Faculty Bibliography

OBJECTIVE:To assess the correlation of pre-operative symptoms, pre-operative diagnostic imaging for cartilage loss, and intra-operative cartilage findings in patients undergoing hip arthroscopy for femoroacetabular impingement syndrome. MATERIALS AND METHODS/METHODS:Three radiologists performed retrospective independent reviews of pre-operative MRIs in 96 hips for acetabular/femoral cartilage loss utilizing a simplified "high-low" classification and the International Cartilage Repair Society grading system. Severity of supra-foveal central femoral head cartilage loss was separately noted. Pre-operative radiographs were graded using the Tonnis and Kellgren-Lawrence systems and for central joint space narrowing. Pre-operative patient symptoms were prospectively gathered utilizing the Nonarthritic Hip Score and the modified Harris Hip Score. Intra-operatively, cartilage loss was recorded using the Outerbridge system. RESULTS: CONCLUSION/CONCLUSIONS:Despite MRI underestimation of cartilage loss, the very weak-to-weak correlation of clinical symptoms with pre-operative imaging and intra-operative findings emphasizes the importance of MRI in pre-operative evaluation.

BACKGROUND:Toll-like receptor (TLR) agonists and radiation therapy hold promise for cancer immunotherapy. We conducted a phase I/II trial combining topical imiquimod (IMQ, a TLR-7 agonist) and local radiotherapy (RT) in patients with metastatic breast cancer accompanied by longitudinal transcriptional analysis of tumor biopsies. METHODS:The primary objective of the trial (NCT01421017) was to assess systemic responses by immune-related response criteria (irRC) after an 8-week cycle of topical IMQ and concurrent local RT (cohort 1). An amendment to the trial added two cohorts, both received one dose of cyclophosphamide (CTX) administered 1 week before study treatment initiation, IMQ/RT/CTX (cohort 2) and RT/CTX control (cohort 3). Cutaneous metastases were prospectively assigned to treatment with IMQ and RT (area A) or IMQ alone (area B). Secondary objectives were safety (Common Terminology Criteria for Adverse Events criteria) and local response in skin metastases. In all IMQ cohorts, tumors were biopsied before treatment and at 2 and 3 weeks. RESULTS:31 patients were enrolled (n=12, n=12, and n=7, in cohort 1, 2, and 3, respectively), with 4 out of 24 patients in the IMQ cohorts showing systemic tumor responses (two complete responses (CR) and two partial responses (PR)). No objective responses were observed in the seven patients enrolled in the control arm (RT alone). The treatment was well-tolerated, no grade 4-5 treatment-related adverse events occurred and grade 3 AEs were manageable (anemia, local pain, and local ulceration, n=1 each). Local objective responses were observed in 19/24 (9 CR and 10 PR) and 5/24 (5 PR) in areas treated with combined IMQ-RT and IMQ alone, respectively (p<0.001). All 24 patients treated with IMQ underwent serial biopsies, and 84 samples yielded sufficient material for transcriptional analyses. These revealed that the presence of a T-helper 1 functional orientation of the tumor microenvironment paralleled by the downregulation of DNA-repair genes was associated with CR after IMQ+RT, but not after IMQ alone. No post-treatment activation of immune-effector functions was observed in stable and progressing lesions. CONCLUSIONS:Our findings support the safety and clinical efficacy of combining topical IMQ with local RT for recurrent breast cancer, with evidence of local and occasional systemic antitumor activity. TRIAL REGISTRATION NUMBER/BACKGROUND:NCT01421017.

Fatigue is a common and often debilitating feature of multiple sclerosis (MS) that lacks reliably effective treatment options for most patients. Transcranial direct current stimulation (tDCS), a safe and well-tolerated type of noninvasive brain stimulation, is a low-cost and home-based approach with the potential to reduce fatigue in MS. We conducted a double-blind, sham-controlled, randomized clinical trial to compare active vs. low-dose (sham) tDCS paired with computer-based cognitive training, delivered as a home-based intervention, to reduce MS-related fatigue. Participants with MS-related fatigue, but without depression, were stratified by neurologic disability using the Extended Disability Status Scale (EDSS) and randomized to complete 30 daily sessions over six weeks of either active or sham tDCS paired with online cognitive training (BrainHQ). The primary outcome was the change in PROMIS Fatigue score from baseline to the end of the intervention. A total of 117 participants were randomized, with 92% completing all treatment sessions. Both groups showed significant reductions in fatigue, with no significant difference between them. This suggests that tDCS does not provide any additional benefit over cognitive training alone in reducing fatigue, but confirms the feasibility and tolerance of this home-based intervention.

