Publications by authors named "Koji Konishi"

56 Publications

Evaluation of Stopping Power Ratio Calculation Using Dual-energy Computed Tomography With Fast Kilovoltage Switching for Treatment Planning of Particle Therapy.

In Vivo 2022 Jan-Feb;36(1):103-110

Department of Radiation Oncology, Osaka International Cancer Institute, Osaka, Japan.

Background/aim: This study evaluated the calculation accuracy of the stopping power ratio (SPR) using dual-energy computed tomography with fast kilovoltage switching (FKSCT) for particle therapy.

Materials And Methods: A tissue characterization phantom with various reference materials was scanned to obtain single-energy computed tomography (SECT) images and generate virtual monochromatic images at 77 keV (VMI) and 140 keV (VMI), water density (WD) images, and effective Z (Z) images. For SECT, VMI and VMI lookup tables were generated to convert the measured Hounsfield value into the theoretical SPR for a normal phantom size. Subsequently, the reference materials were scanned in small and large phantoms. The SPR was calculated using the lookup tables of SECT (SPR) images, VMI (SPR), and VMI (SPR), and it was derived from the WD and Z (SPR).

Results: In the normal-sized phantom, the overall mean difference between SPR and theoretical SPR was -0.3%, and remained below 2% for most reference materials. For the large phantom, the overall mean absolute difference for SPR (3.0%, p=0.006) and SPR (3.2%, p=0.002) for the reference materials was significantly lower than that for SPR (5.9%). For the small phantom, a significant reduction in the mean difference in the SPR calculation was observed in SPR (1.0%, p=0.001) and SPR (1.1%, p=0.013) compared with SPR (2.2%).

Conclusion: VMI generated using FKSCT significantly improves the estimation accuracy of SPR compared with SECT. Thus, FKSCT may be used to improve the dose calculation accuracy for treatment planning of particle therapy.
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http://dx.doi.org/10.21873/invivo.12681DOI Listing
January 2022

Reirradiation for Nasal Cavity or Paranasal Sinus Tumor-A Multi-Institutional Study.

Cancers (Basel) 2021 Dec 16;13(24). Epub 2021 Dec 16.

Radiotherapy Department, Fujimoto Hayasuzu Hospital, Miyakonojo 885-0055, Japan.

We evaluated the efficacy and toxicity of reirradiation of nasal cavity or paranasal sinus tumors. We collected and analyzed multi-institutional data of reirradiation cases. Seventy-eight patients with nasal or paranasal sinus tumors underwent reirradiation. The median survival time was 20 months with a medial follow-up of 10.7 months. The 2-year local control and overall survival rates were 43% and 44%, respectively. Tumor volume (≤25 cm), duration between previous radiotherapy and reirradiation (≤12 months), histology (squamous cell carcinoma), male sex, and lymph node involvement were predisposing factors for poor survival. Distant metastasis was observed in 20 patients (25.6%). Grade ≥ 3 adverse events were observed in 22% of the patients, including five grade 4 (8.6%) cases and one grade 5 (1.2%) case. Tumor location adjacent to the optic pathway was a significant predisposing factor for grade ≥3 visual toxicity. Reirradiation of nasal and paranasal sinus tumors is feasible and effective. However, adverse events, including disease-related toxicities, were significant. Prognostic factors emerge from this study to guide multidisciplinary approaches and clinical trial designs.
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http://dx.doi.org/10.3390/cancers13246315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699758PMC
December 2021

Machine log file-based dose verification using novel iterative CBCT reconstruction algorithm in commercial software during volumetric modulated arc therapy for prostate cancer patients.

Phys Med 2021 Nov 24;92:24-31. Epub 2021 Nov 24.

Department of Radiation Oncology, Osaka International Cancer Institute, Osaka, Japan.

Purpose: To evaluate the utility of the use of iterative cone-beam computed tomography (CBCT) for machine log file-based dose verification during volumetric modulated arc therapy (VMAT) for prostate cancer patients.

Methods: All CBCT acquisition data were used to reconstruct images with the Feldkamp-Davis-Kress algorithm (FDK-CBCT) and the novel iterative algorithm (iCBCT). The Hounsfield unit (HU)-electron density curves for CBCT images were created using the Advanced Electron Density Phantom. The I'mRT and anthropomorphic phantoms were irradiated with VMAT after CBCT registration. Subsequently, fourteen prostate cancer patients received VMAT after CBCT registration. Machine log files and both CBCT images were exported to the PerFRACTION software, and a 3D patient dose was reconstructed. Mean dose for planning target volume (PTV), the bladder, and rectum and the 3D gamma analysis were evaluated.

Results: For the phantom studies, the variation of HU values was observed at the central position surrounding the bones in FDK-CBCT. There were almost no changes in the difference of doses at the isocenter between measurement and reconstructed dose for planning CT (pCT), FDK-CBCT, and iCBCT. Mean dose differences of PTV, rectum, and bladder between iCBCT and pCT were approximately 2% lower than those between FDK-CBCT and pCT. For the clinical study, average gamma analysis for 2%/2 mm was 98.22% ± 1.07 and 98.81% ± 1.25% in FDK-CBCT and iCBCT, respectively.

Conclusions: A similar machine log file-based dose verification accuracy is obtained for FDK-CBCT and iCBCT during VMAT for prostate cancer patients.
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http://dx.doi.org/10.1016/j.ejmp.2021.11.004DOI Listing
November 2021

Whole-body MRI: detecting bone metastases from prostate cancer.

Jpn J Radiol 2021 Oct 25. Epub 2021 Oct 25.

Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, Suita, 565-0871, Japan.

Whole-body magnetic resonance imaging (WB-MRI) is currently used worldwide for detecting bone metastases from prostate cancer. The 5-year survival rate for prostate cancer is > 95%. However, an increase in survival time may increase the incidence of bone metastasis. Therefore, detecting bone metastases is of great clinical interest. Bone metastases are commonly located in the spine, pelvis, shoulder, and distal femur. Bone metastases from prostate cancer are well-known representatives of osteoblastic metastases. However, other types of bone metastases, such as mixed or inter-trabecular type, have also been detected using MRI. MRI does not involve radiation exposure and has good sensitivity and specificity for detecting bone metastases. WB-MRI has undergone gradual developments since the last century, and in 2004, Takahara et al., developed diffusion-weighted Imaging (DWI) with background body signal suppression (DWIBS). Since then, WB-MRI, including DWI, has continued to play an important role in detecting bone metastases and monitoring therapeutic effects. An imaging protocol that allows complete examination within approximately 30 min has been established. This review focuses on WB-MRI standardization and the automatic calculation of tumor total diffusion volume (tDV) and mean apparent diffusion coefficient (ADC) value. In the future, artificial intelligence (AI) will enable shorter imaging times and easier automatic segmentation.
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http://dx.doi.org/10.1007/s11604-021-01205-6DOI Listing
October 2021

Prolonged overall treatment time negatively affects the outcomes of stereotactic body radiotherapy for early-stage non-small-cell lung cancer: A propensity score-weighted, single-center analysis.

