Search

We studied double-strand breaks (DSB) induction and rejoining in clamped and non-clamped transplanted tumours in mice leg after exposure to 80 keV µm−1 carbon ions and X rays. The yields of DSB in the tumours were analysed by a static-field gel electrophoresis. The OER of DSB after X rays was 1.68±0.31, and this value was not changed after 1 h rejoining time (1.40±0.26). These damages in oxygenated conditions were rejoined 60–70 % within 1 h in situ. No difference was found between the exposure to X rays and carbon ions for the induction and rejoining of DSB. Thus, the values of OER and rejoined fraction after exposure to carbon ions were similar to those after X rays, and the calculated relative biological effectivenesses of carbon ion were around 1 under both oxygen conditions. The yields of DSB in vivo depend on exposure doses, oxygen conditions and rejoining time, but not on the types of radiation quality. [ABSTRACT FROM PUBLISHER]

Objectives: Programmed cell death ligand 1 (PD-L1) expression is widely used to predict the effectiveness of PD-(L)1 inhibitors despite its imperfection. Previous studies suggested the utilization of various serum biomarkers; nonetheless, findings are inconclusive because of limited sample sizes or the focus on a single biomarker in many of these studies. This study analyzed multiplex serum biomarkers to explore their predictive ability in a large cohort of patients with advanced non-small-cell lung cancer (NSCLC) treated with a PD-L1 inhibitor in a real-world setting., Materials and Methods: This was a sub-study of J-TAIL, a prospective observational study of atezolizumab monotherapy in pre-treated patients with advanced NSCLC. From April to October 2019, 262 patients were enrolled from 73 sites in Japan. Serum samples were collected at baseline and at the second dose of atezolizumab. Quantification of the 51 serum cytokines, chemokines, growth factors, and vascular endothelial growth factors was performed using the Luminex platform. Baseline values and fold changes of the time of the second dose to the baseline were examined in association with the effectiveness of atezolizumab., Results: Among the 51 proteins assessed, a higher baseline interleukin (IL)-12 level, a higher soluble CD40 ligand fold change, a lower IL-8 fold change were associated with higher objective response rate (ORR). Of these, only the lower IL-8 fold change was associated with better progression-free survival (PFS) (adjusted hazard ratio, 1.98; 95 % confidence interval, 1.45-2.70; P < 0.01). Multivariate analysis demonstrated that the lower IL-8 fold change was an independent factor for both the ORR and PFS. The IL-8 fold change was independent of the neutrophil/lymphocyte ratio, and durable PFS was observed in patients with both low., Conclusion: Comprehensive serum biomarker analysis revealed that a lower fold change in serum IL-8 was associated with better outcomes in pre-treated patients with advanced NSCLC receiving atezolizumab., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hiroaki Akamatsu has received grants or contracts from Amgen, Eli Lilly, and Chugai; payment or honoraria for lectures, presentations, speaker’s bureau, manuscript writing, or educational events from Amgen, Ono, AstraZeneca, Pfizer, Boehringer Ingelheim, Takeda, Bristol Myers Squibb, Taiho, Chugai, Eli Lilly, MSD, Nippon Kayaku, and Novartis; and has participated in Data Safety Monitoring Boards or Advisory Boards for Amgen and Janssen. Yasuhiro Koh has received grants or contracts from Daiichi Sankyo, AstraZeneca, Boehringer Ingelheim, Takeda, Zeon, and Chugai; payment or honoraria for lectures, presentations, speaker’s bureau, manuscript writing, or educational events from Amgen, Takeda, Chugai, Guardant Health, CytoGen, Tosoh, and Novartis; and has participated in Data Safety Monitoring Boards or Advisory Boards for Tosoh. Makoto