Future oncology最新文献

Background: Nasopharyngeal carcinoma (NPC) is increasingly diagnosed in elderly populations. However, prognostic tools that incorporate both tumor biology and host vulnerability remain limited.

Methods: In this retrospective cohort study, a total of 185 elderly patients (aged ≥65 years) with histologically confirmed NPC treated with concurrent chemoradiotherapy (CCRT) between March 2020 and June 2023 were evaluated. This study assessed the independent and combined prognostic value of the pan-immune-inflammation value (PIV) and frailty index for overall survival (OS) and progression-free survival (PFS).

Results: Both high PIV and frailty independently predicted shorter OS and PFS (p < 0.001). Combined classification into four subgroups yielded clear prognostic separation: Low PIV + Non-frail patients achieved the best 3-year OS (88.5%) and PFS (82.1%), whereas High PIV + Frail patients had the poorest outcomes (3-year OS 38.6%, PFS 30.4%). The combined model improved the C-index for OS prediction from 0.68 to 0.79 and the AUC for PFS from 0.70 to 0.81 compared with the baseline clinical models. Prognostic value remained robust in stage- and ECOG-stratified analyses with no significant interaction effects.

Conclusion: The combination of PIV and frailty provides a highly discriminative prognostic tool in elderly NPC patients undergoing CCRT.

Aim: This study evaluated the long-term safety and effectiveness of ruxolitinib in Japanese patients with polycythemia vera in clinical practice.

Patients and methods: This multicenter, single-arm, non-interventional, prospective, observational study assessed patients receiving ruxolitinib after approval.

Results: Of 550 patients (median age: 71 years, mean disease duration: 5.43 years, median treatment duration: 1091 days), 51.27% reported adverse drug reactions (ADRs) and 12.18% had serious ADRs, with anemia being the most common ADR. The highest incidence of ADRs (40%) was observed from treatment initiation to Day 182, with no tendency for increased incidence thereafter. ADRs of special interest included myelosuppression (27.64%), hepatic impairment (13.45%), infections (9.27%), hemorrhagic events (5.64%), cardiac failure (1.27%), malignancy (1.09%), interstitial lung disease (0.36%), and tuberculosis (0.18%). Baseline hepatic impairment did not increase the incidence of ADRs, but numerical incidence was higher in patients with baseline renal impairment, with similar events being observed in patients with or without renal impairment. At 36 months, spleen response and symptom improvement were observed in 31.43% and 61.14% of patients, respectively. Reductions in hematocrit, white blood cell count, and platelet count were observed throughout the treatment duration.

Conclusion: Ruxolitinib demonstrated sustained effectiveness with no new safety concerns in the real-world setting.

Aims: To define anterior peritoneal reflection (APR) as a more reasonable boundary for upper rectal cancer (URC) and assess the effect of neoadjuvant chemoradiotherapy (CRT) on locally advanced rectal cancer (LARC) above the APR.

Materials & methods: MRI identified patients with LARC above the APR, excluding T4b cases. Patients were grouped by CRT status, and differences in their treatments and outcomes were compared. Propensity score matching was applied to adjust for baseline differences.

Results: Of 1869 patients, 1702 (91.1%) had visible APR, with median heights of 7.5 cm for females and 8.6 cm for males. From 2011 to 2018, 479 patients with LARC above the APR were included. No significant differences were found between CRT and non-CRT groups in disease-free survival (DFS) (76.9% vs. 79.5%, P = 0.629), local recurrence-free survival (LRFS) (93.6% vs. 90.4%, P = 0.353) and overall survival (OS) (88.5% vs. 87.8%, P = 0.722). Cox regression showed CRT was not an independent influencing factor for DFS or OS.

Conclusions: It was feasible to accurately identify APR using MRI and distinguish upper and lower rectal cancer. CRT might not be essential for LARC patients above the APR after excluding T4b cases, which can avoid unnecessary treatment.

Purpose: Mathematical comparisons of lung adenocarcinoma (LUAD) with epidermal growth factor receptor (EGFR) mutations of L858R and 19DEL.

Methods: A total of 1,980 surgically resected LUAD cases were analyzed, comprising 1,195 ground glass opacity LUAD (GGO-LUAD) and 785 pure solid lung adenocarcinomas (pSD-LUAD). LUAD cases were grouped based on EGFR mutation status. Correlations between tumor size (x) and frequency ratio (y) were analyzed using exponential equations.

Results: Multivariate logistic regression analysis showed that the 19DEL mutation was more frequently observed in younger individuals (OR: 1.60, 95% CI: 1.29-1.99, p < 0.0001) and high-grade tumors (OR: 1.46, 95% CI: 1.01-2.11, p = 0.004). Equations were fitted as follows: y = e^{-0.046 + 0.48} × (x ≤ 2.5 cm, p = 0.0016) (1), y = e^{-2.09 + 0.37} × (x ≤ 4 cm, p < 0.0001) (2), y = e^{-1.65 + 0.38} × (x ≤ 4 cm, p = 0.0001) (3).

