Implementation of a financial navigation program in gynecologic oncology.

BACKGROUND: "Financial Toxicity" (FT) is the financial burden imposed on patients due to disease and its treatment. Approximately 50% of gynecologic oncology patients experience FT. This study describes the implementation and outcomes of a novel financial navigation program (FNP) in gynecologic oncology. METHODS: Patients presenting for initial consultation with a gynecologic oncologist from July 2022 to September 2023 were included. A FNP was launched inclusive of hiring a financial navigator (FN) in July 2022, and implementing FT screening in October 2022. We prospectively captured patient referrals to the FN, collecting clinical, demographic, financial and social needs information, along with FN interventions and institutional support service referrals. Referrals to the FN and support services were quantified before and after screening implementation. RESULTS: There were 1029 patients with 21.6% seen before and 78.4% after screening initiation. Median age was 58 (IQR 46-68). The majority were non-Hispanic white (60%) with private insurance (61%). A total of 10.5% patients were referred to the FN. Transportation (32%), financial assistance (20.5%) and emotional support (15.4%) were the most common needs identified. A higher proportion of patients referred to the FN identified as Black, had government-funded insurance or diagnoses of uterine or cervical cancers (p < 0.05). Post-screening referrals to FN increased (5% vs. 12.9%, p < 0.001), while referrals to other support services decreased (9.5% vs. 2.9%, p < 0.001). CONCLUSIONS: Implementation of the FNP was feasible, though presence of both a FN and FT screening maximized its effectiveness. Further investigation is needed to understand screening barriers and evaluate longer-term impact.

Transdifferentiation of diffuse large B-cell lymphoma to a poorly differentiated neoplasm following CAR T-cell therapy.

Chimeric antigen receptor T-cell (CAR-T) therapy is a recent advancement in precision medicine with promising results for patients with relapsed or refractory B-cell malignancies. However, rare post-therapy morphologic, immunophenotypic, and genomic alterations can occur. This study is to present a case of a patient with diffuse large B-cell lymphoma (DLBCL) who underwent anti-CD19 CAR-T therapy with disease in the uterus that showed transdifferentiation to a poorly differentiated malignant neoplasm that failed to express any lineage specific markers. In immunohistochemistry, fluorescence in situ hybridization (FISH) and targeted next-generation sequencing (NGS) were utilized to fully characterize the diagnostic DLBCL sample in comparison to the poorly differentiated neoplasm of the uterus. Analysis of the diagnostic DLBCL and the poorly differentiated neoplasm demonstrated evidence of a clonal relationship as well as revealing acquisition of mutations associated with CAR-T resistance. Furthermore, downregulation of B-cell associated antigens was observed, underscoring a mechanistic link to CAR-T evasion as well as demonstrating diagnostic confusion. This case illustrates the utility of employing multiple diagnostic modalities in elucidating a pathologic link between a B-cell lymphoma and poorly differentiated neoplasm following targeted therapy.

Management of recurrent cervical cancer with peritoneal carcinomatosis with HIPEC.

Cervical cancer is the fourth most common malignancy in women in the world; however, a substantial portion of these malignancies are declining with increasingly sophisticated screening. Unfortunately, recurrent cervical cancer has a dismal prognosis and its management continues to be a growing area of research. While the foundation of treatment remains platinum-based chemotherapies, new techniques such as HIPEC have been evaluated. We present two patients with recurrent cervical adenocarcinoma with peritoneal carcinomatosis who were treated with HIPEC during de-bulking surgery with substantial disease-free survival. One of our patients had 15 months of disease-free survival before developing biliary metastases and the other remains disease free for over 24 months.

Endometrioid Tubal Intraepithelial Neoplasia (E-TIN) of the Fallopian Tube: A Case Series.