Nishio has received payment or honoraria for lectures from Ono, Chugai, Taiho, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, AstraZeneca, MSD, AbbVie, Takeda, Pfizer, Boehringer Ingelheim, Novartis, Nippon Kayaku, Merck, and Janssen. Yasushi Goto has received grants or contracts from AstraZeneca, and Pfizer; grants for the institution from AbbVie, Eli Lilly, Bristol Myers Squibb, Ono, Novartis, Kyorin, Daiichi Sankyo, Novartis, and Preferred Network; payment or honoraria for lectures, presentations, speaker’s bureau, manuscript writing, or educational events from Eli Lilly, Chugai, Taiho, Boehringer Ingelheim, Ono, Bristol Myers Squibb, Pfizer, MSD, Novartis, Merck, and Thermo Fisher; has participated in Data Safety Monitoring Boards or Advisory Boards for AstraZeneca, Chugai, Boehringer Ingelheim, Eli Lilly, Taiho, Pfizer, Novartis, Guardant Health, Illumina, Daiichi Sankyo, Ono, Bristol Myers Squibb, and MSD; and had a leadership or fiduciary role in Cancer Net Japan and JAMT. Hidetoshi Hayashi has received grants or contracts from IQVIA Services, Syneos Health, EPS Corporation, Nippon Kayaku, Takeda, MSD, Amgen, Taiho, Bristol Myers Squibb, Janssen, CMIC, Pfizer, Labcorp Drug Development, Kobayashi, Eisai, EP-CRSU, Shionogi, Otsuka, GlaxoSmithKline, Sanofi, Chugai, Nippon Boehringer Ingelheim, SRL Medisearch, PRA Health Sciences, Astellas Pharma, Ascent Development Services, Bayer Yakuhin, Parexel, Kissei, EPS Corporation, Daiichi Sankyo, Ono, PPD-SNBL, SymBio, Mebix, AstraZeneca, Mochida, Japan Clinical Research Operations, Eli Lilly, Novartis, Otsuka, and SRL; payment or honoraria for lectures, presentations, speaker’s bureau, manuscript writing, or educational events from Ono, Daiichi Sankyo, AstraZeneca, Eli Lilly, Chugai Pharmaceutical, MSD, Pfizer, Nippon Boehringer Ingelheim, Merck, 3H Clinical Trial, Novartis, Bristol Myers Squibb, Amgen, Sysmex Corporation, Takeda, and Guardant Health. Satoru Miura has received payment or honoraria for lectures from Chugai, Taiho, Ono, AstraZeneca, Bristol Myers Squibb, Eli Lilly, Boehringer Ingelheim, and Takeda. Hiroshi Kagamu has received payment or honoraria for lectures from Chugai, Ono, AstraZeneca, and Bristol Myers Squibb. Ichiro Yoshino has received grants or contracts from AstraZeneca, Chugai, Daiichi Sankyo, and Taiho; consulting fees from AstraZeneca, Chugai, Covidien, and Johnson & Johnson; and payment or honoraria for lectures from AstraZeneca, Chugai, Daiichi Sankyo, Eli Lilly, Covidien, Johnson & Johnson, Taiho, Amgen, MSD, CSL Behring, KM Biologics, Intuitive Surgical, Shionogi, Tsumura, and Takeda. Toshihiro Misumi has received honoraria for lectures, presentations, speaker’s bureau, manuscript writing, or educational events from Chugai, AstraZeneca, and Miyarisan. Atsuto Mouri has received payment or honoraria for lectures from Chugai. Noriko Yanagitani has received consulting fee from Chugai and payment or honoraria for lectures from AstraZeneca, Eli Lilly, Pfizer, Chugai, Takeda, Bayer Yakuhin, Ono, and Bristol Myers Squibb. Hiroshi Nokihara has received payment or honoraria for lectures from MSD, Ono, AstraZeneca, and Chugai. Masahiro Seike has received payment or honoraria for lectures from Chugai, AstraZeneca, Bristol Myers Squibb, Pfizer, Takeda, Nippon Kayaku, Merck Biopharma, MSD, Taiho, Ono, Nippon Boehringer Ingelheim, Novartis, Kyowa-Kirin, and Daiichi-Sankyo. Masahide Mori has received research funding from Chugai, Ono, MSD, and Delta-fly; and payment or honoraria for lectures from AstraZeneca, Boehringer Ingelheim, MSD, Eli Lilly, Novartis, Chugai, Taiho, Kyowa-Kirin, Ono, Otsuka, Nihon-Kayaku, Pfizer, Daiichi Sankyo, Takeda, and Shionogi. Tetsuya Mitsudomi has received grants or contracts from MSD, Ono, AstraZeneca, and Chugai; payment or honoraria for speaker’s bureau from MSD, Ono, Bristol Myers Squibb, AstraZeneca, and Chugai; has