Long-term clinical outcomes after 12-fractionated carbon-ion radiotherapy for localized prostate cancer.

There are no clinical reports of long-term follow-up after carbon-ion radiotherapy (CIRT) using a dose of 51.6 Gy (relative biological effectiveness [RBE]) in 12 fractions for localized prostate cancer, or of a comparison of clinical outcomes between passive and scanning beam irradiation. A total of 256 patients with localized prostate cancer who received CIRT at a dose of 51.6 Gy (RBE) in 12 fractions using two different beam delivery techniques (passive [n = 45] and scanning [n = 211]), and who were followed for more than 1 year, were analyzed. The biochemical relapse-free (bRF) rate was defined by the Phoenix definition, and the actuarial toxicity rates were evaluated using the Kaplan-Meier method. Of the 256 patients, 41 (16.0%), 111 (43.4%), and 104 (40.6%) were classified as low, intermediate, and high risk, respectively, after a median follow-up of 7.0 (range 1.1-10.4) years. Androgen deprivation therapy was performed in 212 patients (82.8%). The 5-year bRF rates of the low-, intermediate-, and high-risk patients were 95.1%, 90.9%, and 91.1%, respectively. The 5-year rates of grade 2 late gastrointestinal and genitourinary toxicities in all patients were 0.4% and 6.3%, respectively. No grade ≥3 toxicities were observed. There were no significant differences in the rates of bRF or grade 2 toxicities in patients who received passive irradiation versus scanning irradiation. Our long-term follow-up results showed that a CIRT regimen of 51.6 Gy (RBE) in 12 fractions for localized prostate cancer yielded a good therapeutic outcome and low toxicity rates irrespective of the beam delivery technique.

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

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.

Feasibility of carbon-ion radiotherapy for re-irradiation of locoregionally recurrent, metastatic, or secondary lung tumors.

Intrathoracic recurrence after carbon-ion radiotherapy for primary or metastatic lung tumors remains a major cause of cancer-related deaths. However, treatment options are limited. Herein, we report on the toxicity and efficacy of re-irradiation with carbon-ion radiotherapy for locoregionally recurrent, metastatic, or secondary lung tumors. Data of 95 patients with prior intrathoracic carbon-ion radiotherapy who were treated with re-irradiation with carbon-ion radiotherapy at our institution between 2006 and 2016 were retrospectively analyzed. Seventy-three patients (76.8%) had primary lung tumors and 22 patients (23.2%) had metastatic lung tumors. The median dose of initial carbon-ion radiotherapy was 52.8 Gy (relative biological effectiveness) and the median dose of re-irradiation was 66.0 Gy (relative biological effectiveness). None of the patients received concurrent chemotherapy. The median follow-up period after re-irradiation was 18 months. In terms of grade ≥3 toxicities, one patient experienced each of the following: grade 5 bronchopleural fistula, grade 4 radiation pneumonitis, grade 3 chest pain, and grade 3 radiation pneumonitis. The 2-year local control and overall survival rates were 54.0% and 61.9%, respectively. In conclusion, re-irradiation with carbon-ion radiotherapy was associated with relatively low toxicity and moderate efficacy. Re-irradiation with carbon-ion radiotherapy might be an effective treatment option for patients with locoregionally recurrent, metastatic, or secondary lung tumors.

Changes in arrhythmogenic properties and five-year prognosis after carbon-ion radiotherapy in patients with mediastinum cancer.

