International Journal of Clinical Oncology最新文献

Background: Malignant ascites occur in 10-15% of patients with gastrointestinal tract cancers. The abundance of immune cells in the peritoneum and ascitic fluid, along with the immunosuppressive environment created by cancer cells, suggests the potential utility of intraperitoneal (IP) immune checkpoint inhibitors for controlling malignant ascites.

Methods: Patients with gastrointestinal or pancreaticobiliary tract cancer and cytologically confirmed malignant ascites received IP nivolumab. Twenty mg of nivolumab diluted in 100 mL of saline was infused into the peritoneal cavity over 10 min following paracentesis. IP treatment was repeated after each subsequent paracentesis until deemed ineffective by the treating physician, upon the occurrence of unacceptable toxicity, or discontinued at the patient's request. This study was registered at ClinicalTrials.gov (NCT05745233).

Results: The median age of the nine enrolled patients was 55 years. Underlying malignancies included pancreatic (n = 4), biliary tract (n = 3), and gastric cancers (n = 2). After a median of 3 (range: 2-5) treatment cycles, seven patients (77.8%) showed a clinical response, as evidenced by reduced ascitic fluid and prolonged intervals between paracenteses. The only adverse effect observed was grade 1 tenderness at the puncture sites. Reduction in tumor cell count in ascites, rather than changes in the total lymphocyte count or lymphocyte subpopulations, correlated with clinical response. Responders consistently exhibited increased vascular endothelial growth factor A and decreased interleukin-1α levels following nivolumab administration.

Conclusion: Intraperitoneal administration of nivolumab effectively controlled malignant ascites with minimal adverse effects. However, further validation in a larger cohort is required.

Background: Sepsis and septic shock are major causes of non-relapse mortality in cancer patients, with chemotherapy-induced neutropenia increasing infection risk. The prognostic impact of neutropenia remains unclear across cancer subtypes.

Patients and methods: We conducted a retrospective cohort study using the TriNetX Research Network, comprising deidentified data from over 141 million patients across 105 U.S. health care organizations. Adults with select solid cancers who received chemotherapy and developed severe sepsis with septic shock from 2013 to 2024 were included. Patients were stratified by neutropenia severity (< 0.5 × 103/µL vs. 0.5-1.5 × 103/µL), and propensity score matching was applied to balance demographics, comorbidities, and treatment variables. Outcomes including short- and long-term mortality, organ failure, bacteremia, and immune-related adverse events were assessed using Kaplan-Meier survival analysis.

Results: Among 1083 eligible patients (184 severe, 899 mild-moderate neutropenia), severe neutropenia was associated with significantly worse survival at all timepoints, with median survival of 13 days versus 106 days and hazard ratios of 1.56-2.03 from 30 days to 1 year (all p < 0.001). Secondary outcomes showed no difference in immune-related adverse events, a nonsignificant trend toward increased organ failure, and higher rates of bacteremia in the severe neutropenia cohort.

Conclusions: Greater severity of chemotherapy-associated neutropenia is linked to worse short-term survival and increased complications in cancer patients with septic shock. Stratifying by neutrophil count bands revealed that severe neutropenia (< 0.5 × 10³/µL) independently predicts poorer outcomes, emphasizing its value for risk stratification and guiding clinical management.

Background: Carboplatin (CBDCA) is highly emetogenic when administered at an area under the curve (AUC) ≥ 4, requiring triple antiemetic therapy, including an NK₁ receptor antagonist (NK₁ RA). Fosnetupitant (F-NTP), a long-acting NK₁ RA, may provide sustained receptor occupancy; however, its direct comparisons with aprepitant (APR) in CBDCA-based regimens between 0 and 168 h remain lacking. We aimed to evaluate the antiemetic efficacy of F-NTP versus APR during 1 week following chemotherapy.

Methods: This retrospective single-center observational study included patients with cancer receiving CBDCA (AUC ≥ 4)-based regimens. Propensity score matching was performed using clinical factors. The primary endpoint was the complete response (CR; no emesis or rescue medication) rate between 0 and 168 h. The secondary endpoints included phase-specific CR rates, time to treatment failure (TTF), and adverse events (AEs).

Results: After matching, 242 patients were included in each group. The overall CR rate at 0-168 h was significantly higher with F-NTP (83.5%) than with APR (69.4%) (p < 0.001). F-NTP significantly prolonged TTF (hazard ratio = 0.48, 95% confidence interval: 0.33-0.71, p < 0.001). The multivariate analysis revealed female sex, younger age, and high CBDCA dose as significant risk factors for non-CR, while F-NTP use was a protective factor. AEs did not differ significantly between the groups and were mostly Grade 1.

Conclusion: F-NTP demonstrated superior antiemetic efficacy to that of APR in CBDCA-based regimens, particularly maintaining higher CR rates through the acute and delayed phases. F-NTP was also well tolerated, supporting its potential as a strong prophylactic agent for preventing chemotherapy-induced nausea and vomiting.

Purpose: This retrospective study compared the outcomes of radiotherapy (RT) and chemoradiotherapy (CRT) in patients with T2N0 hypopharyngeal cancer.

