Publications by authors named "Hideomi Yamashita"

157 Publications

Phase II study of stereotactic body radiotherapy with hydrogel spacer for prostate cancer: acute toxicity and propensity score-matched comparison.

Radiat Oncol 2021 Jun 12;16(1):107. Epub 2021 Jun 12.

Department of Radiology, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyoku, Tokyo, 113-8655, Japan.

Background: The efficacy of a hydrogel spacer in stereotactic body radiotherapy (SBRT) has not been clarified. We evaluated the safety and efficacy of SBRT in combination with a hydrogel spacer for prostate cancer.

Methods: This is a prospective single-center, single-arm phase II study. Prostate cancer patients without lymph node or distant metastasis were eligible. All patients received a hydrogel spacer insertion, followed by SBRT of 36.25 Gy in 5 fractions with volumetric modulated arc therapy. The primary endpoint was physician-assessed acute gastrointestinal (GI) toxicity within 3 months. The secondary endpoints were physician-assessed acute genitourinary (GU) toxicity, patient-reported outcomes evaluated by the EPIC and FACT-P questionnaires, and dosimetric comparison. We used propensity score-matched analyses to compare patients with the hydrogel spacer with those without the spacer. The historical data of the control without a hydrogel spacer was obtained from our hospital's electronic records.

Results: Forty patients were enrolled between February 2017 and July 2018. A hydrogel spacer significantly reduced the dose to the rectum. Grade 2 acute GI and GU toxicity occurred in seven (18%) and 17 (44%) patients. The EPIC bowel and urinary summary score declined from the baseline to the first month (P < 0.01, < 0.01), yet it was still significantly lower in the third month (P < 0.01, P = 0.04). For propensity score-matched analyses, no significant differences in acute GI and GU toxicity were observed between the two groups. The EPIC bowel summary score was significantly better in the spacer group at 1 month (82.2 in the spacer group and 68.5 in the control group).

Conclusions: SBRT with a hydrogel spacer had the dosimetric benefits of reducing the rectal doses. The use of the hydrogel spacer did not reduce physician-assessed acute toxicity, but it improved patient-reported acute bowel toxicity.

Trial Registration: Trial registration: UMIN-CTR, UMIN000026213. Registered 19 February 2017, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000029385 .
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http://dx.doi.org/10.1186/s13014-021-01834-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199395PMC
June 2021

Prognostic value of pre-treatment maximum standardized uptake value and CRP in radiotherapy of esophageal cancer.

Mol Clin Oncol 2021 Jul 25;15(1):146. Epub 2021 May 25.

Department of Radiology, University of Tokyo Hospital, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

The aim of the present study was to evaluate the prognostic value of the pre-treatment maximum standardized uptake value (SUV) and CRP in patients who underwent chemoradiotherapy for esophageal squamous cell carcinoma. A retrospective review of 69 consecutive patients with esophageal cancer who underwent concurrent chemoradiotherapy between 2013 and 2016 was performed. The total radiotherapy doses were 50, 50.4 or 60 Gy. The endpoints of the present study were overall survival (OS) and disease-free survival (DFS). The median follow-up for censored cases was 45.7 months. In 56 patients, F-fluorodeoxyglucose positron emission tomography was performed within 1 month prior to chemoradiotherapy. Data on CRP within 1 month prior to chemoradiotherapy were available for all patients. In the group of SUV >12.85, the rates of 2-year OS and DFS were 49.0 and 35.7%, respectively. In the group of SUV ≤12.85, these values were 72.4 and 67.1%, respectively (P=0.048 and P=0.057, respectively). In the group of CRP ≥1 mg/dl, these percentages were 38.5 and 25.0%, respectively. In the group of CRP <1 mg/dl, these rates were 71.2 and 59.7%, respectively (P=0.013 and P<0.001, respectively). A multivariate analysis revealed that pre-treatment serum CRP levels remained an independent prognostic factor for both OS and DFS [OS: hazard ratio (HR), 0.25, P=001; DFS: HR, 0.28, P=0.005]. In conclusion, high SUV was associated with lower OS, while high CRP was associated with lower OS and DFS.
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http://dx.doi.org/10.3892/mco.2021.2308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165700PMC
July 2021

Prognostic Factors for Patients With Brain Metastases Treated With Single-fraction Gamma Knife Radiosurgery.

Anticancer Res 2021 Jun;41(6):3179-3185

Department of Radiology, The University of Tokyo Hospital, Tokyo, Japan.

Background/aim: The aim of this study was to identify prognostic factors for brain metastases treated with Gamma knife radiosurgery.

Patients And Methods: Multivariate Cox proportional hazards regression analyses were conducted for patients who received treatment between June 2013 and March 2018.

Results: A total of 131 consecutive patients were included. The median follow-up period was 16.0 months (range=1.5-61.5 months). Brain metastases [hazard ratio (HR)=0.42, 95%CI=0.27-0.67, p<0.001], history of systemic therapy (HR=2.23, 95%CI=1.28-3.89, p=0.005), and active extracranial disease (HR=2.49, 95%CI=1.30-4.76, p=0.006) were independent predictors of overall survival. Number of brain metastases (HR=0.39, 95%CI=0.26-0.59, p<0.001) and history of systemic therapy (HR=1.90, 95%CI=1.17-3.08, p=0.005) were independent predictors of intracranial progression-free survival.

Conclusion: The number of brain metastases and the history of systemic therapy are associated with patient overall survival and intracranial progression-free survival.
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http://dx.doi.org/10.21873/anticanres.15104DOI Listing
June 2021

Palliative radiotherapy for gross hematuria in patients with advanced cancer.

Sci Rep 2021 May 5;11(1):9533. Epub 2021 May 5.

Department of Radiology, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyoku, Tokyo, 113-8655, Japan.

This study assessed the efficacy of palliative radiotherapy for gross hematuria caused by advanced cancer. Patients who received palliative radiotherapy to control gross hematuria in two hospitals between October 2006 and May 2020 were retrospectively reviewed. We evaluated the gross hematuria response, gross hematuria control duration, blood transfusion rate, blood transfusion-free duration, and overall survival. Cox multivariate analysis was performed to examine factors associated with hematuria control duration. Fifty-three consecutive patients were included. The most frequently used dose fractionation regimen was 30 Gy in 10 fractions (BED = 39 Gy), followed by 20 Gy in 5 fractions (BED = 20 Gy). Forty patients (76%) became gross hematuria free. The median hematuria control duration was 4.3 months (95% confidence interval 1.9-6.6). Twenty-six patients received blood transfusion 3 months before radiotherapy; 17 of them (65%) were free from blood transfusion 1 month after radiotherapy. A high BED (≥ 36 Gy) was a statistically significant factor for hematuria control duration in the multivariate analysis (P = 0.02). Palliative radiotherapy can effectively relieve gross hematuria irrespective of the primary tumor site. A high BED may be recommended for a prolonged hematuria control duration if patients have a good prognosis.
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http://dx.doi.org/10.1038/s41598-021-88952-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100132PMC
May 2021

Radiotherapy for symptom palliation of splenomegaly in patients with haematological malignancies.

