Publications by authors named "Hirokazu Makishima"

33 Publications

Light flash and odor during proton beam therapy for pediatric patients: a prospective observational study.

Front Oncol 2022 1;12:863260. Epub 2022 Aug 1.

Department of Radiation Oncology, University of Tsukuba, Tsukuba, Japan.

Light flash and odor during radiation therapy are well-known phenomena, but the details are poorly understood, particularly in pediatric patients. Therefore, we conducted a prospective observational study of these events in pediatric patients (age ≤20 years old) who received radiotherapy at our center from January 2019 to November 2021. Light flash and odor were evaluated using a patient-reported checklist including the presence, strength, and duration of the phenomenon, and color of light or type of odor. 53 patients who received proton therapy (n=47) and photon radiotherapy (n=6) were enrolled in this study. The median age of the patients was 10, ranged from 5 to 20. The patients who was able to see the light flash was 4, and all of them received retina irradiation. This was equivalent to 57% of the patients who received radiotherapy to retina (n=7). The light was bright and colored mainly blue and purple, which seemed to be consistent with Cherenkov light. Odor was sensed by 9 (17%) patients, and seven patients of the 9 received nasal cavity irradiation. This was equivalent to 41% of the patients who received nasal cavity irradiation (n=17). Other 2 patients received proton therapy to brain tumor. The odors were mainly described as plastic, burnt and disinfectant, which may be caused by ozone generated during irradiation. These data suggest that pediatric patients with retinal and nasal cavity irradiation frequently sense light flashes or odor. So adequate care is necessary so that these patients are not worried about this phenomenon.
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http://dx.doi.org/10.3389/fonc.2022.863260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9376462PMC
August 2022

Carbon-ion radiotherapy versus radiofrequency ablation as initial treatment for early-stage hepatocellular carcinoma.

Hepatol Res 2022 Aug 11. Epub 2022 Aug 11.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Aim: Carbon-ion radiotherapy (C-ion RT) has shown potential as a curative treatment for patients with hepatocellular carcinoma (HCC). However, no reports have compared the effectiveness of C-ion RT and radiofrequency ablation (RFA). This study aimed to compare clinical outcomes between C-ion RT and RFA for patients with early-stage HCC.

Methods: Medical records of consecutive patients with HCC (single lesion ≤5 cm or 2-3 lesions ≤3 cm) who received either C-ion RT or RFA as initial treatment were retrospectively reviewed. Propensity score matching (PSM) was performed to adjust for clinical factors between both groups.

Results: A total of 560 patients were included herein, among whom 69 and 491 received C-ion RT and RFA, respectively. After PSM (C-ion RT: 54 patients, RFA: 95 patients), both groups were well balanced. C-ion RT had significantly lower cumulative intra-subsegmental recurrence rate after PSM compared to RFA (p = 0.004) (2-year: 12.6% vs. 31.7%, 5-year: 15.5% vs. 49.6%, respectively). However, no significant difference in cumulative local recurrence rate, stage progression-free survival, and overall survival (OS) was observed between both groups. In the RFA group, 6 of 491 patients (1.2%) showed grade 3 adverse events, whereas no grade 3 or higher adverse events were observed in the C-ion RT group.

Conclusion: C-ion RT provided lower cumulative intra-subsegmental recurrence rate, but a comparable cumulative local recurrence rate, stage progression-free survival, and OS compared to RFA. Thus, C-ion RT appears to be one of the effective treatment options for early-stage HCC when RFA is deemed not indicated. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/hepr.13827DOI Listing
August 2022

Abnormal sensation during total body irradiation: a prospective observational study.

J Radiat Res 2022 Jul 11. Epub 2022 Jul 11.

Department of Radiation Oncology, University of Tsukuba, Tsukuba, Ibaraki 305-8576, Japan.

Light flash and odor during radiotherapy are well-known phenomena. Two prospective observational studies have indicated that 55% of patients observed a light flash during irradiation of the retina and 27% of patients sensed an odor during radiotherapy for the nasal cavity. A prospective observational study was performed in all patients at our hospital who received total body irradiation (TBI) between January 2019 to October 2021. Light flash and odor during TBI were examined using the same method as that used in previous studies. A total of 32 patients received TBI during the study period. The patients had a median age of 41 (18-60) years, and included 20 males and 12 females. A survey checklist showed that 14 patients (44%) sensed light and 14 patients (44%) sensed odor during TBI,. The color of the light during irradiation was yellow in six cases, white in four cases, and blue in four cases. The intensity of the light was 2-5 (median 3, 1 is very weak, 5 is very strong) and the time over which the light flash was felt was 4-60 s (median 10 s). Two patients each sensed smells of plastic, ozone and bleach, and others sensed one smell each. The intensity of the odor was 1-4 (median 3, 1 is very weak, 5 is very strong) and the time over which the odor was sensed was 1-25 s (median 3 s). We conclude that light flashes and odors are each sensed by 44% of patients during TBI. Various types of light flashes and odors were reported in this study.
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http://dx.doi.org/10.1093/jrr/rrac042DOI Listing
July 2022

Proton Beam Therapy for Multifocal Hepatocellular Carcinoma (HCC) Showing Complete Response in Pathological Anatomy After Liver Transplantation.

Cureus 2022 Jun 8;14(6):e25744. Epub 2022 Jun 8.

Department of Radiation Oncology, Proton Medical Research Center, University of Tsukuba Hospital, Tsukuba, JPN.

