Comparison of peripheral leukocyte parameters in patients receiving conventionally and hypofractionated radiotherapy schemes for the treatment of newly diagnosed glioblastoma.

Introduction: Treatment for glioblastomas, aggressive and nearly uniformly fatal brain tumors, provide limited long-term success. Immunosuppression by myeloid cells in both the tumor microenvironment and systemic circulation are believed to contribute to this treatment resistance. Standard multi-modality therapy includes conventionally fractionated radiotherapy over 6 weeks; however, hypofractionated radiotherapy over 3 weeks or less may be appropriate for older patients or populations with poor performance status. Lymphocyte concentration changes have been reported in patients with glioblastoma; however, monocytes are likely a key cell type contributing to immunosuppression in glioblastoma. Peripheral monocyte concentration changes in patients receiving commonly employed radiation fractionation schemes are unknown. Methods: To determine the effect of conventionally fractionated and hypofractionated radiotherapy on complete blood cell leukocyte parameters, retrospective longitudinal concentrations were compared prior to, during, and following standard chemoradiation treatment. Results: This study is the first to report increased monocyte concentrations and decreased lymphocyte concentrations in patients treated with conventionally fractionated radiotherapy compared to hypofractionated radiotherapy. Discussion: Understanding the impact of fractionation on peripheral blood leukocytes is important to inform selection of dose fractionation schemes for patients receiving radiotherapy.

A linear optimization model for high dose rate brachytherapy using a novel distance metric.

Purpose.We propose a linear network-based optimization model (LNBM) for high dose rate brachytherapy (HDR-BT) that uses a novel distance metric to measure the discrepancy between the dose delivered and the prescription. Unlike models in the literature, LNBM takes advantage of the adjacency structure of the patients' voxels by formalizing them into a network.Methods.We apply LNBM to a set of 7 cervical cancer cases treated with HDR-BT. State-of-the-art commercial optimization software solves LNBM to global optimality. The results of LNBM are compared with those of inverse planning by simulated annealing (IPSA) based on tumor coverage, dosimetric indices for the critical organs at risk (OARs), isodose contour plots, and two metrics of homogeneity new to this work (hot-spots volumes and diameters).Results.LNBM produces plans with improved tumor coverage and with improved isodose contour plots and dosimetric indices for OARs that receive highest dose (bladder and rectum in this study) when compared with IPSA. Using new metrics of homogeneity, we also demonstrate that LNBM produces more homogeneous plans on these cases. An analysis of the solutions of LNBM shows that they use a significant part of the voxel network structure, providing evidence that the plans produced are different from those created using traditional penalty approaches and are more directly guided by the geometry of the patients' anatomy.Conclusions.The proposed linear network-based optimization model efficiently generates more homogeneous high quality treatment plans for HDR-BT.

Clinical Outcomes and Patterns of Failure in Esthesioneuroblatoma: A Single Institutional Experience.

Esthesioneuroblastoma (ENB) is a rare sinonasal malignancy that is typically managed with a combination of surgical resection, radiotherapy and chemotherapy. Data used to guide therapeutic decision making are scant and typically obtained from small retrospective series due to the relative infrequency of the diagnosis. Here, we report our own institutional experience in the management of patients with ENB to help compliment these prior single institutional reports. Records from patients receiving treatment for ENB at the University of Minnesota Medical Center were obtained from 1994 to 2019. A total of 17 patients were identified from our retrospective review. Kadish stage at initial presentation was A in 2 (12%), B in 5 (29%), C in 9 (53%) and D in 1 (6%). All patients underwent surgical resection. Adjuvant radiotherapy was utilized in 12 (71%) patients with concurrent chemotherapy administered in 3 (18%) patients. One patient received neoadjuvant chemoradiotherapy followed by surgical resection. Four patients developed recurrent disease with locoregional failure presenting as the most common site of initial relapse within our study population. Isolated local recurrence occurred in 2 patients, one patient developed combined local and regional failure, while another had combined regional and distant failure with osseous metastases. Recurrent disease was managed by either combined salvage surgery and radiotherapy (RT) or RT alone. Three of the 4 patients who developed recurrence eventually succumbed to their disease. Estimates for 5-year DFS and OS were 65% and 90%, respectively, for the entire cohort.

