Nikhil G. Thaker

Intensity-modulated proton beam therapy (IMPT) versus intensity-modulated photon therapy (IMRT) for patients with oropharynx cancer - A case matched analysis.

BACKGROUND Owing to its physical properties, intensity-modulated proton therapy (IMPT) used for patients with oropharyngeal carcinoma has the ability to reduce the dose to organs at risk compared to intensity-modulated radiotherapy (IMRT) while maintaining adequate tumor coverage. Our aim was to compare the clinical outcomes of these two treatment modalities. METHODS We performed a 1:2 matching of IMPT to IMRT patients. Our study cohort consisted of IMPT patients from a prospective quality of life study and consecutive IMRT patients treated at a single institution during the period 2010-2014. Patients were matched on unilateral/bilateral treatment, disease site, human papillomavirus status, T and N status, smoking status, and receipt of concomitant chemotherapy. Survival analyzes were performed using a Cox model and binary toxicity endpoints using a logistic regression analysis. RESULTS Fifty IMPT and 100 IMRT patients were included. The median follow-up time was 32months. There were no imbalances in patient/tumor characteristics except for age (mean age 56.8years for IMRT patients and 61.1years for IMPT patients, p-value=0.010). Statistically significant differences were not observed in overall survival (hazard ratio (HR)=0.55; 95% confidence interval (CI): 0.12-2.50, p-value=0.44) or in progression-free survival (HR=1.02; 95% CI: 0.41-2.54; p-value=0.96). The age-adjusted odds ratio (OR) for the presence of a gastrostomy (G)-tube during treatment for IMPT vs IMRT were OR=0.53; 95% CI: 0.24-1.15; p-value=0.11 and OR=0.43; 95% CI: 0.16-1.17; p-value=0.10 at 3months after treatment. When considering the pre-planned composite endpoint of grade 3 weight loss or G-tube presence, the ORs were OR=0.44; 95% CI: 0.19-1.0; p-value=0.05 at 3months after treatment and OR=0.23; 95% CI: 0.07-0.73; p-value=0.01 at 1year after treatment. CONCLUSION Our results suggest that IMPT is associated with reduced rates of feeding tube dependency and severe weight loss without jeopardizing outcome. Prospective multicenter randomized trials are needed to validate such findings.

Dosimetric advantages of intensity-modulated proton therapy for oropharyngeal cancer compared with intensity-modulated radiation: A case-matched control analysis

A potential advantage of intensity-modulated proton therapy (IMPT) over intensity-modulated (photon) radiation therapy (IMRT) in the treatment of oropharyngeal carcinoma (OPC) is lower radiation dose to several critical structures involved in the development of nausea and vomiting, mucositis, and dysphagia. The purpose of this study was to quantify doses to critical structures for patients with OPC treated with IMPT and compare those with doses on IMRT plans generated for the same patients and with a matched cohort of patients actually treated with IMRT. In this study, 25 patients newly diagnosed with OPC were treated with IMPT between 2011 and 2012. Comparison IMRT plans were generated for these patients and for additional IMRT-treated controls extracted from a database of patients with OPC treated between 2000 and 2009. Cases were matched based on the following criteria, in order: unilateral vs bilateral therapy, tonsil vs base of tongue primary, T-category, N-category, concurrent chemotherapy, induction chemotherapy, smoking status, sex, and age. Results showed that the mean doses to the anterior and posterior oral cavity, hard palate, larynx, mandible, and esophagus were significantly lower with IMPT than with IMRT comparison plans generated for the same cohort, as were doses to several central nervous system structures involved in the nausea and vomiting response. Similar differences were found when comparing dose to organs at risks (OARs) between the IMPT cohort and the case-matched IMRT cohort. In conclusion, these findings suggest that patients with OPC treated with IMPT may experience fewer and less severe side effects during therapy. This may be the result of decreased beam path toxicities with IMPT due to lower doses to several dysphagia, odynophagia, and nausea and vomiting-associated OARs. Further study is needed to evaluate differences in long-term disease control and chronic toxicity between patients with OPC treated with IMPT in comparison to those treated with IMRT.

