Interval Debulking Surgery Research Articles

Individualization in the first-line treatment of advanced ovarian cancer based on the mechanism of action of molecularly targeted drugs.

With the development of poly(ADP-ribose) polymerase inhibitors, the treatment of advanced ovarian cancer is changing dramatically. The purpose of this narrative review is to provide a direction for the individualization of advanced ovarian cancer treatment based on the mechanism of action of molecularly targeted drugs currently used in Japan. The PAOLA-1 study showed very good progression-free survival in patients with homologous recombination deficiency tumors who underwent complete surgery with primary debulking surgery and who received olaparib plus bevacizumab. Niraparib has high intratumor penetration, and in a subgroup analysis of the PRIMA study, it was most effective in patients with residual tumors after interval debulking surgery. These data suggest the importance of achieving complete surgery and aiming for cure in the treatment of ovarian cancer and how the use of bevacizumab, olaparib, and niraparib should be individualized.

Complications after advanced ovarian cancer surgery-Apopulation-based cohort study.

Surgical complications after primary or interval debulking surgery in advanced ovarian cancer were investigated and associations with patient characteristics and surgical outcomes were explored. A population-based cohort study including all women with ovarian cancer, FIGO III-IV, treated with primary or interval debulking surgery, 2013-2017. Patient characteristics, surgical outcomes and complications according to the Clavien-Dindo (CD) classification system ≤30 days postoperatively, were registered. Uni- and multivariable regression analyses were performed with severe complications (CD ≥ III) as endpoint. PFS in relation was analyzed using the Kaplan-Meier method. The cohort included 384 women, where 304 (79%) were treated with primary and 80 (21%) with interval debulking surgery. Complications CD I-V were registered in 112 (29%) patients and CD ≥ III in 42 (11%). Preoperative albumin was significantly lower in the CD ≥ III cohort compared with CD0-II (P=0.018). For every increase per unit in albumin, the risk of complications decreased by a factor of 0.93. There was no significant difference in completed chemotherapy between the cohorts CD0-II 90.1% and CD ≥ III 83.3% (P=0.236). In the univariable analysis; albumin <30 g/L, primary debulking surgery, complete cytoreduction and intermediate/high surgical complexity score (SCS) were associated with CD ≥ III. In the following multivariable analysis, only intermediate/high SCS was found to be an independent significant prognostic factor. Low (n=180) vs intermediate/high SCS (n=204) showed a median PFS of 17.2 months (95% confidence interval [CI] 15.2-20.7) vs 21.5 months (95% CI 18.2-25.7), respectively, with a significant log-rank; P=0.038. Advanced ovarian cancer surgery is associated with complications but no significant difference was seen in completion of adjuvant chemotherapy when severe complications occur. Importantly, our study shows that intermediate/high SCS is an independent prognostic risk factor for complications. Low albumin, residual disease and primary debulking surgery were found to be associated with severe complications. These results may facilitate forming algorithms in the decision-making procedure of surgical treatment protocols.

The impact of secondary cytoreductive surgery in platinum sensitive recurrent ovarian cancer treated with upfront neoadjuvant chemotherapy and interval debulking surgery

ObjectiveThe aims of the present study were to assess the oncological outcomes of platinum-sensitive recurrent ovarian cancer patients undergoing secondary cytoreduction (SCS) after treatment with neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) at diagnosis and to compare the performance of different selection models in these patients. MethodsRetrospective, observational, single-center cohort study including patients with platinum-sensitive recurrent epithelial ovarian cancer with abdominal/inguinal/cardiophrenic disease between November 2012 and November 2020. Patients were selected as surgical candidates with PET/CT-scan and with diagnostic laparoscopy. Results272 patients were included in the study. Of these, 165 (60.7%) patients were treated with PDS at diagnosis and 107 (39.3%) with IDS. SCS was performed in 178 (65.4%) cases, with complete gross resection achieved in 155/178 (87.1%). No progression-free survival (PFS) difference was demonstrated when patients treated with PDS were compared with those treated with NACT+IDS at first diagnosis (median 21 versus 21 months; p = 0.684); no post-recurrence survival (PRS) difference was evident between the two groups (median 81 versus 77 months, respectively; p = 0.574). Current selection models to candidate patients to SCS adequately performed in patients treated with IDS at diagnosis, as well as in the PDS group, with combination of PET/CT-scan and laparoscopy being an accurate tool in prediction of no gross residual disease at SCS in this pre-selected population. ConclusionsPatients with platinum-sensitive recurrent epithelial ovarian cancer treated with NACT/IDS as primary treatment have similar post-recurrence survival outcomes of those treated with PDS. Current models to select patients for SCS can be safely applied to IDS patients.

