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Background: Distant metastasis (DM) development in Oropharyngeal Squamous Cell Carcinoma (OPSCC) represents an important prognostic factor. The identification of a phenotype of metastatic patients may better define therapeutic and follow‐up programs. Methods: We included 408 patients with OPSCC, non‐metastatic at the time of diagnosis, and treated with curative intent. The Overall Survival (OS) analyses were performed and the impact of developing DM on survival was analyzed through Cox proportional‐hazard regression model. Results: 57 (14%) patients develop DM. 302 (74%) were p16+ OPSCC and 35 of them experienced DM. Advanced clinical stage, smoking, p16‐status, response to primary treatment, and loco‐regional relapse influence the DM rate. Only in the p16+ group, DM onset results in a greater impact on OS (p < 0.0001). Lung metastases have a better OS compared to non‐pulmonary ones (p = 0.049). Conclusion: This retrospective study shows a possible stratification of OPSCC patients based on the risk of the development of DMs. [ABSTRACT FROM AUTHOR]

Simple Summary: Around 2–4% of lung adenocarcinoma harbors BRAF mutations. Dabrafenib and Trametinib represent the first treatment-choice for BRAF V600Emut NSCLC, regardless of the line of therapy, while non-V600Emut receive standard immunotherapy or chemo-immunotherapy. Our real-life multicenter study on 44 BRAF mutant NSCLC responds to the urgent need to characterize this subset of patients in-depth, potentially offering new valuable biological and clinical insights. We specifically focused on similarities/discrepancies between V600E and non-V600E populations, providing consistent data about clinicopathologic characteristics, treatment response, and survival outcome. Introduction: BRAF mutation involved 2–4% of lung adenocarcinoma. Differences in clinicopathologic features and patient outcome exist between V600E and non-V600E BRAF mutated NSCLC. Thus, we sought to assess the frequency and clinical relevance of BRAF mutations in a real-life population of advanced-NSCLC, investigating the potential prognostic significance of distinct genetic alterations. Materials and Methods: The present multicenter Italian retrospective study involved advanced BRAF mutant NSCLC. Complete clinicopathologic data were evaluated for BRAF V600E and non-V600E patients. Results: A total of 44 BRAFmut NSCLC patients were included (V600E, n = 23; non-V600E, n = 21). No significant differences in survival outcome and treatment response were documented, according to V600E vs. non-V600E mutations, although a trend towards prolonged PFS was observed in the V600E subgroup (median PFS = 11.3 vs. 6.0 months in non-V600E). In the overall population, ECOG PS and age significantly impacted on OS, while bone lesions were associated with shorter PFS. Compared to immunotherapy, first-line chemotherapy was associated with longer OS in the overall population, and especially in the BRAF V600E subtype. Conclusions: Here, we report on real-life data from a retrospective cohort of advanced-NSCLC harboring BRAF alterations. Our study offers relevant clues on survival outcome, therapeutic response, and clinicopathologic correlations of BRAF-mutant NSCLC. [ABSTRACT FROM AUTHOR]

