Vijayananda Kundapur

Preservation of Memory With Conformal Avoidance of the Hippocampal Neural Stem-Cell Compartment During Whole-Brain Radiotherapy for Brain Metastases (RTOG 0933): A Phase II Multi-Institutional Trial

PURPOSE Hippocampal neural stem-cell injury during whole-brain radiotherapy (WBRT) may play a role in memory decline. Intensity-modulated radiotherapy can be used to avoid conformally the hippocampal neural stem-cell compartment during WBRT (HA-WBRT). RTOG 0933 was a single-arm phase II study of HA-WBRT for brain metastases with prespecified comparison with a historical control of patients treated with WBRT without hippocampal avoidance. PATIENTS AND METHODS Eligible adult patients with brain metastases received HA-WBRT to 30 Gy in 10 fractions. Standardized cognitive function and quality-of-life (QOL) assessments were performed at baseline and 2, 4, and 6 months. The primary end point was the Hopkins Verbal Learning Test-Revised Delayed Recall (HVLT-R DR) at 4 months. The historical control demonstrated a 30% mean relative decline in HVLT-R DR from baseline to 4 months. To detect a mean relative decline ≤ 15% in HVLT-R DR after HA-WBRT, 51 analyzable patients were required to ensure 80% statistical power with α = 0.05. RESULTS Of 113 patients accrued from March 2011 through November 2012, 42 patients were analyzable at 4 months. Mean relative decline in HVLT-R DR from baseline to 4 months was 7.0% (95% CI, -4.7% to 18.7%), significantly lower in comparison with the historical control (P < .001). No decline in QOL scores was observed. Two grade 3 toxicities and no grade 4 to 5 toxicities were reported. Median survival was 6.8 months. CONCLUSION Conformal avoidance of the hippocampus during WBRT is associated with preservation of memory and QOL as compared with historical series.

Risk of Hippocampal Metastases in Small Cell Lung Cancer Patients at Presentation and After Cranial Irradiation: A Safety Profile Study for Hippocampal Sparing During Prophylactic or Therapeutic Cranial Irradiation

PURPOSE Neurocognitive impairment (NI) in patients with small cell lung cancer (SCLC) after whole brain radiation treatment (WBRT) is a significant cause of morbidity. Hippocampal avoidance (HA) during WBRT may mitigate or prevent NI in such patients. However, this has not been tested in SCLC patients. The estimated risk of metastases in the HA region (HM) in patients with SCLC at diagnosis or after WBRT is unknown. Our study aimed to determine the risk of HM in patients with SCLC and to assess correlated clinical factors. METHODS AND MATERIALS Patients with SCLC who experienced brain metastases (BM) at presentation (de novo) or after WBRT treated at the Saskatoon Cancer Centre between 2005 and 2012 were studied. Relevant neuroimaging was independently reviewed by a neuroradiologist. HM was defined as metastases within 5 mm of the hippocampus. Logistic regression analysis was performed to assess correlation between various clinical variables and HM. RESULTS Seventy eligible patients were identified. Of 59 patients presenting with de novo BM, 3 patients (5%, 95% confidence interval [CI]: 0%-10.7%) had HM. Collectively there were 359 (range, 1-33) de novo BM with 3 (0.8%, 95% CI: 0%-1.7%) HM deposits. Twenty patients experienced progression of metastatic disease in the brain after WBRT. Of the 20 patients, only 1 patient (5%, 95% CI: 0%-14.5%) experienced HM. On logistic regression, no factors significantly correlated with HM. CONCLUSION The overall incidence of HM before or after WBRT in SCLC patients is low, providing preliminary support for the safety of HA during planned clinical trials of HA-WBRT for SCLC.