INTRODUCTION: Carbon-ion irradiation of rabbit hearts has improved left ventricular conduction abnormalities through upregulation of gap junctions. However, to date, there has been no investigation on the effect of carbon-ion irradiation on electrophysiological properties in human. We investigated this effect in patients with mediastinum extra-cardiac cancer treated with carbon-ion radiotherapy that included irradiating the heart. METHODS AND RESULTS: In April-December 2009, eight patients were prospectively enrolled (including two male, aged 72.5 ± 13.0 years). They were treated with 44-72 Gray equivalent (GyE), with their hearts exposed to 1.3-19.1 GyE. High-resolution ambulatory electrocardiography was performed before and after radiotherapy to investigate arrhythmic events, late potentials (LPs), and heart rate variability. Five patients had pre-existing premature ventricular contraction (PVC)/atrial contraction (PAC) or paroxysmal atrial fibrillation (PAF)/AF; after irradiation, this improved in four patients with PVC/PAF/AF and did not deteriorate in one patient with PAC. Ventricular LP findings did not deteriorate and improved in one patient. In eight cases with available atrial LP findings, there was no deterioration, and two patients showed improvements. The low frequency/high frequency ratio of heart rate variability improved or did not deteriorate in the six patients who received radiation exposure to the bilateral stellate ganglions. During the five-year follow-up for the prognosis, six of the eight patients died because of cancer; there was no history of hospitalization for cardiac events. CONCLUSION: Although this preliminary study has several limitations, carbon-ion beam irradiation to the heart is not immediately cardiotoxic and demonstrates consistent signals of arrhythmia reduction.

A prospective nonrandomized phase I/II study of carbon ion radiotherapy in a favorable subset of locally advanced non-small cell lung cancer (NSCLC).

BACKGROUND: Although concurrent chemoradiotherapy (CCRT) has become the standard approach for unresectable locally advanced non-small cell lung cancer (LA-NSCLC), most patients are not candidates for this treatment because of comorbidities. We evaluated the safety and efficacy of carbon ion radiotherapy (CIRT) in LA-NSCLC patients. METHODS: Patients with stage IIA to IIIA (UICC 7th edition) LA-NSCLC were enrolled in a sequential phase I/II trial. For a phase I dose escalation study, the total prescribed dose was increased by 4 Gray equivalents (GyE) in 2 steps, from 68 to 72 GyE and then to 76 GyE, using 16 fractions over 4 weeks. After determining the recommended dose, the phase II trial was started in an expanded cohort. RESULTS: Of the 36 patients treated in phase I, 2 grade 3 adverse events (radiation pneumonitis and tracheoesophageal fistula) were observed in the 76 GyE group. Accordingly, for phase II, the next consecutive 26 patients were treated with 72 GyE, with no grade 3 to 5 toxicities resulting. A total of 62 eligible patients were recruited. The majority of patients (49 of 62) were N0 or N1 patients, and the rest (13 of 62) were single-station N2 patients. The median follow-up period was 25.2 months. The 2-year local control rate (LCR) and overall survival (OS) for the entire cohort were 93.1% and 51.9%, respectively. In particular, patients with cT3-4N0 had an excellent prognosis; the 2-year OS and LCR were 69.3% and 100%, respectively. CONCLUSIONS: Short-course CIRT monotherapy shows promise as an effective nonsurgical treatment for inoperable LA-NSCLC.

Modeling of the resensitization effect on carbon-ion radiotherapy for stage I non-small cell lung cancer.

Objective. To investigate the effect of redistribution and reoxygenation on the 3-year tumor control probability (TCP) of patients with stage I non-small cell lung cancer (NSCLC) treated with carbon-ion radiotherapy.Approach. A meta-analysis of published clinical data of 233 NSCLC patients treated by carbon-ion radiotherapy under 18-, 9-, 4-, and single-fraction schedules was conducted. The linear-quadratic (LQ)-based cell-survival model incorporating the radiobiological 5Rs, radiosensitivity, repopulation, repair, redistribution, and reoxygenation, was developed to reproduce the clinical TCP data. Redistribution and reoxygenation were regarded together as a single phenomenon and termed 'resensitization' in the model. The optimum interval time between fractions was investigated for each fraction schedule using the determined model parameters.Main results.The clinical TCP data for 18-, 9-, and 4-fraction schedules were reasonably reproduced by the model without the resensitization effect, whereas its incorporation was essential to reproduce the TCP data for all fraction schedules including the single fraction. The curative dose for the single-fraction schedule was estimated to be 49.0 Gy (RBE), which corresponds to the clinically adopted dose prescription of 50.0 Gy (RBE). For 18-, 9-, and 4-fraction schedules, a 2-to-3-day interval is required to maximize the resensitization effect during the time interval. In contrast, the single-fraction schedule cannot benefit from the resensitization effect, and the shorter treatment time is preferable to reduce the effect of sub-lethal damage repair during the treatment.Significance.The LQ-based cell-survival model incorporating the radiobiological 5Rs was developed and used to evaluate the effect of the resensitization on clinical results of NSCLC patients treated with hypo-fractionated carbon-ion radiotherapy. The incorporation of the resensitization into the cell-survival model improves the reproducibility to the clinical TCP data. A shorter treatment time is preferable in the single-fraction schedule, while a 2-to-3-day interval between fractions is preferable in the multi-fraction schedules for effective treatments.

