RESUMO
Clinical nomograms based on Gleason grade, tumor stage, and serum PSA are still the best predictors of prostate cancer (PC) outcome. The biotechnological advancements achieved in the last decade represent a remarkable source for new prognostic and predictive tissue and serum molecular biomarkers. In this review, we will summarize conventional PC prognostic biomarkers and focus on novel identified biomarkers for PC early diagnosis and progression that might be used in the future. Although they are not ready for widespread, routine use, there are reasons to believe that future models will combine these markers with traditional pretreatment and treatment-related variables and will improve our ability to predict outcome and select the optimal treatment.
Assuntos
Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/terapia , Biomarcadores/análise , Humanos , Masculino , Oncogenes , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/genéticaRESUMO
BACKGROUND: Worldwide, lung cancer is one of the leading causes of cancer death. Nevertheless, new therapeutic agents have been developed to treat lung cancer that could change this mortality-rate. Interestingly, incredible advances have occurred in recent years in the development and application of nanotechnology in the detection, diagnosis, and treatment of lung cancer. AIM: Nanoparticles (NPs) have the ability to incorporate multiple drugs and targeting agents and therefore lead to an improved bioavailability, sustained delivery, solubility, and intestinal absorption. RELEVANCE FOR PATIENTS: This review briefly summarizes the latest innovations in therapeutic nanomedicine in lung cancer with examples on magnetic, lipid, and polymer NP. Emphasis will be placed on future studies and ongoing clinical trials in this field.
RESUMO
Radiotherapy of cancer has been traditionally considered as a local therapy without noticeable effects outside the irradiated fields. However, ionizing radiation exerts multiple biological effects on both malignant and stromal cells that account for a complex spectrum of mechanisms beyond simple termination of cancer cells. In the era of immunotherapy, interest in radiation-induced inflammation and cell death has considerably risen, since these mechanisms lead to profound changes in the systemic immune response against cancer antigens. Immunotherapies such as immunomodulatory monoclonal antibodies (anti-PD-1, anti-CTLA-4, anti-CD137, anti-OX40, anti-CD40, anti-TGFß), TLR-agonists, and adoptive T-cell therapy have been synergistically combined with radiotherapy in mouse models. Importantly, radiation and immunotherapy combinations do not only act against the irradiated tumor but also against distant non-irradiated metastases (abscopal effects). A series of clinical trials are exploring the beneficial effects of radioimmunotherapy combinations. The concepts of crosspriming of tumor neoantigens and immunogenic cell death are key elements underlying this combination efficacy. Proinflamatory changes in the vasculature of the irradiated lesions and in the cellular composition of the leukocyte infiltrates in the tumor microenvironment contribute to raise or dampen cancer immunogenicity. It should be stressed that not all effects of radiotherapy favor antitumor immunity as there are counterbalancing mechanisms such as TGFß, and VEGFs that inhibit the efficacy of the antitumor immune response, hence offering additional therapeutic targets to suppress. All in all, radiotherapy and immunotherapy are compatible and often synergistic approaches against cancer that jointly target irradiated and non-irradiated malignant lesions in the same patient.
Assuntos
Metástase Neoplásica/radioterapia , Neoplasias/radioterapia , Radioimunoterapia , Animais , Humanos , Neoplasias/patologiaRESUMO
BACKGROUND: To compare thermoplastic masks (TMP) and vacuum cushion system (VCS) to assess differences in interfraction set up accuracy in patients treated with stereotactic radiotherapy (SBRT) for oligometastatic lung cancer. Secondarily, to survey radiotherapy technologists to assess their satisfaction with the two systems. METHODS: Retrospective study of patients treated with lung SBRT between 2008 to 2012 at our institution. Immobilization was performed for 73 treatment sessions (VCS = 40; TMP = 33). A total of 246 cone-beams were analysed. Patients considered ineligible for surgery with a life expectancy ≥6 months and performance status > 1 were included. Target lesion location was verified by cone beam computed tomography (CBCT) prior to each session, with displacements assessed by CBCT simulation prior to each treatment session. Couch shifts were registered prospectively in vertical, longitudinal, and latero-lateral directions to obtain Kernel coordinates (3D representation). Technologists were surveyed to assess their satisfaction with indexing, positioning, and learning curve of the two systems. Setup displacements were obtained in all patients for each treatment plan and for each session. To assess differences between the immobilization systems, a t-test (Welch) was performed. RESULTS: Mean displacements for the TMP and VC systems, respectively, were as follows: session one, 0.64 cm vs 1.05 cm (p = 0.0002); session two, 0.49 cm vs 1.02 cm (p < 0.0001), and session three, 0.56 vs 0.97 cm (p = 0.0011). TMP resulted in significantly smaller shifts vs. VCS in all three treatment sessions. Technologists rated the learning curve, set up, and positioning more highly for TMP versus VCS. CONCLUSIONS: Due to the high doses and steep gradients in lung SBRT, accurate and reproducible inter-fraction set up is essential. We found that thermoplastic masks offers better reproducibility with significantly less interfractional set up displacement than vacuum cushions. Moreover, radiotherapy technologists rated the TMP system higher. Taken together, these two findings suggest that TMP may be preferable to VCS. However, more research is needed to determine both inter- and intrafraction error to identify the optimal immobilisation system for use in lung SBRT.
Assuntos
Neoplasias Pulmonares/cirurgia , Radiocirurgia/instrumentação , Restrição Física/instrumentação , Humanos , Máscaras , Dosagem Radioterapêutica , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
PURPOSE: The present study analyzed the expression by immunochemistry of the novel markers P21-activated protein kinase 6 (PAK6) and proteasome beta-4 subunit (PSMB4) in men with localized prostate cancer (PC) who were treated with dose-escalation radiotherapy (RT) and androgen deprivation therapy. MATERIALS AND METHODS: Between 1996 and 2004, a cohort of 129 patients with PC who underwent diagnostic biopsies pretreatment and 24 to 36 months following RT were enrolled in this study. Suitable archival diagnostic tissue was obtained from 89 patients. Median follow-up was 129 months (48-198). Correlation analysis was done to assess association between PAK6 and PSMB4 expression and clinical outcome. RESULTS: PAK6 and PSMB4 were expressed in the cytoplasm in 62% and 96.7% of diagnostic biopsies, respectively. Increased staining for PAK6 was significantly (P = 0.04) correlated with higher Gleason scores. In the multivariate analysis, the intensity of PSMB4 staining was an independent predictor of local relapse (hazard ratio = 8.6, P = 0.04). CONCLUSIONS: To our knowledge, this is the first description of PAK6 and PSMB4 expression in the diagnostic specimens of men with PC who were treated with RT. If confirmed by further studies, increased expression of these genes could be used to identify patients at a high risk of developing local failure following high-dose RT, thus better tailoring treatments for the individual patient.