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Anticancer drug therapy for cancer is developing rapidly, including molecular-targeted drugs and immune checkpoint inhibitors that are used in clinical settings in addition to conventional cytotoxic drugs. In daily clinical practice, clinicians sometimes encounter situations in which the effects of these chemotherapeutic agents are considered unacceptable in high-risk patients with liver or renal dysfunction, those undergoing dialysis and older adults. There is no clear evidence regarding anticancer drugs administration to patients with renal dysfunction. However, there are indications for dose setting based on the theory of the renal function responsible for drug excretion and past administration experience. This review outlines anticancer drugs’ administration in patients with renal dysfunction.

Comprehensive cancer genome profiling (CGP) has been nationally reimbursed in Japan since June 2019. Less than 10% of the patients have been reported to undergo recommended treatment. Todai OncoPanel (TOP) is a dual DNA–RNA panel as well as a paired tumor–normal matched test. Two hundred patients underwent TOP as part of Advanced Medical Care B with approval from the Ministry of Health, Labour and Welfare between September 2018 and December 2019. Tests were carried out in patients with cancers without standard treatment or when patients had already undergone standard treatment. Data from DNA and RNA panels were analyzed in 198 and 191 patients, respectively. The percentage of patients who were given therapeutic or diagnostic recommendations was 61% (120/198). One hundred and four samples (53%) harbored gene alterations that were detected with the DNA panel and had potential treatment implications, and 14 samples (7%) had a high tumor mutational burden. Twenty‐two samples (11.1%) harbored 30 fusion transcripts or MET exon 14 skipping that were detected by the RNA panel. Of those 30 transcripts, 6 had treatment implications and 4 had diagnostic implications. Thirteen patients (7%) were found to have pathogenic or likely pathogenic germline variants and genetic counseling was recommended. Overall, 12 patients (6%) received recommended treatment. In summary, patients benefited from both TOP DNA and RNA panels while following the same indication as the approved CGP tests. (UMIN000033647). Todai OncoPanel (TOP) is a dual DNA‐RNA panel as well as a paired tumor‐normal matched test. Pharmaceuticals and Medical Devices Agency (PMDA) indications for comprehensive cancer genomic profiling were followed in this study. The percentage of patients who were given therapeutic or diagnostic recommendations was 61%, including patients with fusion or MET exon 14 skipping transcripts that led to recommendations.

Programmed death (PD)‐1/PD‐ligand 1 (PD‐L1) antibodies have shown an intense clinical effect in some patients with PD‐L1+ tumors, and their applications have rapidly expanded to various cancer types with or without the application of new companion diagnostics (CDx) with a lower cutoff value and inclusion of macrophage evaluation. However, the pathological background explaining the difference in the cutoff value remains unknown. To address this, we evaluated tissue array samples from 231 patients with lung adenocarcinoma, 186 with lung squamous cell carcinoma, and 38 with renal cell carcinoma (RCC) who were not receiving PD‐1/PD‐L1 antibodies to investigate the relationship between PD‐L1 expression on tumor cells and CD8+ T‐cell infiltration in tumor tissues. PD‐L1 expression in RCC was clearly lower than that in non–small‐cell lung cancer (NSCLC) tissue, whereas CD8+ T‐cell infiltration was low in all cancers. We next analyzed PD‐L1 expression by interferon (α, β, and γ) and LPS stimulation in both macrophages and 41 cancer cell lines derived from various organs and histological types. The PD‐L1 expression patterns were classified into three types, which differed depending on each organ or tissue type. Interestingly, NSCLC cell lines showed highly diverse PD‐L1 expression patterns compared with RCC cell lines. Conversely, PD‐L1 expression was stronger and more prolonged in macrophages than in typical cell lines. Here, we revealed the diversity of the PD‐L1 expression patterns in tumor cells and macrophages, demonstrating the pathological and cytological significance of the transition of cutoff values in PD‐L1 CDx for PD‐1/PD‐L1 antibody administration. The diversity of PD‐L1 expression patterns in tumor cell lines and macrophages explains the differences in cutoff values for PD‐L1 companion diagnostics for different organs and tissue types. we evaluated tissue array samples from 231 patients with lung adenocarcinoma, 186 with lung squamous cell carcinoma, and 38 with renal cell carcinoma. We also analyzed PD‐L1 expression in macrophages and 41 cancer cell lines derived from various organs and histological types.