Mol Clin Oncol 2021 Jun 7;14(6):114. Epub 2021 Apr 7.

Department of Radiology, The University of Tokyo Hospital, Bunkyo, Tokyo 113-8655, Japan.

Splenomegaly severely compromises the quality of life of those affected. The aim of the present study was to describe the clinical characteristics of patients with haematological disorders who receive radiotherapy for splenomegaly, particularly focusing on the changes in spleen volume. The present study conducted a retrospective analysis of consecutive patients with haematological disorders who underwent splenic radiotherapy with palliative intent at the Department of Radiology of the University of Tokyo Hospital between June 2008 and June 2019. Pre- and post-radiotherapy spleen volumes were measured from computed tomography images. A total of 8 patients (5 men and 3 women) with a median age of 59 years (range, 46-76 years) were included. The median total prescription and fractional doses were 4.5 Gy (range, 1.5-10 Gy) and 0.78 Gy (range, 0.5-2.0 Gy), respectively. A total of 5 patients (62.5%) experienced a reduction in spleen volume. The mean ± SD spleen sizes pre- and post-radiotherapy were 1,887±1,011 and 1,368±577 ml, respectively. The mean variation rate in spleen volume was -19.1±24.7%, and the case with the most notable improvement in the present study exhibited a -52.4% change. Of the 5 patients who experienced pain prior to radiotherapy, 3 achieved pain relief, 1 did not experience any change and 1 patient was not assessed post-radiotherapy. Therefore, the findings of the present study revealed that palliative radiotherapy for splenomegaly may achieve symptom palliation and radiological volumetric effects in patients with haematological disorders.
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http://dx.doi.org/10.3892/mco.2021.2276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060855PMC
June 2021

Metastasis-Directed Radiotherapy for Oligometastatic Castration-Resistant Prostate Cancer.

Cureus 2021 Feb 7;13(2):e13199. Epub 2021 Feb 7.

Radiology, The University of Tokyo Hospital, Tokyo, JPN.

The treatment effects of metastasis-directed therapy in patients with oligometastatic disease have received much attention. In our case, a 72-year-old man with oligometastatic castration-resistant prostate cancer was referred to our hospital. The patient had undergone radical radiotherapy with a total dose of 76 Gy in 36 fractions for localized prostate cancer nine years prior to the first visit. Positron emission tomography showed a slight increase in accumulation in the para-aortic lymph nodes. The patient received conventional radiotherapy at a total dose of 50 Gy in 25 fractions to the para-aortic region as oligometastasis-directed local therapy. After radiotherapy, his prostate-specific antigen (PSA) level decreased slightly, but it increased again soon after. According to the results of positron emission tomography, the accumulation around the para-aortic lymph nodes had decreased; however, a slight increase in accumulation in the sub/supra-clavicular lymph nodes was observed. He received radiotherapy at a total dose of 50 Gy in 25 fractions to the sub/supra-clavicular region. We confirmed a significant reduction in lesion volume and a downward trend in PSA levels. Metastasis-directed therapy has shown remarkable effectiveness in controlling disease without severe treatment-related adverse events. Metastasis-directed therapy is considered as one of the treatment options in patients who need salvage therapy.
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http://dx.doi.org/10.7759/cureus.13199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943180PMC
February 2021

Esophageal cancer patients' survival after complete response to definitive chemoradiotherapy: a retrospective analysis.

Esophagus 2021 Jul 24;18(3):629-637. Epub 2021 Feb 24.

Department of Gastrointestinal Surgery, The University of Tokyo Graduate School of Medicine, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-8655, Japan.

Background: Chemoradiotherapy is an alternative to surgery for esophageal cancer, with a putatively equivalent outcome. However, disease recurrence after a complete response is common and if follow-up surveillance detects recurrence, salvage treatments for potentially curable disease must follow.

Methods: We conducted a nation-wide questionnaire survey of institutions in Japan certified by the Japanese Esophageal Society to investigate outcomes of primary thoracic esophageal cancer patients initially treated by chemoradiotherapy with complete response diagnoses. The primary endpoint was overall survival, the secondary endpoint disease recurrence. Outcomes of patients who had undergone salvage treatments were also investigated. Cases were excluded from analysis if endoscopic study, endoscopic biopsy, or computed tomography data were lacking.

Results: At 41 institutes 544 case records were collected; valid data on 392 patients were obtained; 5-year survival was 74.8%, 5-year disease-free survival, 66.8%. Clinical staging before treatment significantly affected both overall and disease-free survival rates, but differences between adjoining stages were unexpectedly small. The primary relapse site was classified as primary site (n = 58), regional lymph nodes (n = 36), or distant disease (n = 34). Salvage treatments with curative intent (surgery, endoscopic treatments, and additional radiation) were performed on 38, 23, and 4 cases; 5-year survival after esophagectomy (n = 22), endoscopic treatment (n = 23), and lymphadenectomy (n = 9) was 47.4%, 70.9%, and 33.3%, respectively.

Conclusions: A quarter of patients developed recurrent disease, mostly locoregional, after complete response. Complete response patients with originally advanced stage disease had fair clinical outcomes; salvage treatments after locoregional recurrence achieved modest long-term survival.
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http://dx.doi.org/10.1007/s10388-021-00817-1DOI Listing
July 2021

A retrospective analysis of radiotherapy in the treatment of external auditory canal carcinoma.

Mol Clin Oncol 2021 Mar 13;14(3):45. Epub 2021 Jan 13.

Department of Radiology, The University of Tokyo Hospital, Bunkyo-ku, Tokyo 113-8655, Japan.

