[This corrects the article DOI: 10.3389/fonc.2025.1598125.].

BACKGROUND: Evidence on the benefits of eicosapentaenoic acid (EPA) supplementation in cancer patients remains inconsistent, likely due to heterogeneity in tumor types, stages, treatment modalities, and nutritional strategies. This study aimed to assess the impact of EPA as a standalone supplement on body weight, body mass index (BMI), and muscle mass preservation in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) undergoing curative-intent treatment. METHODS: We conducted a double-blind, placebo-controlled randomized trial between December 2015 and September 2018, enrolling 54 patients with advanced SCCHN. Participants received either 2.7 g/day of oral EPA or placebo, alongside standard nutritional support according to European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines. Assessments were performed at baseline (T0), post-induction chemotherapy (T1), and post-treatment (T2), including body composition, nutritional status, functionality, and inflammatory biomarkers. Plasma EPA (% of total fatty acids) was used as a biochemical marker of compliance. RESULTS: Both groups were balanced at baseline (median age 58.9 years; 46.3% malnourished). Neither the intention-to-treat nor per-protocol analyses showed statistically significant differences between groups in weight loss, BMI, or body composition (p > 0.05). In the per-protocol analysis, estimated mean weight loss was –3.81 kg (95% CI: –5.70 to –1.91) in the EPA group, compared to –7.72 kg (95% CI: –12.8 to –6.40) in the placebo group. No differences were observed in nutritional status, energy or protein intake, physical function, or treatment-related toxicity. Complete response rates after oncological treatment were comparable (77.8% EPA vs. 66.7% placebo). Only half of the patients in the EPA group reached an increase in plasma EPA levels consistent with supplementation, and 31.5% discontinued the intervention due to intolerance. CONCLUSIONS: Our study did not demonstrate a clear benefit of EPA supplementation on weight, BMI, or muscle preservation in patients with locally advanced SCCHN receiving curative-intent treatment. While EPA was safe and feasible, the findings do not provide sufficient evidence to support a clinically significant effect. Further research with larger sample sizes and more robust designs is warranted to better understand the potential role of EPA in this population. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02715596 (registered on March 22, 2016 at ClinicalTrials.gov).

Background/Objectives: Few large cohorts with relatively uniform treatment approaches and long-term follow-up are available for assessing clinical outcomes for breast cancer (BC) patients. The Institut Català d’Oncologia (ICO) Breast Cancer Cohort was designed to well characterize treatment patterns and overall survival outcomes at 5 and 10 years, with a particular focus on patients < 40 and ≥70 years old, age groups often underrepresented in clinical trials. Methods: In this retrospective, observational study, we included all pathologically confirmed invasive BC patients diagnosed and treated between 2010 and 2014 at ICO, a Spanish reference cancer center, with a follow-up until November 2023. We collected comprehensive real-world data on clinicopathologic characteristics and treatment modalities. Overall survival (OS) was estimated using the Kaplan–Meier technique and was reported stratified by prognostic factors for the age groups of ≤40, 41–69 and ≥70. The Multivariate Cox model was used to estimate the risk of death for subgroups of age, adjusting for subtype, stage and grade. Results: Overall, 3451 patients with stage I to IV BC were diagnosed and treated, with a mean age of 58 years (range 19–98); 371 (10.8%) were diagnosed ≤40 years, and 756 (21.9%) were ≥70 years. With a mean follow-up of 9.9 years (SD = 3.5), the 5- and 10-year OS were 89% (95% CI: 86–92%) and 85% (95% CI: 81–88%) for patients ≤ 40, respectively; for those aged 41–69 years, 91% (95% CI: 90–92%) and 85% (95% CI: 83–86%), respectively; and 70% (95% CI: 66–73%) and 50% (95% CI: 47–54%) for those ≥70 years, respectively. The 5- and 10-year relative survival (RS) were 92% and 88% for patients < 70 years, respectively, and 82% and 77% for those ≥70 years, respectively. The Multivariate Cox model identified a HR of 4.90 (95% CI: 3.44–6.97, p < 0.001) for patients ≥ 70 years compared to those between 41 and 69 years. Conclusions: The ICO Breast Cancer Cohort, as far as we know, the largest in Spain with long-term follow-up, underscores the critical role of age and subtype in determining overall survival outcomes in patients with breast cancer.

