Mehee Choi

Markov model and cost-effectiveness analysis of bevacizumab in HER2-negative metastatic breast cancer.

Purpose:Metastatic breast cancer (MBC) remains an incurable disease despite advances in treatment modalities. In 2008, the FDA approved bevacizumab with paclitaxel for the initial treatment of HER2-negative MBC. The approval was then officially revoked by the FDA in November 2011. However, both the European Medicines Agency and NCCN still endorse bevacizumab for this indication. One of the greatest challenges facing health care worldwide is reconciling incremental clinical benefits with exponentially rising costs. This study aimed to assess the cost-effectiveness of bevacizumab with paclitaxel for HER2-negative MBC. Methods:A Markov decision tree using Data 3.5 (TreeAge Software Inc.) was created for decision and cost-effectiveness analyses of using bevacizumab plus paclitaxel versus paclitaxel alone as first-line chemotherapy in HER2-negative MBC using efficacy and toxicity data from the E2100 study. The model was designed from the patient and payer perspectives and sensitivity analyses were run. Results:The marginal cost between paclitaxel alone versus bevacizumab and paclitaxel was 86k with a marginal efficacy of 0.369 quality-adjusted life-years and marginal cost effectiveness of 232,720.72 USD. The expected outcome value was 1.86 for bevacizumab and paclitaxel and 1.67 for paclitaxel alone. The combination was not cost effective and only a marginal survival advantage was observed. Conclusions:This study demonstrates that, despite a significant progression-free survival advantage, the addition of bevacizumab to paclitaxel is not cost effective for the cohort of patients with HER2-negative MBC included in our analysis. Such data could be informative to policymakers who consider the health economics and incremental cost-effectiveness of medical therapies.

Decision Trees Predicting Tumor Shrinkage for Head and Neck Cancer Implications for Adaptive Radiotherapy

Objective: To develop decision trees predicting for tumor volume reduction in patients with head and neck (H&N) cancer using pretreatment clinical and pathological parameters. Methods: Forty-eight patients treated with definitive concurrent chemoradiotherapy for squamous cell carcinoma of the nasopharynx, oropharynx, oral cavity, or hypopharynx were retrospectively analyzed. These patients were rescanned at a median dose of 37.8 Gy and replanned to account for anatomical changes. The percentages of gross tumor volume (GTV) change from initial to rescan computed tomography (CT; %GTVΔ) were calculated. Two decision trees were generated to correlate %GTVΔ in primary and nodal volumes with 14 characteristics including age, gender, Karnofsky performance status (KPS), site, human papilloma virus (HPV) status, tumor grade, primary tumor growth pattern (endophytic/exophytic), tumor/nodal/group stages, chemotherapy regimen, and primary, nodal, and total GTV volumes in the initial CT scan. The C4.5 Decision Tree induction algorithm was implemented. Results: The median %GTVΔ for primary, nodal, and total GTVs was 26.8%, 43.0%, and 31.2%, respectively. Type of chemotherapy, age, primary tumor growth pattern, site, KPS, and HPV status were the most predictive parameters for primary %GTVΔ decision tree, whereas for nodal %GTVΔ, KPS, site, age, primary tumor growth pattern, initial primary GTV, and total GTV volumes were predictive. Both decision trees had an accuracy of 88%. Conclusions: There can be significant changes in primary and nodal tumor volumes during the course of H&N chemoradiotherapy. Considering the proposed decision trees, radiation oncologists can select patients predicted to have high %GTVΔ, who would theoretically gain the most benefit from adaptive radiotherapy, in order to better use limited clinical resources.

Stereotactic radiosurgery boost to the resection cavity for cerebral metastases: Report of overall survival, complications, and corticosteroid protocol

Background: This report focuses on the overall survival and complications associated with treatment of cerebral metastases with surgical resection followed by stereotactic radiosurgery (SRS). Management and complications of corticosteroid therapy are underreported in the literature but represent an important source of morbidity for patients. Methods: Fifty-nine consecutive patients underwent surgical resection of a cerebral metastasis followed by SRS to the cavity. Patient charts were reviewed retrospectively to ascertain overall survival, local control, surgical complications, SRS complications, and corticosteroid complications. Results: Our mean follow-up was 14.4 months (median 12.0 months, range 0.9-62.9 months). Median overall survival in this series was 15.25 months and local control was 98.3%. There was a statistically significant survival benefit conferred by Radiation Therapy Oncology Group recursive partitioning analysis Classes 1 and 2. The surgical complication rate was 6.8% while the SRS complication rate was 2.4%. Corticosteroid complications are reported and dependence at 1 month was 20.3%, at 3 months 6.8%, at 6 months 1.7%, and at 12 months no patients remained on corticosteroid therapy. Conclusions: Overall survival and local control with this treatment paradigm compare well to the other published literature. Complications associated with this patient population are low. A corticosteroid tapering protocol is proposed and demonstrated lower rates of steroid-related complications and dependence than previously reported.