External auditory canal carcinoma (EACC) is a rare disease. The current study aimed to evaluate the clinical outcomes of patients treated with external beam radiotherapy (EBRT) for EACC. The present study retrospectively reviewed 34 consecutive patients treated for EACC with EBRT between February 2001 and January 2019 at the University of Tokyo Hospital. Clinical staging was performed according to the modified Pittsburgh classification. Of all the included patients, seven patients were in the early stages (I or II) and 27 in the advanced stages (III or IV) of EACC. A total of 16 patients underwent EBRT and surgery (S+RT) pre- and/or postoperatively, while 18 patients underwent definitive radiotherapy (dRT). The median prescribed doses for the S+RT and dRT groups were 66 and 70 Gy, respectively. The median follow-up period for all patients was 22.4 months (range, 2-205 months). The 5-year overall survival rates of the S+RT and dRT groups were 66.7 and 45.1%, respectively. The progression-free survival rate at 5-year was 55.6% (95% confidence interval: 36.5-71.1%) for the entire cohort. A total of 14 patients experienced disease relapse after treatment, consisting of 11 locoregional recurrences and three distant metastases. The current study revealed the clinical outcomes of EBRT for EACC.
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http://dx.doi.org/10.3892/mco.2021.2207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818098PMC
March 2021

Helical Skin Radiation Therapy Including Total Skin Radiation Therapy Using Tomotherapy for Primary Cutaneous Lymphoma With Bone Marrow Suppression as a Related Adverse Event.

Pract Radiat Oncol 2021 May-Jun;11(3):e308-e321. Epub 2021 Jan 10.

Department of Radiology, University of Tokyo Hospital, Hongo, Bunkyo-ku, Tokyo, Japan.

Purpose: Total skin electron beam therapy (TSEBT) is useful for primary cutaneous lymphoma. However, helical skin radiation therapy (HSRT) using tomotherapy may avoid the complexity and uncertainty of TSEBT.

Methods And Materials: All patients with primary cutaneous lymphoma who underwent HSRT at our hospital between June 2015 and July 2019 were investigated, including 7 patients registered in a clinical trial approved by an institutional review board (ID UMIN000022142). HSRT was performed in 3 partitioned skin areas: head and neck, trunk and arms, and legs.

Results: A total of 24 patients with 53 skin areas (including 8 patients with 24 skin areas who had undergone sequential total skin irradiation), with a median follow-up time of 13 months (range, 2-50), were investigated. Twenty patients (83.3%) had mycosis fungoides (MF). For 41 of 53 (77.4%) cases, a dose of 20 Gy in 10 fractions was used. The overall response rate in the treated fields of each HSRT in patients with MF was 100%, including 38 (80.9%) complete response, 4 (8.5%) good partial response, and 5 (10.6%) partial response. Eight patients with MF who underwent sequential total skin irradiation showed a 100% complete response. For patients with MF, the median survival time after a first round of HSRT was 22 months (95% confidence interval [CI], 13.6-30.4 months), the median response duration of each HSRT was 5 months (95% CI, 3.67-6.32 months), and the median time to in-field reirradiation for each HSRT was 15 months (95% CI, 9.76-20.24 months). Bone marrow suppression (grade ≥3) often occurred (94.1%) with HSRT on trunk and arm skin. An early patient died of HSRT-caused grade 5 leukopenia.

Conclusions: HSRT targeting trunk and arm skin induced severe bone marrow suppression that led to a temporary palliative effect. TSEBT should still be considered standard treatment for primary cutaneous lymphoma covering the total body surface area.
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http://dx.doi.org/10.1016/j.prro.2020.11.007DOI Listing
January 2021

Prognostic Value of Epithelial Cell Adhesion Molecules in T1-2N0M0 Glottic Cancer.

Laryngoscope 2021 07 28;131(7):1522-1527. Epub 2020 Dec 28.

Division of Radiation Oncology, Department of Radiology, Showa University School of Medicine, Tokyo, Japan.

Objective: This is an ancillary study of a multi-institutional randomized non-inferiority phase III trial of accelerated fractionation (AF) versus standard fractionation (SF) radiation therapy for T1-2N0M0 glottic cancer (JCOG0701). Biopsy specimens of tumors from the patients enrolled in the JCOG0701 are collected and the association between clinical outcomes and histopathologic features such as expression of epithelial cell adhesion molecule (EpCAM), p53, and p16 were investigated.

Methods: Five slices of undyed slides from biopsy specimens were sent to the National Cancer Center Hospital and all the specimens were assessed for the expression of EpCAM, p53, and p16. The primary objective was to investigate the association between 3-year progression-free survival (PFS) and expression of EpCAM, p53, and p16.

Results: A total of 88 out of 370 patients were enrolled in this ancillary study. The 3-year PFS for tumors with strong expression of EpCAM was 70.6% (95% CI 43.1%-86.6%), while that of tumors without strong expression of EpCAM was 77.5% (95% CI 65.9%-85.5%) with no remarkable difference between groups (P = .67). Likewise, there was no significant difference in 3-year PFS between tumors regardless of p53 or p16 status. However, in a subgroup analysis for 17 patients with a strong expression of EpCAM, AF showed better 3-year PFS than SF (100% vs 54.5%, P = .07).

Conclusions: From the current study, it could not be concluded that EpCAM, p16, and p53 were prognostic factors for early-stage glottic cancer after primary radiation therapy. AF might be an appropriate fractionation for tumors with a strong expression of EpCAM.

Level Of Evidence: 3 Laryngoscope, 131:1522-1527, 2021.
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http://dx.doi.org/10.1002/lary.29348DOI Listing
July 2021

[Improvement in Image Quality of CBCT during Treatment by Cycle Generative Adversarial Network].

Nihon Hoshasen Gijutsu Gakkai Zasshi 2020 ;76(11):1173-1184

Department of Radiology, University of Tokyo Hospital.

Purpose: Volumetric modulated arc therapy (VMAT) can acquire projection images during rotational irradiation, and cone-beam computed tomography (CBCT) images during VMAT delivery can be reconstructed. The poor quality of CBCT images prevents accurate recognition of organ position during the treatment. The purpose of this study was to improve the image quality of CBCT during the treatment by cycle generative adversarial network (CycleGAN).

Method: Twenty patients with clinically localized prostate cancer were treated with VMAT, and projection images for intra-treatment CBCT (iCBCT) were acquired. Synthesis of PCT (SynPCT) with improved image quality by CycleGAN requires only unpaired and unaligned iCBCT and planning CT (PCT) images for training. We performed visual and quantitative evaluation to compare iCBCT, SynPCT and PCT deformable image registration (DIR) to confirm the clinical usefulness.

Result: We demonstrated suitable CycleGAN networks and hyperparameters for SynPCT. The image quality of SynPCT improved visually and quantitatively while preserving anatomical structures of the original iCBCT. The undesirable deformation of PCT was reduced when SynPCT was used as its reference instead of iCBCT.