Abstract Off‐label use (OLU) is quite common in oncology due to the complexity of cancer and the time‐consuming regulatory process. However, outcomes of OLU in cancer treatment remain unclear. This study aimed to evaluate the overall survival (OS), event‐free survival (EFS), duration of treatment (DOT), and reason for treatment discontinuation in patients receiving immune checkpoint inhibitors (ICI) as OLU for solid tumors from 2011 to 2020. The study collected data on 356 episodes (353 patients), with a median age of 64.4 years, 36.2% women, and 14.6% ECOG ≥ 2. Median OS was 15.7 (11.9–18.7) months, and median EFS was 5.4 (3.8–6.6) months. Men, patients with metastatic disease or ECOG‐PS higher than 1, had worse survival outcomes. The findings derived from this study provide valuable information regarding the real‐world use of ICI‐OLU and contributes to enhancing the decision‐making process for individuals with cancer. Further research on immunotherapy outcomes of OLU in cancer is needed.

BACKGROUND:Squamous cell carcinoma of the head and neck (SCCHN) is an aggressive disease with poor prognosis. It is known that the activation of STAT3 signaling pathways promotes the development and progression of this neoplasia and it has been described the role of PTPRT as a negative regulator of STAT3. Then, we have evaluated the impact of them as biomarkers of outcome in a series of patients with recurrent and/or metastatic SCCHN treated with weekly paclitaxel-plus-cetuximab (ERBITAX) regimen. PATIENTS AND METHODS:Between 2008 and 2017, 52 patients with recurrent/metastatic SCCHN were treated with ERBITAX at our center, 34 of whom had available tumor samples. Phosphorylated STAT3 (pSTAT3) protein expression was analyzed by immunohistochemistry, STAT3 mRNA expression by qPCR, and PTPRT promoter methylation by methylation-specific PCR. Molecular results were correlated with response rate (RR), progression-free survival (PFS), and overall survival (OS). RESULTS:pSTAT3 overexpression was detected in 67% and PTPRT promoter hypermethylation in 41% of tumor samples. PTPRT promoter hypermethylation showed a trend towards an association with lower RR (21% vs. 60%; p = 0.06). A lower RR was also observed in patients with pSTAT3 overexpression (36% vs. 54%) and in those with high STAT3 mRNA levels (43% vs. 64%), but these differences did not reach statistical significance. PTPRT promoter hypermethylation correlated with pSTAT3 overexpression (p = 0.009) but not with STAT3 mRNA overexpression. OS and PFS was shorter in patients with activated STAT3, but the difference did not reach statistical significance. CONCLUSIONS:Although this was a relatively small retrospective study, it provides preliminary indications of the potential role of the STAT3 pathway on outcome in SCCHN and confirms that PTPRT acts as a negative regulator of STAT3. Our findings warrant investigation in a larger patient cohort to determine if inactivating this pathway through specific targeted treatments could improve outcomes in recurrent/metastatic SCCHN patients.

Objectives: Immune checkpoint inhibitors (ICIs) have provided a breakthrough in the treatment of non-small cell lung cancer (NSCLC) patients, but only some patients benefit substantively. Identifying definitive predictive biomarkers could overcome this limitation. Materials and methods: We selected 146 metastatic NSCLC patients treated with anti-PD-(L)1. Immunohistochemistry of HLA-I, PD-L1 and CD73 was performed in 122 tumor biopsies at diagnosis. The association with patients, tumor parameters, and the predictive value to ICI treatment were determined. Results: In our cohort, 42 %, 25 %, and 21 % of the tumors exhibited high levels of HLA-I, PD-L1, and CD73, respectively. Lung adenocarcinomas displayed elevated CD73 levels, compared with lung squamous cell carcinomas (P = 0.026). High PD-L1 was significantly correlated with high levels of HLA-I (P = 0.005) and of CD73 (P = 0.025). Patients with high-level HLA-I tumors exhibited more favorable clinical outcomes following ICI, with a median overall survival of 30.7 months (95 % confidence interval [CI]: 18.3 months-not reached), compared with 18.2 months (95 % CI: 12.4-25.2 months) in patients with low-level HLA-I tumors (P = 0.016). The median progression-free survival (PFS) for patients with high-level HLA-I tumors was 18.5 months (95 % CI: 11.1-57.1 months), longer than patients with low-level HLA-I tumors, whose median PFS was 9.2 months (95 % CI: 7.2-11.9 months) (P = 0.006). In a multivariable analysis, high-level HLA-I was independently associated with lower risk of progression to ICI (HR = 0.46, 95 % CI 0.24-0.87; P = 0.018). Conclusions: High-level HLA-I were associated with better clinical outcomes to ICI in our cohort of NSCLC patients. Therefore, further investigations are warranted to refine this biomarker and validate its efficacy in prospective and larger set of patients.

