Letters of recommendation for gynecologic oncology fellowship differ by gender and race.

INTRODUCTION: Letters of recommendation (LOR) play a significant role in applicant selection for gynecologic oncology (GO) fellowship. LORs can be agentic, associated with competence, independence and strength, or communal, associated with being accommodating, cooperative and empathetic. Agentic LORs have been shown to reflect favorably on applicants, making them more likely to be selected for interview. The primary goal of this study was to determine linguistic differences in LORs for applicants applying to GO fellowship based on applicant gender and race. METHODS: All applications to a single academic institution from the years 2018-2020 were analyzed. LORs were extracted from all applicants who self-reported their gender and race/ethnicity. Analysis was performed using Linguistic Inquiry Word Count (LIWC) in terms of agentic and communal language. All analysis was done using SAS version 9.4. RESULTS: From 2018 to 2020, there were 239 GO fellowship applications to a single academic institution. There were 186 (78.1%) applicants who identified as female and 52 (21.8%) who identified as male. Female applicants were more likely to have more research (p = 0.047) and volunteer activities (p = 0.02) than male applicants. There were no differences between female and male applicants in terms of age, geographic location of residency, USMLE scores, AOA status, number of publications or attending a Doximitiy-rated top 20 residency program. There were 139 (60.7%) applicants who identified as White, 46 (20.1%) as Asian, 16 (7.0%) as Black, 19 (8.3%) as Latinx and 9 (3.9%) as other. On multivariable analysis, LORs written for male applicants had higher agentic scores compared to females (p < 0.05), and LORs of female applicants received higher communal scores (p < 0.05). LORs for applicants who identified as Black or Latinx were found to have lower agentic scores compared to individuals who identified as White(p < 0.05 for both). CONCLUSION: There were demonstrated linguistic differences in LOR for GO fellowship based on applicant gender and race/ethnicity. LORs written for white, male applicants were more likely to have higher agentic scores compared to minority, female applicants. LORs written for female applicants were more likely to have higher communal scores. As LORs have been shown to be instrumental in GO fellowship interview selection and linguistic differences exist based on applicant gender and race/ethnicity, this study highlights the need for a more objective GO fellowship application process. DISCLOSURES: Portion of this paper was presented at the Society for Gynecologic Oncology as part of a focus plenary.

Outcomes for patients with high-risk endometrial cancer undergoing sentinel lymph node assessment versus full lymphadenectomy.

