004 (NCT03180294) randomized phase II dose-finding trial was change from baseline to 9 weeks on the FSFI desire subscale score. Similar to the parent study, the primary outcome for this ancillary data study was the FSFI desire subscale score at 5 and 9 weeks. RESULTS: Overall, 230 participants completed the FSFI at baseline and 189 at 9 weeks. The strongest correlations were between lubrication and pain at baseline (all participants, rho = 0.77; bupropion arms, rho = 0.82), week 5 (all participants, rho = 0.71; bupropion arms, rho = 0.68), and week 9 (all participants, rho = 0.75; bupropion arms, rho = 0.78), and the weakest correlations were between desire and pain. In patients in the treatment arms there were no interactions between lubrication or pain.The impact of various covariates on the FSFI score for desire at 9 weeks demonstrated that participants of non-White race (odds ratio [OR], 0.42; 95% CI, 0.21-0.81; P = .010), with a high lubrication score (OR, 0.36; 95% CI, 0.21-0.61; P = .0002), with a high pain score (less pain) (OR, 0.50; 95% CI, 0.29-0.87; P = .014), or with prior pelvic surgery (OR, 0.38; 95% CI, 0.23-0.63; P = .0002) had lower odds of having low desire. CLINICAL IMPLICATIONS: Acute estrogen-deprivation symptoms should be addressed prior to sexual desire intervention. STRENGTHS AND LIMITATIONS: This secondary analysis was not powered to examine all variables. CONCLUSION: Lubrication and pain were predictors of low desire. Therefore, vulvovaginal atrophy and associated genitourinary symptoms of menopause such as vaginal dryness and dyspareunia should be addressed prior to or in parallel with interventions for sexual desire.

Veliparib with First-Line Chemotherapy and as Maintenance Therapy in Ovarian Cancer.

BACKGROUND: Data are limited regarding the use of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors, such as veliparib, in combination with chemotherapy followed by maintenance as initial treatment in patients with high-grade serous ovarian carcinoma. METHODS: In an international, phase 3, placebo-controlled trial, we assessed the efficacy of veliparib added to first-line induction chemotherapy with carboplatin and paclitaxel and continued as maintenance monotherapy in patients with previously untreated stage III or IV high-grade serous ovarian carcinoma. Patients were randomly assigned in a 1:1:1 ratio to receive chemotherapy plus placebo followed by placebo maintenance (control), chemotherapy plus veliparib followed by placebo maintenance (veliparib combination only), or chemotherapy plus veliparib followed by veliparib maintenance (veliparib throughout). Cytoreductive surgery could be performed before initiation or after 3 cycles of trial treatment. Combination chemotherapy was 6 cycles, and maintenance therapy was 30 additional cycles. The primary end point was investigator-assessed progression-free survival in the veliparib-throughout group as compared with the control group, analyzed sequentially in the BRCA-mutation cohort, the cohort with homologous-recombination deficiency (HRD) (which included the BRCA-mutation cohort), and the intention-to-treat population. RESULTS: A total of 1140 patients underwent randomization. In the BRCA-mutation cohort, the median progression-free survival was 34.7 months in the veliparib-throughout group and 22.0 months in the control group (hazard ratio for progression or death, 0.44; 95% confidence interval [CI], 0.28 to 0.68; P<0.001); in the HRD cohort, it was 31.9 months and 20.5 months, respectively (hazard ratio, 0.57; 95 CI, 0.43 to 0.76; P<0.001); and in the intention-to-treat population, it was 23.5 months and 17.3 months (hazard ratio, 0.68; 95% CI, 0.56 to 0.83; P<0.001). Veliparib led to a higher incidence of anemia and thrombocytopenia when combined with chemotherapy as well as of nausea and fatigue overall. CONCLUSIONS: Across all trial populations, a regimen of carboplatin, paclitaxel, and veliparib induction therapy followed by veliparib maintenance therapy led to significantly longer progression-free survival than carboplatin plus paclitaxel induction therapy alone. The independent value of adding veliparib during induction therapy without veliparib maintenance was less clear. (Funded by AbbVie; VELIA/GOG-3005 ClinicalTrials.gov number, NCT02470585.).

