Kenneth D Westover1, Billy W Loo2, David E Gerber3, Puneeth Iyengar1, Hak Choy1, Maximilian Diehn2, Randy Hughes3, Joan Schiller3, Jonathan Dowell3, Zabi Wardak1, David Sher4, Alana Christie5, Xian-Jin Xie5, Irma Corona1, Akanksha Sharma6, Margaret E Wadsworth7, Robert Timmerman8. 1. Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas. 2. Department of Radiation Oncology, Stanford University, Stanford, California. 3. Division of Hematology-Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas. 4. Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois. 5. Department of Clinical Science, Southwestern Medical Center, Dallas, Texas. 6. School of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas. 7. Radiation Oncology of Mississippi, Jackson, Mississippi. 8. Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address: Robert.Timmerman@utsouthwestern.edu.
Abstract
PURPOSE: Treatment regimens for locally advanced non-small cell lung cancer (NSCLC) give suboptimal clinical outcomes. Technological advancements such as radiation therapy, the backbone of most treatment regimens, may enable more potent and effective therapies. The objective of this study was to escalate radiation therapy to a tumoricidal hypofractionated dose without exceeding the maximally tolerated dose (MTD) in patients with locally advanced NSCLC. METHODS AND MATERIALS: Patients with stage II to IV or recurrent NSCLC and Eastern Cooperative Oncology Group performance status of 2 or greater and not candidates for surgical resection, stereotactic radiation, or concurrent chemoradiation were eligible. Highly conformal radiation therapy was given to treat intrathoracic disease in 15 fractions to a total of 50, 55, or 60 Gy. RESULTS: Fifty-five patients were enrolled: 15 at the 50-Gy, 21 at the 55-Gy, and 19 at the 60-Gy dose levels. A 90-day follow-up was completed in each group without exceeding the MTD. With a median follow-up of 12.5 months, there were 93 grade ≥ 3 adverse events (AEs), including 39 deaths, although most AEs were considered related to factors other than radiation therapy. One patient from the 55- and 60-Gy dose groups developed grade ≥ 3 esophagitis, and 5, 4, and 4 patients in the respective dose groups experienced grade ≥ 3 dyspnea, but only 2 of these AEs were considered likely related to therapy. There was no association between fraction size and toxicity (P = .24). The median overall survival was 6 months with no significant differences between dose levels (P = .59). CONCLUSIONS: Precision hypofractionated radiation therapy consisting of 60 Gy in 15 fractions for locally advanced NSCLC is generally well tolerated. This treatment regimen could provide patients with poor performance status a potent alternative to chemoradiation. This study has implications for the cost effectiveness of lung cancer therapy. Additional studies of long-term safety and efficacy of this therapy are warranted.
PURPOSE: Treatment regimens for locally advanced non-small cell lung cancer (NSCLC) give suboptimal clinical outcomes. Technological advancements such as radiation therapy, the backbone of most treatment regimens, may enable more potent and effective therapies. The objective of this study was to escalate radiation therapy to a tumoricidal hypofractionated dose without exceeding the maximally tolerated dose (MTD) in patients with locally advanced NSCLC. METHODS AND MATERIALS: Patients with stage II to IV or recurrent NSCLC and Eastern Cooperative Oncology Group performance status of 2 or greater and not candidates for surgical resection, stereotactic radiation, or concurrent chemoradiation were eligible. Highly conformal radiation therapy was given to treat intrathoracic disease in 15 fractions to a total of 50, 55, or 60 Gy. RESULTS: Fifty-five patients were enrolled: 15 at the 50-Gy, 21 at the 55-Gy, and 19 at the 60-Gy dose levels. A 90-day follow-up was completed in each group without exceeding the MTD. With a median follow-up of 12.5 months, there were 93 grade ≥ 3 adverse events (AEs), including 39 deaths, although most AEs were considered related to factors other than radiation therapy. One patient from the 55- and 60-Gy dose groups developed grade ≥ 3 esophagitis, and 5, 4, and 4 patients in the respective dose groups experienced grade ≥ 3 dyspnea, but only 2 of these AEs were considered likely related to therapy. There was no association between fraction size and toxicity (P = .24). The median overall survival was 6 months with no significant differences between dose levels (P = .59). CONCLUSIONS: Precision hypofractionated radiation therapy consisting of 60 Gy in 15 fractions for locally advanced NSCLC is generally well tolerated. This treatment regimen could provide patients with poor performance status a potent alternative to chemoradiation. This study has implications for the cost effectiveness of lung cancer therapy. Additional studies of long-term safety and efficacy of this therapy are warranted.
Authors: Michelle Iocolano; Aaron T Wild; Margaret Hannum; Zhigang Zhang; Charles B Simone; Daphna Gelblum; Abraham J Wu; Andreas Rimner; Annemarie F Shepherd Journal: Acta Oncol Date: 2019-10-12 Impact factor: 4.089
Authors: N Rodríguez de Dios; X Sanz; P Foro; I Membrive; A Reig; A Ortiz; R Jiménez; M Algara Journal: Clin Transl Oncol Date: 2016-08-23 Impact factor: 3.405
Authors: Puneeth Iyengar; Elizabeth Zhang-Velten; Laurence Court; Kenneth Westover; Yulong Yan; Mu-Han Lin; Zhenyu Xiong; Mehul Patel; Douglas Rivera; Joe Chang; Mark Saunders; Anand Shivnani; Andrew Lee; Randall Hughes; David Gerber; Jonathan Dowell; Ang Gao; John Heinzerling; Ying Li; Chul Ahn; Hak Choy; Robert Timmerman Journal: JAMA Oncol Date: 2021-10-01 Impact factor: 33.006