Aims: There is a need for the adequate distribution of healthcare resources in Southeast Asia. Many countries in the region have more patients with advanced breast cancer who are eligible for postmastectomy radiotherapy (PMRT). Therefore, it is critical that hypofractionated PMRT is effective in most of these patients. This study investigated the significance of postoperative hypofractionated radiotherapy in patients with breast cancer, including advanced breast cancer, in these countries.Materials and methods: Eighteen facilities in 10 Asian countries participated in this prospective, interventional, single-arm study. The study included two independent regimens: hypofractionated whole-breast irradiation (WBI) for patients who had undergone breast-conserving surgery and hypofractionated PMRT for patients who had undergone total mastectomy at a dose of 43.2 Gy in 16 fractions. In the hypofractionated WBI group, patients with high-grade factors received additional 8.1 Gy boost irradiation sessions for the tumour bed in three fractions.Results: Between February 2013 and October 2019, 227 and 222 patients were enrolled in the hypofractionated WBI and hypofractionated PMRT groups, respectively. The median follow-up periods in the hypofractionated WBI and hypofractionated PMRT groups were 61 and 60 months, respectively. The 5-year locoregional control rates were 98.9% (95% confidence interval 97.4-100.0) and 96.3% (95% confidence interval 93.2-99.4) in the hypofractionated WBI and hypofractionated PMRT groups, respectively. Regarding adverse events, grade 3 acute dermatitis was observed in 2.2% and 4.9% of patients in the hypo -fractionated WBI and hypofractionated PMRT groups, respectively. However, no other adverse events were observed.Conclusion: Although further follow-up is required, hypofractionated radiotherapy regimens for postoperative patients with breast cancer in East and Southeast Asian countries are effective and safe. In particular, the proven efficacy of hypofractionated PMRT indicates that more patients with advanced breast cancer can receive appropriate care in these countries. Hypofractionated WBI and hypofractionated PMRT are reasonable approaches that can contain cancer care costs in these countries. Long-term observation is required to validate our findings.& COPY; 2023 The Author(s). Published by Elsevier Ltd on behalf of The Royal College of Radiologists. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

CIRT for early-stage breast cancer is expected to be effective with mild adverse events, and it is considered meaningful to continue research.

PurposeStereotactic body radiation therapy (SBRT) is a postoperative treatment option for spinal metastases. Because data on surgery with SBRT are limited to retrospective studies, this single-center, single-arm, phase 2 study aimed to prospectively evaluate the outcomes of separation surgery and SBRT for metastatic epidural spinal cord compression (MESCC).Methods and MaterialsPatients with symptomatic MESCC due to a solid carcinoma were enrolled. The protocol for treatments comprised preoperative embolization, separation surgery, and spine SBRT. Surgical procedures were performed via the posterior approach, with decompression and a fixation procedure. The prescribed dose for spine SBRT was 24 Gy in 2 fractions. The primary endpoint was the 12-month local failure rate. The secondary endpoints were ambulatory functions and adverse effects.ResultsA total of 33 patients were registered between November 2017 and October 2019. All patients met the inclusion criteria, and all but 1 completed the protocol treatment. Of the included patients, 23 (70%) had radioresistant lesions. The Bilsky grade at registration was 1c in 3 patients, 2 in 8 patients, and 3 in 21 patients. The median follow-up duration after registration was 15 months (range, 3-35 months). Three months after the administration of treatments according to the protocol, 90% of patients (26 of 29) had disease of Bilsky grade ≤1. The 12-month local failure rate was 13%. Twenty patients could walk normally or with a cane 12 months after registration. Radiation-induced myelopathy, radiculopathy, and vertebral compression fracture were observed in 0, 1, and 6 patients, respectively.ConclusionsSeparation surgery with SBRT for MESCC was effective in decompression and long-term local control. These findings suggest that larger randomized controlled trials are warranted to compare SBRT with conventional radiation therapy.

