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Pancreatic Neoplasms: HELP
Articles by Akira Nakamura
Based on 20 articles published since 2010
(Why 20 articles?)
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Between 2010 and 2020, Akira Nakamura wrote the following 20 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review International Association of Pancreatology (IAP)/European Pancreatic Club (EPC) consensus review of guidelines for the treatment of pancreatic cancer. 2016

Takaori, Kyoichi / Bassi, Claudio / Biankin, Andrew / Brunner, Thomas B / Cataldo, Ivana / Campbell, Fiona / Cunningham, David / Falconi, Massimo / Frampton, Adam E / Furuse, Junji / Giovannini, Marc / Jackson, Richard / Nakamura, Akira / Nealon, William / Neoptolemos, John P / Real, Francisco X / Scarpa, Aldo / Sclafani, Francesco / Windsor, John A / Yamaguchi, Koji / Wolfgang, Christopher / Johnson, Colin D / Anonymous8350852. ·Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan. Electronic address: takaori@kuhp.kyoto-u.ac.jp. · Department of Surgery and Oncology, Pancreas Institute, University of Verona, Verona, Italy. · Academic Unit of Surgery, University of Glasgow, Glasgow, United Kingdom. · Department of Radiation Oncology, University Hospitals Freiburg, Germany. · Department of Pathology and Diagnostics, University of Verona, Verona, Italy. · Department of Pathology, Royal Liverpool University Hospital, Liverpool, United Kingdom. · Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom. · Pancreatic Surgery Unit, Università Vita e Salute, Milano, Italy. · HPB Surgical Unit, Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, United Kingdom. · Department of Medical Oncology, Kyorin University School of Medicine, Tokyo, Japan. · Endoscopic Unit, Paoli-Calmettes Institute, Marseille, France. · NIHR Pancreas Biomedical Research Unit, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, United Kingdom. · Department of Radiation Oncology and Image-applied Therapy, Kyoto University Hospital, Kyoto, Japan. · Division of General Surgery, Yale University, New Haven, CT, United States of America. · Epithelial Carcinogenesis Group, CNIO-Spanish National Cancer Research Centre, Madrid, Spain. · Department of Surgery, University of Auckland, HBP/Upper GI Unit, Auckland City Hospital, Auckland, New Zealand. · Department of Advanced Treatment of Pancreatic Disease, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. · Department of Surgery, The Johns Hopkins University, Baltimore, MD, United States of America. · University Surgical Unit, Southampton General Hospital, Southampton, United Kingdom. ·Pancreatology · Pubmed #26699808.

ABSTRACT: BACKGROUND: Pancreatic cancer is one of the most devastating diseases with an extremely high mortality. Medical organizations and scientific societies have published a number of guidelines to address active treatment of pancreatic cancer. The aim of this consensus review was to identify where there is agreement or disagreement among the existing guidelines and to help define the gaps for future studies. METHODS: A panel of expert pancreatologists gathered at the 46th European Pancreatic Club Meeting combined with the 18th International Association of Pancreatology Meeting and collaborated on critical reviews of eight English language guidelines for the clinical management of pancreatic cancer. Clinical questions (CQs) of interest were proposed by specialists in each of nine areas. The recommendations for the CQs in existing guidelines, as well as the evidence on which these were based, were reviewed and compared. The evidence was graded as sufficient, mediocre or poor/absent. RESULTS: Only 4 of the 36 CQs, had sufficient evidence for agreement. There was also agreement in five additional CQs despite the lack of sufficient evidence. In 22 CQs, there was disagreement regardless of the presence or absence of evidence. There were five CQs that were not addressed adequately by existing guidelines. CONCLUSION: The existing guidelines provide both evidence- and consensus-based recommendations. There is also considerable disagreement about the recommendations in part due to the lack of high level evidence. Improving the clinical management of patients with pancreatic cancer, will require continuing efforts to undertake research that will provide sufficient evidence to allow agreement.

2 Clinical Trial Elective nodal irradiation with simultaneous integrated boost stereotactic body radiotherapy for pancreatic cancer: Analyses of planning feasibility and geometrically driven DVH prediction model. 2019

Nakamura, Akira / Prichard, Hugh A / Wo, Jennifer Y / Wolfgang, John A / Hong, Theodore S. ·Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. ·J Appl Clin Med Phys · Pubmed #30636367.

ABSTRACT: PURPOSE: We evaluate the feasibility of the elective nodal irradiation strategy in stereotactic body radiotherapy (SBRT) for pancreatic cancer. METHODS: Three simultaneous integrated boost (SIB)-SBRT plans (Boost1, Boost2, and Boost3) were retrospectively generated for each of 20 different patients. Boost1 delivered 33 and 25 Gy to PTV1 and PTV2, respectively. Boost2 delivered 40, 33, and 25 Gy to boostCTV, PTV1, and PTV2, respectively. Boost3 delivered 33 and 25 Gy to PTV1 and PTV3, respectively. PTV1 covered the initial standard SBRT plan (InitPlan) gross tumor volume (GTV). PTV2 covered CTVgeom which was created by a 10-mm expansion (15 mm posterior) of GTV. PTV3 covered CTVprop which included elective nodal regions. The boostCTV included GTV as well as involved vasculature. The planning feasibility in each scenario and dose-volume histograms (DVHs) were analyzed and compared with the InitPlan (delivered 33 Gy only to PTV1) by paired t-test. Next, a novel DVH prediction model was developed and its performance was evaluated according to the prediction accuracy (AC) of planning violations. Then, the model was used to simulate the impacts of GTV-to-organs at risk (OAR) distance and gastrointestinal (GI) OAR volume variations on planning feasibility. RESULTS: Significant dose increases were observed in GI-OARs in SIB-SBRT plans when compared with InitPlan. All dose constraints were met in 63% of cases in InitPlan, Boost1, and Boost2, whereas Boost3 developed DVH violations in all cases. Utilizing previous patient anatomy, the novel DVH prediction model achieved a high AC in the prediction of violations for GI-OARs; the positive predictive value, negative predictive value, and AC were 66%, 90%, and 84%, respectively. Experiments with the model demonstrated that the larger proximity volume of GI-OAR at the shorter distance substantially impacted on planning violations. CONCLUSIONS: SIB-SBRT plan with geometrically defined prophylactic areas can be dosimetrically feasible, but including all nodal areas with 25 Gy in five fractions appears to be unrealistic.

