Per Munck af Rosenschöld

Radiobiological risk estimates of adverse events and secondary cancer for proton and photon radiation therapy of pediatric medulloblastoma.

Abstract Introduction. The aim of this model study was to estimate and compare the risk of radiation-induced adverse late effects in pediatric patients with medulloblastoma (MB) treated with either three-dimensional conformal radiotherapy (3D CRT), inversely-optimized arc therapy (RapidArc® (RA)) or spot-scanned intensity-modulated proton therapy (IMPT). The aim was also to find dose-volume toxicity parameters relevant to children undergoing RT to be used in the inverse planning of RA and IMPT, and to use in the risk estimations. Material and methods. Treatment plans were created for all three techniques on 10 pediatric patients that have been treated with craniospinal irradiation (CSI) at our institution in 2007–2009. Plans were generated for two prescription CSI doses, 23.4 Gy and 36 Gy. Risk estimates were based on childhood cancer survivor data when available and secondary cancer (SC) risks were estimated as a function of age at exposure and attained age according to the organ-equivalent dose (OED) concept. Results. Estimates of SC risk was higher for the RA plans and differentiable from the estimates for 3D CRT at attained ages above 40 years. The risk of developing heart failure, hearing loss, hypothyroidism and xerostomia was highest for the 3D CRT plans. The risks of all adverse effects were estimated as lowest for the IMPT plans, even when including secondary neutron (SN) irradiation with high values of the neutron radiation weighting factors (WRneutron). Conclusions. When comparing RA and 3D CRT treatment for pediatric MB it is a matter of comparing higher SC risk against higher risks of non-cancer adverse events. Considering time until onset of the different complications is necessary to fully assess patient benefit in such a comparison. The IMPT plans, including SN dose contribution, compared favorably to the photon techniques in terms of all radiobiological risk estimates.

Patient QA systems for rotational radiation therapy: A comparative experimental study with intentional errors

PURPOSE The purpose of the present study was to investigate the ability of commercial patient quality assurance (QA) systems to detect linear accelerator-related errors. METHODS Four measuring systems (Delta(4®), OCTAVIUS(®), COMPASS, and Epiqa™) designed for patient specific quality assurance for rotational radiation therapy were compared by measuring four clinical rotational intensity modulated radiation therapy plans as well as plans with introduced intentional errors. The intentional errors included increasing the number of monitor units, widening of the MLC banks, and rotation of the collimator. The measurements were analyzed using the inherent gamma evaluation with 2% and 2 mm criteria and 3% and 3 mm criteria. When applicable, the plans with intentional errors were compared with the original plans both by 3D gamma evaluation and by inspecting the dose volume histograms produced by the systems. RESULTS There was considerable variation in the type of errors that the various systems detected; the failure rate for the plans with errors varied between 0% and 72%. When using 2% and 2 mm criteria and 95% as a pass rate the Delta(4®) detected 15 of 20 errors, OCTAVIUS(®) detected 8 of 20 errors, COMPASS detected 8 of 20 errors, and Epiqa™ detected 20 of 20 errors. It was also found that the calibration and measuring procedure could benefit from improvements for some of the patient QA systems. CONCLUSIONS The various systems can detect various errors and the sensitivity to the introduced errors depends on the plan. There was poor correlation between the gamma evaluation pass rates of the QA procedures and the deviations observed in the dose volume histograms.

Real-time dynamic MLC tracking for inversely optimized arc radiotherapy

BACKGROUND AND PURPOSE Motion compensation with MLC tracking was tested for inversely optimized arc radiotherapy with special attention to the impact of the size of the target displacements and the angle of the leaf trajectory. MATERIALS AND METHODS An MLC-tracking algorithm was used to adjust the MLC positions according to the target movements using information from an optical real-time positioning management system. Two plans with collimator angles of 45 degrees and 90 degrees , respectively, were delivered and measured using the Delta(4)(R) dosimetric device moving in the superior-inferior direction with peak-to-peak displacements of 5, 10, 15, 20 and 25 mm and a cycle time of 6s. RESULTS Gamma index evaluation for plan delivery with MLC tracking gave a pass rate higher than 98% for criteria 3% and 3 mm for both plans and for all sizes of the target displacement. With no motion compensation, the average pass rate was 75% for plan 1 and 70% for plan 2 for 25 mm peak-to-peak displacement. CONCLUSION MLC tracking improves the accuracy of inversely optimized arc delivery for the cases studied. With MLC tracking, the dosimetric accuracy was independent of the magnitude of the peak-to-peak displacement of the target and not significantly affected by the angle between the leaf trajectory and the target movements.

Estimated clinical benefit of protecting neurogenesis in the developing brain during radiation therapy for pediatric medulloblastoma.