Differences in Patterns of Recurrence Between Primary and Interval Debulking Surgery for Advanced Ovarian Cancer.

This study aimed to identify differences in the pattern and timing of recurrence in patients with advanced ovarian cancer undergoing primary (PDS) or interval debulking surgery after neoadjuvant chemotherapy (NACT). Data were prospectively collected on 105 patients from June 2016 to March 2020. There were 30 (50%) recurrences in the PDS group compared to 32 (72.7%) in the NACT group (p=0.020). An intra-abdominal relapse was more common in NACT compared to PDS patients (64.4% vs. 38.3%, p=0.008) and a recurrence in two or more sites (NACT: 44.4% vs. PDS: 23.3%, p=0.010). Among completely cytoreduced patients, a pelvic recurrence was more frequent in NACT patients (NACT: 50% vs. 22.4% in PDS, p=0.011). Progression-free survival (PFS) was longer in PDS compared to NACT (27 vs. 16 months, p=0.039). NACT patients experienced an unfavorable distribution and timing of recurrent disease compared to patient who underwent PDS.

Characteristics of Pelvic Cytology in Patients with Gynecologic Malignancies: Comparison of Pre and Post-Neoadjuvant Specimens

Introduction: The presence of tumor cells in pelvic cytology (PC) specimens can portend a worse outcome for patients undergoing gynecologic surgery. Primary debulking surgery (PDS) was a mainstay for most of these tumors; however, recent advances have triaged selected patients to neoadjuvant chemotherapy (NACT) with interval debulking surgery (IDS). Reduction in tumor cellularity and histologic alterations has been noted in these cases; however, similar cytologic characterization has not been performed. Materials and Methods: PC was searched to find those in NACT patients. Additional PDS were included as controls. Cases were scored for cellularity of malignant cells and background components were described, and when available, pretreatment and posttreatment specimens from the same patients were compared. Results: In all, 19 specimens from 16 patients were found, 6 (32%) of which were paired PTS and IDS from the same patient. Only 6/19 (32%) were from IDS, the remainder PTS. A majority (15/19; 79%) of specimens were malignant; all negative cases were PTS. Few (4/16; 24%) were endometrial primaries; the remainder were pelvic high-grade serous carcinoma. No difference in tumor cell morphology or inflammatory component was noted between the 2 groups, though in 3/3 paired specimens from PDS and IDS, the cellularity of malignant cells decreased in the IDS specimens. Discussion/Conclusion: No identifiable trend was noted regarding cellularity of specimens in the pre compared to the post-neoadjuvant setting. A trend toward reduced cellularity was noted in individual patients, but no alteration in background cells or tumor morphology was noted.

Effectiveness and Safety of Niraparib as Neoadjuvant Therapy in Advanced Ovarian Cancer With Homologous Recombination Deficiency (NANT): Study Protocol for a Prospective, Multicenter, Exploratory, Phase 2, Single-Arm Study.

