Evaluation of the availability of single-position treatment with a rotating gantry and the validity of deformable image registration dose assessment for pancreatic cancer carbon-ion radiotherapy.

BACKGROUND: This study aimed to evaluate the clinical acceptability of rotational gantry-based single-position carbon-ion radiotherapy (CIRT) to reduce the gastrointestinal (GI) dose in pancreatic cancer. We also evaluated the usefulness of the deformable image registration (DIR)-based dosimetry method for CIRT. MATERIAL AND METHODS: Fifteen patients with pancreatic cancer were analyzed. The treatment plans were developed for four beam angles in the supine (SP plan) and prone (PR plan) positions. In the case of using multiple positions, the treatment plan was created with two angles for each of the supine and prone position (SP + PR plan). Dose evaluation for multiple positions was performed in two ways: by directly adding the values of the DVH parameters for each position treatment plan (DVH sum), and by calculating the DVH parameters from the accumulative dose distribution created using DIR (DIR sum). The D2cc and D6cc of the stomach and duodenum were recorded for each treatment plan and dosimetry method and compared. RESULTS: There were no significant differences among any of the treatment planning and dosimetry methods (p > 0.05). The DVH parameters for the stomach and duodenum were higher in the PR plan and SP plan, respectively, and DVH sum tended to be between the SP and PR plans. DVH sum and DIR sum, DVH sum tended to be higher for D2cc and DIR sum tended to be higher for D6cc . CONCLUSION: There were no significant differences in the GI dose, which suggests that treatment with a simple workflow performed in one position should be clinically acceptable. In CIRT, DIR-based dosimetry should be carefully considered because of the potential for increased uncertainty due to the steep dose distributions.

Current status of remote radiotherapy treatment planning in Japan: findings from a national survey†.

The purpose of this study was to investigate the status of remote-radiotherapy treatment planning (RRTP) in Japan through a nationwide questionnaire survey. The survey was conducted between 29 June and 4 August 2022, at 834 facilities in Japan that were equipped with linear accelerators. The survey utilized a Google form that comprised 96 questions on facility information, information about the respondent, utilization of RRTP between facilities, usage for telework and the inclination to implement RRTPs in the respondent's facility. The survey analyzed the utilization of the RRTP system in four distinct implementation types: (i) utilization as a supportive facility, (ii) utilization as a treatment facility, (iii) utilization as a teleworker outside of the facility and (iv) utilization as a teleworker within the facility. The survey response rate was 58.4% (487 facilities responded). Among the facilities that responded, 10% (51 facilities) were implementing RRTP. 13 served as supportive facilities, 23 as treatment facilities, 17 as teleworkers outside of the facility and 5 as teleworkers within the facility. In terms of system usage between supportive and treatment facilities, 70-80% of the participants utilized the system for emergencies or as overtime work for external workers. A substantial number of facilities (38.8%) reported that they were unfamiliar with RRTP implementation. The survey showed that RRTP utilization in Japan is still limited, with a significant number of facilities unfamiliar with the technology. The study highlights the need for greater understanding and education about RRTP and financial funds of economical compensation.

Concurrent chemoradiotherapy using proton beams can reduce cardiopulmonary morbidity in esophageal cancer patients: a systematic review.

This systematic review was performed to investigate the superiority of proton beam therapy (PBT) to photon-based radiotherapy (RT) in treating esophageal cancer patients, especially those with poor cardiopulmonary function. The MEDLINE (PubMed) and ICHUSHI (Japana Centra Revuo Medicina) databases were searched from January 2000 to August 2020 for studies evaluating one end point at least as follows; overall survival, progression-free survival, grade ≥ 3 cardiopulmonary toxicities, dose-volume histograms, or lymphopenia or absolute lymphocyte counts (ALCs) in esophageal cancer patients treated with PBT or photon-based RT. Of 286 selected studies, 23 including 1 randomized control study, 2 propensity matched analyses, and 20 cohort studies were eligible for qualitative review. Overall survival and progression-free survival were better after PBT than after photon-based RT, but the difference was significant in only one of seven studies. The rate of grade 3 cardiopulmonary toxicities was lower after PBT (0-13%) than after photon-based RT (7.1-30.3%). Dose-volume histograms revealed better results for PBT than photon-based RT. Three of four reports evaluating the ALC demonstrated a significantly higher ALC after PBT than after photon-based RT. Our review found that PBT resulted in a favorable trend in the survival rate and had an excellent dose distribution, contributing to reduced cardiopulmonary toxicities and a maintained number of lymphocytes. These results warrant novel prospective trials to validate the clinical evidence.