Methods: We analyzed patients with T2N0 hypopharyngeal squamous cell carcinoma treated with RT or CRT between 2011 and 2016 using data from the Head and Neck Cancer Registry of Japan.

Results: Among 53,512 patients, 457 with T2N0 disease received RT (n = 165) or CRT (n = 292; median follow-up, 41.8 months; median age, 70 years). Tumor sites included the pyriform sinus (72.9%), postcricoid region (12.3%), posterior wall (11.8%), and unknown (3.1%). The groups differed in terms of age and alcohol use. Before weighing, CRT was associated with longer PFS and a lower cumulative incidence of locoregional recurrence compared with RT. However, in the IPTW-adjusted analysis, CRT did not significantly improve OS (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.59-1.62) or PFS (HR, 0.79; 95% CI, 0.53-1.16) compared with RT. PFS was associated with alcohol/smoking history, performance status, and primary site of the tumor.

Conclusion: In T2N0 hypopharyngeal cancer, CRT reduced the locoregional recurrence compared to RT. However, CRT did not confer a significant OS or PFS advantage over RT after adjustment for baseline imbalances. RT alone may, therefore, be a reasonable definitive treatment option for selected patients.

Background: The evolving prognosis of colorectal cancer (CRC) over extended periods following surgery has not been comprehensively characterized. This study aimed to delineate long-term patterns in conditional survival (CS), evaluate the changing relevance of CRC recurrence surveillance versus management of fatal non-cancer conditions, and suggest follow-up indicators tailored to postoperative duration.

Methods: We examined trends in conditional overall survival (cOS), disease-specific survival (cDSS), and non-disease-specific survival (cNDSS) by tumor stage in 2,996 patients (stage 0-IV) who underwent surgical resection for CRC. Furthermore, we conducted a multivariate analysis in a cohort of 1,529 patients surviving more than 5 years to identify predictors of long-term survival.

Results: Over a median observation period of 60.4 months, 745 deaths were recorded (478 CRC-related, 243 unrelated to CRC, and 24 unknown). Stage-wise CS analyses revealed crossover points of cDSS and cNDSS at 3 years post-surgery in stage II and at 6 years in stages III/IV. Multivariate analysis identified age ≥ 80, CEA ≥ 5.0 ng/mL, CA19-9 ≥ 37.0 U/mL, albumin ≤ 4.1 g/dL, anemia, RDW ≥ 14.9%, and platelet count ≤ 150 × 10⁹/L as independent risk factors in 5-year survivors.

Conclusions: The importance of CRC recurrence surveillance was most prominent within the first 3 years after surgery in stage II and within 6 years in stages III/IV. Our findings underscore the need to customize surveillance strategies based on duration since surgery and indicate that the aforementioned clinical parameters may serve as useful markers in 5-year survivors.

Background: Anal canal carcinoma (ACC) is reported to be a rare cancer worldwide. In Japan, while the incidence rate is similarly low compared to Western countries, its histological distribution differs. This paper aimed to clarify the epidemiological characteristics of ACC, particularly anal canal squamous cell carcinoma (SCC), in Japan and to compare them with Western data.

Methods: The epidemiological data were taken from the Japanese Society for Cancer of the Colon and Rectum (JSCCR) registry and a nationwide multi-institutional study. Clinicopathological features, human papillomavirus (HPV) status, treatment trends, and survival were analyzed. The comparative data were derived from major Western registry studies.

Results: In Japan, adenocarcinoma accounted for 66.8-75.5% of the ACC cases, while SCC represented only 16.2-24.4%, in contrast to the 70-85% SCC predominance reported in Western countries. Among Japanese SCC cases, women accounted for 71.5%, a higher proportion than in Western countries. HPV was positive in 85% of the SCC cases, with HPV-16 as the most prevalent genotype, which is consistent with global patterns. The adoption of chemoradiotherapy (CRT) increased from 14% in the 1990 s to over 80% after 2010, achieving survival outcomes comparable to surgery.

Conclusions: In Japan, adenocarcinoma was the predominant type of ACC, while SCC was less common. However, the characteristics of HPV-associated SCC were similar to those observed in Western countries. Standardization of classification and staging criteria and the expansion of HPV vaccination may be essential to improve clinical management and facilitate international comparisons.

Background: Assessment of molecular residual disease (MRD) using circulating tumor DNA (ctDNA) is a powerful prognostic tool for detecting postoperative recurrence in colorectal cancer (CRC). However, ctDNA-based MRD testing has been available only within clinical trials in Japan, and its clinical utility in patients ineligible for trials due to age or comorbidities remains unclear. We conducted a prospective observational study to describe the real-world implementation and clinical findings of postoperative ctDNA testing in CRC.

Methods: CRC patients who underwent tumor-agnostic ctDNA MRD testing after curative-intent resection were prospectively enrolled. When ctDNA was detected, early imaging was performed to assess recurrence. Clinical outcomes were analyzed according to ctDNA status.

