Amy S. Harrison

Radiotherapy Protocol Deviations and Clinical Outcomes: A Meta-analysis of Cooperative Group Clinical Trials

BACKGROUND Noncompliance with radiotherapy (RT) protocol guidelines has been linked to inferior clinical outcomes. We performed a meta-analysis of cooperative group trials to examine the association between RT quality assurance (QA) deviations and disease control and overall survival (OS). METHODS We searched MEDLINE and the Cochrane Central Register of Controlled Trials for multi-institutional trials that reported clinical outcomes in relation to RT QA results. Hazard ratios (HRs) describing the association between RT protocol noncompliance and patient outcomes were extracted directly from the original studies or calculated from survival curves. Inverse variance meta-analyses were performed to assess the association between RT QA deviations and OS. A second meta-analysis tested the association between RT QA deviations and secondary outcomes, including local or locoregional control, event-free survival, and relapse. Random-effects models were used in cases of statistically significant (P < .10) effect heterogeneity. The Egger test was used to detect publication bias. All statistical tests were two-sided. RESULTS Eight studies (four pediatric, four adult) met all inclusion criteria and were incorporated into this analysis. The frequency of RT QA deviations ranged from 8% to 71% (median = 32%). In a random-effects model, RT deviations were associated with a statistically significant decrease in OS (HR of death = 1.74, 95% confidence interval [CI] = 1.28 to 2.35; P < .001). A similar effect was seen for secondary outcomes (HR of treatment failure = 1.79, 95% CI = 1.15 to 2.78; P = .009). No evidence of publication bias was detected. CONCLUSION In clinical trials, RT protocol deviations are associated with increased risks of treatment failure and overall mortality.

Evolution of advanced technologies in prostate cancer radiotherapy

Conventional treatment options for clinically localized, low-risk prostate cancer include radical prostatectomy, external-beam radiotherapy (EBRT) and low-dose-rate brachytherapy. Advances in image-guided radiotherapy (IGRT) since the 1980s, the development of intensity-modulated radiotherapy (IMRT) during the 1990s and evidence from radiobiological models—which support the use of high doses per fraction—have developed alongside novel advanced radiotherapy modalities that include high-dose-rate brachytherapy (HDR-BT), stereotactic body radiotherapy (SBRT) and proton beam therapy. The relationship between the outcomes of and toxicities experienced by patients with prostate cancer treated with HDR-BT, SBRT and particle-beam therapy should provide urologists and oncologists an understanding of the continually evolving technology in prostate radiotherapy. On the basis of published evidence, conventionally fractionated EBRT with IMRT is considered the standard of care over conventional 3D conformal radiotherapy, whereas HDR-BT boost is an acceptable treatment option for selected patients with intermediate-risk and high-risk prostate cancer. SBRT and proton therapy should not be used for patients (regardless of disease risk group) outside the setting of a clinical trial. Finally, comparative effectiveness research should be conducted to provide a framework for evaluating advanced radiotherapy technologies by comparing the benefits and harms of available therapeutic options to optimize the risk:benefit ratio and improve cost effectiveness.

Dosimetric verification using monte carlo calculations for tissue heterogeneity-corrected conformal treatment plans following RTOG 0813 dosimetric criteria for lung cancer stereotactic body radiotherapy.

