Impact of MRI resolution for Linac-based stereotactic radiosurgery.

Objective: Magnetic resonance imaging (MRI) is a standard imaging modality in intracranial stereotactic radiosurgery (SRS) for defining target volumes. However, wide disparities in MRI resolution exist, which could directly impact accuracy of target delineation. Here, sequences with various MRI resolution were acquired on phantoms to evaluate the effect on volume definition and dosimetric consequence for cranial SRS. Materials/Methods: Four T1-weighted MR sequences with increasing 3D resolution were compared, including two Spin Echo (SE) 2D acquisitions with 5mm and 3mm slice thickness (SE5mm, SE3mm) and two gradient echo 3D acquisitions (TFE, BRAVO). The voxel sizes were 0.4×0.4×5.0, 0.5×0.5×3.0, 0.9×0.9×1.25, and 0.4×0.4×0.5 mm3, respectively. Four phantoms with simulated lesions of different shape and volume (range, 0.53-25.0 cm3) were imaged, resulting in 16 total sets of MRIs. Four radiation oncologists provided contours on individual MR image set. All observer contours were compared with ground truth, defined on CT image according to the absolute dimensions of the target structure, using Dice similarity coefficient (DSC), Hausdorff distance (HD), mean distance-to-agreement (MDA), and the ratio between reconstructed and true volume (Ratiovol ). For dosimetric consequence, SRS plans targeting observer volumes were created. The true Paddick conformity index ( C I p a d d i c k t r u e ), calculated with true target volume, was correlated with quality of observer volume. Results: All measures of observer contours improved as increasingly higher MRI resolution was provided from SE5mm to BRAVO. The improvement in DSC, HD and MDA was statistically significant (p<0.01). Dosimetrically, C I p a d d i c k t r u e   strongly correlated with DSC of the planning observer volume (Pearson's r=0.94, p<0.00001). Conclusions: Significant improvement in target definition and reduced inter-observer variation was observed as the MRI resolution improved, which also improved the quality of SRS plans. Results imply that high resolution 3D MR sequences should be used to minimize potential errors in target definition, and multi-slice 2D sequences should be avoided.

Outcomes of Primary Mucosal Head and Neck Squamous Cell Carcinoma in Solid Organ Transplant Recipients.

Introduction Patients who undergo solid organ transplants have a higher risk of developing malignancies and subsequent recurrences. Clinical outcomes in transplant recipients with primary mucosal head and neck squamous cell carcinoma (HNSCC) are not well described in the published literature. Therefore, we retrospectively studied the outcomes in this group of patients.  Methods This Institutional Review Board (IRB)-approved analysis included patients who had previously undergone solid organ transplants and subsequently were diagnosed with primary mucosal HNSCC between 2006 and 2021. Our institutional database of solid organ transplant recipients was cross-referenced with our head and neck cancer database to identify the patients included in this cohort. In addition, Kaplan-Meier analyses were performed to calculate overall and disease-free survival. Results Of 1,221 patients, 20 met the inclusion criteria. The median time from organ transplant to HNSCC diagnosis was 5.9 years (range: 0.5-18.5 years). A total of 11 (55.0%) and 9 (45.0%) patients presented with localized and locally advanced disease, respectively. Two-year overall and disease-free survivals were 59.1% and 73.5%, respectively. After initial treatment, six (30.0%) patients experienced a recurrence. All patients who developed a recurrence died within the follow-up period. The median time of death after recurrence for all six patients was 11.5 months (range: 2-22 months).  Conclusion This series highlights a high mortality rate following recurrence among patients with primary mucosal HNSCC and a solid organ transplant history. A better understanding of how solid organ transplant history adversely impacts the course of HNSCC could help properly guide treatment, follow-up, and survivorship decisions.

Application of Continuous Positive Airway Pressure for Thoracic Respiratory Motion Management: An Assessment in a Magnetic Resonance Imaging-Guided Radiation Therapy Environment.