Planning Target Volume Margin Evaluation and Critical Structure Sparing for Rectal Cancer Patients Treated Prone on a Bellyboard

AIMS To calculate a planning target volume (PTV) margin that would account for inter-fractional systematic and random clinical target volume positional errors for patients treated prone on a recently available couch top bellyboard and to evaluate potential critical structure dose reduction using intensity-modulated radiotherapy (IMRT) techniques. MATERIALS AND METHODS Twenty-four patients (12 men and 12 women) were included in this study, all treated on a commercial bellyboard. Cone beam computed tomography (CBCT) data were acquired once every five fractions for a total of five images per patient. A three-dimensional-three-dimensional bony anatomy auto-match was carried out off-line and the residual difference in position used as a surrogate for clinical target volume inter-fractional positional errors. Systematic (Σ) and random (σ) variations were evaluated and used in PTV(margin)=1.96Σ+0.7σ. The influence of intra-fractional positional errors was evaluated in the margin analysis by introducing published values. Critical structure sparing, as a function of PTV(margin) size, was investigated through the evaluation of three-dimensional conformal radiation therapy (3DCRT) and IMRT treatment plans developed using the margin derived from this work, the American Society for Radiation Oncology Contouring Atlas and the Radiation Therapy Oncology Group 0822 trial specifications. RESULTS The PTV(margin) that accounts for only the inter-fractional positional errors was calculated to be (anterior-posterior (AP), superior-inferior (SI), left-right (LR))=(5.2mm, 3.1mm, 2.8mm). If we assumed a combined intra-fractional motion up to 3.0mm then the required PTV(margin) increased to (AP, SI, LR)=(7.0mm, 5.0mm, 5.0mm). Treatment plan evaluation showed that the bellyboard provides excellent small bowel sparing regardless of planning technique. In most cases, IMRT reduced the average femoral head, bladder and small bowel dose by 20, 15 and 40% with respect to 3DCRT planning. CONCLUSION A PTV(margin) expansion of (AP, SI, LR)=(7.0mm, 5.0mm, 5.0mm) is required to account for all positional uncertainties. The use of a bellyboard with IMRT provides better critical structure sparing when compared with a bellyboard with 3DCRT.

Using kV-kV and CBCT imaging to evaluate rectal cancer patient position when treated prone on a newly available belly board

The goal of this work was to use daily kV-kV imaging and weekly cone-beam CT (CBCT) to evaluate rectal cancer patient position when treated on a new couch top belly board (BB). Quality assurance (QA) of the imaging system was conducted weekly to ensure proper performance. The positional uncertainty of the combined kV-kV image match and subsequent couch move was found to be no more than ± 1.0 mm. The average (1 SD) CBCT QA phantom match was anterior-posterior (AP) = -0.8 ± 0.2 mm, superior-inferior (SI) = 0.9 ± 0.2 mm, and left-right (LR) = -0.1 ± 0.1 mm. For treatment, a set of orthogonal kV-kV images were taken and a bony anatomy match performed online. Moves were made along each axis (AP, SI, and LR) and recorded for analysis. CBCT data were acquired once every 5 fractions for a total of 5 images per patient. The images were all taken after the couch move but before treatment. A 3-dimensional (3D-3D) bony anatomy auto-match was performed offline and the residual difference in position recorded for analysis. The average (± 1 SD) move required from skin marks, calculated over all 375 fractions (15 patients × 25 fractions/patient), were AP = -2.6 ± 3.7 mm, SI = -0.3 ± 4.9 mm, and LR = 1.8 ± 4.5 mm. The average residual difference in patient position calculated from the weekly CBCT data (75 total) were AP = -1.7 ± 0.4 mm, SI = 1.1 ± 0.6 mm, and LR = -0.5 ± 0.2 mm. These results show that the BB does provide simple patient positioning that is accurate to within ± 2.0 mm when using online orthogonal kV-kV image matching of the pelvic bony anatomy.