PURPOSE The recently activated Radiation Therapy Oncology Group (RTOG) studies of stereotactic body radiation therapy (SBRT) for non-small-cell lung cancer (NSCLC) require tissue density heterogeneity correction, where the high and intermediate dose compliance criteria were established based on superposition algorithm dose calculations. The study was aimed at comparing superposition algorithm dose calculations with Monte Carlo (MC) dose calculations for SBRT for NSCLC and to evaluate whether compliance criteria need to be adjusted for MC dose calculations. METHODS AND MATERIALS Fifteen RTOG 0236 study sets were used. The planning tumor volumes (PTV) ranged from 10.7 to 117.1 cm(3). SBRT conformal treatment plans were generated using XiO (CMS Inc.) treatment planning software with superposition algorithm to meet the dosimetric high and intermediate compliance criteria recommended by the RTOG 0813 protocol. Plans were recalculated using the MC algorithm of a Monaco (CMS, Inc.) treatment planning system. Tissue density heterogeneity correction was applied in both calculations. RESULTS Overall, the dosimetric quantities of the MC calculations have larger magnitudes than those of the superposition calculations. On average, R(100%) (ratio of prescription isodose volume to PTV), R(50%) (ratio of 50% prescription isodose volume to PTV), D(2 cm) (maximal dose 2 cm from PTV in any direction as a percentage of prescription dose), and V(20) (percentage of lung receiving dose equal to or larger than 20 Gy) increased by 9%, 12%, 7%, and 18%, respectively. In the superposition plans, 3 cases did not meet criteria for R(50%) or D(2 cm). In the MC-recalculated plans, 8 cases did not meet criteria for R(100%), R(50%), or D(2 cm). After reoptimization with MC calculations, 5 cases did not meet the criteria for R(50%) or D(2 cm). CONCLUSIONS Results indicate that the dosimetric criteria, e.g., the criteria for R(50%) recommended by RTOG 0813 protocol, may need to be adjusted when the MC dose calculation algorithm is used.

Intensity-modulated radiation therapy and volumetric-modulated arc therapy for adult craniospinal irradiation—A comparison with traditional techniques

Craniospinal irradiation (CSI) poses a challenging planning process because of the complex target volume. Traditional 3D conformal CSI does not spare any critical organs, resulting in toxicity in patients. Here the dosimetric advantages of intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) are compared with classic conformal planning in adults for both cranial and spine fields to develop a clinically feasible technique that is both effective and efficient. Ten adult patients treated with CSI were retrospectively identified. For the cranial fields, 5-field IMRT and dual 356° VMAT arcs were compared with opposed lateral 3D conformal radiotherapy (3D-CRT) fields. For the spine fields, traditional posterior-anterior (PA) PA fields were compared with isocentric 5-field IMRT plans and single 200° VMAT arcs. Two adult patients have been treated using this IMRT technique to date and extensive quality assurance, especially for the junction regions, was performed. For the cranial fields, the IMRT technique had the highest planned target volume (PTV) maximum and was the least efficient, whereas the VMAT technique provided the greatest parotid sparing with better efficiency. 3D-CRT provided the most efficient delivery but with the highest parotid dose. For the spine fields, VMAT provided the best PTV coverage but had the highest mean dose to all organs at risk (OAR). 3D-CRT had the highest PTV and OAR maximum doses but was the most efficient. IMRT provides the greatest OAR sparing but the longest delivery time. For those patients with unresectable disease that can benefit from a higher, definitive dose, 3D-CRT-opposed laterals are the most clinically feasible technique for cranial fields and for spine fields. Although inefficient, the IMRT technique is the most clinically feasible because of the increased mean OAR dose with the VMAT technique. Quality assurance of the beams, especially the junction regions, is essential.

Clinical experience transitioning from IMRT to VMAT for head and neck cancer.

To quantify clinical differences for volumetric modulated arc therapy (VMAT) versus intensity modulated radiation therapy (IMRT) in terms of dosimetric endpoints and planning and delivery time, twenty head and neck cancer patients have been considered for VMAT using Nucletron Oncentra MasterPlan delivered via an Elekta linear accelerator. Differences in planning time between IMRT and VMAT were estimated accounting for both optimization and calculation. The average delivery time per patient was obtained retrospectively using the record and verify software. For the dosimetric comparison, all contoured organs at risk (OARs) and planning target volumes (PTVs) were evaluated. Of the 20 cases considered, 14 had VMAT plans approved. Six VMAT plans were rejected due to unacceptable dose to OARs. In terms of optimization time, there was minimal difference between the two modalities. The dose calculation time was significantly longer for VMAT, 4 minutes per 358 degree arc versus 2 minutes for an entire IMRT plan. The overall delivery time was reduced by 9.2 ± 3.9 minutes for VMAT (51.4 ± 15.6%). For the dosimetric comparison of the 14 clinically acceptable plans, there was almost no statistical difference between the VMAT and IMRT. There was also a reduction in monitor units of approximately 32% from IMRT to VMAT with both modalities demonstrating comparable quality assurance results. VMAT provides comparable coverage of target volumes while sparing OARs for the majority of head and neck cases. In cases where high dose modulation was required for OARs, a clinically acceptable plan was only achievable with IMRT. Due to the long calculation times, VMAT plans can cause delays during planning but marked improvements in delivery time reduce patient treatment times and the risk of intra-fraction motion.

