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Background and Purpose: In this study, we explore the quality aspects of radiation care from the patient's perspective in order to develop a draft Consumer Quality Index (CQI) Radiation Care instrument., Materials and Methods: Four focus group discussions with (former) cancer patients were held to explore the aspects determining the quality of radiation care. The list of aspects generated was categorised based on similarity and importance in a concept mapping procedure., Results: Four focus group discussions revealed seven main themes related to the quality of radiation care: information provision, a patient-centred approach, professional competence, planning and waiting times, accessibility, cooperation and communication, and follow-up care. Results of concept mapping procedures revealed which items the patients considered to be most important. A radiation oncologist who is up to date about the patient's file is of paramount importance for cancer patients receiving radiotherapy., Conclusions: The quality aspects found through focus group discussions provided useful insight into how patients experience radiation care. Furthermore, concept mapping made these results more solid. To evaluate the quality of radiation care from the patient's perspective, these quality aspects will be guiding in the development of a CQI Radiation Care., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Our increased understanding of the molecular processes underlying cellular sensitivity to ionizing radiation has led to the identification of novel targets for intervention. New agents have become available for combined use to overcome radioresistance and enhance the clinical efficacy of radiotherapy. This rational selection of potential radiosensitizers contrasts with the empirical approach that has dominated the field of chemo-radiotherapy over the last decades. It allows the identification of those patients who will benefit most from a specific combination by exploiting new predictive biomarkers of response. In this review we present several approaches of targeted radiosensitization and discuss the available in vitro and in vivo results that support their translation into clinical trials. We focus on EGFR-inhibiting, anti-angiogenic, apoptosis-modulating and PARP-interfering strategies., (2010 Elsevier Ltd. All rights reserved.)

Background and purpose: In this study we developed a workflow for fully-automated generation of deliverable IMRT plans for a 1.5 T MR-Linac (MRL) based on contoured CT scans, and we evaluated automated MRL planning for rectal cancer. Methods: The Monte Carlo dose calculation engine used in the clinical MRL TPS (Monaco, Elekta AB, Stockholm, Sweden), suited for high accuracy dose calculations in a 1.5 T magnetic field, was coupled to our in-house developed Erasmus-iCycle optimizer. Clinically deliverable plans for 23 rectal cancer patients were automatically generated in a two-step process, i.e., multi-criterial fluence map optimization with Erasmus-iCycle followed by a conversion into a deliverable IMRT plan in the clinical TPS. Automatically generated plans (AUTOplans) were compared to plans that were manually generated with the clinical TPS (MANplans). Results: With AUTOplanning large reductions in planning time and workload were obtained; 4–6 h mainly hands-on planning for MANplans vs ∼1 h of mainly computer computation time for AUTOplans. For equal target coverage, the bladder and bowel bag Dmean was reduced in the AUTOplans by 1.3 Gy (6.9%) on average with a maximum reduction of 4.5 Gy (23.8%). Dosimetric measurements at the MRL demonstrated clinically acceptable delivery accuracy for the AUTOplans. Conclusions: A system for fully automated multi-criterial planning for a 1.5 T MR-Linac was developed and tested for rectal cancer patients. Automated planning resulted in major reductions in planning workload and time, while plan quality improved. Negative impact of the high magnetic field on the dose distributions could be avoided. [ABSTRACT FROM AUTHOR]

