Clinical & Translational Oncology最新文献

Adolescent and young adult cancer survivors (AYACS) represent a specific cancer patient population with unique chronic health issues difficult to identify in early, reversible phases with standard monitoring protocols. This review, conducted by a group of Spanish experts, provides recommendations for managing AYACS, focusing on key areas, such as cardiac toxicities, neurotoxicity and neurocognitive disorders, metabolic syndrome, secondary primary malignancies, bone toxicities, sexuality and fertility, psychosocial aspects, and other treatment-related toxicities.

Purpose: To build a mathematical model with predictive capacity for the risk of recurrence in patients with early-stage breast cancer, based on four variables: the result of the MammaPrint®(MMP) test, postoperative radiotherapy (RT), tumor phenotype, and clinicopathological criteria. To estimate overall survival functions stratified by the dose of radiotherapy received.

Methods: A retrospective cohort of 156 patients with early-stage breast cancer was analyzed. Patients were classified according to their MammaPrint®genomic risk (ultralow, low, or high). Multivariate logistic regression using Firth's method was employed to evaluate the risk of recurrence, adjusting for biologically effective dose (BED), molecular subtype, their MammaPrint®classification and clinico-pathologic features. Receiver operating characteristic (ROC) analysis was used to assess model discrimination. The Kaplan-Meier method was used to estimate overall survival (OS) functions. To assess statistically significant differences in survival between patient groups, the log-rank test was applied.

Results: The predictive model, incorporating BED, genomic risk, molecular phenotype, and clinico-pathological classification, showed good calibration and discrimination (AUC: 0.755). The evaluation of OS according to the different BED levels provides clearer results regarding the clinical benefit of radiotherapy. This study reports statistically significant differences when comparing the group without radiotherapy (BED = 0 Gy) to the low-dose group (BED < 60 Gy), with a p-value of 0.0475.

Conclusion: The predictive model fitted using Firth's penalized logistic regression demonstrated an adequate discriminative ability (AUC = 0.755). MMP was the variable with the greatest weight, followed by RT. These variables allow for a more accurate prediction of recurrence risk than traditional clinicopathological factors, supporting their value in the personalization of treatment. This study reports statistically significant differences when comparing the group without radiotherapy (BED = 0 Gy) to the low-dose group (BED < 60 Gy), with a p-value of 0.0475.

Purpose: To determine the real-world incidence and predictive factors for venous and arterial thromboembolic events (VTE/AT) in ovarian cancer patients treated with poly-(ADP-ribose) polymerase inhibitors (iPARP).

Methods/patients: A multicenter retrospective study involving 329 ovarian cancer patients who initiated iPARP treatment between January 2015 and December 2022. The primary outcome was the incidence of VTE/AT. Secondary outcomes included predictive factors for thrombosis and the impact of thrombosis on overall survival (OS). Data were analyzed using logistic regression and Kaplan-Meier survival analysis.

Results: The incidence of VTE/AT was 4.9% (16/329). BRCA2 mutations were significantly more prevalent among patients who developed VTE/AT (56.3% vs. 19.2%; p < 0.001). Combined treatment with bevacizumab was significantly associated with a decreased risk of thrombosis (OR: 0.262; 95% CI: 0.095-0.724; p = 0.010). No statistically significant differences were observed in the median OS between patients who experienced VTE/ATE (63 months) and those who did not (47 months), with a p value of 0.876.

Conclusions: BRCA2 mutations could be a significant predictor for VTE/AT among ovarian cancer patients treated with iPARP. Concomitant treatment with bevacizumab may offer protection against thrombotic events, although a concomitant bias cannot be ruled out. These findings may be of interest when designing future clinical trials in the field of thromboprophylaxis.

Cellular metabolism has emerged as a pivotal factor influencing the viability and functionality of cancer cells. To satisfy their substantial anabolic requirements, tumor cells adopt a distinct metabolic reprogramming divergent from that of non-transformed somatic cells. This review aims to examine metabolic reprogramming in head and neck squamous cell carcinoma (HNSCC), examining its role as a fundamental aspect of cancer progression and resistance to treatment. The article systematically summarizes the key mechanisms of metabolic reprogramming in HNSCC, including enhanced glycolysis, remodeling of amino acid metabolism, and dysregulation of lipid synthesis, and discusses how these metabolic pathways facilitate tumor proliferation and metastasis by influencing the microenvironment, antioxidant defenses, and resistance to ferroptosis. Additionally, the review examines the dynamic interactions between metabolic reprogramming and the tumor microenvironment, particularly focusing on HIF-1α-driven metabolic adaptation and immune evasion mechanisms under hypoxic conditions. Finally, the potential of metabolic-targeted therapies is discussed, highlighting future research directions and their applications in personalized treatment strategies.

Antibody-drug conjugates (ADCs) represent a promising therapeutic approach in gynecologic cancers, particularly ovarian and cervical malignancies. Agents such as mirvetuximab soravtansine, and tisotumab vedotin, targeting folate receptor alpha and tissue factor, respectively, reported clinical efficacy in patients with limited options. However, their use is associated with ocular toxicities, including keratopathy, blurred vision, and dry eye, which may impact adherence and quality of life. This review summarizes current evidence on the incidence, pathophysiology, and clinical presentation of ADC-related ocular adverse events in gynecologic oncology. It also provides practical, evidence-based strategies for the prevention, monitoring, and management of these adverse events. Interventions include prophylactic topical therapies, supportive care measures, treatment delays or dose modifications, and herpes zoster vaccination. Comprehensive management of ocular toxicities is essential to ensure the safe and sustained use of ADCs, preserving both therapeutic benefit and patient well-being. Further research is warranted to optimize preventive and management protocols.

