Impact of MRI resolution for Linac-based stereotactic radiosurgery.

OBJECTIVE: Magnetic resonance imaging (MRI) is a standard imaging modality in intracranial stereotactic radiosurgery (SRS) for defining target volumes. However, wide disparities in MRI resolution exist, which could directly impact accuracy of target delineation. Here, sequences with various MRI resolution were acquired on phantoms to evaluate the effect on volume definition and dosimetric consequence for cranial SRS. MATERIALS/METHODS: Four T1-weighted MR sequences with increasing 3D resolution were compared, including two Spin Echo (SE) 2D acquisitions with 5mm and 3mm slice thickness (SE5mm, SE3mm) and two gradient echo 3D acquisitions (TFE, BRAVO). The voxel sizes were 0.4×0.4×5.0, 0.5×0.5×3.0, 0.9×0.9×1.25, and 0.4×0.4×0.5 mm(3), respectively. Four phantoms with simulated lesions of different shape and volume (range, 0.53-25.0 cm(3)) were imaged, resulting in 16 total sets of MRIs. Four radiation oncologists provided contours on individual MR image set. All observer contours were compared with ground truth, defined on CT image according to the absolute dimensions of the target structure, using Dice similarity coefficient (DSC), Hausdorff distance (HD), mean distance-to-agreement (MDA), and the ratio between reconstructed and true volume (Ratio(vol) ). For dosimetric consequence, SRS plans targeting observer volumes were created. The true Paddick conformity index ( CIpaddicktrue ), calculated with true target volume, was correlated with quality of observer volume. RESULTS: All measures of observer contours improved as increasingly higher MRI resolution was provided from SE5mm to BRAVO. The improvement in DSC, HD and MDA was statistically significant (p\u3c0.01). Dosimetrically, CIpaddicktrue strongly correlated with DSC of the planning observer volume (Pearson\u27s r=0.94, p\u3c0.00001). CONCLUSIONS: Significant improvement in target definition and reduced inter-observer variation was observed as the MRI resolution improved, which also improved the quality of SRS plans. Results imply that high resolution 3D MR sequences should be used to minimize potential errors in target definition, and multi-slice 2D sequences should be avoided

Multi-Institutional Datasets Validate the Recursive Partitioning Analysis for Overall Survival in Patients Undergoing Spine Radiosurgery for Spine Metastasis

Purpose/Objective(s): The recently published spine radiosurgery (sSRS) recursive partitioning analysis (RPA) for overall survival (OS) separated patients into 3 distinct prognostic groups. We sought to externally validate this RPA using a multi-institutional dataset. Materials/Methods: A total of 444 patients were utilized to develop the recently published sSRS RPA predictive of OS in patients with spine metastases. The RPA identified three distinct prognostic classes. RPA Class 1 was defined as KPS \u3e70 and controlled systemic disease (n=142); RPA Class 2 was defined as KPS\u3e70 with uncontrolled systemic disease or KPS ≤70, age ≥54 and absence of visceral metastases (n=207); RPA Class 3 was defined as KPS ≤70 and age \u3c54 years or KPS≤70, age ≥54 years and presence of visceral metastases (n=95). We utilized data from large tertiary care centers to validate this RPA. A total of 749 patients were in the validation cohort and were divided based on their RPA Class. Kaplan-Meier method was used to estimate OS and log-rank test was used to compare OS between RPA classes. Results: In the validation cohort (749 patients), the median OS was 11.0 months. One-hundred-thirteen (15.1%) patients were in RPA Class 1, 432 (57.7%) patients in RPA Class 2 and 204 (27.2%) patients in RPA Class 3. The median OS in the validation cohort based on RPA Class was 27.1 months for Class 1, 13.0 months for Class 2 and 3.5 months for Class 3. Patients in RPA Class 1 had a significantly better OS compared to those in Class 2 of the validation cohort (p\u3c0.01). Similarly, patients in RPA Class 2 had a significantly better OS compared to those in Class 3 (p\u3c0.01). Conclusion: The external datasets from two large centers validated the spine SRS RPA successfully for RPA for OS for patients undergoing sSRS for spinal metastases. This is the first RPA for OS to have been externally validated using a large dataset. Based on this validation, upfront spine SRS is strongly supported for patients in RPA Class 1. Upfront SRS is also supported for RPA Class 2 patients. Patients in RPA Class 3 would benefit most from upfront conventional radiotherapy given their poor expected survival. Given successful external validation, this RPA helps guide physicians to identify those patients with spinal metastases who most benefit from sSRS