PURPOSE/OBJECTIVE:As the pancreas is a low contrast visibility organ, pancreatic ductal adenocarcinoma detection is challenging due to subtle attenuation differences between tumor and pancreatic parenchyma. Photon counting CT (PCCT) has superior iodine contrast-to-noise ratio than conventional CT and also affords the creation of low keV virtual monoenergetic images, both of which increase adenocarcinoma conspicuity. The purpose therefore was to identify the optimal virtual monoenergy for visualizing PDAC during the pancreatic parenchymal phase of enhancement at PCCT using both quantitative and qualitative analyses. METHODS:Consecutive patients with pancreatic parenchymal phase PCCT source data were retrospectively identified by PACS search. For the quantitative analysis, region of interest (ROI) measurements were drawn in the pancreatic head, body, tail, pancreatic adenocarcinoma (if present), and psoas muscles on 40-120 keV virtual monoenergetic images in 10 keV increments. Based on the quantitative analysis results and vendor recommendations, four virtual monoenergies(40 keV, 55 keV, 70 keV, and 85 keV) were selected for additional qualitative analysis. Three radiologists blinded to four virtual monoenergies assessed overall image quality, image noise, pancreatic enhancement, and pancreatic mass conspicuity on 5-point Likert scales. RESULTS:54 patients (28/54 male, mean[SD] age: 62 [13] years) were included. Quantitatively, 40 keV had the highest pancreatic parenchymal CNR and attenuation difference between the adenocarcinoma and parenchyma, but also the highest noise (HUsd). Qualitatively, 70 keV had the best overall image quality (Mean [SE]: 3.7[0.1]) and lower noise than 40 and 55 keV (3.6[0.08] vs. 1.8[0.07] and 2.7[0.05], respectively, p < .001). 40 keV had the greatest pancreatic enhancement (mean[SE] 4.6[0.11]). Adenocarcinoma conspicuity ratings were greatest at 40 keV and 55 keV, and not significantly different from each other (mean[SE] 4.4[0.13] and 4.3[0.14], respectively, Tukey adj-p =.20). 55 keV had greater overall image quality and lower noise than 40 keV (mean[SE] 3.4[0.08] vs. 2.5[0.08], Tukey adj-p < .001 and 2.7[0.05] vs. 1.8[0.07], Tukey adj-p < .001 respectively). CONCLUSION/CONCLUSIONS:55 keV pancreatic parenchymal phase virtual monoenergetic images afford optimal pancreatic assessment at PCCT for the visualization of pancreatic adenocarcinoma. Routinely viewing 55 keV virtual monoenergetic images at PCCT may improve PDAC detection.

PURPOSE/OBJECTIVE:In patients with breast cancer, prone radiation therapy (RT) has been shown to reduce heart and lung dose. Though prone positioning is routinely used for whole breast RT, its use when treating the regional lymph nodes is not widespread. METHODS AND MATERIALS/METHODS:In this phase 1/2 trial for stage IB-IIA breast cancer treated with lumpectomy or mastectomy, patients received 40.5 Gy in 15 fractions to the breast or chest wall and regional lymph nodes with an integrated tumor bed boost for lumpectomy patients. Primary endpoints were grade >2 acute toxicity and dosimetric feasibility. Secondary endpoints were the incidence of resimulation to improve dosimetry and late toxicity. Exploratory endpoints were local recurrence, disease-free survival, distant recurrence-free survival, and overall survival. RESULTS:From 2009 to 2016, 97 patients were enrolled (68% lumpectomy and 32% mastectomy), among which 92 were treated in the prone position. Five patients were resimulated and treated supine. Among the prone-treated patients, there were no acute toxicities greater than grade 2. A total of 92%, 98%, and 89% met a planning target volume tumor V48 Gy ≥98%, breast V40.5 Gy ≥95%, and nodal V38.5 Gy ≥95%, respectively. All met the heart V5 Gy <5%, contralateral lung V5 Gy <15%, spinal cord dose maximum (Dmax) ≤37.5 Gy, esophagus V30 Gy <50%, and Dmax ≤40.5 Gy. Ninety-eight percent met the ipsilateral lung V10 Gy. Brachial plexus Dmax <42 Gy was met in 74% with a mean increase of 1.61 Gy (SD, 1.96 Gy) over the target. At a median follow-up of 8 years, grade 2 to 3 late toxicity was 23% for prone patients. There were 2 local recurrences (2%) and no chest wall or nodal recurrences. The 8-year distant recurrence-free survival, disease-free survival, and overall survival were 88% (95% CI, 81%-95%), 86% (95% CI, 78%-95%), and 91% (95% CI, 84%-98%), respectively. CONCLUSIONS:Toxicity was low, and outcomes were excellent in this prospective trial of prone hypofractionated nodal RT.

