Toshiyuki Okumura - Academia.edu (original) (raw)

Papers by Toshiyuki Okumura

Journal of Radiation Research

Lymphocytes play an important role in the cancer immune system. In the present study, we aimed to... more Lymphocytes play an important role in the cancer immune system. In the present study, we aimed to evaluate the associations of lymphopenia during proton beam therapy (PBT) and concurrent chemotherapy with clinical outcomes and to determine whether lung or bone is more influential on lymphopenia during PBT. Data from 41 patients with stage III non-small cell lung cancer (NSCLC) who received PBT of 74 GyE with concurrent chemotherapy between 2007 and 2017 were reviewed retrospectively. The correlation between dosimetry parameters obtained from dose–volume histograms of the bone and lung and lymphopenia during PBT were analyzed. Minimum absolute lymphocyte count (ALCmin) and maximum neutrophil/lymphocyte ratio (NLRmax) were used as indicators of lymphopenia. Bone V5–20 and lung V5–50 were significantly correlated with the ALCmin and NLRmax during PBT. Multivariable analysis showed that the NLRmax, but not the ALCmin, was associated with overall survival (OS), progression-free survival ...

Igaku butsuri : Nihon Igaku Butsuri Gakkai kikanshi = Japanese journal of medical physics : an official journal of Japan Society of Medical Physics, 2012

Recent advance in the field of radiation oncology, especially in medical physics for radiation th... more 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.

Cureus, 2021

Background and objective Postoperative radiotherapy is usually indicated for both grade 3 glioma ... more Background and objective Postoperative radiotherapy is usually indicated for both grade 3 glioma and grade 4 glioblastoma. However, the treatment results and tumor features of grade 3 glioma clearly differ from those of glioblastoma. There is limited information on outcomes and tumor progression for grade 3 glioma. In this study, we evaluate the result of postoperative radiotherapy for grade 3 glioma and focus on the correlation of MRI findings with prognosis. Methods In this study, 99 of 110 patients with grade 3 glioma who received postoperative radiotherapy and were followed up for more than one year were retrospectively analyzed. The total irradiation dose was 60.0 Gy in 30 fractions, and daily temozolomide or two cycles of nimustine (ACNU) was concurrently administered during radiotherapy. The median follow-up period was 46 months (range: 2-151 months). Results In multivariate analysis, pathology [anaplastic oligodendroglioma (AO) vs. anaplastic astrocytoma (AA)], the status of surgical resection (biopsy vs. partial resection or more), and contrast enhancement (enhanced by MRI image or not) were significant factors for overall survival (OS). The five-year OS for AO vs. AA cases were 76.8% vs. 46.1%, total to partial resection vs. biopsy cases were 72.7% vs. 21.0%, and non-enhanced vs. enhanced cases were 82.5% vs. 45.6%, respectively. In multivariate analysis, the status of surgical resection and longer extension of preoperative edema (PE) were significant factors for progression-free survival (PFS). The five-year PFS for the total to partial resection vs. biopsy cases were 52.9% vs. 10.7%, and non-extensive PE vs. extensive PE (EPE) cases were 62.2% vs. 19.1%, respectively. Conclusion Our results suggest that a contrast-enhanced tumor on MRI and a longer PE may also be significantly associated with OS and PFS among grade 3 glioma patients.

Background: Lymphocytes play an important role in the cancer immune system. We investigated influ... more Background: Lymphocytes play an important role in the cancer immune system. We investigated influences of irradiated doses and volumes of the bone on lymphopenia and survivals in chemoradiotherapy for stage III non-small cell lung cancer (NSCLC).Methods: Data from 41 patients with stage III unresectable NSCLC who received definitive proton beam therapy (PBT) of 74 GyE with concurrent chemotherapy between 2007 and 2017 were retrospectively reviewed. The correlation between dosimetry parameters obtained from dose-volume histograms (DVHs) of the bone, lung, and heart and lymphopenia during PBT were analyzed. Maximum and minimum absolute lymphocyte counts (ALCmax and ALCmin) and maximum neutrophil/lymphocyte ratio (NLRmax) were used as indicators of lymphopenia. Clinical factors, dosimetry parameters, and indicators of lymphopenia were also evaluated for the correlation with overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS).Results: Sign...