SBML Level 3: an extensible format for the exchange and reuse of biological models

Abstract Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction‐based models and packages that extend the core with features suited to other model types including constraint‐based models, reaction‐diffusion models, logical network models, and rule‐based models. The format leverages two decades of SBML and a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single‐cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and how SBML Level 3 provides the foundation needed to support this evolution

SBML Level 3: an extensible format for the exchange and reuse of biological models

Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction-based models and packages that extend the core with features suited to other model types including constraint-based models, reaction-diffusion models, logical network models, and rule-based models. The format leverages two decades of SBML and a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single-cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and how SBML Level 3 provides the foundation needed to support this evolution

External Beam Versus Brachytherapy as Adjuvant Radiation Therapy Modality in Patients with Stage II Endometrial Cancer: A Single Institution Experience

Background: Current NCCN guidelines allow for the physician to choose between EBRT, brachytherapy, or a combination of both to treat FIGO stage II endometrial cancer. Physicians will typically choose the type of treatment based off of other risk factors such as grade, histology, size, depth of myometrial invasion, age, and presence of lymphovascular invasion. Henry Ford has a large database of patients who have been treated for endometrial cancer with adjuvant radiation following surgery and we sought to use this database to explore this area. Objectives: To determine the impact of adjuvant radiation treatment (RT) modality on overall survival (OS), recurrence-free survival (RFS), and disease-specific survival (DSS) in patients with FIGO stage II uterine endometrioid carcinoma (EC). Methods: Our prospectively-maintained database was quired for women with stage II uterine EC who underwent hysterectomy between 1990 and 2018. 100 patients were identified. None received adjuvant chemotherapy. OS, RFS, DSS were all calculated from the date of surgery by use of Kaplan-Meier analysis. Cox regression analysis was used to examine risks associated with changes in OS, RFS, or DSS. Results: The median follow-up time for the study cohort was 110.6 months, and the median age was 66 years. Lymphadenectomy was performed in 78%, peritoneal cytology in 85%. On pathology, 42% of patients were grade 1, 39% grade 2, and 19% grade 3. Adjuvant treatment was external beam radiation therapy (EBRT) alone in 15% of patients, HDR vaginal cuff brachytherapy (BT) alone in in 29% and both in 56% of patients. 5-year RFS for the study cohort was 77%, DSS was and OS was 70%. On multivariate analysis grade 3 vs 1 was a significant predictor for OS (HR 3.11, p 0.0228), RFS (HR 5.1, p 0.0333), but not DSS (HR 6.06, p 0.12). Radiation treatment modality (EBRT, BT, or both) were not found to be significant predictors for any of survival endpoint. Conclusions: In our group of stage II endometrial cancer patients adjuvant RT modality was not predictive of OS, RFS, or DSS. The only independent significant predictor in this group was grade 3 vs 1, and this was only significant for OS and RFS

Bone marrow suppression as a complication of total skin helical tomotherapy in the treatment of mycosis fungoides

