The role of obesity in treatment planning for early-stage cervical cancer.

OBJECTIVES: Optimal management of obese patients with early-stage cervical cancer is debated despite evidence of non-inferior survival in obese patients undergoing radical hysterectomy with pelvic lymphadenectomy (RH) compared to primary radiation with or without radiosensitizing chemotherapy (RT). Objectives included describing patient factors affecting disposition to RH versus RT; comparing RH outcomes for obese (BMI >30 mg/m2) and non-obese patients; and comparing differences in recurrence free survival (RFS) and overall survival (OS). METHODS: This was a single institution cohort study of all cervical cancer patients who underwent RH or were candidates for RH based on clinical stage. Demographic, clinicopathologic and treatment outcomes were collected and analyzed. RESULTS: RT patients (n = 39, 15%) had a higher BMI (p = 0.004), older age (p < 0.001), more life-limiting comorbidities (LLC) (p < 0.001), larger tumor size (p = 0.001), and higher clinical stage (p = 0.013) compared to RH patients (n = 221, 85%). On multivariable survival analysis there was no difference in OS based on treatment modality; significant predictors of worse OS were larger tumor size, higher number of LLC and recurrence. Among the RH group, obese patients had a longer operative time (p = 0.01) and more LLC (p = 0.02); there were no differences in demographic or clinicopathologic characteristics, operative outcomes, RFS or OS compared to non-obese patients. CONCLUSION: In this cohort of RH-eligible cervical cancer patients, BMI was independently associated with disposition to RT. Studies demonstrate that RH is feasible and safe in obese patients with no difference in RFS or OS when compared to non-obese patients. Thus, the decision for disposition to RT should not be based on obesity alone.

Association of allostatic load with overall survival in epithelial ovarian cancer.

OBJECTIVE: Elevated allostatic load (AL), an integrated, cumulative marker of physiologic damage due to socioenvironmental stress, is associated with increased mortality in patients with breast, lung, and other cancers. The relationship between allostatic load and mortality in ovarian cancer patients remains unknown. We examined the relationship between allostatic load and overall survival in ovarian cancer patients. METHODS: This cross-sectional study used data from 201 patients enrolled in a prospective observational ovarian cancer cohort study at a National Cancer Institute-designated Comprehensive Cancer Center from October 2012 through June 2022. All patients underwent debulking surgery and completed a full course of standard-of-care platinum-based chemotherapy. Follow-up was completed through January 2024. Allostatic load was calculated as a summary score by assigning one point to the worst sample quartile for each of ten biomarkers measured within 45 days before the ovarian cancer diagnosis. High allostatic load was defined as having an allostatic load in the top quartile of the summary score. A Cox proportional hazard model with robust variance tested the association between allostatic load and overall survival. RESULTS: There were no associations between allostatic load and ovarian cancer clinical characteristics. After accounting for demographic, clinical, and treatment factors, high allostatic load was associated with a significant increase in mortality (hazard ratio 2.17 [95%CI, 1.13-4.15]; P = 0.02). CONCLUSION: Higher allostatic load is associated with worse survival among ovarian cancer patients. Allostatic load could help identify patients at risk for poorer outcomes who may benefit from greater socioenvironmental support during treatment.

CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study.

BACKGROUND: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. METHODS: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. RESULTS: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. CONCLUSION: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC.

Same-day Hospital Discharge after Minimally Invasive Hysterectomy in a Gynecologic Oncology Practice: Feasibility, Safety, Predictors of Admission, and Adverse Outcomes.