Purpose There is an increasing interest for dose differentiation in prostate radiotherapy. The purpose of our study was to analyze the spatial distribution of tumor satellites inside the prostate. Methods and materials 61 prostatectomy specimens were stained with H&E. Tumor regions were delineated by the uro-pathologist. Volumes, distances and cell densities of all delineated tumor regions were measured and further analyzed. Results Multifocal disease was seen in 84% of the patients. The median number of tumor foci was 3. The median distance between the index lesion and the satellites was 1.0 cm, with a maximum of 4.4 cm. The index lesions accounted for 88% of the total tumor volume. The contribution of tumor foci < 0.1 cm 3 to the total tumor volume was 2%. The median cell density of the index lesion and all satellites, regardless of size, were significantly higher than that of the prostate. Conclusions Satellites do not appear in a limited margin around the index lesion (GTV). Consequently, a fixed CTV margin would not effectively cover all satellites. Thus if the aim is to treat all tumor foci, the entire prostate gland should be considered CTV. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy is one of the mainstays in the treatment for cancer, but its success can be limited due to inherent or acquired resistance. Mechanisms underlying radioresistance in various cancers are poorly understood and available radiosensitizers have shown only modest clinical benefit. There is thus a need to identify new targets and drugs for more effective sensitization of cancer cells to irradiation. Compound and RNA interference high-throughput screening technologies allow comprehensive enterprises to identify new agents and targets for radiosensitization. However, the gold standard assay to investigate radiosensitivity of cancer cells in vitro, the colony formation assay (CFA), is unsuitable for high-throughput screening. Methods: We developed a new high-throughput screening method for determining radiation susceptibility. Fast and uniform irradiation of batches up to 30 microplates was achieved using a Perspex container and a clinically employed linear accelerator. The readout was done by automated counting of fluorescently stained nuclei using the Acumen eX3 laser scanning cytometer. Assay performance was compared to that of the CFA and the CellTiter-Blue homogeneous uniform-well cell viability assay. The assay was validated in a whole-genome siRNA library screening setting using PC-3 prostate cancer cells. Results: On 4 different cancer cell lines, the automated cell counting assay produced radiation dose response curves that followed a linear-quadratic equation and that exhibited a better correlation to the results of the CFA than did the cell viability assay. Moreover, the cell counting assay could be used to detect radiosensitization by silencing DNA-PKcs or by adding caffeine. In a high-throughput screening setting, using 4 Gy irradiated and control PC-3 cells, the effects of DNA-PKcs siRNA and non-targeting control siRNA could be clearly discriminated. Conclusions: We developed a simple assay for radiation susceptibility that can be used for high-throughput screening. This will aid the identification of molecular targets for radiosensitization, thereby contributing to improving the efficacy of radiotherapy. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To evaluate the safety and efficacy of an absorbable hydrogel when injected between the rectum and prostate to reduce rectal radiation toxicity in adult men undergoing Intensity Modulated Radiotherapy (IMRT) for treatment of low and intermediate risk prostate cancer. Methods: This prospective, non-randomized, multi-center, single arm, open-label study included 52 men with a confirmed diagnosis of prostate cancer. They received transperineal injection of the hydrogel and 3–5days after injection the simulation scans. All patients received IMRT (78Gy delivered, 2Gy per fraction). Space stability was evaluated by using MRI or CT. Gastrointestinal (GI) and genitourinary (GU) toxicity was assessed using RTOG/EORTC scoring system and proctoscopy after 12months. The median follow up time was 12months. Results: Hydrogel application was straight forward using brachytherapy equipment and techniques, with minimal patient discomfort. Six patients (12%) experienced acute GI Grade 2 toxicity, with no patients experiencing Grade 3 or 4 toxicity. In addition, no patients had early late GI toxicity⩾Grade 2 after 12months. The gel was stable during the course of radiotherapy and was not detectable in MRI after 9–12months due to absorption in 42 of 43 patients. Conclusion: These data demonstrated that the hydrogel is a safe method to displace the rectal wall away from the prostate therefore substantially reducing toxicity to the rectum. [Copyright &y& Elsevier]

Purpose: To compare conformal radiotherapy (CRT), intensity-modulated radiotherapy (IMRT), and respiration-gated radiotherapy (RGRT) planning techniques for pancreatic cancer. All target volumes were determined using four-dimensional computed tomography scans (4D CT). Methods and Materials: The pancreatic tumor and enlarged regional lymph nodes were contoured on all 10 phases of a planning 4D CT scan for 10 patients, and the planning target volumes (PTVall phases) were generated. Three consecutive respiratory phases for RGRT delivery in both inspiration and expiration were identified, and the corresponding PTVs (PTVinspiration and PTVexpiration) and organ at risk volumes created. Treatment plans using CRT and IMRT, with and without RGRT, were created for each PTV. Results: Compared with the CRT plans, IMRT significantly reduced the mean volume of right kidney exposed to 20 Gy from 27.7% ± 17.7% to 16.0% ± 18.2% (standard deviation) (p < 0.01), but this was not achieved for the left kidney (11.1% ± 14.2% to 5.7% ± 6.5%; p = 0.1). The IMRT plans also reduced the mean gastric, hepatic, and small bowel doses (p < 0.01). No additional reductions in the dose to the kidneys or other organs at risk were seen when RGRT plans were combined with either CRT or IMRT, and the findings for RGRT in end-expiration and end-inspiration were similar. Conclusion: 4D CT–based IMRT plans for pancreatic tumors significantly reduced the radiation doses to the right kidney, liver, stomach, and small bowel compared with CRT plans. The additional dosimetric benefits from RGRT appear limited in this setting. [Copyright &y& Elsevier]

Background PARP inhibitors are currently evaluated in combination with radiotherapy and/or chemotherapy. As sensitizers, PARP inhibitors are active at very low concentrations therefore requiring highly sensitive pharmacodynamic (PD) assays. Current clinical PD-assays partly fail to provide such sensitivities. The aim of our study was to enable sensitive PD evaluation of PARP inhibitors for clinical sensitizer development. Material and methods PBMCs of healthy individuals and of olaparib and radiotherapy treated lung cancer patients were collected for ELISA-based PD-assays. Results PAR-signal amplification by ex vivo irradiation enabled an extended quantification range for PARP inhibitory activities after ex vivo treatment with inhibitors. This “radiation-enhanced-PAR” (REP) assay provided accurate IC50 values thereby also revealing differences among healthy individuals. Implemented in clinical radiotherapy combination Phase I trials, the REP-assay showed sensitive detection of PARP inhibition in patients treated with olaparib and establishes strong PARP inhibitory activities at low daily doses. Conclusions Combination trials of radiotherapy and novel targeted agent(s) often require different and more sensitive PD assessments than in the monotherapy setting. This study shows the benefit and relevance of sensitive and adapted PD-assays for such combination purposes and provides proof of clinically relevant cellular PARP inhibitory activities at low daily olaparib doses. [ABSTRACT FROM AUTHOR]

