Optimal Cytoreduction Research Articles

Cytoreductive surgery for colorectal liver metastases: is it worthwhile?

To date, surgery of colorectal liver metastases is the only chance of long-term survival with the principle of resecting all the metastases to be potentially curative (R0-R1 resection). However, 10-20% of patients are initially resectable. Along with the increasing efficacy of chemotherapy, around 20% of initially unresectable patients could be switched to secondary resectability after tumor downsizing with real hope of long-term survival. However, still a majority of patients remain "curatively" unresectable while responding to chemotherapy, owing to the impossibility to resect all the initial tumoral disease. For such extensive cases, cytoreductive surgery might provide a survival benefit, provided an objective tumor response with chemotherapy and optimal cytoreduction with almost no macroscopic residual disease.

Tumor Load Matters - the Peritoneal Cancer Index in Patients With High-grade Serous Ovarian Cancer.

The aim of this study was to analyze the predictive and prognostic value of the peritoneal cancer index (PCI) with regard to complete cytoreduction and clinical outcomes in patients with high-grade serous ovarian cancer. In a cohort comprising 188 patients with high-grade serous ovarian cancer, the PCI was retrospectively assessed. Clinical factors and perioperative complications were analyzed according to different PCI groups. Five-year disease-free survival (DFS) and overall survival (OS) were calculated based on the Kaplan-Meier Log rank analysis. Receiver operating characteristic (ROC) analysis was applied to detect associations of PCI and complete cytoreduction. Multivariate survival analysis was performed by Cox proportional hazards model. In our study, the PCI was predictive of complete cytoreduction (ROC analysis; AUC 0.8227). In patients with optimal cytoreduction, higher PCI scores were associated with poorer 5-year OS (p<0.001) and 5-year DFS (p<0.001). Complications (G1-G5) were significantly more frequent in patients with PCI scores >9 (p=0.0023). Five-year OS was reduced in patients with severe complications compared to patients with none or mild complications (30.88% versus 51.01%; p=0.001). There were significant OS (p<0.001) and DFS (p<0.001) differences between patients with none or mild versus severe complications following complete cytoreduction within the PCI subgroups (PCI: 9-11, PCI: 12-18, PCI >18). The PCI score showed high predictability for complete cytoreduction and was associated with clinical outcomes. In presence of severe complications, higher PCI scores were associated with poorer survival. Hence, in patients with high tumor load, the prevention of severe perioperative complications is of utmost importance in all cases where complete cytoreduction is deemed to be feasible.

Does Timing of Treatment Have an Effect on Survival in Ovarian Carcinoma?

Background and Purpose: Optimal cytoreduction (CRS) is the main treatment modality in epithelial ovarian cancer (OC). Inoperable OC at the time of diagnosis may become eligible for CRS after neoadjuvant chemotherapy (NACT). We aimed to investigate the effect of the time between NACT-CRS and CRS-adjuvant chemotherapy on survival in OC patients.&#x0D; Materials and Methods: Demographic and clinicopathological characteristics of sixty-nine patients with OC who underwent CRS after NACT between December 2009 and May 2020 were analyzed retrospectively.&#x0D; Results: The median age was 61.1, and the median overall survival (OS) was 75.8 months. The median time from the end of NACT to CRS was 6.53 weeks, and the median time from CRS to initiation of adjuvant therapy was 4.8 weeks. The mean OS was 123.4 months in patients with a NACT-CRS interval of 6.53 weeks or less, and it was 61.6 months in patients above this period (p&gt;0.05). The OS was 75.7 months in patients with an interval between CRS and adjuvant therapy of 4.8 weeks or less and 55.1 months compared to those with 4.8 weeks or more (p&gt;0.05). &#x0D; Conclusion: It was shown numerically, although not statistically significant, that a long time between NACT and CRS and CRS-adjuvant therapy had a negative effect on OS.

Combined BRCA2 and MAGEC3 Expression Predict Outcome in Advanced Ovarian Cancers.

