Genomic alterations underlie a pan-cancer metabolic shift associated with tumour hypoxia.

Background: Altered metabolism is a hallmark of cancer. However, the role of genomic changes in metabolic genes driving the tumour metabolic shift remains to be elucidated. Here, we have investigated the genomic and transcriptomic changes underlying this shift across ten different cancer types.

Adjuvant Chemoradiation in Pancreatic Cancer: A Pooled Analysis in Elderly (≥75 years) Patients.

Aim: To determine the impact of postoperative chemoradiation (POCR) on overall survival (OS) after resection of pancreatic adenocarcinoma (PAC) in elderly (≥75 years) patients.

Materials And Methods: A multi-center retrospective review of 1248 patients who underwent complete resection with macroscopically negative margins (R0-1) for invasive PAC was performed. Exclusion criteria included age <75 years, metastatic or unresectable disease at surgery, macroscopic residual disease (R2), treatment with intraoperative radiotherapy (IORT) and postoperative death.

TH-302 in Combination with Radiotherapy Enhances the Therapeutic Outcome and Is Associated with Pretreatment [18F]HX4 Hypoxia PET Imaging.

Purpose: Conventional anticancer treatments are often impaired by the presence of hypoxia. TH-302 selectively targets hypoxic tumor regions, where it is converted into a cytotoxic agent. This study assessed the efficacy of the combination treatment of TH-302 and radiotherapy in two preclinical tumor models.

Selection of appropriate end-points (pCR vs 2yDFS) for tailoring treatments with prediction models in locally advanced rectal cancer.

Purpose: Personalized treatments based on predictions for patient outcome require early characterization of a rectal cancer patient's sensitivity to treatment. This study has two aims: (1) identify the main patterns of recurrence and response to the treatments (2) evaluate pathologic complete response (pCR) and two-year disease-free survival (2yDFS) for overall survival (OS) and their potential to be relevant intermediate endpoints to predict.

Methods: Pooled and treatment subgroup analyses were performed on five large European rectal cancer trials (2795 patients), who all received long-course radiotherapy with or without concomitant and/or adjuvant chemotherapy.

Nomograms for prediction of outcome with or without adjuvant radiation therapy for patients with endometrial cancer: a pooled analysis of PORTEC-1 and PORTEC-2 trials.

Background: Postoperative radiation therapy for stage I endometrial cancer improves locoregional control but is without survival benefit. To facilitate treatment decision support for individual patients, accurate statistical models to predict locoregional relapse (LRR), distant relapse (DR), overall survival (OS), and disease-free survival (DFS) are required.

Methods And Materials: Clinical trial data from the randomized Post Operative Radiation Therapy for Endometrial Cancer (PORTEC-1; N=714 patients) and PORTEC-2 (N=427 patients) trials and registered group (grade 3 and deep invasion, n=99) were pooled for analysis (N=1240).

Nomogram predicting response after chemoradiotherapy in rectal cancer using sequential PETCT imaging: a multicentric prospective study with external validation.

Purpose: To develop and externally validate a predictive model for pathologic complete response (pCR) for locally advanced rectal cancer (LARC) based on clinical features and early sequential (18)F-FDG PETCT imaging.

Materials And Methods: Prospective data (i.a.

Multi-institutional pooled analysis on adjuvant chemoradiation in pancreatic cancer.

Purpose: To determine the impact of chemoradiation therapy (CRT) on overall survival (OS) after resection of pancreatic adenocarcinoma.

Methods And Materials: A multicenter retrospective review of 955 consecutive patients who underwent complete resection with macroscopically negative margins (R0-1) for invasive carcinoma (T1-4; N0-1; M0) of the pancreas was performed. Exclusion criteria included metastatic or unresectable disease at surgery, macroscopic residual disease (R2), treatment with intraoperative radiation therapy (IORT), and a histological diagnosis of no ductal carcinoma, or postoperative death (within 60 days of surgery).

International data-sharing for radiotherapy research: an open-source based infrastructure for multicentric clinical data mining.

Extensive, multifactorial data sharing is a crucial prerequisite for current and future (radiotherapy) research. However, the cost, time and effort to achieve this are often a roadblock. We present an open-source based data-sharing infrastructure between two radiotherapy departments, allowing seamless exchange of de-identified, automatically translated clinical and biomedical treatment data.

'Rapid Learning health care in oncology' - an approach towards decision support systems enabling customised radiotherapy'.

Purpose: An overview of the Rapid Learning methodology, its results, and the potential impact on radiotherapy.

Material And Results: Rapid Learning methodology is divided into four phases. In the data phase, diverse data are collected about past patients, treatments used, and outcomes.

Predicting outcomes in radiation oncology--multifactorial decision support systems.

With the emergence of individualized medicine and the increasing amount and complexity of available medical data, a growing need exists for the development of clinical decision-support systems based on prediction models of treatment outcome. In radiation oncology, these models combine both predictive and prognostic data factors from clinical, imaging, molecular and other sources to achieve the highest accuracy to predict tumour response and follow-up event rates. In this Review, we provide an overview of the factors that are correlated with outcome-including survival, recurrence patterns and toxicity-in radiation oncology and discuss the methodology behind the development of prediction models, which is a multistage process.

