Zadnja postignuća u radioterapiji raka prostate

Radiotherapy is the attractive treatment option for prostate cancer and has a clear role in all stages of the disease. Over the last decade, advances in technology, imaging capabilities, and improved radiobiological understanding have deeply transformed radiotherapy for prostate cancer, allowing dose escalation and wide adoption of hypofractionation. Furthermore, the integration of magnetic resonance imaging (MRI) and improved physical precision of dose delivery have given an impetus to additionally target intraprostatic tumor lesions, previously agnostic to conventional radiotherapy target definition concept. The emerging data from randomized clinical trials and observation research show that ultra-hypofractionation is a safe approach while further follow-up is needed to assess its efficacy compared to standard fractionation. There is an ongoing uncertainty surrounding true alpha/beta ratio for prostate cancer since hypofractionation has so far failed to yield theoretically envisioned superior biochemical control outcomes. Finally, recently published randomized trial settled ongoing controversy regarding the role of elective pelvic lymph node radiotherapy in patients with high-risk prostate cancer, showing clear benefit when pelvic nodes were treated to 50 Gy. The role of partial gland dose escalation/tumor boosting is evolving, and more data is needed to adopt this approach in routine clinical care. Going forward, molecular imaging will be crucial to assess biology of the disease, predict a response potentially, and optimally personalize radiotherapy treatment decisions. In this narrative review, we critically analyzed the published literature and provided practical summary of recent prostate radiotherapy advances for busy clinicians.Radioterapija je neizostavan oblik liječenja raka prostate i ima ulogu u svim fazama bolesti. Zadnjeg desetljeća napreci u tehnologiji i radiobiologiji su preobrazili radioterapiju raka prostate te omogućili eskalaciju doze i hipofrakcioniranje. Nadalje, integracija magnetske rezonance i povećana fizikalna preciznost isporuke radioterapije omogućila je ciljanje intraprostatičkih tumora. Mnoge studije pokazuju da je ultra hipofrakcioniranje obećavajući koncept liječenja, iako postoje mnoge nejasnoće o pravom alfa-beta omjeru raka prostate te posljedičnom stvarnom terapijskom benefitu hipofrakcioniranja. Recentno objavljena studija ukazala je na korist elektivne radioterapije zdjeličnih limfnih čvorova u bolesnika sa visokorizičnim rakom prostate. Nadalje, u tijeku su studije koje će ocijeniti valjanost daljnje intraprostatičke eskalacije doze. Moderno molekularno oslikavanje donosi veliku promjenu u načinu kako shvaćamo i liječimo rak prostate. U ovom preglednom članku kritički smo analizirali literaturu i dali smjernice za svakodnevnu radioterapijsku kliničku praksu

Weak expression of cyclooxygenase-2 is associated with poorer outcome in endemic nasopharyngeal carcinoma: analysis of data from randomized trial between radiation alone versus concurrent chemo-radiation (SQNP-01)

<p>Abstract</p> <p>Background</p> <p>Over-expression of cyclooxygenase-2 (COX-2) enzyme has been reported in nasopharyngeal carcinoma (NPC). However, the prognostic significance of this has yet to be conclusively determined. Thus, from our randomized trial of radiation versus concurrent chemoradiation in endemic NPC, we analyzed a cohort of tumour samples collected from participants from one referral hospital.</p> <p>Methods</p> <p>58 out of 88 patients from this institution had samples available for analysis. COX-2 expression levels were stratified by immunohistochemistry, into negligible, weak, moderate and strong, and correlated with overall and disease specific survivals.</p> <p>Results</p> <p>58% had negligible or weak COX-2 expression, while 14% and 28% had moderate and strong expression respectively. Weak COX-2 expression conferred a poorer median overall survival, 1.3 years for weak versus 6.3 years for negligible, 7.8 years, strong and not reached for moderate. There was a similar trend for disease specific survival.</p> <p>Conclusion</p> <p>Contrary to literature published on other malignancies, our findings seemed to indicate that over-expression of COX-2 confer a better prognosis in patients with endemic NPC. Larger studies are required to conclusively determine the significance of COX-2 expression in these patients.</p

A novel prostate cancer subtyping classifier based on luminal and basal phenotypes

