MRIO: the Magnetic Resonance Imaging Acquisition and Analysis Ontology.

Magnetic resonance imaging of the brain is a useful tool in both the clinic and research settings, aiding in the diagnosis and treatments of neurological disease and expanding our knowledge of the brain. However, there are many challenges inherent in managing and analyzing MRI data, due in large part to the heterogeneity of data acquisition. To address this, we have developed MRIO, the Magnetic Resonance Imaging Acquisition and Analysis Ontology. MRIO provides well-reasoned classes and logical axioms for the acquisition of several MRI acquisition types and well-known, peer-reviewed analysis software, facilitating the use of MRI data. These classes provide a common language for the neuroimaging research process and help standardize the organization and analysis of MRI data for reproducible datasets. We also provide queries for automated assignment of analyses for given MRI types. MRIO aids researchers in managing neuroimaging studies by helping organize and annotate MRI data and integrating with existing standards such as Digital Imaging and Communications in Medicine and the Brain Imaging Data Structure, enhancing reproducibility and interoperability. MRIO was constructed according to Open Biomedical Ontologies Foundry principles and has contributed several classes to the Ontology for Biomedical Investigations to help bridge neuroimaging data to other domains. MRIO addresses the need for a "common language" for MRI that can help manage the neuroimaging research, by enabling researchers to identify appropriate analyses for sets of scans and facilitating data organization and reporting.

SBRT for Liver Tumors: What the Interventional Radiologist Needs to Know.

This review summarizes the clinical evidence supporting the utilization of stereotactic body radiotherapy (SBRT) for liver tumors, including hepatocellular carcinoma, liver metastases, and cholangiocarcinoma. Emerging prospective evidence has demonstrated the benefit and low rates of toxicity across a broad range of clinical contexts. We provide an introduction for the interventional radiologist, with a discussion of underlying themes such as tumor dose-response, mitigation of liver toxicity, and the technical considerations relevant to performing liver SBRT. Ultimately, we recommend that SBRT should be routinely included in the armamentarium of locoregional therapies for liver malignancies, alongside those liver-directed therapies offered by interventional radiology.

MRIO: The Magnetic Resonance Imaging Acquisition and Analysis Ontology.

Objective: Magnetic resonance imaging of the brain is a useful tool in both the clinic and research settings, aiding in the diagnosis and treatments of neurological disease and expanding our knowledge of the brain. However, there are many challenges inherent in managing and analyzing MRI data, due in large part to the heterogeneity of data acquisition. Materials and Methods: To address this, we have developed MRIO, the Magnetic Resonance Imaging Acquisition and Analysis Ontology. Results: MRIO provides well-reasoned classes and logical axioms for the acquisition of several MRI acquisition types and well-known, peer-reviewed analysis software, facilitating the use of MRI data. These classes provide a common language for the neuroimaging research process and help standardize the organization and analysis of MRI data for reproducible datasets. We also provide queries for automated assignment of analyses for given MRI types. Discussion: MRIO aids researchers in managing neuroimaging studies by helping organize and annotate MRI data and integrating with existing standards such as Digital Imaging and Communications in Medicine and the Brain Imaging Data Structure, enhancing reproducibility and interoperability. MRIO was constructed according to Open Biomedical Ontologies Foundry principals and has contributed several terms to the Ontology for Biomedical Investigations to help bridge neuroimaging data to other domains. Conclusion: MRIO addresses the need for a "common language" for MRI that can help manage the neuroimaging research, by enabling researchers to identify appropriate analyses for sets of scans and facilitating data organization and reporting.

Adjuvant chemotherapy versus observation following neoadjuvant therapy and surgery for resectable stage I-II pancreatic cancer.