Conclusion: pGGO-LUAD with L858R EGFR mutations grew more rapidly than those with 19DEL mutations, but the solidification rate of L858R-mutated GGO-LUAD was lower compared to 19DEL-mutated GGO-LUAD.

Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) was historically associated with a very poor prognosis in the pre-tyrosine kinase inhibitors (TKIs) era. While consolidation with allogeneic hematopoietic cell transplantation (HCT) was associated with improved outcomes in patients with Ph+ ALL treated with chemotherapy alone, the advent of BCR::ABL1-targeting TKIs revolutionized the therapeutic landscape, enhancing response rates, increasing the proportion of patients proceeding to HCT, and improving survival. Compared to earlier generation TKIs, ponatinib, a third-generation TKI, is more potent and overcomes a broader array of preexisting and emerging resistant mutations, and clinical studies have illustrated superiority in attaining a negative measurable residual disease (MRD) state, leading to excellent long-term survival outcomes, even without the application of consolidative allogeneic HCT. Ponatinib has been successfully integrated into various treatment regimens, including both low- and high-intensity chemotherapy regimens, and in combination with blinatumomab, for adult patients with newly diagnosed Ph+ ALL. Herein, we summarize landmark trials, specifically their efficacy and toxicity profile, that established ponatinib as a standard of care for patients with newly diagnosed Ph+ ALL who are suitable medically for it.

Aims: Immune checkpoint inhibitors (ICIs) have improved outcomes in several malignancies, but survival remains poor for patients with unresectable advanced or recurrent esophageal or gastric cancer. Recent evidence suggests that modulation of the intestinal microbiota may influence the therapeutic response to ICIs. This study aims to evaluate the safety and preliminary efficacy of fecal microbiota transplantation following antibiotic pretreatment (A-FMT) in patients scheduled to receive ICI-containing regimens.

Methods: This phase I - II, single-institution clinical trial enrolls patients with unresectable advanced or recurrent esophageal or gastric cancer. Participants receive a 1-week course of oral antibiotics (amoxicillin, fosfomycin, and metronidazole) prior to transplantation. A single dose of donor-derived intestinal microbiota solution is administered via colonoscopy, followed by initiation of ICI-based therapy on the next day. The primary endpoint is the incidence of dose-limiting toxicity. Secondary endpoints include response rate, disease control rate, progression-free survival, overall survival, and adverse events. Comprehensive translational research is conducted using stool, blood, and tissue samples to characterize immune responses and identify biomarkers associated with A-FMT and ICI efficacy.Trial registration: jRCTs031240170.The study is ongoing, and patients are currently being enrolled. Enrollment started in June 2024. A total of 7 patients have been enrolled as of August 2025. This protocol is version 3.2.

Trastuzumab deruxtecan (T-DXd), a human epidermal growth factor receptor 2 (HER2)-targeted antibody - drug conjugate with a potent topoisomerase I inhibitor payload, has addressed considerable unmet needs in advanced HER2-positive gastric cancer or gastroesophageal junction cancer (GC/GEJC), particularly among patients showing disease progression following trastuzumab-based therapy. The present review summarizes the clinical development, real-world management, and future directions of T-DXd. The superiority of T-DXd was first demonstrated in the DESTINY-Gastric01 trial and subsequently confirmed in the recent global phase III DESTINY-Gastric04 trial, where it showed remarkable efficacy over chemotherapy, establishing it as the second-line standard of care. However, this efficacy must be balanced against its distinct safety profile, with interstitial lung disease representing most critical adverse event requiring vigilant monitoring and proactive management. Resistance mechanisms, including decreased HER2 expression and impaired internalization, remained the important challenges to overcome. Ongoing studies are exploring the role of T-DXd in first-line treatments, HER2-low tumors, and perioperative settings, with the aim of further expanding its therapeutic applications. These efforts hold promise for broadening the clinical utility of T-DXd and redefining the treatment algorithms for a wider population of GC/GEJC patients.

The fixed-duration combination of ibrutinib and venetoclax has shown significant benefits in the first-line treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) through clinical studies with follow-up extending up to 5.5 years. However, there remains an important gap in real-world data regarding efficacy and tolerability outcomes of this regimen outside of clinical trial settings. The REALITY-Worldwide study has been initiated as a prospective observational study aimed at understanding the usage, factors for therapy decision, and clinical response of first-line fixed-duration ibrutinib-venetoclax in routine clinical practice. The primary endpoint is physician-assessed overall response rate according to 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria. Secondary endpoints and outcomes of interest include duration of response, progression-free survival, overall survival, time to next treatment, tumor lysis syndrome risk, adverse events, patient-reported outcomes, factors associated with physician decision to initiate fixed-duration ibrutinib-venetoclax in clinical practice, medical resource utilization, and patient-reported outcomes. The study aims to enroll approximately 200 patients across Europe, the Middle East, and Latin America. A pooled analysis will include subsets of data collected from REALITY-WW and the ongoing multicenter REALITY-2 study in Germany.