Five-Year Survival Outcomes After Carbon-Ion Radiotherapy for Operable Stage I NSCLC: A Japanese National Registry Study (J-CROS-LUNG).

INTRODUCTION: The standard therapy for stage I NSCLC is surgery, but some operable patients refuse this option and instead undergo radiotherapy. Carbon-ion radiotherapy (CIRT) is a type of radiotherapy. The Japanese prospective nationwide registry study on CIRT began in 2016. Here, we analyzed real-world clinical outcomes of CIRT for operable patients with stage I NSCLC. METHODS: All patients with operable stage I NSCLC treated with CIRT in Japan between 2016 and 2018 were enrolled. The dose fractionations for CIRT were selected from several options approved by the Japanese Society for Radiation Oncology. CIRT was delivered to the primary tumor, not to lymph nodes. RESULTS: The median follow-up period was 56 months. Among 136 patients, 117 (86%) had clinical stage IA NSCLC and 19 (14%) had clinical stage IB NSCLC. There were 50 patients (37%) diagnosed clinically without having been diagnosed histologically. Most tumors (97%) were located in the periphery. The 5-year overall survival, cause-specific survival, progression-free survival, and local control rate were 81.8% (95% confidence interval [CI]: 75.1-89.2), 91.2% (95% CI: 86.0-96.8), 65.9% (95% CI: 58.2-74.6), and 95.8% (95% CI: 92.3-99.5), respectively. Multivariate analysis identified age as a significant factor for overall survival (p = 0.018), whereas age and consolidation/tumor ratio (p = 0.010 and p = 0.004) were significant factors for progression-free survival. There was no grade 4 or higher toxicity. Grade 3 radiation pneumonitis occurred in one patient. CONCLUSIONS: This study reports the long-term outcomes of CIRT for operable NSCLC in the real world. CIRT for operable patients has been found to have favorable outcomes, with tolerable toxicity.

Safety and Efficacy of Single-Fraction Carbon-Ion Radiotherapy for Early-Stage Lung Cancer with Interstitial Pneumonia.

Patients with lung cancer complicated by interstitial pneumonia (IP) often lose treatment options early owing to acute exacerbation of IP concerns. Carbon-ion radiotherapy (CIRT) can provide superior tumor control and low toxicity at high dose concentrations. We conducted a retrospective analysis of the efficacy and tolerability of a single-fraction CIRT using 50 Gy for IP-complicated lung cancer. The study included 50 consecutive patients treated between April 2013 and September 2022, whose clinical stage of lung cancer (UICC 7th edition) was 1A:1B:2A:2B = 32:13:4:1. Of these, 32 (64%) showed usual interstitial pneumonia patterns. With a median follow-up of 23.5 months, the 3-year overall survival (OS), cause-specific survival, and local control rates were 45.0, 75.4, and 77.8%, respectively. The median lung V5 and V20 were 10.0 and 5.2%, respectively (mean lung dose, 2.6 Gy). The lung dose, especially lung V20, showed a strong association with OS (p = 0.0012). Grade ≥ 2 pneumonia was present in six patients (13%), including two (4%) with suspected grade 5. CIRT can provide a relatively safe and curative treatment for patients with IP-complicated lung cancer. However, IP increases the risk of severe radiation pneumonitis, and further studies are required to assess the appropriate indications.