OBJECTIVE: The objective of this study was to determine the progression free survival (PFS) and overall survival (OS) among patients with high-risk endometrial cancer (EC) who underwent sentinel lymph node (SLN) mapping and dissection compared to patients who underwent pelvic +/- para-aortic lymphadenectomy (LND). METHODS: Patients with newly diagnosed high-risk EC were identified. Inclusion criteria included patients who underwent primary surgical management from January 1, 2014 to September 1, 2020 at our institution. Patients were categorized into either the SLN or LND group based on their method of planned lymph node assessment. Patients in the SLN group had dye injected followed by successful bilateral lymph node mapping, retrieval, and processing per our institutional protocol. Clinicopathological and follow-up data were extracted from patient's medical records. The t-test or Mann-Whitney test was used to compare continuous variables and Chi-squared or Fisher's exact test were used for categorical variables. Progression-free survival (PFS) was calculated from the date of initial surgery to the date of progression, death, or last follow-up. Overall survival (OS) was calculated from the date of surgical staging to the date of death or last follow-up. Three-year PFS and OS were calculated using the Kaplan-Meier method, and the log-rank test was used to compare cohorts. Multivariable Cox regression models were used to assess the relationship between nodal assessment cohort and OS/PFS while adjusting for age, adjuvant therapy, and surgical approach. A result was considered statistically significant at the p < 0.05 level of significance and all statistical analysis was done using SAS version 9.4 (SAS Institute, Cary, NC). RESULTS: Out of 674 patients diagnosed with EC during the study period, 189 were diagnosed with high-risk EC based on our criteria. Forty-six (23.7%) patients underwent SLN assessment and 143 (73.7%) underwent LND. No difference was observed between the two groups in regards to age, histology, stage, body mass index, tumors myometrial invasion, lymphovascular space invasion, or peritoneal washing positivity. Patients in the SLN group underwent robotic-assisted procedures more frequently than those in the LND group (p < 0.0001). The three-year PFS rate was 71.1% (95% CI 51.3-84.0%) in the SLN group and 71.3% (95% CI 62.0-78.6%) in the LND group (p = 0.91). The unadjusted hazard ratio (HR) for recurrence in the SLN versus LND group was 1.11 (95% CI 0.56-2.18; p = 0.77), and after adjusting for age, adjuvant therapy, and surgical approach, the HR for recurrence was 1.04 (95% CI 0.47-2.30, p = 0.91). The three-year OS rate was 81.1% (95% CI 51.1-93.7%) in the SLN group and 95.1% (95% CI 89.4-97.8%) in the LND group (p = 0.009). Although the unadjusted HR for death was 3.74 in the SLN vs LND group (95% CI 1.39-10.09; p = 0.009), when adjusted for age, adjuvant therapy, and surgical approach, it was no longer significant with a HR of 2.90 (95% CI 0.94-8.95, p = 0.06). CONCLUSIONS: There was no difference in three-year PFS in patients diagnosed with high-risk EC who underwent SLN evaluation compared to those who underwent full LND in our cohort. The SLN group did experience shorter unadjusted OS; however, when adjusting for age, adjuvant therapy and surgical approach, there was no difference OS in patients who underwent SLN compared to LND.

Missing a chance to prevent: disparities in completion of genetic evaluation in high-risk patients with endometrial cancer.

OBJECTIVE: The primary goal of this study is to examine disparities in high-risk endometrial cancer (EC) patients in relation to rates of genetic referrals (GR), testing (GT), and counseling (GC). METHODS: This is a retrospective analysis of patients with newly diagnosed EC between January 1, 2014 and September 1, 2020 at a single institution. Patients were defined as high-risk EC patients when they were 1) diagnosed at 50 years or younger, 2) had a positive family history for cancer or 3) had evidence of loss of mismatch repair protein expression on tumor immunohistochemistry. Rates of GR, GT and GC were analyzed based on race, ethnicity, primary language and insurance status. RESULTS: During the study period, 674 patients were diagnosed with EC and 249 (36.9%) were considered high-risk EC patients. Among high-risk patients, 128 (51.2%) were referred to GT and GC. Of those referred, 103 (80.5%) underwent GT and 85 (66.4%) completed GC. Out of all high-risk patients, 20 (18.4%) were positive for LS on GT and 29 (28.2%) had VUS results. In multivariate analysis, the odds of GT and GC referral were lower among patients who identified as Hispanic (OR=0.40; 95% CI=0.19-0.87; p=0.020). Patients who identified as black were less likely to receive GC when compared to patients of other races (p=0.030). CONCLUSION: It is our hope that through this data we will increase awareness around existing disparities in genetic evaluation for patients with EC and ultimately create strategies to improve equitable access to care for all patients.

Inflammatory markers in gynecologic oncology patients hospitalized with COVID-19 infection.