Cytological sampling of fallopian tubes using a hysteroscopic catheter: A multi-center study.

OBJECTIVE: To assess the feasibility of a novel hysteroscopic catheter to collect fallopian tube cytologic samples and to correlate cytologic findings with histopathology. METHODS: This was a prospective, multicenter, single-arm pilot study. Women undergoing salpingo-oophorectomy for a pelvic mass suspicious for malignancy or for prevention of cancer for BRCA mutation carriers were recruited from 3 gynecologic oncology centers (October 2016-August 2017). Cytologic samples were collected from the fallopian tube using a novel FDA-cleared hysteroscopic catheter and evaluated by a pathologist blinded to surgical or pathologic findings. The correlation between cytologic results and final surgical pathology was assessed. RESULTS: Of the 50 patients enrolled, 42 were eligible. Hysteroscopies were completed in 40 patients with 78 fallopian tubes, of which 65 ostia (83%) were identified. Of these, 61 (72%) were successfully catheterized resulting in 44 (68%) cytology samples adequate for further evaluation: 5 were classified as positive (3 neoplastic and 2 malignant) and 39 as negative (34 benign and 5 reactive/atypical). A comparison of cytology results with fallopian tube histopathology showed a concordance rate of 95% (42/44). Of the two samples with discordant results, both had positive cytology but negative tubal pathology, and both were stage I ovarian cancers with malignant ovary histology. CONCLUSIONS: Deployment of the device yielded an evaluable cytologic sample in 68% of cases with a high rate of concordance with histopathology. Further evaluation of the device's ability to detect malignancy in high risk populations is warranted.

Streamlining genetic testing for women with ovarian cancer in a Northern California health care system.

OBJECTIVE: Referral to Genetics for pre-testing counseling may be inefficient for women with ovarian cancer. This study assesses feasibility of gynecologic oncologists directly offering genetic testing. METHODS: A prospective pilot study was conducted at two gynecologic oncology hubs in an integrated healthcare system from May 1 to November 6, 2019. Gynecologic oncologists offered multigene panel testing to women with newly diagnosed ovarian cancer, followed by selective genetic counseling. Outcomes were compared between study participants and women from other hubs in the health system. RESULTS: Of ovarian cancer patients at study sites, 40 participated and all underwent genetic testing. Of 101 patients diagnosed at other sites, 85% were referred to genetics (p = .0061 compared to pilot participants) and 67% completed testing (p < .0001). The time from diagnosis to blood draw and notification of result was 18.5 and 34 days for the pilot group compared to 25.5 and 53 days at other sites. Panel testing detected 9 (22.5%) and 7 (10.3%, p = .08) pathogenic mutations in each group, respectively. Patients and providers were highly satisfied with the streamlined process. CONCLUSION: Genetic testing performed at the gynecologic oncology point of care for patients with ovarian cancer is feasible, increases uptake of testing, and improves time to results.

Advanced communication: A critical component of high quality gynecologic cancer care: A Society of Gynecologic Oncology evidence based review and guide.

Effective communication between gynecologic oncology providers and patients is vital to patient-centered care. Skilled communication improves the patient's knowledge retention, builds trust in providers, enhances shared decision-making, and alleviates anxiety of both patients and caregivers. Effective communication is also associated with reduced provider burnout due to improved comfort from possessing the skills to handle emotionally charged situations. Therefore, training in serious illness communication skills is critically important to gynecologic oncology practice and benefits patients, providers, and the healthcare system. Like surgical skills, communication skills can be learned and improved upon, particularly by making use of communication skills courses and other resources. While the purpose of each conversation will vary based on the medical setting, most communication roadmaps incorporate four basic components: 1) Assess patient knowledge and understanding, 2) inform patient in accordance with her communication preferences, 3) recognize and respond to emotion 4) elicit patient values, and create a plan that aligns with those values. Improved patient outcomes associated with addressing patient emotions underscore a critical need to recognize and address emotional cues during difficult conversations. We present strategies for delivering serious news, and for discussing prognosis and goals of care. In each strategy, we highlight skills for recognizing and responding to patient and family emotional cues.