Although serous tubal intraepithelial carcinoma has been well described in the distal fallopian tube as precancers of pelvic high-grade serous carcinoma, endometrioid precancers have drawn less attention. Recently, endometrioid precursor lesions have been identified and reported to have a specific immunophenotype (PAX2-, ALDH1+, diffuse nuclear beta-catenin), as well as an association with both uterine and ovarian endometrioid carcinomas. These have been referred to as endometrioid (or type II) secretory cell outgrowths. A subset of endometrioid secretory cell outgrowths show architectural complexity resembling hyperplasia of the endometrium and have been referred to as endometrioid tubal intraepithelial neoplasia. We report 4 cases of endometrioid tubal intraepithelial neoplasia with clinical correlation and morphologic differential diagnosis.

Adoption of enhanced recovery after laparotomy in gynecologic oncology.

INTRODUCTION: Enhanced recovery after surgery (ERAS) pathways combine a comprehensive set of peri-operative practices that have been demonstrated to hasten patient post-operative recovery. We aimed to evaluate the adoption of ERAS components and assess attitudes towards ERAS among gynecologic oncologists. METHODS: We developed and administered a cross-sectional survey of attending, fellow, and resident physicians who were members of the Society of Gynecologic Oncology in January 2018. The χ2 test was used to compare adherence to individual components of ERAS. RESULTS: There was a 23% survey response rate and we analyzed 289 responses: 79% were attending physicians, 57% were from academic institutions, and 64% were from institutions with an established ERAS pathway. Respondents from ERAS institutions were significantly more likely to adhere to recommendations regarding pre-operative fasting for liquids (ERAS 51%, non-ERAS 28%; p<0.001), carbohydrate loading (63% vs 16%; p<0.001), intra-operative fluid management (78% vs 32%; p<0.001), and extended duration of deep vein thrombosis prophylaxis for malignancy (69% vs 55%; p=0.003). We found no difference in the use of mechanical bowel preparation, use of peritoneal drainage, or use of nasogastric tubes between ERAS and non-ERAS institutions. Nearly all respondents (92%) felt that ERAS pathways were safe. DISCUSSION: Practicing at an institution with an ERAS pathway increased adoption of many ERAS elements; however, adherence to certain guidelines remains highly variable. Use of bowel preparation, nasogastric tubes, and peritoneal drainage catheters remain common. Future work should identify barriers to the implementation of ERAS and its components.

Financial toxicity in gynecologic oncology.

OBJECTIVES: Financial toxicity is increasingly recognized as an adverse outcome of cancer treatment. Our objective was to measure financial toxicity among gynecologic oncology patients and its association with demographic and disease-related characteristics; self-reported overall health; and cost-coping strategies. METHODS: Follow-up patients at a gynecologic oncology practice completed a survey including the COmprehensive Score for Financial Toxicity (COST) tool and a self-reported overall health assessment, the EQ-VAS. We abstracted disease and treatment characteristics from medical records. We dichotomized COST scores into low and high financial toxicity and assessed the correlation (r) between COST scores and self-reported health. We calculated risk ratios (RR) and 95% confidence intervals (CI) for the associations of demographic and disease-related characteristics with high financial toxicity, as well as the associations between high financial toxicity and cost-coping strategies. RESULTS: Among 240 respondents, median COST score was 29. Greater financial toxicity was correlated with worse self-reported health (r = 0.47; p < 0.001). In the crude analysis, Black or Hispanic race/ethnicity, government-sponsored health insurance, lower income, unemployment, cervical cancer and treatment with chemotherapy were associated with high financial toxicity. In the multivariable analysis, only government-sponsored health insurance, lower income, and treatment with chemotherapy were significantly associated with high financial toxicity. High financial toxicity was significantly associated with all cost-coping strategies, including delaying or avoiding care (RR: 7.3; 95% CI: 2.8-19.1). CONCLUSIONS: Among highly-insured gynecologic oncology patients, many respondents reported high levels of financial toxicity. High financial toxicity was significantly associated with worse self-reported overall health and cost-coping strategies, including delaying or avoiding care.

