Upfront debulking surgery versus interval debulking surgery for advanced tubo‐ovarian high‐grade serous carcinoma and diffuse peritoneal metastases treated with peritonectomy procedures plus HIPEC

2019 ◽  
Vol 120 (7) ◽  
pp. 1208-1219 ◽  
Author(s):  
Daniele Biacchi ◽  
Fabio Accarpio ◽  
Luca Ansaloni ◽  
Antonio Macrì ◽  
Antonio Ciardi ◽  
...  
Keyword(s):  
Peritoneal Metastases ◽  
Serous Carcinoma ◽  
High Grade ◽  
Debulking Surgery ◽  
Interval Debulking Surgery ◽  
Peritonectomy Procedures

scholarly journals Prognostic impact of intraoperative peritoneal cytology in interval debulking surgery for pelvic high‐grade serous carcinoma

2019 ◽  
Vol 8 (10) ◽  
pp. 4598-4604
Author(s):  
Naoki Kojima ◽  
Hiroshi Yoshida ◽  
Ikumi Kuno ◽  
Takashi Uehara ◽  
Masaya Uno ◽  
...  
Keyword(s):  
Serous Carcinoma ◽  
Peritoneal Cytology ◽  
Prognostic Impact ◽  
High Grade ◽  
Debulking Surgery ◽  
Interval Debulking Surgery

Chemotherapy Response Score: Development and Validation of a System to Quantify Histopathologic Response to Neoadjuvant Chemotherapy in Tubo-Ovarian High-Grade Serous Carcinoma

2015 ◽  
Vol 33 (22) ◽  
pp. 2457-2463 ◽  
Author(s):  
Steffen Böhm ◽  
Asma Faruqi ◽  
Ian Said ◽  
Michelle Lockley ◽  
Elly Brockbank ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Scoring System ◽  
Validation Cohort ◽  
Serous Carcinoma ◽  
Chemotherapy Response ◽  
High Grade ◽  
Debulking Surgery ◽  
Interval Debulking Surgery ◽  
Response Score ◽  
Response To Neoadjuvant Chemotherapy

Purpose To develop and validate a histopathologic scoring system for measuring response to neoadjuvant chemotherapy in interval debulking surgery specimens of stage IIIC to IV tubo-ovarian high-grade serous carcinoma. Patients and Methods A six-tier histopathologic scoring system was proposed and applied to a test cohort (TC) of 62 patients treated with neoadjuvant chemotherapy and interval debulking surgery. Adnexal and omental sections were independently scored by three pathologists. On the basis of TC results, a three-tier chemotherapy response score (CRS) system was developed and applied to an independent validation cohort of 71 patients. Results The initial system showed moderate interobserver reproducibility and prognostic stratification of TC patients when applied to the omentum but not to the adnexa. Condensed to a three-tier score, the system was highly reproducible (kappa, 0.75). When adjusted for age, stage, and debulking status, the score predicted progression-free survival (PFS; score 2 v 3; median PFS, 11.3 v 32.1 months; adjusted hazard ratio, 6.13; 95% CI, 2.13 to 17.68; P < .001). The three-tier CRS system applied to omental samples from the validation cohort showed high reproducibility (kappa, 0.67) and predicted PFS (CRS 1 and 2 v 3: median, 12 v 18 months; adjusted hazard ratio, 3.60; 95% CI, 1.69 to 7.66; P < .001). CRS 3 also predicted sensitivity to first-line platinum therapy (94.3% negative predictive value for progression < 6 months). A Web site was established to train pathologists to use the CRS system. Conclusion The CRS system is reproducible and shows prognostic significance for high-grade serous carcinoma. Implementation in international pathology reporting has been proposed by the International Collaboration on Cancer Reporting, and the system could potentially have an impact on patient care and research.

scholarly journals Targeting progesterone signaling prevents metastatic ovarian cancer

2020 ◽  
Vol 117 (50) ◽  
pp. 31993-32004
Author(s):  
Olga Kim ◽  
Eun Young Park ◽  
Sun Young Kwon ◽  
Sojin Shin ◽  
Robert E. Emerson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Deleterious Mutation ◽  
Peritoneal Metastases ◽  
Cancer Development ◽  
Serous Carcinoma ◽  
Cancer Type ◽  
High Grade ◽  
Primary Tumors ◽  
High Risk Populations ◽  
Genetic Deletion

