Measure what matters.

Top Line: Back at ASTRO 2019, we heard from a phase IIB trial comparing proton beam therapy (PBT) and intensity modulated radiation therapy (IMRT) for unresectable esophageal cancer. 
The Study: Here we have the full publication. The 145 patients randomized (107 evaluated) had either resectable or potentially resectable stage II-III esophageal cancer with either squamous or adeno histology located anywhere from the cervical esophagus to the gastric cardia. Both radiation arms received a fairly standard 50.4 Gy with chemotherapy. There were two endpoints: progression free survival (PFS) and total toxicity burden (TTB). TTB is relatively new to us. It’s a composite measure of all the toxicities experienced by a patient during a course of treatment. Importantly, it assigns severity weights to the same grades of different complications. Following chemoradiation, just over half of patients in each arm went for surgery. Disease outcomes were similar with a nearly identical 30% complete response rate and 44.5% 3-year PFS rate. When it came to TTB, though, IMRT had 2.3 times higher TTB than PBT. In particular, the higher TTB was felt to be driven largely by the nearly 8 times higher post-op complication rate with IMRT. However, that large difference in TTB did not translate into a difference in patient-reported quality of life. Nevertheless, the cardiopulmonary effects of thoracic radiation and their potential detriment to toxicity and survival outcomes should not be underestimated. But we also need to learn more about the meaning and validity of TTB before deciding if it’s a slam dunk for PBT.
TBL: Proton-based chemoradiation for locally advanced esophageal cancer reduces the cumulative burden of toxicity and post-op complications compared to IMRT, but without a significant improvement in survival outcomes or quality of life. | Lin, J Clin Oncol 2020

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