PLoS One 2021 18;16(6):e0253203. Epub 2021 Jun 18.

Department of Radiation Oncology, Osaka International Cancer Institute, Osaka, Japan.

Previous studies have reported conflicting results for the effect of overall treatment time with stereotactic body radiotherapy on tumor control in early-stage non-small-cell lung cancer. To examine this effect, we conducted a propensity score-weighted, retrospective, observational study at a single institution. We analyzed the data of 200 patients with early-stage non-small-cell lung cancer who underwent stereotactic body radiotherapy (48 Gy in 4 fractions) at our institution between January 2007 and October 2013. Patients were grouped into consecutive (overall treatment time = 4-5 days, n = 116) or non-consecutive treatment groups (overall treatment time = 6-10 days, n = 84). The outcomes of interest were local control and overall survival. The Cox regression model was used with propensity score and inverse probability of treatment weighting. The median overall treatment times in the consecutive and non-consecutive groups were 4 and 6 days, respectively. The 5-year local control and overall survival rates in the consecutive vs. the non-consecutive group were 86.3 vs. 77.2% and 55.5 vs. 51.8%, respectively. After propensity score weighting, consecutive stereotactic body radiotherapy was associated with positive local control (adjusted hazard ratio 0.30, 95% confidence interval 0.14-0.65; p = 0.002) and overall survival (adjusted hazard ratio 0.56, 95% confidence interval 0.34-0.91; p = 0.019) benefits. The prolonged overall treatment time of stereotactic body radiotherapy treatment negatively affected the outcomes of patients with early-stage non-small-cell lung cancer. To our knowledge, this is the first study to show that in patients with early-stage non-small-cell lung cancer treated with the same dose-fractionation regimen, consecutive stereotactic body radiotherapy has a more beneficial effect on tumor control than non-consecutive stereotactic body radiotherapy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253203PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213186PMC
November 2021

Impact of Multileaf Collimator Width on Dose Distribution in HyperArc Fractionated Stereotactic Irradiation for Multiple (-) Brain Metastases.

Anticancer Res 2021 Jun;41(6):3153-3159

Department of Radiation Oncology, Osaka International Cancer Institute, Osaka, Japan.

Background/aim: To assess the impact of the width of multileaf collimator (MLC) on dose distributions on HyperArc fractionated stereotactic irradiation for multiple (5-10) brain metastases.

Patients And Methods: Twenty-one HyperArc (HA) plans were generated using the high definition (HD) MLC (2.5 mm) to deliver 30-35 Gy in 3-5 fractions (HA-HD). The HyperArc plans using Millennium (ML) MLC (5 mm) were retrospectively generated (HA-ML) using the same planning parameters with HA-HD. Dosimetric parameters between the planning target volume (PTV) and organs at risk (OARs) were compared.

Results: The conformity index was significantly higher (p<0.0001) in the HA-HD plans (0.95±0.04) than that in the HA-ML plans (0.92±0.06). The HA-HD provided significantly lower (p<0.0001) gradient index (5.6±2.5) than HA-ML (6.2±3.5). For the brainstem and retina (right), a statistically significant difference (p<0.05) was observed between the HA-HD (12.8±10.9 and 2.8±1.7 Gy, for brainstem and retina, respectively) and HA-ML (13.6±11.1 and 3.0±1.8 Gy) plans. For the brain tissue, the HA-HD plans statistically significantly reduced dosimetric parameters (p<0.0001) in all evaluated dose range (V-V).

Conclusion: The narrower MLC provided significantly higher conformity, steeper dose gradient, and better normal tissue sparing.
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http://dx.doi.org/10.21873/anticanres.15101DOI Listing
June 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

Elective Nodal Irradiation for Non-small Cell Lung Cancer Complicated With Chronic Obstructive Pulmonary Disease Affects Immunotherapy Αfter Definitive Chemoradiotherapy.

Anticancer Res 2020 Dec 7;40(12):6957-6970. Epub 2020 Dec 7.

Department of Radiation Oncology, Osaka International Cancer Institute, Osaka, Japan.

Background/aim: The aim of this retrospective study was to detect the frequency, reasons, and significant factors for not receiving immunotherapy after chemoradiotherapy in non-small cell lung cancer (NSCLC) patients.

Patients And Methods: Thirty-four patients with NSCLC received definitive chemoradiotherapy. The endpoint of this study was receiving durvalumab within 45 days after chemoradiotherapy for NSCLC.

Results: Twenty-five of 34 (73%) patients received immunotherapy within 45 days after chemoradiotherapy. The reasons for not receiving immunotherapy were radiation pneumonitis (50%), radiation esophagitis (10%), and four other reasons (40%). Univariate analysis showed that significant factors for not receiving immunotherapy were elective nodal irradiation (ENI)+ and chronic obstructive pulmonary disease (COPD)+. The rate of immunotherapy was 100% (17/17 cases) in the COPD- and ENI- group, and 16% (1/6 cases) in the COPD+ and ENI+ group.

Conclusion: ENI for NSCLC complicated with COPD decreased the rate of immunotherapy after definitive chemoradiotherapy.
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http://dx.doi.org/10.21873/anticanres.14720DOI Listing
December 2020

Death unrelated to cancer and death from aspiration pneumonia after definitive radiotherapy for head and neck cancer.

Radiother Oncol 2020 10 29;151:266-272. Epub 2020 Aug 29.

Department of Radiation Oncology, Osaka International Center Institute, Osaka, Japan.

Background And Purpose: The incidence of hypopharyngeal and supraglottic cancer (HSC) is high in Japan. This study aimed to retrospectively identify risk factors for death unrelated to cancer and death from aspiration pneumonia after definitive radiotherapy (RT) for HSC.

Materials And Methods: Overall, 391 patients who began definitive RT for HSC between 2006 and 2014 were identified from the Osaka International Cancer Institute electronic database. Among 391 patients, 33 had a history of surgery for esophageal cancer (EC) and 19 received simultaneous RT for synchronous EC. The cause of death was divided into 3 main categories: "cancer under study," "other malignancy," and "unrelated to cancer." Cox proportional hazard model was used to estimate the hazard ratio (HR).