participated in Advisory Boards for MSD, Ono, Bristol Myers Squibb, AstraZeneca, and Chugai; and has been a President at IASLC. The remaining authors have no conflict of interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Infantile traumatic brain injury (TBI) with a biphasic clinical course and late reduced diffusion (TBIRD) has recently been reported as a distinct type of TBI in infancy. However, the pathological and prognostic factors of TBIRD remain unknown. We aimed to compare patients with and without TBIRD and evaluate the pathomechanism of TBIRD using magnetic resonance spectroscopy (MRS)., Methods: Ten Japanese patients with TBI were admitted to our hospital and underwent MRS between September 2015 and September 2022 (age range, 3-15 months; median age, 8.5 months). TBIRD was diagnosed in six patients. MRS data were compared among patients with TBIRD, patients without TBIRD, and controls. Neurological prognosis was classified into grades 1 (normal) to 3 (severe)., Results: In patients with TBIRD, MRS revealed an increase in the glutamine (Gln) level on days 3-29, which subsequently became close to normal. The degree of Gln elevation in the non-TBIRD group was smaller (117-158 % of controls) than that in the TBIRD group (210-337 %) within 14 days. MRS in the TBIRD group showed decreased N-acetyl aspartate (NAA) concentrations. The degree of NAA decrease was more prominent in grade 3 than in grades 1 and 2. NAA levels in the non-TBIRD group were almost normal., Conclusions: Patients with TBI and markedly elevated Gln levels on MRS may develop TBIRD. Neuro-excitotoxicity is a possible pathological mechanism of TBIRD. Decreased NAA levels may be useful for predicting the prognosis of patients with TBIRD., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Many clinical studies showed a synergy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) and vascular endothelial growth factor inhibitors. We hypothesized afatinib plus bevacizumab exerts clinical potency after developing various osimertinib resistant mechanisms., Methods: EGFR-mutant non-small cell lung cancer patients were enrolled after osimertinib resistance. Afatinib at 30-40 mg/day and bevacizumab at 15 mg/kg tri-weekly were administered until progression. Plasma/histologic rebiopsied samples after osimertinib failure were analyzed to examine resistant mechanisms: gene alterations/copy-number gain using cancer personalized profiling by deep sequencing., Results: Between January 2018 and October 2020, 28 patients were enrolled. Response and disease control rates were 17.9 % and 78.6 %, respectively. Median duration of response was 9.0 (range, 4.2-22.3) months. Median progression-free and overall survivals were 2.7 and 9.3 months, respectively. Twenty-eight (100 %) plasma and/or 21 (75 %) histologic rebiopsies identified: 17 (61 %) TP53; 15 (54 %) T790M; 9 (32 %) uncommon EGFR; 9 (32 %) MET; 6 (21 %) C797S; 3 (11 %) BRAF; 2 (7 %) HER2; 2 (7 %) KRAS; and 2 (7 %) PI3K mutations. One (17 %) of 6 C797S patients showed complete response. Three (33 %) of 9 uncommon EGFR-mutated patients achieved radiographic response. Neither 15 T790M-positive nor 6 EGFR downstream signaling mutations: BRAF; KRAS; or PI3K-positive patients responded, but 5 (38 %) of 13 T790M-negative patients responded. Adverse events ≥ grade 3 and incidence ≥ 5 % were: hypertension (29 %); proteinuria (7 %); and diarrhea (7 %). There were neither treatment-related death nor interstitial lung disease., Conclusions: Selected population could obtain clinical benefit from afatinib plus bevacizumab, based on rebiopsy results after osimertinib resistance., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Akito Hata: grants from MSD, Eli Lilly, Chugai, Taiho, Boehringer Ingelheim, AstraZeneca, AbbVie, and personal fees from AstraZenaca, Eli Lilly, MSD, Chugai, Pfizer, Boehringer Ingelheim, Taiho. Nobuyuki