Comparative costs of advanced proton and photon radiation therapies: lessons from time-driven activity-based costing in head and neck cancer.

Advanced technology in the USA is, in part, responsible for driving improvements in cancer care outcomes but also steep increases in the cost of cancer care delivery [1–3]. Whether or not the US healthcare system delivers highvalue care, which is defined as the quality of health outcomes divided by the cost of achieving those outcomes, is controversial. Despite much emphasis on comparative effectiveness analyses, cost–effectiveness analyses of costly therapies, such as advanced technologies, have been under emphasized. Although the Patient Protection and Affordable Care Act has limited the role of cost analysis in the federally funded Patient-Centered Outcomes Research Institute, given the controversy and fear of rationing of healthcare services [4], successful transformation from volume to value will require patients, providers and payors to understand the comparative effectiveness and cost–effectiveness of competing technological treatment modalities.

Communicating Value in Health Care Using Radar Charts: A Case Study of Prostate Cancer

PURPOSE The transformation from volume to value will require communication of outcomes and costs of therapies; however, outcomes are usually nonstandardized, and cost of therapy differs among stakeholders. We developed a standardized value framework by using radar charts to visualize and communicate a wide range of patient outcomes and cost for three forms of prostate cancer treatment. MATERIALS AND METHODS We retrospectively reviewed data from men with low-risk prostate cancer who were treated with low-dose rate brachytherapy (LDR-BT), proton beam therapy, or robotic-assisted prostatectomy. Patient-reported outcomes comprised the Expanded Prostate Cancer Index Composite-50 domains for sexual function, urinary incontinence and/or bother, bowel bother, and vitality 12 months after treatment. Costs were measured by time-driven activity-based costing for the first 12 months of the care cycle. Outcome and cost data were plotted on a single radar chart for each treatment modality. RESULTS Outcome and cost data from patients who were treated with robotic-assisted prostatectomy (n = 381), proton beam therapy (n = 165), and LDR-BT (n = 238) were incorporated into the radar chart. LDR-BT seemed to deliver the highest overall value of the three treatment modalities; however, incorporation of patient preferences regarding outcomes may allow other modalities to be considered high-value treatment options. CONCLUSION Standardization and visualization of outcome and cost metrics may allow more comprehensive and collaborative discussions about the value of health care services. Communicating the value framework by using radar charts may be an effective method to present total value and the value of all outcomes and costs in a manner that is accessible to all stakeholders. Variations in plotting of costs and outcomes will require future focus group initiatives.

Survival outcomes for patients with stage IVB vulvar cancer with grossly positive pelvic lymph nodes: Time to reconsider the FIGO staging system?

OBJECTIVE To evaluate treatment outcomes for patients with vulvar cancer with grossly positive pelvic lymph nodes (PLNs). METHODS From a database of 516 patients with vulvar cancer, we identified patients with grossly positive PLNs without distant metastasis at initial diagnosis. We identified 20 patients with grossly positive PLNs; inclusion criteria included PLN 1.5cm or larger in short axis dimension on CT/MRI (n=11), FDG-avid PLN on PET/CT (n=3), or biopsy-proven PLN disease (n=6). Ten patients were treated with chemoradiation therapy (CRT), 4 with RT alone, and 6 with various combinations of surgery, RT or CRT. Median follow-up time for patients who had not died of cancer was 47months (range, 4-228months). RESULTS Mean primary vulvar tumor size was 6.4cm; 12 patients presented with 2009 AJCC T2 and 8 with T3 disease. All patients had grossly positive inguinal nodes, and the mean inguinal nodal diameter was 2.8cm. The 5-year overall survival and disease specific survival rates were 43% and 48%, respectively. Eleven patients had recurrences, some at multiple sites. There were 9 recurrences in the vulva, but no isolated nodal recurrences. Four patients developed distant metastasis within 6months of starting radiation therapy. CONCLUSIONS Aggressive locoregional treatment can lead to favorable outcomes for many patients with grossly involved PLNs that is comparable to that of grossly involved inguinal nodes only. We recommend modification of the FIGO stage IVB classification to more accurately reflect the relatively favorable prognosis of patients with PLN involvement.

