International Journal of Clinical Oncology最新文献

Background: De-escalation strategies have gained increasing attention for human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). We previously introduced an approach using upfront neoadjuvant chemotherapy (NAC) to facilitate less invasive surgery and potentially omit postoperative radiotherapy (PORT) or chemoradiotherapy (POCRT). This study evaluated the long-term outcomes and late toxicities of NAC followed by surgery after a 5-year follow-up.

Methods: We retrospectively analyzed 41 patients with resectable HPV-positive OPSCC who received NAC followed by primary tumor resection, with or without neck dissection. Patients were treated with triplet NAC comprising either docetaxel, cisplatin, and 5-fluorouracil (TPF) or carboplatin, paclitaxel, and cetuximab.

Results: A pathological complete response (pCR) at both the primary site and lymph nodes was achieved in 25 patients (61.0%), and PORT/POCRT was required in 6 patients (14.6%). Among the 36 patients who received NAC-TPF, the number of TPF cycles administered in the pCR group was significantly higher than in the non-pCR group (p = 0.0401). The median follow-up period was 5.3 years, with 5-year overall and progression-free survival rates of 92.4% and 80.1%, respectively. Recurrence occurred in 25% of the non-pCR group and 8% of the pCR group. All patients resumed oral intake without nutritional intervention within 35 days after treatment, and no severe late toxicities impairing daily life were observed.

Conclusion: Long-term follow-up demonstrated that NAC followed by surgery-aimed at achieving less invasive procedures and avoiding PORT/POCRT-is feasible and promising in terms of survival and late toxicities in patients with resectable HPV-associated OPSCC.

Background: In the phase 3 EV-302 study, enfortumab vedotin-pembrolizumab (EV + P) significantly prolonged overall survival (OS) and progression-free survival (PFS) versus chemotherapy in patients with untreated locally advanced/metastatic urothelial carcinoma (la/mUC). We present a post hoc analysis in a pan-Asian population.

Methods: Patients from China, Japan, Singapore, South Korea, Taiwan, and Thailand received 3-week cycles of EV (1.25 mg/kg; intravenously; Days 1 and 8) plus P (200 mg; intravenously; Day 1) or chemotherapy (gemcitabine [Days 1 and 8] plus cisplatin/carboplatin [Day 1]). Primary endpoints were PFS and OS. Secondary endpoints included objective response rate (ORR) and safety.

Results: Overall, 176 patients were included (EV + P, n = 94; chemotherapy, n = 82). Median follow-up was 28.9 months for EV + P recipients and 26.6 months for chemotherapy recipients. EV + P prolonged PFS and OS versus chemotherapy, reducing the risk of disease progression or death by 63% (hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.24-0.57) and death by 67% (HR, 0.33; [95% CI, 0.20-0.54]), respectively. Confirmed ORR was 72.2% versus 35.0%. Grade ≥ 3 treatment-related adverse events occurred in 66.0% of EV + P recipients and 68.4% of chemotherapy recipients. Most commonly maculopapular rash (11.7%) and hyperglycemia (10.6%) for EV + P and neutropenia (25.0%), anemia (19.7%), and neutrophil count decreased (18.4%) for chemotherapy.

Conclusion: EV + P demonstrated a clinically meaningful survival benefit in Asian patients with untreated la/mUC, with no new safety signals observed, consistent with the global EV-302 study. Results support guideline recommendations for EV + P as preferred first-line therapy in la/mUC.

Clinical trial registration: NCT04223856 (registered January 8, 2020).

Purpose: The JCOG1806 trial (jRCTs031190129) is underway to evaluate the omission of surgery in patients with human epidermal growth factor receptor (HER2)-positive early breast cancer who have a clinical complete response (cCR) after primary systemic therapy (PST). We aimed to assess the cCR rate in this trial and identify predictive factors.

Methods: HER2-positivity was defined as an immunohistochemistry (IHC) score of 3 + or in situ hybridization-positivity. A cCR was defined as the absence of detectable lesions upon palpation, contrast-enhanced magnetic resonance imaging, and ultrasonography; biopsy-based confirmation was optional in hormone receptor (HR)-negative cases and mandatory in HR-positive cases. Multivariate logistic regression analyses were used to identify predictors of a cCR.