OBJECTIVE: Elevated inflammatory markers are predictive of COVID-19 infection severity and mortality. It is unclear if these markers are associated with severe infection in patients with cancer due to underlying tumor related inflammation. We sought to further understand the inflammatory response related to COVID-19 infection in patients with gynecologic cancer. METHODS: Patients with a history of gynecologic cancer hospitalized for COVID-19 infection with available laboratory data were identified. Admission laboratory values and clinical outcomes were abstracted from electronic medical records. Severe infection was defined as infection requiring ICU admission, mechanical ventilation, or resulting in death. RESULTS: 86 patients with gynecologic cancer were hospitalized with COVID-19 infection with a median age of 68.5 years (interquartile range (IQR), 59.0-74.8). Of the 86 patients, 29 (33.7%) patients required ICU admission and 25 (29.1%) patients died of COVID-19 complications. Fifty (58.1%) patients had active cancer and 36 (41.9%) were in remission. Patients with severe infection had significantly higher ferritin (median 1163.0 vs 624.0 ng/mL, p < 0.01), procalcitonin (median 0.8 vs 0.2 ng/mL, p < 0.01), and C-reactive protein (median 142.0 vs 62.3 mg/L, p = 0.02) levels compared to those with moderate infection. White blood cell count, lactate, and creatinine were also associated with severe infection. D-dimer levels were not significantly associated with severe infection (p = 0.20). CONCLUSIONS: The inflammatory markers ferritin, procalcitonin, and CRP were associated with COVID-19 severity in gynecologic cancer patients and may be used as prognostic markers at the time of admission.

Impact of the coronavirus disease 2019 pandemic on the quality of life for women with ovarian cancer.

BACKGROUND: The coronavirus disease 2019 pandemic has resulted in unprecedented challenges for the oncology community. For people living with cancer, treatments are interrupted, surgeries cancelled, and regular oncology evaluations rescheduled. People with cancer and their physicians must balance plausible fears of coronavirus disease 2019 and cancer treatment with the consequences of delaying cancer care. OBJECTIVE: We aim to evaluate the experience of women with ovarian cancer during the coronavirus disease 2019 pandemic. STUDY DESIGN: Women with a current or previous diagnosis of ovarian cancer completed an online survey focusing on treatment interruptions and quality of life. The quality of life was measured with the Cancer Worry Scale and Hospital Anxiety and Depression Scale. The survey was distributed through survivor networks and social media. Univariate and multivariable linear regression analysis were used to evaluate the effect of participant characteristics on quality of life survey scores. RESULTS: A total of 603 women, from 41 states, visited the survey website between March 30, 2020, and April 13, 2020, and 555 (92.0%) completed the survey. The median age was 58 years (range, 20-85). At the time of survey completion, 217 participants (43.3%) were in active treatment. A total of 175 participants (33%) experienced a delay in some component of their cancer care. Ten (26.3%) of the 38 participants scheduled for surgery experienced a delay, as did 18 (8.3%) of the 217 participants scheduled for nonsurgical cancer treatment. A total of 133 participants (24.0%) had a delayed physician appointment, 84 (15.1%) laboratory tests, and 53 (9.6%) cancer-related imaging. Among the cohort, 88.6% (489) reported significant cancer worry, 51.4% (285) borderline or abnormal anxiety, and 26.5% (147) borderline or abnormal depression. On univariate analysis, age less than 65 years, being scheduled for cancer treatment or cancer surgery, delay in oncology care, being self-described as immunocompromised, and use of telemedicine were all associated with higher levels of cancer worry. Higher anxiety scores were associated with age less than 65 years and being self-described as immunocompromised. Higher depression scores were associated with age less than 65 years, being scheduled for cancer surgery, delay in oncology care, being self-described as immunocompromised, and use of telemedicine. On multivariable linear regression analysis, age less than 65 and being self-described as immunocompromised were independently predictive of greater cancer worry, anxiety, and depression, and delay in cancer care was predictive of anxiety and depression. CONCLUSION: The coronavirus disease 2019 crisis is affecting care of patients with ovarian cancer; surgeries, treatments, scheduled physician appointments, laboratory tests, and imaging are cancelled or delayed. Younger age, presumed immunocompromise, and delay in cancer care were associated with significantly higher levels of cancer worry, anxiety, and depression. Providers must work with patients to balance competing risks of coronavirus disease 2019 and cancer, recognizing that communication is a critical clinical tool to improve quality of life in these times.

HIV-positive women with anal high-grade squamous intraepithelial lesions: a study of 153 cases with long-term anogenital surveillance.

