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Background: A recent phase I/II study determined the optimal dose of definitive carbon-ion radiotherapy (CIRT) for cT1bN0M0 esophageal cancer. This study aimed to further confirm the efficacy and feasibility of the recommended dose fractionation of CIRT with long-term follow-up results in a larger sample size. Methods: This single center retrospective study evaluated patients with cT1bN0M0 esophageal squamous cell carcinoma treated with the recommended dose fractionation of 50.4 Gy relative biological effectiveness in 12 fractions, between 2012 and 2022. Results: Thirty-eight patients underwent CIRT at our hospital. Although eight (21.1%) patients were older than 80 years, 15 (39.5%) had high surgical risk, and seven (18.4%) were at high risk for chemotherapy, all patients underwent CIRT as scheduled. Grade 3 esophagitis occurred in eight (21.1%) patients and grade 3 pneumonia in one (2.6%) patient in this study, but no grade 4 adverse events occurred. The only grade 3 late adverse event was pneumonia in one patient (2.6%). The 5-year overall survival rate, local control rate, and disease-free survival rates were 76.6% (95% CI, 90.9–62.4), 74.9% (95% CI, 90.7–59.0), and 66.4% (95% CI, 83.3–49.5), respectively. Additionally, post CIRT recurrence was as follows: seven (18.4%) patients had recurrence in another part of the esophagus, three (7.9%) in the primary site, three (7.9%) in lymph nodes outside the irradiated area, and one (2.6%) patient had liver metastasis. Conclusions: Our study demonstrates that CIRT using the recommended dose fractionation is feasible and effective for cT1bN0M0 esophageal squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Dose verification of treatment plans is an essential step in radiotherapy workflows. In this work, we propose a novel method of treatment planning based on nanodosimetric quantity-weighted dose (NQWD), which could realize biological representation using pure physical quantities for biological-oriented carbon ion-beam treatment plans and their direct verification. The relationship between nanodosimetric quantities and relative biological effectiveness (RBE) was studied with the linear least-squares method for carbon-ion radiation fields. Next, under the framework of the matRad treatment planning platform, NQWD was optimized using the existing RBE-weighted dose (RWD) optimization algorithm. The schemes of NQWD-based treatment planning were compared with the RWD treatment plans in term of the microdosimetric kinetic model (MKM). The results showed that the nanodosimetric quantity F3 − 10 had a good correlation with the radiobiological effect reflected by the relationship between RBE and F3 − 10. Moreover, the NQWD-based treatment plans reproduced the RWD plans generally. Therefore, F3 − 10 could be adopted as a radiation quality descriptor for carbon-ion treatment planning. The novel method proposed herein not only might be helpful for rapid physical verification of biological-oriented ion-beam treatment plans with the development of experimental nanodosimetry, but also makes the direct comparison of ion-beam treatment plans in different institutions possible. Thus, our proposed method might be potentially developed to be a new strategy for carbon-ion treatment planning and improve patient safety for carbon-ion radiotherapy. [ABSTRACT FROM AUTHOR]

A few reports have discussed the influence of inter-fractional position error and intra-fractional motion on dose distribution, particularly regarding a spread-out Bragg peak. We investigated inter-fractional and intra-fractional prostate position error by monitoring fiducial marker positions. In 2020, data from 15 patients with prostate cancer who received carbon-ion beam radiotherapy (CIRT) with gold markers were investigated. We checked marker positions before and during irradiation to calculate the inter-fractional positioning and intra-fractional movement and evaluated the CIRT dose distribution by adjusting the planning beam isocenter and clinical target volume (CTV) position. We compared the CTV dose coverages (CTV receiving 95% [V95%] or 98% [V98%] of the prescribed dose) between skeletal and fiducial matching irradiation on the treatment planning system. For inter-fractional error, the mean distance between the marker position in the planning images and that in a patient starting irradiation with skeletal matching was 1.49 ± 1.11 mm (95th percentile = 1.85 mm). The 95th percentile (maximum) values of the intra-fractional movement were 0.79 mm (2.31 mm), 1.17 mm (2.48 mm), 1.88 mm (4.01 mm), 1.23 mm (3.00 mm), and 2.09 mm (8.46 mm) along the lateral, inferior, superior, dorsal, and ventral axes, respectively. The mean V95% and V98% were 98.2% and 96.2% for the skeletal matching plan and 99.5% and 96.8% for the fiducial matching plan, respectively. Fiducial matching irradiation improved the CTV dose coverage compared with skeletal matching irradiation for CIRT for prostate cancer. [ABSTRACT FROM AUTHOR]