Conclusion: We have performed image synthesis with preservation of organ position by CycleGAN for iCBCT and confirmed the clinical usefulness.
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http://dx.doi.org/10.6009/jjrt.2020_JSRT_76.11.1173DOI Listing
November 2020

Analyses of the local control of pulmonary Oligometastases after stereotactic body radiotherapy and the impact of local control on survival.

BMC Cancer 2020 Oct 14;20(1):997. Epub 2020 Oct 14.

Department of Radiation Oncology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.

Background: Successful local therapy for oligometastases may lead to longer survival. The purpose of this multicentre retrospective study was to investigate factors affecting the local control (LC) of pulmonary oligometastases treated by stereotactic body radiotherapy (SBRT) and to investigate the impact of LC on survival.

Methods: The inclusion criteria included 1 to 5 metastases, the primary lesion and other extrathoracic metastases were controlled before SBRT, and the biological effective dose (BED) of the SBRT was 75 Gy or more. The Cox proportional hazards model was used for analyses.

Results: Data of 1378 patients with 1547 tumours from 68 institutions were analysed. The median follow-up period was 24.2 months. The one-year, 3-year and 5-year LC rates were 92.1, 81.3 and 78.6%, respectively, and the 1-year, 3-year and 5-year overall survival rates were 90.1, 60.3 and 45.5%, respectively. Multivariate analysis for LC showed that increased maximum tumour diameter (p = 0.011), type A dose calculation algorithm (p = 0.005), shorter overall treatment time of SBRT (p = 0.035) and colorectal primary origin (p < 0.001 excluding oesophagus origin) were significantly associated with a lower LC rate. In the survival analysis, local failure (p < 0.001), worse performance status (1 vs. 0, p = 0.013; 2-3 vs. 0, p < 0.001), oesophageal primary origin (vs. colorectal origin, p = 0.038), squamous cell carcinoma (vs. adenocarcinoma, p = 0.006) and increased maximum tumour diameter (p < 0.001) showed significant relationships with shorter survival.

Conclusions: Several factors of oligometastases and SBRT affected LC. LC of pulmonary oligometastases by SBRT showed a significant survival benefit compared to patients with local failure.
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http://dx.doi.org/10.1186/s12885-020-07514-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559191PMC
October 2020

Factors related to primary cancer death and non-primary cancer death in patients treated with stereotactic body radiotherapy for pulmonary oligometastases.

Cancer Med 2020 12 6;9(23):8902-8911. Epub 2020 Oct 6.

Department of Radiation Oncology, Graduate School of Medicine, Tohoku University, Sendai, Japan.

Cancer-specific death (CSD) and non-cancer-specific death (non-CSD) after stereotactic body radiotherapy (SBRT) for pulmonary oligometastases have not been studied in detail. The aim of this study was to determine the cumulative incidences of CSD and non-CSD and to reveal prognostic factors. Data from a large survey of SBRT for pulmonary oligometastases were used for analyses, and patients with unknown cause of death were excluded from current analyses. CSD was primary cancer death and non-CSD was non-primary cancer death including a series of cancer treatment-related deaths. Cumulative incidences were calculated using the Kaplan-Meier method and a stratified Cox regression model was used for multivariate analyses (MVA). Fifty-two patients with an unknown death were excluded and a total of 1326 patients was selected. CSD and non-CSD occurred in 375 and 109 patients, respectively. The median OS period was 53.2 months and the cumulative incidences of 1-, 3-, and 5-year CSD vs. non-CSD rates were 6.5% vs. 2.3%, 29.5% vs. 8.6%, and 41.2% vs. 11.0%, respectively. In MVA, the incidence of CSD was related to performance status (1 vs. 0; p < 0.001, 2-3 vs. 0; p = 0.011), oligometastatic state (sync-oligometastases vs. oligo-recurrence, p = 0.026) and maximum tumor diameter (p = 0.009), and the incidence of non-CSD was related to age (p = 0.001), sex (p = 0.030), performance status (2-3 vs. 0; p = 0.002), and irradiated tumor-located lung lobe (left lower lobe vs. other lobes, p = 0.036). CSD was main cause of death, but non-CSD was not rare after SBRT. Prognostic factors for CSD and non-CSD were different, and an understanding of the factors would help in treatment.
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http://dx.doi.org/10.1002/cam4.3508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724498PMC
December 2020

Linear accelerator-based stereotactic body radiation therapy in the treatment of oligometastatic disease.

Mol Clin Oncol 2020 Aug 9;13(2):109-114. Epub 2020 Jun 9.

Department of Radiology, University of Tokyo Hospital, Tokyo 113-8656, Japan.

The present study reports the clinical outcomes of hypofractionated stereotactic body radiation therapy (SBRT) for oligometastasis (OM) originating from various tumors. Between February 2012 and April 2017, 40 patients with unresectable OM were treated with SBRT. Of these patients, 92% showed a solitary nodal metastasis and the rest had up to three metastases. The dose prescription was 50 Gy in 10 fractions with three-dimensional conformal techniques or volumetric intensity-modulated arc therapy. Median follow-up was 14 months. Of the 40 patients, none showed local progression at the site of SBRT, but 20 patients showed tumor growth at distant sites during follow-up. The 2- and 3-year overall survival rates were 45.1 and 36.1%, respectively. The 2- and 3-year progression-free survival rates were 35.4 and 26.5%, respectively. The interval between diagnosis and detection of OM (<2 vs. >2 years) and primary tumor site (esophagus vs. others) emerged as significant variables affecting survival. Grade 3 subacute and grade 4 chronic toxicities were observed in 1 and 2 patients, respectively. SBRT of 50 Gy in 10 fractions for OM from various primary tumors was shown to lead to good clinical outcomes from the viewpoints of local control and toxicity frequency. However, additional studies are required to identify the patient groups likely to receive maximal benefits from such treatment.
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http://dx.doi.org/10.3892/mco.2020.2065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366231PMC
August 2020

Retrospective dose reconstruction of prostate stereotactic body radiotherapy using cone-beam CT and a log file during VMAT delivery with flattening-filter-free mode.

Radiol Phys Technol 2020 Sep 12;13(3):238-248. Epub 2020 Jul 12.

