Faculty Bibliography
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306
Perioperative Therapy for Resectable and Borderline Resectable Pancreatic Adenocarcinoma: An Academic Gastrointestinal Cancer Consortium (AGICC) Study
BACKGROUND:Surgical resection without visible or residual microscopic disease (R0 resection) is known as the optimal path to cure localized pancreatic cancer (PDAC). Neoadjuvant therapy (NAT) is used to improve R0 resection rates; however, the optimal regimen is unclear. We assessed the safety and efficacy of peri-operative gemcitabine/nab-paclitaxel (GEM/NAB) and pre-operative stereotactic body radiotherapy (SBRT) in patients with resectable (R-PDAC) and borderline resectable PDAC (BR-PDAC). PATIENTS AND METHODS/METHODS:This was a prospective, multicenter single arm phase 2 study in patients with R-PDAC and BR-PDAC. Patients received three cycles of GEM/NAB prior to SBRT followed by surgery and three cycles of adjuvant GEM/NAB. Primary endpoint was R0 surgical resection rate in each cohort. Secondary endpoints included safety and overall survival (OS). RESULTS:Eighty-six patients consented and following radiologic screening, 49 were enrolled into two cohorts: R-PDAC (n = 20) and BR-PDAC (n = 29) between June 2016 and April 2021. Seventy percent of R-PDAC (14/20) and 55.2% of BR-PDAC patients (16/29) completed all NAT. Eleven R-PDAC (55.0%) and 11 BR-PDAC patients (37.9%) underwent surgical resection. Nine R-PDAC (45.0%) and 9 BR-PDAC patients (31.0%) had R0 resections. The median OS for R-PDAC and BR-PDAC patients with R0 resections was 22 months (95% CI: 17.7months-NA) and 39 months (95%CI:13.21months-NA), respectively. CONCLUSION/CONCLUSIONS:While the trial failed to meet one of its primary objectives as only 45% of R-PDAC patients had an R0 resection, the objective of 30% R0 resection for the BR-PDAC group was met. NAT should be part of current therapeutic strategies for BR-PDAC; however, our trial does not answer what is the best NAT for BR-PDAC.
PMID: 40972532
ISSN: 1549-490x
CID: 5935632
Evaluating Breast Cancer Intravoxel Incoherent Motion MRI Biomarkers across Software Platforms
Purpose To evaluate intravoxel incoherent motion (IVIM) biomarkers across different MRI vendors and software programs for breast cancer characterization in a two-site study. Materials and Methods This institutional review board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study included 106 patients (with 18 benign and 88 malignant lesions) who underwent bilateral diffusion-weighted imaging (DWI) between February 2009 and March 2013. DWI was performed using 1.5-T (n = 6) or 3-T MRI scanners from two vendors using single-shot spin-echo echo-planar imaging or twice-refocused, bipolar gradient single-shot turbo spin-echo readout with multiple b values between 0 and 1000 sec/mm2. IVIM parameters tissue diffusivity (Dt
PMID: 40910883
ISSN: 2638-616x
CID: 5936402
Multi-modal proton and sodium MRI for outcome prediction in mild traumatic brain injury
OBJECTIVES/OBJECTIVE:In mild traumatic brain injury, imaging biomarkers are needed to support clinical management. In four antecedent publications, we used two new (sodium and fingerprinting) and two established (spectroscopy and diffusion) MR techniques in a longitudinally followed patient cohort. Here we report final results and combine all data to determine which marker(s) from the four modalities offer the greatest utility for detecting injury and predicting outcomes. We also leverage the independent specificities offered by each modality to explore injury mechanisms. MATERIALS AND METHODS/METHODS:The longitudinal spectroscopy data were analysed to complete a full data set of proton (spectroscopy, fingerprinting, diffusion) and sodium MRI, acquired alongside symptomatic, cognitive, and functional assessments in 27 patients at 1, 3, and 12 months following injury. Twenty-three matched controls were scanned once. Testing for associations between nine MR markers and three outcome measures was standardized across the entire data set, and performed using Spearman correlations and logistic regression. RESULTS:from fingerprinting (marker of the cellular microenvironment). CONCLUSIONS:We identified independent, dynamic, metabolic and ionic changes, with choline and creatine from spectroscopy fulfilling the most criteria for a clinical biomarker.
PMID: 40794310
ISSN: 1432-1459
CID: 5907082
International journal of radiation oncology biology physics. 2025:122(5):1128-1139.DOI: 10.1016/j.ijrobp.2024.12.027
Phase 1-2 Study of Prone Hypofractionated Accelerated Breast and Nodal Intensity Modulated Radiation Therapy
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.
PMID: 39788388
ISSN: 1879-355x
CID: 5805232
Novel Wash-In Characteristics of Background Parenchymal Enhancement on Ultrafast Dynamic Contrast-Enhanced Breast MRI
PMID: 40266709
ISSN: 1546-3141
CID: 5830282
Optimal virtual monoenergy for the detection of pancreatic adenocarcinoma during the pancreatic parenchymal phase on photon counting CT
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.
PMID: 39775026
ISSN: 2366-0058
CID: 5773212
Time to Enhancement of Foci Relative to Background Parenchymal Enhancement on Ultrafast Breast MRI: A Single-Center Retrospective Study
PMID: 40202353
ISSN: 1546-3141
CID: 5823862
Reliability of pre-operative symptoms, radiographs, and MRI for the assessment of cartilage loss in patients with femoroacetabular impingement syndrome with intra-operative correlation
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.
PMID: 40312549
ISSN: 1432-2161
CID: 5834262
Topical TLR7 agonist and radiotherapy in patients with metastatic breast cancer
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.
PMID: 40187749
ISSN: 2051-1426
CID: 5819522
Home-based transcranial direct current stimulation paired with cognitive training to reduce fatigue in multiple sclerosis
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.
PMCID:11802740
PMID: 39915560
ISSN: 2045-2322
CID: 5784342