We describe a patient with multifocal recurrent hepatocellular carcinoma (HCC) who received proton beam therapy (PBT) and then underwent donation after brain dead (DBD) liver transplantation. The anatomy of the explanted diseased liver was examined pathologically post-transplantation. The patient was a 52-year-old male with hepatitis B virus infection and liver cirrhosis of Child-Pugh class B. Right lobe and caudate lobectomy were performed for primary HCC. However, three recurrent tumors appeared in the remnant liver in segments S2 (two sites) and S4, of sizes 23 mm, 10 mm, and 32 mm, respectively. Liver transplantation was required due to these multiple HCCs and liver cirrhosis, but the patient was ineligible for living donor liver transplantation (LDLT) based on Milan criteria. He was registered as a candidate on the waiting list for DBD transplantation. In consideration of the long waiting time for a deceased donor transplant for more than one year, the progression of multiple recurrent HCCs, and the risk of death, the patient had limited treatment options other than PBT for poor liver function and multifocal HCC and eventually received 65 GyE/18 fractions of PBT. Eleven months after the start of PBT, the tumors remained progression-free and liver function did not deteriorate, allowing the patient to wait for liver transplantation. After transplantation, the histopathology of the explanted liver showed that the left lobe of the liver treated by PBT showed no evidence of solid tumors and tumor cells in visual and microscopic examinations. There was also no significant damage to normal liver tissue. This case demonstrates that PBT is a prospective option for patients with HCC with poor liver function, multiple tumors, and no other treatment options. PBT can achieve control or even complete response of HCC while maintaining liver function and may be an effective pre-transplant method for tumor downstaging and prolonging survival. PBT may enable more people to wait for a donor liver or to become eligible for liver transplantation.
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http://dx.doi.org/10.7759/cureus.25744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9264287PMC
June 2022

Olfactory Sensations During Proton and Photon Radiotherapy: A Multicenter Prospective Observational Study.

Cureus 2022 Mar 8;14(3):e22964. Epub 2022 Mar 8.

Radiation Oncology, University of Tsukuba Hospital, Tsukuba, JPN.

Purpose: Patients often report a sense of smell during radiation therapy (RT), but the details of these events are not well understood. The purpose of the study was to evaluate events of smell during photon RT and proton beam therapy (PBT).

Methods And Materials: The subjects were all adult patients (≥20 years old) treated with photon RT or PBT at two centers from January 2019 to August 2020, with the exclusion of those with communication difficulties or olfactory abnormality. The presence of smell, odor type, intensity (five levels), and time period was examined prospectively using a weekly checklist.

Results: A total of 649 courses were examined in 620 patients who received photon RT (n=415) or PBT (n=205). A smell during the procedure was sensed by 51 patients (8.2%). In multivariate logistic regression analysis, nasal cavity dose (p=0.002), age (p<0.001), and photon RT (p=0.018) were identified as significant factors associated with a sense of smell. Smell occurred in only 23/515 patients (4.5%) in whom the nasal cavity was not irradiated, but in 4/19 (21.1%) and 24/86 (27.9%) with nasal cavity maximum isodose lines of 10%-50% and 60%-100%, respectively. Patients who received photon RT sensed a smell (43/415; 10.4%) more frequently than those treated with PBT (8/205; 3.9%). Of the 51 patients who sensed a smell, 32 (63%) reported a burnt smell, eight (16%) a chemical smell, two (4%) a sour smell, and nine another smell (copier machine, sweet, garbage, etc.).

Conclusions: The sense of a smell appears to be common during RT and this sensation is significantly associated with the nasal cavity dose, younger age, and photon RT.
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http://dx.doi.org/10.7759/cureus.22964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8989623PMC
March 2022

Durvalumab with or without tremelimumab combined with particle therapy for advanced hepatocellular carcinoma with macrovascular invasion: protocol for the DEPARTURE phase Ib trial.

BMJ Open 2022 04 8;12(4):e059779. Epub 2022 Apr 8.

National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.

Introduction: Advanced hepatocellular carcinoma (HCC) with macrovascular invasion (MVI) has the worst prognosis among all phenotypes. This trial aims to evaluate whether treatment with durvalumab, alone or in combination with tremelimumab, plus particle therapy is a safe and synergistically effective treatment in patients with advanced HCC and MVI.

Methods And Analysis: This phase Ib, multicentre (two sites in Japan), open-label, single-arm, investigator-initiated clinical trial will assess durvalumab monotherapy in combination with particle therapy (cohort A) and that of durvalumab plus tremelimumab in combination with particle therapy (cohort B) for patients with advanced HCC with MVI. Cohort A will receive 1500 mg durvalumab every 4 weeks. Cohort B will receive 1500 mg durvalumab every 4 weeks in principle and 300 mg tremelimumab only on day 1 of the first cycle. Carbon-ion radiotherapy will be administered after day 8 of the first cycle. The primary endpoints are rates of any and severe adverse events, including dose-limiting toxicities (DLTs); secondary endpoints are overall survival, 6-month survival, objective response, 6-month progression-free survival and time to progression. Patients are initially enrolled into cohort A. If cohort A treatment is confirmed to be tolerated (ie, no DLT in three patients or one DLT in six patients), the trial proceeds to enrol more patients into cohort B. Similarly, if cohort B treatment is confirmed to be tolerated (ie, no DLT in three patients or one DLT in six patients), a total of 15 patients will be enrolled into cohort B.

Ethics And Dissemination: This study was approved by the ethics committees of the two participating institutions (Chiba University Hospital and National Institutes for Quantum (approval number: 2020040) and Radiological Science and Technology, QST Hospital (approval number: C20-001)). Participants will be required to provide written informed consent. Trial results will be reported in a peer-reviewed journal publication.

Trial Registration Number: jRCT2031210046.
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http://dx.doi.org/10.1136/bmjopen-2021-059779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8995959PMC
April 2022

Acute toxicity and patient-reported symptom score after conventional versus moderately hypofractionated proton therapy for prostate cancer.

J Med Radiat Sci 2022 Jun 19;69(2):198-207. Epub 2021 Oct 19.

Department of Radiation Oncology and Proton Medical Research Center, University of Tsukuba, Tsukuba, Japan.

Introduction: To confirm the feasibility of hypofractionated proton beam therapy (PBT), we compared the acute adverse event rates and International Prostate Symptom Score (IPSS) in prostate cancer patients treated with hypofractionated versus conventionally fractionated (2.0 Gy relative biological effectiveness (RBE)/fraction) PBT.

Methods: We reviewed 289 patients with prostate cancer, of whom 73, 100, and 116 patients were treated with 2.0, 2.5, and 3.0 Gy (RBE)/fraction, respectively. The endpoints were acute genitourinary and gastrointestinal toxicities and the IPSS, evaluated up to 6 months after PBT initiation.

Results: No significant differences were found in acute toxicity rates or the IPSS among the fractionation schedules. Diabetes mellitus, age, and androgen deprivation therapy were not identified as factors associated with the IPSS.

Conclusion: There were no significant differences in adverse events or quality of life among the three fractionation schedules early after PBT.
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http://dx.doi.org/10.1002/jmrs.551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9163454PMC
June 2022

Carbon-ion Radiotherapy for Colorectal Cancer.