The master protocol trial design aims to increase efficiency in terms of trial infrastructure and protocol administration which may accelerate development of (technical) innovations in radiation oncology. A master protocol to study feasibility of techniques/software for MR-guided adaptive radiotherapy with the MR-Linac is described and discussed. [ABSTRACT FROM AUTHOR]

Purpose To assess early changes in rectal tumor volume and morphology on sequential MRIs performed during 5 weeks of chemoradiotherapy. Materials and methods Thirteen patients underwent weekly T2W-MRI during 5 weeks of preoperative radiotherapy (total 50 Gy), starting after the first week of radiation. Two radiologists visually evaluated tumor volume and morphology and one reader manually segmented tumors for each time point to quantitatively calculate tumor volumes. Evolution in tumor volume/morphology was assessed over time and compared between good responders (tumor regression grade (TRG) 1–2) and poor responders (TRG 3–5). Results Tumor volumes decreased significantly during radiation. Early signs of response were also visually apparent: in the majority of good responders an early fibrotic transformation (week 2–3) as well as a visually estimated early volume reduction of >1/3 (week 1–2), was observed while these early changes only occurred in a minority of poor responders. Conclusion Results of this exploratory pilot study suggest that changes in rectal tumor morphology (fibrosis) and volume can already be observed early during radiation, both when measured quantitatively and when assessed visually. These changes appear to be indicative of the final treatment outcome. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the toxicity and efficacy of the combination of external beam radiation therapy (EBRT) followed by high-dose-rate endorectal brachytherapy (HDREBT) boost in elderly and medically inoperable patients with rectal cancer.Methods and Materials: A phase 1 dose-escalation study was performed. Treatment consisted of EBRT (13 × 3 Gy) followed by 3 weekly brachytherapy applications 6 weeks later. The HDREBT dose started at 5 Gy per fraction, increasing with 1 Gy per fraction if dose-limiting toxicity (DLT, defined as grade ≥3 proctitis <6 weeks after HDREBT) occurred in ≤2 patients per dose level. The primary endpoint was the maximum tolerated dose, defined as 1 dose level below the dose at which 3 patients experienced DLT. Secondary endpoints were toxicity, clinical tumor response, freedom from local progression, and local progression-free and overall survival (L-PFS and OS).Results: Thirty-eight patients with a median age of 83 years were included in the study. Thirty-two were evaluable for DLT and late toxicity and 33 for response evaluation. Maximum delivered dose was 8 Gy per fraction, resulting in a recommended dose of 7 Gy per fraction. Response occurred in 29 of 33 patients (87.9%), with 60.6% complete response (CR). The L-PFS and OS rates were 42% and 63%, respectively, at 2 years. Patients with CR showed a significantly improved L-PFS (60% at 2 years, P=.006) and a trend in improved OS (80% at 2 years, P=.11). Severe late toxicity occurred in 10 of 32 patients.Conclusion: We found that HDREBT after EBRT results in a high overall response rate, with improved L-PFS for patients with a CR. The high observed rate of severe late toxicity requires further evaluation of the risks and benefits of an HDREBT boost. [ABSTRACT FROM AUTHOR]

Purpose: Respiratory gating can mitigate the effect of tumor mobility in radiotherapy (RT) for lung cancer. Because the tumor is generally not visualized, external surrogates of tumor position are used to trigger respiration-gated RT. We evaluated the suitability of the carina position as a surrogate in respiration-gated RT. Methods and Materials: A total of 30 four-dimensional (4D) computed tomography (CT) scans from 14 patients with lung cancer were retrospectively analyzed. Both uncoached (free breathing) and audio-coached 4D-CT scans were acquired from 9 patients, and 12 uncoached 4D-CT scans were acquired from 5 other patients during a 2–4-week period of stereotactic RT. The repeat scans were co-registered. The carina position was identified on the coronal cut planes in all 4D-CT phases. The correlation between the carina position and the total lung volume for each phase was determined, and the reproducibility of the carina position was studied in the 5 patients with repeat uncoached 4D-CT scans. Results: The mean extent of carina motion in 21 uncoached scans was 5.3 ± 1.6 mm in the craniocaudal (CC), 2.3 ± 1.4 mm in the anteroposterior, and 1.5 ± 0.7 mm in the mediolateral direction. Audio coaching resulted in a twofold increase in carina mobility in all directions. The CC carina position correlated with changes in the total lung volume (R = 0.89 ± 0.14), but the correlation was better for the audio-coached than for the uncoached 4D-CT scans (R = 0.93 ± 0.08 vs. R = 0.85 ± 0.17; paired t test, p = 0.034). Preliminary data from the 5 patients indicated that the CC carina motion correlated better with tumor motion than did the motion of the diaphragm. Conclusions: The CC position of the carina correlated well with the total lung volume, indicating that the carina is a good surrogate for verifying the total lung volume during respiration-gated RT. [Copyright &y& Elsevier]