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Abstract: Background and purpose: Currently, most available patient alignment tools based on implanted markers use manual marker matching and rigid registration transformations to measure the needed translational shifts. To quantify the particular effect of prostate gland shrinkage, implanted gold markers were tracked during a course of radiotherapy including an isotropic scaling factor to model prostate shrinkage. Materials and methods: Eight patients with prostate cancer had gold markers implanted transrectally and seven were treated with (neo) adjuvant androgen deprivation therapy. After patient alignment to skin tattoos, orthogonal electronic portal images (EPIs) were taken. A semi-automated 2D/3D marker-based registration was performed to calculate the necessary couch shifts. The registration consists of a rigid transformation combined with an isotropic scaling to model prostate shrinkage. Results: The inclusion of an isotropic shrinkage model in the registration algorithm cancelled the corresponding increase in registration error. The mean scaling factor was 0.89±0.09. For all but two patients, a decrease of the isotropic scaling factor during treatment was observed. However, there was almost no difference in the translation offset between the manual matching of the EPIs to the digitally reconstructed radiographs and the semi-automated 2D/3D registration. A decrease in the intermarker distance was found correlating with prostate shrinkage rather than with random marker migration. Conclusions: Inclusion of shrinkage in the registration process reduces registration errors during a course of radiotherapy. Nevertheless, this did not lead to a clinically significant change in the proposed table translations when compared to translations obtained with manual marker matching without a scaling correction. [Copyright &y& Elsevier]

Background: The primary objective of this study was to determine the maximum tolerated dose (MTD) of escalating doses of radiotherapy (RT) concomitantly with a fixed dose of gemcitabine (300 mg/m²/week) within the same overall treatment time. Methods: Thirteen patients were included. Gemcitabine 300 mg/m²/week was administered prior to RT. The initial dose of RT was 45 Gy in 1.8 Gy fractions, escalated by adding 5 fractions of 1.8 Gy (one/week) to a dose of 54 Gy with a total duration kept at 5 weeks. All patients received a dynamic MRI to assess the pancreatic respiratory related movements. Toxicity was scored using the RTOG-EORTC toxicity criteria. Results: Three of six patients experienced an acute dose limiting toxicity (DLT) at the 54 Gy dose level. For these patients a grade III gastro-intestinal toxicity (GI) was noted. Patients treated at the 45 Gy dose level tolerated therapy without DLT. The 54 Gy dose level was designated as the MTD and was deemed not suitable for further investigation. Between both dose levels, there was a significant difference in percentage weight loss (p = 0.006) and also in cumulative GI toxicity (p = 0.027). There was no grade 3 toxicity in the 45 Gy cohort versus 4 grade 3 toxicity events in the 54 Gy cohort. The mean dose to the duodenum was significantly higher in the 54 Gy cohort (38.45 Gy vs. 51.82 Gy; p = 0.001). Conclusion: Accelerated dose escalation to a total dose of 54 Gy with 300 mg/m²/week gemcitabine was not feasible. GI toxicity was the DLT. Retrospectively, the dose escalation of 9 Gy by accelerated radiotherapy might have been to large. A dose of 45 Gy is recommended. Considering the good patient outcomes, there might be a role for the investigation of a fixed dose of gemcitabine and concurrent RT with small fractions (1.8 Gy/day) in borderline resectable or unresectable non-metastatic locally advanced pancreatic cancer. [ABSTRACT FROM AUTHOR]

Abstract: The EORTC 22881-10882 trial in 5178 conservatively treated early breast cancer patients showed that a 16Gy boost dose significantly improved local control, but increased the risk of breast fibrosis. To investigate predictors for the long-term risk of fibrosis, Cox regression models of the time to moderate or severe fibrosis were developed on a random set of 1797 patients with and 1827 patients without a boost, and validated in the remaining set. The median follow-up was 10.7 years. The risk of fibrosis significantly increased (P <0.01) with increasing maximum whole breast irradiation (WBI) dose and with concomitant chemotherapy, but was independent of age. In the boost arm, the risk further increased (P <0.01) if patients had post-operative breast oedema or haematoma, but it decreased (P <0.01) if WBI was given with >6MV photons. The c-index was around 0.62. Nomograms with these factors are proposed to forecast the long-term risk of moderate or severe fibrosis. [Copyright &y& Elsevier]

Abstract: Introduction: EORTC trial 22991 was designed to evaluate the addition of concomitant and adjuvant short-term hormonal treatments to curative radiotherapy in terms of disease-free survival for patients with intermediate risk localized prostate cancer. In order to assess the compliance to the 3D conformal radiotherapy protocol guidelines, all participating centres were requested to participate in a dummy run procedure. An individual case review was performed for the largest recruiting centres as well. Materials and methods: CT-data of an eligible prostate cancer patient were sent to 30 centres including a description of the clinical case. The investigator was requested to delineate the volumes of interest and to perform treatment planning according to the protocol. Thereafter, the investigators of the 12 most actively recruiting centres were requested to provide data on five randomly selected patients for an individual case review. Results: Volume delineation varied significantly between investigators. Dose constraints for organs at risk (rectum, bladder, hips) were difficult to meet. In the individual case review, no major protocol deviations were observed, but a number of dose reporting problems were documented for centres using IMRT. Conclusions: Overall, results of this quality assurance program were satisfactory. The efficacy of the combination of a dummy run procedure with an individual case review is confirmed in this study, as none of the evaluated patient files harboured a major protocol deviation. Quality assurance remains a very important tool in radiotherapy to increase the reliability of the trial results. Special attention should be given when designing quality assurance programs for more complex irradiation techniques. [Copyright &y& Elsevier]