Transcatheter Arterial Chemoembolization Imaging Features in MR-Linac Radiation Therapy Planning for the Liver.

For MR-guided radiation therapy treatment planning, an MRI and CT of the intended treatment site are typically acquired. Patients' prior treatments or procedures can cause image artifacts in one or both scans, which may impact treatment planning or the radiation dose calculation. In this case report, a patient with several previous transcatheter arterial chemoembolization (TACE) procedures was planned for radiation therapy on a low-field MR-linac, and the impact of residual iodinated oil on the radiation dose calculation and MR-guided adaptive workflow was evaluated.

Toward magnetic resonance fingerprinting for low-field MR-guided radiation therapy.

PURPOSE: The acquisition of multiparametric quantitative magnetic resonance imaging (qMRI) is becoming increasingly important for functional characterization of cancer prior to- and throughout the course of radiation therapy. The feasibility of a qMRI method known as magnetic resonance fingerprinting (MRF) for rapid T1 and T2 mapping was assessed on a low-field MR-linac system. METHODS: A three-dimensional MRF sequence was implemented on a 0.35T MR-guided radiotherapy system. MRF-derived measurements of T1 and T2 were compared to those obtained with gold standard single spin echo methods, and the impacts of the radiofrequency field homogeneity and scan times ranging between 6 and 48 min were analyzed by acquiring between 1 and 8 spokes per time point in a standard quantitative system phantom. The short-term repeatability of MRF was assessed over three measurements taken over a 10-h period. To evaluate transferability, MRF measurements were acquired on two additional MR-guided radiotherapy systems. Preliminary human volunteer studies were performed. RESULTS: The phantom benchmarking studies showed that MRF is capable of mapping T1 and T2 values within 8% and 10% of gold standard measures, respectively, at 0.35T. The coefficient of variation of T1 and T2 estimates over three repeated scans was < 5% over a broad range of relaxation times. The T1 and T2 times derived using a single-spoke MRF acquisition across three scanners were near unity and mean percent errors in T1 and T2 estimates using the same phantom were < 3%. The mean percent differences in T1 and T2 as a result of truncating the scan time to 6 min over the large range of relaxation times in the system phantom were 0.65% and 4.05%, respectively. CONCLUSIONS: The technical feasibility and accuracy of MRF on a low-field MR-guided radiation therapy device has been demonstrated. MRF can be used to measure accurate T1 and T2 maps in three dimensions from a brief 6-min scan, offering strong potential for efficient and reproducible qMRI for future clinical trials in functional plan adaptation and tumor/normal tissue response assessment.

Rapid multicontrast brain imaging on a 0.35T MR-linac.

PURPOSE: Magnetic resonance-guided radiation therapy (MRgRT) has shown great promise for localization and real-time tumor monitoring. However, to date, quantitative imaging has been limited for low field MRgRT. This work benchmarks quantitative T1, R2*, and Proton Density (PD)mapping in a phantom on a 0.35 T MR-linac and implements a novel acquisition method, STrategically Acquired Gradient Echo (STAGE). To further validate STAGE in a clinical setting, a pilot study was undertaken in a cohort of brain tumor patients to elucidate opportunities for longitudinal functional imaging with an MR-linac in the brain. METHODS: STAGE (two triple-echo gradient echo (GRE) acquisitions) was optimized for a 0.35T low-field MR-linac. Simulations were performed to choose two flip angles to optimize signal-to-noise ratio (SNR) and T1-mapping precision. Tradeoffs between SNR, scan time, and spatial resolution for whole-brain coverage were evaluated in healthy volunteers. Data were inputted into a STAGE processing pipeline to yield four qualitative images (T1-weighted, enhanced T1-weighted, proton-density (PD) weighted, and simulated FLuid-Attenuated Inversion Recovery (sFLAIR)), and three quantitative datasets (T1, PD, and R2*). A benchmarking ISMRM/NIST phantom consisting of vials with variable NiCl2 and MnCl2 concentrations was scanned using variable flip angles (VFA) (2-60 degrees) and inversion recovery (IR) methods at 0.35 T. STAGE and VFA T1 values of vials were compared to IR T1 values. As measures of agreement with reference values and repeatability, relative error (RE) and coefficient of variability (CV) were calculated, respectively, for quantitative MR values within the phantom vials (spheres). To demonstrate feasibility, longitudinal STAGE data (pretreatment, weekly, and ~ 2 months post-treatment) were acquired in an IRB-approved pilot study of brain tumor cases via the generation of temporal and differential quantitative MRI maps. RESULTS: In the phantom, RE of measured VFA T1 and STAGE relative to IR reference values were 7.0 ± 2.5% and 9.5 ± 2.2% respectively. RE for the PD vials was 8.1 ± 6.8% and CV for phantom R2* measurements was 10.1 ± 9.9%. Simulations and volunteer experiments yielded final STAGE parameters of FA = 50°/10°, 1 × 1 × 3 mm3 resolution, TR = 40 ms, TE = 5/20/34 ms in 10 min (64 slices). In the pilot study of brain tumor patients, differential maps for R2* and T1 maps were sensitive to local tumor changes and appeared similar to 3 T follow-up MRI datasets. CONCLUSION: Quantitative T1, R2*, and PD mapping are promising at 0.35 T agreeing well with reference data. STAGE phantom data offer quantitative representations comparable to traditional methods in a fraction of the acquisition time. Initial feasibility of implementing STAGE at 0.35 T in a patient brain tumor cohort suggests that detectable changes can be observed over time. With confirmation in a larger cohort, results may be implemented to identify areas of recurrence and facilitate adaptive radiation therapy.