Clinical studies of ion beam therapy have been performed at the Lawrence Berkeley Laboratory (LBL), National Institute of Radiological Sciences (NIRS), Gesellschaft für Schwerionenforschung (GSI), and Deutsches Krebsforschungszentrum (DKFZ), in addition to the development of equipment, biophysical models, and treatment planning systems. Although cancers, including brain tumors and pancreatic cancer, have been treated with the Bevalac's neon-ion beam at the LBL (where the first clinical research was conducted), insufficient results were obtained owing to the limited availability of neon-ion beams and immaturity of related technologies. However, the 184-Inch Cyclotron's helium-ion beam yielded promising results for chordomas and chondrosarcomas at the base of the skull. Using carbon-ion beams, NIRS has conducted clinical trials for the treatment of common cancers for which radiotherapy is indicated. Because better results than X-ray therapy results have been obtained for lung, liver, pancreas, and prostate cancers, as well as pelvic recurrences of rectal cancer, the Japanese government recently approved the use of public medical insurance for carbon-ion radiotherapy, except for lung cancer. GSI obtained better results than LBL for bone and soft tissue tumors, owing to dose enhancement enabled by scanning irradiation. In addition, DKFZ compared treatment results of proton and carbon-ion radiotherapy for these tumors. This article summarizes a series of articles (Parts 1–3) and describes future issues of immune ion beam therapy and linear energy transfer optimization. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the efficacy and safety of particle beam radiotherapy (PBRT) in the management of patients with WHO grade 2 and 3 meningiomas. Methods: Thirty-six consecutive and non-selected patients with WHO grade 2 (n = 28) and grade 3 (n = 8) meningiomas were treated at the Shanghai Proton and Heavy Ion Center, from May 2015 to March 2022. The median age of the cohort at PBRT was 48 years. There were 25 and 11 patients treated with PBRT in the setting of newly diagnosed diseases and progressive/recurrent diseases, respectively. PBRT was utilized as re-irradiation in 5 patients. Proton radiotherapy (PRT) and carbon-ion radiotherapy (CIRT), with a median dose of 60 Gy-Equivalent (GyE), were provided to 30 and 6 patients, respectively. Results: With a median follow-up of 23.3 months, the local control rates were 92.0%, 82.0%, and 82.0% at 1, 2, and 3 years for the entire cohort, respectively. Patients with WHO grade 2 meningiomas (100%, 94.1%, 94,1% at 1,2,3 years) had a much better local control than those with WHO grade 3 meningiomas (50%, 25%, 25% at 1,2,3 years; P < 0.001). Three patients, all with WHO grade 3 meningiomas, had deceased at the time of this analysis. Multivariate analyses revealed that WHO grade (grade 2 vs. 3) (p = 0.016) was a significant prognosticator for local control. No severe toxicities (G3 or above) were observed. Conclusions: Treatment-induced efficacy and toxicities to PBRT in WHO grade 2 and 3 meningiomas were both highly acceptable. Longer follow-up is needed to evaluate the long-term outcome in terms of disease control, survival, as well as potential late effects. [ABSTRACT FROM AUTHOR]

