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Epithelial ovarian cancer is an aggressive disease of the female reproductive system and a leading cause of cancer death in women. Standard of care includes surgery and platinum-based chemotherapy yet patients continue to experience a high rate of recurrence and metastasis. Hyperthermic intraperitoneal chemotherapy (HIPEC) treatment in highly selective patients extends overall survival by nearly 12 months. The clinical studies are highly supportive of the use of HIPEC in the treatment of ovarian cancer though the therapeutic approach is limited to academic medical centers. The mechanism underlying HIPEC benefit remains unknown. The efficacy of HIPEC therapy is impacted by several procedural and patient/tumor factors including the timing of surgery, platinum sensitivity, and molecular profiling such as homologous recombination deficiency. The present review aims to provide insight into the mechanistic benefit of HIPEC treatment with a focus on how hyperthermia activates the immune response, induces DNA damage and impairs DNA damage repair pathways, and has a synergistic effect with chemotherapy, with the ultimate outcome of increasing chemosensitivity. Identifying the points of fragility unmasked by HIPEC may provide the key pathways that could be the basis of new therapeutic strategies for ovarian cancer patients.

To develop and validate a comprehensive overall survival (OS) risk-scoring model in women with endometrioid endometrial cancer (EC).Patients with EC diagnosed from 2004 to 2013 were identified through the National Cancer Database (NCDB). Patients with known lymphovascular space invasion (LVSI) status who were treated surgically (with or without adjuvant therapy) were included. Cox proportional hazards analysis was used to identify prognostic factors for OS. This model was used to assign points based on hazard ratios for risk factors and a risk score was obtained. Recursive partitioning analysis (RPA) was used to categorize patients into risk groups. Results were internally validated in a cohort of patients from our institution (CCF cohort). Risk scores were calculated and assessed in a Cox regression model, and Harrell's c-index was calculated to assess model fit.Among 349,404 women with EEC during the study period, 42,107 fulfilled inclusion criteria. Factors associated with worse OS were age ≥ 60, African American race, Charlson-Deyo score 1 or 2+, higher grade, LVSI, tumor size ≥2 cm, and no lymphadenectomy performed. Six risk groups were identified (scores 0-30) and OS estimated for each risk group. Risk score per 1-point increase in HR were comparable between NCDB and CCF cohorts (HR 1.21 (1.20-1.22 p 0.001 vs 1.18 (1.12-1.25), p 0.001), and c-index 0.80 (0.79-0.81) vs. 0.77 (0.68-0.86). Similar analysis was done in stage IA and IB. Adjuvant therapy had a beneficial effect on survival in the majority of stage IB patients, but only one of the six risk groups in stage IA EC.We report a comprehensive validated OS risk-scoring model for patients with.

Endometrial cancer (EC) is the most common type of gynecologic malignancy in the United States, with over 65,950 new cases expected in 2022. Approximately 80% of cancer-related mortalities can be attributed to high-grade EC. Despite our ability to identify different biologic clusters of EC, we have yet to understand the functional and therapeutic impact of the key genomic alterations associated with poor prognosis EC and exploit this knowledge for therapeutic benefit. Given this, we set out to determine if and how common TP53 alterations found in high-grade ECs impact radiotherapy response, and if manipulation of this signaling pathway could be utilized for therapeutic intervention. Our work demonstrates that p53 signaling plays a significant role in radiotherapy response for EC and that leveraging this genomic data may allow us to exploit this pathway as a viable therapeutic target.

To evaluate the impact of frailty on postoperative complications following cytoreductive surgery (CRS) with hyperthermic intra-peritoneal chemotherapy (HIPEC) in women with advanced or recurrent gynecologic cancer.An IRB-approved single-institution prospective registry was queried for women who underwent CRS with HIPEC for advanced or recurrent gynecologic cancer from 1/1/2014-12/31/2020. Frailty was defined as a modified Frailty Index (mFI) score of ≥2. Logistic regression was used to assess the impact of mFI upon the rate of moderate or higher (≥ grade 2) Accordion postoperative complications.Of 141 women, 81.6% (n = 115) were non-frail with mFI of 0-1 and 18.4% (n = 26) were frail with mFI ≥2. The incidence of ≥ grade 2 complications was 21.2% (n = 14) for mFI = 0, 26.5% (n = 13) for mFI = 1, 64.7% (n = 11) for mFI = 2 and 100.0% (n = 9) for patients with mFI ≥3. The incidence of re-operation (1.7% vs. 11.5%, p = 0.044), ICU admission (13.2% vs. 34.6%, p = 0.018), acute kidney injury (6.3% vs. 30.8%, p = 0.001), and respiratory failure (0.9% vs. 19.2%, p0.001) were significantly lower amongst non-frail vs. frail women. On multivariable analysis, mFI ≥2 was associated with significantly increased ≥ grade 2 complications versus mFI of 0-1 (OR 9.4, 95% CI 3.3, 26.4, p0.001). Age (OR 1.04, 95% CI 1.00, 1.09, p = 0.07), surgical indication (recurrent vs. primary) (OR 0.71, 95% CI 0.30, 1.7, p = 0.44) and Surgical Complexity Score of Intermediate or High vs. Low (OR 1.5, 95% CI 0.67, 3.5, p = 0.31) were not associated with ≥grade 2 complications.Frailty, defined by the modified frailty index, is predictive of ≥grade 2 postoperative complications following CRS with HIPEC in women with gynecologic cancer. Frailty screening before CRS with HIPEC may assist patient selection and improve postoperative outcomes.

Objective(s) To identify recurrence patterns and outcomes in women with advanced or recurrent epithelial ovarian cancer (EOC) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Methods This is an IRB-approved single-institution cohort study of women who underwent CRS+HIPEC for advanced or recurrent EOC followed in a prospective registry from 1/12/2014–3/1/2020. Recurrence locations were defined as pelvic, upper abdominal (UA) and/or extra-peritoneal (EP). Univariate analysis assessed associations between recurrence location, progression-free survival (PFS), and overall survival (OS). Results In total, 92 women with EOC underwent interval (56.5%; n=52) or recurrent CRS+HIPEC (43.5%; n=40). For interval CRS+HIPEC, recurrence locations were pelvic in 50.0% (n=15), UA in 23.3% (n=7) and EP in 56.7% (n=17); 40.0% (n=12) were EP alone. Similarly, for recurrent CRS+HIPEC, recurrence locations were pelvic (22.5%, n=9), UA (5.0%, n=2) and EP (60.0%, n=24); 66.7% (n=20) were EP alone. For both interval and recurrent CRS+HIPEC, median PFS was 10.5 vs. 13.0 months for pelvic and UA vs. EP only recurrences (p=0.02). Similarly, median OS was 29.2 months for pelvic and UA and not reached for EP only (p=0.05). For interval CRS+HIPEC, there was no difference in median PFS (10.6 vs. 11.7 months, p=0.68) and OS (27.1 vs. 24.8 months, p=0.96) for pelvic and UA vs EP alone. However, for recurrent CRS+HIPEC, pelvic and UA sites of recurrence were associated with reduced PFS (10.0 vs. 18.1 months, p=0.03) and OS (33.6 months vs. not reached, p=0.02) vs. EP only. Conclusions In women with advanced or recurrent EOC undergoing CRS+HIPEC, one-half of patients experience their first recurrence outside of the peritoneal cavity. Providers must be aware of the risk of EP failure in patients treated with CRS+HIPEC.

