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Cardiac implantable electronic devices (CIEDs) were believed to have a tolerance dose and that direct irradiation has to be avoided. Thus, no clinical guidelines have mentioned the feasibility of total body irradiation (TBI) with a CIED directly. The purpose of this work was to study a feasible and safe condition for TBI using a CIED. Eighteen CIEDs were directly irradiated by a 6-MV X-ray beam, where a non-neutron producible beam was employed for the removal of any neutron contribution to CIED malfunction. Irradiation up to 10 Gy in accumulated dose was conducted with a 100-cGy/min dose rate, followed by up to 20 Gy at 200 cGy/min. An irradiation test of whether inappropriate ventricular shock therapy was triggered or not was also performed by using a 6-MV beam of 5, 10, 20 and 40 cGy/min to two CIEDs. No malfunction was observed during irradiation up to 20 Gy at 100 and 200 cGy/min without activation of shock therapy. These results were compared with typical TBI, suggesting that a CIED in TBI will not encounter malfunction because the prescribed dose and the dose rate required for TBI are much safer than those used in this experiment. Several inappropriate shock therapies were, however, observed even at 10 cGy/min if activated. The present result suggested that TBI was feasible and safe if a non-neutron producible beam was employed at low dose-rate without activation of shock therapy, where it was not inconsistent with clinical and non-clinical data in the literature. The feasibility of TBI while using a CIED was discussed for the first time.

Cardiac metastasis is uncommon and rarely diagnosed antemortem. Here, we describe a case of symptomatic cardiac metastasis from esophageal adenocarcinoma. A 64-year-old man developed chest symptoms 26 months after curative esophagogastrectomy for esophageal adenocarcinoma. Initially, ischemic cardiac disease was suspected based on electrocardiography findings, but an infiltrative tumor was seen morphologically in the wall of the interventricular septum and apex. No other lesions were detected. Histological examination of a transcatheter biopsy specimen indicated that the cardiac tumor was metastasis from esophageal adenocarcinoma. Chemoradiotherapy with cisplatin relieved his symptoms, and he had resumed normal activities. However, he opted not to undergo further aggressive treatment due to severe adverse effects from cisplatin. Seventeen months after completion of chemoradiotherapy, metastases to the right ventricle and the left thighbone were detected and he died 27 and 24 months after the diagnosis of cardiac metastasis and completion of chemoradiotherapy, respectively.

Hepatocellular carcinoma (HCC) with extrahepatic metastasis is rare, and its prognosis is extremely poor. There is no standard treatment for HCC with extrahepatic metastasis. We report a case of abscopal effect in HCC with multiple pleural metastases in a patient who was treated with focal radiotherapy to extrahepatic metastasis, and achieved long-term survival. We performed radiotherapy only to the tumor in inferior vena cava and the proximal pleural tumor. The regimen comprised a total dose of 30 Gy administered in ten fractions to these tumors, followed by 12 Gy administered in four fractions (a total of 42 Gy in 14 fractions) as boost irradiation to the remaining tumor, and a complete regression was achieved. There have been some case reports on abscopal effects in HCC, but no reports on patients with multiple pleural metastases. To our knowledge, this is the first case report on the abscopal effect of focal radiotherapy resulting in complete regression of distant multiple pleural metastases.

Background A rapid increase in human papilloma virus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is a global trend. Although HPV-positive patients have a more favorable prognosis, distant metastases occur, warranting new, systemic treatment options. The aim of this study was to investigate the effect of combining proteasome or MDM2 inhibitors with cisplatin on an HPV-positive oropharyngeal squamous cell carcinoma cell line (LU-HNSCC-26).Methods The LU-HNSCC-26 cells were treated with proteasome inhibitor (bortezomib, carfilzomib or ixazomib) or MDM2 inhibitor (RG7112) in combination with cisplatin. Combinatorial effects were analyzed by isobolograms. Protein expression was investigated by Western blotting and cell cycle phase distribution by flow cytometry. Results There was no synergy between the substances and cisplatin. All proteasome inhibitors displayed antagonistic effects while the MDM2 inhibitor was additive in combination with cisplatin. The expression of p53 was only marginally affected and apoptosis was not detected. The cell cycle progression was halted in G0/G1 with all inhibitors and in S phase with cisplatin. The expression of p21 increased by bortezomib or carfilzomib, ixazomib increased p21 in combination with cisplatin while RG7112 did not affect p21. There was no effect on ERCC1 with any of the substances.Conclusions In the investigated HPV16-positive OPSCC cell line, proteasome inhibition decreased the effect of cisplatin. A possible mechanism for this includes low effects on p53 expression with concomitant increase in p21 expression and blocking of cell cycle progression in G0/G1 with preserved DNA damage repair. The combination of proteasome inhibition with ordinary cytotoxic treatment for HPV-positive OPSCC patients is thus questionable, and clinical trials should be preceded by thorough testing in adequate models.