Predicting Glioblastoma Cellular Motility from In Vivo MRI with a Radiomics Based Regression Model.

Characterizing the motile properties of glioblastoma tumor cells could provide a useful way to predict the spread of tumors and to tailor the therapeutic approach. Radiomics has emerged as a diagnostic tool in the classification of tumor grade, stage, and prognosis. The purpose of this work is to examine the potential of radiomics to predict the motility of glioblastoma cells. Tissue specimens were obtained from 31 patients undergoing surgical resection of glioblastoma. Mean tumor cell motility was calculated from time-lapse videos of specimen cells. Manual segmentation was used to define the border of the enhancing tumor T1-weighted MR images, and 107 radiomics features were extracted from the normalized image volumes. Model parameter coefficients were estimated using the adaptive lasso technique validated with leave-one-out cross validation (LOOCV) and permutation tests. The R-squared value for the predictive model was 0.60 with p-values for each individual parameter estimate less than 0.0001. Permutation test models trained with scrambled motility failed to produce a model that out-performed the model trained on the true data. The results of this work suggest that it is possible for a quantitative MRI feature-based regression model to non-invasively predict the cellular motility of glioblastomas.

Stereotactic Laser Ablation (SLA) followed by consolidation stereotactic radiosurgery (cSRS) as treatment for brain metastasis that recurred locally after initial radiosurgery (BMRS): a multi-institutional experience.

INTRODUCTION: The optimal treatment paradigm for brain metastasis that recurs locally after initial radiosurgery remains an area of active investigation. Here, we report outcomes for patients with BMRS treated with stereotactic laser ablation (SLA, also known as laser interstitial thermal therapy, LITT) followed by consolidation radiosurgery. METHODS: Clinical outcomes of 20 patients with 21 histologically confirmed BMRS treated with SLA followed by consolidation SRS and > 6 months follow-up were collected retrospectively across three participating institutions. RESULTS: Consolidation SRS (5 Gy × 5 or 6 Gy × 5) was carried out 16-73 days (median of 26 days) post-SLA in patients with BMRS. There were no new neurological deficits after SLA/cSRS. While 3/21 (14.3%) patients suffered temporary Karnofsky Performance Score (KPS) decline after SLA, no KPS decline was observed after cSRS. There were no 30-day mortalities or wound complications. Two patients required re-admission within 30 days of cSRS (severe headache that resolved with steroid therapy (n = 1) and new onset seizure (n = 1)). With a median follow-up of 228 days (range: 178-1367 days), the local control rate at 6 and 12 months (LC6, LC12) was 100%. All showed diminished FLAIR volume surrounding the SLA/cSRS treated BMRS at the six-month follow-up; none of the patients required steroid for symptoms attributable to these BMRS. These results compare favorably to the available literature for repeat SRS or SLA-only treatment of BMRS. CONCLUSIONS: This multi-institutional experience supports further investigations of SLA/cSRS as a treatment strategy for BMRS.

GammaTile® brachytherapy in the treatment of recurrent glioblastomas.

BACKGROUND: GammaTile® (GT) is a recent U.S. Food and Drug Administration (FDA) cleared brachytherapy platform. Here, we report clinical outcomes for recurrent glioblastoma patients after GT treatment following maximal safe resection. METHODS: We prospectively followed twenty-two consecutive Isocitrate Dehydrogenase (IDH) wild-type glioblastoma patients (6 O6-Methylguanine-DNA methyltransferase methylated (MGMTm); sixteen MGMT unmethylated (MGMTu)) who underwent maximal safe resection of recurrent tumor followed by GT placement. RESULTS: The cohort consisted of 14 second and eight third recurrences. In terms of procedural safety, there was one 30-day re-admission (4.5%) for an incisional cerebrospinal fluid leak, which resolved with lumbar drainage. No other wound complications were observed. Six patients (27.2%) declined in Karnofsky Performance Score (KPS) after surgery due to worsening existing deficits. One patient suffered a new-onset seizure postsurgery (4.5%). There was one (4.5%) 30-day mortality from intracranial hemorrhage secondary to heparinization for an ischemic limb. The mean follow-up was 733 days (range 279-1775) from the time of initial diagnosis. Six-month local control (LC6) and twelve-month local control (LC12) were 86 and 81%, respectively. Median progression-free survival (PFS) was comparable for MGMTu and MGMTm patients (~8.0 months). Median overall survival (OS) was 20.0 months for the MGMTu patients and 37.4 months for MGMTm patients. These outcomes compared favorably to data in the published literature and an independent glioblastoma cohort of comparable patients without GT treatment. CONCLUSIONS: This clinical experience supports GT brachytherapy as a treatment option in a multi-modality treatment strategy for recurrent glioblastomas.