3 Clinical Trial Phase II study of radiation therapy combined with weekly low-dose gemcitabine for locally advanced, unresectable pancreatic cancer. 2011

Shibuya, Keiko / Oya, Natsuo / Fujii, Takashi / Doi, Ryuichiro / Nakamura, Akira / Matsuo, Yukinori / Mitsumori, Michihide / Hiraoka, Masahiro. ·Department of Radiation Oncology and Image-Applied Therapy, Kyoto University Graduate School of Medicine, Kyoto, Japan. kei@kuhp.kyoto-u ·Am J Clin Oncol · Pubmed #20065850.

ABSTRACT: BACKGROUND: Through a phase I study with a fixed radiation dose of 54 Gy and escalating doses of weekly gemcitabine, we established a recommended dose of gemcitabine at 250 mg/m in combination with radiation therapy for patients with unresectable pancreatic cancer. OBJECTIVE: The purpose of this phase-II study was to evaluate the safety and efficacy of the regimen which was established in the phase I study. METHODS: In all patients with unresectable stage III and limited stage IV pancreatic cancer with no distant metastasis except for para-aortic lymph node involvement at a level as low as the left renal vein, a total dose of 54 Gy was delivered in 30 fractions of 1.8 Gy/d. Gemcitabine was given weekly at a dose of 250 mg/m. RESULTS: Between December 2002 and March 2006, 22 patients were enrolled in this study and one withdrew after enrollment. Twenty of 21 patients (95%) completed the protocol therapy. Radiologic partial response was observed in 6 and stable disease was noted in 15. Normalization of the tumor marker (CA19-9) occurred in 61% of patients. The 1-year survival rate was 74% and the median survival time was 16.6 months. The major toxicity was leucopenia; grade 3 in 14 (67%), anorexia grade 3 in 2 (9.5%), and grade 3 gastric ulcer in 2 (10%) in National Cancer Institute's Common Terminology Criteria for Adverse Events version 3.0 (NCI-CTCAE v3.0). Neither grade 4 nor 5 was recognized. CONCLUSION: Treatment with gemcitabine combined with radiation therapy according to the present schedule is well tolerated and can provide prolonged survival in patients with localized, unresectable pancreatic cancer.

4 Article Evaluation of Dynamic Tumor-tracking Intensity-modulated Radiotherapy for Locally Advanced Pancreatic Cancer. 2018

Nakamura, Akira / Hiraoka, Masahiro / Itasaka, Satoshi / Nakamura, Mitsuhiro / Akimoto, Mami / Ishihara, Yoshitomo / Mukumoto, Nobutaka / Goto, Yoko / Kishi, Takahiro / Yoshimura, Michio / Matsuo, Yukinori / Yano, Shinsuke / Mizowaki, Takashi. ·Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan. · Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan. hiraok@kuhp.kyoto-u.ac.jp. · Department of Radiation Oncology, Kurashiki Central Hospital, Kurashiki, Japan. ·Sci Rep · Pubmed #30459454.

ABSTRACT: Intensity-modulated radiotherapy (IMRT) is now regarded as an important treatment option for patients with locally advanced pancreatic cancer (LAPC). To reduce the underlying tumor motions and dosimetric errors during IMRT as well as the burden of respiratory management for patients, we started to apply a new treatment platform of the dynamic tumor dynamic tumor-tracking intensity-modulated radiotherapy (DTT-IMRT) using the gimbaled linac, which can swing IMRT toward the real-time tumor position under patients' voluntary breathing. Between June 2013 and March 2015, ten patients were treated, and the tumor-tracking accuracy and the practical benefits were evaluated. The mean PTV size in DTT-IMRT was 18% smaller than a conventional ITV-based PTV. The root-mean-squared errors between the predicted and the detected tumor positions were 1.3, 1.2, and 1.5 mm in left-right, anterior-posterior, and cranio-caudal directions, respectively. The mean in-room time was 24.5 min. This high-accuracy of tumor-tracking with reasonable treatment time are promising and beneficial to patients with LAPC.

5 Article Clinical evaluation of intensity-modulated radiotherapy for locally advanced pancreatic cancer. 2018

Goto, Yoko / Nakamura, Akira / Ashida, Ryo / Sakanaka, Katsuyuki / Itasaka, Satoshi / Shibuya, Keiko / Matsumoto, Shigemi / Kanai, Masashi / Isoda, Hiroyoshi / Masui, Toshihiko / Kodama, Yuzo / Takaori, Kyoichi / Hiraoka, Masahiro / Mizowaki, Takashi. ·Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, 54 Shogoin, Kawaracho, Sakyo-ku, Kyoto, Japan. ygoto@kuhp.kyoto-u.ac.jp. · Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, 54 Shogoin, Kawaracho, Sakyo-ku, Kyoto, Japan. · Department of Radiation Oncology, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan. · Department of Clinical Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan. · Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan. · Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan. · Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan. · Department of Radiation Oncology, Japanese Red Cross Society Wakayama Medical Center, Wakayama, Japan. ·Radiat Oncol · Pubmed #29940984.

