Concomitant Chemotherapy and Radiotherapy with SBRT Boost for Unresectable Stage III Non–Small Cell Lung Cancer: A Phase I Study

Kristin A. Higgins, Rathi N. Pillai, Zhengjia Chen, Sibo Tian, Chao Zhang, Pretesh Patel, Suchita Pakkala, Jay Shelton, Seth D. Force, Felix G. Fernandez, Conor E. Steuer, Taofeek K. Owonikoko, Suresh S. Ramalingam, Jeffrey D. Bradley, Walter J. Curran

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17 Scopus citations

Abstract

Objectives Stereotactic body radiation therapy (SBRT) is now the standard of care in medically inoperable stage I NSCLC, yielding high rates of local control. It is unknown whether SBRT can be safely utilized in the locally advanced NSCLC setting. This multi-institution phase I study evaluated the safety of 44 Gy of conventionally fractionated thoracic radiation with concurrent chemotherapy plus dose-escalated SBRT boost to both the primary tumor and involved mediastinal lymph nodes. The primary end point of this study was to establish the maximum tolerated dose (MTD) of the SBRT boost. Methods Inclusion criteria included unresectable stage IIIA or IIIB disease, primary tumor 8 cm or smaller, and N1 or N2 lymph nodes 5 cm or smaller. Tumors were staged with positron emission tomography/computed tomography (CT), and four-dimensional CT simulation was used for radiation planning. The treatment schema was 44 Gy of thoracic radiation (2 Gy/d) with weekly carboplatin and paclitaxel chemotherapy. A second CT simulation was obtained after 40 Gy had been delivered, and a SBRT boost was planned to the remaining gross disease at the primary site and involved mediastinal lymph nodes. Consolidation chemotherapy was given at the discretion of the treating medical oncologist. Four SBRT boost dose cohorts were tested: cohort 1 (9 Gy × 2), cohort 2 (10 Gy × 5), cohort 3 (6 Gy × 5), and cohort 4 (7 Gy × 5). Patients were treated in cohorts of three patients, and the Bayesian escalation with overdose control method was used to determine the MTD of the SBRT boost. Dose-limiting toxicities (DLTs) were defined as any grade 3 or higher toxicities within 30 days of treatment attributed to treatment, not including hematologic toxicity, or any grade 5 toxicity attributed to treatment. Results The study enrolled 19 patients from November 2012 to December 2016. There were four screen failures, and 15 patients were treated on study. There were no DLTs in dose cohort 1 (n = 3) and 2 (n = 6). DLT developed in one patient in dose cohort 3 (n = 3) and in 2 patients in dose cohort 4 (n = 3). The calculated MTD was 6 Gy × 5. The DLT observed at this dose level was a tracheoesophageal fistula; given this substantial toxicity, there was investigator reluctance to enroll further patients at this dose level. Thus, the calculated MTD was 6 Gy × 5; however, 10 Gy × 2 is thought to be a reasonable dose as well, given that no grade 5 toxicities occurred with that dose. Conclusions The MTD of a SBRT boost combined with 44 Gy of thoracic chemoradiation was 6 Gy × 5. A SBRT boost dose of 10 Gy × 2 could be considered safer, with no grade 3 or higher toxicities observed at this dose level during the follow-up period in this study.

Original languageEnglish
Pages (from-to)1687-1695
Number of pages9
JournalJournal of Thoracic Oncology
Volume12
Issue number11
DOIs
StatePublished - Nov 2017

Keywords

  • Lung cancer
  • Radiation
  • SABR
  • SBRT
  • Stage III

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    Higgins, K. A., Pillai, R. N., Chen, Z., Tian, S., Zhang, C., Patel, P., Pakkala, S., Shelton, J., Force, S. D., Fernandez, F. G., Steuer, C. E., Owonikoko, T. K., Ramalingam, S. S., Bradley, J. D., & Curran, W. J. (2017). Concomitant Chemotherapy and Radiotherapy with SBRT Boost for Unresectable Stage III Non–Small Cell Lung Cancer: A Phase I Study. Journal of Thoracic Oncology, 12(11), 1687-1695. https://doi.org/10.1016/j.jtho.2017.07.036