Adaptive Radiotherapy for Head and Neck Cancer: Implications for Clinical and Dosimetry Outcomes.

Objective: To investigate the effects of adaptive radiotherapy on dosimetric, clinical, and toxicity outcomes for patients with head and neck cancer undergoing chemoradiotherapy with intensity-modulated radiotherapy. Methods: Fifty-one patients with advanced head and neck cancer underwent definitive chemoradiotherapy with the original plan optimized to deliver 70.2 Gy. All patients were resimulated at a median dose of 37.8 Gy (range, 27.0-48.6 Gy) due to changes in tumor volume and/or patient weight loss (>15% from baseline). Thirty-four patients underwent adaptive replanning for their boost planning (21.6 Gy). The dosimetric effects of the adaptive plan were compared to the original plan and the original plan copied on rescan computed tomography. Acute and late toxicities and tumor local control were assessed. Gross tumor volume reduction rate was calculated. Results: With adaptive replanning, the maximum dose to the spinal cord, brain stem, mean ipsilateral, and contralateral parotid had a median reduction of −4.5%, −3.0%, −6.2%, and −2.5%, respectively (median of 34 patients). Median gross tumor volume and boost planning target volume coverage improved by 0.8% and 0.5%, respectively. With a median follow-up time of 17.6 months, median disease-free survival and overall survival was 14.8 and 21.1 months, respectively. Median tumor volume reduction rate was 35.2%. For patients with tumor volume reduction rate ≤35.2%, median disease-free survival was 8.7 months, whereas it was 16.9 months for tumor volume reduction rate >35.2%. Four patients had residual disease after chemoradiotherapy, whereas 64.7% (20 of 34) of patients achieved locoregional control. Conclusion: Implementation of adaptive radiotherapy in head and neck cancer offers benefits including improvement in tumor coverage and decrease in dose to organs at risk. The tumor volume reduction rate during treatment was significantly correlated with disease-free survival and overall survival.

Development of a standardized method for contouring the larynx and its substructures

ObjectivesLimiting radiation dose to the larynx can diminish effects of laryngeal dysfunction. However, no clear guidelines exist for defining the larynx and its substructures consistently on cross-sectional imaging. This study presents computed tomography (CT)- and magnetic resonance imaging (MRI)-based guidelines for contouring laryngeal organs-at-risk (OARs).Materials and MethodsStandardized guidelines for delineating laryngeal OARs were devised and used to delineate on CT and MRI for head-and-neck cancer patients. Volumetric comparisons were performed to evaluate consistency and reproducibility of guideline-based contours.ResultsFor the initial 5 patients the mean CT and MRI based larynx volume did not differ significantly between imaging modalities; 34.39 ± 9.85 vs. 35.01 ± 9.47 (p = .09). There was no statistical difference between the CT based mean laryngeal volume in the subsequent 44 patients compared to the initial 5 patients outlined on CT and the MRI scan (p = 0.53 and 0.62). The OAR volume for laryngeal substructures were not statistically different among patients or between imaging modalities. Once established, the guidelines were easy to follow.ConclusionThe guidelines developed provide a precise method for delineating laryngeal OARs. These guidelines need to be validated and clinical significance of outlining laryngeal substructures and dose-volume constraints should be investigated before routine implementation in clinic practice.

Evaluation of Deformable Image Registration-Based Contour Propagation From Planning CT to Cone-Beam CT:

Purpose: We evaluated the performance of organ contour propagation from a planning computed tomography to cone-beam computed tomography with deformable image registration by comparing contours to manual contouring. Materials and Methods: Sixteen patients were retrospectively identified based on showing considerable physical change throughout the course of treatment. Multiple organs in the 3 regions (head and neck, prostate, and pancreas) were evaluated. A cone-beam computed tomography from the end of treatment was registered to the planning computed tomography using rigid registration, followed by deformable image registration. The contours were copied on cone-beam computed tomography image sets using rigid registration and modified by 2 radiation oncologists. Contours were compared using Dice similarity coefficient, mean surface distance, and Hausdorff distance. Results: The mean physician-to-physician Dice similarity coefficient for all organs was 0.90. When compared to each physician’s contours, the overall mean for rigid was 0.76 (P < .001), and it was improved to 0.79 (P < .001) for deformable image registration. Comparing deformable image registration to physicians resulted in a mean Dice similarity coefficient of 0.77, 0.74, and 0.84 for head and neck, prostate, and pancreas groups, respectively; whereas, the physician-to-physician mean agreement for these sites was 0.87, 0.90, and 0.93 (P < .001, for all sites). The mean surface distance for physician-to-physician contours was 1.01 mm, compared to 2.58 mm for rigid-to-physician contours and 2.24 mm for deformable image registration-to-physician contours. The mean physician-to-physician Hausdorff distance was 11.32 mm, and when compared to any physician’s contours, the mean for rigid and deformable image registration was 12.1 mm and 12.0 mm (P < .001), respectively. Conclusion: The physicians had a high level of agreement via the 3 metrics; however, deformable image registration fell short of this level of agreement. The automatic workflows using deformable image registration to deform contours to cone-beam computed tomography to evaluate the changes during treatment should be used with caution.