Department of Radiology, University of Tokyo Hospital, 3-7-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

This study aimed to reconstruct the dose distribution of single fraction of stereotactic body radiotherapy for patients with prostate cancer using cone-beam computed tomography (CBCT) and a log file during volumetric-modulated arc therapy (VMAT) delivery with flattening-filter-free (FFF) mode. Twenty patients with clinically localized prostate cancer were treated with FFF-VMAT, and projection images for in-treatment CBCT (iCBCT) imaging were concomitantly acquired with a log file. A D dose of 36.25 Gy in five fractions was prescribed to each planning target volume (PTV) on each treatment planning CT (pCT). Deformed pCT (dCT) was obtained from the iCBCT using a hybrid deformable image registration algorithm. Dose distributions on the dCT were calculated using Pinnacle v9.10 by converting the log file data to Pinnacle data format using an in-house software. Dose warping was performed by referring to deformation vector fields calculated from pCT and dCT. Reconstructed dose distribution was compared with that of the original plan. Dose differences between the original and reconstructed dose distributions were within 3% at the isocenter and observed in PTV and organ-at-risk (OAR) regions. Differences in OAR regions were relatively larger than those in the PTV, presumably because OARs were more deformed than the PTV. Therefore, our method can be used successfully to reconstruct the dose distributions of one fraction using iCBCT and a log file during FFF-VMAT delivery.
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http://dx.doi.org/10.1007/s12194-020-00574-3DOI Listing
September 2020

Clinical outcome of adjuvant radiotherapy for squamous cell carcinoma of the breast; a multicenter retrospective cohort study.

Breast 2020 Aug 14;52:88-94. Epub 2020 May 14.

Department of Radiology, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. Electronic address:

Background: Because primary squamous cell carcinoma (SCC) of the breast is a rare disease, the standard therapy has not been established. We examined the clinical outcomes of postoperative adjuvant radiotherapy for breast SCC.

Material And Methods: We conducted a multicenter retrospective cohort study. Patients diagnosed with primary breast SCC who received adjuvant radiotherapy as part of their primary definitive treatment were included. Overall survival (OS), breast cancer-specific survival (BCSS), and recurrence-free interval (RFi) were evaluated.

Results: Between January 2002 and December 2017, 25 breast SCC patients received adjuvant radiotherapy as a primary treatment were included. Median follow-up time was 43.5 months. Three (12%), fifteen (60%) and seven (28%) patients had clinical stage I, II and III disease, respectively. Fourteen patients underwent breast-conserving surgery and subsequent adjuvant radiotherapy. Eleven patients underwent mastectomy and post-mastectomy radiotherapy. Ten patients received regional lymph node irradiation. Nine (36%) patients had disease recurrence. The first site of recurrence was locoregional in five, but distant metastasis arose in one. Concurrent local and distant metastasis were seen in two. Six cases of local recurrence occurred within the irradiated site. Seven patients died, and six of the deaths were due to breast cancer. Five-year OS, BCSS, and Rfi were 69%, 70%, and 63%, respectively. In multivariate analysis, age and lymphatic invasion were associated with increased risk of recurrence.

Conclusion: Breast SCC has a high incidence of locoregional recurrence and poor prognosis. Age and lymphatic invasion are significant risk factors for recurrence.
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http://dx.doi.org/10.1016/j.breast.2020.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375603PMC
August 2020

Significant reduction of oncologic pulmonary death by local control for pulmonary oligometastases treated with stereotactic body radiotherapy.

Radiother Oncol 2020 06 26;147:86-91. Epub 2020 Mar 26.

Department of Radiation Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Background And Purpose: The rate of oncologic pulmonary death after stereotactic body radiotherapy for pulmonary oligometastases has never been reported. The purpose of current study was to investigate the rate of freedom from oncologic pulmonary death (FOPD) and to analyze factors affecting for FOPD.

Materials And Methods: The inclusion criteria for this retrospective study were that SBRT was performed between 2004 and 2015, the number of metastases was 5 or less, the primary lesion and extrathoracic metastases needed to be controlled before SBRT and a biological effective dose (BED) of 75 Gy or more was needed. The Kaplan-Meier estimator and the log-rank test were used to calculate and compare the stratified rates of FOPD. The Cox proportional hazards model was used for multivariate analyses (MVA). Primary disease death from a non-oncologic pulmonary cause was censored in model 1 and was excluded in model 2.

Results: A total of 1172 patients with 1315 tumors were enrolled. During a median follow-up period of 24.5 months, oncologic pulmonary deaths accounted for 101 of 221 primary disease deaths. The 1-year, 3-year and 5-year FOPD rates in model 1 were 98.2%, 89.4% and 84.0%, respectively. MVA for FOPD revealed that local failure of the irradiated tumor, squamous cell carcinoma pathology, and chemotherapy after SBRT had significant relationships with lower FOPD rates in both model 1 and model 2.

Conclusions: Successful local control of pulmonary oligometastases by SBRT contributed to a higher FOPD rate.
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http://dx.doi.org/10.1016/j.radonc.2020.03.019DOI Listing
June 2020

Stereotactic Body Radiotherapy for Pulmonary Oligometastases from Esophageal Cancer: Results and Prognostic Factors.

Anticancer Res 2020 Apr;40(4):2065-2072

Department of Radiation Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Background/aim: The aim of this multi-center retrospective study was to investigate the results of stereotactic body radiotherapy (SBRT) for pulmonary oligometastases from esophageal cancer.

Patients And Methods: Oligometastases from the esophagus were identified from a dataset of a Japanese survey. The Kaplan-Meier method and Cox regression were applied to perform analyses.

Results: A total of 114 patients with 132 pulmonary oligometastases were collected. The 3-year local control rate, freedom from further metastasis (FFFM) rate and overall survival (OS) rate were 70.2%, 25.3% and 37.5%, respectively. Performance status (PS) (PS 1 vs. PS 0, p<0.01), disease-free interval (p=0.03) and history of local therapy for metastasis (p=0.01) had significant relationships with FFFM and only PS was an independent prognostic factor for OS (PS 1 vs. PS 0, p=0.02; PS 2-3 vs. PS 0, p=0.04).

Conclusion: SBRT for pulmonary oligometastases from esophageal cancer provided good local control and survival.
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http://dx.doi.org/10.21873/anticanres.14164DOI Listing
April 2020

Salvage stereotactic body radiotherapy for post-operative oligo-recurrence of non-small cell lung cancer: A single-institution analysis of 59 patients.

Oncol Lett 2020 Apr 17;19(4):2695-2704. Epub 2020 Feb 17.

Department of Radiology, University of Tokyo Hospital, Tokyo 113-8655, Japan.