STUDY OBJECTIVES: (1) Determine the feasibility and safety of same-day hospital discharge (SDHD) after minimally invasive hysterectomy (MIH) in a gynecologic oncology practice and (2) detail predictors of immediate postoperative hospital admission and multiple 30-day adverse outcomes. DESIGN: Retrospective cohort study. SETTING: University of Pittsburgh Medical Center Magee-Womens Hospital. PATIENTS: MIH by a gynecologic oncologist between January 2017 and July 2019. INTERVENTIONS: Clinicopathologic, operative, and medical characteristics, as well as 30-day postoperative complications, emergency department (ED) encounters, and hospital readmissions were extracted. Admitted and SDHD patients were compared using descriptive, chi-square, Fisher's exact, t test, and logistic regression analyses. Univariate and multivariable analyses (MVA) revealed predictors of postoperative hospital admission, 30-day readmission, and a 30-day composite adverse event variable (all-reported postoperative complications, ED encounter, and/or readmission). MEASUREMENTS AND MAIN RESULTS: A total of 1124 patients were identified, of which 77.3% had cancer or precancer; 775 patients (69.0%) underwent SDHD. On MVA, predictors of postoperative admission included older age, distance from hospital, longer procedure length, operative complications, start time after 2 PM, radical hysterectomy, minilaparotomy, adhesiolysis, cardiac disease, cerebrovascular disease, venous thromboembolism, diabetes, and neurologic disorders (p <.05). Moreover, 30-day adverse outcomes were rare (complication 8.7% National Surgical Quality Improvement Program/11.9% all-reported; ED encounter 5.0%; readmission 3.6%). SDHD patients had fewer all-reported complications (10.3% vs 15.5%, p = .01), no difference in ED encounters (4.6% vs 5.7%, p = .44), and fewer observed readmissions (2.8% vs 5.2%, p = .05). Predictors of readmission were identified on univariate; MVA was not feasible given the low number of events. Longer procedure length and cardiac and obstructive pulmonary disease were predictors of the composite adverse event variable (p <.05). CONCLUSION: SDHD is feasible and safe after MIH within a representative gynecologic oncology practice. Clinicopathologic, medical, and surgical predictors of multiple adverse outcomes were comprehensively described. By identifying patients at high risk of postoperative adverse events, we can direct SDHD selection in the absence of standardized institutional and/or national consensus guidelines and identify patients for prehabilitation and increased perioperative support.

Validation of the surprise question in gynecologic oncology: A one-question screen to promote palliative care integration and advance care planning.

OBJECTIVE: The "surprise question" ("Would you be surprised if this patient died in the next year?") has been shown to be predictive of 12-month mortality in multiple populations, but has not been studied in gynecologic oncology (GO) patients. We sought to evaluate the prognostic performance of the surprise question in GO patients among physician and non-physician providers. METHODS: GO providers at two tertiary care centers were asked the surprise question about a cohort of their patients undergoing chemotherapy or radiation. Demographic and clinical information was chart abstracted. Mortality data were collected at one year; relative risk of death at one year based on response to the surprise question was then calculated. RESULTS: 32 providers (12 MDs, 7 APPs, 13 RNs) provided 942 surprise question assessments for 358 patients. Fifty-seven % had ovarian cancer and 54% had recurrent disease. Eighty-three (24%) patients died within a year. Patients whose physician answered "No" to the surprise question had a 43% one-year mortality (compared to 10% for "Yes"). Overall RR of 12-month mortality for "No" was 3.76 (95% CI 2.75-5.48); this association remained significant in all provider types. Among statistically significant predictors of 12-month mortality (including recurrent disease and >2 prior lines of chemotherapy), the surprise question had the highest RR. CONCLUSIONS: The surprise question is a simple, one question tool that effectively identifies GO patients increased risk of 12-month mortality. The surprise question could be used to identify patients for early referral to palliative care and initiation advance care planning.

Dose-escalated intensity modulated radiation therapy in patients with locally-advanced vulvar cancer - does it increase response rate?

PURPOSE: GOG 205 safely increased clinical (cCR) and pathologic complete response (pCR) in locally-advanced vulvar cancer through dose escalation using three-dimensional radiotherapy (RT). The aim of this study is to assess the response of dose-escalated intensity modulated radiotherapy (IMRT) in locally-advanced vulvar cancer. METHODS: A retrospective review of patients treated with dose-escalated (≥ 55Gy) IMRT from 2012 to 2018 for locally-advanced vulvar cancer was performed. Patients treated with preoperative or definitive intent were included. Rates of cCR and pCR were assessed, and predictors of disease-free survival (DFS) were analyzed using the Kaplan Meier method with log rank test between groups and a parsimonious multivariate Cox model. RESULTS: Median dose to the vulva was 66.0 Gy (Interquartile Range [IQR]: 66.0-68.0) for definitive and 59.4 Gy (IQR: 58.0-59.4) for preoperative IMRT. The overall rates of cCR and pCR were 76% and 70%, respectively. DFS at two years was 65% (95% Confidence Interval [CI] 50-80%) for all patients, 81% (95% CI 63% - 98%) for definitive IMRT, and 55% (95% CI 35% - 76%) for preoperative IMRT. On multivariate analysis, cCR predicted for disease-free survival (HR 0.21; 95% CI 0.06-0.76; p = 0.02), and pCR predicted for OS (HR 0.12; 95% CI 0.02-0.60; p = 0.01). Grade 3 acute and late RT toxicity was seen in 14 (29%) and 3 (6%) of patients, respectively. CONCLUSION: Dose-escalated IMRT for locally-advanced vulvar cancer is well tolerated, with rates of cCR and pCR that compare favorably with published data.