National Cancer Database Analysis of the effect of brachytherapy on overall survival in patients with base of tongue cancer.

BACKGROUND: We performed an analysis of the National Cancer Database (NCDB) to evaluate overall survival (OS) in patients with base of tongue (BOT) cancer treated with external beam radiation therapy (EBRT) combined with brachytherapy (BT). METHODS: The tongue NCDB Participant User File was used to obtain demographic and clinical patient data. The Kaplan-Meier method was used to determine OS. Significance was determined using univariable and multivariable Cox proportional hazards models. RESULTS: At 3 years, OS was 69.6%, 77.1%, and 63.7% for patients treated with EBRT (n = 27 954), EBRT + BT (n = 209), or BT alone (n = 154), respectively (P = .01). On multivariable analysis, the instantaneous hazard of death for patients receiving EBRT + BT was 25% (Hazard ratio [HR] = 0.75, 95% CI: 0.58-0.98) lower than patients receiving only EBRT (P = .03). CONCLUSIONS: The addition of BT to EBRT in BOT cancer has an OS benefit.

Pretreatment computed tomographic gross tumor volume as predictor of persistence of tracheostomy and percutaneous endoscopic gastrostomy tube in patients undergoing larynx preservation.

BACKGROUND: Although larynx preservation affords patients improvements in laryngectomy-free survival, little has been reported regarding the functional outcomes after larynx preservation. The purpose of this study was to report the predictive value of pretreatment CT-gross tumor volume (GTV) for persistence of tracheostomy and percutaneous endoscopic gastrostomy (PEG) tube in larynx preservation patients. METHODS: Each patient had a CT scan before initiation of therapy and the GTV was contoured. RESULTS: Using recursive partitioning analysis (RPA), threshold GTVs of 27.16 cc and 12 cc were identified for association of time with tracheostomy and PEG tube, respectively. Median (95% confidence interval [CI]) times above and below these thresholds were 1.84 (1.06-not reached [NR]) and 0.75 (0.63-1.26) years, respectively (p = .03) for time with tracheostomy and 1.75 (1.34-NR) and 0.84 (0.46-NR) years, respectively (p = 0.10) for time with PEG tube. CONCLUSION: This study demonstrates that pretreatment CT-GTV is predictive of an approximately 2.5-fold and approximately 2-fold, respectively, increase in time with tracheostomy and PEG tube. © 2016 Wiley Periodicals, Inc. Head Neck 38: First-1458, 2016.

Intratumoral lymphatic vessel density as a predictor of progression-free and overall survival in locally advanced laryngeal/hypopharyngeal cancer.

