Radiation Response Assessment Research Articles

Longitudinal Profiling of Tumor RNA Expression Signatures Reveal Key Biological Features Associated with Response to Neoadjuvant Stereotactic Body Radiation Therapy in High-Risk Prostate Cancer

Stereotactic body radiation therapy (SBRT) is a safe and effective treatment for localized prostate cancer (PCa). PREPARE-SBRT is a clinical trial testing the safety of neoadjuvant MRI-guided SBRT for men with high-risk localized PCa. We leveraged paired samples from pre-treatment biopsy and irradiated prostatectomy (RP) specimens to evaluate transcriptomic changes in irradiated tumors at acute time points following neoadjuvant SBRT. Tumor RNA expression profiles were generated using Decipher GRID by Veracyte on 12 subjects with paired pre- and post-SBRT tissues (n = 24). Descriptive statistics using gene expression profiles describing key biological features [DNA damage & repair (DDR), tumor proliferation, suppressed immune, activated immune, tumor microenvironment (TME)] and an exploratory analysis of RT sensitivity score with binary classification as sensitive or resistant were reported. A control cohort of transcriptomic profiles of 803 matched untreated biopsy and matching RP samples from the same subjects were used to control for signature differences attributable to sample type. Key tumor biology signatures most frequently observed were DDR (15/24), TME (11/24) and tumor proliferation (11/24). Signatures associated with tumor proliferation were disproportionately represented in pre-treatment samples (10/11) whereas TME-associated signatures were enriched predominantly in irradiated RP samples (8/11). Collectively, immune-related immune signatures skewed towards immune activation. All 3 samples annotated with suppressed immune signatures were from pre-treatment specimens whereas 75% (6/8) of samples annotated with activated immune status were from irradiated specimens. Additionally, conversion from suppressed to activated immune status was observed in 2 of 3 subjects (66%). In total, 42% of specimens (10/24) were designated as radio-resistant by RT sensitivity score. Among 8 baseline specimens annotated with RT resistant status, 75% of subjects (6/8) converted to RT sensitive status after neoadjuvant SBRT. Interestingly, in the two subjects with persistent radio-resistant status in pre- and post-samples there was associated with upregulation of TGF-β or PI3K-AKT pathway activation signatures. Pre- and post-SBRT transcriptomic signatures were heterogeneous and dynamic in a cohort of 12 patients with high-risk localized PCa highlighting the importance of studying longitudinal changes in individual patients. These data highlight an opportunity to leverage tumor RNA expression profiles to personalize patient and treatment selection and augment radiation response assessment. gov ID (NCT03663218).

18F-DCFPyL (PSMA) PET as a radiotherapy response assessment tool in metastatic prostate cancer.

Prostate Specific Membrane Antigen (PSMA) - positron emission tomography (PET) guides metastasis-directed radiotherapy (MDRT) in prostate cancer (PrCa). However, its value as a treatment response assessment tool after MDRT remains unclear. Importantly, there is limited understanding of the potential of radiotherapy (RT) to alter PSMA gene (folate hydrolase 1; FOLH1) expression. We reviewed a series of 11 men with oligo-metastatic PrCa (25 metastasis sites) treated with MDRT before re-staging with 18F-DCFPyL (PSMA) PET upon secondary recurrence. Acute effects of RT on PSMA protein and mRNA levels were examined with qPCR and immunoblotting in human wild-type androgen-sensitive (LNCap), castrate-resistant (22RV1) and castrate-resistant neuroendocrine (PC3 and DU145) PrCa cell lines. Xenograft tumors were analyzed with immunohistochemistry. Further, we examined PSMA expression in untreated and irradiated radio-resistant (RR) 22RV1 (22RV1-RR) and DU145 (DU145-RR) cells and xenografts selected for survival after high-dose RT. The majority of MDRT-treated lesions showed lack of PSMA-PET/CT avidity, suggesting treatment response even after low biological effective dose (BED) MDRT. We observed similar high degree of heterogeneity of PSMA expression in both human specimens and in xenograft tumors. PSMA was highly expressed in LNCap and 22RV1 cells and tumors but not in the neuroendocrine PC3 and DU145 models. Single fraction RT caused detectable reduction in PSMA protein but not in mRNA levels in LNCap cells and did not significantly alter PSMA protein or mRNA levels in tissue culture or xenografts of the other cell lines. However, radio-resistant 22RV1-RR cells and tumors demonstrated marked decrease of PSMA transcript and protein expression over their parental counterparts. PSMA-PET may be a promising tool to assess RT response in oligo-metastatic PrCa. However, future systematic investigation of this concept should recognize the high degree of heterogeneity of PSMA expression within prostate tumors and the risk for loss of PSMA expression in tumor surviving curative courses of RT.

