Cancer cells may use PARP enzymes and Homologous Recombination to repair single and double strand breaks caused by genotoxic insults. In this study, the PARP-1 inhibitor Rucaparib was utilized to increase the sensitivity to chemoradiotherapy treatment in BRCA-2-deficient and -proficient pancreatic cancer cells. We used the pancreatic cancer cell lines, Capan-1 with mutated BRCA-2 and Panc-1, AsPC-1 and MiaPaCa-2 with BRCA-1/2 wild type. Cells were treated with Rucaparib and/or radiotherapy (4-10 Gy) plus Gemcitabine then the capability to proliferate was evaluated by colony formation, cell counting and MTT assays. Flow cytometry, immunocytochemistry and western blotting were utilized to assess cell response to Rucaparib plus irradiation. The antitumour effectiveness of combining the PARP-1 inhibitor before, together and after radiotherapy evidenced the first as the optimal schedule in blocking cell growth. Pre-exposure to Rucaparib increased the cytotoxicity of Gemcitabine plus radiotherapy by heavily inducing the accumulation of cells in G2/M phase, impairing mitosis and finally inducing apoptosis and authophagy. The upregulation of p-Akt and downregulation of p53 were evidenced in MiaPaCa-2 which displayed replication stress features. For the first time, the rationale of using a PARP inhibitor as chemoradiosensitizer in pancreatic cancer models has been hypothesized and demonstrated.

Background and purposeTo investigate the hypothesis on low-dose bath exposure related to radiation-induced nausea and vomiting (RINV) in adjuvant breast volumetric modulated arch therapy (VMAT).Methods and materialsA total of 106 consecutive breast cancer patients (pts) treated with adjuvant radiotherapy (RT) with VMAT from January 2013 to May 2016 were evaluated retrospectively. For each pt, a planning CT was reimported and the coeliac plexus and gastroesophageal junction with gastric mouth (GEJCPs) were contoured as a new organ at risk (OAR) in the upper abdominal area. RINV was associated with Dmax and Dmean to GEJCPs. Univariate analysis with χ2, t-test, and Pearson’s covariance was used for statistical analysis.ResultsOf 106 pts, 64% complained of acute RINV according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. RINV was related to Dmax > 10 Gy and Dmean > 3 Gy to GEJCPs (P < 0.005). The radiation breast side and planning target volume (PTV) correlated with RINV.ConclusionsRINV in VMAT breast radiotherapy could be a new emerging acute side effect due to a low dose bath to upper abdominal structures such as the GEJCPs. A Dmax < 10 Gy and Dmean < 3 Gy to GEJCPs should be constrained in VMAT planning to minimize RINV risk in breast radiotherapy.

The aim of this current study was to assess whether the tumour grade and molecular subtypes have influenced local control in the whole breast hypofractionated radiotherapy (HRT) over standard radiotherapy (SRT) in early breast node negative cancer patients by a retrospective control group study.Data of 215 patients treated with hypofractionated radiotherapy at our institution from 2008 to 2011 were prospectively collected and then compared with 215 pts treated with SRT in a control group study. The local relapse free survival (LRFS) in both arms was compared on the basis of variables defined by tumour grade (Nottingham Grading System), and Molecular subtypes. Kaplan-Meier method was applied to estimate the LRFS in both groups. Chi-squared and univariate Cox proportional hazards model were conducted for all variables in both groups to assess the impact on local control. Statistical significance was assumed at P < .05. Statistical significant variables at univariate analysis were then included in multivariate Cox proportional hazards model. The median follow up duration was 9.5 years (7–13 yrs); the Kaplan Meyer 8 year LRFS did not reach any statistical significant difference between the two groups (P = . 836). At univariate Cox analysis tumour grade 3 was significantly related to local relapse only in the SRT group (P = .041) while, among molecular subtypes, no differences were found for all groups; for Her2 + noL no difference was found (P = .233). Multivariate analysis confirmed Her2 non-luminal subtype as an independent variable for local relapse regardless the fractionation arm (P = .045). Breast cancer subtypes show a different radiosensitivity, which is independent by fractionation.

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