•Thyroid angiosarcoma (TAS) is a rare entity and its management is still debated.•This is the largest updated analysis of literature data in TAS patients.•This analysis suggests that early diagnosis ...and multidisciplinary approach could influence outcome.
Thyroid angiosarcoma (TAS) is rare and represents a very aggressive malignancy. Its rarity is principally linked to two major pitfalls. Firstly, TAS histopathology diagnosis can be difficult; second, the limited clinical experience with this condition can make its management complex.
We conducted a detailed systematic review, focusing on the knowledge available regarding TAS etiopathogenesis, treatment options and prognosis. The aim is to present the main TAS characteristics and to summarize the clinical experiences described worldwide, in order to provide a useful clinical tool.
Abstract Purpose To analyze diffusion-weighted magnetic resonance imaging (DW-MRI) for treatment response assessment in locally advanced rectal cancer (LARC). Patients and methods Patients with ...histologically proven rectal adenocarcinoma, stage II-III disease, were enrolled and underwent surgery following neoadjuvant chemoradiotherapy (nCRT). All patients were referred for a DW-MRI protocol on a 3 Tesla MR-system, consisting of axial T2-weighted and DWI sequences prior (I), during (II) and after (III) nCRT. Corresponding apparent diffusion coefficient (ADC) values were calculated. Results Between February 2011 and June 2015, 37 patients participated in the study. All patients completed programmed treatment. Overall, 11 patients (29.7%) had pathologic complete response (pCR). No correlation between the mean pre- (ADC-I), during (ADC-II), post- (ADC-III) ADC and the reduction in tumor size after nCRT was recorded. No substantial difference in the ADC distribution was found between pCR and no-pCR patients. The ADC-II level significantly increased in the pCR cases (T= 1.675; p < 0.05). Conclusion ADC value could be useful for discriminating between the pCR patients and the no-pCR patients. Further studies are necessary to identify the optimal MRI parameters combination to predict tumor response to nCRT. It is hoped that these data will provide the basis for a more solid scientific evidence.
Purpose
To analyse the classification performances of a decision tree method applied to predictor variables in survival outcome in patients with locally advanced rectal cancer (LARC). The aim was to ...offer a critical analysis to better apply tree-based approach in clinical practice and improve its interpretation.
Materials and methods
Data concerning patients with histological proven LARC between 2007 and 2014 were reviewed. All patients were treated with trimodality approach with a curative intent. The Kaplan–Meier method was used to estimate overall survival (OS). Decision tree methods were was used to select important variables in outcome prediction.
Results
A total of 100 patients were included. The 5-year and 7-year OS rates were 76.4% and 71.3%, respectively. Age, co-morbidities, tumor size, clinical tumor classification (cT) and clinical nodes classification (cN) were the important predictor variables to the tree’s construction. Overall, 13 distinct groups of patients were defined. Patients aged < 65 years with cT3 disease and elderly patients with a tumor size < 5 cm seemed to have highest rates of survival. But the process over-fitted the data, leading to poor algorithm performance.
Conclusion
We proposed a decision tree algorithm to identify known and new pre-treatment clinical predictors of survival in LARC. Our analysis confirmed that tree-based machine learning method, especially classification trees, can be easily interpreted even by a non-expert in the field, but controlling cross validation errors is mandatory to capture its statistical power. However, it is necessary to carefully analyze the classification error trend to chose the important predictor variables, especially in little data. Machine learning approach should be considered the new unexplored frontier in LARC. Based on big datasets, decision trees represent an opportunity to improve decision-making process in clinical practice.
•The role of immune check-point inhibitors is being tested in glioblastoma multiforme (GBM).•This is the largest updated analysis of preclinical and clinical trials in GBM.•This analysis suggests ...that immune check-point inhibitors could influence outcomes in GBM.
Glioblastoma multiforme (GBM) represents one of the main frequent and aggressive primary brain neoplasms among adults worldwide. Despite a first-line multimodal treatment, including radical surgery and adjuvant radiation therapy with concomitant temozolomide-based chemotherapy, GBM prognosis continues to be unfavourable. During this decade, different research groups have explored immune check-point inhibitors role in order to improve response to therapy and subsequently prolong survival rate. The aim of this review was to analyze published literature to support immune check-point inhibitors use in the management of patients with GBM diagnosis. The hope was to help physicians for better decision-making.
Objectives
To report outcomes of stereotactic body radiotherapy (SBRT) in metastatic castration-resistant prostate cancer (mCRPC) patients with oligoprogression (≤ 5 metastases) during first-line ...treatment with androgen receptor-targeted therapy (ARTT).
Patients and methods
Retrospective multi-institutional analysis of mCRPC patients treated with SBRT to oligoprogressive lesions during ARTT. End-points were time to next-line systemic treatment (NEST), radiological progression-free survival (r-PFS) and overall survival (OS). Toxicity was registered according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Survival analysis was performed using the Kaplan–Meier method, univariate and multivariate analysis (MVA) were performed.
Results
Data from 34 patients were analyzed. Median NEST-free survival, r-PFS, and OS were 16.97, 13.47, and 38.3 months, respectively. At MVA, factors associated with worse NEST-free survival and r-PFS were polymetastatic burden at diagnosis of metastatic hormone-sensitive disease (hazard ratio HR 3.66,
p
= 0.009; HR 3.03,
p
= 0.034), PSA ≤ 7 ng/ml at mCRPC diagnosis (HR 0.23,
p
= 0.017; HR 0.19,
p
= 0.006) and PSADT ≤ 3 months at mCRPC diagnosis (HR 3.39,
p
= 0.026; HR 2.79,
p
= 0.037). Polymetastatic state at mHSPC diagnosis was associated with a decreased OS (HR 4.68, p = 0.029). No patient developed acute or late grade ≥ 2 toxicity.