Rapid Interval Recurrence of Glioblastoma Following Gross Total Resection: A Possible Indication for GammaTileⓇ Brachytherapy.

Glioblastoma recurrence between initial resection and standard-of-care adjuvant chemoradiotherapy (CRT) is a negative prognostic factor in an already highly aggressive disease. Re-resection with GammaTileⓇ(GT Medical Technologies Inc., Tempe, AZ) placement affords expedited adjuvant radiation to mitigate the likelihood of such growth. Here, we report a glioblastoma patient who underwent re-resection and GammaTileⓇ (GT) placement within two months of the initial gross total resection due to regrowth that reached the size of the original presenting tumor. The patient subsequently received concurrent temozolomide and 60 Gy external beam to regions outside of the brachytherapy range, fulfilling the generally accepted Stupp regimen. The patient tolerated the treatment without complication. The dosimetrics and implications of the case presentation are reviewed.

Machine learning model development for quantitative analysis of CT heterogeneity in canine hepatic masses may predict histologic malignancy.

Tumor heterogeneity is a well-established marker of biologically aggressive neoplastic processes and is associated with local recurrence and distant metastasis. Quantitative analysis of CT textural features is an indirect measure of tumor heterogeneity and therefore may help predict malignant disease. The purpose of this retrospective, secondary analysis study was to quantitatively evaluate CT heterogeneity in dogs with histologically confirmed liver masses to build a predictive model for malignancy. Forty dogs with liver tumors and corresponding histopathologic evaluation from a previous prospective study were included. Triphasic image acquisition was standardized across dogs and whole liver and liver mass were contoured on each precontrast and delayed postcontrast dataset. First-order and second-order indices were extracted from contoured regions. Univariate analysis identified potentially significant indices that were subsequently used for top-down model construction. Multiple quadratic discriminatory models were constructed and tested, including individual models using both postcontrast and precontrast whole liver or liver mass volumes. The best performing model utilized the CT features voxel volume and uniformity from postcontrast mass contours; this model had an accuracy of 0.90, sensitivity of 0.67, specificity of 1.0, positive predictive value of 1.0, negative predictive value of 0.88, and precision of 1.0. Heterogeneity indices extracted from delayed postcontrast CT hepatic mass contours were more informative about tumor type compared to indices from whole liver contours, or from precontrast hepatic mass and whole liver contours. Results demonstrate that CT radiomic feature analysis may hold clinical utility as a noninvasive method of predicting hepatic malignancy and may influence diagnostic or therapeutic approaches.

A radiomics-based model for predicting local control of resected brain metastases receiving adjuvant SRS.

PURPOSE: Adjuvant radiosurgery to the cavities of surgically resected brain metastases provides excellent local tumor control while reducing the risk of deleterious cognitive decline associated with whole brain radiotherapy. A subset of these patients, however, will develop disease recurrence following radiosurgery. In this study, we sought to assess the predictive capability of radiomic-based models, as compared with standard clinical features, in predicting local tumor control. METHODS: We performed a retrospective chart review of patients treated with adjuvant radiosurgery for resected brain metastases at the "Institution" from 2009 to 2019. Shape, intensity and texture based radiomics features of the cavities were extracted from the pre-radiosurgery treatment planning MRI scans and trained using a gradient boosting technique with K-fold cross validation. RESULTS: In total, 71 cavities from 67 treated patients were included for analysis. The 6 and 12 month local control estimates were 86% and 76%, respectively. The 6 and 12 month overall survival was 78% and 55%, respectively. Thirty-six patients developed intracranial failures outside of the surgical cavity. The predictive model for local control trained on imaging features from the whole cavity achieved an area-under-the-curve (AUC) of 0.73 on the validation set versus an AUC of 0.40 for the clinical features. CONCLUSIONS: Here we report a single institutional experience using radiomic-based predictive modeling of local tumor control following adjuvant Gamma Knife radiosurgery for resected brain metastases. We found the radiomics features to provide more robust predictive models of local control rates versus clinical features alone. Such techniques could potentially prove useful in the clinical setting and warrant further investigation.

