Clinical & Translational Oncology最新文献

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.

Background/objectives: Hypofractionated radiation therapy (Hypo-RT) schedules may offer radiobiological, patient convenience, and healthcare resource advantages over standard fractionated radiation therapy (S-RT) for glioblastoma (GBM). Additionally, simulated integrated boost (SIB) Hypo-RT is proven to be an effective and safe treatment. We report on our experience regarding progression-free survival (PFS), overall survival (OS), and RT-related toxicities in GBM patients treated with Hypo-RT and S-RT.

Methods: Patients with IDH-wild-type GBM received either Hypo-RT (40.05-52.5 Gy/15 fractions) or S-RT (60-70 Gy/30 fractions). Volumetric modulated arc therapy was performed for all patients. Concomitant temozolomide (75 mg/m²/day) and adjuvant chemotherapy (TMZ 150-200 mg/m² for 5 days every 28 days) were administered. OS and PFS were estimated using the Kaplan-Meier method.

Results: Ninety-five patients were treated (Hypo-RT: 52, S-RT: 43). With a median follow-up of 25 months (range 9-63), the median age was 65 and 54 years for the Hypo-RT and S-RT groups, respectively. All patients tolerated the treatment well; no significant adverse effects were observed in either group. No acute or late neurological side effects of grade ≥ 2 were reported during RT. Grade 3-4 hematologic toxicity occurred in five cases, all of which interrupted concomitant TMZ (all happening in the S-RT arm). The time to progression for the S-RT and Hypo-RT groups was 13.7 and 11.1 months, respectively (p = 0.243). Regarding OS, the S-RT group had a median OS of 28.8 months compared to 17.5 months in the Hypo-RT group (p = 0.007).

Conclusions: Although further investigations are ongoing, a statistically significant difference exists between Hypo-RT and S-RT in OS. Hypo-RT could potentially become the standard of care not only for elderly patients but also for those with poor prognosis. Further investigation with additional data is necessary to determine the most effective standard approach.

Purpose: This study aims to investigate the role of hepatocyte growth factor (HGF) overexpression in mediating resistance to KRAS G12C inhibitors in lung adenocarcinoma and to explore potential combination therapies to attenuate this resistance.

Methods: Lentiviral transfection was used to establish HGF-overexpressing lung adenocarcinoma cell lines harboring the KRAS G12C mutation (H23 and H358). Cells were treated with KRAS G12C inhibitors either as monotherapy or in combination with inhibitors targeting the NF-κB, MEK/ERK, or PI3K/AKT/mTOR pathways. Drug sensitivity was assessed using pharmacological assays, and underlying mechanisms were evaluated through Western blot analysis.

Results: HGF-induced resistance to KRAS G12C inhibitors varied significantly between the two cell lines. H23 cells overexpressing HGF exhibited only mild resistance, which could be reversed using MEK, mTOR, NF-κB, or MET inhibitors. In contrast, H358 cells developed strong resistance following HGF overexpression. Inhibitors of the NF-κB pathway were especially effective in counteracting this resistance, likely by modulating crosstalk among multiple KRAS downstream signaling pathways.

Conclusion: These results indicate that targeting the NF-κB pathway may represent a promising therapeutic strategy to attenuate HGF- induced resistance to KRAS G12C inhibitors in lung adenocarcinoma.

Background: The presence of malignant pleural effusion (MPE) remains a challenge in clinical treatment. This study aimed to evaluate the safety and efficacy of intrapleural administration of anti-programmed cell death 1 (PD-1) antibody, specifically targeting patients with advanced non-small cell lung cancer (NSCLC) complicated by MPE.

Methods: From May 2019 to December 2023, a total of 16 advanced NSCLC patients with MPE were enrolled. Each patient received a single intrapleural dose of 100 mg of sintilimab. The primary outcome was safety, while secondary outcomes included the proportion of participants who achieved successful pleurodesis by day 35 and day 70 post-intervention; median pleural progression-free survival (mPPFS); the objective response rate (ORR) of extra-pleural tumor at both day 35 and day 70.

Results: Among the 16 patients, the proportion of participants with successful pleurodesis at day 35 was 75.0% (12/16), which decreased to 56.3% (9/16) by day 70. The mPPFS was 10.4 weeks (95% CI 7.6-13.3 weeks). The ORR of extrapleural tumors at day 35 was 12.5%, with 12.5% (2/16) of patients achieving partial remission (PR), 81.3% (13/16) maintaining stable disease (SD), and 6.3% (1/16) experiencing disease progression (PD). As for safety, the treatment-related adverse events (TRAEs) were well-tolerated. However, 93.8% (15/16) patients experienced treatment-emergent adverse events (TEAEs). The incidence rate of grade 3 TEAEs was 25.0% (4/16), and no grade 4 TEAEs occurred in any patients.