Comparison of [18F]FIMP, [11C]MET, and [18F]FDG PET for early-phase assessment of radiotherapy response

Several limitations of [18F]FDG have been reported, such as nonspecific uptake of inflammation foci. Moreover, [11C]MET has been found to accumulate in normal and inflammatory tissues as well as tumors. To increase specificity to tumor tissues, PET probes with tumor-specific molecular targets have been actively developed. [18F]FIMP was found to be highly accumulated in LAT1-positive tumors but not in inflamed tissue. The aim of this study was to explore whether [18F]FIMP can be used for the early-phase evaluation of radiotherapy accompanied by inflammation, and compare its effectiveness with those of [11C]MET and [18F]FDG. Tumor uptake of [18F]FIMP decreased at day 1 after irradiation, and remained low until day 14. Comparatively, that of [18F]FDG initially decreased at day 3 but was transiently elevated at day 7 and then decreased again at day 10. Decreased tumor uptake of [11C]MET was observed at day 10. In line with the uptake of [18F]FIMP, the ratio of Ki-67 immuno-positive cells in tumor tissues significantly decreased at day 1, 7, and 10 as compared with that in the control. These findings suggest that [18F]FIMP may be a PET probe involved in the early detection and prediction of radiotherapy efficacy, although further clarification is needed.

Evaluation of Radiation Sensitivity Differences in Mouse Liver Tumor Organoids Using CRISPR/Cas9-Mediated Gene Mutation.

To assess the radiosensitivity of liver tumors harboring different genetic mutations, mouse liver tumors were generated in vivo through the hydrodynamic injection of clustered regularly interspaced short palindromic repeat/caspase 9 (CRISPR/Cas9) constructs encoding single-guide RNAs (sgRNAs) targeting Tp53, Pten, Nf1, Nf2, Tsc2, Cdkn2a, or Rb1. The plasmid vectors were delivered to the liver of adult C57BL/6 mice via hydrodynamic tail vein injection. The vectors were injected into 10 mice in each group. Organoids were generated from mouse liver tumors. The radiation response of the organoids was assessed using an ATP cell viability assay. The mean survival period of mice injected with vectors targeting Nf2 (4.8 months) was lower than that of other mice. Hematoxylin and eosin staining, immunohistochemical (IHC) staining, and target sequencing analyses revealed that mouse liver tumors harbored the expected mutations. Tumor organoids were established from mouse liver tumors. Histological evaluation revealed marked morphological similarities between the mouse liver tumors and the generated tumor organoids. Moreover, IHC staining indicated that the parental tumor protein expression pattern was maintained in the organoids. The results of the ATP cell viability assay revealed that the tumor organoids with mutated Nf2 were more resistant to high-dose radiation than those with other gene mutations. This study developed a radiation response assessment system for mouse tumors with mutant target genes using CRISPR/Cas9 and organoids. The Tp53 and Pten double mutation in combination with the Nf2 mutation increased the radiation resistance of tumors. The system used in this study can aid in elucidating the mechanism underlying differential intrinsic radiation sensitivity of individual tumors.

Magnetic Resonance Imaging Downstaging, Pathological Response, and Microsatellite Instability Status in Patients with Signet-Ring Cell Carcinoma Rectum Undergoing Preoperative Long-course Chemoradiation

Aim and Objective: To assess the magnetic resonance imaging (MRI) downstaging, pathological response, and the relationship between microsatellite instability (MSI) and radiotherapy response in signet-ring cell carcinoma rectum. Materials and Methods: Twenty two patients were recruited prospectively and retrospectively in this observational study. Six weeks following radiotherapy, the response was assessed using an MRI pelvis, and patients who were operable underwent total mesorectal excision followed by adjuvant chemotherapy. The outcome of radiotherapy was correlated with post radiation MRI downstaging, pathological response, and MSI status. Results: The post radiotherapy response assessment MRI showed tumor regression grading (TRG) 5 in 5 patients. TRG 4 seen in 12, TRG 3 in 3, and TRG 2 in 1 patient. Fifteen patients were operable and post-operativ histopathology showed that 40% had pathological complete response (pCR) and 26.7% had near-complete response. Even those who had no response in MRI had pCR. MSI done 17 patients were stable. Of the 6 patients who had complete pathological response, two were MRI TRG 5, three were MRI TRG 4, and one was MRI TRG 3. The median survival was 23 months. The 2-year and 3-year disease-free survival was 46% and 38%, respectively. Conclusion: The predictive value of MRI downstaging in these tumors following neoadjuvant long-course chemoradiation therapy is not often in concurrence with the histopathological response and needs to be interpreted carefully. Even though the pCR rate seen in this cohort is encouraging, this needs to be evaluated in studies with large cohorts.

