Oncology Scan—Promising Strategies for the Treatment of Locally-Advanced Non-Small Cell Lung Cancer

Abstract

The standard treatment for inoperable locally advanced non-small cell lung cancer (NSCLC) is concurrent chemoradiation therapy (chemo-RT) ( 1 Curran Jr., W.J. Paulus R. Langer C.J. et al. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: Randomized phase 3 trial RTOG 9410. J Natl Cancer Inst. 2011; 103: 1452-1460 Crossref PubMed Scopus (875) Google Scholar ). However, the optimal radiation dose and fraction schema to be given concurrently with chemotherapy remains controversial ( 2 Bradley JD, Paulus R, Komaki R, et al. Randomized phase 3 comparison of standard-dose (60 Gy) versus high-dose (74 Gy) conformal chemoradiotherapy ± cetuximab for stage IIIA/IIIB non-small cell lung cancer: preliminary findings on radiation dose in RTOG 0617. Abstract presented at the 53rd Annual Meeting of the American Society for Radiation Oncology; Oct 3, 2011; Miami Beach, FL. Google Scholar ). Retrospective and phase 2 clinical studies have shown that higher biological effective doses (BEDs) of radiation are associated with improved local control and potentially with survival ( 3 Bradley J.D. Bae K. Graham M.V. et al. Primary analysis of the phase 2 component of a phase 1/2 dose intensification study using three-dimensional conformal radiation therapy and concurrent chemotherapy for patients with inoperable non-small cell lung cancer: RTOG 0117. J Clin Oncol. 2010; 28: 2475-2480 Crossref PubMed Scopus (121) Google Scholar , 4 Kong F.M. Ten Haken R.K. Schipper M.J. et al. High-dose radiation improved local tumor control and overall survival in patients with inoperable/unresectable non-small-cell lung cancer: Long-term results of a radiation dose escalation study. Int J Radiat Oncol Biol Phys. 2005; 63: 324-333 Abstract Full Text Full Text PDF PubMed Scopus (407) Google Scholar ). Stereotactic ablative radiation therapy (SABR, also known as stereotactic body radiation therapy), in which BEDs in excess of 100 Gy are delivered to the planning target volume, has demonstrated local control rates exceeding 95% and survival comparable to that after surgery for stage I NSCLC ( 5 Timmerman R. Paulus R. Galvin J. et al. Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA. 2010; 303: 1070-1076 Crossref PubMed Scopus (1867) Google Scholar , 6 Shirvani S.M. Jiang J. Chang J.Y. et al. Comparative effectiveness of 5 treatment strategies for early-stage non-small cell lung cancer in the elderly. Int J Radiat Oncol Biol Phys. 2012; 84: 1060-1070 Abstract Full Text Full Text PDF PubMed Scopus (214) Google Scholar ). However, a recent phase 3 randomized study (Radiation Therapy Oncology Group [RTOG] 0617) ( 2 Bradley JD, Paulus R, Komaki R, et al. Randomized phase 3 comparison of standard-dose (60 Gy) versus high-dose (74 Gy) conformal chemoradiotherapy ± cetuximab for stage IIIA/IIIB non-small cell lung cancer: preliminary findings on radiation dose in RTOG 0617. Abstract presented at the 53rd Annual Meeting of the American Society for Radiation Oncology; Oct 3, 2011; Miami Beach, FL. Google Scholar ) indicated that a higher radiation dose (74 Gy, BED 88.8 Gy) given with concurrent chemotherapy was associated with poorer median survival as compared with the conventional 60-Gy dose (BED 72 Gy). After the findings of RTOG 0617 were presented at the American Society for Radiation Oncology Annual Meeting in Miami in 2011, the RTOG set the “standard radiation dose” for use with concurrent chemotherapy for stage III NSCLC as 60 Gy for future studies.