Conclusions: Intrapleural injection of anti-PD-1 antibody demonstrates promising efficacy and a tolerable safety profile as a novel therapeutic strategy for managing MPE in advanced NSCLC.

Trial registration: This trial was registered with the Chinese Clinical Trial Registry (identifier: ChiCTR2400087743).

Introduction: Taxanes are drugs commonly used in the treatment of breast cancer. Despite their proven therapeutic efficacy, they can induce severe toxicities, which can be investigated by pharmacogenomics. In this context, the aim of this study was to investigate 26 molecular biomarkers in 17 pharmacogenes (CYP2C8, ABCB1, CYP1A1, CYP1B1, CYP19A1, CYP3A5, ERCC1, ERBB2, VEGFA, ERCC2, MDM2, MTHFR, RAD51, SOD2, TP53, TANC1 and XRCC1), in women with Breast Cancer undergoing Taxane treatment in the Brazilian Amazon region.

Methods: This study was carried out with 279 women diagnosed with BC, undergoing antineoplastic chemotherapy treatment based on Taxanes (Docetaxel and Paclitaxel), in Brazilian Amazon region. 26 pharmacogenetic markers located in 17 genes involved in the metabolic pathway of Taxanes and related toxicities were selected. Single nucleotide variants were genotyped by allelic discrimination using TaqMan OpenArray Genotyping technology.

Results: The study population showed significant associations of Taxane toxicities with ten variants of nine genes: CYP1A1, CYP19A1, CYP3A5, ERCC1, VEGFA, ERCC2, MTHFR, TANC1 and XRCC1. Notably, variants in TANC1 and XRCC1, previously associated with radiotoxicity, were also implicated in Taxane-induced toxicities. The study demonstrated that novel biomarkers may be important for investigating Taxane-induced toxicities in breast cancer.

Conclusions: These findings represent a unique contribution to the field, potentially enabling more precise chemotherapy selection, particularly for populations such as Amazonian women.

Background: Classically, risk assessment models have focused on classic, clinically symptomatic thrombotic events, such as deep vein thrombosis (DVT) and pulmonary embolism (PE), not taking into account incidental thrombosis or non-conventional thrombotic events such as catheter-related thrombosis (CRT) or splenic vein thrombosis (SVT), although they contribute to morbidity and increase the consumption of health resources.

Methods: The primary objective was to evaluate and compare the predictive performance of the Khorana, PROTECHT, CONKO, modified VIENA-CATS (excluding P-selectin values), and MICA-CATS scores in assessing all type of thrombotic events in cancer patients (p) in the second cohort of the observational, multicenter, prospective ONCOTHROMB12-01 study. Data from 391 patients undergoing ambulatory systemic therapy across 11 Spanish hospitals between 2018 and 2021 were analyzed.

Results: 95 patients (24.3%) developed a thrombotic event. MICA-CATS score showed the best predictive capacity for all thrombotic events, as assessed by both the AUROC and the AUPRC, with an AUROC of 0.61 (95% CI 0.54-0.67) and an AUPRC of 0.38 (95% CI 0.30-0.46). For incidental thrombotic events, both the PROTECHT (0.62, 95% CI 0.55-0.68) and MICA-CATS (0.60, 95% CI 0.51-0.68) scores demonstrated utility.

Conclusions: Our findings demonstrate that MICA-CATS score has the best predictive capacity for overall venous thromboembolism (VTE) in cancer patients.

Chimeric antigen receptor (CAR) T cell therapy has revolutionized oncology but is fraught with a potentially lethal toxicity: cytokine release syndrome (CRS). While much focus is placed on pharmaceutical interventions, the pivotal role of nursing in the frontline detection, management, and rescue of patients from CRS remains under-championed in the literature. This narrative review synthesizes the current evidence to formally position nursing at the vanguard of CRS rescue. We delineate the intricate immunobiology of CRS as a primer for advanced practice and deconstruct its clinical spectrum to empower precise assessment. A novel four-pillar framework is presented, outlining nursing's critical role in pre-infusion preparedness, vigilant predictive monitoring, graded algorithm-driven intervention, and multidisciplinary coordination. Furthermore, we pioneer the discussion on defining nursing-sensitive outcomes (NSOs) specific to CRS to quantify nursing's impact on patient safety and efficacy. Finally, we explore future directions, including point-of-care testing and specialized nursing roles, advocating for a paradigm shift where nurses are recognized as essential leaders in optimizing safety and unlocking the full potential of CAR-T cell therapy.