Optimizing patient positioning for intensity modulated radiation therapy in hippocampal-sparing whole brain radiation therapy

PURPOSE Sparing the hippocampus during whole brain radiation therapy (WBRT) offers potential neurocognitive benefits. However, previously reported intensity modulated radiation therapy (IMRT) plans use multiple noncoplanar beams for treatment delivery. An optimized coplanar IMRT template for hippocampal-sparing WBRT would assist in clinical workflow and minimize resource utilization. In this study, we sought to determine the optimal patient position to facilitate coplanar treatment planning and delivery of hippocampal-sparing WBRT using IMRT. METHODS AND MATERIALS A variable angle, inclined board was utilized for patient positioning. An anthropomorphic phantom underwent computed tomography simulation at various head angles. The IMRT goals were designed to achieve target coverage of the brain while maintaining hippocampal dose-volume constraints designed to conform to the Radiation Therapy Oncology Group 0933 protocol. Optimal head angle was then verified using data from 8 patients comparing coplanar and noncoplanar WBRT IMRT plans. RESULTS Hippocampal, hippocampal avoidance region, and whole brain mean volumes were 1.1 cm(3), 12.5 cm(3), and 1185.1 cm(3), respectively. The hippocampal avoidance region occupied 1.1% of the whole brain planning volume. For the 30-degree head angle, a 7-field coplanar IMRT plan was generated, sparing the hippocampus to a maximum dose of 14.7 Gy; D100% of the hippocampus was 7.4 Gy and mean hippocampal dose was 9.3 Gy. In comparison, for flat head positioning the hippocampal Dmax was 22.9 Gy with a D100% of 9.2 Gy and mean dose of 11.7 Gy. Target coverage and dose homogeneity was comparable with previously published noncoplanar IMRT plans. CONCLUSIONS Compared with conventional supine positioning, an inclined head board at 30 degrees optimizes coplanar whole brain IMRT treatment planning. Clinically acceptable hippocampal-sparing WBRT dosimetry can be obtained using a simplified coplanar plan at a 30-degree head angle, thus obviating the need for complex and time consuming noncoplanar IMRT plans.

Clinical implementation and failure mode and effects analysis of HDR skin brachytherapy using Valencia and Leipzig surface applicators

PURPOSE The planning procedure for Valencia and Leipzig surface applicators (VLSAs) (Nucletron, Veenendaal, The Netherlands) differs substantially from CT-based planning; the unfamiliarity could lead to significant errors. This study applies failure modes and effects analysis (FMEA) to high-dose-rate (HDR) skin brachytherapy using VLSAs to ensure safety and quality. METHOD A multidisciplinary team created a protocol for HDR VLSA skin treatments and applied FMEA. Failure modes were identified and scored by severity, occurrence, and detectability. The clinical procedure was then revised to address high-scoring process nodes. RESULTS Several key components were added to the protocol to minimize risk probability numbers. (1) Diagnosis, prescription, applicator selection, and setup are reviewed at weekly quality assurance rounds. Peer review reduces the likelihood of an inappropriate treatment regime. (2) A template for HDR skin treatments was established in the clinics electronic medical record system to standardize treatment instructions. This reduces the chances of miscommunication between the physician and planner as well as increases the detectability of an error. (3) A screen check was implemented during the second check to increase detectability of an error. (4) To reduce error probability, the treatment plan worksheet was designed to display plan parameters in a format visually similar to the treatment console display, facilitating data entry and verification. (5) VLSAs are color coded and labeled to match the electronic medical record prescriptions, simplifying in-room selection and verification. CONCLUSIONS Multidisciplinary planning and FMEA increased detectability and reduced error probability during VLSA HDR brachytherapy. This clinical model may be useful to institutions implementing similar procedures.