Journal of General and Family Medicine, 2017

In recent years, radiotherapy for liver cancer has accomplished much technical progress. The hist... more In recent years, radiotherapy for liver cancer has accomplished much technical progress. The history of radiotherapy for liver cancer shows an endeavor to overcome the problem of how to raise the irradiation dose to lesions while suppressing the unnecessary irradiation dose to normal liver tissue. With the appearance of treatment using X‐ray radiotherapy represented by three‐dimensional conformal radiotherapy, stereotactic body radiotherapy and particle beam therapy using proton beams and carbon ion beams, radiotherapy has become a safe and effective treatment option for liver cancers.

World Journal of Gastroenterology, 2005

Esophageal squamous cell carcinoma is generally sensitive to chemoradiotherapy (CRT), but some ca... more Esophageal squamous cell carcinoma is generally sensitive to chemoradiotherapy (CRT), but some cases are not. Using a retrospective analysis, we aimed to identify the predictors of the response by esophageal squamous cell carcinoma to definitive CRT. METHODS: The intensities of expression of p53, Ki67, Bcl-2, Bax, cyclin D1, VEGF, CDC25B, and metallothionein (MT) were evaluated immunohistochemically in the biopsy specimens obtained before CRT, and the intensities of their expression were tested for correlations with the clinical effects of CRT. RESULTS: The esophageal squamous cell carcinomas with negative p53, positive CDC25B, and negative MT expression were found to be significantly more sensitive to CRT. In addition, p53 positivity and CDC25B positivity respond well to CRT. CONCLUSION: Esophageal squamous cell carcinomas with negative p53,positive CDC25B, and negative MT expressions respond well to CRT. Even with p53 positivity, if with CDC25B positivity, CRT can be expected.

Journal of neuro-oncology, Oct 17, 2016

To evaluate the safety and efficacy of postoperative proton beam therapy (PBT) combined with nimu... more To evaluate the safety and efficacy of postoperative proton beam therapy (PBT) combined with nimustine hydrochloride (ACNU) or temozolomide (TMZ) for glioblastoma multiforme (GBM). The subjects were 46 patients with GBM who were treated with high dose (96.6 GyE) PBT. There were 24 males and 22 females, and the median age was 58 years old (range 24-76). The Karnofsky performance status was 60, 70, 80, 90 and 100 in 5, 10, 12, 11 and 8 patients, respectively. Total resection, partial resection, and biopsy were performed for 31, 14 and 1 patients, respectively. Photon beams were delivered to high intensity areas on T2-weighted magnetic resonance imaging (MRI) in the morning (50.4 Gy in 28 fractions). More than 6 h later, PBT was delivered to the enhanced area plus a 10 mm margin in the first half of the protocol (23.1 GyE in 14 fractions) and to the enhanced volume in the second half (23.1 GyE in 14 fraction). Concurrent chemotherapy with ACNU during weeks 1 and 4 or daily TMZ was admi...

Neurologia medico-chirurgica, 2012

A total of 29 cerebral arteriovenous malformations (AVMs) treated at the University of Tsukuba wi... more A total of 29 cerebral arteriovenous malformations (AVMs) treated at the University of Tsukuba with multimodality treatment including proton beam (PB) radiotherapy for cerebral AVMs between 2005 and 2011 were retrospectively evaluated. Eleven AVMs were classified as Spetzler-Martin grades I and II, 10 as grade III, and 8 as grades IV and V. For AVMs smaller than 2.5 cm and located on superficial and non-eloquent areas, surgical removal with/without embolization was offered as a first-line treatment. For some small AVMs located in deep or eloquent lesions, gamma knife (GK) radiosurgery was offered. Some AVMs were treated with only embolization. AVMs larger than 2.5 cm were embolized to achieve reduction in size, to enhance the safety of the surgery, and to render the AVM amenable to GK radiosurgery. For larger AVMs located in deep or eloquent areas, PB radiotherapy was offered with/without embolization. Immediately after the treatment, 24 patients exhibited no neurological worsening. Four patients had moderate disability, and 1 patient had severe disability. Three patients suffered brain damage after surgical resection, and 2 patients suffered embolization complications. However, no neurological worsening was observed after either GK radiosurgery or PB radiotherapy, but 3 patients treated by PB radiotherapy suffered delayed hemorrhage. Fractionated PB radiotherapy for cerebral AVMs seems to be useful for the treatment of large AVMs, but careful long-term follow up is required to establish the efficacy and safety.