Small cell carcinomas (SCC) make up only 1% of malignancies of the prostate. Reports of several case series have described outcomes of surgery and chemotherapy for SCC of the prostate, but few reports address radiotherapy. We treated a case of SCC of the prostate with intensity-modulated radiation therapy (IMRT) consisting of 70 Gy administered in 35 fractions followed by hormonal therapy using only luteinizing hormone-releasing hormone (LH-RH) agonist. The tumor volume decreased remarkably by 4 months after IMRT. The rapid decrease in tumor size of this SCC of the prostate seemed to suggest a similar high radiosensitivity to that of SCC of the lung, but the tumor increased rapidly thereafter within the radiation fields, and pelvic lymph node metastases had developed by 24 months after IMRT. By 28 months after IMRT, multiple lung metastases developed, and the patient died of SCC of the prostate 31 months after initial diagnosis.

Purpose Cardiac implantable electronic devices (CIEDs) were believed to possess a tolerance dose to malfunction during radiotherapy. Although recent studies have qualitatively suggested neutrons as a cause of malfunction, numerical understanding has not been reached. The purpose of this work is to quantitatively clarify the contribution of secondary neutrons from out-of-field irradiation to the malfunction of CIEDs as well as to deduce the frequency of malfunctions until completion of prostate cancer treatment as a typical case. Materials and methods Measured data were gathered from the literature and were re-analyzed. Firstly, linear relationship for a number of malfunctions to the neutron dose was suggested by theoretical consideration. Secondly, the accumulated number of malfunctions of CIEDs gathered from the literature was compared with the prescribed dose, scattered photon dose, and secondary neutron dose for analysis of their correlation. Thirdly, the number of malfunctions during a course of prostate treatment with high-energy X-ray, passive proton, and passive carbon-ion beams was calculated while assuming the same response to malfunctions, where X-rays consisted of 6-MV, 10-MV, 15-MV, and 18-MV beams. Monte Carlo simulation assuming simple geometry was performed for the distribution of neutron dose from X-ray beams, where normalization factors were applied to the distribution so as to reproduce the empirical values. Results Linearity between risk and neutron dose was clearly found from the measured data, as suggested by theoretical consideration. The predicted number of malfunctions until treatment completion was 0, 0.02 ± 0.01, 0.30 ± 0.08, 0.65 ± 0.17, 0.88 ± 0.50, and 0.14 ± 0.04 when 6-MV, 10-MV, 15-MV, 18-MV, passive proton, and passive carbon-ion beams, respectively, were employed, where the single model response to a malfunction of 8.6 ± 2.1 Sv- 1 was applied. Conclusions Numerical understanding of the malfunction of CIEDs has been attained for the first time. It has been clarified that neutron dose is a good scale for the risk of CIEDs in radiotherapy. Prediction of the frequency of malfunction as well as discussion of the risk to CIEDs in radiotherapy among the multiple modalities have become possible. Because the present study quantitatively clarifies the neutron contribution to malfunction, revision of clinical guidelines is suggested.

INTRODUCTION AND OBJECTIVES:Multiparametric magnetic resonance imaging (mp-MRI) and Prostate Imaging Reporting and Data System (PI-RADS) score have been reported to be a likely radiographic biomark...