Pre-operative assessment and post-operative outcomes of elderly women with gynecologic cancers, primary analysis of NRG CC-002: An NRG oncology group/gynecologic oncology group study.

INTRODUCTION: CC-002 is a prospective cooperative group study conducted by NRG Oncology to evaluate whether a pre-operative GA-GYN score derived from a predictive model utilizing components of an abbreviated geriatric assessment (GA) is associated with major post-operative complications in elderly women with suspected ovarian, fallopian tube, primary peritoneal or advanced stage papillary serous uterine (GYN) carcinoma undergoing primary open cytoreductive surgery. METHODS: Patients 70 years or older with suspected advanced gynecologic cancers undergoing evaluation for surgery were eligible. A GA-GYN score was derived from a model utilizing the GA as a pre-operative tool. Patients were followed for six weeks post-operatively or until start of chemotherapy. Post-operative events were recorded either directly as binary occurrence (yes or no) using CTCAE version 4.0. RESULTS: There were 189 eligible patients, 117 patients with primary surgical intervention and 37 patients undergoing interval cytoreduction surgery. The association between higher GA-GYN score and major postoperative complications in patients undergoing primary surgery was not significant (p = 0.1341). In a subgroup analysis of patients with advanced staged malignant disease who underwent primary cytoreductive surgery, there was a trend towards an association with the GA-GYN score and post-operative complications. CONCLUSION: The pre-operative GA-GYN score derived from a predictive model utilizing components of an abbreviated geriatric assessment was not predictive of major post-operative complications in elderly patients undergoing primary open cytoreductive surgery. However, there was an association between GA-GYN score and post-operative complications in a subgroup of patients with advanced staged malignant disease.

Adjuvant gemcitabine-docetaxel chemotherapy for stage I uterine leiomyosarcoma: Trends and survival outcomes.

OBJECTIVE: To assess recent trends of administering adjuvant gemcitabine-docetaxel (GD) chemotherapy for Stage I uterine leiomyosarcoma, and to compare disease-free and overall survival between women who received and did not receive adjuvant GD chemotherapy. METHODS: All patients diagnosed with Stage I uterine leiomyosarcoma in a California-Colorado population-based health plan inclusive of 2006-2013 were included in a retrospective cohort. Adjuvant GD chemotherapy rates, clinico-pathologic characteristics and survival estimates were assessed. RESULTS: Of 111 women with Stage I uterine leiomyosarcoma, 33 received adjuvant GD (median 4cycles), 77 received no chemotherapy, and 1 patient excluded for non-GD chemotherapy. GD-chemotherapy and no-chemotherapy groups were similar with respect to age, stage (IA/IB), uterine weight, mitotic index, body mass index, and Charlson comorbidity score. Non-Hispanic white women were twice as likely to receive adjuvant chemotherapy as non-white or Hispanic women (37.7 vs. 17.1%, P=0.02). The proportion of women receiving adjuvant GD chemotherapy increased from 6.5% in 2006-2008 to 46.9% in 2009-2013 (P<0.001). There was no significance difference in unadjusted Kaplan-Meyer estimated disease-free (P=0.95) or overall survival (P=0.43) between GD-chemotherapy and no-chemotherapy cohorts. Corresponding adjusted Cox proportional hazard ratios for adjuvant GD chemotherapy compared to no chemotherapy were 1.01 (95% confidence interval [CI] 0.57-1.80, P=0.97) for recurrence and 1.28 (95% CI 0.69-2.36, P-0.48) for mortality. CONCLUSIONS: Use of adjuvant GD chemotherapy for Stage I uterine leiomyosarcoma has increased significantly in the last decade, despite unclear benefit. Compared to no chemotherapy, 4-6cycles of adjuvant GD chemotherapy does not appear to alter survival outcomes.

Does Surgical Teaching Take Time? Resident Participation in Minimally Invasive Hysterectomy for Endometrial Cancer.