Long-Term Outcomes of Ablative Carbon-Ion Radiotherapy for Central Non-Small Cell Lung Cancer: A Single-Center, Retrospective Study.

The aim of this study is to assess the efficacy and safety of ablative carbon ion radiotherapy (CIRT) for early stage central non-small cell lung cancer (NSCLC). We retrospectively reviewed 30 patients who had received CIRT at 68.4 Gy in 12 fractions for central NSCLC in 2006-2019. The median age was 75 years, and the median Karnofsky Performance Scale score was 90%. All patients had concomitant chronic obstructive pulmonary disease, and 20 patients (67%) were considered inoperable. In DVH analysis, the median lung V5 and V20 were 15.5% and 10.4%, and the median Dmax, D0.5cc, D2cc of proximal bronchial tree was 65.6 Gy, 52.8 Gy, and 10.0 Gy, respectively. At a median follow-up of 43 months, the 3-year overall survival, disease-specific survival, and local control rates were 72.4, 75.8, and 88.7%, respectively. Two patients experienced grade 3 pneumonitis, but no grade ≥3 adverse events involving the mediastinal organs occurred. Ablative CIRT is feasible and effective for central NSCLC and could be considered as a treatment option, especially for patients who are intolerant of other curative treatments.

Proton and carbon ion radiotherapy for operable early-stage lung cancer; a prospective nationwide registry.

BACKGROUND AND PURPOSE: To investigate the toxicity and survival outcomes of proton and carbon ion radiotherapy for patients with operable early-stage lung cancer who are eligible for lobectomy. MATERIALS AND METHODS: This multicenter nationwide prospective cohort study included patients with operable early-stage lung cancer. Proton and carbon ion radiotherapy was performed according to the schedule stipulated in the unified treatment policy. Progression-free survival (PFS), overall survival (OS) and treatment-related toxicities were evaluated. RESULTS: A total of 274 patiets were enrolled and included in efficacy and safety analyses. The most common tumor type was adenocarcinoma (44 %), while 105 cases (38 %) were not histologically confirmed or diagnosed clinically. Overall, 250 (91 %) of the 274 patients had tumors that were peripherally situated, while 138 (50 %) and 136 (50 %) patients were treated by proton and carbon ion radiotherapy, respectively. The median follow-up time for all censored patients was 42.8 months (IQR 36.7-49.0). Grade 3 or severe treatment-related toxicity was observed in 4 cases (1.5 %). Three-year PFS was 80.5 % (95 % CI: 75.7 %-85.5 %) and OS was 92.5 % (95 % CI: 89.3 %-95.8 %). Pathological confirmation and clinical stage were factors significantly associated with PFS, while tumor location and particle-ion type were not. Meanwhile, clinical stage was significantly associated with OS, but pathological confirmation, tumor location, and particle-ion type were not. CONCLUSIONS: Particle therapy for operable early-stage lung cancer resulted in excellent 3-year OS and PFS in each subset. In this disease context, proton and carbon ion beam therapies are feasible alternatives to curative surgery.

Outcomes of carbon ion radiotherapy compared with segmentectomy for ground glass opacity-dominant early-stage lung cancer.

PURPOSE: This study aimed to compare the outcomes of patients with ground-grass opacity (GGO)-dominant non-small cell lung cancer (NSCLC) who were treated with carbon ion radiotherapy (CIRT) versus segmentectomy. METHODS: A retrospective review of medical records was conducted. The study included 123 cases of clinical stage 0/IA peripheral NSCLC treated with single-fraction CIRT from 2003 to 2012, 14 of which were determined to be GGO-dominant and were assigned to CIRT group. As a control, 48 consecutive patients who underwent segmentectomy for peripheral GGO-dominant clinical stage IA NSCLC were assigned to segmentectomy group. RESULTS: The patients in CIRT group, compared with segmentectomy group, were significantly older (75 ± 7.2 vs. 65 ± 8.2 years, P = 0.000660), more likely to be male (13/14 vs. 22/48, P = 0.00179), and had a lower forced vital capacity (91 ± 19% vs. 110 ± 13%, P = 0.0173). There was a significant difference in the 5-years overall survival rate (86% vs. 96%, P = 0.000860), but not in the 5-years disease-specific survival rate (93% vs. 98%, P = 0.368). DISCUSSION: Compared with segmentectomy, CIRT may be an alternative option for patients with early GGO-dominant NSCLC who are poor candidates for, or who refuse, surgery.

