Safety and patterns of survivorship in recurrent GBM following resection and surgically targeted radiation therapy: Results from a prospective trial.

BACKGROUND: Treatment of recurrent glioblastoma (GBM) remains problematic with survival after additional therapy typically less than 12 months. We prospectively evaluated whether outcomes might be improved with resection plus permanent implantation of a novel radiation device utilizing the gamma-emitting isotope Cs-131 embedded within bioresorbable collagen tiles. METHODS: Recurrent histologic GBM were treated in a single-arm trial. Following radiation, the surgical bed was lined with the tiles. Subsequent treatments were at the treating physician's discretion. RESULTS: 28 patients were treated (20 at first recurrence, range 1-3). Median age was 58 years, KPS was 80, female:male ratio was 10:18. Methylguanine methyltransferase (MGMT) was methylated in 11%, unmethylated in 18%, and unknown in 71%. Post implant, 17 patients (61%) received ≥1 course of systemic therapy. For all patients, Kaplan-Meier estimates of median time to local failure were 12.1 months, post-implant survival was 10.7 months for all patients and 15.1 months for patients who received systemic therapy; for all patients, median overall survival from diagnosis was 25.0 months (range 9.1-143.1). Sex, age, and number of prior progressions were not statistically significant. Local control was continuously maintained in 46% of patients. Two deaths within 30 days occurred, one from intracranial hemorrhage and one after persistent coma. Three symptomatic adverse events occurred: one wound infection requiring surgery and two late radiation brain injury, resolved non-surgically. CONCLUSION: This pre-commercial trial demonstrated acceptable safety and favorable post-treatment local control and survival. The device has received FDA clearance for use in newly diagnosed malignant and all recurrent intracranial neoplasms.

Re-Irradiation Using Brachytherapy for Recurrent Intracranial Tumors: A Systematic Review and Meta-Analysis of the Literature.

Introduction We aim to compare the efficacy and toxicity of re-irradiation using brachytherapy for patients with locally recurrent brain tumors after previous radiation therapy.  Methods We performed a systematic review of the major biomedical databases from 2005 to 2020 for eligible studies where patients were treated with re-irradiation for recurrent same site tumors using brachytherapy. Tumor types included high-grade gliomas (HGG) (World Health Organization (WHO) Grades 3 and 4), meningiomas, and metastases. The outcomes of interest were median overall survival (OS) and progression-free survival (PFS) after re-irradiation, the incidence of radiation necrosis (RN), and other relevant radiation-related adverse events (AE). We used a fixed-effect meta-analysis regression moderation model to compared results of interstitial versus intracavitary therapy, treatment with low-dose-rate (LDR) versus high-dose-rate (HDR) techniques, and outcomes by tumor type. Results The search resulted in a total of 194 articles. A total of 16 articles with 695 patients fulfilled the inclusion criteria and were selected for analysis. For high-grade glioma, meningioma, and brain metastasis the pooled meta-analysis showed mean symptomatic RN rates of 3.3% (standard error (SE) = 0.8%), 17.3% (SE = 5.0%), and 22.4% (SE = 7.0%), respectively, and mean rates of RN requiring surgical intervention of 3.0% (SE = 1.0%), 11.9% (SE = 5.3%), and 10.0% (SE = 7.3%), respectively. The mean symptomatic RN rates in the meta-analysis comparing interstitial versus intracavitary therapy were 3.4% and 4.9%, respectively (p = 0.36), and for the comparison of LDR versus HDR, the rates were 2.6% and 5.7%, respectively (p = 0.046). In comparing the symptomatic RN rates in comparison to HGG versus meningioma, the means were 3.3% and 17.3%, respectively (p = 0.006), and in HGG versus metastatic tumors, the means were 3.3% and 22.4%, respectively (p = 0.007). There was no significant difference in rates of RN requiring surgery in any of these groups. Due to the small number of studies and inconsistent recording of OS and PFS, statistical analysis of these parameters could not be performed. Conclusion Published literature on the same site re-irradiation using brachytherapy for recurrent brain tumors is highly limited, with inconsistent reporting of safety and efficacy outcomes. To overcome these shortcomings, we utilized a structured meta-analysis approach to show that re-irradiation with modern brachytherapy is generally safe in terms of the risks of symptomatic RN. We also found that symptomatic RN rates for brachytherapy are significantly lower in recurrent HGG compared to recurrent meningiomas (p = 0.006) and metastatic tumors (p = 0.007). Re-irradiation with brachytherapy is a feasible option for appropriately selected patients. The availability of Cesium-131 (Cs-131) shows promise in reducing toxicity while achieving excellent local control due to its physical properties, and the recent introduction of a novel surgically targeted radiation therapy device, that makes brachytherapy less technically demanding, may allow for more widespread adoption. Prospective trials with consistent reporting of endpoints are needed to explore whether these advances improve safety and efficacy in patients with recurrent, previously irradiated tumors.