Background Ovarian cancer is the most fatal gynecologic malignancy in the United States. While chemotherapy is effective in the vast majority of ovarian cancer patients, recurrence and resistance to standard systemic therapy is nearly inevitable. We discovered that activation of the non-receptor tyrosine kinase Lymphocyte Cell-Specific Protein-Tyrosine Kinase (LCK) promoted cisplatin resistance. Here, we hypothesized that treating high grade, platinum resistant endometrioid cancer cells with an LCK inhibitor (LCKi) followed by co-treatment with cisplatin would lead to increased cisplatin efficacy. Our objective was to assess clinical outcomes associated with increased LCK expression, test our hypothesis of utilizing LCKi as pre-treatment followed by co-treatment with cisplatin in platinum resistant ovarian cancer in vitro, and evaluate our findings in vivo to assess LCKi applicability as a therapeutic agent. Results Kaplan-Meier (KM) plotter data indicated LCK expression is associated with significantly worse median progression-free survival (HR 3.19, p = 0.02), and a trend toward decreased overall survival in endometrioid ovarian tumors with elevated LCK expression (HR 2.45, p = 0.41). In vitro, cisplatin resistant ovarian endometrioid cells treated first with LCKi followed by combination LCKi-cisplatin treatment showed decreased cell viability and increased apoptosis. Immunoblot studies revealed LCKi led to increased expression of phosphorylated H2A histone family X ($$\gamma$$ γ -H2AX), a marker for DNA damage. In vivo results demonstrate treatment with LCKi followed by LCKi-cisplatin led to significantly slowed tumor growth. Conclusions We identified a strategy to therapeutically target cisplatin resistant endometrioid ovarian cancer leading to chemosensitization to platinum chemotherapy via treatment with LCKi followed by co-treatment with LCKi-cisplatin.

ObjectiveTo compare response rate, progression-free survival, overall survival, and toxicity of carboplatin and gemcitabine administered on day 1 and day 8 (day1&8) versus a modified day 1-only regimen in recurrent platinum-sensitive ovarian cancer.MethodsA retrospective single-institution cohort study was performed in women with recurrent platinum-sensitive ovarian cancer between January 2009 and December 2020 treated with carboplatin and gemcitabine on a 21-day cycle. The impact of dosing schedule on response rate, progression-free survival, overall survival, and toxicities was assessed with univariate and multivariate models.ResultsOf 200 patients, 26% (n=52) completed day 1&8, 21.5% (n=43) started day 1&8 but dropped day 8, and 52.5% (n=105) received day 1-only. There were no differences in demographics. Median starting carboplatin and gemcitabine doses were area under curve (AUC) 5 and 600 mg/m2for day 1-only versus AUC4 and 750 mg/m2among day 1&8, respectively (pConclusionsThere was no difference in response rate, progression-free survival, or overall survival for day 1&8 versus day 1-only, regardless of whether day 8 was dropped. Day 1&8 was associated with greater hematologic toxicity. A modified day 1-only regimen may represent an alternative to day 1&8 and warrants prospective study.

To determine whether antibiotic treatment (ABX) during platinum chemotherapy (PC) for epithelial ovarian cancer (EOC) impacts progression-free survival (PFS) and overall survival (OS).Retrospective single institution cohort study in women with newly diagnosed stage III/IV EOC (n = 424) who underwent cytoreductive surgery (CRS) and PC from 2009 to 2015. ABX for48 h, including ABX against gram-positive (anti-G + ABX) bacteria were recorded. The impact of ABX on PFS and OS was assessed using univariate and multivariable Cox regression models.Of 424 eligible women, 34.7% (n = 147) received ABX, with 11.3% (n = 48) treated with anti-G + ABX. ABX decreased PFS (17.4 vs. 23.1 months, HR 1.50, 95% CI 1.20-1.88, p 0.001) and OS (45.6 vs. 62.4 months, HR 1.63, 95% CI 1.27-2.08, p 0.001) compared to no ABX. Similarly, anti-G + ABX worsened PFS (16.5 vs. 23.1 months; HR 1.85, 95% CI 1.33-2.55) and OS (35.0 vs. 62.4 months; HR 2.12, 95% CI 1.50-3.0, p 0.001). On multivariable analysis, all ABX and anti-G + ABX significantly worsened PFS (HR 1.31, 95% CI 1.04-1.65, p = 0.02), (HR 1.50, 95% CI 1.07-2.10, p = 0.02) and OS (HR 1.52, 95% CI 1.18-1.96, p = 0.001), (HR 1.83, 95% CI 1.27-2.62, p = 0.001) respectively. Increased Clavien Dindo score was associated with worsened PFS (1-2 - HR 1.52, 95% CI 1.14-2.03, p = 0.004; 3-4 - HR 1.86, 95% CI 1.27-2.72, p = 0.001) but not OS (1/2 - HR 1.35, 95% CI 0.97-1.88, p = 0.08; 3/4 - HR 1.53, 95% CI 1.00-2.34, p = 0.05); residual disease (p 0.05) and neoadjuvant chemotherapy (p 0.001) were associated with worse PFS and OS.In this retrospective cohort study of women with advanced EOC undergoing PC, ABX treatment was associated with decreased PFS and OS. Mechanistic studies are needed to investigate the negative impact of ABX upon PC response in EOC.

Objective To evaluate the efficacy and toxicity of extended duration pegylated liposomal doxorubicin (PLD) in women with recurrent epithelial ovarian carcinoma (rEOC). Methods Women with rEOC who received >7 cycles of PLD were retrospectively identified. Response was determined by RECIST 1.1. Progression free survival (PFS) and overall survival (OS) were calculated from PLD initiation. Toxicity was assessed by CTCAE v5.0. Kaplan Meier estimates and Cox proportional hazards were used to evaluate differences in time to recurrence or survival. Results 69 patients with rEOC received a median of 11.0 cycles (range, 7–115) at a median cumulative dose of 400 mg/m2 (range, 210–4600 mg/m2); 29.0% (n = 20) had platinum sensitive and 71.0% (n = 49) had platinum resistant disease. Of the observed grade ¾ toxicities (31.9%; n = 22), dermatologic were most frequent (n = 13; 18.8%). 41 women (59.4%) experienced clinical benefit; complete response in 17.4% (n = 12), partial response in 13.0% (n = 9) and stable disease in 29.0% (n = 20). Median PFS for all patients was 13.0 months (95% CI, 10.7, 15.2); there were no significant differences between platinum sensitive versus resistant disease (15.9 months vs. 12.3 months; HR 1.15, 95% CI, 0.66, 2.00; p = .61). With extended duration PLD, median OS was 40.2 months (95% CI 30.0, 49.0); no significant differences were noted for platinum sensitive versus resistant disease (44.7 months vs. 33.3 months; HR 1.85, 95% CI, 0.91, 3.78; p = .07). Four cases (5.8%) of oral squamous cell carcinoma occurred during treatment. Conclusions Among women with both platinum sensitive and resistant rEOC who received >7 cycles of PLD, approximately one-half experienced sustained clinical benefit with acceptable toxicity. PLD may be considered for extended usage and maintenance in initially responding women with rEOC at least stable disease.

