Artificial intelligence-guided tissue analysis combined with immune infiltrate assessment predicts stage III colon cancer outcomes in PETACC08 study.

OBJECTIVE: Diagnostic tests, such as Immunoscore, predict prognosis in patients with colon cancer. However, additional prognostic markers could be detected on pathological slides using artificial intelligence tools. DESIGN: We have developed a software to detect colon tumour, healthy mucosa, stroma and immune cells on CD3 and CD8 stained slides. The lymphocyte density and surface area were quantified automatically in the tumour core (TC) and invasive margin (IM). Using a LASSO algorithm, DGMate (DiGital tuMor pArameTErs), we detected digital parameters within the tumour cells related to patient outcomes. RESULTS: Within the dataset of 1018 patients, we observed that a poorer relapse-free survival (RFS) was associated with high IM stromal area (HR 5.65; 95% CI 2.34 to 13.67; p<0.0001) and high DGMate (HR 2.72; 95% CI 1.92 to 3.85; p<0.001). Higher CD3+ TC, CD3+ IM and CD8+ TC densities were significantly associated with a longer RFS. Analysis of variance showed that CD3+ TC yielded a similar prognostic value to the classical CD3/CD8 Immunoscore (p=0.44). A combination of the IM stromal area, DGMate and CD3, designated 'DGMuneS', outperformed Immunoscore when used in estimating patients' prognosis (C-index=0.601 vs 0.578, p=0.04) and was independently associated with patient outcomes following Cox multivariate analysis. A predictive nomogram based on DGMuneS and clinical variables identified a group of patients with less than 10% relapse risk and another group with a 50% relapse risk. CONCLUSION: These findings suggest that artificial intelligence can potentially improve patient care by assisting pathologists in better defining stage III colon cancer patients' prognosis.

Quality of life and cost of strategies of two chemotherapy lines in metastatic colorectal cancer: results of the FFCD 2000-05 trial.

Objectives: This study compared the cost and quality of life (QoL) of 407 advanced colorectal cancer patients, randomly assigned to receive LV5FU2 followed by FOLFOX6 (sequential strategy) or FOLFOX6 followed by FOLFIRI (combination strategy). Methods: Costs were compared from the French health insurance perspective, until the end of the second line of treatment. Consumed resources, collected during the trial, included medicines, hospitalizations, examinations, and transportation. Valuations were made using 2009 and 2016 tariffs. QoL was assessed using the QLQ-C30 questionnaire and clinically significant variations were searched. Results: In 2009, the mean cost per patient was significantly lower for the sequential strategy compared to the combination strategy (18,061€ and 23,119€, p = 0.001). In 2016, the difference was no longer significant (16,876€ and 18,090€, p = 0.41) because oxaliplatin and irinotecan became generics. The QoL analysis (292 patients) showed that there was significantly less improvement of global health status in the sequential strategy than in the combination strategy (29% and 42%; p = 0.02) during first-line therapy. No significant differences were observed for emotional functioning (p = 0.45) and physical functioning (p = 0.07) or during second-line therapy. Conclusion: The choice to treat patients with advanced colorectal cancer using one or the other strategy cannot be based on costs or QoL.

Early Gastric Cancer: Trends in Incidence, Management, and Survival in a Well-Defined French Population.

BACKGROUND: Little is known about the epidemiology of early gastric cancer (EGC) in Western countries. The aim of this study was to analyze trends in the incidence, management, and survival of EGC in a well-defined population over a 30 year period. METHODS: Data were obtained from the population-based cancer Registry of Burgundy (France). Incidence rates were calculated by sex, age, and 10 year period of diagnosis. Net survival rates were calculated and a multivariate relative survival analysis performed. RESULTS: EGC represented 6.7 % of gastric cancer diagnosed between 1982 and 2011. Age-standardized incidence rates were higher in men (0.79/100,000) than in women (0.40/100,000). Between the periods 1982-1991 and 2002-2011, it decreased from 0.97 to 0.53 per 100,000 in men and from 0.44 to 0.30 per 100,000 in women. Overall, 19 % of the tumors were limited to the mucosa, 69 % to the submucosa, and 15 % invaded lymph nodes. Node invasion and male sex were the only significant prognostic factors. Five-year net survival was 50 % in node-positive patients and 85 % in node-negative patients (p < 0.001). In multivariate analysis, the relative risk of death in men compared to women was 2.3 and was 10.4 in patients with positive nodes compared to patients with negative nodes. CONCLUSIONS: EGCs are rare in France. The prognosis is favorable, except for node-positive cancers, which may benefit from the recently developed adjuvant chemotherapy for gastric cancer.