Adnexal mass staging CT with a disease-specific structured report compared to simple structured report.

OBJECTIVES: To assess a disease-specific structured report (dsSR) for CT staging of ovarian malignancy compared to a simple structured report (sSR). METHODS: This is a HIPAA-compliant, IRB-approved study with waiver of informed consent. An adnexal mass-specific structured reporting CT template was developed in collaboration between gynecologic oncologists and diagnostic radiologists. The study population included 24 consecutive women who had a staging CT prior to undergoing debulking surgery for a primary ovarian malignancy. Objective evaluation by radiologists for the presence of 19 key features and subjective evaluation by gynecologic oncologists were performed to assess the clarity and usefulness for procedural planning of dsSR and sSR. Accuracy, sensitivity, and specificity were assessed using operating room notes and pathology reports as the reference standard. RESULTS: Fewer key features were missing from dsSR than sSR: 0.2 ± 0.8 (range 0-2) vs.10.2 ± 1.7 (range 7-14), respectively (p < 0.0001). Compared to sSR, gynecologic oncologists deemed dsSR more helpful (4.3 ± 0.7 vs. 3.7 ± 0.8, p < 0.0001) and easier to understand (4.3 ± 0.6 vs. 3.9 ± 0.7, p = 0.0057) (on a scale 0-5, 0 not helpful/very difficult to understand; 5 extremely helpful/very clear to understand). Gynecologic oncologists reported a higher rate of potential to modify their surgical approach based on dsSR (33-42%) compared to sSR (13-17%), p = 0.004. CONCLUSIONS: Disease-specific structured reports were more reliable than simple structured reports in describing key features essential for procedural planning. dsSR was described as more helpful and easier to understand and more likely to lead to modification of the surgical approach by gynecologic oncologists compared to sSR. KEY POINTS: • Disease-specific structured report is easier to understand and more helpful for planning gynecological surgery as compared with simple structured report. • Disease-specific structured report for pre-operative evaluation of ovarian cancer provides better documentation of essential features required for surgical planning as compared with simple structured report. • Disease-specific structured report has the potential to modify the surgical approach as assessed by gynecologic oncologists.

Participation in global health delivery: Survey results from the Society of Gynecologic Oncology.

•Gynecologic oncologists face multiple barriers in participating in global health.•Several barriers may be addressed at the institutional level.•Most global health experiences involved direct patient care, while only a small proportion involved research.•Gynecologic oncologists receive little structured training in global health.

Influence of a novel histone deacetylase inhibitor panobinostat (LBH589) on the growth of ovarian cancer.

BACKGROUND: Pre-clinical studies have demonstrated that natural and synthetic histone deacetylase (HDAC) inhibitors can impede the in vitro and in vivo growth of cell lines from a variety of gynecologic and other malignancies. We investigated the anti-tumor activity of panobinostat (LBH589) both in vitro and in vivo as either a single agent or in combination with conventional cytotoxic chemotherapy using patient-derived xenograft (PDX) models of primary serous ovarian tumors. METHODS: The ovarian cancer cell lines OVCAR8, SKOV3 and their paclitaxel-resistant derivatives OVCAR8-TR and SKOV3-TR were treated with increasing doses of LBH589. The effect of LBH589 on cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Serially transplanted primary human high-grade serous ovarian adenocarcinoma tissue was utilized to generate xenografts in 6-week old female NOD/SCID mice. The mice were then randomized into one of 4 treatment groups: (1) vehicle control; (2) paclitaxel and carboplatin (P/C); (3) LBH589; or (4) P/C + LBH589. Mice were treated for 21 days and tumor volumes and mouse weights were obtained every 3 days. These experiments were performed in triplicate with three different patient derived tumors. Wilcoxan rank-sum testing was utilized to assess tumor volume differences. RESULTS: In vitro treatment with LBH589 significantly reduced the viability of both taxol-sensitive and taxol-resistant ovarian cancer cell lines (p < 0.01). In vivo treatment with LBH589 alone appeared tumorstatic and reduced tumor growth when compared to vehicle treatment (p < 0.007) after 21 days. This single agent activity was confirmed in two additional experiments with other PDX tumors (p < 0.03, p < 0.05). A potential additive effect of LBH589 and P/C, manifested as enhanced tumor regression with the addition of LBH589 compared to vehicle (p < 0.02), in one of the three analyzed serous PDX models. CONCLUSIONS: Our findings suggest that pan-HDAC inhibition with panobinostat precludes the growth of ovarian cancer cell lines in vitro and PDXs in vivo. Added benefit of LBH589 to standard P/C therapy was observed in one of three PDX models suggesting improved response in a subset of serous ovarian cancers.