Katakami: grants from MSD, Ono, Delta-Fly, AstraZeneca, AbbVie, Chugai, and personal fees from Ono, Chugai, Pfizer, AstraZeneca, Boehringer Ingelheim, Taiho, MSD, Novartis, Bristol-Myers Squibb, Takeda, GlaxoSmithKline. Naoto Takase: personal fees from Taiho, Eisai, Merck, MSD, AstraZeneca, Nippon Kayaku, Eli Lilly, Ono, Bristol-Myers Squibb, Eisai, Daiichi-Sankyo, Boehringer Ingelheim, Chugai, Takeda, and Kyorin. Motohiro Tamiya: grants from Boehringer Ingelheim, MSD, Eisai, Janssen, Ono, Daiichi-Sankyo, Chugai, and personal fees from Boehringer Ingelheim, AstraZeneca, Eli Lilly, Asahikasei, Bristol-Myers Squibb, Amgen, Daiichi-Sankyo, Chugai, Taiho, Pfizer Ono, MSD, Kyowa-Kirin. Masahide Mori: grants from Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Delta-fly, MSD, Janssen, Ono, and personal fees from Astrazeneca, Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Eli Lilly, Kyowa-kirin, MSD, Nippon Kayaku, Novaritis, Ono, Otsuka, Pfizer, Shionogi, Taiho, Takeda. Takashi Kijima: grants from Chugai, Taiho, GlaxoSmithKline, and personal fees from Chugai, AstraZeneca, Ono, Bristol-Myers Squibb, and GlaxoSmithKline. Satoshi Morita: personal fees from AstraZeneca, Bristol-Myers Squibb, Chugai, Eli Lilly, MSD, Pfizer, and Boehringer Ingelheim. Kazuko Sakai: personal fees from Hitachi, Life Technologies, Chugai, Takeda, and Qiagen. Kazuto Nishio: grants from Boehringer Ingelheim, West Japan Oncology Group, Clinical Research Support Center Kyushu, Nichirei Biosciences, Eli Lilly, Hitachi, Sysmex, Otsuka, consulting fees from SymBio, Solasia, Eli Lilly, Otsuka, and personal fees from Chugai, Pfizer, Eli Lilly, MSD, Novartis, AstraZeneca, Amgen, Merck, Roche Diagnostics, Yakult, Guardant Health, Takeda, Boehringer Ingelheim, Fujirebio, Bristol-Myers Squibb, Merck, Janssen, Daiichi-Sankyo, Ono. All other authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Real-world, large-scale studies on the association between immune-related adverse events (irAE) and immune checkpoint inhibitor therapy effectiveness are limited. We evaluated overall survival (OS) and progression-free survival based on the occurrence and grade of irAEs., Patients and Methods: We used data from Japanese patients with unresectable advanced or recurrent non-small cell lung cancer (NSCLC) who received atezolizumab and were enrolled in J-TAIL, a multicenter, prospective, single-arm observational study., Results: Among the 1,002 patients, 190 (19.0%) developed irAEs. The most common irAEs were skin disorders (3.8%) of any grade and interstitial lung disease (1.5%) of grade ≥3. Patients who developed irAEs within 4 or 6 weeks of treatment initiation had higher baseline C-reactive protein levels than those without irAEs. OS was longer in patients with irAEs [HR, 0.66; 95% confidence interval (CI), 0.54-0.82], particularly in those with low-grade irAEs (HR, 0.45; 95% CI, 0.33-0.62), than in patients without irAEs. The HR (95% CI) for OS in patients with low-grade and high-grade skin or endocrine disorder-related irAEs was 0.42 (0.28-0.64) and 0.37 (0.15-0.88), respectively. The HR (95% CI) for OS in patients with low-grade and high-grade irAEs other than skin or endocrine disorders was 0.44 (0.30-0.65) and 1.27 (0.96-1.69), respectively., Conclusions: In patients with unresectable advanced or recurrent NSCLC treated with atezolizumab in real-world settings, irAEs are associated with a clinical benefit except in those with high-grade irAEs other than skin and endocrine disorders., Significance: Immune checkpoint inhibitors are useful for treating NSCLC but can cause life-threatening irAEs. This study had a large sample size and stratified the analysis by irAE type and grade. The results suggest that improved management of irAEs may improve the therapeutic effect of atezolizumab., (©2024 The Authors; Published by the American Association for Cancer Research.)