Hypofractionated radiotherapy using fewer and larger fractional doses may be more beneficial than conventional external-beam radiotherapy for localized prostate cancer. We evaluated the 5-year outcomes of moderately hypofractionated radiotherapy for localized prostate cancer. We retrospectively evaluated 195 patients with localized prostate cancer (T1–3N0M0) who underwent intensity-modulated radiotherapy (IMRT) (66 Gy delivered in fractions of 3 Gy every other weekday) between May 2005 and December 2011. Patients received androgen deprivation therapy depending on the perceived intermediate or high risk of their disease. A prostate-specific antigen nadir +2.0 ng/ml indicated biochemical failure. We assessed toxicity using the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria, and patient-reported outcomes using the Expanded Prostate Cancer Index Composite (EPIC). The risk classifications (proportion) were low risk (13.8%), intermediate risk (35.9%), and high risk (50.3%). The median follow-up was 69 months. Thirteen (6.66%) patients experienced biochemical failure within a median of 40 months (interquartile range, 25–72 months). The 5-year overall survival rate and no biological evidence of disease rate were 97.7% and 92.4%, respectively. Based on the RTOG/EORTC criteria, no patient experienced acute or late toxicity of grade 3 or higher. The EPIC scores revealed significant differences in the average value of all domains (p

Objective To evaluate the correlations between the changes in the quality-of-life scores and the dose-volume histogram parameters in patients receiving high-dose-rate brachytherapy combined with hypofractionated external beam radiation therapy for localized prostate cancer. Methods Among the patients who were treated with high-dose-rate brachytherapy (18 Gy in two fractions) combined with hypofractionated external beam radiation therapy (45 Gy in 15 fractions), the data of 118 consecutive patients followed up for >24 months were prospectively analyzed. The disease-specific quality of life was assessed using the expanded prostate cancer index composite, and the acute genitourinary toxicities were graded based on the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer Toxicity criteria. Results The median follow-up duration was 58 months (42-84 months). Thirteen patients (11%) developed Grade 2 or more severe acute genitourinary toxicities. The score for the general urinary domain of the expanded prostate cancer index composite quality-of-life scores dropped significantly at 1 month after high-dose-rate brachytherapy, and then returned to the baseline level by 3 months. Among the dose-volume histogram parameters, the reduction of the expanded prostate cancer index composite quality-of-life scores for the general urinary domain and its subscales at 12 months after high-dose-rate brachytherapy was significantly greater in the patients for whom the V150 or urethral D10 was within the upper 20% of the range than in those in whom the values of these dosimetric parameters were within the lower 20% of the range. Conclusion The high-dose area of the prostate gland (V150) or urethra (D10) might influence the quality-of-life scores for the urinary domain and its subscales over the long term.

Adenosquamous carcinoma of the pancreas (ASCP) is very rare, comprising only 1–4 % of exocrine malignancies of the pancreas. Several reports have described surgical outcomes for ASCP, but there are few reports of radiotherapy. We treated a case of ASCP with radiotherapy with 50.4 Gy in 28 fractions. The tumor disappeared completely at the end of the radiotherapy but recurred rapidly within the radiation fields, and multiple liver metastases with ascites developed 2 months after treatment, which indicated the possibly high radiosensitivity of the tumor. Initial serum levels of carcinoembryonic antigen, 8.6 ng/mL, and squamous cell-related antigen, 45.8 ng/mL, decreased to within normal limits at the end of radiation therapy, but these 2 tumor markers increased rapidly thereafter.

Purpose To report outcomes and risk factors of high-dose-rate (HDR) brachytherapy combined with external beam radiotherapy with or without androgen deprivation therapy (ADT) in prostate cancer patients. Materials and Methods This multi-institutional retrospective analysis comprised 3424 patients with localized prostate cancer at 16 Asian hospitals. One-thirds (27.7%) of patients received only neoadjuvant ADT, whereas almost half (49.5%) of patients received both neoadjuvant and adjuvant ADT. Mean duration of neoadjuvant and adjuvant ADT were 8.6 months and 27.9 months, respectively. Biochemical failure was defined by Phoenix ASTRO consensus. Biochemical control rate, clinical disease-free survival (cDFS), cause-specific survival, and overall survival (OS) were calculated. Results Median followup was 66 months. Ten-year biochemical control, cDFS, cause-specific survival, and OS rate were 81.4%, 81.0%, 97.2%, and 85.6%, respectively. Receiving both neoadjuvant and adjuvant ADT was detected as a favorable factor for biochemical control, cDFS, and OS, but pelvic irradiation was detected as an adverse factor for cause-specific survival, and OS. Ten-year cumulative rates of late Grade ≥2 genitourinary and gastrointestinal toxicities were 26.8% and 4.1%, respectively; receiving both neoadjuvant and adjuvant ADT was detected as a favorable factor for preventing both toxicities. Conclusions HDR combined with external beam radiotherapy was an effective and safe treatment for localized prostate cancer. Combination of long-term ADT was suggested to be necessary, even for HDR brachytherapy, and was useful in suppressing late toxicities. Meanwhile, pelvic irradiation was suggested to have an adverse effect on OS of our study population.

