Platinum-sensitive Recurrence Research Articles

Efficacy of a platinum-based chemotherapy rechallenge for platinum-sensitive recurrence after PARP inhibitor maintenance

ObjectivePlatinum-free interval (PFI) is the period from the end of platinum-based chemotherapy to the date of recurrence. If the PFI is > 6 months, a platinum-based chemotherapy rechallenge is considered; however, its efficacy after poly adenosine 5′-diphosphate-ribose polymerase (PARP) inhibitor maintenance therapy is unknown. This study aimed to examine the efficacy of a platinum-based chemotherapy rechallenge after PARP inhibitor therapy. MethodsWe retrospectively evaluated patients with ovarian cancer with a PFI≥6 months with PARP inhibitor maintenance therapy, receiving platinum-based chemotherapy. Duration of PARP inhibitor therapy, best response to subsequent platinum chemotherapy rechallenge, and clinical characteristics were collected from medical records. Tumor response was assessed according to RECIST 1.1. Correlations were calculated using Spearman’s correlation coefficients. ResultsAmong the 10 included patients, seven (70 %) received PARP inhibitors after primary chemotherapy, and three (30 %) received chemotherapy for platinum-sensitive relapse. One and five patients harbored a germline BRCA1 and BRCA wild-type mutations, respectively, and two had homologous recombination proficiency. The median PFI was 303.5 (182–602) days, and PARP inhibitor therapy duration was 249 (147–570) days. Platinum chemotherapy rechallenge efficacy was complete and partial response and stable disease in one (10 %), six (60 %), and three (30 %) patients, respectively. The longer the duration of PARP inhibitor treatment, better the response to platinum agents (Spearman correlation coefficient 0.284, p = 0.0288). ConclusionPlatinum-based chemotherapy rechallenge is reasonable for patients with platinum-sensitive disease, using the traditional PFI cutoff of 6 months, even when the PFI is obtained with a maintenance PARP inhibitor.

Efficacy and safety of oxaliplatin-based hyperthermic intraperitoneal chemotherapy with secondary cytoreduction for platinum resistant recurrent ovarian cancer: A single-center retrospective cohort study

Background/purposeThis retrospective study evaluated the efficacy and adverse effects of oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) with secondary cytoreductive surgery (CRS) in patients with recurrent ovarian cancer. MethodsPatients diagnosed with recurrent epithelial ovarian cancer, including fallopian tube and peritoneal origin, who underwent oxaliplatin-based HIPEC with secondary CRS, were enrolled. The primary outcome was progression-free survival (PFS), and the secondary outcomes were overall survival (OS) and adverse events. ResultsA total of 33 patients were included in the analysis. The mean PFS and OS were 20.4 months (95% CI 16.3–24.5 months) and 26.7 months (95% CI 23.7–29.7), respectively. Furthermore, the OS and PFS between platinum-sensitive and resistant recurrence showed no significant difference. Univariate and multivariate analysis of PFS identified a pre-operative peritoneal carcinomatosis index (PCI) score of ≥5 as a poor prognostic factor. Among them, the incidence of acute kidney injury was 9.0 % & none had grade ≧3 adverse events. ConclusionOxaliplatin-based HIPEC with secondary CRS might provide a survival benefit for patients with recurrent ovarian cancer with a decreased incidence of renal toxicity compared to cisplatin-based regimens. It might be effective and feasible in selected recurrent ovarian cancer patients, regardless of platinum-sensitive or resistant.

Do all patients that undergo a ‘complete’ secondary cytoreductive surgery for platinum-sensitive recurrent ovarian cancer, benefit from it?

Abstract Following the results of three randomized trials (GOG-213, DESKTOP-III, and SOC-1), secondary cytoreductive surgery (sCRS) is recommended as a therapeutic option for all patients with platinum-sensitive recurrence by the NCCN guidelines and for oligometastatic recurrence by the ESMO-ESGO guidelines. Criteria for predicting a complete gross resection (CGR) were used to select patients for sCRS in all three trials. No trial used surgical prognostic factors like disease sites or disease extent for stratification. The outcomes of sCRS varied in preplanned/post-hoc subgroup analyses. The survival following an incomplete CRS was worse than with systemic chemotherapy alone. Not all patients will benefit similarly from sCRS, even if a CGR is obtained. No trial evaluated the benefit of sCRS in patients receiving poly-ADP ribose polymerase (PARP) inhibitors. While GOG-213 showed no benefit of sCRS when bevacizumab was used, the role of bevacizumab in patients having a CGR was not evaluated. The use of targeted therapies during first-line therapy is increasing, affecting treatment decisions and future clinical trial designs. New trials on sCRS should stratify patients according to surgical prognostic factors; sub-group analyses should be performed only in patients with CGR.

