International Journal of Clinical Oncology最新文献

Background: The EXTREME regimen is the standard first-line treatment for recurrent or metastatic squamous cell carcinoma of the head and neck (R/M HNSCC), but it is poorly tolerated in Asian patients. We aimed to compare the efficacy and safety of the modified EXTREME (mEXTREME) and modified TPEx (mTPEx) regimens in Japanese patients.

Methods: This was a multicenter, randomized, exploratory study. The dose of chemotherapeutic agents was reduced by 25% for the mEXTREME regimen compared to the EXTREME regimen and by 20% for the mTPEX regimen compared to the TPEx regimen. Six and four cycles were repeated every 21 days for the mEXTREME and mTPEx regimens, respectively. In both regimens, weekly 250 mg/m² cetuximab was continued as maintenance therapy in case of disease control.

Results: Sixty-one patients were enrolled and assigned to the two treatment arms (30 to mEXTREME, 31 to mTPEx). Median PFS was 6.0 months and 5.3 months (p = 0.28), and median overall survival was 17.4 months and 18.7 months (p = 0.72) for the mEXTREME and mTPEx groups, respectively. Twenty-seven patients in the mEXTREME group and 29 patients in the mTPEx group had grade 3 or worse adverse events during chemotherapy (p = 0.61). Early tumor shrinkage was 20% in the mEXTREME group and 44% in the mTPEx group (p = 0.01).

Conclusions: No significant differences in survival were observed between the two groups, with similar toxicity profiles. As early tumor shrinkage was favorable in the mTPEx group, the mTPEx regimen may be the first-line standard of care for Asian patients with R/M HNSCC, particularly those who are not candidates for up-front pembrolizumab due to CPS < 1 or the presence of immunologically related complications and those who need rapid tumor shrinkage to relieve tumor-related symptoms.

Trial registration: UMIN000025436.

Background: Achieving a complete response (CR) with immune checkpoint inhibitor (ICI)-based combination therapy is important in metastatic renal cell carcinoma (mRCC) systemic treatment. Surgical intervention for residual localized disease after ICI therapy may contribute to complete disease eradication and improved outcomes.

Methods: We retrospectively evaluated the clinical significance of medical CR (complete radiologic disappearance of all target lesions with ICI therapy) and surgical CR (radiographic CR after local surgery following ICI-based therapy) for patients with mRCC treated with ICI-based combination therapy. Patients were categorized into the IOIO (dual ICI therapy) and IOTKI (ICI + tyrosine kinase inhibitor therapy) groups.

Results: Of the 250 study patients, 107 and 143 received IOIO and IOTKI, respectively. The overall medical objective response and medical CR rates were 55.6% and 10.4%, respectively. Surgical CR and medical CR were achieved in 16.4% and 26.8% of individuals, respectively. Patients who achieved both medical CR and surgical CR experienced similarly favorable progression-free survival and overall survival (OS). Among those who achieved either surgical CR or medical CR, OS was longer in the IOIO group; however, no other significant intergroup differences were observed. Patients with primary tumors exhibited higher medical CR rates. No significant differences in treatment-related adverse events, treatment discontinuation, or steroid use between the medical CR and medical non-CR groups were observed.

Conclusion: Approximately 25% of patients with mRCC achieved medical CR with ICI-based combination therapy. Treatment efficacy was comparable between the two regimen groups. A multidisciplinary strategy may lead to complete disease eradication for select patients.

Background: Combination therapy is the standard treatment for curatively unresectable gastric cancer; however, its effectiveness in patients aged ≥ 75 years remains unclear. This study investigated the effectiveness of combination therapy in enhancing overall survival.

Methods: We retrospectively analyzed nationwide medical claims data for patients with unresectable advanced gastric cancer who received chemotherapy between October 2010 and May 2023. Overall survival and real-world progression-free survival were the primary and secondary outcomes, respectively. Patient characteristics were adjusted using inverse probability of treatment weighting, and inverse probability of treatment weighting-adjusted hazard ratios were calculated.