STUDY OBJECTIVE: To determine the association between resident involvement and operative time for minimally invasive surgery (MIS) for endometrial cancer. DESIGN: A retrospective cohort study (Canadian Task Force classification II-2). SETTING: An integrated health care system in Northern California. PATIENTS: A total of 1433 women who underwent MIS for endometrial cancer and endometrial intraepithelial neoplasia from January 2009 to January 2014. INTERVENTIONS: Resident participation in 430 of 688 laparoscopic cases (62%) and 341 of 745 robotic cases (46%). MEASUREMENTS AND MAIN RESULTS: The primary outcome was the impact of resident involvement on surgical time. When residents were involved in laparoscopic and robotic surgery, there was an increase of 61 minutes (median operative time, 186 vs 125 minutes; p < .001) and 31 minutes (median operative time, 165 vs 134 minutes; p < .001), respectively. Resident participation was associated with increased operative times in all levels of surgical complexity from hysterectomy alone to hysterectomy with pelvic and para-aortic lymph node dissection. Resident participation was also associated with increased major intraoperative complications (3.4% vs 1.8%, p = .02) as well as major postoperative complications (6.4% vs 3.8%, p = .003). CONCLUSION: The presence of a resident was associated with a 32% increase in operative time for minimally invasive cases in gynecologic oncology for endometrial cancer. Because of the retrospective nature, we cannot infer causality of operative outcomes because residents were also involved in more high-risk patients and complex cases. For health care systems using surgical metrics, there may be a need to allocate more time for resident involvement.

Venous thromboembolism following minimally invasive surgery among women with endometrial cancer.

OBJECTIVE: To determine the rate of venous thromboembolism (VTE) among women undergoing minimally invasive surgery (MIS) for endometrial cancer. METHODS: Women undergoing robotic or laparoscopic hysterectomy for endometrial carcinoma or complex hyperplasia with atypia were identified between January 2009 and 2014 in a community based health care system. Patient data including age, race, cancer stage, grade, procedure type, length of hospital stay, use of prophylaxis, and diagnosis of VTE were collected retrospectively. The primary outcome was the rate of VTE within 30days following surgery. Fischer's exact tests were performed to evaluate factors associated with VTE. RESULTS: During the study period, 1433 patients underwent MIS for endometrial cancer, with 20 excluded due to known thrombophilia, VTE history, or long-term anticoagulation. A total of 1413 patients were included (739 robotic and 674 laparoscopic cases). All women received mechanical prophylaxis per hospital policy and 61% had additional pharmacologic prophylaxis. The rate of VTE was 0.35% (5/1413), which did not differ among those who received pharmacologic compared to mechanical prophylaxis (0.23% [2/865] versus 0.55% [3/548] respectively, p=0.38). No factors were associated with increased risk of VTE due to the low event rate. CONCLUSION: VTE in patients undergoing MIS for endometrial cancer was very low irrespective of the mode of prophylaxis received in this large cohort. National guidelines for VTE prophylaxis need to differentiate the low risk associated with MIS surgery from the risk associated with laparotomy for endometrial cancer. We recommend mechanical prophylaxis is sufficient for these women undergoing MIS.

Classification of Postoperative Complications in Robotic-assisted Compared With Laparoscopic Hysterectomy for Endometrial Cancer.

