Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

Surgical treatment of giant cell tumour of long bone with anhydrous alcohol adjuvant

This study was designed to evaluate the feasibility and effectiveness of the use of anhydrous alcohol as an adjuvant treatment for giant cell tumours (GCTs) of long bone. Between October 1989 and January 2004, 42 GCT patients were treated and followed up for an average of 4.1 years (range 1–13 years). Mean patient age was 34 years (range 17–67 years). After curettage and additional burring, anhydrous alcohol was used as an adjuvant therapy in all patients before the bone defect was filled with bone graft or cement. Four patients (9.5%) experienced local recurrence. There were no alcohol-related complications. Recurrence-free probability was 87.6% at final follow-up (13 years) after index surgery by Kaplan–Meyer analysis. Our data suggest that anhydrous alcohol can be used as an effective safe adjuvant for the treatment of GCT of long bone