Despite a multimodal radical treatment, mortality of advanced epithelial ovarian cancer (AEOC) remains high. Host-related factors, such as systemic inflammatory response and its interplay with the immune system, remain underexplored. We hypothesized that the prognostic impact of this response could vary between patients undergoing primary debulking surgery (PDS) and those undergoing interval debulking surgery (IDS). Therefore, we evaluated the outcomes of two surgical groups of newly diagnosed AEOC patients according to the neutrophil, monocyte and platelet to lymphocyte ratios (NLR, MLR, PLR), taking median ratio values as cutoffs. In the PDS group (n = 61), low NLR and PLR subgroups showed significantly better overall survival (not reached (NR) vs. 72.7 months, 95% confidence interval [CI]: 40.9-95.2, p = 0.019; and NR vs. 56.1 months, 95% CI: 40.9-95.2, p = 0.004, respectively) than those with high values. Similar results were observed in progression free survival. NLR and PLR-high values resulted in negative prognostic factors, adjusting for residual disease, BRCA1/2 status and stage (HR 2.48, 95% CI: 1.03-5.99, p = 0.043, and HR 2.91, 95% CI: 1.11-7.64, p = 0.03, respectively). In the IDS group (n = 85), ratios were not significant prognostic factors. We conclude that NLR and PLR may have prognostic value in the PDS setting, but none in IDS, suggesting that time of surgery can modulate the prognostic impact of baseline complete blood count (CBC).

Patient characteristics and molecular subtypes

Purpose: Medicines in special situations (MSS) refer to off-label or to unlicensed drugs under investigation (compassionate use). Our objectives were to evaluate characteristics and to estimate overall survival (OS), event-free survival (EFS), and the duration of treatment (DT) of MSS used for cancer treatment at a multicentre comprehensive cancer institution.Methods: Retrospective cohort study on adult cancer patients for whom an MSS treatment was requested (January 2011-December 2020). A descriptive analysis was performed and median OS and EFS and 95% confidence intervals (CIs) were estimated. Survival curves were stratified by type of tumor, ECOG (Eastern Cooperative Oncology Group) performance status (PS), age, sex, treatment stage and type of drug (mechanism of action and target).Results: Treatment was initiated in 2092 episodes (1930 patients) out of 2377 MSS episodes (2189 patients) requested, 33% for hematological treatment and 87% for advanced stage cancer. Median OS (months) was 21.1 (95% CI 19.4-22.7), median EFS was 5.6 (95% CI 5.1-6.0) months, and median DT was 4.5 [0.0; 115.3] months.OS and EFS statistically significantly favored female patients, ECOG PS =2 episodes showed worse OS and EFS outcomes (p < 0.0001). Statistically significant differences in survival were found within solid and hematological cancer, disease stage, drug mechanism of action, and type of cancer (p < 0.001) but not for age. Survival outcomes by tumor subtype and drug are presented both globally and separately based on disease stage.Conclusion: MSS uses are practiced across almost all cancer types, mostly for advanced disease. ECOG PS =2, along with advanced disease, was related to worse survival. Information about real-world outcomes is valuable and contributes to better decision-making regarding MSS and our experience in this field could be of interest for other colleagues.

