Hypofractionated Radiation Therapy (Hypo-RT) for the Treatment of Localized Bladder Cancer.

BACKGROUND: Various radiotherapeutic regimens are used in the treatment of bladder cancer. OBJECTIVE: We aimed to evaluate early toxicity and outcomes associated with hypofractionated radiation therapy (Hypo-RT), 55Gy in 20 fractions. MATERIAL AND METHODS: We identified 40 patients who received definitive Hypo-RT for localized bladder cancer. Most patients were men (62.5%), elderly (median age 82), had high Charlson Comorbidity Index score (median 7, range 4-9) and were nonsurgical candidates (80%). Sixty-eight percent had a macroscopically complete transurethral resection of bladder tumor (TURBT) and 33 patients (82.5%) received concurrent chemotherapy. Acute (< =3mo) and late (>3mo) toxicities were assessed according to CTCAE v4.0. Survival outcomes were estimated using the Kaplan-Meier method. Median follow up after Hypo-RT was 32 months (95% CI: 28-49 months). RESULTS: Overall rates of acute grade 2 genitourinary (GU) and gastrointestinal (GI) toxicities were 40% each, most commonly urinary frequency and diarrhea. Two cases of acute grade 3 GU/GI toxicity occurred. Late grade 2+ toxicity occurred in 3 patients (7.5%): 2 grade 2 GU and 1 grade 3 GI. Seventy-seven percent achieved a complete response (CR). Six patients (20%) developed disease recurrence at a median time of 9.1 months. The estimated 2-year DFS and 2-year DSS rate were 59% (95% CI, 45-78%) and 78% (95% CI, 65-93%), respectively. Receipt of concurrent chemotherapy (p = 0.003) and achieving a CR (p = 0.018) were univariably associated with improved DSS. Tis component was associated with worse DSS (p = 0.015). CONCLUSION: Hypo-RT had a favorable toxicity profile and encouraging cancer control outcomes in this mostly elderly and frail patient cohort.

Application of Community Detection Algorithm to Investigate the Correlation between Imaging Biomarkers of Tumor Metabolism, Hypoxia, Cellularity, and Perfusion for Precision Radiotherapy in Head and Neck Squamous Cell Carcinomas.

The present study aimed to investigate the correlation at pre-treatment (TX) between quantitative metrics derived from multimodality imaging (MMI), including 18F-FDG-PET/CT, 18F-FMISO-PET/CT, DW- and DCE-MRI, using a community detection algorithm (CDA) in head and neck squamous cell carcinoma (HNSCC) patients. Twenty-three HNSCC patients with 27 metastatic lymph nodes underwent a total of 69 MMI exams at pre-TX. Correlations among quantitative metrics derived from FDG-PET/CT (SUL), FMSIO-PET/CT (K1, k3, TBR, and DV), DW-MRI (ADC, IVIM [D, D*, and f]), and FXR DCE-MRI [Ktrans, ve, and τi]) were investigated using the CDA based on a "spin-glass model" coupled with the Spearman's rank, ρ, analysis. Mean MRI T2 weighted tumor volumes and SULmean values were moderately positively correlated (ρ = 0.48, p = 0.01). ADC and D exhibited a moderate negative correlation with SULmean (ρ ≤ -0.42, p < 0.03 for both). K1 and Ktrans were positively correlated (ρ = 0.48, p = 0.01). In contrast, Ktrans and k3max were negatively correlated (ρ = -0.41, p = 0.03). CDA revealed four communities for 16 metrics interconnected with 33 edges in the network. DV, Ktrans, and K1 had 8, 7, and 6 edges in the network, respectively. After validation in a larger population, the CDA approach may aid in identifying useful biomarkers for developing individual patient care in HNSCC.

Quantifying clinical severity of physics errors in high-dose rate prostate brachytherapy using simulations.

PURPOSE: To quantitatively evaluate through automated simulations the clinical significance of potential high-dose rate (HDR) prostate brachytherapy (HDRPB) physics errors selected from our internal failure-modes and effect analysis (FMEA). METHODS AND MATERIALS: A list of failure modes was compiled and scored independently by 8 brachytherapy physicists on a one-to-ten scale for severity (S), occurrence (O), and detectability (D), with risk priority number (RPN) = SxOxD. Variability of RPNs across observers (standard deviation/average) was calculated. Six idealized HDRPB plans were generated, and error simulations were performed: single (N = 1722) and systematic (N = 126) catheter shifts (craniocaudal; -1cm:1 cm); single catheter digitization errors (tip and connector needle-tips displaced independently in random directions; 0.1 cm:0.5 cm; N = 44,318); and swaps (two catheters swapped during digitization or connection; N = 528). The deviations due to each error in prostate D90%, urethra D20%, and rectum D1cm3 were analyzed using two thresholds: 5-20% (possible clinical impact) and >20% (potentially reportable events). RESULTS: Twenty-nine relevant failure modes were described. Overall, RPNs ranged from 6 to 108 (average ± 1 standard deviation, 46 ± 23), with responder variability ranging from 19% to 184% (average 75% ± 30%). Potentially reportable events were observed in the simulations for systematic shifts >0.4 cm for prostate and digitization errors >0.3 cm for the urethra and >0.4 cm for rectum. Possible clinical impact was observed for catheter swaps (all organs), systematic shifts >0.2 cm for prostate and >0.4 cm for rectum, and digitization errors >0.2 cm for prostate and >0.1 cm for urethra and rectum. CONCLUSIONS: A high variability in RPN scores was observed. Systematic simulations can provide insight in the severity scoring of multiple failure modes, supplementing typical FMEA approaches.