International Journal of Radiation Oncology*Biology*Physics, 2014

Background/Aim: The aim of the present study was to evaluate the outcomes of proton beam therapy ... more 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.

International Cancer Conference Journal, 2012

We describe the case of a patient with large hepatocellular carcinoma (HCC) with portal vein tumo... more We describe the case of a patient with large hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) who was successfully treated with two courses of proton beam therapy (PBT) followed by liver transplantation. The patient was a 69-year-old man with hepatitis C viral infection who was diagnosed with a diffuse HCC, 8 cm in size, and a PVTT that occluded the right portal vein and reached the main trunk of the portal vein. A large tumor in the right lobe and PVTT in the main and right main portal vein were treated by PBT. PVTT in the left main portal vein developed thereafter and was treated with a second course of PBT. Although the tumor was well controlled with two courses of PBT, liver function gradually deteriorated to an irreversible status 20 months after initiation of the first course of PBT. Liver transplantation was successfully performed to maintain liver function. The patient is still alive with no evidence of disease 7 years after the first course of PBT. This case shows that aggressive PBT can be used for treating advanced HCC, with subsequent liver transplantation for hepatic failure that may be caused by PBT.

Neurologia medico-chirurgica, 1996

A 39-year-old male presented with a small pontine hemorrhage and subarachnoid hemorrhage. An giog... more A 39-year-old male presented with a small pontine hemorrhage and subarachnoid hemorrhage. An giography showed a small left pontine arteriovenous malformation (AVM) associated with a small aneurysm on the pedicle feeding the AVM. The pedicle aneurysm was occluded by microcoils. The AVM was then treated by proton-beam radiosurgery. Follow-up angiography 2 years later revealed that the AVM had disappeared completely without neurological deficit. The combination of em bolization and proton-beam radiosurgery was curative in this patient with a pontine AVM associated with an aneurysm on the feeding artery, showing that these techniques can be used to treat inoper able vascular lesions safely.

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 2014

Aeration in the nasal cavity and paranasal sinus (NCPS) was investigated during the course of pro... more Aeration in the nasal cavity and paranasal sinus (NCPS) was investigated during the course of proton therapy (PT), and the influence of aeration on the dose distribution was determined. Twenty patients with NCPS cancer (10 nasal cavity, 10 paranasal sinus) were analyzed. All the patients received a total proton beam irradiation dose of 38-78.4 Gray equivalents (GyE). Two to five CT examinations were performed during the course of treatment. The aeration ratio inside the cavity/sinus was calculated for each CT observation. Moreover, a simulation study supposing that the first treatment plan had been continued until the end of treatment was performed using the subsequent CT findings. The aeration ratio was increased in 18 patients. The largest increase was from 15% to 82%. Three patients had a simulated maximum cumulative dose in the brainstem of beyond 60 GyE, while 10 patients had a simulated maximum cumulative dose in the optic chiasm of beyond 50 GyE. The shortest simulated time p...

Neurologia medico-chirurgica, 2011

The effectiveness of proton beam (PB) radiosurgery for large lesions is greater than for other tr... more The effectiveness of proton beam (PB) radiosurgery for large lesions is greater than for other treatment modalities. At our institute, PB radiosurgery is used to treat arteriovenous malformations (AVMs). We report the outcome of PB radiosurgery for AVMs over a period of 15 years, focusing on the efficacy of PB radiosurgery combined with embolization for AVMs AE30 mm in diameter. We retrospectively analyzed 11 patients with AVMs AE30 mm in diameter who were treated with PB radiosurgery between June 1990 and September 2005 at the Proton Medical Research Center of the University of Tsukuba. The mean irradiation dose was 25.3 gray-equivalent, and the mean duration of clinical follow up was 134.2 months (median 138 months). Pre-radiosurgical embolization was performed in all cases. Complete obliteration was achieved in 9 of the 11 patients. One patient experienced post-radiosurgical hemorrhage, and 1 patient experienced radiation-related aggravation of clinical symptoms due to radiation necrosis. Eight patients had excellent outcomes. The multimodal therapy approach of combining pre-radiosurgical embolization and PB radiosurgery for AVMs yielded a favorable outcome for AVMs AE30 mm in diameter. Thus, PB radiosurgery is a viable treatment option for AVMs AE30 mm in diameter.