Simple SummaryEarly detection of ovarian cancer is a significant clinical challenge, with most women presenting with advanced stages of disease at initial diagnosis. The aim of this study was to evaluate the role of MAGEC3 and BRCA2 in epithelial ovarian cancer progression. We evaluated the effect of MAGEC3 and BRCA2 on the other’s expression. We tested this in humans using immunohistochemical staining of human tumor samples obtained from patients with epithelial ovarian cancer (n = 357). We found a weak inverse correlation between MAGEC3 and BRCA2 expression in epithelial ovarian cancers. Further, our data suggest that the combined expression of MAGEC3 and BRCA2 may be a better predictor of outcomes in patients than the individual markers alone.Like BRCA2, MAGEC3 is an ovarian cancer predisposition gene that has been shown to have prognostic significance in ovarian cancer patients. Despite the clinical significance of each gene, no studies have been conducted to assess the clinical significance of their combined expression. We therefore sought to determine the relationship between MAGEC3 and BRCA2 expression in ovarian cancer and their association with patient characteristics and outcomes. Immunohistochemical staining was quantitated on tumor microarrays of human tumor samples obtained from 357 patients with epithelial ovarian cancer to ascertain BRCA2 expression levels. In conjunction with our previously published MAGEC3 expression data, we observed a weak inverse correlation of MAGEC3 with BRCA2 expression (r = −0.15; p < 0.05) in cases with full-length BRCA2. Patients with optimal cytoreduction, loss of MAGEC3, and detectable BRCA2 expression had better overall (median OS: 127.9 vs. 65.3 months, p = 0.035) and progression-free (median PFS: 85.3 vs. 18.8 months, p = 0.002) survival compared to patients that were BRCA2 expressors with MAGEC3 normal levels. Our results suggest that combined expression of MAGEC3 and BRCA2 serves as a better predictor of prognosis than each marker alone.

Neoadjuvant Chemotherapy Versus Primary Debulking Surgery in FIGO Stage III and IV Epithelial Ovarian, Tubal or Peritoneal Cancer: A Systematic Review and Meta-Analysis.

Objective: To investigate whether neoadjuvant chemotherapy (NACT) confers superior outcomes compared to primary debulking surgery (PDS) in patients with stage III and IV epithelial ovarian, tubal or peritoneal cancer as well as in patients with high tumour load. Methods: We searched the electronic databases PubMed, Cochrane Central Register of Controlled trials, and Scopus from inception to March 2021. We considered randomised controlled trials (RCTs) comparing NACT with PDS for women with epithelial ovarian cancer (EOC) stages III and IV. The primary outcomes were overall survival and progression-free survival. Secondary outcomes were optimal cytoreduction rates, peri-operative adverse events, and quality of life. Results: Six RCTs with a total of 1901 participants were included. Meta-analysis demonstrated similar overall survival (HR = 0.96, 95% CI [0.86-1.07]) and progression-free survival (HR = 0.98, 95% CI [0.89-1.08]) between NACT and PDS. Subgroup analyses did not demonstrate higher survival for stage IV patients (HR = 0.88, 95% CI [0.71-1.09]) nor for patients with metastatic lesions >5cm (HR = 0.86, 95% CI [0.69-1.08]) treated with NACT, albeit with some uncertainty due to imprecision. Similarly, no survival benefit was observed in the subgroup of patients with metastatic lesions >10cm (HR = 0.94, 95% CI [0.78-1.12]). NACT was associated with significantly higher rates of complete cytoreduction (RR = 2.34, 95% CI [1.48-3.71]). Severe peri-operative adverse events were less frequent in the NACT arm (RR = 0.34, 95% CI [0.16-0.72]. Conclusion: Patients with stage III and IV epithelial ovarian cancer undergoing NACT or PDS have similar overall survival. NACT is likely associated with higher rates of complete cytoreduction and lower risk of severe adverse events and peri-operative death.

Advanced low grade serous ovarian cancer: A retrospective analysis of surgical and chemotherapeutic management in two high volume oncological centers

Simple summaryLow-grade serous ovarian cancer (LGSOC) represents an uncommon histotype of serous ovarian cancer (accounting for approximately 5% of all ovarian cancer) with a distinct behavior compared to its high-grade serous counterpart, characterized by a better prognosis and low response rate to chemotherapeutic agents. Similar to high-grade serous ovarian cancer, cytoreductive surgery is considered crucial for patient survival. This retrospective study aimed to analyze the outcomes of women affected by advanced stages (III–IV FIGO) of LGSOC from two high-volume oncological centers for ovarian neoplasm. In particular, we sought to evaluate the impact on survival outcomes of optimal cytoreductive surgery [i.e., residual disease (RD) <10 mm at the end of surgery]. The results of our work confirm the role of complete cytoreduction (i.e., no evidence of disease after surgery) in the survival of patients and even the positive prognostic role of a minimal RD (i.e., <10 mm), whenever complete cytoreduction cannot be achieved.BackgroundLow-grade serous ovarian cancer (LGSOC) is a rare entity with different behavior compared to high-grade serous (HGSOC). Because of its general low chemosensitivity, complete cytoreductive surgery with no residual disease is crucial in advanced stage LGSOC. We evaluated the impact of optimal cytoreduction on survival outcome both at first diagnosis and at recurrence.MethodsWe retrospectively studied consecutive patients diagnosed with advanced LGSOCs who underwent cytoreductive surgery in two oncological centers from January 1994 to December 2018. Survival curves were estimated by the Kaplan–Meier method, and 95% confidence intervals (95% CI) were estimated using the Greenwood formula.ResultsA total of 92 patients were included (median age was 47 years, IQR 35–64). The median overall survival (OS) was 142.3 months in patients with no residual disease (RD), 86.4 months for RD 1–10 mm and 35.2 months for RD >10 mm (p = 0.002). Progression-free survival (PFS) was inversely related to RD after primary cytoreductive surgery (RD = 0 vs RD = 1–10 mm vs RD >10 mm, p = 0.002). On multivariate analysis, RD 1–10 mm (HR = 2.30, 95% CI 1.30–4.06, p = 0.004), RD >10 mm (HR = 3.89, 95% CI 1.92–7.88, p = 0.0004), FIGO stage IV (p = 0.001), and neoadjuvant chemotherapy (NACT) (p = 0.010) were independent predictors of PFS. RD >10 mm (HR = 3.13, 95% CI 1.52–6.46, p = 0.004), FIGO stage IV (p <0.0001) and NACT (p = 0.030) were significantly associated with a lower OS.ConclusionsOptimal cytoreductive surgery improves survival outcomes in advanced stage LGSOC s . When complete debulking is impossible, a RD <10 mm confers better OS compared to an RD >10 mm in this setting of patients.

