Clinical & Translational Oncology最新文献

Objective: The purpose of this research was to examine the impact of FEZ family zinc finger 1 antisense RNA 1 (FEZF1-AS1) on ferroptosis regulation in non-small cell lung cancer (NSCLC) cells and to understand its molecular mechanism.

Methods: The effects of FEZF1-AS1 silencing on NSCLC cell proliferation, invasion, migration, and apoptosis were evaluated through functional assays, utilizing the Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, flow cytometry, and Transwell assays. The levels of cellular reactive oxygen species, malondialdehyde, glutathione, and Fe²⁺ were measured using commercial assay kits. Proteins related to ferroptosis and the tumor necrosis factor-alpha (TNF-α)/nuclear factor-κB (NF-κB) axis were analyzed using Western blot. Finally, rescue experiments were carried out by treating the cells with TNF-α.

Results: FEZF1-AS1 expression was significantly upregulated in NSCLC cells. Moreover, FEZF1-AS1 silencing suppressed proliferation, migration, and invasion, while enhancing ferroptosis sensitivity in NSCLC cell lines. This knockdown also inhibited the TNF-α/NF-κB pathway. TNF-α attenuated both pro-ferroptotic and anti-tumor effects of FEZF1-AS1 silencing in NSCLC cells. Mechanistically, knockdown of FEZF1-AS1 modulates ferroptosis and malignant behaviors in NSCLC cells through suppression of the TNF-α/NF-κB axis.

Conclusion: Our study uncovers a previously unrecognized mechanistic axis in which FEZF1-AS1 promotes NSCLC progression through suppressing ferroptosis by activating the TNF-α/NF-κB axis.

RASSF1A is a tumor suppressor and is underexpressed in most cancers including genitourinary malignancies. RASSF1A is most frequently inactivated epigenetically following biallelic hypermethylation of its CpG islands involving DNA methyltransferases. Genitourinary malignancies result in profound morbidity and mortality especially in the old age people and hence discovery of novel therapeutic agents targeting the molecular aberrations are demanded for improved survival. In bladder cancer, RASSF1A downregulation is associated with modulation of key signaling process such as Hippo signaling pathway. Also, pharmacological activation of RASSF1A could augment the cytotoxicity induced by chemotherapeutic agents. Promoter methylation in RASSF1A in combination with other tumor suppressor genes (such as GSTP1 and MGMT) is also observed in the cancers of the male reproductive system and may aid in pathological classification as well as differentiation. In prostate cancer, RASSF1A promoter hypermethylation status could have key role in early diagnosis or modulating therapeutic response. Genitourinary malignancies having RASSF1A hypermethylation are also linked to poor patient prognosis. Evaluating RASSF1A methylation in a panel consisting of other tumor suppressor genes could plausibly improve the diagnostic accuracy in genitourinary cancers. Also, novel hypomethylating agents targeting the RASSF1A promoters could potentially enhance its reactivation in genitourinary cancers.

Background: Patients with colorectal cancer frequently experience sleep disturbance, psychological distress, and impaired quality of life after surgery. These symptoms are interrelated through inflammatory and neuroendocrine pathways but are rarely addressed using integrated interventions.

Methods: We conducted a prospective, single-center randomized controlled trial at the First Affiliated Hospital of Soochow University (September 2021-September 2023). A total of 300 patients with stage I-III colorectal cancer were randomized (1:1) to standard oncological care or to a combined intervention including sleep hygiene education, relaxation training, stimulus control, and cognitive-behavioral therapy-based psychological support. Outcomes included Pittsburgh Sleep Quality Index (PSQI), Visual Analog Scale (VAS) pain, Zung Anxiety (SAS) and Depression (SDS) scales, and EORTC QLQ-C30 Global Health/Quality of Life (GHS/QL). Analyses followed the intention-to-treat principle, with multiple imputation for missing data and analysis of covariance (ANCOVA) adjusted for baseline scores.