Dose-volume relationship for laryngeal substructures and aspiration in patients with locally advanced head-and-neck cancer.

BACKGROUND: Literature has shown a significant relationship between radiation dose to the larynx and swallowing disorders. We prospectively studied the dose-volume relationship for larynx substructures and aspiration. METHODS: Forty nine patients with stage III/IV head-and-neck (H&N) squamous cell carcinoma were prospectively enrolled in this IRB-approved, federally funded study. All patients received IMRT-based chemoradiation therapy (CRT) and were scheduled for videofluorography (VFG) prior to CRT and at 3, 6, 9, 12, and 24 months post-CRT. Twelve laryngeal substructures were contoured in each patient: thyroid cartilage, cricoid cartilage, total epiglottis, suprahyoid epiglottis, infrahyoid epiglottis, total larynx, supraglottic larynx, subglottic larynx, glottic larynx, arytenoids, aryepiglottic (AE) folds, and glossoepiglottic fold. After exclusions, 29 patients were included in the final analysis. Incidence of aspiration at 1 year following CRT was correlated with dose-volume data to laryngeal substructures using logistic regression. RESULTS: The median age was 54 years with 79% being non-smokers. Tumor sites included oropharynx (22), unknown primary (6), and hypopharynx (1). One year following CRT, 10/29 (34%) showed aspiration on VFG. Dose to the AE folds showed the highest correlation with aspiration at 12 months and was significant on multivariate analysis (p = 0.025). A mean dose cutpoint of 6500 cGy or higher to the AE folds was associated with an increased risk of aspiration at 1 year [positive likelihood ratio (+LR) 2.81, positive predictive value (PPV) 60%, negative predictive value (NPV) 92.9%, relative risk (RR) 8.4]. CONCLUSIONS: In this analysis, mean dose to the AE folds was associated with an increased risk of aspiration at 1 year. However, these are hypothesis-generating data that require further research and validation in a larger patient subset.

An in-silico quality assurance study of contouring target volumes in thoracic tumors within a cooperative group setting.

INTRODUCTION: Target delineation variability is a significant technical impediment in multi-institutional trials which employ intensity modulated radiotherapy (IMRT), as there is a real potential for clinically meaningful variances that can impact the outcomes in clinical trials. The goal of this study is to determine the variability of target delineation among participants from different institutions as part of Southwest Oncology Group (SWOG) Radiotherapy Committee's multi-institutional in-silico quality assurance study in patients with Pancoast tumors as a "dry run" for trial implementation. METHODS: CT simulation scans were acquired from four patients with Pancoast tumor. Two patients had simulation 4D-CT and FDG-FDG PET-CT while two patients had 3D-CT and FDG-FDG PET-CT. Seventeen SWOG-affiliated physicians independently delineated target volumes defined as gross primary and nodal tumor volumes (GTV_P & GTV_N), clinical target volume (CTV), and planning target volume (PTV).Six board-certified thoracic radiation oncologists were designated as the 'Experts' for this study. Their delineations were used to create a simultaneous truth and performance level estimation (STAPLE) contours using ADMIRE software (Elekta AB, Sweden 2017). Individual participants' contours were then compared with Experts' STAPLE contours. RESULTS: When compared to the Experts' STAPLE, GTV_P had the best agreement among all participants, while GTV_N showed the lowest agreement among all participants. There were no statistically significant differences in all studied parameters for all TVs for cases with 4D-CT versus cases with 3D-CT simulation scans. CONCLUSIONS: High degree of inter-observer variation was noted for all target volume except for GTV_P, unveiling potentials for protocol modification for subsequent clinically meaningful improvement in target definition. Various similarity indices exist that can be used to guide multi-institutional radiotherapy delineation QA credentialing.