Pilot Study of Meaningful Use of Electronic Health Records in Radiation Oncology

PURPOSE Adoption and meaningful use of electronic health record (EHR) systems is an important national goal. We undertook a pilot study to determine the level of adoption and barriers to implementation of meaningful use (MU) of EHR systems as defined by the Centers for Medicare & Medicaid Services (CMS) in US radiation oncology practices. MATERIALS AND METHODS We administered a Web-based survey instrument to a convenience sample of 40 departments of radiation oncology. We determined the current status of EHR system use at each facility, attitudes toward EHR systems, knowledge of MU criteria, plans and barriers to implementation, and whether selected interventions would be helpful with regard to compliance with MU criteria. RESULTS Twenty-one of 40 radiation oncology facilities completed the survey, for a 53% response rate. Respondents were mostly large academic practices with a median of six (range, one to 32) full-time physicians and 70 (range, eight to 650) patients treated daily. Most facilities (81%) currently used an EHR system. The majority (84%) of facilities were aware of MU criteria, and of these, 67% expected to implement MU-compliant systems by the year 1 reporting deadline of October 1, 2011. The most frequently cited barriers to implementation were high cost, difficulty integrating with hospital systems, and a lack of national guidelines for implementation. CONCLUSION Most large academic radiation oncology practices have already incorporated EHR systems into practice and plan to meet MU requirements. Further work should focus on assessment of needs for smaller practices. Radiation oncology-specific guidelines may improve widespread adoption.

Evaluation of Elekta 4D cone beam CT-based automatic image registration for radiation treatment of lung cancer

OBJECTIVE The study was aimed to evaluate the precision of Elekta four-dimensional (4D) cone beam CT (CBCT)-based automatic dual-image registrations using different landmarks for clipbox for radiation treatment of lung cancer. METHODS 30 4D CBCT scans from 15 patients were studied. 4D CBCT images were registered with reference CT images using dual-image registration: a clipbox registration and a mask registration. The image registrations performed in clinic using a physician-defined clipbox, were reviewed by physicians, and were taken as the standard. Studies were conducted to evaluate the automatic dual registrations using three kinds of landmarks for clipbox: spine, spine plus internal target volume (ITV) and lung (including as much of the lung as possible). Translational table shifts calculated from the automatic registrations were compared with those of the standard. RESULTS The mean of the table shift differences in the lateral direction were 0.03, 0.03 and 0.03 cm, for clipboxes based on spine, spine plus ITV and lung, respectively. The mean of the shift differences in the longitudinal direction were 0.08, 0.08 and 0.08 cm, respectively. The mean of the shift differences in the vertical direction were 0.03, 0.03 and 0.03 cm, respectively. CONCLUSION The automatic registrations using three different landmarks for clipbox showed similar results. One can use any of the three landmarks in 4D CBCT dual-image registration. Advance in knowledge: The study provides knowledge and recommendations for application of Elekta 4D CBCT image registration in radiation therapy of lung cancer.

Reirradiation of head and neck cancer with high-dose-rate brachytherapy: A customizable intraluminal solution for postoperative treatment of tracheal mucosa recurrence

PURPOSE Delivering adequate dose to tracheal mucosa recurrence after multiple prior courses of surgery and radiation presented a challenge for radiation delivery. Tumor bed location and size, combined with previous doses to surrounding areas, complicated the use of external beam therapy with either photons or electrons. High-dose-rate (HDR) brachytherapy was explored to provide sufficient dose coverage. METHODS AND MATERIALS A 45-year-old gentleman presented with recurrent head and neck cancer. After undergoing additional excision of gross tumor in the tracheal region, radiation was recommended to improve local control. The region of residual tumor was confined to a small superficial lesion at the posterior-superior aspect of the trachea, involving mucosa located along the bend of the trachea, immediately deep to the stoma. External beam treatment was discussed but was not recommended based on recurrence location in the prior radiation field and patients flexed chin position. HDR technique with a custom applicator was preferred. RESULTS A three-dimensional HDR plan based on computed tomography used a single catheter optimized to cover gross tumor volume as delineated by physician. Prescribed dose was 5 Gy/fraction for six fractions (two fractions/wk). The applicator position was verified daily with computed tomography and physician setup approval before treatment. The patient was positioned on a wing board to allow access to the stoma. HDR brachytherapy was well tolerated. CONCLUSIONS Intraluminal HDR brachytherapy is a viable option for providing dose to region inside tracheal stoma. Advantages over photon and electron beam therapy include reduced dose to surrounding tissues previously irradiated, skin dose, and reproducibility of treatment delivery.