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Introduction: Although hereditary male neoplasms are quite rare, individuals harbouring germline BRCA1/2 pathogenic variants (PVs) may have a risk of developing tumours associated with Hereditary Breast and Ovarian Cancer (HBOC) syndrome, including male breast (MBC), prostate (PCa) and pancreatic (PC) cancers, and melanoma. Women and men showed a comparable genetic architecture of cancer susceptibility, but there are some gender-specific features. Since little is known about cancer genetic susceptibility in male population, our study was aimed at investigating the frequency of BRCA1/2 PVs in men with HBOC syndrome-associated tumors, in order to understand whether differences in gender may reflect in the prevalence and spectrum of germline alterations. Patients and methods: We retrospectively collected and analysed clinical information of 352 HBOC-associated male cancer patients genetically tested for germline BRCA1/2 PVs by Next-Generation Sequencing analysis, enrolled, from February 2018 to January 2024, at the "Regional Center for the prevention, diagnosis and treatment of rare and heredo-familial tumors of adults" of the University-Hospital Policlinico "P. Giaccone" of Palermo (Italy). Results: Our investigation revealed that 7.4% of patients was carrier of a germline BRCA PV, with an almost total prevalence of BRCA2 alterations. In particular, 65.4% of BRCA-positive patients developed MBC, 19.2% had PC, 11.6% developed PCa, and only 3.8% had melanoma. Specifically, MBC individuals showed a BRCA-associated genetic predisposition in 17% of cases, whereas patients with PCa or PC exhibited a lower frequency of BRCA2 PVs, taking into account the current national criteria for access to germline genetic testing. Discussion: Our study showed a high heterogeneity in prevalence of germline BRCA2 PVs among men which could reflect a potential gender-specific genetic heterogeneity. Therefore, BRCA-associated male tumours could be due to BRCA2 PVs different from those usually detected in women. In the event that it is demonstrated, in future, that male cancers are genetically distinct entities from those female this could improve personalized risk evaluation and guide therapeutic choices for patients of both sexes, in order to obtain a gender equality in cancer care.
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Introduction Penile metastases (PM) are a rare clinical presentation mainly related to advanced stages of disease. Considering the low incidence, an optimal treatment approach has not yet been defined; surgery, chemotherapy, and radiotherapy are different options used in the vast majority with palliative intent. The advances in modern RT can represent an innovative tool in PM management and a curative option. This paper aims to report the case of a PM patient treated with Stereotactic Body Radiotherapy (SBRT) and perform a systematic literature review of current evidence on the RT approach to PM. Case report We reported the case of an 80-year-old patient with PM from primary bladder cancer. Following the surgical approach for the primary tumor, evidence of PM was shown, and the patient was admitted to SBRT treatment on PM after an adjuvant RT course on the pelvis. A 25 Gy in 5 fractions SBRT treatment was performed, and a complete clinical response was shown at the first follow-up. Methods A Pubmed/MEDLINE and Embase systematic review was carried out. The search strategy terms were [('penile metastasis'/exp OR 'penile metastasis' OR (penile AND ('metastasis'/exp OR metastasis))) AND ('radiotherapy'/exp OR radiotherapy)] and only original articles up to the 24.10.2023 were considered. Results A total of 174 studies were obtained using the previously mentioned search strategy, and the analysis was performed on 15 papers obtained following the complete selection process. All reported evidence was focused on the palliative approach of PM showing good results in terms of symptom control. Discussion The potential role of modern RT in the management of PM has yet to be defined. The reported case showed the feasibility and the clinical impact of SBRT in PM treatment.
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INTRODUCTION: Breast cancer (BC) is one of the most common tumors; better screening policies and multidisciplinary approach allow personalized treatment. Radiotherapy (RT) plays a central role in the multimodal approach in BC, and recent evidence has shown the non-inferiority of hypofractionated treatments. The aim of this study was to describe the feasibility and validity of stereotactic RT (SBRT) in BC in a neoadjuvant and exclusive setting. METHODS: A PubMed/MEDLINE and Embase systematic review was conducted to assess the role of radiomics in BC. The search strategy was "breast [All Fields] AND "stereotactic" [All Fields] AND "radiotherapy" [All Fields]" and only original articles referred to BC in humans in the English language were considered. RESULTS: A total of 2,149 studies were obtained using the mentioned search strategy on PubMed and Embase. After the complete selection process, a total of 12 papers were considered eligible for the analysis of the results. SBRT in BC was described in 8 studies regarding neoadjuvant approach and 4 papers regarding exclusive approach. CONCLUSIONS: Relative low toxicity rates, the reduced treatment volumes in the neoadjuvant setting, and the possibility to replace surgery when not feasible in exclusive setting resulted to be main advantages for SBRT in BC. Current evidence shows that both the neoadjuvant and the definitive settings seem to be promising clinical scenarios for SBRT, especially for EBC.
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Neoplasias da Mama , Radiocirurgia , Humanos , Feminino , Terapia Neoadjuvante , Radiocirurgia/métodosRESUMO
Bullous pemphigoid (BP) is a common autoimmune bullous disease generally occurring in elderly patients. Itchy and tense blisters on normal skin or erythematous and edematous lesions on the trunk and extremities usually characterize BP. Trigger factors are still unclear while several case reports suggest a potential role of radiotherapy (RT) as BP trigger for disease onset or recrudescence. A review was performed to provide an update of literature. A case report of a patient affected by BP undergoing two radiotherapy courses for a primary breast cancer was also reported. A comprehensive review of the published literature was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The review included studies describing BP and its relationships with RT treatments. A total of 13 articles were reviewed. Studies characteristics analysis resulted in eleven case reports, one case series and one large-scale case- control study. Literature update confirms the existence of a reasonable connection between RT and BP. Case report showed that a multidisciplinary management seems to assure the feasibility of RT in patients affected by BP, not depriving them of standard therapeutic opportunities.