Purpose/Objective(s)Our institute conducted clinical trials of curative partial breast irradiation using carbon ion radiotherapy (CIRT) to patients with stage 0 and I breast cancer since 2013. The purpose of this report is to evaluate treatment outcomes up to now.Materials/MethodsTo date, we have conducted three clinical trials and one advanced medical treatment (NIRS9404: AMT). The first study (UMIN000010848: known as Breast I) was 4 fractions partial breast CIRT for stage I luminal patients aged 60 years or older. The AMT protocol was provided in parallel with Breast I in same manner for stage I breast cancer patients who was difficult to register due to minor variant or reject to participate in Breast I. In principle, these patients received maintenance hormone therapy. The next clinical trial (UMIN000029478: known as Breast II) enrolled patients aged 20 years and older without 2 mm or more metastasis in sentinel lymph node for all types of Tis-1N0M0, tumor size 2 cm or less. In this study, 4 fractions CIRT partial breast irradiations were combined with standard systemic therapy and x-ray whole-breast irradiation. And the latest clinical trial (UMIN000046859: known as Breast III) is a single dose of CIRT for luminal Tis-1N0M0 patients aged 50 years and older. All Breast III patients received maintenance hormone therapy. In all trials, Phase I was a dose-escalation study and Phase II was treated with the recommended dose determined in Phase I.ResultsBy December 2021, 56 cases have been enrolled. A total of 19 were enrolled In Breast I, 7 in Phase I, 12 in Phase II with a recommended dose of 60.0 Gy (RBE), and total of 14 were enrolled in AMT. A total of 17 were enrolled In Breast II, 5 in Phase I, 12 in Phase II with a recommended dose of 60.0 Gy (RBE). A total of 6 were enrolled in Breast III, 3 in Phase I, 3 in Phase II with a recommended dose of 50.0 Gy (RBE). As acute adverse effects, acute radiation dermatitis (grade 2 in 1, Grade1 in 37), mastitis (grade 1 in 6) and myositis (grade 1 in 7) were observed. As late adverse effects, grade 3 pneumonia of unknown causality were observed in 1 case. The cosmetic results of breast were excellent in all cases. Tumor disappearance after CIRT took 3 to 24 months. Local recurrence with axillary lymph node metastasis was observed in one high-risk AMT patient who refused any systemic therapy, but no other recurrences or metastases have been observed.ConclusionCIRT for early-stage breast cancer is expected to be effective with mild adverse events, and it is considered meaningful to continue research.

SBRT for bone oligo-metastases provided long term systemic disease control in about 20% of cases. SBRT is effective treatment option for bone OMD especially for the cases with long interval from upfront treatment.

The PP bleeding response rate increased to 90% during the 8-week follow-up period. The frequent occurrence of death from shortly after enrollment lowered the ITT response rate and shortened the duration of response. BED was not significantly associated with survival, bleeding response, or re-bleeding.

In this study, we proposed a theoretically determined margin calculation formula for RTTT based on a combination of the GUM and the probability distribution of the tracking errors. The proposed formula appropriately calculated the practical margin size in fiducial marker-based RTTT for lung, liver, and pancreatic cancer.

Introduction: We investigated the outcomes and prognostic factors for fractionated stereotactic radiation therapy (FSRT) for large brain metastases and evaluated whether FSRT could negate the need for surgery, which is the mainstream treatment for large brain metastases. Methods: Patients with brain metastases measuring ≥2 cm treated with FSRT were retrospectively examined. Patients undergoing FSRT postoperatively were excluded. Local failure, intracranial failure, and adverse events were evaluated. Results: Overall, 106 lesions in 98 patients were evaluated. Performance status was 0–1, 2–4, and unknown in 79, 25, and 2 patients, respectively. The median maximum tumor diameter was 25 mm, and the median prescription dose was 35 Gy in 3 fractions. The median follow-up period after FSRT was 7 months. The 1-year rates of local failure, intracranial failure, and overall survival were 13.0%, 57.8%, and 48.0%, respectively. In multivariate analysis, the maximum dose for target ≥135 Gy (biological equivalent dose of a/b of 10 Gy) and good performance status were independent positive prognostic factors for local failure. Sixteen patients (16.3%) were treated with whole-brain radiotherapy after FSRT owing to multiple intracranial recurrences, while surgery was performed for three patients (3.1%) owing to local recurrence. Conclusions: FSRT for large brain metastases achieved good local control and only 3% of patients needed surgery after FSRT, suggesting that FSRT is a potential alternative to surgery. In FSRT, a higher maximum tumor dose was useful for local control.

