Real world clinical outcomes from targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy for breast cancer: data from a large cohort at a national cancer institute.

Introduction: Randomised evidence supports the use of partial breast irradiation (PBI) with targeted intraoperative radiotherapy (TARGIT-IORT) for early stage breast cancer, but prospective data from real-world adoption of this technique is also important. The aim of this study was to determine if the outcome reported in TARGIT-A trial could be replicated in large cohort of early stage breast cancer treated with TARGIT-IORT.

Methods: This prospective observational study analysed all patients treated with TARGIT-IORT between 2004 and 2021 in a single national cancer institute.

Metronomic Chemotherapy: Anti-Tumor Pathways and Combination with Immune Checkpoint Inhibitors.

Increasing evidence pinpoints metronomic chemotherapy, a frequent and low dose drug administration with no prolonged drug-free intervals, as a potential tool to fight certain types of cancers. The primary identified targets of metronomic chemotherapy were the tumor endothelial cells involved in angiogenesis. After this, metronomic chemotherapy has been shown to efficiently target the heterogeneous population of tumor cells and, more importantly, elicit the innate and adaptive immune system reverting the "cold" to "hot" tumor immunologic phenotype.

LINE-1 hypomethylation is associated with poor outcomes in locoregionally advanced oropharyngeal cancer.

Background And Purpose: Currently, human papillomavirus (HPV) positivity represents a strong prognostic factor for both reduced risk of relapse and improved survival in patients with oropharyngeal squamous cell carcinoma (OPSCC). However, a subset of HPV-positive OPSCC patients still experience poor outcomes. Furthermore, HPV-negative OPSCC patients, who have an even higher risk of relapse, are still lacking suitable prognostic biomarkers for clinical outcome.

Emerging Role of Immunomonitoring to Predict the Clinical Outcome of Patients With Malignant Pleural Mesothelioma Treated With Radical Radiation Therapy.

Purpose: The present study aimed at evaluating the baseline immune profile and the immunomodulating effects of radical hemithoracic radiation therapy (RT) in patients affected by malignant pleural mesothelioma (MPM) to identify potential predictive biomarkers of therapy response, toxicity development, and eligibility for further immunotherapeutic treatments.

Methods And Materials: Blood samples were collected from 55 patients with MPM, enrolled in a phase 3 trial comparing radical hemithoracic RT (interventional arm, n = 28) with local palliative RT (control arm, n = 27). Immunomonitoring was performed before RT, at the end of treatment, and 1 month after therapy, characterizing natural killer cells, B and T lymphocytes, activated CD4 and CD8 T cells, interferon-γ- and tumor necrosis factor-α-producing T helper (Th) 1 cells, regulatory T cells, and Th17 and Th22 lymphocytes, through flow cytometry.

Radiation recall dermatitis induced by COVID-19 vaccination in breast cancer patients treated with postoperative radiation therapy.

Background: and purpose: Radiation recall dermatitis is an adverse event predominantly due to systemic therapy administration after a previous radiation therapy course. Few case reports describe radiation recall dermatitis in breast cancer patients treated with postoperative radiation therapy following COVID-19 vaccination. In this study we investigated the incidence and severity of radiation recall dermatitis after COVID-19 vaccination in irradiated breast cancer patients.

Prognostic Significance of PD-L1 Expression In Patients With Primary Oropharyngeal Squamous Cell Carcinoma: A Meta-Analysis.

Background: At present, the prognostic significance of programmed cell death receptor ligand 1 (PD-L1) expression in oropharyngeal squamous cell carcinoma (OPSCC) patients is still controversial. In this study, we aim to synthesize relevant studies that have assessed the prognostic value of PD-L1 in patients with primary OPSCC treated according to the current standard-of-care.

Methods: A systematic search of Medline/PubMed, Cochrane, Embase, Web of Science, and Scopus was conducted to define the prognostic role of PD-L1 expression in OPSCC.

The Molecular and Microenvironmental Landscape of Glioblastomas: Implications for the Novel Treatment Choices.

Glioblastoma (GBM) is the most frequent and aggressive primary central nervous system tumor. Surgery followed by radiotherapy and chemotherapy with alkylating agents constitutes standard first-line treatment of GBM. Complete resection of the GBM tumors is generally not possible given its high invasive features.

Loss of Spry1 reduces growth of BRAF-mutant cutaneous melanoma and improves response to targeted therapy.

Mitogen-activated protein kinase (MAPK) pathway activation is a central step in BRAF-mutant cutaneous melanoma (CM) pathogenesis. In the last years, Spry1 has been frequently described as an upstream regulator of MAPK signaling pathway. However, its specific role in BRAF-mutant CM is still poorly defined.