Results: Among 6213 patients (mean age 80.0 years, 70.3% men), 4988 received monotherapy and 1225 received combination therapy. The median (interquartile range) number of first-line therapy cycles and duration of first-line therapy were three cycles and 4.4 (2.1-7.9) months for monotherapy and four cycles and 5.3 (2.7-9.1) months for combination therapy, respectively. The median overall survival was 9.7 and 11.3 months (significant adjusted hazard ratio) while real-world progression-free survival was 4.4 and 5.1 months (significant adjusted hazard ratio) for monotherapy and combination therapy, respectively. In multivariate analysis, the adjusted hazard ratio for overall survival was not significant.

Conclusions: After adjusting for background factors, compared with monotherapy, combination therapy did not extend overall survival; however, an extension of real-world progression-free survival was observed. These results suggest that combination therapy is an effective treatment option for older patients with unresectable gastric cancer. Further studies considering the systemic condition of older patients are necessary.

Background: Long-term outcomes in patients with lung metastases from sarcomas remain unreported. We retrospectively evaluated the clinical utility of lung radiofrequency ablation (RFA) in 52 patients with musculoskeletal sarcoma-derived lung metastases.

Patients: The study cohort included 29 men and 23 women with a mean age of 55 years at the time of the initial lung RFA, with a mean follow-up duration of 49.2 months. Complete treatment was defined as achieving a tumor-free status following the initial lung RFA. Cases failing to achieve this were classified as incomplete treatment.

Results: At the final follow-up, 14 patients remained alive, while 38 had died from this disease. Multivariate analysis confirmed that complete ablation and longer disease-free interval were significant prognostic factors. The median survival time for the 27 patients with complete treatment was 96.7 months, compared with 13.1 months for the 25 patients with incomplete treatment. The 3- and 5-year survival rates after the initial RFA in the 27 patients with complete treatment were 55.3% and 51.4%, respectively, whereas the corresponding rates for the incomplete treatment group were 16% and 10.7%. Of the 27 patients who achieved complete treatment, 4 had no new lung metastases, whereas 23 developed new lung metastases and/or local relapse. Local tumor progression occurred in 30 of 266 lung tumors (11%); larger tumors showed a higher incidence of progression. No procedure-related mortality was reported.

Conclusions: Lung RFA can be a valuable option for treating lung metastases in patients with musculoskeletal sarcoma.

Background: Denosumab, a bone-modifying agent, reduces the incidence of skeletal-related events (SREs), but its optimal use in real-world metastatic castration-resistant prostate cancer (mCRPC) settings remains unclear.

Methods: We conducted a retrospective cohort study of 235 patients with bone mCRPC treated with denosumab between 2015 and 2024. The primary endpoint was identification of risk factors associated with symptomatic skeletal events (SSEs) after denosumab initiation. Secondary endpoints were risk factors for SREs occurring prior to denosumab. Multivariate Cox regression analyses assessed independent predictors.

Results: Over a median follow-up of 11 months, 27 patients (11.5%) developed an SSE. The most common events were EBRT to bone (7.7%) and pathologic fractures (4.3%). The 2-year SSE-free survival rate was 79.4%. A prior history of SREs was independently associated with a significantly increased risk of subsequent SSEs (hazard ratio [HR]: 2.09; 95% confidence interval: 1.02-4.92; p = 0.047). In a separate analysis of SREs occurring prior to denosumab, grade 2 and ≥ 3 disease at the time of bone metastasis diagnosis were associated with higher risk (HR: 2.62 and 2.32, respectively; both p < 0.05). Denosumab was discontinued in 62.6% of patients, primarily due to clinical deterioration, death, or difficulty attending appointments.

Conclusion: In this real-world study, approximately 10% of patients with bone mCRPC developed SSEs during denosumab therapy, mostly within the first year. A prior SRE and high baseline bone tumor burden were significant predictors of skeletal complications, underscoring the importance of early risk stratification and timely initiation of bone-targeted therapies.

Background: PARP inhibitors have been shown to improve progression-free survival in patients with recurrent ovarian cancer. However, their potential for long-term response and cure remains unclear in real-world practice.

Methods: We conducted a multicenter, retrospective study of patients with recurrent ovarian, fallopian tube, or peritoneal cancer who were treated with olaparib maintenance therapy in the Kansai Clinical Oncology Group. We analyzed clinical outcomes according to histological tissue type, platinum sensitivity, BRCA mutation status, and SLFN11 expression. Epithelial ovarian cancers were classified into type I (low-grade serous carcinoma, clear cell carcinoma, low-grade endometrioid carcinoma) and type II (high-grade serous carcinoma, high-grade endometrioid carcinoma and undifferentiated carcinoma).