PURPOSE: Patient tolerability of magnetic resonance (MR)-guided radiation treatment delivery is limited by the need for repeated deep inspiratory breath holds (DIBHs). This volunteer study assessed the feasibility of continuous positive airway pressure (CPAP) with and without DIBH for respiratory motion management during radiation treatment with an MR-linear accelerator (MR-linac). METHODS AND MATERIALS: MR imaging safety was first addressed by placing the CPAP device in an MR-safe closet and configuring a tube circuit via waveguide to the magnet bore. Reproducibility and linearity of the final configuration were assessed. Six healthy volunteers underwent thoracic imaging in a 0.35T MR-linac, with one free breathing (FB) and 2 DIBH acquisitions being obtained at 5 pressures from 0 to 15 cm-H2O. Lung and heart volumes and positions were recorded; repeatability was assessed by comparing 2 consecutive DIBH scans. Blinded reviewers graded images for motion artifact using a 3-point grading scale. Participants completed comfort and perception surveys before and after imaging sessions. RESULTS: Compared with FB alone, FB-10, FB-12, and FB-15 cm H2O significantly increased lung volumes (+23%, +34%, +44%; all P <.05) and inferiorly displaced the heart (0.86 cm, 0.96 cm, 1.18 cm; all P < . 05). Lung volumes were significantly greater with DIBH-0 cm H2O compared with FB-15 cm H2O (+105% vs +44%, P = .01), and DIBH-15 cm H2O yielded additional volume increase (+131% vs +105%, P = .01). Adding CPAP to DIBH decreased lung volume differences between consecutive breath holds (correlation coefficient 0.97 at 15 cm H2O vs 0.00 at 0 cm H2O). The addition of 15 cm H2O CPAP reduced artifact scores (P = .03) compared with FB; all DIBH images (0-15 cm H2O) had less artifact (P < .01). CONCLUSIONS: This work demonstrates the feasibility of integrating CPAP in an MR-linac environment in healthy volunteers. Extending this work to a larger patient cohort is warranted to further establish the role of CPAP as an alternative and concurrent approach to DIBH in MR-guided radiation therapy.

Color temperature tunable white light based on monolithic color-tunable light emitting diodes.

A color-temperature tunable white light-emitting diode (LED) based on a newly developed monolithic color-tunable LED structure was demonstrated. The color-tunable LED structure consists of three different sets of quantum wells separated by intermediate carrier blocking layers that can independently emit visible lights from 460 to 650 nm under different injection currents. To generate white light, the color-tunable LED is operated under pulsed conditions with each pulse consisting of multiple steps of different current amplitudes and widths emitting different colors. The combined spectrum of different colors is aimed to mimic that of the blackbody radiation light source. The pulse rate is designed to be higher than the human eye response rate, so the human eye will not discern the emission of successive colors but a singular emission of white light. Results of a two-step pulse design show this method is able to generate white light from 2700 K - 6500 K. Moreover, their color coordinates fall within the 4-step MacAdam ellipses about the Planckian locus while achieving the Color Rendering Index (CRI) in the 80-90 range. Finally, simulations show improvement of CRI into the 90-100 range is possible with further optimization to the color-tunable LED spectral emission and use of three-step pulses.

Improvement of Multiparametric MR Image Segmentation by Augmenting the Data With Generative Adversarial Networks for Glioma Patients.

Every year thousands of patients are diagnosed with a glioma, a type of malignant brain tumor. MRI plays an essential role in the diagnosis and treatment assessment of these patients. Neural networks show great potential to aid physicians in the medical image analysis. This study investigated the creation of synthetic brain T1-weighted (T1), post-contrast T1-weighted (T1CE), T2-weighted (T2), and T2 Fluid Attenuated Inversion Recovery (Flair) MR images. These synthetic MR (synMR) images were assessed quantitatively with four metrics. The synMR images were also assessed qualitatively by an authoring physician with notions that synMR possessed realism in its portrayal of structural boundaries but struggled to accurately depict tumor heterogeneity. Additionally, this study investigated the synMR images created by generative adversarial network (GAN) to overcome the lack of annotated medical image data in training U-Nets to segment enhancing tumor, whole tumor, and tumor core regions on gliomas. Multiple two-dimensional (2D) U-Nets were trained with original BraTS data and differing subsets of the synMR images. Dice similarity coefficient (DSC) was used as the loss function during training as well a quantitative metric. Additionally, Hausdorff Distance 95% CI (HD) was used to judge the quality of the contours created by these U-Nets. The model performance was improved in both DSC and HD when incorporating synMR in the training set. In summary, this study showed the ability to generate high quality Flair, T2, T1, and T1CE synMR images using GAN. Using synMR images showed encouraging results to improve the U-Net segmentation performance and shows potential to address the scarcity of annotated medical images.