BACKGROUND: Lymphatic vessel density (LVD) has been shown to be an important predictor of survival in head and neck cancers. We report the predictive value of LVD for progression-free survival (PFS) and overall survival (OS) in laryngeal/hypopharyngeal cancer. METHODS: Fifty-five untreated patients with T3/T4 laryngeal and T4 hypopharyngeal cancer underwent laryngectomy between 1999 and 2010. Surgical specimens were immunostained with D2-40, a specific lymphatic marker. LVDs were determined in tumor vessel "hot spots." Recursive partitioning analysis identified LVD thresholds for both peritumoral (LVDpt) and intratumoral (LVDit) vessels for association with PFS and OS. RESULTS: Patients with mean LVDit of <11 vessels/mm(2) had 2-year PFS and OS rates of 58% and 65%, respectively, compared to 13% and 13% for those with LVDit ≥11 vessels/mm(2) (p = .06 and .04, respectively). CONCLUSION: Intratumoral lymphatic vessel density is predictive of PFS and OS in locally advanced laryngeal/hypopharyngeal cancer. © 2015 Wiley Periodicals, Inc. Head Neck 38: E417-E420, 2016.

Platelet-derived growth factor-C (PDGF-C) activation by serine proteases: implications for breast cancer progression.

The PDGF (platelet-derived growth factor) family members are potent mitogens for cells of mesenchymal origin and serve as important regulators of cell migration, survival, apoptosis and transformation. Tumour-derived PDGF ligands are thought to function in both autocrine and paracrine manners, activating receptors on tumour and surrounding stromal cells. PDGF-C and -D are secreted as latent dimers, unlike PDGF-A and -B. Cleavage of the CUB domain from the PDGF-C and -D dimers is required for their biological activity. At present, little is known about the proteolytic processing of PDGF-C, the rate-limiting step in the regulation of PDGF-C activity. In the present study we show that the breast carcinoma cell line MCF7, engineered to overexpress PDGF-C, produces proteases capable of cleaving PDGF-C to its active form. Increased PDGF-C expression enhances cell proliferation, anchorage-independent cell growth and tumour cell motility by autocrine signalling. In addition, MCF7-produced PDGF-C induces fibroblast cell migration in a paracrine manner. Interestingly, PDGF-C enhances tumour cell invasion in the presence of fibroblasts, suggesting a role for tumour-derived PDGF-C in tumour-stromal interactions. In the present study, we identify tPA (tissue plasminogen activator) and matriptase as major proteases for processing of PDGF-C in MCF7 cells. In in vitro studies, we also show that uPA (urokinase-type plasminogen activator) is able to process PDGF-C. Furthermore, by site-directed mutagenesis, we identify the cleavage site for these proteases in PDGF-C. Lastly, we provide evidence suggesting a two-step proteolytic processing of PDGF-C involving creation of a hemidimer, followed by GFD-D (growth factor domain dimer) generation.

A potential oncogenic activity of platelet-derived growth factor d in prostate cancer progression.

The platelet-derived growth factor (PDGF) proteins are potent stimulators of cell proliferation/transformation and play a major role in cell-cell communication. For over two decades, PDGFs were thought to exist as three dimeric polypeptides (the homodimers AA and BB and the heterodimer AB). Recently, however, the PDGF C and D chains were discovered in a BLAST search of the expressed sequence tag databases. The PDGF CC and DD dimers have a unique two-domain structure with an NH(2)-terminal CUB (compliment subcomponents C1r/C1s, Uegf, and Bmp1) domain and a COOH-terminal PDGF/vascular endothelial growth factor domain. Whereas secreted PDGF AA, BB, and AB readily activate their cell surface receptors, it was suggested that extracellular proteolytic removal of the CUB domain is required for the PDGF/vascular endothelial growth factor domain of PDGF CC and DD to activate PDGF receptors. In the present study, we examined the processing of latent PDGF D into its active form and the effects of PDGF D expression on prostate cancer progression. We show that LNCaP cells auto-activate latent PDGF DD into the active PDGF domain, which can induce phosphorylation of the beta-PDGF receptor and stimulates LNCaP cell proliferation in an autocrine manner. Additionally, LNCaP-PDGF D-conditioned medium induces migration of the prostate fibroblast cell line 1532-FTX, indicating LNCaP-processed PDGF DD is active in a paracrine manner as well. In a severe combined immunodeficient mouse model, PDGF DD expression accelerates early onset of prostate tumor growth and drastically enhances prostate carcinoma cell interaction with surrounding stromal cells. These demonstrate a potential oncogenic activity of PDGF DD in the development and/or progression of prostate cancer.