STUDY OBJECTIVE: To compare intraoperative and postoperative surgical complications and outcomes between robotic-assisted and laparoscopic surgical management of endometrial cancer using a standardized classification system. DESIGN: A retrospective cohort study (Canadian Task Force classification II-2). SETTING: An integrated health care system in Northern California. PATIENTS: One thousand four hundred thirty-three women with a diagnosis of complex atypical hyperplasia and endometrial cancer managed by minimally invasive hysterectomy and surgical staging from January 2009 to January 2014. INTERVENTIONS: Seven hundred forty-five robotic-assisted and 688 laparoscopic hysterectomies were evaluated. MEASUREMENTS AND MAIN RESULTS: The primary outcome was intraoperative and postoperative complications within 30 days. All complications were categorized using the Clavien-Dindo classification system. Secondary outcomes included total operative time, estimated blood loss, transfusion rates, length of stay, conversion to laparotomy, and number of pelvic and para-aortic lymph nodes retrieved. The modality of hysterectomy was not associated with either overall intraoperative complications or major postoperative complications (p > .1). However, there were significantly fewer minor postoperative complications with robotic surgery (16.6% vs 25.6%, p < .01). Statistically significant differences were also noted in the following outcomes: decreased median operative time, length of stay, estimated blood loss, conversion to laparotomy, and median number of lymph nodes retrieved in the robotic group when compared with the laparoscopic group. CONCLUSION: There was no difference in the rate of major complication between robotic and laparoscopic surgery using the Clavien-Dindo system of categorizing surgical complications; however, there were clinically significant differences favoring the robotic approach, including a lower rate of minor complications and conversion rate to laparotomy.

Osteoporosis risk and management in BRCA1 and BRCA2 carriers who undergo risk-reducing salpingo-oophorectomy.

OBJECTIVE: Characterize current management of osteoporosis risk in BRCA carriers following risk-reducing salpingo-oophorectomy (RRSO). METHODS: Women with a BRCA1 or BRCA2 mutation who underwent RRSO were identified from a community-based health system in Northern California from 1995 to 2012. Retrospective chart review using the electronic medical record was performed. The primary outcome was the number of women who had a dual-energy X-ray absorptiometry scan post-RRSO. Secondary outcomes included new diagnoses of osteopenia, osteoporosis, and fracture. Information on the following risk factors was also recorded: calcium and vitamin D use, history of breast cancer, chemotherapy, use of aromatase inhibitors, and use of hormone replacement therapy. RESULTS: Two hundred and twenty five women tested positive for a BRCA1 or BRCA2 mutation and underwent RRSO. Median follow-up was 41 months from testing. Ninety-nine (44.0%) had at least one DXA scan following testing. The median time from RRSO to a diagnosis of bone disease was 29 months (range 1-170). Seventy-two percent had only one DXA scan (range 1-7) following testing. Thirty-two percent had normal results, 55.6% had osteopenia and 12.1% had osteoporosis. Four percent of women had an atraumatic fracture after surgery. Age, breast cancer history, prior chemotherapy, and tamoxifen or aromatase inhibitor (AI) use were not associated with having osteoporosis or osteopenia. CONCLUSIONS: Women with BRCA mutations who undergo RRSO have many risk factors for bone loss. The majority of these women are not being screened for bone loss. A clear guideline for screening needs to be established to improve detection of post-RRSO bone disease.

Clinical outcomes and prognostic markers in uterine leiomyosarcoma: a population-based cohort.

OBJECTIVE: The aim was to identify clinical parameters and immunohistochemical markers predictive of recurrence and overall survival (OS) in a community cohort of patients with primary uterine leiomyosarcoma (ULMS). METHODS/MATERIALS: All patients with new diagnosis of ULMS from 1999 to 2007 were identified from the Kaiser Permanente Northern California pathology database. A retrospective chart review was performed to gather demographic and clinical data. The primary outcomes were recurrence-free survival and OS. In addition, a subset of tumor samples was available to analyze 3 immunohistochemical markers using tissue microarray techniques; these are as follows: estrogen receptor (ER) alpha, epidermal growth factor receptor (EGFR), and Ki-67. RESULTS: Seventy-five patients with ULMS were identified, of which 63 had adequate tumor tissue available for immunohistochemical evaluation. The median follow-up for all stages was 28 months. The rate of recurrence or progressive disease was 76% for stage I patients compared with 85% for stage II to IV patients. At 3 years, 37% of stage I patients were recurrence free compared with 27% of stage II to IV patients. Overall survival for stage I patients declined from 64% to 38% between 3 and 5 years while remaining stable at 30% for stage II to IV patients. In multivariable analysis, increasing mitotic counts were associated with increased risk of recurrence (hazards ratio [HR], 3.2; P = 0.013) and a trend toward decreased OS (HR, 2.2; P = 0.10). Expression of ER (HR, 1.0), EGFR expression (HR, 1.0), and Ki-67 expression (HR, 1.0) were not predictive of recurrence or OS. CONCLUSIONS: Recurrence rate of 76% for patients with stage I ULMS was higher than previously published cohorts. Mitotic counts were associated with increased recurrence and decreased OS. Expressions of ER, EGFR, and Ki-67 were not useful for predicting overall recurrence or survival.

