International Journal of Clinical Oncology最新文献

Background: Liquid biopsy using circulating tumor DNA (ctDNA) is a minimally invasive approach for detecting tumor-associated genomic alterations. Although ctDNA analysis has been widely explored in solid tumors, its application to cervical cancer remains limited. Cancer personalized profiling by deep sequencing (CAPP-Seq) enables sensitive ctDNA profiling via molecular barcoding and digital error suppression.

Methods: We evaluated the feasibility of ctDNA-based mutation profiling in cervical cancer using the CAPP-Seq platform by analyzing plasma samples from 38 patients.

Results: The cohort included three patients with stage I disease, nine with stage II, 19 with stage III, and seven with stage IV. Somatic gene alterations were detected in 33 of the 38 cases (87%), including squamous cell carcinoma (27/29 [93%]) and adenocarcinoma (6/9 [67%]). Non-synonymous mutations were identified in 23 patients (59%), with PIK3CA being the most frequently mutated gene [13/38 (34%)]. Copy number gains of EGFR, MET, and ERBB2 were observed in 24%, 11%, and 5% of cases, respectively. The median blood tumor mutational burden was 17.7 mutations/Mb, and 50% of the patients exhibited a hypermutated phenotype. In a subset of four patients who received concurrent chemoradiotherapy, longitudinal changes in ctDNA mutation profiles between pre- and post-treatment samples were associated with treatment response.

Conclusions: This study demonstrates the feasibility of ctDNA-based mutation profiling using CAPP-Seq in cervical cancer, with a high detection rate of tumor-associated genomic alterations across histological subtypes. ctDNA analysis may represent a minimally invasive approach for the molecular characterization and disease monitoring of cervical cancer.

Background: Metastatic bladder urothelial carcinoma has poor survival, and large comparative genomic studies using uniform targeted sequencing of paired primary and metastatic lesions remain limited. We compared gene- and pathway-level alterations between primary and metastatic tumors METHODS: We analyzed 2,880 bladder urothelial carcinoma samples (2,305 primary; 575 metastatic) from 2,343 patients profiled with MSK-IMPACT. Somatic mutations and copy number alterations were integrated per gene and compared between primary and metastatic samples in the full cohort and in a paired subset using standard statistical tests.

Results: Primary and metastatic samples showed broadly similar driver landscapes. In the full cohort, KDM6A, FGFR3, STAG2, and ERCC2 were more frequently altered in primary tumors, whereas no individual genes were enriched in metastases; these differences were not significant in paired analyses. At the pathway level, TP53 pathway alterations were relatively more frequent in metastases, while DNA damage response alterations were enriched in primary tumors; other pathways showed comparable alteration rates. Apoptosis-focused analyses identified no significant gene-level differences, but suggested a trend toward higher alteration rates in the TP53 pathway and apoptosis regulators in metastases.

Conclusion: Primary and metastatic lesions of bladder urothelial carcinoma show broadly similar gene- and pathway-level alteration profiles on targeted DNA sequencing. TP53 pathway and apoptosis-related alterations are modestly more frequent in metastases, consistent with impaired stress responses and apoptosis evasion.

Background: The 9th edition of the UICC TNM classification redefined N categories and clinical stages for salivary gland cancer (SGC). We validated the prognostic utility of this redefinition and evaluated the impact of anatomical nodal spread.

Methods: We retrospectively analyzed 166 patients with SGC and 93 parotid gland cancer (PGC) patients treated with curative surgery. Cases were restaged according to the TNM classification of the UICC 9th edition. Kaplan-Meier survival curves, Cox models, and statistical indices (AIC, likelihood ratio χ², C-index) were used to compare the findings based on the 8th and 9th editions. Nodal metastases were classified as "Intraparotid lymph nodes (LNs) only", "Limited to levels I-III LNs", and "Beyond levels I-III LNs".