BackgroundOvarian cancer (OC) is a heterogeneous gynecological malignancy with a poor prognosis as the majority of patients are diagnosed at an advanced stage. Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is recommended for patients who cannot achieve optimal cytoreduction or cannot endure primary debulking surgery (PDS). As there is an increased risk of chemoresistance for platinum-based NACT, it is important to investigate an alternative option. A Poly (ADP-ribose) polymerase inhibitor (PARPi), niraparib, has shown high anti-tumor activity, especially in homologous recombination deficiency (HRD) positive patients with OC. Thus, niraparib as a neoadjuvant treatment agent may help improve surgery accessibility and create survival benefits.MethodsThis multicenter, prospective, single-arm, open-label, phase II study plans to recruit 53 patients (aged 18-75 years) with newly diagnosed HRD positive, unresectable (Fagotti score ≥ 8 or upper abdominal computed tomography [CT] score ≥ 3) International Federation of Gynecology and Obstetrics (FIGO) stage III-IV OC. The HRD status was detected by next-generation sequencing and HRD positive patients will be counseled for study participation. Enrolled patients will receive niraparib capsules QD (200mg or 300mg per day) for two cycles (4 weeks/cycle). After neoadjuvant niraparib treatment, patients exhibiting complete response (CR), partial response (PR), or stable disease (SD) will undergo tumor reduction surgery and subsequent standard carboplatin/paclitaxel-based chemotherapy. The primary objectives include the objective response rate (ORR) and R0 resection rate. The rate of treatment interruption/termination and progression-free survival (PFS) will be secondary objectives. The study uses Simon’s optimal two-stage design (24 and 21 patients for the first and second stage respectively). The data manager will record all adverse events (AEs).DiscussionThis is the first prospective study to evaluate the effectiveness and safety of niraparib in neoadjuvant treatment for advanced OC. The result of this study will provide a solid base for further expanding the clinical applications of the PAPRi and exploring more therapeutic possibilities for patients with HRD positive advanced OC. Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT04507841.

Significance of platinum distribution to predict platinum resistance in ovarian cancer after platinum treatment in neoadjuvant chemotherapy

Most patients with ovarian cancer experience recurrence and develop resistance to platinum-based agents. The diagnosis of platinum resistance based on the platinum-free interval is not always accurate and timely in clinical settings. Herein, we used laser ablation inductively coupled plasma mass spectrometry to visualize the platinum distribution in the ovarian cancer tissues at the time of interval debulking surgery after neoadjuvant chemotherapy in 27patients with advanced high-grade serous ovarian cancer. Two distinct patterns of platinum distribution were observed. Type A (n = 16): platinum accumulation at the adjacent stroma but little in the tumor; type B (n = 11): even distribution of platinum throughout the tumor and adjacent stroma. The type A patients treated post-surgery with platinum-based adjuvant chemotherapy showed significantly shorter periods of recurrence after the last platinum-based chemotherapy session (p = 0.020) and were diagnosed with “platinum-resistant recurrence”. Moreover, type A was significantly correlated with worse prognosis (p = 0.031). Post-surgery treatment with non-platinum-based chemotherapy could be effective for the patients classified as type A. Our findings indicate that the platinum resistance can be predicted prior to recurrence, based on the platinum distribution; this could contribute to the selection of more appropriate adjuvant chemotherapy, which may lead to improves prognoses.

BRCA status and platinum sensitivity in advanced ovarian cancer according to Chemotherapy Response Score

ObjectiveTo evaluate a relation between BRCA1/2 status and the Chemotherapy Response Score in patients with epithelial ovarian cancer undergoing neoadjuvant chemotherapy and interval debulking surgery.MethodsData were retrospectively collected on patients...

103. The prognostic significance of chemotherapy response score and lymphocytic infiltration in patients with ovarian cancer treated with neoadjuvant chemotherapy

Introduction and aims of the study: Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) for the management of advanced epithelial ovarian cancer (EOC) represents an alternative approach to primary debulking with comparable survival outcomes. Histopathologic examination of the IDS specimens and the evaluation of Chemotherapy Response Score (CRS) have been proposed as significant markers of response to NACT. The objective of our study was to evaluate the prognostic significance of CRS in OC patients treated with NACT. Methods: Medical records of patients with OC stage ≥ III who were selected to receive NACT in our institution from 2011 to 2018 were retrospectively evaluated. CRS was assessed on both omental and ovarian samples according to International Collaboration on Cancer Reporting (ICCR) recommendation. Lymphocytic infiltration, presence of necrosis and mitotic index were also assessed. Results: A total of 60 patients with median age of 65 years at diagnosis were included. A total of 20 and 10 patients received score 3 in CRS at omentum and ovarian samples, respectively. Patients with CRS3 at omentum had significantly prolonged median Progression Free Survival (PFS) compared to CRS1 and CRS2 (19 vs 10 vs 15 months, respectively, p = 0.002), while no difference was observed in the respective OS among the groups (42 vs 28 vs 32.3 months, respectively). Lymphocytic infiltration in pre-treatment biopsies was related to improved PFS and OS (log-rank p = 0.01 and p = 0.015, respectively). No effect on either PFS or OS was observed in patients who received bevacizumab post-IDS, while in patients with lymphocytic infiltration bevacizumab negatively affected PFS. Conclusions: Our study highlights the role of CRS in the prediction of the postoperative course of EOC patients who undergo NACT and IDS. Further studies are needed to decipher the exact role of CRS and lymphocytic infiltration so as to personalize the treatment of EOC patients.