New insights into the pharmacological, immunological, and CAR-T-cell approaches in the treatment of hepatocellular carcinoma.

The tyrosine kinase inhibitor (TKI) sorafenib continues to be the anchor drug in the treatment of advanced stage hepatocellular carcinoma (HCC). Other TKIs as well as immune checkpoint inhibitors (ICIs) have also been approved, however the response rates remain poor and heterogeneous among HCC patients, largely due to antitumor drug resistance. Studies aimed at identifying novel biomarkers and developing new strategies to improve the response to current treatment and to overcome drug resistance, are urgently needed.

The Dual Role of the Liver in Nanomedicine as an Actor in the Elimination of Nanostructures or a Therapeutic Target.

The development of nanostructures for therapeutic purpose is rapidly growing, following the results obtained in vivo in animal models and in the clinical trials. Unfortunately, the potential therapeutic efficacy is not completely exploited, yet. This is mainly due to the fast clearance of the nanostructures in the body.

A Pan-Cancer Approach to Predict Responsiveness to Immune Checkpoint Inhibitors by Machine Learning.

Immunotherapy by using immune checkpoint inhibitors (ICI) has dramatically improved the treatment options in various cancers, increasing survival rates for treated patients. Nevertheless, there are heterogeneous response rates to ICI among different cancer types, and even in the context of patients affected by a specific cancer. Thus, it becomes crucial to identify factors that predict the response to immunotherapeutic approaches.

New Insight into Therapies Targeting Angiogenesis in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a malignancy characterized by neoangiogenesis that is determined by an augmented production of proangiogenesis factors by tumor and adjacent cells. This unbalanced angiogenesis process is a key feature of HCC carcinogenesis and progression. Proangiogenic factors also have a relevant role in the generation and maintenance of an immunosuppressive tumor microenvironment.

Novel immunotherapeutic approaches for hepatocellular carcinoma treatment.

The introduction of immune checkpoint inhibitors has been lately proposed for the treatment of hepatocellular carcinoma (HCC) with respect to other cancer types. Several immunotherapeutic approaches are now under evaluation for HCC treatment including: i) antibodies acting as immune checkpoint inhibitors; ii) antibodies targeting specific tumor-associated antigens; iii) chimeric antigen receptor redirected T (CAR-T) cells targeting specific tumor-associated antigens; iv) vaccination strategies with tumor-specific epitopes. Areas covered: The review provides a wide description of the clinical trials investigating the efficacy of the main immunotherapeutic approaches proposed for the treatment of patients affected by HCC.

Low prevalence of HPV-driven head and neck squamous cell carcinoma in North-East Italy.

Objectives: To investigate the frequency of Human papillomavirus (HPV)-driven head and neck squamous cell carcinoma (HNSCC) among patients living in North-East Italy, by assessing HPV-DNA positivity in all tumors and additional markers whenever possible.

Material And Methods: HPV types, viral load, viral RNA, HPV16/18 E6 protein and p16 and pRb expression were determined in primary tumor tissues from 247 HNSCC patients. Tumor-specific HPV seropositivity was analyzed in 102 patients.

Multicenter research into the quality of life of patients with advanced oropharyngeal carcinoma with long-term survival associated with human papilloma virus.

The treatment of advanced-stage oropharyngeal squamous cell carcinoma may utilize various modes, including combining surgery with chemoradiotherapy (CTRT), or primary CTRT followed by rescue surgery. In previous literature it has been revealed how patients treated with combined modes report a low quality of life (QoL) and severe consequences following surgery, radiotherapy and chemotherapy, in the short and in the long-term. The decrease in the QoL of patients treated with high-intensity multi-modal strategies highlights the necessity of modifying treatments, particularly for young HPV-positive patients, where an increased survival rate has already been reported.

Human papillomavirus as prognostic marker with rising prevalence in neck squamous cell carcinoma of unknown primary: A retrospective multicentre study.

Patients with neck squamous cell carcinomas of unknown primary tumour (NSCCUP) present with lymph node metastasis without evidence for a primary tumour. Most patients undergo an aggressive multimodal treatment, which induces severe, potentially unnecessary toxicity. Primary tumours of NSCCUP can be hidden in the oropharynx.

Sensitivity and specificity of antibodies against HPV16 E6 and other early proteins for the detection of HPV16-driven oropharyngeal squamous cell carcinoma.

