Baseline clinical prognostic factors for recurrent and/or metastatic (RM) head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy are lacking. CT-based radiomics may provide additional prognostic information. A total of 85 patients with RM-HNSCC were enrolled for this study. For each tumor, radiomic features were extracted from the segmentation of the largest tumor mass. A pipeline including different feature selection steps was used to train a radiomic signature prognostic for 10-month overall survival (OS). Features were selected based on their stability to geometrical transformation of the segmentation (intraclass correlation coefficient, ICC > 0.75) and their predictive power (area under the curve, AUC > 0.7). The predictive model was developed using the least absolute shrinkage and selection operator (LASSO) in combination with the support vector machine. The model was developed based on the first 68 enrolled patients and tested on the last 17 patients. Classification performance of the radiomic risk was evaluated accuracy and the AUC. The same metrics were computed for some baseline predictors used in clinical practice (volume of largest lesion, total tumor volume, number of tumor lesions, number of affected organs, performance status). The AUC in the test set was 0.67, while accuracy was 0.82. The performance of the radiomic score was higher than the one obtainable with the clinical variables (largest lesion volume: accuracy 0.59, AUC = 0.55; number of tumoral lesions: accuracy 0.71, AUC 0.36; number of affected organs: accuracy 0.47; AUC 0.42; total tumor volume: accuracy 0.59, AUC 0.53; performance status: accuracy 0.41, AUC = 0.47). Radiomics may provide additional baseline prognostic value compared to the variables used in clinical practice.

Background: There are currently few data about the safety and effectiveness of chemotherapy for patients with metastatic non-small-cell lung cancer (NSCLC) who have progressed from prior immunotherapy. Methods: Data from patients with consecutive stage IIIB–IV, ECOG performance status (PS) 0–2, non-small-cell lung cancer (NSCLC) treated with combination or single-agent chemotherapy following progression on an earlier immunotherapy regimen were retrospectively gathered. Recorded were baseline attributes, outcome metrics, and toxicities. The neutrophil/lymphocyte (N/L) ratio’s predictive usefulness was examined through an exploratory analysis. Results: The analysis comprised one hundred subjects. The adeno/squamous carcinoma ratio was 77%/23%, the M/F ratio was 66%/34%, the ECOG PS was 0/1/≥2 47%/51%/2%, and the median PD-L1 expression was 50% (range 0–100). The median age was 67 (range 39–81) years. Prior immunotherapy included a single-agent treatment in 83% of cases, with pembrolizumab use being prevalent, and a median N/L ratio of four prior to chemotherapy. The overall median time-to-progression on previous immunotherapy was 6 months. After immunotherapy, just 33% of subjects underwent chemotherapy. A median of 4 (range 1–16) cycles of chemotherapy were administered; platinum doublets (primarily carboplatin) were delivered in only 31% of cases, vinorelbine accounted for 25%, taxanes for 25%, and gemcitabine for 8%. The median clinical benefit was 55%, while the overall response rate was 21%. The median overall survival was 5 months (range 1–22) and the median time to progression was 4 months (range 1–17). Subgroups with low and high N/L ratios were compared, but there was no discernible difference in survival. Conclusions: After immunotherapy, a small percentage of patients with advanced NSCLC had chemotherapy. Following immunotherapy advancement, chemotherapy demonstrated a moderate level of therapeutic effectiveness; no adverse concerns were noted. The effectiveness of chemotherapy following immunotherapy was not predicted by the baseline N/L ratio.

Background: The treatment of advanced hormone receptor-positive (HR+) breast cancer has seen relevant changes in last years. However, bevacizumab remains an option when combined with paclitaxel, but no certified pharmacogenetic profiles are now usable for the prediction of its response in breast cancer patients. This study aimed to explore the pharmacogenetic interactions among single nucleotide polymorphisms (SNPs) of genes involved in the angiogenic process and their impact on progression-free survival (PFS) and overall survival (OS) in hormone receptor-positive (HR+) metastatic breast cancer subjects administered with bevacizumab plus paclitaxel, or with paclitaxel alone (clinicaltrial.gov identifier NCT01935102). Methods: Germline DNA extracted from blood samples was analyzed using real-time polymerase chain reaction to investigate SNPs. The multifactor dimensionality reduction (MDR) analysis was employed to assess interactions between these genetic variants. A total of 168 eligible patients were analyzed. Among these, 106 patients received both paclitaxel and bevacizumab, while 62 received paclitaxel alone. Results: In the combination therapy group, MDR analysis identified two pharmacogenetic interaction profiles involving specific genotypes of vascular endothelial growth factor-A(VEGF-A) rs833061 and vascular endothelial growth factor receptor-2 (VEGFR-2) rs1870377. Patients with a favorable genetic profile had a median PFS (mPFS) of 22.9 months, compared to 8.7 months in those with an unfavorable profile (p = 0.001). Cox proportional hazards analysis displayed an adjusted hazard ratio of 0.443 (95% CI: 0.284–0.691; p < 0.0001). The median OS (mOS) was 50.2 months for the favorable profile vs. 23.5 months for the unfavorable (p = 0.003), with an adjusted hazard ratio (HR) of 0.404 (95% CI: 0.249–0.657; p < 0.0001). In the 62 subjects administered with just paclitaxel, no significant differences in PFS (p = 0.820) or OS (p = 0.143) were observed between favorable and unfavorable genetic profiles. Conclusions: The MDR analysis of VEGF-A rs833061 and VEGFR-2 rs1870377 genotypes can detect a subgroup of bevacizumab-administered+ metastatic breast cancer patients with improved PFS and OS.