Residual tumor and primary debulking surgery vs interval debulking surgery in stage IV epithelial ovarian cancer.

It is debated whether women with FIGO (International Federation of Gynecology and Obstetrics) Stage IV epithelial ovarian cancer should be offered primary debulking surgery (PDS) or interval debulking surgery (IDS). Furthermore, the impact of complete resection of intra-abdominal disease (R0) despite their extra-abdominal metastases is questioned. The objective of this study was to investigate the impact of intra-abdominal residual tumor, Stage IVA vs IVB, the localization and number of metastases defining Stage IV disease on overall survival (OS) comparing PDS and IDS in FIGO Stage IV epithelial ovarian cancer. We included 2091 women registered with Stage IIIC-IV ovarian cancer in the Danish Gynecological Cancer Database during 2009-2016. The impact of residual tumor was evaluated using univariate and multivariate analyses. In total, 681 patients had stage IV disease, of whom 26% underwent PDS, 38% IDS, and 36% chemotherapy only. Overall survival for PDS and IDS were similar. Patients achieving R0 at PDS showed a tendency towards a higher OS than patients achieving R0 at IDS, though the difference was non-significant. In women with Stage IVA and IVB disease there was a survival benefit in achieving R0 both when treated with PDS and IDS. Women with Stage IVB disease treated with chemotherapy only had a significantly lower OS than patients achieving R0 at both PDS and IDS. Malignant pleural effusion and having five metastatic sites compared with having one was associated with a poorer OS. Our study shows similar OS in patients with Stage IV disease treated with IDS compared with PDS. Complete intra-abdominal tumor resection improves the prognosis in both PDS and IDS in Stage IV ovarian cancer. Malignant pleural effusion seems to be a negative prognostic factor and should have more focus in future studies.

Complete Laparoscopic Interval Debulking Surgery for Advanced Ovarian Cancer Achieves Similar Survival Outcomes to Open Approach: A Propensity-Matched Study

Background: To assess the laparoscopic interval debulking surgery (IDS) outcomes compared to laparotomy, by analyzing the overall survival (OS) and the progression free survival (PFS), as well as the intra- and post-operative morbidity. Methods: In this retrospective propensity-score-matched cohort study, all patients with stage III or IV FIGO (International Federation of Gynecology and Obstetrics) serous ovarian cancer, undergoing complete IDS after neoadjuvant chemotherapy, from January 1st of 2009 to June 1st 2019, were included. Results: Thirty-seven patients were included in the laparoscopy group and 40 in the laparotomy group. There was no significant difference in terms of median OS between laparoscopy and laparotomy (23.1 months [95% CI 15.7–29.7] versus 26.3 months [95% CI 21.7–31.7], respectively, p = 0.17) and median PFS (14.8 months [95% CI 10.6–21.5] versus 12 months [95% CI 11–15.1], p = 0.057). After applying the propensity score, 25 patients were included in each group. Laparoscopy was associated with significantly less early postoperative complications (6 versus 17, p = 0.01) and shorter hospital stay (7.6 days versus 12.1, p < 0.001) and a significantly better OS (HR 0.45 [95% CI 0.19–0.95], p = 0.04), but with no significant difference in terms of PFS (HR 0.71 [95% CI 0.27–1.88], p = 0.49). Conclusion: In carefully-selected patients with advanced ovarian cancer, complete laparoscopic interval debulking surgery achieves similar survival outcomes to open laparotomy. Therefore, laparoscopy appears as a safe alternative to laparotomy for IDS after NACT in selected patients with advanced ovarian cancer and a low burden of disease.