Background: There is currently no established imaging method for assessing liver reserve capacity prior to carbon-ion radiotherapy (CIRT) for liver tumors. In order to perform safe CIRT, it is essential to estimate the post-therapeutic residual reserve capacity of the liver. Purpose: To evaluate the ability of pre-treatment 99mTc-galactosyl human serum albumin (99mTc-GSA) scintigraphy to accurately estimate the residual liver reserve capacity in patients treated with CIRT for liver tumors. Materials and methods: This retrospective study evaluated patients who were performed CIRT for liver tumors between December 2018 and September 2020 and underwent 99mTc-GSA scintigraphy before and 3 months after CIRT, and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI within 1 month before CIRT were evaluated. The maximal removal rate of 99mTc-GSA (GSA-Rmax) was analyzed for the evaluation of pre-treatment liver reserve capacity. Then, the GSA-Rmax of the estimated residual liver (GSA-RL) was calculated using liver SPECT images fused with the Gd-EOB-DTPA-enhanced MRI. GSA-RL before CIRT and GSA-Rmax at 3 months after CIRT were compared using non-parametric Wilcoxon signed-rank test and linear regression analysis. Results: Overall, 50 patients were included (mean age ± standard deviation, 73 years ± 11; range, 29–89 years, 35 men). The median GSA-RL was 0.393 [range, 0.057–0.729] mg/min, and the median GSA-Rmax after CIRT was 0.369 [range, 0.037–0.780] mg/min (P =.40). The linear regression equation representing the relationship between the GSA-RL and GSA-Rmax after CIRT was y = 0.05 + 0.84x (R2 = 0.67, P <.0001). There was a linear relationship between the estimated and actual post-treatment values for all patients, as well as in the group with impaired liver reserve capacity (y = − 0.02 + 1.09x (R2 = 0.62, P =.0005)). Conclusions: 99mTc-GSA scintigraphy has potential clinical utility for estimating the residual liver reserve capacity in patients undergoing carbon-ion radiotherapy for liver tumors. Trial registration: UMIN000038328, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000043545. [ABSTRACT FROM AUTHOR]

Radiation therapy for cancer using the Bragg peak of an ion beam has been making steady progress after being proposed by Robert Wilson in 1946. At the end of 2020, 12 dedicated treatment devices existed in operation worldwide, and approximately 40,000 patients have been treated with ion beams (mostly carbon ions). To date, ion beam therapy is superior to other treatments for rare cancers in the head and neck as well as bone and soft tissues; however, most recently, evidence submitted in Japan for the 2022 revision of public health insurance shows that ion beam therapy outperforms photon therapy for intractable common cancers such as pancreatic cancer and liver cancer. This may greatly expand its indications. Lawrence Berkeley Laboratory in the United States started research of ion beam therapy, National Institute of Radiological Sciences in Japan built the first dedicated device Heavy Ion Accelerator in Chiba and started systematic clinical research, and GSI in Germany developed the scanning irradiation method and rotating gantry for the first time. This paper presents the history and future challenges of ion beam therapy in three fields: accelerator and beam delivery system, physical/biological model and treatment planning system, and clinical research. This study is divided into three parts describing the achievements and roles of the three laboratories. In Part 1, accelerator and beam delivery system are described. [ABSTRACT FROM AUTHOR]

Background: Carbon-ion radiotherapy (CIRT) for esophageal cancer has been receiving significant attention given its high local control rates and minimal damage to normal tissues. However, the efficacy and safety of salvage surgery after CIRT for esophageal cancer remain unclear. We report the case of a patient who underwent salvage thoracoscopic surgery after CIRT. Case presentation: A 51-year-old woman underwent upper gastrointestinal endoscopy and a type 0-IIa + 0-IIc esophageal squamous cell carcinoma located 27–29 cm from the patient's incisors, classified as clinical stage I (T1bN0M0), was detected. She received CIRT (50.4 Gy [relative biological effectiveness, RBE]/12 fr) for localized esophageal cancer and achieved complete remission after 4 months. Six years after CIRT, follow-up endoscopic examination demonstrated a type 0-IIa + 0-IIc tumor in the previously treated area. In addition, a type 0-IIa lesion located 20–22 cm from the incisors was found. We diagnosed localized ESCC, classified as clinical stage I (T1bN0M0). Salvage thoracoscopic surgery was performed in the prone position with five access ports. Although the esophagus tightly adhered to the thoracic descending aorta and left main bronchus with severe fibrosis, the esophagus could be separated from the surrounding organs with careful forceps manipulation. The operation time and blood loss were 8 h 45 min and 253 mL, respectively. The patient was discharged from our hospital 17 days after the salvage surgery without any complications. Pathological findings revealed two squamous cell carcinomas. Both tumors were localized in the lamina propria mucosa, and lymph node metastasis was not detected. The tumors were diagnosed as pathological stage IA (pT1aN0M0) according to the TNM criteria. Moreover, pathological examinations showed severe fibrosis of the previously irradiated tissues compared to the normal esophagus located outside of the irradiation field. Following the surgery, the patient had no recurrence for 1 year and 6 months. Conclusions: Thoracoscopic radical esophagectomy can be performed as salvage surgery. Careful and discreet surgery is integral to perform salvage surgery after CIRT since CIRT may cause severe adhesions and fibrosis in the irradiated field. [ABSTRACT FROM AUTHOR]

