10 research outputs found
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Feasibility of Adaptive Radiation Therapy for Human-Papilloma Virus-Positive Oropharyngeal Cancer Patients Using MR-Guided RT
Human-papilloma virus (HPV)-positive oropharyngeal cancer (OPC) is a potentially curable disease with a rising incidence in the United States. Despite improved radiation therapy (RT) techniques, toxicities remain a concern. Adaptive RT (ART) can reduce radiation to organs-at-risk (OARs) without sacrificing tumoricidal dose to target volumes, but there are barriers to routine implementation. These include (1) technical barriers to ART and (2) timing of ART for shrinking tumor volumes or changes in body contours (such as weight loss or contracture of OARs). Magnetic resonance (MR)-Linacs allow for frequent, online, and standardized plan adaption, made possible by improved visualization of tumors and OARs as well as an integrated planning system. This study aims to: (1) develop an ART workflow protocol using an online adapt-to-shape approach on our MR-Linac while (2) identifying barriers to performance (such as treatment times and the influence to quality of life) and (3) characterizing quantitative imaging biomarkers during RT.
Sixteen eligible participants with non-metastatic HPV+ OPC will be enrolled. All participants will undergo simulation on our institution's MR-Linac. Participants will receive concurrent chemoRT with a dose prescription of 70 Gy in 35 fractions on the MR-Linac. ART planning will occur every 5th fraction of RT (i.e. the 6th, 11th, 16th, 21st, 26th, and 31st fractions). At 3-months follow-up, participants will undergo another MRI scan on the MR-Linac. The primary endpoint is to assess the accuracy of ART by (1) calculating the percent difference between initial and weekly ART plans and (2) confirming accuracy of deformable imaging registration. Secondary endpoints include (1) treatment times, calculated from guidelines set by the MR-Linac Consortium Head and Neck Tumor Site, as well as (2) quality of life measurements using study questionnaires (i.e. EORTC QLQs Core 30 and H&N43) at all study timepoints. As an exploratory endpoint, quantitative imaging biomarkers of tumor and nodal volume regression will be descriptively characterized.
This study is a trial-in-progress and has not reached pre-specified endpoints for analysis.
MR-Linacs are underutilized in the treatment of OPC patients, despite previous validation of clinically acceptable head and neck RT plans. For OPC patients, replanning is often static (i.e. at one timepoint), offline, and limited in standardization. This work will help clarify the role of MR-guided ART in HPV+ OPC: its feasibility, quality, and overall patient experience
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MRI Relaxometry for Glioblastoma Response Assessment during Radiation Therapy on a 0.35 T MRI Linear Accelerator
Radiation therapy (RT) by an MRI-linear accelerator (Linac) enables daily MRI for glioblastoma (GBM) RT adaptation. Multiparametric MRI (mpMRI) may further enhance adaptive RT decisions using physiologic tumor changes reflected in quantitative imaging. This abstract analyzes the ability of T1, T2, and T2* relaxometry to serve as predictors for early GBM progression. The purpose of our study was to discover how multiparametric MRI values change during RT and compare them to patient outcomes.
29 patients (11 Female; median age of 64) with newly diagnosed GBM underwent chemoradiation on a 0.35 T MRI-Linac with 60 Gy in 30 fractions and temozolomide. IRB-approved research imaging was acquired on alternate days of treatment with a scanning protocol including Strategically Acquired Gradient Echo (STAGE: TR = 42 ms; TE = 5/20.63/34.14 ms; Voxel size = 1.5×1.5×4mm; FA = 10/50°) and multi-echo T2 (TR = 4000 ms; TE = 29/73/131 ms; Voxel size = 1.6×1.6×6 mm) sequences. T1, PD (Proton Density), T2*, and T2 maps were generated using developed code. Map values within region of interest (ROI) (Lesion/Cavity on balanced Steady State Free Precession image +1 cm and excluding the resection cavity) were calculated. Parametric response maps (PRM) were defined as voxel-by-voxel percent change between every fraction and pre-RT by classifying each ROI voxel as either decreased >5 %, increased >5 % or unchanged (+/-5%). Patients were divided into 2 groups based on early clinical response to treatment: NP (no progression) and TP (true progression). Non-progressors included patients with pseudoprogression as well. Statistical analysis included analysis of variance of PRMs for every response group and stepwise multinominal logistical regression with two outcomes: NP and TP. Correlation with overall survival (OS) was evaluated by Cox proportional hazards models. The results were considered statistically significant at the two-sided 5% comparison-wise significance level.
