Clinical outcomes of carbon‐ion radiotherapy for locally advanced non‐small‐cell lung cancer

Abstract

The efficacy and safety of carbon‐ion radiotherapy (CIRT) for locally advanced non‐small‐cell lung cancer (LA‐NSCLC) remain unclear. We reported the clinical outcomes of CIRT for LA‐NSCLC. Data for 141 eligible patients who received CIRT between 1995 and 2015 were retrospectively analyzed. Local control (LC), locoregional control (LRC), progression‐free survival (PFS) and overall survival (OS) were calculated using the Kaplan‐Meier method. The median age was 75.0 years. Overall, 21 (14.9%), 57 (40.4%), 43 (30.5%) and 20 (14.2%) patients had T1, T2, T3 and T4 disease, respectively. Moreover, 51 (36.2%), 45 (31.9%), 40 (28.4%) and 5 (3.5%) patients had N0, N1, N2 and N3 disease, respectively. Furthermore, 34 (24.1%), 42 (29.8%), 45 (31.9%) and 20 (14.2%) patients had stages IIA, IIB, IIIA and ΙΙΙB disease, respectively. Overall, 62 (44.0%), 60 (42.6%), 8 (5.7%) and 11 (7.8%) patients had adenocarcinoma, squamous cell carcinoma, large cell carcinoma, and others, respectively. The median dose was 72.0 Gy (relative biological effectiveness). No patient received concurrent chemotherapy. Median follow‐up periods were 29.3 (1.6‐207.7) and 40.0 (10.7‐207.7) months for all patients and survivors, respectively. Two‐year LC, PFS and OS rates were 80.3%, 40.2% and 58.7%, respectively. Overall, 1 (0.7%), 5 (3.5%) and 1 (0.7%) patient developed Grades 4 (mediastinal hemorrhage), 3 (radiation pneumonitis) and 3 (bronchial fistula) toxicities, respectively. Multivariate analysis showed adenocarcinoma and N2/3 classification as significant poor prognosticators of PFS. CIRT is an effective treatment with acceptable toxicity for LA‐NSCLC, especially for elderly patients or patients with severe comorbidities who cannot be treated with surgery or chemoradiotherapy.

Estimating the Number of Patients Eligible for Carbon Ion Radiotherapy in the United States

“…The number of patients eligible for CIRT was then estimated for each disease site, based on inclusion criteria from previously published protocols and retrospective studies from Germany and Japan. The following disease sites were included: glioblastoma (based on the CLEOPATRA protocol, using CIRT as a boost [17]), hepatocellular carcinoma (PROMETHEUS-01 protocol/NCT01167374 [18]), cholangiocarcinoma (J-CROS study [19]), locally advanced pancreatic cancer (PHOENIX and CIPHER/NCT03536182 studies [9]), early and locally advanced non-small cell lung cancer (multiple retrospective studies [20][21][22][23]), localized prostate cancer (multiple retrospective studies [23][24][25][26]), soft tissue sarcomas (multiple retrospective studies [27,28]) and head and neck cancers, including salivary gland cancers (COSMIC protocol/NCT01154270 [29]), sinonasal cancers (NCT01220752 and retrospective studies [30]) and nasopharyngeal cancers (multiple retrospective studies [31,32]). Further histologic classification (such as adenoid cystic carcinoma or mucosal melanoma) of the general disease sites was possible given the limitations of the various databases used ( Table 1).…”

High-dose hypofractionated pencil beam scanning carbon ion radiotherapy for lung tumors: Dosimetric impact of different spot sizes and robustness to interfractional uncertainties

“…Excellent preliminary results are reported for peripheral early stage NSCLC treated with single-fraction CIRT [8]. The efficacy and safety of CIRT for locally advanced NSCLC were recently reported by Hayashi et al [9].…”

Carbon-ion radiotherapy for octogenarians with locally advanced non-small-cell lung cancer

“…in patients with LA-NSCLC [8,13]. The incidence of grade 3-4 toxicities ranged from 3.2% to 4.9%, and none of the evaluated patients experienced grade 5 toxicities.…”

“…CIRT has good dose-localizing properties [7], and thus can deliver a higher dose to the target volume than conventional photon radiotherapy while avoiding irradiation to the adjacent critical organs at risk, such as the lung, esophagus, trachea, and heart. CIRT alone can clinically achieve high local control (LC) rates with low toxicity [8][9][10][11][12][13]. Two published studies from our hospital have reported 2 year LC and overall survival (OS) rates of 83.5-93.1% and 51.9-68.0%, respectively, with CIRT alone 1 3…”