Purpose: The clinical significance of carbon-ion radiotherapy (CIRT) for octogenarians with locally advanced non-small-cell lung cancer (LA-NSCLC) remains unclear. We aimed to evaluate the clinical outcomes of CIRT alone for octogenarians with LA-NSCLC. Materials and methods: We evaluated 32 patients who underwent CIRT alone between 1997 and 2015. The median age was 82.0 years (range, 80–88 years). In terms of clinical stage (UICC 7th edition), 7 (21.9%), 10 (31.3%), 11 (34.4%), and 4 (12.5%) patients had stage IIA, IIB, IIIA, and ΙΙΙB disease, respectively. The median CIRT dose was 72.0 Gy (relative biological effectiveness), and the median follow-up period was 33.1 months. Results: All patients successfully completed CIRT. Regarding grade ≥ 2 toxicities, 1 (3.1%), 3 (9.4%), and 4 (0.7%) patients developed grade 3 radiation pneumonitis, grade 2 radiation pneumonitis, and grade 2 dermatitis, respectively. No grade ≥ 4 toxicities were observed. The 2 year LC, PFS, and OS rates were 83.5%, 46.7%, and 68.0%, respectively. Conclusion: CIRT alone is safe and effective for octogenarians with LA-NSCLC. [ABSTRACT FROM AUTHOR]

Radical treatments of hepatocellular carcinoma (HCC) with hepatic encephalopathy (HE) can be often difficult due to poor liver function or disturbance of consciousness. An effective treatment requires a combinatorial approach incorporating a treatment for HE and radical therapy for HCC that does not compromise liver function. Here, we report a case of a 78-year-old Japanese male with HCC and HE caused by splenorenal shunt. Serum ammonia levels were high. He was not suitable for surgery, percutaneous radiofrequency ablation, or transarterial chemoembolization due to the location of the tumor and poor liver function, which included HE. Thus, he underwent BRTO, with an immediate improvement in both HE and serum ammonia levels. After BRTO, he received C-ion RT as a radical treatment for HCC. After treatment, HCC was well controlled; however, at 35 months post-initiation of C-ion RT, he developed local recurrence without a further reduction in liver function status. Therefore, we repeated C-ion RT. The patient remains alive at 3 months post-treatment, with no evidence of local recurrence, distant metastasis, or toxicity. Although this is a single case report, it suggests that a combinatorial treatment consisting of BRTO and C-ion RT may increase survival rates of patients with HCC and HE. [ABSTRACT FROM AUTHOR]

Purpose: To describe the characteristic features of post-carbon-ion radiotherapy (CIRT) vertebral pathological fractures (VPFs) in upper cervical primary malignant spinal tumors (PMSTs) treated by occipito-cervical (OC) fusion.Methods: OC fusion was performed for three consecutive patients with post-CIRT VPFs. The clinical results and imaging findings, including bone single-photon emission computed tomography (SPECT)/CT were prospectively collected.Results: No surgery-related wound complication and surgical site infection were noted. One patient experienced re-fracture and displacement of dens with the loosening of occipital screws and was treated by posterior revision surgery. At the final follow-up, all patients were alive without evidence of disease, and the solid OC fusion was confirmed. Bone SPECT/CT clearly revealed the effect of CIRT on bone turnover in the irradiated field.Conclusion: The OC fusion with autologous bone grafts was a reliable option for the treatment of post-CIRT VPCs in the patients with upper cervical PMSTs. In addition, evaluation of the bone turnover at the irradiated field by bone SPECT/CT would help surgeons select an effective plan of care, such as fusion level and postoperative care. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the clinical outcome of combination of carbon-ion radiotherapy with separation surgery (CIRT-SS) in patients with primary spinal/paraspinal sarcoma (PSPS) and epidural spinal cord compression (ESCC). Methods: CIRT-SS was performed in 11 consecutive patients. Patients treated in the primary and salvage settings were categorized into Group A (n = 8) and Group B (n = 3), respectively. Clinical results and imaging findings were collected, with a particular focus on ESCC grade, treatment-associated adverse events (AEs), and the locoregional control (LRC) rate and overall survival (OS). Results: The median follow-up period from the start of CIRT-SS was 25 months (7–57 months). ESCC was improved by SS in all cases. No patients exhibited radiation-induced myelopathy (RIM), but three developed Grade 3 vertebral compression fracture (VCF) during follow-up. Locoregional recurrences were observed in four patients [Group A: 1 (12.5%), Group B: 3 (100%)]. Over the entire follow-up period, three patients developed distant metastases and two patients died. The 2-year LRC rate and OS were 70% and 80%, respectively. Conclusion: CIRT-SS in the primary setting achieved acceptable LRC and OS without RIM in patients with PSPS and with ESCC. VCF was the most frequent AE associated with CIRT-SS. [ABSTRACT FROM AUTHOR]