Chemotherapy in older adult gynecologic oncology patients: Can a phenotypic frailty score predict tolerance?

OBJECTIVE: Evaluate the ability of an office-administered phenotypic frailty assessment to predict chemotherapy tolerance in older adult gynecologic oncology patients, and describe practice patterns for chemotherapy administration in this population. METHODS: Prospective, single-institution cohort study of gynecologic oncology patients 65 or older initiating chemotherapy. Phenotypic frailty testing at an office visit encompassed components of two validated frailty assessments: Fried Score (physical testing and patient response) and FRAIL Scale (patient response only). Patients were followed through three cycles of neoadjuvant chemotherapy or six cycles of adjuvant chemotherapy. Standard statistics examined the relationship of frailty to chemotherapy regimen, ability to complete chemotherapy, and complications. RESULTS: Eighty patients were included, 65% with ovarian and 34% with endometrial cancer. On average 57% of patients were fit, 32% intermediately frail, and 11% frail. 68% received adjuvant chemotherapy versus 32% neoadjuvant. The majority (81%) received IV chemotherapy on a 21-day cycle and 81% initially received a regimen consistent with standard-of-care chemotherapy (SOCC). Age was not associated with receiving SOCC, or tolerance or completion of chemotherapy. Frailty was associated with non-initiation of SOCC in all patients and inability to complete SOCC in adjuvant patients. Complications and regimen alterations were common but were not associated with frailty. CONCLUSIONS: There is a need to develop tools to help physicians predict chemotherapy tolerance among older adult gynecologic oncology patients in order to prevent both under- and over-treatment while minimizing morbidity. However, in this study phenotypic frailty assessment had limited predictive utility. Among adjuvant chemotherapy patients, frailty was associated with inability to complete SOCC and thus may be helpful in selecting patients appropriate for less aggressive chemotherapy regimens.

Unplanned postoperative intensive care unit admission for ovarian cancer cytoreduction is associated with significant decrease in overall survival.

OBJECTIVES: Previous studies have identified age, nutritional status, and hematocrit as risk factors for unplanned ICU admission in gynecologic oncology patients. We sought to identify additional perioperative factors that can be predictive of unplanned ICU admission and its impact on outcomes in women with ovarian cancer undergoing ovarian cancer cytoreductive procedures. METHODS: This was a case-control study of patients with unplanned ICU admission after primary surgery for ovarian cancer from January 2007 to December 2013. Controls were selected in a 2:1 ratio matching for primary surgeon and date of surgery. Clinical data was abstracted and compared between cases and controls using conditional logistic regression. RESULTS: The dataset consisted of 324 patients (108 ICU admissions, 216 controls). On multivariable analysis, failure to optimally cytoreduce (p = 0.001, OR 3.76) and higher EBL (p < 0.001, OR 1.20 per 100 cm3) remained significant predictors of unplanned ICU admission. On multivariable analysis of outcomes, ICU admission was independently associated with increased length of stay (12 days vs. 6 days, p < 0.001), increased number of postop complications (2 vs. 0, p < 0.001), and increased risk of readmission within 30 days (p = 0.041, OR 2.46). Even controlling for debulking status, ICU admission remained associated with a worse median OS (27.3 vs 57.9 months, p < 0.001). CONCLUSIONS: ICU admission for women undergoing cytoreductive surgery for ovarian cancer is associated with a significant decrease in OS and increase in number of postoperative complications. For this inherently high-risk population, this information is critical when counseling patients about peri-operative risks in primary cytoreductive surgery.

