Clinical & Translational Oncology最新文献

Purpose: To determine the incidence of VTE and clinical outcomes in a cohort of cancer patients and COVID-19 infection, and to establish possible predictive factors of VTE.

Methods/patients: A single-center retrospective cohort study was performed to determine the incidence of VTE and mortality in 118 cancer patients with SARS-CoV-2 infection from March to August 2020. We calculated individual Khorana Risk and CATS-MICA scores in order to evaluate their utility to identify risk of VTE or death. Continuous variables were compared using Wilcoxon or Student's T test, and categorical variables were compared using the Chi-Square or Fisher's exact text among patients with and without VTE. A Log-Rank test was performed to detect mortality differences between the groups.

Results: A total of 118 patients were included. VTE global incidence was 4.2% (n = 5), and mortality 25.4% (n = 30). Obesity (p = 0.05), recent chemotherapy (p = 0.049) and use of steroids (p = 0.006) were related to higher risk of VTE in the univariate analysis, although they were not confirmed in the multivariate analysis as independent risk factors. Statistically significant differences in all-cause, COVID-19-related and cancer-related mortality according to the Khorana risk score (KRS) were observed. CATS-MICA score (CMS) also showed statistically significant differences in mortality between low- and high-risk patients. Prediction of risk of VTE development with these scores showed a tendency towards significance.

Conclusions: In this cohort, VTE incidence was similar to previously reported in the general population with SARS-CoV-2 infection. KRS was associated with overall and specific-cause mortality, and might be a useful prognostic tool in this setting.

Objective: Wnt-induced signaling protein 1 (WISP1) and Dickkopf-1 (DKK1) are highly expressed in esophageal squamous cell carcinoma (ESCC), but no direct connection was identified between them. Phenotypic plasticity is a hallmark of ESCC. This research intended to identify the association between WISP1 and DKK1 and their roles in the phenotypic plasticity of ESCC.

Methods: Genes differentially expressed in esophageal carcinoma were analyzed in the GEO database, followed by analyses of GO and KEGG enrichment to screen the hub gene. WISP1 expression and DKK1 secretion was assessed in ESCC tissues and cells. The tumor xenograft and in vivo metastasis models were established by injecting ESCC cells into nude mice. Functional deficiency and rescue experiments were conducted, followed by assays for cell proliferation, migration/invasion, stemness, epithelial-mesenchymal transition (EMT), and apoptosis, as well as tumor volume, weight, proliferation, stemness, and lung metastasis. The binding relationship and co-expression of WISP1 and DKK1 were determined.

Results: WISP1 and DKK1 were upregulated in ESCC cells and tissues, and WISP1 was enriched in the cell stemness and Wnt pathways. WISP1 knockdown subdued proliferation, migration/invasion, EMT activity, and stemness but enhanced apoptosis in ESCC cells. WISP1 knockdown restrained ESCC growth, proliferation, stemness, and metastasis in vivo. WISP1 bound to DKK1 in ESCC. DKK1 overexpression abolished the repressive impacts of WISP1 knockdown on the malignant behaviors of ESCC cells in vitro and of ESCC tumor in vivo.

Conclusion: Knockdown of WISP1/DKK1 restrains the phenotypic plasticity in esophageal squamous cell carcinoma by suppressing epithelial-mesenchymal transition and stemness.

Background: Pain in cancer patients has enormous impact on their quality-of-life. Radiation therapy (RT) is a cornerstone in cancer treatment. The objective of the PREDORT study is to estimate the prevalence of pain in patients attending at Radiation Oncology (RO) Services.

Methods: A prospective, multicenter study was designed for patients treated at the RO Services of reference hospitals. Patients were seen in their initial Nursing consultation, during which key data was collected, including demographic and comorbidities data, medical history, and oncological and pain characteristics. The study has received approval from the Ethics Committee of Navarra, and all patients signed the Informed Consent.

Results: Of the 860 participating patients, 306 reported some type of pain, which implies a prevalence of 35.6%. Of them, 213 identified a cause of oncological origin. The proportion of pain was similar among sexes, but the proportion of non-cancer pain was higher among women (p < 0.05). Regarding pain intensity, the magnitude of breakthrough pain in patients with oncological pain is nearly 1 point greater than in patients with non-oncological pain (7.53 vs 6.81; p = 0.064). Cancer pain is more likely to be limiting of normal life than non-cancer pain (59% versus 38%, p < 0.001). Regarding analgesic treatment, only 60/306 patients (19.6%) were receiving strong opioids. There were 68 patients with pain without any treatment (22.2%).