Splenectomy at the time of primary or interval cytoreductive surgery for epithelial ovarian carcinoma: A review of outcomes

ObjectivesWe describe post-operative complications after cytoreductive surgery with and without splenectomy for Stage III or IV epithelial ovarian cancer, and identify areas for quality improvement in post-splenectomy care. MethodsAll patients with ovarian cancer cytoreductive surgery from 2008 to 2018 were identified using an institutional database Gynecologic Oncology Longitudinal Data Collection and Utilization Program (GOLD CUP). We compared patients who had and did not have splenectomy as part of cytoreductive surgery by demographics, comorbidities, stage, operative and post-operative data, readmission rates, progression free survival, overall survival and death from disease. Quality metrics reported include receipt of post-splenectomy education handouts and encapsulated-organism vaccines. Statistical analysis was completed in STATA SE 16.0. ResultsWe identified 47 patients who underwent splenectomy and 454 who did not during primary or interval cytoreductive surgery. Final stage was IIIB in 1 (2.1%), IIIC in 26 (55.3%), IVA in 7 (14.9%), and IVB in 13 (27.7%) patients. Those with splenectomy had significantly higher stage. Surgery duration and hospital length of stay were longer and blood transfusion more common after splenectomy, but there were no differences in post-operative infection, readmission, or overall survival. Pancreatic leaks were seen in 4/47 (8.5%) patients. Post-splenectomy vaccinations were documented in 42/47 (89.4%) patients. Only 2/47 (4.3%) received post-splenectomy discharge instructions and 3/7 (42.9%) received aspirin for platelets 1 million or more. ConclusionsWhile splenectomy adds morbidity, it continues to offer benefit in those patients who can achieve optimal cytoreduction. Areas for quality improvement in post-splenectomy care include receipt of vaccinations, patient discharge information, and timely pancreatic fistula management.

Role of reactive thrombocytosis after primary cytoreductive surgery in advanced ovarian cancer.

We investigated the incidence of reactive thrombocytosis after maximal cytoreductive surgery in advanced epithelial ovarian cancer (EOC) and its role in patient survival. We retrospectively reviewed the electronic medical records of patients who underwent primary cytoreductive surgery for advanced EOC from 1 January 2012 to 31 December 2017. We analyzed the serum platelet counts at various time points from before surgery, during the peri-operative period, and after each cycle of adjuvant chemotherapy. A total of 474 patients were eligible for the analysis. Among them, 401 patients (84.6%) had FIGO stage III disease status. The most common histology type was serous adenocarcinoma (405 patients, 85.4%). Seventy-nine patients (22.6%) received splenectomy, and optimal cytoreduction was achieved in 326 patients (68.8%). A week after surgery, thrombocytosis was observed in 165 patients (34.8%) in the entire cohort. Higher platelet counts were observed in patients with splenectomy compared with patients without splenectomy. In particular, thrombocytosis on the fifth cycle of adjuvant chemotherapy showed the most significant effects on overall survival in multivariate analysis. In a logistic regression model, splenectomy was significantly attributed to thrombocytosis on the fifth cycle of chemotherapy. Reactive thrombocytosis after primary cytoreductive surgery is associated with poor survival in advanced EOC, particularly when thrombocytosis is observed during adjuvant chemotherapy.