Women living with HIV (WLHIV) are at increased risk for human papillomavirus (HPV)-associated anal cancer. Given the "field effect" of HPV pathogenesis, some recommend that anal cancer screening should be limited to WLHIV with prior genital disease. This study aimed to characterize the relationship between anal and genital disease in WLHIV in order to better inform anal cancer screening guidelines. We retrospectively studied 153 WLHIV with biopsy-proven anal high-grade squamous intraepithelial lesions (AHSIL) and long-term evaluable cervical/vaginal/vulvar histopathology. Based on the absence or presence of genital HSIL, subjects were categorized as having isolated AHSIL or multicentric HSIL. Demographics, HIV parameters and cervical/anal HPV status were recorded. Chi-square test was used for bivariate analyses. Of 153 WLHIV with AHSIL, 110 (72%) had isolated AHSIL, while 43 (28%) had multicentric HSIL (28 cervical, 16 vulvar, and 8 vaginal HSIL). The median genital surveillance was 8 years (range 1-27). Cervical HPV16/18 infection was associated with multicentric disease (P = 0.001). Overall, 53% of multicentric cases presented genital HSIL preceding AHSIL with median interval 13 years (range 2-23). Paired anal and cervical high-risk HPV results were available for 60 women within 12 months of AHSIL diagnosis: 30 (50%) had anal infection alone, while 30 (50%) had anal/cervical coinfection by 16/18 (15%), non-16/18 (13%), or different types (22%). In conclusion, WLHIV frequently develop AHSILs without pre-existing genital disease or after long latency following a genital HSIL diagnosis. Our findings support anal cancer screening for WLHIV irrespective of prior genital disease.

Sentinel Lymph Node Ultra-staging as a Supplement for Endometrial Cancer Intraoperative Frozen Section Deficiencies.

For endometrial cancer (EC), most surgeons rely on intraoperative frozen section (IFS) to determine the risk of nodal metastasis and necessity of lymphadenectomy. IFS remains a weak link in this practice due to its susceptibility to diagnostic errors. As a less invasive alternative, sentinel lymph node (SLN) mapping and ultra-staging have gradually gained acceptance for EC. We aimed to establish the SLN success rate, negative predictive value, and whether SLNs provide useful information for cases misdiagnosed on IFS. From 2013 to 2017, 100 patients (63 low-risk and 37 high-risk EC) underwent hysterectomy, bilateral salpingo-oophorectomy, and SLN. Among them, 56 had additional pelvic lymphadenectomy. A total of 337 SLNs were obtained in 86 cases: 55 bilaterally and 31 unilaterally. The remaining 14 cases failed because of patient obesity or leiomyoma. Pathology ultra-staging detected 2 positive SLNs from 2 patients (1 with isolated tumor cells, 1 with micrometastases). One of 773 nonsentinel pelvic nodes was positive on the contralateral hemi-pelvis in a patient who was mapped unilaterally, resulting in negative predictive value of 100%. During IFS, tumor grade and/or depth of myometrial invasion was misdiagnosed in 22 cases (22%). These errors would have resulted in under-staging in 10 high-risk patients or over-staging in 4 low-risk patients. SLNs were mapped in these misestimated patients, with one revealing metastases. SLN provides invaluable information on nodal status while detecting occult metastases in cases misdiagnosed on IFS. Our findings justify the incorporation of SLN in initial surgery for EC as an offset to IFS diagnostic errors, minimizing their negative impact on patient care.

Feasibility and diagnostic performance of hybrid PET/MRI compared with PET/CT for gynecological malignancies: a prospective pilot study.