Abstract Background Total skin electron beam therapy (TSEBT) is an effective treatment in mycosis fungoides. Total skin helical tomotherapy (TSHT) may be an alternative to TSEBT and may offer several dosimetric and treatment advantages. There are currently very few published treatment results using TSHT in place of TSEBT for treatment of mycosis fungoides. Case presentation Two patients with mycosis fungoides were treated at our institution using TSHT. The first patient was a 69-year-old Caucasian female with stage IVA2 (T2 N3 M0 B2) disease who was treated to a dose of 12 Gy in 8 fractions, with a bone marrow mean dose of 1.66 Gy and V10 = 0.41%. Two weeks after ending treatment the patient developed myelosuppression including grade 4 thrombocytopenia and required blood and platelet transfusions. The second patient was a 29-year-old Caucasian female with stage I (T2 N0 M0 B0) disease. This patient previously had been treated for mycosis fungoides using helical tomotherapy (HT) at a dose of 20 Gy to a localized region and experienced mild thrombocytopenia at that time. The patient then underwent retreatment 17 months later with TSHT to a dose of 12 Gy in 6 fractions with a mean bone marrow dose of 2.3 Gy and V10 = 4.28%. This patient once again experienced myelosuppression that included grade 4 thrombocytopenia. She also required blood and platelet transfusions. Conclusions Both patients treated with TSHT experienced severe bone marrow suppression including grade 4 thrombocytopenia. This was more severe than expected considering the relatively low overall prescription dose and despite a planning constraint placed on the bone marrow of a mean dose of < 2 Gy. These outcomes suggest that patients treated using TSHT should be closely monitored for myelosuppression and caution used even when treating to a dose of 12 Gy

Impact of MRI Sequence Resolution for Target Volume Definition in Stereotactic Radiosurgery

Purpose/Objective(s): MRI is a standard image modality in cranial radiosurgery (SRS) for defining the target volume. There is disparity with different MRI sequences however due to differences in acquisition resolution, which can directly impact accuracy of target segmentation. Here we acquired MRI using different sequences on phantoms to evaluate the effect on volume delineation in the context of cranial SRS. Materials/Methods: Four different T1-weight MR pulse sequences were included: (1) SE5mm: axial and coronal Spin Echo (SE) 2D acquisition with 0.4 × 0.4 mm2 in-plane resolution and 5 mm cross-plane; (1) SE3mm: axial and coronal SE with 0.5 × 0.5 mm2 in-plane and 3 mm cross-plane; (3) TFE: gradient echo 3D acquisition with 0.92 × 0.92 mm2 in axial plane and 1.25 mm cross-plane; (4) BRAVO: gradient echo 3D with 0.4 × 0.4 mm2 in axial plane and 0.5 mm cross-plane. Four phantoms with different shape and volume (0.54 to 25 cm3) were imaged, resulting in 16 sets of MRIs. Four radiation oncologists provided contours on individual sets of MRIs. All observer contours were compared with ground truth, which was defined on CT image according to the absolute dimensions of the phantom structures. Dice coefficients (DSC), Hausdorff distance (MaxHD, MeanHD, σHD) as well as ratio between reconstructed and true volume (Ratiovol) were evaluated between observer and ground truth contours. A two-sided signed-rank test was performed to determine whether differences were statistically significant. Results: The comparison to ground truth as a function of MR sequence is presented in the Table. All indices improved as the MR resolution increased from SE5mm to BRAVO. All differences, with the exception of Ratiovol between SE3mm and TFE, were statistically significant (P \u3c 0.01). Inter-observer variation which must be considered was likely due to: (1) differences in user window/level preferences and related impact on visualization of target boundaries; (2) discrepancies in visualization at the superior/inferior aspect of the target. The first factor leads to systematic over- or under-estimation of the target volume. The second factor affects only SE5mm and SE3mm and leads to over- or under-estimation at superior/inferior aspect of the target. Both factors have ramification in clinical SRS treatment planning. Conclusion: Significant improvement in target definition was observed as the MR image resolution improved. Results imply that the highest resolution 3D MR sequences should be used to minimize potential errors in target definition, and multi-slice 2D sequence should be avoided

Impact of MRI Sequence Resolution for Target Volume Definition in Stereotactic Radiosurgery