INTRODUCTION/UNASSIGNED:The intravoxel incoherent motion (IVIM) model of diffusion weighted imaging (DWI) provides imaging biomarkers for breast tumor characterization. It has been extensively applied for both diagnostic and prognostic goals in breast cancer, with increasing evidence supporting its clinical relevance. However, variable performance exists in literature owing to the heterogeneity in datasets and quantification methods. METHODS/UNASSIGNED: RESULTS/UNASSIGNED: DISCUSSION/UNASSIGNED:

PURPOSE/OBJECTIVE:A digital visual communication tool was recently developed by MyCareGorithm which incorporates explanations of treatments and procedures for cancer patients. This study will evaluate if this novel tool can enhance both patient and provider satisfaction. METHODS:In an IRB approved, prospective, pilot study, patients and caregivers at a single institution receiving head and neck cancer radiation underwent an initial consult using this digital tool and completed a survey of 6 questions to evaluate their understanding of their disease. Providers completed a 7-question survey to rate their satisfaction. Patients and caregivers with 4 or more "Yes" answers and providers with 5 or more "Yes" answers were defined as "Satisfied". In order to obtain 90% power to detect that the proportion of "Satisfied" patients (assumed 75%) is greater than 50% with a significance level 5% using a one-sided Z test, we planned to enroll 30 patients. RESULTS:Thirty patients enrolled and completed all surveys. Most patients were male (66%), white (60%) and spoke English as a primary language (93%). Patients most commonly had oropharyngeal cancer (23%). Overall, 27 out of 30 of patients (90%; one sided 95%CI: 76.1%) were satisfied (z = 4.38, p < 0.05), 16 of the 17 caregivers (94%; one sided 95% CI: 74.8%) were satisfied and 100% of providers were satisfied with the digital tool. Most patients (90%) and caregivers (94%) felt that the tool improved their understanding of the disease. One male answered "No" for all 6 questions commenting that it was only marginally helpful. One female also answered "No" for all questions commenting that she did not find it helpful on its own without the provider explanation. Out of the 30 patients, 26 (87%) stayed at our institution to receive treatment. CONCLUSIONS:These findings showed high rates of patient, caregiver and provider satisfaction with their initial consult when incorporating a digital visual tool. Its routine use in clinical practice should be strongly considered.

Adult polyglucosan body disease (APBD) is a rare autosomal recessive glycogen storage disorder that leads to slowly progressive multi-organ dysfunction in adulthood. A novel disease-specific patient-reported outcome measure was created and administered to assess symptom burden and health-related quality of life (HR-QOL) in APBD. Thirty-six participants between 30 and 79 years of age (83% ≥60 years, 56% male) completed the anonymous questionnaire independently or with a caregiver proxy (75% self-report). Unemployment predicted an 18.3 (95% CI: 2.8, 33.8; p = 0.028) higher composite disease severity score and a 28.8 (95% CI: 8.2, 49.4; p = 0.010) higher composite HR-QOL score. Use of one or more assistive devices also predicted a 29.3 (95% CI: 8.3, 50.4; p = 0.011) higher composite disease severity score and a 41.8 (95% CI: 10.9, 72.8; p = 0.013) higher composite HR-QOL score. Proxy survey completion predicted a 19.4 (95% CI: 4.1, 34.7; p = 0.020) higher composite disease severity score compared to self-report. Older age at survey completion predicted a 27.4 higher composite HR-QOL score (95% CI: 2.5, 52.4; p = 0.039) for participants in their sixties compared to those between 30 and 59 years old. The development of the Adult Polyglucosan Body Disease questionnaire on Symptom burden and health-related Quality of life (APBD-SQ) marks an important stride forward in capturing the patient experience as a tool for disease monitoring and future research.