Image-based multichannel vaginal cylinder brachytherapy for the definitive treatment of gynecologic malignancies in the vagina.

PURPOSE: Brachytherapy is integral to vaginal cancer treatment and is typically delivered using an intracavitary single-channel vaginal cylinder (SCVC) or an interstitial brachytherapy (ISBT) applicator. Multi-channel vaginal cylinder (MCVC) applicators allow for improved organ-at-risk (OAR) sparing compared to SCVC while maintaining target coverage. We present clinical outcomes of patients treated with image-based high dose-rate (HDR) brachytherapy using a MCVC. METHODS AND MATERIALS: Sixty patients with vaginal cancer (27% primary vaginal and 73% recurrence from other primaries) were treated with combination external beam radiotherapy (EBRT) and image-based HDR brachytherapy utilizing a MCVC if residual disease thickness was 7 mm or less after EBRT. All pts received 3D image-based BT to a total equivalent dose of 70-80 Gy. RESULTS: The median high-risk clinical target volume was 24.4 cm3 (interquartile range [IQR], 14.1), with a median dose to 90% of 77.2 Gy (IQR, 2.8). After a median follow-up of 45 months (range, 11-78), the 4-year local-regional control, distant control, DFS, and OS rates were 92.6%, 76.1%, 64.0%, and 67.2%, respectively. The 4-year LRC rates were similar between the primary vaginal (92%) and recurrent (93%) groups (p = 0.290). Pts with lymph node positive disease had a lower rate of distant control at 4 years (22.7% vs. 89.0%, p < 0.001). There were no Grade 3 or higher acute complications. The 4-year rate of late Grade 3 or higher toxicity was 2.7%. CONCLUSIONS: Clinical outcomes of pts with primary and recurrent vaginal cancer treated definitively in a systematic manner with combination EBRT with image-guided HDR BT utilizing a MCVC applicator demonstrate high rates of local control and low rates of severe morbidity. The MCVC technique allows interstitial implantation to be avoided in select pts with ≤7 mm residual disease thickness following EBRT while maintaining excellent clinical outcomes with extended 4-year follow-up in this rare malignancy.

Outcomes of stage II endometrial cancer: The UPMC Hillman Cancer Center experience.

PURPOSE: Previous studies of stage II endometrial cancer have included cancers with cervical glandular involvement, a factor no longer associated with risk of recurrence. In order to better assess relapse patterns and the impact of adjuvant therapy, a retrospective analysis was conducted for patients with modern stage II endometrial cancer, defined as cervical stromal invasion. MATERIALS AND METHODS: Patients diagnosed with surgically staged FIGO stage II endometrial cancer at the UPMC Hillman Cancer Center from 1990-2013 were reviewed. Factors associated with rates of locoregional control (LRC), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS) were analyzed using the log rank test. RESULTS: 110 patients with FIGO stage II disease were identified. Most (84.5%) received EBRT±BT, with 13.6% receiving BT alone. With a median follow-up of 64.6months, the 5-year actuarial rates of LRC, DM, DFS, and OS were 94.9%, 85.1%, 67.9%, and 75.0%, respectively. With 5 locoregional failures, the only factor predictive of LRC was pelvic lymph node dissection. Characteristics associated with DM included age, LVSI, depth of myometrial invasion, and receipt of chemotherapy. Factors predictive of both DFS and OS were age, grade, adverse histology, LVSI, depth of myometrial invasion, and receipt of chemotherapy. CONCLUSIONS: This represents the largest single-institution study for modern stage II endometrial cancer, confirming high rates of pelvic disease control after surgery and adjuvant therapy. With most patients receiving adjuvant radiotherapy, the predominant mode of failure, albeit low in absolute number, remains distant metastases.

Image-guided tandem and cylinder brachytherapy as monotherapy for definitive treatment of inoperable endometrial carcinoma.