Background: The efficacy of carbon-ion radiotherapy (C-ion RT) for lymph node (LN) oligo-recurrence has only been evaluated in limited single-center studies. We aimed to investigate the benefit of C-ion RT for LN oligo-recurrence in a large multi-center study. Methods: Patients who received C-ion RT between December 1996 and December 2015 at 4 participating facilities and who met the following eligibility criteria were included: (i) histological or clinical diagnosis of LN recurrence; (ii) controlled primary lesion; (iii) no recurrence other than LN; (iv) LN recurrence involved in a single lymphatic site; and (v) age ≥ 20 years. Results: A total of 323 patients were enrolled. Median follow-up period was 34 months for surviving patients. The most common dose fractionation of C-ion RT was 48.0 Gy (relative biological effectiveness) in 12 fractions. Forty-seven patients had a history of RT at the recurrent site. The 2-year local control (LC) and overall survival (OS) rates after C-ion RT were 85% and 63%, respectively. Only 1 patient developed grade-3 toxicity. Factors such as LN diameter, histology, and history of previous RT did not correlate with LC. Smaller diameters (< 30 mm) and numbers (≤ 3) of LN metastases as well as longer disease-free intervals post-primary therapy (≥ 16 months) were associated with significantly better OS. Conclusions: C-ion RT for LN oligo-recurrence appeared to be effective and safe. C-ion RT may provide a survival benefit to patients with LN oligo-recurrence, particularly to those with few LN metastases, smaller LN diameters, and longer disease-free intervals. [ABSTRACT FROM AUTHOR]

A treatment of carbon-ion radiotherapy (CIRT) is generally evaluated using the dose weighted by relative biological effectiveness (RBE) while ignoring the radiation quality varying in the patient. In this study, we have developed a method of estimating linear energy transfer (LET) from the RBE in an archived treatment plan to represent the radiation quality of the treatment. The LET in a beam database was associated with the RBE by two fitting functions per energy, one for the spread-out Bragg peak (SOBP) and the other for shallower depths, to be differentiated by RBE per energy per modulation. The estimated LET was generally consistent with the original calculation within a few keV/μm, except for the overkill region near the distal end of SOBP. The knowledge of experimental radiobiology can thereby be associated with CIRT treatments through LET, which will potentially contribute to deeper understanding of clinical radiobiology and further optimization of CIRT. [ABSTRACT FROM AUTHOR]

Objective: The aim of our study was to investigate the predictive role of apparent diffusion coefficient (ADC) values in evaluating for therapeutic changes from carbon-ion radiotherapy (CIRT) in prostate cancer patients. Materials and methods: Thirty-one patients with prostate cancer treated with CIRT were enrolled in this retrospective study. Diffusion-weighted imaging (DWI) at 3-T was performed before and after CIRT. Before and after treatment, ADC values were measured in the tumors and in the benign tissues of the prostate, and serum prostate-specific antigen (PSA) levels were also assessed. We divided the patients into two groups: PSA response (PSA declines ≥50 %) and non-PSA response group (PSA declines <50 %). Results: After CIRT treatment, the mean ADC value of the tumors (1.23 × 10mm/s) was significantly increased as compared with the pretreatment value (1.07 × 10mm/s) ( p < 0.001), whereas the ADC values of the benign tissues after treatment did not significantly increase compared with the pretreatment values ( p = 0.235). The mean PSA level was significantly reduced from 2.027 ng/mL before treatment to 0.822 ng/mL, respectively, after treatment ( p = 0.0063). The mean of ADC changes in PSA response group before and after CIRT was significantly higher than that in non-PSA response group (∆ADC value: 0.217 vs 0.097 × 10mm/s, p = 0.0229), and the rate of patients with PSA response was higher in the high ∆ADC group (∆ADC ≥ 0.10) than in the low ∆ADC group (∆ADC < 0.10) (72.7 and 33.3 %, respectively), but marginally significant ( p = 0.056). Additionally, the baseline tumor ADC values revealed a negative correlation with changes in PSA levels after treatment (correlation coefficient, ρ = −0.524; p = 0.0025). Conclusion: Our preliminary results suggest that ADC vales measurement may be a useful imaging biomarker for prediction and early assessment of therapeutic response of prostate cancer to CIRT. [ABSTRACT FROM AUTHOR]

