With an estimated incidence of 2%-4% per year, the development of a second primary malignancy (SPM) in patients with head and neck tumors (HNTs) is not a rare event. The present study aimed to (i) assess the frequency of SPMs in patients with HNTs treated in a university hospital over a five-year period and (ii) provide a demographic characterization of these patients. Retrospective single-centre study of patients with more than one primary tumor (including at least one HNT) diagnosed between January 1, 2015, and December 31, 2019. Data were retrieved from patients’ clinical records and anonymized for analysis purposes. A total of 53 out of 824 (6.43%) patients with multiple primary malignancies were identified, 18 of which synchronous and 35 metachronous. The median follow-up was 25 months. Thirteen patients were diagnosed with more than one HNT. Forty patients were diagnosed with at least one HNT and one non-HNT. The most frequently diagnosed non-HNT SPMs were lung cancer (n=17) and esophageal cancer (n=8). The five-year survival rate was 53% for patients with multiple HNSCCs and 47% for patients with at least one non-HNT (log-rank p=0.729). The median overall survival was 14 months for synchronous and 58 months for metachronous SPMs (log-rank p=0.002). Findings from this study highlight the importance of long-term follow-up of HNT patients for early detection of SPMs, increasing the chance of providing treatment with curative intent and improving patient outcomes and survival.

Oral squamous cell carcinoma is the most common malignant epithelial neoplasm affecting the oral cavity. While surgical resection is the cornerstone of a multimodal curative approach, some tumors are deemed recurrent or metastatic (R/M) and often not suitable for curative surgery. This mainly occurs due to the extent of lesions or when surgery is expected to result in poor functional outcomes. Amongst the main non-surgical therapeutic options for oral squamous cell carcinoma are radiotherapy, chemotherapy, molecular targeted agents, and immunotherapy. Depending on the disease setting, these therapeutic approaches can be used isolated or in combination, with distinct efficacy and side effects. All these factors must be considered for treatment decisions within a multidisciplinary approach. The present article reviews the evidence regarding the treatment of patients with R/M oral squamous cell carcinoma. The main goal is to provide an overview of available treatment options and address future therapeutic perspectives.

Breast sarcomas (BSs), phyllodes tumors (PTs), and desmoid tumors (DTs) are rare entities that arise from connective tissue. BSs can be classified as either primary or secondary, whether they develop de novo or after radiation exposure or lymphedema. PIK3CA seems to play an important common role in different BS. Malignant PTs show similar behavior to BSs, while DTs are locally aggressive but rarely metastasize. BSs usually present as unilateral, painless, rapidly growing masses with rare nodal involvement. The diagnosis should be based on magnetic resonance imaging and a core needle biopsy. Staging should comprise a chest computed tomography (CT) scan (except for benign PT and DT), while abdominal and pelvic CT scans and bone scans should be added in certain subtypes. The mainstay of treatment for localized BS is surgery, with margin goals that vary according to subtype. Radiotherapy and chemotherapy can be used as neoadjuvant or adjuvant approaches, but their use in these settings is not standard. Advanced BS should be treated with systemic therapy, consistent with recommendations for advanced soft tissue sarcomas of other topographies. Given the rarity and heterogeneity of these entities, multidisciplinary and multi-institutional collaboration and treatment at reference centers are critical.

Precision oncology is the ultimate goal of cancer treatment, i.e., to treat cancer and only cancer, leaving all the remaining cells and tissues as intact as possible. Classical chemotherapy and radiotherapy, however, are still effective in many patients with cancer by effectively inducing apoptosis of cancer cells. Cancer cells might resist apoptosis via the anti-apoptotic effects of the inhibitor of apoptosis proteins. Recently, the inhibitors of those proteins have been developed with the goal of enhancing the cytotoxic effects of chemotherapy and radiotherapy, and one of them, xevinapant, has already demonstrated effectiveness in a phase II clinical trial. This class of drugs represents an example of synergism between classical cytotoxic chemo- and radiotherapy and new targeted therapy.

Considerable advances in cancer therapies in recent decades have reshaped the prognosis of cancer patients. There are now estimated to be over 20 million cancer survivors in the USA and Europe, numbers unimaginable a few years ago. However, this increase in survival, along with the aging of the patient population, has been accompanied by a rise in adverse cardiovascular effects, particularly when there is a previous history of heart disease. The incidence of cardiotoxicity continues to grow, which can compromise the effectiveness of cancer therapy. Cardiotoxicity associated with conventional therapies, especially anthracyclines and radiation, is well known, and usually leads to left ventricular dysfunction. However, heart failure represents only a fraction of the cardiotoxicity associated with newer therapies, which have diverse cardiovascular effects. There are few guidelines for early detection, prevention and treatment of cardiotoxicity of cancer treatments, and no well-established tools for screening these patients. Echocardiography is the method of choice for assessment of patients before, during and after cancer treatment. It therefore makes sense to adopt a multidisciplinary approach to these patients, involving cardiologists, oncologists and radiotherapists, collaborating in the development of new training modules, and performing clinical and translational research in a cardio-oncology program. Cardio-oncology is a new frontier in medicine and has emerged as a new medical subspecialty that concentrates knowledge, understanding, training and treatment of cardiovascular comorbidities, risks and complications in patients with cancer in a comprehensive approach to the patient rather than to the disease.

The combination of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) with endocrine therapy (ET) is the standard-of-care for estrogen receptor (ER)-positive, HER2-negative (ER+/HER2− advanced/metastatic breast cancer (mBC). However, the impact of CDK4/6i on circulating immune cells and circulating tumor cells (CTCs) in patients receiving CDK4/6i and ET (CDK4/6i+ET) remains poorly understood. This was a prospective cohort study including 44 patients with ER+/HER2− mBC treated with CDK4/6i+ET in either first or second line. Peripheral blood samples were collected before (baseline) and 3 months (t2) after therapy. Immune cell’s subsets were quantified by flow cytometry, and microfluidic-captured CTCs were counted and classified according to the expression of cytokeratin and/or vimentin. Patients were categorized according to response as responders (progression-free survival [PFS] ≥ 6.0 months; 79.1%) and non-responders (PFS < 6.0 months; 20.9%). CDK4/6i+ET resulted in significant changes in the hematological parameters, including decreased hemoglobin levels and increased mean corpuscular volume, as well as reductions in neutrophil, eosinophil, and basophil counts. Specific immune cell subsets, such as early-stage myeloid-derived suppressor cells, central memory CD4+ T cells, and Vδ2+ T cells expressing NKG2D, decreased 3 months after CDK4/6i+ET. Additionally, correlations between the presence of CTCs and immune cell populations were observed, highlighting the interplay between immune dysfunction and tumor dissemination. This study provides insights into the immunomodulatory effects of CDK4/6i+ET, underscoring the importance of considering immune dynamics in the management of ER+/HER2− mBC.