Clinical outcome in patients with primary epithelial ovarian cancer and germline BRCA1/2-mutation - real life data.

BACKGROUND: We evaluated the clinical impact of germline (g)BRCA1/2-mutation on initial disease presentation, surgical implications, surgical morbidity and survival in patients with advanced epithelial ovarian cancer (EOC) undergoing debulking surgery (DS). METHODS: Data of all consecutive EOC patients with stage III/IV, high-grade serous disease and known gBRCA1/2 status (gBRCA; non-gBRCA), who underwent DS at our department between 01/2011 and 06/2019 were analyzed. Associations between gBRCA-status and severe postoperative complications and survival were analyzed. RESULTS: gBRCA-status was determined in 50.1% (612/1221) of all patients. gBRCA was present in 21.9% (134/612). Significant differences were observed in terms of median age (p = 0.001) and histology (high-grade serous histology gBRCA: 98.5%, non-gBRCA 76.2%; p < 0.001). gBRCA-status had no impact on intraoperative disease presentation, surgical complexity or complete resection rate (gBRCA: 74.4%, non-gBRCA: 69.0%; p = 0.274). gBRCA-status was not predictive for severe postoperative complication (gBRCA: 12.0%, non-gBRCA: 19.1%; p = 0.082). Median PFS and OS was 31/22 and 71/53 months in patients with/without gBRCA-mutation, respectively. gBRCA was a significant prognostic factor for PFS (HR 0.57 p < 0.001) and for OS (HR 0.64, p = 0.048) after adjusting for established prognostic factors. CONCLUSIONS: gBRCA-status had no impact on initial disease presentation, surgical results or postoperative complications. gBRCA patients have a significantly longer PFS but the impact on the long term prognosis is unclear. Complete resection remains the most important prognostic factor in patients with EOC independent of gBRCA-status.

Skeletal Muscle Attenuation (Sarcopenia) Predicts Reduced Overall Survival in Patients with Advanced Epithelial Ovarian Cancer Undergoing Primary Debulking Surgery.

BACKGROUND: Sarcopenia was reported as a prognostic factor in cancer patients. Using computed tomography (CT), we analyzed the impact of sarcopenia on overall survival (OS) in patients with advanced epithelial ovarian cancer (EOC) after primary debulking surgery (PDS). METHODS: Preoperative CT scans of consecutive EOC patients (n = 323) were retrospectively assessed for skeletal muscle index (SMI) and muscle attenuation (MA; Hounsfield units [HU]). The optimal cut-off point for MA (32 HU) was calculated using the Martingale residuals method, and previously reported cut-offs for SMI were used. Logistic regression was used to determine univariate and multivariate factors associated with OS. RESULTS: Sarcopenia defined as SMI < 38.5, < 39, and 41 cm2/m2 was detected in 29.4, 33.7, and 47.1% of patients, respectively; however, none of these SMI cut-off levels were associated with OS. MA < 32 HU was present in 21.1% (68/323) of the total cohort. Significant differences between patients with MA < 32 and ≥ 32 HU were detected for median age (67 vs. 57 years), Eastern Cooperative Oncology Group (ECOG) > 0 (13.2 vs. 3.1%), comorbidity (age-adjusted Charlson Comorbidity Index [ACCI] ≥ 4; 36.8 vs. 13.3%), median body mass index (BMI; 27 vs. 24 kg/m2), International Federation of Gynecology and Obstetrics (FIGO) stage, histology (high-grade serous 95.6 vs. 84.7%), and complete resection (38.2 vs. 68.2%). MA < 32 HU remained a significant prognostic factor for OS in multivariate Cox regression analysis (hazard ratio 1.79, p = 0.003). Median OS in patients with MA < 32 HU versus MA ≥ 32 HU was 28 versus 56 months (p < 0.001). Furthermore, MA < 32 HU was significantly associated with OS in the prognostically poor population of patients with residual tumor (p = 0.015). CONCLUSIONS: Low MA was significantly associated with poor survival, especially in patients with residual tumor after PDS. MA assessment could be used for risk stratification after PDS.

Prognostic Value of the Age-Adjusted Charlson Comorbidity Index (ACCI) on Short- and Long-Term Outcome in Patients with Advanced Primary Epithelial Ovarian Cancer.

BACKGROUND: We evaluated the prognostic impact of the age-adjusted Charlson Comorbidity Index (ACCI) on both postoperative morbidity and overall survival (OS) in patients with advanced epithelial ovarian cancer (EOC) treated at a tertiary gynecologic cancer center. PATIENTS AND METHODS: Exploratory analysis of our prospectively documented tumor registry was performed. Data of all consecutive patients with stage IIIB-IV ovarian cancer who underwent primary cytoreductive surgery (PDS) from January 2000 to June 2016 were analyzed. Patients were divided into three groups, based on their ACCI: low (0-1), intermediate (2-3), and high (≥4), and postoperative surgical complications were graded according to the Clavien-Dindo classification (CDC). The Fisher's exact test, log-rank test, and Cox regression models were used to investigate the predictive value of the ACCI on postoperative complications and OS. RESULTS: Overall, 793 consecutive patients were identified; 328 (41.4%) patients were categorized as low ACCI, 342 (43.1%) as intermediate ACCI, and 123 (15.5%) as high ACCI. A high ACCI was significantly associated with severe postoperative complications (CDC 3-5; odds ratio 3.27, 95% confidence interval 1.97-5.43, p < 0.001). Median OS for patients with a low, intermediate, or high ACCI was 50, 40, and 23 months, respectively (p < 0.001), and the ACCI remained a significant prognostic factor for OS in multivariate analysis (p = 0.001). The same impact was observed in a sensitivity analysis including only those patients with complete tumor resection. CONCLUSION: The ACCI is associated with perioperative morbidity in patients undergoing PDS for EOC, and also has a prognostic impact on OS. The potential role of the ACCI as a selection criteria for different therapy strategies is currently under investigation in the ongoing, prospective, multicenter AGO-OVAR 19 trial.

65 YEARS OF THE DOUBLE HELIX: Genetics informs precision practice in the diagnosis and management of pheochromocytoma.

Although the authors of the present review have contributed to genetic discoveries in the field of pheochromocytoma research, we can legitimately ask whether these advances have led to improvements in the diagnosis and management of patients with pheochromocytoma. The answer to this question is an emphatic Yes! In the field of molecular genetics, the well-established axiom that familial (genetic) pheochromocytoma represents 10% of all cases has been overturned, with >35% of cases now attributable to germline disease-causing mutations. Furthermore, genetic pheochromocytoma can now be grouped into five different clinical presentation types in the context of the ten known susceptibility genes for pheochromocytoma-associated syndromes. We now have the tools to diagnose patients with genetic pheochromocytoma, identify germline mutation carriers and to offer gene-informed medical management including enhanced surveillance and prevention. Clinically, we now treat an entire family of tumors of the paraganglia, with the exact phenotype varying by specific gene. In terms of detection and classification, simultaneous advances in biochemical detection and imaging localization have taken place, and the histopathology of the paraganglioma tumor family has been revised by immunohistochemical-genetic classification by gene-specific antibody immunohistochemistry. Treatment options have also been substantially enriched by the application of minimally invasive and adrenal-sparing surgery. Finally and most importantly, it is now widely recognized that patients with genetic pheochromocytoma/paraganglioma syndromes should be treated in specialized centers dedicated to the diagnosis, treatment and surveillance of this rare neoplasm.