Background: Prostate cancer (PCa) is a clinically heterogeneous disease. The creation of an expression-based subtyping model based on prostate-specific biological processes was sought. Methods: Unsupervised machine learning of gene expression profiles from prospectively collected primary prostate tumors (training, n = 32,000; evaluation, n = 68,547) was used to create a prostate subtyping classifier (PSC) based on basal versus luminal cell expression patterns and other gene signatures relevant to PCa biology. Subtype molecular pathways and clinical characteristics were explored in five other clinical cohorts. Results: Clustering derived four subtypes: luminal differentiated (LD), luminal proliferating (LP), basal immune (BI), and basal neuroendocrine (BN). LP and LD tumors both had higher androgen receptor activity. LP tumors also had a higher expression of cell proliferation genes, MYC activity, and characteristics of homologous recombination deficiency. BI tumors possessed significant interferon γactivity and immune infiltration on immunohistochemistry. BN tumors were characterized by lower androgen receptor activity expression, lower immune infiltration, and enrichment with neuroendocrine expression patterns. Patients with LD tumors had less aggressive tumor characteristics and the longest time to metastasis after surgery. Only patients with BI tumors derived benefit from radiotherapy after surgery in terms of time to metastasis (hazard ratio [HR], 0.09; 95% CI, 0.01–0.71; n = 855). In a phase 3 trial that randomized patients with metastatic PCa to androgen deprivation with or without docetaxel (n = 108), only patients with LP tumors derived survival benefit from docetaxel (HR, 0.21; 95% CI, 0.09–0.51). Conclusions: With the use of expression profiles from over 100,000 tumors, a PSC was developed that identified four subtypes with distinct biological and clinical features. Plain language summary: Prostate cancer can behave in an indolent or aggressive manner and vary in how it responds to certain treatments. To differentiate prostate cancer on the basis of biological features, we developed a novel RNA signature by using data from over 100,000 prostate tumors—the largest data set of its kind. This signature can inform patients and physicians on tumor aggressiveness and susceptibilities to treatments to help personalize cancer management

Testosterone in androgen receptor signaling and DNA repair:Enemy or frenemy?

Abstract Androgen suppression mediates transcriptional downregulation of DNA repair genes. Stimulation with supraphysiologic levels of dihydrotestosterone induces formation of lethal DNA breaks through recruitment of topoisomerase II enzymes to fragile DNA sites. Bipolar castration and stimulation that contributes to increasing DNA damage represents a novel strategy of sensitizing prostate cancer to cytotoxic therapies, including radiotherapy. Clin Cancer Res; 22(13); 3124–6. ©2016 AACR. See related article by Hedayati et al., p. 3310</jats:p

Carcinogenesis of nasopharyngeal carcinoma: an alternate hypothetical mechanism

Abstract Current proposed mechanisms implicate both early and latent Epstein–Barr virus (EBV) infection in the carcinogenic cascade, whereas epidemiological studies have always associated nasopharyngeal carcinoma (NPC) with early childhood EBV infection and with chronic ear, nose, and sinus conditions. Moreover, most patients with NPC present with IgA antibody titers to EBV capsid antigen (VCA-IgA), which can precede actual tumor presentation by several years. If early childhood EBV infection indeed constitutes a key event in NPC carcinogenesis, one would have to explain the inability to detect the virus in normal nasopharyngeal epithelium of patients at a high risk for EBV infection. It is perhaps possible that EBV resides within the salivary glands, instead of the epithelium, during latency. This claim is indirectly supported by observations that the East Asian phenotype shares the characteristics of an increased susceptibility to NPC and immature salivary gland morphogenesis, the latter of which is influenced by the association of salivary gland morphogenesis with an evolutionary variant of the human ectodysplasin receptor gene (EDAR), EDARV370A. Whether the immature salivary gland represents a more favorable nidus for EBV is uncertain, but in patients with infectious mononucleosis, EBV has been isolated in this anatomical organ. The presence of EBV-induced lymphoepitheliomas in the salivary glands and lungs further addresses the possibility of submucosal spread of the virus. Adding to the fact that the fossa of Rosen Müller contains a transformative zone active only in the first decade of life, one might be tempted to speculate the possibility of an alternative carcinogenic cascade for NPC that is perhaps not dissimilar to the model of human papillomavirus and cervical cancer

Recent advances in radiation therapy and photodynamic therapy

10.1063/5.0060424APPLIED PHYSICS REVIEWS8

A Review of the Current Clinical Evidence for Loco-Regional Moderate Hyperthermia in the Adjunct Management of Cancers

Regional hyperthermia therapy (RHT) is a treatment that applies moderate heat to tumours in an attempt to potentiate the effects of oncological treatments and improve responses. Although it has been used for many years, the mechanisms of action are not fully understood. Heterogenous practices, poor quality assurance, conflicting clinical evidence and lack of familiarity have hindered its use. Despite this, several centres recognise its potential and have adopted it in their standard treatment protocols. In recent times, significant technical improvements have been made and there is an increasing pool of evidence that could revolutionise its use. Our narrative review aims to summarise the recently published prospective trial evidence and present the clinical effects of RHT when added to standard cancer treatments. In total, 31 studies with higher-quality evidence across various subsites are discussed herein. Although not all of these studies are level 1 evidence, benefits of moderate RHT in improving local tumour control, survival outcomes and quality of life scores were observed across the different cancer subsites with minimal increase in toxicities. This paper may serve as a reference when considering this technique for specific indications

Pan-cancer analysis connects tumor matrisome to immune response

10.1038/s41698-019-0087-0NPJ PRECISION ONCOLOGY3

Improving the therapeutic ratio of radiotherapy against radioresistant cancers: Leveraging on novel artificial intelligence-based approaches for drug combination discovery

10.1016/j.canlet.2021.04.019Cancer Letters51156-6