ABSTRACT: BACKGROUND: The purpose was to retrospectively evaluate the effect of intensity-modulated radiotherapy (IMRT) on gastrointestinal (GI) toxicities and outcomes compared to three-dimensional conformal radiotherapy (3DCRT) for locally advanced pancreatic cancer (LAPC). METHODS: We included 107 consecutive patients who underwent CRT for LAPC from September 2001 to March 2015; 80 patients underwent 3DCRT and 27 patients underwent IMRT. They were compared for GI toxicities, locoregional progression free survival (LRPFS), distant metastasis free survival (DMS), and overall survival (OS). RESULTS: Median radiation dose and fractions for 3DCRT and IMRT were 54 Gy/30 fr. and 48 Gy/15 fr. The regimens of CRT consisted of weekly gemcitabine 250 mg/m CONCLUSIONS: LAPC patients treated with hypofractionated full-dose gemcitabine IMRT had improved OS and LRPFS without increased GI toxicities when compared to those of patients treated with conventionally fractionated low dose gemcitabine 3DCRT. In IMRT patients, higher dose was an independent favorable prognostic factor for better LRPFS and OS, which suggests that dose escalation with IMRT for LAPC is a promising strategy.

6 Article Clinical results of dynamic tumor tracking intensity-modulated radiotherapy with real-time monitoring for pancreatic cancers using a gimbal mounted linac. 2018

Goto, Yoko / Ashida, Ryo / Nakamura, Akira / Itasaka, Satoshi / Shibuya, Keiko / Akimoto, Mami / Mukumoto, Nobutaka / Matsumoto, Shigemi / Kanai, Masashi / Isoda, Hiroyoshi / Masui, Toshihiko / Kodama, Yuzo / Nakamura, Mitsuhiro / Takaori, Kyoichi / Mizowaki, Takashi / Hiraoka, Masahiro. ·Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan. · Department of Radiation Oncology, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan. · Department of Clinical Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. · Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan. · Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. · Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. · Department of Radiation Oncology, Japanese Red Cross Society Wakayama Medical Center, Wakayama, Japan. ·Oncotarget · Pubmed #29805762.

ABSTRACT: Objectives: We performed dynamic tumor-tracking IMRT (DTT-IMRT) in locally advanced pancreatic cancer (LAPC) patients using a gimbaled linac of Vero4DRT. The purpose of this study is to report the first clinical results. Methods: From June 2013 to June 2015, eleven LAPC patients enrolled in this study and DTT-IMRT was successfully performed. The locoregional progression free survival (LRPFS), distant metastasis free survival (DMFS), overall survival (OS), hematologic and gastrointestinal (GI) toxicities were evaluated. Oncologic outcomes were estimated using Kaplan-Meier analysis, and toxicities using CTCAE v4.0. Results: The median radiation dose was 48 Gy (range, 45-51) in 15 fractions. Concurrent chemoradiotherapy (CCRT) was performed using gemcitabine in 9 patients and S-1 in one, while one patient refused. With a median follow-up of 22.9 months, 1-year LRPFS, DMFS, and OS rates were 90.9%, 70.7%, and 100%, respectively. Median survival time was 23.6 months. Grade-3 leucopenia and neutropenia were observed in two (18%) and one patient (9%), respectively. Grade-2 acute GI toxicity occurred in 2 patients (18%) and late grade-3 in 1 patient (9%). Conclusions: Preliminarily application of DTT-IMRT using a gimbaled linac on CCRT in LAPC patients resulted in excellent locoregional control and OS without severe toxicity.

7 Article Inter- and Intrafractional Variation in the 3-Dimensional Positions of Pancreatic Tumors Due to Respiration Under Real-Time Monitoring. 2017

Akimoto, Mami / Nakamura, Mitsuhiro / Nakamura, Akira / Mukumoto, Nobutaka / Kishi, Takashi / Goto, Yoko / Mizowaki, Takashi / Hiraoka, Masahiro. ·Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan. · Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Electronic address: m_nkmr@kuhp.kyoto-u.ac.jp. ·Int J Radiat Oncol Biol Phys · Pubmed #28721905.

ABSTRACT: PURPOSE: To quantify the 3-dimensional pancreatic tumor motion during the overall treatment course using real-time orthogonal kilovoltage X-ray imaging. METHODS AND MATERIALS: This study included 10 patients with pancreatic cancer who underwent 6-port static intensity modulated radiation therapy with real-time tumor tracking in 15 fractions, except for 1 patient (5 fractions). The tumor and abdominal wall positions were acquired simultaneously during the overall treatment course. Then the tumor motion amplitude and reference positions were determined. RESULTS: The mean tumor amplitudes were 4.9, 6.5, and 13.4 mm in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions, respectively. The intrafractional variations of the reference tumor position were up to 5.4, 10.2, and 10.7 mm in the LR, AP, and SI directions, and those of the reference abdominal position were up to 10.5 mm. The reference tumor position drifted significantly in the AP and SI directions after 10 minutes, and that of abdominal wall motion drifted during the first 15 minutes (P<.05). The interfractional variation of the reference tumor position after setup correction, based on bony structures, was up to 8.9, 9.8, and 11.0 mm in the LR, AP, and SI directions, respectively. CONCLUSIONS: Appropriate respiratory motion management techniques should be applied for the accurate localization of pancreatic tumors.

8 Article Personalized Management of Pancreatic Ductal Adenocarcinoma Patients through Computational Modeling. 2017

Yamamoto, Kimiyo N / Yachida, Shinichi / Nakamura, Akira / Niida, Atsushi / Oshima, Minoru / De, Subhajyoti / Rosati, Lauren M / Herman, Joseph M / Iacobuzio-Donahue, Christine A / Haeno, Hiroshi. ·Department of Biology, Kyushu University, Fukuoka, Japan. kimiyo@jimmy.harvard.edu kyamamoto@kyushu-u.org haeno@kyushu-u.org. · Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts. · Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts. · Departments of General and Gastroenterological Surgery, Osaka Medical College Hospital, Osaka, Japan. · Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan. · Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts. · Division of Health Medical Computational Science, Health Intelligence Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. · Department of Gastroenterological Surgery, Kagawa University, Kagawa, Japan. · Department of Biostatistics and Informatics, University of Colorado School of Medicine, Colorado. · Department of Radiation Oncology & Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Pathology, David M. Rubenstein Center for Pancreatic Cancer Research, and the Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York. ·Cancer Res · Pubmed #28381541.