Results: The median follow-up for survivors was 8 (range 3.6-14.1) years. At the last follow-up, 202 patients died. Death from "cancer under study," "other malignancy," and "unrelated to cancer" occurred in 92 (45.5%), 55 (27.2%), and 55 (27.2%) patients, respectively. Twelve patients died from aspiration pneumonia. In multivariate analysis for death unrelated to cancer and death from aspiration pneumonia, history of surgery for EC (HR: 3.87, p < 0.001; HR: 6.84, p = 0.007, respectively) and simultaneous RT for synchronous EC (HR: 3.74, p = 0.006; HR: 16.37, p < 0.001, respectively) were significant risk factors.

Conclusion: The laryngeal preservation approach by RT for HSC patients with a history of surgery for EC and simultaneous RT for synchronous EC should be used with caution.
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http://dx.doi.org/10.1016/j.radonc.2020.08.015DOI Listing
October 2020

Preoperative Stereotactic Body Radiotherapy to Portal Vein Tumour Thrombus in Hepatocellular Carcinoma: Clinical and Pathological Analysis.

Sci Rep 2020 03 5;10(1):4105. Epub 2020 Mar 5.

Department of Radiation Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan.

The prognosis of hepatocellular carcinoma (HCC) with portal vein tumour thrombus (PVTT) is poor. We conducted a prospective study to evaluate the efficacy and safety of tri-modality therapy, including preoperative stereotactic body radiotherapy (SBRT) and surgery, followed by hepatic arterial infusion chemotherapy (HAIC) in HCC patients with PVTT. In this report, we investigated the pathology of the irradiated PVTT specimen in resected cases and SBRT-related acute toxicity. A total of 8 HCC patients with PVTT received preoperative SBRT targeting the PVTT at a dose of 48 Gy in 4 fractions at our institute from 2012 to 2016. Of the eight patients, six underwent surgery, while the remaining two did not because of disease progression. At the pathological examination, all patients' irradiated PVTT specimens showed necrotic tissue, and three of six patients showed complete pathological response. Two patients showed 30% necrosis with high degeneration and one patient, with 30% necrosis without degeneration, was the only recurrent case found during the follow-up period (median: 22.5, range: 5.9-49.6 months). No SBRT-related acute toxicity worse than grade 2 was observed from SBRT to surgery. In conclusion, the preoperative SBRT for HCC was pathologically effective and the acute toxicities were tolerable.
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http://dx.doi.org/10.1038/s41598-020-60871-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057983PMC
March 2020

Failure patterns after adjuvant chemoradiotherapy following endoscopic resection for superficial esophageal squamous cell carcinoma.

Cancer Med 2019 08 20;8(10):4547-4554. Epub 2019 Jun 20.

Department of Radiation Oncology, Osaka International Cancer Institute, Osaka, Japan.

Background: This study evaluated the locations of lymph node recurrence and their association with irradiation fields used for radiotherapy after adjuvant chemoradiotherapy following endoscopic resection for superficial esophageal squamous cell carcinoma.

Methods: Medical records of 96 consecutive patients with superficial esophageal squamous cell carcinoma who underwent adjuvant chemoradiotherapy following endoscopic resection were reviewed. Computed tomography was used to identify whether nodal recurrences were within the elective nodal irradiation field. The cumulative incidence of recurrence was calculated, accounting for death as a competing risk. Univariate and multivariate analyses identified factors predicting nodal recurrence.

Results: The median follow-up period was 61 months (range: 6-137 months). Seven patients (7.3%) developed lymph node recurrence only; two patients (2.1%) developed nodal plus local recurrence. Six of the seven cases without local recurrence involved the elective nodal irradiation field, with five cases involving the recurrent nerve lymph nodes. The 5-year cumulative incidence of lymph node recurrence was higher for T1b tumors with lymphovascular invasion than for T1a tumors with lymphovascular invasion (17.6% vs 6.2%, P = 0.086; HR: 3.74, 95% CI: 0.80-17.52, P = 0.094) and T1b tumors without lymphovascular invasion (17.6% vs 3.3%, P = 0.031; HR: 6.78, 95% CI: 0.80-57.63, P = 0.080).

Conclusions: Lymph node recurrence frequently involved the elective nodal irradiation field, with recurrent nerve lymph nodes being common metastasis sites. The high incidence of nodal recurrence for T1b tumors with lymphovascular invasion highlights a need for new strategies for treating this subset of superficial esophageal squamous cell carcinomas.
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http://dx.doi.org/10.1002/cam4.2365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712456PMC
August 2019

Predictors of Acute Radiation Esophagitis in Non-small Cell Lung Cancer Patients Treated With Accelerated Hyperfractionated Chemoradiotherapy.

Anticancer Res 2019 Jan;39(1):491-497

Department of Radiation Oncology, Osaka International Cancer Institute Hospital, Osaka, Japan.

Background/aim: To identify the clinical and dosimetric predictors of severe acute radiation esophagitis (RE) in patients with non-small cell lung cancer (NSCLC) treated with accelerated hyperfractionated concurrent chemoradiotherapy (AH-CCRT) with concomitant boost technique.

Patients And Methods: A total of 159 patients who underwent AH-CCRT (64 Gy in 40 fractions twice daily) were retrospectively identified. Severe RE was designated as grade 3 or higher according to the Common Terminology Criteria for Adverse Events, version 4.0.

Results: The incidence rate of grade 3 RE was 15.1% (24/159). The multivariate analysis that incorporated the Eastern Cooperative Oncology Group performance status (ECOG PS, ≥1 vs. 0) and the relative esophagus volume irradiated with at least 60 Gy (V) was optimal. Patients with a V of ≥15% had a 37.8% risk of grade 3 RE compared to a 6.1% risk among those with a V of <15%.

Conclusion: ECOG PS (≥1 vs. 0) and the V were found to be significant risk factors for severe RE in NSCLC patients who underwent AH-CCRT.
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http://dx.doi.org/10.21873/anticanres.13139DOI Listing
January 2019

Radiation Dose Escalation in Accelerated Hyperfractionated Radiotherapy for Stage III Non-small-cell Lung Cancer.

Anticancer Res 2018 Oct;38(10):5951-5958

Department of Radiation Oncology, Osaka University Graduate School of Medicine, Osaka, Japan.

Aim: To identify clinical benefits of dose escalation in accelerated hyperfractionated radiotherapy (AH-RT) for stage III non-small-cell lung cancer (NSCLC) using propensity score-matched (PSM) analysis.

Materials And Methods: Our study retrospectively examined 294 patients undergoing definitive radiotherapy [131 patients, conventional once-daily radiotherapy (OD-RT); and 163, AH-RT] who were followed-up for a median of 40.4 months. The impact of overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) was investigated.

