Isotoxic hypofractionation to personalize radiation for NSCLC

2022

Lucas Vitzthum, MD

Stanford University/VA Palo Alto

Palo Alto

The purpose of this study is to develop and evaluate a method for personalized radiation therapy in patients with locally advanced NSCLC. Patients will be assessed regarding their expected risk of treatment toxicity, and those at lower risk will be treated in a fewer number of treatments with a more intensified dose of radiation. If successful, this could be used to inform optimal radiation treatment protocols as well as potentially reduce treatment and financial burden for patients, with a major impact on quality of life.

Research Summary

Like all medical interventions, optimal management of lung cancer requires a careful assessment of risks and benefits with treatment. Patients presenting with larger lung tumors or those with cancer that has spread to the lymph nodes are often treated with definitive radiation therapy delivered daily over the course of several weeks. Depending on the location and size of tumors the risk of toxicity can vary greatly between patients. Despite these differences in presentation, patients are generally treated with a "one size fits all" approach to radiation dosing that is unlikely to adequately account for their risk from tumor progression versus treatment toxicity. The purpose of this proposal is to develop and test a method to personalize radiation therapy dosing based on a patient’s expected risk of treatment toxicity. Patients with a lower risk of toxicity will be treated in a fewer number of treatments which results in more time away from the clinic, lower costs, and a more ‘potent’ effective dose of radiation. We will enroll patients in a clinical trial to determine if this approach is safe and without significant toxicity. We will also evaluate how effective this regimen is at treating the cancer. The results of this study may be used to inform optimal radiation treatment for lung cancer or further guide subsequent larger randomized studies.

Technical Abstract

Despite recent advances, locally advanced non-small cell lung cancer (LA-NSCLC) continues to have a high degree of morbidity and mortality related to both disease progression and sequelae from treatment. The purpose of this study is to develop and evaluate a more personalized radiation therapy (RT) approach with the potential to reduce time and financial burden to patients and increase tumor control. Patients undergoing fractionated RT with concurrent systemic therapy for LA-NSCLC will be treated to a total dose of 60 Gy with the number of fractions determined by ability to meet key dose constraints resulting in a shorter treatment course and higher biologic effective dose (BED) among those treated with shorter fractionation. To reduce the iterative time to determine fractionation schedule and standardize the"‘isotoxic hypofractionation" approach, we will employ a previously developed automated RT planning technique after delineation of the tumor and organs at risk. Fifty patients will be enrolled in a prospective non-randomized 2-stage trial to test the primary objective of whether isotoxic hypofractionation results in an acceptable rate of grade 2 or higher toxicity. Secondary endpoints will include G3+ toxicity, local control, progression free survival and overall survival. Finally, to better inform future "isotoxic" dosing strategies we will evaluate additional predictors of radiation toxicity using established retrospective cohorts through the Stanford Cancer Institute and the Veteran’s Affairs Information and Computing Infrastructure (VINCI).

Isotoxic hypofractionation to personalize radiation for NSCLC

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