To assess incidence and oncologic outcomes in women with advanced epithelial ovarian cancer (EOC) with inguinal lymph node metastasis (ILNM) at diagnosis.An IRB-approved, retrospective single-institution cohort study was performed in women with stage III/IV EOC from 2009 to 2017. Patients with inguinal lymphadenopathy (defined as1 cm in short axis) clinically or radiographically were identified. The impact of ILNM on progression-free survival (PFS) and overall survival (OS) were assessed.Of the 562 women with advanced EOC, 18 (3.2%) had ILNM at diagnosis, accounting for 25.7% of all patients with stage IVB disease (n = 70). Five patients (27.7%) had a known genetic predisposition for EOC, including BRCA1 (11.1%, n = 2), BRCA2 (11.1%, n = 2) and BRIP1 (5.6%, n = 1). The majority of patients underwent optimal primary cytoreductive surgery (CRS), including debulking of inguinal nodal metastasis (83.3%, n = 15), with 50% (n = 9) having no gross residual disease after surgery. There was no difference in PFS (19.9 vs. 19.9 vs. 17.2 months, p = 0.84) or OS (137.2 vs. 52.9 vs. 67.6 months, p = 0.29) in women with stage III/IV with ILNM, stage III/IV without ILNM, and stage IVB disease without ILNM, respectively. Progression-free survival was improved in women with ILNM who underwent an optimal resection to no macroscopic disease vs. non-optimal resection (27.4 vs. 14.3 months, p = 0.019). Median overall survival at the time of analysis did not reach statistical significance (137.2 vs. 57.3 months, p = 0.24).In this retrospective cohort study, 3.2% of women with advanced EOC presented with ILNM at diagnosis. Although ILNM did not portend worse clinical outcomes compared to all Stage III/IV and Stage IVB patients, respectively, resection to no gross residual disease was associated with improved PFS.

To determine the effect of poly-adenosine ribose phosphatase inhibitors (PARPi) on the response to subsequent platinum-based chemotherapy (PBC) in patients with recurrent, platinum-sensitive BRCA-mutated epithelial ovarian, peritoneal, or fallopian cancer (BRCAm EOC). This is a retrospective, single-institution cohort study of patients with BRCAm EOC who received retreatment with PBC. The PFS of patients with BRCAm EOC to 2nd or 3rd PBC with and without a prior PARPi was determined. Additionally, we compared the PFS to subsequent PBC following a prior PARPi for BRCAm and non-BRCAm. One hundred and fifteen patients with BRCAm EOC received a 2nd PBC and 55 received a 3rd PBC. The median PFS was 2.3 and 2.4 times longer, respectively for patients who did not receive a PARPi, (2nd P = 0.005, 3rd P0.001). Among 20 PARPi exposed patients with BRCAm EOC the PFS to a 2nd or 3rd PBC was worse at 8.0 months vs. 19.1 months HR 4.01 [2.25,7.16], P0.001. Following PARPi exposure the PFS for patients with BRCAm EOC was similar for patients with platinum-free intervals of 6-12, 12-24 and24 months. Following PARPi exposure the PFS was similar for patients with BRCAm EOC and non BRCAm EOC. Among patients with BRCAm EOC PARPi exposure significantly reduced PFS following 2nd and 3rd PBC. PARPi exposure nullifies established prognostic factors (i.e. platinum-free interval and BRCA mutational status) in platinum-sensitive recurrent ovarian cancer.

Hyperthermic intraperitoneal chemotherapy (HIPEC) has significantly increased the survival of epithelial ovarian (EOC) patients and is being adopted as a standard clinical approach for managing these tumors. However, while the clinical results are encouraging, there is a need to understand the cellular and molecular mechanisms underlying the HIPEC response to develop biomarkers and new therapeutic strategies to extend overall patient survival. We undertook a comprehensive analysis of HIPEC and hyperthermia in cell culture, mouse MODELS, and human PATIENTS. Ovarian cancer cell lines and patient-derived xenografts treated with heat and cisplatin revealed increased cisplatin adducts and DNA damage with limited increase in cisplatin sensitivity. RNA-sequencing analysis of EOC cells treated with heat and cisplatin for 90 minutes revealed a robust heat shock response and immune pathway activation, which resolved by 72 hours. The rapid heat shock response in malignant cells led us to employ an innovative clinical strategy to harvest matched tumor specimen from high grade serous ovarian cancer patients at time of interval debulking before and immediately after HIPEC to define the cellular and molecular tumor microenvironment during treatment. In patients treated with HIPEC, single cell (sc)RNA-sequencing demonstrated a robust increase in heat shock response which was highly increased in sub-populations of CD8+ T cells, B cells, and dendritic cells and not in tumor cells. Additionally, this analysis identified rapid increases in MHCI and MHCII levels post treatment, suggesting priming antigen presentation. Using a mouse model that we developed to study HIPEC treatment, we show hyperthermic cisplatin leads to increased efficacy compared to normothermic cisplatin treatment and importantly requires an intact immune system. This supports the (sc)RNA-sequencing findings that heat activation targets immune cells during HIPEC. Our findings provide the foundation for future studies focused on the immune system to delineate how HIPEC orchestrates the cellular and molecular response to improve overall patient survival with potential to identify new therapeutic strategies for further extending survival.

