Clinical & Translational Oncology最新文献

Background and aims: Primary digestive system lymphoma (PDSL) is an important entity of extranodal lymphoma, yet updated epidemiologic and survival data are lacking.

Methods: Patients diagnosed with PDSL between 1975 and 2020 were identified from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier analysis estimated survival outcomes. Multivariable Cox regression identified independent risk factors, and nomograms were developed to predict 1-, 3-, and 5-year overall survival (OS) and cancer-specific survival (CSS).

Results: A total of 30,568 patients with PDSL were identified, with 57.9% being male and 80.4% white. The most frequent tumor site was the stomach (48.7%) and diffuse large B-cell lymphoma (DLBCL) was the predominant histologic subtype (45.0%). The overall incidence from 2016 to 2020 was 11.11 per 1,000,000 persons, with a decrease observed in lymphoma rates for the stomach, small intestine, large intestine, and pancreas. Long-term trends showed an initial rise in PDSL incidence, followed by a decline since the 1990s. The median OS across all patients was 103 months, with appendiceal lymphoma showing the highest median OS of 253 months. Factors including diagnosis year, age, sex, race, primary tumor site, histologic subtype, stage, and treatment modalities were significantly associated with OS and CSS. Nomograms achieved C-indices of 0.720 for OS and 0.723 for CSS in the training cohort.

Conclusion: The incidence of PDSL initially increased but has recently declined. Survival for all PDSL patients has improved over time. Nomograms to predict survival for patients with DLBCL exhibited good predictive and discriminating abilities.

Objectives: EGFR exon 20 insertion (EGFRex20ins) mutations are found in up to 4% of all patients with non-small cell lung cancer (NSCLC). These patients are often insensitive to EGFR-tyrosine kinase inhibitors (TKIs) and have worse prognosis than patients with more common EGFR mutations. In this multicenter, retrospective, real-world study, we sought to determine whether the administration of recently approved treatments that specifically target EGFRex20ins mutations could significantly improve outcomes in this patient population.

Materials and methods: We evaluated the clinical features of 41 patients diagnosed with NSCLC and EGFRex20ins mutations, their evolution, and response to treatments received across 7 hospitals in the Valencian Community, Spain, between 31st December 2012 and 31st December 2022.

Results: 32 patients (72%) developed metastatic disease, and 29 (71%) of them received oncological treatment. We found that administering a targeted therapy against EGFRex20ins mutations (amivantamab, mobocertinib and/or sunvozertinib) at some point during the course of treatment, significantly increased the median OS of metastatic patients from 8 months (95% CI 0-21.7) to 30 months (95% CI 11.1-48.8; Hazard ratio = 0.297, p = 0.02).

Conclusion: Our findings contribute to the evolving standard of care for this specific population and highlight the clinical benefits of targeted cancer therapies.

Background: Degarelix is a third-generation GnRH receptor antagonist approved for the treatment of prostate cancer, however, the decision to use a GnRH agonist or an antagonist depends on several factors. We aimed to perform a meta-analysis comparing the cardiovascular disease risk between degarelix and gonadotropin-releasing hormone agonists in patients with all stages of prostate cancer.

Methods: Databases were searched for randomized control trials (RCTs) and observational studies that compared the risk of cardiovascular disease between degarelix and GnRH agonists in patients with prostate cancer. We computed for binary endpoints risk ratio (RR) or hazard ratio (HR) with 95% confidence intervals (CI) which were analyzed using a random-effects model.

Results: A total of 15 studies were included with 123,969 patients and follow-up ranging from 3 to 13 months. Degarelix was associated with a significantly lower incidence of major adverse cardiovascular events (RR 0.59; 95% CI 0.41-0.84; p = 0.003; I² = 84%). Incidence of stroke (RR 0.89; 95% CI 0.56-1.42; p = 0.62; I² = 0%), all-cause mortality (RR 0.64; 95% CI 0.37-1.13; p = 0.12; I² = 41%), hypertension (RR 0.71; 95% CI 0.48, 1.04; p = 0.08; I² = 0%), myocardial infarction (HR 1.04; 95% CI 0·59-1·84; p = 0·86; I² = 66%), heart failure (HR 0.79; 95% CI 0.38-1.62; p = 0.52; I2 = 79%) and arrhythmia (RR 0.63; 95% CI 0.28-1.41; p = 0.86; I² = 37%), did not reach a statistically significant difference between groups.

Conclusion: In patients with prostate cancer, degarelix is associated with a significantly lower incidence of major adverse cardiovascular events.

