Radiotherapy Alone or Concurrent Chemoradiation for Esophageal Squamous Cell Carcinoma in Elderly Patients

Abstract

There is a lack of information to guide treatment decisions for elderly patients with esophageal cancer. Because substantially more toxicities could result from double agents concurrent chemoradiotherapy (dCCRT), some studies using oral capecitabine or S-1 to replace infusional fluorouracil had shown excellent safety and efficacy results. However, many of these studies reflect small retrospective samples using somewhat heterogeneous treatment approaches, making them less useful in determining optimal CCRT/RT approaches. We have embarked on this study to address the definitive treatment approach in a large cohort of elderly Chinese ESCC patients aged ≥70 years using modern radiotherapy approaches. We aim to identify the efficacy and factors for optimal treatment approaches for elderly esophageal squamous cell carcinoma (ESCC) treated with RT alone or concurrent chemoradiation (CCRT). This study included 184 I-III elderly ESCC patients aged ≥70 years treated by oral Single chemotherapy agents CCRT (sCCRT) (capecitabine or S1) or double agents dCCRT or RT alone at a single institution in China. RT was delivered with Intensity Modulated Irradiation Therapy (IMRT) or Volumetric-Modulated Arc Therapy (VMAT). Sequential or simultaneous integrated boost (SIB) approach was applied for GTV dose escalation. All radiation doses were converted into the equivalent dose in 2 Gy fraction (EQD2). Toxicities were evaluated by criteria of Radiation Therapy Oncology Group. Statistical analyses were performed on survival and prognostic factors. Patient and treatment characteristics across three different treatment modalities were mostly well balanced. At a median follow-up time of 15.5 months (interquartile range 8.0-25.4 months), the 2- and 3-year estimated OS, LRFFS, DMFS and PFS were 43.5%, 60.5%, 79.9% and 34.6%, and 35.2%, 58.5%, 77.8% and 29.4%, respectively. sCCRT was significantly associated with higher OS, LRFS, and DFS when compared with RT alone and no difference was observed between sCCRT and dCCRT. Multivariate analysis showed that T and N stage, GTV dose (cutoff value 56Gy), SIB technique and CCRT were significant predictors for the outcomes. 44% experienced treatment failure, among whom 65.4% developed local failure. 81.3% local failure occurred in GTV and 70.6% regional failuresoccurred out of radiation field. dCCRT was the only prediction for grade ≥ 2 neutropenia and gastrointestinal reactions. However, no significant difference in toxicities was observed between sCCRT and RT alone. Our results demonstrated that CCRT in elderly patients had significant survival benefit compared to RT alone, especially using Single oral agent. sCCRT had less toxicities compared to dCCRT, and the toxicity was similar to RT alone. GTV dose ≥ 56 Gy and SIB technique were optimal approaches for radiotherapy.