Future oncology最新文献

Aims: To explore the prognostic value of the combined SII-PNI (Systemic Immune-Inflammation Index + Prognostic Nutritional Index) in cholangiocarcinoma (CCA) patients.

Methods: Retrospective analysis of 149 CCA patients' clinical data was conducted, with the SII-PNI scoring system used to assess its prognostic impact.

Results: Chi-square analysis showed SII-PNI correlated with CEA and CA19-9 (p < 0.05). Kaplan-Meier curves revealed significant progression-free survival (PFS) differences among SII-PNI groups (p < 0.005). Cox univariate analysis identified AST, CA19-9, and CEA as PFS prognostic factors (p < 0.05), but only SII-PNI was an independent factor in multivariate analysis (p < 0.005).

Conclusion: SII-PNI (integrating inflammation and nutrition) effectively predicts CCA's PFS (HR = 1.51, p < 0.005), outperforming conventional biomarkers like CA19-9. Its cost-effectiveness supports CCA risk stratification. However, SII-PNI-based dynamic treatment response monitoring is unvalidated (retrospective limitation) and needs prospective trials; no intensified treatment recommendations are made.

Background: Durvalumab was initially approved for stage III unresectable non-small cell lung cancer (NSCLC) post-concurrent chemoradiation at 10 mg/kg every two weeks, and starting in November 2020, at 1500 mg every four weeks (Q4W). Real-world evidence is limited on durvalumab Q4W dosing utilization and discontinuation, especially in community-based oncology settings.

Methods: In this retrospective cohort, we examined patients with stage III unresectable NSCLC who initiated durvalumab between 3 January 2019 and 12/31/2021, including those who switched to Q4W dosing or received Q4W dosing only, with follow-up until durvalumab discontinuation, health plan disenrollment, death, or study's end.

Results: Of the 102 patients (mean age: 71 years; 46.1% female; 46.1% non-White; 80.4% formerly smoked), 40 switched to Q4W dosing, and 62 received Q4W dosing only. Median duration of treatment (DoT) was 10.0 months overall and 7.5 months for Q4W only. About one-third of patients receiving Q4W dosing completed treatment. Discontinuation occurred in 51.5% of all patients and 65.5% receiving Q4W dosing only. The most common discontinuation reasons were disease progression (17.7%) and pneumonitis (14.7%).

Conclusion: In this diverse community-based cohort, Q4W dosing outcomes, including DoT and completion rate, were comparable to other real-world studies with Q2W dosing and the PACIFIC and PACIFIC-R trials.

Endocrine therapy (ET) resistance is a major concern when treating estrogen receptor-positive (ER+) human epidermal growth factor receptor 2-negative (HER2-) breast cancer. A combination of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) and ET is the current first-line standard of care (SOC) for patients with ER+, HER2- advanced breast cancer. Despite the benefits of ET plus a CDK4/6i, disease progression due to endocrine resistance remains a significant challenge. More effective ETs that can overcome resistance are needed to improve clinical outcomes and maintain quality of life by delaying chemotherapy. Palazestrant is a novel oral, complete estrogen receptor antagonist (CERAN) and selective estrogen receptor degrader (SERD) that blocks both transcriptional activation function domains, AF1 and AF2, resulting in complete inhibition of ER-driven transcription, regardless of estrogen receptor 1 (ESR1) mutation status. As monotherapy, palazestrant showed tolerable safety, favorable pharmacokinetics, and antitumor efficacy in heavily pretreated patients during phase I/II studies. OPERA-01 (NCT06016738) is a phase III study designed to evaluate the safety and efficacy of palazestrant monotherapy compared to SOC ET in patients with ER+, HER2- locally advanced or metastatic breast cancer, regardless of ESR1 mutation status, whose disease advanced following treatment with at least one ET in combination with a CDK4/6i.Clinical Trial Registration: Clinicaltrials.gov NCT06016738. Registered 17 August 2023.

The role of perioperative immunotherapy as a chemotherapy-free option for patients with resectable mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) colon cancer is evolving, with early-phase neoadjuvant studies reporting favorable long-term outcomes. AZUR-2 is an ongoing global, Phase III, open-label, randomized study evaluating the efficacy of perioperative dostarlimab monotherapy compared with standard of care (SoC) (adjuvant chemotherapy or surveillance) in adult patients with previously untreated, pathologically confirmed, radiologically evaluable T4N0 or Stage III resectable dMMR/MSIH colon adenocarcinoma. Patients will be randomized 2:1 to receive neoadjuvant dostarlimab 500 mg every 3 weeks (4 cycles), followed by surgery, then adjuvant dostarlimab 1000 mg every 6 weeks (6 cycles), or to receive immediate surgery followed by SoC. The primary endpoint is event-free survival assessed by blinded independent central review. The key secondary endpoint is overall survival; additional secondary endpoints include pathological response assessed by residual viable tumor determined by local assessment, safety, and tolerability.Clinical trial registration: NCT05855200 (www.clinicaltrials.gov).