Defining the dose-volume criteria for laryngeal sparing in locally advanced oropharyngeal cancer utilizing split-field IMRT, whole-field IMRT and VMAT.

PURPOSE: To determine the optimal dose-volume constraint for laryngeal sparing using three commonly employed intensity modulated radiation therapy (IMRT) approaches in patients with oropharyngeal cancer treated to the bilateral neck. MATERIALS AND METHODS: Thirty patients with stage II-IVA oropharynx cancers received definitive radiotherapy with split-field IMRT (SF-IMRT) to the bilateral neck between 2008 and 2013. Each case was re-planned using whole-field IMRT (WF-IMRT) and volumetric modulated arc therapy (VMAT) and plan quality metrics and dose to laryngeal structures was evaluated. Two larynx volumes were defined and compared on the current study: the Radiation Therapy Oncology Group (RTOG) larynx as defined per the RTOG 1016 protocol and the MDACC larynx defined as the components of the larynx bounded by the superior and inferior extent of the thyroid cartilage. RESULTS: Target coverage, conformity, and heterogeneity indices were similar in all techniques. The RTOG larynx mean dose was lower with WF-IMRT than SF-IMRT (22.1 vs 25.8 Gy; P < 0.01). The MDACC larynx mean dose was 17.5 Gy ± 5.4 Gy with no differences between the 3 techniques. WF-IMRT and VMAT plans were associated with lower mean doses to the supraglottic larynx (42.1 vs 41.2 vs 54.8 Gy; P < 0.01) and esophagus (18.1 vs 18.2 vs 36 Gy; P < 0.01). CONCLUSIONS: Modern whole field techniques can provide effective laryngeal sparing in patients receiving radiotherapy to the bilateral neck for advanced oropharyngeal cancers. SUMMARY: We evaluated laryngeal dose in patients with locally advanced oropharyngeal cancer treated to the bilateral neck using split-field IMRT (SF-IMRT), whole-field IMRT (WF-IMRT) and volumetric arc therapy (VMAT). All three techniques provided good sparing of laryngeal structures and were able to achieve a mean larynx dose < 33 Gy. There were no significant differences in dose to target structures or non-laryngeal organs at risk among techniques.

A prospective parallel design study testing non-inferiority of customized oral stents made using 3D printing or manually fabricated methods.

BACKGROUND AND PURPOSE: Customized mouth-opening-tongue-depressing-stents (MOTDs) may reduce toxicity in patients with head and neck cancers (HNC) receiving radiotherapy (RT). However, making MOTDs requires substantial resources, which limits their utilization. Previously, we described a workflow for fabricating customized 3D-printed MOTDs. This study reports the results of a prospective trial testing the non-inferiority of 3D-printed to standard and commercially-available (TruGuard) MOTDs as measured by patient reported outcomes (PROs). MATERIALS AND METHODS: PROs were collected at 3 time points: (t1) simulation, (t2) prior to RT, (t3) between fractions 15-25 of RT. Study participants received a 3D-printed MOTDs (t1, t2, t3), a wax-pattern (t1), an acrylic-MOTDs (t2, t3) and an optional TruGuard (t1, t2, t3). Patients inserted the stents for 5-10 min and completed a PRO-questionnaire covering ease-of-insertion and removal, gagging, jaw-pain, roughness and stability. Inter-incisal opening and tongue-displacement were recorded. With 39 patients, we estimated 90% power to detect a non-inferiority margin of 2 at a significance level of 0.025. Matched pairs and t-test were used for statistics. RESULTS: 41 patients were evaluable. The 3D-printed MOTDs achieved a significantly better overall PRO score compared to the wax-stent (p = 0.0007) and standard-stent (p = 0.0002), but was not significantly different from the TruGuard (p = 0.41). There was no difference between 3D-printed and standard MOTDs in terms of inter-incisal opening (p = 0.4) and position reproducibility (p = 0.98). The average 3D-printed MOTDs turn-around time was 8 vs 48 h for the standard-stent. CONCLUSIONS: 3D-printed stents demonstrated non-inferior PROs compared to TruGuard and standard-stents. Our 3D-printing process may expand utilization of MOTDs.