Conclusions: The prevalence of pain in cancer patients referred to RO services is 35.6%, with the prevalence of exclusively oncological pain being 24.8%. Understanding and addressing oncological pain is essential to provide comprehensive care to patients.

Purpose: Malignant melanoma is an aggressive cancer, and there is a notable dearth on epidemiology, clinical and treatment characterization within the Portuguese population. We performed a scoping review to identify real-world evidence studies focused in Portuguese adult patients with malignant melanoma.

Methods: A comprehensive search was conducted. After screening, we described the studies by design, sample size, geographics, setting, population, and outcomes reported.

Results: The search yielded 54 studies, mainly retrospective (79.6%). The population assessed was heterogeneous varying from patients with melanoma in general to specific types of melanoma, or even more restricted to patients with specific conditions. The evidence found was mostly concerning clinical outcomes (n=46), patients' clinical profile (n=44) and demographic characterization (n=48). Treatment information was described in 30 studies whereas only 18 reported epidemiological parameters. Studies were mainly performed by the major oncology centers in Lisbon, Oporto and Coimbra, and only two evaluated the entire Portuguese population. To allow comparability, only studies including patients with cutaneous malignant melanoma were considered (13 of the 54) for outcomes evaluation analysis. Median OS varied from 18 to 36 months, assessed after melanoma treatment. Incidence was the most reported epidemiological parameter, confirming the increasing number of cutaneous malignant melanoma patients over the years. Only one study reported prevalence and four reported mortality rates.

Conclusions: The evidence found confirms the lack of information about malignant melanoma in Portugal, highlighting the need of real-world studies to assess melanoma prevalence and incidence rates, current treatment approaches, and clinical characterization of these patients.

Purpose: The objective of this investigation is to explore the capability of baseline ¹⁸F-FDG PET/CT radiomics to predict the prognosis of diffuse large B-cell lymphoma (DLBCL) with extranodal involvement (ENI).

Methods: 126 patients diagnosed with DLBCL with ENI were included in the cohort. The least absolute shrinkage and selection operator (LASSO) Cox regression was utilized to refine the optimum subset from the 1328 features. Cox regression analyses were employed to discern significant clinical variables and conventional PET parameters, which were then employed with radiomics score to develop combined model for predicting both progression-free survival (PFS) and overall survival (OS). The fitness and the predictive capability of the models were assessed via the Akaike information criterion (AIC) and concordance index (C-index).

Results: 62 patients experienced disease recurrence or progression and 28 patients ultimately died. The combined model exhibited a lower AIC value compared to the radiomics model and SDmax/clinical variables for both PFS (507.101 vs. 510.658 vs. 525.506) and OS (215.667 vs. 230.556 vs. 219.313), respectively. The C-indices of the combined model, radiomics model, and SDmax/clinical variables were 0.724, 0.704, and 0.615 for PFS, and 0.842, 0.744, and 0.792 for OS, respectively. Kaplan--Meier curves showed significantly higher rates of relapse and mortality among patients classified as high-risk compared to those classified as low-risk (all P < 0.05).

Conclusions: The combined model of clinical variables, conventional PET parameters, and baseline PET/CT radiomics features demonstrates a higher accuracy in predicting the prognosis of DLBCL with ENI.

Purpose: Immunotherapy using immune checkpoint inhibitors (ICIs) has shown several benefits over traditional therapies. However, the eligible population remains small. Antibiotic (ATB) use might reduce immunotherapy efficacy by disrupting the gut microbiota. However, in China, ATB effect on ICI therapy efficacy remains unelucidated. We aimed to assess the effects of ATBs on the anti-tumor efficacy of ICIs to provide a reference for clinical use.

Methods: We included 134 patients with advanced tumors undergoing ICI therapy at Shanghai Jiading District Central Hospital from January 1, 2021, to October 1, 2023. They were divided into Non-ATB and ATB groups based on ATB use within 30 days before and after ICI administration. Moreover, we compared progression-free (PFS) and overall (OS) survival between the groups.