Effect of Hospital Case-Volume on Mortality after Ovarian Cancer Surgery: A Population-Based Retrospective Cohort Study

Objectives: The goal of ovarian cancer surgery has recently shifted from optimal cytoreduction to more complete resection. This study attempted to reassess and update the association between surgical case-volume and both in-hospital and long-term mortality after ovarian cancer surgery using recent data. Design: This study is a population-based retrospective cohort study. Participants/Material: Data from all adult patients who underwent ovarian cancer surgery in Korea between 2005 and 2019 were obtained from the national database. A total of 24,620 patients underwent ovarian cancer surgery in 362 hospitals during the period. Setting: In-hospital and 1-, 3-, 5-year mortality were set as primary and secondary outcomes. Methods: Hospitals were categorized into high-volume (>90 cases/year), medium-volume (20–90 cases/year), and low-volume (<20 cases/year) centers considering overall distribution of case-volume. Postoperative in-hospital and long-term mortality were analyzed using logistic regression after adjusting for potential risk factors. Results: Compared to high-volume centers (0.54%), in-hospital mortality was significantly higher in medium-volume (1.40%; adjusted odds ratio, 2.92; confidence interval, 1.82–3.73; p < 0.001) and low-volume (1.61%; adjusted odds ratio, 2.94; confidence interval, 2.07–4.17; p < 0.001) centers. In addition, 1-year mortality was 6.26%, 7.06%, and 7.94% for high-volume, medium-volume, and low-volume centers, respectively, and the differences among the groups were significant. However, case-volume effect was not apparent in 3- and 5-year mortality after ovarian cancer surgery. Limitations: Lacking clinical information such as staging or histologic diagnosis due to the nature of the administrative data should be considered in interpreting the data. Conclusions: Case-volume effect was observed for in-hospital and 1-year mortality after ovarian cancer surgery, while it was not clearly found in 3- or 5-year mortality. Dilution of the case-volume effect might be attributed to the high accessibility to care.

Response to treatment and prognostic significance of supradiaphragmatic disease in patients with high-grade serous ovarian cancer

ObjectivesThis study was designed to investigate the response to chemotherapy of supradiaphragmatic disease diagnosed by preoperative imaging. As secondary objectives, oncologic outcomes of patients affected by supradiaphragmatic disease and their pattern of recurrence were also evaluated. MethodsData of consecutive patients with newly diagnosed FIGO stage IV (for supradiaphragmatic disease) epithelial ovarian cancer undergoing either primary debulking surgery or neoadjuvant chemotherapy plus interval debulking surgery between 2004 and 2021, were retrospectively collected. All patients were preoperatively evaluated by chest/abdominal CT scan or 18F-FDG PET/CT preoperatively and at follow-up to evaluate response to chemotherapy. At follow-up visits, site of recurrence diagnosed by imaging techniques was systematically recorded as it occurred. Progression-free and overall survival were measured by using Kaplan-Meier and Cox models. ResultsA total of 130 patients was included in this study with a median (range) follow-up of 32.9 (12.8–176.7) months. Complete or partial response was achieved in most of the patients after 3 cycles (77.7%) and 6 cycles (85.4%) of chemotherapy. At follow-up, recurrence occurred in 96 (73.8%) patients and the main site of recurrence was abdomen only in 64 (66.7%) patients. At multivariate analysis, residual disease after surgery was the only variable influencing survival outcomes. ConclusionsSupradiaphragmatic disease respond to chemotherapy in most patients affected by advanced EOC and recurrence mainly occurs in the abdomen. Results from this study confirms that abdominal optimal cytoreduction is the main surgical goal in the treatment of women affected by FIGO stage IV EOC.

Using a machine learning algorithm to predict outcome of cytoreduction in advanced ovarian cancer (079)

Using a machine learning algorithm to predict outcome of cytoreduction in advanced ovarian cancer (079)

FDG PET/CT parameters and CA-125 levels to predict optimal cytoreduction at primary cytoreductive surgery for advanced ovarian cancer (149)