Results: Kaplan-Meier curves showed clearer separation by N category and clinical stage for the 9th edition, although its prognostic performance by statistical indices was similar to that of the 8th edition. In the PGC surgery subset, LN metastasis, particularly N2 in the 9th edition, was the strongest adverse prognostic factor, and the new 9th edition pathological N categories were also useful. Additionally, prognosis worsened with increasing nodal extent. Twelve patients with metastases beyond levels I-III developed distant metastases despite standard treatment, and 10 with salivary duct carcinoma, indicating potential benefit from adjuvant systemic therapy.

Conclusions: Kaplan-Meier analyses suggested that the 9th edition provided better intercategory discrimination than the 8th edition, despite no statistical superiority being demonstrated. Nodal metastasis extending beyond levels I-III may be a useful biomarker for selecting patients for adjuvant systemic therapy.

Background: Early detection of cancer and precise recurrence monitoring remain major unmet needs in oncology. Conventional screening is limited to a few cancer types, leaving nearly half of cancers without established programs. Multi-cancer early detection (MCED) tests based on circulating tumor biomarkers have shown promise, but sensitivity for early-stage remains a challenge. In parallel, detection of molecular residual disease (MRD) using circulating tumor DNA (ctDNA) has emerged as a powerful prognostic and predictive tool, though current assays remain limited in sensitivity and specificity. This study aims to integrate multi-omics data to develop more refined and highly sensitive MCED and MRD assays.

Methods: This study leverages clinical information and biospecimens from patients with cancer and cancer-naïve individuals. Samples from patients with cancers will be derived from the MONSTAR-SCREEN-3 study, while those from cancer-naïve individuals will be obtained from the Tohoku Medical Megabank Project. Comprehensive analyses will include whole-genome sequencing (WGS), whole-exome sequencing (WES), whole-transcriptome sequencing (WTS), proteomics, metabolomics, and microbiome profiling using stool and saliva. Artificial intelligence (AI)-based multi-omics integration will be performed to develop novel MCED and MRD assays and to evaluate their clinical performance. The primary endpoints are the sensitivity and specificity of MCED and MRD assays.

Discussion: This is the first large-scale study to integrate comprehensive multi-omics profiling with AI for MCED and MRD assay development. The findings are expected to advance precision oncology by improving early diagnosis and recurrence monitoring.

Trial registration: UMIN000053815, approved by the Institutional Review Board of the National Cancer Center Hospital East.

Immune-checkpoint blockade (ICB) elicits profound and durable responses in mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) gastrointestinal (GI) cancers, yet most microsatellite-stable (MSS) cancers derive minimal benefit. This gap reflects the limited ability of tumor mutational burden (TMB)-a widely used ICB biomarker-to capture true tumor immunogenicity. Only a small fraction of somatic mutations generates peptides that are processed, presented on HLA molecules, and recognized by T cells, and this pool is further restricted by defects in antigen-presentation pathways, including interferon unresponsiveness, epigenetic repression, and irreversible loss of B2M or HLA class I. These limitations have shifted attention toward neoantigen quality, defined by the presentability, clonal expression, and structural distinctiveness of mutation-derived peptides. Yet even high-quality neoantigens remain functionally irrelevant when presentation is impaired. To integrate these layers, we propose effective immunogenic burden (EIB) as a conceptual framework that describes the state in which tumor mutations generate high-quality neoantigen peptides that are successfully presented on HLA molecules for T-cell recognition. By integrating neoantigen quality and antigen-presentation capacity beyond TMB, EIB provides a clinically interpretable basis for understanding heterogeneous responses to ICB in GI cancers.

Background: Robot-assisted radical prostatectomy (RARP) is a standard treatment for localized prostate cancer. This procedure provides favorable oncologic outcomes but poses functional challenges, particularly urinary incontinence and sexual dysfunction, that can affect patients' quality of life (QOL). This study examined predictive factors for postoperative recovery of urinary, sexual, and bowel functions using the Expanded Prostate Cancer Index Composite (EPIC) questionnaire.