Clinical results of carbon ion radiotherapy for inoperable stage I non-small cell lung cancer: A Japanese national registry study (J-CROS-LUNG).

BACKGROUND AND PURPOSE: Radiotherapy is a standard treatment for inoperable stage I non-small cell lung cancer (NSCLC), and carbon-ion radiation therapy (CIRT) may be used for such treatment. Although CIRT for stage I NSCLC has demonstrated favorable outcomes in previous reports, the reports covered only single-institution studies. We conducted a prospective nationwide registry study including all CIRT institutions in Japan. MATERIALS AND METHODS: Ninety-five patients with inoperable stage I NSCLC were treated by CIRT between May 2016 and June 2018. The dose fractionations for CIRT were selected from several options approved by the Japanese Society for Radiation Oncology. RESULTS: The median patient age was 77 years. Comorbidity rates for chronic obstructive pulmonary disease and interstitial pneumonia were 43% and 26%, respectively. The most common schedule for CIRT was 60 Gy (relative biological effectiveness (RBE)) in four fractions, and the second most common was 50 Gy (RBE) in one fraction. The 3-year overall survival, cause-specific survival, and local control rates were 59.3%, 77.1%, and 87.3%, respectively. Female sex and ECOG performance status of 0-1 were favorable prognostic factors for overall survival in a multivariate analysis. No grade 4 or higher adverse event was observed. The 3-year cumulative incidence of grade 2 or higher radiation pneumonitis was 3.2%. The risk factors for grade 2 or higher radiation pneumonitis were a force expiratory volume in 1 second (FEV1) of <0.9 L and a total does of ≥ 67 Gy(RBE). CONCLUSION: This study provides real-world treatment outcomes of CIRT for inoperable. stage I NSCLC in Japan.

Clinical results of carbon-ion radiotherapy for stage I non-small cell lung cancer with concomitant interstitial lung disease: a Japanese national registry study (J-CROS-LUNG).

Anti-cancer treatments for lung cancer patients with interstitial lung disease (ILD) are challenging. The treatment options for ILD are often limited because of concerns that treatments can cause acute exacerbation (AE) of ILD. This study aimed to analyze the outcomes of carbon-ion radiotherapy (CIRT) for stage I non-small cell lung cancer (NSCLC) with ILD, using a multi-institutional registry. Patients with ILD who received CIRT for stage I NSCLC in CIRT institutions in Japan were enrolled. The indication for CIRT was determined by an institutional multidisciplinary tumor board, and CIRT was performed in accordance with institutional protocols. Thirty patients were eligible. The median follow-up duration was 30.3 months (range, 2.5-58 months), and the total dose ranged from 50 Gy (relative biological effectiveness [RBE]) to 69.6 Gy (RBE), and five different patterns of fractionation were used. The beam delivery method was passive beam in 19 patients and scanning beam in 11 patients. The 3-year overall survival (OS), cause-specific survival, disease-free survival (DFS) and local control (LC) rates were 48.2%, 62.2%, 41.2% and 88.1%, respectively. Grade > 2 radiation pneumonitis occurred in one patient (3.3%). In conclusion, CIRT is a safe treatment modality for stage I NSCLC with concomitant ILD. CIRT is a safe and feasible treatment option for early lung cancer in ILD patients.