Positron emission tomography (PET) is a practical tool for range verification in charged particle therapy. We aimed to apply in-beam PET imaging for tracking the evolution of irradiated particles in living tissue. The quantitative biological washout rate of the positron emitters has a potential usefulness as a diagnostic index that provides a unique opportunity to probe the status of tumor viability, but the modeling for this has not been established. Therefore, we measured biological washout rates of tumor-bearing nude rat and performed kinetic analysis on dynamic PET data to explore the biological washout mechanism. C6 rat glioma cells were implanted into right shoulder subcutaneous regions of six nude rats. Tumors volume reached to about 3 cm3 on day 14 after implantation. Tumor tissue (right shoulder) and normal tissue (left shoulder) were irradiated by 11C radioactive ion beam. Time activity curves (TACs) of the irradiated field were acquired by our original PET prototype. The biological washout rate was quantified based on the two-washout model assuming medium decay rate (k2m) and slow decay rate (k2s). In this model, k2m is speculated as the component which spread out via interstitial fluid, and k2s is speculated as the trapping component by the stable molecules in the tissue. After irradiation and PET dynamic scan, pathological morphology of tumor tissue (Hematoxylin & Eosin staining) was observed under microscope. The two-washout model fitted the experimental TACs well for five of six nude-rats irradiation studies. The observed k2m of tumor irradiation was 0.31+/-0.04 min-1, which was consistent with the normal tissue irradiation. While k2s of tumor irradiation was faster (0.017 +/-0.002 min-1) than that of normal tissue irradiation (0.006 +/-0.002 min-1). These results suggested that the component, which was trapped in normal tissue, diffused out more smoothly from tumor tissue due to vascular hyperpermeability which characterizes pathological tumor-angiogenesis. For one of six nude rats, only slow washout component (k2s = 0.014 +/-0.003 min-1) was observed in tumor irradiation study. Necrosis in tumor was observed in pathological tissue sample of this nude rat. It is also suggested that the decrease of washout rate was caused by the decrease of blood flow in the necrotic region. We measured the biological washout rate of irradiated 11C ion beam in tumor tissue and normal tissue. The physiological difference of tissue condition reflected the biological washout rates. This effect may be used as a clinical diagnostic index to monitor the dose response of the tumors in individual patients as well as the observation of the functional metabolism of tumor.

Accelerated hypofractionated radiation therapy (AHRT) has been considered effective in treating central tumors of lung in decreasing severe complications regarding serial organs at risk (OARs). We have been treating AHRT using 75 Gy/25 fr/5 wks regimen. To support the safety of AHRT, we investigated the doses to the OARs. Central tumor is defined as those located within 2cm from proximal bronchial tree (PBT) and/or located very close to mediastinal organs. Among central tumors ultracentral tumor is defined as those which is faced with lobar bronchus, esophagus, and/or major arteries, and/or whose planning target volume (PTV) overlaps trachea and/or main bronchus. Internal target volume (ITV) was created using 4-DCT. Then 5mm PTV margin was added to create PTV. D50% of PTV volume was set at the prescribed dose. AHRT was delivered with 7-8 fixed non-coplanar converging beams using 6MV X-rays. Usually, IMRT was used to decrease the dose to the OARs. No elective nodal irradiation was performed. Regarding OARs, average D1ccs of pulmonary artery (PA), aorta, superior vena cava (SVC), and proximal bronchial tree (PBT) were calculated. Also, average BED3Gys of D1cc in each OAR were calculated to evaluate late toxicities of late responding tissues. Sixty-six cases with 70 tumors treated between January 2013 and February 2019 were analyzed. Fifty-one tumors were primary, and 19 tumors were metastatic. Thirty-eight tumors were ultracentral and 32 tumors were central. Total dose ranged from 51 Gy to 75 Gy with the median of 75 Gy. Total dose was decreased depending on the high dose to OARs. Median follow-up period was 28.3 months. For ultracentral tumors, average D1cc of PA (15 cases), aorta (11 cases), SVC (2 cases), and PBT (17 cases) were 69.56 Gy±9.29 Gy, 71.72 Gy±5.19 Gy, 74.56 Gy±1.48 Gy, 59.60 Gy±13.64 Gy, respectively. Corresponding BED3Gys of D1cc were 139.53 Gy±25.16 Gy, 142.87 Gy±14.18 Gy, 150.20 Gy±2.31 Gy, 113.65 Gy±34.95 Gy, respectively. Corresponding figures for central tumors were relatively low compared with ultracentral tumors. No severe serial organ toxicity has been encountered. Overall local control rate at 2 years was 79.4%. Overall survival rate of overall cases at 2 years was 81.9%. AHRT was relatively safe treatment method in treating central and ultracentral tumors of lung without severe serial organ toxicities and the doses to OARs were restricted at the reasonably low level compared with ordinal SBRT, the BED3Gy of which would reach 200Gy.

