Nhu-Tram A Nguyen1, Naghmeh Isfahanian1, Gregory Pond2, Wael Hanna3, Jean-Claude Cutz4, James Wright1, Anand Swaminath1, Yaron Shargall3, Tom Chow5, Marcin Wierzbicki5, Gordon Okawara1, Kimmen Quan1, Christian Finley6, Rosalyn Juergens7, Theodoros Tsakiridis8. 1. Division of Radiation Oncology, Juravinski Cancer Centre, Hamilton, Ontario, Canada; Department of Oncology, McMaster University, Hamilton, Ontario, Canada. 2. Department of Oncology, McMaster University, Hamilton, Ontario, Canada; Ontario Clinical Oncology Group, Hamilton, Ontario, Canada. 3. Division of Thoracic Surgery, St Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada; Department of Surgery, McMaster University, Hamilton, Ontario, Canada. 4. Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada. 5. Medical Physics, Juravinski Cancer Centre, Hamilton, Ontario, Canada. 6. Department of Surgery, McMaster University, Hamilton, Ontario, Canada; Division of Medical Oncology, Juravinski Cancer Centre, Hamilton, Ontario, Canada. 7. Department of Oncology, McMaster University, Hamilton, Ontario, Canada; Division of Medical Oncology, Juravinski Cancer Centre, Hamilton, Ontario, Canada. 8. Division of Radiation Oncology, Juravinski Cancer Centre, Hamilton, Ontario, Canada; Department of Oncology, McMaster University, Hamilton, Ontario, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada. Electronic address: theos.tsakiridis@hhsc.ca.
Abstract
BACKGROUND: Despite improved staging and surgical techniques, the rate of incomplete resection (R1) of non-small-cell lung cancer (NSCLC) has not significantly decreased. Patients with R1 resection have worse survival compared with those with complete resection (R0). Stereotactic body radiotherapy (SBRT) is a rapid and convenient radiotherapy treatment that delivers high-dose radiotherapy to tumors with high precision while sparing normal organs. Although its efficacy in treating small lung tumors is documented, its use as neoadjuvant therapy for locally advanced (LA) NSCLC has not been examined. We hypothesized that a short course of preoperative SBRT is feasible and can be delivered safely as a neoadjuvant therapy in patients at risk for incomplete resection. METHODS: In this phase I study, 20 patients with cT3 to 4, N0 to 1, M0 NSCLC at risk for incomplete resection will be treated with neoadjuvant SBRT followed by surgery and adjuvant chemotherapy. Four groups of 5 patients will be treated with escalating doses (35, 40, 45, and 50 Gy) in 10 daily fractions. The primary outcome is feasibility (ie, the ability to complete SBRT and surgery as planned; within 7 weeks). Secondary outcomes include acute and late adverse events; R0, R1, and R2 rates; and secondary surrogates of feasibility and safety. RELEVANCE: This study is an important first step in introducing a new therapeutic modality to patients with LA NSCLC that could improve surgical outcomes in the future. If neoadjuvant SBRT is found to be feasible and safe for LA NSCLC, its effect in achieving R0 resection could be investigated in randomized trials.
BACKGROUND: Despite improved staging and surgical techniques, the rate of incomplete resection (R1) of non-small-cell lung cancer (NSCLC) has not significantly decreased. Patients with R1 resection have worse survival compared with those with complete resection (R0). Stereotactic body radiotherapy (SBRT) is a rapid and convenient radiotherapy treatment that delivers high-dose radiotherapy to tumors with high precision while sparing normal organs. Although its efficacy in treating small lung tumors is documented, its use as neoadjuvant therapy for locally advanced (LA) NSCLC has not been examined. We hypothesized that a short course of preoperative SBRT is feasible and can be delivered safely as a neoadjuvant therapy in patients at risk for incomplete resection. METHODS: In this phase I study, 20 patients with cT3 to 4, N0 to 1, M0 NSCLC at risk for incomplete resection will be treated with neoadjuvant SBRT followed by surgery and adjuvant chemotherapy. Four groups of 5 patients will be treated with escalating doses (35, 40, 45, and 50 Gy) in 10 daily fractions. The primary outcome is feasibility (ie, the ability to complete SBRT and surgery as planned; within 7 weeks). Secondary outcomes include acute and late adverse events; R0, R1, and R2 rates; and secondary surrogates of feasibility and safety. RELEVANCE: This study is an important first step in introducing a new therapeutic modality to patients with LA NSCLC that could improve surgical outcomes in the future. If neoadjuvant SBRT is found to be feasible and safe for LA NSCLC, its effect in achieving R0 resection could be investigated in randomized trials.