Purpose: This study aimed to investigate the impact of oligometastasis and the M descriptor on survival in small cell lung cancer (SCLC).

Methods: This multicenter, retrospective study included patients with newly diagnosed extensive-stage SCLC(ES-SCLC) from 2010 to 2020. Subgroups: Group 1: single metastasis in a single organ, Group 2: 2-5 metastases in a single organ, Group 3: 6 or more metastases in a single organ, and Group 4: metastases in two or more organs. This classification was based on the 9th Staging-M descriptor. Three-year progression-free survival (PFS) and overall survival (OS) analyses were conducted.

Results: The mean age of the 439 patients was 62 ± 10 years, and 89.5% of them were male. The mean PFS for Groups 1, 2, 3, 4 was 10.7 months (95% CI 8.9-12.5), 7.5 months (95% CI 5.6-9.4), 4.3 months (95% CI 2.9-5.7), and 5.4 months (95% CI 4.7-6.1), respectively. PFS in Group 2 was significantly higher. The mean OS for Groups 1, 2, 3, 4 was 13.3 months (95% CI 11.2-15.3), 9.5 months (95% CI 7.1-11.9), 7.1 months (95% CI 4.5-9.7), and 6.9 months (95% CI 6.0-7.9), respectively. OS in Group 1 was significantly higher. OS and PFS in the M1b group were significantly higher than in the M1c1 and M1c2 groups (p < 0.05) with no statistical difference between the M1c1 and M1c2 groups.

Conclusion: There is no significant difference in survival between the M1c1 and M1c2 groups. In ES-SCLC, the number of metastases may be a more predictive factor for prognosis than the number of metastatic organs.

Purpose: There is an unmet need for new treatment options and biomarkers for patients with glioblastoma (GBM). Here we investigated three non-invasive biomarkers: type VI collagen degraded by granzyme B (C4G) and matrix metalloproteases (C4M), respectively, and ADAM10-degraded Tau (Tau-A).

Methods: Biomarker levels in pre- and on-treatment serum samples from patients with recurrent GBM (n = 39) treated with nivolumab and bevacizumab (NCT03890952) were compared to healthy levels (n = 22) and associated with overall survival (OS) outcome (median cutpoint). Longitudinal changes in biomarkers were investigated by a Mixed-effects analysis.

Results: Tau-A (p < 0.0001) and C4G (p = 0.005), but not C4M (p = 0.106), were increased in patients. High Tau-A and C4G associated with improved OS (Tau-A: HR = 0.41, 95%CI = 0.20-0.86, C4G: HR = 0.47, 95%CI = 0.24-0.94). Only C4G increased with treatment (p = 0.024-0.005).

Conclusions: Tau-A and C4G are elevated in serum from patients with recurrent GBM and prognostic for OS. If validated, these biomarkers could be applied to clinical trials.

Background: Breast cancer has distinct causes and prognoses in patients with premenopausal and postmenopausal status. The expression status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are analyzed by immunohistochemistry (IHC) to classify molecular subtypes of breast cancer among which large differences in prognosis exist.

Methods: The mRNA expression of ESR1 (encoding ERα), ESR2 (encoding ERβ), PGR (encoding PR), and ERBB2 (encoding HER2) was analyzed based on menopausal status (pre- vs post-menopausal) in tumors from breast cancer patients with different receptor status, in R programming environment, using transcriptomics data from TCGA-BRCA project.

Results: In ER-positive or PR-positive or HER2-negative breast tumors, ESR1 transcript levels were found to be higher in tumors from postmenopausal women than those from premenopausal women; in contrast, ESR2 transcript levels were lower in tumors from postmenopausal women than those from premenopausal women. Furthermore, PGR mRNA expression was lower in breast tumors from postmenopausal women than those from premenopausal women, only in those with ER + or PR + status. The expression of these genes between tumors from pre- and post-menopausal patients with breast cancer was also analyzed based on the combination of status of three receptors.

Conclusion: Together, the results suggest that mRNA expression of ESR1, ESR2, and PGR might differ depending on menopausal status in breast tumors with certain receptor status. More importantly, the change in the expression of ESR1 and ESR2 following menopause is in the opposite directions in breast cancer patients showing the need to identify particular molecular mechanisms regulating the expression of ER isoforms post-menopause in different directions in breast cancer patients, considering the high clinical importance of these receptors in terms of the prognosis of patients with breast cancer.

Background: Regulated cell death (RCD) pathways play significant roles in tumorigenesis. However, systematic investigation into correlations between RCD and various molecular and clinical features, particularly anti-tumor immunity and immunotherapy response in pan-cancer remains lacking.