ABSTRACT: Phenotypic diversity in pancreatic ductal adenocarcinoma (PDAC) results in a variety of treatment responses. Rapid autopsy studies have revealed a subgroup of PDAC patients with a lower propensity to develop metastatic disease, challenging the common perception that all patients die of widely metastatic disease, but questions remain about root causes of this difference and the potential impact on treatment strategies. In this study, we addressed these questions through the development of a mathematical model of PDAC progression that incorporates the major alteration status of specific genes with predictive utility. The model successfully reproduced clinical outcomes regarding metastatic patterns and the genetic alteration status of patients from two independent cohorts from the United States and Japan. Using this model, we defined a candidate predictive signature in patients with low metastatic propensity. If a primary tumor contained a small fraction of cells with

9 Article Comparative evaluation of respiratory-gated and ungated FDG-PET for target volume definition in radiotherapy treatment planning for pancreatic cancer. 2016

Kishi, Takahiro / Matsuo, Yukinori / Nakamura, Akira / Nakamoto, Yuji / Itasaka, Satoshi / Mizowaki, Takashi / Togashi, Kaori / Hiraoka, Masahiro. ·Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Japan. · Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Japan. · Department of Radiation Oncology, Kurashiki Central Hospital, Japan. ·Radiother Oncol · Pubmed #27492203.

ABSTRACT: OBJECTIVE: The purpose of this study was to evaluate the usefulness of respiratory-gated positron emission tomography (4D-PET) in pancreatic cancer radiotherapy treatment planning (RTTP). MATERIALS AND METHODS: Fourteen patients with 18F-fluorodeoxyglucose (FDG)-avid pancreatic tumours were evaluated between December 2013 and March 2015. Two sets of volumes were contoured for the pancreatic tumour of each patient. The biological target volume in three-dimensional RTTP (BTV3D) was contoured using conventional respiratory un-gated PET. The BTV3D was then expanded using population-based margins to generate a series of internal target volume 3D (ITV3D) values. The ITV 4D (ITV4D) was contoured using 4D-PET. Each of the five phases of 4D-PET was used for 4D contouring, and the ITV4D was constructed by summing the volumes defined on the five individual 4D-PET images. The relative volumes and normalized volumetric overlap were computed between ITV3D and ITV4D. RESULTS: On average, the FDG-avid tumour volumes were 1.6 (range: 0.8-2.3) fold greater in the ITV4D than in the BTV3D. On average, the ITV3D values were 2.0 (range: 1.1-3.4) fold larger than the corresponding ITV4D values. CONCLUSION: The ITV generated from 4D-PET can be used to improve the accuracy or reduce normal tissue irradiation compared with conventional un-gated PET-based ITV.

10 Article Pretreatment C-reactive protein level predicts outcome and patterns of failure after chemoradiotherapy for locally advanced pancreatic cancer. 2015

Kishi, Takahiro / Nakamura, Akira / Itasaka, Satoshi / Shibuya, Keiko / Matsumoto, Shigemi / Kanai, Masashi / Kodama, Yuzo / Takaori, Kyoichi / Mizowaki, Takashi / Hiraoka, Masahiro. ·Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, Kyoto, 606-8507, Japan. · Department of Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine, Kyoto, 606-8507, Japan. Electronic address: akiran@kuhp.kyoto-u.ac.jp. · Department of Radiation Oncology, Kurashiki Central Hospital, Kurashiki, 710-0052, Japan. · Department of Therapeutic Radiology, Graduate School of Medicine, Yamaguchi University, Ube, 755-8505, Japan. · Department of Clinical Oncology and Pharmacogenomics, Kyoto University Graduate School of Medicine, Kyoto, 606-8507, Japan. · Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, 606-8507, Japan. · Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, 606-8507, Japan. ·Pancreatology · Pubmed #26601881.

ABSTRACT: OBJECTIVES: In this study we evaluated the predictive value of pretreatment C-reactive protein (CRP) levels on patterns of failure and survival outcomes in patients with locally advanced pancreatic cancer (LAPC) who received chemoradiotherapy (CRT). METHODS: Data from 65 patients who underwent CRT for LAPC from July 2001 to May 2013 were retrospectively collected. Factors, including age, gender, Eastern Cooperative Oncology Group performance status (PS), histological confirmation, tumor size, tumor location, biliary drainage, stage, induction chemotherapy, CRP levels, neutrophil-to-lymphocyte ratio, platelet-lymphocyte ratio, albumin and carbohydrate antigen 19-9, were evaluated with regard to overall survival (OS) and patterns of failure using a Cox proportional hazards model. RESULTS: The 1-year OS and median follow-up for all of the patients were 63.9% and 15.2 months, respectively. The median survival time and 1-year OS were 18.0 months and 72.5%, respectively, in the patients with lower CRP levels (≤3.0 mg/L), whereas 11.0 months and 30.8%, respectively, in the patients with higher CRP levels (>3.0 mg/L). Thirty-seven patients had tumor recurrence after CRT. All of the patients with higher CRP levels developed distant metastases as a primary sign of treatment failure. In a multivariate analysis, higher CRP levels were significantly correlated with distant disease-free survival (p = 0.004, HR = 4.50) and OS (p = 0.004, HR = 3.001). By contrast, local progression-free survival was not significantly different between the CRP subgroups. CONCLUSION: The CRP levels were a significant predictor of survival and distant disease control for the LAPC patients who received CRT.

