Hypofractionated Intensity-Modulated Radiation Therapy for Stage III Non–Small-Cell Lung Cancer: A Retrospective Study

Abstract

The application of SBRT with its high dose per fraction has yielded superior local control in early-stage NSCLC. Concurrent chemoradiation is the standard of care for locally advanced NSCLC. Meta-analyses demonstrated this survival benefit is likely attributable to improvement in local tumor control. However, the feasibility of escalating dose per fraction to achieve improved local control and further be translated to survival benefit in treatment of stage III NSCLC remains an unanswered key question. We studied clinical outcomes after 15 fractions of 4 Gy over 3 weeks to stage III tumors in patients unsuitable for or unwilling to undergo surgery. Disease control and toxicity were preliminarily evaluated. A total of 50 consecutive patients with stage III (according to the 7th AJCC staging system) NSCLC underwent HypoRT with a dose prescription of 60 Gy in 15 fractions between August 2012 and December 2016 in our hospital. The majority (n=43, 86%) received combined chemotherapy/radiation, of whom 27 were treated with induction chemotherapy followed by radiation. Six cases (12%) received radiotherapy alone, and one (2%) received targeted therapy followed by radiation. No patients received concurrent chemotherapy. Involved field irradiation omitting elective nodal irradiation was performed. Patient characteristics were: male/female 43/7; median age 63 years (range 25-84). Pathological diagnosis consisted of: adenocarcinoma 20, squamous cell carcinoma 26, adenosquamous carcinoma 2, NSCLC NOS 2. By T- and N-stage classification, 7 patients were T1, 19 T2, 8 T3, and 16 T4; 3 patients were N0, 3 N1, 28 N2, and 16 N3. The volume of PTV ranged from 55 to 504 cm3 (median, 214 cm3). Clinical follow-up was generally performed every 3 months after treatment, with a diagnostic CT scan done at each visit. Overall survival was measured from the start of radiation until death or last follow-up. All toxicities were graded according to the CTCAE version 3.0. The time-to-event outcomes were calculated with the Kaplan-Meier method. Statistical analysis was performed using statistical software. There were 8 incidents (16%) of grade 3 radiation pneumonitis, of whom one patient died as a result of unexplained interstitial lung diseases with bilateral lung infiltrates in the absence of disease progression 7 months after RT. 14% of patients (n=7) experienced grade 3 esophagitis and 2% (n=1) had grade 4 esophageal toxicity. Two cases (4%) developed lobar bronchial collapse after RT. The 1-, 2-, 3-, and 5-year OS rates for all patients were 80%, 63%, 48% and 20%, respectively. Median OS was 36 months (95% CI: 19–53). The proposed schedule of 60 Gy in 3 weeks (15 fractions of 4 Gy) in patients with locally advanced NSCLC yielded impressive results. The increased risk of grade 3 or higher toxicity, especially esophagitis, is of potential concern. Additional work is needed to confirm the indication of this scheme and clinical benefit for patients with locally advanced NSCLC.