Objectives: To develop models predicting optimal cytoreduction in primary cytoreductive surgery (CRS) using clinical-pathologic characteristics and FDG PET/CT-derived parameters in advanced ovarian cancer. Methods: We retrospectively identified patients with stage III-IV ovarian cancer who underwent primary CRS between June 2013 and February 2020 at our center. We calculated the following 18 parameters: maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), visual grade, and the number of lesions in three divided areas of the abdominal cavity. Optimal cytoreduction was defined as grossly no residual tumor after CRS. We constructed various predictive models for optimal cytoreduction by combining clinical-pathologic characteristics and FDG PET/CT-derived parameters. The predictive performance of each model was assessed based on the area under the receiver operating characteristic curve (AUC). Results: In total, 159 patients were included in the study. The median age was 55 years. The most common histologic subtype was serous (74.2%). Stage III and stage IV were 73.6% and 26.4%, respectively. Optimal cytoreduction was achieved in 104 patients (65.4%). The median CA-125 was 764 IU/ml. As a single variable, MTV, TLG, number of lesions above the renal vein showed high AUC for optimal cytoreduction, at 0.749, 0.748, and 0.748, respectively. The best predictive multivariable model consisted of CA-125 (<750 or ≥750 IU/ml), the number of lesions above the renal vein (<2 or ≥2), and MTV above the renal vein with an AUC of 0.770 for optimal cytoreduction. Conclusions: We successfully developed FDG PET/CT-based predictive model for optimal cytoreduction. This result may help determine patients’ treatment plans. Objectives: To develop models predicting optimal cytoreduction in primary cytoreductive surgery (CRS) using clinical-pathologic characteristics and FDG PET/CT-derived parameters in advanced ovarian cancer. Methods: We retrospectively identified patients with stage III-IV ovarian cancer who underwent primary CRS between June 2013 and February 2020 at our center. We calculated the following 18 parameters: maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), visual grade, and the number of lesions in three divided areas of the abdominal cavity. Optimal cytoreduction was defined as grossly no residual tumor after CRS. We constructed various predictive models for optimal cytoreduction by combining clinical-pathologic characteristics and FDG PET/CT-derived parameters. The predictive performance of each model was assessed based on the area under the receiver operating characteristic curve (AUC). Results: In total, 159 patients were included in the study. The median age was 55 years. The most common histologic subtype was serous (74.2%). Stage III and stage IV were 73.6% and 26.4%, respectively. Optimal cytoreduction was achieved in 104 patients (65.4%). The median CA-125 was 764 IU/ml. As a single variable, MTV, TLG, number of lesions above the renal vein showed high AUC for optimal cytoreduction, at 0.749, 0.748, and 0.748, respectively. The best predictive multivariable model consisted of CA-125 (<750 or ≥750 IU/ml), the number of lesions above the renal vein (<2 or ≥2), and MTV above the renal vein with an AUC of 0.770 for optimal cytoreduction. Conclusions: We successfully developed FDG PET/CT-based predictive model for optimal cytoreduction. This result may help determine patients’ treatment plans.

Effect of genomic loss of heterozygosity and homologous recombination deficiency on platinum sensitivity and clinical course in women with epithelial ovarian cancer (175)

Effect of genomic loss of heterozygosity and homologous recombination deficiency on platinum sensitivity and clinical course in women with epithelial ovarian cancer (175)

Ten-year conditional probability of survival for patients with ovarian cancer: A new metric for the new millennium (480)

