Search

Highlights • Pancreatic exocrine function deterioration was initiated early in C-ion RT. • The rate in development of pancreatic exocrine insufficiency was 57.6%. • The most effective factor of the pancreatic exocrine insufficiency was V, Background and purpose In radiotherapy (RT) for pancreatic cancer, the pancreas is considered an important organ at risk. However, there are insufficient reports on pancreatic function deterioration after X-ray RT as organ at risk, and there are no reports on those after carbon ion (C-ion) RT. Here, we evaluated pancreatic exocrine insufficiency (PEI) after C-ion RT using dose-volume histogram (DVH) analysis. Materials and methods Data were retrospectively collected from patients who had undergone C-ion RT for pancreatic cancer between July 2013 and June 2019. The prescribed C-ion doses were 55.2 Gy (relative biological effectiveness) in 12 fractions. Serum pancreatic amylase and lipase values were measured before and after C-ion RT. In DVH analysis, we assessed V5Gy–50Gy and V

Definitive radiotherapy for cervical cancer consists of external-beam radiotherapy (EBRT) and brachytherapy. In EBRT, a central shield (CS) reduces the dose to the rectum and bladder. The combination of whole-pelvic (WP)- and CS-EBRT and brachytherapy is the standard radiotherapy protocol in Japan. Despite clinical studies, including multi-institutional clinical trials, showing that the Japanese treatment protocol yields favorable treatment outcomes with low rates of late radiation toxicities, dose–volume parameters for the Japanese treatment protocol remain to be established. We conducted a retrospective dose–volume analysis of 103 patients with uterine cervical cancer treated with the Japanese protocol using computed tomography–based adaptive brachytherapy. The 2-year overall survival and 2-year local control rates according to FIGO stage were 100% and 100% for Stage I, 92% and 94% for Stage II, and 85% and 87% for Stage III–IV, respectively. Late adverse effects in the rectum and bladder were acceptable. Receiver operating characteristic analysis discriminated recurrence within the high-risk clinical target volume (HR-CTV) (n = 5) from no local recurrence (n = 96), with the optimal response obtained at a dose of 36.0 GyEQD2 for HR-CTV D90 and 28.0 GyEQD2 for HR-CTV D98. These values were used as cut-offs in Fisher exact tests to show that high HR-CTV D90 and HR-CTV D98 doses for brachytherapy sessions were significantly associated with tumor control within the HR-CTV. These data suggest a contribution of brachytherapy to local tumor control in WP- and CS-EBRT and brachytherapy combination treatment, warranting validation in multi-institutional prospective studies.

Simple Summary Quality of life (QOL) and functional outcomes in patients with inoperable bone and soft tissue sarcoma treated with definitive carbon-ion radiotherapy (CIRT) were prospectively investigated. CIRT showed favorable clinical efficacy and safety, maintaining the physical component of QOL and functional outcomes, and improving the mental component of QOL. The physical component of QOL was positively correlated with functional outcomes. Poor performance status at diagnosis and female gender were independent predictors of the physical component of QOL and functional outcomes after CIRT. Abstract Carbon-ion radiotherapy (CIRT) represents a definitive treatment for inoperable bone and soft tissue sarcoma (BSTS). This prospective study analyzed 61 patients with inoperable BSTS who were treated with CIRT to evaluate QOL, functional outcomes, and predictive factors in patients with inoperable BSTS treated with definitive CIRT. The Musculoskeletal Tumor Society (MSTS) scoring system and the Short Form (SF)-8 questionnaire were completed before and at 1, 3, 6, 12, and 24 months after CIRT. The median follow-up period was 38 months. The main site of primary disease was the pelvis (70.5%), and the most common pathologic diagnosis was chordoma (45.9%). The 3-year overall survival and local control rates were 87.8% and 83.8%, respectively. The MSTS score and physical component score (PCS) of SF-8 did not change significantly between the baseline and subsequent values. The mental component score of SF-8 significantly improved after CIRT. Multivariate analysis showed that the normalized MSTS and normalized PCS of SF-8 at the final follow-up were significantly affected by performance status at diagnosis and sex. CIRT showed clinical efficacy, preserving the physical component of QOL and functional outcomes and improving the mental component of QOL, suggesting its potential value for the treatment of patients with inoperable BSTS.

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.

