International Journal of Clinical Oncology最新文献

Background: The safety and efficacy of neoadjuvant FLOT (Fluorouracil, Leucovorin, Oxaliplatin, Docetaxel) and DOS (Docetaxel, Oxaliplatin, S-1) regimens for locally advanced gastric cancer (LAGC) have not been compared.

Methods: Patients with histologically confirmed LAGC (stage ≥ cT3 or cN + , no metastasis) treated between 2017-2021 were retrospectively included and propensity-matched into FLOT (4 cycles, n = 72) and DOS (3 cycles, n = 72) groups. Outcomes included RECIST response, grade 3/4 adverse events, surgical/pathological results, and R0 resection rates, and long-term survival (overall survival [OS] and progression-free survival [PFS]).

Results: RECIST response rates were 41.7% (FLOT) vs. 47.2% (DOS); R0 resection rates were 63.9% vs. 72.2%. No significant differences were observed in operative time, blood loss, hospital stay, histopathological regression (TRG1a: 2.8% vs. 8.3%; TRG1b: 13.9% vs. 16.7%), postoperative morbidity (29.8% vs. 24.5%), or grade 3/4 toxicity (20.8% vs. 13.9%). The 5-year OS rates were 42.7% and 50.4% (p = 0.652), and the PFS rates were 33.7% and 41.4% (p = 0.548) for the FLOT and DOS groups, respectively.

Conclusion: DOS demonstrated no significant but favorable feasibility, safety, and efficacy compared to FLOT in LAGC. Shorter hospital stay with DOS may enhance patient comfort and reduce healthcare burden.

Background: Discussions on do-not-attempt-resuscitation (DNAR) orders are considered critical end-of-life discussions with patients with advanced cancer; however, patients are not necessarily involved in these discussions. Therefore, we aimed to clarify oncologists' practice, perceptions, values, and attitudes regarding DNAR orders and to identify factors associated with oncologists' attitudes toward confirming patients' preference for DNAR orders.

Methods: Oncologists in designated cancer hospitals in Japan were surveyed using a self-administered questionnaire. Multivariate analyses were performed to identify attributes to attitudes toward confirmation of patients' preferences.

Results: Among 688 participating oncologists, 477 (69%) indicated that they would confirm patients' preferences when issuing a DNAR order if they were competent. Independent variables for positive attitudes toward confirming patients' preferences before issuing DNAR orders included "Talking about DNAR is severely distressing for family" (Odds ratio (OR) = 2.459, p < 0.001) and "It is burdensome to prepare for discussions regarding DNAR orders" (OR = 1.450, p = 0.002) and the value "Non-maleficence" (OR = 1.384, p = 0.012). On the other hand, independent variables for negative attitudes included "Patients do not need to know about DNAR if their family members know about it" (OR = 0.329, p < 0.001) and "Talking about DNAR orders is severely distressing for patients" (OR = 0.443, p ≤ 0.001) and the values "Preference of family" (OR = 0.687, p = 0.012), "Lack of training and education on discussing DNAR orders," (OR = 0.731, p = 0.006), and "It is hard to talk about death" (OR = 0.758, p = 0.026).

Conclusion: Oncologists' discomfort talking about death and their perceived distress for patients and their families were associated with their attitudes towards discussions about DNAR orders.

Background: Chemotherapy-induced hiccups are one of the frequently appearing adverse events. Previous reports have suggested that cisplatin (CDDP) combined with dexamethasone and neurokinin 1 (NK1) receptor antagonists is particularly associated with these symptoms. Consequently, we aimed to identify additional factors involved in the development of problematic hiccups during the real-world treatment.

Methods: Patients with thoracic cancer first receiving CDDP-containing treatment (≥ 75 mg/m²) with dexamethasone, palonosetron, and aprepitant were retrospectively assessed (n = 286). The primary endpoint was the evaluation of risk factors for grade ≥ 2 hiccups during the first cycle. Secondary endpoints were the evaluation of factors for all-grade symptoms and the efficacy of rescue medication.

