Prognostic factors and survival outcomes of women with uterine leiomyosarcoma: A Turkish Uterine Sarcoma Group Study-003

To assess the clinicopathological features, prognostic factors, and survival rates associated with uterine leiomyosarcoma (uLMS). Databases from 15 participating gynecological oncology centers in Turkey were searched retrospectively for women who had been treated for stage I-IV uLMS between 1996 and 2018. Of 302 consecutive women with uLMS, there were 234 patients with Federation of Gynecology and Obstetrics (FIGO) stage I disease and 68 with FIGO stage II-IV disease. All patients underwent total hysterectomy. Lymphadenectomy was performed in 161 (54.5%) cases. A total of 195 patients received adjuvant treatment. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 42% and 54%, respectively. Presence of lymphovascular space invasion (LVSI), higher degree of nuclear atypia, and absence of lymphadenectomy were negatively correlated with DFS, while LVSI, mitotic count, higher degree of nuclear atypia, FIGO stage II-IV disease, and suboptimal surgery significantly decreased OS. LVSI and higher degree of nuclear atypia appear to be prognostic indicators for uLMS. Lymphadenectomy seems to have a significant effect on DFS but not on OS.     

The case for aflatoxins in the causal chain of gallbladder cancer

Chronic aflatoxin exposure has long been related to hepatocellular carcinoma (HCC). Recently, its association with gallbladder cancer (GBC) was postulated. Here we present the data supporting this hypothesis in Chile, the country with the highest GBC mortality worldwide with age-standardized mortality rates (ASMR) of 10.3 in women and 5.04 in men.The highest GBC rates occur in Southern Chile (ASMR = 18), characterized by: high Amerindian ancestry, associated with high bile acid synthesis and gallstones; high poverty and high cereal agriculture, both associated with aflatoxin exposure. Aflatoxins have been detected in imported and locally grown foods items. We estimated population dietary exposure ranging from 0.25 to 35.0 ng/kg-body weight/day. The only report on human exposure in Chile found significantly more aflatoxin biomarkers in GBC than in controls (Odds Ratio = 13.0).The hypothesis of aflatoxin-GBC causal link in the Chilean population is supported by: genetically-determined rapid cholesterol excretion and high gallstones prevalence (49.4%); low prevalence of HCC (ASMR = 4.9) and low HBV infection (0.15%) the main co-factor of aflatoxins in HCC risk.If the association between aflatoxins and GBC were confirmed, public health interventions based on food regulation could have a substantial public health impact.     

First-line nivolumab plus chemotherapy vs chemotherapy in patients with advanced gastric,gastroesophageal junction and esophageal adenocarcinoma: CheckMate 649 Chinese subgroup analysis

First-line chemotherapy for advanced/metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric/gastroesophageal junction cancer (GC/GEJC) has poor median overall survival (OS; <1 year). We report efficacy and safety results from Chinese patients in the phase III global CheckMate 649 study of nivolumab plus chemotherapy vs chemotherapy for the first-line treatment of GC/GEJC/esophageal adenocarcinoma (EAC). Chinese patients with previously untreated advanced or metastatic GC/GEJC/EAC were randomized to receive nivolumab (360 mg Q3W or 240 mg Q2W) plus chemotherapy (XELOX [capecitabine and oxaliplatin] Q3W or FOLFOX [oxaliplatin, leucovorin and 5-fluorouracil] Q2W), nivolumab plus ipilimumab (not reported) or chemotherapy alone. OS, blinded independent central review-assessed progression-free survival (PFS), objective response rate (ORR), duration of response (DOR) and safety are reported. Of 1581 patients enrolled and randomized, 208 were Chinese. In these patients, nivolumab plus chemotherapy resulted in clinically meaningful improvement in median OS (14.3 vs 10.2 months; HR 0.61 [95% CI: 0.44-0.85]), median PFS (8.3 vs 5.6 months; HR 0.57 [95% CI: 0.40-0.80]), ORR (66% vs 45%) and median DOR (12.2 vs 5.6 months) vs chemotherapy, respectively. The safety profile was acceptable, with no new safety signals observed. Consistent with results from the global primary analysis of CheckMate 649, nivolumab plus chemotherapy demonstrated a clinically meaningful improvement in OS and PFS and higher response rate vs chemotherapy and an acceptable safety profile in Chinese patients. Nivolumab plus chemotherapy represents a new standard first-line treatment for Chinese patients with non-HER2-positive advanced GC/GEJC/EAC.