The aim of this study was to compare the dosimetric parameters of whole-pelvic radiotherapy (WPRT) for cervical cancer among plans involving 3D conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), or spot-scanning proton therapy (SSPT). The dose distributions of 3D-CRT-, IMRT-, and SSPT-based WPRT plans were compared in 10 patients with cervical cancer. All of the patients were treated with a prescribed dose of 50.4 Gy in 1.8-Gy daily fractions, and all of the plans involved the same planning target volume (PTV) constrictions. A 3D-CRT plan involving a four-field box, an IMRT plan involving seven coplanar fields, and an SSPT plan involving four fields were created. The median PTV D95% did not differ between the 3D-CRT, IMRT and SSPT plans. The median conformity index 95% and homogeneity index of the IMRT and SSPT were better than those of the 3D-CRT. The homogeneity index of the SSPT was better than that of the IMRT. SSPT resulted in lower median V20 values for the bladder wall, small intestine, colon, bilateral femoral heads, skin, and pelvic bone than IMRT. Comparing the Dmean values, SSPT spared the small intestine, colon, bilateral femoral heads, skin and pelvic bone to a greater extent than the other modalities. SSPT can reduce the irradiated volume of the organs at risk compared with 3D-CRT and IMRT, while maintaining excellent PTV coverage. Further investigations of SSPT are warranted to assess its role in the treatment of cervical cancer.

Two prospective phase II trials were designed to assess the efficacy and safety of image-guided proton therapy (IGPT) for either medically inoperable or operable stage I non-small cell lung cancer (NSCLC). The present study reports the interim results of these trials. Fifty-five patients with histologically confirmed stage I NSCLC (IA in 33 patients and IB in 22 patients; inoperable in 21 patients and operable in 34 patients) who received IGPT between July 2013 and February 2017 were analyzed. The median patient age was 71 years (range: 48–88 years). IGPT with fiducial metallic marker matching was performed for suitable patients, and a respiratory gating method for motion management was used for all treatments. Peripherally located tumors were treated with 66 Gy relative biological effectiveness equivalents (Gy(RBE)) in 10 fractions (n = 49) and centrally located tumors were treated with 72.6 Gy(RBE) in 22 fractions (n = 6). Treatment associated toxicities were evaluated using Common Toxicity Criteria for Adverse Events (v.4.0). Median follow-up was 35 months (range: 12–54 months) for survivors. For all patients, the 3-year overall survival, progression-free survival, and local control rates were 87% (95% confidence interval: 73–94%), 74% (58–85%), and 96% (83–99%), respectively. Fiducial marker matching was used in 39 patients (71%). Grade 2 toxicities observed were radiation pneumonitis in 5 patients (9%), rib fracture in 2 (4%), and chest wall pain in 5 (9%). There were no grade 3 or higher acute or late toxicities. IGPT appears to be effective and well tolerated for all patients with stage I NSCLC. Lung-001, 13–02-09 (9), registered 11 June 2013 and Lung-002, 13–02-10 (10), registered 11 June 2013.

To investigate optimal treatment planning using proton beams for non-squamous cell carcinoma of the head and neck (NSCHN), the dose distributions of plans involving pencil beam scanning (PBS) with or without a patient-specific aperture system (PSAS), passive-scattering proton therapy (PSPT) and X-ray intensity-modulated radiotherapy (IMRT) were compared. As clinical results, toxicities of PBS with PSAS, including changes in quality of life, were reported. Between April 2014 and August 2016, a total of 30 patients were treated using PBS with PSAS. In 20 patients selected at random, the dose distributions of PBS with or without the PSAS, PSPT and IMRT plans were compared. Neutron exposure by proton therapy was calculated using a Monte Carlo simulation. Toxicities were scored according to CTCAE ver. 4.0. Patients completed EORTC quality of life survey forms (QLQ-C30 and QLQ-HN35) before and 0–12 months after proton therapy. The 95% conformity number of PBS with the PSAS plan was the best, and significant differences were detected among the four plans (P < 0.05, Bonferroni tests). Neutron generation by PSAS was ~1.1-fold higher, but was within an acceptable level. No grade 3 or higher acute dermatitis was observed. Pain, appetite loss and increased weight loss were more likely at the end of treatment, but recovered by the 3 month follow-up and returned to the pretreatment level at the 12 month follow-up. PBS with PSAS reduced the penumbra and improved dose conformity in the planning target volume. PBS with PSAS was tolerated well for NSCHN.

Background: Interstitial pneumonia (IP) is a disease with a poor prognosis. In addition, IP patients are more likely to develop lung cancer. Since IP patients frequently develop toxicities during cancer treatment, minimally invasive cancer treatment is warranted for such patients to maintain their quality of life. This study retrospectively investigated the efficacy and safety of proton therapy (PT) for non-small cell lung cancer (NSCLC) in patients with IP.Methods: Twenty-nine NSCLC patients with IP were treated with PT between September 2013 and December 2019. The patients had stage IA to IIIB primary NSCLC. Ten of the 29 patients exhibited the usual interstitial pneumonia pattern. The prescribed dose was 66–74 Grays (relative biological effectiveness) in 10–37 fractions.Results: The median follow-up period was 21.1 months [interquartile range (IQR), 15.6–37.3] for all patients and 37.2 months (IQR, 24.0–49.9) for living patients. The median patient age was 77 years (IQR, 71–81). The median planning target volume was 112.0 ml (IQR, 56.1–246.3). The 2-year local control, progression-free survival, and overall survival rates were 85% (95% confidence interval: 57–95), 30% (15–47), and 45% (26–62), respectively. According to the Common Terminology Criteria for Adverse Events (version 4.0), grade 3 acute radiation pneumonitis (RP) was observed in 1 patient. Two patients developed grade 3 late RP, but no other patients experienced serious toxicities. The patients’ quality of life (European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-LC13 and SF-36) scores had not changed after 3 months.Conclusions: PT may be a relatively safe treatment for NSCLC patients with IP, without deteriorating quality of life scores within 3 months.

This study retrospectively investigated the efficacy and safety of image-guided proton therapy (IGPT) for elderly (≥80 years old) hepatocellular carcinoma (HCC) patients. Proton therapy was performed using respiratory-gated and image-guided techniques. Seventy-one elderly HCC patients were treated using IGPT. The Child–Pugh score was A5 in 49 patients, A6 in 15, and B7-9 in 7. Forty-seven patients with a peripherally located tumor were administered 66 gray relative biological effectiveness (GyRBE) in 10 fractions, whereas 24 with a centrally located tumor received 72.6 GyRBE in 22 fractions. The median follow-up period of surviving patients was 33 months (range: 9–68). Two-year overall survival (OS) and local control (LC) rates estimated by the Kaplan–Meier method were 76% (95% confidence interval: 66–87%) and 88% (80–97%), respectively. According to the Common Terminology Criteria for Adverse Events version 4.0, no grade 2 or higher radiation-induced liver disease was observed, and only 1 patient developed grade 3 dermatitis. The quality of life score (European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 version 3.0, QLQ-HCC18, and SF-36) did not change after 1 year, except for the three-mental component summary (SF-36, improvement). IGPT is a safe and effective treatment for HCC in elderly patients.