PO-1757 A framework for in-vivo, voxel-based assessment of radiation response through multimodal imaging

PO-1757 A framework for in-vivo, voxel-based assessment of radiation response through multimodal imaging

Overcoming Radiation Resistance in Gliomas by Targeting Metabolism and DNA Repair Pathways.

Gliomas represent a wide spectrum of brain tumors characterized by their high invasiveness, resistance to chemoradiotherapy, and both intratumoral and intertumoral heterogeneity. Recent advances in transomics studies revealed that enormous abnormalities exist in different biological layers of glioma cells, which include genetic/epigenetic alterations, RNA expressions, protein expression/modifications, and metabolic pathways, which provide opportunities for development of novel targeted therapeutic agents for gliomas. Metabolic reprogramming is one of the hallmarks of cancer cells, as well as one of the oldest fields in cancer biology research. Altered cancer cell metabolism not only provides energy and metabolites to support tumor growth, but also mediates the resistance of tumor cells to antitumor therapies. The interactions between cancer metabolism and DNA repair pathways, and the enhancement of radiotherapy sensitivity and assessment of radiation response by modulation of glioma metabolism are discussed herein.

Radiotherapy Response Assessment of Multiple Myeloma: A Dual-Energy CT Approach With Virtual Non-Calcium Images.

BackgroundLife expectancy of patients with multiple myeloma (MM) has increased over the past decades, underlining the importance of local tumor control and avoidance of dose-dependent side effects of palliative radiotherapy (RT). Virtual noncalcium (VNCa) imaging from dual-energy computed tomography (DECT) has been suggested to estimate cellularity and metabolic activity of lytic bone lesions (LBLs) in MM.ObjectiveTo explore the feasibility of RT response monitoring with DECT-derived VNCa attenuation measurements in MM.MethodsThirty-three patients with 85 LBLs that had been irradiated and 85 paired non-irradiated LBLs from the same patients were included in this retrospective study. Irradiated and non-irradiated LBLs were measured by circular regions of interest (ROIs) on conventional and VNCa images in a total of 216 follow-up measurements (48 before and 168 after RT). Follow-ups were rated as therapy response, stable disease, or local progression according to the MD Anderson criteria. Receiver operating characteristic (ROC) analysis was performed to discriminate irradiated vs. non-irradiated and locally progressive vs. stable/responsive LBLs using absolute attenuation post-irradiation and percentage attenuation change for patients with pre-irradiation DECT, if available.ResultsAttenuation of LBLs decreased after RT depending on the time that had passed after irradiation [absolute thresholds for identification of irradiated LBLs 30.5–70.0 HU [best area under the curve [AUC] 0.75 (0.59–0.91)] and -77.0 to -22.5 HU [best AUC 0.85 (0.65–1.00)]/-50% and -117% to -167% proportional change of attenuation on conventional and VNCa images, respectively]. VNCa CT was significantly superior for identification of RT effects in LBLs with higher calcium content [best VNCa AUC 0.96 (0.91–1.00), best conventional CT AUC 0.64 (0.45–0.83)]. Thresholds for early identification of local irradiation failure were >20.5 HU on conventional CT [AUC 0.78 (0.68–0.88)] and >-27 HU on VNCa CT [AUC 0.83 (0.70–0.96)].ConclusionTherapy response of LBLs after RT can be monitored by VNCa imaging based on regular myeloma scans, which yields potential for optimizing the lesion-specific radiation dose for local tumor control. Decreasing attenuation indicates RT response, while above threshold attenuation of LBLs precedes local irradiation failure.