Positron emission tomography (PET) is a practical tool for range verification of hadron therapy. As well, the quantitative washout of the positron emitters has a potential usefulness as a diagnostic index, but the modelling for this has not been established. In this study, we measured washout rates of rabbit brain and performed kinetic analysis to explore the washout mechanism. Six rabbit brains were irradiated by 11 C and 15 O ion beams, and dynamic PET scan was performed using our original depth of interest (DOI)-PET prototype. The washout rate was obtained based on the two-compartment model, where efflux from tissue to blood (k 2 ), influx (k 3 ) and efflux (k 4 ) from the first to second compartments in tissue were evaluated. The observed k 2 , k 3 and k 4 of 11 C were 0.086, 0.137 and 0.007 min −1 , and those of 15 O were 0.502, 0.360 and 0.007 min −1 , respectively. It was suggested permeability of a molecule containing 11 C atoms might be regulated by a transporter. The k 2 of 15 O was comparable with 15 O-water. This study provides basic data for modelling of the washout effect.

The aim of this study is to report the primary result of a multicenter single-arm prospective phase II trial of hypofractionated dynamic tumor-tracking intensity modulated radiation therapy (DTT-IMRT) for locally advanced pancreatic cancer (LAPC). The main eligibility criteria for the study were as follows: locally advanced pancreatic carcinoma with a diameter of 8 cm or less, no obvious gastrointestinal invasion, ECOG-PS of 0 to 1, and respiratory motion of 10 mm or more. Prior to radiation treatment planning, a gold marker was implanted inside or near the primary tumor as an internal surrogate marker for the tumor position. Patients received hypofractionated DTT-IMRT (48 Gy in 15 fr.) using a gimbal mounted Linac with real-time monitoring concurrently with gemcitabine or S-1. The gross tumor volume (GTV) included the primary tumor and metastatic lymph nodes. The clinical target volume (CTV) was defined as GTV plus a 5-mm margin in all directions, in addition to the retropancreatic space and para-aortic lymph node area between the celiac axis and the superior mesenteric artery. PTV was determined as CTV plus margins compensating errors related to positional variations between CTV and the fiducials, correlation models, and mechanical errors, with a minimum of 5 mm. The prescription dose was specified as D95% to PTV-boost, a volume that subtracted the stomach plus 5mm and the duodenum plus 3mm margins from PTV. The primary endpoint was the rate of freedom from locoregional progression (FFLP) at 1 year. Gastrointestinal (GI) toxicity was also analyzed using the Common Terminology Criteria for Adverse Events, version 4.0. From September 2015 to November 2018, 25 LAPC patients were enrolled in four institutions. The median age was 69 years (range; 52-77) and 13 patients were males. Primary tumors were located in 14/11 patients in pancreatic head/body. The median tumor size was 33 mm (range, 20-70). Nineteen and six patients were treated with gemcitabine and S-1 as neoadjuvant chemotherapy, and 18 and 7 patients received gemcitabine and S-1 concurrently with radiation therapy, respectively. The median PTV volumes were 226 cc (range, 138-482). The radiation treatment was completed in all 25 patients. Twenty patients had recurrence, and the first sites of recurrence were local/metastatic/both lesions in 2/15/3 patients, respectively. One-year FFLP was 75.3 %. Acute/late grade-3 GI toxicities occurred in 2/2 patients, respectively. No grade 4/5 GI toxicities were observed. Hypofractionated DTT-IMRT for LAPC resulted in good locoregional control and acceptable GI toxicities. To the best of our knowledge, the present study is the first phase II trial evaluating DTT-IMRT for LAPC in a multi-institutional setting. (Funded by the Japan Agency for Medical Research and Development; and UMIN Clinical Trials Registry number, UMIN000017521).