Real-world TRAE association between niraparib and platinum-based chemotherapy.

Pre-clinical studies showed the anti-tumor mechanisms of PARP inhibitors (PARPi) and platinum have some crossover and overlap in the DNA damage repair pathway, patients who respond to platinum-based chemotherapy are also more likely to be sensitive to PARPi. This real-world study mainly aimed to evaluate whether TRAE (treatment-related adverse event) between platinum based chemotherapy (PBC) and niraparib are also associated. Patients received niraparib as maintenance treatment or salvage therapy for advanced ovarian cancer at the First Affiliated Hospital of Gannan Medical University from January 2020 to August 2023 were included. Survival data of niraparib treatment and adverse events occurred during the last platinum-based chemotherapy cycle before starting niraparib treatment and during niraparib treatment are documented. Fisher's exact test were used for correlation analysis. 1. 40 patients treated with niraparib were included in the analysis, including 31 patients treated with niraparib for 1st-line maintenance therapy, 6 patients for PSR (platinum-sensitive recurrence) maintenance therapy, and 3 patients for salvage therapy. The overall median follow-up time was 15.0 months (ranged from 2.2 months to 32.1 months). 2. Overall grade≥3 TRAE (40% vs 70%, p=0.012) including anemia (20% vs 45%, p=0.041) and neutrophil count decreased (17.5% vs 57.5%, p<0.001) was significantly lower during niraparib treatment compared to during chemotherapy. 3. Any grade TRAE (75% vs 100%, p=0.002) including white blood cell count decreased (47.5% vs 87.5%, p<0.001), red blood cell count decreased (57.5% vs 92.5%, p<0.001), anemia (55% vs 87.5%, p<0.001) and neutrophil count decreased (35% vs 85%, p<0.001) were also significantly lower in niraparib treatment group compared with chemotherapy group. No new safety signals were identified. 1. In this real-world practice, we observed that patients with advanced ovarian cancer who experienced any grade and grade ≥3 TRAE during chemotherapy were well tolerated when treated with niraparib, particularly the incidence of any grade and grade ≥3 anemia, and neutrophil count decreased during niraparib treatment were significantly lower compared with that during chemotherapy. 2. For patients with ovarian cancer who have experienced grade ≥3 hematological adverse reactions during prior platinum-based chemotherapy, greater attention should be paid to the monitoring and management of hematological adverse reactions during subsequent treatment with niraparib.

Platinum desensitization therapy and its impact on the prognosis of ovary high-grade serous adenocarcinoma: a real world-data.

To examine the value of five-step platinum desensitization therapy in epithelial ovarian cancer. A retrospective study was conducted on the high-grade serous adenocarcinoma of the ovary (HGSAO) patients who developed a platinum allergy during treatment and received desensitization therapy between January, 2016 and December, 2020. The logistic-regression was adopted to analyze the relationship between platinum desensitization therapy and prognosis in HGSAO patients. 92 HGSAO patients were included in the study. Among these, 35 patients (38.0%) experienced mild allergic reactions, 51 (55.4%) experienced moderate allergic reactions, and 6 (6.5%) experienced severe allergic reactions. The desensitization therapy was successful in 86 patients (93.5%). Six patients had desensitization failure, of which five experienced severe allergic reactions during desensitization. The logistic-regression analysis revealed no significant correlation between platinum desensitization therapy and progression-free survival (PFS) or overall survival (OS) of patients (P < 0.05). However, the subgroup analysis demonstrated that the success or failure of platinum desensitization therapy significantly impacted the OS of patients who were platinum-sensitive recurrence. The patients who had successful desensitization therapy had a superior OS. Five-step platinum desensitization therapy has potential application value in patients who were platinum-sensitive recurrence after first-line treatment but may bear the risk of severe allergic reactions.

Current treatment strategies for ovarian cancer in the East Asian Gynecologic Oncology Trial Group (EAGOT).