Immunotherapy, and in particular immune-checkpoints blockade therapy (ICB), represents a new pillar in cancer therapy. Antibodies targeting Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) and Programmed Death 1 (PD-1)/Programmed Death Ligand-1 (PD-L1) demonstrated a relevant clinical value in a large number of solid tumors, leading to an improvement of progression free survival and overall survival in comparison to standard chemotherapy. However, across different solid malignancies, the immune-checkpoints inhibitors efficacy is limited to a relative small number of patients and, for this reason, the identification of positive or negative predictive biomarkers represents an urgent need. Despite the expression of PD-L1 was largely investigated in various malignancies, (i.e., melanoma, head and neck malignancies, urothelial and renal carcinoma, metastatic colorectal cancer, and pancreatic cancer) as a biomarker for ICB treatment-patients selection, it showed an important, but still imperfect, role as positive predictor of response only in nonsmall cell lung cancer (NSCLC). Importantly, other tumor and/or microenvironments related characteristics are currently under clinical evaluation, in combination or in substitution of PD–L1 expression. In particular, tumor-infiltrating immune cells, gene expression analysis, mismatch- repair deficiency, and tumor mutational landscape may play a central role in predicting clinical benefits of CTLA-4 and/or PD-1/PD-L1 checkpoint inhibitors. In this review, we will focus on the clinical evaluation of emerging biomarkers and how these may improve the naïve vision of a single- feature patients-based selection. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer is one of the most debated problems all over the world. Cancer stem cells are considered responsible of tumor initiation, metastasis, drug resistance, and recurrence. This subpopulation of cells has been found into the tumor bulk and showed the capacity to self-renew, differentiate, up to generate a new tumor. In the last decades, several studies have been set on the molecular mechanisms behind their specific characteristics as the Wnt/β-catenin signaling, Notch signaling, Hedgehog signaling, transcription factors, etc. The most powerful part of CSCs is represented by the niches as "promoter" of their self-renewal and "protector" from the common oncological treatment as chemotherapy and radiotherapy. In our review article we highlighted the primary mechanisms involved in CSC tumorigenesis for the setting of further targets to control the metastatic process. Emerging evidence suggests that a small subpopulation of cancer stem cells (CSCs) is responsible for initiation, progression, and metastasis cascade in tumors. CSCs share characteristics with normal stem cells, i.e., self-renewal and differentiation potential, suggesting that they can drive cancer progression. Consequently, targeting CSCs to prevent tumor growth or regrowth might offer a chance to lead the fight against cancer. CSCs create their niche, a specific area within tissue with a unique microenvironment that sustains their vital functions. Interactions between CSCs and their niches play a critical role in regulating CSCs' self-renewal and tumorigenesis. Differences observed in the frequency of CSCs, due to the phenotypic plasticity of many cancer cells, remain a challenge in cancer therapeutics, since CSCs can modulate their transcriptional activities into a more stem-like state to protect themselves from destruction. This plasticity represents an essential step for future therapeutic approaches. Regarding self-renewal, CSCs are modulated by the same molecular pathways found in normal stem cells, such as Wnt/β-catenin signaling, Notch signaling, and Hedgehog signaling. Another key characteristic of CSCs is their resistance to standard chemotherapy and radiotherapy treatments, due to their capacity to rest in a quiescent state. This review will analyze the primary mechanisms involved in CSC tumorigenesis, with particular attention to the roles of CSCs in tumor progression in benign and malignant diseases; and will examine future perspectives on the identification of new markers to better control tumorigenesis, as well as dissecting the metastasis process. [ABSTRACT FROM AUTHOR]

The complete pathological response after primary chemotherapy could represent an important prognostic factor in patients affected by colorectal liver metastases. In recent studies, increasing complete pathological response seems to be correlated with longer overall survival periods and it is recognized as an important prognostic factor in patients treated with pre-operative chemotherapy. The correlation of radiological information on residual neoplastic disease after neoadjuvant treatment, obtained with CT and PET, has to be evaluated; in fact the complete disappearance of liver metastasis on radiological imaging does not always mean a complete disappearance of tumor tissue on histological examination; when it is documented with surgical procedures and confirmed by pathologist's examination, we can consider the complete pathological response. In recent years the addition of monoclonal antibodies to conventional chemotherapy may further increase the proportion of patients referred for surgery; bevacizumab before surgery has been shown to be feasible and safe, although concerns still exist regarding possible post-surgical and wound healing complications or bleeding. The limitation of the radiologic assessment of response as a surrogate for pathological response is even more relevant when antiangiogenic treatments are used. Excellent responses to bevacizumab-containing regimens do occur and referral to surgical oncology is a crucial step for documentation of complete pathological response. [ABSTRACT FROM AUTHOR]

PURPOSE: In advanced rectal cancer, chemoradiation can induce downstaging until complete disappearance of the tumor or its persistence in minimal form. The complete sterilized and the minimal residual disease often are considered similar. We evaluated the specific incidence of these two conditions and analyzed their impact in terms of local recurrence, distant metastasis, and survival. METHODS: We studied 139 uT3/T4 N0/N+ rectal cancers, treated with preoperative chemoradiation and curative surgery after six to eight weeks. We evaluated ypTNM stage and tumoral regression, according to the five degrees proposed by Dworak, with special attention to 4 and 3 (sterilized and minimal residual disease). RESULTS: Tumor downstaging occurred in 65 patients (46.7 percent), including 25 sterilized lesions (17.9 percent) and 24 minimal residual disease (17.2 percent). In median follow-up of 30 months, none of the patients with sterilized disease developed local or distant recurrence. Among patients with minimal residual disease, none developed local recurrence, whereas two (8.3 percent) developed distant metastasis, and one died from disease. In patients with gross residual disease (Grade 2, 1, 0) the percentage of local recurrence was 8.8 percent, distant recurrence 26.6 percent, and 13.3 percent died from disease. The difference between three groups is statistically significant as regards local and distant recurrence. CONCLUSIONS: After preoperative therapy, the sterilized disease shows an excellent prognosis. The minimal residual disease has an important numeric incidence. Its outcome is different, with a not-negligible risk of distant recurrence. The minimal residual disease has a much better prognosis in comparison with the gross residual disease. [ABSTRACT FROM AUTHOR]