A standard treatment for patients with early-stage non-small cell lung cancer (NSCLC) who undergo surgery, and subsequently develop local failure or intrathoracic oligo-recurrence, has not yet been established. The present study aimed to assess the feasibility of stereotactic body radiotherapy (SBRT) for this subgroup of patients. Consequently, a retrospective analysis was conducted of patients with NSCLC recurrence who were treated with SBRT, and previously underwent curative surgical resection between October 2011 and October 2016. Post-SBRT survival [overall survival (OS); progression-free survival (PFS); and local control (LC)] and toxicity were analyzed. Prognostic factors for OS were identified using univariate and multivariate analysis. A total of 52 patients and 59 tumors were analyzed. The median follow-up time was 25 months (35 months for surviving patients), and median OS following salvage SBRT was 32 months. The 1- and 3-year OS rates were 84.4 and 67.8%, respectively. 1- and 3-year PFS rates were 80.8 and 58.7%, respectively. Only 4 patients (7.7%) developed local failure. Median LC was 71 months and 1- and 3-year LC rate were 97.9 and 94.9%, respectively. A total of 4 patients experienced grade 3 or higher adverse events (AEs) and two experienced grade 5 AEs (pneumonitis and hemoptysis). Central tumor location and the possibility of re-operation were independent prognostic factors for OS. The present study indicated that post-operative salvage SBRT is a promising therapeutic option for patients with NSCLC with locoregional or intrathoracic oligo-recurrence. We regard toxicity was also acceptable. However, further research is required on the appropriate selection of subjects, and stratification of the analysis by certain risk factors would increase the accuracy of the conclusions.
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http://dx.doi.org/10.3892/ol.2020.11407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068670PMC
April 2020

Efficacy of a hydrogel spacer in three-dimensional conformal radiation therapy for prostate cancer.

Jpn J Clin Oncol 2020 Mar;50(3):303-309

Department of Radiology, The University of Tokyo Hospital, Tokyo, Japan.

Objectives: We aimed to compare the dose constraints fulfillment rate of the three-dimensional conformal radiotherapy treatment plan before and after a hydrogel spacer insertion.

Methods: The planning computed tomography scans of 39 patients who received stereotactic body radiotherapy for prostate cancer were used. All patients inserted a hydrogel spacer and underwent computed tomography scans before and after spacer insertion. The three-dimensional conformal radiotherapy plans according to NCCN classification, low-, intermediate- and high-risk, were made for each patient. Clinical target volume included prostate and seminal vesicle 2 cm for high risk, prostate and seminal vesicle 1 cm for intermediate risk and prostate only for low risk. Three-dimensional conformal radiotherapy including a seven-field conformal technique with 76 Gy in 38 fractions. Dose constraints for rectum and bladder were V70 Gy ≤ 15%, V65 Gy ≤ 30% and V40 Gy ≤ 60%.

Results: Among 39 patients, 35 (90%), 19 (49%) and 13 (33%) and 38 (97%), 38 (97%) and 34 (87%) patients before and after the spacer insertion fulfilled rectum dose constraints for low-, intermediate- and high-risk plans, respectively. A hydrogel spacer significantly reduced rectum dose and improved the rectum dose constraints fulfillment rate in intermediate (P < 0.01) and high (P < 0.01), but no difference was found in low-risk plan (P = 0.25). On multivariate analysis, spacer use was associated with the higher rectum dose constraints fulfillment rate.

Conclusions: A hydrogel spacer reduced rectum dose and improved the dose constraints fulfillment rate in three-dimensional conformal radiotherapy plan. Although IMRT is the standard treatment, 3D-CRT using a hydrogel spacer may be a treatment option.
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http://dx.doi.org/10.1093/jjco/hyz171DOI Listing
March 2020

Pulmonary Oligometastases Treated by Stereotactic Body Radiation Therapy: A Nationwide Survey of 1,378 Patients.

Anticancer Res 2020 Jan;40(1):393-399

Department of Radiation Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Aim: This study was performed to confirm the superior overall survival (OS) after pulmonary oligo-recurrence compared to pulmonary sync-oligometastases in a large nationwide study.

Patients And Methods: Patients that met the following criteria were included: 1 to 5 lung-only metastases at the beginning of stereotactic body radiation therapy (SBRT) was performed between January 2004 and June 2015, and the biological effective dose (BED) of SBRT was 75 Gy or more. The parameters included in the analyses were age, gender, ECOG PS, primary lesion, pathology, oligoetastatic state, SBRT date, chemotherapy before SBRT, chemotherapy concurrent SBRT, chemotherapy after SBRT, maximum tumor diameter, number of metastases, field coplanarity, dose prescription, BED, OTT of SBRT.

Results: In total, 1,378 patients with 1,547 tumors were enrolled. Oligo-recurrence occurred in 1,016 patients, sync-oligometastases in 118, and unclassified oligometastases in 121. The three-year OS was 64.0% for oligo-recurrence and 47.5% for sync-oligometastasis (p<0.001). In the multivariate analysis, the hazard ratio (HR) for sync-oligometastases versus oligo-recurrence was 1.601 (p=0.014). Adverse events of Grade 5 were occurred in 3 patients.

Conclusion: This is the first nationwide to indicate that the OS of patients with pulmonary oligo-recurrence is better than that of patients with sync-oligometastases.
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http://dx.doi.org/10.21873/anticanres.13965DOI Listing
January 2020

Long-term outcomes of multimodal therapy combining definitive chemoradiotherapy and salvage surgery for T4 esophageal squamous cell carcinoma.

Int J Clin Oncol 2020 Apr 11;25(4):552-560. Epub 2019 Dec 11.

Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Background: Survival outcomes of patients with cT4 esophageal squamous cell carcinoma (ESCC) remain extremely poor. We aimed to investigate long-term outcomes and identify prognostic factors in patients treated by definitive chemoradiotherapy (dCRT) alone or with dCRT plus salvage surgery (SALV) for cT4 ESCC.

Patients And Methods: In total, 73 patients completing dCRT were analyzed. Patients achieving clinical complete response (CR) received follow-up evaluations thereafter. For patients diagnosed with clinical partial response (PR), potentially curative SALV was generally performed. Possible prognostic factors included demographic data, tumor staging, blood chemistry profiles, and esophageal stenosis.

Results: The 1- and 3-year overall survival (OS) rates of the 73 patients were 67.1% and 40.8%, respectively. Twenty-one patients (29%) achieved clinical CR with dCRT alone. Among 35 patients (48%) with clinical PR, 31 underwent SALV and 4 opted for non-surgical treatments. In the dCRT-alone group (n = 42), patients with clinical CR-PR (n = 25) showed significantly better 3-year OS than those who responded poorly to dCRT (stable or progressive) (n = 17) (67.5% vs. 0%, P < 0.001). In the SALV group (n = 31), curative SALV (n = 22, 73%) provided significantly better 3-year OS than non-curative SALV (58.7% vs. 0%, P < 0.001). Multivariable analysis revealed stenosis before dCRT (P = 0.02) and pretreatment elevated CRP (P = 0.02) to be independently associated with poor outcomes.