National Cancer Database Analysis of the effect of brachytherapy on overall survival in patients with base of tongue cancer.

BACKGROUND: We performed an analysis of the National Cancer Database (NCDB) to evaluate overall survival (OS) in patients with base of tongue (BOT) cancer treated with external beam radiation therapy (EBRT) combined with brachytherapy (BT). METHODS: The tongue NCDB Participant User File was used to obtain demographic and clinical patient data. The Kaplan-Meier method was used to determine OS. Significance was determined using univariable and multivariable Cox proportional hazards models. RESULTS: At 3 years, OS was 69.6%, 77.1%, and 63.7% for patients treated with EBRT (n = 27 954), EBRT + BT (n = 209), or BT alone (n = 154), respectively (P = .01). On multivariable analysis, the instantaneous hazard of death for patients receiving EBRT + BT was 25% (Hazard ratio [HR] = 0.75, 95% CI: 0.58-0.98) lower than patients receiving only EBRT (P = .03). CONCLUSIONS: The addition of BT to EBRT in BOT cancer has an OS benefit.

Industry Funding Is Correlated With Publication Productivity of US Academic Radiation Oncologists.

PURPOSE: Industry payments to physicians are financial conflicts of interest and may influence research findings and medical decisions. We aim to (1) characterize industry payments within radiation oncology; and (2) explore the potential correlation between receiving disclosed industry payments and academic productivity. MATERIALS/METHODS: CMS database was used to extract 2015 industry payments. For academic radiation oncologists, research productivity was characterized by h- and m-indices, as well as receipt of National Institutes of Health (NIH) funding, which is not an industry payment. Logistic regression models were used to determine whether publication metrics (m-index, h-index) and other study characteristics such as gender, PhD status, NIH institution funding status, were associated with the endpoints, research and general payments. Associations between the amount of payments (if any) and publication metrics were further studied using linear regression models. RESULTS: A total of 22,543 individual payments totaling $25,532,482 to 2,995 radiation oncologists were included. Among the 1,189 academic radiation oncologists, 75% received less than $167; on the other hand, 10 (<1%) individuals received $6,425,728 (51%) of payments. On multiple logistic regression, research payments were significantly associated with the m-index, odds ratio 2.86 (95% confidence interval, 1.84-4.45, p-value <0.0001); as well as with the h-index, odds ratio 1.03 (95% confidence interval, 1.01-1.05, p-value <0.0001). The linear regression model shows that both m-index and h-index were significantly positively associated with the amount of general payments (p-values <0.0001). CONCLUSION: There is an association between disclosed payment from the industry and increased individual research productivity metrics. Further research to find the cause behind this association is warranted.

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.

Adaptive Radiotherapy for Head and Neck Cancer.

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.

Factors associated with increased academic productivity among US academic radiation oncology faculty.

OBJECTIVES: Publication productivity metrics can help evaluate academic faculty for hiring, promotion, grants, and awards; however, limited benchmarking data exist, which makes intra- and interdepartmental comparisons difficult. Therefore, we sought to evaluate the scholarly activity of physician faculty at academic radiation oncology (RO) departments and establish factors associated with increased academic productivity. METHODS AND MATERIALS: Citation database searches were performed for all physician-faculty in US residency-affiliated academic RO departments. Demographics, National Institutes of Health (NIH) funding, and bibliometrics (number of publications, Hirsch-[h]-index, and m-index [Hirsch index divided by the number of years since first publication]) were collected and stratified by academic rank. Senior academic rank was defined as full professor, professor, and/or chair. Junior academic rank was defined as all others. Logistic regression was performed to determine the association of academic rank and other factors with h- and m-indices. RESULTS: A total of 1191 academic RO physician faculty from 75 institutions were included in the analysis. The mean (standard deviation) number of publications and h- and m-indices were 48.2 (71.2), 14.5 (15), and 0.86 (0.83), respectively. The median (interquartile range) number of publications and h- and m-indices were 20 (6-61), 9 (4-20), and 0.69 (0.38-1.10), respectively. Recursive partitioning analysis revealed a statistically significant numeric h-index threshold of 21 between junior and senior faculty (LogWorth 114; receiver operating characteristic, 0.828). Senior faculty status, receipt of NIH funding, and a larger department size were associated with increased h- and m-indices. CONCLUSIONS: Current academic RO departments have relatively high objective metrics of scholastic productivity compared with prior benchmarking analyses of RO departments and compared with published metrics from other academic medicine subspecialties. An h-index of 21 or greater was associated with senior faculty status. Additionally, receipt of NIH funding and greater departmental size were associated with a higher h-index. These data may be of interest to faculty preparing for promotion or award applications as well as institutional leadership evaluating their departments.