Furthermore, her anti-nuclear antibodies and anti-neutrophil cytoplasmic antibody were negative. [...]the diagnosis of G-CSF-associated aortitis was made, and treatment with 60 mg of intravenous methylprednisolone (1·0 mg/kg/day) was initiated. Typical clinical features include fever, chest or back pain, elevated leukocyte count and C-reactive protein level, and contrast-enhanced wall thickening of the aorta on CT scan. [...]it is essential to consider the possibility of G-CSF-associated aortitis in patients on chemotherapy.

PurposeRhabdomyolysis, which is primarily characterized by serum creatine kinase (CK) elevation, is a potentially fatal disease, and it can occur in a variety of etiologies, including drug-induced. Cabozantinib is one of the standard treatments for patients with renal cell carcinoma (RCC). This retrospective case series aimed to investigate the frequency of cabozantinib-induced CK elevation and rhabdomyolysis, and to reveal their detailed clinical features.MethodsTo investigate the frequency of cabozantinib-induced serum CK elevation and rhabdomyolysis, we retrospectively reviewed the clinical information and laboratory data of the patients with advanced RCC who received cabozantinib monotherapy at our institution from April 2020 to April 2023. Data were retrieved from the electronic medical records and the RCC database of our institution. Primary endpoint of the current case series was the frequency of CK elevation and rhabdomyolysis.ResultsSixteen patients were retrieved form the database and 13 were included in the case series (excluded by clinical trial enrollment [n = 2] and short-term administration [n = 1]). Eight (61.5%) patients among them experienced serum CK elevation, including five patients who were classified into grade 1. CK elevation occurred a median of 14 days after initiation of cabozantinib. Two patients with grade 2 or 3 of CK elevation developed rhabdomyolysis with muscle weakness and/or acute kidney injury.ConclusionsCK elevation may frequently happen during cabozantinib treatment, and in most cases, it may be asymptomatic and may not be clinically problematic. However, medical providers should be aware that symptomatic CK elevations suggestive of rhabdomyolysis may occasionally occur.

PurposeCumulative sensory neurotoxicity induced by oxaliplatin impairs patients’ quality of life and treatment continuation. This study investigated the relationship between physician-assessed and patient-reported oxaliplatin-induced peripheral neuropathy (OIPN) during treatment of metastatic colorectal cancer (mCRC) over time.MethodsA post hoc analysis was conducted for 191 patients with mCRC who received mFOLFOX6 plus bevacizumab in the WJOG4407G trial. Physician-assessed OIPN was graded by CTCAE every 2 weeks. Patient-reported OIPN was assessed with the FACT/GOG-Ntx (11 items, best score 44) at baseline and at 3, 6, and 9 months. Physician underestimation was defined as when the highest scores of the NTX1–4 sensory subscale/CTCAE grade were 2/0, 3/0–1, or 4/0–1, and overestimation as 0/2–3, 1/2–3, or 2/3.ResultsThe median total dose (range) of oxaliplatin was 762 (85–5950) mg/m2. Overall, the least squares mean of FACT/GOG-Ntx scores (standard error), estimated by a linear mixed model, were 36 (0.8), 34 (0.9), 29 (1.0), and 27 (1.1) for CTCAE grades 0, 1, 2, and 3, respectively. FACT/GOG-Ntx scores were weakly-to-moderately correlated with CTCAE grade (Spearman’s r = − 0.24 [p = 0.0026], − 0.46 [p < 0.0001], and − 0.56 [p < 0.0001] at 3, 6, and 9 months, respectively). OIPN was underestimated in 85/159 (54%), 43/109 (39%), and 18/69 (26%) patients at 3, 6, and 9 months, respectively. In contrast, OIPN was overestimated in less than 5% of the patients at any time.ConclusionDuring early treatment, physician underestimation of OIPN in patients with mCRC is likely.

Background While denosumab has been shown to prevent skeletal-related events in patients with bone metastasis, there is a concern that it may cause atypical femoral fracture (AFF). While AFF has been reported in patients with osteoporosis receiving denosumab, data are scarce in the context of AFF occurring in patients with bone metastasis receiving monthly denosumab therapy. Methods To analyze the incidence of AFF in patients with bone metastasis, we reviewed the medical records of patients who had received monthly denosumab (120 mg) treatment from May 2012 to June 2017 at any of the three participant institutions. Results The study population consisted of 277 patients who had received a median of 10 doses (range, 1–79) of denosumab. Five patients were diagnosed as having AFF or symptomatic atypical femoral stress reaction (AFSR) needing surgical intervention, representing an incidence rate of 1.8% (95% confidence interval, 0.77–4.2). These patients had received 15, 45, 45, 46 or 47 doses of denosumab, respectively. Four of the patients had received prior zoledronic acid treatment. The results of our analysis suggested that long-term use of denosumab, especially for more than 3.5 years, and prior use of zoledronic acid were risk factors for the development of AFF. Conclusions We found the AFF events in 5 patients (1.8%) among 277 cancer patients who had received monthly denosumab (120 mg) treatment. Long-term denosumab treatment and prior zoledronic acid treatment were identified as risk factors for the development of AFF.