AbstractBackgroundAlthough carbon‐ion radiotherapy (C‐ion RT) with concurrent chemotherapy (chemo‐C‐ion RT) is a promising treatment for adenocarcinoma (AC) of the uterine cervix, its long‐term efficacy remains unclear. We evaluated the long‐term significance of concurrent weekly cisplatin and C‐ion RT for locally advanced AC of the uterine cervix.MethodsWe performed a pooled analysis of patients with stage IIB–IVA AC of the uterine cervix who underwent C‐ion RT alone or chemo‐C‐ion RT between September 2007 and December 2018 at our institution. Patients received 74.4 Gy (relative biological effectiveness) with or without cisplatin (40 mg/m2 per week for up to 5 weeks), underwent no prior pelvic RT or systemic therapy, and had a performance status of 0‐2. Propensity score matching was based on the year of diagnosis, regional lymph node metastasis, and stage.ResultsThe matched cohort contained 26 patients who underwent C‐ion RT and 26 who underwent chemo‐C‐ion RT. The median age and follow‐up period were 57 (range, 28‐79) years and 34 (range, 2‐126) months, respectively. The 5‐year overall survival rate was significantly better in the chemo‐C‐ion RT group (72%) than in the C‐ion RT group (46%; P = .041). The 5‐year distant metastatic‐free rate was also significantly better in the chemo‐C‐ion RT group (66%) than in the C‐ion RT group (41%; P = .048). The incidence of grade ≥ 3 late toxicities was comparable between the two groups.ConclusionsChemo‐C‐ion RT for locally advanced AC of the uterine cervix is associated with a long‐term survival benefit.

The standard treatment of potentially resectable pancreatic cancer is surgery followed by adjuvant chemotherapy. Recently there have been some prospective reports that neoadjuvant therapy has improved survival. At our institution, we have been conducting both neoadjuvant chemoradiotherapy (NACRT) and adjuvant chemotherapy (AdjCx) for resectable (R) and borderline resectable (BR) pancreatic cancer patients. The aim of this study is to evaluate outcomes and feasibility of this strategy. From 2008 to 2018, 104 consecutive pancreatic cancer patients who were treated with NACRT at our institution were reviewed retrospectively. NCCN criteria 2016 were used for resectability. All patients were planned to be treated with concurrent chemotherapy (Gemcitabine; GEM, Gemcitabine+S-1;GS or S-1) and radiotherapy (50.4Gy in 28 fractions). Approximately one month after the end of the NACRT, patients were evaluated for resectability using CT and MRI. Patients without newly detected distant metastases or unresectable features were referred for surgery. After surgery, patients were referred to receive AdjCx (S-1 or GEM). Seventy-nine patients were diagnosed as R, and 25 patients were diagnosed as BR. UICC clinical stage IA/IB/IIA/IIB/III were 10/7/65/13/9. Concurrent chemotherapy regimens were GEM/GS/S-1 in 1/1/102 cases. One-hundred two patients completed NACRT, and among them 26 patients needed interruption. There were acute grade 3 hematological and non-hematological toxicities in 10 (10%) and 13 (13%) of cases, respectively. There were no grade 4 or greater toxicities. Resection was performed in 72 (69%) of patients; the reasons for unresectability were as follows, distant metastasis in 14 cases, local progression in 5 cases, patient refusal in 9 cases and other medical condition in 4 cases. The median OS, 2-year OS and 5-year OS for resected patients were 44.6 months, 69% and 35%, respectively, and those for unresected patients were 17.0months, 23% and not available, respectively (p<0.05). Among resected patients, R0 resection rate was 93%. 83% of patients could receive AdjCx. The median OS were 47.0 months for R patients and 18.5 months for BR patients (p<0.05). Recurrence was observed in 39 (54%) of 72 resected patients, the first recurrence in local site were 5 (7%) cases and in distant site were 34 (47%) cases. Based on our results, neoadjuvant chemoradiotherapy was feasible with its favorable prognosis and limited toxicity. Further experience is necessary.