Objectives: To demonstrate the utility of conditional probability of survival (CPS) as a metric in analyzing survival outcomes for women with ovarian cancer. Methods: We analyzed the records of all patients (pts) with newly diagnosed high-grade epithelial ovarian cancer who underwent treatment at our institution from January 2001 to December 2009. Pts lost to follow-up were excluded if they had less than three years of follow-up. CPS was defined as the probability of surviving additional years (y) based on the condition that a patient had already survived at a given time (x): S(x + y)/S(x). Confidence intervals (CIs) were estimated using a variation of Greenwood’s formula. Results: A total of 916 pts met the inclusion criteria. The median age at diagnosis was 60 years (range: 25-95) with 37% (337/916) <65 years old (yo). FIGO stage was as follows: stage I 14% (132/916), stage II 6% (59/916), stage III 57% (519/916), and stage IV 23% (206/916). Histology was high-grade serous in 83% pts (759/916). Among the 907 pts who underwent surgical management, 64% (584/907) had a primary debulking surgery, 16% (143/907) had an interval debulking after neoadjuvant chemotherapy and 20% (180/907) underwent staging. A total of 84% (757/907) had an optimal cytoreduction (<1 cm of residual disease), whereas 49% (440/907) had a complete gross resection. The Median follow-up time for the entire cohort was 55 months, and the median overall survival (OS) was 57 months. Twenty percent (183/916) had an OS >10-years. Ten-year OS for pts aged <65 yo with early-stage I/II, stage III, and stage IV ovarian cancer was 48%, 24%, and 11%, respectively. For patients >65 yo, 10-year OS was 22%, 11%, and 4%, respectively. For patients <65 yo, the 10-year CPS for 5-year survivors was: early-stage I/II, 90.0 % (95% CI: 85.4%-94.6%); stage III, 56.8% (95%CI 51.0%-62.7%); stage IV, 38.8% (95% CI: 24.3%- 53.4%). For patients >65y, the 10-year CPS for 5-year survivors was: early-stage I/II, 63.1% (95% CI: 52.6%-73.5%); stage III, 43.8% (95% CI: 31.7%-55.9%); stage IV, 22.5% (95% CI: 6.6%-38.3%). Conclusions: For long-term 5-year survivors with advanced OC, CPS can provide a more representative estimate of future survival than conventional OS ratesl OS. Objectives: To demonstrate the utility of conditional probability of survival (CPS) as a metric in analyzing survival outcomes for women with ovarian cancer. Methods: We analyzed the records of all patients (pts) with newly diagnosed high-grade epithelial ovarian cancer who underwent treatment at our institution from January 2001 to December 2009. Pts lost to follow-up were excluded if they had less than three years of follow-up. CPS was defined as the probability of surviving additional years (y) based on the condition that a patient had already survived at a given time (x): S(x + y)/S(x). Confidence intervals (CIs) were estimated using a variation of Greenwood’s formula. Results: A total of 916 pts met the inclusion criteria. The median age at diagnosis was 60 years (range: 25-95) with 37% (337/916) <65 years old (yo). FIGO stage was as follows: stage I 14% (132/916), stage II 6% (59/916), stage III 57% (519/916), and stage IV 23% (206/916). Histology was high-grade serous in 83% pts (759/916). Among the 907 pts who underwent surgical management, 64% (584/907) had a primary debulking surgery, 16% (143/907) had an interval debulking after neoadjuvant chemotherapy and 20% (180/907) underwent staging. A total of 84% (757/907) had an optimal cytoreduction (<1 cm of residual disease), whereas 49% (440/907) had a complete gross resection. The Median follow-up time for the entire cohort was 55 months, and the median overall survival (OS) was 57 months. Twenty percent (183/916) had an OS >10-years. Ten-year OS for pts aged <65 yo with early-stage I/II, stage III, and stage IV ovarian cancer was 48%, 24%, and 11%, respectively. For patients >65 yo, 10-year OS was 22%, 11%, and 4%, respectively. For patients <65 yo, the 10-year CPS for 5-year survivors was: early-stage I/II, 90.0 % (95% CI: 85.4%-94.6%); stage III, 56.8% (95%CI 51.0%-62.7%); stage IV, 38.8% (95% CI: 24.3%- 53.4%). For patients >65y, the 10-year CPS for 5-year survivors was: early-stage I/II, 63.1% (95% CI: 52.6%-73.5%); stage III, 43.8% (95% CI: 31.7%-55.9%); stage IV, 22.5% (95% CI: 6.6%-38.3%). Conclusions: For long-term 5-year survivors with advanced OC, CPS can provide a more representative estimate of future survival than conventional OS ratesl OS.

Patterns of treatment and survival outcomes with use of neoadjuvant chemotherapy in ovarian cancer (481)

Patterns of treatment and survival outcomes with use of neoadjuvant chemotherapy in ovarian cancer (481)

Survival comparison of chemotherapy vs. chemotherapy plus surgery for women with ovarian cancer with distant metastatic disease (387)

<b>Objectives:</b> Standard treatment of advanced epithelial ovarian cancer (EOC) is a combination of surgical cytoreduction and chemotherapy. However, the impact of cytoreductive surgery for patients with unresectable metastatic disease, in whom optimal cytoreduction is not feasible, is not well described. <b>Methods:</b> The National Cancer Database (NCDB) was used to identify patients with Stage IV EOC with distant organ metastasis at the time of diagnosis, treated from 2005 to 2016. Distant organ metastasis was defined as metastasis to the brain, lung, liver, bone, or distant lymph node. To represent unresectable distant metastasis, a restricted population with only metastasis to the brain, lung, or bone was also analyzed. All patients received chemotherapy with or without surgery. Overall survival was analyzed using the Kaplan-Meier method, Cox proportional hazards models, and propensity score-weighted analyses. In these analyses, the variables included were surgery, age, year of diagnosis, race, Charlson/Deyo Comorbidity Condition (CDCC) Score, facility type, primary insurance, histology, site of metastasis, urban versus rural residence, education, and median household income. <b>Results:</b> We identified 9025 patients with EOC with distant organ metastasis in the NCDB. Among these patients, 2074 received chemotherapy alone, and 6951 received chemotherapy plus surgery (C+S). Those who received chemotherapy alone were older with higher CDCC scores, lived in areas of lower median household incomes, and had lower high school graduation rates. These individuals had a higher proportion of metastatic disease to the liver, bone, or brain. Race was significantly different between groups, with a higher proportion of those receiving chemotherapy alone being Black (12.7% vs 8.2%). Survival was significantly improved for patients who received C+S (HR: 0.46, p<0.0001). Propensity score-weighted analysis similarly showed improved survival for patients undergoing C+S (HR: 0.49, p<0.0001). Individuals who received single-agent chemotherapy had worse overall survival (HR: 1.35, p<0.0001). When accounting for the impact of single-agent chemotherapy on the survival comparison, the benefit of surgery remained significant (HR: 0.47, p<0.0001). In the group defined as unresectable distant metastasis, we identified 1424 patients, of which 396 received chemotherapy alone and 1028 received C+S. A survival benefit was again shown for patients who received C+S, by Cox model (HR: 0.42, p<0.0001) and propensity score-weighted analysis (HR: 0.44, p<0.0001). <b>Conclusions:</b> Despite the poor prognosis associated with Stage IV EOC, obtaining local control with surgery in addition to chemotherapy may provide an added oncologic benefit. Because of the retrospective nature of this analysis, the absolute benefit of surgery for patients with Stage IVB EOC cannot be established. However, this study may provide added value to patient-centered counseling on the role of surgical resection in the setting of ovarian cancer with distant metastatic disease.