Trends in incidence and management of cancer of the ampulla of Vater.

AIM: To provide trends in incidence, management and survival of cancer of the ampulla of Vater in a well-defined French population. METHODS: Data were obtained from the population-based digestive cancer registry of Burgundy over a 34-year period. Age-standardized incidence rates were computed using the world standard population. Average annual variations in incidence rates were estimated using a poisson regression. A univariate and multivariate relative survival analysis was performed. RESULTS: Age-standardized incidence rates were 0.46 and 0.30 per 100000 inhabitants for men and women, respectively. Incidence rate increased from 0.26 (1976-1984) to 0.58 (2003-2009) for men and remained stable for women. Resection for cure was performed in 48.3% of cases. This proportion was stable over the study period. Among cases with curative resection, pancreatico-duodenectomy was performed in 94.0% of cases and ampullectomy in 6.0% of cases. A total of 50.8% of cancers of the ampulla of Vater were diagnosed at an advanced stage. Their proportion remained stable throughout the study period. The overall 1- and 5-year relative survival rates were 60.2% and 27.7%, respectively. Relative survival did not vary over time. Treatment and stage at diagnosis were the most important determinants of survival. The 5-year relative survival rate was 41.5% after resection for cure, 9.5% after palliative surgery and 6.7% after symptomatic treatment. In multivariate analysis, only stage at diagnosis significantly influenced the risk of death. CONCLUSION: Cancer of the ampulla of Vater is still uncommon, but its incidence increased for men in Burgundy. Diagnosis is often made at an advanced stage, dramatically worsening the prognosis.

Trends in the incidence and management of biliary tract cancer: a French population-based study.

BACKGROUND & AIMS: The trends in incidence and management of biliary tract cancer (BTC) were investigated in a well-defined French population over a 30-year period (1976-2005). METHODS: Data were obtained from the Burgundy digestive cancer registry. Age-standardised incidence rates and trends in incidence were determined. Treatment and stage at diagnosis were also investigated. Five-year survival rates were calculated. RESULTS: Six hundred and fifteen cases of BTC were recorded. There was no significant change in BTC incidence over the 30-year period. For extrahepatic BTC age-standardised incidence rates were 1.1/100,000 for 1976-80 and 2001-2005. These rates were respectively 0.3 and 0.2/100,000 for intrahepatic BTC. The proportion of patients undergoing resection for cure increased over time from 4.8% to 14.2% (p<0.001). The proportion of stage I-II cases ranged from 3.2% to 7.1% but did not vary significantly over time (p=0.55). Most cases were metastatic or unresectable at diagnosis. Five-year relative survival rates were 4.5% for 1976-85 and 6.7% for 1996-2005, ranging from 35.1% for stages I-II to 4.3% for advanced BTC. Age and stage at diagnosis were independent prognostic factors. CONCLUSIONS: The incidence of BTC has remained stable in Burgundy over the past 30 years. BTC prognosis remains poor and has only improved slightly over time.

Incidence and management of primary malignant small bowel cancers: a well-defined French population study.