Comparison of risk management strategies between women testing positive for a BRCA variant of unknown significance and women with known BRCA deleterious mutations.

PURPOSE: The aim of this article is to describe cancer risk-reducing behaviors of women with BRCA variants of unknown significance. METHODS: A retrospective chart review from 1995 to 2012 identified women with BRCA mutations in a northern California community system. Exclusion criteria included loss of membership/death within 1 year of testing, prior ovarian cancer, or bilateral salpingo-oophorectomy. Primary outcomes were rate of risk-reducing mastectomy and risk-reducing salpingo-oophorectomy. RESULTS: The mean age of the 69 variant of unknown significance carriers was 50 vs. 47 years for the 305 women with a deleterious mutation. Women with a variant of unknown significance were followed for a median of 69 months. Among women with a variant of unknown significance, 30% underwent risk-reducing salpingo-oophorectomy and 11% underwent risk-reducing mastectomy, as compared with 74 and 44%, respectively, for women with a deleterious mutation. Women with a deleterious mutation were more likely to undergo surveillance in the first year after testing. The odds ratios are as follows: 2.1 for mammogram, 6.0 for magnetic resonance imaging, 7.7 for Ca-125, and 5.0 for transvaginal ultrasound. Fifty-six percent of women with a variant of unknown significance were reclassified after a median of 39 months, longer than the median time to risk-reducing salpingo-oophorectomy (18.6 months) or risk-reducing mastectomy (20.1 months). CONCLUSION: Uptake of risk-reducing strategies among women with a variant of unknown significance is lower than among women with a deleterious mutation. Given the prognostic uncertainty and high rate of reclassification for women with a variant of unknown significance, individualizing counseling and directing efforts toward surveillance, chemoprevention, or salpingectomy are recommended.

Risk management options elected by women after testing positive for a BRCA mutation.

OBJECTIVE: To assess the uptake of risk-reducing options for the management of ovarian and breast cancer risk in BRCA mutation carriers in a large community based integrated health system in Northern California. METHODS: A retrospective cohort of deleterious BRCA mutation carriers (1995-2012) was evaluated for consistency with NCCN guidelines for risk reducing salpingo-oophorectomy (RRSO) by age of 35-40, risk reducing mastectomy (RRM), as well as surveillance practices, including pelvic ultrasound, CA 125, mammogram, and breast MRI. Secondary outcomes included the use of chemoprevention and hormone replacement. RESULTS: Of the 305 eligible women, 170 were BRCA1 positive, and 135 were BRCA2 positive. Seventy four percent underwent RRSO with only 17% under age 40, while 44% underwent RRM. The median time from the test to both RRSO and RRM was 6 months. In the first year after BRCA diagnosis, 45% underwent a pelvic ultrasound, dropping to 2.3% by year 5. In year 1, 47% had a CA 125, dropping to 2% by year 5. The number of women undergoing annual MRI and mammogram fell similarly over time. Sixteen percent of BRCA carriers used oral contraceptives (OCPs) and only one patient used tamoxifen for chemoprevention. CONCLUSION: Uptake of RRSO in BRCA carriers in a population based health system is high, however the majority of women do not have RRSO by the NCCN recommended age. Compliance with surveillance is low and rapidly declines even 1 year out from testing. Attention needs to be focused on the earlier identification of BRCA mutation carriers with consolidated and standardized care to improve risk reduction.

Risk of cervical precancer and cancer in women with cervical intraepithelial neoplasia grade 1 on endocervical curettage.