J Anus Rectum Colon 2021 28;5(2):113-120. Epub 2021 Apr 28.

QST Hospital, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.

Heavy-ion radiotherapy (RT) is a kind of particle RT, and carbon-ion beam constitutes the primary delivery method of heavy-ion RT. Unlike the conventional photon modalities, particle RT, in particular carbon-ion radiotherapy (CIRT), offers unique physical and biological advantages. Particle therapy allows for substantial dose delivery to tumors with minimal surrounding tissue damage. In addition, CIRT in particular possesses biological advantages such as inducing increased double-strand breaks in DNA structures, causing irreversible cell damage independently of cell cycle or oxygenation, more so than proton or photon. It can be expected that CIRT is effective on radioresistant cancers such as colorectal cancers (CRCs). We introduced the results of CIRT for local recurrent rectal cancer, lung metastasis, liver metastasis, and lymph node metastasis.
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http://dx.doi.org/10.23922/jarc.2020-082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084540PMC
April 2021

[Ⅰ.Carbon-Ion Radiotherapy for Hepatocellular Carcinoma].

Gan To Kagaku Ryoho 2020 Oct;47(10):1423-1427

National Institutes for Quantum and Radiological Science and Technology, QST Hospital.

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October 2020

Assessment of SPECT-CT fusion images and semi-quantitative evaluation using SUV in I-IMP SPECT in patients with choroidal melanoma.

Ann Nucl Med 2020 Nov 9;34(11):864-872. Epub 2020 Sep 9.

Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST), 4-9-1 Anagawa, Inage-ku, Chiba City, Chiba, 263-8555, Japan.

Objectives: The aim of this study was to assess the diagnostic ability of N-isopropyl-p-[I-123] iodoamphetamine (IMP) SPECT semi-quantitative evaluation based on the standardized uptake value (SUV) in patients with choroidal melanoma. The secondary aim was to investigate the 6-h IMP SPECT imaging in comparison with 24-h imaging.

Methods: Twenty-five patients (14 males and 11 females, mean age of 59.2-year-old) were analyzed in this retrospective study. Patients underwent 24-h IMP SPECT imaging with a gamma camera after intravenous injection of IMP. Twelve of 25 patients underwent 6-h SPECT imaging in addition to the 24-h imaging. All acquired SPECT images were fused with CT images using an image-analysis software. To assess the utility of semi-quantitative evaluation method, we introduced an image evaluation method using SUVmax comparing with conventional count-based uptake index (UI) evaluation of the lesion. Volumes-of-interest (VOIs) for SUVmax and regions-of-interest (ROIs) for UI were drawn referring to the SPECT-CT fusion image. Then the relationship between the 6- and 24-h images was examined both in SUV and UI evaluation. Furthermore, the relationship between the size category classification (SCC) by UICC/AJCC: 1-4 scales and each semi-quantitative value using SUVmax and UI was also assessed.

Results: SUVmax of the tumor was significantly higher than that of the normal side; 2.37 ± 0.88 and 1.77 ± 0.39 (P < 0.05) on 6-h image, 4.17 ± 1.73 and 2.04 ± 0.45 (P < 0.001) on 24-h image, respectively. UI of the tumor was also significantly higher than that of the normal side; 2.24 ± 0.67 and 1.53 ± 0.35 (P < 0.01) on 6-h image, 3.79 ± 1.24 and 1.67 ± 0.44 (P < 0.001) on 24-h image, respectively. There was a strong significant linear relationship in the evaluation with SUVmax between 6- and 24-h on the tumor side (R = 0.88, P < 0.0001), compared to that with Tumor-UI (R = 0.35, P < 0.05). In addition, SUVmax of the tumor clearly differentiated the SCC of the tumor category 4 from that of category 1, where SUVmax of the tumor for categories 1‒4 were 2.56 ± 0.59, 4.33 ± 1.92, 4.63 ± 1.45, and 5.73 ± 1.69, respectively (P < 0.05, for categories 1 and 4).

Conclusions: The semi-quantitative evaluation by SUV of I-IMP SPECT images fused with CT images is useful for detecting choroidal melanoma. Moreover, 6-h imaging with SUV-based evaluation of I-IMP SPECT is promising compared to the conventional count-based UI evaluation method. Trial registration This study is registered in UMIN Clinical Trials Registry (UMIN-CTR) as UMIN study ID: UMIN000038174.
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http://dx.doi.org/10.1007/s12149-020-01517-zDOI Listing
November 2020

Long-Term Results of High-Dose 2-Fraction Carbon Ion Radiation Therapy for Hepatocellular Carcinoma.

Adv Radiat Oncol 2020 Mar-Apr;5(2):196-203. Epub 2019 Sep 27.

International University of Health and Welfare, Mita Hospital, Tokyo, Japan.

Purpose: Carbon ion beams have several physical and biological advantages compared with conventional radiation for cancer therapy. The objective of this study is to evaluate the safety and effectiveness of 2-fraction carbon ion radiation therapy (CIRT) in patients with hepatocellular carcinoma (HCC).

Methods And Materials: Between December 2008 and March 2013, 57 patients with localized HCC were treated with CIRT at a total dose of 45 Gy (relative biological effectiveness) in 2 fractions and retrospectively analyzed after long-term observation. The main endpoints of this study were treatment-related toxicity and local tumor control. Toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Changes in the Child-Pugh score from before to after CIRT were also examined to evaluate hepatic toxicity. Local control was defined as no progression of the irradiated lesion according to the modified Response Evaluation Criteria in Solid Tumors.

Results: The median age of the patients was 75 years (range, 49-89 years). Of these patients, 41 had a newly diagnosed lesion, and 16 had residual or recurrent lesions after previous treatments. The median follow-up duration was 54 months (range, 7-103 months). All surviving patients were followed for more than 51 months. Two patients experienced grade 3 acute skin reactions, but no other grade 3 or higher toxicities were observed in any organ. No patient exhibited an increase in the Child-Pugh score of 2 or more points after CIRT. The local tumor control rates at 1, 3, and 5 years were 98%, 91%, and 91% after CIRT, respectively. All lesions that failed to respond to previous treatments were successfully controlled by CIRT. The 1-, 3-, and 5-year overall survival rates were 97%, 67%, and 45%, respectively.

