Radiation dose and pathological response in oesophageal cancer patients treated with neoadjuvant chemoradiotherapy followed by surgery: a multi-institutional analysis

Authors

  • Melissa Thomas Laboratory of Experimental Radiotherapy, Department of Oncology, KU Leuven – University of Leuven, Leuven, Belgium;  Department of Radiation Oncology, UZ Leuven – University Hospitals Leuven, Leuven, Belgium
  • Alicia S. Borggreve Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands;  Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
  • Peter S. N. van Rossum Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
  • Christiaan Perneel Department of Applied Mathematics, Royal Military Academy, Brussels, Belgium
  • Johnny Moons Department of Thoracic Surgery, UZ Leuven – University Hospitals Leuven, Leuven, Belgium
  • Elke Van Daele Department of Gastrointestinal Surgery, Ghent University Hospital, Ghent, Belgium
  • Richard van Hillegersberg Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
  • Wei Deng Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • Piet Pattyn Department of Gastrointestinal Surgery, Ghent University Hospital, Ghent, Belgium
  • Stella Mook Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
  • Tom Boterberg Department of Radiation Oncology, Ghent University Hospital, Ghent, Belgium
  • Jelle P. Ruurda Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
  • Philippe Nafteux Department of Thoracic Surgery, UZ Leuven – University Hospitals Leuven, Leuven, Belgium
  • Steven H. Lin Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • Karin Haustermans Laboratory of Experimental Radiotherapy, Department of Oncology, KU Leuven – University of Leuven, Leuven, Belgium;  Department of Radiation Oncology, UZ Leuven – University Hospitals Leuven, Leuven, Belgium

DOI:

https://doi.org/10.1080/0284186X.2019.1646432

Abstract

Purpose: To explore whether a higher neoadjuvant radiation dose increases the probability of a pathological complete response (pCR) or pathological major response (pMR) response in oesophageal cancer patients.

Material and methods: Between 2000 and 2017, 1048 patients from four institutions were stratified according to prescribed neoadjuvant radiation doses of 36.0 Gy (13.3%), 40.0 Gy (7.4%), 41.4 Gy (20.1%), 45.0 Gy (25.5%) or 50.4 Gy (33.7%) in 1.8–2.0 Gy fractions. Endpoints were pCR (tumour regression grade (TRG) 1) and pMR (TRG 1 + 2). Multivariable binary (TRG 1 + 2 vs. TRG > 2) and ordinal (TRG 1 vs. TRG 2 vs. TRG > 2) logistic regression analyses were performed, with subgroup analyses according to histology (squamous cell carcinoma (SCC) vs. adenocarcinoma (AC)). Variables entered in the regression model along with neoadjuvant radiation dose were clinical tumour stage (cT), histology, chemotherapy regimen, induction chemotherapy and time from neoadjuvant chemoradiation to surgery.

Results: A pCR was observed in 312 patients (29.8%); in 22.7% patients with AC and in 49.6% patients with SCC. No radiation dose–response relation was observed for pCR (OR = 1.01, 95% CI: 0.98–1.05 for AC and OR = 1.03, 95% CI: 0.96–1.10 for SCC). A pMR was observed in 597 patients (57.0%); in 53.4% patients with AC and in 67.2% patients with SCC. A higher radiation dose increased the probability of achieving pMR (OR = 1.04, 95% CI: 1.02–1.05). Factors reducing this probability were advanced cT stage (reference = cT1–2; cT3: OR = 0.54, 95% CI: 0.37–0.80; cT4: OR = 0.45, 95% CI: 0.24–0.84), AC histology (reference = SCC; OR = 0.62, 95% CI: 0.44–0.88), the use of non-platinum based chemotherapy in SCC patients (OR = 0.30, 95% CI: 0.10–0.91) and platinum based chemotherapy without induction chemotherapy in patients with AC (OR = 0.56, 95% CI: 0.42–0.76). The radiation dose–response relation was confirmed in a subgroup analysis of histologic subtypes (OR = 1.02, 95% CI: 1.01–1.04 for AC and OR = 1.05, 95% CI: 1.02–1.08 for SCC).

Conclusions: Neoadjuvant radiation dose impacts pathological response in terms of pMR in oesophageal cancer patients. No radiation dose–response effect was observed for pCR. Further prospective trials are needed to investigate the dose–response relation in terms of pCR

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Published

2019-10-03

How to Cite

Thomas, M., Borggreve, A. S., van Rossum, P. S. N., Perneel, C., Moons, J., Van Daele, E., … Haustermans, K. (2019). Radiation dose and pathological response in oesophageal cancer patients treated with neoadjuvant chemoradiotherapy followed by surgery: a multi-institutional analysis. Acta Oncologica, 58(10), 1358–1365. https://doi.org/10.1080/0284186X.2019.1646432

Issue

Vol. 58 No. 10 (2019): Acta Oncologica

Section

Articles