Background: Consolidative thoracic radiotherapy (RT) following chemo-immunotherapy is increasingly used in extensive-stage small cell lung cancer (ES-SCLC). This study investigates the prognostic value of the estimated radiation dose to immune cells (EDRIC) and its determinants in these patients.

Methods: This retrospective study included 173 ES-SCLC patients between 2020 and 2023. EDRIC was calculated as a function of the number of fractions and the average doses to the lungs, heart, and remaining body. Kaplan-Meier and Cox regression analyses were performed to evaluate overall survival (OS) and progression-free survival (PFS).

Results: GTV, PTV, and N stage were positively correlated with EDRIC (r = 0.2577, p = 0.0006; r = 0.3541, p < 0.01; r = 0.2259, p = 0.0028), while lymphocyte nadir was negatively correlated (r = -0.2190, p = 0.0038). Median OS and PFS were longer in the EDRIC ≤4.68 Gy group (OS: 24.9 vs. 17.4 months, p = 0.003; PFS: 12.4 vs. 10.1 months, p = 0.038). Patients in the EDRIC ≤4.68 Gy group had significantly better OS (HR = 0.56, p = 0.003) and PFS (HR = 0.68, p = 0.039). Bone metastasis was associated with worse OS (HR = 1.88, p = 0.002), and liver metastasis with shorter PFS (HR = 2.05, p = 0.001).

Conclusions: EDRIC is an independent predictor of OS and PFS in ES-SCLC. These findings highlight the need to optimize radiation exposure to the immune system in cancer treatment.

Aims: To investigate the association between primary cancer type and the tissues affected by immune-related adverse events (irAEs) in patients treated with immune checkpoint inhibitors (ICIs).

Patients & methods: A retrospective chart review was conducted on 241 patients representing 262 treatment lines involving ICIs at a single institution.

Results: No significant association was found between cancer type and tissue-specific irAEs. irAE incidence was higher with combination PD-1/CTLA-4 inhibitors vs. PD-1 inhibitors alone (61% vs. 46%, p = 0.042). Median time to first irAE was 7.88 months for PD-1 monotherapy versus 2.30 months for combination therapy (log-rank p = 0.00011), a difference of 5.58 months.

Conclusions: Primary cancer type was not significantly associated with tissue-specific irAEs in ICI-treated patients. The 5.58-month difference in median time to irAE onset has important implications for monitoring protocols. Further research is needed to identify factors predicting irAE patterns and severity.

Background: Cancer-related fatigue (CRF) reduces physical performance and quality of life (QoL). Some authors suggest including moderate-intensity physical exercise to manage CRF; however, the optimal timing to offer rehabilitation remains unclear. The primary aim is to investigate the feasibility of a pulmonary rehabilitation (PR) program, including physical exercise and educational sessions, for lung cancer patients undergoing cancer treatments; secondary objectives are to investigate its effect on CRF, physical performance, and QoL.

Methods: This randomized controlled trial enrolls 40 patients with stage II or III non-small-cell lung cancer undergoing chemotherapy, radiotherapy, or immunotherapy. Patients are randomly assigned to one of two groups: Group A (early-PR) begins PR after enrollment, at the beginning of non-surgical therapies, while Group B (delayed-PR) begins PR for 3 months after enrollment. The PR program consists of two education sessions focused on CRF management and eight supervised exercise sessions, including aerobic, strengthening, stretching, and breathing exercises, combined with home exercises. CRF, QoL, activity level, and endurance are assessed at the baseline (T0) and at 3 and 6 months (T1-T2). One year after T0, survival is assessed along with the CRF, QoL, and activity level (T3). Feasibility will be assessed at 3 and 6 months.Clinical Trial Registration: www.clinicaltrials.gov identifier is NCT06051136.

Mitochondrial DNA (mtDNA) is integral to cellular function. Alterations in mtDNA can lead to significant disruptions in mitochondrial function, including cellular energy production, metabolism, and apoptosis regulation. Mitochondrial dysfunction has emerged as a crucial factor in the progression of cancer, including head and neck squamous cell carcinoma (HNSCC). Based on a literature search conducted from August 2024 to March 2025 on PubMed and Google Scholar, our review summarizes the relevance of mtDNA alterations in HNSCC development. HNSCC has been found to cause significant variations in mtDNA, including mutations, copy number variations (or known as mtDNA content) and large-scale deletions. Notably, these alterations varied by disease stage, different key aspects of mitochondrial function, such as cellular growth, senescence, metabolism and apoptosis, and cell-specific genetic context. We further suggest that drugs that modulate mitochondrial pathways, mitochondrial transplantation, and gene-editing technologies, are future treatment strategies for HNSCC. Lastly, we discuss the potential of co-roles of nuclear DNA mutations with mtDNA alterations in HNSCC to provide a holistic view of HNSCC pathogenesis and the possibility for combined therapeutic strategies in HNSCC.