Stereotactic ablative radiotherapy after concomitant chemoradiotherapy in non-small cell lung cancer: A TITE-CRM phase 1 trial

Radiother Oncol. 2018 May;127(2):239-245. doi: 10.1016/j.radonc.2018.03.024. Epub 2018 Apr 9.

Abstract

Background and purpose: Platinum based chemoradiotherapy is the standard of care for inoperable non-small cell lung cancer (NSCLC). With evidence that NSCLC can have a dose dependent response with stereotactic ablative radiotherapy (SABR), we hypothesize that a SABR boost on residual tumor treated with chemoradiotherapy could increase treatment efficacy. The purpose of this study was to determine feasibility of such an approach.

Material and methods: A prospective phase I trial was performed including 26 patients. Time-to-event continual reassessment method (TITE-CRM) was used for dose escalation which ranged from 3 × 7 to 3 × 12 Gy for the stereotactic boost, after 46 Gy (2 Gy per day) of chemoradiotherapy.

Results: Median follow-up was of 37.1 months (1.7-60.7), and 3, 4, 3, 3, 9 and 4 patients were included at the dose levels 1, 2, 3, 4, 5 and 6, respectively. During chemoradiotherapy, 9 patients experienced grade 3 toxicity. After stereotactic radiotherapy, 1 patient experienced an esophageal fistula (with local relapse) at the 3 × 11 Gy level, and 1 patient died from hemoptysis at the 3 × 12 Gy level. The 2-year rate of local control, locoregional free survival, metastasis-free survival, and overall survival was 70.3%, 55.5%, 44.5% and 50.8%, respectively.

Conclusion: In the treatment of NSCLC with chemoradiotherapy followed by a stereotactic boost, the safe recommended dose in our protocol was a boost dose of 3 × 11 Gy.

Keywords: Boost; Chemoradiotherapy; Non-small cell lung cancer; Phase 1; Stereotactic ablative radiotherapy.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / diagnostic imaging
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / radiotherapy*
  • Chemoradiotherapy / methods
  • Cisplatin / administration & dosage
  • Docetaxel
  • Female
  • Humans
  • Lung Neoplasms / diagnostic imaging
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / radiotherapy*
  • Male
  • Middle Aged
  • Neoplasm, Residual
  • Positron Emission Tomography Computed Tomography
  • Prospective Studies
  • Radiosurgery / methods*
  • Taxoids / administration & dosage
  • Treatment Outcome

Substances

  • Taxoids
  • Docetaxel
  • Cisplatin