Representative images comparing high versus low immunohistochemical expression of (A,B) EGFR,(C,D) PTEN, (E,F) SOX-2, (G,H) SHC1, (I,J) TCIRG1,(K,L) IDH1R132H (K:positive, L: negative), (M,N) Olig2,and (O,P) Ki67

IHC protein expression of IDH1, EGFR (intensity 3 as high versus 0-2), high intensity, PTEN, OLIG2, Ki67 and SOX2 by IGS (first row) and TCGA subtype (second row: KNN, third row: SVM, fourth row: ssGSEA). Significant differences were seen between mesenchymal and classical or proneural tumors. See Supplementary Data File S1e for results simplified in Table 1.

Key resource identifiers (RRIDs), antibodies, methods, and scoring systems used for immunohistochemistry analyses

Excel spreadsheets showing: (S1a) the differential expression analysis between mesenchymal vs proneural tumors; (S1b) the differential expression analysis between classical vs mesenchymal tumors; (S1c) the differential expression analysis between classical vs proneural tumors; (S1d) classification of tumor samples based on the RNA-Seq results into the three TCGA molecular subtypes (according to the GlioVis algorithms KNN, SVM, and ssGSEA) and classification according to the IGS clusters; (S1e) immunohistochemical results of samples classified in the three TCGA molecular subtypes (according to the GlioVis algorithms KNN, SVM, and ssGSEA) and IGS clusters; and (S1f) results of the gene fusion analysis in the tumor samples, the molecular subtype of the tumor (according to the GlioVis algorithms KNN, SVM, and ssGSEA), and the tumor IGS clusters

Approximately 20% of lung adenocarcinomas harbor activating mutations at KRAS, an oncogene with the ability to alter the tumor immune microenvironment. In this retrospective study, we examined 103 patients with KRAS-mutant lung adenocarcinoma who were treated with immunotherapy-based regimens and we evaluated the clinical outcomes according to PD-L1 expression and the type of KRAS mutation. Among all patients included, 47% carried KRAS G12C mutation whereas 53% harbored KRAS non-G12C mutations. PD-L1 status was available for 77% of cases, with higher expression among KRAS G12C tumors (p = 0.01). Better overall survival and progression-free survival were observed in high PD-L1 expression tumors, regardless of KRAS mutation type. The heterogeneous nature of KRAS-mutant tumors and the presence of other co-mutations may contribute to different outcomes to immunotherapy-based strategies.

Spearman correlation between gene and protein expression for the four antibodies selected according to RNA-Seq differential expression.

In 38 sequenced samples classified according to the Support Vector Machine (SVM) algorithm, heatmaps were plotted to compare the expression of the top 50 genes between (A) classical and mesenchymal, (B) mesenchymal and proneural, and (C) classical and proneural subtypes.

e14039 Background: Glioblastoma (GB) is the most prevalent primary brain tumor in adults. The first-line treatment is based on standard brain surgery and adjuvant radio-chemotherapy. Indoleamine 2,3-dioxygenase 1 (IDO1) is a catabolic enzyme that plays a role in the metabolism of tryptophan (Trp), thereby promoting a state of immunosuppression. New treatments inhibiting this pathway are being tested in GB. This study aims to assess the expression of IDO in GB patients to determine whether this enzyme may be an actionable target for the treatment of GB. Methods: This is a retrospective transversal study whose database comes from the GLIOCAT project. Expression of IDO protein and mRNA was evaluated in tumor specimens of newly diagnosed GB patients by immunohistochemistry (IHC) (percentage of positive tumor cells) with an antibody anti-IDO1 (Sigma-Aldrich Cat#HPA027772) and by RNA sequencing (RNA-seq). RNA-seq (IIlumina HiSeq2000) in paired-end mode with a read length of 2x76bp using TruSeq SBS Kit v4). Reads were mapped to the human reference genome version hg38 with STAR. Genes were quantified with RSEM using gencode annotation version 24. Normalization of gene expression was performed with the trimmed-mean of M values (TMM) method. IDO gene expression values of -6 logCPM were considered as not expressed. Results: From the 255 samples assessed by IHC, 199 patients (78%) did not express IDO1 protein (mean 0.8±2.73, range 0-21%). From the 139 samples assessed by RNA-seq, TMM values, were negative for 49.6%, while low expression was detected for the other samples (mean -3.36 +/- 3.15 logCPM, range -6.12-4.32). Conclusions: Although IDO1 is barely expressed in normal brain tissue, certain studies show that its expression is upregulated in GB, either by tumor cells or indirectly induced in host antigen presenting cells, leading to immune evasion. Therefore, the metabolism of Trp is an attractive pathway to be targeted for the treatment of GB; however, our results show that IDO may not be the main target to be inhibited due to its undetectable or very low levels of expression.