Objective: To analyse long-term mortality trends in Spain (1999-2023) for four colorectal cancer (CRC) subsites-colon, rectosigmoid junction, rectum, and anus/anal canal-by sex, age, and birth cohort.

Methods: This ecological time-trend study used national mortality data from the Spanish National Statistics Institute, classified by ICD-10 codes C18-C21. Age-standardised mortality rates were calculated using the 2013 European Standard Population. Joinpoint regression estimated annual percentage changes, and age-period-cohort models evaluated generational and temporal effects.

Results: Colon cancer mortality showed sex-specific patterns: a biphasic trend in men (initial rise, followed by decline) and a steady decrease in women. Rectal cancer mortality declined consistently in women, with a recent downward trend in men after years of stability. Mortality from rectosigmoid junction cancer remained relatively unchanged in both sexes. Anal cancer mortality increased steadily in men and, after an early decline, rose significantly in women, narrowing the sex gap. Mortality increased with age across all subsites, with men showing higher rates overall-except for anal cancer, where younger women's rates matched or surpassed those of men. Cohort analysis revealed generational declines in colon and rectal cancer mortality, contrasting with rising anal cancer risks, likely linked to increased HPV exposure. Period effects indicated notable mortality reductions for colon and rectal cancers but rising trends for anal cancer.

Conclusions: While mortality has declined for colon and rectal cancers, stagnation in rectosigmoid junction and rising anal cancer deaths-especially among women-underscore the need for subsite-specific prevention strategies, including HPV-targeted interventions.

Anal cancer is rare but increasingly common, currently accounting for 2% of all digestive neoplasms. Some 50% of anal cancers are diagnosed at the localized stage, 29% as locoregional disease, and 12% as metastatic disease. When clinical suspicion of anal cancer exists, histological confirmation, correct local staging with MRI and distant staging with thoraco-abdominal CT, and management by a multidisciplinary team are mandatory. Chemoradiotherapy with 5-FU and mitomycin C (MMC) is the standard of care for early and locally advanced disease, while combination chemotherapy with a platinum-containing compound and taxanes is the treatment of choice for metastatic disease.

Purpose: Colorectal carcinoma constitutes a predominant etiology of oncological mortality globally. This systematic review and meta-analysis elucidated the prognostic utility of circulating tumor DNA (ctDNA) as a predictive biomarker for postsurgical recurrence in colorectal cancer patients.

Methods: Two independent investigators conducted systematic literature search across PubMed, Web of Science, Embase, Scopus, and clinical trial registries. Studies investigating ctDNA prognostic significance for colorectal cancer recurrence were incorporated. Random-effects models were implemented utilizing restricted maximum likelihood methodology. The study quality was assessed using Newcastle-Ottawa Scale.

Results: Following screening of 2259 records, 11 studies were incorporated. ctDNA-positive patients exhibited significantly elevated recurrence risk as compared to ctDNA-negative counterparts (pooled HR: 2.34; 95% CI: 1.90-2.79; p < 0.001). Moderate heterogeneity was observed (I² = 66.40%), attributable to patient stage distribution, sampling timing, detection platforms, and mutational panel variations. Stage I-III patients demonstrated exceptional consistency (HR: 2.04, I² = 0.00%). Detection platforms showed robust performance: droplet digital PCR (HR: 3.63), next-generation sequencing (HR: 2.67), and Safe-SeqS (HR: 2.16), with no significant differences (p = 0.10). Adjuvant chemotherapy analysis revealed differential performance: treated patients (HR: 2.50; 95% CI: 2.08-2.93) versus untreated (HR: 1.70; 95% CI: 1.07-2.34; p = 0.04). Extended analysis confirmed prognostic utility for overall survival (HR: 2.24) and surveillance recurrence-free survival (HR: 3.54).

Conclusions: ctDNA represents a robust prognostic biomarker for postsurgical colorectal cancer recurrence with consistent cross-platform performance. Enhanced prognostic value in adjuvant chemotherapy patients supports personalized surveillance implementation, though methodological standardization remains warranted.