Purpose: Primary spinal osteosarcoma is quite rare, and the 5-year survival rate is very low. Because of its rarity, successful treatment experience with spinal osteosarcoma is limited. The purpose of this study is to report the effect of therapy of primary osteosarcoma of spine by carbon-ion radiotherapy (CIRT) and long-term follow.Methods: A 70-year-old with primary spinal osteosarcoma who received CIRT underwent combined anterior artificial vertebral body replacement and posterior lumbar fusion (L1-L5) 3 years later.Results: According to the surgical resection of tumoral lesion, pathological results showed that the intertrabecular space previously filled with tumor cells on the initial biopsy sample now contained necrotic tissue without tumor cells. This means that primary osteosarcoma of the spine was completely eliminated and achieved local control with CIRT, with a 7-year follow-up after the initial treatment.Conclusions: Carbon ion beam treatment is an effective local treatment for patients with spinal osteosarcoma for whom surgical resection is not a feasible option, especially for elderly patients. However, more patients need to be evaluated over a longer term to assess the curative effect of CIRT. [ABSTRACT FROM AUTHOR]

Particle irradiation of cancerous disease has gained great traction in recent years. The ability for particle therapy centers to deliver radiation with a highly conformal dose distribution while maintaining minimal exit or excess dose delivered to normal tissue, coupled with various biological advantages particularly found with heavy-ion beams, enables treatment of diseases inapproachable with conventional radiotherapy. Here, we present a review of the current status of particle therapy with regard to cancers of the gastrointestinal tract, including esophagus, liver, pancreas, and recurrent rectal cancer. [ABSTRACT FROM AUTHOR]

The standard treatment for metastatic liver tumor from breast cancer is systemic medical treatment, and there is controversy regarding the value of local treatment. However, there are some exceptional cases that do benefit from local therapy. We describe the case of a 54-year-old woman with systemic therapy-resistant liver metastasis from breast cancer successfully treated with a single shot of 36-GyE carbon-ion radiotherapy and surviving more than 8 years without local recurrence. This case represents a good example of the usefulness and safety of carbon-ion radiotherapy, and who might benefit from local therapy. [ABSTRACT FROM AUTHOR]

Breast cancer is increasingly being detected at earlier stages, and partial breast irradiation for patients with low-risk-group tumor has come to be applied in the US and Europe as an alternative to whole-breast irradiation. Based on those experiences, some institutes have tried using particle beams for partial breast irradiation for postoperative or radical intent for early breast cancer, but technical difficulties have hindered its progress. The National Institute of Radiological Sciences has been preparing for carbon-ion radiotherapy (C-ion RT) with radical intent for stage I breast cancer since 2011, and we carried out the first treatment in April 2013. In this case report, we explain our first experience of C-ion RT as a treatment procedure for breast tumor and present the radiation techniques and preliminary treatment results as a reference for other institutes trying to perform the same kind of treatment. [ABSTRACT FROM AUTHOR]