Methods: This single-center retrospective study included 279 patients who underwent RARP between 2011 and 2023. Health-related QOL was assessed preoperatively and up to 18 months postoperatively using the EPIC questionnaire. Recovery was defined as achieving ≥90% of baseline scores at 18 months. Firth's penalized logistic regression and baseline-adjusted analyses were performed to identify factors associated with poor recovery.

Results: Urinary function improved gradually, but 39.8% of patients showed suboptimal recovery at 18 months. In multivariable Firth's penalized logistic regression analysis, longer console time was independently associated with poor urinary incontinence recovery (OR 2.15, 95% CI 1.14-4.17). Ratio-based analyses suggested age-related differences in sexual recovery; however, baseline-adjusted analyses demonstrated a dissociation between postoperative sexual function and sexual bother. Nerve-sparing status was not independently associated with urinary and sexual recovery. Bowel function remained stable.

Conclusion: Longer console time was independently associated with poorer recovery of urinary continence after RARP, likely reflecting surgical complexity rather than a direct causal effect. Baseline-adjusted analyses revealed a dissociation between postoperative sexual function and sexual bother, underscoring the limitations of function-based QOL assessment and the need for patient-centered counseling and shared decision-making in RARP.

Background: For patients with left-sided metastatic colorectal cancer (mCRC), the recommended first-line treatment is anti-epidermal growth factor receptor (anti-EGFR) antibodies, such as cetuximab or panitumumab, plus doublet chemotherapy. However, the differences in outcomes between cetuximab and panitumumab remain unknown.

Methods: Clinical data of patients with left-sided all RAS or KRAS wild-type mCRC who received cetuximab or panitumumab plus doublet chemotherapy were retrospectively collected from 24 institutions in Japan. The patients were divided into two groups: the cetuximab and panitumumab groups. Overall survival (OS), progression-free survival (PFS), and response rate (RR) were compared between the two groups.

Results: A total of 233 patients were enrolled: 87 (37.3%) in the cetuximab group and 146 (62.7%) in the panitumumab group. Median OS, PFS, and RR of the cetuximab and panitumumab groups were 26.6 months (95% confidence interval [CI], 19.7-33.4) versus 31.8 months (95% CI, 25.7-37.9), 9.7 months (95% CI, 6.9-12.5) versus 12.4 months (11.1-13.7), and 57.8% versus 71.0%, respectively. In multivariate analysis, OS and RR were significantly better in the panitumumab group than in the cetuximab group (adjusted hazard ratio 0.69, 95% CI 0.50-0.99, p = 0.04; adjusted odds ratio 2.00, 95% CI 1.07-3.73, p = 0.03) and PFS was similar between the two groups (adjusted hazard ratio 0.75, 95% CI 0.55-1.01, p = 0.05).

Conclusion: As a first-line treatment for patients with left-sided all RAS or KRAS wild-type mCRC, panitumumab plus doublet chemotherapy may be suggested better efficacy outcomes than cetuximab plus doublet chemotherapy.

Background: The efficacy of neoadjuvant chemotherapy (NACT) before radical hysterectomy (RH) in cervical cancer remains unclear. We evaluated stage-specific outcomes of NACT-RH at a high-volume center.

Methods: This retrospective cohort study included patients with non-metastatic cT1b1-2b cervical cancer who underwent RH between 2013 and 2022. For cT1b cases, prognostic outcomes were compared between patients with cT1b3 (any N) who underwent NACT-RH (High-risk, NACT(+)) and those with cT1b1-1b2 N0 who underwent primary RH (Low-risk, NACT(-)), using propensity score matching. For cT2 cases, NACT-RH versus primary RH was compared using inverse probability weighting to adjust for baseline differences.

Results: Among 191 patients who underwent RH (cT1: n = 99; cT2: n = 92), the matched cT1 cohort comprised 15 High-risk, NACT(+) and 30 Low-risk, NACT(-) patients. Five-year progression-free survival (PFS) was 75.0% (95% confidence interval [CI], 53.4-100.0%) versus 89.9% (95% CI, 79.6-100.0%) (p = 0.427). Overall survival (OS) was 100% in both groups with a median follow-up of > 70 months. In cT2, NACT-RH (n = 73) versus primary RH (n = 19) showed hazard ratios of 2.88 for PFS (95% CI, 0.69-11.97) and 5.64 for OS (95% CI, 0.70-45.35) after baseline adjustment. Among cT2 patients who underwent NACT-RH, PFS and OS were worse in those without an objective response to NACT (n = 18, all cT2b) than in responders.