Ovarian cancer, notable for its severe prognosis among gynecologic cancers, has seen substantial progress in treatment approaches recently. Enhanced protocols in chemotherapy and the introduction of poly (ADP-ribose) polymerase (PARP) inhibitors for maintenance therapy have markedly improved outcomes for patients with specific genetic profiles, such as those positive for BRCA mutations or exhibiting homologous recombination deficiency (HRD). Additionally, the method of intraperitoneal chemotherapy administration has emerged as a valuable alternative to traditional transvenous routes, showing promise for wider clinical adoption. The field of surgery has also evolved, with increasing exploration into the benefits and feasibility of laparoscopic methods over more invasive traditional surgeries, aiming for complete tumor removal but with reduced patient impact. The hereditary nature of ovarian cancer underscores the importance of genetic testing, which has become integral in tailoring treatment strategies, particularly in determining suitability for PARP inhibitors. The formation of the East Asian Gynecologic Oncology Trial Group (EAGOT) aims to optimize treatment across Japan, Korea, China, and Taiwan. The ovarian cancer committee of EAGOT shared the current policies, focusing on 5 topics: 1) strategies for maintenance therapy after initial surgery and chemotherapy, 2) drug regimens for platinum-sensitive and platinum-resistant recurrence, 3) intraperitoneal chemotherapy, 4) laparoscopic surgery as an alternative to laparotomy, and 5) current status of genetic testing (BRCA, HRD, and panel tests) for ovarian cancer and its prospects. EAGOT's multi-national trials aim to harmonize these evolving treatment strategies, ensuring that the latest and most effective protocols are accessible across the region, thereby significantly impacting patient outcomes in East Asia.

Platinum-free Interval May Predict Duration of Maintenance Bevacizumab and Survival in Platinum-sensitive Recurrent Ovarian Cancer.

We investigated factors affecting the long-term duration of bevacizumab-based maintenance therapy (BMT) and survival in patients with the first platinum-sensitive recurrence of ovarian cancer (PSR). We included patients with the first PSR in two tertiary centers from January 2015 till August 2021. All patients received six cycles of paclitaxel, carboplatin, and bevacizumab followed by BMT. We collected data including age at recurrence, histologic types, the status of BRCA mutation, platinum-free interval (PFI), extent of secondary cytoreductive surgery (SCS), presence of extra-abdominal disease, numbers of recurred lesions, cycles of BMT, progression-free survival (PFS), and cancer-specific survival (CSS). The median cycles of BMT were 13 (range=1-108). A total 103 patients were included, who consisted of the short-term (<13 cycles; n=49; 47.6%) and long-term users of BMT (≥13 cycles; n=54; 52.4%). High-grade serous carcinoma (HGSC), PFI >12 months, and optimal cytoreduction during SCS were favorable factors for the long-term duration of BMT. Moreover, PFI >12 months and the long-term duration of BMT were factors for improved PFS, and HGSC and PFI >12 months were related to improved CSS. PFI >12 months may be associated with the long-term duration of BMT and improved survival in patients with the first PSR.

Prognosis Following Surgery for Recurrent Ovarian Cancer and Diagnostic Criteria Predictive of Cytoreduction Success: A Systematic Review and Meta-Analysis.

For women achieving clinical remission after the completion of initial treatment for epithelial ovarian cancer, 80% with advanced-stage disease will develop recurrence. However, the standard treatment of women with recurrent platinum-sensitive diseases remains poorly defined. Secondary (SCS), tertiary (TCS) or quaternary (QCS) cytoreduction surgery for recurrence has been suggested to be associated with increased overall survival (OS). We searched five databases for studies reporting death rate, OS, cytoreduction rates, post-operative morbidity/mortality and diagnostic models predicting complete cytoreduction in a platinum-sensitive disease recurrence setting. Death rates calculated from raw data were pooled based on a random-effects model. Meta-regression/linear regression was performed to explore the role of complete or optimal cytoreduction as a moderator. Pooled death rates were 45%, 51%, 66% for SCS, TCS and QCS, respectively. Median OS for optimal cytoreduction ranged from 16-91, 24-99 and 39-135 months for SCS, TCS and QCS, respectively. Every 10% increase in complete cytoreduction rates at SCS corresponds to a 7% increase in median OS. Complete cytoreduction rates ranged from 9-100%, 35-90% and 33-100% for SCS, TCS and QCS, respectively. Major post-operative thirty-day morbidity was reported to range from 0-47%, 13-33% and 15-29% for SCS, TCS and QCS, respectively. Thirty-day post-operative mortality was 0-6%, 0-3% and 0-2% for SCS, TCS and QCS, respectively. There were two externally validated diagnostic models predicting complete cytoreduction at SCS, but none for TCS and QCS. In conclusion, our data confirm that maximal effort higher order cytoreductive surgery resulting in complete cytoreduction can improve survival.