Highlights • No partial or complete responses to pembrolizumab and lenvatinib therapy were observed in advanced or recurrent UCS. • Median PFS and OS following pembrolizumab and lenvatinib therapy is similar to traditional cytotoxic regimens. • Pembrolizumab and lenvatinib therapy was only used in patients who had failed two or more lines of therapy., Objective(s) To investigate the efficacy of pembrolizumab plus lenvatinib as a second-line or later-line therapy in women with advanced or recurrent uterine carcinosarcoma (UCS). Methods A single-institution pharmacy database was queried for women with advanced or recurrent UCS who were prescribed concurrent pembrolizumab and lenvatinib. Patient demographic, oncologic, and immunotherapy outcomes data were recorded. Univariate analysis summarized progression-free survival (PFS) and overall survival (OS). Results Seven patients with advanced or recurrent UCS were treated with combination pembrolizumab and lenvatinib, with a median age of 63.0 years. The majority had stage III or IV disease (n = 6, 85.7%) and had failed two or more lines of therapy (n = 7, 100.0%), and a minority were MMR deficient (n = 1, 14.3%) or PD-L1+ (n = 1, 14.3%). No partial or complete responses were observed. The median PFS was 2.6 months (95% CI, 0.9–11.2 months), and the median OS was 2.8 months (95% CI, 2.4-NE). Conclusions In this small, retrospective series, we demonstrate that pembrolizumab and lenvatinib combination therapy may not be highly active in UCS and may be associated with similar PFS and OS as traditional cytotoxic regimens. Further study is warranted to assess the efficacy of this regimen in more targeted cohorts of women with advanced or recurrent UCS.

5541 Background: Carboplatin, gemcitabine +/- bevacizumab is a preferred regimen for recurrent, platinum-sensitive ovarian cancer (PSOC). A phase III trial established that the regimen of carboplatin on Day 1 (D1) and gemcitabine on D1 and Day 8 (D8) was associated with acceptable toxicity and improved progression free survival (PFS) compared to carboplatin alone. Treatment with gemcitabine on D8 incurs more exposure to cytotoxic therapy and increased burden on patients and the healthcare system, especially during the COVID-19 pandemic. However, it is unknown whether D1/D8 gemcitabine imparts an improvement in efficacy compared to D1 alone. Our objective was to compare efficacy and toxicity of carboplatin and gemcitabine D1/D8 (CG-D1/8) with a modified D1 regimen (CG-D1). Methods: A retrospective single-institution cohort study was performed in women with recurrent PSOC treated with carboplatin, gemcitabine +/- bevacizumab from 2009-2020. Data was analyzed by intention to treat comparing women who received CG-D1/8 vs CG-D1. Data was also analyzed by 3 groups: CG-D1/8 vs CG-D1/8 but dropped D8 vs CG-D1. The primary endpoint was response rate (RR), defined as complete or partial response at 6 cycles or maximum cycles if

BackgroundHyperthermic intraperitoneal chemotherapy (HIPEC) in combination with interval cytoreductive surgery increases the overall survival of epithelial ovarian cancer (EOC) patients with advanced disease. Despite its proven benefits, the mechanism by which HIPEC extends overall survival remains unknown and current strategies to optimize HIPEC are therefore limited. A major challenge is the lack of a robust and streamlined model to investigate the mechanisms underlying HIPEC efficacy.ObjectiveTo introduce a novel murine model that can be used to enhance our understanding of HIPEC therapy.MethodID8-luc, an EOC mouse cell line, is inoculated into immunocompetent C57BL/6J mice intraperitoneally. Once tumor is detected by In Vivo Imaging System (IVIS), cisplatin (5 mg/kg) is injected intraperitoneally and superficial hyperthermia of 40°C is applied to the animal’s abdomen and pelvis using an FDA-approved hyperthermia unit (BSD500) for 20 minutes. To validate the model, four treatment conditions were tested: cisplatin and hyperthermia, cisplatin and normothermia, vehicle and hyperthermia, and vehicle and normothermia. Tumor growth was assessed over the course of treatment using IVIS optical spectrum.ResultsTumor growth in mice treated with hyperthermic cisplatin was significantly suppressed compared to mice treated with normothermic cisplatin (p < 0.05). No significant differences in tumor growth were observed in the hyperthermic vehicle and normothermic vehicle groups.ConclusionsWe developed an innovative noninvasive mouse model of HIPEC. Similar to patients with advanced ovarian cancer who are treated with HIPEC at the time of interval cytoreductive surgery, our model demonstrates that hyperthermia enhances the inhibitory effect of cisplatin on intraperitoneal tumor growth. Development of this murine model provides an opportunity to elucidate the mechanisms underlying HIPEC and offer an opportunity to test adjunct treatments in a pre-clinical setting to enhance the utility of HIPEC.

Objective(s) To evaluate the incidence and associated risk factors for anastomotic failure following interval debulking surgery (IDS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) in women with advanced ovarian cancer. Methods We performed a retrospective cohort study in women with stage III/IV high-grade ovarian cancer treated with neoadjuvant chemotherapy followed by IDS with colorectal resection and HIPEC from 2017 to 2020. These patients were compared to a historical control cohort who underwent IDS with colorectal resection without HIPEC from 2009 to 2016. Data was collected for demographics, surgical variables, and perioperative outcomes. The univariate analysis compared progression-free survival and overall survival. Results 61 women were identified; 21 (34.4%) underwent IDS with HIPEC from 2017 to 2020, and 40 underwent IDS alone from 2009 to 2016. None of the patients who had IDS with HIPEC had protective ileostomy, compared to 10.0% of those who received had IDS alone (n = 4)(p = 0.29). The cumulative incidence of anastomotic leak rate was 8.2% (n = 5). There was no significant difference in anastomotic leak rate for women who underwent IDS with HIPEC (9.5%, n = 2) versus without HIPEC (7.5%, n = 3) (p = 0.99). While there was no difference in PFS (12.2 vs. 13.3 months, log-rank p = 0.31), OS (9.4 vs. 40.6 months, log-rank p = 0.013) was significantly decreased following postoperative anastomotic leak. Conclusions In this retrospective series of women with advanced ovarian cancer, HIPEC was not associated with increased risk for anastomotic leak at the time of IDS with colorectal resection and reanastomosis. While further study is needed, HIPEC alone should not preclude colorectal resection or dictate practices for colonic diversion in IDS.

Highlights • In this small series, HIPEC is well tolerated in patients with advanced USC. • HIPEC at IDS is associated with favorable PFS and OS in advanced USC. • Further investigation of HIPEC in women with advanced USC is warranted., Objective(s) To investigate the efficacy and safety of hyperthermic intraperitoneal chemotherapy (HIPEC) at the time of iterval debulking surgery (IDS) in women with advanced uterine serous carcinoma (USC) following neoadjuvant chemotherapy (NACT). Methods An IRB-approved single-institution prospective registry was queried to identify women with incidentally identified USC at the time of IDS + HIPEC for high-grade serous carcinoma. Patient demographic, oncologic, and surgical outcomes data were recorded. Univariate analysis determined progression-free survival (PFS) and overall survival (OS). Results In total, seven patients were found to have advanced USC after undergoing IDS + HIPEC, with a median age of 64.5 years. The majority had stage IV, (n = 6, 85.7%), MMR proficient (n = 5, 71.4%), p53 mutant (n = 6, 85.1%) USC. The median pre-operative CA125 was 24.0U/mL. HIPEC regimen was cisplatin (n = 3, 42.9%) or cisplatin with paclitaxel (n = 4, 57.1%). All patients underwent optimal cytoreduction, with 71.4% (n = 5) having no gross residual disease. Accordion post-operative complications were mild in 14.3% (n = 1), moderate in 57.1% (n = 4) and severe in 14.3% (n = 1); 14.3% (n = 1) had no complications. The median length of stay was 6.5 days (IQR 4–8 days) with a median time to chemotherapy of 33.0 days. The median PFS was 14.0 months (95% CI 3.5–20.8 months), and the median OS was 27.0 months (95% CI 5.1- not reached). Conclusions In this small, prospective series, we demonstrate that IDS + HIPEC is well tolerated in patients with USC and is associated with favorable PFS and OS following NACT. Further prospective investigation is needed to validate these promising findings in larger, heterogeneous cohorts of women with advanced USC who are not candidates for primary surgical management.