Conclusion
Our results suggest that SBRT in oligoprogressive mCPRC is safe, effective and seems to prolong the efficacy of the ongoing systemic treatment positively affecting disease progression. Prospective trials are needed.
We assessed the efficacy and safety of total neoadjuvant therapy, including targeted agent plus FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) induction chemotherapy followed by ...intensified chemoradiotherapy (CRT) and surgical resection, in patients with locally advanced rectal cancer.
This was a single-arm, single-centre phase II trial. Eligible patients had non-metastatic locally advanced rectal adenocarcinoma. Based on Ras-BRAF status, patients were treated with bevacizumab (mutated Ras-BRAF) or panitumumab/cetuximab (wild-type Ras-BRAF) plus FOLFOXIRI regimen followed by oxaliplatin–5-fluorouracil-based CRT and surgery. The primary end point was pathological complete response rate. Secondary end points were toxicity, compliance, tumour downstaging, complete resection, surgical complications, local and distant failures and overall survival. The sample size was planned to expect an absolute 20% improvement in pathological complete response rate over historical literature data with an α error of 0.05 and a power of 80%.
Between October 2015 and September 2019, 28 patients (median age 66 years) were enrolled. All patients had regional lymph node involvement at diagnosis. FOLFOXIRI plus bevacizumab was administered in 11 mutated Ras-BRAF patients, whereas the 17 wild-type Ras-BRAF patients received FOLFOXIRI plus panitumumab/cetuximab. Overall, total neoadjuvant therapy was well tolerated and 26 patients (92.9%) completed the programmed strategy. A complete response was achieved in nine cases (32.1%) and a nearly pathological complete response (ypT1 ypN0) in two patients (7.2%). There was no evidence of febrile neutropenia and no grade 4 adverse events were recorded. Radical resection was achieved in all cases.
FOLFOXIRI plus targeted agent-based induction chemotherapy and intensified CRT before surgery showed promising clinical activity and was well tolerated in locally advanced rectal cancer patients. This phase II trial provides a strong rationale for phase III studies.
We have previously reported that the MEK/ERK pathway sustains in vitro and in vivo transformed phenotype and radioresistance of embryonal rhabdomyosarcoma (ERMS) cell lines. Furthermore, we found ...that aberrant MEK/ERK signaling activation promotes c-Myc oncoprotein accumulation. In this study, the role of c-Myc in sustaining the ERMS transformed and radioresistant phenotype is characterized. RD and TE671 cell lines conditionally expressing MadMyc chimera protein, c-Myc-dominant negative and shRNA directed to c-Myc were used. Targeting c-Myc counteracted in vitro ERMS adherence and in suspension, growth motility and the expression of pro-angiogenic factors. c-Myc depletion decreased MMP-9, MMP-2, u-PA gelatinolytic activity, neural cell adhesion molecule sialylation status, HIF-1α, VEGF and increased TSP-1 protein expression levels. Rapid but not sustained targeting c-Myc radiosensitized ERMS cells by radiation-induced apoptosis, DNA damage and impairing the expression of DNA repair proteins RAD51 and DNA-PKcs, thereby silencing affected ERMS radioresistance. c-Myc sustains ERMS transformed phenotype and radioresistance by protecting cancer cells from radiation-induced apoptosis and DNA damage, while promoting radiation-induced DNA repair. This data suggest that c-Myc targeting can be tested as a promising treatment in cancer therapy.
Purpose
Radiotherapy toxicity is related to oxidative stress-mediated endothelial dysfunction. Here, we investigated on radioprotective properties of Vitamin D (Vit.D) on human endothelial cells ...(HUVEC).
Methods
HUVEC, pre-treated with Vit.D, were exposed to ionizing radiation (IR): ROS production, cellular viability, apoptosis, senescence and western blot for protein detection were performed. The role of MAPKs pathway was investigated by using U0126 (10 μM) MEKs/ERKs-, SB203580 (2.5 μM) p38-inhibitor or by over/expressing MKK6 p38-upstream activator.
Results
Vit.D reduced IR-induced ROS production protecting proliferating and quiescent HUVEC from cellular apoptosis or senescence, respectively, by regulating MAPKs pathways. In proliferating HUVEC, Vit.D prevented IR-induced apoptosis by activating ERKs while in quiescent HUVEC counteracted IR-induced senescence by inhibiting the p38-IR-induced activation. MEKs&ERKs inhibition in proliferating or MKK6/mediated p38 activation in quiescent HUVEC, respectively, reverted anti-apoptotic or anti-senescent Vit.D properties. SirT1 protein expression levels were up-regulated by Vit.D. ERKs inhibition blocked Vit.D-induced SirT1 protein up-regulation in proliferating cells. In quiescent HUVEC cells, p38 inhibition counteracted the IR-induced SirT1 protein down-regulation, while MKK6 transfection abrogated the Vit.D positive effects on SirT1 protein levels after irradiation. SirT1 inhibition by sirtinol blocked the Vit.D radioprotective effects.
Conclusion
Vit.D protects HUVEC from IR induced/oxidative stress by positively regulating the MAPKs/SirT1 axis.
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