Purpose/Objective(s): MRI is a standard image modality in cranial radiosurgery (SRS) for defining the target volume. There is disparity with different MRI sequences however due to differences in acquisition resolution, which can directly impact accuracy of target segmentation. Here we acquired MRI using different sequences on phantoms to evaluate the effect on volume delineation in the context of cranial SRS. Materials/Methods: Four different T1-weight MR pulse sequences were included: (1) SE5mm: axial and coronal Spin Echo (SE) 2D acquisition with 0.4 × 0.4 mm2 in-plane resolution and 5 mm cross-plane; (1) SE3mm: axial and coronal SE with 0.5 × 0.5 mm2 in-plane and 3 mm cross-plane; (3) TFE: gradient echo 3D acquisition with 0.92 × 0.92 mm2 in axial plane and 1.25 mm cross-plane; (4) BRAVO: gradient echo 3D with 0.4 × 0.4 mm2 in axial plane and 0.5 mm cross-plane. Four phantoms with different shape and volume (0.54 to 25 cm3) were imaged, resulting in 16 sets of MRIs. Four radiation oncologists provided contours on individual sets of MRIs. All observer contours were compared with ground truth, which was defined on CT image according to the absolute dimensions of the phantom structures. Dice coefficients (DSC), Hausdorff distance (MaxHD, MeanHD, σHD) as well as ratio between reconstructed and true volume (Ratiovol) were evaluated between observer and ground truth contours. A two-sided signed-rank test was performed to determine whether differences were statistically significant. Results: The comparison to ground truth as a function of MR sequence is presented in the Table. All indices improved as the MR resolution increased from SE5mm to BRAVO. All differences, with the exception of Ratiovol between SE3mm and TFE, were statistically significant (P \u3c 0.01). Inter-observer variation which must be considered was likely due to: (1) differences in user window/level preferences and related impact on visualization of target boundaries; (2) discrepancies in visualization at the superior/inferior aspect of the target. The first factor leads to systematic over- or under-estimation of the target volume. The second factor affects only SE5mm and SE3mm and leads to over- or under-estimation at superior/inferior aspect of the target. Both factors have ramification in clinical SRS treatment planning. Conclusion: Significant improvement in target definition was observed as the MR image resolution improved. Results imply that the highest resolution 3D MR sequences should be used to minimize potential errors in target definition, and multi-slice 2D sequence should be avoided

Racial Disparities Among Pancreatic Adenocarcinoma Patients: A Retrospective Survival Analysis of Non-Metastatic Pancreatic Cancer Patients

Purpose/Objective(s): It is predicted that in 2020, approximately 57,600 individuals will be diagnosed with pancreatic cancer (PaC). Based on SEER database analysis, there are conflicting opinions in literature about the overall treatment and outcomes in African-American patients with PaC. The purpose of this study was to determine if there was a racial disparity in overall survival rates between African Americans (AAs) and non-African Americans (non-AAs) diagnosed with PaC who received neoadjuvant radiation therapy (RT) in a tertiary-care cancer center with an established multi-disciplinary PaC tumor board and clinic. Materials/Methods: An IRB-approved retrospective chart analysis was completed on 100 patients who were diagnosed with pancreatic adenocarcinoma and treated with neoadjuvant RT between 2017-2019. Patients who were deemed resectable, borderline resectable (BR), or locally advanced/unresectable (LA) at initial diagnosis were included in the analysis. The following baseline characteristics were collected for each patient: staging, gender, age and ECOG score at initial diagnosis, tumor site and size, clinical T and N stage, CA19-9, and treatment variables (i.e., surgery, chemotherapy, and RT type). Overall survival was calculated from the RT start date. In order to identify any baseline differences among the AA group and the non-AA group, a two-sample t-test and Chi-square were employed. A log-rank test and Kaplan-Meier were used to determine any differences in overall survival among the two groups. Results: Of the 100 patients included in the analysis, 25 were AA and 58 were female. There were 17 (68%) BR and 8 (32%) LA patients in the AA group. In the non-AA group, there were 2 (3%) resectable, 47 (63%) BR, and 26 (35%) LA patients. There were no statistically significant differences detected in any of the baseline characteristics except a trend for increased CA19-9 values of 399.8 U/mL for AAs and 229 U/mL for non-AAs. There was no statistically significant difference in receipt of chemotherapy and RT between the two groups. The estimated median survival rates were 11.5 months for non-AAs and 8.4 months for AAs. One-year overall survival was 45% for AAs versus 48% for non-AAs (p = 0.57). Conclusion: There was no difference in overall survival among AAs and non-AAs who received neoadjuvant RT+/- chemotherapy for PaC at our institution between 2017-2019. Contrary to previous publications based on large SEER database analysis, there does not appear to be any difference in overall survival based on race if patients receive treatment in a comprehensive multi-disciplinary collaborative center