We sought to assess the feasibility and estimate the benefit of sparing the neurogenic niches when irradiating the brain of pediatric patients with medulloblastoma (MB) based on clinical outcome data. Pediatric MB survivors experience a high risk of neurocognitive adverse effects, often attributed to the whole-brain irradiation that is part of standard management. Neurogenesis is very sensitive to radiation, and limiting the radiation dose to the hippocampus and the subventricular zone (SVZ) may preserve neurocognitive function. Radiotherapy plans were created using 4 techniques: standard opposing fields, intensity-modulated radiotherapy (IMRT), intensity-modulated arc therapy (IMAT), and intensity-modulated proton therapy (IMPT). Mean dose to the hippocampus and SVZ (mean for both sites) could be limited to 88.3% (range, 83.6%-91.0%), 77.1% (range, 71.5%-81.3%), and 42.3% (range, 26.6%-51.2%) with IMAT, IMRT, and IMPT, respectively, while maintaining at least 95% of the prescribed dose in 95% of the whole-brain target volume. Estimated risks for developing memory impairment after a prescribed dose of 23.4 Gy were 47% (95% confidence interval [CI], 21%-69%), 44% (95% CI, 21%-65%), 41% (95% CI, 22%-60%), and 33% (95% CI, 23%-44%) with opposing fields, IMAT, IMRT, and IMPT, respectively. Neurogenic niche sparing during cranial irradiation of pediatric patients with MB is feasible and is estimated to lower the risks of long-term neurocognitive sequelae. Greatest sparing is achieved with intensity-modulated proton therapy, thus making this an attractive option to be tested in a prospective clinical trial.

Life years lost—comparing potentially fatal late complications after radiotherapy for pediatric medulloblastoma on a common scale

The authors developed a framework for estimating and comparing the risks of various long‐term complications on a common scale and applied it to 3 different techniques for craniospinal irradiation in patients with pediatric medulloblastoma.

A dosimetric comparison of real-time adaptive and non-adaptive radiotherapy: A multi-institutional study encompassing robotic, gimbaled, multileaf collimator and couch tracking.

Purpose A study of real-time adaptive radiotherapy systems was performed to test the hypothesis that, across delivery systems and institutions, the dosimetric accuracy is improved with adaptive treatments over non-adaptive radiotherapy in the presence of patient-measured tumor motion. Methods and materials Ten institutions with robotic(2), gimbaled(2), MLC(4) or couch tracking(2) used common materials including CT and structure sets, motion traces and planning protocols to create a lung and a prostate plan. For each motion trace, the plan was delivered twice to a moving dosimeter; with and without real-time adaptation. Each measurement was compared to a static measurement and the percentage of failed points for γ-tests recorded. Results For all lung traces all measurement sets show improved dose accuracy with a mean 2%/2 mm γ-fail rate of 1.6% with adaptation and 15.2% without adaptation (p < 0.001). For all prostate the mean 2%/2 mm γ-fail rate was 1.4% with adaptation and 17.3% without adaptation (p < 0.001). The difference between the four systems was small with an average 2%/2 mm γ-fail rate of <3% for all systems with adaptation for lung and prostate. Conclusions The investigated systems all accounted for realistic tumor motion accurately and performed to a similar high standard, with real-time adaptation significantly outperforming non-adaptive delivery methods.

ARTIFACTS IN CONVENTIONAL COMPUTED TOMOGRAPHY (CT) AND FREE BREATHING FOUR-DIMENSIONAL CT INDUCE UNCERTAINTY IN GROSS TUMOR VOLUME DETERMINATION

PURPOSE Artifacts impacting the imaged tumor volume can be seen in conventional three-dimensional CT (3DCT) scans for planning of lung cancer radiotherapy but can be reduced with the use of respiration-correlated imaging, i.e., 4DCT or breathhold CT (BHCT) scans. The aim of this study was to compare delineated gross tumor volume (GTV) sizes in 3DCT, 4DCT, and BHCT scans of patients with lung tumors. METHODS AND MATERIALS A total of 36 patients with 46 tumors referred for stereotactic radiotherapy of lung tumors were included. All patients underwent positron emission tomography (PET)/CT, 4DCT, and BHCT scans. GTVs in all CT scans of individual patients were delineated during one session by a single physician to minimize systematic delineation uncertainty. The GTV size from the BHCT was considered the closest to true tumor volume and was chosen as the reference. The reference GTV size was compared to GTV sizes in 3DCT, at midventilation (MidV), at end-inspiration (Insp), and at end-expiration (Exp) bins from the 4DCT scan. RESULTS The median BHCT GTV size was 4.9 cm(3) (0.1-53.3 cm(3)). Median deviation between 3DCT and BHCT GTV size was 0.3 cm(3) (-3.3 to 30.0 cm(3)), between MidV and BHCT size was 0.2 cm(3) (-5.7 to 19.7 cm(3)), between Insp and BHCT size was 0.3 cm(3) (-4.7 to 24.8 cm(3)), and between Exp and BHCT size was 0.3 cm(3) (-4.8 to 25.5 cm(3)). The 3DCT, MidV, Insp, and Exp median GTV sizes were all significantly larger than the BHCT median GTV size. CONCLUSIONS In the present study, the choice of CT method significantly influenced the delineated GTV size, on average, leading to an increase in GTV size compared to the reference BHCT. The uncertainty caused by artifacts is estimated to be in the same magnitude as delineation uncertainty and should be considered in the design of margins for radiotherapy.