OBJECTIVES: Management of endometrial cancer consists of surgical staging with adjuvant therapy guided by risk factors, though some women cannot undergo surgery due to comorbidities. We present a series of women treated with definitive high-dose rate image-guided tandem and cylinder brachytherapy (HDR-IGBT) alone. METHODS: Patients with grade 1-2, clinical stage I endometrial adenocarcinoma, <50% myometrial invasion, and tumor≤2cm were reviewed. Definitive treatment consisted of 5-6 fractions HDR-IGBT alone with CT- or MRI-based planning. Local-regional control (LRC) was defined as complete imaging response and/or cessation of vaginal bleeding. RESULTS: From 2007 to 2016, 45 patients were treated to a median dose of 37.5Gy. The median gross tumor volume (GTV) and clinical target volume (CTV) were 5.9cm3 (range, 0.7-18.7) and 80.9cm3 (17.2-159.0), respectively. The median cumulative dose to 90% (D90) of the GTV was 132.8Gy (76.5-295.6) equivalent 2Gy dose, and the median CTV D90 was 49.7Gy (34.5-57.2). Median follow-up among living patients was 18.6months (3.0-64.3). Cessation of vaginal bleeding occurred in 98%. Among those with post-treatment MRI (64%), complete radiographic response was demonstrated in 90%. The 2-year LRC, cancer-specific survival, and overall survival rates were 90%, 86%, and 97%, respectively. No grade 3+ acute or late toxicity was observed. CONCLUSIONS: HDR-IGBT alone for treatment of early-stage, medically inoperable endometrial cancer is feasible with excellent response rates and clinical results. This approach also allows sparing of critical organs and ensures target coverage, which contributed to the low toxicity rate and high LRC in comparison with 2D point-based series.

Surgical Outcomes of Patients Undergoing Extrafascial Hysterectomy After Neoadjuvant Radiotherapy With or Without Chemotherapy for Locally Advanced Endometrial Cancer Clinically Extending to the Cervix or Parametria.

OBJECTIVES: Recent data have shown high rates of clinical and pathologic responses to neoadjuvant radiation therapy for locally advanced endometrial cancer. There are limited data on the surgical outcomes of these patients in the era of modern radiation and surgical techniques. We sought to characterize surgical outcomes after extrafascial hysterectomy in this population. METHODS: Patients with endometrial cancer of all histologies clinically involving the cervix or parametria treated with neoadjuvant brachytherapy followed by extrafascial hysterectomy from 1999 to 2014 were identified. Patient charts were reviewed for data regarding treatment characteristics and postoperative outcomes. Pearson χ and logistic regression analyses were used to assess correlations between surgical complications and treatment-related variables. RESULTS: Twenty-nine patients met inclusion criteria. Mean operating time for the cohort was 115 minutes. Mean estimated blood loss was 100 mL. No visceral injuries occurred. Mean length of hospital stay was 1 and 4 days for the minimally invasive and laparotomy groups, respectively. Rates of postoperative ileus, blood transfusion, wound infection, and readmission were 3%, 3%, 6%, and 3%, respectively. No case of prolonged urodynamic dysfunction was noted. The rate of vaginal complications was significantly higher in the group of patients who underwent minimally invasive surgery as compared with laparotomy (33% vs 5%, P < 0.041). CONCLUSIONS: These data support adjuvant extrafascial hysterectomy after neoadjuvant radiotherapy for endometrial cancer with cervical or parametrial involvement as a safe and viable procedure, with low rates of postoperative complications. Extra care should be taken when closing the vaginal cuff to reduce the risk of vaginal cuff complications.

Symptom management in women with recurrent ovarian cancer: Do patients and clinicians agree on what symptoms are most important?