Radiomics: extracting more information from medical images using advanced feature analysis.

Solid cancers are spatially and temporally heterogeneous. This limits the use of invasive biopsy based molecular assays but gives huge potential for medical imaging, which has the ability to capture intra-tumoural heterogeneity in a non-invasive way. During the past decades, medical imaging innovations with new hardware, new imaging agents and standardised protocols, allows the field to move towards quantitative imaging.

Nomograms for predicting local recurrence, distant metastases, and overall survival for patients with locally advanced rectal cancer on the basis of European randomized clinical trials.

Purpose: The purpose of this study was to develop accurate models and nomograms to predict local recurrence, distant metastases, and survival for patients with locally advanced rectal cancer treated with long-course chemoradiotherapy (CRT) followed by surgery and to allow for a selection of patients who may benefit most from postoperative adjuvant chemotherapy and close follow-up.

Patients And Methods: All data (N = 2,795) from five major European clinical trials for rectal cancer were pooled and used to perform an extensive survival analysis and to develop multivariate nomograms based on Cox regression. Data from one trial was used as an external validation set.

PET-based treatment response evaluation in rectal cancer: prediction and validation.

Purpose: To develop a positron emission tomography (PET)-based response prediction model to differentiate pathological responders from nonresponders. The predictive strength of the model was validated in a second patient group, treated and imaged identical to the patients on which the predictive model was based.

Methods And Materials: Fifty-one rectal cancer patients were prospectively included in this study.

Development and external validation of a predictive model for pathological complete response of rectal cancer patients including sequential PET-CT imaging.

Purpose: To develop and validate an accurate predictive model and a nomogram for pathologic complete response (pCR) after chemoradiotherapy (CRT) for rectal cancer based on clinical and sequential PET-CT data. Accurate prediction could enable more individualised surgical approaches, including less extensive resection or even a wait-and-see policy.

Methods And Materials: Population based databases from 953 patients were collected from four different institutes and divided into three groups: clinical factors (training: 677 patients, validation: 85 patients), pre-CRT PET-CT (training: 114 patients, validation: 37 patients) and post-CRT PET-CT (training: 107 patients, validation: 55 patients).

The ESTRO Breur Lecture 2009. From population to voxel-based radiotherapy: exploiting intra-tumour and intra-organ heterogeneity for advanced treatment of non-small cell lung cancer.

Evidence is accumulating that radiotherapy of non-small cell lung cancer patients can be optimized by escalating the tumour dose until the normal tissue tolerances are met. To further improve the therapeutic ratio between tumour control probability and the risk of normal tissue complications, we firstly need to exploit inter patient variation. This variation arises, e.

Blood glucose level normalization and accurate timing improves the accuracy of PET-based treatment response predictions in rectal cancer.

Purpose: To quantify the influence of fluctuating blood glucose level (BGLs) and the timing of PET acquisition on PET-based predictions of the pathological treatment response in rectal cancer.

Material And Methods: Thirty patients, diagnosed with locally advanced-rectal-cancer (LARC), were included in this prospective study. Sequential FDG-PET-CT investigations were performed at four time points during and after pre-operative radiochemotherapy (RCT).

Evaluation of early metabolic responses in rectal cancer during combined radiochemotherapy or radiotherapy alone: sequential FDG-PET-CT findings.

Background And Purpose: The purpose of this study was to prospectively investigate metabolic changes of rectal tumors after 1 week of treatment of either radiochemotherapy (28 x 1.8 Gy+Capecitabine) (RCT) or hypofractionated radiotherapy (5 x 5 Gy) alone (RT).

Materials And Methods: Fourty-six rectal cancer patients, 25 RCT- and 21 RT-patients, were included in this study.

Accurate prediction of pathological rectal tumor response after two weeks of preoperative radiochemotherapy using (18)F-fluorodeoxyglucose-positron emission tomography-computed tomography imaging.

Purpose: To determine the optimal time point for repeated (18)F-fluorodeoxyglucose-positron emission tomography (PET)-CT imaging during preoperative radiochemotherapy (RCT) and the best predictive factor for the prediction of pathological treatment response in patients with locally advanced rectal cancer.

Methods And Materials: A total of 30 patients referred for preoperative RCT treatment were included in this prospective study. All patients underwent sequential PET-CT imaging at four time points: prior to therapy, at day 8 and 15 during RCT, and shortly before surgery.

Altered calcium handling is an early sign of streptozotocin-induced diabetic cardiomyopathy.

The main objective of the present study was to determine alterations of calcium handling in the diabetic rat heart during the transition from adaptive to maladaptive phase of cardiomyopathy. By inhibiting the nuclear enzyme poly(ADP-ribose) polymerase (PARP), we also investigated the possible role of this enzyme in the sequence of pathological events. Six weeks after induction of type I diabetes by injection of streptozotocin in rats, the hearts were perfused according to Langendorff.