Efficacy of poly (ADP-ribose) polymerase inhibitors monotherapy and the impact to subsequent platinum-based chemotherapy in breast cancer susceptibility genes1/2-mutated ovarian cancer patients with secondary platinum-sensitive relapse

BackgroundThe therapeutic effect of poly (ADP-ribose) polymerase inhibitors (PARPi) monotherapy compared with platinum-based chemotherapy, and the impact to subsequent platinum-based chemotherapy after PARPi resistance were inconclusive in breast cancer susceptibility genes (BRCA)1/2-mutated ovarian cancer patients with secondary platinum-sensitive relapse.MethodsBRCA1/2-mutated patients with secondary platinum-sensitive relapse included in this study did not receive any maintenance regimen after first- and second-line platinum-based chemotherapy, and the secondary platinum-free interval (PFI) was more than 6 months. Patients in study group were treated with PARPi monotherapy until disease progression, and patients in control group were treated with platinum-based chemotherapy without restriction. Progression-free survival (PFS) was defined as the time from third-line therapy to disease progression or death, PFS2 was defined as the time from platinum-based chemotherapy after PARPi resistance to next subsequent therapy or death. Post-recurrence survival (PRS) refers to the survival time after secondary platinum-sensitive relapse.ResultsA total of 119 patients were retrospectively analyzed, including 71 (59.7%) in study group and 48 (40.3%) in control group. The objective response rate (ORR: 77.5% vs. 80.0%, p=0.766) and PFS (median: 11.2 vs. 11.0 months, p=0.962) were comparable. The benefit of subsequent platinum-based chemotherapy after PARPi resistance was more pronounced in patients with PARPi treatment for more than 12 months (median PFS2: 8.6 vs. 4.3 months, p=0.040). PARPi monotherapy had no adverse effect on PRS compared with platinum-based chemotherapy (median PRS:41.2 vs. 42.8 months, p=0.323). Compared to patients in control group who had never received PARPi, PARPi monotherapy (median PRS: 41.2 vs. 33.7 months, p=0.019) and post-line treatment with PARPi in the control group (median PRS: 48.1 vs. 33.7 months, p=0.002) could prolong PRS for patients with secondary platinum-sensitive relapse.ConclusionsPARPi monotherapy was similar to platinum-based chemotherapy for BRCA1/2-mutated ovarian cancer patients with secondary platinum-sensitive recurrence, and could improve prognosis.

Triplet maintenance therapy of olaparib, pembrolizumab and bevacizumab in women with BRCA wild-type, platinum-sensitive recurrent ovarian cancer: the multicenter, single-arm phase II study OPEB-01/APGOT-OV4

In this multicenter, open-label, single-arm, Phase II study with Simon two-stage optimum design (NCT04361370), we investigate the efficacy and safety of triplet maintenance (olaparib, pembrolizumab, bevacizumab) in patients with platinum-sensitive recurrent ovarian cancer who are wild-type for BRCA 1/2. A total of 44 patients were enrolled, and the median follow-up duration was 22.9 months (interquartile range: 17.4–24.7). The primary outcome was 6-months progression-free survival (PFS), which was 88.6% (95% confidence interval [CI] 75.4–96.2), meeting the pre-specified primary endpoint. The secondary outcomes reported here include median PFS, 12-months PFS, and overall survival and safety. The median PFS was 22.4 months (20.4–∞), with a 12-months PFS rate of 84.0% (95% CI 69.3–92.0). The median overall survival was 28.6 months (27.3–∞). The combination demonstrated tolerable toxicity with manageable side effects. Other secondary outcomes include time-to-progression, time to subsequent treatment, time to second treatment and PFS2; however, this data is not reported, as treatment is still ongoing in a majority of patients. Exploratory analysis shows that patients who were homologous recombination deficiency-positive or had a programmed death-ligand 1 combined positive score ≥1 showed a favorable response (P = 0.043 and P < 0.001, respectively). Thus, triplet maintenance shows durable efficacy with tolerable safety in patients with platinum-sensitive recurrence.