Conclusion: NACT-RH was associated with encouraging long-term outcomes in cT1b3, whereas outcomes in cT2 cases remain uncertain, supporting careful selection and response-adapted strategies.

Background: The prognostic value of the creatinine-cystatin C ratio (CCR) in individuals with cancer has been investigated in numerous studies, but the findings vary. To accurately identify the prognostic value of CCR in individuals with cancer, we conducted this meta-analysis.

Methods: Pertinent studies were retrieved across PubMed, Web of Science, Embase and Cochrane from their establishment to June 8, 2024. Additional searches were conducted until November 16, 2024. In this study, the calculation of the hazard ratio (HR) and its 95% confidence interval (CI) allowed us to determine the prognostic value of CCR in individuals with cancer. Additionally, Newcastle-Ottawa scale (NOS) was employed for quality evaluation, Cochrane I² statistic for heterogeneity assessment, funnel plots for publication bias evaluation, and Egger test for quantitative identification. Significant publication bias is indicated by a P < 0.05. A software called STATA 15.1 was utilized for statistical analysis.

Results: Initially, 2001 articles were retrieved in total, and this study comprised twelve trials with 4439 individuals with cancer overall. Our findings demonstrated a substantial correlation between a low CCR and a reduced overall survival (OS) in individuals with cancer (HR 1.71, 95% CI 1.49-1.96). Similarly, a strong correlation between CCR and progression-free survival (PFS) CCR was also noted (HR 1.51, 95% CI 1.29-1.77).

Conclusion: This meta-analysis revealed that in individuals with cancer, a low CCR was strongly correlated with OS and PFS. Therefore, in clinical practice, CCR may be a promising and affordable prognostic biomarker for individuals with cancer.

Background: Alcohol consumption is a well-established risk factor for multiple cancer types, yet its contribution to the global cancer burden remains insufficiently quantified. This study systematically assesses the global, regional, and national burden of alcohol-attributable cancers (AAC) from 1990 to 2021.

Methods: AAC mortality and disability-adjusted life-years (DALYs), as well as corresponding age-standardized rates, were extracted from the Global Burden of Disease (GBD) 2021 database. Temporal trends were evaluated using Joinpoint regression, and future burden was projected with a Bayesian age-period-cohort (BAPC) model. Decomposition analysis quantified the contributions of population growth, aging, and epidemiological changes, while frontier analysis evaluated the efficiency of AAC control across countries.

Results: Between 1990 and 2021, global AAC deaths increased from 195,525 to 343,370, despite a decline in the age-standardized deaths rate (ASDR) from 4.87 to 3.97 per 100,000 (AAPC: -0.67%; 95% CI -0.79 to -0.55). Similar trends were observed for DALYs, with a 23% reduction in the age-standardized DALYs rate. Socioeconomic disparities persisted, with high-SDI regions experiencing a decline in ASDR despite rising absolute deaths, while low-SDI regions exhibited minimal change. Regionally, East Asia exhibited the highest AAC burden, whereas high-income North America had the lowest burden but showed a slight increase in ASDR. Liver, esophageal, and colorectal cancers accounted for the largest AAC burden. Decomposition analysis identified population aging and growth as primary contributors to increasing AAC burden, while frontier analysis highlighted disparities in AAC control, with Mongolia exhibiting the highest prevention gap. Projections suggest a continued decline in ASDR, while the absolute AAC burden is expected to rise.

Conclusions: Although the ASDR of AAC has declined globally and is expected to further decrease over the next 25 years, the absolute burden of AAC continues to grow. Hence, enhancing and refining global alcohol control policies is necessary to alleviate the global burden of AAC.