Conclusions: The multimodal treatment strategy combining dCRT and SALV is rational for treating cT4 ESCC patients. When curative resection is feasible, SALV can provide good long-term survival outcome for patients who responded to dCRT but did not achieve clinical CR with dCRT alone.
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http://dx.doi.org/10.1007/s10147-019-01590-zDOI Listing
April 2020

Acceptable fetal dose using flattening filter-free volumetric arc therapy (FFF VMAT) in postoperative chemoradiotherapy of tongue cancer during pregnancy.

Clin Transl Radiat Oncol 2020 Jan 14;20:9-12. Epub 2019 Oct 14.

Department of Radiology, The University of Tokyo Hospital, Tokyo, Japan.

Optimizing irradiation protocols for pregnant women is challenging, because there are few cases and a dearth of fetal dosimetry data. We cared for a 36-year-old pregnant woman with tongue cancer. Prior to treatment, we compared three intensity-modulated radiation therapy (IMRT) techniques, including helical tomotherapy, volumetric arc therapy (VMAT), and flattening-filter free VMAT (FFF-VMAT) using treatment planning software. FFF-VMAT achieved the minimum fetal exposure and was selected as the optimal modality. We prescribed 66 Gy to the involved nodes, 60 Gy to the tumor bed and ipsilateral neck, and 54 Gy to the contralateral neck over 33 fractions. To confirm the out-of-field exposure per fraction, surface doses and the rectal dose were measured during FFF-VMAT delivery. Postoperative chemoradiotherapy was delivered using IMRT and a cisplatin regimen. Without any shielding, the total fetal dose was 0.03 Gy, within the limits established by the ICRP. A healthy girl was born vaginally at 37 weeks' gestation.
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http://dx.doi.org/10.1016/j.ctro.2019.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6833340PMC
January 2020

Improvement of the robustness to set up error by a virtual bolus in total scalp irradiation with Helical TomoTherapy.

Radiol Phys Technol 2019 Dec 23;12(4):433-437. Epub 2019 Oct 23.

Department of Radiology, University of Tokyo Hospital, 7-3-1Bunkyo-ku, HongoTokyo, 113-8655, Japan.

Intensity-modulated radiation therapy has recently been used for total scalp irradiation. In inverse planning, the treatment planning system increases the fluence of tangential beam near the skin surface to counter the build-up region. Consequently, the dose to the skin surface increases even with small setup errors. Replacing the electron density of the surrounding air of some thickness with a virtual bolus during optimization could suppress the extremely high fluence near the skin. We confirmed the usefulness of a virtual bolus in total scalp irradiation. For each patient, two beams were planned, one with and the other without a virtual bolus. The dose distribution was calculated using computed tomography images that were shifted to simulate setup errors. The hot spot dose was suppressed in the plans using a virtual bolus. In conclusion, using a virtual bolus improved the robustness to setup errors.
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http://dx.doi.org/10.1007/s12194-019-00539-1DOI Listing
December 2019

Standardization of imaging features for radiomics analysis.

J Med Invest 2019 ;66(1.2):35-37

Department of Radiology, The University of TokyoHospital, Tokyo, Japan.

Radiomics has the potential to provide tumor characteristics with noninvasive and repeatable way. The purpose of this paper is to evaluate the standardization effect of imaging features for radiomics analysis. For this purpose, we prepared two CT databases ; one includes 40 non-small cell lung cancer (NSCLC) patients for whom tumor biopsies was performed before stereotactic body radiation therapy in The University of Tokyo Hospital, and the other includes 29 early-stage NSCLC datasets from the Cancer Imaging Archive. The former was used as the training data, whereas the later was used as the test data in the evaluation of the prediction model. In total, 476 imaging features were extracted from each data. Then, both training and test data were standardized as the min-max normalization, the z-score normalization, and the whitening from the principle component analysis. All of standardization strategies improved the accuracy for the histology prediction. The area under the receiver observed characteristics curve was 0.725, 0.789, and 0.785 in above standardizations, respectively. Radiomics analysis has shown that robust features have a high prognostic power in predicting early-stage NSCLC histology subtypes. The performance was able to be improved by standardizing the data in the feature space. J. Med. Invest. 66 : 35-37, February, 2019.
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http://dx.doi.org/10.2152/jmi.66.35DOI Listing
December 2019

Long-term results of a multicenter phase II study of preoperative chemoradiotherapy with S-1 plus oxaliplatin for locally advanced rectal cancer (JACCRO CC-04: SHOGUN Trial).

Radiother Oncol 2019 05 26;134:199-203. Epub 2019 Feb 26.

Japan Clinical Cancer Research Organization, Tokyo, Japan.

Purpose: The study was designed to evaluate the safety and efficacy of adding oxaliplatin to py (CRT) with S-1 in patients with locally advanced rectal carcinoma (LARC). We report here the final results of the study.

Patients And Methods: Patients with histopathologically confirmed LARC (cT3-T4, any N) were eligible. They received oral S-1 (80 mg/m/day on days 1-5, 8-12, 22-26, and 29-33) and infusional oxaliplatin (60 mg/m/day on days 1, 8, 22, 29) plus radiotherapy (1.8 Gy/day, total dose of 50.4 Gy in 28 fractions), with a chemotherapy gap in the third week of radiotherapy. Primary endpoint of the study was pathological complete response (pCR) rate. Secondary endpoints were rates of R0 resection, down-staging, cumulative 3-year local recurrence, 3-year disease-free survival (DFS), and toxicity.

Results: Forty-five patients were enrolled at six centers in Japan. All patients received CRT, and 44 underwent operation. The pCR rate was 27.3% (12/44). The R0 resection rate was 95.5% (42/44). T-down-staging rate was 59.1% (26/44), and N-down staging rate was 65.9% (29/44); the combined pathological down-staging rate was 79.5% (35/44). There were no grade 4 adverse events, but 11.1% of the patients had grade 3 adverse events. Cumulative 3-year local recurrence rate was 0%. However, 13 (30.0%) patients suffered from distant metastasis, and one patient suffered from secondary esophageal cancer that was unrelated to rectal cancer. Eight patients had lung metastasis, 4 had liver metastasis, and 3 patients died of the metastatic disease. The 3-year DFS rate of the 44 patients was 67.5% (median follow-up 36.3 months), and the 3-year overall survival (OS) rate was 93.0% (median follow-up 39.6 months). The patients were then divided into the pCR (12 patients) group and non pCR (32 patients) group. The 3-year rate of DFS for each group was 91.7% and 58.1% and that of OS was 100% and 90.3%, respectively.