Background: The survival benefit of adjuvant chemotherapy after surgical resection of oligometastases from colorectal cancer (CRC) remains unclear. The prognostic role of circulating-tumor DNA (ctDNA) was reported recently and a risk stratification strategy based on monitoring minimal/molecular residual disease (MRD) has been proposed, however, which drug regimen is most effective for ctDNA-positive patients is unknown., Methods/design: Oligometastatic CRC patients planning to undergo surgery were registered in this study. After metastasectomy, the registered patients were enrolled in the treatment arm, in which 8 courses of modified-FOLFOXIRI (mFOLFOXIRI; irinotecan 150 mg/m 2 , oxaliplatin 85 mg/m 2 , l-leucovorin (l-LV) 200 mg/m 2 , and 46-h continuous infusion of 5-fluorouracil (5-FU) 2400 mg/m 2 every 2 weeks) followed by 4 courses of 5-FU/l-LV are administered. The patients who did not meet the eligibility criteria for the treatment arm or did not consent to mFOLFOXIRI enrolled in the observation arm in which standard of care treatment is provided. Prospective blood collections for retrospective ctDNA analysis are scheduled pre-surgery, and at 28 days, 4 and 7 months after surgery. The primary endpoint is treatment compliance at 8 courses of mFOLFOXIRI and the key secondary endpoints are the ctDNA-positivity rate and survival outcomes in ctDNA-positive and -negative groups. A total of 85 patients will be enrolled from 11 institutions. First patient-in was on July 2020. Accrual completed in February 2024., Discussion: This study will potentially identify a better treatment strategy for patients with resectable oligometastatic CRC having postsurgical ctDNA positivity, compared to the current standard of care approaches., Competing Interests: Conflicts of Interest Kozo Kataoka receives honoraria from Merck, Takeda, and Eli Lilly, and research grant from Japanese Society of Clinical Oncology. Kentaro Yamazaki receives lecture fees from Merck Biopharma, Takeda, Chugai, Taiho, Yakult, Ono, Eli Lily, MSD and Bristol. Keita Mori receives lecture fees from Chugai, Ono, Daiichi Sankyo and Eli Lilly. Nobuhisa Matsuhashi receives honoraria from Abbott, AMCO, Asahi Kasei Pharma, AstraZeneca, Bayer Yakuhin, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, EA Pharma, Eisai, Eli Lilly, Gunze Medical Limited, Kaken Pharm., Kyowa Kirin, MC Medical, Merck Biopharma, Miyarisan Pharm., MSD, Novartis, Ono, Taiho, Takeda Pharm., TERUMO, Tsumura, Viatris, Yakult Honsha; research funding from Daiichi Sankyo, EP-CRSU, EPS Corporation, MSD, Ono Pharm., ShiftZero K.K., Taiho Pharm. Masahiro Goto receives honoraria from Daiichi Sankyo, MSD, Taiho, and Ono Pharm and research funding from Taiho, Chugai Pharma and Nippon Kayaku. Manabu Shiozawa received lecture fees from Merck Biopharma, Takeda, Yakult Honsha, Ono Pharmaceutical, and Eli Lilly. Shruti Sharma, Joe Ensor, Adham Jurdi and Minetta C. Liu are employees at Natera, Inc. with stock or option to own stock. Minetta C. Liu received grants (funding to Mayo Clinic) from Eisai, Exact Sciences, Genentech, Genomic Health, GRAIL, Menarini Silicon Biosystems, Merck, Novartis, Seattle Genetics, and Tesaro; travel support from AstraZeneca, Genomic Health, and Ionis; and Ad hoc advisory board meetings (all funds to Mayo Clinic): AstraZeneca, Celgene, Roche/Genentech, Genomic Health, GRAIL, Ionis, Merck, Pfizer, Seattle Genetics, Syndax. Masataka Ikeda receives honoraria from Taiho, Bayer, Pfizer, and consulting fee from Daiichi Sankyo. The remaining authors have declared no conflict of interest., (Copyright © 2024 The Japan Society of Coloproctology.)