MRI Grading Scale Predicts Ambulatory Function After Radiotherapy for Metastatic Spinal Cord Compression: A Prospective Single-Institution Observational Study.

INTRODUCTION: Although magnetic resonance imaging (MRI) is an important modality for the diagnosis of metastatic spinal cord compression (MSCC), there are only a few reports on MSCC findings and symptoms after radiotherapy. We aimed to reveal the factors related to ambulatory function after treatment, including the MRI findings, in a prospective observational study. METHODS: Patients with suspected MSCC who were treated with radiotherapy were included in this study. Orthopedic surgeons evaluated the neurological function according to the Frankel grade. All patients underwent spinal MRI, and the degree of spinal cord compression was assessed by a radiologist and a radiation oncologist using an MRI grading scale. One month after treatment, orthopedic surgeons reassessed the Frankel grade. Twenty-three patients who were evaluated 1 month after radiotherapy were included in the analysis. RESULTS: Before radiotherapy, 17 patients were ambulatory and six were unable to walk. Furthermore, 13 patients were diagnosed with grade 3 compression on MRI (spinal cord compression with no cerebrospinal fluid seen on axial T2-weighted imaging). Patients with grade 3 MSCC were significantly more likely to be non-ambulatory at 1 month. CONCLUSIONS: The MRI grading scale for MSCC may be a prognostic factor for ambulatory function after radiotherapy. MRI findings could aid in determining the indication for radiotherapy.

Implementation rate and effects of multidisciplinary team meetings on decision making about radiotherapy: an observational study at a single Japanese institution.

BACKGROUND: Cancer treatment requires a multidisciplinary approach. Therefore, multidisciplinary team meetings (MDTMs) have been widely used to determine the direction of treatment. However, no standard provisions exist for conducting MDTMs, and recommendations discussed in MDTMs are sometimes not implemented. ​This study analyzed the indications for radiotherapy discussed and recommended at MDTMs, identified the rate of radiotherapy recommendations for patients that were not implemented, and clarified the reasons at a single academic center in Japan. METHODS: This was a cross-sectional study that analyzed the minutes and electronic medical records of cases discussed at MDTMs held between April 2012-March 2017 at Yamagata University Hospital. We categorized how radiotherapy was initially presented at MDTMs, determined the rate of radiotherapy recommendations made through MDTMs, analyzed whether treatment recommendations were subsequently implemented, and examined the causes of non-implementation. We performed a statistical analysis to assess some clinical factors (sex, age, number of multidisciplinary team meetings, and classification of planned treatment) associated with the non-implementation of radiotherapy recommendations from MDTMs. RESULTS: A total of 1813 cases were discussed at MDTMs, of which 71% (1293 cases) were presented with treatment plans, including radiotherapy. Further, 66% (1205 cases) were recommended for radiotherapy through the MDTMs. Recommendations from MDTMs were not implemented in 7% (142 cases). The most typical reason for non-implementation was the clinician's opinion (30%), followed by patient preferences (27%) and disease progression (20%). Change in cancer stage and improvement in symptoms were 12% and 4%, respectively. These ratios were similar each year. We could not find the factors associated with the non-implementation of radiotherapy recommendations from MDTMs. CONCLUSIONS: MDTMs had a significant effect on the recommendation of radiotherapy for each patient with a tumor. The primary reason for the non-implementation of decisions made at MDTMs was the opinion of clinicians and the patient's preference. These results were similar to previous studies. We need to establish a monitoring system where patients themselves can decide the treatments based on their choices while using the recommendations from MDTMs.

Prediction of the minimum spacer thickness required for definitive radiotherapy with carbon ions and photons for pelvic tumors: an in silico planning study using virtual spacers.