Clinical Application of a Hybrid RapidArc Radiotherapy Technique for Locally Advanced Lung Cancer.

OBJECTIVE: Radiation treatment planning for locally advanced lung cancer can be technically challenging, as delivery of ≥60 Gy to large volumes with concurrent chemotherapy is often associated with significant risk of normal tissue toxicity. We clinically implemented a novel hybrid RapidArc technique in patients with lung cancer and compared these plans with 3-dimensional conformal radiotherapy and RapidArc-only plans. MATERIALS/METHODS: Hybrid RapidArc was used to treat 11 patients with locally advanced lung cancer having bulky mediastinal adenopathy. All 11 patients received concurrent chemotherapy. All underwent a 4-dimensional computed tomography planning scan. Hybrid RapidArc plans concurrently combined static (60%) and RapidArc (40%) beams. All cases were replanned using 3- to 5-field 3-dimensional conformal radiotherapy and RapidArc technique as controls. RESULTS: Significant reductions in dose were observed in hybrid RapidArc plans compared to 3-dimensional conformal radiotherapy plans for total lung V20 and mean (-2% and -0.6 Gy); contralateral lung mean (-2.92 Gy); and esophagus V60 and mean (-16.0% and -2.2 Gy; all P < .05). Contralateral lung doses were significantly lower for hybrid RapidArc plans compared to RapidArc-only plans (all P < .05). Compared to 3-dimensional conformal radiotherapy, heart V60 and mean dose were significantly improved with hybrid RapidArc (3% vs 5%, P = .04 and 16.32 Gy vs 16.65 Gy, P = .03). However, heart V40 and V45 and maximum spinal cord dose were significantly lower with RapidArc plans compared to hybrid RapidArc plans. Conformity and homogeneity were significantly better with hybrid RapidArc plans compared to 3-dimensional conformal radiotherapy plans ( P < .05). Treatment was well tolerated, with no grade 3+ toxicities. CONCLUSION: To our knowledge, this is the first report on the clinical application of hybrid RapidArc in patients with locally advanced lung cancer. Hybrid RapidArc permitted safe delivery of 60 to 66 Gy to large lung tumors with concurrent chemotherapy and demonstrated advantages for reduction in low-dose lung volumes, esophageal dose, and mean heart dose.

Observer Evaluation of a Metal Artifact Reduction Algorithm Applied to Head and Neck Cone Beam Computed Tomographic Images.

PURPOSE AND OBJECTIVES: To quantify, through an observer study, the reduction in metal artifacts on cone beam computed tomographic (CBCT) images using a projection-interpolation algorithm, on images containing metal artifacts from dental fillings and implants in patients treated for head and neck (H&N) cancer. METHODS AND MATERIALS: An interpolation-substitution algorithm was applied to H&N CBCT images containing metal artifacts from dental fillings and implants. Image quality with respect to metal artifacts was evaluated subjectively and objectively. First, 6 independent radiation oncologists were asked to rank randomly sorted blinded images (before and after metal artifact reduction) using a 5-point rating scale (1 = severe artifacts; 5 = no artifacts). Second, the standard deviation of different regions of interest (ROI) within each image was calculated and compared with the mean rating scores. RESULTS: The interpolation-substitution technique successfully reduced metal artifacts in 70% of the cases. From a total of 60 images from 15 H&N cancer patients undergoing image guided radiation therapy, the mean rating score on the uncorrected images was 2.3 ± 1.1, versus 3.3 ± 1.0 for the corrected images. The mean difference in ranking score between uncorrected and corrected images was 1.0 (95% confidence interval: 0.9-1.2, P<.05). The standard deviation of each ROI significantly decreased after artifact reduction (P<.01). Moreover, a negative correlation between the mean rating score for each image and the standard deviation of the oral cavity and bilateral cheeks was observed. CONCLUSION: The interpolation-substitution algorithm is efficient and effective for reducing metal artifacts caused by dental fillings and implants on CBCT images, as demonstrated by the statistically significant increase in observer image quality ranking and by the decrease in ROI standard deviation between uncorrected and corrected images.