Background: Spatial and temporal heterogeneities of RAS and other molecular genes should be considered in the treatment of metastatic colorectal cancer (mCRC) treated with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs); acquired RAS mutation is sometimes observed at disease progression of treatment with the anti-EGFR mAb. At the same time, discrepancy of RAS status from tissues and circulating tumor DNA (ctDNA) in the same patient is sometimes observed. Based on this, we commenced two observational studies to clarify these heterogeneities of RAS and BRAF in mCRC, using next generation sequencing from liquid biopsy., Methods/design: RAS-trace study is an observational study to monitor ctDNA RAS/BRAF/PIK3CA status every 4-12 weeks using the Plasma-SeqSensei™ CRC RUO Kit (Sysmex Inostics GmbH) in mCRC with RAS/BRAF wild-type (wt) on tumor tissue. The primary endpoint was the time to the acquired RAS mutations. A total of 42 patients has been accrued. RAS-trace-2 study is also an observational study aimed at comparing the efficacy of the anti-EGFR mAb in ctDNA RAS/BRAF wt with ctDNA RAS or BRAF mutant mCRC patients, whose RAS/BRAF are wt in tumor tissue. The primary endpoint was progression-free survival in patients with ctDNA RAS/BRAF wt and RAS or BRAF mutant. A total of 240 patients will be accrued over 2 years., Discussion: These trials will help us understanding the clinical significance of spatial and temporal heterogeneities of RAS, BRAF and other genes, while optimizing the anti-EGFR mAb treatment strategies in mCRC., Competing Interests: Conflicts of Interest KK received lecture fees from Merck, Takeda, and Eli Lilly, and research funds from Sysmex Corporation. JF is an employee of the Sysmex Inostics GmbH. MS received lecture fees from Merck, Takeda, Yakult, Ono, and Eli Lilly. JW received lecture fees from Eli Lilly and Takeda. TK received lecture fees from Daiichi Sankyo, Taiho, Bristol-Myers Squibb, Ono, and Eli Lilly. NM received lecture fees from Takeda and scholarship endowments from Yakult. KY received lecture fees from Merck, Takeda, Chugai, Taiho, Yakult, Ono, Eli Lily, MSD and Bristol. KM received lecture fees from Chugai, Ono, Daiichi Sankyo and Eli Lilly. The rest of the authors do not have any conflicts of interest., (Copyright © 2024 The Japan Society of Coloproctology.)