Results: Of 356 patients screened, 300 were randomized (150 per group). At 3 months, the intervention group showed greater improvement in PSQI (aMD - 7.5, 95% CI - 8.4 to - 6.6, p < 0.001), VAS pain (aMD - 3.2, 95% CI - 3.6 to - 2.8, p < 0.001), SAS (aMD - 13.2, 95% CI - 14.7 to - 11.7, p < 0.001), and SDS (aMD - 13.5, 95% CI - 15.1 to - 12.0, p < 0.001). Global quality of life improved significantly (aMD + 12.5, 95% CI + 10.9 to + 14.1, p < 0.001). All changes exceeded minimal clinically important differences. Intervention adherence was high (93.3%), and no adverse events occurred.

Conclusion: An integrated program of sleep and psychological interventions produced clinically and statistically significant improvements in postoperative sleep quality, pain, anxiety, depression, and overall quality of life in colorectal cancer patients. This safe, feasible, and replicable strategy may complement enhanced recovery after surgery (ERAS) protocols and warrants multicenter evaluation with extended follow-up.

Background: Adjuvant programmed cell death protein 1 (PD-1) inhibitors (nivolumab, pembrolizumab) improve recurrence-free survival (RFS) in stage IIB-IIC melanoma, yet no head-to-head trial directly compares them. Traditional indirect methods estimate relative efficacy but often fail to integrate toxicity and patient-level trade-offs. Reinforcement learning (RL) provides a framework to simulate decision-making under uncertainty and competing clinical priorities.

Methods: We developed an RL model treating each simulated patient as the environment, with state variables including age, ECOG status, stage, time-to-recurrence, and adverse event (AE) outcomes. Actions were treatment choices between nivolumab and pembrolizumab. Rewards combined gains in RFS (+ 1 per 2 months) with penalties for grade 3-4 AEs and discontinuations, incorporating both raw and placebo-adjusted AE rates. Q-learning was iterated across 1000 virtual trial episodes until policy convergence.

Results: The RL-derived policies reflected conditional treatment preferences rather than a single optimal agent. In scenarios weighted toward tolerability, nivolumab was favored due to lower grade 3-4 AE and discontinuation rates. When incremental RFS gains were prioritized, pembrolizumab emerged as the preferred option. Placebo-adjusted versus raw AE modeling materially influenced the balance of preferences, underscoring the importance of attribution in comparative safety assessment.

Conclusion: Our RL framework complements existing comparative methods by making treatment trade-offs explicit and scenario-dependent. Rather than declaring a universal "best" PD-1 inhibitor, the model contextualizes efficacy-toxicity balances, supporting transparent decision-making in settings where small absolute differences may meaningfully influence patient and clinician preferences.

Background: Small cell lung cancer (SCLC) is an aggressive malignancy frequently complicated by systemic inflammation, cachexia, and metabolic dysfunction. While 18F-FDG PET/CT is routinely used for disease staging, its potential to reflect host metabolic status through tissue-specific uptake metrics remains underexplored. We investigated the prognostic significance of the liver-to-rectus femoris mean standardized uptake value ratio (LRF) alongside systemic inflammatory markers in patients with SCLC.

Methods: This retrospective study included 155 newly diagnosed SCLC patients who underwent baseline 18F-FDG PET/CT prior to systemic therapy. Quantitative PET/CT metrics-particularly LRF SUVmean-were analyzed in relation to clinical characteristics, inflammatory indices (CRP-to-albumin ratio [CAR], neutrophil-to-lymphocyte ratio [NLR]), and survival outcomes. Kaplan-Meier and multivariate Cox regression analyses were used to assess progression-free survival (PFS) and overall survival (OS).