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.

Establishing a targeted plan for prophylactic dental extractions in patients with laryngeal cancer receiving adjuvant radiotherapy.

OBJECTIVE: The purpose of this study was to determine dose delivered to individual mandibular tooth-bearing regions during adjuvant intensity-modulated radiotherapy for laryngeal cancers. STUDY DESIGN: Twenty patients with laryngeal cancer treated with intensity-modulated radiotherapy were included. Individual mandibular tooth-borne areas were manually contoured. Average doses were calculated for individual teeth. RESULTS: Doses to individual teeth increased with more posterior location. Highest dose was observed for third molar (M3) (43.1 Gy; P < .001). Doses to molars and premolars correlated with T- and N-stage (P = .007; P < .001, respectively). For ipsilateral nodal disease, there was no difference between the doses to ipsilateral teeth and contralateral teeth. Only in N2 c tumors, dose was above our threshold for extraction for M3 only (51.5 Gy). CONCLUSIONS: T- and N-stage drive dose to individual mandibular tooth-borne areas. With the exception of the posterior molars, particularly in node-positive patients, radiation exposure falls below the threshold reported for pre-RT tooth extractions (50 Gy). We concluded that a more conservative approach to prophylactic tooth extraction with a greater emphasis on dental management may be warranted for the prevention of osteoradionecrosis in patients with laryngeal cancer receiving adjuvant RT.

Conditional Survival in Anal Carcinoma Using the National Population-Based Survey of Epidemiology and End Results Database (1988-2012).

BACKGROUND: Conditional survival can provide valuable information for both patients and healthcare providers about the changing prognosis in surviving patients over time. OBJECTIVE: This study estimated conditional survival for patients with anal cancer in the United States through analysis of a national population-based cancer registry. DESIGN: Log-rank test identified significant covariates of cause-specific survival (defined as time from diagnosis until death from anal cancer). Significant covariates were considered in the multivariable regression of cause-specific survival using Cox proportional hazards models. SETTINGS: Covariates included cancer stage and demographic variables. PATIENTS: Patients in Surveillance, Epidemiology, and End Results regions diagnosed with anal squamous cell carcinoma as their first and only cancer diagnosis from 1988 to 2012 were selected from this database, and 5145 patients were included in the retrospective cohort study. MAIN OUTCOME MEASURE: Five-year conditional survival stratified by each variable in the final Cox models was measured RESULTS: : The final multivariable models of overall and cause-specific survivals included stage, grade, sex, age, race, and relationship status. Over the first 6 years after diagnosis, conditional survival of distant stage increased from 37% to 89%, whereas regional stage increased from 65% to 93% and localized stage increased from 84% to 96%. The other variables had increasing prognosis as well, but the subgroups increased at a more similar rate over time. LIMITATIONS: The data source used does not include information on chemotherapy treatment, patient comorbidities, or socioeconomic status. CONCLUSIONS: Conditional survival showed improvement over time. Patients with advanced stage had the greatest improvement in conditional survival. This is the first study to provide specific conditional survival probabilities for patients with anal cancer.

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.

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.

Combination Trimodality Therapy Using Vismodegib for Basal Cell Carcinoma of the Face.