Conclusions: Two-fraction CIRT was a well-tolerated and effective treatment for patients with HCC.
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http://dx.doi.org/10.1016/j.adro.2019.09.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136623PMC
September 2019

Heavy charged particles for gastrointestinal cancers.

J Gastrointest Oncol 2020 Feb;11(1):203-211

Department of Radiation Oncology, Hospital of the National Institute of Radiological Science, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.

Carbon ion beams constitute the primary delivery method of heavy ion radiotherapy. It offers improved dose distribution, and enables concentration of dose within target volumes with minimal extraneous exposure of normal tissue, while delivering superior biological effect in comparison with photon and proton technologies. Here, we review the application of this technology to various gastrointestinal cancers.
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http://dx.doi.org/10.21037/jgo.2019.03.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052771PMC
February 2020

Key considerations in reviewing "a comparison of the outcomes between surgical resection and proton beam therapy for single primary hepatocellular carcinoma": the importance of scientific objective perspectives in clinical studies.

Surg Today 2020 Aug 21;50(8):944-945. Epub 2020 Jan 21.

Proton Medical Research Center, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.

Proton beam therapy and carbon-ion radiotherapy, also known as particle beam therapy, are gaining popularity in cancer care and liver tumor treatment is one of the main areas of interest. Comparative studies are in high demand and the article highlights this. While the data presented in this article are without doubt valuable, we raise concerns about their interpretation.
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http://dx.doi.org/10.1007/s00595-020-01961-4DOI Listing
August 2020

Reference region extraction by clustering for the pharmacokinetic analysis of dynamic contrast-enhanced MRI in prostate cancer.

Magn Reson Imaging 2020 02 2;66:185-192. Epub 2019 Sep 2.

Department of Charged Particle Therapy Research, National Institute of Radiological Sciences, QST, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.

Purpose: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) measures changes in the concentration of an administered contrast agent to quantitatively evaluate blood circulation in a tumor or normal tissues. This method uses a pharmacokinetic analysis based on the time course of a reference region, such as muscle, rather than arterial input function. However, it is difficult to manually define a homogeneous reference region. In the present study, we developed a method for automatic extraction of the reference region using a clustering algorithm based on a time course pattern for DCE-MRI studies of patients with prostate cancer.

Methods: Two feature values related to the shape of the time course were extracted from the time course of all voxels in the DCE-MRI images. Each voxel value of T1-weighted images acquired before administration were also added as anatomical data. Using this three-dimensional feature vector, all voxels were segmented into five clusters by the Gaussian mixture model, and one of these clusters that included the gluteus muscle was selected as the reference region.

Results: Each region of arterial vessel, muscle, and fat was segmented as a different cluster from the tumor and normal tissues in the prostate. In the extracted reference region, other tissue elements including scattered fat and blood vessels were removed from the muscle region.

Conclusions: Our proposed method can automatically extract the reference region using the clustering algorithm with three types of features based on the time course pattern and anatomical data. This method may be useful for evaluating tumor circulatory function in DCE-MRI studies.
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http://dx.doi.org/10.1016/j.mri.2019.08.034DOI Listing
February 2020

First prospective feasibility study of carbon-ion radiotherapy using compact superconducting rotating gantry.

Br J Radiol 2019 Nov 24;92(1103):20190370. Epub 2019 Jul 24.

Hospital of the National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Sciences and Technology, Chiba, Japan.

Objective: We had developed compact rotating gantry for carbon ion using superconducting magnets in 2015 which became clinically operational in 2017. The objective of this study was to assess the clinical feasibility and safety of using compact rotating gantry with three-dimensional active scanning in delivery of carbon-ion radiotherapy (C-ion RT) for relatively stationary tumours.

Methods: A prospective feasibility study was conducted with 10 patients who had been treated with C-ion RT using compact rotating gantry between April 2017 and April 2018 at Hospital of the National Institute of Radiological Sciences (NIRS) for head and neck and prostate cancers. The primary end point was evaluation of acute toxicities within 3 months of starting C-ion RT.

Results: Out of 10 cases 8 were of head and neck cancers and 2 were of prostate cancers. All of those eight head and neck cases were of locally advanced stages. Both of the prostate cancer patients belong to intermediate risk categories. None of the patients developed even Grade 2 or more severe skin reactions. Six out of eight cases with head and neck cancers experienced Grade 2 mucosal reactions; however, nobody developed Grade 3 or more severe mucosal reactions. There was no gastrointestinal reaction observed in prostate cancer patients. One patient developed Grade 2 genitourinary reaction.

Conclusion: C-ion RT using compact rotating gantry and three-dimensional active scanning is a safe and feasible treatment for relatively less mobile tumours.

Advances In Knowledge: This study will be the first step to establish the use of superconducting rotating gantry in C-ionRT in clinical setting paving the way for treating large number of patients and make it a standard of practice in the future.
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http://dx.doi.org/10.1259/bjr.20190370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849685PMC
November 2019

Key considerations when reviewing subsequent primary cancers following radiotherapy - Authors' reply.

Lancet Oncol 2019 06;20(6):e292

National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan.

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http://dx.doi.org/10.1016/S1470-2045(19)30342-0DOI Listing
June 2019

Risk of subsequent primary cancers after carbon ion radiotherapy, photon radiotherapy, or surgery for localised prostate cancer: a propensity score-weighted, retrospective, cohort study.

Lancet Oncol 2019 05 15;20(5):674-685. Epub 2019 Mar 15.

National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan; Graduate School of Medicine, Chiba University, Chiba, Japan.

Background: The risk of subsequent primary cancers in patients with prostate cancer after treatment with photon radiotherapy is small in absolute numbers, but it is higher than that after surgical treatment. Carbon ion radiotherapy has a theoretically lower risk of inducing secondary malignancies than photon radiotherapy, but this risk has not been investigated in practice because of the low number of facilities offering such therapy worldwide and the limited data on long-term follow-up because the therapy has only been available since 1994. We aimed to analyse the risk of subsequent primary cancers after treatment with carbon ion radiotherapy in patients with localised prostate cancer and to compare it with that after photon radiotherapy or surgery in this setting.

