Of the 670 patients randomly assigned to a study treatment, 632 (94.3%) were eligible and started the treatment. The majority of these patients had extensive stage IIIC or IV disease at primary debulking surgery (metastatic lesions that were larger than 5 cm in diameter in 74.5% of patients and larger than 10 cm in 61.6%). The largest residual tumor was 1 cm or less in diameter in 41.6% of patients after primary debulking and in 80.6% of patients after interval debulking. Postoperative rates of adverse effects and mortality tended to be higher after primary debulking than after interval debulking. The hazard ratio for death (intention-to-treat analysis) in the group assigned to neoadjuvant chemotherapy followed by interval debulking, as compared with the group assigned to primary debulking surgery followed by chemotherapy, was 0.98 (90% confidence interval [CI], 0.84 to 1.13; P = 0.01 for noninferiority), and the hazard ratio for progressive disease was 1.01 (90% CI, 0.89 to 1.15). Complete resection of all macroscopic disease (at primary or interval surgery) was the strongest independent variable in predicting overall survival. Conclusions Neoadjuvant chemotherapy followed by interval debulking surgery was not inferior to primary debulking surgery followed by chemotherapy as a treatment option for patients with bulky stage IIIC or IV ovarian carcinoma in this study. Complete resection of all macroscopic disease, whether performed as primary treatment or after neoadjuvant chemotherapy, remains the objective whenever cytoreductive surgery is performed. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00003636.)

/pdf/neoadjuvant-chemotherapy-or-primary-surgery-in-stage-iiic-or-4g0pf97gmf.pdf

Neoadjuvant Chemotherapy or Primary Surgery in Stage IIIC or IV Ovarian Cancer

BACKGROUND:
Primary surgery followed by platinum-taxane based chemotherapy has been the standard therapy in advanced ovarian cancer. However, the prognostic role of complete and so-called optimal and suboptimal debulking and its interaction with biological factors has not been not fully defined.

METHODS:
Exploratory analysis was conducted of 3 prospective randomized trials (AGO-OVAR 3, 5, and 7) investigating platinum-taxane based chemotherapy regimens in advanced ovarian cancer conducted between 1995 and 2002.

RESULTS:
A total of 3126 patients were analyzed. Approximately one-third each fulfilled criteria for complete resection (group A), small residual tumor burden of 1-10 mm (group B), or macroscopic residual disease exceeding 1 cm in diameter (group C). Multivariate analysis showed improved progression-free and overall survival for group A with complete resection compared with groups B or C (P < .0001). The impact of so-called optimal debulking as in group B showed a smaller prognostic impact compared with group C. Further independent prognostic factors for overall survival were age, performance status, grade, FIGO stage, and histology, namely the mucinous subtype. An interaction between residual tumor and some biologic factors was demonstrated.

CONCLUSIONS:
The goal of primary surgery should be complete resection. The prognostic impact of tumor biology seemed to be partially overruled by residual tumor and further evaluation of biologic factors should stratify for residual tumor. Cancer 2009. © 2009 American Cancer Society.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.24149

Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials: by the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and the Groupe d'Investigateurs Nationaux Pour les Etudes des Cancers de l'Ovaire (GINECO).

Prognostic significance of tumor-infiltrating T cells in ovarian cancer: A meta-analysis

Improved progression-free and overall survival in advanced ovarian cancer as a result of a change in surgical paradigm

Context Attempts to determine the clinical significance of BRCA1/2 mutations in ovarian cancer have produced conflicting results. Objective To determine the relationships between BRCA1/2 deficiency (ie, mutation and promoter hypermethylation) and overall survival (OS), progression-free survival (PFS), chemotherapy response, and whole-exome mutation rate in ovarian cancer. Design, Setting, and Patients Observational study of multidimensional genomics and clinical data on 316 high-grade serous ovarian cancer cases that were made public between 2009 and 2010 via The Cancer Genome Atlas project. Main Outcome Measures OS and PFS rates (primary outcomes) and chemotherapy response (secondary outcome). Results BRCA2 mutations (29 cases) were associated with significantly better OS (adjusted hazard ratio [HR], 0.33; 95% CI, 0.16-0.69; P = .003 and 5-year OS, 61% for BRCA2-mutated vs 25% for BRCA wild-type cases) and PFS (adjusted HR, 0.40; 95% CI, 0.22-0.74; P = .004 and 3-year PFS, 44% for BRCA2-mutated vs 16% for BRCA wild-type cases), whereas neither BRCA1 mutations (37 cases) nor BRCA1 methylation (33 cases) was associated with prognosis. Moreover, BRCA2 mutations were associated with a significantly higher primary chemotherapy sensitivity rate (100% for BRCA2-mutated vs 82% [P = .02] and 80% [P = .05] for BRCA wild-type and BRCA1-mutated cases, respectively) and longer platinum-free duration (median platinum-free duration, 18.0 months for BRCA2-mutated vs 11.7 [P = .02] and 12.5 [P = .04] months for BRCA wild-type and BRCA1-mutated cases, respectively). BRCA2-mutated, but not BRCA1-mutated cases, exhibited a “mutator phenotype” by containing significantly more mutations than BRCA wild-type cases across the whole exome (median mutation number per sample, 84 for BRCA2-mutated vs 52 for BRCA wild-type cases, false discovery rate Conclusion Among women with high-grade serous ovarian cancer, BRCA2 mutation, but not BRCA1 deficiency, was associated with improved survival, improved chemotherapy response, and genome instability compared with BRCA wild-type.

