Clinical & Translational Oncology最新文献

Background: Acral melanoma (AM) is uncommon in non-Asian race. Limited data exist in non-Asian population.

Objective: To analyze the activity of immunotherapy in patients diagnosed with AM in Spain.

Methods: We analyzed clinical outcomes of AM in the nationwide Spanish Melanoma Group Registry.

Results: 69 AM (17 stage III; 52 stage IV) and 724 cutaneous melanoma (CM) (190 stage III; 534 stage IV), predominantly non-Hispanic white. Regarding stage IV, AM patients were older (median 73.6 vs. 66.6 years, p = 0.001) and less often BRAF mutant (9.6% vs. 60.7%, p = 0.0001). First line immunotherapy (49 AM; 316 CM), response rate was 15.0% vs 39.1% (p = 0.0033), median progression free survival was 5.5 (95% CI 3.97-8.23) vs 15.3 months (95% CI 8.97- 26.3) (p = 0.001) and median OS was 17.3 (95% CI 13.32-39.97) versus 43.0 months (95% CI 30.81, NR) (p = 0.007), for AM and CM, respectively. Stage III AM were deeper (T4b in 52.9% vs. 25.3%, p = 0.02). In adjuvant anti PD-1-treated patients (14 AM; 156 CM) median RFS was 10.23 months (95% CI 6.0-NR) in AM versus NR (54.5-NR) in CM (p = 0.017) and 5 year OS was 36.1% vs. 75.8% (p = 0.034).

Conclusions: Our data confirms a poor outcome of AM in the Spanish population.

Cancer is a complex and heterogeneous disease driven by a multitude of genetic alterations, including mutations, chromosomal rearrangements, and epigenetic modifications. Advances in genomic technologies have significantly enhanced our understanding of the genetic landscape of cancer, enabling the identification of key oncogenes, tumor suppressor genes, and DNA repair mechanisms that influence tumor progression. This review examines the molecular mechanisms underlying cancer development, focusing on the roles of mutations in genes such as TP53, KRAS, and EGFR. Furthermore, it explores the implications of genomic instability, tumor microenvironment interactions, and the emergence of precision medicine in oncology. The integration of next-generation sequencing and bioinformatics has facilitated the discovery of novel therapeutic targets, paving the way for personalized treatment strategies. Despite these advancements, challenges remain, including treatment resistance, tumor heterogeneity, and ethical considerations in genetic research. Addressing these complexities requires a multidisciplinary approach that combines molecular biology, bioinformatics, and clinical research. This review synthesizes current knowledge on cancer genetics, highlighting its importance in developing targeted therapies and enhancing patient outcomes.

Introduction: Significant progress has been made in understanding and treating lung cancer. In the unique context of the Amazonian indigenous population, it is crucial to identify genetic variants in genes important for the risk of developing this cancer. There is a limitation of research on the broader genomic profile of indigenous peoples, especially in the Amazon region, in relation to lung cancer.

Methods: We evaluated the genomic profile of seven genes (KRAS, MET, RET, ERBB2, BRAF, PDL2 and PD-L1) related to lung cancer by sequencing the exome of 64 indigenous individuals belonging to 12 ethines from the Brazilian Amazon.

Results: Our study identified six variants of moderate impact already described in the literature, located in the RET, ERBB2, PDL2 and PD-L1 genes. We discovered six new variants unique to the Amazonian Amerindian population, one located in the KRAS gene, two located in the ERBB2 gene, and three located in the PDL2 gene.

Conclusions: The variants studied can potentially exert a significant influence on the heredity and carcinogenesis of lung cancer.

Objective: To evaluate the clinical significance of serum response factor (SRF) expression and its association with microvascular density (MVD) and postoperative recurrence in glioblastoma (GBM) patients.

Methods: This retrospective study included 92 patients with pathologically confirmed GBM who underwent surgical resection between July 2021 and July 2023. Tumor and adjacent normal brain tissues were analyzed via immunohistochemistry to assess SRF expression and CD105-labeled MVD. Spearman's correlation was used to determine the association between SRF and MVD. Postoperative recurrence was monitored for 12 months, and multivariate logistic regression was conducted to identify independent predictors of recurrence.