PURPOSE: The purpose of the study was to assess the feasibility and diagnostic performance of FDG-PET/MR imaging compared to PET/CT for staging of patients with a gynecological malignancy. METHODS: 25 patients with a gynecological malignancy were prospectively enrolled into this pilot study. Patients underwent sequential full-body PET/CT and PET/MR of the abdomen and pelvis after administration of a single dose of F-18 FDG. PET/MRI and PET/CT images were independently reviewed by two expert radiologists. Readers were blinded to the results of the other imaging procedures. Clinical and pathologic information was abstracted from medical charts. RESULTS: 18 patients were included in the final analysis with a median age of 62 years (range 31-88). 61% of patients (11/18) had cervical cancer, while the remaining patients had endometrial cancer. PET/MRI as compared to PET/CT detected all primary tumors, 7/7 patients with regional lymph nodes, and 1/1 patient with an abdominal metastasis. Two patients had additional lymph nodes outside of the abdominopelvic cavity detected on PET/CT that were not seen on PET/MRI, whereas 6 patients had parametrial invasion and one patient had invasion of the bladder seen on PET/MRI not detected on PET/CT. Five cervical cancer patients had discordant clinical vs. radiographic staging based on PET/MRI detection of soft tissue involvement. Management changed for two patients who had clinical stage IB1 and radiographic stage IIB cervical cancer. CONCLUSIONS: PET/MRI is feasible and has at least comparable diagnostic ability to PET/CT for identification of primary cervical and endometrial tumors and regional metastases. PET/MRI may be superior to PET/CT for initial radiographic assessment of cervical cancers.

Laparoscopic Assessment to Determine the Likelihood of Achieving Optimal Cytoreduction in Patients Undergoing Primary Debulking Surgery for Ovarian, Fallopian Tube, or Primary Peritoneal Cancer.

OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of laparoscopic assessment to determine the likelihood of achieving optimal cytoreduction (OC) in patients undergoing primary debulking surgery (PDS) for ovarian cancer. METHODS: All patients who underwent diagnostic laparoscopy and PDS at our institution from January 2008 to December 2013 were identified. We determined the likelihood of achieving optimal cytoreduction by laparoscopic assessment based on tumor site, pattern of spread, and disease burden. Sensitivity was defined as the number of patients who achieved optimal cytoreduction after laparoscopic assessment divided by the number of patients with disease deemed resectable by laparoscopy. RESULTS: We identified 55 patients during study period. Twenty-one of the 55 patients (38%) were early stage disease. Six (10.9%) patients had disease deemed unresectable and 49 (89.1%) had disease deemed resectable at the time of laparoscopy. OC was achieved in 48 of 49 (97.9%) patients. The sensitivity of laparoscopy in predicting OC was 98% (95% confidence interval, 89.3%-99.9%). The operation was completed laparoscopically in 23 of 49 patients (47%); in 26 of 49 (53%), PDS was performed by laparotomy. There were no port site metastases reported. The rate of postoperative complications was 16%. With a median follow-up of 30 months, the median overall survival was not reached and the 75th percentile for overall survival was 37 months. CONCLUSIONS: Laparoscopy was shown to have a high sensitivity in predicting OC and is a feasible tool in triaging patients with ovarian cancer. Laparoscopy is not associated with adverse surgical outcomes.

Secondary Surgery Versus Chemotherapy for Recurrent Ovarian Cancer.

OBJECTIVE: The best course of treatment for recurrent ovarian cancer is uncertain. We sought to determine whether secondary cytoreductive surgery for first recurrence of ovarian cancer improves overall survival compared with other treatments. MATERIALS AND METHODS: We assessed survival using Surveillance, Epidemiology and End Results-Medicare data for advanced stage ovarian cancer cases diagnosed from January 1, 1997 to December 31, 2007 with survival data through 2010 using multinomial propensity weighted finite mixture survival regression models to distinguish true from misclassified recurrences. Of 35,995 women ages 66 years and older with ovarian cancer, 3439 underwent optimal primary debulking surgery with 6 cycles of chemotherapy; 2038 experienced a remission. RESULTS: One thousand six hundred thirty-five of 2038 (80%) women received treatment for recurrence of whom 72% were treated with chemotherapy only, 16% with surgery and chemotherapy and 12% received hospice care. Median survival of women treated with chemotherapy alone, surgery and chemotherapy, or hospice care was 4.1, 5.4, and 2.2 years, respectively (P<0.001). Of those receiving no secondary treatments, 75% were likely true nonrecurrences with median survival of 15.9 years and 25% misclassified with 2.4 years survival. Survival among women with recurrence was greater for those treated with surgery and chemotherapy compared with chemotherapy alone (hazard ratio=1.67; 95% confidence interval, 1.13-2.47). Women who were older with more comorbidities and high-grade cancer had worse survival. CONCLUSIONS: Secondary surgery with chemotherapy to treat recurrent ovarian cancer increases survival by 1.3 years compared with chemotherapy alone and pending ongoing randomized trial results, may be considered a standard of care.

