Dose Escalation in Radical Radio(chemo)therapy for Cervical and Upper Thoracic Esophageal Cancer with 3DCRT/IMRT (ChC&UES): A Multi-center Real world Study

Abstract

Background Cervical and upper thoracic esophageal cancer (ESCA) presents treatment challenges due to limited clinical evidence. This multi-center study (ChC&UES) explores radical radio(chemo)therapy efficacy and safety, especially focusing on radiation dose. Method We retrospectively analyzed clinical data from 1,422 cases across 8 medical centers. According to the radiation dose for primary gross tumor, patients were divided into standard dose radiotherapy (SD, 50-55 Gy) or high dose (HD, >55 Gy) radiotherapy. HD was further subdivided into conventional- high-dose group (HD-conventional, 55Gy-63Gy) and ultra-high-dose group (HD-ultra, ≥63Gy). Primary outcome was Overall Survival (OS). Results The median OS was 33.0 months (95% CI: 29.401-36.521) in the whole cohort. Compared with SD, HD shown significant improved survival in cervical ESCA in Kaplan-Meier (P=0.026) and cox multivariate regression analysis (P=0.018) while shown comparable survival in upper thoracic ESCA (P=0.734). No significant difference existed between HD-conventional and HD-ultra in cervical (P=0.976) and upper thoracic (P=0.610) ESCA. Incidences of radiation esophagitis and pneumonia from HD were comparable to SD (P=0.097, 0.240), while myosuppression risk was higher(P=0.039). The Bonferroni method revealed that, for both cervical and upper thoracic ESCA, HD-ultra enhance the objective response rate (ORR) compared to SD (P< 0.05). Combination of chemotherapy was an dependent prognosis factor of OS (P=0.000,0.039), no survival advantage was found with different chemotherapy regimens or prolonged chemotherapy >4 cycles (All P＞0.05). Conclusion: HD radiotherapy benefits cervical but not upper thoracic ESCA, while increasing bone marrow suppression risk. Further dose escalating (≥ 63Gy) doesn't improve survival but enhances ORR.