Clinical Outcomes of Pencil Beam Scanning Proton Therapy in Locally Advanced Non-Small Cell Lung Cancer: Propensity Score Analysis

Abstract

This study compared the efficacy and safety of pencil beam scanning proton therapy (PBSPT) versus intensity-modulated (photon) radiotherapy (IMRT) in patients with stage III non-small cell lung cancer (NSCLC). We retrospectively reviewed 219 patients with stage III NSCLC who received definitive concurrent chemoradiotherapy between November 2016 and December 2018. Twenty-five patients (11.4%) underwent PBSPT (23 with single-field optimization) and 194 patients (88.6%) underwent IMRT. Rates of locoregional control (LRC), overall survival, and acute/late toxicities were compared between the groups using propensity score-adjusted analyses. Patients treated with PBSPT were older (median: 67 vs. 62 years) and had worse pulmonary function at baseline (both FEV1 and DLCO) compared to those treated with IMRT. With comparable target coverage, PBSPT exhibited superior sparing of the lung, heart, and spinal cord to radiation exposure compared to IMRT. At a median follow-up of 21.7 (interquartile range: 16.8–26.8) months, the 2-year LRC rates were 72.1% and 84.1% in the IMRT and PBSPT groups, respectively (p = 0.287). The rates of grade ≥ 3 esophagitis were 8.2% and 20.0% after IMRT and PBSPT (p = 0.073), respectively, while corresponding rates of grade ≥ 2 radiation pneumonitis were 28.9% and 16.0%, respectively (p = 0.263). PBSPT appears to be an effective and safe treatment technique even for patients with poor lung function, and it does not jeopardize LRC.

Prospective Study of Proton Therapy for Lung Cancer Patients with Poor Lung Function or Pulmonary Fibrosis

“…Our previous retrospective study showed that PBT was associated with tendencies of better survival and decreased incidences of severe treatment-related toxicity compared to X-ray RT in patients with IPF, but the differences were not statistically significant because of the limited number of patients [18]. Because of the limited capacity and waiting time for PBT, most patients with locally advanced NSCLC received IMRT in our institution [20]. Patients treated with PBT had worse pulmonary function at baseline compared to those treated with IMRT.…”

“…Breath-hold or respiratory gating was applied for patients with tumor motion ≥ 1 cm. The prescribed dose was 60 GyE or higher, and dose fractionation was individualized according to the tumor size, location, and stage [20,26]. For peripherally located, small-sized tumors, 60 GyE in 4 fractions was prescribed.…”

“…The median and mean CTVs were 133.4 cm 3 and 183.8 cm 3 , respectively. For patients with early-stage disease, 64 GyE in 8 fractions (n = 14, 25.9%) and 60 GyE in 4 fractions (n = 13, 24.1%) were the most frequently prescribed dose schedule, and 66 GyE in 30 fractions was the most frequently adopted dose schedule in patients with locally advanced disease (n = 10, 18.5%; 9 of them received CCRT) [20]. Overall, the median total dose of 64.0 GyE (range, 60.0-70.4 GyE) with a fraction dose of 7.0 GyE (range 2.2-15.0 GyE) was delivered.…”

Radiation induced lung injury (RILI) after postoperative intensity modulated proton therapy (IMPT) in a patient with stage III locally advanced lung adenocarcinoma: a case report

“…Radiation induced lung injury (RILI) after postoperative intensity modulated proton therapy (IMPT) in a patient with stage III locally advanced lung adenocarcinoma: a case report the risk of locoregional recurrence reached as evidently as 20-40% even after complete resection, adjuvant and postoperative chemotherapy (1,2). Postoperative radiation therapy (PORT) improved the locoregional recurrence survival (LRFS) in resected pIIIa-N2 NSCLC (3).…”

“…It has been demonstrated that postoperative chemotherapy can reduce distant metastasis for patients with positive lymph nodes. However, the risk of locoregional recurrence reached as evidently as 20–40% even after complete resection, adjuvant and postoperative chemotherapy ( 1 , 2 ). Postoperative radiation therapy (PORT) improved the locoregional recurrence survival (LRFS) in resected pIIIa-N2 NSCLC ( 3 ).…”