Diffusion and Perfusion MRI Predicts Response Preceding and Shortly After Radiosurgery to Brain Metastases: A Pilot Study.

BACKGROUND AND PURPOSE: To determine the ability of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict long-term response of brain metastases prior to and within 72 hours of stereotactic radiosurgery (SRS). METHODS: In this prospective pilot study, multiple b-value DWI and T1-weighted DCE-MRI were performed in patients with brain metastases before and within 72 hours following SRS. Diffusion-weighted images were analyzed using the monoexponential and intravoxel incoherent motion (IVIM) models. DCE-MRI data were analyzed using the extended Tofts pharmacokinetic model. The parameters obtained with these methods were correlated with brain metastasis outcomes according to modified Response Assessment in Neuro-Oncology Brain Metastases criteria. RESULTS: We included 25 lesions from 16 patients; 16 patients underwent pre-SRS MRI and 12 of 16 patients underwent both pre- and early (within 72 hours) post-SRS MRI. The perfusion fraction (f) derived from IVIM early post-SRS was higher in lesions demonstrating progressive disease than in lesions demonstrating stable disease, partial response, or complete response (q = .041). Pre-SRS extracellular extravascular volume fraction, ve , and volume transfer coefficient, Ktrans , derived from DCE-MRI were higher in nonresponders versus responders (q = .041). CONCLUSIONS: Quantitative DWI and DCE-MRI are feasible imaging methods in the pre- and early (within 72 hours) post-SRS evaluation of brain metastases. DWI- and DCE-MRI-derived parameters demonstrated physiologic changes (tumor cellularity and vascularity) and offer potentially useful biomarkers that can predict treatment response. This allows for initiation of alternate therapies within an effective time window that may help prevent disease progression.

Quantitative Non-Gaussian Intravoxel Incoherent Motion Diffusion-Weighted Imaging Metrics and Surgical Pathology for Stratifying Tumor Aggressiveness in Papillary Thyroid Carcinomas.

We assessed a priori aggressive features using quantitative diffusion-weighted imaging metrics to preclude an active surveillance management approach in patients with papillary thyroid cancer (PTC) with tumor size 1-2 cm. This prospective study enrolled 24 patients with PTC who underwent pretreatment multi-b-value diffusion-weighted imaging on a GE 3 T magnetic resonance imaging scanner. The apparent diffusion coefficient (ADC) metric was calculated from monoexponential model, and the perfusion fraction (f), diffusion coefficient (D), pseudo-diffusion coefficient (D*), and diffusion kurtosis coefficient (K) metrics were estimated using the non-Gaussian intravoxel incoherent motion model. Neck ultrasonography examination data were used to calculate tumor size. The receiver operating characteristic curve assessed the discriminative specificity, sensitivity, and accuracy between PTCs with and without features of tumor aggressiveness. Multivariate logistic regression analysis was performed on metrics using a leave-1-out cross-validation method. Tumor aggressiveness was defined by surgical histopathology. Tumors with aggressive features had significantly lower ADC and D values than tumors without tumor-aggressive features (P < .05). The absolute relative change was 46% in K metric value between the 2 tumor types. In total, 14 patients were in the critical size range (1-2 cm) measured by ultrasonography, and the ADC and D were significantly different and able to differentiate between the 2 tumor types (P < .05). ADC and D can distinguish tumors with aggressive histological features to preclude an active surveillance management approach in patients with PTC with tumors measuring 1-2 cm.

Intravoxel incoherent motion diffusion-weighted MRI during chemoradiation therapy to characterize and monitor treatment response in human papillomavirus head and neck squamous cell carcinoma.

PURPOSE: Characterize and monitor treatment response in human papillomavirus (HPV) head and neck squamous cell carcinoma (HNSCC) using intra-treatment (intra-TX) imaging metrics derived from intravoxel incoherent motion (IVIM) diffusion-weighted magnetic resonance imaging (DW-MRI). MATERIALS AND METHODS: Thirty-four (30 HPV positive [+] and 4 HPV negative [-]) HNSCC patients underwent a total of 136 MRI including multi-b value DW-MRI (pretreatment [pre-TX] and intra-TX weeks 1, 2, and 3) at 3.0 Tesla. All patients were treated with chemo-radiation therapy. Monoexponential (yielding apparent diffusion coefficient [ADC]) and bi-exponential (yielding perfusion fraction [f], diffusion [D], and pseudo-diffusion [D*] coefficients) fits were performed on a region of interest and voxel-by-voxel basis, on metastatic neck nodes. Response was assessed using RECISTv1.1. The relative percentage change in D, f, and D* between the pre- and intra-TX weeks were used for hierarchical clustering. A Wilcoxon rank-sum test was performed to assess the difference in metrics within and between the complete response (CR) and non-CR groups. RESULTS: The delta (Δ) change in volume (V)1wk-0wk for the CR group differed significantly (P = 0.016) from the non-CR group, while not for V2wk-0wk and V3wk-0wk (P > 0.05). The mean increase in ΔD3wk-0wk for the CR group was significantly higher (P = 0.017) than the non-CR group. ADC and D showed an increasing trend at each intra-TX week when compared with pre-TX in CR group (P < 0.003). Hierarchical clustering demonstrated the existence of clusters in HPV + patients. CONCLUSION: After appropriate validation in a larger population, these IVIM imaging metrics may be useful for individualized treatment in HNSCC patients. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:1013-1023.