Results: Pre-PSM, the median OS, PFS, and LRC durations were 23.1 vs. 39.9 (p=0.03), 8.9 vs. 13.5 (p<0.01), and 12.9 vs. 50.3 (p<0.01) months in the OD-RT and AH-RT groups, respectively. After-PSM (two matched groups of 144 patients), AH-RT was associated with better LRC [adjusted hazard ratio (aHR)=0.59, 95% confidence interval (CI)=0.33-0.99, p=0.04] and marginally better PFS (aHR=0.65, 95% CI=0.41-1.03; p=0.06), but not OS (aHR=0.75, 95% CI=0.46-1.24; p=0.26).

Conclusion: After PSM analysis, dose escalation using AH-RT improved LRC and PFS in patients with locally advanced NSCLC. AH-RT can be a promising option for patients with advanced NSCLC.
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http://dx.doi.org/10.21873/anticanres.12941DOI Listing
October 2018

Stereotactic body radiotherapy to treat small lung lesions clinically diagnosed as primary lung cancer by radiological examination: A prospective observational study.

Lung Cancer 2018 08 29;122:107-112. Epub 2018 May 29.

Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Japan; Department of Radiation Medicine, Hokkaido University Faculty of Medicine, Japan.

Objectives: Even with advanced image guidance, biopsies occasionally fail to diagnose small lung lesions, which are highly suggestive of primary lung cancer by radiological examination. The aim of this study was to evaluate the outcome of stereotactic body radiotherapy (SBRT) to treat small lung lesions clinically diagnosed as primary lung cancer.

Materials And Methods: This is a prospective, multi-institutional observation study. Strict inclusion and exclusion criteria were determined in a nation-wide consensus meeting and used to include patients who were clinically diagnosed with primary lung cancer using precise imaging modalities, for whom further surgical intervention was not feasible, who refused watchful waiting, and who were highly tolerable of SBRT with informed consent. SBRT was performed with 48 Gy in 4 fractions at the tumor isocenter.

Results: From August 2009 to August 2014, 62 patients from 11 institutions were enrolled. Their median age was 80 years. The tumors ranged in size from 9 to 30 mm in diameter (median, 18 mm). The median follow-up interval was 55 months. The 3-year overall survival rate was 83.3% (95% confidence interval (CI) 71.1-90.7%) for all the patients and 94.7% (95% CI 68.1-99.2%) for the patients younger than 75 years. Local failure, regional lymph node metastases and distant metastases occurred in 4 (6.4%), 3 (4.8%) and 11 (17.7%) patients, respectively. Grades 3 and 4 toxicities were observed in 8 (12.9%) patients and 1 (1.6%) patient, respectively. No grade 5 toxicities were observed.

Conclusions: SBRT is safe and effective for patients with small lung lesions clinically diagnosed as primary lung cancer that satisfied the proposed strict indication criteria as previously reported. A prospective interventional study is required to ascertain if SBRT is an alternative strategy for these patients.
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http://dx.doi.org/10.1016/j.lungcan.2018.05.025DOI Listing
August 2018

A phase I study of oral UFT/leucovorin and irinotecan, plus radiation for locally recurrent rectal cancer.

J Anus Rectum Colon 2017 25;1(2):50-55. Epub 2018 May 25.

Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.

Objectives: The aim of this phase I study is to identify the maximum tolerated dose (MTD) and recommended dose (RD) of CPT-11 in combination with UFT/LV and radiation in patients with locally recurrent rectal cancer.

Methods: Patients with histologically proven rectal cancer with local recurrence were eligible for this study. Escalating doses of CPT-11 (30-60 mg/m) were administered on days 3, 10, 24, and 31. UFT (300 mg/m) and LV (75 mg/body) were given on days 1-5, 8-12, 22-26, and 29-33. Radiotherapy doses consisted of 50 Gy in daily fractions of 2.0 Gy each, 5 times per week, for total 5 weeks.

Results: We recruited 27 patients, and the MTD of CPT-11 was 60 mg/m due to the occurrence of dose-limiting toxicity of grade 3 diarrhea. Major grade 3 adverse events were neutropenia (5/27; 18.5%) and diarrhea (6/27; 22.2%). No grade 4 adverse event was observed throughout this treatment.

Conclusions: The combined chemoradiotherapy with oral UFT/LV plus CPT-11 is feasible and promising. The recommended dose for further phase II trials is determined to be 50 mg/m of CPT-11.
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http://dx.doi.org/10.23922/jarc.2016-009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768668PMC
May 2018

Radiotherapy for locally advanced resectable T3-T4 laryngeal cancer-does laryngeal preservation strategy compromise survival?

J Radiat Res 2018 Jan;59(1):77-90

Department of Radiation Oncology, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.

With the advancement of chemotherapy, a laryngeal preservation (LP) strategy was explored with the aim of improving maintenance of quality of life. Induction chemotherapy (ICT) following radiotherapy (RT) was considered a viable option because of its high initial response rate without hampering of overall survival (OS). Subsequently, concurrent chemoradiotherapy (CCRT) using CDDP became the standard of care for LP, showing the best LP ratio. For enhancing treatment intensity, ICT with taxan + CDDP + 5-FU (TPF-ICT) followed by RT showed superiority over ICT with CDDP + 5-FU (PF-ICT) followed by RT. Given that almost all randomized controlled trials investigating ICT include not only operable (endpoint, LP) but also inoperable (endpoint, OS) cases, physicians are faced with a dilemma regarding application in daily practice. In addition, increased treatment intensity causes augmentation of adverse events, which might reduce compliance. Thereafter, cetuximab, an effective drug with fewer adverse effects [bioradiotherapy (BRT)], emerged as another option. However, little evidence has confirmed its superiority over RT (or CCRT) in laryngeal cancer subpopulations. In spite of these developments, the OS of patients with laryngeal cancer has not improved for several decades. In fact, several studies indicated a decrease in OS during the 1990s, probably due to overuse of CCRT. Fortunately, the latter was not the case in most institutions. Currently, no other treatment has better OS than surgery. The eligibility criteria for LP and/or surgery largely depend upon the available expertise and experience, which differ from one institution to another. Therefore, a multidisciplinary team is required for the treatment of LP.
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http://dx.doi.org/10.1093/jrr/rrx063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778501PMC
January 2018

Strategies for reducing ovarian dose in volumetric modulated arc therapy (VMAT) for postoperative uterine cervical cancer.

Br J Radiol 2018 Jan 3;91(1081):20160777. Epub 2017 Nov 3.

1 Department of Radiation Oncology, Osaka International Cancer Institute, Osaka Japan.

Objective: To reduce the ovarian dose with volumetric modulated arc therapy (VMAT), an original VMAT was designed with two types of arcs to restrict angles and fields (R-VMAT).