OBJECTIVE: We sought to compare symptoms identified as a priority by patients with recurrent ovarian cancer to symptoms most frequently documented by their clinicians, and examine the association between clinician documentation of symptoms and subsequent clinical intervention. METHODS: Single-institution, retrospective chart review of patients enrolled in WRITE Symptoms Study (GOG 259), a randomized controlled trial of internet-based recurrent ovarian cancer symptom management. As part of the trial, women completed the Symptom Representation Questionnaire for 28 symptoms and selected 3 priority symptoms (PS). We compared patient-reported PS to clinician documentation of symptoms and interventions over the time period corresponding to study enrollment. RESULTS: At least one PS was documented in 92% of patients. Of 150 PS reported by patients, 53% were never documented by clinicians; these symptoms tended to be less directly related to disease or treatment status. Symptoms not identified by patients as PS were frequently documented by clinicians; these symptoms tended to relate to physiologic effects of disease and treatment toxicity. 58% of patients had at least one PS intervention. PS intervened for were documented at 2.58 visits vs 0.50 visits for PS not receiving intervention (p≤0.0001). CONCLUSIONS: Discordance was identified between symptoms reported by patients as important and symptoms documented by clinicians. Symptoms more frequently documented were also more frequently intervened for. Our study illustrates the need to improve identification of symptoms important to patients, and suggests that improving communication between patients and clinicians could increase intervention rates to enhance quality of life in women with recurrent ovarian cancer.

Continuous epidural infusion anesthesia and analgesia in gynecologic oncology patients: less pain, more gain?

OBJECTIVE: There is a lack of consistent data regarding gynecologic oncology (GO) patients and the use of neuraxial anesthesia for post-operative pain management. Our objective was to compare the use of continuous epidural infusion (CEI) as part of post-operative pain management to more traditional management schemes. METHODS: GO patients undergoing laparotomy from July 1st, 2011 through July 31st, 2012 were identified. Patient demographic data and peri-operative details were abstracted from the medical record. The primary outcome was a mean patient visual analog pain score. Secondary outcomes included length of stay, post-operative urinary tract infection (UTI) and venous thromboembolic (VTE) events. RESULTS: There were 237 laparotomies during the study time period. Fifty-six women had CEI for post-operative pain management and 181 did not. Patients with CEI had lower pain scores on POD #0 (3.8 vs 5.3, p < 0.01), #1 (2.6 vs 4.0, p < 0.01) and #2 (2.5 vs 3.5, p < 0.01) compared to women without CEI. There was no difference in the length of stay between those with and without CEI (103 vs 94 h, p = 0.32). Women with CEI did have a longer length of urinary catheterization (56 vs 26 h, p = 0.01) but not an increased rate of UTI (5.5% vs 1.8%, p = 0.24). There was a higher rate of post-operative VTE events among women with CEI (8.9% vs 1.7%, p = 0.02). CONCLUSIONS: In this small series, GO patients undergoing laparotomy had improved post-operative pain control when their analgesia regimen included CEI. However, the higher rate of VTE events among CEI users is concerning and merits further investigation.

Improvement in symptom burden within one day after palliative care consultation in a cohort of gynecologic oncology inpatients.

OBJECTIVE: The aim of this study is to evaluate the magnitude and time course of change in symptom burden after palliative care (PC) consultation in a cohort of gynecologic oncology inpatients. METHODS: Women with a gynecologic malignancy and PC consultation for symptom management between 3/1/12 and 2/28/13 were identified. Charts were reviewed for demographic and disease characteristics. Symptom scores on a modified Edmonton Symptom Assessment System (ESAS) scale were abstracted for pain, anorexia, fatigue, depression, anxiety, nausea and dyspnea. Prevalence of moderate-to-severe symptom intensity was compared between the day of PC consultation (D1), the day after PC consultation (D2) and the last recorded symptoms before discharge (DLast). RESULTS: PC was consulted for symptom management during 129 admissions of 95 unique patients. Median age was 59, 84% were white and 67% had stage III/IV disease, with ovarian the most common site (52%). Symptom prevalence on D1 for at least mild intensity ranged 14% (dyspnea) to 80% (pain) and for at least moderate intensity from 3% (dyspnea) to 50% (pain). Statistically significant decreases in prevalence of moderate to severe symptom intensity between D1 and DLast occurred for pain, anorexia, fatigue and nausea (magnitude 58-66%) and between D1 and D2 for pain, fatigue and nausea (magnitude 50-55%). The majority of the improvement that occurred between D1 and DLast happened by D2. CONCLUSIONS: PC consultation is associated with improvement in symptom burden, the majority of which occurs within one day of consultation. PC may be an effective tool for symptom management in patients with moderate to severe symptom intensity even during short hospitalizations and should be considered early in the hospitalization to effect timely symptom relief.

Needs assessment of palliative care education in gynecologic oncology fellowship: we're not teaching what we think is most important.