Background: Infantile traumatic brain injury (TBI) with a biphasic clinical course and late reduced diffusion (TBIRD) has been reported as a type of TBI. However, it remains uncertain which pediatric patients with TBI develop TBIRD., Methods: Patients with TBI who were admitted to our hospital and underwent magnetic resonance imaging (MRI) between December 2006 and October 2022 were included in this study. A diagnosis of TBIRD was made in patients with or suspected TBI, with initial symptoms being convulsions or disturbance of consciousness and late-onset subcortical reduced diffusion, the so-called bright tree appearance. Clinical features, neuroimaging (computed tomography (CT) and MRI) findings, laboratory data, and Tada score were retrospectively compared between TBIRD and non-TBIRD patients. Neurological prognosis was assessed using the Pediatric Cerebral Performance Category scale., Results: Of 21 patients who met the inclusion criteria, a diagnosis of TBIRD was made in 7 patients (median age: 8 months). The factors contributing to TBIRD development were seizures lasting over 30 min as the initial symptom (5/7 in TBIRD vs. 0/14 in non-TBIRD), tracheal intubation during initial treatment (5/7 vs. 0/14), and brain parenchymal lesions on CT (3/7 vs. 0/14), suggesting that severe TBI may progress to TBIRD. The Tada score was more positive in patients with TBIRD (6/7) than in those without (0/14)., Conclusions: It is important to monitor infant patients with severe TBI for the development of TBIRD. The Tada score can be a useful tool for TBIRD prediction., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Primary cardiac angiosarcomas are extremely rare and their prognosis is poor. Surgical resection is the first-line treatment; however, no clear standard of care has been clearly established because of the rarity of these tumors., Case Presentation: A 61-year-old man who had presented with dyspnea on exertion was referred to our hospital. Contrast-enhanced computed tomography revealed massive pericardial effusion and a 40-mm enhanced mass adherent to the anterior wall of the right atrium and involving the right coronary artery. Having diagnosed the mass as a cardiac tumor, we resected the mass under the guidance of epi-cardiac echocardiography guidance, which showed continuity between the tumor and the right atrium, reconstructed the right atrial free wall with a bovine pericardial patch, and performed coronary artery bypass grafting to the right coronary artery using the great saphenous vein. The right atrial wall was resected with adequate tumor-free margin. On the right ventricular side, we resected the right atrial wall 1 cm from the tumor, 2 cm from the atrioventricular groove. Because hemodynamic deterioration occurred after aortic declamping, intra-aortic balloon pumping and veno-arterial extracorporeal membrane oxygenation were instituted. Postoperatively, circulatory support devices were removed safely, and the patient was discharged on the 25th postoperative day. Histopathological examination of the surgical specimens resulted in a diagnosis of angiosarcoma, with positive surgical margins. Chemotherapy and radiotherapy (69 Gy in 30 fractions) were therefore initiated after discharge. To date, the patient has been alive and well with no recurrence of tumor for 4 years and 10 months since surgery., Discussion: This case study suggests the usefulness of multimodality treatment comprising surgical resection and adjuvant therapy, for cardiac angiosarcoma., (© 2023. The Author(s).)

Background: Zoledronic acid (ZA) reduces the incidence of skeletal-related events (SREs) in patients with bone metastases from solid tumors. However, the optimal dosing interval of ZA for patients with lung cancer is uncertain., Methods: We conducted a randomized, open-label, feasibility phase 2 trial at eight Japanese hospitals. Patients with bone metastases from lung cancer were randomly assigned to receive either 4 mg of ZA every four weeks (4wk-ZA) or every eight weeks (8wk-ZA). The primary endpoint was the time to the first SRE and the rate and types of SREs after one year. SREs were defined as pathologic bone fracture, bone radiation therapy or surgery, and spinal cord compression. Secondary endpoints were the SRE incidence at six months, pain assessment, changes in analgesic consumption, serum N-telopeptide, toxicity, and overall survival., Results: Between November 2012 and October 2018, 109 patients were randomly assigned to the 4wk-ZA group (54 patients) and the 8wk-ZA group (55 patients). The number of patients who received chemotherapy or molecular-targeted agents was 30 and 23 and 18 and 16 in the 4wk-ZA and 8wk-ZA groups, respectively. The median time to the first SRE could not be calculated because of a low SRE. The time to the first SRE of all patients did not differ between the groups (P = 0.715, HR = 1.18, 95% CI = 0.48, 2.9). The SRE rate of all patients after 12 months was 17.6% (95% CI = 8.4, 30.9%) in the 4wk-ZA and 23.3% (95% CI = 11.8, 38.6%) in the 8wk-ZA group, without significant differences between the groups. There was no difference in any secondary endpoint between groups, and these endpoints did not differ among treatment modalities., Conclusions: An eight-week ZA interval does not increase the SRE risk for patients with bone metastasis from lung cancer and could be considered clinically., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Takashi Nishimura, Yu Hidaka, Akito Hata, Tomonori Hirashima, Naoto Takase, Hisashi Ohnishi, Satoshi Morita, Yukimasa Hatachi; no conflict of interest with this manuscript. Masahide Mori, Toshihiko Kaneda, Kazumi Nishino and Nobuyuki Katakami(、)received lecture fees from Novartis Pharmaceutical. Nobuyuki Katakami received Kobe City General Hospital Scientific Fund., (Copyright © 2023. Published by Elsevier B.V.)

