Oligometastatic non-small-cell lung cancer (OMD-NSCLC) has emerged as a biologically and clinically distinct subtype of advanced disease, characterized by limited metastatic burden and a more indolent course. In this narrative review, we examine the current definition of OMD-NSCLC, diagnostic tests, possible biomarkers, and current therapeutic strategies. Biological insights highlight the role of microRNAs in differentiating true oligometastatic state from polymetastatic disease. The main local ablative therapies (LAT) include surgery and radiotherapy. The integration of LAT with systemic therapies has been explored in clinical trials, yielding promising but occasionally inconsistent results. As the therapeutic landscape of OMD-NSCLC patients continues to evolve, refining definitions, identifying predictive biomarkers, and individualizing care are essential steps toward achieving the potential of radical-intent therapy.

Gastroesophageal adenocarcinoma (GEA) represents a heterogenous disease with poor prognosis, in which biomarker-driven strategies have gained relevance to optimize treatment selection. Epstein-Barr virus positive GEA (EBV-GEA) is an immune-enriched molecular subtype defined by TCGA suggested to have potential sensitivity to immune checkpoint inhibitors. However, clinical evidence supporting the efficacy of immunotherapy in this subgroup remains limited, and EBV testing is not yet considered a validated biomarker in international clinical guidelines. We report a case of a 74-year-old male with locally advanced, HER-2 negative, mismatch repair-proficient, EBV-positive gastric adenocarcinoma, with high PD-L1 expression (CPS 69), who experienced disease progression during perioperative FLOT chemotherapy. The patient subsequently received first-line treatment with nivolumab plus FOLFOX, achieving a marked radiological response. Salvage surgery revealed a complete pathological response and no further treatment with nivolumab was administered after surgery. This case illustrates the potential benefit of immunotherapy in EBV-positive gastric cancer, even in the microsatellite-stable setting. The overlap of biomarkers in this patient may have contributed to immune response, highlighting the importance of comprehensive molecular profiling in GEA and supporting EBV status as a promising predictor of immunotherapy benefit.

ALK rearrangements are rare but actionable oncogenic drivers in thyroid cancer, particularly in aggressive histologies such as poorly differentiated thyroid carcinoma (PDTC), and evidence supporting sequential ALK inhibition in this setting is scarce. We report a 19-year-old male with ALK-rearranged, radioiodine-refractory PDTC who started systemic therapy with ceritinib, achieving a complete metabolic response. After treatment discontinuation and subsequent progression despite ceritinib reintroduction, lorlatinib was initiated. Treatment with the third-generation ALK inhibitor led to a deep and durable complete metabolic response, sustained for more than four years, including persistence of remission after treatment discontinuation, with minimal toxicity. This case highlights the potential role of sequential ALK inhibition to overcome acquired resistance in ALK-rearranged TC and underscores the importance of comprehensive molecular profiling to guide personalized treatment strategies in rare aggressive thyroid cancers.

Background: In glioblastoma, first‐line treatment can influence subsequent treatment lines. Therefore, progression‐free survival 2 (PFS2), the time from initial randomization to progression on subsequent treatment or death, may better predict overall survival (OS) compared to PFS. However, this association needs validation in glioblastoma, particularly with novel targeted agents in early clinical trials. Methods: Medical records of glioblastoma patients from a multicentric Spanish cohort with genomic profiling treated between 2018 to 2023 were analyzed. Correlations between OS and PFS or PFS2 were calculated using an iterative multiple imputation approach and time‐to‐event endpoints with Kaplan–Meier methods. Results: We analyzed 405 patients. Median OS, PFS, and PFS2 were 25.4, 8.7 and 16.4 months, respectively. Correlation between OS‐PFS was 0.69 (95% CI, 0.62–0.75), whilst for OS‐PFS2 it was 0.83 (95% CI, 0.78–0.87). In patients who received targeted therapy, OS‐PFS correlation was 0.51 (95% CI, 0.02–0.81), whilst for OS‐PFS2, it was 0.72 (95% CI, 0.30–0.91). For patients with ESCAT tier I‐II molecular targets, OS‐PFS correlation was 0.69 (95% CI, 0.26–0.89), weaker than OS‐PFS2 (0.83 [95% CI, 0.29–0.97]). PFS2 also performed better than PFS in ESCAT III‐IV patients (0.80 [95% CI, 0.75–0.85] vs. 0.69 [95% CI, 0.61–0.75]) and in those without targetable alterations (0.86 [95% CI, 0.74–0.92] vs. 0.68 [95% CI, 0.51–0.80]). Conclusions: Progression‐free survival 2 (PFS2) is a more robust surrogate for OS than PFS in glioblastoma, including patients receiving targeted therapies or without actionable targets. These findings support adoption of PFS2 as a candidate surrogate endpoint in glioblastoma, offering a balance between trial feasibility and meaningful survival outcomes.

Epstein–Barr virus-positive gastroesophageal adenocarcinoma (EBV-GEA) is a distinct molecular subtype characterized by recurrent genomic and epigenetic alterations, frequent PD-L1/PD-L2 upregulation, and an immune-enriched tumor microenvironment. These features provide a strong biological rationale for immune checkpoint inhibition (ICI); however, clinical evidence remains limited, and EBV positivity is not currently established as an independent predictive biomarker for immunotherapy. We retrospectively identified consecutive patients with locally advanced or metastatic EBV-GEA treated with ICI-based regimens at a single tertiary cancer center between January 2016 and August 2025. EBV positivity was confirmed by Epstein–Barr virus-encoded RNA in situ hybridization. Clinical, pathological, treatment, and molecular data were collected. Treatment outcomes included best overall response, objective response rate (ORR), disease control rate (DCR), progression-free survival and disease-free survival when curative-intent surgery was performed. In patients with adequate tumor tissue, the tumor immune microenvironment was exploratorily characterized by immunohistochemical quantification of CD3+ and CD8+ T-cell densities. Eight patients with EBV-GEA were included. The ORR was 62.5% and the DCR was 75%. No consistent relationship between clinical outcome and HER2, PD-L1, Claudin 18.2 or mismatch repair status was observed. Tumor immune microenvironment assessment was feasible in five patients. Notably, the three patients with the highest CD3+ T-cell densities (>2000 cells/mm², post hoc threshold) experienced the most favorable clinical outcomes, including two radiological partial responses followed by pathologic complete response and one prolonged partial response. In contrast, CD8+ T-cell density showed greater interpatient variability. ICI-based therapy demonstrated clinically meaningful activity in this small retrospective cohort of EBV-GEA, but benefit was not universal, highlighting substantial clinical and biological heterogeneity within this molecular subtype.