11 Article The evolution of tumor metastasis during clonal expansion with alterations in metastasis driver genes. 2015

Yamamoto, Kimiyo N / Nakamura, Akira / Haeno, Hiroshi. ·Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka 812-8581, Japan. · Department of Radiation Oncology and Image-Applied Therapy, Kyoto University, Kyoto, Japan. ·Sci Rep · Pubmed #26515895.

ABSTRACT: Metastasis is a leading cause of cancer-related deaths. Carcinoma generally initiates at a specific organ as a primary tumor, but eventually metastasizes and forms tumor sites in other organs. In this report, we developed a mathematical model of cancer progression with alterations in metastasis-related genes. In cases in which tumor cells acquire metastatic ability through two steps of genetic alterations, we derive formulas for the probability, the expected number, and the distribution of the number of metastases. Moreover, we investigate practical pancreatic cancer disease progression in cases in which both one and two steps of genetic alterations are responsible for metastatic formation. Importantly, we derive a mathematical formula for the survival outcome validated using clinical data as well as direct simulations. Our model provides theoretical insights into how invisible metastases distribute upon diagnosis with respect to growth rates, (epi)genetic alteration rates, metastatic rate, and detection size. Prediction of survival outcome using the formula is of clinical importance in terms of determining therapeutic strategies.

12 Article Interfraction positional variation in pancreatic tumors using daily breath-hold cone-beam computed tomography with visual feedback. 2015

Nakamura, Mitsuhiro / Akimoto, Mami / Ono, Tomohiro / Nakamura, Akira / Yano, Shinsuke / Nakata, Manabu / Itasaka, Satoshi / Mizowaki, Takashi / Shibuya, Keiko / Hiraoka, Masahiro. ·Kyoto University. m_nkmr@kuhp.kyoto-u.ac.jp. ·J Appl Clin Med Phys · Pubmed #26103180.

ABSTRACT: We assessed interfraction positional variation in pancreatic tumors using daily breath-hold cone-beam computed tomography at end-exhalation (EE) with visual feedback (BH-CBCT). Eleven consecutive patients with pancreatic cancer who underwent BH intensity-modulated radiation therapy with visual feedback were enrolled. All participating patients stopped oral intake, with the exception of drugs and water, for > 3 hr before treatment planning and daily treatment. Each patient was fixed in the supine position on an individualized vacuum pillow. An isotropic margin of 5 mm was added to the clinical target volume to create the planning target volume (PTV). The prescription dose was 42 to 51 Gy in 15 fractions. After correcting initial setup errors based on bony anatomy, the first BH-CBCT scans were performed before beam delivery in every fraction. BH-CBCT acquisition was obtained in three or four times breath holds by interrupting the acquisition two or three times, depending on the patient's BH ability. The image acquisition time for a 360° gantry rotation was approximately 90 s, including the interruption time due to BH. The initial setup errors were corrected based on bony structure, and the residual errors in the target position were then recorded. The magnitude of the interfraction variation in target position was assessed for 165 fractions. The systematic and random errors were 1.2 and 1.8 mm, 1.1 and 1.8 mm, and 1.7 and 2.9 mm in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions, respectively. Absolute interfraction variations of > 5 mm were observed in 18 fractions (11.0%) from seven patients because of EE-BH failure. In conclusion, target matching is required to correct interfraction variation even with visual feedback, especially to ensure safe delivery of escalated doses to patients with pancreatic cancer.

13 Article Radiotherapy for patients with isolated local recurrence of primary resected pancreatic cancer. Prolonged disease-free interval associated with favorable prognosis. 2014

Nakamura, Akira / Itasaka, Satoshi / Takaori, Kyoichi / Kawaguchi, Yoshiya / Shibuya, Keiko / Yoshimura, Michio / Matsuo, Yukinori / Mizowaki, Takashi / Uemoto, Shinji / Hiraoka, Masahiro. ·Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, 606-8507, Kyoto, Japan, akiran@kuhp.kyoto-u.ac.jp. ·Strahlenther Onkol · Pubmed #24599344.

ABSTRACT: BACKGROUND AND PURPOSE: To evaluate the treatment outcomes of radiotherapy and prognostic factors for recurrent pancreatic cancer. PATIENTS AND METHODS: The study comprised 30 patients who developed a locoregional recurrence of primarily resected pancreatic cancer and received radiotherapy between 2000 and 2013 with a median dose of 54 Gy (range, 39-60 Gy). Concurrent chemotherapy included gemcitabine for 18 patients and S-1 for seven patients. The treatment outcomes and prognostic factors were retrospectively analyzed. RESULTS: The median follow-up after radiotherapy was 14.6 months. The 1-year overall survival, local control, and progression-free survival rates were 69%, 67%, and 32%, respectively. The median overall survival and progression-free survival rates were 15.9 and 6.9 months, respectively. Tumor marker reduction and ≥ 50% reduction were observed in 18 and two patients, respectively. Of the seven patients who exhibited pain symptoms, four and two patients were partly and completely relieved, respectively. Late grade 3 ileus and gastroduodenal bleeding were observed in one patient each. Among the clinicopathological factors evaluated, only a disease-free interval of greater than 18.9 months exhibited a significant association with improved overall survival (p = 0.017). CONCLUSIONS: Radiotherapy for isolated locally recurrent pancreatic cancer resulted in encouraging local control, overall survival, and palliative effects with mild toxicity, particularly in patients with a prolonged disease-free interval. This treatment strategy should be prospectively evaluated.

14 Article Effects of interportal error on dose distribution in patients undergoing breath-holding intensity-modulated radiotherapy for pancreatic cancer: evaluation of a new treatment planning method. 2013

Takakura, Toru / Nakamura, Mitsuhiro / Shibuya, Keiko / Nakata, Manabu / Nakamura, Akira / Matsuo, Yukinori / Shiinoki, Takehiro / Higashimura, Kyoji / Teshima, Teruki / Hiraoka, Masahiro. ·Kyoto University Hospital, Osaka University. toru1@kuhp.kyoto-u.ac.jp. ·J Appl Clin Med Phys · Pubmed #24036858.