Primary brain calcification (PBC), also known as idiopathic basal ganglia calcification (IBGC), primary familial brain calcification (PFBC) and so on, is a rare intractable disease characterized by abnormal mineral deposits, including mostly calcium in the basal ganglia, thalamus, and cerebellum. The causative gene of familial PBC is SLC20A2, which encodes the phosphate transporter PiT-2. Despite this knowledge, the molecular mechanism underlying SLC20A2-associated PBC remains unclear. In the present study, we investigated whether haploinsufficiency or a dominant-negative mechanism reduced Pi uptake in two PiT-2 variants (T115 M and R467X). We demonstrated that the presence of T115 M or R467X had no dominant-negative effect on Pi transport activity of wild-type (WT). In addition, the subcellular localization of R467X completely differed from that of WT, indicating that there is no interaction between R467X and WT. Conversely, T115 M and WT showed almost the same localization. Therefore, we examined the interaction between T115 M and WT using the bioluminescence resonance energy transfer (BRET) method. Although WT and T115 M interact with each other, T115 M does not inhibit WT's Pi transport activity. These results suggest that the role of SLC20A2 in the pathogenesis of PBC may involve decreased intracellular Pi uptake by a haploinsufficiency mechanism rather than a dominant-negative mechanism; agents promoting PiT-2 dimerization may be promising potential therapeutic agents for PBC., Competing Interests: Declaration of competing interest The authors declared no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: A number of Farmer-type ionization chambers were tested against storage humidity to confirm whether they satisfied the criteria for the long-term stability of reference-class ionization chambers., Methods: The ionization chambers were stored for several months in an environment with relative humidity adjustable from 20% to 80%. The ionization chambers were removed from the storage environment at variable intervals ranging from 1 to 70 days and irradiated in a Co-60 radiation beam. The responses for each ionization chamber were evaluated from the measured currents corrected for the atmospheric air density, and were compared with those predicted by the Co-60 half-life., Results: Certain ionization chambers gave a constant relative response regardless of the storage humidity, while the relative responses of two types of ionization chambers changed as a function of the storage humidity. The difference between the relative responses for the low (20-30%) and high (70-80%) storage relative humidity was ∼ $\sim$ 0.7%. The response was larger for the high relative humidity storage. Immediately after the storage humidity changed, the relative response started to change by the day, and it took approximately 2 weeks to 2 months for the relative response to converge. For one type of the ionization chamber, the plastic outer wall and the outer electrode were replaced with those made of solid graphite, and it was confirmed that the remodeled ionization chamber did not exhibit the response change., Conclusions: The present results and previous reports by other authors indicate that the magnitude of the change depends on the magnitude of the water absorption of the plastic used for the outer wall and/or the electrode of the ionization chamber. Thus, it is important in the selection of the reference-class ionization chamber to note the material and structure of the outer wall and electrode of the ionization chamber. If the ionization chamber has a hygroscopic wall and electrode and it is used as a reference ionization chamber, it is necessary to pay additional attention to the humidity difference for the storage, daily irradiation, and yearly calibration especially in regions with large seasonal humidity fluctuations., (© 2022 American Association of Physicists in Medicine.)