Magnetic Resonance Guided Stereotactic Ablative Radiation Therapy Versus External Beam RT with Chemotherapy For Pancreatic Cancer: Single Institution Toxicity Analysis Of Patients Treated In An Urban Academic Center

Purpose/Objective(s): Several academic institutions have investigated stereotactic MR guided adaptive radiation therapy (SMART) to safely dose escalate for locally advanced and borderline resectable pancreatic cancer with initial favorable toxicity and survival outcomes. However, it is not clear that this treatment is safe or effective in more challenging populations, such as in an urban academic center. The purpose of this abstract was to review outcomes immediately before and after implementing dose escalated MR guided adaptive radiation therapy for pancreatic cancer. Materials/Methods: In this IRB approved analysis, we retrospectively reviewed 57 consecutive patients from 2017-2019 with locally advanced or borderline resectable pancreatic cancer who were treated with neoadjuvant radiation therapy. Initially all patients received standard fractionated chemoradiation (chemoRT) to a dose of 50.4 Gy in 28 fractions. In September 2018 our institutional treatment guidelines were changed to recommend SMART (50Gy in 5 fractions) for these patients. Toxicity outcomes evaluated were grade 3+ GI toxicity based on CTCAE v5.0 as well as unplanned hospital admissions, both at 90 and 180 days. Treatment differences were analyzed using two sample t-test and chi-square test. Overall survival was evaluated at 180 days, and by Kaplan-Meier and log-rank test and was calculated from first day of radiation therapy. Results: 29 patients received chemoRT and 28 received SMART. Median follow up for the chemoRT group was 294 days and for SMART was 185 days. Groups did not have significant differences in age, performance status, stage, gender, CA 19-9, or neoadjuvant chemotherapy. Grade 3+ GI toxicity at 90 days was seen in 28% and 11% (p = 0.11) in the chemoRT and SMART groups, respectively. Types of toxicity were overall comparable with most being abdominal pain and duodenal bleeds. Hospital admissions at 90 days occurred in 38% and 21% of patients (p = 0.17) and at 180 days in 33% and 44% (p = 0.48). Surgical resection was achieved in 24% of chemoRT and 36% of SMART patients (p = 0.34). When evaluated using Kaplan-Meier and log-rank test there was a trend to overall survival benefit in the SMART group (p = 0.07). There was also a statistically significant 180-day survival improvement in SMART patients of 94% vs 70% in chemoRT patients (p = 0.046). Conclusion: Dose escalated SMART for locally advanced and borderline pancreatic cancer does not cause significant increase in GI grade 3+ GI toxicity at 90 days or hospitalization at 90 or 180 days as compared to chemoRT. Dose escalated SMART appears to be both safe and effective in our urban population. OS in the chemoRT group was comparable to previous trials such as LAP07. There is a trend to OS improvement on Kaplan-Meier analysis in the SBRT group (p = 0.07), as well as statistically significant improvement in 180-day survival; which supports the ongoing multi-institutional SMART study (NCT03621644). Updated results to be presented at the meeting