Background. For large basal cell carcinomas (BCCs) of the head and neck, definitive surgery often requires extensive resection and reconstruction that may result in prolonged recovery and limited cosmesis. Vismodegib, a small-molecule inhibitor of the hedgehog pathway, is approved for advanced and metastatic BCCs. We present a case of advanced BCC treated with combination of vismodegib, radiotherapy, and local excision resulting in excellent response and cosmesis. Case Presentation. A 64-year-old gentleman presented with a 5-year history of a 7 cm enlarging right cheek mass, with extensive vascularization, central ulceration, and skin, soft tissue, and buccal mucosa involvement. Biopsy revealed BCC, nodular type. Up-front surgical option involved a large resection and reconstruction. After multidisciplinary discussion, we recommended and he opted for combined modality of vismodegib, radiotherapy, and local excision. The patient tolerated vismodegib well and his right cheek lesion decreased significantly in size. He was then treated with radiotherapy followed by local excision that revealed only focal residual BCC. Currently, he is without evidence of disease and has excellent cosmesis. Conclusions. We report a case of locally advanced BCC treated with trimodality therapy with vismodegib, radiotherapy, and local excision, resulting in excellent outcome and facial cosmesis, without requiring extensive resection or reconstructive surgery.

Successful delivery of adjuvant external beam radiotherapy for ependymoma in a patient with Ondine׳s curse.

Ondine׳s curse is a rare, potentially life-threatening disorder characterized by loss of automatic breathing during sleep and preserved voluntary breathing. It is seldom encountered in the radiotherapy clinic but can pose significant technical challenges and safety concerns in the delivery of a prescribed radiation course. We report a unique case of successful delivery of radiotherapy for ependymoma in a patient with Ondine׳s curse. A 53-year-old gentleman presented with vertigo when lying down. Brain magnetic resonance imaging revealed an enhancing mass in the floor of the fourth ventricle. He underwent maximal safe resection. Pathology revealed ependymoma. The patient was referred for radiotherapy. Computed tomography simulation was performed in supine position with 3-point thermoplastic mask immobilization. Sequential TomoTherapy plans were developed. At first scheduled treatment, shortly after mask placement, his arms went limp and he was unresponsive. Vitals showed oxygen saturation 83%, pulse 127, and blood pressure 172/97mmHg. He was diagnosed with Ondine׳s curse thought secondary to previous brainstem damage; the combination of lying flat and pressure from the mask was causing him to go into respiratory arrest. As supine positioning did not seem clinically advisable, he was simulated in prone position. A RapidArc plan and a back-up conformal plan were developed. Prescriptions were modified to meet conservative organs-at-risk constraints. Several strategies were used to minimize uncertainties in set-up reproducibility associated with prone positioning. He tolerated prone RapidArc treatments well. The report highlights the importance of applying practical patient safety and treatment planning/delivery strategies in the management of this challenging case.

Brachial plexus dose tolerance in head and neck cancer patients treated with sequential intensity modulated radiation therapy.

PURPOSE: We aimed to study the radiation induced brachial plexopathy in patients with head and neck squamous cell carcinoma (HNSCC) treated with Sequential Intensity Modulated Radiation Therapy (S-IMRT). METHODS AND MATERIALS: This IRB approved study included 68 patients with HNSCC treated consecutively. Detailed dose volume histogram data was generated for ipsilateral and contralateral brachial plexus (BP) volumes receiving a specified dose (Vds) i.e. V50-V75 and dose in Gray covering specified percent of BP volume (Dvs) i.e. D5-D30 and maximum point doses (Dmax). To assess BP injury all patients' charts were reviewed in detail for sign and symptoms of BP damage. Post-hoc comparisons were done using Tukey-Kramer method to account for multiple significance testing. RESULTS: The mean and maximum doses to BP were significantly different (p < .05) based on tumor site, nodal status and tumor stage. The mean volume to the ipsilateral BP for V50, V60, V70, and V75 were 7.01 cc, 4.37 cc, 1.47 cc and 0.24 cc, respectively. The mean dose delivered to ≤5% of ipsilateral BP was 68.70 Gy (median 69.5Gy). None of the patients had acute or late brachial plexopathy or any other significant neurological complications, with a minimum follow up of two years (mean 54 months). CONCLUSIONS: In this study cohort, at a minimum of two-years follow up, the mean dose of 68.7Gy, a median dose to 69.5Gy to ≤5% of ipsilateral BP, and a median Dmax of 72.96Gy did not result in BP injury when patients were treated with S-IMRT technique. However, longer follow up is needed.