BackgroundHepatocellular carcinoma (HCC) involving a major branch of the portal or hepatic vein is in a locally advanced stage and remains difficult to cure. This study aimed to evaluate the clinical effects of carbon ion radiotherapy (C-ion RT) in locally advanced HCC (LAHCC).MethodsThe data of 11 consecutive patients with LAHCC who received C-ion RT were analyzed. The C-ion RT doses of 52.8 Gy (relative biological effectiveness [RBE]) and 60.0 Gy (RBE) were delivered in 4 fractions for standard cases, and the 60.0 Gy dose was delivered in 12 fractions for close-to-gastrointestinal-tract cases. Survival and local control probabilities were calculated using the Kaplan-Meier method.ResultsThe median follow-up duration after C-ion RT was 36.4 months. The median age at the time of registration for C-ion RT was 76 years. The median tumor size was 53 mm. The numbers of treatment-naive and recurrent HCC patients were 1 and 10, respectively. Direct invasion of the major branch of the portal vein, hepatic vein, or both portal and hepatic veins was observed in three, five, and three patients, respectively. The 3-year overall survival, local control, and progression-free survival rates were 64, 78, and 18%, respectively. No patient developed radiation-induced liver diseases or grade 3 or higher toxicities in the acute and late phases.ConclusionsC-ion RT showed favorable clinical outcomes with a high rate of local control and minimal toxicities in LAHCC. Our findings suggest that C-ion RT is a promising multidisciplinary treatment option in LAHCC.

Mouthpieces are used to fix the positions of the lower jaw and teeth during carbon-ion radiotherapy for head and neck tumors. We used a customized mouthpiece to reduce radiation mucositis by displacing the tongue. Acute radiation mucositis gradually increased for the palate and tongue after approximately six irradiation fractions (maximal mean grade: palate, 2.5 during radiation fractions 15; tongue, 0.8 during radiation fractions 12 and 13). The mean grade of mucositis was significantly lower for the tongue than for the palate from irradiation fraction six until two weeks after irradiation. Keywords: Carbon-ion radiotherapy, Head and neck tumor, Customized mouthpiece

Photon radiation therapy is a major curative treatment for cancer. However, the lack of robust predictive biomarkers for radiosensitivity precludes personalized radiation therapy. Clonogenic assays are the gold standard method for measuring the radiosensitivity of cancer cells. Although a large number of publications describe the use of clonogenic assays to measure cancer cell radiosensitivity, the robustness of results from different studies is unclear. To address this, we conducted a comprehensive detailed literature search of 256 common cancer cell lines and identified the eight cell lines most-frequently examined for photon sensitivity using clonogenic assays. Survival endpoints and experimental parameters from all 620 relevant experiments were compiled and analyzed. We found that the coefficients of variation for SF2 (surviving fraction after 2 Gy irradiation) and for D10 (dose that yields a surviving fraction of 10%) were below 30% for all cell lines, indicating that SF2 and D10 have acceptable inter-assay precision. These data support further analysis of published data on clonogenic assays using SF2 and D10 as survival endpoints, which facilitates robust identification of biological profiles representative of cancer cell sensitivity to photons.

Radiotherapy is an essential component of cancer therapy. Despite advances in cancer genomics, the mutation signatures of radioresistant tumors have not yet been fully elucidated. To address this issue, we analyzed a unique set of clinical specimens from a uterine cervical cancer that repeatedly locally recurred after multiple rounds of radiotherapy. Exon sequencing of 409 cancer-related genes in the treatment-naive tumor and the tumors that recurred after initial and secondary radiotherapy identified (i) activating mutations in PIK3CA and KRAS, and putative inactivating mutations in SMAD4, as trunk mutation signatures that persisted over the clinical course; and (ii) mutations in KMT2A, TET1, and NLRP1 as acquired mutation signatures observed only in recurrent tumors after radiotherapy. Comprehensive mining of published in vitro genomics data pertaining to radiosensitivity revealed that simultaneous mutations in KRAS and SMAD4, which have not been described previously in uterine cervical cancer, are associated with cancer cell radioresistance. The association between this mutation signature and radioresistance was validated by isogenic cell-based experiments. These results provide proof-of-principle for the analytical pipeline employed in this study, which explores clinically relevant mutation signatures for radioresistance, and demonstrate that this approach is worth pursuing with larger cohorts in the future.

We aimed to clarify the accuracy of rigid image registration and deformable image registration (DIR) in carbon-ion radiotherapy (CIRT) for pancreatic cancer. Six patients with pancreatic cancer who were treated with passive irradiation CIRT were enrolled. Three registration patterns were evaluated: treatment planning computed tomography images (TPCT) to CT images acquired in the treatment room (IRCT) in the supine position, TPCT to IRCT in the prone position, and TPCT in the supine position to the prone position. After warping the contours of the original CT images to the destination CT images using deformation matrices from the registration, the warped delineated contours on the destination CT images were compared with the original ones using mean displacement to agreement (MDA). Four contours (clinical target volume (CTV), gross tumor volume (GTV), stomach, duodenum) and four registration algorithms (rigid image registration [RIR], intensity-based DIR [iDIR], contour-based DIR [cDIR], and a hybrid iDIR-cDIR ([hDIR]) were evaluated. The means &plusmn, standard deviation of the MDAs of all contours for RIR, iDIR, cDIR, and hDIR were 3.40 &plusmn, 3.30, 2.2 1&plusmn, 2.48, 1.46 &plusmn, 1.49, and 1.46 &plusmn, 1.37 mm, respectively. There were significant differences between RIR and iDIR, and between RIR/iDIR and cDIR/hDIR. For the pancreatic cancer patient images, cDIR and hDIR had better accuracy than RIR and iDIR.