Methods: In this retrospective cohort study, we reviewed records of patients who received carbon ion radiotherapy for prostate cancer between June 27, 1995, and July 10, 2012, at the National Institute of Radiological Sciences (NIRS) in Japan. We also retrieved the records of patients diagnosed and treated for prostate cancer between Jan 1, 1994, and Dec 31, 2012, from the Osaka Cancer Registry. Eligible patients had histologically confirmed localised prostate cancer and a minimum follow-up of at least 3 months; no age restrictions were applied. We excluded patients with metastasis, node-positive disease, or locally invasive (T4 stage) prostate cancer, those with previous or synchronous malignancies, and those who received previous radiotherapy or chemotherapy. We did a multivariable analysis to estimate predictors of subsequent cancers after carbon ion radiotherapy treatment. We also used propensity score inverse probability weighting to retrospectively compare the incidence of subsequent cancers in patients with localised prostate cancer treated with carbon beams, photon radiotherapy, or surgery.

Findings: Of 1580 patients who received carbon radiotherapy for prostate cancer at the NIRS, 1455 (92%) patients met the eligibility criteria. Of 38 594 patients with prostate cancer identified in the Osaka registry, 1983 (5%) patients treated with photon radiotherapy and 5948 (15%) treated with surgery were included. Median follow-up durations were 7·9 years (IQR 5·9-10·0) for patients who received carbon ion radiotherapy (after limiting the database to 10-year maximum follow-up), 5·7 years (4·5-6·4) for patients who received photon radiotherapy, and 6·0 years (5·0-8·6) for those who received surgery. 234 subsequent primary cancers were diagnosed in the carbon ion radiotherapy cohort; some patients developed several tumours. On multivariable analysis, age (p=0·0021 for 71-75 years vs ≤60 years; p=0·012 for >75 years vs ≤60 years) and smoking (p=0·0005) were associated with a higher risk of subsequent primary cancers in patients treated with carbon ion radiotherapy. In the propensity score-weighted analyses, carbon ion radiotherapy was associated with a lower risk of subsequent primary cancers than photon radiotherapy (hazard ratio [HR] 0·81 [95% CI 0·66-0·99]; p=0·038) or surgery (HR 0·80 [0·68-0·95]; p=0·0088), whereas photon radiotherapy was associated with a higher risk of subsequent primary cancers than surgery (HR 1·18 [1·02-1·36]; p=0·029).

Interpretation: Our analysis suggests that patients with localised prostate cancer treated with carbon ion radiotherapy appear to have a lower risk of subsequent primary cancers than those treated with photon radiotherapy. Although prospective evaluation with longer follow-up is warranted to support these results, our data supports a wider adoption of carbon ion radiotherapy for patients with expected long-term overall survival or those with poor outcomes after receiving conventional treatments.

Funding: Research Project for Heavy Ions at the National Institute of Radiological Sciences (Japan).
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http://dx.doi.org/10.1016/S1470-2045(18)30931-8DOI Listing
May 2019

Prospective clinical trial of 12-fraction carbon-ion radiotherapy for primary renal cell carcinoma.

Oncotarget 2019 Jan 1;10(1):76-81. Epub 2019 Jan 1.

Hospital of the National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.

The aims of this study were to clarify the safety and efficacy of 12-fraction carbon-ion radiotherapy (CIRT) for primary renal cell carcinoma (RCC) and to confirm the recommended dose in a prospective clinical trial. This clinical trial was planned as a non-randomized, open-label, single-center phase I/II study of CIRT monotherapy. The incidence of acute adverse events was the primary endpoint. Dose-limiting toxicities (DLTs) were defined as grade ≥3 skin, gastrointestinal tract, or urologic adverse events. Based on the eligibility criteria, 8 patients with primary RCC, including 3 medically inoperable patients and 5 patients with tumors >4 cm, were enrolled. Of the 8 patients, 5 were treated with 66 Gy (relative biological effectiveness [RBE]), and subsequently, the dose was escalated to 72 Gy (RBE) for the remaining 3 patients. The median follow-up time was 43.1 months. No DLTs were observed at any dose level though the end of follow-up. Although 1 patient died of pneumonia 3 months after CIRT, which was determined to be unrelated to CIRT, no grade 3 or higher adverse events were observed, and both local control and cancer-specific survival rates were 100%. In conclusion, the safety and efficacy of CIRT hypofractionation using 12-fractions for the treatment of eligible RCC patients, including those with inoperable or tumor size >4 cm, were confirmed in this prospective trial, and a recommended dose of 72 Gy (RBE) was established.
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http://dx.doi.org/10.18632/oncotarget.26539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343760PMC
January 2019

Single fraction carbon ion radiotherapy for colorectal cancer liver metastasis: A dose escalation study.

Cancer Sci 2019 Jan 12;110(1):303-309. Epub 2018 Dec 12.

National Institute of Radiological Sciences Hospital, National Institutes for Quantum and Radiological Sciences and Technology, Chiba, Japan.

Prognosis is usually grim for those with liver metastasis from colorectal cancer (CRC) who cannot receive resection. Radiation therapy can be an option for those unsuitable for resection, with carbon ion radiotherapy (CIRT) being more effective and less toxic than X-ray due to its physio-biological characteristics. The objective of this study is to identify the optimal dose of single fraction CIRT for colorectal cancer liver metastasis. Thirty-one patients with liver metastasis from CRC were enrolled in the present study. Twenty-nine patients received a single-fraction CIRT, escalating the dose from 36 Gy (RBE) in 5% to 10% increments until unacceptable incidence of dose-limiting toxicity was observed. Dose-limiting toxicity was defined as grade ≥3 acute toxicity attributed to radiotherapy. The prescribed doses were as follows: 36 Gy (RBE) (3 cases), 40 Gy (2 cases), 44 Gy (4 cases), 46 Gy (6 cases), 48 Gy (3 cases), 53 Gy (8 cases) and 58 Gy (3 cases). Dose-limiting toxicity was not observed, but late grade 3 liver toxicity due to biliary obstruction was observed in 2 patients at 53 Gy (RBE). Both cases had lesions close to the hepatic portal region, and, therefore, the dose was escalated to 58 Gy (RBE), limited to peripheral lesions. The 3-year actuarial overall survival rate of all 29 patients was 78%, and the median survival time was 65 months. Local control improved significantly at ≥53 Gy (RBE), with a 3-year actuarial local control rate of 82%, compared to 28% in lower doses. Treatment for CRC liver metastasis with single-fraction CIRT appeared to be safe up to 58 Gy (RBE) as long as the central hepatic portal region was avoided.
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http://dx.doi.org/10.1111/cas.13872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317930PMC
January 2019

Updated long-term outcomes after carbon-ion radiotherapy for primary renal cell carcinoma.