Genomic landscape and immune-related gene expression profiling of epithelial ovarian cancer after neoadjuvant chemotherapy

Platinum-based neoadjuvant chemotherapy followed by interval debulking surgery is an accepted treatment for patients with stage III or IV epithelial ovarian cancer who are not suitable for primary debulking surgery. The identification of suitable adjuvant treatments in these patients is an unmet need. Here, we explore potential genomic characteristics (mutational and immune-associated expression profiles) in a series of patients undergoing neoadjuvant chemotherapy. Tumor samples from biopsy and interval debulking surgery were analyzed for mutational landscape and immune profiling, together with detailed immunohistochemistry using different immune cell markers, and correlated with clinicopathological characteristics and potential response to neoadjuvant chemotherapy. No major differences in the mutational landscape were observed in paired biopsy and surgery samples. Genomic loss of heterozygosity was found to be higher in patients with total/near-total tumor response. The immune gene expression profile after neoadjuvant chemotherapy revealed activation of several immune regulation-related pathways in patients with no/minimal or partial response. In parallel, neoadjuvant therapy caused a significant increase of tumor-infiltrating lymphocyte population abundance, primarily due to an augmentation of the CD8+ T cell population. Remarkably, these changes occurred irrespective of potential homologous recombination defects, such as those associated with BRCA1/2 mutations. Our study strengthens the use of loss of heterozygosity as a biomarker of homologous repair deficiency. The changes of immune states during neoadjuvant chemotherapy reveal the dynamic nature of tumor-host immune interactions and suggest the potential use of immune checkpoint inhibitors or their combination with poly-ADP polymerase inhibitors in high stage and grade epithelial ovarian cancer patients undergoing neoadjuvant therapy.

The Frailty Based on the Memorial Sloan Kettering Frailty Index for Prediction of Surgical Outcome in Advance Epithelial Ovarian Cancer-Experience of a Single Center in Mexico.

Retrospective impact evaluation of frailty as measured by the Memorial Sloan Kettering Frailty Index (MSK-FI) on outcomes in older women surgically treated for advanced epithelial ovarian cancer (EOC). Women ≥ 60years with stage IIIC/IV EOC who underwent primary debulking surgery (PDS) or interval debulking surgery (IDS) were included. Medical records were reviewed for patients' characteristics and outcomes. We retrospectively applied the MSK-FI which included 10 comorbidities and functional assessment that were extracted from medical records. The MSK-FI ranges from 0 to 11; a score of ≥ 3 was considered frail. Associations were assessed using logistic regression and Cox proportional hazards regression. We identified 79 patients treated with PDS (n = 36, 45.5%) or IDS (n = 43, 54.4%) with complete data. The prevalence of frailty based on MSK-FI was 25%. Almost half of the frail patients (47.3%) were admitted to the ICU compared to 16% of non-frail patients (p = 0.006). In univariable analysis, the MSK-FI was associated with postoperative complications [OR 1.57 (95% CI 1.04-2.37), p = 0.03] and ICU admission [OR 2.05 (95% CI 1.30-3.23), p = 0.002], but not with readmission rate [OR 1.29 (95% CI 0.65-2.59), p = 0.5], postoperative mortality [OR 1.02 (95% CI 0.51-2.00), p = 0.9], and hospital stay [β 0.60 (95% CI - 1.19-2.41)]. In multivariable analysis, the frailty index was independently associated with postoperative complications [OR 1.54 (95% CI 1.02-2.34), p = 0.04] and ICU admissions [OR 1.97 (95% CI 1.23-3.16), p = 0.004]. Frailty, based on the Memorial Sloan Kettering Frailty Index, is associated with adverse postoperative outcomes in older women with advanced ovarian cancer, suggesting that MSK-FI can improve the predictive ability of current surgical assessment tools.

Nomogram to predict feasibility of minimally invasive interval debulking surgery in advanced ovarian cancer

ObjectiveCurrently, there is no clear guidance defining the ideal candidate for minimally invasive interval debulking surgery. This study aimed to identify predictive factors for a minimally invasive approach in patients...