Urothelial carcinoma represents one of the deadliest urological tumors, due to its biological aggressiveness and the ephemeral response to platinum-based chemotherapy of advanced-stage disease. The use of immune checkpoint inhibitors has positively impacted the prognosis of these patients, although only a proportion of them achieve long lasting disease control. As with other solid tumors, in the last decade, there has been a growing interest in the molecular characterization of urothelial carcinoma in order to identify new therapeutic targets and improve survival in these patients. The aim of this narrative review is to summarize the main evidence available in the literature concerning the role of targeted therapies in urothelial carcinoma, especially focusing on related molecular targets, published data on clinical efficacy, and on future perspectives. Specifically, the effort of this review aims to strengthen the clinical impact of well-known molecular patterns and relative target treatments (such as FGFR inhibitors and Nectin-4-directed antibody–drug conjugates) and to examine the role and preliminary data of drugs targeting biomarkers that are not yet commonly used in clinical practice (such as HER2).

Cyclin-Dependent Kinase 4/6 inhibitors (CDK 4/6i) represented a paradigm shift in the treatment of patients with metastatic hormone-receptor-positive (HR+), HER2-negative (HER2-) breast cancer patients. When disease progression occurs and further hormonal manipulations or target therapies fail, chemotherapy remains a therapeutic choice. For these reasons, resources should be invested in redesigning the best treatment strategy with the current chemotherapy drugs available. Nevertheless, the preferred strategy typically remains a planned sequence of single chemotherapeutic agents. This approach endeavors to extend overall survival and maintain quality of life. Within this complex and evolving therapeutic scenario, where the necessity for effective and treatment options is crucial, we explore in the present paper a perspective for a hypothetical new role of bevacizumab combined with paclitaxel for patients with metastatic HR+, HER2- breast cancer patients resistant to hormone therapy. Recent findings from our preliminary published pharmacogenetic studies, could suggest the efficacy of bevacizumab as linked to a well-defined genomic profile of genes implicated in the process of neoangiogenesis (e.g., favorable profile: VEGF-A rs833061/VEGFR-2 rs1870377: CT/AT, CT/AA, TT/AA, TT/TT, CC/TT), concluding the present perspective underlying the fact that bevacizumab combined with paclitaxel will be reconsidered with this new potential use only if well-designed prospective trials confirm what has been observed from our retrospective data.

Background/Objectives: Metronomic chemotherapy offers a well-tolerated option for heavily pretreated metastatic gastrointestinal cancer patients, but reliable prognostic biomarkers for patient selection are lacking. This study aimed to identify exploratory circulating cytokine signatures associated with outcomes in patients treated with metronomic chemotherapy. Methods: We analyzed plasma samples from 34 patients enrolled in the COMET trial (EudraCT 2007-000065-38), a phase II study of metronomic UFT, cyclophosphamide, and celecoxib. An 88-cytokine Luminex^® (Luminex Corporation, Austin, TX, USA) panel was measured at baseline and at four treatment timepoints. Partial least squares discriminant analysis identified candidate biomarkers, followed by systematic combinatorial analysis using Manciu’s method to construct 3-cytokine composite risk scores. Results: Twenty-one patients (61.8%) experienced progressive disease and 13 (38.2%) achieved stable disease. Six biomarkers showed significant discriminative power: IL-16, MCP-4, THBS-2, Eotaxin-1, PDGF-AB/BB, and TRAIL. Three 3-cytokine panels achieved statistically significant risk stratification (all p < 0.05), with hazard ratios for overall survival ranging from 2.59 to 6.24. For the representative IL-16 + MCP-4 + THBS-2 panel, high-risk patients showed a median PFS of 2.0 vs. 4.0 months (HR 3.24, p = 0.0046) and a median OS of 5.8 vs. 11.1 months (HR 4.19, p = 0.0010). Conclusions: This exploratory pharmacodynamic biomarker analysis identifies three 3-cytokine panels associated with prognostic risk stratification in metronomic chemotherapy for metastatic gastrointestinal cancer. As this single-arm trial cannot distinguish prognostic from predictive value, findings are hypothesis-generating. Prospective external validation is required before clinical translation, and exploration in combination with immune checkpoint inhibitors is warranted.