Results: SRF was positively expressed in 56.5% of tumor samples, significantly higher than in adjacent normal tissue (2.2%, P < 0.001). SRF-positive tumors demonstrated increased MVD compared to SRF-negative tumors (86.79 ± 14.12 vs. 70.58 ± 8.77 vessels/field, P < 0.05). A strong positive correlation was found between SRF expression and MVD (r = 0.749, P < 0.05). At 1-year follow-up, 24 patients (26.1%) experienced recurrence. SRF positivity, tumor diameter ≥ 5 cm, poor differentiation, high histological grade, and incomplete resection were significantly associated with recurrence (all P < 0.05). Multivariate analysis confirmed these as independent predictors (all P < 0.01).

Conclusion: SRF is overexpressed in glioblastoma and closely linked to tumor angiogenesis and postoperative recurrence. High SRF expression may promote tumor progression through vascular remodeling, suggesting its potential utility as a prognostic biomarker and therapeutic target in GBM management.

Purpose: The objective of this study was to analyze the association between mean PM_2.5 levels from 2000 to 2020 and the prevalence of epidermal growth factor receptor (EGFR) mutations worldwide.

Patients and methods: We fitted linear regression models weighted by the total number of non-small cell lung cancer (NSCLC) to estimate the association strength. Adjusted R² values were calculated, with values closer to 1 indicating a stronger association. Data from sixty-nine countries were available. PM_2.5 data for 2015‒2020 were obtained from the Organisation for Economic Co-operation and Development database ( https://stats.oecd.org/ ). Mean PM_2.5 levels, EGFR mutation prevalence data, and total NSCLC cases were acquired from published literature and national cancer registries.

Results: The association between PM_2.5 levels and EGFR-mutant prevalence ranged between moderate and weak (R² = 0.34, 95% Confidence interval [CI] 0.02‒0.67). The association further weakened (R² < 0.15 in all comparisons) when stratified by area (European, Asian, or Latin American). Although certain countries had high air pollution and EGFR-mutant lung cancer prevalence (China: PM_2.5, 46.9% and 45.7%, respectively), the association was inconsistent.

Conclusions: The discrepancy between PM_2.5 levels and the prevalence of EGFR-mutant lung cancer could be attributed to differences in access to lung cancer genomic profiling, potential over- or underestimation of EGFR-mutant prevalence, non-homogeneous PM_2.5 levels within countries, inclusion of all patients with lung cancer regardless of smoking patterns, and other factors, such as genomic background and ancestry. These factors should be considered as potential limitations in directly associating PM_2.5 with EGFR-mutated lung cancer development.

Purpose: Socazolimab, in combination with chemotherapy, has been shown to prolong progression-free survival (PFS) and overall survival (OS) compared with chemotherapy alone in patients with extensive-stage small cell lung cancer (ES-SCLC). This study is the first to evaluate its cost-effectiveness from the perspectives of both the U.S. payer and Chinese healthcare systems.

Methods: A Markov state-transition model was employed to conduct an economic evaluation, incorporating clinical and economic parameters from both the U.S. and China. Baseline patient characteristics and key clinical inputs were sourced from a randomized phase 3 trial, whereas cost and utility values were derived from open-access databases and published literature. The primary outcomes assessed included quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), incremental net health benefit (INHB), and incremental net monetary benefit (INMB). Model uncertainty was addressed through probabilistic sensitivity, one-way sensitivity, and scenario analyses.

Results: In the base-case scenario, the addition of socazolimab to chemotherapy resulted in a marginal QALY gain of 0.09, at an incremental cost of $14,504.53, leading to an ICER of $152,228.60 per QALY. This ICER was below China's willingness-to-pay (WTP) threshold of $40,354.27 per QALY, making it not cost-effective, with an INHB of -0.26 QALYs and an INMB of -$10,523.93. In the U.S., while the incremental QALY gain remained at 0.10, the additional cost increased to $85,599.55, yielding an ICER of $878,912.80 per QALY, far exceeding that of the U.S. WTP threshold of $150,000.00, confirming its lack of cost-effectiveness.

Conclusions: The combination of socazolimab with chemotherapy is not a cost-effective first-line treatment option for ES-SCLC in either China or the United States, highlighting the need for price adjustments and alternative treatment strategies to improve economic viability.

Purpose: Metastatic colorectal cancer (mCRC) presents significant therapeutic challenges, with variability in the definition and classification of lines of treatment (LoTs). This study aimed to achieve consensus among Spanish oncology experts on the classification of LoTs through the application of the Delphi methodology.

