BackgroundRadiation therapy is an indispensable part of various treatment modalities for breast cancer. Specifically, for non-inflammatory locally advanced breast cancer (LABC) patients, preoperative radiotherapy (pRT) is currently indicated as a second line therapy in the event of lack of response to neoadjuvant chemotherapy. Still approximately one third of patients fails to respond favourably to pRT. The aim of this study was to explore molecular mechanisms underlying differential response to radiotherapy (RT) to identify predictive biomarkers and potential targets for increasing radiosensitivity.MethodsThe study was based on a cohort of 134 LABC patients, treated at the Institute of Oncology and Radiology of Serbia (IORS) with pRT, without previous or concomitant systemic therapy. Baseline transcriptional profiles were established using Agilent 60 K microarray platform in a subset of 23 formalin-fixed paraffin-embedded (FFPE) LABC tumour samples of which 11 radiotherapy naïve and 3 post-radiotherapy samples passed quality control and were used for downstream analysis. Biological networks and signalling pathways underlying differential response to RT were identified using Ingenuity Pathways Analysis software. Predictive value of candidate genes in the preoperative setting was further validated by qRT-PCR in an independent subset of 60 LABC samples of which 42 had sufficient quality for data analysis, and in postoperative setting using microarray data from 344 node-negative breast cancer patients (Erasmus cohort, GSE2034 and GSE5327) treated either with surgery only (20%) or surgery with RT (80%).ResultsWe identified 192 significantly differentially expressed genes (FDR < 0.10) between pRT-responsive and non-responsive tumours, related to regulation of cellular development, growth and proliferation, cell cycle control of chromosomal replication, glucose metabolism and NAD biosynthesis II route. APOA1, MAP3K4, and MMP14 genes were differentially expressed (FDR < 0.20) between pRT responders and non-responders in preoperative setting, while MAP3K4 was further validated as RT-specific predictive biomarker of distant metastasis free survival (HR = 2.54, [95%CI:1.42–4.55], p = 0.002) in the postoperative setting.ConclusionsThis study pinpoints MAP3K4 as a putative biomarker of response to RT in both preoperative and postoperative settings and a potential target for radiosensitising combination therapy, warranting further pre-clinical studies and prospective clinical validation.Electronic supplementary materialThe online version of this article (10.1186/s13014-018-1129-4) contains supplementary material, which is available to authorized users.
Inflammatory myofibroblastic tumor (IMT) is an aggressive benign mass that may arise from various tissues and organs with a great variability of histological and clinical appearances. Due to variable and nonspecific imaging findings, diagnosis of IMT is not obtained before surgery. The aim of this paper is to present CT and MRI findings during four-year follow-up of complete, spontaneous regression of IMT of the uterus. The diagnosis was made by histology and immunohistochemistry analysis of the open excisional biopsy specimen. At that time, the organ of origin was not specified. After analysis of the follow-up imaging findings and the mode of tumor regression, the uterus was proclaimed as the probable site of origin. IMT of the uterus is extremely rare and has been reported in ten cases up to now. The gradual, complete regression of uterine IMT documented by CT and MRI may contribute to understanding of its nature.
Background Historically, the treatment of choice for anal cancer had been abdominoperineal resection (APR). Radical radiotherapy with concurrent 5-fluorouracil plus mitomycin C chemotherapy was later established as standard therapy, although with a failure rate of 20–30%. The aim of this study was to evaluate the outcomes after radical chemoradiotherapy (CRT), prognostic and predictive factors and patterns of failure. Patients and methods This study included 47 patients treated with radical CRT for patohistologicaly confirmed anal squamous cell carcinoma. Analysed haematological parameters included: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and haemoglobin level. The final logistic regression model included treatment break period. Tumour response was assessed at 24 weeks from CRT completion. Follow-up was performed every 3 months during the first two years, and every 6 months thereafter. Results A complete clinical response (CR) was detected in 30 patients (63.8%). Patients who did not achieve a 6-months CR and those who had a CR after 6 months but then relapsed were referred to surgical treatment. With combined CRT and surgical salvage treatment the CR rate was 80.9%. Patients with CR after 6 months had significantly longer disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS). A significant effect on the 6-month response was confirmed for PLR (p = 0.03). Conclusions Important prognostic factors associated with CR were baseline haemoglobin level and period of treatment interruptions. Potential haematological prognostic factors could be PLR and NLR, which can be routinely determined by low-cost and minimally invasive methods.
During radiotherapy treatment for cervical cancer, up to 84% of patients exhibit some form of acute radiation toxicity (ART). The primary aim of this clinical study is to determine the impact of angiotensin-converting enzyme (ACE) inhibitors, β-blockers and other risk factors such as the patient’s anatomical characteristics on ART emergence in patients with locally advanced cervical cancer treated by chemoradiotherapy. This is a combination of two nested case–control studies within the cohort of patients with locally advanced cervical cancer based on the analysis of potential risk factors for the onset of ART in patients treated with 3D conformal radiotherapy (3D-CRT) and 2D conventional radiotherapy (2D-RT), prospectively followed up from January 2017 to September 2018 in a tertiary care hospital. The ACE inhibitors and bladder volume were identified as factors that significantly affect the occurrence of ART in patients treated with 3D-CRT. In patients treated with 2D-RT, the factors that significantly affect the occurrence of ART were ACE inhibitors, body mass index (BMI), brachytherapy rectal and bladder dose. This study has shown that BMI, radiation dose received by the bladder and rectum are of exceptional importance for the occurrence of the ART and also that therapy with ACE inhibitors was associated with the decreased chances of the ART.
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