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

PURPOSE: The clinical significance of carbon-ion radiotherapy (CIRT) for octogenarians with locally advanced non-small-cell lung cancer (LA-NSCLC) remains unclear. We aimed to evaluate the clinical outcomes of CIRT alone for octogenarians with LA-NSCLC. MATERIALS AND METHODS: We evaluated 32 patients who underwent CIRT alone between 1997 and 2015. The median age was 82.0 years (range, 80-88 years). In terms of clinical stage (UICC 7th edition), 7 (21.9%), 10 (31.3%), 11 (34.4%), and 4 (12.5%) patients had stage IIA, IIB, IIIA, and ΙΙΙB disease, respectively. The median CIRT dose was 72.0 Gy (relative biological effectiveness), and the median follow-up period was 33.1 months. RESULTS: All patients successfully completed CIRT. Regarding grade ≥ 2 toxicities, 1 (3.1%), 3 (9.4%), and 4 (0.7%) patients developed grade 3 radiation pneumonitis, grade 2 radiation pneumonitis, and grade 2 dermatitis, respectively. No grade ≥ 4 toxicities were observed. The 2 year LC, PFS, and OS rates were 83.5%, 46.7%, and 68.0%, respectively. CONCLUSION: CIRT alone is safe and effective for octogenarians with LA-NSCLC.

The Risk Factors for Radiation Pneumonitis After Single-Fraction Carbon-Ion Radiotherapy for Lung Cancer or Metastasis.

There are no studies on the risk factors of radiation pneumonitis (RP) after carbon-ion radiotherapy at a dose of 50 Gy (relative biological effectiveness (RBE)) in a single fraction. The objective of this study was to identify factors associated with RP after radiotherapy, including dose-volume parameters. Ninety-eight patients without a history of thoracic radiotherapy who underwent treatment for solitary lung tumors between July 2013 and April 2016 were retrospectively analyzed. Treatment was planned using Xio-N. The median follow-up duration was 53 months, and the median clinical target volume was 32.3 mL. Three patients developed grade 2 RP, and one patient developed grade 3 interstitial pneumonitis. None of the patients developed grade 4 or 5 RP. The dose-volume parameters of the normal lung irradiated at least with 5-30 Gy (RBE), and the mean lung dose was significantly lower in patients with grade 0-1 RP than in those with grade 2-3 RP. Pretreatment with higher SP-D and interstitial pneumonitis were significant factors for the occurrence of symptomatic RP. The present study showed a certain standard for single-fraction carbon-ion radiotherapy that does not increase the risk of RP; however, further validation studies are needed.

[Particle therapy--carbon ion radiotherapy for non-small cell lung cancer].

Carbon ion radiotherapy (CIRT) is a promising modality because of its excellent dose localization and high biological effect on the tumor. Our clinical trials led us to conclude that irradiation with heavy particle beams, notably carbon ion beams, offers a significant potential for improving tumor control without increasing toxicity risks. In lung cancer treatment, between 1994 and 1999, a phase I/II study of the treatment for stage I non-small cell lung cancer by CIRT was first conducted using a dose escalation method to determine the optimal dose. Furthermore, definite tumor control was also confirmed by the autopsies of CIRT-treated patients and in cases treated by surgery. In the present study, a phase II clinical trial and a phase I/II dose escalation clinical trial are reported.

Safety and Efficacy of Carbon-ion Radiotherapy Alone for Stage III Non-small Cell Lung Cancer.

BACKGROUND/AIM: We evaluated the efficacy and safety of carbon-ion radiotherapy (CIRT) alone for Stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Data of 65 patients (median age=73 years) with Stage III NSCLC who underwent CIRT alone in the QST Hospital, Chiba, Japan, between 1997 and 2015 were retrospectively analysed. The median dose was 72.0 Gy (relative biological effectiveness). RESULTS: The median follow-up was 27.6 months (range=1.6-207.7 months). Two-year local control, progression-free survival (PFS), and overall survival (OS) rates were 73.9%, 38.6%, and 54.9%, respectively. Overall, 1 (2%), 4 (6%), and 1 (2%) patient developed Grade 4 (mediastinal haemorrhage), Grade 3 (radiation pneumonitis), and Grade 3 (bronchial fistula) toxicities, respectively. On univariate analysis, clinical T and N stage and CIRT timing were significant predictors of PFS and OS; clinical target volume was a significant predictor of PFS. CONCLUSION: CIRT alone is effective with acceptable toxicity for Stage III NSCLC.