Collimator design for experimental minibeam radiation therapy

PURPOSE To design and optimize a minibeam collimator for minibeam radiation therapy studies using a 250 kVp x-ray machine as a simulated synchrotron source. METHODS A Philips RT250 orthovoltage x-ray machine was modeled using the EGSnrc/BEAMnrc Monte Carlo software. The resulting machine model was coupled to a model of a minibeam collimator with a beam aperture of 1 mm. Interaperture spacing and collimator thickness were varied to produce a minibeam with the desired peak-to-valley ratio. RESULTS Proper design of a minibeam collimator with Monte Carlo methods requires detailed knowledge of the x-ray source setup. For a cathode-ray tube source, the beam spot size, target angle, and source shielding all determine the final valley-to-peak dose ratio. CONCLUSIONS A minibeam collimator setup was created, which can deliver a 30 Gy peak dose minibeam radiation therapy treatment at depths less than 1 cm with a valley-to-peak dose ratio on the order of 23%.

Patient-Reported Toxicity During Pelvic Intensity-Modulated Radiation Therapy: NRG Oncology–RTOG 1203

Purpose NRG Oncology/RTOG 1203 was designed to compare patient-reported acute toxicity and health-related quality of life during treatment with standard pelvic radiation or intensity-modulated radiation therapy (IMRT) in women with cervical and endometrial cancer. Methods Patients were randomly assigned to standard four-field radiation therapy (RT) or IMRT radiation treatment. The primary end point was change in patient-reported acute GI toxicity from baseline to the end of RT, measured with the bowel domain of the Expanded Prostate Cancer Index Composite (EPIC). Secondary end points included change in patient-reported urinary toxicity, change in GI toxicity measured with the Patient-Reported Outcome Common Terminology Criteria for Adverse Events, and quality of life measured with the Trial Outcome Index. Results From 2012 to 2015, 289 patients were enrolled, of whom 278 were eligible. Between baseline and end of RT, the mean EPIC bowel score declined 23.6 points in the standard RT group and 18.6 points in the IMRT group ( P = .048), the mean EPIC urinary score declined 10.4 points in the standard RT group and 5.6 points in the IMRT group ( P = .03), and the mean Trial Outcome Index score declined 12.8 points in the standard RT group and 8.8 points in the IMRT group ( P = .06). At the end of RT, 51.9% of women who received standard RT and 33.7% who received IMRT reported frequent or almost constant diarrhea ( P = .01), and more patients who received standard RT were taking antidiarrheal medications four or more times daily (20.4% v 7.8%; P = .04). Conclusion Pelvic IMRT was associated with significantly less GI and urinary toxicity than standard RT from the patients perspective.

Medical linear accelerator mounted mini-beam collimator: design, fabrication and dosimetric characterization.

The goal of this work was to design, build and experimentally characterize a linear accelerator mounted mini-beam collimator for use at a nominal 6 MV beam energy. Monte Carlo simulation was used in the design and dosimetric characterization of a compact mini-beam collimator assembly mounted to a medical linear accelerator. After fabrication, experimental mini-beam dose profiles and central axis relative output were measured and the results used to validate the simulation data. The simulation data was then used to establish traceability back to an established dosimetric code of practice. The Monte Carlo simulation work revealed that changes in collimator blade width have a greater influence on the valley-to-peak dose ratio than do changes in blade height. There was good agreement between the modeled and measured profile data, with the exception of small differences on either side of the central peak dose. These differences were found to be systematic across all depths and result from limitations associated with the collimator fabrication. Experimental mini-beam relative output and simulation data agreed to better than ± 2.0%, which is well within the level of uncertainty required for dosimetric traceability of non-standard field geometries. A mini-beam collimator has now been designed, built and experimentally characterized for use with a commercial linear accelerator operated at a nominal 6 MV beam energy.

Sci-Thur PM – Colourful Interactions: Highlights 01: Design to delivery of spatially fractionated mini-beam canine radiotherapy