Assessing the Quality of a Radiation Oncology Case-Based, Peer-Review Program in an Integrated Academic and Community Cancer Center Network

PURPOSE Academic centers increasingly find a need to define a comprehensive peer-review program that can translate high-quality radiation therapy (RT) to community network sites. In this study, we describe the initial results of a quarterly quality audit program that aims to improve RT peer-review and provider educational processes across community sites. MATERIALS AND METHODS An electronic tool was used by community-based certified member (CM) sites to enter clinical treatment information about patients undergoing peer review. At least 10% of the patient load for each CM physician was selected for audit on a quarterly basis by expert academic faculty. Quality metrics included the review of the management plan, technical plan, and other indicators. RT was scored as being concordant or nonconcordant with institutional guidelines, national standards, or expert judgment. RESULTS A total of 719 patients were entered into the peer-review database by the first four CM sites. Of 14% of patients audited, 17% (18 of 104) were deemed nonconcordant. Nonconcordance rates were lowest in prevalent disease sites, such as breast (16%), colorectal (14%), and lung (12%), whereas rates were highest in lymphoma (50%), brain (44%), and gynecology (27%). Deficiencies included incomplete staging work-up, incorrect target and normal tissue delineation, and nonadherence to accepted dose-volume constraints. CONCLUSION Given the high rate of nonconcordance, we recommend prospective, pre-RT peer review of all patients, and, in particular, expert review of patients that are from low-volume or complex disease sites. An integrated approach to peer review holds a promise of improving the quality, safety, and value of cancer therapy in the community setting.

Defining the value of magnetic resonance imaging in prostate brachytherapy using time-driven activity-based costing

Magnetic resonance imaging (MRI) simulation and planning for prostate brachytherapy (PBT) may deliver potential clinical benefits but at an unknown cost to the provider and healthcare system. Time-driven activity-based costing (TDABC) is an innovative bottom-up costing tool in healthcare that can be used to measure the actual consumption of resources required over the full cycle of care. TDABC analysis was conducted to compare patient-level costs for an MRI-based versus traditional PBT workflow. TDABC cost was only 1% higher for the MRI-based workflow, and utilization of MRI allowed for cost shifting from other imaging modalities, such as CT and ultrasound, to MRI during the PBT process. Future initiatives will be required to follow the costs of care over longer periods of time to determine if improvements in outcomes and toxicities with an MRI-based approach lead to lower resource utilization and spending over the long-term. Understanding provider costs will become important as healthcare reform transitions to value-based purchasing and other alternative payment models.

American College of Radiology (ACR) Radiation Oncology Practice Accreditation: A pattern of change

PURPOSE The American College of Radiology (ACR) Radiation Oncology Practice Accreditation (ROPA) program has accredited more than 600 sites since 2006, including practices within academic, hospital-based, and freestanding settings. The purpose of this report is to evaluate and compare patterns of change in common deficiencies over time. METHODS AND MATERIALS The ACR database was queried to analyze the common deficiencies noted by the ACR ROPA program between 2012 and 2014. Deficiencies were ranked and compared to the top 10 items that were reported in 2006. RESULTS Between 2012 and 2014, 272 new applications and 306 renewals were received. Timely verification of port films, documentation of physician peer review, inclusion of essential elements of a treatment prescription, evidence of a final physicist chart review, documentation of weekly treatment visits, and inclusion of key elements of brachytherapy documentation all improved when compared with 2000-2005. Deficiencies ranked higher on the current review compared with the previous analysis included documentation of a robust quality assurance program, missing elements from the history and physical documentation, and documentation of follow-up visits. CONCLUSIONS Our analysis of changes in patterns of deficiencies across radiation oncology practices reflects changes in our field such as the growing reliance on electronic records and imaging. Accreditation continues to play an integral role in establishing national standards and a nonpunitive, peer-reviewed method to evaluate a practices compliance with national quality guidelines.