Outcomes for patients with head and neck squamous cell carcinoma presenting with N3 nodal disease.

BACKGROUND: The present study evaluated clinical outcomes for patients with head and neck squamous cell carcinoma presenting with N3 nodal disease. METHODS: A retrospective analysis of N3 head and neck squamous cell carcinoma patients was performed. Pearson chi-square and Wilcoxon signed-rank tests were used to analyze patient demographics, disease characteristics, and treatment variables. Survival was evaluated using Kaplan-Meier curves with the log-rank test. Univariate analysis using Cox proportional hazards models was used to define factors associated with overall survival. Patient and tumor characteristics associated with treatment assignments were analyzed by univariate multinomial logistic regression. RESULTS: We identified 36 patients with radiographically-defined N3 disease. For the entire cohort, median follow-up was 23.6 (range 2.8-135.0) months, and overall survival was 60% at 2 years and 30% at 5 years. Overall survival was similar between patients receiving primary surgery, radiotherapy, or chemoradiotherapy (p = 0.10). Primary, regional, and distant control at 5 years was 71%, 66%, and 53%, respectively. There was a trend towards improved regional control with primary surgery (p = 0.07). Planned neck dissection following primary chemoradiotherapy did not improve regional control (p = 0.55). Patients with p16-positive tumors exhibited improved overall (p = 0.05) and metastatic recurrence-free survival (p < 0.05). There were no factors predictive of treatment assignment nor factors associated with overall survival, local and regional control, or distant metastases free-survival on univariate analysis. CONCLUSIONS: Patients with N3 head and neck squamous cell carcinoma exhibit 5-year overall survival rates of approximately 30% regardless of treatment modality. Planned neck dissection does not improve regional control in patients undergoing definitive chemoradiotherapy. p16-positive patients represent a favorable cohort. Distant failure comprises the major failure pattern and should be the focus of future studies in improving the outcome of this patient cohort.

Merkel Cell Carcinoma Analysis of Outcomes: A 30-Year Experience.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy with poor prognosis. Limited data exists to guide treatment decisions. Here we report on our institutional experience and outcomes treating patients with MCC. METHODS: A database search (1984-2014) of patients treated at the University of Wisconsin Hospital and Clinics was used to identify patients with histologically confirmed MCC. Patient, tumor, and treatment characteristics were examined via review of medical records. Statistical analyses were performed to assess outcomes and associated prognostic factors. RESULTS: A total of 87 patients with MCC were identified with a median follow-up of 17 months (mean: 38, range: 0-210 months). Two and five-year overall survival rates were 53.9% and 32.8%, respectively. Recurrence was documented in 31.0% of patients (85.2% locoregional, 48.1% distant and 33.3% both). Patients with a history of immunosuppression exhibited significantly worse survival (hazard ratio, 2.01; 95% CI, 1.1-3.7) when compared to immune-competent individuals. The head and neck region was the most common location of primary lesion (N=49) followed by the extremities (N=31). Upper extremity primaries predicted significantly better overall survival (hazard ratio, 0.48; 95% CI, 0.23-0.99) while lower extremity primaries did not have significantly better results (hazard ratio, 0.5; 95% CI, 0.21-1.2) in comparison to head and neck site of primary. Nodal involvement (hazard ratio, 2.95; 95% CI, 1.5-5.79) was also a negative prognostic factor associated with poor overall survival when compared with clinically node negative patients. Primary tumor size > 2 cm (hazard ratio, 1.76; 95% CI, 0.91-3.4) was not associated with survival. CONCLUSIONS: This study highlights the role of various factors in determining prognosis of Merkel cell carcinoma; history of immunosuppression, nodal involvement, and head/neck primary predicted worse overall survival. These findings suggest that improvements in both distant and locoregionally directed therapies might play an important role in control of MCC and identify areas for future study.