Spatial fractionation of radiation using arrays of narrow parallel micro-planar beams (less than 1 mm), is a relatively new concept with many unknowns specifically within the underlying biology of cell death. A tungsten collimator has been designed to produce mini-beams with a Varian linear accelerator for translational animal research into the effectiveness of spatial fractionation mini-beam radiotherapy (MBRT). This work presents the treatment planning process and workflow for the application of MBRT treatments within a clinical study. For patient dose calculations, the MBRT collimator was incorporated into a Monte Carlo based treatment planning system called MMCTP. Treatment planning was split between Eclipse and MMCTP, as the field apertures were determined within Eclipse prior to being sent to MMCTP for dose calculations. The calculated plan was transferred back into Aria with updated MUs per field for patient treatment. Patients were positioned within a vac-lock bag lying prone with a bite block and a thermoplastic mask to immobilize the head. Prior to treatment, a delivery verification plan was created within MMCTP. DQA output measurements of the treatment fields agreed with the calculated dose to within 1.5%. We have presented a workflow for MBRT treatments that include the planning technique, dose calculation method, DQA process and data integration into a record and verify system. The clinical study following this workflow represent the first series of linac based MBRT patients and depending on the clinical outcome of the study, our technique could be applied to human MBRT treatments.

Poster - 23: Dosimetric Characterization and Transferability of an Accessory Mounted Mini-Beam Collimator

Objective: The dosimetric characterization of an accessory-mounted mini-beam collimator across three beam matched linear accelerators. Materials and Methods: Percent depth dose and profiles were measured for the open and mini-beam collimated fields. The average beam quality and peak-to-valley dose ratio (PVDR), the ratio of average peak dose to average valley dose, were obtained from these measurements. The open field relative output and the mini-beam collimator factor, the ratio of the mini-beam dose to open field dose at the beam center, were measured for square fields of side 2, 3, 4, and 5 cm. Mini-beam output as a function of collimator inclination angle relative to the central axis was also investigated. Results and Discussion: Beam quality for both the open and mini-beam collimated fields agreed across all linacs to within ±1.0%. The PVDR was found to vary by up to ±6.6% from the mean. For the 2, 3, and 4 cm fields the average open field relative output with respect to the 5 cm field was 0.874±0.4%, 0.921±0.3%, and 0.962±0.1%. The average collimator factors were 0.450±3.9%, 0.443±3.9%, 0.438±3.9%, and 0.434±3.9%. A decrease in collimator factor greater than 7% was found for an inclination angle change of 0.09°. Conclusion: The mini-beam collimator has revealed a difference between the three linacs not apparent in the open field data, yet transferability can still be attained through thorough dosimetric characterization.

SU‐E‐T‐292: CBCT Imaging and the Assessment of PTV Margin Size for Rectal Cancer Patients Treated Prone on Belly Board

Purpose: The goal of this work was to use CBCTimages taken at the time of treatment to derive PTV margin sizes that would account for inter and intra‐fractional systematic and random errors associated with CTV position for patients treated prone on a new couch top belly board (CDR Systems Inc.). Methods: Twenty‐four patients (12 male and 12 female) were included in this study. CBCT data was acquired once every 5 fractions for a total of 5 images per patient. A 3D‐3D bony anatomy auto‐match was performed offline and the residual difference used as a surrogate for inter‐fractional positional errors of the CTV. Systematic and random variations in CTV position were evaluated in a manner consistent with that of Stroom et al and used in PTVmargin = 1.96Σ + 0.7σ. The influence of hypothetical intra‐fractional motion was included in the margin evaluation by introducing the following values: 1.0, 2.0 and 3.0mm.Results: PTVmargin required to account for inter‐fraction positional errors was found to be (AP, SI, LR) = (5.2 mm, 3.1 mm, 2.8 mm). If we assume any intra‐fractional motion to be similar to that presented by Xu et al, then the required PTVmargin increases to (AP, SI, LR) = (7.0 mm, 5.0 mm, 5.0 mm). A 7.0 mm AP expansion is consistent with that quoted in the “Elective Clinical Target Volumes in Anorectal Cancer: An RTOG Consensus Contouring Atlas“, which recommends a margin between 7.0 and 10.0 mm. However, 7.0 mm is 2.0 mm greater than the 5.0 mm margin specified in the RTOG 0822 trial. Conclusions: A PTVmargin expansion of (AP, SI, LR) = (7.0 mm, 5.0 mm, 5.0 mm) will account for inter and intra‐fractional systematic and random errors associated with CTV position for patients treated prone on a new couch top belly board.