We aimed to predict the minimum distance between a tumor and the gastrointestinal (GI) tract that can satisfy the dose constraint by creating simulation plans with carbon-ion (C-ion) radiotherapy (RT) and photon RT for each case assuming insertion of virtual spacers of various thicknesses. We enrolled 55 patients with a pelvic tumor adjacent to the GI tract. Virtual spacers were defined as the overlap volume between the GI tract and the volume expanded 7-17 mm from the gross tumor volume (GTV). Simulation plans (70 Gy in 35 fractions for at least 95% of the planning target volume [PTV]) were created with the lowest possible dose to the GI tract under conditions that meet the dose constraints of the PTV. We defined the minimum thickness of virtual spacers meeting D2 cc of the GI tract <50 Gy as 'MTS'. Multiple regression was used with explanatory variables to develop a model to predict MTS. We discovered that MTSs were at most 9 mm and 13 mm for C-ion RT and photon RT plans, respectively. The volume of overlap between the GI tract and a virtual spacer of 14 mm in thickness (OV14)-PTV was found to be the most important explanatory variable in the MTS prediction equation for both C-ion and photon RT plans. Multiple R2 values for the regression model were 0.571 and 0.347 for C-ion RT and photon RT plans, respectively. In conclusion, regression equations were developed to predict MTS in C-ion RT and photon RT.

Efficacy and feasibility of re-irradiation using carbon ions for pancreatic cancer that recurs after carbon-ion radiotherapy.

BACKGROUND AND PURPOSE: Patients who receive carbon-ion radiotherapy (C-ion RT) for primary pancreatic cancer may experience locoregional recurrence; however, the treatment options for such patients are limited. We aimed to investigate the feasibility and efficacy of carbon-ion re-irradiation for patients with pancreatic cancer who experienced recurrence after initial C-ion RT. MATERIALS AND METHODS: Twenty-one patients with recurrent pancreatic cancer who underwent repeat C-ion RT between December 2010 and November 2016 at our institute were retrospectively evaluated. The sites of post-initial C-ion RT failure were in-field central in 16 patients (76.2%) and marginal in 5 (23.8%). The median doses of initial and repeat C-ion RT were both 52.8 Gy (relative biological effectiveness [RBE]). Thirteen patients (61.9%) received concurrent chemotherapy with re-irradiation, while 11 (52.4%) received adjuvant chemotherapy. RESULTS: The median follow-up period after re-irradiation was 11 months. The 1-year local control, progression-free survival, and overall survival rates were 53.5%, 24.5%, and 48.7%, respectively. Toxicity data was obtained from the patients' charts. Only 1 patient (4.8%) developed grade 3 acute toxicities and none developed grade ≥3 late toxicities. Univariate analysis indicated that patients who received adjuvant chemotherapy had significantly improved local control rates compared with those who did not; the 1-year local control rates were 80.0% and 0.0%, respectively (P = 0.0469). CONCLUSION: Repeating C-ion RT may be a reasonable option with tolerable toxicity for patients with recurrent pancreatic cancers. Adjuvant chemotherapy appears to improve the local control rate. This is the first study to examine re-irradiation using C-ion for recurrent pancreatic cancer after initial C-ion RT.

Comparison of the effects of radiotherapy doses of 50.4 Gy and 60 Gy on outcomes of chemoradiotherapy for thoracic esophageal cancer: subgroup analysis based on the Comprehensive Registry of Esophageal Cancer in Japan from 2009 to 2011 by the Japan Esophageal Society.

BACKGROUND: In definitive chemoradiotherapy (CRTx) for esophageal cancer, a radiotherapy (RT) dose of 50.4 Gy in 28 fractions has been the standard in many countries, while 60 Gy in 30 fractions has been frequently used in Japan. To clarify the optimal RT dose in CRTx for esophageal cancer, we compared clinical outcomes with the two doses using data from the Comprehensive Registry of Esophageal Cancer in Japan by the Japan Esophageal Society (JES). METHODS: Of the patients enrolled in the registry for 2015-2017 surveys (patients treated between 2009 and 2011), 996 patients who received definitive CRTx with 50.4 Gy or 60 Gy for thoracic esophageal cancer were eligible for analysis. RESULTS: The complete response (CR) rates in the 50.4 Gy and 60 Gy groups were 49.1% and 46.4%, respectively (p = 0.5851). The 5-year overall survival (OS) rates in the 50.4 Gy group and 60 Gy group for stages I, II/III and IV were 64.2% and 57.2%, 35.0% and 27.0%, and 18.0% and 15.3%, respectively. Since no significant difference was found between the two groups, the 50.4 Gy group was not inferior to the 60 Gy group with regard to OS. CONCLUSIONS: The analysis revealed that the 50.4 Gy group had a non-inferior outcome in comparison with the 60 Gy group for stages I, II/III and IV thoracic esophageal cancer. These results were obtained from a large database for the first time in Japan.