Effective cancer prevention requires the discovery and intervention of a factor critical to cancer development. Here we show that ovarian progesterone is a crucial endogenous factor inducing the development of primary tumors progressing to metastatic ovarian cancer in a mouse model of high-grade serous carcinoma (HGSC), the most common and deadliest ovarian cancer type. Blocking progesterone signaling by the pharmacologic inhibitor mifepristone or by genetic deletion of the progesterone receptor (PR) effectively suppressed HGSC development and its peritoneal metastases. Strikingly, mifepristone treatment profoundly improved mouse survival (∼18 human years). Hence, targeting progesterone/PR signaling could offer an effective chemopreventive strategy, particularly in high-risk populations of women carrying a deleterious mutation in the BRCA gene.

scholarly journals The Added Value of CA125 Normalization Before Interval Debulking Surgery to the Chemotherapy Response Score for the Prognostication of Ovarian Cancer Patients Receiving Neoadjuvant Chemotherapy for Advanced Disease

2020 ◽  
Author(s):  
Wei-feng Liang ◽  
Li-juan Wang ◽  
Jie-ying Wu ◽  
Chang-hao Liu ◽  
Miao-fang Wu ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Cox Regression ◽  
Risk Group ◽  
Serous Carcinoma ◽  
Chemotherapy Response ◽  
Debulking Surgery ◽  
Cox Regression Analysis ◽  
Stratification Method ◽  
Interval Debulking Surgery ◽  
Two Factors

Abstract Objective: To investigate whether CA125 normalization following neoadjuvant chemotherapy (NACT) can complement the chemotherapy response system (CRS) in the prognostication of patients with tubo-ovarian high-grade serous carcinoma (HGSC).Methods: In total, 106 HGSC patients who received NACT followed by interval debulking surgery (IDS) for FIGO stage IIIC-IV disease were included, and their clinical data were retrospectively reviewed. The primary endpoint was progression-free survival (PFS). Cox regression analysis was performed to identify predictors of PFS.Results: Following NACT, CRS3 was noted in 24 patients (22.6%), and CA125 normalization (≤ 35 U/ml) was noted in 54 patients (50.9%). Both CRS3 and CA125 normalization were identified as independent prognosticators of PFS. Combining these two factors, we stratified the 106 patients into three groups with different risks of recurrence: low-risk group (CRS3 + post-NACT CA125≤ 35 U/ml; n = 17, 16.0%), intermediate-risk group (CRS3 + post-NACT CA125 > 35 U/ml; n = 7, 6.6%) and high-risk group (CRS1-2; n= 82, 77.4%). The differences in PFS between the three groups were significant (log-rank test, P < 0.0001). In Cox regression analyses, the new stratification method was found to have an independent prognostic effect.Conclusion: Both the CRS system and the normalization of CA125 following NACT could reliably predict the risk of recurrence following primary treatment. The combination of the two factors refined the prognostic stratification of HGSC patients who were treated with NACT and IDS.

Total Infragastric Omentectomy Including the Vascular Perigastric Arcade in Patients With Advanced Serous Ovarian Tumors

2017 ◽  
Vol 27 (2) ◽  
pp. 252-257
Author(s):  
Gloria Cordeiro Vidal ◽  
Sabrina Croce ◽  
Frédéric Guyon ◽  
Guillaume Babin ◽  
Denis Querleu
Keyword(s):  
Ovarian Cancer ◽  
Advanced Ovarian Cancer ◽  
Ovarian Tumors ◽  
Serous Carcinoma ◽  
Pathological Examination ◽  
Low Grade ◽  
Debulking Surgery ◽  
Macroscopic Appearance ◽  
Primary Debulking Surgery ◽  
Interval Debulking Surgery

ObjectiveThe aim of this study was to document the need of including the perigastric area when performing omentectomy in patients with stage III to IV serous epithelial ovarian tumors.Patients and MethodsPatients undergoing omentectomy in the setting of surgery for advanced epithelial serous ovarian cancer between February and September 2015 were included. Patients with macroscopic involvement of the perigastric area, nonepithelial serous tumors, and recurrences of ovarian cancer were excluded. The perigastric area was isolated and comprehensively processed for pathological examination.ResultsTwenty-four patients were included. Six patients underwent primary debulking surgery, and 18 patients underwent an interval debulking surgery. The mean number of pathologic blocks in the perigastric area was 24 (range, 8–41). Microscopic involvement of the perigastric omentum area was found in 62.5% of the cases. One patient had a low-grade serous carcinoma, with microscopic involvement of the perigastric area. Among the 23 patients with a high-grade serous carcinoma, 10 (83%) of 12 patients with a gross involvement of the rest of the omentum had a microscopic involvement of the perigastric area. The presence of microscopic disease in the perigastric arcade was found in 4 (36.3%) of 11 patients with a macroscopically normal omentum.ConclusionsIn this study, evidence is given that total omentectomy including the perigastric area is a necessary component of complete cytoreductive surgery in advanced ovarian cancer, whatever the macroscopic appearance of the omentum.

