Lessons Learned from Radiation Oncology Clinical Trials

Abstract

A Workshop entitled “Lessons Learned from Radiation Oncology Trials” was held on December 7–8th, 2011 in Bethesda, MD, to present and discuss some of the recently conducted Radiation Oncology clinical trials with a focus on those that failed to refute the null hypothesis. The objectives of this Workshop were to summarize and examine the questions that these trials provoked, to assess the quality and limitations of the pre-clinical data that supported the hypotheses underlying these trials, and to consider possible solutions to these challenges for the design of future clinical trials. Several themes emerged from the discussions, including the: a) opportunities to learn from null-hypothesis trials through tissue and imaging studies; b) value of pre-clinical data supporting the design of combinatorial therapies; c) significance of validated biomarkers; d) necessity of quality assurance in radiotherapy delivery; e) conduct of sufficiently-powered studies to address the central hypothesis; and f) importance of publishing results of the trials regardless of the outcome. The fact that well-designed hypothesis-driven clinical trials produce null or negative results is expected given the limitations of trial design, and complexities of cancer biology. It is important to understand the reasons underlying such null results however, in order to effectively merge the technological innovations with the rapidly evolving biology for maximal patient benefit, through the design of future clinical trials.

Tumor Radiosensitization by Monomethyl Auristatin E: Mechanism of Action and Targeted Delivery

“…We have therefore initially evaluated a strategy using MMP and cRGD binding integrin targeted ACPP delivery of MMAE in combination with focal IR (17). A major limitation to the therapeutic utility of radiosensitizers is the lack of tumor specific delivery (22, 23). Radiosensitizer delivery that is non-targeted can result in increased radiosensitization of not only tumor cells, but also surrounding normal tissue.…”

Tumour and normal tissue radiobiology in mouse models: how close are mice to mini-humans?

“…This workshop "Lessons Learned from Radiation Oncology Trials" 42 concluded that preclinical studies must conduct at least in vitro clonogenic assay and contact the Radiation Research Program at the US National Cancer Institute (NCI), which is coordinating the preclinical and clinical studies for multiple targeted agents combined with RT in panels of human cancer cells, before embarking on combinatorial therapies and generate in vivo data using different human cancer xenograft models. Orthotopic models are encouraged.…”

Integrative Analysis of DCE-MRI and Gene Expression Profiles in Construction of a Gene Classifier for Assessment of Hypoxia-Related Risk of Chemoradiotherapy Failure in Cervical Cancer

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