Carbon-ion radiotherapy for locally recurrent rectal cancer: Japan Carbon-ion Radiation Oncology Study Group (J-CROS) Study 1404 Rectum.

PURPOSE: We investigated the efficacy and safety of carbon-ion radiotherapy (C-ion RT) for locally recurrent rectal cancer (LRRC). PATIENTS AND METHODS: Data from patients with LRRC treated with C-ion RT from November 2003 to December 2014 at three institutions were retrospectively analyzed. The endpoints of this clinical trial were overall survival (OS), local control (LC), and acute/late toxicity. RESULTS: A total of 224 patients' data were collected. The prescribed dose was 70.4 Gy (relative biological effectiveness [RBE]-weighted absorbed dose) or 73.6 Gy (RBE) in 16 fractions. The median follow-up period from the initiation of C-ion RT was 62 months (range 6-169 months). The OS rates were 73% (95% confidence interval [CI], 67%-79%) at 3 years and 51% (95%CI 44%-58%) at 5 years. The LC rates were 93% (95%CI 88%-96%) at 3 years, and 88% (95%CI 82%-93%) at 5 years. Grade 3 acute toxicity was observed in three patients: gastrointestinal toxicity (n = 1) and pelvic infection (n = 2). Grade 3 late toxicity was observed in 12 patients: skin reaction (n = 2), gastrointestinal toxicity (n = 2), neuropathy (n = 1), and pelvic infection (n = 7). There was no grade 4 or 5 acute or late toxicity. CONCLUSIONS: This first multi-institutional analysis of C-ion RT for LRRC indicated relatively favorable outcomes with limited toxicities.

Multi-institutional Study of Carbon-ion Radiotherapy for Locally Advanced Pancreatic Cancer: Japan Carbon-ion Radiation Oncology Study Group (J-CROS) Study 1403 Pancreas.

PURPOSE: The aim of this multi-institutional study was to evaluate the efficacy and safety of carbon-ion radiotherapy (C-ion RT) for locally advanced pancreatic cancer (LAPC). METHODS AND MATERIALS: Patients with LAPC treated with C-ion RT from April 2012 to December 2014 at 3 institutions were retrospectively analyzed. Patients with pathologically-confirmed invasive ductal adenocarcinoma of the pancreas were eligible. The prescribed dose was 52.8 Gy (relative biological effectiveness weighted absorbed dose; RBE) or 55.2 Gy (RBE) in 12 fractions. Overall survival (OS), distant metastasis-free survival (DMFS), local recurrence (LR), and toxicity were evaluated. RESULTS: In total, 72 patients were included in this study. Tumors in the head of the pancreas were seen in 30 patients (42%), while those in the body or tail of the pancreas were seen in 42 patients (58%). Fifty-six patients (78%) received concurrent chemotherapy. The OS rates were 73% (95% confidence interval [CI], 62%-84%) at 1 year, and 46% (95% CI, 31%-61%) at 2 years with a median OS of 21.5 months (95% CI, 11.8-31.2 months). The 1- and 2-year DMFS rates were 41% (95% CI, 29%-52%) and 28% (95% CI, 16%-40%), respectively. The 1- and 2-year cumulative incidences of LR were 16% (95% CI, 9%-26%) and 24% (95% CI, 14%-36%), respectively. Nineteen patients (26%) experienced acute grade 3 or 4 hematological toxicities. Two patients (3%) had grade 3 anorexia. Late gastrointestinal (GI) grade 3 toxicity was observed in 1 patient (1%). No patients developed late grade 4 or 5 toxicity. CONCLUSIONS: The first multi-institutional analysis of C-ion RT for LAPC indicated relatively favorable outcomes with limited toxicities, especially for tumors not in close proximity to GI tract.

Carbon-ion radiotherapy for locoregional recurrence after primary surgery for pancreatic cancer.

The efficacy and safety of carbon ion radiotherapy (C-ion RT) for locoregional recurrence after surgery for pancreatic cancer were retrospectively evaluated. The results for 30 patients showed that C-ion RT was performed safely with relatively long overall survival, good local control, and minimal toxicity.

Carbon-ion radiotherapy for isolated para-aortic lymph node recurrence from colorectal cancer.