Results: Median PFS and OS were lower in the ATB than in the Non-ATB group (PFS: 4.0 vs. 5.5 months; OS: 5.4 vs. 6.5 months). Univariate analysis revealed that ATB use significantly affected PFS (hazard ratio [HR] = 2.318, 95% confidence interval [CI] = 1.281-4.194, P = 0.005) and OS (HR = 2.115, 95% CI = 1.161-3.850, P = 0.014). Moreover, multivariate analysis revealed poor PFS (HR = 2.573, 95% CI = 1.373-4.826, P = 0.003) and OS (HR = 2.452, 95% CI = 1.298-4.632, P = 0.006) in patients who received ATBs during ICI therapy.

Conclusions: ATB use is negatively correlated with ICI therapy efficacy, leading to reduced PFS and OS in patients undergoing such treatment. Owing to the significant impact of ATBs on the human gut microbiome, regulation of the gut microbiome may emerge as a novel therapeutic target that can enhance the clinical activity of ICIs.

Background: The nod-like receptor protein 3 (NLRP3) is one of the most characterized inflammasomes involved in the pathogenesis of several cancers, including hepatocellular carcinoma (HCC). However, the effects of genetic variants in the NLRP3 inflammasome-related genes on survival of hepatitis B virus (HBV)-related HCC patients are unclear.

Methods: We performed multivariable Cox proportional hazards regression analysis to evaluate associations between 299 single-nucleotide polymorphisms (SNPs) in 16 NLRP3 inflammasome-related genes and overall survival (OS) of 866 patients with HBV-related HCC. We further performed expression quantitative trait loci (eQTL) analysis using the data from the GTEx project and 1000 Genomes projects, and performed differential expression analysis using the TCGA dataset to explore possible molecular mechanisms underlying the observed associations.

Results: We found that two functional SNPs (PANX1 rs3020013 A > G and APP rs9976425 C > T) were significantly associated with HBV-related HCC OS with the adjusted hazard ratio (HR) of 0.83 [95% confidence interval (CI) = 0.73-0.95, P = 0.008], and 1.26 (95% CI = 1.02-1.55, P = 0.033), respectively. Moreover, the eQTL analysis revealed that the rs3020013 G allele was correlated with decreased mRNA expression levels of PANX1 in both normal liver tissues (P = 0.044) and whole blood (P < 0.001) in the GTEx dataset, and PANX1 mRNA expression levels were significantly higher in HCC samples and associated with a poorer survival of HCC patients. However, we did not observe such correlations for APP rs9976425.

Conclusions: These results indicated that SNPs in the NLRP3 inflammasome-related genes may serve as potential biomarkers for HBV-related HCC survival, once replicated by additional larger studies.

Background: Metastatic hormone-sensitive prostate cancer (mHSPC) is treatment-resistant and generally considered incurable. The development of prostate-specific membrane antigen positron emission-computed tomography (PSMA PET/CT) has generated immense expectations due to its diagnostic accuracy in prostate cancer (PCa). PSMA expression of the primary tumor, quantified by SUVmax, is a predictor of oncological outcomes. The role of PSMA-PET/CT SUVmax in metachronous mHSPC treated with ADT plus second-generation antiandrogens (ARSI) is unknown. The main aim of this study was to evaluate ⁶⁸Ga-PSMA-11expression (SUVmax) as a potential prognostic biomarker in patients with metachronous mHSPC treated with ADT and first or second-generation antiandrogens. A second aim was to determine the association between PSMA SUVmax and PSA response to hormone therapy.

Material and methods: Patients diagnosed with metachronous mHSPC between July 2017 and February 2023 who developed biochemical recurrence following radical surgery (with or without salvage radiotherapy and/or ADT) or external radiation therapy (with or without ADT) were included. All patients underwent ⁶⁸ Ga-PSMA-11 PET/CT imaging and the SUVmax value was determined for all measurable locations. The SUVmax value was used for the semiquantitative analysis. The Wilcoxon method was used to compare responders (PSA reduction ≥ 50%) to non-responders (PSA reduction < 50%). The SUVmax value and hormone therapy were evaluated as independent variables relative to the PSA response rate or PSA reduction using the linear regression method. A mixed-effects model (ANOVA) was used for the comparisons.