Abstract OT-19-01: Phase I study to evaluate the safety and feasibility of preoperative ablative radiotherapy (SABER) for selected early stage breast cancer

Abstract Background: Breast conserving therapy is an established option for early stage breast cancer. Shorter postoperative radiotherapy (RT) regimens have similar efficacy in lower risk breast cancer, including hypofractionated whole breast RT and Accelerated Partial Breast Irradiation (APBI). Despite similar efficacy results for APBI, RAPID trial showed worse cosmetic outcomes for patients receiving APBI compared to whole breast RT. Larger postoperative lumpectomy cavity volumes and the used dose regimen could have had an impact on cosmesis. There are only few published preoperative APBI pilot studies with different dosimetric schemes treating smaller RT target volumes that would potentially translate into less toxicity. Our study is designed to evaluate the safety and feasibility of preoperative ablative RT in patients with early stage breast cancer. An array of ancillary imaging, blood and tissue biomarker collection is also planned in order to study the radiation response in breast cancer. Trial Design: This phase I study uses a modification of the standard 3+3 Phase I design to identify the recommended phase 2 dose of preoperative SABER for treatment of selected breast cancer patients. Participants will be treated with assigned dose level of preoperative SABER, once a day, for 5 fractions given on non-consecutive days, over a period of 2 weeks. The tested dose levels are: Level I=35 Gy (7 Gy x 5), Level II (starting dose)= 40 Gy (8 Gy x 5), Level III=45 Gy (9 Gy x 5), Level IV=50 Gy (10 Gy x 5). Standard partial mastectomy and axillary surgery will be performed 4-6 weeks after preoperative SABER. Adjuvant systemic therapy will be per standard of care. Exploratory studies will be performed pre/post RT and postoperative, including multiparametric breast MRI, biomarkers in blood (CTC’s, SNPs, cytokines, CRP) and tissue (assessment of radiation response, expression of PD-L1, PD1, TILs). Cosmesis and QoL assessment will be performed at scheduled 1, 6, 12, 24 months follow-up. Eligibility criteria: Women, 50 or older, clinical stage T1 unifocal, N0, ER/PR+/HER2 negative, ECOG 0-1, able to undergo MRI with contrast are eligible. Specific Aims: Aim 1. To identify the recommended phase II dose of preoperative SABER; Aims 2.a) to determine the safety, tolerability, Dose Limiting Toxicity (DLT) and toxicity profile of delivering SABER; b) to determine the rate of complete pathological response after preoperative SABER; c) To assess cosmetic results (by MD and patient’s assessment) and QoL after SABER and standard partial mastectomy/axillary surgery. Exploratory aims: a) to determine biomarkers in blood and tissue, and multiparametric MRI radiographic changes and associate them with toxicity and radiation tumor response; b) to assess locoregional recurrence, disease-free survival, and overall survival; c) to assess sentinel lymph node biopsy identification rates after SABER. Statistical Methods: In this novel phase I study, escalation to the next higher dose level will occur only if 0 or only 1 out of 6 patients has DLT. Present accrual and target accrual: A total of 12 to 18 evaluable patients will be enrolled. Expected enrollment period is 3 years and time to complete the study is about 5 years. Open for accrual in 06/2020. Clinical trial information: NCT04360330 Citation Format: Cristiane Takita, Isildinha M. Reis, Radka Stoyanova, John C. Ford, Brian Marples, Jose Net, Monica Yepes, Carmen Gomez, Susan Kesmodel. Phase I study to evaluate the safety and feasibility of preoperative ablative radiotherapy (SABER) for selected early stage breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-19-01.

Heterogeneity analysis of MRI T2 maps for measurement of early tumor response to radiotherapy.

External beam radiotherapy (XRT) is a widely used cancer treatment, yet responses vary dramatically among patients. These differences are not accounted for in clinical practice, partly due to a lack of sensitive early response biomarkers. We hypothesize that quantitative magnetic resonance imaging (MRI) measures reflecting tumor heterogeneity can provide a sensitive and robust biomarker of early XRT response. MRI T2 mapping was performed every 72 hours following 10 Gy dose XRT in two models of pancreatic cancer propagated in the hind limb of mice. Interquartile range (IQR) of tumor T2 was presented as a potential biomarker of radiotherapy response compared with tumor growth kinetics, and biological validation was performed through quantitative histology analysis. Quantification of tumor T2 IQR showed sensitivity for detection of XRT-induced tumor changes 72 hours after treatment, outperforming T2-weighted and diffusion-weighted MRI, with very good robustness. Histological comparison revealed that T2 IQR provides a measure of spatial heterogeneity in tumor cell density, related to radiation-induced necrosis. Early IQR changes were found to correlate to subsequent tumor volume changes, indicating promise for treatment response prediction. Our preclinical findings indicate that spatial heterogeneity analysis of T2 MRI can provide a translatable method for early radiotherapy response assessment. We propose that the method may in future be applied for personalization of radiotherapy through adaptive treatment paradigms.