The Evolution of Radiation Therapy for Retinoblastoma: The MD Anderson Cancer Center Experience

Purpose The role of radiation therapy (RT) for retinoblastoma (Rb) has significantly evolved from first-line to salvage therapy. The objectives of our study were to evaluate efficacy of proton RT (PRT) and other advanced RT techniques for Rb and to observe evolving trends in RT use. Materials and Methods An analysis of patients with Rb who received RT between 1990 and 2012 was conducted. Thirty-nine patients with 70 affected eyes were identified. Of these, 47 eyes were treated with RT with photon or electron RT (ERT), PRT, or brachytherapy (BRT). The clinical history, treatment details, and tumor outcomes were reviewed for all patients. Results Radiation therapy was first-line treatment in 14 eyes, second-line in 4, postoperative in 4, and salvage in 25. Median length of follow-up was 8 years for all patients, and 10, 3, and 5 years for ERT, PRT, and BRT, respectively. Overall survival was 97.4%. In total, 16 (34.0%) eyes required enucleation after RT. Median PRT dose was 36 Gy (RBE) (range, 36-45 Gy [RBE]), ERT dose was 45 Gy (range, 36-46 Gy), and BRT dose was 45 Gy (range, 36-45 Gy). A higher proportion of PRT patients (93.8%) than ERT patients (51.9%) were treated in the salvage setting (P < .01). Among patients with International Classification for Intraocular Retinoblastoma stage D and E disease, 6 of 11 (54.5%) ERT patients required enucleation and 5 of 13 (38.5%) PRT patients required enucleation. Conclusion This study represents a large series of patients treated with PRT, ERT, and BRT for Rb and reports favorable efficacy and toxicity. Patients treated with salvage PRT are typically heavily pretreated and have advanced disease. Despite more advanced disease, patients treated with PRT with lower RT doses achieve comparable salvage and enucleation-free rates to ERT. Chemoreduction followed by focal treatments should be standard of care when clinically feasible, with PRT considered in the salvage setting.

Auto-segmentation of the brachial plexus assessed with TaCTICS – A software platform for rapid multiple-metric quantitative evaluation of contours

Segmentation of organs-at-risk (OARs) remains a highly variable yet critical operator-dependent step in radiation planning [1]. With the increased conformality of intensity-modulated radiotherapy (IMRT) delivery, the ability to spare OARs is markedly increased, enabling more targeted treatment with sparing of specific tissues. However, manual segmentation of target volumes and OARs remains highly variable. For this reason, auto-segmentation approaches are attractive mechanisms to potentially reduce inter-observer region of interest (ROI) variation [2,3], allow assessment of OARs that might otherwise be subject to beam path toxicities [3,4] and improve workflow-time parameters [4-6]. Auto-segmentation techniques have been developed that implement a priori atlas libraries of normal tissue ROIs, with deformable image registration to transfer these ROIs from the reference library to a patient DICOM file [7]. While several commercial and in-house auto-segmentation approaches have been presented and show promise, rigorous quality assessment should be performed before clinical implementation [1,6] given the clinical implications of over-or under-contouring [8]. However, individual institutions may have significant difficulty systematically evaluating competing auto-segmentation platforms, as evaluation of registration and segmentation typically requires substantial effort for multi-ROI segmentation assessment [9,10]. Consequently, we surmised that there exists an unmet need for an open-source, web-based software solution for comparison of auto-segmented ROIs with reference manually segmented ROIs. We have previously reported the development of an open-source web-based software called TaCTICS (Target Contour Testing/Instructional Computer Software, https://github.com/kalpathy/tacticsRT) that provides quantitative and qualitative comparison of submitted and reference manually segmented ROIs in order to provide feedback to users about their performance on contouring target volumes and OARs [11,12]. For this reason we sought to investigate the feasibility and utility of TaCTICS in evaluating the quality of auto-segmentation algorithms by comparing their results to composite expert contours using two brachial plexus ROIs as index OARs. The specific aims of the current study were to assess the feasibility of utilizing TaCTICS to report multi-metric analysis of an auto-segmentation algorithm of the brachial plexus relative to a TaCTICS-generated probabilistic multi-expert manual segmentation, define a performance benchmark comparison of an auto-segmentation algorithm of the brachial plexus to that of a set of reference resident contours and finally, to establish a quality-assessment workflow for the future evaluation of commercial/in-house auto-segmentation algorithm performance.