Adjuvant radiation therapy is associated with improved overall survival in high-intermediate risk stage I endometrial cancer: A national cancer data base analysis.

PURPOSE: Adjuvant radiation therapy (RT) was shown to improve local control in patients with high-intermediate risk (HIR) stage I endometrial cancer (EC) in randomized trials. Overall survival (OS) was not significantly different with adjuvant RT in these trials or subsequent meta-analyses; however, they were underpowered to assess OS. We used the National Cancer Data Base (NCDB) to examine the impact of adjuvant RT on OS in HIR EC patients. METHODS: The NCDB was queried for patients diagnosed with FIGO (2009) Stage I endometrioid adenocarcinoma from 1998 to 2012 who underwent surgery±adjuvant RT. Per ASTRO guidelines, HIR risk was defined as stage IB and/or grade 3. Patients were excluded if: non-surgical primary therapy, RT>180days after surgery, unknown stage/grade/RT status, or RT to targets outside pelvis/vagina. Kaplan-Meier plots and Cox proportional hazards regression were used. RESULTS: 33,600 patients met criteria. 18,070 patients (53.8%) received surgery alone, 15,530 patients (46.2%) received surgery+adjuvant RT. Of patients who received adjuvant RT, 42.2% received external beam RT, 44.7% brachytherapy, and 13.1% received both. 5-year OS was 79.2% for the surgery alone group and 83.3% for the surgery+adjuvant RT (p<0.0001). On multivariate analysis, adjuvant RT was independently associated with improved OS vs. surgery alone (HR 0.7; 95% CI 0.8-0.9, p<0.0001). CONCLUSIONS: Our results show that surgery+adjuvant RT was associated with a statistically significant 4.1% improvement in 5-year OS vs. surgery alone in stage I HIR EC. This data along suggests that the improvement in local control with adjuvant RT leads to improved OS.

A Validation Study of Administrative Claims Data to Measure Ovarian Cancer Recurrence and Secondary Debulking Surgery.

OBJECTIVE: Administrative claims data offer an alternative to chart abstraction to assess ovarian cancer recurrence, treatment and outcomes. Such analyses have been hindered by lack of valid recurrence and treatment algorithms. In this study, we sought to develop claims-based algorithms to identify ovarian cancer recurrence and secondary debulking surgery, and to validate them against the gold-standard of chart abstraction. METHODS: We conducted chart validation studies; 2 recurrence algorithms and 1 secondary surgery among 94 ovarian cancer patients treated at one hospital between 2003-2009. A new recurrence algorithm was based on treatment timing (≥6 months after primary treatment) and a previously validated algorithm was based on secondary malignancy codes. A secondary debulking surgery algorithm was based on surgical billing codes. RESULTS: The new recurrence algorithm had: sensitivity=100% (95% confidence interval [CI]=87%-=100%), specificity=89% (95%CI=78%-95%), kappa=84% (SE=10%) while the secondary-malignancy-=code recurrence algorithm had: sensitivity=84% (95%CI=66%-94%), specificity=44% (95%CI=31%-=57%), kappa=23% (SE=8%). The secondary surgery algorithm had: sensitivity=77% (95%CI=50%-92%), = specificity= 92% (95%CI=83%-97%), kappa=66% (SE=10%).=. CONCLUSIONS: A recurrence algorithm based on treatment timing accurately identified ovarian cancer =recurrence. If validated in other populations, such an algorithm can provide a tool to compare effectiveness of recurrent ovarian cancer treatments.