A convolutional neural network for contouring metastatic lymph nodes on diffusion-weighted magnetic resonance images for assessment of radiotherapy response.

Retrieving quantitative parameters from magnetic resonance imaging (MRI), e.g. for early assessment of radiotherapy treatment response, necessitates contouring regions of interest, which is time-consuming and prone to errors. This becomes more pressing for daily imaging on MRI-guided radiotherapy systems. Therefore, we trained a deep convolutional neural network to automatically contour involved lymph nodes on diffusion-weighted (DW) MRI of head and neck cancer (HNC) patients receiving radiotherapy. DW-images from 48 HNC patients (18 induction-chemotherapy+chemoradiotherapy; 30 definitive chemoradiotherapy) with 68 involved lymph nodes were obtained on a diagnostic 1.5T MR-scanner prior to and 2-3 timepoints throughout treatment. A radiation oncologist delineated the lymph nodes on the b=50s/mm2 images. A 3D U-net was trained to contour involved lymph nodes. Its performance was evaluated in all 48 patients using 8-fold cross-validation and calculating the Dice similarity coefficient (DSC) and the absolute difference in median apparent diffusion coefficient (ΔADC) between the manual and generated contours. Additionally, the performance was evaluated in an independent dataset of three patients obtained on a 1.5T MR-Linac. In the definitive chemoradiotherapy patients (n=96 patients/lymphnodes/timepoints) the DSC was 0.87 (0.81-0.91) [median (1st-3rd quantiles)] and ΔADC was 1.9% (0.8-3.4%) and both remained stable throughout treatment. The network performed worse in the patients receiving induction-chemotherapy (n=65), with DSC=0.80 (0.71-0.87) and ΔADC=3.3% (1.6-8.0%). The network performed well on the MR-Linac data (n=8) with DSC=0.80 (0.75-0.82) and ΔADC=4.0% (0.6-9.1%). We established accurate automatic contouring of involved lymph nodes for HNC patients on diagnostic and MR-Linac DW-images.

Development and Radiation Response Assessment in A Novel Syngeneic Mouse Model of Tongue Cancer: 2D Culture, 3D Organoids and Orthotopic Allografts.

Oral squamous cell carcinoma (OSCC) are aggressive cancers that contribute to significant morbidity and mortality in humans. Although numerous human xenograft models of OSCC have been developed, only a few syngeneic models of OSCC exist. Here, we report on a novel murine model of OSCC, RP-MOC1, derived from a tongue tumor in a C57Bl/6 mouse exposed to the carcinogen 4-nitroquinoline-1-oxide. Phenotypic characterization and credentialing (STR profiling, exome sequencing) of RP-MOC1 cells was performed in vitro. Radiosensitivity was evaluated in 2D culture, 3D organoids, and in vivo using orthotopic allografts. RP-MOC1 cells exhibited a stable epithelial phenotype with proliferative, migratory and invasive properties. Exome sequencing identified several mutations commonly found in OSCC patients. The LD50 for RP-MOC1 cells in 2D culture and 3D organoids was found to be 2.4 Gy and 12.6 Gy, respectively. Orthotopic RP-MOC1 tumors were pan-cytokeratin+ and Ki-67+. Magnetic resonance imaging of orthotopic RP-MOC1 tumors established in immunocompetent mice revealed marked growth inhibition following 10 Gy and 15 Gy fractionated radiation regimens. This radiation response was completely abolished in tumors established in immunodeficient mice. This novel syngeneic model of OSCC can serve as a valuable platform for the evaluation of combination strategies to enhance radiation response against this deadly disease.

PET Radiotherapy Response Assessment Using Encoder-Decoder Convolutional Neural Network and Pre-treatment Information: A Feasibility of Oropharynx Cancer IMRT

PET Radiotherapy Response Assessment Using Encoder-Decoder Convolutional Neural Network and Pre-treatment Information: A Feasibility of Oropharynx Cancer IMRT

Utility of Multi-Parametric Quantitative Magnetic Resonance Imaging for Characterization and Radiotherapy Response Assessment in Soft-Tissue Sarcomas and Correlation With Histopathology.