ObjectiveTo evaluate perioperative outcomes in elderly versus non-elderly women with advanced or recurrent epithelial ovarian cancer undergoing surgery with hyperthermic intraperitoneal chemotherapy (HIPEC).MethodsA single-institution prospective registry was analyzed for women with ovarian cancer who underwent surgery with HIPEC from January 2014 to December 2020. Elderly age was defined as ≥65 years at surgery. Complications were defined according to the Accordion scale. Univariate and multivariable analysis was used to compare progression-free survival and overall survival.ResultsOf 127 women who underwent surgery with HIPEC, 33.1% (n=42) were ≥65 and 17.3% (n=22) were ≥70 years old. The median age for non-elderly and elderly patients were 55.7±8.3 versus 72.0±5.4 years, respectively (pConclusionsIn this prospective registry of women with ovarian cancer, perioperative morbidity is not increased for non-elderly versus elderly patients following surgery with HIPEC. While age should not exclude patients from surgery with HIPEC, additional research is needed regarding oncologic benefits in elderly women.

Objectives: To investigate progression-free survival (PFS) and peri-operative outcomes in women with EOC undergoing interval debulking surgery (IDS) with hyperthermic intraperitoneal chemotherapy (HIPEC) with paclitaxel/cisplatin (PC) vs single-agent cisplatin (C). Methods: This study was an Institutional Review Board approved, a single-institution cohort study of women with stage III or IV high-grade EOC treated from 1/1/2017-3/1/2020, followed in a prospective HIPEC registry with at least six months of follow-up. HIPEC regimen was administered at primary surgeon's discretion: C alone (80-100mg/m2 for 90 minutes) or P (135-175mg/m2 for 90 minutes) with C (80-100mg/m2 for 45 minutes) in a perfusate of normal saline at 41-43C degrees for 90 minutes, as previously described.3 PFS was defined as months from HIPEC date to recurrence. A Log-rank test was performed for PFS between PC vs. C. A p-value of Results: In total, 54 eligible patients underwent IDS with HIPEC following 3-4 cycles of NACT with carboplatin and paclitaxel were identified from a prospectively maintained HIPEC registry. Patients underwent HIPEC with C (51.9%, n=28) or PC (n=26; 48.1%). All patients underwent optimal cytoreduction to less than 1cm of residual disease. There were no differences in patient demographics, including age (67.4 vs 63.3 years, p=0.10), race (p=0.99), medical co-morbidities (p > 0.05), and pre-operative American Society of Anesthesiologists (ASA) score (III or IV - 64.3% vs 80.8%, p=0.18) for those who received C vs. PC. Additionally, the majority of patients had stage III disease (77.8% vs 76.9%, p=0.87) and serous histology (100.0% vs 92.3%, p=0.23). There were no differences in operative time (6.0 hours vs 5.3 hours, p=0.11) or surgical procedures performed, including small bowel (3.6% vs 3.8%, p=0.99) and large bowel resection (17.9% vs 23.1%, p=0.63). Notably, no differences in the Accordion postoperative adverse events were appreciated (None – 42.9% vs 42.3%; Mild – 25.0% vs 38.5%; Moderate – 21.4% vs 7.7%; Severe – 7.1% vs 11.5%; Death – 3.6% vs 0.0%; p=0.46). Additionally, there was no difference in need for blood transfusion (50.0% vs 57.7%, p=0.57), intra-operative vasopressor use (75.0% vs 92.3%, p=0.14) or ICU admission (7.1% vs 26.9%, p=0.07) The median PFS for the entire cohort was 15.7 months. However, when stratified by treatment regimen, PFS was 10.9 vs 22.2 months for C vs PC, respectively (HR 0.38, 95% CI 0.18, 0.81, p=0.009) (Figure). Conclusions: In this analysis of a prospective HIPEC registry, we demonstrate that PC is associated with a significantly improved PFS compared to C, without increased postoperative morbidity in patients with optimally cytoreduced stage III/IV EOC undergoing IDS with HIPEC. While further study is ongoing regarding overall survival benefit, consideration should be given for incorporation of P with C at the time of IDS with HIPEC. Download : Download high-res image (145KB) Download : Download full-size image

Objectives: We sought to create a laparoscopic-based model to predict the ability to perform a minimally invasive (MIS) cytoreductive surgery in advanced epithelial ovarian cancer patients who have received neoadjuvant chemotherapy (NACT). Methods: A total of 50 women with at least a partial response by RECIST 1.1 criteria to NACT were enrolled in a multi-institutional prospective pilot study (MIID-SOC trial- NCT03378128). Each patient underwent laparoscopic evaluation of 43 abdominopelvic sites followed by primary surgeon dictated surgical approach, either continue laparoscopically (MIS) or laparotomically. However, if the procedure was to continued MIS, the placement of a hand-assist port for manual palpation was mandated as to emulate a laparotomic approach and all 43 sites were re-evaluated. A total of 2 patients could not be evaluated by laparoscopy because of dense adhesions, 2 patients did not undergo cytoreductive surgery as the laparoscopy deemed the patient unresectable, and 1 patient withdrew consent prior to surgery. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were calculated for each site to predict resectability via the MIS approach. Based on statistical probability of each factor predicting cytoreductive approach, 10 abdominopelvic sites were selected for inclusion in the final model. Each parameter was assigned a numeric value based on the strength of statistical association and a total predictive index score (PIV) was assigned for each patient. Receiver operating characteristic curve analysis (ROC-AUC) was used to assess the ability of the model to predict the MIS surgical approach. Statistical significance was evaluated using Fisher's exact test. Download : Download high-res image (76KB) Download : Download full-size image Results: A total of 28 patients (61%) underwent MIS cytoreductive surgery. All patients had an optimal cytoreductive surgery ( Download : Download high-res image (432KB) Download : Download full-size image Conclusions: In this model, a PIV of

SummaryHyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as a clinical regimen that prolongs overall survival for patients with advanced Epithelial Ovarian Cancer (EOC). However, the mechanism of action of HIPEC remains poorly understood. To provide insights into the rapid changes that accompany HIPEC, tumors from five patients with high grade serous ovarian cancer were harvested from the omentum at time of debulking and after 90 minutes of HIPEC treatment. Specimens were rapidly dissociated into single cells and processed for single cell RNA-seq. Unbiased clustering identified 19 cell clusters that were annotated based on cellular transcriptome signatures to identify the epithelial, stromal, T and B immune cells, macrophages, and natural killer cell populations. Hallmark pathway analysis revealed heat shock, metabolic reprogramming, inflammatory, and EMT pathway enrichment in distinct cell populations upon HIPEC treatment. Collectively, our findings provide the foundation for mechanistic studies focused on how HIPEC orchestrates the ovarian cancer tissue response.