Stereotactic body radiation therapy (SBRT) is a treatment modality with curative intent for oligometastatic cancer patients, commonly defined by a low-burden metastatic disease with 1–5 systemic metastases. Better knowledge of the clinical profile and prognostic factors in oligometastatic cancer patients could help to improve the selection of candidates who may obtain most benefits from SBRT. The objective of this study was to describe the clinical data and outcome in term of overall survival (OS) of patients with oligometastatic disease treated with SBRT over a 6-year period. From 2013 to 2018, 284 solid tumor cancer patients with 1–5 oligometastases underwent SBRT at a large university-affiliated oncological center in Barcelona, Spain. Variables related to the patient profile, tumor, oligometastatic disease, and treatment were evaluated. A total of 327 metastatic tumors were treated with SBRT. In 65.5

Background: Despite impressive progression-free survival (PFS) results from PARP inhibitors (PARPi) in ovarian cancer, concerns about their effect on post-progression treatment outcomes have recently arisen, particularly when administered in the relapsed setting. Overlapping mechanisms of resistance between PARPi and platinum have been described, and optimal therapies upon progression to PARPi are unknown. We communicate real-world data (RWD) on outcomes of subsequent chemotherapy upon progression to PARPi used as maintenance in ovarian cancer relapses, particularly focusing on platinum rechallenge, according to BRCA status. Methods: Data from high-grade serous or endometrioid ovarian cancer patients who received subsequent chemotherapy after progression to maintenance PARPi in the relapsed setting, in 16 Catalan hospitals between August 2016 and April 2021, and who were followed-up until July 2021, were included. Endpoints were overall response rate (ORR), and PFS and overall survival (OS) measured from the subsequent chemotherapy starting date. Results: 111 patients were included [46 (41.4%) presented pathological BRCA1/2 mutations, 8 (7.5%) in other homologous recombination-related genes]. Sixty-four patients (57.7%) had received two prior chemotherapy lines, including the one immediately prior to PARPi. PARPi were niraparib (n = 60, 54.1%), olaparib (n = 49, 44.1%), and rucaparib (n = 2, 1.8%). A total of 81 patients remained platinum-sensitive (PS population) after progression to PARPi (when progression-free interval [PFI] was >6 months after the last cycle of prior platinum) [median PFI 12.0 months (interquartile range, IQR, 8.8–17.1)]. Of those, 74 were treated with subsequent platinum regimens, with the following results: ORR of 41.9%, median PFS (mPFS) of 6.6 months (95% CI 6–9.2), and median OS (mOS) of 20.6 months (95% CI 13.6–28.9). Analysis of these 74 patients according to BRCA status showed that PFIs for BRCA mutant and non BRCA-mutant patients were 13.6 [IQR11.2–22.2] and 10.3 [IQR 7.4–14.9] months, respectively (p = 0.010); ORR were 40.0% versus 43.6%, respectively; Rates of progression (as best response) to subsequent platinum were 45.7% versus 17.9%, respectively (p = 0.004); mPFS and mOS were 3.5 (95% CI 2.5–8.6) versus 7.5 months (95% CI 6.5–10.1, p = 0.03), and 16.4 (95% CI 9.3–27.5) versus 24.2 months (95% CI 17.2–NR, p = 0.036), respectively. Conclusion: This is the largest series of real-world data on ovarian cancer patients retreated with platinum in the post-PARPi scenario, separately analyzing BRCA mutant and non-mutant patients, to our knowledge. In our platinum-sensitive population, rechallenge with platinum after progression upon PARPi in the 3rd or later lines for ovarian cancer relapses shows relevant ORR and similar PFS outcomes to historical series of the prePARPi era. However, BRCA mutant patients presented significantly higher rates of progression under subsequent platinum and worse survival outcomes associated with subsequent platinum than non-BRCA-mutant patients.