Purpose: To evaluate repeatability of quantitative multi-parametric MRI in retroperitoneal sarcomas, assess parameter changes with radiotherapy, and correlate pre-operative values with histopathological findings in the surgical specimens.Materials and Methods: Thirty patients with retroperitoneal sarcoma were imaged at baseline, of whom 27 also underwent a second baseline examination for repeatability assessment. 14/30 patients were treated with pre-operative radiotherapy and were imaged again after completing radiotherapy (50.4 Gy in 28 daily fractions, over 5.5 weeks). The following parameter estimates were assessed in the whole tumor volume at baseline and following radiotherapy: apparent diffusion coefficient (ADC), parameters of the intra-voxel incoherent motion model of diffusion-weighted MRI (D, f, D*), transverse relaxation rate, fat fraction, and enhancing fraction after gadolinium-based contrast injection. Correlation was evaluated between pre-operative quantitative parameters and histopathological assessments of cellularity and fat fraction in post-surgical specimens (ClinicalTrials.gov, registration number NCT01902667).Results: Upper and lower 95% limits of agreement were 7.1 and −6.6%, respectively for median ADC at baseline. Median ADC increased significantly post-radiotherapy. Pre-operative ADC and D were negatively correlated with cellularity (r = −0.42, p = 0.01, 95% confidence interval (CI) −0.22 to −0.59 for ADC; r = −0.45, p = 0.005, 95% CI −0.25 to −0.62 for D), and fat fraction from Dixon MRI showed strong correlation with histopathological assessment of fat fraction (r = 0.79, p = 10−7, 95% CI 0.69–0.86).Conclusion: Fat fraction on MRI corresponded to fat content on histology and therefore contributes to lesion characterization. Measurement repeatability was excellent for ADC; this parameter increased significantly post-radiotherapy even in disease categorized as stable by size criteria, and corresponded to cellularity on histology. ADC can be utilized for characterizing and assessing response in heterogeneous retroperitoneal sarcomas.

Changes in apparent diffusion coefficient radiomics features during dose-painted radiotherapy and high dose rate brachytherapy for prostate cancer.

Background and purposeDose escalation has improved cancer outcomes for patients with localized prostate cancer. Targeting subprostatic tumor regions for dose intensification may further improve outcomes. Apparent Diffusion Coefficient (ADC) maps may enable early radiation response assessment and dose adaptation. This study was a proof-of-principle investigation of early changes in ADC radiomics features for patients undergoing radiotherapy with dose escalation to the gross tumor volume (GTV).Materials and methodsFifty-nine patients were enrolled on a prospective tumor dose-escalation trial. Multi-parametric MRI was performed at baseline and week six, corresponding to the time of peak ADC change. GTV and prostate contours were deformably registered between baseline and week six T2-weighted images, and applied to ADC maps, to account for diminished image contrast post-EBRT and possible differences in prostate gland volume, shape, and orientation. A total of 101 radiomics features were tested for significant change post-EBRT using two-tailed Student’s t-test. All ADC features of the prostate and GTV volumes were correlated using Pearson’s coefficient (p < 0.00008, based on Bonferroni correction).ResultsADC feature extraction was insensitive to b = 0 s/mm2 exclusion, and to gradient non-linearity bias. GTV presented predominant changes in first-order features, particularly 10Percentile, and prostate volumes presented predominant changes in second-order features. Changes in both first and second-order features of GTV and prostate ROIs were strongly correlated.ConclusionsOur data confirmed significant changes in numerous GTV and prostate features assessed from ADC and T2-weighted images during radiotherapy; all of which may be potential biomarkers of early radiation response.

Repeated diffusion MRI reveals earliest time point for stratification of radiotherapy response in brain metastases