OBJECTIVE: This study aimed to characterize the 24-month risk of cervical intraepithelial neoplasia grade 2 or worse (CIN 2+) and grade 3 or worse (CIN 3+) in women with low-risk cytological finding and CIN 1 on endocervical curettage (ECC). MATERIALS AND METHODS: Cervical screening tests and cervical biopsy results from Kaiser Permanente Northern California were reviewed for years 2004 to 2008. Women with index cytological result of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion who underwent excisional procedure within 24 months of CIN 1 diagnosis were grouped by ECC status. A third cohort comprised women with ECC-CIN 1 followed up without excisional procedure. The 24-month cumulative incidence of CIN 2+ and CIN 3+ was calculated for each cohort. RESULTS: Excisional procedures were performed in 224 women; 54 had ECC-CIN 1 with ectocervical biopsy CIN 1 or less, and 170 had ectocervical CIN 1 with negative ECC finding. The 24-month risk of CIN 2+ was lower in the ECC-CIN 1 cohort compared with the ECC-negative (ectocervical CIN 1) cohort (24.1 vs 44.7%, p = .018) and nonsignificantly lower for CIN 3+ (7.4% vs 14.1%, p = .23). Among 203 women with ECC-CIN 1 followed up without excisional procedure but with follow-up ECC at a median of 21.7 months from index ECC, CIN 2 was found in 21 (10.3%, 95% CI = 6.7%-15.6%), and CIN 3 was found in 3 (1.5%, 95% CI = 0.4%-4.6%). CONCLUSIONS: A diagnosis of CIN 1 on ECC preceded by atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion does not increase the risk of CIN 2+ compared with women with ectocervical CIN 1 and negative ECC. The risk of CIN 2+ in women followed up without excisional procedure is sufficiently low that it is reasonable to offer conservative management similar to that for ectocervical CIN 1.

Palliative care in gynecologic oncology: a narrative review of current literature and vision for the future.

BACKGROUND AND OBJECTIVE: Several professional societies have recommended incorporating palliative care into routine oncology care, yet palliative care remains underutilized among women with gynecologic cancers. This narrative review highlights current evidence regarding utilization of palliative care in gynecologic oncology care. Additionally, the authors offer recommendations to increase early integration and utilization of palliative care services, improve education for current and future gynecologic oncology providers, and expand the palliative care workforce. METHODS: The authors reviewed studies of palliative care interventions in oncology settings, with an emphasis on studies that included women with gynecologic malignancies. A panel of author/experts were gathered for a semi-structured interview to discuss the future of palliative care in gynecologic cancer care. The interview was recorded and reviewed to highlight themes. KEY CONTENT AND FINDINGS: Data supports routine integration of palliative care into gynecologic oncology practice. To expand delivery of palliative care, additional research that investigates implementation of palliative care across different healthcare settings is needed. There is a shortage of palliative care providers in the United States. Therefore, it is critical for gynecologic oncologists to receive a robust education in primary palliative care skillsets. Additionally, to expand the specialty palliative care workforce, palliative medicine leaders should recruit more gynecologic oncologists and other surgeons into palliative care fellowship programs. CONCLUSIONS: Expanded utilization of palliative care offers an opportunity to improve quality of care and outcomes for women with gynecologic cancers.

A Randomized, Phase III Trial to Evaluate Rucaparib Monotherapy as Maintenance Treatment in Patients With Newly Diagnosed Ovarian Cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45).