1993年1月から2005年8月に当科で根治的放射線治療が施行された中咽頭癌IVA-B期患者57例を対象として治療成績の検討を行った。年齢は34～84歳（中央値62歳），性別は男性43例，女性14例であり，発生部位は前壁16例，側壁39例，後壁1例，上壁1例であった。全身化学療法が49例で施行されたが，導入化学療法（induction chemotherapy: ICT）：25例，ICT+同時併用化学放射線療法（concurrent chemoradiotherapy: CCRT）：15例，CCRT：9例であった。37例に1.2Gy1日2回の多分割照射法で60～82Gy（中央値72Gy），20例には通常分割照射法で60～72Gy（中央値66Gy）の放射線治療が施行された。初期治療として放射線治療後の救済手術が5例に施行された。5年粗生存率，無病生存率はそれぞれ52.9%，51.4%であった。T3以上，N2c以上，高分化型であった症例で有意に予後不良であった。しかし，全身化学療法の有無，施行時期，照射スケジュールには生存率に有意を認めなかった。未だ治療成績は良好とは言えず，さらなる治療成績改善のための検討が必要と考えられた。

‘Dropped head syndrome’ (DHS) is characterized by severe weakness of the muscles of the back of the neck, resulting in chin-on-chest deformity. Dropped head syndrome induced by radiotherapy is very rare. We report a case of DHS following chemoradiotherapy with a total of 64.8 Gy in 36 fractions for nasopharyngeal carcinoma.

Benign and malignant pulmonary lesions usually are differentiated by 18F-FDG PET with a semiquantitative 18F-FDG standardized uptake value (SUV) of 2.5. However, the frequency of malignancies with an SUV of2.5 is significant, and pulmonary nodules with low 18F-FDG uptake often present diagnostic challenges.Among 360 consecutive patients who underwent 18F-FDG PET to evaluate pulmonary nodules found on CT, we retrospectively analyzed 43 who had solid pulmonary lesions (excluding lesions with ground-glass opacity, infiltration, or benign calcification) with an SUV of2.5. The uptake of 18F-FDG was graded by a visual method (absent, faint, moderate, or intense) and 2 semiquantitative methods (SUV and contrast ratio [CR]). Final classification was based on histopathologic findings or at least 6 mo of clinical follow-up.We found 16 malignant (diameter, 8-32 mm) and 27 benign (7-36 mm) lesions. When faint visual uptake was the cutoff for positive 18F-FDG PET results, the receiver-operating-characteristic (ROC) analysis correctly identified all 16 malignancies and yielded false-positive results for 10 of 27 benign lesions. Sensitivity was 100%, specificity was 63%, and the positive and negative predictive values were 62% and 100%, respectively. When an SUV of 1.59 was the cutoff for positive 18F-FDG PET results, the ROC analysis revealed 81% sensitivity, 85% specificity, and positive and negative predictive values of 77% and 89%, respectively. At a cutoff for positive 18F-FDG PET results of a CR of 0.29, the ROC analysis revealed 75% sensitivity, 82% specificity, and positive and negative predictive values of 71% and 85%, respectively. The areas under the curve in ROC analyses did not differ significantly among the 3 analyses (visual, 0.84; SUV, 0.81; and CR, 0.82). Analyses of intra- and interobserver variabilities indicated that visual and SUV analyses were quite reproducible, whereas CR analysis was poorly reproducible.These results suggested that for solid pulmonary lesions with low 18F-FDG uptake, semiquantitative approaches do not improve the accuracy of 18F-FDG PET over that obtained with visual analysis. Pulmonary lesions with visually absent uptake indicate that the probability of malignancies is very low. In contrast, the probability of malignancy in any visually evident lesion is about 60%.