Results: 56 CRC patients who underwent ctDNA testing 4-8 weeks after surgery between June 2023 and June 2025 were analyzed. 18 (32.1%) were ctDNA-positive and 38 (67.9%) were ctDNA-negative. Radiological recurrence occurred in 10 of 16 evaluable ctDNA-positive patients (62.5%), including liver metastases in 4 and no lung metastases. In contrast, recurrence was observed in 5 of 37 ctDNA-negative patients (13.5%), including lung metastases in 3 and no liver metastases. Three ctDNA-positive patients (18.8%) achieved ctDNA clearance after adjuvant chemotherapy and remained recurrence-free, whereas persistent-ctDNA positivity predicted disease progression. In the ctDNA-negative cohort, 84.5% remained disease-free regardless of adjuvant therapy.

Conclusions: This interim report demonstrates the feasibility of implementing postoperative ctDNA testing in real-world clinical practice. While exploratory and descriptive in nature, the findings suggest that ctDNA status may reflect recurrence risk and provide useful information for postoperative management in resectable CRC.

Perioperative systemic therapy, administered either preoperatively (neoadjuvant therapy) or postoperatively (adjuvant therapy), has been considered a strategy to improve the long-term prognosis of pancreatic cancer. While adjuvant therapy following resection has demonstrated a clear long-term prognostic benefit, the significance of neoadjuvant therapy remains uncertain. This manuscript reviews previously published randomized controlled trials and provides a scientific discussion on the value of neoadjuvant therapy. To date, eight phase II or phase III randomized controlled trials have been conducted, but their results have been inconsistent. Clear evidence has not been established due to several factors, including differences in chemotherapy agents used across trials, variations in primary endpoints, and the inclusion of borderline resectable pancreatic cancer cases. Ongoing randomized controlled trials are expected to clarify the role of neoadjuvant therapy in resectable pancreatic cancer.

Objective: The prevalence of MSI-H and MLH1 promoter hypermethylation (MLH1-PHM) as well as Lynch syndrome in Japanese patients with endometrial cancer (EC) has not been fully revealed. There is also a recent report that the prognosis of MLH1-PHM is worse than MLH1 non-PHM in EC; however, no large-scale studies have been conducted in Japan. We investigated the prevalence of MSI-H, MLH1-PHM and Lynch syndrome in EC cases and characteristic and prognosis of them.

Methods: The 677 patients who were pathologically diagnosed with EC at the Saitama Cancer Center Hospital between 2013 and 2023 were investigated in this study. The MSI and abnormal DNA methylation of the MLH1 promoter were tested in all cases. Patients with MSI-H EC or a family history provided informed consent and examined germline testing for Lynch syndrome.

Results: Among the 677 ECs, 170 (25.1%) were MSI-high (MSI-H), and 105 were involved MLH1 hypermethylation. Two of 13 Lynch syndrome cases had MLH1-PHM in ECs. The MSI-H group had more G3 histology, but had a favorable prognosis with 5-year PFS and OS compared with the MSS group. The group with MLH1-PHM have more patients with G1/2 histology and more advanced disease. There was no difference in prognosis between MLH1-PHM and non-PHM groups.

Conclusion: This study provides information on the prevalence of MSI-H and MLH1-PHM in EC in Japan. Besides, the prognostic of the MSI-H group is better than that of the MSS group, but no differences were found between the MLH1-PHM and MLH1 non-PHM groups.

Background: Sinonasal mucosal melanoma (SNMM) is an aggressive malignancy with limited prognostic markers. This study aimed to determine whether immune markers, including the CD8 to CD4 lymphocyte ratio, CD56-positive lymphocytes, and PD-L1 expression, provide prognostic information beyond established clinicopathological factors.

Methods: We retrospectively reviewed 67 patients with surgically treated SNMM at two tertiary medical centers in Taiwan between 2004 and 2023. Standard histopathologic parameters and immunohistochemical assessments of the CD8/CD4 ratio, CD56-positive lymphocytes, and PD-L1 expression in tumor and stromal immune cells were evaluated. Disease-specific survival (DSS) and recurrence-free survival (RFS) were analyzed using Kaplan-Meier estimates and multivariable Cox proportional hazards models.

Results: The median patient age was 62 years, and 60% were male. During a median follow-up of 42 months, 63% of patients experienced recurrence, and 54% died of the disease. An increased CD8/CD4 ratio and the presence of CD56-positive lymphocytes were associated with better DSS (5-year DSS, 64.3% vs. 32.1% and 70.1% vs. 35.8%, respectively), whereas PD-L1 positivity was associated with shorter RFS (5-year RFS, 28.6% vs. 54.3%). In multivariable analysis, mitotic activity of ≥ 10/mm² (hazard ratio [HR] 2.31, 95% confidence interval [CI] 1.12-4.78) and PD-L1 positivity (HR 1.92, 95% CI 1.01-3.67) independently predicted worse outcomes, while an increased CD8/CD4 ratio remained associated with improved DSS (HR 0.48, 95% CI 0.23-0.99).

Conclusions: Immune markers, particularly the CD8/CD4 ratio and CD56-positive lymphocytes, were significantly associated with survival outcomes independent of traditional histopathologic factors. Incorporating immune profiling into risk stratification may improve prognostication and guide the development of immune-targeted strategies in SNMM.