Adenoid Cystic Carcinoma of Bartholin's Gland: Case Report.

Primary adenoid cystic carcinoma (ACC) of Bartholin's gland is a rare gynecologic malignancy. We report a case of locally advanced ACC of Bartholin's gland. A 62-year-old presented with left Bartholin's gland carcinoma and underwent left radical vulvectomy, left-sided inguinal-femoral lymph node dissection, posterior pelvic exenteration, and pedicle abdominal muscle flap. On her 3 months follow-up exam she was disease free.Pelvic exenteration for thetreatment of this rare disease in the vulva is a potential curative option.

Ovarian Cancer Treatment and Survival Trends Among Women Older Than 65 Years of Age in the United States, 1995-2008.

OBJECTIVE: To evaluate whether overall survival is improving among women in the United States with advanced ovarian cancer. METHODS: This retrospective cohort study evaluated trends in treatment and overall survival for women older than 65 years diagnosed with stage III and IV epithelial ovarian cancer between 1995 and 2008 using Surveillance, Epidemiology, and End Results-Medicare data. Parametric and semiparametric multivariate survival analyses were used to assess comparative treatment survival rates and factors affecting survival and recurrence. RESULTS: Of 7,938 women who met study criteria, 2.9% received no treatment, 15.4% underwent surgery only, 24.8% received chemotherapy only, 41.8% underwent primary debulking surgery and chemotherapy in an optimal timeframe, and 15.1% had primary debulking surgery and chemotherapy, but the timing was not optimal or patients did not complete all six cycles of chemotherapy. Those who underwent surgery only had similar survival as those who received no treatment (2.2 compared with 1.7 months), whereas those who received chemotherapy only had a better overall survival (14.4 months). Optimal treatment was associated with the longest survival time (P<.001, median overall survival 39.0 months). Additionally, survival time associated with optimal treatment increased over the past decade. However, the proportion of women who received optimal treatment has decreased over the past decade. CONCLUSION: Elderly women with advanced ovarian cancer have the best survival with optimal therapy. When this is not offered or possible, chemotherapy alone offers better survival than surgery alone.

Personalized Circulating Tumor DNA Biomarkers Dynamically Predict Treatment Response and Survival In Gynecologic Cancers.

BACKGROUND: High-grade serous ovarian and endometrial cancers are the most lethal female reproductive tract malignancies worldwide. In part, failure to treat these two aggressive cancers successfully centers on the fact that while the majority of patients are diagnosed based on current surveillance strategies as having a complete clinical response to their primary therapy, nearly half will develop disease recurrence within 18 months and the majority will die from disease recurrence within 5 years. Moreover, no currently used biomarkers or imaging studies can predict outcome following initial treatment. Circulating tumor DNA (ctDNA) represents a theoretically powerful biomarker for detecting otherwise occult disease. We therefore explored the use of personalized ctDNA markers as both a surveillance and prognostic biomarker in gynecologic cancers and compared this to current FDA-approved surveillance tools. METHODS AND FINDINGS: Tumor and serum samples were collected at time of surgery and then throughout treatment course for 44 patients with gynecologic cancers, representing 22 ovarian cancer cases, 17 uterine cancer cases, one peritoneal, three fallopian tube, and one patient with synchronous fallopian tube and uterine cancer. Patient/tumor-specific mutations were identified using whole-exome and targeted gene sequencing and ctDNA levels quantified using droplet digital PCR. CtDNA was detected in 93.8% of patients for whom probes were designed and levels were highly correlated with CA-125 serum and computed tomography (CT) scanning results. In six patients, ctDNA detected the presence of cancer even when CT scanning was negative and, on average, had a predictive lead time of seven months over CT imaging. Most notably, undetectable levels of ctDNA at six months following initial treatment was associated with markedly improved progression free and overall survival. CONCLUSIONS: Detection of residual disease in gynecologic, and indeed all cancers, represents a diagnostic dilemma and a potential critical inflection point in precision medicine. This study suggests that the use of personalized ctDNA biomarkers in gynecologic cancers can identify the presence of residual tumor while also more dynamically predicting response to treatment relative to currently used serum and imaging studies. Of particular interest, ctDNA was an independent predictor of survival in patients with ovarian and endometrial cancers. Earlier recognition of disease persistence and/or recurrence and the ability to stratify into better and worse outcome groups through ctDNA surveillance may open the window for improved survival and quality and life in these cancers.