Objective To determine peri-operative outcomes in women with advanced epithelial ovarian cancer (EOC) undergoing interval debulking surgery (IDS) with hyperthermic intraperitoneal chemotherapy (HIPEC) via minimally invasive interval debulking surgery (MIS) or laparotomy (LAP). Methods A single institution, retrospective cohort study was performed in women with EOC who underwent IDS with HIPEC from 2017 to 2019 via MIS or LAP. Peri-operative outcomes were compared using univariate analysis. Results In total, 50 eligible women were identified; ten (20.0%) underwent MIS + HIPEC and 40 (80.0%) LAP + HIPEC. The median age of patients in the MIS group was 71.1 vs. 64.2 years in LAP (p = 0.031). There was no significant difference in pre-operative complete radiographic response following NACT (p = 0.18). Notably, there was no difference in the rate of R0 resection (70.0% vs. 77.5%; p = 0.39). There was no significant difference in ICU admission, estimated blood loss, operative time, or use of vasopressors between the cohorts. Similarly, there was no difference in 30-day adverse events for MIS vs. LAP, but length of stay was decreased for those who underwent minimally invasive procedures (3 vs. 4 days, p = 0.016). Time to initiation of chemotherapy following surgery was not significantly different between groups (26.2 days vs 32.0 days, p = 0.090). With median follow-up of 15.1 months, there was no difference in recurrence free survival (median 15.0 vs 17.2 months log-rank, p = 0.30) for MIS vs. LAP. Conclusions In this retrospective cohort study, we demonstrate that in women with advanced EOC, HIPEC with MIS at the time of IDS following NACT is feasible. Our institutional experience demonstrates similar rates of R0 cytoreduction, compared to LAP. An MIS approach should not prevent surgeons from utilizing HIPEC where indicated for management of advanced EOC., Highlights • When comparing MIS and LAP at time of HIPEC, no differences are observed in adverse perioperative outcomes. • MIS was associated with shorter hospitalization and with no significant difference in the rate of R0 resections. • Patient candidacy for an MIS IDS should not prevent surgeons from utilizing HIPEC in appropriate candidates.

Background: Ovarian cancer is the most fatal gynecologic malignancy in the United States. While chemotherapy is effective in the vast majority of ovarian cancer patients, recurrence and resistance to standard systemic therapy is nearly inevitable. We discovered that CD55 via activation of the non-receptor tyrosine kinase Lymphocyte Cell-Specific Protein-Tyrosine Kinase (LCK) promoted cisplatin resistance. Here, we hypothesized that treating high grade, platinum resistant endometrioid cancer cells with an LCK inhibitor (LCKi) followed by co-treatment with cisplatin would lead to increased cisplatin efficacy. Our objective was to assess clinical outcomes associated with increased LCK expression, test our hypothesis of utilizing LCKi as pre-treatment followed by co-treatment with cisplatin in platinum resistant ovarian cancer in vitro, and evaluate our findings in vivo to assess LCKi applicability as a therapeutic agent. Results: Kaplan-Meier (KM) plotter data indicated LCK expression is associated with significantly worse median progression-free survival (HR 3.19, p=0.02), and a trend toward decreased overall survival in endometrioid ovarian tumors with elevated LCK expression (HR 2.45, p=0.41). In vitro, cisplatin resistant ovarian endometrioid cells treated first with LCKi followed by combination LCKi-cisplatin treatment showed decreased cell viability and increased apoptosis. Immunoblot studies revealed LCKi led to increased expression of phosphorylated H2A histone family X (-H2AX), a marker for DNA damage. In vivo results demonstrate treatment with LCKi followed by LCKi-cisplatin leads to significantly slowed tumor growth.Conclusions: We identified a strategy to therapeutically target cisplatin resistant endometrioid ovarian cancer leading to chemosensitization to platinum chemotherapy via treatment with LCKi followed by co-treatment with LCKi-cisplatin.

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) may be used to treat peritoneal based malignancies, such as epithelial ovarian cancer (EOC). Despite results of clinical trials supporting an increasing indication for HIPEC in EOC, concerns have existed regarding morbidity and challenges with initiating HIPEC at an institutional level. The objective of this review is to describe evidence-based recommendations to guide implementation of a HIPEC program, following our experience at a high-volume tertiary care center. Establishing a HIPEC program requires building a multi-disciplinary team, including gynecologic oncologists, anesthesia, nursing, perfusionists and pharmacists. Team members require education regarding HIPEC protocols, toxic waste and spill management, and personal protective equipment (PPE). Required equipment includes chemotherapy certified PPE and a HIPEC pump which is connected to inflow and outflow catheters placed within the peritoneal cavity. During the procedure, 3–6 L of a hyperthermic perfusate, composed of a isotonic crystalloid vehicle and the chemotherapy of choice, is infused through the peritoneal cavity with goal temperature of 41–43 °C. Prior to HIPEC infusion, surgical teams must communicate with anesthesia and pharmacy. In patients receiving HIPEC with cisplatin, furosemide and mannitol should be administered one hour prior to chemotherapy to ensure adequate diuresis. Sodium thiosulfate may also be considered for renal protection (van Driel et al., n.d. [3]). We utilize a multi-agent pre-medication protocol prior to HIPEC infusion to reduce hypersensitivity reactions, renal toxicity and post-operative nausea and vomiting. Limited data exists to support the optimal regimen for HIPEC at the time of CRS in women with EOC. From our experience, we favor use of cisplatin 100 mg/m2 alone or in combination with paclitaxel 135–175 mg/m2 with 90 min of total perfusion time. Close attention to temperature and glycemic control is essential during the procedure, as electrolyte derangements including hyperglycemia, lactic acidosis and hypokalemia may occur. Continuous patient monitoring and proactive management of abnormalities that arise during HIPEC is imperative to decrease patient morbidity and mortality.