ABSTRACT: In patients with pancreatic cancer, intensity-modulated radiotherapy (IMRT) under breath holding facilitates concentration of the radiation dose in the tumor, while sparing the neighboring organs at risk and minimizing interplay effects between movement of the multileaf collimator and motion of the internal structures. Although the breath-holding technique provides high interportal reproducibility of target position, dosimetric errors caused by interportal breath-holding positional error have not been reported. Here, we investigated the effects of interportal breath-holding positional errors on IMRT dose distribution by incorporating interportal positional error into the original treatment plan, using random numbers in ten patients treated for pancreatic cancer. We also developed a treatment planning technique that shortens breath-holding time without increasing dosimetric quality assurance workload. The key feature of our proposed method is performance of dose calculation using the same optimized fluence map as the original plan, after dose per fraction in the original plan was cut in half and the number of fractions was doubled. Results confirmed that interportal error had a negligible effect on dose distribution over multiple fractions. Variations in the homogeneity index and the dose delivered to 98%, 2%, and 50% of the volume for the planning target volume, and the dose delivered to 1 cc of the volume for the duodenum and stomach were ±1%, on average, in comparison with the original plan. The new treatment planning method decreased breath-holding time by 33%, and differences in dose-volume metrics between the original and the new treatment plans were within ± 1%. An additional advantage of our proposed method is that interportal errors can be better averaged out; thus, dose distribution in the proposed method may be closer to the planned dose distribution than with the original plans.

15 Article Interfractional dose variations in the stomach and the bowels during breathhold intensity-modulated radiotherapy for pancreatic cancer: Implications for a dose-escalation strategy. 2013

Nakamura, Akira / Shibuya, Keiko / Nakamura, Mitsuhiro / Matsuo, Yukinori / Shiinoki, Takehiro / Nakata, Manabu / Mizowaki, Takashi / Hiraoka, Masahiro. ·Department of Radiation Oncology and Image-applied Therapy, Kyoto University, Kyoto, Japan. ·Med Phys · Pubmed #23387724.

ABSTRACT: PURPOSE: This study aims to evaluate the interfractional dose variations in the organs-at-risk (OARs) during pancreatic breathhold intensity-modulated radiotherapy (IMRT) and to assess the impacts of "planning organs-at-risk volume" (POV) structures generated by isotropically expanding the dose-limiting OARs, based on the comparison of the interfractional doses to the OARs between IMRT plans and conventional three-dimensional-conformal radiotherapy (3D-CRT) plans. METHODS: Thirty repeat CT scans were acquired from ten consecutive patients who were receiving chemoradiotherapy for pancreatic cancer. Six IMRT plans for each patient with two levels of prescription (45 and 51 Gy in 15 fractions) and 3 POV margin sizes (5, 7, and 10 mm) were generated based on the initial CT scan under predetermined constraints. Two 3D-CRT plans (39 and 42 Gy in 15 fractions) were simultaneously generated. The dose distribution of all of the treatment plans was recalculated with the repeat CT scans. The interfractional dose variations in the three OARs (stomach, duodenum, and small intestine) were evaluated, and the absolute volumes ≥39 Gy (V39Gy) of the OARs in the IMRT plans were compared to those in the 3D-CRT plans. Regression analyses were performed to assess the relative impact of the factors of interest on the interfractional dose variations of the OARs. RESULTS: Substantial dose excesses to the three OARs were observed at all of the prescription dose levels and the POV margin sizes on the repeat CT scans. The safety threshold based on the mean stomach V39Gy on the recalculated 39 Gy-3D-CRT plans was 1.9 ml. Statistically significant and marginally insignificant mean V39Gy values above the safety thresholds were observed in the stomach in the 51 Gy-IMRT plans (2.6 and 2.1 ml with the 5- and 7-mm PRV margins, respectively (P = 0.015 and 0.085)). Only in the case of the 10-mm POV margin did the metric fall below the safety threshold to 1.5 ml (P = 0.634). The duodenum and the small intestine did not violate the safety thresholds (1.4 and 3.8 ml, respectively). From the multiple regression analyses, only the margin size (P < 0.001) and the POV V39Gy (P < 0.001) were significantly associated with the distribution of recalculated V39Gy for the stomach. Multiple factors, including the margin size (P = 0.020) and the POV V39Gy (P < 0.001) were associated with the recalculated V39Gy for the duodenum. However, none of the POV parameters for the small intestine were associated with the recalculated V39Gy. CONCLUSIONS: Considerable interfractional dose variation was observed in three critical OARs. At the escalated prescription dose of breathhold IMRT, the dose variations could exceed the dose variations using 3D-CRT at the safe prescription dose level, indicating that a dose-escalation strategy based solely on the initial advantageous dose distribution in a breathhold IMRT can be problematic. Given the current limitations for predicting or coping with variation throughout the treatment course, the use of POV should be considered for safely delivering escalated doses to patients with pancreatic cancer.

16 Article Analysis of dosimetric parameters associated with acute gastrointestinal toxicity and upper gastrointestinal bleeding in locally advanced pancreatic cancer patients treated with gemcitabine-based concurrent chemoradiotherapy. 2012

Nakamura, Akira / Shibuya, Keiko / Matsuo, Yukinori / Nakamura, Mitsuhiro / Shiinoki, Takehiro / Mizowaki, Takashi / Hiraoka, Masahiro. ·Department of Radiation Oncology and Image-Applied Therapy, Kyoto University Graduate School of Medicine, Kyoto, Japan. ·Int J Radiat Oncol Biol Phys · Pubmed #22381898.