BACKGROUND AND AIM: Few data are available from population-based statistics on small bowel cancers. The aim of this study was to report on their incidence and management. METHODS: Data were obtained from the population-based Digestive Cancer Registry of Burgundy over a 26-yr period. Incidence rates were calculated by gender, age group, histological type, and 5-yr period. Treatment and stage at diagnosis were investigated. Prognosis was determined using crude and relative survival rates. A multivariate relative survival analysis was performed. RESULTS: Age-standardized incidence rates were 1.2/100,000 inhabitants for men and 0.8/100,000 inhabitants for women. The mean 5-yr variation in incidence were, respectively, +46.7% (P < 0.01) and + 53.2% (P < 0.05). There were four main histological types: adenocarcinoma (40.4%), malignant endocrine tumors (30.5%), lymphoma (20.1%), and sarcoma (9.0%). Resection for cure was performed in 56.6% of the cases. Cancer was not extending beyond the organ in 33.2% of the cases, was associated with lymph node metastasis in 32.1%, and with distant metastasis or unresectability in 34.7%. The 5-yr relative survival rate was 37.4%. It varied between 56.8% for endocrine tumors and 17.8% for sarcoma. In the multivariate analysis, age, histology, and stage at diagnosis significantly influenced the prognosis. CONCLUSIONS: Small bowel cancers represent a heterogeneous group of rare tumors. Prognosis at a population level is worse than in hospital series. In the short term, new therapeutic possibilities represent the best way to improve prognosis.

Epidemiology and management of liver metastases from colorectal cancer.

OBJECTIVE/BACKGROUND: Little is known about the epidemiology and the management of liver metastases from colorectal cancer at a population level. The aim of this population-based study was to report on the incidence, treatment, and prognosis of synchronous and metachronous liver metastases. METHODS: Data were obtained from the population-based cancer registry of Burgundy (France). RESULTS: The proportion of patients with synchronous liver metastases was 14.5%. Age-standardized incidence rates were 7.6 per 100,000 in males, 3.7 per 100,000 in females. The 5-year cumulative metachronous liver metastasis rate was 14.5%. It was 3.7% for TNM stage I tumors, 13.3% for stage II, and 30.4% for stage III (P < 0.001). The risk of liver metastasis was also associated to gross features. Resection for cure was performed in 6.3% of synchronous liver metastases and 16.9% of metachronous liver metastases. Age, presence of another site of recurrence, and period of diagnosis were independent factors associated with the performance of a resection for cure. The 1- and 5-year survival rates were 34.8% and 3.3% for synchronous liver metastases. Their corresponding rates were, respectively, 37.6% and 6.1% for metachronous liver metastases. CONCLUSION: Liver metastases from colorectal cancer remain a substantial problem. More effective treatments and mass screening represent promising approaches to decrease this problem.

Trends in incidence and management of esophageal adenocarcinoma in a well-defined population.

OBJECTIVES: Little epidemiological data is available concerning esophageal adenocarcinomas in France. The aim of this study was to study epidemiological characteristics and management of esophageal adenocarcinoma in a well-defined population. METHODS: Data were collected by the Burgundy Digestive Cancer Registry covering a population of 1 052 000, over a 28-year period (1976-2001). Incidence, treatment and stage at diagnosis were noted. Univariate and multivariate analysis of survival was performed. RESULTS: Age standardized incidence rates were 1.60/100,000 in men and 0.15/100,000 in women. The mean increase in incidence rates by 5-year periods were respectively + 68.1% (P<0.001) and + 97.4% (P<0.001). Overall, 69.9% of the cancers were located in the lower third of the esophagus. Surgical resection was performed in 32.1% of patients. Among the surgical patients, the tumor was limited to the esophageal wall in 11.4%, lymph node metastases were present in 18.1% and non-resectable distant metastases in 70.5%. There was no improvement of stage at diagnosis over time. Survival rates were 14.4% at 3 years and 9.2% at 5 years. Five-year survival rates varied from 38.4% for cases limited to the esophageal wall to 1.8% for metastatic and non resectable cases. Stage at diagnosis was the only significant prognostic factor in the multivariate analysis. CONCLUSION: Esophageal adenocarcinomas are rare cancers characterized by a sharp rise in incidence over the past years in France. Stage at diagnosis and prognosis are worse than reported in hospital statistics.