Results: The incidence of grade ≥ 2 hiccups was 32.9%, with all-grade symptoms of 44.8%. Grade 3 severe hiccups were observed in 5.2% of the patients. Most patients (96.8%) received metoclopramide as first-line treatment, and the efficacy of the first medication was confirmed in 59.6% of patients. Multivariate logistic regression analyses identified male sex, baseline hypoalbuminemia, and concomitant bevacizumab as significant risk factors for grade ≥ 2 problematic hiccups (adjusted odds ratio with 95% confidence interval 10.32 [4.38-24.32], P < 0.0001 for males; 2.41 [1.06-5.50], P = 0.04 for hypoalbuminemia; and 3.42 [1.25-9.36], P = 0.02 for concomitant bevacizumab). Moreover, male sex was identified as a singular risk factor for all-grade symptoms (7.94 [4.14-15.22], P < 0.0001).

Conclusion: Our study revealed that male sex, hypoalbuminemia, and concomitant bevacizumab use were significant risk factors for clinically problematic hiccups in patients receiving CDDP-containing treatment along with dexamethasone and NK1 receptor inhibitors for thoracic cancer.

Background: An increased risk of infection has been suggested for patients with triple-negative breast cancer (TNBC) treated with atezolizumab plus nab-paclitaxel based on the IMpassion130 trial.

Methods: This Japanese postmarketing study aimed to compare the incidence of severe infections in patients with TNBC treated with atezolizumab plus nab-paclitaxel versus nab-paclitaxel alone. Anonymized patient records regarding medical claims and laboratory tests were extracted from the Japanese Medical Data Vision database. Patients with a drug index date of November 27, 2019,-May 31, 2022, were included in the analysis. Based on the published literature, severe infections were declared when a patient had a confirmed diagnosis of infection, a hospitalization record, infection as the primary reason for hospitalization, and a record of immunological infection tests. In the sensitivity analysis, the definition of severe infections was modified as a combination of confirmed infection diagnosis and intravenous antibacterial drug prescription records.

Results: Overall, 321 and 319 patients were included in the exposure (atezolizumab plus nab-paclitaxel) and control (nab-paclitaxel alone) groups, respectively. After adjusting for standardized mortality/morbidity ratio weighting, the baseline characteristics were balanced between the groups. The incidence rate ratio (exposure/control) of severe infections was estimated at 3.29 (95% confidence interval [CI]: 0.93-13.53) originally and 1.05 (95% CI: 0.56-1.84) in the sensitivity analysis. Additional analyses supported the appropriateness of the revised definition of severe infections.

Conclusions: Overall, our results did not indicate a significant increase in the risk of severe infections with atezolizumab plus nab-paclitaxel in daily clinical practice. Further research is required.

Background: Hand-foot syndrome (HFS) and hand-foot skin reaction (HFSR) are adverse effects induced by cytotoxic chemotherapeutic agents, such as capecitabine, pegylated liposomal doxorubicin, and multi-kinase inhibitors. HFS/HFSR can significantly reduce patients' quality of life and impact cancer treatment intensity due to severe pain in the hands and feet. Although several recommendations and guidelines have been published, most focus on European and American populations, with no management guidelines specifically addressing Asian patients. Given that Asian skin types differ from those of Europeans and Americans, treatment recommendations tailored to Asian populations are needed.

Methods: A narrative review of published articles retrieved following a systematic search of PubMed, the Cochrane Library, Medical Online, and Ichushi-Web between January 2000 and March 2025 was conducted. The search strategy targeted clinical trials using keywords related to HFS, palmar-plantar erythrodysesthesia, HFSR, prevention, therapy, and relevant anticancer agents. The review adhered to the PRISMA 2020 guidelines; However, formal quality assessment tools such as GRADE or the Cochrane risk-of-bias tool were not applied.

Results: In total, 53 articles were included in this review, which found different recommendations from European countries due to the differences in skin type. Among the recommended treatments was topical diclofenac, suggested as a potential and novel prevention strategy for capecitabine-induced HFS. However, high potent topical steroids, such as lidocaine patches, or antiseptic solutions, were not recommended.

Conclusions: This review provides evidence-based recommendations for the prevention and treatment of HFS/HFSR in Asian patients, taking into account their unique skin characteristics.