Background: Treatment for unresectable Ewing's sarcoma family of tumors (ESFT) is a formidable challenge because of its high tendency for local and distant failure. Recently, carbon-ion radiotherapy (CIRT) has been applied to unresectable bone and soft tissue sarcoma. Additionally, high-dose chemotherapy (HDC) with stem cell rescue has been used to improve the survival of patients with relapsed ESFT. Here we report our experience with CIRT and HDC in the treatment of unresectable ESFT. Methods: Five unresectable ESFT patients including 4 who underwent CIRT and HDC and one who underwent CIRT from 1999−2009 were retrospectively studied. After neoadjuvant chemotherapy, CIRT was conducted at the National Institute of Radiological Sciences in Chiba as local therapy. Consecutively, we employed HDC including busulfan, melphalan, and thiotepa with stem cell rescue. Results: Two patients showed tumor shrinkage after CIRT, including 1 patient who achieved partial response. No severe acute toxicity related to CIRT was observed. Local failure was observed in only 1 patient at 22 months after CIRT. Four patients conducted HDC with stem cell rescue after CIRT and 1 patient suffered from veno-occlusive disease just after HDC. Distant failure was observed in 3 patients after completion of the treatment. Conclusions: CIRT and HDC for unresectable ESFT patients show favorable local control, with unsatisfactory results for distant control. [ABSTRACT FROM AUTHOR]

In carbon-ion radiotherapy, it is important to evaluate the biological dose because the relative biological effectiveness values vary greatly in a patient's body. The microdosimetric kinetic model (MKM) is a method of estimating the biological effect of radiation by use of microdosimetry. The lateral biological dose distributions were estimated with a modified MKM, in which we considered the overkilling effect in the high linear-energy-transfer region. In this study, we used the Monte Carlo calculation of the Geant4 code to simulate a horizontal port at the Heavy Ion Medical Accelerator in Chiba of the National Institute of Radiological Sciences. The lateral biological dose distributions calculated by Geant4 were almost flat as the lateral absorbed dose in the flattened area. However, in the penumbra region, the lateral biological dose distributions were sharper than the lateral absorbed dose distributions. Furthermore, the differences between the lateral absorbed dose and biological dose distributions were dependent on the depth for each multi-leaf collimator opening size. We expect that the lateral biological dose distribution presented here will enable high-precision calculations for a treatment-planning system. [ABSTRACT FROM AUTHOR]

We tested the ability of two separate nuclear reaction models, the binary cascade and JQMD (Jaeri version of Quantum Molecular Dynamics), to predict the dose distribution in carbon-ion radiotherapy. This was done by use of a realistic simulation of the experimental irradiation of a water target. Comparison with measurement shows that the binary cascade model does a good job reproducing the spread-out Bragg peak in depth-dose distributions in water irradiated with a 290 MeV/u (per nucleon) beam. However, it significantly overestimates the peak dose for a 400 MeV/u beam. JQMD underestimates the overall dose because of a tendency to break a nucleus into lower- Z fragments than does the binary cascade model. As far as shape of the dose distribution is concerned, JQMD shows fairly good agreement with measurement for both beam energies of 290 and 400 MeV/u, which favors JQMD over the binary cascade model for the calculation of the relative dose distribution in treatment planning. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer has a very high mortality rate worldwide, and about 30-40% of all patients have extensive vascular involvement at initial diagnosis that precludes surgical intervention. Here, we describe our experience in a patient with locally advanced pancreatic cancer (LAPC) who underwent R0 conversion surgery after undergoing a combination of chemotherapy and carbon-ion radiotherapy (CIRT), which led to long-term relapse-free survival (23 months).Case presentation: A 41-year-old woman presented a month ago with epigastralgia referred to our facility and was subsequently diagnosed with pancreatic cancer cStage III (Ph, TS2 (35 mm), cT4, cCH1, cDU1, cS1, cRP1, cPL1, cVsm0, cAsm1, cN0, cM0) that was also categorized as an unresectable LAPC. She immediately underwent 3 cycles of induction chemotherapy (gemcitabine + nanoparticle albumin-bound (nab-) paclitaxel) followed by CIRT with concurrent gemcitabine. Although significant shrinkage of the primary tumor occurred, frequent cholangitis due to duodenal stenosis of unknown etiology prevented continued chemotherapy, and 9 months after the first visit, she underwent a radical, subtotal, stomach-preserving, pancreaticoduodenectomy (SSPPD). Histopathologic examination of the resected tissue revealed a R0 resection with a histological response of Evans grade IIB. She was administered an almost full dose of S-1 as adjuvant chemotherapy for 6 months and has shown no signs of recurrence in 23 months.Conclusions: We report a first case of successful conversion surgery for an initially unresectable LAPC after rapid induction GEM + nab-PTX chemotherapy followed by CIRT. Rapid induction GEM + nab-PTX chemotherapy followed by CIRT for LAPC might be a safe and effective treatment option. [ABSTRACT FROM AUTHOR]