Analysis of olaparib efficacy in patients with serous ovarian cancer

Modern treatment of ovarian cancer is impossible without understanding the carcinogenesis and the structure of malignant epithelial ovarian tumors and carrying out molecular genetic testing for homologous recombination deficiency. The choice of maintenance therapy depends on the presence of a mutation in the BRCA1/2 genes and the HRD status of the tumor. Targeted drugs, such as bevacizumab and olaparib, are used in the treatment of ovarian cancer. The aim of the work is to determine the effectiveness of olaparib in first-line maintenance therapy and in the treatment of platinum-sensitive recurrence of ovarian cancer. A retrospective study included 67 patients with high-grade serous ovarian cancer stages I–IV who were prescribed olaparib in first-line maintenance therapy or in maintenance therapy for the treatment of disease progression, provided a complete or partial response to platinum-containing chemotherapy in the period from 2016 to 2022. The median life expectancy of the patients receiving first-line maintenance treatment coincides with the median time to progression; only one patient died due to the progression of the disease, and the rest are alive. The median time to progression in the group of patients with maintenance therapy of relapses was 23.0 ± 1.5 months, and the median life expectancy was 24.7 ± 2.3 months. When comparing the patients of the first group, depending on the term of surgical treatment performed, the median life expectancy was statistically higher with primary cytoreduction and constituted 46.0 months, while in the interval cytoreduction group, it was 25.0 months (p = 0.018). When comparing the patients of the second group, depending on the mutation in the BRCA1 and BRCA2 genes, the median life expectancy was statistically higher in the patients with a mutation in the BRCA2 gene — by 38.6 months (p = 0.020). The addition of olaparib to the treatment of BRCA-associated ovarian cancer in first-line maintenance therapy and in the treatment of platinum-sensitive relapses of the disease makes it possible to increase the median time to progression and median life expectancy.

Real-world Efficacy and Safety of Bevacizumab for Advanced or Recurrent Müllerian Cancer: A Single-institutional Experience.

The efficacy and safety of bevacizumab for ovarian cancer have been reported in randomized phase III clinical trials. It is important to gather experience and data in a real-world setting. The objective of the present study was to evaluate the efficacy and safety of bevacizumab for patients with ovarian cancer in a real-world setting. For front-line settings, patients with FIGO stage III-IV ovarian cancer treated using bevacizumab and chemotherapy after debulking surgery (Chemo + Bev group, n=79), in addition to those treated with only chemotherapy after debulking surgery (Chemo group; n=66), at our institute were reviewed retrospectively. For recurrent settings, patients with recurrent ovarian cancers treated with bevacizumab and any chemotherapy were reviewed retrospectively (n=65). In the front-line setting, the disease-free survival was significantly longer in the Chemo + Bev group compared with that in the Chemo group (p=0.021). Hypertension and proteinuria were found to be statistically more frequent in the Chemo + Bev group compared with that in the Chemo group (p=0.002 and p=0.004). In the recurrent setting, in platinum-sensitive patients, the response rate (RR) and the disease control ratio (DCR) were 78.4 and 94.1%, respectively. In platinum-resistant patients, the RR and the DCR were 28.6 and 57.1% respectively. The median progression-free survival was 18.3 and 7.1 months for platinum-sensitive recurrence and platinum-resistant recurrence, respectively. The major ≥ grade 3 adverse event was neutropenia. The present study provided encouraging real-world evidence of the efficacy and safety of bevacizumab for ovarian cancer in real-world.

Optimum selection criteria for secondary cytoreductive surgery in patients with recurrent epithelial ovarian cancer: A multicenter study from the Gynecologic Oncology Research Investigators coLLaborAtion group (GORILLA-3001).

To identify those most likely to benefit from secondary cytoreductive surgery (SCS), we evaluated the survival outcomes and factors predictive of prognosis in patients with recurrent ovarian cancer. We retrospectively reviewed the medical records of patients with recurrent ovarian cancer treated at five high-volume Korean hospitals between 2010 and 2021. Recurrence characteristics, treatment methods, and potential predictors of survival were compared between the chemotherapy and surgery groups. Among all 670 patients, 88.1% had initial stage III/IV disease, and 215 (32.1%) underwent SCS. Among patients who underwent SCS, only those who achieved complete resection exhibited improved survival. Even in patients with residual disease < 1 cm after SCS, we observed no significant survival benefit (p = 0.942). In the multivariate Cox analysis, residual disease at primary surgery, progression-free interval, recurrence sites (≤3 regions or limited carcinomatosis), ascites, and SCS were significant predictors of survival. Meanwhile, the only factor predictive of complete resection after SCS was recurrence sites (p < 0.001). The benefits of SCS appear to be exclusive to cases of complete resection. We propose limited regional platinum-sensitive recurrence (≤3 regions or limited carcinomatosis) without ascites as the optimum selection criteria for SCS.