OBJECTIVES: We sought to characterize gynecologic oncology fellowship directors' perspectives on (1) inclusion of palliative care (PC) topics in current fellowship curricula, (2) relative importance of PC topics and (3) interest in new PC curricular materials. METHODS: An electronic survey was distributed to fellowship directors, assessing current teaching of 16 PC topics meeting ABOG/ASCO objectives, relative importance of PC topics and interest in new PC curricular materials. Descriptive and correlative statistics were used. RESULTS: Response rate was 63% (29/46). 100% of programs had coverage of some PC topic in didactics in the past year and 48% (14/29) have either a required or elective PC rotation. Only 14% (4/29) have a written PC curriculum. Rates of explicit teaching of PC topics ranged from 36% (fatigue) to 93% (nausea). Four of the top five most important PC topics for fellowship education were communication topics. There was no correlation between topics most frequently taught and those considered most important (rs=0.11, p=0.69). All fellowship directors would consider using new PC curricular materials. Educational modalities of greatest interest include example teaching cases and PowerPoint slides. CONCLUSIONS: Gynecologic oncology fellowship directors prioritize communication topics as the most important PC topics for fellows to learn. There is no correlation between which PC topics are currently being taught and which are considered most important. Interest in new PC curricular materials is high, representing an opportunity for curricular development and dissemination. Future efforts should address identification of optimal methods for teaching communication to gynecologic oncology fellows.

Predictors of palliative care consultation on an inpatient gynecologic oncology service: are we following ASCO recommendations?

OBJECTIVE: Determine predictors of inpatient palliative care (PC) consultation and characterize PC referral patterns with respect to recommendations from the American Society of Clinical Oncology (ASCO). METHODS: Women with a gynecologic malignancy admitted to the gynecologic oncology service 3/2012-8/2012 were identified. Demographic information, disease and treatment details and date of death were abstracted from medical records. Student's t-test, Fischer's exact test or χ(2)-test was used for univariate analysis. Binomial logistic regression was used for multivariate analysis. RESULTS: Of 340 patients analyzed, 82 (24%) had PC consultation. Univariate predictors of PC consultation included race, cancer type and stage, recurrent disease, admission frequency, admission for symptom management or malignant bowel obstruction (MBO), discharge to skilled nursing facility (SNF) and number of lines of chemotherapy. On multivariate analysis, significant predictors of PC consultation were recurrent disease (OR 2.4, 95% CI 1.1-5.3), number of admissions (≥ 3, OR 10.9, 95% CI 3.4-34.9), admission for symptom management (OR 19.4, 95% CI 7.5-50.1), discharge to SNF (OR 5, 95% CI 1.9-13.5) and death within 6 months (OR 16.5, 95% CI 6.9-39.5). Of patients considered to meet ASCO guidelines, 53% (63/118) had PC referral. Of patients referred to PC, 51.2% (42/82) died within 6 months of last admission. CONCLUSIONS: Patients referred to inpatient PC have high disease and symptom burden and poor prognosis. High-risk patients, including those meeting ASCO recommendations, are not captured comprehensively. We continue to use PC referrals primarily for patients near the end of life, rather than utilizing early integration as recommended by ASCO.

Neoadjuvant radiotherapy with or without chemotherapy followed by extrafascial hysterectomy for locally advanced endometrial cancer clinically extending to the cervix or parametria.