Results: The cCR rate was 57.6% (196/340 patients; 95% confidence interval [CI]: 52.2-63.0%). Strongly estrogen-receptor (ER)-positive tumors (≥ 10%) were significantly less likely to have a cCR than ER-negative tumors (odds ratio [OR], 0.41; 95% CI: 0.20-0.81). IHC 3 + tumors had higher cCR rates than IHC 1 + or 2 + tumors (OR, 2.19; 95% CI: 1.01-4.74). Compared with histological grade I tumors, cCR odds were higher in grade II (OR: 2.92; 95% CI: 1.07-7.93) and III (OR: 4.90; 95% CI: 1.76-13.7) tumors. Among patients without a cCR patients undergoing surgery, 22.2% were diagnosed with ypT0 tumors upon analysis of surgical specimens.

Conclusion: ER-negativity, an IHC score of 3 + , and a higher histological grade were independent predictors of a cCR. Identifying these features may improve the feasibility and safety of surgery omission for patients with HER2-positive early breast cancer.

Background: JO40295 (jRCT2080223801) evaluated the efficacy and safety of subcutaneous (SC) mosunetuzumab, in combination with lenalidomide and as monotherapy, in Japanese patients with relapsed/refractory (R/R) follicular lymphoma (FL). We report outcomes from the interim analysis of the FLMOON-2 (≥ 1 prior therapy; mosunetuzumab plus lenalidomide) and primary analysis of the FLMOON-3 (≥ 2 prior therapies; mosunetuzumab monotherapy) cohorts.

Methods: Mosunetuzumab SC was administered with Cycle (C)1 step-up dosing in both cohorts: C1 Day (D)1, 5 mg; C1D8, D15 and C2 onwards, 45 mg. In FLMOON-2, oral lenalidomide was administered from C2 onwards, on D1-21 of each cycle. Treatment was administered up to C12 in FLMOON-2 and C8 or C17 in FLMOON-3. The primary endpoint was independent review facility-assessed complete response (CR) rate.

Results: At the clinical cut-off date (FLMOON-2: April 4, 2024; FLMOON-3: March 4, 2024), in the efficacy-evaluable populations, CR rate was 92.3% in FLMOON-2 (n = 13) and 100% in FLMOON-3 (n = 5). In the safety-evaluable populations (FLMOON-2, n = 17; FLMOON-3, n = 5), Grade 3/4 adverse events (AEs) occurred in 64.7% of patients in FLMOON-2 and 20.0% in FLMOON-3. No Grade 5 AEs or AEs leading to treatment discontinuation occurred in either cohort. Cytokine release syndrome was reported in 47.1% of patients in FLMOON-2 and 20.0% in FLMOON-3. Serum mosunetuzumab concentration peaked with the third dose of mosunetuzumab in C1 and reached a steady state with repeated dosing.

Conclusion: Mosunetuzumab SC, in combination with lenalidomide and as monotherapy, demonstrated promising efficacy with a manageable safety profile in Japanese patients with R/R FL.

Background: Cervical cancer poses a significant global health burden, particularly in its metastatic and recurrent forms, for which treatment options are limited. Although immune checkpoint inhibitors (ICIs) such as pembrolizumab have improved outcomes, predictive markers for efficacy are still undefined. This retrospective study investigated changes in peripheral blood eosinophil and lymphocyte counts as potential prognostic indicators in patients with metastatic or recurrent cervical cancer undergoing pembrolizumab-based therapy.

Methods: Forty-one patients treated with pembrolizumab plus taxane-platinum chemotherapy (± bevacizumab) were analyzed. Peripheral blood eosinophil and lymphocyte counts were measured before and 3 weeks after treatment initiation. Statistical analyses included Kaplan-Meier curves, Cox regression, and log-rank tests.

Results: Immune-related adverse events ≥ grade 2 emerged as a significant independent factor associated with prolonged progression-free survival (PFS) in this cohort (p = 0.014). Patients with decreased eosinophil count ratios post-treatment demonstrated longer PFS, particularly among those with recurrence and those who had received prior radiotherapy (p = 0.0001). Conversely, increased lymphocyte count ratios correlated with improved PFS in patients undergoing primary treatment (p = 0.018).

Conclusion: Changes in peripheral eosinophil and lymphocyte counts following pembrolizumab initiation may serve as predictive indicators of treatment efficacy in specific cervical cancer subgroups. Incorporating these hematologic parameters could help optimize patient selection and therapeutic strategies. Further research is needed to clarify their role as predictive markers of pembrolizumab efficacy in cervical cancer.

