Association between radiation dose and pathological complete response after preoperative radiochemotherapy in esophageal squamous cell cancer

Anticancer Res. 2014 Dec;34(12):7255-61.

Abstract

Aim: This study was undertaken to examine the impact of radiation dose on pathological complete response (pCR) rates following neoadjuvant radiochemotherapy (N-RCT) for squamous cell esophageal cancer (ESCC).

Patients and methods: From 1988 to 2011, 218 patients were treated with 30-30.6 Gy (1.8-2 Gy per fraction), 39.6-40 Gy (1.8-2 Gy per fraction) or 44-45 Gy (1.8-2 Gy per fraction) and concomitant cisplatin ± 5-fluorouracil (5-FU), oxaliplatin + 5-FU or 5-FU alone. The most commonly used concomitant chemotherapy was continuous infusion of 5-FU-alone with a dose of 300 mg/m(2)/day during the whole course of treatment (n=111). To eliminate the dispersing effect of potentially different efficacy levels of these drug regimens on pCR, we excluded patients with regimens other than 5-FU-alone.

Results: Histomorphological regression grade 1a (0% residual tumor), 1b (<10% residual tumor), 2 (10-50% residual tumor) and 3 (>50% residual tumor) was observed in 26 (23%), 24 (22%), 36 (32%) and 25 (23%) patients, respectively. pCR was observed in 9 out of 71 (13%) patients treated with 30 Gy-30.6 Gy, 13 of 34 (38%) patients treated with 39.6-40 Gy and 4 of 6 (67%) patients treated with 44-45 Gy (p=0.001). Median follow-up time from the start of N-RCT was 191 months (range=2-262 months). The estimated 5-year overall survival (OS) was 33% for the whole cohort. OS at 5 years was 58% for patients with pCR compared to 25% for patients with less favorable response to N-RCT (p=0.009), respectively.

Conclusion: The dose of radiation correlates significantly with the likelihood of achieving a pCR in stage II/III squamous cell esophageal cancer patients. Prospective randomized trials are required to definitively evaluate the impact of application of higher radiation doses on efficacy and safety/tolerability in the context of N-RCT on the clinical outcomes.

Keywords: Neoadjuvant radiochemotherapy; esophageal cancer; pCR; radiation dose effect; regression; squamous cell carcinoma.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / radiotherapy*
  • Chemoradiotherapy / methods*
  • Cisplatin / therapeutic use
  • Combined Modality Therapy
  • Dose-Response Relationship, Radiation
  • Esophageal Neoplasms / drug therapy
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / radiotherapy*
  • Esophageal Squamous Cell Carcinoma
  • Female
  • Fluorouracil / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Organoplatinum Compounds / therapeutic use
  • Oxaliplatin
  • Radiation Dosage*
  • Survival Rate

Substances

  • Organoplatinum Compounds
  • Oxaliplatin
  • Cisplatin
  • Fluorouracil