Interferon regulatory factor 1 is an independent predictor of platinum resistance and survival in high-grade serous ovarian carcinoma.

OBJECTIVE: High-grade serous ovarian cancer (HGSOC) that is resistant to platinum-based chemotherapy has a particularly poor prognosis. Response to platinum has both prognostic survival value and dictates secondary treatment strategies. Using transcriptome analysis, we sought to identify differentially expressed genes/pathways based on a tumor's platinum response for discovering novel predictive biomarkers. METHODS: Seven primary HGSOC tumor samples, representing two extremes of platinum sensitivity/timing of disease recurrence, were analyzed by RNA-Seq, Ingenuity Pathways Analysis (IPA) and Upstream Regulator Analysis (URA), and used to explore differentially expressed genes and prevalent molecular and cellular processes. Progression-free and overall survival (PFS, OS) was estimated using the Kaplan-Meier method in two different sample sets including GEO and TCGA data sets. RESULTS: IPA and URA highlighted an IRF1-driven transcriptional program (P=0.0017; z-score of 3.091) in the platinum sensitive improved PFS group. QRT-PCR analysis of 31 HGSOC samples demonstrated a significant difference in PFS between low and high IRF1 expression groups (P=0.048) and between groups that were platinum sensitive versus not (P=0.016). In a larger validation data set, increased levels of IRF1 were associated with both increased PFS (P=0.043) and OS (P=0.019) and the effect on OS was independent of debulking status (optimal debulking, P=0.025; suboptimal, P=0.041). CONCLUSION: Transcriptome analysis identifies IRF1, a transcription factor that functions both in immune regulation and as a tumor suppressor, as being associated with platinum sensitivity and an independent predictor of both PFS and OS in HGSOC.

Role of FDG PET/CT in staging of recurrent ovarian cancer.

Ovarian cancer is the fifth leading cause of cancer death among women in the United States and has a high likelihood of recurrence despite aggressive treatment strategies. Detection and exact localization of recurrent lesions are critical for guiding management and determining the proper therapeutic approach, which may prolong survival. Because of its high sensitivity and specificity compared with those of conventional techniques such as computed tomography (CT) and magnetic resonance (MR) imaging, fluorine 18 fluorodeoxyglucose positron emission tomography (PET) combined with CT is useful for detection of recurrent or residual ovarian cancer and for monitoring response to therapy. However, PET/CT may yield false-negative results in patients with small, necrotic, mucinous, cystic, or low-grade tumors. In addition, in the posttherapy setting, inflammatory and infectious processes may lead to false-positive PET/CT results. Despite these drawbacks, PET/CT is superior to CT and MR imaging for depiction of recurrent disease.

Laparoscopic radical parametrectomy and partial vaginectomy for recurrent endometrial cancer.

BACKGROUND: Endometrial cancer recurrences in the vagina after surgery and radiation therapy are traditionally treated with pelvic exenteration. However, this operation is associated with significant morbidity and mortality, and thus alternative surgical options should be explored. CASE: We present a case of laparoscopic resection of recurrent endometrial cancer at the vaginal apex in the setting of prior brachytherapy and 32P intraperitoneal therapy. CONCLUSION: Laparoscopic radical parametrectomy and partial vaginectomy may be an option for patients with small central recurrences of endometrial cancer.