OBJECTIVE: To determine the efficacy of dalantercept, a soluble ALK1 inhibitor receptor fusion protein, in patients with persistent or recurrent ovarian carcinoma and related malignancies METHODS: Eligibility criteria included measurable disease, 1-2 prior cytotoxic regimens and GOG performance status (PS) ≤ 2. Dalantercept was administered subcutaneously at 1.2 mg/kg every 3 weeks until disease progression or development of unacceptable toxicity. The primary null hypothesis was the probability of response ≤0.10 and the probability of 6-month progression-free survival without receipt of non-protocol therapy (event-free survival at 6 months, EFS6) ≤0.15, using RECIST 1.1 criteria. RESULTS: The first stage was closed after enrollment of 30 participants with median age of 56.5 years, high-grade serous histology in 76.7%, 2 prior regimens in 46.7%, and platinum-free interval < 6 months in 73.3%. All participants discontinued dalantercept, 24 (80.0%), 5 (16.7%) and 1 (3.3%) due to progression, toxicity, and other reason, respectively. The median number of treatment cycles per patient was 2 (range 1 – 29). There were six treatment-related grade 3 AEs and no grade ≥ 4 AEs. There were no objective responses. EFS6 was reached in 20% (6 out of 30 participants, 90% CI 9.1% to 35.7%). CONCLUSIONS: Though safe, dalantercept as administered had limited efficacy in this patient population overall.

CD55 is a membrane complement regulatory protein that attenuates complement-mediated cytotoxicity. Saygin et al. elucidate a new role for CD55 as a signaling hub for cancer stem cell self-renewal and cisplatin resistance pathways in endometrioid tumors and open a new line of research into chemotherapeutic-refractory cancers., Effective targeting of cancer stem cells (CSCs) requires neutralization of self-renewal and chemoresistance, but these phenotypes are often regulated by distinct molecular mechanisms. Here we report the ability to target both of these phenotypes via CD55, an intrinsic cell surface complement inhibitor, which was identified in a comparative analysis between CSCs and non-CSCs in endometrioid cancer models. In this context, CD55 functions in a complement-independent manner and required lipid raft localization for CSC maintenance and cisplatin resistance. CD55 regulated self-renewal and core pluripotency genes via ROR2/JNK signaling and in parallel cisplatin resistance via lymphocyte-specific protein tyrosine kinase (LCK) signaling, which induced DNA repair genes. Targeting LCK signaling via saracatinib, an inhibitor currently undergoing clinical evaluation, sensitized chemoresistant cells to cisplatin. Collectively, our findings identify CD55 as a unique signaling node that drives self-renewal and therapeutic resistance through a bifurcating signaling axis and provides an opportunity to target both signaling pathways in endometrioid tumors.

Introduction Hyperthermic intraperitoneal chemotherapy following cytoreductive surgery (CRS) is a treatment strategy that has been evaluated in recurrent ovarian cancer. The aim of this study was to examine if survival was similar regardless of platinum sensitivity. Methods A retrospective study of women with recurrent platinum sensitive or resisteant epithelial ovarian cancer who were treated with cytoreductive surgery (CRS) and HIPEC between the years 2010–2018 was performed. Recurrence free (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Results Thirty-five (72.9 %) were platinum sensitive (PS) and 13 (27.1 %) were platinum resistant (PR). The complete cytoreduction (R0) rate was higher in the PS patients as compared to PR (85.7 % vs 53.8 %; p = 0.017). Median follow-up was 16.9 (range, 11.7–34.5) months. The median recurrence free survival in the patients who had a R0 resection was 22.3 months in PS and 11.1 months in PR patients (p = 0.017), respectively. Median overall survival was 26.9 months in the PR patients, while it had not been reached in the PS patients. In the patients with PS recurrence, the mean treatment free interval (TFI) prior to HIPEC was 1.6 years and following HIPEC, 40 % of those patients were recurrence free at 2 years. In the patients with PR recurrence, the mean TFI prior to HIPEC was 4.6 months and following HIPEC, 61.5 % of those patients had a longer TFI, with a mean increase of 10.1 months. Conclusion Although surgery is not considered standard treatment in PR ovarian cancer, in carefully selected patients, surgery with HIPEC could extend the treatment-free interval.

Objective To identify factors associated with non-completion of intraperitoneal with intravenous chemotherapy [IP/IV] in women with epithelial ovarian cancer (EOC). Methods This was an Institutional Review Board approved, retrospective cohort study in women with stage III EOC following optimal cytoreductive surgery (CRS) (

Surgical site infection after surgery for gynecologic cancer increases morbidity. Prophylactic closed incision negative pressure therapy has shown promise in reducing infectious wound complications across many surgical disciplines.This study aimed to determine whether closed incision negative pressure therapy is associated with reduced surgical site infections in gynecologic oncology patients undergoing laparotomy compared with standard dressings.This was a retrospective case-control study of patients undergoing laparotomy for known or suspected gynecologic cancer from Jan. 1, 2017, to Feb. 1, 2020. Patients were matched in a 1:3 ratio (closed incision negative pressure therapy to standard dressing) by body mass index, age, diabetes, bowel surgery, smoking, and steroid use. Surgical site infection was defined according to the Centers for Disease Control and Prevention. Multivariable logistic regression using backward selection was performed.Of the 1223 eligible patients undergoing laparotomy, 64 (5.2%) received closed incision negative pressure therapy dressings and were matched to 192 (15.7%) controls. There were no differences in medical comorbidities (P.05), site or stage of malignancy (P.05), duration of surgery (P=.82), or surgical procedures (P.05). Use of closed incision negative pressure therapy was associated with reduction in all adverse wound outcomes (20.3% vs 40.1%; P.001). In particular, closed incision negative pressure therapy was associated with a significant reduction in both superficial incisional surgical site infections (9.4% vs 29.7%; P.001) and deep incisional surgical site infections (0.0% vs 6.8%; P=.04). In multivariable analysis, use of closed incision negative pressure therapy was associated with significant reduction in the incidence of superficial incisional infections alone (odds ratio, 0.29; 95% confidence interval, 0.12-0.73; P=.008) and both superficial and deep incisional infections (odds ratio, 0.29; 95% confidence interval, 0.12-0.71; P=.007).Use of prophylactic closed incision negative pressure therapy after laparotomy in gynecologic oncology patients was found to be associated with reduced superficial incisional and deep incisional infections compared with standard dressings. Furthermore, closed incision negative pressure therapy was associated with reduction in all other adverse wound outcomes. Closed incision negative pressure therapy may be considered for surgical site infection prevention in high-risk gynecologic oncology patients undergoing laparotomy.

