Background: Carbon ion Radiotherapy for prostate cancer is widely used, however reports are limited from single institute or short follow up. We performed a prospective observational study (GUNMA0702) to evaluate the feasibility and efficacy of carbon ion radiotherapy for localized and locally advanced prostate cancer. Methods: Between June 2010 and August 2013, 304 patients with localized prostate cancer were treated, with a median follow-up duration of 60 months. All patients received carbon ion radiotherapy with 57.6 Gy (RBE) in 16 fractions over 4 weeks. Hormonal therapy was given according to the risk group. Toxicity was reported according to the Common Toxicity Criteria for Adverse Event, Version 4.0 by the National Cancer Institute. Results: The overall 5-year biochemical relapse-free rate was 92.7%, with rates of 91.7, 93.4, and 92.0% in low-risk, intermediate-risk, and high-risk patients, respectively. The 5-year local control and overall survival rates were 98.4 and 96.6%, respectively. Acute grade 3 or greater toxicity was not observed. Late grade 2 and grade 3 genitourinary and gastrointestinal toxicity rates were 9 and 0.3%, and 0.3, and 0%, respectively. Conclusions: The present protocol of carbon ion radiotherapy for prostate cancer provided low genitourinary and gastrointestinal toxicity with good biochemical control within 5 years. Trial registration: University Medical Information Network Clinical Trial Registry number: UMIN000003827.

The treatment strategy of central lung tumors is not established. Intraluminal brachytherapy (ILBT) is widely used for palliative treatment of endobronchial tumors, however, it is also a promising option for curative treatment with limited data. This study evaluates the results after ILBT for endobronchial carcinoma. Sixteen-endobronchial carcinoma of 13 patients treated with ILBT in curative intent for 2000 to 2008 were retrospectively reviewed. ILBT using high dose rate 192 iridium thin wire system was performed with 5 Gy/fraction at mucosal surface. The patient age ranged from 57 to 82 years old with median 75 years old. The 16 lesions consisted of 13 central endobronchial cancers including 7 roentgenographically occult lung cancers and 3 of tracheal cancers. Of them, 10 lesions were treated with ILBT of median 20 Gy combined with external beam radiation therapy of median 45 Gy and 6 lesions were treated with ILBT alone of median 25 Gy. Median follow-up time was 32.5 months. Two-year survival rate and local control rate were 92.3% and 86.2%, respectively. Local recurrences were observed in 2 lesions. Three patients died due to lung cancer (1 patient) and intercurrent disease (2 patients). Complications greater than grade 2 were not observed except for one grade 3 dyspnea. ILBT combined with or without EBRT might be a curative treatment option in inoperable endobronchial carcinoma patients with tolerable complication.

Lung cancer is a leading cause of cancer-related deaths worldwide. Radiotherapy is an essential treatment modality for inoperable non-small cell lung cancer (NSCLC). Stereotactic body radiotherapy (SBRT) is the standard treatment for early-stage NSCLC because of its favorable local control (LC) compared to conventional radiotherapy. Carbon ion radiotherapy (CIRT) is a kind of external beam radiotherapy characterized by a steeper dose distribution and higher biological effectiveness. Several prospective studies have shown favorable outcomes. However, there is no direct comparison study between CIRT and SBRT to determine their benefits in the management of early-stage NSCLC. Thus, we conducted a retrospective, single-institutional, and contemporaneous comparison study, including propensity score-adjusted analyses, to clarify the differences in oncologic outcomes. The 3-year overall survival (OS) was 80.1% in CIRT and 71.6% in SBRT (p = 0.0077). The 3-year LC was 87.7% in the CIRT group and 79.1% in the SBRT group (p = 0.037). Multivariable analyses showed favorable OS and LC in the CIRT group (hazard risk [HR] = 0.41, p = 0.047; HR = 0.30, p = 0.040, respectively). Log-rank tests after propensity score matching and Cox regression analyses using propensity score confirmed these results. These data provided a positive efficacy profile of CIRT for early-stage NSCLC.

Lung cancer is a leading cause of cancer-related deaths worldwide despite advances in treatment. In the past few decades, radiotherapy has achieved outstanding technical advances and is being widely used as a definitive, prophylactic, or palliative treatment of patients with lung cancer. The anti-tumor effects of radiotherapy are considered to result in DNA damage in cancer cells. Moreover, recent evidence has demonstrated another advantage of radiotherapy: the induction of anti-tumor immune responses, which play an essential role in cancer control. In contrast, radiotherapy induces an immunosuppressive response. These conflicting reactions after radiotherapy suggest that maximizing immune response to radiotherapy by combining immunotherapy has potential to achieve more effective anti-tumor response than using each alone. Immune checkpoint molecules, such as cytotoxic T-lymphocyte-associated protein 4, programmed cell death-1/programmed death-ligand 1, and their inhibitors, have attracted significant attention for overcoming the immunosuppressive conditions in patients with cancer. Therefore, the combination of immune checkpoint inhibitors and radiotherapy is promising. Emerging preclinical and clinical studies have demonstrated the rationale for these combination strategies. In this review, we outlined evidence suggesting that combination of radiotherapy, including particle therapy using protons and carbon ions, with immunotherapy in lung cancer treatment could be a promising treatment strategy.

Interstitial lung disease (ILD) is a risk factor both for the development and treatment failure of lung cancer. In this retrospective study, we analyzed the outcome of carbon-ion radiotherapy (CIRT) in 124 patients with clinical stage I non-small cell lung cancer (NSCLC), of whom 26 (21%) had radiological signs of pre-existing ILD. ILD was diagnosed retrospectively by a pulmonologist based on critical review of CT-scans. Ninety-eight patients were assigned to the non-ILD group and 26 patients (21.0%) to the ILD group. There were significant differences in pre-treatment KL-6 values between the two groups. The three year overall survival and cause-specific survival rates were 83.2% and 90.7%, respectively, in the non-ILD group, and 59.7% and 59.7%, respectively, in the ILD group (between-group differences, p = 0.002 and p < 0.001). Radiation pneumonitis worse than Grade 2 was observed in three patients (3.0%) in the non-ILD group and two patients (7.6%) in the ILD group (p = 0.29). There were no cases of acute exacerbation in the ILD group. CIRT for stage I NSCLC was as safe in the ILD group as in the non-ILD group. Coexisting ILD was a poor prognostic factor in CIRT for clinical stage I lung cancer.

This study aimed to assess dose distributions for stage I non-small cell lung cancer (NSCLC) with passive scattering carbon-ion radiotherapy (C-ion RT) using daily computed tomography (CT) images. We enrolled 10 patients with stage I NSCLC and acquired a total of 40 pre-fractional CT image series under the same settings as the planning CT images. These CT images were registered with planning CT images for dose evaluation using both bone matching (BM) and tumor matching (TM). Using deformable image registration, we generated accumulated doses. Moreover, the volumetric dose parameters were compared in terms of tumor coverage and lung exposure and statistical analyses were performed. Overall, 25% of 40 fractional dose distributions were unacceptable with BM, compared with 2.5% with TM (P < 0.001). Using BM, three patients’ accumulated dose distributions were unacceptable; however, all were satisfactory with TM (P < 0.001). No differences were observed in water-equivalent path length (WEL). The required margins in patients with poor dose distribution were 5.9 and 4.4 mm for BM and TM, respectively. This study establishes that CT image-based TM is robust compared with conventional BM for both daily and accumulated dose distributions. The effects of changes in WEL seem to be limited. Hence, daily CT alignment is recommended for patients with stage I NSCLC receiving C-ion RT.