Background: Lisocabtagene maraleucel (liso-cel), an anti-CD19 CAR T cell therapy, has demonstrated efficacy in relapsed/refractory (R/R) large B cell lymphoma (LBCL). However, real-world data from commercial settings outside the United States remain limited.

Methods: To evaluate the safety and effectiveness of commercial-use liso-cel in Japan, we conducted a single-center retrospective study of patients with R/R LBCL who received commercial-use liso-cel at our institution between November 2021 and November 2024.

Results: 56 patients received liso-cel infusion. The median age was 66.5 years, and 55.4% had primary refractory disease. Liso-cel was administered as second-line therapy in 14 patients (25.0%) and as third-line or later therapy in 42 patients (75.0%). The best overall response rate was 80.4%, with a complete response rate of 78.6%. At a median follow-up of 12.3 months, 1 year progression-free survival (PFS) and overall survival rates were 69.5% and 86.4%, respectively. The 1 year PFS rates were 68.5% for diffuse large B cell lymphoma not otherwise specified, 100% for primary mediastinal large B cell lymphoma (PMBCL), and 30% for high-grade B cell lymphoma (HGBCL). Grade ≥ 3 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome were observed in one patient each. Multivariate analysis identified HGBCL subtype and higher pre-infusion metabolic tumor volume as independent adverse factors for PFS.

Conclusion: Commercial-use liso-cel demonstrated high response rates and favorable safety in Japanese patients with R/R LBCL. Patients with PMBCL had excellent outcomes, whereas those with HGBCL showed poorer prognosis, indicating a need for further therapeutic strategies.

Background: Currently, there are no reports on the subsequent treatment of patients with ovarian cancer who exhibited platinum-resistant recurrence during treatment with poly (ADP-ribose) polymerase (PARP) inhibitors. This retrospective study was aimed at evaluating the efficacy and safety of single-agent chemotherapy combined with bevacizumab (BEV) in such patients.

Patients and methods: The efficacy and safety of the treatment were evaluated in 16 patients with ovarian cancer, fallopian tube cancer, or primary peritoneal cancer diagnosed with platinum-resistant recurrence during PARP inhibitor treatment between April 2019 and June 2025. Chemotherapy was administered with paclitaxel alone or nogitecan alone in combination with BEV and generally continued until the disease progressed.

Results: The median number of single-agent chemotherapy cycles with BEV was 6 (range: 1-20). The objective response and disease control rates were 31.3% and 75.0%, respectively. The median progression-free survival 2 and post-progression survival were 5.5 months [95% confidence interval (CI) = 4.0-6.0] and 17 months (95%CI = 10.0-29.0), respectively. Grade 3 or higher hematological toxicities were observed, including leukopenia, neutropenia, anemia, and thrombocytopenia in 7, 9, 1, and 3 patients, respectively. Non-hematological toxicities included hypertension in three patients and nausea, vomiting, fatigue, proteinuria, thrombosis, ileus, and heart failure in one patient each. None of the patients discontinued chemotherapy because of adverse events or treatment-related deaths.

Conclusion: BEV-combined single-agent chemotherapy has potential efficacy even in the challenging setting of platinum-resistant recurrence during PARP inhibitor treatment of ovarian cancer.

Background: Cisplatin-based concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced cervical cancer; however, its nephrotoxicity and gastrointestinal toxicity often limit treatment eligibility and completion. Nedaplatin, a cisplatin analogue with reduced renal and gastrointestinal toxicity, has been increasingly used in East Asia, but its comparative efficacy and safety in cervical cancer have not been comprehensively evaluated.

Methods: We systematically searched MEDLINE, Embase, CENTRAL, CNKI, Ichushi Web, ICTRP, and ClinicalTrials.gov for randomized controlled trials comparing nedaplatin versus cisplatin-based CCRT. The primary efficacy outcome was all-cause mortality at 3 years, and the primary safety outcome was renal toxicity. Secondary outcomes included mortality at 1 and 5 years, progression or mortality, hematologic and gastrointestinal toxicities, liver dysfunction, and quality of life. Random-effects meta-analyses were performed using risk ratios.