Conclusions: The study showed a high pCR rate with no severe toxicity, good follow-up results, and good loco-regional control. Therefore, addition of oxaliplatin to preoperative CRT with S-1 in patients with LARC might be feasible and lead to better local control than standard treatment.
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http://dx.doi.org/10.1016/j.radonc.2019.02.006DOI Listing
May 2019

Editorial on comparison between stereotactic body radiotherapy and surgery in early stage NCSLC by Scotti .

J Thorac Dis 2019 Mar;11(Suppl 3):S275-S279

The University of Tokyo Hospital, Department of Radiology, Tokyo, Japan.

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http://dx.doi.org/10.21037/jtd.2019.01.79DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6424768PMC
March 2019

Successful definitive concurrent chemoradiotherapy in a patient with esophageal cancer and Child-Pugh B cirrhosis of the liver.

J Cancer Res Ther 2019 Jan-Mar;15(1):255-257

Department of Radiology, The University of Tokyo Hospital, Tokyo, Japan.

This case report demonstrates successful concurrent chemoradiotherapy for esophageal cancer without severe adverse events in a patient with cirrhotic disease. A 63-year-old Japanese male with alcoholic liver cirrhosis was referred to our hospital for treatment of superficial esophageal cancer. Endoscopic submucosal dissection was performed and the patient was diagnosed as having squamous cell carcinoma of the esophagus that was pathologically staged as pT1bN0M0. When a superficial tumor involves the submucosa, esophagectomy is usually recommended. However, the patient was at high risk of perioperative morbidity and mortality because of impaired liver function. As an alternative to esophagectomy, the patient received concurrent chemoradiotherapy, comprising nedaplatin 64 mg/m on days 1 and 34 and S-1 80 mg/body orally on days 1-14 and 34-47 with concurrent radiotherapy of 50 Gy in daily fractions of 2 Gy. He has shown no signs of recurrence in the 30 months since his treatment.
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http://dx.doi.org/10.4103/jcrt.JCRT_338_17DOI Listing
July 2019

Case Series of 23 Patients Who Developed Fatal Radiation Pneumonitis After Stereotactic Body Radiotherapy for Lung Cancer.

Technol Cancer Res Treat 2018 01;17:1533033818801323

8 Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

The purpose of this study was to examine the characteristics and treatment plans of patients who experienced fatal radiation pneumonitis after stereotactic body radiation therapy for primary or oligometastatic lung cancer. Records of 1789 patients treated with stereotactic body radiation therapy for primary or oligometastatic lung cancer were retrospectively reviewed to identify those who developed fatal radiation pneumonitis. Twenty-three (1.3%; 18 men and 5 women) patients developed fatal radiation pneumonitis after stereotactic body radiation therapy for lung cancer; their median age was 74 years. The mean Krebs von den Lungen-6 level and percent vital capacity were 1320 U/mL and 82%, respectively. Prestereotactic body radiation therapy computed tomography revealed pulmonary interstitial change in 14 (73.7%) of 19 patients in whom computed tomography data could be reviewed. Seven (30.4%) of 23 patients had regularly used steroids. The median time duration between stereotactic body radiation therapy commencement and pneumonia symptom appearance was 75 (range: 14-204) days. Median survival time following pneumonia symptom appearance was 53 (range: 4-802) days. The 6- and 12-month overall survival rates were 34.8% and 13.0%, respectively. The 6-month overall survival rates in patients with and without heart disease were 50.0%, 16.7%, and 46.7% for heart disease existence, respectively. There were 4 patients in whom fatal radiation pneumonitis occurred within 2 months after stereotactic body radiation therapy and who died within 1 month. Three of them had no pulmonary interstitial change before stereotactic body radiation therapy, but had heart disease. In summary, the survival time in this case series was generally short but varied widely. More than half of the patients had pulmonary interstitial change before stereotactic body radiation therapy, although immediately progressive fatal radiation pneumonitis was also observed in patients without pulmonary interstitial change. True risk factors for fatal radiation pneumonitis should be examined in a prospective study with a larger cohort.
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http://dx.doi.org/10.1177/1533033818801323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6174642PMC
January 2018

Stereotactic body radiotherapy for centrally-located lung tumors with 56 Gy in seven fractions: A retrospective study.

Oncol Lett 2018 Oct 23;16(4):4498-4506. Epub 2018 Jul 23.

Department of Radiology, University of Tokyo Hospital, Tokyo 113-8655, Japan.

Stereotactic body radiotherapy (SBRT) for centrally-located lung tumors remains a challenge because of the increased risk of treatment-related adverse events (AEs), and uncertainty around prescribing the optimal dose. The present study reported the results of central tumor SBRT with 56 Gy in 7 fractions (fr) at the University of Tokyo Hospital. A total of 35 cases that underwent SBRT with or without volumetric-modulated arc therapy consisting of 56 Gy/7 fr for central lung lesions between 2010 and 2016 at the University of Tokyo Hospital were reveiwed. A central lesion was defined as a tumor within 2 cm of the proximal bronchial tree (RTOG 0236 definition) or within 2 cm in all directions of any critical mediastinal structure. Local control (LC), overall survival (OS), and AEs were investigated. The Kaplan-Meier method was used to estimate LC and OS. AEs were scored per the Common Terminology Criteria for Adverse Events Version 4.0. Thirty-five patients with 36 central lung lesions were included. Fifteen lesions were primary non-small cell lung cancer (NSCLC), 13 were recurrences of NSCLC, and 8 had oligo-recurrences from other primaries. Median tumor diameter was 29 mm. Eighteen patients had had prior surgery. At a median follow-up of 13.1 months for all patients and 18.3 months in surviving patients, 22 patients had died, ten due to primary disease (4 NSCLC), while three were treatment-related. The 1- and 2-year OS were 57.3 and 40.4%, respectively, and median OS was 15.7 months. Local recurrence occurred in only two lesions. 1- and 2-year LC rates were both 96%. Nine patients experienced grade ≥3 toxicity, representing 26% of the cohort. Two of these were grade 5, one pneumonitis and one hemoptysis. Considering the background of the subject, tumor control of our central SBRT is promising, especially in primary NSCLC. However, the safety of SBRT to central lung cancer remains controversial.
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http://dx.doi.org/10.3892/ol.2018.9188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6126178PMC
October 2018
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