Age appropriate.

Top Line: More than 40% of patients diagnosed with esophageal cancer are 70 years or older.

The Study: Only a minority of this population can tolerate chemoradiation with standard platinum-based systemic therapy, with the default typically being radiation alone. Is there a better compromise? Enter S-1 again. This Chinese phase 3 trial enrolled 298 patients ages 70-85 receiving definitive radiation for locally advanced esophageal cancer with or without concurrent S-1. Radiation alone was prescribed to 60Gy/30 and chemoradiation was 54Gy/30 with S-1 prescribed 70 mg/m2 orally on days 1 to 14 and 29 to 42. In each group, radiation completion rate was 89-90%, and S-1 completion rate was 79%. Complete radiographic response was achieved in 27% after radiation alone and 42% after radiation with S-1. More impressive was the improvement in overall survival at 2 years from 36% → 53% with the addition of S-1. While there is a clear advantage in chemo completion among this older population with oral S-1 here as compared to an historical rate as low as 15% with intravenous agents, the authors also pose an interesting hypothesis that S-1 may actually be a superior radiosensitizer because the plasma half-life of fluorouracil during S-1 treatment is longer than when fluorouracil is intravenously administered.

TBL: The authors conclude oral S-1 concurrent to radiation should be the new standard for locally-advanced esophageal cancer among patients 70 or older, notwithstanding the fact it is not FDA-approved on this side of the globe. | Ji, JAMA Oncol 2021