The role of radical surgery in the management of acquired uterine arteriovenous malformation.

BACKGROUND: Acquired arteriovenous malformations (AVMs) can develop after uterine instrumentation. The increased risks of vascular changes, including abnormal placentation, after repeated cesarean sections are well studied. Herein, we describe a patient with delayed hemorrhage from a uterine AVM, following dilation and curettage for a cesarean scar pregnancy. CASE: A 32-year-old G3P2 presented with a cesarean scar ectopic pregnancy managed with dilation and curettage, which incurred a 1,500-ml blood loss. Within 6 weeks, she returned with 2 episodes of vaginal bleeding. Initial angiography demonstrated a high-flow arteriovenous fistula, which was coiled. Vaginal hemorrhage recurred; repeat angiography demonstrated a large AVM. Gelfoam embolization of the bilateral internal iliac arteries reduced the vascularity of the AVM. The AVM's location, starting at the left lateral apex of the cesarean scar and extending into the parametrium, necessitated a radical hysterectomy. Pathologic examination revealed a placenta percreta extending into the parametrium. CONCLUSION: The prevalence of uterine AVMs has increased with the rise in surgical obstetrics. In patients with a failed prior interventional procedure, surgical management is necessary to prevent life-threatening hemorrhage. The location of the AVM within the abnormal uterine scar tissue requires familiarity with radical pelvic surgical techniques that are normally used in cancer surgery in order to definitively treat this delayed obstetrical complication.

Modest benefit of total parenteral nutrition and chemotherapy after venting gastrostomy tube placement.

OBJECTIVE: The aim of the study is to review a single institution's experience with gastrostomy tubes (GTs) performed for malignant bowel obstruction from gynecologic cancers. METHODS: Women with gynecologic cancers who underwent venting GT placement from 2000 to 2008 were identified and clinical data were extracted. Logistic regression and spearman correlational coefficients were used to determine relationships between variables. Survival analysis was performed using the Kaplan-Meier method and a Cox proportional hazard model. RESULTS: We identified 115 women who underwent GT placement, the majority of whom were diagnosed with ovarian cancer (84%). Median time from cancer diagnosis to GT placement was 2.2 years. Median survival following GT placement was 5.6 weeks. A majority (56%) developed GT complications requiring GT revision. While burden of disease as assessed on CT scan by the validated peritoneal cancer index (PCI) was not associated with survival, low CA-125 within one week of GT placement was associated with improved survival (p<0.01). TPN was administered in 36% of women, was associated with concurrent chemotherapy (p<0.001) and a 5 week survival benefit (p<0.01). Chemotherapy after GT was administered in 40% of women and was associated with a 10 week survival benefit (p<0.001). Age-adjusted multivariate analysis identified chemotherapy as the only independent variable associated with survival. CONCLUSIONS: Women with malignant bowel obstructions from gynecologic cancers requiring palliative GT placement had a guarded prognosis measured in weeks. Gastrostomy tubes near the end of life had a high rate of complications requiring medical intervention. Chemotherapy after GT was associated with TPN administration, and both were associated with a modest extension in survival.