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OBJECTIVE: Radiotherapy (RT) in the head and neck (H&N) site are undoubtedly the most challenging treatments for patients. Older and frail patients are not always able to tolerate it, and there are still no clear guidelines on the type of treatments to be preferred for them. The recommendations for Risk-Adapted H&N Cancer Radiation Therapy during the coronavirus disease 2019 (COVID-19) pandemic provided by the ASTRO-ESTRO consensus statement achieved a strong agreement about hypofractionated RT (HFRT). A systematic literature review was conducted in order to evaluate the feasibility and safety of HFRT for older patients affected by H&N malignancies. MATERIALS AND METHODS: A systematic database search was performed on PubMed and Embase according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Original studies, case series, and case reports describing the use of HFRT (with at least 2.2 Gy fractions) in patients with mean age ≥65 years were included. The analysis was based on the type of study, number of patients, mean age, tumor site, histology, performance status (PS), RT details, concomitant chemotherapy (CT), and described clinical outcomes. All the reported doses have been calculated in equivalent dose in 2 Gy fractions (EQD2) and biologically effective dose (BED) using α/ß = 10 Gy or α/ß = 12 Gy. RESULTS: We selected 17 papers that met the inclusion criteria and divided them in 4 categories: 6 articles analyze HFRT performed twice daily in repeated cycles, 3 once a day in repeated cycles, 4 in alternative days, and the last 4 in consecutive days. CONCLUSION: HFRT seems to be a good treatment with an acceptable prolonged disease control. In older patients fit for radical treatments, a 55 Gy in 20 fractions regimen can be proposed as a valid alternative to the standard fractionated RT, but there are a multitude of hypofractionated regimens, ranging from single fraction, quad shot, and 1-, 2-, 3-, 4-, and 5-week schedules that all may be appropriate. The correct regimen for a patient depends on many factors, and it represents the result of a more specific and complex decision.
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Introduction: The therapeutic options for NSCLC are limited barring targeted drugs, such as EGFR tyrosine-kinase inhibitors and anaplastic lymphoma kinase inhibitors, for patients bearing oncogenic mutations. Platinum-based chemotherapy remains the best strategy for most patients. New targeted drugs, including mAbs and small molecules, are currently under clinical investigation for treating NSCLC patients. Areas covered: The authors of this article focus on farletuzumab , a mAb targeting folate receptor, which has been studied in ovarian cancer and various other malignancies. In this review, the authors review its potential as therapy for NSCLC, because of the biological rationale provided by the expression of folate receptor α in most of lung adenocarcinoma. The authors provide details of farletuzumab's mechanism of action and discuss the results from completed Phase I and Phase II clinical trials. They also highlight ongoing trials. Expert opinion: There are an increasing number of treatment options for NSCLC and it is hoped that farletuzumab could be added to them. That being said, further evidence for its use with NSCLC patients is still needed. It could have a synergic effect with pemetrexed, because these two drugs have a similar target, namely the folate pathway. This combined action could provide an improved efficacy, although there are some concerns about increased toxicity. However, the authors do note that the combination of farletuzumab with other cytotoxic drugs has not been shown to increase toxicity alone.
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INTRODUCTION: Angiogenesis is fundamental for tumor development and progression. Hence, anti-angiogenic drugs have been developed to target VEGF and its receptors (VEGFRs). Several tyrosine kinase inhibitors (TKIs) have been developed over the years and others are still under investigation, each anti-VEGFR TKI showing a different cardiotoxic profile. Knowledge of the cardiac side-effects of each drug and the magnitude of their expression and frequency can lead to a specific approach. AREAS COVERED: This work reviews the mechanism of action of anti-VEGFR TKIs and the pathophysiological mechanisms leading to cardiotoxicity, followed by close examination of the most important drugs individually. A literature search was conducted on PubMed selecting review articles, original studies and clinical trials, with a focus on Phase III studies. EXPERT OPINION: Side-effects on the cardiovascular system could lead both to the worsening of general health status of cancer patients and to the discontinuation of the cancer treatment affecting its efficacy. Cardiologists often have to face new triggers of heart disease in these patients. They need a specific approach, which must be carried out in cooperation with oncologists. It must start before cancer treatment, continue during it and extend after its completion.
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Antineoplásicos/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Drogas em Investigação/efeitos adversos , Coração/efeitos dos fármacos , Terapia de Alvo Molecular , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Tirosina Quinases/antagonistas & inibidores , Antineoplásicos/uso terapêutico , Drogas em Investigação/uso terapêutico , Humanos , Modelos Biológicos , Neoplasias/irrigação sanguínea , Neoplasias/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
INTRODUCTION: Treatment of ovarian cancer has been long standardized with the inclusion of surgery and chemotherapy based on platinum and taxanes, this strategy reaching high remission rates. However, when this treatment fails, further options are available with little benefit. Since ovarian cancer has specific immunologic features, actually immunotherapy is under evaluation to overcome treatment failure in patients experiencing recurrence. AREAS COVERED: Immunogenicity of ovarian cancer and its relationship with clinical outcomes is briefly reviewed. The kinds of immunotherapeutic strategies are summarized. The clinical trials investigating immunotherapy in recurrent ovarian cancer patients are reported. EXPERT OPINION: The results of these clinical trials about immunotherapy are interesting, but little clinical benefit has been achieved until now. For this reason, we could conclude that immunotherapy is quite different from other treatment options and it could change the global approach for recurrent ovarian cancer treatment. However, to date only fragmentary findings are available to define the real role of immunotherapy in this setting.