Methods: Using the single-sample gene set enrichment analysis, we quantified the activities of six RCD pathways (apoptosis, autophagy, ferroptosis, cuproptosis, necroptosis, and pyroptosis) in each cancer specimen. Then, we explored associations of these six RCD pathways with tumor immunity, genomic instability, tumor phenotypes and clinical features, and responses to immunotherapy and targeted therapies in pan-cancer by statistical analyses.

Results: Our results showed that the RCD (except autophagy) activities were oncogenic signatures, as evidenced by their hyperactivation in late stage or metastatic cancer patients, positive correlations with tumor proliferation, stemness, genomic instability and intratumor heterogeneity, and correlation with worse survival outcomes in cancer. In contrast, autophagy was a tumor suppressive signature as its associations with molecular and clinical features in cancer shows an opposite pattern compared to the other RCD pathways. Furthermore, heightened RCD (except cuproptosis) activities were correlated with increased sensitivity to immune checkpoint inhibitors. Additionally, elevated activities of pyroptosis, autophagy, cuproptosis and necroptosis were associated with increased drug sensitivity in a broad spectrum of anti-tumor targeted therapies, while the elevated activity of ferroptosis was correlated with decreased sensitivity to numerous targeted therapies.

Conclusion: RCD (except autophagy) activities correlate with unfavorable cancer prognosis, while the autophagy activity correlate with favorable clinical outcomes. RCD (except cuproptosis) activities are positive biomarkers for anti-tumor immunity and immunotherapy response.

Purpose: To evaluate the prognostic effects of apparent diffusion coefficient (ADC) values, qualitative MRI findings, and XRCC1 polymorphism in patients with pancreatic ductal adenocarcinoma (PDAC).

Methods: Between January 2019 and December 2021, 41 PDAC patients (23 males; 66.6 ± 8.9 years) diagnosed with MRI and treated with chemotherapy were included in this prospective, unicenter study. Quantitative b:0-800 ADC values were calculated at the workstation using a circular region of interest with a diameter of 2 cm². Polymerase chain reaction restriction fragment length polymorphism was used to detect XRCC1 genotypes from blood samples. Demographic data, MRI findings, and survival times were recorded. Sensitivity, specificity of ADCmin values, and relationship between XRCC1 genes in predicting survival were calculated and compared.

Results: The median overall survival time was calculated as 9.27 ± 1.4 months. The cut-off value of ADCmin was found to be 0.996 × 10^-3 mm²/s for predicting a 4.6-month survival with 77.3% sensitivity and 84.2% specificity. The distribution of XRCC1 codon 399 polymorphism was determined as 26.8% (n = 11) GG, 65.9% (n = 27) AG, and 7.3% (n = 3) AA. There was no statistical correlation between ADCmin values and XRCC1 gene polymorphism (p > 0.05). ADCmin < 0.996 × 10^-3 and the XRCC1 codon 399 AG/AA genotype was the subgroup with the worst prognosis (p = 0.035). The mean age at diagnosis was 71.0 ± 9.1 years in cases with GG genotype, while it was 64.6 ± 8.9 years in cases with AG/AA genotype, which was statistically significant (p = 0.038).

Conclusions: ADCmin values are useful for predicting prognosis in patients with PDAC. XRCC1 gene polymorphism may affect the age at diagnosis.

Colorectal cancer (CRC) has a 5-year overall survival rate of over 60%. The decrease in the rate of metastatic disease is due to screening programs and the population's awareness of healthy lifestyle. Similarly, advancements in surgical methods and the use of adjuvant chemotherapy have contributed to a decrease in the recurrence of resected disease. Before evaluating a patient's treatment, it is recommended to be discussed in a multidisciplinary tumor board. In stage II tumors, the pathologic characteristics of poor prognosis must be known (T4, number of lymph nodes analyzed less than 12, lymphovascular or perineural invasion, obstruction or perforation, poor histologic grade, presence of tumor budding) and it is mandatory to determine the MSI/MMR status for avoiding administering fluoropyridimidines in monotherapy to patients with MSI-H/dMMR tumors. In stage III tumors, the standard treatment consists of a combination of fluoropyrimidine (oral or intravenous) with oxaliplatin for 6 months although the administration of CAPOX can be considered for 3 months in low-risk tumors. Neoadjuvant treatment is not consolidated yet although immunotherapy is achieving very good preliminary results in MSI-H patients. The use of ctDNA to define the treatment and monitoring of resected tumors is only recommended within studies. These guidelines are intended to help decision-making to offer the best management of patients with non-metastatic colon cancer.