Surveillance Imaging after Autologous Hematopoietic Cell Transplantation Predicts Survival in Patients with Diffuse Large B Cell Lymphoma.

The utility of surveillance imaging after autologous hematopoietic cell transplantation (AHCT) in relapsed/refractory diffuse large B cell lymphoma (DLBCL) remains unclear. The purpose of this study was to determine whether surveillance imaging predicts survival after AHCT. At the University of Minnesota, serial imaging for early relapse detection has been used prospectively for all consecutive AHCT recipients treated since 2010. The present analysis included 91 AHCT recipients with DLBCL who underwent 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) scan at day +100 post-AHCT. 18F-FDG-PET parameters included the Deauville (D) 5-point scale, peak standardized uptake values (SUVmax), total legion glycolysis (TLG), and total metabolic tumor volume (TMTV). Survival of patients with clinically symptomatic versus asymptomatic radiographically detected relapsed DLBCL after AHCT was compared. Sixty patients experienced relapse; 35% was detected on day +100 surveillance PET scan. 5-year overall survival (OS) by 18F-FDG-PET scan at day +100 post-AHCT was significantly lower in D4 and D5 patients (37%; 95% confidence interval [CI], 14% to 100% versus 25%; 95% CI, 43% to 89%) compared with patients with D1 and D2 (62%; 95% CI, 43% to 89% versus 62%; 95% CI, 46% to 84%). TLG and TMTV were not prognostic. SUVmax at day +100 varied from 1.5 (D1) to 17.9 (D5). In multivariate analysis, only SUVmax was predictive of relapse and OS; mortality increased 1.8-fold with each SUVmax doubling (hazard ratio [HR], 1.8; 95% CI, 1.3 to 2.3; P < .01). At a median follow-up of 3.3 years (range, 1 to 12 years), lymphoma-related mortality was 1.8-fold higher among patients whose relapse was detected clinically (symptomatic) versus radiographically on surveillance scan (HR, 1.8; 95% CI, .9 to 3.4; P = .08). In patients with relapsed/refractory DLBCL, a routine PET imaging at day +100 post-AHCT detects asymptomatic relapse and high SUVmax identifies patients with poor expected survival of less than 1 year. Identifying this high-risk cohort can potentially highlight patients who might benefit from preemptive interventions to prevent or delay relapse.

Creating customized oral stents for head and neck radiotherapy using 3D scanning and printing.

BACKGROUND: To evaluate and establish a digital workflow for the custom designing and 3D printing of mouth opening tongue-depressing (MOTD) stents for patients receiving radiotherapy for head and neck cancer. METHODS: We retrospectively identified 3 patients who received radiation therapy (RT) for primary head and neck cancers with MOTD stents. We compared two methods for obtaining the digital impressions of patients' teeth. The first method involved segmentation from computed tomography (CT) scans, as previously established by our group, and the second method used 3D scanning of the patients' articulated stone models that were made during the conventional stent fabrication process. Three independent observers repeated the process to obtain digital impressions which provided data to design customized MOTD stents. For each method, we evaluated the time efficiency, dice similarity coefficient (DSC) for reproducibility, and the 3D printed stents' accuracy. For the 3D scanning method, we evaluated the registration process using manual and automatic approaches. RESULTS: For all patients, the 3D scanning method demonstrated a significant advantage over the CT scanning method in terms of time efficiency with over 60% reduction in time consumed (p < 0.0001) and reproducibility with significantly higher DSC (p < 0.001). The printed stents were tested over the articulated dental stone models, and the trueness of fit and accuracy of dental anatomy was found to be significantly better for MOTD stents made using the 3D scanning method. The automated registration showed higher accuracy with errors < 0.001 mm compared to manual registration. CONCLUSIONS: We developed an efficient workflow for custom designing and 3D-printing MOTD radiation stents. This workflow represents a considerable improvement over the CT-derived segmentation method. The application of this rapid and efficient digital workflow into radiation oncology practices can expand the use of these toxicity sparing devices to practices that do not currently have the support to make them.