18 patients (62 %) had NP and 11 (38 %) had TP. We observed a significant difference between non-progressors and true-progressors in voxels with increasing of T2 (NP: 40 ± 2.3 %; TP: 47 ± 3.7%, P = 0.02) and T2* values (NP: 8 ± 0.3 %; TP: 10 ± 0.5 %; P = 0.04) more than 30% on 1st and 2nd week of RT. The increasing of T2 and T2* values more than 30% at week 2 was correlated with OS (HR = 4 and 3.08, respectively, P < 0.05). Based on Akaike's information criteria, the significant predictors of response in the models were increasing of T2 and T2* values more than 30% (P < 0.001).
mpMRI PRMs demonstrated significant differences mostly in T2* and T2 values in the 1st and 2nd weeks of RT in poorly responding GBMs. As such patients have the worst prognosis, they might benefit from early therapy intensification or adaptation with MRI-Linac and/or other therapies
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Comparison of MRI-Linac to Standalone MRI Volumes in Glioblastoma: Implications for Adaptive Radiotherapy and Contrast Imaging
Contrast MRI after chemoradiotherapy (chemoRT) shows areas of possible tumor growth in ∼50% of glioblastoma patients compared to pre-RT, but changes during chemoRT are rarely investigated due to logistics of frequent standalone MRI. Daily MRI is feasible with MRI-linac, but the frequency of gadolinium contrast imaging for adaptive RT remains undefined. To identify the need for contrast during chemoRT, we analyzed findings on MRI-linac T2-weighted (T2) MRI and compared those to standalone T1-post contrast (T1+C) and T2 MRI.
Using an IRB-approved prospective cohort of glioblastoma patients undergoing 30 fractions of chemoRT to 60 Gy, standalone MRIs (1.5 or 3T) at 3 timepoints: 1) 1 week pre-RT, 2) mid-RT (end of week 4/beginning of week 5 of treatment) when available, and 3) 1-month post-RT, were compared with T2 treatment set-up scans on 0.35T MRI-linac. Two regions of interest (ROI) were contoured: 1) lesion and 2) cavity (post-surgical resection cavity). Lesion was defined as tumor and edema on T2 MRI, and as enhancing disease on T1+C MRI. ROI volumes from MRI-linac and standalone MRI acquired on the same day were compared using linear fits. Percent change from pre- to post-treatment was calculated for lesion.
Thirty-five patients that underwent RT on MRI-linac were analyzed. Defined on the MRI-linac pre-RT T2 planning scan, 8 patients had visible cavity only, 15 had a mix of both cavity and lesion, and 12 had lesion only (n=23 for cavity, n=27 for lesion). R2 values for linear fits between standalone MRI vs. MRI-linac can be seen in the table (n=number of comparisons included in model). There was a moderate correlation between T1+C and MRI-linac lesion, despite MRI-linac T2’s inability to separate contrast enhancement from surrounding non-enhancing tumor and edema. From pre- to post-treatment, standalone T1+C and MRI-linac T2 lesions changed together – shrank (n=7) or grew (n=11) – in 18 (51%) patients. Another 9 patients (26%) had growth on MRI-linac T2 while the T1+C component shrank. In no patient did T1+C lesion grow while the MRI-linac T2 shrank. No patients with cavity only on MRI-linac (n=8, 23%) had any lesion growth on T1+C from pre- to post-treatment.
Daily low-field MRI-linac non-contrast imaging demonstrates changes in resection cavity and tumor/edema during chemoRT. We found that these changes can be used as a signal for when to consider IV contrast for adaptive MRI-RT in glioblastoma. If T1+C volumes are desired for adaptation, a selective approach can be employed where MRI-linac T2/non-contrast lesion growth (n=20, 57%) can be used to trigger contrast injection at selected timepoints. In patients with no lesion growth on non-contrast imaging/MRI-linac (n=15, 43%), contrast administration may not be needed
Fungal genus Hypocrea/Trichoderma: from barcodes to biodiversity* §
Hypocrea/Trichoderma is a genus of soil-borne or wood-decaying fungi containing members important to mankind as producers of industrial enzymes and biocontrol agents against plant pathogens, but also as opportunistic pathogens of immunocompromised humans and animals, while others can cause damage to cultivated mushroom. With the recent advent of a reliable, BarCode-aided identification system for all known taxa of Trichoderma and Hypocrea, it became now possible to study some of the biological fundamentals of the diversity in this fungal genus in more detail. In this article, we will therefore review recent progress in (1) the understanding of the geographic distribution of individual taxa; (2) mechanisms of speciation leading to development of mushroom diseases and facultative human mycoses; and (3) the possible correlation of specific traits of secondary metabolism and molecular phylogeny