Methods: The subjects were 11 patients who underwent ovarian transposition with clips left by a surgeon. Three methods, intensity-modulated radiotherapy (IMRT), standard VMAT (S-VMAT) and R-VMAT, were optimized for assessment of the ovarian dose with the target coverage kept high.

Results: The homogeneity and conformity indexes for the planning target volume (PTV) were similar for the three methods. However, the average ± SD of the ovarian mean dose (OMD) was 5.0 ± 1.5, 4.9 ± 1.9 and 3.5 ± 1.4 Gy, and the percentage of ovarian volume exceeding 5 Gy (V5) was 41.5 ± 34.1%, 34.1 ± 38.05% and 8.4 ± 20.5% for IMRT, S-VMAT and R-VMAT, respectively. The OMD and V5 were significantly smaller for R-VMAT than for the other plans (p < 0.01). Correlation values between the OMD and the lateral distance from the ovaries to the PTV surface were 0.86, 0.81 and 0.82 for IMRT, S-VMAT and R-VMAT, respectively.

Conclusion: These findings suggest that R-VMAT delivered the lowest dose to the ovaries. To reduce the OMD to less than 3 Gy, ovaries should be transposed laterally 6.1 cm away from the PTV surface when R-VMAT is used. Advances in knowledge: When organs with high susceptibility to radiation, such as ovaries, are near the PTV, R-VMAT is superior to IMRT and S-VMAT.
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http://dx.doi.org/10.1259/bjr.20160777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966198PMC
January 2018

Radiotherapy for laryngeal cancer-technical aspects and alternate fractionation.

J Radiat Res 2017 Jul;58(4):495-508

Department of Radiation Oncology, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, 565-0871 Osaka, Japan.

Early laryngeal, especially glottic, cancer is a good candidate for radiotherapy because obvious early symptoms (e.g. hoarseness) make earlier treatment possible and with highly successful localized control. This type of cancer is also a good model for exploring the basic principles of radiation oncology and several key findings (e.g. dose, fractionation, field size, patient fixation, and overall treatment time) have been noted. For example, unintended poor outcomes have been reported during transition from 60Cobalt to linear accelerator installation in the 1960s, with usage of higher energy photons causing poor dose distribution. In addition, shell fixation made precise dose delivery possible, but simultaneously elevated toxicity if a larger treatment field was necessary. Of particular interest to the radiation therapy community was altered fractionation gain as a way to improve local tumor control and survival rate. Unfortunately, this interest ceased with advancements in chemotherapeutic agents because alternate fractionation could not improve outcomes in chemoradiotherapy settings. At present, no form of acceleration can potentially compensate fully for the lack of concurrent chemotherapy. In addition, the substantial workload associated with this technique made it difficult to add extra fractionation routinely in busy clinical hospitals. Hypofractionation, on the other hand, uses a larger single fractionation dose (2-3 Gy), making it a reasonable and attractive option for T1-T2 early glottic cancer because it can improve local control without the additional workload. Recently, Japan Clinical Oncology Group study 0701 reprised its role in early T1-T2 glottic cancer research, demonstrating that this strategy could be an optional standard therapy. Herein, we review radiotherapy history from 60Cobalt to modern linear accelerator, with special focus on the role of alternate fractionation.
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http://dx.doi.org/10.1093/jrr/rrx023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569999PMC
July 2017

Metabolic tumor volume of primary tumor predicts survival better than T classification in the larynx preservation approach.

Cancer Sci 2017 Oct 30;108(10):2030-2038. Epub 2017 Aug 30.

Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University School of Medicine, Osaka, Japan.

We aimed to determine whether pretreatment metabolic tumor volume of the primary tumor (T-MTV) or T classification would be a better predictor of laryngectomy-free survival (LFS) and overall survival (OS) after chemoradiotherapy in patients with locally advanced laryngeal or hypopharyngeal cancer requiring total laryngectomy. We analyzed 85 patients using a Cox proportional hazards model and evaluated its usefulness by Akaike's information criterion. A T-MTV cut-off value was determined by time-dependent receiver operating characteristic curve analysis. Interobserver reliability for measuring T-MTV was estimated by the intraclass correlation coefficient (ICC). After adjustment for covariables, T-MTV, irrespective of whether a continuous or dichotomized variable, and T classification remained independent predictors of LFS and OS. Large T-MTV (>28.7 mL) was associated with inferior LFS (hazard ratio [HR], 4.16; 95% confidence interval [CI], 1.97-8.70; P = 0.0003) and inferior OS (HR, 3.18; 95% CI, 1.47-6.69; P = 0.004) compared with small T-MTV (≤28.7 mL). The T-MTV model outperformed the T classification model in predicting LFS and OS (P = 0.007 and 0.01, respectively). Three-year LFS and OS rates for patients with small versus large T-MTV were 68% vs 9% (P < 0.0001) and 77% vs 25% (P < 0.0001), respectively, whereas those for patients with T2-T3 versus T4a were 61% vs 31% (P = 0.003) and 71% vs 48% (P = 0.10), respectively. ICC was 0.99 (95% CI, 0.99-1.00). Given the excellent interobserver reliability, T-MTV is better than T classification to identify patients who would benefit from the larynx preservation approach.
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http://dx.doi.org/10.1111/cas.13345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5623730PMC
October 2017

Efficacy and Safety of Endoscopic Resection Followed by Chemoradiotherapy for Superficial Esophageal Squamous Cell Carcinoma: A Retrospective Study.

Clin Transl Gastroenterol 2017 Aug 3;8(8):e110. Epub 2017 Aug 3.

Department of Radiation Oncology, Osaka International Cancer Institute, Osaka, Japan.

Objectives: The reported 1- and 3-year overall survival rates after esophagectomy for stage I superficial esophageal squamous cell carcinoma (SESCC) are 95-97% and 86%, and those after definitive chemoradiotherapy (CRT) are 98% and 89%, respectively. This study was performed to elucidate the efficacy and safety of another treatment option for SESCC: endoscopic resection (ER) followed by CRT.

Methods: We retrospectively reviewed the overall survival, recurrence, and grade ≥3 adverse events of consecutive patients who refused esophagectomy and underwent ER followed by CRT for SESCC from 1 January 2006 to 31 December 2012.