ABSTRACT: PURPOSE: To identify the dosimetric parameters associated with gastrointestinal (GI) toxicity in patients with locally advanced pancreatic cancer (LAPC) treated with gemcitabine-based chemoradiotherapy. METHODS AND MATERIALS: The data from 40 patients were analyzed retrospectively. Chemoradiotherapy consisted of conventional fractionated three-dimensional radiotherapy and weekly gemcitabine. Treatment-related acute GI toxicity and upper GI bleeding (UGB) were graded according to the Common Toxicity Criteria Adverse Events, version 4.0. The dosimetric parameters (mean dose, maximal absolute dose which covers 2 cm(3) of the organ, and absolute volume receiving 10-50 Gy [V(10-50)]) of the stomach, duodenum, small intestine, and a composite structure of the stomach and duodenum (StoDuo) were obtained. The planning target volume was also obtained. Univariate analyses were performed to identify the predictive factors for the risk of grade 2 or greater acute GI toxicity and grade 3 or greater UGB, respectively. RESULTS: The median follow-up period was 15.7 months (range, 4-37). The actual incidence of acute GI toxicity was 33%. The estimated incidence of UGB at 1 year was 20%. Regarding acute GI toxicity, a V(50) of ≥ 16 cm(3) of the stomach was the best predictor, and the actual incidence in patients with V(50) <16 cm(3) of the stomach vs. those with V(50) of ≥ 16 cm(3) was 9% vs. 61%, respectively (p = 0.001). Regarding UGB, V(50) of ≥ 33 cm(3) of the StoDuo was the best predictor, and the estimated incidence at 1 year in patients with V(50) <33 cm(3) of the StoDuo vs. those with V(50) ≥ 33 cm(3) was 0% vs. 44%, respectively (p = 0.002). The dosimetric parameters correlated highly with one another. CONCLUSION: The irradiated absolute volume of the stomach and duodenum are important for the risk of acute GI toxicity and UGB. These results could be helpful in escalating the radiation doses using novel techniques, such as intensity-modulated radiotherapy, for the treatment of pancreatic cancer.

17 Article Dosimetric investigation of breath-hold intensity-modulated radiotherapy for pancreatic cancer. 2012

Nakamura, Mitsuhiro / Kishimoto, Shun / Iwamura, Kohei / Shiinoki, Takehiro / Nakamura, Akira / Matsuo, Yukinori / Shibuya, Keiko / Hiraoka, Masahiro. ·Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Kyoto 606-8507, Japan. m_nkmr@kuhp.kyoto-u.ac.jp ·Med Phys · Pubmed #22225274.

ABSTRACT: PURPOSE: To experimentally investigate the effects of variations in respiratory motion during breath-holding (BH) at end-exhalation (EE) on intensity-modulated radiotherapy (BH-IMRT) dose distribution using a motor-driven base, films, and an ionization chamber. METHODS: Measurements were performed on a linear accelerator, which has a 120-leaf independently moving multileaf collimator with 5-mm leaf width at the isocenter for the 20-cm central field. Polystyrene phantoms with dimensions of 40 × 40 × 10 cm were set on a motor-driven base. All gantry angles of seven IMRT plans (a total of 35 fields) were changed to zero, and doses were then delivered to a film placed at a depth of 4 cm and an ionization chamber at a depth of 5 cm in the phantom with a dose rate of 600 MU/min under the following conditions: pulsation from the abdominal aorta and baseline drift with speeds of 0.2 mm/s (BD(0.2mm/s)) and 0.4 mm/s (BD(0.4mm/s)). As a reference for comparison, doses were also delivered to the chamber and film under stationary conditions. RESULTS: In chamber measurements, means ± standard deviations of the dose deviations between stationary and moving conditions were -0.52% ± 1.03% (range: -3.41-1.05%), -0.07% ± 1.21% (range: -1.88-4.31%), and 0.03% ± 1.70% (range: -2.70-6.41%) for pulsation, BD(0.2mm/s), and BD(0.4mm/s), respectively. The γ passing rate ranged from 99.5% to 100.0%, even with the criterion of 2%/1 mm for pulsation pattern. In the case of BD(0.4mm/s), the γ passing rate for four of 35 fields (11.4%) did not reach 90% with a criterion of 3%/3 mm. The differences in γ passing rate between BD(0.2mm/s) and BD(0.4mm/s) were statistically significant for each criterion. Taking γ passing rates of > 90% as acceptable with a criterion of 3%/3 mm, large differences were observed in the γ passing rate between the baseline drift of ≤5 mm and that of >5 mm (minimum γ passing rate: 92.0% vs 82.7%; p < 0.01). CONCLUSIONS: This study suggested that the baseline drift of >5 mm should be avoided in the BH-IMRT.

18 Article Interfractional dose variations in intensity-modulated radiotherapy with breath-hold for pancreatic cancer. 2012

Nakamura, Mitsuhiro / Shibuya, Keiko / Nakamura, Akira / Shiinoki, Takehiro / Matsuo, Yukinori / Nakata, Manabu / Sawada, Akira / Mizowaki, Takashi / Hiraoka, Masahiro. ·Department of Radiation Oncology and Image-Applied Therapy, Kyoto University Graduate School of Medicine, Kyoto, Japan. ·Int J Radiat Oncol Biol Phys · Pubmed #21477941.