52P Real-world data of niraparib in platinum sensitive relapsed ovarian cancer: A multicenter experience of the MITO group

PARP (poly ADP–ribose polymerase) inhibitors are approved as maintenance therapy in platinum sensitive ovarian cancer (OC), in first line and in the recurrent setting, regardless BRCA mutational status. Real-world data after the introduction of these agents are needed to evaluate whether the benefit observed in phase III trials can be translated into clinical practice. The aim of our study was to provide real-life data on efficacy and safety of niraparib administered as maintenance in platinum sensitive relapsed OC patients (PSROC). This retrospective/prospective multicenter study included relapsed OC patients treated in 17 MITO centers and receiving niraparib as maintenance, according to the label, at the time of first or subsequent platinum sensitive recurrence. Clinical data at the time of diagnosis and at the time of recurrence before Niraparib treatment were collected from the patients´ medical records at each institution, centralized into an electronic CRF at the coordinating center (Fondazione Policlinico Gemelli) and analyzed. The efficacy and safety analysis, as primary objectives, was performed. Median progression free survival (PFS) and overall survival (OS) were calculated as the time from start of niraparib treatment to subsequent radiologically confirmed relapse and death or last contact, respectively. The study included 304 patients with median age of 58 years (range 51-66). 260 (85%) enrolled patients were BRCA wild-type and 36 (11.9%) were BRCA mutated. At the time of diagnosis, most of patients (65.8%) underwent complete debulking surgery and were diagnosed with III-IV FIGO stage (78.8%). At the time of recurrence before niraparib maintenance 179 patients (58.9%) had received 2 previous lines of platinum-based chemotherapy and carboplatin in combination with PDL was the most frequent administered regimen (31.3%). Complete and partial radiological response to platinum-based CT was recorded in 44.4% and 27.0% of patients, respectively. Median PFS was 9.1 months (95% CI: 7.6-10.7) and median OS was 41.7 months (95% CI: 32.4-51.1). In a real-life setting, niraparib maintenance in patients with PSROC showed efficacy comparable with the published phase III data.

Real-world applications of PARPi maintenance therapy for recurrent ovarian cancer: A single-center study in China

ObjectiveTo assess the actual clinical application of poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi) maintenance therapy in Chinese patients with recurrent ovarian cancer, and to explore prognostic factors associated with progression-free survival (PFS). MethodsWe retrospectively assessed real-world clinical data from our hospital using the inclusion and exclusion criteria of representative randomized controlled trials, analyzed the prognosis, and performed univariate and multivariate analyses of prognostic factors. ResultsBetween 2019 and 2022, the proportion of platinum-sensitive recurrence ovarian cancer patients who received PARPi maintenance therapy increased to 29.6%, 53.3%, 43.8% and 62.2%, respectively, each year. A total of 48 patients were included in the prognostic analysis, of which 32 and 16 received olaparib and niraparib, respectively. Using the criteria of the Study19 and SOLO2 studies, the olaparib group in our patients had coincidence rates of 56.3% and 18.8%, respectively. Using the criteria of the NOVA and NORA studies, the niraparib group had coincidence rates of 31.3% and 37.5%, respectively. Median PFS was 26.1 months (95% CI 20.2–32.1). Response to primary therapy was an independent prognostic factor for PFS (relative risk, 3.248; 95% CI 1.081–9.757, P = 0.036). ConclusionsPARPi maintenance therapy was also effective in real world applications. Complete response (CR) to primary therapy was an independent factor favorably affecting PFS. Therefore, primary treatment choices aimed at optimal cytoreduction during primary surgery and improving the CR rate should still be considered, which positively affects the long-term prognosis of patients in the new treatment mode.

Novel inflammatory markers and prognostic importance of platinum-sensitive ovarian carcinoma relapse

Introduction/Objective. Ovarian carcinomas are the deadliest gynecological tumors. Despite advances in treatment options, survival rates are still not at the desired level. Since clinical signs are not typical in early-stage disease, two-thirds of patients are diagnosed late. Carbohydrate Antigen 125 (CA125) does not have sufficient sensitivity and specificity in early-stage disease and early post-relapse progression. There is a need for a simple and cost-effective marker that correlates with CA125. For this purpose, we aimed to evaluate the potential of systemic inflammatory markers? as diagnostic aids. Methods. Patients with platinum-sensitive recurrent ovarian carcinomas were preferred because the treatment options were more diverse than the resistant group. Using retrospective data collection, 105 patients with platinum-sensitive recurrent ovarian carcinoma, admitted in the last four years were included in the study. Complete blood count data was recorded based on recurrence and progression periods. Results. When the systemic immune inflammatory index (SII) values were evaluated in combination with CA125 in terms of progression during the control visits after platinum-sensitive disease recurrence treatment, progression detection proportions increased to 97.5%, which was 82.9% when only CA125 was used. On the other hand, false positivity, which was 18.5% for CA125 alone, decreased to 2.5% when combined with SII. Furthermore, neutrophil lymphocyte ratio, white blood cells, and neutrophil values showed correlations with high CA125 values. Conclusion. The SII value could be used together with CA125 because it is easy to use, accessible, and has low cost in clinical practice, as well as to increase the accuracy rate and make precise corrections in the false positivity rate.

