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Background: The phase 3 CheckMate-743 trial demonstrated a prolonged overall survival (OS) benefit with nivolumab plus ipilimumab over chemotherapy as first-line treatment in patients with unresectable pleural mesothelioma (PM). However, given that Latin American (LATAM) patients were notably underrepresented in this trial, we retrospectively assessed the effectiveness and safety of this regimen in this population., Methods: This retrospective study included patients from 15 centers in LATAM with unresectable or metastatic PM treated with first-line nivolumab plus ipilimumab in a real-world data (RWD) scenario. Demographic, clinicopathological characteristics, and safety data were collected from medical charts. Progression-free survival (PFS), and OS were calculated using the Kaplan-Meier method., Results: From June 2017, and January 2024 96 patients were included: epithelioid 78% (n = 75), 81% were ECOG 0-1 (n = 78). With a median follow-up of 24.1 months, median PFS and OS were 8 months (95% CI, 6.6-9.4), and 22 months (95% CI, 18.9-25), respectively. No statistical difference in OS was observed between epithelioid versus nonepithelioid histology (median 23 months vs. 19 months, respectively; P = .29). Treatment efficacy was also consistent among different clinical subgroups. Any and grade 3-4 adverse events were found in 43.1% (n = 28), and 18.5% (n = 12) of patients, respectively. Remarkably, no OS impact was observed in patients who had dose delay or treatment discontinuation due to immune-related adverse events, and those who experienced any adverse event., Conclusions: This multicenter RWD study demonstrated the clinically meaningful benefit of first-line ipilimumab and nivolumab in LATAM patients with unresectable or metastatic PM, and data is consistent with previous trial findings., Competing Interests: Disclosure The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Programmed death ligand-1 (PD-L1) expression is a well-known predictive biomarker of response to immune checkpoint blockade in non-small cell lung cancer (NSCLC). However, there is limited evidence of the relationship between PD-L1 expression, clinicopathological features, and their association with major driver mutations in NSCLC patients in Latin America., Methods: This retrospective study included patients from Argentina with advanced NSCLC, and centralized evaluation of PD-L1 expression concurrently with genomic alterations in the driver genes EGFR, ALK, ROS1, BRAF, and/or KRAS G12C in FFPE tissue samples., Results: A total of 10 441 patients with advanced NSCLC were analyzed. Adenocarcinoma was the most frequent histological subtype (71.1%). PD-L1 expression was categorized as PD-L1 negative (45.1%), PD-L1 positive low-expression 1%-49% (32.3%), and PD-L1 positive high-expression ≥50% (22.6%). Notably, current smokers and males were more likely to have tumors with PD-L1 tumor proportion score (TPS) ≥50% and ≥ 80% expression, respectively (p < 0.001 and p = 0.013). Tumors with non-adenocarcinoma histology had a significantly higher median PD-L1 expression (p < 0.001). Additionally, PD-L1 in distant nodes was more likely ≥50% (OR 1.60 [95% CI: 1.14-2.25, p < 0.01]). In the multivariate analysis, EGFR-positive tumors were more commonly associated with PD-L1 low expression (OR 0.62 [95% CI: 0.51-0.75], p < 0.01), while ALK-positive tumors had a significant risk of being PD-L1 positive (OR 1.81 [95% CI: 1.30-2.52], p < 0.01)., Conclusions: PD-L1 expression was associated with well-defined clinicopathological and genomic features. These findings provide a comprehensive view of the expression of PD-L1 in patients with advanced NSCLC in a large Latin American cohort., (© 2024 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Background: The role of the molecular tumour board (MTB) is to recommend personalised therapy for patients with cancer beyond standard-of-care treatment. A comprehensive molecular analysis of the tumour in a molecular pathology laboratory is important for all targeted therapies approaches. Here we report the 1-year experience of the Instituto Alexander Fleming Molecular Tumour Board., Patients and Methods: The MTB of the Instituto Alexander Fleming was launched in December 2019 in a monthly meeting. In each interactive monthly session, five cases were presented and discussed by the members. These cases were referred by the treating oncologists. The MTB recommendations were sent to each physician individually, and to the rest of the meeting participants. This was discussed with the patients/families by the treating oncologist. The final decision to choose therapy was left to the treating physicians. Of the 32 patients presented at MTB, 28 (87.5%) had potentially actionable alterations and only 4 (12.5%) had no actionable mutation. Six (19%) patients received a local regulatory agency approved drug recommendation, nine (28%) patients received an off-label approval treatment recommendation and three (9%) patients did not receive the treatment due to access and reimbursement of the drug., Conclusion: In most of the cases evaluated, the MTB was able to provide treatment recommendations based on targetable genetic alterations. Molecular-guided extended personalised patient care is effective for a small but clinically significant proportion of patients in challenging clinical situations. We believe that the implementation of a MTB is feasible in the Latin America (LATAM) region., Competing Interests: None of the authors have conflicts of interest to declare., (© the authors; licensee ecancermedicalscience.)