Novel design and development of a 3D-printed conformal superficial brachytherapy device for the treatment of non-melanoma skin cancer and keloids.

BACKGROUND: Skin tumors are the most predominant form of cancer in the United States. Radiation therapy, particularly high dose-rate (HDR) brachytherapy, provides an effective form of cancer control when surgery is not possible or when surgical margins are incomplete. The treatment of superficial skin cancers on irregular surfaces, such as the nose, lips or ears, present challenges for treatment. To address this issue, we designed and constructed a novel conformal superficial brachytherapy (CSBT) device prototype to improve patient-specific treatment for complex sites. The device is mounted on an automated remote after-loader, providing limited radiation exposure to operating personnel, is inexpensive to construct, and offers a unique method of conformal surface radiation therapy. RESULTS: A prototype of the CSBT device was successfully manufactured. A computed tomography (CT) scan of a Rando phantom was used to plan the target treatment area. The CSBT device has a hexagonal lattice array of retractable rods with radioactive seeds placed at the tip of each rod. A 3D-printed conformal shape insert with a hexagonal array of cylindrical projections of varying length is driven into the rods by a single linear actuator. The rods are displaced to conform to the patient's skin. This elegant device design permits the delivery of radiation to complex targets using readily available beta-emitting radionuclides, such as Yttrium-90 (Y-90) or Strontium-90 (Sr-90). CONCLUSION: A working prototype of a novel CSBT device was built using 3D-printing technology that provides a safe and economically attractive means of improving radiation delivery to complex treatment sites.

Dose calibration of Gafchromic EBT3 film for Ir-192 brachytherapy source using 3D-printed PLA and ABS plastics.

3D printing technology has allowed the creation of custom applicators for high dose rate (HDR) brachytherapy, especially for complex anatomy. With conformal therapy comes the need for advanced dosimetric verification. It is important to demonstrate how dose to 3D printed materials can be related to dose to water. This study aimed to determine dose differences and uncertainties using 3D printed PLA and ABS plastics for Radiochromic film calibration in HDR brachytherapy.Gafchromic EBT3 film pieces were irradiated in water with an Ir-192 source at calculated dose levels ranging from 0 to 800 cGy, to create the control calibration curve. Similarly, film was placed below 3D printed PLA and ABS blocks and irradiated at the same dose levels calculated for water, ranging from 0 to 800 cGy. After a 72-h development time, film pieces were scanned on a flatbed scanner and the median pixel value was recorded in the region of highest dose. This value was converted to net optical density (NOD). A rational function was used to fit a calibration curve in water that relates NOD to dose for red, green, and blue color channels. Based on this fitted curve, ABS and PLA NOD values were used to estimate dose in 3D printed plastics.From the fitted calibration curve, mean residual error between measured and planned dose to water was less than 1% for each color channel at high dose levels. At high dose levels, ABS and PLA mean residual errors were about 6.9 and 7.8% in the red channel, while 5.2 and 5.7% in the green channel. Combined uncertainties measured to be about 6.9% at high dose levels. This study demonstrated dose differences and uncertainties using 3D printed applicators for HDR Ir-192 brachytherapy.

Malignant paraganglioma presenting as a mandibular metastasis.

BACKGROUND: Metastatic paragangliomas are rare neuroendocrine tumors. Bony metastases most commonly occur in the ribs, vertebrae, and pelvis. Few cases of mandibular metastases have been reported. METHODS: A 75-year-old female presented with a 6-month history of an enlarging mandibular mass. A biopsy was consistent with a paraganglioma. RESULTS: Staging workup with 18 F-fluorodeoxyglucose positron emission tomography demonstrated 2 hypermetabolic intra-abdominal lesions adjacent to the inferior vena cava. These were confirmed as paraganglioma by biopsy and presumed as the primary lesions. The patient underwent left segmental mandibulectomy and neck dissection with osteocutaneous fibula free tissue reconstruction. CONCLUSION: A rare case of malignant paraganglioma presenting as a mandibular metastasis is described. Nuclear medicine studies for paraganglioma are reviewed.