Abnormal cytology in 2012: management of atypical squamous cells, low-grade intraepithelial neoplasia, and high-grade intraepithelial neoplasia.

Cervical cancer and human papillomavirus-related diseases continue to cause significant morbidity and mortality in the United States and worldwide. As we begin to understand the natural course of human papillomavirus infection, and the consequences of both its detection and treatment, changes have been made to our clinical approaches. The purpose of this review is to outline the management guidelines for the management of abnormal cytology. Successful triage of abnormal cytology in 2012 will allow for continued detection of precancerous lesions reducing the incidence of cervical cancer and increasing the detection of early stage disease.

Endometriosis-associated ovarian malignancy: a retrospective analysis of presentation, treatment, and outcome.

OBJECTIVE: To investigate the relationship of age and tumors associated with endometriosis and outcome of different histologies of epithelial ovarian cancer arising from endometriosis. STUDY DESIGN: We identified cases of epithelial ovarian cancers with clear cell, endometrioid, or mixed clear cell and endometrioid histologies from January 2001 to March 2009. Tumors were classified as either "arising in" endometriosis, "associated with" endometriosis or "controls" (not associated with endometriosis). We collected information regarding patient demographics, past medical history, presentation at diagnosis, treatment, and outcome. RESULTS: Of 140 patients identified, 42 (30.0%) had clear cell, 92 (65.7%) had endometrioid, and 6 (4.3%) had mixed. Of those, 28.6% of tumors were associated with endometriosis (n = 40), 37.1% were arising in endometriosis (n = 52), and 34.3% were controls (n = 48). Premenopausal women had tumors that were more likely arising from or associated with endometriosis as compared to tumors in postmenopausal women (p = 0.005). Premenopausal patients were also more likely to present with early stage disease as compared to postmenopausal women (80.4% vs. 63.6%, p = 0.04) and better overall survival (p < 0.008). Survival analyses of the entire cohort showed that improved survival was associated with stage (p < 0.001), grade (p < 0.001), endometrioid histology (p < 0.005), and with tumors associated with or arising in endometriosis (p < 0.04). Multivariate analysis controlling for menopausal status showed the presence of endometriosis was no longer associated with a survival advantage (p = 0.08). CONCLUSION: The association with endometriosis does appear, at least in endometrioid tumors, to provide a survival benefit. Overall, menopausal status, stage, and grade are more powerful variables associated with improved survival.

Laparoendoscopic single-site radical hysterectomy: the first report of LESS type III hysterectomy involves a woman with cervical cancer.

Laparoendoscopic single-site surgery is a logical advance in the evolution of minimally invasive surgery and is being utilized to perform increasingly complex procedures. We report its use for completion of radical hysterectomy as treatment for cervical cancer.

An international series on abdominal radical trachelectomy: 101 patients and 28 pregnancies.

OBJECTIVES: Abdominal radical trachelectomy (ART) is a type C resection (uterine vessels ligated at origin from the hypogastric vessels). Questions arise as to whether fertility is maintained after ART, particularly when uterine vessels are sacrificed. We report an international series on ART to describe fertility and oncologic outcomes. METHODS: Databases at 3 institutions were queried to identify patients planned for ART from 1999 to 2011. Clinical and demographic data were gathered. RESULTS: One hundred one patients underwent ART. Mean age was 31 years (range, 19-43 years). Histologic classifications were adenocarcinoma (n = 54), squamous cell carcinoma (n = 40), adenosquamous carcinoma (n = 6), and clear cell carcinoma (n = 1). Twenty patients (20%) required conversion to hysterectomy (10 margins and 10 nodes). Eight patients underwent completion hysterectomy owing to the following: positive margins on final pathology (n = 3), patient's choice (n = 4), or recurrence (n = 1). Postoperatively, 20 patients (20%) received adjuvant chemotherapy and/or radiation (4 final pathology margins and 16 nodes). Four patients (4%) had recurrence and lived 22 to 35 months after diagnosis. Of the 70 women who had neither hysterectomy nor adjuvant therapy, 38 (54%) attempted pregnancy and 28 (74%) achieved pregnancy. Thirty-one pregnancies resulted in 16 (52%) third trimester deliveries. Six patients are currently pregnant with outcomes pending. CONCLUSIONS: These data demonstrate that ART preserves fertility and maintains excellent oncologic outcomes. Most women (74%) attempting pregnancy after ART are able to achieve pregnancy and deliver in the third trimester (52%). Preservation of the uterine vasculature is not necessary for fertility; obstetrical outcomes are similar to those of the historical vaginal radical trachelectomy cohorts.

