Showing papers by "Barbara Fisher published in 2019"

A prospective feasibility study evaluating the role of multimodality imaging and liquid biopsy for response assessment in locally advanced rectal carcinoma.

Abstract: Colorectal cancer is a commonly encountered disease that poses several diagnostic and therapeutic challenges. The inherent heterogeneity of tumor biology and propensity to relapse despite “curative” resection pose significant challenges with regard to response assessment. Although MR imaging already plays a key role in primary staging of patients with rectal carcinoma, its reliability in restaging after neoadjuvant therapy is debatable (Van der broek et al. in Dis Colon Rectum 60(3):274–283, 2017). Therefore, there is significant interest in developing additional methods which may improve diagnostic accuracy. This study aims to evaluate the role of multimodality imaging and liquid biopsy in therapeutic response assessment. Seventeen patients were enrolled into the study over a span of 24 months. All underwent hybrid PET-MRI and CT-perfusion (CT-P), prior to and following neoadjuvant therapy for locally advanced rectal carcinoma. Twelve of the 17 patients also underwent liquid biopsy, which consisted of blood sampling and analysis of circulating tumor cells (CTCs) and extracellular vesicles (EVs), including cell fragments and microparticles (MPs), using the Cell Search System (Menarini Silicon Biosystems). SUV, DWI, and ADC were calculated during PET-MRI, and several parameters were evaluated during CT-perfusion, including average perfusion, blood flow (BF), blood volume (BV), mean transit time (MTT), permeability-surface area product (PS), contrast extraction efficiency (E), and K-trans (K). Changes observed pre- and post-neoadjuvant therapy in each modality were compared to tumor response at histopathology using a modified Ryan tumor regression grading system. Of the 17 patients included in the study, 14 were classified as non-responders, and 3 were classified as responders as determined by the modified Ryan Tumor Regression Grade (TRG) scoring system (Van der broek et al. in Dis Colon Rectum 60(3):274–283, 2017). When combined, blood markers and CT-P parameters (mean transit time (MTT), K-trans, and permeability-surface area product (PS)) produced the strongest models (p < 0.01). PET (SUV measurement) combined with CT-P-derived K-trans produced a marginally significant (p = 0.057) model for predicting response. MRI-derived ADC value did not provide a significant model for response prediction. A model of CT-P parameters plus liquid biopsy more accurately predicts tumor response than PET-MRI, CT-P alone, or liquid biopsy alone. These results suggest that in the evaluation of treatment response, liquid biopsy could provide additional information to functional imaging modalities such as CT-P and should therefore be explored further in a trial with larger sample size.

Ncog-01. neurocognitive function (ncf) and quality of life (qol) results from a phase ii study of temozolomide-based chemoradiotherapy regimen for high risk low-grade gliomas

Abstract: RTOG 0424 reported a 73.5% 3-year overall survival (OS) rate. This secondary analysis describes changes in NCF and QOL after therapy. Patients with HR-LGG were treated with radiation and concurrent and adjuvant temozolomide. Standardized NCF tests were performed at baseline, 6 and 12 months (mos). Rates of NCF decline were examined using the reliable change index on Hopkins Verbal Learning Test (HVLT), Trail Making Test (TMT), and Controlled Oral Word Association. Relationships between NCF and subjective cognitive concerns (MOS-Cognitive Function [MOS-CF] scale) were evaluated with Wilcoxon Rank Sum Test. QOL was assessed using FACT-Brain. Longitudinal modeling using maximum likelihood estimation evaluated predictors of change in QOL. Cox models assessed the association of baseline NCF with OS after adjusting for age, anticonvulsants, number of high risk factors, EORTC OS risk group, and tumor crossing the midline. From 1/2005 to 8/2009, 129 evaluable patients were accrued, and 93 (72%) completed at least one NCF/QOL measurement with completers having better neurologic function than noncompleters (p=0.04). Compliance across measures was 55–59% and 54–57% at 6 and 12mos. Deterioration occurred in 50%/40% at 6mos/12mos, respectively, and was most frequent on HVLT (21%/20%), TMTA (29%/20%), and TMTB (22%/14%). Patients with HVLT deterioration at 12mos, compared to patients without deterioration, had significantly greater decrease in MOS-CF (p=0.01). No NCF test at baseline was independently associated with OS. FACT Emotional (p=0.02) and Functional Well-Being (p=0.004) subscales improved over time. EORTC OS high-risk group was associated with worse QOL on all subscales (p< 0.05 to 0.001) except Emotional Well-Being, tumor crossing the midline was associated with worse Emotional Well-Being (p=0.04), and unmethylated MGMT status was associated with better Physical Well-Being (p=0.05). Approximately half of patients with HR-LGG experience NCF decline in the first year after treatment with temozolomide-based concurrent chemoradiation. QOL remained stable or improved.