Optimizing laryngeal sparing with intensity modulated radiotherapy or volumetric modulated arc therapy for unilateral tonsil cancer.

BACKGROUND AND PURPOSE: Minimizing radiation dose exposure to nearby organs is key to limiting clinical toxicities associated with radiotherapy. Several treatment modalities such as split- or whole-field intensity-modulated radiotherapy (SF-IMRT, WF-IMRT) and volumetric modulated arc therapy (VMAT) are being used to treat tonsillar cancer patients with unilateral neck radiotherapy. Herein, we provide a modern dosimetric comparison of all three techniques. MATERIALS AND METHODS: Forty patients with tonsillar cancer treated with definitive, ipsilateral neck SF-IMRT were evaluated. Each patient was re-planned with WF-IMRT and VMAT techniques, and doses to selected organs-at-risk (OARs) including the larynx, esophagus, and brainstem were compared. RESULTS: No significant differences in target coverage existed between plans; however, the heterogeneity index improved using WF-IMRT and VMAT relative to SF-IMRT. Compared to SF-IMRT, WF-IMRT and VMAT plans had significantly lower mean doses to the supraglottic larynx (31 Gy, 18.5 Gy, 17 Gy; p < 0.01), the MDACC-defined larynx (13.4 Gy, 10.5 Gy, 9.8 Gy; p < 0.01), and RTOG-defined larynx (15.8 Gy, 12.1 Gy, 11.1 Gy; p < 0.01), respectively. Mean esophageal dose was lowest with SF-IMRT over WF-IMRT and VMAT (5.9 Gy, 12.2 Gy, 11.1 Gy; p < 0.01) but only in the absence of lower neck disease. On average, VMAT plans had shorter treatment times and required less monitor units than both SF-IMRT and WF-IMRT. CONCLUSION: In the setting of unilateral neck radiotherapy, WF-IMRT and VMAT plans can be optimized to significantly improve dose sparing of critical structures compared to SF-IMRT. VMAT offers additional advantages of shorter treatment times and fewer required monitor units.

Imaging-based biomarkers: Changes in the tumor interface of pancreatic ductal adenocarcinoma on computed tomography scans indicate response to cytotoxic therapy.

BACKGROUND: The assessment of pancreatic ductal adenocarcinoma (PDAC) response to therapy remains challenging. The objective of this study was to investigate whether changes in the tumor/parenchyma interface are associated with response. METHODS: Computed tomography (CT) scans before and after therapy were reviewed in 4 cohorts: cohort 1 (99 patients with stage I/II PDAC who received neoadjuvant chemoradiation and surgery); cohort 2 (86 patients with stage IV PDAC who received chemotherapy), cohort 3 (94 patients with stage I/II PDAC who received protocol-based neoadjuvant gemcitabine chemoradiation), and cohort 4 (47 patients with stage I/II PDAC who received neoadjuvant chemoradiation and were prospectively followed in a registry). The tumor/parenchyma interface was visually classified as either a type I response (the interface remained or became well defined) or a type II response (the interface became poorly defined) after therapy. Consensus (cohorts 1-3) and individual (cohort 4) visual scoring was performed. Changes in enhancement at the interface were quantified using a proprietary platform. RESULTS: In cohort 1, type I responders had a greater probability of achieving a complete or near-complete pathologic response (21% vs 0%; P = .01). For cohorts 1, 2, and 3, type I responders had significantly longer disease-free and overall survival, independent of traditional covariates of outcomes and of baseline and normalized cancer antigen 19-9 levels. In cohort 4, 2 senior radiologists achieved a κ value of 0.8, and the interface score was associated with overall survival. The quantitative method revealed high specificity and sensitivity in classifying patients as type I or type II responders (with an area under the receiver operating curve of 0.92 in cohort 1, 0.96 in cohort 2, and 0.89 in cohort 3). CONCLUSIONS: Changes at the PDAC/parenchyma interface may serve as an early predictor of response to therapy. Cancer 2018;124:1701-9. © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.