Remote robotic-assisted surgery (RRAS), a form of telesurgery, offers a potential solution to Japan's surgeon shortage and regional disparities in care. Despite advances in robotic systems and modern communication technologies, including both 5G wireless and wired networks, clinical adoption remains limited due to regulatory, infrastructural, and institutional barriers. This review consolidates five years (2020-2025) of technical and operational validation of the hinotori™ Surgical Robot System-a domestically developed platform-in alignment with the 2022 Japanese Remote Surgery Guidelines. Based on over 30 remote-session evaluations by Kobe University, Medicaroid, and NTT DOCOMO, we summarize system performance across key domains: communication latency, QoS-based prioritization, VPN redundancy, fail-safe mechanisms, electromagnetic compatibility, human-system interaction, and legal compliance. Under optimized Sub6 5G SA conditions, the system consistently achieved a round-trip latency of approximately 100 ms and stable stereoscopic video transmission, even during simulated 1 Gbps congestion. Safety was ensured through automatic standby, dual-cockpit fallback, and real-time monitoring. Although hinotori™ meets technical and safety criteria, full-scale implementation remains constrained by legal requirements-particularly the mandate for an on-site physician under Article 20 of the Medical Practitioners Act. Supervised telesurgery, where remote surgeons assist on-site teams, is legally permissible and may serve as a transitional model. This review integrates technical findings with policy considerations, proposing a path toward safe, equitable, and sustainable RRAS deployment in Japan. To our knowledge, this is the first comprehensive review aligning domestic telesurgical validation with national policy benchmarks, offering a foundation for future regulation, accreditation, and digital surgical integration.

Background: The survival benefit of combining chemotherapy (chemo) with immune checkpoint inhibitors (ICIs) in older patients with advanced non-small cell lung cancer (NSCLC) remains unclear. We evaluated the lung immune prognostic index (LIPI) as a predictive biomarker in this NEJ057 secondary analysis.

Methods: This analysis included 600 patients aged ≥ 75 years with NSCLC and a programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) ≥ 1% enrolled in the NEJ057 study. LIPI was categorized as good, intermediate, or poor based on derived neutrophil-to-lymphocyte ratio and lactate dehydrogenase levels. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier analysis and multivariate Cox proportional hazards models. Subgroup analyses focused on patients with a PD-L1 TPS of 1-49% and intermediate/poor LIPI to evaluate predictive factors for ICI-chemo benefit.

Results: The survival outcomes of ICI-chemo and ICI-alone varied across different patient characteristics, with LIPI identified as a predictive biomarker. Among patients with a PD-L1 TPS of 1-49% and intermediate/poor LIPI scores, ICI-chemo was associated with significantly longer OS (median: 18.3 months [95% confidence interval {CI} 10.7-26.7] vs. 8.6 months [95% CI 4.5-12.4], p = 0.007; hazard ratio [HR]: 0.56 [95% CI 0.36-0.86]) and PFS (median: 7.8 months [95% CI 6.2-9.7] vs. 3.3 months [95% CI 1.5-5.0], p = 0.002; HR: 0.56 [95% CI 0.39-0.81]) compared with ICI-alone. No significant survival benefit was observed in patients with a PD-L1 TPS of ≥ 50% or good LIPI scores.

Conclusions: LIPI is a useful biomarker for guiding treatment decisions in older patients with NSCLC and a PD-L1 TPS of 1-49%, particularly those with intermediate/poor LIPI scores. Its application might facilitate establishing more personalized strategies and improve outcomes.

Background: Cisplatin-based chemotherapy and radical cystectomy are standard treatments for muscle-invasive bladder cancer (MIBC), but their impact on neuromuscular integrity and functional capacity remains elusive. We investigated plasma biomarkers of neuromuscular junction degradation (c-terminal agrin-fragment-22; CAF22) and neuronal injury (Neurofilament light-chain; NfL) in relation to physical capacity in MIBC patients.

Methods: In this prospective study, 42 MIBC patients undergoing neoadjuvant cisplatin-gemcitabine chemotherapy and radical cystectomy were assessed before (T1) and after (T2) chemotherapy, and 4-6 weeks post-surgery (T3). Age- and BMI-matched controls (n = 46) were evaluated once. Plasma CAF22 and NfL were measured alongside handgrip strength (HGS), gait speed (GS), appendicular skeletal muscle index (ASMI), and short physical performance battery (SPPB).