Multicenter Clinicopathological Study of High-Grade Serous Carcinoma Presenting as Primary Peritoneal Carcinoma

2018 ◽  
Vol 28 (4) ◽  
pp. 657-665 ◽  
Author(s):  
Shinichi Komiyama ◽  
Yoshihiro Nishijima ◽  
Haruhiro Kondo ◽  
Hiroyuki Nomura ◽  
Satoshi Yamaguchi ◽  
...  
Keyword(s):  
Gynecologic Oncology ◽  
Progression Free Survival ◽  
Residual Tumor ◽  
Serous Carcinoma ◽  
Tumor Diameter ◽  
Gynecologic Oncology Group ◽  
High Grade ◽  
Debulking Surgery ◽  
Free Survival ◽  
Primary Debulking Surgery

ObjectiveWe conducted a multicenter clinicopathological study to characterize patients with high-grade serous carcinoma presenting as primary peritoneal carcinoma (clinical PPC).MethodsAt 9 sites in Japan, patients with clinical PPC diagnosed according to Gynecologic Oncology Group criteria were enrolled retrospectively. The Gynecologic Oncology Group criteria allow for minor ovarian involvement by high-grade serous carcinoma. There was no systematic detailed histopathological review of the fallopian tubes to determine whether they were involved by serous carcinoma.ResultsThere were 139 patients and 64% were aged 60 years or older. Median pretreatment serum CA-125 was 1653.5 IU/mL. Pretreatment performance status was poor in more than 50%, endometrial cytology was positive in 40.3%, and the preoperative clinical diagnosis was correct in 72.7%. Primary debulking surgery was performed in 36% of patients, whereas 64% underwent neoadjuvant chemotherapy (NAC) with interval debulking surgery (IDS). The main tumor sites were the upper abdomen (greater omentum), extrapelvic peritoneum, mesentery, and diaphragm. Lymph node metastasis was found in 46.8% of patients undergoing systematic retroperitoneal node dissection. The optimal surgery rate was 32.0% with primary debulking surgery versus 53.9% with NAC and IDS (P = 0.0139). The response rate was 82.0% with NAC and 80.6% with postoperative chemotherapy. Median progression-free survival was 19.0 months and median overall survival was 41.0 months. Multivariate analysis showed that prognostic factors for progression-free survival were NAC and residual tumor diameter after debulking surgery, whereas the only prognostic factor for overall survival was the residual tumor diameter.ConclusionsThis study identified various characteristics of clinical PPC. Neoadjuvant chemotherapy with IDS is a reasonable treatment strategy, and complete debulking surgery is optimum.

scholarly journals Pathologic distribution at the time of interval tumor reductive surgery informs personalized surgery for high-grade ovarian cancer

2020 ◽  
pp. ijgc-2020-001597
Author(s):  
Courtney D Bailey ◽  
Rebecca Previs ◽  
Bryan M Fellman ◽  
Tarrik Zaid ◽  
Marilyn Huang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Large Bowel ◽  
Primary Tumor ◽  
High Grade ◽  
Debulking Surgery ◽  
Primary Surgery ◽  
Surgery Group ◽  
Interval Debulking Surgery ◽  
Interval Surgery

IntroductionThe surgical approach for interval debulking surgery after neoadjuvant chemotherapy has been extrapolated from primary tumor reductive surgery for high-grade ovarian cancer. The study objective was to compare pathologic distribution of malignancy at interval debulking surgery versus primary tumor reductive surgery.MethodsPatients with a diagnosis of high-grade serous or mixed, non-mucinous, epithelial ovarian, fallopian tube or primary peritoneal cancer who underwent neoadjuvant chemotherapy or primary tumor reductive surgery and had at least 6 months of follow-up were identified through tumor registry at a single institution from January 1995 to April 2016. Pathologic involvement of organs was categorized as macroscopic, microscopic, or no tumor. Statistical analyses included Mann-Whitney and Fisher’s exact tests.ResultsOf 918 patients identified, 366 (39.9%) patients underwent interval debulking surgery and 552 (60.1%) patients underwent primary tumor reductive surgery. Median age was 62.3 years (range 25.3–92.5). The majority of patients in the interval debulking surgery group were unstaged (261, 71.5%). In the patients who had a primary tumor reductive surgery, 406 (74.6%) had stage III disease. In both groups, the majority of patients had serous histology: 325 (90%) and 435 (78.8%) in the interval debulking and primary tumor reductive surgery groups, respectively. There was a statistically significant difference between disease distribution on the uterus between the groups; 31.4% of the patients undergoing interval debulking surgery had no evidence of uterine disease compared with 22.1% of primary tumor reductive surgery specimens (p<0.001). In the adnexa, there was macroscopic disease present in 253 (69.2%) and 482 (87.4%) of cases in the interval vs primary surgery groups, respectively (p<0.001). Within the omentum, no tumor was present in the omentum in 52 (14.2%) in the interval surgery group versus 91 (16.5%) in the primary surgery group (p<0.001). In the interval surgery group, there was no tumor involving the small and large bowel in 49 (13.4%) and 28 (7.7%) pathologic specimens, respectively. This was statistically significantly different from the small and large bowel in the primary surgery group, of which there was no tumor in 20 (3.6%, p<0.001) and 16 (2.9%, p<0.001) of cases, respectively.ConclusionIn patients undergoing interval debulking surgery, there was less macroscopic involvement of tumor in the uterus, adnexa and bowel compared with patients undergoing primary cytoreductive surgery.