The aim of this multi-center, retrospective/prospective cohort observational study was to evaluate outcomes in routine clinical practice of first-line chemo-immunotherapy with cis/carboplatin, pemetrexed and pembrolizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC) in 33 Italian centers. The outcome measure was to evaluate overall survival (OS) in a real-world patient population. Secondary endpoints were: progression-free survival (PFS), objective response rate (ORR), duration of response (DoR) and incidence of treatment-related adverse events (AEs). 1068 patients were enrolled at the time of data cut-off (January 31st, 2023), and 812 (76.0%) belonged to the retrospective cohort. Median age was 66 years (27−85), ECOG PS was ≥ 2 in 91 (8.6%) patients; 254 (23.8%) patients had brain metastases at baseline; 38 (3.6%) patients had tumor with PD-L1 expression ≥ 50%. After a median follow-up of 17.0 months (95% CI, 16.1–17.9), median OS was 16.1 months (95% CI, 14.4–18.8) and PFS was 9.9 months (95% CI, 8.8–11.2). Median DoR (n = 493) was 14.7 months (95% CI, 13.6–17.1). ORR was 43.4% (95% CI, 40.4–46.4). Any-grade AEs occurred in 636 (59.6%) patients and grade ≥ 3 in 253 (23.7%) patients. Most common grade ≥ 3 AEs were neutropenia (6.3%) and anemia (6.3%). First-line chemo-immunotherapy was effective and tolerable in this large, real-world Italian study of patients with advanced non-squamous NSCLC. Our results were in line with the KEYNOTE-189 registration study, also considering the low number of PD-L1 ≥ 50% patients included in our study. [Display omitted] • Chemo-immunotherapy is the standard front-line treatment for advanced non-squamous NSCLC. • Real-world data about platinum, pemetrexed and pembrolizumab regimen are needed. • We conducted a retrospective-prospective real-world study in 33 Italian Centers. • KEYNOTE-189 regimen was effective and safe in daily clinical practice. [ABSTRACT FROM AUTHOR]

Objectives: Given a lack of universally-accepted standard-of-care treatment for patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), study objectives were to assess treatment utilization and survival outcomes for R/M HNSCC in the real-world setting.Materials and Methods: A multi-site retrospective chart review was conducted in Europe (Germany, United Kingdom, Italy, Spain), Asia Pacific (Australia, South Korea, Taiwan), and Latin/North America (Brazil and Canada) to identify patients who initiated first-line systemic therapy for R/M HNSCC between January 2011 and December 2013. Patients were followed through December 2015 to collect clinical characteristics, treatment and survival data.Results: Among 733 R/M HNSCC patients across 71 sites, median age was 60 years (inter-quartile range 54-67), 84% male, and 70% Eastern Cooperative Oncology Group performance status 0-1; 32% had oral cavity and 30% oropharyngeal cancers. The most common first-line regimen across all countries consisted of platinum-based combinations (73%), including platinum + 5-fluorouracil (5-FU) (26%), cetuximab + platinum ± 5-FU (22%), or taxane + platinum ± 5-FU (16%). However, use of different platinum-based combinations varied substantially; administration of cetuximab + platinum ± 5-FU was frequent in Italy (81%), Germany (46%) and Spain (38%), whereas use in other countries was limited. Median follow-up was 22.6 months (95% confidence interval [CI]: 21.5-24.6 months). Median real-world overall survival was only 8.0 months (95% CI: 7.0-8.0), with one-year survival reaching only 30.9% (95% CI: 27.5-34.3).Conclusion: Systemic therapies used in clinical practice for patients with R/M HNSCC vary substantially across countries. Prognosis remains poor in this patient population, highlighting the need for newer, more efficacious treatments. [ABSTRACT FROM AUTHOR]