Relationship between Treatment Plan Dosimetry, Toxicity, and Survival following Intensity-Modulated Radiotherapy, with or without Chemotherapy, for Stage III Inoperable Non-Small Cell Lung Cancer

SIMPLE SUMMARY: Various radiotherapy treatment methods are available for patients with stage III non-small-cell lung cancer (NSCLC). A multidisciplinary tumor board review is recommended to determine the best treatment strategy. In fit patients with inoperable tumors, concurrent chemoradiotherapy (cCRT) is preferred over sequential CRT (sCRT), due to better survival. Nonetheless, the use of cCRT in stage III NSCLC varies significantly, with concerns about treatment toxicity being a contributory factor. Many reports describing the relationship between overall survival, toxicity, and dosimetry in patients with locally advanced NSCLC are based on clinical trials, with strict criteria for patient selection, including good performance status, pulmonary function, etc. These trials have not always mandated the use of IMRT/VMAT. We therefore performed an institutional analysis to study the relationship between dosimetric parameters and overall survival and toxicity in patients with stage III NSCLC treated with IMRT/VMAT-based techniques in routine clinical practice. ABSTRACT: Concurrent chemoradiotherapy (cCRT) is the preferred treatment for stage III NSCLC because surgery containing multimodality treatment is often not appropriate. Alternatives, often for less fit patients, include sequential CRT and RT alone. Many reports describing the relationship between overall survival (OS), toxicity, and dosimetry are based on clinical trials, with strict criteria for patient selection. We performed an institutional analysis to study the relationship between dosimetric parameters, toxicity, and OS in inoperable patients with stage III NSCLC treated with (hybrid) IMRT/VMAT-based techniques in routine clinical practice. Eligible patients had undergone treatment with radical intent using cCRT, sCRT, or RT alone, planned to a total dose ≥ 50 Gy delivered in ≥15 fractions. All analyses were performed for two patient groups, (1) cCRT (n = 64) and (2) sCRT/RT (n = 65). The toxicity rate differences between the two groups were not significant, and OS was 29 and 17 months, respectively. For sCRT/RT, no dosimetric factors were associated with OS, whereas for cCRT, PTV-volume, esophagus V50 Gy, and contralateral lung V5 Gy were associated. cCRT OS was significantly lower in patients with esophagitis ≥ G2. The overall rate of ≥G3 pneumonitis was low (3%), and the rate of high-grade esophagitis the OS in this real-world patient population was comparable to those reported in clinical trials. Based on this hypothesis-generating data, more aggressive esophageal sparing merits consideration. Institutional auditing and benchmarking of the planning strategy, dosimetry, and outcome have an important role to play in the continuous quality improvement process.