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Several studies have examined the use of positron emission tomography (PET) using [68Ga]Ga-radiolabeled fibroblast-activation protein inhibitors (FAPi) across multiple subtypes of head and neck cancer (HNC). The purpose of the present study was to evaluate the diagnostic accuracy of a newly developed molecular imaging approach in the context of HNC through a comprehensive review and meta-analysis. A thorough literature review was conducted to identify scholarly articles about the diagnostic effectiveness of FAP-targeted PET imaging. The present study incorporates original publications assessing the efficacy of this innovative molecular imaging test in both newly diagnosed and previously treated HNC patients. This systematic review examined eleven investigations, of which nine were deemed suitable for inclusion in the subsequent meta-analysis. The quantitative synthesis yielded a pooled detection rate of 99% for primary HNC lesions. Additionally, on a per patient-based analysis, the pooled sensitivity and specificity for regional lymph node metastases were found to be 90% and 84%, respectively. The analysis revealed a statistical heterogeneity among the studies for the detection rate of primary HNC lesions. The quantitative findings presented in this study indicate a favorable diagnostic performance of FAP-targeted PET imaging in detecting primary HNC tumors. In contrast, discordant results concerning the diagnostic accuracy of lymph node metastases were found. However, further multicentric trials are required to validate the efficacy of FAP-targeted PET in this specific group of patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunotherapy has positively modified the natural history of head and neck cancer (HNC), however, adequate biomarkers to identify resistant patients have not yet been identified. We analyzed 18 circulating Th1, antitumor, and Th2, protumor, cytokines in patients with relapsed/metastatic HNC treated with the immune checkpoint inhibitor nivolumab. Blood samples were collected at baseline (T0) and after 3 cycles of nivolumab (T1). Data extracted at T0 have been related to survival; the comparison between T0 and T1 explored the effect of immunotherapy. Elevated IL-6 and TGF-β values at T0 identified patients with poor survival. Increases of CCL-4, IL-15, IL-2 and CXCL-10, all Th1 cytokines, occurred between T0 and T1 but did not correlate with survival. We suggest that circulating cytokines may represent a tool to identify patients resistant to immunotherapy. The increase of circulating Th1 cytokines during treatment with nivolumab suggests that the drug modulates the tumor microenvironment. However, the lack of correlation between these changes and survival highlights that immunosuppressive mechanisms can prevail. This finding supports the combination of immune checkpoint inhibitors with agents that inhibit other immunosuppressive pathways. Background: The immunotherapy of head and neck cancer induces a limited rate of long-term survivors at the cost of treating many patients exposed to toxicity without benefit, regardless of PD-L1 expression. The identification of better biomarkers is warranted. We analyzed a panel of cytokines, chemokines and growth factors, hereinafter all referred to as 'cytokines', as potential biomarkers in patients with head and neck cancer treated with nivolumab. Materials and methods: A total of 18 circulating cytokines were analyzed. Samples were gathered at baseline (T0) and after 3 courses of nivolumab (T1) in patients with relapsed/metastatic disease. The data extracted at T0 were linked to survival; the comparison of T0–T1 explored the effect of immunotherapy. Results: A total of 22 patients were accrued: 64% current heavy smokers, 36% female and 14% had PS = 2. At T0, ROC analysis showed that IL-6, IL-8, IL-10 and TGF-β were higher in patients with poor survival. Cox analysis demonstrated that only patients with the IL-6 and TGF-β discriminate had good or poor survival, respectively. Longitudinal increments of CCL-4, IL-15, IL-2 and CXCL-10 were observed in all patients during nivolumab treatment. Conclusion: In this small population with poor clinical characteristics, this study highlights the prognostic role of IL-6 and TGF-β. Nivolumab treatment is associated with a positive modulation of some Th1 cytokines, but it does not correlate with the outcome. [ABSTRACT FROM AUTHOR]

Metastatic colorectal cancer is frequently associated with poor clinical conditions that may limit therapeutic options. Regorafenib is a small molecule approved for the treatment of metastatic colorectal cancer, but it is hampered by significative toxicities. Moreover, only a relatively limited number of patients benefit from the treatment. Therefore, the identification of reliable markers for response is an unmet need. Eighteen cytokines, selected based on their prevalent Th1 or Th2 effects, were collected. Peripheral blood samples were gathered at baseline in 25 metastatic colorectal cancer patients treated with regorafenib. Data extracted have been linked to progression-free survival. ROC identified the best cytokines associated with outcome. The relative value of the selected cytokines was determined by PCA. Data analysis identified 8 cytokines (TGF-β, TNF-α, CCL-2, IL-6, IL-8, IL-10, IL-13 and IL-21), used to create a signature (TGF-β, TNF-α high; CCL-2, IL-6, IL-8, IL-10, IL-13 and IL-21 low) corresponding to patients with a significantly longer progression-free survival. This report suggests that the analysis of multiple cytokines might identify a cytokine signature related to a patient's outcome that is able to recognize patients who will benefit from treatment. If confirmed, future studies, also based on different drugs, using this approach and including larger patient populations, might identify a signature allowing the a priori identification of patients to be treated. [ABSTRACT FROM AUTHOR]

Most head and neck squamous cell carcinomas (HNSCCs) are caused by lifestyle, such as cigarette smoking, or by viruses, such as human papillomavirus (HPV) and Epstein–Barr virus (EBV). HNSCC remains a clinical challenge, notwithstanding the improvements observed in the past years, involving surgery, radiotherapy, and chemotherapy. Recurrent/metastatic (R/M) disease represents an unmet clinical need. Immunotherapy has improved the prognosis of a small proportion of these patients, but most still do not benefit. In the last decade, several preclinical and clinical studies have explored the HNSCC tumor immune microenvironment (TIME), identifying important differences between smoking-associated and virus-associated HNSCCs. This review aims to present how different etiologies affect the HNSCC TIME, affecting immune escape mechanisms and sensitivity to immunotherapy. [ABSTRACT FROM AUTHOR]