Tumor-Bowel Fistula as a Rare Form of Recurrent Ovarian Cancer-Imaging and Treatment: Preliminary Report.

The aim of this pilot study was to evaluate the value of imaging techniques, including computed tomography (CT) and magnetic resonance imaging (MRI), in the diagnosis of a tumor-bowel fistula as a rare form of epithelial ovarian cancer (EOC) relapse. We also performed an initial assessment of the effectiveness of the treatment of this form of relapse. The study group consisted of eight patients with suspected platinum-sensitive recurrence in the form of a tumor/bowel fistula. All patients finished their first line of chemotherapy and subsequently showed complete remission for 6 months or more. To qualify patients for further treatment, CT and MRI were performed, which suggested the presence of a fistula between the recurrent tumor and intestine. DESKTOP study criteria were used to qualify patients for secondary cytoreduction. Second-line chemotherapy was given after secondary debulking. In all patients, fistulas formed between the tumor and large bowel. On CT, the fistulas were indirectly visible. In all cases, the fistula was visible on MR images, which showed hypointensity on the T2 and T1 post-contrast sequences but did not show restricted diffusion on the diffusion-weighted imaging (DWI) sequence. Patients who were qualified for the study underwent secondary debulking with bowel resection. In all eight cases, the fistula between the tumor and surrounding organs was confirmed. During surgery, seven intestinal anastomoses and one colostomy were performed. No residual macroscopic tumor remained in seven cases (resection R0-87.5%). The progression-free survival (PFS) was 8.4-22.6 months (median 13.4). In the group with cytoreduction R0, the median PFS was 15.5 months (12-22). In patients with suspected EOC recurrence with clinically suspected fistula, CT scan is not sufficient. In CT, the presence of a fistula is suspected based on indirect symptoms. MRI, as a method with much greater tissue resolution, confirms the diagnosis. In addition, MRI can identify the point of the tumor/bowel junction. This is especially true with a large infiltration covering several intestinal parts. Bowel resection with simultaneous anastomosis is a good and safe solution for these patients. However, appropriate qualification for the procedure is necessary, which will allow for surgery without residual macroscopic disease (R0 surgery). Due to the small number of cases, our results cannot be generalized. We treat them as a hypothesis that can be verified in a larger study.

Clinical characteristics and survival analysis of Chinese ovarian cancer patients with RAD51D germline mutations

ObjectivesWe aimed to describe the behavior among Chinese ovarian cancer patients with RAD51D germline mutations at our institution.MethodsNext-generation sequencing (NGS) was conducted for the entire coding regions and exon/intron boundaries of the RAD51D genes in 781 Chinese ovarian cancer patients treated at our institution from January 1, 2015 to August 1, 2021. Clinicopathological characteristics, treatment modalities, and outcomes were assessed for ovarian cancer patients with RAD51D germline mutations.ResultsRAD51D germline pathogenic mutations were detected in 1.7% (13/781) of patients in this cohort. RAD51D c. 270_271dup (p. Lys91fs) mutation was the most common mutation which was found in 7 patients (7/13, 53.1%). Patients median age at diagnosis was 58 years (range: 45–69 years). 46.2% (6/13) of them were diagnosed after 60 years. Only 1 patient (1/13, 7.7%) had a family history of ovarian or breast cancer. And 1 patient (1/13, 7.7%) had a personal history of breast cancer. The FIGO 2014 distribution by stage was: stage II in 1 patient (7.7%), stage III in 9 patients (69.2%) and stage IV in 3 patient (23.1%). 92.3% (12/13) patients had high-grade serous carcinoma. 2 patients (2/13, 15.4%) had a primary peritoneal cancer. The majority of patients in the entire cohort were reported to be platinum sensitive (92.3%, 12/13) with a platinum-free interval (PFI) of > 6 months.For patients who received PARPis for 2nd line maintenance treatment (n = 5), 2 patients discontinued PARPis treatment after 33.5 and 8.1 months of duration. Other 3 patients are still on therapy with a duration of 2.4, 13.8 and 30.1 months at the date of data cutoff. 1 patient received PARPi as salvage treatment with a duration of only 1.2 months.Nine patients (9/13, 69.2%) relapsed during follow up and all of them relapsed within 2 years after diagnosis, among which 88.9% (8/9) were classified as platinum-sensitive recurrence (PSR), and only 1 patient was classified as platinum-resistant recurrence (PRR). Median PFS for the entire cohort was 17.3 months. Median PFS for the PSR subgroup was 15.9 months. 2 patients died during follow-up. The OS of these 2 patients was 17.2 and 39.6 months. The 5-year OS rate was 67.5%.ConclusionsRAD51D germline mutations are more frequent in Chinese ovarian cancer patients than other population. Few patients have a family history of ovarian or breast cancer, and personal history of breast cancer. Most patients are diagnosed after 50 years. The sensitivity to PARP inhibitors of patients with RAD51D germline mutations need a further analysis.