Effects of Neoadjuvant Chemotherapy in Ovarian Cancer Patients With Different Germline BRCA1/2 Mutational Status: A Retrospective Cohort Study.

BackgroundWhether neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) against primary debulking surgery (PDS) has a differential effect on prognosis due to Breast Cancer Susceptibility Genes (BRCA)1/2 mutations has not been confirmed by current studies.MethodsAll patients included in this retrospective study were admitted to Qilu Hospital of Shandong University between January 2009 and June 2020, and germline BRCA1/2 mutation were tested. Patients in stage IIIB, IIIC, and IV, re-staged by International Federation of Gynecology and Obstetrics (FIGO) 2014, were selected for analysis. All patients with NAC received 1-5 cycles of platinum-containing (carboplatin, cisplatin, or nedaplatin) chemotherapy. Patients who received maintenance therapy after chemotherapy were not eligible for this study. All relevant medical records were collected.ResultsA total of 322 patients were enrolled, including 112 patients with BRCA1/2 mutations (BRCAmut), and 210 patients with BRCA1/2 wild-type (BRCAwt). In the two groups, 40 BRCAmut patients (35.7%) and 69 BRCAwt patients (32.9%) received NAC. The progression-free survival (PFS) of BRCAmut patients was significantly reduced after NAC (median: 14.9 vs. 18.5 months; p=0.023); however, there was no difference in overall survival (OS) (median: 75.1 vs. 72.8 months; p=0.798). Whether BRCAwt patients received NAC had no significant effect on PFS (median: 13.5 vs. 16.0 months; p=0.780) or OS (median: 54.0 vs. 56.4 months; p=0.323). Multivariate analyses in BRCAmut patients showed that the predictors of prolonged PFS were PDS (p=0.001), the absence of residual lesions (p=0.012), and FIGO III stage (p=0.020); Besides, PARP inhibitor was the independent predictor for prolonged OS in BRCAmut patients (p=0.000), for BRCAwt patients, the absence of residual lesions (p=0.041) and history of PARP inhibitors (p=0.000) were beneficial factors for OS prolongation.ConclusionsFor ovarian cancer patients with FIGO IIIB, IIIC, and IV, NAC-IDS did not adversely affect survival outcomes due to different BRCA1/2 germline mutational status.

Effect of neoadjuvant chemotherapy combined with intraperitoneal chemotherapy after interval tumor cell reduction on the prognosis of advanced epithelial ovarian cancer

Objectives: To investigate the effect of neoadjuvant chemotherapy combined with intraperitoneal chemotherapy after interval tumor cell reduction on the prognosis of advanced epithelial ovarian cancer. Methods: A retrospective study was performed among 210 patients with advanced ovarian cancer who were treated with neoadjuvant chemotherapy from May 1, 2007 to December 1, 2015. 121 patients with NACT-IDS (Neoadjuvant chemotherapy followed by interval debulking surgery) were enrolled. The patients were divided into observation group (NACT-IDS + IP group, n = 28) and control group (NACT-IDS + IV group, n = 93) depending on whether intraperitoneal chemotherapy was used after interval debulking surgery. The effects of intraperitoneal chemotherapy after NACT-IDS on PFS (progression-free survival) and OS (overall survival) were analyzed and the influencing factors were explored through multivariate analysis. The competitive model was used to analyze the effect of intraperitoneal chemotherapy after NACT-IDS on tumor recurrence. Toxicities associated with adjuvant chemotherapy were also analyzed between two groups. The effect of neoadjuvant chemotherapy cycles on prognosis and the correlation between postoperative CA125 decline and recurrence were evaluated. Results: Intraperitonal chemotherapy and R0 (no gross residual) were independent factors for PFS, with HRs of 0.560 (95% CI, 0.342–0.918, p = 0.022) and 0.578 (95% CI, 0.377–0.887, p = 0.012). There was no independent factor associated with OS. Significant difference in PFS was detected among the R0 + IP group, R0 + IV group, non-R0 + IP group and non-R0 + IV group. In patients with R0 tumor reduction, IP patients showed significantly better PFS, bonferronei adjusted p = 0.036. In patients without R0 tumor reduction, no significant difference was detected between IP and IV group, bonferronei adjusted p = 0.28. There were no significant differences of grade 3–4 toxicities, abdominal pain, treatment delays, dose reductions, and treatment modifications in NACT-IDS + IP group and NACT-IDS + IV group. Neoadjuvant chemotherapy cycles (≤3 and &gt;3) were not the influencing factors of PFS or OS and did not affect platinum-sensitive relapse or platinum-resistant relapse. The decrease in postoperative CA125 was not related to platinum-sensitive recurrence or platinum-resistant recurrence. Conclusions: Neoadjuvant chemotherapy combined with intraperitoneal chemotherapy after interval debulking surgery could improve the PFS of patients with advanced epithelial ovarian cancer compared to intravenous chemotherapy without significant differences in toxicity.

