Adherence to consensus-based diagnosis and treatment guidelines in adult soft-tissue sarcoma patients: a French prospective population-based study.

BACKGROUND: Soft-tissue sarcomas (STSs) are rare tumors with varied histological presentations. Management and treatment are thus complex, but crucial for patient outcomes. We assess adherence to adult STS management guidelines across two French regions (10% of the French population). We also report standardized incidence. PATIENTS AND METHODS: STS patients diagnosed from 1 November 2006 to 31 December 2007 were identified from pathology reports, medical hospital records, and cancer registries. Guideline adherence was assessed by 23 criteria (validated by Delphi consensus method), and age and sex-standardized incidence rates estimated. Associations between patient, treatment, and institutional factors and adherence with three major composite criteria relating to diagnostic imaging and biopsy as well as multidisciplinary team (MDT) case-review are reported. RESULTS: Two hundred and seventy-four patients were included (57.7% male, mean age 60.8 years). Practices were relatively compliant overall, with over 70% adherence for 10 criteria. Three criteria with perfect Delphi consensus had low adherence: receiving histological diagnosis before surgery, adequacy of histological diagnosis (adherence around 50% for both), and MDT discussion before surgery (adherence <30%). Treatment outside of specialized centers was associated with lower adherence for all three composite criteria, and specific tumor sites and/or features were associated with lower adherence for diagnostic imaging, methods, and MDT meetings. STS standardized incidence rates were 4.09 (European population) and 3.33 (World) /100 000 inhabitants. CONCLUSIONS: Initial STS diagnosis and treatment across all stages (imaging, biopsy, and MDT meetings) need improving, particularly outside specialized centers. Educational interventions to increase surgeon's sarcoma awareness and knowledge and to raise patients' awareness of the importance of seeking expert care are necessary.

Immunogenic death of colon cancer cells treated with oxaliplatin.

Both the pre-apoptotic exposure of calreticulin (CRT) and the post-apoptotic release of high-mobility group box 1 protein (HMGB1) are required for immunogenic cell death elicited by anthracyclins. Here, we show that both oxaliplatin (OXP) and cisplatin (CDDP) were equally efficient in triggering HMGB1 release. However, OXP, but not CDDP, stimulates pre-apoptotic CRT exposure in a series of murine and human colon cancer cell lines. Subcutaneous injection of OXP-treated colorectal cancer (CRC), CT26, cells induced an anticancer immune response that was reduced by short interfering RNA-mediated depletion of CRT or HMGB1. In contrast, CDDP-treated CT26 cells failed to induce anticancer immunity, unless recombinant CRT protein was absorbed into the cells. CT26 tumors implanted in immunocompetent mice responded to OXP treatment in vivo, and this therapeutic response was lost when CRT exposure by CT26 cells was inhibited or when CT26 cells were implanted in immunodeficient mice. The knockout of toll-like receptor 4 (TLR4), the receptor for HMGB1, also resulted in a deficient immune response against OXP-treated CT26 cells. In patients with advanced (stage IV, Duke D) CRC, who received an OXP-based chemotherapeutic regimen, the loss-of-function allele of TLR4 (Asp299Gly in linkage disequilibrium with Thr399Ile, reducing its affinity for HMGB1) was as prevalent as in the general population. However, patients carrying the TLR4 loss-of-function allele exhibited reduced progression-free and overall survival, as compared with patients carrying the normal TLR4 allele. In conclusion, OXP induces immunogenic death of CRC cells, and this effect determines its therapeutic efficacy in CRC patients.