Results: In total, 66 patients with SESCC underwent ER followed by CRT during the study period, and complete follow-up data were available for all patients. The median age was 67 (range, 45-82) years, and the median observation period was 51 (range, 7-103) months. Local and metastatic recurrences occurred in 2 (3%) and 6 (9%) patients, respectively, and 17 (26%) patients died. The 1-, 3-, and 5-year overall survival rates were 98%, 87%, and 75%, respectively. One of the 23 patients with mucosal cancer and 5 of 43 with submucosal cancer developed metastatic recurrences (P=0.65). Five of the 61 patients with negative vertical resection margin and 1 of 5 with positive vertical resection margin developed metastatic recurrences (P=0.39). None of the 30 patients without lymphovascular involvement developed metastatic recurrences; however, 6 of 36 patients with lymphovascular involvement developed metastatic recurrences (P=0.0098). Grade ≥3 adverse events occurred in 21 (32%) patients and all adverse events were associated with CRT, hematological adverse events in 13 (20%), and non-hematological adverse events in 9 (14%).

Conclusions: ER followed by CRT provides survival comparable with that of esophagectomy or definitive CRT and has a low local recurrence rate. A particularly favorable outcome is expected for cancers without lymphovascular involvement.
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http://dx.doi.org/10.1038/ctg.2017.36DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587838PMC
August 2017

Clinical outcome of patients treated with re-irradiation for spine or pelvic bone metastasis: A multi-institutional analysis of 98 patients.

Mol Clin Oncol 2017 Jun 8;6(6):871-875. Epub 2017 May 8.

Department of Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.

The present study aimed to describe the clinical results of re-irradiation (Re-RT) for spine or pelvic bone metastasis at the same initial irradiated area. Between April 2010 and March 2014, cases involving 98 patients with spine or pelvic bone metastasis who had undergone Re-RT at five institutions were reviewed. The clinical outcomes following Re-RT were evaluated, including overall survival (OS) and severe adverse events. The median time interval from initial radiation therapy (RT) to Re-RT was 439 days (range, 23-4,993 days), and the median duration of patient follow-up was 256 days (range, 11-2,284 days). The median biological effective dose for the Re-RT was 150 Gy (range, 17-240 Gy; α/β = 2). Severe late adverse events occurred in two patients who underwent three-dimensional conformal radiotherapy for lumbar spine or pelvic bone metastases, which may be associated with tumor progression. The median survival time following Re-RT was 255 days, and the actuarial OS rate at 1 year was 36%. The interval between initial RT and Re-RT, and their performance statuses (PS) were significant independent prognostic factors for OS rates in multivariate analysis. Re-RT for spine or pelvic bone metastases is a relatively acceptable option with low risk of anticipated severe adverse events, particularly for patients with good PS following a long disease-free interval.
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http://dx.doi.org/10.3892/mco.2017.1245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451871PMC
June 2017

Nationwide, Multicenter, Retrospective Study on High-Dose-Rate Brachytherapy as Monotherapy for Prostate Cancer.

Int J Radiat Oncol Biol Phys 2017 04 18;97(5):952-961. Epub 2016 Dec 18.

Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan.

Purpose: To present, analyze, and discuss results of a nationwide, multicenter, retrospective study on high-dose-rate brachytherapy (HDR-BT) as monotherapy for low-, intermediate-, and high-risk prostate cancer.

Methods And Materials: From 1995 through 2013, 524 patients, 73 (14%) with low-risk, 207 (40%) with intermediate-risk, and 244 (47%) with high-risk prostate cancer, were treated with HDR-BT as monotherapy at 5 institutions in Japan. Dose fractionations were 27 Gy/2 fractions for 69 patients (13%), 45.5 Gy/7 fractions for 168 (32%), 49 Gy/7 fractions for 149 (28%), 54 Gy/9 fractions for 130 (25%), and others for 8 (2%). Of these patients, 156 (30%) did not receive androgen deprivation therapy, and 202 patients (39%) did receive androgen deprivation therapy <1 year, 112 (21%) for 1-3 years, and 54 (10%) for >3 years. Median follow-up time was 5.9 years (range, 0.4-18.1 years), with a minimum of 2 years for surviving patients.

Results: After 5 years, respective actuarial rates of no biochemical evidence of disease, overall survival, cause-specific survival, and metastasis-free survival for all patients were 92%, 97%, 99%, and 94%. For low/intermediate/high-risk patients, the 5-year no biochemical evidence of disease rates were 95%/94%/89%, the 5-year overall survival rates were 98%/98%/94%, the 5-year cause-specific survival rates were 98%/100%/98%, and the 5-year metastasis-free survival rates were 98%/95%/90%, respectively. The cumulative incidence of late grade 2 to 3 genitourinary toxicity at 5 years was 19%, and that of late grade 3 was 1%. The corresponding incidences of gastrointestinal toxicity were 3% and 0% (0.2%). No grade 4 or 5 of either type of toxicity was detected.

Conclusions: The findings of this nationwide, multicenter, retrospective study demonstrate that HDR-BT as monotherapy was safe and effective for all patients with low-, intermediate-, and high-risk prostate cancer.
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http://dx.doi.org/10.1016/j.ijrobp.2016.12.013DOI Listing
April 2017

Risk factors for vertebral compression fractures in preoperative chemoradiotherapy with gemcitabine for pancreatic cancer.

Radiother Oncol 2016 Mar 21;118(3):424-9. Epub 2016 Jan 21.

Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan.

Background And Purpose: Preoperative chemoradiotherapy (CRT) with gemcitabine (GEM) for pancreatic cancer is often accompanied by vertebral compression fractures (VCFs). This study aimed to establish the incidence of VCFs and identify the related risk factors (RFs) to elucidate how to decrease the overall incidence of VCF.

Material And Methods: We investigated 220 patients with resectable or borderline-resectable pancreatic cancers who had completed preoperative CRT between 2006 and 2011. The RFs associated with VCF were analyzed in a total of 1308 thoracolumbar vertebral bodies.

Results: Thirty-seven VCFs occurred in 25 patients (11%); the cumulative incidence at two years was 18.9%. Univariate analysis revealed female sex, age and high daily GEM concentration during radiotherapy as RFs for VCF. The multivariate mixed effects logistic regression model demonstrated that the most responsible factor was radiation dose (p<0.001). We estimated the radiation condition resulting in a fracture incidence of ⩽5% by counting the patient's number of the three RFs. For patients with three factors, the mean vertebral dose was 22.0 Gy.

Conclusions: The RFs for VCF after CRT were identified. The side effect of VCF might be avoided by regulating the radiation dose to neighboring vertebral bodies after considering the RFs.
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http://dx.doi.org/10.1016/j.radonc.2016.01.006DOI Listing
March 2016

Selective neck irradiation for supraglottic cancer: focus on Sublevel IIb omission.

Jpn J Clin Oncol 2016 Jan 20;46(1):51-6. Epub 2015 Oct 20.

Department of Radiation Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka.

Objective: To estimate selective neck irradiation omitting surgical Sublevel IIb.