Sarcoma regimens for gynecologic carcinosarcoma: Is there a benefit? (186)

<b>Objectives:</b> To compare differences in overall survival (OS) in patients with carcinosarcomas of endometrial or ovarian origin who were ever treated with sarcoma chemotherapy regimens compared to those who only received traditional carcinoma regimens. <b>Methods:</b> We conducted a single-institution, retrospective cohort study of patients with a confirmed histologic diagnosis of uterine or ovarian carcinosarcoma diagnosed since the year 2000. Clinical, pathology, and outcomes data were collected. Patients were considered to have received a sarcoma-based regimen if any of their treatment courses included ifosfamide, combination gemcitabine/ docetaxel, or any other regimens listed on the NCCN guidelines for soft tissue sarcomas. Clinical and demographic characteristics were compared across groups using Chi-square, Fisher's exact, or Wilcoxon rank-sum tests. OS was evaluated using a log-rank test. <b>Results:</b> A total of 88 patients with carcinosarcoma of endometrial (77%) or ovarian (22%) origin were identified, 78 of whom had chemotherapy information available. Sixteen (23%) of the patients received chemotherapy that included a sarcoma regimen, 51 (65%) received only carcinoma regimens, and 13 (16%) did not receive any chemotherapy. We excluded ten patients for whom there was no chemotherapy information from the analysis. Among those who received any chemotherapy, there were no significant differences in age, BMI, race, use of radiation, number of lines of chemotherapy received, disease stage, or optimal cytoreduction rate between the two regimen groups. Patients were more likely to have an endometrial primary if they ever received a sarcoma regimen (Table 1). There was no difference in OS between the sarcoma regimen and non-sarcoma regimen groups (HR: 0.71, 95% CI: 0.30-1.64). Older age, stage IV disease, and suboptimal debulking status were associated with shorter OS in this group of patients (p<0.05). <b>Conclusions:</b> Patients who ever received a sarcoma-based regimen did not have longer OS. Since sarcoma regimens tend to have more toxicity, exclusive use of carcinoma regimens for patients with gynecologic carcinosarcomas may be beneficial.

Systematic review and meta-analysis of neoadjuvant chemotherapy compared to primary debulking surgery in advanced endometrial cancer (538)

Systematic review and meta-analysis of neoadjuvant chemotherapy compared to primary debulking surgery in advanced endometrial cancer (538)

Incidence of venous thromboembolism (VTE) in ovarian cancer patients on low dose aspirin (312)

<b>Objectives:</b> Patients with ovarian cancer are at high risk for malignancy- associated venous thromboembolism (VTE). Recent guidelines recommend anticoagulation with low molecular weight heparin (LMWH) or direct oral anticoagulant (DOAC) for high-risk patients receiving chemotherapy. Neither of these medications is ideal owing to the route of administration and cost, respectively. Aspirin has been suggested as a possible low-cost, easily administered alternative to LMWH and DOAC for VTE prophylaxis. The goal of our study was to examine the association between aspirin use and the rate of VTE in ovarian cancer patients. <b>Methods:</b> A single-institution retrospective study was conducted among patients diagnosed with epithelial ovarian cancer between 2005 and 2020. The primary exposure of interest was aspirin use at diagnosis. The outcome of interest was VTE incidence during treatment. Demographic and clinical data were abstracted from the electronic medical record. Descriptive statistics and t-tests, Chi-square, and Fisher's exact tests were used to analyze and compare clinical variables. A multivariable analysis was performed with multiple logistic regression, controlling for age, stage, BMI, and histology. Statistical significance was set at p=0.05. <b>Results:</b> A total of 201 patients with ovarian cancer were included in this study. The median age was 59 years. Most women underwent primary cytoreduction (87%) via laparotomy (83%), and 78% achieved optimal cytoreduction. Within this cohort, 39 (19.4%) women were taking daily aspirin at the time of diagnosis. VTE after diagnosis was observed in a total of 32 (15.9%) women. Of those who were taking aspirin at diagnosis, seven (21.9%) developed VTE, compared to 25 (15%) in the control group (p = 0.7). Aspirin is not independently associated with VTE (OR: 0.81, 95% CI: 0.32-2.25). Most VTEs were diagnosed during adjuvant treatment (43.8%). There were no statistically significant differences in histology, stage, surgery type, rate of optimal debulking, or time to finish adjuvant therapy between women who developed VTE versus those who did not. On multivariable analyses, neither ASA status nor high-grade serous histology was associated with VTE (OR: 1.09, 95% CI: 0.48-2.49; and OR: 0.81, 95% CI: 0.32-2.25, respectively). It should be noted that the timeframe studied included low rates of neoadjuvant therapy. <b>Conclusions:</b> In line with previous reports, nearly 16% of this cohort developed VTE in association with an ovarian cancer diagnosis. VTE rate among women using aspirin was not different from those not on aspirin. While limited by sample size, our data suggest that aspirin alone appears insufficient for prophylaxis against VTE in women with ovarian cancer.