BACKGROUND: The safety and effectiveness of carbon-ion radiotherapy (CIRT) for isolated para-aortic lymph node (PALN) metastasis was evaluated retrospectively. METHODS: CIRT for isolated PALN metastasis from CRC was performed in 34 cases from June 2006 to August 2015 in our institute. A median dose of 52.8 Gy(RBE) (range, 48-52.8 Gy(RBE)) was delivered with a median daily dose of 4.4 Gy(RBE) (range, 4.0-4.4 Gy(RBE)). RESULTS: The median follow-up duration for all patients was 24.4 months (range, 7-82.8 months). There were 13 cases (38.2%) who achieved complete response after treatment. The local control rates at 2 and 3 years were 70.1% and 70.1%, respectively. The overall survival rates at 2 and 3 years were 83.3% and 63.0%, respectively. The 3-year survival rates for Stage I-III were 68.7%, while those for Stage IV was 0%. The overall survival of cases with rectal cancer or with high CA19-9 values pre-CIRT tended to be worse. The median survival period was 41.7 months. Twelve of the 34 patients survived for more than 3 years. There were no adverse effects of Grade 3 or higher. CONCLUSIONS: CIRT for isolated PALN recurrence after curative resection for CRC appears effective and safe, and it is considered a promising therapy.

Dose escalation study with respiratory-gated carbon-ion scanning radiotherapy using a simultaneous integrated boost for pancreatic cancer: simulation with four-dimensional computed tomography.

OBJECTIVE: Pancreatic cancer is a difficult to treat disease with a persistently high mortality rate. We evaluated dose distribution simulation with respiratory-gated carbon-ion pencil beam scanning (C-PBS) with a simultaneous integrated boost (SIB) to increase tumour dose, sparing organs at risk (OARs). METHODS: Using four-dimensional CT data of 12 patients, we delineated gross tumour volume and two clinical target volumes (CTVs). To consider beam range intrafractional uncertainty, we calculated field-specific target volumes, from which two planning target volumes (PTVs) were generated. PTV1 would receive a planned dose of 55.2 Gy [relative biological effectiveness (RBE)-weighted absorbed dose] in 12 fractions, and PTV2 would receive an SIB dose up to 67.2 Gy (RBE). Dose assessments were conducted with regard to the targets and OARs. RESULTS: CTV2 dose covering 95% of the volume (D95%) increased from 50.3 ± 5.1 Gy (RBE) to 62.5 ± 3.5 Gy (RBE) for a planned dose from 55.2 Gy (RBE) to 67.2 Gy (RBE). For 4 of 12 patients with a distance of ≥5 mm between the tumour and the gastrointestinal tract, CTV2 D95% was ≥95% of planned dose at all dose levels. CONCLUSION: We quantified dose escalation with respiratory-gated C-PBS using SIB for pancreatic cancer and revealed that OAR dose was not affected to the same degree as the tumour dose. Advances in knowledge: A simulation study on respiratory-gated C-PBS with SIB for pancreatic cancer was performed. The results indicated the feasibility of dose escalation for pancreatic cancer, which should be confirmed in clinical trials.

Reirradiation of spinal metastases with intensity-modulated radiation therapy: an analysis of 23 patients.

This study aimed to evaluate the efficacy and safety of reirradiation with intensity-modulated radiation therapy (IMRT) for spinal metastases. We retrospectively analyzed 23 patients with spinal metastases who underwent IMRT reirradiation between December 2006 and July 2013. We evaluated the spinal radiation doses during the first and second radiation therapy courses, the interval between the courses, and the clinical outcomes after reirradiation, including skeletal-related events, local control rates (LCRs), overall survival (OS), and toxicities. The median time from the first irradiation to reirradiation was 13 months (range, 2-75 months). The median reirradiation dose delivered to 90% of the planning target volume was 24.5 Gy in 5 fractions (range, 14.7-50 Gy in 3-25 fractions). Nineteen patients experienced pain at reirradiation, and 15 of these attained pain relief. Two of the three patients with paresis in the upper or lower extremities upon initiation of reirradiation demonstrated improvement. Local progression was identified in four patients. The median time to local progression was 37 months. The 1- and 2-year LCRs after reirradiation were 88% and 75%, respectively. The 1- and 2-year OS rates after reirradiation were 45% and 20%, respectively, with a median OS of 12 months. No late toxicities occurred. In conclusion, spinal metastasis reirradiation using IMRT appears safe; pain relief and paresis improvement and/or prevention can be expected, along with a reduced risk of radiation-induced toxicity, especially in the spinal cord.