Chemotherapy is much more effective in immunocompetent mice than in immunodeficient ones, and it is now acknowledged that an efficient immune system is necessary to optimize chemotherapy activity and efficacy. Furthermore, chemotherapy itself may reinvigorate immune response in different ways: by targeting cancer cells through the induction of cell stress, the release of damage signals and the induction of immunogenic cell death, by targeting immune cells, inhibiting immune suppressive cells and/or activating immune effector cells; and by targeting the host physiology through changes in the balance of gut microbiome. All these effects acting on immune and non-immune components interfere with the tumor microenvironment, leading to the different activity and efficacy of treatments. This article describes the correlation between chemotherapy and the immune changes induced in the tumor microenvironment. Our ultimate aim is to pave the way for the identification of the best drugs or combinations, the doses, the schedules and the right sequences to use when chemotherapy is combined with immunotherapy. [ABSTRACT FROM AUTHOR]

Cancer induces immune suppression to overcome its recognition and eradication by the immune system. Cytokines are messengers able to modulate immune response or suppression. There is great interest in the evaluation of their changes during treatment in order to identify their relationship with clinical outcome. We evaluated 18 cytokines in breast cancer patients treated with eribulin before starting treatment (T0) and after four courses of therapy (T1). Longitudinal modifications were considered and cytokine clusters through PCA and HCPC correlated to patients' outcomes were identified. Forty-one metastatic breast cancer patients and fifteen healthy volunteers were included. After clustering, we identified at T0 six patient clusters with different risk of relapse and death. At T1, only four clusters were identified, and three of them accounted for thirty-eight of forty-one patients, suggesting a possible role of treatment in reducing heterogeneity. The cluster with the best survival at T1 was characterized by low levels of IL-4, IL-6, IL-8, IL-10, CCL-2, CCL-4, and TGF-β. The cluster showing the worst survival encompassed high levels of IL-4, IL-6, IL-8, IL-10, CCL-2, and IFN-γ. A subgroup of patients with short progression-free survival (PFS) and long overall survival (OS) was comprised in the cluster characterized by low levels of CCL-2, IL-6, IL-8, IL-10, and IL-12 at T0. Our data support the prognostic significance of longitudinal serum cytokine analysis. This approach may help identify patients for whom early treatment stop avoids needless toxicity or might justify treatment beyond early progression. Further investigations are required to validate this hypothesis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Published data suggest that immunotherapy plays a role even in patients with very advanced tumours. We investigated the immune profile of end-stage cancer patients treated with immunotherapy to identify changes induced by treatment. Breast, colon, renal and prostate cancer patients were eligible. Treatment consisted of metronomic cyclophosphamide, low-dose interleukin-2 (IL-2) and a single radiation shot. A panel of 16 cytokines was assessed using automated ELISA before treatment (T0), after radiation (RT; T1), at cycle 2 (T2) and at disease progression (TPD). Receiving operating characteristic (ROC) analysis was used to identify cytokine cut-off related to overall survival (OS). Principal component analysis (PCA) was used to identify the immune profile correlating better with OS and progression-free survival. Twenty-three patients were enrolled. High IL-2, low IL-8 and CCL-2 correlated with OS. The PCA identified a cluster of patients, with high IL-2, IL-12 and IFN-γ levels at T0 having longer PFS and OS. In all cohorts, IL-2 and IL-5 increased from T0 to T2; a higher CCL-4 level compared to T2 and a higher IL-8 level compared to T0 were found at TPD. The progressive increase of the IL-10 level during treatment negatively correlated with OS. Our data suggested that baseline cytokine levels may predict patients' outcome and that the treatment may affect their kinetic even in end-stage patients. Cytokine profiling of end-stage patients might offer a tool for medical decisions (EUDRACT: 2016-000578-39). [ABSTRACT FROM AUTHOR]

Background: Angiotensin Converting Enzyme inhibitors (ACEis) and beta-blockers (BB) are suggested to prevent and treat trastuzumab-related cardiac toxicity. We performed a prospective clinical trial in women experiencing mild cardiac toxicity (MCT) while on adjuvant treatment with trastuzumab. Methods: MCT was defined as an asymptomatic absolute decrease in LVEF of ≥ 10 percentage units to >50%. Treatment consisted of enalapril 2.5 mg bid and carvedilol 3.75 mg bid, which were up-titrated to 10 mg bid for the enalapril and 6.25 mg bid of carvedilol. In patients receiving study drug, the primary study end-point was LVEF recovery, which was defined as a post-trastuzumab LVEF returning to no less than −5 percentage points of the baseline value. Results: 103 patients were enrolled, 100 started trastuzumab, and 98 completed the planned treatment. Sixteen patients (16%) had MCT and received study drugs until trastuzumab completion. None of these patients achieved a post-trastuzumab LVEF recovery. Nevertheless, treated patients had significantly higher median LVEF recovery from nadir to post-trastuzumab LVEF in (8% points vs. 4% points, respectively, p = 0.004), resulting in no difference in post-treatment LVEF values compared to patients without MCT. Conclusion: Treatment of MCT with ACEis and BB allows faster LVEF recovery from nadir values and should be further studied in this setting. [ABSTRACT FROM AUTHOR]