Prognostic Role of CRS in High Grade Serous Ovarian Tumour Patients Receiving Neoadjuvant Chemotherapy in a Tertiary Care Hospital of Central India

Introduction: Ovarian tumours are rarely diagnosed early, patients presents only when the abdominal mass is appreciable in size. The current mode of treatment involves neoadjuvant chemotherapy with interval debulking surgery, followed by completion of the chemotherapy. The pathological examination of the interval debulking specimen allows an evaluation of the extent of the response to the chemotherapy and sensitivity of the tumour to the same. The Chemotherapy Response Score (CRS) developed by Bohm S et al., is being used to predict the prognosis of these patients. The advent of molecular genetics has allowed us to categorise tumours as per the mutations they possess, the prominent in High Grade Serous Carcinoma (HGSC) being TP53, BRCA1/2 and Homologous Recombination Deficiency (HRD). This knowledge is used to cater to the specific therapeutic needs of the patients. Aim: To apply the CRS to cases of high grade serous carcinomas of the ovary, presenting to the centre and association of the score with their survival. Materials and Methods: A total of 30 patients of high grade serous carcinoma of ovary who received neoadjuvant chemotherapy and had interval debulking surgery were included in the study. The histopathological examination of the resected specimen was done with special emphasis on the omental deposits and the degree of necrosis, fibrosis, inflammation, macrophages and residual tumour. Chi square statistics with p-value association of was done, to establish significance. Results: The histological parameters of necrosis, chronic inflammation and residual tumour in the omental deposits were found to be the most significant in association of to the CRS scores. Also, the CRS grading was associated with the survival of the patients. Conclusion: The CRS was found to associate well with the survival of the patients. This study recommends that CRS score be done in all post NACT high grade serous ovarian tumours, which will guide further treatment.

Prognostic value of complete metabolic response on ¹⁸F-FDG-PET/CT after three cycles of neoadjuvant chemotherapy in advanced high-grade serous ovarian cancer.

ObjectiveWe investigated the prognostic value of complete metabolic response (CMR) on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) after 3 cycles of neoadjuvant chemotherapy (NAC) in advanced high-grade serous ovarian cancer (HGSC).MethodsPET/CT at baseline and after 3 cycles of NAC were performed; peak standardized uptakes were measured. PET parameters were compared with NAC parameter: cancer antigen-125 (CA-125) normalization before interval debulking surgery (IDS) and chemotherapy response score (CRS) to predict platinum-sensitivity. Kaplan-Meier analysis was used to determine correlations between PET parameters and survival. Prognostic factors were obtained by multivariate Cox regression analysis.ResultsBetween 2007 and 2020, 102 patients were recruited: 19 (18.6%) were designated as CMR group and 83 (81.4%) as non-CMR group. CMR after 3 cycles of NAC showed the highest accuracy in predicting platinum-sensitivity (area under the curve [AUC]=0.729; 95% confidence interval [CI]=0.552–0.823; p=0.017), compared with CA-125 normalization before IDS (AUC=0.626; 95% CI=0.542–0.758; p=0.010) and CRS (AUC=0.613; 95% CI=0.490–0.735; p=0.080). CMR demonstrated better prognosis than non-CMR in progression-free survival (PFS) (median PFS, 23.9 months vs. 16.4 months; p=0.021) and overall survival (OS) (median OS, not reached vs. 69.7 months; p=0.025). In multivariate analysis, CMR was associated with a lower risk of recurrence (adjusted hazard ratio [aHR]=0.50; 95% CI=0.27–0.92; p=0.027) and death (aHR=0.23; 95% CI=0.05–0.99; p=0.048).ConclusionCMR after 3 cycles of NAC can be a prognostic factor for both recurrence and death in advanced HGSC.