Patients with non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) have shown benefit from anti-PD-1 therapies. However, not all patients experience tumor shrinkage, durable responses or prolonged survival, demonstrating the need to find response markers. In blood samples from NSCLC and RCC patients obtained before and after anti-PD-1 treatment, we studied leukocytes by complete blood cell count, lymphocyte subsets using flow cytometry and plasma concentration of nine soluble mediators, in order to find predictive biomarkers of response and to study changes produced after anti-PD-1 therapy. In baseline samples, discriminant analysis revealed a combination of four variables that helped differentiate stable disease-response (SD-R) from progressive disease (PD) patients: augmented frequency of central memory CD4 + T cells and leukocyte count was associated with response while increased percentage of PD-L1 + natural killer cells and naïve CD4 +  T cells was associated with lack of response. After therapy, differential changes between responders and non-responders were found in leukocytes, T cells and TIM-3 + T cells. Patients with progressive disease showed an increase in the frequency of TIM-3 expressing CD4 + and CD8 + T cells, whereas SD-R patients showed a decrease in these subsets. Our findings indicate that a combination of immune variables from peripheral blood (PB) could be useful to distinguish response groups in NSCLC and RCC patients treated with anti-PD-1 therapy. Frequency of TIM-3 + T cells showed differential changes after treatment in PD vs SD-R patients, suggesting that it may be an interesting marker for monitoring progression during therapy.

Introduction: Imatinib is the standard first-line therapy for advanced gastrointestinal stromal tumor. (18)F-fluorodeoxyglucose PET computed tomography (FDG PET/CT) shows a faster response than computed tomography in nonpretreated patients., Patients & Methods: After disease progression on imatinib 400 mg, 16 patients were exposed to 800 mg. Tumor response was evaluated by FDG PET/CT on days 7 and 37. Primary objective was to correlate early metabolic response (EMR) with progression-free survival (PFS)., Results: EMR by FDG PET/CT scan was not predictive of PFS. Median PFS in these patients was 3 months. Overall survival was influenced by gastric primary site (p = 0.05)., Conclusion: The assessment of EMR by FDG PET/CT in patients with advanced gastrointestinal stromal tumor exposed to imatinib 800 mg was not predictive of PFS or overall survival.

We analyzed 43 women (61%) and 28 men (39%) surgically treated for carcinoid tumors from Jan/1975 to Dec/2011. Median age: 38 years (13-67). Typical carcinoid (TC) appeared in 63 (89%) patients, 8 (11%) suffered from atypical carcinoid (AC). Median follow-up: 4 years (1-24). TC stages were: IA = 33 (52%), IB = 10 (16%), IIA = 2 (3%), IIB = 2 (3%), IIIA = 12 (19%) and IIIB = 2 (3%); AC stages were: IA = 1 (12.5%), IIB = 1 (12.5%), IIIA = 2 (25%) and IIIB = 4 (50%). TNM classification did not show significant differences on 5-years survival period by stage (p = 0.689), even according to histological type (TC: p = 0.547; AC: p = 0.592). The disease-free survival rate was significantly lower (TC: 3 years vs. AC: 2 years, p = 0.000) and relapses were more frequent in AC (AC: 50% vs. TC: 2%, p = 0.000). The 7th TNM staging was not influential in estimating survival from carcinoid tumours in our population. The histological subtype was a better prognostic factor.

Juvenile breast cancer is rare and poorly known. We studied a series of five breast cancer patients diagnosed within 25 years of age that included two adolescents, 12- and 15-years-old, and 3 young women, 21-, 21-, and 25-years-old, respectively. All cases were scanned for germline mutations along the entire BRCA1/2 coding sequences and TP53 exons 4-10, using protein truncation test, denaturing high performance liquid chromatography and direct sequencing. Paraffin-embedded primary tumors (available for 4/5 cases), and a distant metastasis (from the 15-years-old) were characterized for histological and molecular tumor subtype, human papilloma virus (HPV) types 16/18 E6 sequences and tumor-associated mutations in TP53 exons 5-8. A BRCA2 germline mutation (p.Ile2490Thr), previously reported in breast cancer and, as compound heterozygote, in Fanconi anemia, was identified in the 21-year-old patient diagnosed after pregnancy, negative for cancer family history. The tumor was not available for study. Only germline polymorphisms in BRCA1/2 and/or TP53 were detected in the other cases. The tumors of the 15- and 12-years-old were, respectively, classified as glycogen-rich carcinoma with triple negative subtype and as secretory carcinoma with basal subtype. The tumors of the 25-year-old and of the other 21-year-old were, respectively, diagnosed as infiltrating ductal carcinoma with luminal A subtype and as lobular carcinoma with luminal B subtype. No somatic TP53 mutations were found, but tumor-associated HPV 16 E6 sequences were retrieved from the 12- and 25-year-old, while both HPV 16 and HPV 18 E6 sequences were found in the tumor of the 15-year-old and in its associated metastasis. Blood from the 15- and 25-year-old, diagnosed with high-stage disease, resulted positive for HPV 16 E6. All the HPV-positive cases were homozygous for arginine at TP53 codon 72, a genotype associated with HPV-related cancer risk, and the tumors showed p16(INK4A) immunostaining, a marker of HPV-associated cancers. Notably menarche at 11 years was reported for the two adolescents, while the 25-year-old was diagnosed after pregnancy and breast-feeding. Our data suggest that high-risk HPV infection is involved in a subset of histopathologically heterogeneous juvenile breast carcinomas associated with menarche or pregnancy and breast-feeding. Furthermore we implicate BRCA2 in a juvenile breast carcinoma diagnosed at 21 years of age, 4 years after an early full-term pregnancy, in absence of cancer family history.