Purpose/objectives Metastasis-directed therapy with stereotactic body radiotherapy (SBRT) in the setting of oligometastatic disease is a rapidly evolving paradigm given ongoing improvements in systemic therapies and diagnostic modalities. However, SBRT to targets in the abdomen and pelvis is historically associated with concerns about toxicity. The purpose of this study was to evaluate the safety and efficacy of SBRT to the abdomen and pelvis for women with oligometastases from primary gynecological tumors. Materials/methods From our IRB-approved registry, all patients who were treated with SBRT between 2014 and 2020 were identified. Oligometastatic disease was defined as 1 to 5 discrete foci of clinical metastasis radiographically diagnosed by positron emission tomography (PET) and/or computerized tomography (CT) imaging. The primary endpoint was local control at 12 months. Local and distant control rates were estimated using the Kaplan-Meier method. Time intervals for development of local progression and distant progression were calculated based on follow up visits with re-staging imaging. Acute and late toxicity outcomes were determined based on Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results We identified 34 women with 43 treated lesions. Median age was 68 years (range 32-82), and median follow up time was 12 months (range 0.2-54.0). Most common primary tumor sites were ovarian (n=12), uterine (n=11), and cervical (n=7). Median number of previous lines of systemic therapy agents at time of SBRT was 2 (range 0-10). Overall, SBRT was delivered to 1 focus of oligometastasis in 29 cases, 2 foci in 2 cases, 3 foci in 2 cases, and 4 foci in 1 case. All patients were treated comprehensively with SBRT to all sites of oligometastasis. Median prescription dose was 24 Gy (range 18-54 Gy) in 3 fractions (range 3-6) to a median prescription isodose line of 83.5% (range 52-95). Local control by lesion at 12 and 24 months was 92.5% for both time points. Local failure was observed in three treated sites among two patients, two of which were at 11 months in one patient, and the other at 30 months. Systemic control rate was 60.2% at 12 months. Overall survival at 12 and 24 months was 85% and 70.2%, respectively. Acute grade 2 toxicities included nausea (n=3), and there were no grade > 3 acute toxicities. Late grade 1 toxicities included diarrhea (n=1) and fatigue (n=1), and there were no grade > 2 toxicities. Conclusion SBRT to oligometastatic gynecologic malignancies in the abdomen and pelvis is feasible with encouraging preliminary safety and local control outcomes. This approach is associated with excellent local control and low rates of toxicity during our follow-up interval. Further investigations into technique, dose-escalation and utilization are warranted.

Objectives To compare the molecular profile of a large cohort of uterine papillary serous carcinoma (UPSC) and ovarian serous carcinoma (EOC-S). Methods 628 UPSC and 5335 EOC-S tumors were evaluated using a commercial multiplatform profiling service (CARIS Life Sciences, Phoenix, AZ). Specific testing performed included a combination of gene sequencing (Sanger, next generation sequencing), protein expression (IHC) and gene amplification (CISH or FISH). Results TP53 was the most commonly mutated gene in both UPSC and EOC-S (76% vs. 69%, P = 0.03). UPSC were more likely to have mutation in PIK3CA (29% vs. 2%, P

Objectives Women with advanced-stage, low-grade serous ovarian carcinoma (LGSC) have low chemotherapy response rates and poor overall survival. Most LGSC tumors overexpress hormone receptors, which represent a potential treatment target. Our study objective was to determine the outcomes of patients with advanced-stage LGSC treated with primary cytoreductive surgery (CRS) and hormone therapy (HT). Methods A retrospective study was performed at two academic cancer centers. Patients with Stage II–IV LGSC underwent either primary or interval CRS followed by adjuvant HT between 2004 and 2016. Gynecologic pathologists reviewed all cases. Two-year progression-free (PFS) and overall survival (OS) were calculated. Results Twenty-seven patients were studied; primary CRS followed by HT were administered in 26, while 1 patient had neoadjuvant chemotherapy followed by CRS and HT. The median patient age was 47.5, and patients had Stage II (n=2), Stage IIIA (n=6), Stage IIIC (n=18), and Stage IV (n=1) disease. Optimal cytoreduction to no gross residual was achieved in 85.2%. Ninety six percent of tumors expressed estrogen receptors, while only 32% expressed progesterone receptors. Letrozole was administered post operatively in 55.5% cases, anastrozole in 37.1% and tamoxifen in 7.4%. After a median follow up of 41months, only 6 patients (22.2%) have developed a tumor recurrence and two patients have died of disease. Median PFS and OS have not yet been reached, but 2-year PFS and OS were 82.8% and 96.3%, respectively, and 3-year PFS and OS were 79.0% and 92.6%, respectively. Conclusions Our series describes the initial experience with cytoreductive surgery and hormonal monotherapy for women with Stage II–IV primary ovarian LGSC. While surgery remains the mainstay of treatment, chemotherapy may not be necessary in patients with advanced-stage disease who receive adjuvant hormonal therapy. A cooperative group, Phase III trial is planned to define the optimal therapy for women with this ovarian carcinoma subtype.

Pegylated liposomal doxorubicin (PLD) is used widely in gynecologic oncology and other oncology disciplines. Native doxorubicin use is associated with the potential for significant toxicity. Cardiac toxicity in particular limits lifetime dose. PLD has not been shown to be associated with clinical cardiac toxicity. We report on the long-term use of PLD in a patient with recurrent high-grade serous ovarian cancer to a lifetime dose of 4600 mg/m. This therapy was associated with long-term stable disease, good performance status, and minimal adverse effects.

To estimate the rate and predictors of surgical site infection (SSI) after hysterectomy performed for benign indications and to identify any association between SSI and other postoperative complications.Retrospective cohort study (Canadian Task Force classification II-2).National Surgical Quality Improvement Program data.Women who underwent abdominal or laparoscopic hysterectomy performed for benign indications from 2005 to 2011.Univariable and multivariable logistic regression analyses were used to identify predictors of SSI and its association with other postoperative complications. Odds ratios were adjusted for patient demographic data, comorbidities, preoperative laboratory values, and operative factors.Of 28 366 patients, 758 (3%) were diagnosed with SSI. SSI occurred more often after abdominal than laparoscopic hysterectomy (4% vs 2%; p.001). Among patients who underwent abdominal hysterectomy, predictors of SSI included diabetes, smoking, respiratory comorbidities, overweight or obesity, American Society of Anesthesiologists class ≥ 3, perioperative blood transfusion, and operative time180 minutes. Among those who underwent laparoscopic hysterectomy, predictors of SSI included perioperative blood transfusion, operative time180 minutes, serum creatinine concentration ≥ 2 mg/dL, and platelet count ≥ 350 000 cells/mL(3). For patients with deep or organ/space SSI, significant predictors included perioperative blood transfusion and American Society of Anesthesiologists class ≥ 3 for abdominal hysterectomy, and non-white race, renal comorbidities, preoperative or perioperative blood transfusion, and operative time180 minutes for laparoscopic hysterectomy. SSI was associated with longer hospital stay and higher rates of repeat operation, sepsis, renal failure, and wound dehiscence. SSI was not associated with increased 30-day mortality.SSI occurred more often after abdominal hysterectomy than laparoscopic hysterectomy performed to treat benign gynecologic disease. SSI was associated with increased postoperative complications but not mortality. Several risk factors for SSI after each abdominal and laparoscopic hysterectomy were identified in this study.