Association between High Diffusion-Weighted Imaging-Derived Functional Tumor Burden of Peritoneal Carcinomatosis and Overall Survival in Patients with Advanced Ovarian Carcinoma.

ObjectiveTo investigate the association between functional tumor burden of peritoneal carcinomatosis (PC) derived from diffusion-weighted imaging (DWI) and overall survival in patients with advanced ovarian carcinoma (OC).Materials and MethodsThis prospective study was approved by the local research ethics committee, and informed consent was obtained. Fifty patients (mean age ± standard deviation, 57 ± 12 years) with stage III–IV OC scheduled for primary or interval debulking surgery (IDS) were recruited between June 2016 and December 2021. DWI (b values: 0, 400, and 800 s/mm2) was acquired with a 16-channel phased-array torso coil. The functional PC burden on DWI was derived based on K-means clustering to discard fat, air, and normal tissue. A score similar to the surgical peritoneal cancer index was assigned to each abdominopelvic region, with additional scores assigned to the involvement of critical sites, denoted as the functional peritoneal cancer index (fPCI). The apparent diffusion coefficient (ADC) of the largest lesion was calculated. Patients were dichotomized by immediate surgical outcome into high- and low-risk groups (with and without residual disease, respectively) with subsequent survival analysis using the Kaplan-Meier curve and log-rank test. Multivariable Cox proportional hazards regression was used to evaluate the association between DWI-derived results and overall survival.ResultsFifteen (30.0%) patients underwent primary debulking surgery, and 35 (70.0%) patients received neoadjuvant chemotherapy followed by IDS. Complete tumor debulking was achieved in 32 patients. Patients with residual disease after debulking surgery had reduced overall survival (p = 0.043). The fPCI/ADC was negatively associated with overall survival when accounted for clinicopathological information with a hazard ratio of 1.254 for high fPCI/ADC (95% confidence interval, 1.007–1.560; p = 0.043).ConclusionA high DWI-derived functional tumor burden was associated with decreased overall survival in patients with advanced OC.

Characteristics of long-term survival in advanced stage ovarian cancer: a nationwide cohort in the Netherlands

Objective: Despite optimal treatment with debulking surgery and chemotherapy, the majority of patients with advanced stage epithelial ovarian cancer (EOC) die within five years. Survival beyond eight years is rare and the mechanisms that lead to such favorable outcomes are incompletely understood. We aimed to identify characteristics associated with long-term survival (LTS) in a population-based cohort of patients with advanced stage EOC. Methods: Patients with advanced stage (FIGO IIB-IV) EOC diagnosed between 2008 and 2012 were identified from the Netherlands Cancer Registry. LTS was defined as survival for more than eight years after diagnosis, based on 20% survival within this cohort. Patient, tumor, and treatment characteristics were analyzed using multivariable logistic regression to find predictors for LTS. Results: We identified 2744 eligible patients of whom 571 were long-term survivors (survival longer than eight years). Younger age, lower tumor stage, low-grade histology, FIGO IV based on extra-abdominal lymph node compared to pleural metastasis, primary debulking surgery vs neo-adjuvant chemotherapy followed by interval debulking surgery, residual disease less than one cm or no macroscopic disease, and ascites less than 100 mL were associated with LTS. Furthermore, less than six chemotherapy cycles compared to six, and carboplatin plus paclitaxel combined with other chemotherapy agents compared to carboplatin plus paclitaxel, were associated with a lower odds of LTS. Conclusion: Characteristics of the tumor, patient and treatment play a substantial role in respect to the prognosis of advanced stage EOC, and can assist in the prediction of LTS.