Results: An elevated LRF ratio (≥ 3.18) was independently associated with shorter PFS (7.52 vs. 10.22 months; p = 0.047) and OS (7.85 vs. 9.40 months; p = 0.021) in extensive-stage SCLC. Similarly, patients with CAR ≥ 0.29 had significantly worse progression-free survival (7.10 vs. 11.50 months; p = 0.001) and overall survival (7.55 vs. 13.74 months; p = 0.008) compared to those with CAR < 0.29. LRF SUVmean positively correlated with CAR and negatively with serum albumin. In contrast, NLR was not significantly associated with survival outcomes.

Conclusion: The LRF SUVmean ratio represents a novel, noninvasive PET/CT-derived biomarker that reflects host metabolic frailty and correlates with systemic inflammation. Integration of metabolic imaging parameters such as LRF with established laboratory markers may improve prognostic stratification in SCLC and guide supportive care strategies.

Purpose: Recent studies have suggested a change in the epidemiologic pattern of testicular germ-cell tumors (TGCTs) and advances in therapeutic strategies have led to significant changes in their treatment over the last decades. Treatment guidelines for early-stage testicular cancer recommend de-escalation of therapy by the adoption of surveillance strategies. This study aimed to describe trends in TGCTs diagnosed over the last 30 years at our center and evaluate the impact of evolving treatment strategies.

Methods: We retrospectively analyzed 277 TGCT patients treated from 1994 to 2023. Clinical characteristics, treatment patterns, and outcomes were assessed across three 10-year periods. Survival and relapse rates were estimated using Kaplan-Meier methods; significance was set at p < 0.05.

Results: A significant increase in incidence was observed (p < 0.05), along more stage I diagnoses (p < 0.05) and older age at diagnosis, including a higher proportion aged ≥ 40 years (p < 0.001). Seminoma incidence doubled, while non-seminoma remained stable. In stage I disease, the use of active surveillance increased significantly, while adjuvant chemotherapy declined (p < 0.0005). Recurrence rates slightly decreased but were not statistically significant. Cause-specific 10-year survival improved from 95% to 97.2%, with overall survival stable at ~ 94%. The risk of second primary malignancies was notable, including contralateral testicular cancer (2.9%) and second malignant neoplasms (SMNs) (5.0%). A substantial burden of non-cancer-related causes of death were also observed.

Conclusions: A real increase in the incidence of TGCTs and age at diagnosis was confirmed. These trends highlight a shift toward less aggressive treatment while maintaining excellent outcomes. However, the notable occurrence of SMNs and non-cancer mortality underscores the need for long-term follow-up that includes survivorship care beyond oncological monitoring.

Nasopharyngeal carcinoma is distinct from other cancers of the head and neck in biology, epidemiology, histology, natural history, and response to treatment. Radiotherapy is the cornerstone of locoregional treatment of non-disseminated disease and, in combination with chemotherapy, improves survival rates. In the case of metastatic disease stages, treatment requires platinum/gemcitabine-based chemotherapy, and patients may achieve a long survival time. In these guidelines (updated in 2025), we summarize current evidence and available therapies for the medical management of advanced nasopharyngeal carcinoma.

Objective: The management of high-risk (HR) prostate cancer represents a challenge for radiation oncologists. This survey investigates the pattern of care in management of HR-prostate cancer across Spanish institutions.

Materials and methods: We conducted a survey among URONCOR members from March to May 2024. This survey was structured in five sections: diagnosis, radiotherapy, hormonal treatment, follow-up, and future perspectives.

