Early Outcomes of Patients With Locally Advanced Non-small Cell Lung Cancer Treated With Intensity-Modulated Proton Therapy Versus Intensity-Modulated Radiation Therapy: The Mayo Clinic Experience

Abstract

There are very little data available comparing outcomes of intensity-modulated proton therapy (IMPT) to intensity-modulated radiation therapy (IMRT) in patients with locally advanced NSCLC (LA-NSCLC). Methods: Seventy-nine consecutively treated patients with LA-NSCLC underwent definitive IMPT (n Z 33 [42%]) or IMRT (n Z 46 [58%]) from 2016 to 2018 at our institution. Survival rates were calculated using the Kaplan-Meier method and compared with the log-rank test. Acute and subacute toxicities were graded based on Common Terminology Criteria for Adverse Events, version 4.03. Results: Median follow-up was 10.5 months (range, 1-27) for all surviving patients. Most were stage III (80%), received median radiation therapy (RT) dose of 60 Gy (range, 45-72), and had concurrent chemotherapy (65%). At baseline, the IMPT cohort was older (76 vs 69 years, P < .01), were more likely to be oxygen-dependent (18 vs 2%, P Z .02), and more often received reirradiation (27 vs 9%, P Z .04) than their IMRT counterparts. At 1 year, the IMPT and IMRT cohorts had similar overall survival (68 vs 65%, P Z .87), freedom from distant metastasis (71 vs 68%, P Z .58), and freedom from locoregional recurrence (86 vs 69%, P Z .11), respectively. On multivariate analyses, poorer pulmonary function and older age were associated with grade þ3 toxicities during and Sources of support: This work had no specific funding. Disclosures: Dr Sio provides strategic and scientific recommendations as a member of the Advisory Board and speaker for Novocure, Inc, which is not in any way associated with the content or disease site as presented in this manuscript. Dr Schild writes for UpToDate on various subjects related to radiation oncology. All other authors have no financial or nonfinancial interests to be declared.

Intensity‐modulated proton therapy (IMPT) interplay effect evaluation of asymmetric breathing with simultaneous uncertainty considerations in patients with non‐small cell lung cancer

“…This would potentially reduce the risk of radiation pneumonitis, pending clinical correlative studies in the future. 70,71 We developed this comprehensive plan robustness evaluation tool by simultaneously assessing the impact from both uncertainties and interplay effect. Different from the previous plan robustness evaluation approach using Monte Carlo simulation, 48 we demonstrated clinical applications of our current method on ten patients by comparing performance between 3D and 4D robustly optimized plans for non-small cell lung cancer.…”

“…However, compared to 3D robustly optimized plans, 4D robustly optimized plans delivered significantly lower mean doses to normal lung. This would potentially reduce the risk of radiation pneumonitis, pending clinical correlative studies in the future 70,71 …”

Dosimetric comparison of distal esophageal carcinoma plans for patients treated with small‐spot intensity‐modulated proton versus volumetric‐modulated arc therapies

“…Compared with IMRT, large‐spot IMPT using three beam angles (anteroposterior, right posterior oblique, and left posterior oblique) has been shown to deliver significantly lower lung D mean , lung V 5Gy[RBE] , V 10Gy[RBE] , and V 20Gy[RBE] , and heart D mean for distal esophageal cancer patients . Compared with large‐spot IMPT, small‐spot IMPT is considered to have two benefits: (a) sharper penumbra, which results from smaller spot sizes, can improve the sparing of organs‐at‐risk and lead to lower radiation toxicities; (b) a larger number of spots, which are needed to cover the same tumors compared to large‐spot IMPT, provides the TPS more freedom to compensate for the impact of uncertainties and interplay effects …”

Scanning Beam Proton Therapy versus Photon IMRT for Stage III Lung Cancer: Comparison of Dosimetry, Toxicity, and Outcomes

“…A comparison of results from select published proton patient series is included in Table 4. [22][23][24] Heart dose has been found to be correlated with survival in some clinical series of locally advanced NSCLC, and more stringent dose constraints have been recommended for the heart in recent years. 3,6 Our cohort of patients treated with proton therapy had significantly reduced mean heart dose compared with our cohort of patients treated with IMRT or VMAT.…”