PURPOSE: For locally-advanced uterine cancer clinically extending to the cervix, two treatment paradigms exist: surgical staging radical hysterectomy with tailored adjuvant therapy or neoadjuvant therapy followed by a less extensive simple hysterectomy. Currently, insufficient data exists to guide consensus guidelines and practical application of preoperative radiotherapy. MATERIALS AND METHODS: Retrospective IRB approved cohort study from 1999 to 2014 of 36 endometrial cancer patients with clinical involvement of cervix±parametria treated with neoadjuvant external beam radiotherapy (45-50.4Gy in 25-28 fractions) and image-based HDR brachytherapy (5-5.5Gy times 3-4 fractions)±chemotherapy followed by extrafascial hysterectomy performed at a median of 6weeks after radiotherapy. RESULTS: All patients had clinical cervical extension, 50% also had parametria extension, and 31% had nodal involvement. At the time of surgery 91% had no clinical cervical involvement, 58% had no pathologic cervical involvement, and all had margin negative resection. The pathologic complete response rate was 24%. Median follow-up from the time of surgery was 20months (range: 0-153). The 3-year local control, regional control, distant control, disease free survival and overall survival rates were 96%, 89%, 84%, 73%, and 100%. The 3-year rate of grade 3 complications was 11%, with no grade 4+ toxicity. CONCLUSIONS: Neoadjuvant radiation therapy±chemotherapy followed by extrafascial hysterectomy appears to be a viable option for patients with endometrial cancer clinically extending to the cervix and parametria. The HDR brachytherapy schema of 5-5.5Gy times 3-4 fractions, for a cumulative EQD2 of 60-70Gy, is well tolerated with high rates of clinical and pathological response.

Para-aortic lymph node dissection for women with endometrial adenocarcinoma and intermediate- to high-risk tumors: does it improve survival?

OBJECTIVE: Literature suggests that para-aortic lymphadenectomy (para-aortic lymph node dissection [PALND]) has a therapeutic benefit for women with intermediate- to high-risk endometrial adenocarcinoma. We hypothesized that the observed survival advantage of PALND is a reflection of the general health of the patient rather than a therapeutic benefit of surgery. METHODS: Women with intermediate- to high-risk endometrial adenocarcinoma diagnosed from 2002 to 2009 at a single institution were identified. Medical comorbidities, pathology, and survival information were abstracted from the medical record. The χ test or the t test was used for univariate analysis. Overall survival (OS) and disease-specific survival (DSS) were calculated using the Kaplan-Meier method. RESULTS: A total of 253 women with a mean age of 64 years were identified. Of these women, 174 had a pelvic lymphadenectomy (pelvic lymph node dissection [PLND]) and 82 had PLND and PALND. The rate of positive nodes was 13% (23/174) for the women who had PLND and was 7% (6/82) for those who had PLND and PALND. Only 1.2% (1/82) of the women who had PLND and PALND had negative pelvic but positive para-aortic nodes. The patients who had PALND had a lower body mass index and were less likely to have significant medical comorbidities. The patients who had PALND had improved 5-year OS (96% vs 82%, P = 0.007) but no difference in 5-year DSS (96% vs 89%, P value = not significant). CONCLUSIONS: Women with intermediate- to high-risk endometrial adenocarcinoma who undergo PALND have improved OS but no improvement in DSS. The lack of difference in DSS supports the hypothesis that underlying comorbidities as opposed to lack of PALND result in poorer outcome.

Concurrent RB1 Loss and BRCA-Deficiency Predicts Enhanced Immunological Response and Long-Term Survival in Tubo-Ovarian High-Grade Serous Carcinoma.

PURPOSE: To evaluate RB1 expression and survival across ovarian carcinoma histotypes, and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC). EXPERIMENTAL DESIGN: RB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes and transcriptomic subtypes. Using CRISPR-Cas9, we deleted RB1 in HGSC cells with and without BRCA1 alterations to model co-loss with treatment response. We performed whole-genome and transcriptome data analyses on 126 primary HGSC to characterize tumors with concurrent BRCA-deficiency and RB1 loss. RESULTS: RB1 loss was associated with longer OS in HGSC, but with poorer prognosis in endometrioid ovarian carcinoma. Patients with HGSC harboring both RB1 loss and pathogenic germline BRCA variants had superior OS compared to patients with either alteration alone, and their median OS was three times longer than those without pathogenic BRCA variants and retained RB1 expression (9.3 vs. 3.1 years). Enhanced sensitivity to cisplatin and paclitaxel was seen in BRCA1-altered cells with RB1 knockout. Combined RB1 loss and BRCA-deficiency correlated with transcriptional markers of enhanced interferon response, cell-cycle deregulation, and reduced epithelial-mesenchymal transition. CD8+ lymphocytes were most prevalent in BRCA-deficient HGSC with co-loss of RB1. CONCLUSIONS: Co-occurrence of RB1 loss and BRCA-deficiency was associated with exceptionally long survival in patients with HGSC, potentially due to better treatment response and immune stimulation.