Hand-foot skin reaction (HFSR) is a common adverse effect of vascular endothelial growth factor receptor (VEGFR) inhibitors that significantly impacts patients’ quality of life. Prevention and management of HFSR require individualized approaches, but risk factors remain unclear. This study aimed to develop artificial intelligence (AI) models to predict grade ≥ 2 HFSR using clinical data and foot sole images from 93 instances of VEGFR inhibitor administration in 76 patients. Image-based, clinical information-based, and ensemble AI models achieved areas under the curve of 0.550, 0.693, and 0.699, respectively. At a high-specificity cutoff, the ensemble AI had a positive predictive value of 0.824, suggesting potential clinical utility for identifying high-risk patients. Feature importance analysis revealed heavier weight, good performance status, lack of prior VEGFR inhibitor exposure, and baseline skin toxicity as risk factors. These findings represent the first AI-based HFSR prediction models and provide insights for preventive interventions, but further accuracy improvements are needed.

We constructed and analyzed the ground surface displacement associated with the 2016 Kumamoto earthquake sequence using satellite radar interferometry images of the Advanced Land Observing Satellite 2. The radar interferogram generally shows elastic deformation caused by the main earthquakes, but many other linear discontinuities showing displacement are also found. Approximately 230 lineaments are identified, some of which coincide with the positions of known active faults, such as the main earthquake faults belonging to the Futagawa and Hinagu fault zones and other minor faults; however, there are much fewer known active faults than lineaments. In each area, the lineaments have a similar direction and displacement to each other; therefore, they can be divided into several groups based on location and major features. Since the direction of the lineaments coincides with that of known active faults or their conjugate faults, the cause of the lineaments must be related to the tectonic stress field of this region. The lineaments are classified into the following two categories: (1) main earthquake faults and their branched subfaults and (2) secondary faults that are not directly related to the main earthquake but whose slip was probably triggered by the main earthquake or aftershocks. Graphical Abstract Identified linear surface ruptures. Small solid lines show identified linear surface ruptures. Long, narrow orange area shows the InSAR decorrelation zone along the Futagawa fault zone. Small circles and triangles show epicenters from April 14 to April 23, and beach ball diagrams are from JMA ( 2016a , b ). Red lines show surface ruptures identified by field survey (Geological Survey of Japan 2016 ).

The programmed death‐1/programmed death‐ligand 1 (PD‐L1) pathway is a negative feedback pathway that suppresses the activity of T cells. Previous studies reported that high PD‐L1 expression on tumor cells (TC) was associated with poor survival in patients with colorectal cancer; however, the prognostic evaluation of these studies was limited because they included patients at various disease stages. The purpose of the present study was to evaluate the relationship between PD‐L1 status in the immune microenvironment and the clinicopathological features of stage III colorectal cancer. Two hundred and thirty‐five patients were included in the analysis. PD‐L1 expression on TC and tumor‐infiltrating mononuclear cells (TIMC) was evaluated by immunohistochemistry. The median follow‐up of thisi study was 52.9 months. A total of 8.1% of stage III colorectal cancer showed high PD‐L1 expression on TC and 15.3% showed high PD‐L1 expression on TIMC. Patients with high PD‐L1 expression on TC had significantly shorter disease‐free survival (DFS) than patients with low expression (hazard ratio [HR] 2.36; 95% confidence interval [CI], 1.21–4.62; P = 0.012). In addition, patients with high PD‐L1 expression on TIMC were associated with longer DFS than patients with low expression (HR 0.40; 95% CI, 0.16–0.98; P = 0.046). These findings suggest that PD‐L1 expression status may be a new predictor of recurrence for stage III colorectal cancer patients and highlight the necessity of evaluating PD‐L1 expression on TC and TIMC separately in the tumor microenvironment. High PD‐L1 expression on tumor cells was significantly associated with a poor prognosis, whereas high PD‐L1 expression on tumor‐infiltrating mononuclear cells positively affected the prognosis of patients with stage III colorectal cancer.