Kilovoltage x-ray dosimetry?an experimental comparison between different dosimetry protocols

Kilovoltage dosimetry protocols by the IAEA (TRS-277 and TRS-398), DIN (6809), IPEMB (with addendum), AAPM (TG-61) and NCS (report 10) were compared experimentally in four clinical beams. The beams had acceleration potentials of 30, 80, 120 and 200 kV, with half-value layers ranging from 0.6 mm Al to 1 mm Cu. Dosimetric measurements were performed and data were collected under reference conditions as stipulated within each separate protocol under investigation. The Monte Carlo method was used to derive backscatter factors for the actual x-ray machine. In general, the agreement of the dosimetric data at the surface of a full-scatter water phantom obtained using the guidelines of the various protocols was fairly good, i.e. within 1-2%. However, the in-air calibration method using the IPEMB and AAPM TG-61 protocols yielded an absorbed dose about 7% lower than the IAEA TRS-398 protocol in the 120 kV beam. By replacing the backscatter factors given in the protocols with Monte Carlo calculated backscatter factors, the convergence between the protocols improved (within 4%). The internal consistency obtained for protocols supporting more than one geometry for dosimetry under reference conditions was better than 0.2% for the DIN protocol (120 kV beam), 2-3% for the AAPM TG-61 (120 and 200 kV beams) and about 2% for the IPEMB protocol (200 kV beam). The present study shows that the current-supported dosimetry protocols in the kilovoltage range were in fairly good agreement, and there were only a few exceptions of clinical significance.

A treatment planning and delivery comparison of volumetric modulated arc therapy with or without flattening filter for gliomas, brain metastases, prostate, head/neck and early stage lung cancer

Abstract Background. Flattening filter-free (FFF) beams are an emerging technology that has not yet been widely implemented as standard practice in radiotherapy centers. To facilitate the clinical implementation of FFF, we attempted to elucidate the difference in plan quality and treatment delivery time compared to flattening filter beams (i.e. standard, STD) for several patient groups. We hypothesize that the treatment plan quality is comparable while the treatment delivery time of volumetric modulated arc therapy (VMAT) is considerably shorter using FFF beams, especially for stereotactic treatments. Methods. A total of 120 patients treated for head and neck (H&N) tumors, high-grade glioma, prostate cancer, early stage lung cancer and intra-cranial metastatic disease (both single and multiple metastases) were included in the study. For each cohort, 20 consecutive patients were selected. The plans were generated using STD- and FFF-VMAT for both 6 MV and 10 MV, and were compared with respect to plan quality, monitor units and delivery time using Wilcoxon signed rank tests. Results. For H&N and high-grade gliomas, there was a significant difference in homogeneity index in favor for STD-VMAT (p < 0.001). For the stereotactic sites there were no differences in plan conformity. Stereotactic FFF-VMAT plans required significantly shorter delivery time compared to STD-VMAT plans (p < 0.001) for higher dose per fraction, on average 54.5% for 6 MV and 71.4% for 10 MV. FFF-VMAT generally required a higher number of MU/Gy (p < 0.001), on average 7.0% for 6 MV and 8.4% for 10 MV. Conclusion. It was generally possible to produce FFF-VMAT plans with the same target dose coverage and doses to organs at risk as STD-VMAT plans. Target dose homogeneity tended to be somewhat inferior for FFF-VMAT for the larger targets investigated. For stereotactic radiotherapy, FFF-VMAT resulted in a considerable time gain while maintaining similar plan quality compared to STD beams.

Injectable Colloidal Gold for Use in Intrafractional 2D Image-Guided Radiation Therapy

In the western world, approximately 50% of all cancer patients receive radiotherapy alone or in combination with surgery or chemotherapy. Image-guided radiotherapy (IGRT) has in recent years been introduced to enhance precision of the delivery of radiation dose to tumor tissue. Fiducial markers are often inserted inside the tumor to improve IGRT precision and to enable monitoring of the tumor position during radiation therapy. In the present article, a liquid fiducial tissue marker is presented, which can be injected into tumor tissue using thin and flexible needles. The liquid fiducial has high radio-opacity, which allows for marker-based image guidance in 2D and 3D X-ray imaging during radiation therapy. This is achieved by surface-engineering gold nanoparticles to be highly compatible with a carbohydrate-based gelation matrix. The new fiducial marker is investigated in mice where they are highly biocompatible and stable after implantation. To investigate the clinical potential, a study is conducted in a canine cancer patient with spontaneous developed solid tumor in which the marker is successfully injected and used to align and image-guide radiation treatment of the canine patient. It is concluded that the new fiducial marker has highly interesting properties that warrant investigations in cancer patients.