Radiation Oncology, 2012

Background: Although proton radiotherapy is a promising new approach for cancer patients, functio... more Background: Although proton radiotherapy is a promising new approach for cancer patients, functional interference is a concern for patients with implantable cardioverter defibrillators (ICDs). The purpose of this study was to clarify the influence of secondary neutrons induced by proton radiotherapy on ICDs. Methods: The experimental setup simulated proton radiotherapy for a patient with an ICD. Four new ICDs were placed 0.3 cm laterally and 3 cm distally outside the radiation field in order to evaluate the influence of secondary neutrons. The cumulative in-field radiation dose was 107 Gy over 10 sessions of irradiation with a dose rate of 2 Gy/min and a field size of 10 × 10 cm 2. After each radiation fraction, interference with the ICD by the therapy was analyzed by an ICD programmer. The dose distributions of secondary neutrons were estimated by Monte-Carlo simulation. Results: The frequency of the power-on reset, the most serious soft error where the programmed pacing mode changes temporarily to a safety backup mode, was 1 per approximately 50 Gy. The total number of soft errors logged in all devices was 29, which was a rate of 1 soft error per approximately 15 Gy. No permanent device malfunctions were detected. The calculated dose of secondary neutrons per 1 Gy proton dose in the phantom was approximately 1.3-8.9 mSv/Gy. Conclusions: With the present experimental settings, the probability was approximately 1 power-on reset per 50 Gy, which was below the dose level (60-80 Gy) generally used in proton radiotherapy. Further quantitative analysis in various settings is needed to establish guidelines regarding proton radiotherapy for cancer patients with ICDs.

Lung Cancer, 2012

Background and Purpose: To investigate the geometrical accuracy in proton beam therapy (PBT) to t... more Background and Purpose: To investigate the geometrical accuracy in proton beam therapy (PBT) to the lung by comparing the location of the fibrosis after PBT and the tumor using less invasive method. Patients and Methods: We examined 50 lung tumors that had been treated by respiratory-gated PBT (33-74 Gray equivalents). Image registration and re-slicing of computed tomography (CT) before and after PBT were performed using an image analysis software system. We investigated whether the location of fibrosis was accurate with the tumor site and which factor among the respiratory rhythm, tumor volume, location, fixation, beam direction and clinical outcome was affected with accuracy. Results: The area of fibrosis was accurate with the tumor in 45 tumors (Group A) and not accurate in 5 tumors (Group B). All lesions with a small irregularity of respiratory rhythm showed fibrosis in an area accurate with 4 the tumor. This percentage (100%) was higher than that of the lesions with a large irregularity of respiratory rhythm (67%, p=0.037). Radiation pneumonitis was found for 1 lesion in group A and 2 lesions in group B (p=0.0009). Conclusion: The geometrical accuracy of beam delivery to the lung was higher in the patients with a regular respiratory rhythm in PBT. The patients of group B had greater risk of pneumonitis.

Journal of Radiation Research, 2012

To investigate the reproducibility of computed tomography (CT) imaging quality in respiratory-gat... more To investigate the reproducibility of computed tomography (CT) imaging quality in respiratory-gated radiation treatment planning is essential in radiotherapy of movable tumors. Seven series of regular and six series of irregular respiratory motions were performed using a thorax dynamic phantom. For the regular respiratory motions, the respiratory cycle was changed from 2.5 to 4 s and the amplitude was changed from 4 to 10 mm. For the irregular respiratory motions, a cycle of 2.5 to 4 or an amplitude of 4 to 10 mm was added to the base data (i.e. 3.5-s cycle, 6-mm amplitude) every three cycles. Images of the object were acquired six times using respiratory-gated data acquisition. The volume of the object was calculated and the reproducibility of the volume was decided based on the variety. The registered image of the object was added and the reproducibility of the shape was decided based on the degree of overlap of objects. The variety in the volumes and shapes differed significantly as the respiratory cycle changed according to regular respiratory motions. In irregular respiratory motion, shape reproducibility was further inferior, and the percentage of overlap among the six images was 35.26% in the 2.5-and 3.5-s cycle mixed group. Amplitude changes did not produce significant differences in the variety of the volumes and shapes. Respiratory cycle changes reduced the reproducibility of the image quality in respiratory-gated CT.

International Journal of Radiation Oncology*Biology*Physics, 2010

ABSTRACT

$Research paper thumbnail of Dose-volume histogram analysis for risk factors of radiation-induced rib fracture after hypofractionated proton beam therapy for hepatocellular carcinoma$