Results: A total of 82 patients were included. Median follow-up was 11.7 months. On the linear regression analysis, patients with a high SUVmax treated with ADT + ARSI showed a greater PSA response (p = 0.034) than those treated with ADT + first-generation antiandrogens. In the mixed-effects model, SUVmax was significant (p = 0.041). On the univariate analysis, PSA at recurrence (HR, 3.2; 95% CI: 1.07-13.6; p = 0.078) and the number of metastases (HR, 4.77; 95% CI 1.1-26.1: p = 0.002) were associated with the type of hormone therapy administered.

Conclusions: PSMA-PET/CT SUVmax is a prognostic biomarker that can be used to predict a PSA response to ADT + ARSI in patients with metachronous mHSPC. However, these findings need to be confirmed in larger prospective studies.

Purpose: Immunotherapy efficacy in elderly patients with comorbidities and poor performance status is not well understood. More knowledge on this topic is needed to identify subgroups that will benefit from immunotherapy. We aimed to evaluate the effect of comorbidity burden in patients receiving immunotherapy.

Methods/patients: Patients older than 18 years of age and diagnosed with various malignancies, followed up in our tertiary cancer center were screened. Patients treated with immunotherapy were included in this study. We used to Charlson Comorbidity Index (CCI) to evaluate patients' comorbidity burden. The primary outcome was overall survival (OS). Hazard ratio (HR) with confidence interval (CI) was evaluated in multivariable analysis.

Results: A total number of 197 patients were included. The median age was 62 years. Patients were grouped based on CCI scores: CCI-low (≤ 8) and CCI-high (> 8). One-hundred and seven patients (54.9%) had metastatic disease at the time of diagnosis. Most frequently used immunotherapy agent was nivolumab (n = 124, 62.9%), followed by pembrolizumab (n = 36, 18.3%). The median OS was shorter in the CCI-high group than in the CCI-low group (10.6 vs. 21.2 months, p = 0.002) In multivariable analysis, treatment with anti-CTLA4 (HR: 1.85, 95% CI 1.07-3.20, p = 0.028), ECOG performance status (2-4 vs. 0-1) (HR: 2.17; 95% CI 1.25-3.75; p = 0.005), and higher CCI scores (CCI-high vs. CCI-low) (HR: 1.97; 95% CI 1.3-3.0; p = 0.001) were independently associated with worse OS.

Conclusions: Comorbidity burden and performance status independently predict survival outcomes in immunotherapy-treated cancer patients. Comprehensive comorbidity assessment is essential for optimizing treatment and improving patient outcomes.

Objective: To evaluate the feasibility and tolerance of ultra-hypofractionated SABR (stereotactic ablative radiation therapy) protocol following radical prostatectomy.

Patients and methods: We included patients undergoing adjuvant or salvage SABR between April 2019 and April 2023 targeting the surgical bed and pelvic lymph nodes up to a total dose of 36.25 Gy (7.25 Gy/fraction) and 26 Gy (5.2 Gy/fraction), respectively, in 5 fractions on alternate days with an urethra sparing protocol. Acute and late adverse effects were assessed using the CTCAE v5.0. Pearson's chi-square test for categorical variables was used to compare characteristics and possible associations among different subgroups.

Results: Adjuvant radiation therapy (ART) was administered to 40 high-risk patients (detectable post-surgery PSA, Grade Group 4/5, nodal involvement, R1/R2 resection margin), while salvage radiotherapy (SRT) was delivered to 60 patients with rising PSA levels post-undetectable values. Elective nodal irradiation was performed in 57 patients, with 11 additional patients receiving a simultaneous integrated boost (total dose: 40 Gy in 5 fractions) for macroscopic nodal disease. Twenty-four high-risk patients underwent 24-months androgen deprivation therapy (ADT). Treatment was well-tolerated with minimal toxicity. The maximum grade of SABR-related toxicity observed was grade 3. Acute gastrointestinal (GI) toxicity included seven cases of grade 2 and one of grade 3, while acute genitourinary (GU) events were limited to grade 2 in eight patients. Early-late toxicity included two cases of grade 3 and seven of grade 2 for GI, and 11 cases of grade 2 for GU. No toxicity above grade 3 was reported. With a median follow-up of 24 months (6-60 months), 14 patients experienced disease recurrence.

Conclusions: Ultra-hypofractionated adjuvant/salvage SABR appears feasible and safe. Longer follow-up is needed to validate observed outcomes.