Cancer Sci 2018 Sep 1;109(9):2873-2880. Epub 2018 Sep 1.

The Hospital of the National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.

Long-term oncological outcomes for primary renal cell carcinoma (RCC) treated with carbon-ion radiotherapy (CIRT) are poorly understood. Patients with primary RCC were treated with 12 or 16-fraction CIRT at The Hospital of the National Institute of Radiological Sciences outside of clinical trials. Outcome data were pooled and retrospectively analyzed for toxicity, local control, and disease-free, cancer-specific, and overall survival. From 1997 to 2014, 19 RCC patients (11 with T1aN0M0, 4 with T1bN0M0, and 4 with inoperable advanced stage [T4N0M0, T3aN1M0, and T1aN0M1]) were treated with CIRT and followed up for a median of 6.6 (range, 0.7-16.5) years; 9 of these patients were inoperable because of comorbidities or advanced-stage disease. Diagnoses were confirmed by imaging in 11 patients and by biopsy in the remaining 8. In 4 of 5 patients with definitive renal comorbidities, including diabetic nephropathy, sclerotic kidney or solitary kidney pre-CIRT progressed to grade 4 chronic kidney disease (CKD). In contrast, the remaining 14 patients without definitive renal comorbidities did not progress to grade 3 or higher CKD. Furthermore, although 1 case of grade 4 dermatitis was observed, there were no other grade 3 or higher non-renal adverse events. Local control rate, and disease-free, cancer-specific, and overall survival rates at 5 years of all 19 patients were 94.1%, 68.9%, 100%, and 89.2%, respectively. This updated retrospective analysis based on long-term follow-up data suggests that CIRT is a safe treatment for primary RCC patients without definitive renal comorbidities pre-CIRT, and yield favorable treatment outcomes, even in inoperable cases.
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http://dx.doi.org/10.1111/cas.13727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125442PMC
September 2018

Evolution of Carbon Ion Radiotherapy at the National Institute of Radiological Sciences in Japan.

Cancers (Basel) 2018 Mar 6;10(3). Epub 2018 Mar 6.

Hospital of the National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.

Charged particles can achieve better dose distribution and higher biological effectiveness compared to photon radiotherapy. Carbon ions are considered an optimal candidate for cancer treatment using particles. The National Institute of Radiological Sciences (NIRS) in Chiba, Japan was the first radiotherapy hospital dedicated for carbon ion treatments in the world. Since its establishment in 1994, the NIRS has pioneered this therapy with more than 69 clinical trials so far, and hundreds of ancillary projects in physics and radiobiology. In this review, we will discuss the evolution of carbon ion radiotherapy at the NIRS and some of the current and future projects in the field.
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http://dx.doi.org/10.3390/cancers10030066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876641PMC
March 2018

A retrospective study of late adverse events in proton beam therapy for prostate cancer.

Mol Clin Oncol 2017 Oct 11;7(4):547-552. Epub 2017 Aug 11.

Department of Radiation Oncology and Proton Medical Research Center, University of Tsukuba, Tsukuba, Ibaraki 305-8576, Japan.

The efficacy and safety of proton beam therapy (PBT) were retrospectively evaluated in 111 consecutive patients with prostate cancer who underwent definitive PBT between 2008 and 2012. Following exclusion of 18 patients due to treatment suspension, loss to follow-up, and histology, the analysis included 93 patients with a median age of 68 years (range, 49-81 years). A total of 7, 32 and 54 prostate cancer patients were classified as low-, intermediate- and high-risk, respectively, as follows: High-risk, T≥3a or prostate-specific antigen (PSA) ≥20 ng/ml or Gleason Score ≥8; low-risk, T ≤2b and PSA≤10 ng/ml and Gleason Score=6; intermediate-risk, all other combinations. The median initial prostate-specific antigen (PSA) level was 9.75 ng/ml (range, 1.4-100 ng/ml) and the median Gleason score was 7 (range, 6-10). Patients with low-risk disease received 74 GyE (relative biological effectiveness=1.1) in 37 fractions, and those at intermediate or higher risk received 78 GyE in 39 fractions. Complete androgen blockade (CAB) therapy was performed from 6 months prior to PBT for patients with intermediate- or high-risk disease. CAB was continued during PBT and then terminated at the end of PBT for intermediate-risk patients. Patients at high risk continued CAB for 3 years. No combination therapy was used for low-risk patients. All the patients were followed up for >2 years after PBT, and all but one were PSA failure-free. The Common Terminology Criteria for Adverse Events v.4.0 was used to evaluate late adverse events. One patient developed grade 3 non-infectious cystitis and hematuria. Grade 2 urinary frequency was observed in 1 patient, and grade 2 rectal bleeding occurred in 4 patients. Of the 4 patients with grade 2 rectal bleeding, 2 received anticoagulant therapy, but none had diabetes mellitus or another high-risk comorbidity. The median time to occurrence of an adverse event of grade ≥2 was 14 months (range, 3-41 months). Therefore, the present retrospective study revealed that PBT at 78 GyE/39 Fr was well-tolerated and achieved good tumor control in patients with prostate cancer.
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http://dx.doi.org/10.3892/mco.2017.1372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5639311PMC
October 2017

Cancer-specific mortality of high-risk prostate cancer after carbon-ion radiotherapy plus long-term androgen deprivation therapy.

Cancer Sci 2017 Dec 3;108(12):2422-2429. Epub 2017 Nov 3.

Hospital of the National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.