Efficacy and safety results from neopembrov study, a randomized phase II trial of neoadjuvant chemotherapy (CT) with or without pembrolizumab (P) followed by interval debulking surgery and standard systemic therapy ± P for advanced high-grade serous carcinoma (HGSC): A GINECO study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5500-5500
Author(s):  
Isabelle Laure Ray-Coquard ◽  
Aude Marie Savoye ◽  
Marie-ange Mouret-Reynier ◽  
Sylvie Chabaud ◽  
Olfa Derbel ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Figo Stage ◽  
Complete Resection ◽  
Serous Carcinoma ◽  
Debulking Surgery ◽  
Randomized Phase Ii ◽  
Interval Debulking Surgery ◽  
Clinical Trial Information

5500 Background: To investigate whether adding Pembrolizumab (P) to neoadjuvant carboplatin-paclitaxel chemotherapy (CP) may increase the optimal debulking rate, assessed by Complete Resection Rate (CRR) after Interval Debulking Surgery (IDS) in patients (pts) with initially unresectable International Federation of Gynecology and Obstetrics (FIGO) stage IIIC/IV ovarian, tubal or peritoneal HGSC. Methods: Multicenter, open-label, non-comparative randomized phase II trial. Pts were randomized (2:1) to receive 4 cycles of CP ± P before IDS. After IDS, all patients received post-operative chemotherapy (2 to 4 cycles) and optional bevacizumab for 15 months in total ± P as maintenance therapy for up to 2 years. Randomization was stratified on center, FIGO stage, Bev planned after IDS and disease volume (<5cm/>5cm). Primary endpoint was the centrally reviewed CRR at IDS. 60 pts were planned in the CP+P arm (A'Hern's single-stage design P0=50%, P1=70%). Safety (particularly due to P addition), surgical morbidity, ORR, PFS and OS were secondary endpoints. Results: 91 pts were randomized from 02/18 to 04/19 with a median Peritoneal Cancer Index at 24 (range 7-39). 80 pts (88%) received Bev in combination with CP followed by bev ± P in maintenance. In the CP+P group (n=61), 58 (95%) pts had IDS and 78% achieved complete resection. The CRR in this group was 74%, statistically superior to the pre-defined hypothesis. In the CP group, CRR was 70% (29/30 pts underwent IDS). Complete resection after strictly 4 cycles of CP±P was obtained for 41 pts (71%) and 17 (58%) pts in CP+P and CP group, respectively (sensitivity analysis). For CP+P group, numerically higher ORRs were observed before IDS compared to CP group (76% vs 61%). Grade ≥3 adverse events (AE) occurred in 75% of the CP+P group and 67% in the CP group: mainly blood and lymphatic, gastrointestinal and vascular disorders. Postoperative AE (mainly infectious, vascular and gastrointestinal) occurred in 20% and 13% of the pts in CP+P and CP arm, respectively. No difference in the number of fatal events between the two arms: 2 in the experimental arm vs 1 in the control arm. Progression free survival rate at 18 months was 61% (95CI% [47-73]) and 57% (95CI% [37-72]) in CP+P and CP arm, respectively. Conclusions: P may be safely added to preoperative treatment in pts deemed non-optimally resectable. The primary objective was met with an improved CRR on CP+P arm. The CRR in the control group was higher than expected. Survival data and translational research including PDL1 status are ongoing to better define P as treatment option in this setting. Clinical trial information: 2016-004-163-39. Clinical trial information: NCT03275506.

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