Methods: Bilateral necks of 47 patients (94 necks) were subjected to definitive radiotherapy for supraglottic cancer. Sixty-nine and 25 necks were clinically node negative (cN-) and clinically node positive (cN+), respectively. We subdivided Sublevel IIb by the international consensus guideline for radiotherapy into Sublevel IIb/a, directly posterior to the internal jugular vein, and Sublevel IIb/b, which was behind Sublevel IIb/a and coincided with surgical Sublevel IIb. Bilateral (Sub)levels IIa, III, IV and IIb/a were routinely irradiated, whereas Sublevel IIb/b was omitted from the elective clinical target volume in 73/94 treated necks (78%).

Results: Two patients presented with ipsilateral Sublevel IIb/a metastases. No Sublevel IIb/b metastasis was observed. Five patients experienced cervical lymph node recurrence; Sublevel IIb/a recurrence developed in two patients, whereas no Sublevel IIb/b recurrence occurred even in the cN- necks of cN+ patients or cN0 patients. The 5-year regional control rates were 91.5% for Sublevel IIb/b-omitted patients and 77.8% for Sublevel IIb/b treated patients.

Conclusions: Selective neck irradiation omitting Sublevel IIb/b did not compromise regional control and could be indicated for cN- neck of supraglottic cancer.
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http://dx.doi.org/10.1093/jjco/hyv156DOI Listing
January 2016

Histopathological effects of preoperative chemoradiotherapy for pancreatic cancer: an analysis for the impact of radiation and gemcitabine doses.

Radiother Oncol 2015 Jan 19;114(1):122-7. Epub 2015 Jan 19.

Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.

Background And Purpose: Histopathological findings of patients who underwent resection for pancreatic adenocarcinoma (PC) after preoperative chemoradiotherapy (CRT) reportedly showed beneficial effects. The purpose of our study was to evaluate the correlation between histopathological effects (HE) of preoperative CRT and treatment parameters [radiation and gemcitabine (GEM) doses].

Material And Methods: HE of CRT were assessed on 158 primary lesions of 157 patients with PC who underwent pancreatic resection after preoperative CRT with GEM between January 2006 and December 2011. The radiation dose delivered to the primary tumor site and surrounding regional nodal areas was 50 Gy until September 2009 followed by the dose escalation of a 10 Gy boost added for delivery with the field-in-field technique to the roots of the celiac and superior mesenteric arteries. Intravenous administration of GEM (1000 /m(2)) was initiated concurrently on days 1, 8, and 15, every 4 weeks and generally repeated for 3 cycles. HE of CRT on the primary tumor were categorized based on the number of tumor cells destroyed.

Results: The median overall survival time was 74.5 months and 3-year and 5-year survival rates were 64.3% and 54.5%, respectively. Dose-volume parameters of radiation such as D33 with a cut-off value of 51.6 Gy were correlated significantly with HE (p=.0230). Lesions having received GEM>7625 mg/m(2) before surgical resection more frequently showed positive HE (p=.0002). Multivariate logistic regression analysis demonstrated that both D33 and cumulative GEM dose were significant predictors of definite HE (p=.0110 and <.0001, respectively).

Conclusions: Our retrospective analysis showed that dose intensity of radiation and GEM is significantly related to HE of preoperative CRT for PC.
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http://dx.doi.org/10.1016/j.radonc.2015.01.004DOI Listing
January 2015

Neoadjuvant gemcitabine-based accelerated hyperfractionation chemoradiotherapy for patients with borderline resectable pancreatic adenocarcinoma.

Jpn J Clin Oncol 2014 Dec 1;44(12):1172-80. Epub 2014 Oct 1.

Department of Surgery, Graduate School of Medicine, Osaka University, Osaka.

Objective: We report the response to pre-operative gemcitabine-based chemoradiotherapy for pancreatic adenocarcinoma.

Methods: Thirty-five consecutive patients with borderline resectable pancreatic adenocarcinoma of UICC Stage II or III with portal vein invasion or tumor abutment of artery received radiotherapy (twice daily fractions of 1.5 Gy, 5 days/week, total dose: 36 Gy; 30 Gy for Phase I Level 1) with weekly intravenous infusions of gemcitabine (400, 600 and 800 mg/m(2)) at Days 1 and 8 for Phase I and 800 mg/m(2) for Phase II. Restaging was repeated after completion of chemoradiotherapy.

Results: Twenty-six of the 35 (74.3%) patients underwent resection. The dose-limiting toxicities were Grade 4 neutropenia and thrombocytopenia. The recommended regimen was total radiation dose of 36 Gy with gemcitabine 800 mg/m(2). Surgical resection was conducted in 11 of the 15 (73.3%) patients in Phase I study and 15 of the 20 (75.0%) in Phase II. After recommended dose chemoradiotherapy and surgical resection, the median disease-free survival was 17.4 months (5-year survival rate = 14.3%). The median overall survival time and 5-year survival rate were 41.2 months and 28.6%, respectively, for the 21 patients who underwent resection and 10.0 months and 0%, respectively, for those 5 who did not (P = 0.004).

Conclusion: Our pre-operative gemcitabine-based chemoradiotherapy was well tolerated and safe.
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http://dx.doi.org/10.1093/jjco/hyu143DOI Listing
December 2014

Comparison of acute and subacute genitourinary and gastrointestinal adverse events of radiotherapy for prostate cancer using intensity-modulated radiation therapy, three-dimensional conformal radiation therapy, permanent implant brachytherapy and high-dose-rate brachytherapy.

Tumori 2014 May-Jun;100(3):265-71

Aims And Background: To examine acute and subacute urinary and rectal toxicity in patients with localized prostate cancer monotherapeutically treated with the following four radiotherapeutic techniques: intensity-modulated radiation therapy, three-dimensional conformal radiation therapy, low-dose-rate permanent implant brachytherapy using I-125 seeds, and high-dose-rate brachytherapy.

Methods: One hundred and fifty-six patients with localized prostate cancer were distributed as follows: 57 underwent intensity-modulated radiation therapy, 35 underwent three-dimensional conformal radiation therapy, 37 underwent I-125 implant, and 27 underwent high-dose-rate brachytherapy. The prescribed doses were 70-74 Gy/35-37 fractions, 70 Gy/35 fractions, 145 Gy, and 45.5 Gy/7 fraction/4 days for intensity-modulated radiation therapy, three-dimensional conformal radiation therapy, I-125 implant, and high-dose-rate brachytherapy, respectively. Toxicities (≤6 months) were retrospectively evaluated using the Common Terminology Criteria for Adverse Events version 4.03.