Purpose: To evaluate the diagnostic accuracy and clinical performance of next-generation sequencing (NGS) compared to conventional techniques for detecting actionable mutations using tissue or liquid biopsy samples in patients with advanced non-small cell lung cancer.

Methods: A systematic review and meta-analysis of diagnostic test studies (PROSPERO: CRD42023450465) were conducted. We included studies with sufficient comparative data, using a t test to analyze turnaround time differences and hypothesis testing for valid result proportions (p < 0.05). The meta-analysis, performed in Stata 17^®, pooled sensitivities and specificities by mutation and evaluation technique. The QUADAS-2 tool assessed study quality.

Results: A total of 56 studies involving 7143 patients were analyzed. No significant differences were found in valid result percentages between standard tests and NGS in tissue (85.57% vs. 85.78%; p = 0.99) and liquid biopsy (81.50% vs. 91.72%; p = 0.277). Liquid biopsy had a significantly shorter turnaround time (8.18 vs. 19.75 days; p < 0.001). NGS demonstrated high accuracy in tissue for EGFR (sensitivity: 93%, specificity: 97%) and ALK rearrangements (sensitivity: 99%, specificity: 98%). In liquid biopsy, NGS was effective for EGFR, BRAF V600E, KRAS G12C, and HER2 (sensitivity: 80%, specificity: 99%) but had limited sensitivity for ALK, ROS1, RET, and NTRK rearrangements.

Conclusions: NGS enables comprehensive mutation analysis, particularly for point mutations. Further validation is required to improve the detection of gene rearrangements.

Purpose: Oroxylin A (OA) is a flavonoid, obtained from the root of Scutellaria baicalensis Georgi which is a traditional Chinese herbal, with antitumor and other pharmacological activities. OA tablets are an innovative drug, and a formal single ascending and multiple dose pharmacokinetic (PK) trial was conducted in humans to evaluate the required to determine the safety and tolerability of OA as well as the effect of food on its PK parameters profile.

Methods: This clinical study consisted of three parts: single ascending dose (400[n = 3], 800, 1600 and 2400 mg OA [n = 8/group] and placebo [n = 6]), multiple dose (1600 or 2400 mg OA [n = 8 / group] and placebo [n = 4] once daily), and food effects (1600 mg OA single dose [n = 12]).

Results: No dose-limiting toxic events (DLT), no serious adverse events (SAEs) or death occurred, and incidence of gastrointestinal AEs were higher in multiple doses than in single dose. OA appeared rapidly in plasma; t_max was approximately 0.17 ~ 5.0 h. The C_max of OA approximately increased in dose-proportional manner (C_max slope 1.114), and the AUC_0-t increased less than dose increasing (AUC_0-t slope 0.7513). After 10 days of continuous administration, OA presented a moderate cumulative effect (1.51-1.73-fold). High-fat diet can increase the C_max of OA (1.6-fold), and its metabolites increased more significantly (p < 0.05), there was no effect of food on t_max or terminal half-life.

Conclusions: The safety and PK profile support once-daily administration of OA, and considering the effects of food, it is recommended to administrate OA tablet after meals in further clinical studies.

Trial registration number: ChiCTR2100051434 http://www.chictr.org/cn/ ; Date of registration: 23 Sep., 2021.

Current standards of clinical practice recommend systemic chemotherapy but no surgical approach for Stage IV pancreatic ductal adenocarcinoma (PDAC), with expected overall median survival between 3 and 6 months. In the last 20 years, a subset of patients with a limited number of metastases to just one or two organs (liver and/or lungs) and a less aggressive biology and growth ability have been identified and defined as "oligometastases" (OM). The continuous improvement in systemic therapy with the arrival of the multiagent FOLFIRINOX and gemcitabine + nab-paclitaxel and the refinements and advances in surgical techniques have shifted the focus from technical resectability to biological treatment for patients with OM from PDAC. In this review we evaluate the existing evidence for metastasectomy in the liver, lungs, interaortocaval lymph nodes and peritoneum, assessing the potential indications for surgery and contributing with some general rules that can be followed.

Purpose: Human epidermal growth factor receptor 2 (HER2)-negative breast cancer includes HER2-zero and HER2-low tumors. Whether their clinical features and survival are different is not fully clarified. The objective was to explore their clinicopathologic differences and survival.

Methods/patients: Retrospective analysis of HER2-negative, stage I-III breast cancer patients from 2006 to 2016 at a single site. Clinicopathological variables, events and survival are analyzed, comparing HER2-low and HER2-zero cases.

Results: Of 535 patients, 351 (65.61%) were HER2-zero and 184 (34.39%) HER2-low (154 (83.70%) score 1 + and 30 (16.30%) score 2 +). The proportion of premenopausal women was higher in the HER2-low subgroup (50.50% vs 39.40%, p = 0.016). For those with HER2-zero tumors, 15.70% were estrogen receptor (ER) negative, whereas only 9.20% (p = 0.045) of HER2-low tumors were ER negative. In HER2-low/ER negative tumors, tumor size, histologic grade, and Ki67 levels were higher. Patients with HER2-zero/ER-negative tumors were younger, had fewer comorbidities, less nodal involvement, a higher frequency of ductal histopathology, and, again, higher histologic grade and Ki67 levels. There were no differences in the events. The overall survival probability at 11.50 years in the HER2-zero subgroup was 0.51 (95% confidence interval (CI 95%) 0.28-0.74) and in the HER2-low subgroup 0.67 (95% CI 0.56-0.77) (p = 0.52).

Conclusions: HER2-zero and HER2-low breast cancers are not distinct clinicopathologic entities. The differences detected in some variables seem to depend on ER status. No prognostic differences were observed.