The treatment outcomes of patients with high-risk localized prostate cancer (PC) after carbon-ion radiotherapy (CIRT) combined with long-term androgen deprivation therapy (LTADT) were analyzed, and compared with those of other treatment modalities, focusing on PC-specific mortality (PCSM). A total of 1247 patients were enrolled in three phase II clinical trials of fixed-dose CIRT between 2000 and 2013. Excluding patients with T4 disease, 608 patients with high-risk or very-high-risk PC, according to the National Comprehensive Cancer Network classification system, who received CIRT with LTADT were evaluated. The median follow-up time was 88.4 months, and the 5-/10-year PCSM rates were 1.5%/4.3%, respectively. T3b disease, Gleason score of 9-10 and percentage of positive biopsy cores >75% were associated with significantly higher PCSM on univariate and multivariate analyses. The 10-year PCSM rates of patients having all three (n = 16), two (n = 74) or one of these risk factors (n = 217) were 27.1, 11.6 and 5.7%, respectively. Of the 301 patients with none of these factors, only 1 PCSM occurred over the 10-year follow-up (10-year PCSM rate, 0.3%), and significant differences were observed among the four stratified groups (P <0.001). CIRT combined with LTADT yielded relatively favorable treatment outcomes in patients with high-risk PC and very favorable results in patients without any of the three abovementioned factors for PCSM. Because a significant difference in PCSM among the high-risk PC patient groups was observed, new categorization and treatment intensity adjustment may be required for high-risk PC patients treated with CIRT.
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http://dx.doi.org/10.1111/cas.13402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5715357PMC
December 2017

Progressive hypofractionated carbon-ion radiotherapy for hepatocellular carcinoma: Combined analyses of 2 prospective trials.

Cancer 2017 Oct 29;123(20):3955-3965. Epub 2017 Jun 29.

Hospital of the National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.

Background: The objective of this study was to evaluate the safety and efficacy of carbon-ion radiotherapy (CIRT) in patients with hepatocellular carcinoma (HCC) with stepwise dose escalation and hypofractionation in 2 combined prospective trials.

Methods: Sequential phase 1/2 (protocol 9603) and phase 2 (protocol 0004) trials were conducted for patients with histologically proven HCC. The phase 1 component of protocol 9603 was a dose-escalation study; CIRT was delivered in 12, 8, or 4 fractions. After determination of the recommended dose, 2 phase 2 trials were performed in an expanded cohort, and the data were pooled to analyze toxicity, local control, and overall survival.

Results: In the phase 1 component of protocol 9603, 69.6, 58.0, and 52.8 Gy (relative biological effectiveness [RBE]) in 12, 8, and 4 fractions, respectively, constituted the maximum tolerated doses, and 52.8 Gy (RBE) in 4 fractions was established as the recommended dose regimen for the 2 phase 2 studies. In 124 patients with a total of 133 lesions, few severe adverse effects occurred, and local-control and overall survival rates at 1, 3, and 5 years were 94.7% and 90.3%, 91.4% and 50.0%, and 90.0% and 25.0%, respectively; this included 1-, 3-, and 5-year local-control rates of 97.8%, 95.5%, and 91.6%, respectively, in the phase 2 study. In a multivariate analysis, Child-Pugh class B and the presence of a tumor thrombus were significant factors for mortality.

Conclusions: The safety and efficacy of CIRT in 12, 8, and 4 fractions were confirmed, with 52.8 Gy (RBE) in 4 fractions established as the recommended treatment course for eligible HCC patients. Cancer 2017;123:3955-65. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.
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http://dx.doi.org/10.1002/cncr.30816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655922PMC
October 2017

Carbon-Ion Radiation Therapy for Pelvic Recurrence of Rectal Cancer.

Int J Radiat Oncol Biol Phys 2016 09 23;96(1):93-101. Epub 2016 Apr 23.

Graduate School of Medicine, Chiba University, Chiba, Japan.

Purpose: Investigation of the treatment potential of carbon-ion radiation therapy in pelvic recurrence of rectal cancer.

Methods And Materials: A phase 1/2 dose escalation study was performed. One hundred eighty patients (186 lesions) with locally recurrent rectal cancer were treated with carbon-ion radiation therapy (CIRT) (phase 1/2: 37 and 143 patients, respectively). The relapse locations were 71 in the presacral region, 82 in the pelvic sidewalls, 28 in the perineum, and 5 near the colorectal anastomosis. A 16-fraction in 4 weeks dose regimen was used, with total dose ranging from 67.2 to 73.6 Gy(RBE); RBE-weighted absorbed dose: 4.2 to 4.6 Gy(RBE)/fraction.

Results: During phase 1, the highest total dose, 73.6 Gy(RBE), resulted in no grade >3 acute reactions in the 13 patients treated at that dose. Dose escalation was halted at this level, and this dose was used for phase 2, with no other grade >3 acute reactions observed. At 5 years, the local control and survival rates at 73.6 Gy(RBE) were 88% (95% confidence interval [CI], 80%-93%) and 59% (95% CI, 50%-68%), respectively.

Conclusion: Carbon-ion radiation therapy may be a safe and effective treatment option for locally recurrent rectal cancer and may serve as an alternative to surgery.
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http://dx.doi.org/10.1016/j.ijrobp.2016.04.022DOI Listing
September 2016

Significant impact of biochemical recurrence on overall mortality in patients with high-risk prostate cancer after carbon-ion radiotherapy combined with androgen deprivation therapy.

Cancer 2016 Oct 28;122(20):3225-3231. Epub 2016 Jun 28.

Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan.

Background: Whether biochemical recurrence (BR) is a significant predictive factor of mortality after definitive radiation therapy for prostate cancer remains unknown. The aim of the current study was to investigate the relation between BR and overall mortality (OAM) in high-risk prostate cancer patients who were treated with carbon-ion radiotherapy (CIRT) and had long-term follow-up in 2 prospective trials.

Methods: In the 2 phase 2 clinical trials, which involved 466 prostate cancer patients who received 63.0 to 66.0 Gy of CIRT (relative biological effect) in 20 fractions between 2000 and 2007, 324 patients who were deemed to be at high risk on the basis of the modified D'Amico classification criteria and received CIRT along with androgen-deprivation therapy (ADT) were examined. The OAM rate was adjusted for the ADT duration, and multivariate analyses using a Cox proportional hazards model were performed for OAM with BR as a time-dependent covariate.

Results: The median follow-up period was 107.4 months, and the 5- and 10-year OAM rates after adjustments for the ADT duration were 7.0% (95% confidence interval [CI], 4.0%-9.4%) and 23.9% (95% CI, 16.4%-26.2%), respectively. A multivariate analysis revealed that the presence of BR (hazard ratio, 2.82; 95% Cl, 1.57-5.08; P = .001) was one of the predictive factors for OAM. On the other hand, the duration of ADT had no impact on OAM.