Results: The frequency of grade 1 or 2 urinary toxicities using three-dimensional conformal radiation therapy (33/35, 94%) was significantly higher than that with high-dose-rate brachytherapy (18/27, 67%) or intensity-modulated radiation therapy (37/57, 65%) (P <0.05). The frequency of grade 1 or 2 urinary toxicities using I-125 implant was 31/37, 84%. The frequency of grade 1 or 2 gastrointestinal toxicities using three-dimensional conformal radiation therapy (17/35, 49%) was significantly higher than that using I-125 implant (4/37, 11%) or high-dose-rate brachytherapy (0/27, 0%) (P <0.05). Using intensity-modulated radiation therapy, the frequency of grade 1 or 2 gastrointestinal toxicities was 18/57 (32%), which was significantly higher than that using high-dose-rate brachytherapy (0/27, 0%) (P <0.05). Grade 3 or greater adverse events were not observed.

Conclusions: Acute and subacute genitourinary toxicities were observed more frequently after three-dimensional conformal radiation therapy than after high-dose-rate brachytherapy or intensity-modulated radiation therapy. Acute and subacute gastrointestinal toxicities were seen more often after three-dimensional conformal radiation therapy than after brachytherapy (I-125 implant or high-dose-rate brachytherapy).
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http://dx.doi.org/10.1700/1578.17198DOI Listing
November 2014

Dosimetry analyses comparing high-dose-rate brachytherapy, administered as monotherapy for localized prostate cancer, with stereotactic body radiation therapy simulated using CyberKnife.

J Radiat Res 2014 Nov 23;55(6):1114-21. Epub 2014 Jun 23.

Department of Radiation Oncology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, Japan.

The purpose of this study was to perform dosimetry analyses comparing high-dose-rate brachytherapy (HDR-BT) with simulated stereotactic body radiotherapy (SBRT). We selected six consecutive patients treated with HDR-BT monotherapy in 2010, and a CyberKnife SBRT plan was simulated for each patient using computed tomography images and the contouring set used in the HDR-BT plan for the actual treatment, but adding appropriate planning target volume (PTV) margins for SBRT. Then, dosimetric profiles for PTVs of the rectum, bladder and urethra were compared between the two modalities. The SBRT plan was more homogenous and provided lower dose concentration but better coverage for the PTV. The maximum doses in the rectum were higher in the HDR-BT plans. However, the HDR-BT plan provided a sharper dose fall-off around the PTV, resulting in a significant and considerable difference in volume sparing of the rectum with the appropriate PTV margins added for SBRT. While the rectum D5cm(3) for HDR-BT and SBRT was 30.7 and 38.3 Gy (P < 0.01) and V40 was 16.3 and 20.8 cm(3) (P < 0.01), respectively, SBRT was significantly superior in almost all dosimetric profiles for the bladder and urethra. These results suggest that SBRT as an alternative to HDR-BT in hypofractionated radiotherapy for prostate cancer might have an advantage for bladder and urethra dose sparing, but for the rectum only when proper PTV margins for SBRT are adopted.
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http://dx.doi.org/10.1093/jrr/rru048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4229914PMC
November 2014

Novel chemoradiotherapy with concomitant boost thoracic radiation and concurrent cisplatin and vinorelbine for stage IIIA and IIIB non-small-cell lung cancer.

Clin Lung Cancer 2014 Jul 19;15(4):281-6. Epub 2014 Feb 19.

Department of Radiation Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.

Introduction: Lung cancer is a leading cause of cancer death in the world. The results from concurrent chemoradiotherapy (CRT) are still disappointing, although long-term survival can be observed in certain populations of patients. Local control is a critical problem in CRT; dose escalation of thoracic radiation (TRT) in CRT has not been effective.

Patients And Methods: The authors developed a novel TRT scheme of accelerated hyperfractionation using concomitant boost TRT (ccbRT). Total doses of 64 Gy and 40 Gy were given to the gross tumor volume and elective clinical target volume, respectively, for 20 working days, combined with systemic chemotherapy with cisplatin (day 1) and vinorelbine (days 1, 8) with a 3-week interval (NP regimen). The purpose of this phase II study was to evaluate the efficacy and toxicity of this novel treatment.

Results: From July 2002 to July 2010, 56 patients were enrolled in this study. One patient was excluded from the analysis. All 55 patients completed ccbRT, and 52 patients (94.5%) underwent at least 2 cycles of NP. Grade 3 esophagitis and grade 3 radiation pneumonitis were observed in 18.2% and 3.6% of the patients. Complete response and partial response were achieved in 24.5% and 69.1% of the patients, resulting in a response rate of 93.6%. The median progression-free survival (PFS) and overall survival (OS) times were 16.7 months and 58.2 months.

Conclusion: CRT using ccbRT with concurrent NP is safe and effective for locally advanced non-small-cell lung cancer, with good PFS and excellent OS.
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http://dx.doi.org/10.1016/j.cllc.2014.02.001DOI Listing
July 2014

Monotherapeutic high-dose-rate brachytherapy for prostate cancer: a dose reduction trial.

Radiother Oncol 2014 Jan 30;110(1):114-9. Epub 2013 Oct 30.

Department of Radiation Oncology, Osaka University Graduate School of Medicine, Japan.

Purpose: To report preliminary results of our second regimen with 45.5 Gy/7 fractions aiming to reduce toxicity, compared with our first regimen with 54 Gy/9 fractions, using high-dose-rate (HDR) brachytherapy as monotherapy for prostate cancer.

Materials And Methods: From 2005 through 2010, 63 patients with localized prostate cancer were treated with HDR brachytherapy alone in 45.5 Gy/7 fractions for 4 days. Thirty-four patients were considered as intermediate-risk and 29 as high-risk. Thirty-seven patients also received neoadjuvant and/or adjuvant hormonal therapy. Biologically effective dose assuming α/β=1.5 Gy (BED₁.₅) was reduced from 270 Gy to 243 Gy, and BED₃.₀ from 162 Gy to 144 Gy, compared to previous 54 Gy/9 fractions for 5 days.

Results: Median follow-up time was 42 months (range 13-72). Grade 2 acute toxicities occurred in six (9.5%), late toxicities in five (7.9%) patients, and Grade 3 or higher in none. Grade 2 late gastrointestinal toxicity rate was 1.6%, compared with 7.1% for the 54 Gy regimen. Three-year PSA failure-free rates for intermediate- and high-risk patients were 96% and 90%, which were comparable to 93% and 85% for the 54 Gy regimen.

Conclusions: Compared to the 54 Gy/9 fractions regimen, dose-reduced regimen of 45.5 Gy/7 fractions using HDR brachytherapy as monotherapy preliminarily showed an equivalent or lower incidence rate for acute and late toxicities without compromising the excellent PSA failure-free rate. Further studies with more patients and longer follow-up are warranted.
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http://dx.doi.org/10.1016/j.radonc.2013.10.015DOI Listing
January 2014
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