Single-arm phase II trial of carboplatin and mirvetuximab soravtansine as neoadjuvant chemotherapy (NACT) for advanced- stage ovarian, fallopian tube or primary peritoneal cancer (EOC) who are folate receptor α positive (NCT04606914) (578)

Objectives: The primary objective is to assess the feasibility and safety of obtaining tissue, assessing alpha-folate receptor status, and initiating treatment based on this data using a 21-day schedule in the advanced-stage ovarian, fallopian tube, or peritoneal cancer patients, without an unacceptable interval debulking surgery (IDS) delay. Secondary objectives include assessing progression-free survival, percentage of disease-free survival at two years, ORR prior to IDS per iRECIST 1.1 and GCIG CA-125 criteria, and percentage of optimal cytoreduction and pathological complete response (pCR) at IDS. Methods: This is a phase II study design with carboplatin and mirvetuximab (FRa receptor monoclonal antibody.) Patients with biopsy-confirmed, newly diagnosed, advanced-stage serous epithelial ovarian cancer appropriate for NACT will have centralized tumor evaluation via immunohistochemistry for FRa receptor overexpression. IHC staining is 2+ in 75% of cells will define eligibility. Patients will receive NACT with one lead-in cycle of single-agent carboplatin AUC 5/6, physician’s choice), followed by AUC 5 carboplatin and Mirvetuximab 6mg/kg adjusted to ideal body weight every 21days for three cycles prior to interval cytoreductive surgery (iCRS.) Patients eligible for surgery will undergo an iCRS no sooner than three weeks but no later than six weeks following the completion of cycle 3. Postoperatively, patients will complete three additional cycles of carboplatin-mirvetuximab for a total of 6 intended cycles. A total of 70 patients will be included. Patients with BRCA mutations are not excluded from this trial and may receive standard of care maintenance therapy, including bevacizumab and/or PARP inhibitors per physician’s choice in the adjuvant setting. After completion of adjuvant treatment, participants will be assessed approximately every 12 weeks by radiologic imaging to monitor disease status using RECIST 1.1 criteria. Objectives: The primary objective is to assess the feasibility and safety of obtaining tissue, assessing alpha-folate receptor status, and initiating treatment based on this data using a 21-day schedule in the advanced-stage ovarian, fallopian tube, or peritoneal cancer patients, without an unacceptable interval debulking surgery (IDS) delay. Secondary objectives include assessing progression-free survival, percentage of disease-free survival at two years, ORR prior to IDS per iRECIST 1.1 and GCIG CA-125 criteria, and percentage of optimal cytoreduction and pathological complete response (pCR) at IDS. Methods: This is a phase II study design with carboplatin and mirvetuximab (FRa receptor monoclonal antibody.) Patients with biopsy-confirmed, newly diagnosed, advanced-stage serous epithelial ovarian cancer appropriate for NACT will have centralized tumor evaluation via immunohistochemistry for FRa receptor overexpression. IHC staining is 2+ in 75% of cells will define eligibility. Patients will receive NACT with one lead-in cycle of single-agent carboplatin AUC 5/6, physician’s choice), followed by AUC 5 carboplatin and Mirvetuximab 6mg/kg adjusted to ideal body weight every 21days for three cycles prior to interval cytoreductive surgery (iCRS.) Patients eligible for surgery will undergo an iCRS no sooner than three weeks but no later than six weeks following the completion of cycle 3. Postoperatively, patients will complete three additional cycles of carboplatin-mirvetuximab for a total of 6 intended cycles. A total of 70 patients will be included. Patients with BRCA mutations are not excluded from this trial and may receive standard of care maintenance therapy, including bevacizumab and/or PARP inhibitors per physician’s choice in the adjuvant setting. After completion of adjuvant treatment, participants will be assessed approximately every 12 weeks by radiologic imaging to monitor disease status using RECIST 1.1 criteria.