Routine use of preoperative breast MRI for patients considered for intraoperative radiotherapy.

This editorial comments on the study by Tallet et al. which reported on the incidence of ipsilateral second breast cancers (BC) detected by preoperative magnetic resonance imaging (MRI) in patients being considered for intraoperative radiotherapy (IORT). Any second BC was detected in 7% of patients; an ipsilateral BC was detected in 4% of patients, precluding them from IORT. The authors comment that in view of detection of a substantial rate of ipsilateral BCs by preoperative MRI, this exam should be used routinely for staging patients being considered for IORT.

Whole-Field Sequential Intensity-Modulated Radiotherapy for Local-Regional Advanced Head-and-Neck Squamous Cell Carcinoma.

Purpose:There is little published data on the technique and results of whole-field (WF) sequential intensity–modulated radiotherapy (S-IMRT) for patients with head-and-neck squamous cell carcinoma (HNSCC). We report the treatment outcomes, adverse events (AEs), and dosimetric parameters in local-regional advanced (LRA) HNSCC patients treated with the WF S-IMRT technique. Methods:The IRB approved this retrospective study. Patients received WF S-IMRT with or without concomitant chemotherapy. Three separate IMRT plans corresponding to 3 planning target volumes were generated. This study reports patient and tumor characteristics, treatment-induced acute AEs based on CTCAE version 3.0, chronic AEs according to RTOG scale and treatment outcomes, local-regional control (LRC), distant metastases (DM), relapse-free survival (RFS), and overall survival (OS). Results:Between January 2003 and December 2010, 103 patients with LRA HNSCC were treated either definitively or postoperatively with WF S-IMRT, with (99 patients) or without (4 patients) concurrent chemotherapy. The median age was 55 years (range, 30 to 89 y). The median cumulative target dose was 70 Gy (range, 60 to 75 Gy). At a median follow-up of 40 months (range, 4 to 95 mo), the 2- and 5-year rates of OS were 94% and 77%, RFS were 90% and 84%, LRC were 97% and 93%, and DM were 9% and 11%, respectively. Grade 3 acute AEs included mucositis (68%), dysphagia (35%), weight loss (19.6%), and xerostomia (7.8%). Chronic worst grade 3 AEs included xerostomia (21.9%), weight loss (12.8%), and dysphagia (12.5%). Chronic grade 3 AEs at last follow-up included weight loss (6.25%), dysphagia (6.2%), and xerostomia (6.2%). No patient had an acute or chronic grade 4 AE, brachial plexopathy, or spinal cord injury. Conclusions:WF S-IMRT results in excellent tumor control and an acceptable toxicity profile in LRA HNSCC patients treated with this technique.

Radiation-associated toxicities in the treatment of high-grade gliomas.

This article gives a brief historical overview of the development of standard management for high-grade gliomas (HGGs). The current standard of care, trimodality therapy with maximal safe resection followed by involved-field radiotherapy (RT) with concomitant/adjuvant temozolomide, confers median survival of 14.6 months, and a modest but measurable proportion (9.8%) of patients survives 5 or more years. We review the toxicities associated with irradiation of the central nervous system for patients with HGG, with focus on the pathophysiology, clinical manifestations, and potential preventative strategies for long-term neurocognitive dysfunction, which remains a pervasive, progressive, and clinically devastating sequela of trimodality therapy. Treatment of cognitive decline after RT is limited, and strategies for preventing this complication are being investigated.

Metal Artifact Reduction in Cone-Beam Computed Tomography for Head and Neck Radiotherapy.

Purpose: To evaluate a method for reducing metal artifacts, arising from dental fillings, on cone-beam computed tomography images. Materials and Methods: A projection interpolation algorithm is applied to cone-beam computed tomography images containing metal artifacts from dental fillings. This technique involves identifying metal regions in individual cone-beam computed tomography projections and interpolating the surrounding values to remove the metal from the projection data. Axial cone-beam computed tomography images are then reconstructed, resulting in a reduction in the streak artifacts produced by the metal. Both phantom and patient imaging data are used to evaluate this technique. Results: The interpolation substitution technique successfully reduced metal artifacts in all cases. Corrected images had fewer or no streak artifacts compared to their noncorrected counterparts. Quantitatively, regions of interest containing the artifacts showed reduced variance in the corrected images versus the uncorrected images. Average pixel values in regions of interest around the metal object were also closer in value to nonmetal regions after artifact reduction. Artifact correction tended to perform better on patient images with less complex metal objects versus those with multiple large dental fillings. Conclusion: The interpolation substitution is potentially an efficient and effective technique for reducing metal artifacts caused by dental fillings on cone-beam computed tomography image. This technique may be effective in reducing such artifacts in patients with head and neck cancer receiving daily image-guided radiotherapy.