PURPOSE: ATHENA (ClinicalTrials.gov identifier: NCT03522246) was designed to evaluate rucaparib first-line maintenance treatment in a broad patient population, including those without BRCA1 or BRCA2 (BRCA) mutations or other evidence of homologous recombination deficiency (HRD), or high-risk clinical characteristics such as residual disease. We report the results from the ATHENA-MONO comparison of rucaparib versus placebo. METHODS: Patients with stage III-IV high-grade ovarian cancer undergoing surgical cytoreduction (R0/complete resection permitted) and responding to first-line platinum-doublet chemotherapy were randomly assigned 4:1 to oral rucaparib 600 mg twice a day or placebo. Stratification factors were HRD test status, residual disease after chemotherapy, and timing of surgery. The primary end point of investigator-assessed progression-free survival was assessed in a step-down procedure, first in the HRD population (BRCA-mutant or BRCA wild-type/loss of heterozygosity high tumor), and then in the intent-to-treat population. RESULTS: As of March 23, 2022 (data cutoff), 427 and 111 patients were randomly assigned to rucaparib or placebo, respectively (HRD population: 185 v 49). Median progression-free survival (95% CI) was 28.7 months (23.0 to not reached) with rucaparib versus 11.3 months (9.1 to 22.1) with placebo in the HRD population (log-rank P = .0004; hazard ratio [HR], 0.47; 95% CI, 0.31 to 0.72); 20.2 months (15.2 to 24.7) versus 9.2 months (8.3 to 12.2) in the intent-to-treat population (log-rank P < .0001; HR, 0.52; 95% CI, 0.40 to 0.68); and 12.1 months (11.1 to 17.7) versus 9.1 months (4.0 to 12.2) in the HRD-negative population (HR, 0.65; 95% CI, 0.45 to 0.95). The most common grade ≥ 3 treatment-emergent adverse events were anemia (rucaparib, 28.7% v placebo, 0%) and neutropenia (14.6% v 0.9%). CONCLUSION: Rucaparib monotherapy is effective as first-line maintenance, conferring significant benefit versus placebo in patients with advanced ovarian cancer with and without HRD.

Risk of cervical precancer and cancer in women aged 30 years and older with an HPV-negative low-grade squamous intraepithelial lesion screening result.

OBJECTIVE: To characterize the 6- and 18-month cumulative risk of cervical intraepithelial neoplasia grade 2 or worse (CIN 2+) and grade 3 or worse (CIN 3+) in women aged 30 years and older after a low-grade squamous intraepithelial lesion (LSIL) cytology and high-risk human papillomavirus (HPV)-negative screening result in routine clinical practice. MATERIALS AND METHODS: Comprehensive quality assurance databases of screening test and biopsy results from the Regional Laboratory of the Kaiser Permanente Northern California Health Plan were reviewed. All women aged 30 years and older with LSIL cytology were sorted by high-risk HPV status. Associated biopsy results were tabulated, and the corresponding risks of CIN 2+ and CIN 3+ diagnosed within 18 months after LSIL cytology were calculated overall and by decade of age. RESULTS: During the 6-year period, from 2003 to 2008, 4,113 LSIL cases were interpreted in women aged 30 years and older for which corresponding high-risk HPV and biopsy results were available. The proportion of women with LSIL testing positive for HPV declined with age, from 89% in the group aged 30 to 39 years to 76% in women older than 50 years (p < .001). Of 622 women with HPV-negative LSIL cytology, there was no case of cancer detected at colposcopy occurring within 6 months of the screening test. The 18-month risks of CIN 2+ and CIN 3+ were 3.5% and 1.4%, respectively. CONCLUSIONS: The risk of CIN 3+ is sufficiently low in women aged 30 years and older with high-risk HPV-negative LSIL that 1 year follow-up rather than immediate colposcopy should be considered when it occurs in routine clinical practice.

Top Ten Tips Palliative Care Clinicians Should Know About Caring for Patients with Cervical Cancer.

Cervical cancer is the most common gynecologic cancer worldwide. Almost all are related to human papillomavirus exposure. Cervical cancer treatment is associated with significant morbidity that is likely to require support from palliative care teams. In these pearls on cervical cancer, we hope to inform providers about the common treatments and issues for cervical cancer patients. Treatment modalities include surgery for early-stage disease, radiation therapy for locally advanced disease, and pelvic exenteration, chemotherapy, or immunotherapy for recurrent disease. Cervical cancer causes pain and bleeding. Radiation can affect ovarian, urinary, and bowel function. Chemotherapy and immunotherapy are associated with fatigue and nausea. Fistulas between the vagina and bowel or bladder can occur due to cancer or to cancer treatments. Physical and emotional supportive care is important for women with cervical cancer.