Results: A total of 72 patients were registered. The median progression-free survival and overall survival were 12.0 and 42.0 months, respectively. Type II tumors exhibited significantly longer progression-free survival than type I tumors (p = 0.027). Among type II tumors, those with platinum-sensitive recurrence and a response to chemotherapy (PSR-R, n = 51) had significantly better progression-free survival than non PSR-R (p < 0.0001). Notably, eight PSR-R patients (15.7%) achieved greater than five years of progression-free survival ("super responders"), and all had no evidence of disease at the last follow-up. BRCA mutations and SLFN11 expression were not associated with progression-free survival or super responders.

Conclusions: In this real-world cohort, a subset of patients with recurrent ovarian cancer achieved durable, potentially curative responses with olaparib maintenance, regardless of their BRCA mutation status. When evaluating PARP inhibitor therapy, long-term progression-free survival should be considered a key endpoint.

Purpose: Chemotherapy-induced constipation frequently occurs with cisplatin-containing treatments, partly because of concomitant neurokinin 1 and serotonin 3 receptor antagonists. We have clinically observed that patients with baseline regular laxative administration, most of whom were on magnesium oxide, exhibited less chemotherapy-induced constipation than those without, and assessed its impact on symptom development in real-world cisplatin-containing treatment.

Methods: Patients with lung cancer receiving cisplatin-containing treatment (n = 240) were divided into a control group without baseline laxative administration and a magnesium group with baseline regular magnesium oxide administration and retrospectively evaluated. The primary endpoint was evaluation of the incidence of grade ≥ 2 constipation during the first 7 days following treatment initiation.

Results: Incidence of grade ≥ 2 constipation was 82.5% in the control group and 50.0% in the magnesium group, which was significantly less in the magnesium group (P < 0.0001). The incidence of all-grade symptoms was also significantly lower in the magnesium group than in the control group (67.5% vs. 84.5%, P = 0.02). Additionally, the administration of new laxatives was less common in the magnesium group (P = 0.007). Multivariable logistic regression analysis suggested that baseline administration of magnesium oxide is a preventive factor for grade ≥ 2 constipation. Furthermore, patients receiving 2 g daily magnesium oxide at baseline developed significantly less grade ≥ 2 constipation than those with < 2 g (19.1% and 84.2%, respectively, P < 0.0001).

Conclusion: The present study suggests that patients with baseline regular magnesium oxide administration exhibit less chemotherapy-induced constipation than those without the administration in cisplatin-containing treatments.

Background: To describe real-world data on health-related quality of life (HRQoL) in patients with locally advanced or metastatic urothelial carcinoma receiving late-line enfortumab vedotin (EV) monotherapy.

Methods: This study included 19 previously treated locally advanced or metastatic urothelial carcinoma patients who received late-line EV monotherapy. Time-course changes in the domains and subscales of the EORTC QLQ-C30, Functional Assessment of Cancer Therapy-General, multi-item short form-8, Pittsburgh Sleep Quality Index (PSQI), and chemotherapy-induced taste alteration scale (CiTAS) questionnaires during EV monotherapy up to 10 cycles were evaluated using linear mixed effects models for repeated measures.

Results: Generally, a negative effect on physical function-related domains was observed during EV monotherapy. In the analysis of the EORTC-QLQ-C30 global health status/QoL subscale, three (16%), nine (47%), and seven (37%) patients experienced clinically meaningful improvement, stability, and clinically meaningful deterioration during EV monotherapy, respectively, and Kaplan-Meier estimation demonstrated that the median number of cycles to deterioration was six. The global PSQI score showed marginally normalized sleep quality, with gradual decrease in population of patients with poor sleep quality (global PSQI score, ≥ 6). After the initiation of EV monotherapy, dysgeusia with worsening subscales in the decline in basic taste and general taste alterations occurred early in the first to fourth cycles. In contrast, the appetite loss score on the EORTC QLQ-C30 questionnaire did not change during EV monotherapy.

Conclusion: Late-line EV monotherapy showed a generally acceptable negative impact on HRQoL. Effective interventions are needed to maintain physical functioning and gustatory abilities in patients receiving EV monotherapy.

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.