Methods: A nationwide Delphi study was conducted in three phases. Twelve experts designed a two-round online survey that consisted of 41 statements across 11 sections. Statements were evaluated with a five-point Likert scale, with ≥ 70% agreement or disagreement as the criterion of consensus.

Results: A total of 110 and 92 oncologists participated in the first and second rounds, respectively, with consensus achieved on 32 of 41 statements. Key agreements included definition of treatment lines before systemic therapy (98.18%), classification of relapses after six months of adjuvant therapy as first line (92.73%), and the inclusion of maintenance therapy as part of first-line treatment (98.18%). Variability arose on the use of biologics in perioperative settings (67.39% disagreement) and progression criteria, and 75% of experts agreed that a switch in biologics constitutes a new line. Thus, it is needed to standardize definitions in clinical practice.

Conclusions: This study highlights significant variability in the definition of LoTs for mCRC, which reflects the evolution of therapeutic landscape. The divergence between clinical trial criteria and real-world practices underscores the need for standardized definitions to enhance consistency in clinical decision-making. Refinement of guidelines on biologic agents, rechallenge strategies, and therapy classification is critical to advance mCRC management and improve patient outcomes. This consensus serves as a foundation for future research and guideline development.

Purpose: To evaluate the correlation between HER2 expression levels measured by HER2 mRNA using Oncotype DX and by immunohistochemistry (IHC) in hormone receptor-positive (HR+) and HER2-negative (HER2-) early breast cancer. In addition, we assessed whether low HER2 expression is associated with distinct clinicopathological characteristics and prognosis in our series.

Methods: We conducted a retrospective study that included 500 patients diagnosed with stage I-III HR+/HER2- breast cancer who underwent surgery and had Oncotype DX recurrence score determined between 2009 and 2023 at Hospital Clínico San Carlos, Madrid, Spain. HER2 mRNA levels obtained through Oncotype DX were compared across IHC groups (HER2 0+, HER2 1+, HER2 2+/ISH-negative). Event-free survival (EFS) was analyzed according to HER2 expression.

Results: Although HER2 mRNA levels increased with higher IHC HER2 categories, variability and overlap were observed between subgroups. Median Oncotype DX recurrence scores also rose slightly across HER2 IHC groups but did not reach statistical significance. EFS did not differ between HER2 expression levels.

Conclusions: We found that HER2 mRNA measurement by Oncotype DX provides a quantitative approach to assess HER2 expression. However, its results overlap within traditional IHC categories. While HER2-low classification may have therapeutic implications for new antibody-drug conjugates, its prognostic relevance appears limited. Further studies are needed to improve HER2 quantification methods for improved clinical decision-making.

This guideline provides a comprehensive overview of the management of localized rectal cancer, highlighting recent major advances in therapeutic strategies. Accurate staging remains essential, as it informs treatment decisions and facilitates risk assessment. A pivotal development in rectal cancer treatment is the adoption of total neoadjuvant therapy (TNT), which has demonstrated improved tumor response, reduced risk of systemic recurrence, and enhanced survival outcomes. This approach enables a "watch-and-wait" strategy and conservative management that may render surgery unnecessary and preserves rectal function in patients who achieve a complete clinical response. By emphasizing a structured approach to staging, multidisciplinary evaluation, and innovative treatment pathways, this guideline aims to improve outcomes while minimizing the morbidity associated with rectal cancer treatment.

Ovarian and endometrial cancers rank among the most common and deadliest cancers affecting women globally. One of the most important factors that impacts patient survival is how early the tumor is detected. Unfortunately, these cancers often present vague symptoms that usually don't show up until the disease is already in an advanced stage. This makes early diagnosis and screening quite difficult. As a result, researchers are actively seeking better diagnostic tools and treatment approaches. In recent years, non-coding RNAs (ncRNAs) have gained significant attention for their key roles in controlling various cellular activities, especially in cancer. Among them, long non-coding RNAs (lncRNAs) are being explored for their potential as therapeutic targets, as well as their usefulness as diagnostic markers and indicators of poor outcomes. This article focuses on how lncRNAs could be crucial in driving or suppressing cell growth, invasion, metastasis, cell death, and resistance to drugs in ovarian and endometrial cancers.