https://jamanetwork.com/journals/jama/articlepdf/1104495/joc15119_1557_1565.pdf

Association of BRCA1 and BRCA2 mutations with survival, chemotherapy sensitivity, and gene mutator phenotype in patients with ovarian cancer

Gallbladder mucocele (GBM) is a commonly diagnosed disease process in dogs that is associated with high morbidity and mortality if not recognized and appropriately managed. Although the exact mechanism of this disease process is not completely understood, previous studies in smaller populations of dogs have identified multiple factors that predispose to the development of GBM and affect survival. The purpose of this cross-sectional, retrospective study was to evaluate the effects of age, breed category, sex, preoperative antibiotic administration, gallbladder rupture, and a positive biliary culture in dogs that had a cholecystectomy performed for the treatment of GBM. The age (median: 11 years) and percentage of dogs that died within 14 days of cholecystectomy (16.7%) are similar to what have been reported in other studies. Gallbladder rupture and a positive biliary culture occurred in 20.4% and 12.5% of dogs, respectively. Dogs with a gallbladder rupture and positive biliary culture were 2.74 and 3.10 times more likely to die within 14 days of cholecystectomy, respectively. This contradicts a recent study that failed to find a significant association between survival and biliary culture result. Interestingly, younger age was associated with an increased occurrence of gallbladder rupture in that population. Because of the potential effect of gallbladder rupture and a biliary tract infection, abdominal imaging, biliary culture, and empirical preoperative antimicrobial therapy are recommended in dogs undergoing cholecystectomy for the treatment of GBM.

Factors affecting survival in 516 dogs that underwent cholecystectomy for the treatment of gallbladder mucocele.

What is the optimal goal of primary cytoreductive surgery for bulky stage IIIC epithelial ovarian carcinoma (EOC)

What constitutes "optimal" cytoreduction for women operated on for ovarian cancer remains uncertain. A majority of studies have employed a cutoff of 1-2 cm to define optimal cytoreduction. Recent studies suggest that removing all gross disease promotes disease-free survival compared to the current Gynecologic Oncology Group threshold of 1 cm or less of residual disease. This prospective database analysis reviewed the records of 465 patients with stage IIIC epithelial ovarian carcinoma (EOC) who had cytoreductive surgery in the years 1989-2003. All participants had bulky abdominal tumor, and maximal cytoreduction was attempted if technically possible. The patients, whose median age was 60 years, were followed up for a median of 38 months. Nearly all the patients received at least 6 cycles of platinum-based systemic chemotherapy. Univariate analysis showed age at the time of surgery and the preoperative platelet count to be significant continuous variables. Categorical variables with prognostic significance included the presence of ascites, the site of the largest tumor mass, extensive upper abdominal cytoreduction, and the extent of residual disease. Multivariate analysis confirmed age, the presence or absence of ascites, and the diameter of residual disease as being significant factors. Median survival was 106 months when there was no gross residual disease, and declined steadily as the amount of residual disease increased. Median survival was 34 months when patients were left with more than 2 cm of residual disease. The major distinctions with regard to survival rate were between no gross residual disease, 1 cm or less of gross disease, and more than 1 cm of residual disease. A trend toward improved survival was noted in patients left with 0.5 cm or less of residual disease compared with those retaining 0.6-1 cm of disease (Fig. 1). The investigators conclude from these findings that removing all evidence of gross stage IIIC EOC prolongs survival and is an appropriate goal of primary cytoreductive surgery. If complete gross resection is not feasible, as little residual tumor as possible should be left behind. An incremental decrease in residual disease below 1 cm can incrementally enhance overall survival.

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Factors affecting survival in 516 dogs that underwent cholecystectomy for the treatment of gallbladder mucocele.

What is the optimal goal of primary cytoreductive surgery for bulky stage IIIC epithelial ovarian carcinoma (EOC)

What is the optimal goal of primary cytoreductive surgery for bulky stage IIIC epithelial ovarian carcinoma (EOC)