Impact of Intensity-Modulated Radiation Therapy Technique for Locally Advanced Non–Small-Cell Lung Cancer: A Secondary Analysis of the NRG Oncology RTOG 0617 Randomized Clinical Trial

Abstract

Purpose Although intensity-modulated radiation therapy (IMRT) is increasingly used to treat locally advanced non-small-cell lung cancer (NSCLC), IMRT and three-dimensional conformal external beam radiation therapy (3D-CRT) have not been compared prospectively. This study compares 3D-CRT and IMRT outcomes for locally advanced NSCLC in a large prospective clinical trial. Patients and Methods A secondary analysis was performed to compare IMRT with 3D-CRT in NRG Oncology clinical trial RTOG 0617, in which patients received concurrent chemotherapy of carboplatin and paclitaxel with or without cetuximab, and 60- versus 74-Gy radiation doses. Comparisons included 2-year overall survival (OS), progression-free survival, local failure, distant metastasis, and selected Common Terminology Criteria for Adverse Events (version 3) ≥ grade 3 toxicities. Results The median follow-up was 21.3 months. Of 482 patients, 53% were treated with 3D-CRT and 47% with IMRT. The IMRT group had larger planning treatment volumes (median, 427 v 486 mL; P = .005); a larger planning treatment volume/volume of lung ratio (median, 0.13 v 0.15; P = .013); and more stage IIIB disease (30.3% v 38.6%, P = .056). Two-year OS, progression-free survival, local failure, and distant metastasis-free survival were not different between IMRT and 3D-CRT. IMRT was associated with less ≥ grade 3 pneumonitis (7.9% v 3.5%, P = .039) and a reduced risk in adjusted analyses (odds ratio, 0.41; 95% CI, 0.171 to 0.986; P = .046). IMRT also produced lower heart doses ( P < .05), and the volume of heart receiving 40 Gy (V40) was significantly associated with OS on adjusted analysis ( P < .05). The lung V5 was not associated with any ≥ grade 3 toxicity, whereas the lung V20 was associated with increased ≥ grade 3 pneumonitis risk on multivariable analysis ( P = .026). Conclusion IMRT was associated with lower rates of severe pneumonitis and cardiac doses in NRG Oncology clinical trial RTOG 0617, which supports routine use of IMRT for locally advanced NSCLC.

Advances in radiotherapy techniques and delivery for non-small cell lung cancer: benefits of intensity-modulated radiation therapy, proton therapy, and stereotactic body radiation therapy

“…Of particular importance were questions on rates of completion of prescribed chemoradiation and concerns about volume of disease, adequacy of margins, and heart dose, with associated cardiac morbidity. A recent secondary analysis of this trial further demonstrated that IMRT was associated with lower cardiac doses and pulmonary toxicities (64). The cardiac dose, particularly V40, was further linked with OS on adjusted analysis (64).…”

“…A recent secondary analysis of this trial further demonstrated that IMRT was associated with lower cardiac doses and pulmonary toxicities (64). The cardiac dose, particularly V40, was further linked with OS on adjusted analysis (64). Notably, this was despite larger PTV, higher PTV/volume of lung ratio, and more stage IIIB disease in patients receiving IMRT (64).…”

“…The cardiac dose, particularly V40, was further linked with OS on adjusted analysis (64). Notably, this was despite larger PTV, higher PTV/volume of lung ratio, and more stage IIIB disease in patients receiving IMRT (64). Lastly, there was no difference in OS between IMRT and 3DCRT.…”

“…Most patients (81%) did not receive neoadjuvant chemotherapy. The authors demonstrated improved local control and OS with higher doses of radiation when patients were divided into three treatment groups (63)(64)(65)(66)(67)(68)(69)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(92)(93)(94)(95)(96)(97)(98)(99)(100)(101)(102)(103).…”

Post-operative radiation therapy in locally advanced non-small cell lung cancer and the impact of sequential versus concurrent chemotherapy

“…In the large meta-analysis published by the PORT meta-analysis group discussed above, 7 of the 9 trials delivered radiation via now outdated Cobalt-60 equipment with conventional techniques lacking CT scan based planning which has been shown to increase morbidity, and may have resulted in reduced tumor control. Further, although treatment was given via high-energy linear accelerator in ANITA, the majority of treatment was given before the era of highly conformal intensity modulated radiation therapy (IMRT) which greatly reduces the toxicity of radiation therapy in lung cancer (10,11).…”