Long Term Results of Single-Fraction Carbon-Ion Radiotherapy for Non-small Cell Lung Cancer.

BACKGROUND: The purpose of the present study was to evaluate the efficacy and safety of single-fraction carbon-ion radiotherapy (CIRT) in patients with non-small cell lung cancer. METHODS: Patients with histologically confirmed non-small cell lung cancer, stage T1-2N0M0, and treated with single-fraction CIRT (50Gy (relative biological effectiveness)) between June 2011 and April 2016 were identified in our database and retrospectively analyzed. Toxicity was evaluated using the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: The study included 57 patients, 22 (38.6%) of whom had inoperable cancer. The median age was 75 years (range: 42-94 years), and the median follow-up time was 61 months (range: 6-97 months). The 3- and 5-year overall survival rates were 91.2% and 81.7%, respectively. All survivors were followed up for more than three years. The 3- and 5-year local control rates were 96.4% and 91.8%, respectively. No case of ≥ grade 2 pneumonitis was recorded. CONCLUSIONS: This study suggests that single-fraction CIRT for T1-2N0M0 non-small cell lung cancer patients is feasible and can be considered as one of the treatment choices, especially in medically inoperable patients.

Carbon ion radiotherapy for elderly patients 80 years and older with stage I non-small cell lung cancer.

Surgical resection is the standard treatment for stage I non-small cell lung cancer (NSCLC). However, elderly patients with NSCLC often suffer from other conditions, such as chronic obstructive pulmonary disease (COPD) or cardiovascular disease, and are not suitable candidates for surgery. Different modalities to treat stage I NSCLC have been developed, such as stereotactic radiotherapy (SRT), proton beam radiotherapy and carbon ion radiotherapy (CIRT). Between April 1999 and November 2003, we treated 129 patients with stage I NSCLC using CIRT. In this study, we focused on 28 patients aged 80 years and older who underwent CIRT, and analyzed the effectiveness of CIRT in treating their lung cancer and the impact on their activity of daily life (ADL). The 5-year local control rate for these patients was 95.8%, and the 5-year overall survival rate was 30.7%, but there were no patients who started home oxygen therapy or had decreased ADL. Our data demonstrate that CIRT was effective in treating elderly patients with stage I NSCLC.

Carbon-ion re-irradiation for recurrences after initial treatment of stage I non-small cell lung cancer with carbon-ion radiotherapy.

PURPOSE: To investigate carbon-ion radiotherapy (CIRT) for in-field recurrence of stage I non-small cell lung cancer (NSCLC) initially treated with CIRT. MATERIALS AND METHODS: From January 2007 to March 2014, patients initially treated for stage I NSCLC with CIRT and relapsed in-field were candidates. Overall survival (OS) rate, local control (LC) rate, progressive free survival (PFS) rate, dose to the lungs and skin, and adverse effects were analyzed. RESULTS: Twenty-nine patients were eligible. Median age at re-irradiation was 74years (range 53-90). Median observation period from the first day of re-irradiation was 29months (4-88months). Median prescribed dose was 46.0Gy (RBE) as initial treatment and 66.0Gy (RBE) in 12 fractions as re-irradiation. Two-year OS, LC, and PFS rates after re-irradiation were 69.0% (95% CI: 50.3-83.0), 66.9% (95% CI: 47.5-81.9), and 51.7% (95% CI: 34.1-68.9). Median skin maximum dose was 53.8Gy (RBE) (range 4.4-103.1) and median of mean lung dose was 7.3Gy (RBE) (range 2.6-14.0). There were no severer than grade 2 adverse effects except one (3.4%) grade 3 bacterial pneumonia, which was not considered radiation-induced. CONCLUSION: CIRT for stage I NSCLC local recurrence is an acceptable definitive re-treatment.