Results: Plasma CAF22 and NfL were significantly elevated in patients versus controls at all time points. NfL showed more modest increases in post-treatment. HGS declined from 22.3 ± 3.9 kg at T1 to 17.2 ± 3.3 kg at T3 (p < 0.05), along with reductions in ASMI and GS. Cumulative SPPB scores dropped from 9.02 ± 1.02 to 8.24 ± 1.32. Sarcopenia prevalence rose from 28.5% at T1 to 52.4% at T3. CAF22 was significantly associated with lower HGS and SPPB at T1 (β = - 0.58 and - 0.42, p < 0.001). CAF22 changes correlated with HGS (r = - 0.80) and SPPB (r = - 0.75), while NfL showed weaker but significant correlations. Lab results indicated declines in hemoglobin, albumin, and renal function markers consistent with treatment effects.

Conclusions: CAF22 showed strong associations with treatment-related decline in skeletal muscle, suggesting its potential as an early biomarker of sarcopenia that warrants validation in larger cohorts.

Background: Precision medicine for esophageal squamous cell carcinoma (ESCC) has not been implemented owing to a lack of site-specific therapeutic markers and biomarkers. We hypothesized that the genomic background of each subsite of the esophagus might be different, allowing us to develop site-specific treatment strategies (cervical, upper thoracic, middle thoracic and lower thoracic).

Methods: This was a single-center retrospective cohort study. Patients diagnosed with ESCC who underwent comprehensive genomic profiling (CGP) at Keio University Hospital between April 2017 and March 2024 were recruited. Genomic profiles were analyzed and compared across esophageal subsites.

Results: Among the 107 patients with ESCC who underwent CGP, 6 were cervical, 16 were upper thoracic, 54 were middle thoracic, and 31 were lower thoracic. The most frequently altered genes were TP53, followed by CDKN2A and NFE2L2. The frequency of NFE2L2 mutations was significantly higher in the middle thoracic region (P = 0.041). The mutation rate increased from Stage I to IV (P = 0.0046). NFE2L2 mutations were rarely observed in early-stage cancers, suggesting that they may subsequently be acquired during growth and metastasis. Furthermore, a significant association was observed between a history of heavy alcohol consumption and NFE2L2 mutations. The overall survival of patients with unresectable or metastatic ESCC harboring NFE2L2 mutations was 12.0 months, compared to 29.7 months in patients without the mutations (HR: 2.37, P = 0.047).

Conclusion: NFE2L2 mutations were more common in the middle thoracic esophagus, appeared to be associated with tumor progression, and were linked to poor prognosis.

Sarcopenia, characterized by loss of skeletal muscle mass and function, is a highly prevalent yet often overlooked condition in patients with gastrointestinal (GI) cancers. Emerging evidence suggests that sarcopenia is a significant predictor of poor prognosis across various stages of GI cancers. Among surgical candidates, preoperative sarcopenia is consistently associated with higher rates of postoperative complications, longer hospital stays, and lower recurrence-free and overall survival rates. Among patients receiving neoadjuvant, adjuvant, or palliative chemotherapy, sarcopenia is associated with increased treatment-related toxicity, reduced adherence to treatment, impaired quality of life, and shorter survival. These findings suggest that sarcopenia is a modifiable risk factor that can critically influence the clinical trajectory of GI cancer patients; i.e., it is not merely a comorbidity. Early detection of sarcopenia through imaging or functional assessment before cancer treatment allows for risk stratification and implementation of targeted interventions such as nutritional optimization and personalized exercise programs. As a primary strategy, the optimal management of sarcopenia in GI cancer patients should combine nutritional and exercise interventions. Pharmacologic therapy, such as anamorelin, may be considered for refractory cachexia accompanied by significant anorexia. Early and sustained multidisciplinary intervention involving collaboration among oncologists, dietitians, physiotherapists, and other specialists is crucial for improving outcomes, enhancing treatment tolerance, and ultimately prolonging survival. This review summarizes the current understanding of sarcopenia in GI cancers, highlights its clinical impact across different treatment settings, and discusses strategies for assessment and integrated management. Addressing sarcopenia is an essential component of personalized cancer care in GI oncology.