Intensity-modulated radiation therapy, also known as IMRT, should be utilized for treatment of locally advanced Non-Small Cell Lung Cancer (NSCLC) to reduce the risk of severe pulmonary toxicity and radiation exposure to the heart.
This is a conclusion based of study results presented at the International Association for the Study of Lung Cancer 2023 World Conference on Lung Cancer, the world’s largest meeting dedicated to lung cancer and other thoracic malignancies being held September 9 – 12, 2023 in Singapore.  The meeting highlighted important advances in the long-term treatment of locally advances NSCLC.
The study was supported by Eli Lily and Company with additional grants from the National Cancer Institute (NCI).
“These findings (presented during the IASLC) provide a crucial contribution to the ongoing discourse on radiation techniques for NSCLC treatment, paving the way for more informed clinical decisions and improved patient outcomes.”-said Stephen G. Chun, MD, a Radiation Oncologist practicing at the MD Anderson Proton Center and West Houston Campus in Texas. As Director of Radiation Oncology Clinical Research for the MD Anderson Houston Area Locations, Chun was responsible for leading the expansion of the radiation oncology clinical trial program across the MD Anderson integrated satellite network and is supported by extramural grant funding from the National Institutes of Health as Principal Investigator.
During the 2023 World Conference on Lung Cancer Chun presented a comprehensive analysis of the phase III trial NRG Oncology-RTOG 0617, comparing intensity-modulated radiation therapy (IMRT) with 3D-conformal radiotherapy (3D-CRT) for long-term outcomes in NSCLC patients.
Beyond standard of care
Concurrent photon-based chemoradiation is an established standard of care for unresectable locally advanced non-small cell lung cancer (NSCLC), However, the choice between IMRT and 3D-CRT has remained contentious due to limited prospective data. As IMRT is more labor-intensive and costlier than 3D-CRT, it is important to justify IMRT utilization based on long-term prospective outcomes.
The secondary analysis of NRG Oncology-RTOG 0617, spanning a median follow-up of 5.2 years, involved 482 patients with locally advanced NSCLC. Among them, 47% received IMRT and 53% received 3D-CRT. The study examined a range of parameters including 5-year overall survival (OS), progression-free survival (PFS), time to local failure (LF), distant metastasis-free survival (DMFS), adverse events, and the development of second malignancies.
Chun’s findings revealed that both IMRT and 3D-CRT groups exhibited similar OS, PFS, time to LF, and DMFS rates at the 5-year mark. Notably, IMRT was associated with a more than two-fold reduction in severe pneumonitis (3.5% vs. 8.2%) compared to 3D-CRT, demonstrating a clear advantage in reducing pulmonary toxicity.
Further analysis indicated a continuous association between heart V20-60Gy and survival, with heart V40Gy less than 20% linked to significantly improved survival rates. Multivariable analysis underscored the significance of heart V40Gy greater to or equal to 20% in predicting worse survival. In contrast, lung V5Gy did not significantly impact survival. Rates of second malignancy development were similar between IMRT and 3D-CRT groups.
Preferred choice for the treatment of locally advanced NSCLC
Chun concluded that IMRT should be the preferred choice for locally advanced NSCLC to mitigate severe pulmonary toxicity and minimize radiation exposure to the heart. The study emphasized the importance of optimizing radiation planning, with special attention to reducing lung V20Gy and heart V20-60Gy, aiming for a heart V40Gy less than 20%. Encouragingly, the study did not find evidence that the low-dose bath (lung V5Gy) had a substantial impact on long-term survival or late severe toxicity.
According to Chum, these findings provide a crucial contribution to the ongoing discourse on radiation techniques for NSCLC treatment, paving the way for more informed clinical decisions and improved patient outcomes.
Based on an earlier analyses of the trial results, published in 2020, investigators concluded that a 60-Gy radiation dose with concurrent chemotherapy should remain the standard of care, with the OS rate being among the highest reported in the literature for stage III NSCLC.
High-Dose or Standard-Dose Radiation Therapy and Chemotherapy With or Without Cetuximab in Treating Patients With Newly Diagnosed Stage III Non-Small Cell Lung Cancer That Cannot Be Removed by Surgery – ClinicalTrials.gov ID NCT00533949
 Chun SG, Hu C, Choy H, Komaki RU, Timmerman RD, Schild SE, Bogart JA, Dobelbower MC, Bosch W, Kavadi VS, Narayan S, Iyengar P., Robinson CG, Rothman J, Raben A, Augspurger ME, McRae RM. Paulus R, Bradley JD. Long-Term Outcomes by Radiation Technique for Locally-Advanced Non-small Lung Cancer: A Secondary Analysis of NRG Oncology-RTOG 0617 at 5-years. Abstract OA17-04. Presented during the 2023, International Association for the Study of Lung Cancer 2023 World Conference on Lung Cancer.
 Bradley JD, Hu C, Komaki RR, Masters GA, Blumenschein GR, Schild SE, Bogart JA, Forster KM, Magliocco AM, Kavadi VS, Narayan S, Iyengar P, Robinson CG, Wynn RB, Koprowski CD, Olson MR, Meng J, Paulus R, Curran WJ Jr, Choy H. Long-Term Results of NRG Oncology RTOG 0617: Standard- Versus High-Dose Chemoradiotherapy With or Without Cetuximab for Unresectable Stage III Non-Small-Cell Lung Cancer. J Clin Oncol. 2020 Mar 1;38(7):706-714. doi: 10.1200/JCO.19.01162. Epub 2019 Dec 16. PMID: 31841363; PMCID: PMC7048161.
How to Cite
Peter Hofland, Ph.D 1
Long-term Outcomes of Radiation Techniques for the Treatment of Locally Advanced NSCLC – Onco Zine – The International Oncology Network, September 12, 2023.
1 Sunvalley Communication, LLC / Onco/Zine