Results: A total of 74 responses from 71 different hospitals were received. Participants have a median professional experienced of 11 years, working most of them (84.9%) in public university hospitals. 97.3% have multidisciplinary tumor board and treat a median of 50 (0-200) HR-prostate cancer patients per year/department. 44.63% of centers use Choline-PET and 28.4% PSMA-PET at diagnosis with 26 different fractionation schedules, the most common is moderate hypofractionation (52.7%): 70 Gy in 28 fractions, followed by 37.5 Gy in 15 fractions + 15 Gy brachytherapy boost (30.4%). 56.8% of the institutions perform whole-pelvic irradiation in N0 patients, with 50.4 Gy in 28 fractions (40.48%) being the most common scheme. 56.8% prescribe an LHRH agonist and 74.6% for 24 months. 75.7% prescribe abiraterone in very high-risk patients. 63.0% use the PHOENIX-criteria to define a recurrence. 38.0% perform PSMA-PET and 39.0% Choline-PET as imaging for recurrence. After local relapse, 73.97% apply a re-irradiation technique with 11 different schedules (32.35%), with HDR-brachytherapy: 13.5 Gy × 2 being the most used (56.16%). 83.8% consider that they achieved good results in HR-prostate cancer.

Conclusion: This study represents the current status of the management of HR-prostate cancer in Spain, highlighting the wide variety of radiotherapy treatments as well as the need for national consensus guidelines.

Purpose: To determine recurrence patterns and prognostic factors in limited disease SCLC (LD-SCLC) and evaluate the effect of TNM classification on prognosis.

Material and methods: We retrospectively evaluated 266 patients with LD-SCLC who underwent curative chemoradiotherapy ± prophylactic cranial irradiation (PCI) between 2003 and 2016. These patients were recruited from 10 centers and restaged using the 7th and 8th TNM staging systems. We assessed the impact of TNM stage, age, gender, and PCI on all survival outcomes through univariate and multivariate analyses. Survival rates were calculated using the Kaplan-Meier method.

Results: The median follow-up period was 42 months. In all cases, the 2- and 5-year local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates were 63.4-41.8%, 50.6-43.2%, and 50.9-27.7%, respectively. In the Cox regression analysis, N2-N3 disease and not receiving PCI were identified as poor prognostic factors for DMFS. In contrast, N2 disease, T4 stage according to the 8th TNM system, not receiving PCI, and thoracic RT doses < 60 Gy were recognized as prognostic factors negatively associated with OS. It was also observed that having N3 disease increases the risk of developing brain metastasis (BM) by a factor of 2.6.

Conclusion: In our cohorts, the N category emerged as the most significant prognostic factor for overall survival, distant metastasis-free survival, and the development of brain metastasis. Considering that the definition of limited disease encompasses a broad spectrum of patients, TNM staging may be more beneficial in predicting patient prognosis and guiding treatment decisions, as suggested.

Purpose: The Breast Cancer Study Group of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) conducted a survey aiming to provide an overview of the policies on radiation therapy (RT) dose and fractionation for whole breast irradiation (WBI), partial breast irradiation (PBI), chest wall (CW) irradiation and regional nodal irradiation (RNI).

Materials and methods: In February 2023, 183 Italian RT centres were invited to answer a survey: after a first section investigating general aspects, the questionnaire focused on radiation oncologists' (ROs) attitude regarding breast cancer post-operative RT dose and fractionation. Surveyed ROs were also asked to express their interest in being involved in prospective trials evaluating post-operative ultra-hypofractionated RT (ultra-HF).

Results: One hundred and twenty/183 (65.6%) centres answered the survey. Regarding WBI 99.1% of ROs prescribed moderate hypofractionated (HF) RT and 70.3% ultra-HF RT, sequential administration is the preferred choice for delivering tumour bed boost (60.4% of centres). Moderate HF was the preferred choice for CW irradiation and RNI in 60.3% and 63.6% of centres, respectively. PBI was adopted in clinical practice in only 57.5% of centres. Furthermore, 29.1% of centres are already involved and 34.6% would like to be involved in prospective studies evaluating ultra-HF RT.

Conclusion: Hypofractionated RT is widely adopted for WBI, while its use in post-mastectomy RT (PMRT) appears uneven. Adoption of ultra-HF RT is high for WBI, but it is not a standard for CW irradiation and RNI. Regarding PBI, the survey highlighted the need for enhanced expertise to improve its adoption.