Results: Seventeen trials met the eligibility criteria. All-cause mortality at 3 years did not differ significantly between the groups (RR 0.88; 95% CI 0.51-1.51; I² = 0%). Nedaplatin significantly reduced renal toxicity (RR 0.25; 95% CI 0.20-0.31; I² = 0%). Short-term outcomes favored nedaplatin, including lower 1 year mortality (RR 0.61; 95% CI 0.40-0.93) and fewer 1 year progression or mortality events (RR 0.63; 95% CI 0.44-0.91). The incidences of anemia and severe nausea/vomiting were also lower with nedaplatin. No eligible study assessed quality of life.

Conclusion: Nedaplatin showed fewer adverse effects and comparable or improved short-term outcomes compared with cisplatin. These findings support nedaplatin as a potential alternative for patients who are cisplatin-intolerant or frail. Confirmation in large, high-quality trials with long-term follow-up and patient-reported outcomes is warranted.

Background: To determine the optimal extent of pelvic lymph node dissection in bladder cancer, evaluating the prognostic relevance of nodal sub-staging, and assessing the feasibility of sentinel lymph node biopsy and omission of contralateral dissection.

Methods: This retrospective study included 180 patients undergoing laparoscopic or robot-assisted radical cystectomy. Sentinel lymph node detection was assessed in 30 cases as a pilot. The obturator region was defined according to lymphatic drainage patterns. The prognostic impact of nodal sub-staging was evaluated using Kaplan-Meier and Cox proportional hazards models. Laterality of tumor location and node metastasis was also analyzed.

Results: Sentinel lymph node biopsy demonstrated a 63% detection rate with a 1.6% false-negative rate. Nodal metastases were observed in 8.9% of pN1 and 8.3% of pN2-3 cases, predominantly in the obturator region (87.5% and 100%, respectively). Lymph node metastases were most frequently located in the obturator region, including 87.5% of stage pN1 and 100% of stage pN2-3 cases. Cancer-specific survival was significantly better in pN1 than in pN2-3 cases (median 61 vs. 7 months, p < 0.001). Cox proportional hazards regression models identified pN2-3 as the strongest prognostic factor (HR for CSS: 25.4). Ipsilateral nodal metastasis was observed in 87.5% of lateral wall tumors.

Conclusions: Although sentinel lymph node biopsy demonstrated limited utility, the obturator region appears to represent the optimal diagnostic target for nodal metastasis. In pN1 disease, this region may be therapeutic, resembling sentinel nodes and showing limited spread with better prognosis than pN2-3 disease.

Background: Sarcopenia is a critical comorbidity in esophageal cancer patients undergoing neoadjuvant therapy (NAT), linked to poor surgical outcomes and survival. However, its reported prevalence varies widely, and a comprehensive synthesis of evidence is lacking.

Objective: To systematically evaluate and quantify the prevalence of the sarcopenia disease in in patients known to be diagnosed with esophageal cancer and receiving preoperative neoadjuvant therapy and examine its association with clinical outcomes.

Methods: Following PRISMA guidelines 2020, This systematic review and meta-analysis that was registered on PROSPERO (CRD420251109294), provides a comprehensive search through PubMed, SCOPUS, Web of Science, and the Cochrane Library to identify research papers reporting sarcopenia prevalence in esophageal cancer patients undergoing neoadjuvant chemotherapy or chemoradiotherapy. Pooled prevalence estimates and outcome associations were calculated using random-effects models. Subgroup and sensitivity analyses were performed to explore heterogeneity, and study quality was assessed using the Newcastle-Ottawa Scale.

Results: Twenty-six research studies comprising 3298 patients were included. The pooled prevalence of sarcopenia following neoadjuvant therapy was 48% (95% CI 38-58%), with considerable heterogeneity (I² = 95.7%). Sarcopenia was significantly associated with worse overall survival (HR: 2.10; 95% CI 1.72-2.57) but showed no statistically significant association with recurrence-free survival or postoperative complications. Most studies were of moderate to high quality, though differences in diagnostic criteria and assessment timing contributed to heterogeneity.

Conclusions: Sarcopenia is highly prevalent among patients with esophageal cancer undergoing neoadjuvant therapy. Although sarcopenia was consistently associated with poorer overall survival, these findings are derived from heterogeneous definitions, variable assessment timing, and unadjusted outcome analyses, and should therefore be interpreted as associative rather than causal. Standardized diagnostic criteria, incorporation of muscle strength assessment, and prospective studies are required in future research.