An imaging biomarker for early prediction of treatment response potentially provides a non-invasive tool for better prognostics and individualized management of the disease. Radiotherapy (RT) response is generally related to changes in gross tumor volume manifesting months later. In this prospective study we investigated the apparent diffusion coefficient (ADC), perfusion fraction and pseudo diffusion coefficient derived from diffusion weighted MRI as potential early biomarkers for radiotherapy response of brain metastases. It was a particular aim to assess the optimal time point for acquiring the DW-MRI scan during the course of treatment, since to our knowledge this important question has not been addressed directly in previous studies. Twenty-nine metastases (N = 29) from twenty-one patients, treated with whole-brain fractionated external beam RT were analyzed. Patients were scanned with a 1 T MRI system to acquire DW-, T2*W-, T2W- and T1W scans, before start of RT, at each fraction and at follow up two to three months after RT. The DW-MRI parameters were derived using regions of interest based on high b-value images (b = 800 s mm−2). Both volumetric and RECIST criteria were applied for response evaluation. It was found that in non-responding metastases the mean ADC decreased and in responding metastases it increased. The volume based response proved to be far more consistently predictable by the ADC change found at fraction number 7 and later, compared to the linear response (RECIST). The perfusion fraction and pseudo diffusion coefficient did not show sufficient prognostic value with either response assessment criteria. In conclusion this study shows that the ADC derived using high b-values may be a reliable biomarker for early assessment of radiotherapy response for brain metastases patients. The earliest response stratification can be achieved using two DW-MRI scans, one pre-treatment and one at treatment day 7–9 (equivalent to 21 Gy).

324P Radiation response assessment by hybrid positron emission tomography/magnetic resonance imaging for cervical cancer treatment

324P Radiation response assessment by hybrid positron emission tomography/magnetic resonance imaging for cervical cancer treatment

324P Radiation response assessment by hybrid positron emission tomography/magnetic resonance imaging for cervical cancer treatment

324P Radiation response assessment by hybrid positron emission tomography/magnetic resonance imaging for cervical cancer treatment

X-ray transport and radiation response assessment (XTRRA) experiments at the National Ignition Facility.

Our team has developed an experimental platform to evaluate the x-ray-generated stress and impulse in materials. Experimental activities include x-ray source development, design of the sample mounting hardware and sensors interfaced to the National Ignition Facility's diagnostics insertion system, and system integration into the facility. This paper focuses on the X-ray Transport and Radiation Response Assessment (XTRRA) test cassettes built for these experiments. The test cassette is designed to position six samples at three predetermined distances from the source, each known to within ±1% accuracy. Built-in calorimeters give in situ measurements of the x-ray environment along the sample lines of sight. The measured accuracy of sample responses as well as planned modifications to the XTRRA cassette is discussed.

SU‐D‐207A‐04: Use of Gradient Echo Plural Contrast Imaging (GEPCI) in MR‐Guided Radiation Therapy: A Feasibility Study Targeting Brain Treatment

Purpose:To implement the Gradient Echo Plural Contrast Imaging(GEPCI) technique in MRI‐simulation for radiation therapy and assess the feasibility of using GEPCI images with advanced inhomogeneity correction in MRI‐guided radiotherapy for brain treatment.Methods:An optimized multigradient‐echo GRE sequence (TR=50ms;TE1=4ms;delta_TE=4ms;flip angle=300,11 Echoes) was developed to generate both structural (T1w and T2*w) and functional MRIs (field and susceptibility maps) from a single acquisition. One healthy subject (Subject1) and one post‐surgical brain cancer patient (Subject2) were scanned on a Philips Ingenia 1.5T MRI used for radiation therapy simulation. Another healthy subject (Subject3) was scanned on a 0.35T MRI‐guided radiotherapy (MR‐IGRT) system (ViewRay). A voxel spread function (VSF) was used to correct the B0 inhomogeneities caused by surgical cavities and edema for Subject2. GEPCI images and standard radiotherapy planning MRIs for this patient were compared focusing the delineation of radiotherapy target region.Results:GEPCI brain images were successfully derived from all three subjects with scan times of &lt;7 minutes. The images derived for Subjects1&amp;2 demonstrated that GEPCI can be applied and combined into radiotherapy MRI simulation. Despite low field, T1‐weighted and R2* images were successfully reconstructed for Subject3 and were satisfactory for contour and target delineation. The R2* distribution of grey matter (center=12,FWHM=4.5) and white matter (center=14.6, FWHM=2) demonstrated the feasibility for tissue segmentation and quantification. The voxel spread function(VSF) corrected surgical site related inhomogeneities for Subject2. R2* and quantitative susceptibility map(QSM) images for Subject2 can be used to quantitatively assess the brain structure response to radiation over the treatment course.Conclusion:We implemented the GEPCI technique in MRI‐simulation and in MR‐IGRT system for radiation therapy. The images demonstrated that it is feasible to adopt this technique in radiotherapy for structural delineation. The preliminary data also enable the opportunity for quantitative assessment of radiation response of the target region and normal tissue.