To determine the sensitivity and specificity of HPV16 serology as diagnostic marker for HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), 214 HNSCC patients from Germany and Italy with fresh-frozen tumor tissues and sera collected before treatment were included in this study. Hundred and twenty cancer cases were from the oropharynx and 94 were from head and neck cancer regions outside the oropharynx (45 oral cavity, 12 hypopharynx and 35 larynx). Serum antibodies to early (E1, E2, E6 and E7) and late (L1) HPV16 proteins were analyzed by multiplex serology and were compared to tumor HPV RNA status as the gold standard.

Telomeres and telomerase in head and neck squamous cell carcinoma: from pathogenesis to clinical implications.

Strongly associated with tobacco use, heavy alcohol consumption, and with high-risk human papillomavirus (HPV) infection, head and neck squamous cell carcinoma (HNSCC) is a frequently lethal, heterogeneous disease whose pathogenesis is a multistep and multifactorial process involving genetic and epigenetic events. The majority of HNSCC patients present with locoregional advanced stage disease and are treated with combined modality strategies that can markedly impair quality of life and elicit unpredictable results. A large fraction of those who undergo locoregional treatment and achieve a complete response later develop locoregional recurrences or second field tumors.

Gene promoter methylation signature predicts survival of head and neck squamous cell carcinoma patients.

Infection with high-risk types of human papilloma virus (HPV) is currently the best-established prognostic marker for head and neck squamous cell carcinoma (HNSCC), one of the most common and lethal human malignancies worldwide. Clinical trials have been launched to address the concept of treatment de-escalation for HPV-positive HNSCC with the final aim to reduce treatment related toxicity and debilitating long-term impacts on the quality of life. However, HPV-related tumors are mainly restricted to oropharyngeal SCC (OPSCC) and there is an urgent need to establish reliable biomarkers for all patients at high risk for treatment failure.

Long-Term Clinical Outcome after Treatment for High-Grade Cervical Lesions: A Retrospective Monoinstitutional Cohort Study.

Background: The aim of this retrospective observational study of women treated for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was to assess the long-term risk of residual/recurrent high-grade CIN.

Materials And Methods: We evaluated 760 women treated by loop electrosurgical excision procedure (684) or conization (76) between 2000 and 2009, and followed up to June 30, 2014 (median follow-up 6.7 years, range 4-14).

Telomere shortening in mucosa surrounding the tumor: biosensor of field cancerization and prognostic marker of mucosal failure in head and neck squamous cell carcinoma.

Objectives: The aim of the present study was to investigate the pattern of telomere length and telomerase expression in cancer tissues and the surrounding mucosa (SM), as markers of field cancerization and clinical outcome in patients successfully treated for with head and neck squamous cell carcinoma (HNSCC).

Materials And Methods: This investigation was a prospective cohort study. Telomere length and levels of telomerase reverse transcriptase (TERT) transcripts were quantified by real-time PCR in cancer tissues and SM from 139 and 90 patients with HNSCC, respectively.

Age and geographic variability of human papillomavirus high-risk genotype distribution in a large unvaccinated population and of vaccination impact on HPV prevalence.

Background: The prevalence of infections with human papillomavirus (HPV) specific genotypes differs by age and areas. Knowledge of these differences will help predicting how prophylactic HPV vaccination and screening program could best be integrated.

Objectives: To investigate variations in the HPV distribution between areas and ages in Italy and the impact of vaccination on HPV prevalence.

Evidence of the causal role of human papillomavirus type 58 in an oropharyngeal carcinoma.

Persistent human papillomavirus infection (HPV) is recognized as an important etiologic factor for a subset of head and neck squamous cell carcinomas (SCC), especially those arising from the oropharynx. Whereas HPV16 accounts for the majority of HPV DNA-positive oropharyngeal SCC, infections with other mucosal high-risk HPV types are quite rare and biological data demonstrating their causal involvement are insufficient. Here we present the first case of an oropharyngeal SCC driven by HPV type 58.

Oral human papillomavirus and human herpesvirus-8 infections among human immunodeficiency virus type 1-infected men and women in Italy.

Background: Oral human papillomavirus (HPV) and human herpesvirus-8 (HHV8) infections are sexually transmitted and respectively associated with the development of oropharyngeal carcinoma and Kaposi sarcoma. The aim of the study was to evaluate HPV prevalence and its possible correlation with HHV8 oral shedding, in relation to sex, human immunodeficiency virus (HIV) behavioral risk factor, and immune function.

Methods: The study population comprised 100 HIV-infected individuals divided into 3 groups: (1) 38 men who have sex with men (MSM), (2) 24 heterosexual men, and (3) 38 women.