ABSTRACT: PURPOSE: To investigate the interfractional dose variations for intensity-modulated radiotherapy (RT) combined with breath-hold (BH) at end-exhalation (EE) for pancreatic cancer. METHODS AND MATERIALS: A total of 10 consecutive patients with pancreatic cancer were enrolled. Each patient was fixed in the supine position on an individualized vacuum pillow with both arms raised. Computed tomography (CT) scans were performed before RT, and three additional scans were performed during the course of chemoradiotherapy using a conventional RT technique. The CT data were acquired under EE-BH conditions (BH-CT) using a visual feedback technique. The intensity-modulated RT plan, which used five 15-MV coplanar ports, was designed on the initial BH-CT set with a prescription dose of 39 Gy at 2.6 Gy/fraction. After rigid image registration between the initial and subsequent BH-CT scans, the dose distributions were recalculated on the subsequent BH-CT images under the same conditions as in planning. Changes in the dose-volume metrics of the gross tumor volume (GTV), clinical target volume (CTV = GTV + 5 mm), stomach, and duodenum were evaluated. RESULTS: For the GTV and clinical target volume (CTV), the 95th percentile of the interfractional variations in the maximal dose, mean dose, dose covering 95% volume of the region of structure, and percentage of the volume covered by the 90% isodose line were within ±3%. Although the volume covered by the 39 Gy isodose line for the stomach and duodenum did not exceed 0.1 mL at planning, the volume covered by the 39 Gy isodose line for these structures was up to 11.4 cm(3) and 1.8 cm(3), respectively. CONCLUSIONS: Despite variations in the gastrointestinal state and abdominal wall position at EE, the GTV and CTV were mostly ensured at the planned dose, with the exception of 1 patient. Compared with the duodenum, large variations in the stomach volume receiving high-dose radiation were observed, which might be beyond the negligible range in achieving dose escalation with intensity-modulated RT combined with BH at EE.

19 Article Interfractional reproducibility in pancreatic position based on four-dimensional computed tomography. 2011

Shiinoki, Takehiro / Shibuya, Keiko / Nakamura, Mitsuhiro / Nakamura, Akira / Matsuo, Yukinori / Nakata, Manabu / Sawada, Akira / Mizowaki, Takashi / Itoh, Akio / Hiraoka, Masahiro. ·Department of Nuclear Engineering, Graduate School of Engineering, Kyoto University, Kyoto, Japan. ·Int J Radiat Oncol Biol Phys · Pubmed #21493016.

ABSTRACT: PURPOSE: To assess the interfractional positional variation of the pancreas using four-dimensional computed tomography (4D-CT) and to determine the suitable phase of respiration for dose delivery methods to account for pancreatic tumor motion. METHODS AND MATERIALS: Fifteen patients with pancreatic cancer were enrolled in this study. For each patient, 4D-CT scans were performed at CT simulation and three times during the course of treatment. Regions of interest were set to the intrapancreatic bile ducts as a surrogate for pancreatic position. The centroids of the regions of interest were calculated at end-inhalation and end-exhalation of the respiration phase. The ranges of respiratory motion and interfractional positional variation were evaluated in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions. RESULTS: The medians of respiratory motion were 1.1 mm (range, 0.0-9.8 mm), 1.5 mm (range, 0.0-7.0 mm), and 5.0 mm (range, 0.0-12.5 mm) in the LR, AP, and SI directions, respectively. The means ± SDs of the interfractional positional variation at end-inhalation were 0.9 ± 5.1 mm (range, -9.2 to 15.6 mm), -1.9 ± 3.9 mm (range, -12.8 to 6.4 mm), and -1.3 ± 6.9 mm (range, -15.0 to 13.7 mm) and those at end-exhalation were 0.0 ± 3.1 mm (range, -7.0 to 5.3 mm), -1.2 ± 3.9 mm (range, -11.2 to 6.7 mm), and 0.1 ± 3.2 mm (range, -9.9 to 5.1 mm) in the LR, AP, and SI directions, respectively. The SDs of the interfractional positional variation in the LR and SI directions were significantly larger at end-inhalation than at end-exhalation (LR, p < 0.001; SI, p < 0.001). CONCLUSIONS: The ranges of respiratory motion during the course of treatment and the interfractional positional variation were not negligible. The interfractional positional reproducibility was higher at end-exhalation than at end-inhalation under free breathing.

20 Article Positional reproducibility of pancreatic tumors under end-exhalation breath-hold conditions using a visual feedback technique. 2011

Nakamura, Mitsuhiro / Shibuya, Keiko / Shiinoki, Takehiro / Matsuo, Yukinori / Nakamura, Akira / Nakata, Manabu / Sawada, Akira / Mizowaki, Takashi / Hiraoka, Masahiro. ·Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan. m_nkmr@kuhp.kyoto-u.ac.jp ·Int J Radiat Oncol Biol Phys · Pubmed #20832187.

ABSTRACT: PURPOSE: To assess positional reproducibility of pancreatic tumors under end-exhalation (EE) breath-hold (BH) conditions with a visual feedback technique based on computed tomography (CT) images. METHODS AND MATERIALS: Ten patients with pancreatic cancer were enrolled in an institutional review board-approved trial. All patients were placed in a supine position on an individualized vacuum pillow with both arms raised. At the time of CT scan, they held their breath at EE with the aid of video goggles displaying their abdominal displacement. Each three-consecutive helical CT data set was acquired four times (sessions 1-4; session 1 corresponded to the time of CT simulation). The point of interest within or in proximity to a gross tumor volume was defined based on certain structural features. The positional variations in point of interest and margin size required to cover positional variations were assessed. RESULTS: The means ± standard deviations (SDs) of intrafraction positional variations were 0.0 ± 1.1, 0.1 ± 1.2, and 0.1 ± 1.0 mm in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions, respectively (p = 0.726). The means ± SDs of interfraction positional variations were 0.3 ± 2.0, 0.8 ± 1.8, and 0.3 ± 1.8 mm in the LR, AP, and SI directions, respectively (p = 0.533). Population-based margin sizes required to cover 95th percentiles of the overall positional variations were 4.7, 5.3, and 4.9 mm in the LR, AP, and SI directions, respectively. CONCLUSIONS: A margin size of 5 mm was needed to cover the 95th percentiles of the overall positional variations under EE-BH conditions, using this noninvasive approach to motion management for pancreatic tumors.