Prognostic determinants in patients with stage I uterine papillary serous carcinoma: a 15-year multi-institutional review.

OBJECTIVE: The aim of this retrospective, multi-institutional study was to evaluate the importance of surgical staging for stage I uterine papillary serous carcinomas (UPSCs) to determine optimal management of this rare tumor. METHODS: With institutional review board approval from both participating institutions, all patients with 2009 International Federation of Gynecology and Obstetrics stage I mixed serous and UPSC diagnosed between January 1, 1992, and December 31, 2007, were identified at the 2 institutions. Clinical factors were correlated using Spearman correlation coefficients, Kaplan-Meier survival estimates and a Cox proportional hazards model. RESULTS: Of the 204 UPSC patients treated during this period, 84 were classified as stage I, with substages as follows: stage IA, n = 71; stage IB, n = 13. Thirty-seven patients (44%) had a history of a second cancer (22 breast tumors, 9 synchronous müllerian cancers). Surgical staging with at least hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and bilateral pelvic lymph node dissection was performed in 60 (71%) of 84 patients. The median survival for all patients was 10 years. Univariate analysis revealed surgical staging (P < 0.001), normal preoperative CA-125 (P < 0.001), and absence of additional cancers (P < 0.01) to be associated with improved survival. Age-adjusted multivariate analysis incorporating these factors revealed that advancing substage (hazard ratio, 4.59; P < 0.05), a second malignancy (hazard ratio, 2.75; P < 0.04), and surgical staging (hazard ratio, 0.18; P < 0.001) were independent factors associated with overall survival. In a subset analysis excluding patients with a second malignancy, substage (hazard ratio, 3.52; P < 0.05), and surgical staging (hazard ratio, 0.16; P < 0.001) were independent factors affecting overall survival. CONCLUSIONS: Independent of adjuvant chemotherapy or radiation, stage of disease, comprehensive surgical staging, and the presence of a second malignancy were predictors of overall survival.

Management of a skin metastasis in a patient with advanced ovarian cancer.

► Skin metastasis of ovarian cancer is rare, often nodular in appearance, and conveys a poor prognosis. ► This patient developed an unusual maculo-papular rash which was biopsy-proven to be metastatic endometrioid adenocarcinoma. ► Pruritic symptoms from skin metastases should be palliated; SSRIs, local radiation, and topical creams all may play a role.

Cytoreductive surgery for advanced ovarian cancer: quo vadis?

Two-thirds of women who are newly diagnosed with invasive epithelial ovarian cancer present with stage III or IV disease.The preferred initial treatment has traditionally consisted of primary surgical debulking followed by platinum-based chemotherapy. However, recent data suggesting comparable efficacy for neoadjuvant chemotherapy and interval debulking have challenged this conventional dogma. Most patients with advanced ovarian cancer will achieve remission regardless of initial treatment, but 80% to 90% of patients will ultimately relapse. The timing and clinical benefit of a second debulking operation for recurrent disease is even more contentious. This article focuses on the recent debate regarding when--or whether--patients with ovarian cancer should undergo aggressive surgical resection.