573P Role of CA125 in patients included in the DESKTOP III/ENGOT-ov20 trial

Complete resection significantly improves survival in ovarian cancer patients with a platinum sensitive recurrence who fulfil the AGO score. We assessed the association of levels of CA125 at relapse with surgical and oncological outcome.

Optimum selection criteria for secondary cytoreductive surgery in patients with recurrent ovarian cancer: A multicenter study from the Gynecologic Oncology Research Investigators coLLaborAtion (GORILLA) group (GORILLA 3001) (546)

Objectives: Optimum selection criteria for secondary cytoreductive surgery (SCS) in recurrent ovarian cancer is often dependent on multiple confounding factors. This study aimed to evaluate the treatment outcomes of recurrent ovarian cancer and investigate the factors identifying patients who most likely benefit from the SCS. Methods: We retrospectively reviewed medical records of recurrent ovarian cancer patients from five referral hospitals in Korea from 2010 to 2020. Recurrent characteristics, following treatment methods and potential factors for survivals were evaluated between the chemotherapy and surgery groups. Results: A total of 670 patients with recurrent ovarian cancer were identified. The patient’s median age was 55 years (24-83), and 88.1% of patients had initial stage III/IV disease. Of all patients, 215 (32.1%) received SCS for the disease recurrence. The median survival was 85 months (95% CI: 65.0-105.0) in the chemotherapy group, whereas the median survival time was not reached in the SCS group. Patients who received the SCS were more likely to be young and had no residual disease at primary surgery, platinum-sensitive recurrence, limited regional recurrence (LRR, ≤3 lesions or regional carcinomatosis) with a low rate of ascites (p<0.001, 0.001, 0.001, 0.001, 0.006, respectively). In multivariate cox analysis, residual disease at primary surgery, PFI, recurrent sites, ascites, and SCS were significant prognostic factors for survival. Meanwhile, predicting factor for complete resection after SCS was only recurrent sites (LRR, p<0.001). Conclusions: SCS resulted in significantly favorable survival outcomes in well-selected patients. Platinum-sensitive recurrence with limited regional diseases (< 3 regions or limited carcinomatosis without ascites) can be considered as optimum criteria for SCS in recurrent ovarian cancer. Objectives: Optimum selection criteria for secondary cytoreductive surgery (SCS) in recurrent ovarian cancer is often dependent on multiple confounding factors. This study aimed to evaluate the treatment outcomes of recurrent ovarian cancer and investigate the factors identifying patients who most likely benefit from the SCS. Methods: We retrospectively reviewed medical records of recurrent ovarian cancer patients from five referral hospitals in Korea from 2010 to 2020. Recurrent characteristics, following treatment methods and potential factors for survivals were evaluated between the chemotherapy and surgery groups. Results: A total of 670 patients with recurrent ovarian cancer were identified. The patient’s median age was 55 years (24-83), and 88.1% of patients had initial stage III/IV disease. Of all patients, 215 (32.1%) received SCS for the disease recurrence. The median survival was 85 months (95% CI: 65.0-105.0) in the chemotherapy group, whereas the median survival time was not reached in the SCS group. Patients who received the SCS were more likely to be young and had no residual disease at primary surgery, platinum-sensitive recurrence, limited regional recurrence (LRR, ≤3 lesions or regional carcinomatosis) with a low rate of ascites (p<0.001, 0.001, 0.001, 0.001, 0.006, respectively). In multivariate cox analysis, residual disease at primary surgery, PFI, recurrent sites, ascites, and SCS were significant prognostic factors for survival. Meanwhile, predicting factor for complete resection after SCS was only recurrent sites (LRR, p<0.001). Conclusions: SCS resulted in significantly favorable survival outcomes in well-selected patients. Platinum-sensitive recurrence with limited regional diseases (< 3 regions or limited carcinomatosis without ascites) can be considered as optimum criteria for SCS in recurrent ovarian cancer.