Conclusions: BR after CIRT combined with ADT is an independent predictive factor for OAM in high-risk prostate cancer patients. The results of this study could be applied to other high-dose radiation therapies. Cancer 2016;122:3225-31. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
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http://dx.doi.org/10.1002/cncr.30050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094521PMC
October 2016

Proton beam therapy for metastatic liver tumors.

Radiother Oncol 2015 Nov 15;117(2):322-7. Epub 2015 Sep 15.

Proton Medical Research Center, University of Tsukuba, Japan.

Purpose: The purpose of this study was to investigate the safety and efficacy of proton beam therapy (PBT) for the treatment of metastatic liver tumors.

Material And Methods: A total of 140 patients with liver metastasis who received PBT were retrospectively investigated. The main primary tumor sites were the colorectum (60) and the pancreas (19).

Results: One hundred thirty-three patients (95%) completed treatment. Two patients experienced late adverse effects (rib fracture and cholangitis). The 5-year overall survival (OS) rate was 24%. In the 85 patients with lesions confined to the liver, the 5-year OS rate of was 28%, and in the 55 patients with lesions both inside and outside the liver, it was 16% (P=0.007). Among the patients with lesions confined to the liver, the 5-year OS rate of the 62 patients who received curative treatment was 30%, and that of the 23 patients who received palliative treatment, 23% (P=0.016). Multivariate analysis showed that the treatment strategy (curative and palliative) alone was associated with the OS rate (P=0.02).

Conclusion: PBT is a potentially safe and effective treatment for metastatic liver tumors.
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http://dx.doi.org/10.1016/j.radonc.2015.09.011DOI Listing
November 2015

Comparison of adverse effects of proton and X-ray chemoradiotherapy for esophageal cancer using an adaptive dose-volume histogram analysis.

J Radiat Res 2015 May 9;56(3):568-76. Epub 2015 Mar 9.

Department of Radiation Oncology and Proton Medical Research Center, University of Tsukuba, 2-1-1 Amakubo, Tsukuba, Ibaraki, 305-8576, Japan.

Cardiopulmonary late toxicity is of concern in concurrent chemoradiotherapy (CCRT) for esophageal cancer. The aim of this study was to examine the benefit of proton beam therapy (PBT) using clinical data and adaptive dose-volume histogram (DVH) analysis. The subjects were 44 patients with esophageal cancer who underwent definitive CCRT using X-rays (n = 19) or protons (n = 25). Experimental recalculation using protons was performed for the patient actually treated with X-rays, and vice versa. Target coverage and dose constraints of normal tissues were conserved. Lung V5-V20, mean lung dose (MLD), and heart V30-V50 were compared for risk organ doses between experimental plans and actual treatment plans. Potential toxicity was estimated using protons in patients actually treated with X-rays, and vice versa. Pulmonary events of Grade ≥2 occurred in 8/44 cases (18%), and cardiac events were seen in 11 cases (25%). Risk organ doses in patients with events of Grade ≥2 were significantly higher than for those with events of Grade ≤1. Risk organ doses were lower in proton plans compared with X-ray plans. All patients suffering toxicity who were treated with X-rays (n = 13) had reduced predicted doses in lung and heart using protons, while doses in all patients treated with protons (n = 24) with toxicity of Grade ≤1 had worsened predicted toxicity with X-rays. Analysis of normal tissue complication probability showed a potential reduction in toxicity by using proton beams. Irradiation dose, volume and adverse effects on the heart and lung can be reduced using protons. Thus, PBT is a promising treatment modality for the management of esophageal cancer.
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http://dx.doi.org/10.1093/jrr/rrv001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4426925PMC
May 2015

Proton beam therapy combined with concurrent chemotherapy for esophageal cancer.

Anticancer Res 2015 Mar;35(3):1757-62

Department of Radiation Oncology, University of Tsukuba, Faculty of Medicine, Ibaraki, Japan.

Background/aim: The aim of the present study was to evaluate the outcomes of proton beam therapy (PBT) concurrently combined with chemotherapy consisting of cisplatin and 5-fluorouracil for esophageal cancer.

Patients And Methods: Forty consecutive patients (stage I in 16 patients, II in 9 and III in 15) treated between 2008 and 2012 were evaluated. A total dose of 60 Gray equivalents (GyE) in 30 fractions was delivered, and an additional boost of 4-10 GyE was given when residual tumors were suspected. The median follow-up time was 24 months (range=7-66 months).

Results: No cardio-pulmonary toxicities of grade 3 or higher were observed. Recurrences were observed in 16 patients, and the 2-year rates of disease-specific survival and locoregional control were 77% and 66%, respectively.

Conclusion: Irrespective of the small sample size and short follow-up time of the study, proton beam therapy combined with chemo therapy seems to be feasible for esophageal cancer.
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March 2015

[Advances in highly conformal radiotherapy for prostate cancer: past, current, and future].

Igaku Butsuri 2012 ;32(3):138-47

Department of Radiation Oncology, Faculty of Medicine, University of Tsukuba, Tennodai, Tsukuba 305-8575, Japan.

Recent advance in the field of radiation oncology, especially in medical physics for radiation therapy (RT), has considerably improved treatment outcomes of various cancers including prostate cancer with regard to both of tumor control and morbidity. Three-dimensionally conformal RT with image-guided radiotherapeutic modalities for accurate tumor localization, such as brachytherapy, intensity-modulated radiation therapy (IMRT), and charged particle beam RT can thereby deliver a large dose to the tumor and allow the sparing of surrounding normal tissues. It is thought that prostate cancer is one of representative cancers which have been treated with RT as a curative intent and benefited from novel conformal RT techniques. Because the number of prostate cancer patients has been increasing year by year in Japan as results from wide spread of PSA screening and rapid change in life style, RT has been recently playing much more important roles in the curative treatment for patients with prostate cancer. Hence, we will review the outcomes of RT for prostate cancer and introduce the benefit of modern RT modalities from clinical aspect. In addition, our future prospect to further yield better disease control with minimum morbidity compared with present RT will be also mentioned in the report.
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April 2014
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