Background: Neoadjuvant therapy (NT), either with systemic treatment alone or in combination with radiation, is often utilized in the management of pancreatic adenocarcinoma to increase the likelihood of margin-negative resection. Following NT and resection, additional adjuvant chemotherapy (AC) can be considered for select patients and has been shown to improve overall survival (OS). This National Cancer Data Base (NCDB) analysis was performed to evaluate the outcomes of AC versus observation for resected pancreatic adenocarcinoma treated with NT. Methods: The NCDB was queried for primary stage I-II cT1-3N0-1M0 resected pancreatic adenocarcinoma treated with NT (2004-2015). Baseline patient, tumor, and treatment characteristics were extracted. The primary endpoint was OS. With a 6-month conditional landmark, Kaplan-Meier analysis, multivariable Cox proportional hazards method, 1:1 propensity score matching were used to analyze the data. Results: A total of 1737 eligible patients were identified, of which 1247 underwent postoperative observation compared to 490 with AC. The overall median follow-up was 34.7 months. The addition of AC showed improved survival on the multivariate analysis (HR 0.78, p<0.001). Of 490 propensity-matched pairs, all variables were well balanced, including age (p=0.61), Charlson-Deyo comorbidity score (p=0.80), ypT stage (p=0.93), ypN stage (p=0.83), surgical margin (p=0.83), duration of postoperative inpatient admission (p=0.96), and 30-day unplanned readmission after resection (p=0.34). AC remained statistically significant for improved OS, with median OS of 26.3 months vs 22.3 months and 2-year OS of 63.9% vs 52.9% for the observation cohort (p<0.001). Treatment interaction analysis showed OS benefit of AC for patients with smaller tumors (HR 0.67, p<0.001 for <3.1 cm vs HR 0.93, p=0.48 for ≥3.1 cm). Conclusion: Using propensity score matched analysis, our findings suggest a survival benefit for adjuvant chemotherapy compared to observation following NT and surgery for resectable pancreatic adenocarcinoma, especially in patients with smaller tumors. Prospective studies are needed to identify subset of patients that would benefit from adjuvant chemotherapy.

Association of survival with stereotactic body radiation therapy following induction chemotherapy for unresected locally advanced pancreatic cancer.

Background: Induction chemotherapy (iC) followed by concurrent chemoradiation has been shown to improve overall survival (OS) for locally advanced pancreatic cancer (LAPC). However, the survival benefit of stereotactic body radiation therapy (SBRT) versus conventionally fractionated radiation therapy (CFRT) following iC remains unclear. Methods: The National Cancer Database (NCDB) was queried for primary stage III, cT4N0-1M0 LAPC (2004-2015). Kaplan-Meier analysis, Cox proportional hazards method, and propensity score matching were used. Results: Among 872 patients, 738 patients underwent CFRT and 134 patients received SBRT. Median follow-up was 24.3 months and 22.9 months for the CFRT and SBRT cohorts, respectively. The use of SBRT showed improved survival in both the multivariate analysis (HR 0.78, p=0.025) and 120 propensity-matched pairs (median OS 18.1 vs 15.9 months, p=0.004) compared to the CFRT. Conclusion: This NCDB analysis suggests survival benefit with the use of SBRT versus CFRT following iC for the LAPC.

Racial/Ethnic Differences and Trends in Pathologic Complete Response Following Neoadjuvant Chemotherapy for Breast Cancer.

The purpose of this study was to evaluate nationwide trends in pathologic complete response (pCR) and its racial variations for breast cancer. The National Cancer Database was queried for women from 2010 to 2017 with non-metastatic breast cancer who underwent neoadjuvant chemotherapy. The primary endpoints, pCR and overall survival, were evaluated using Cochran-Armitage test, logistic, and Cox regression multivariable analyses. A total of 104,161 women were analyzed. Overall, pCR improved from 2010 to 2017 (15.1% to 27.2%, trend p < 0.001). Compared to non-Hispanic White (NHW) women, Hispanic White (HW) women were more likely to have pCR for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-positive tumors (adjusted odds ratio (aOR) 1.29, 95% confidence interval (CI) 1.08-1.53, p = 0.005). Black women were less likely to have pCR for HR-HER2+ tumors (aOR 0.81, 95% CI 0.73-0.89, p < 0.001) and triple negative (aOR 0.82, 95% CI 0.77-0.87, p < 0.001) tumors, but more likely for HR+HER2- tumors (aOR 1.13, 95% CI 1.03-1.24, p = 0.009). Among patients who achieved pCR, Asian or Pacific Islander (API) women were associated with better survival (adjusted hazards ratio (aHR) 0.52, 95% CI 0.33-0.82, p = 0.005) than NHW women. Despite positive trends in pCR rates, the likelihood of pCR and survival outcomes may be intricately dependent on racial/ethnic groups and tumor receptor subtypes.

Evaluation of risk stratification using gene expression assays in patients with breast cancer receiving neoadjuvant chemotherapy.

PURPOSE: To evaluate the association of various gene expression assays with pathologic complete response (pCR) in the setting of neoadjuvant chemotherapy among patients with breast cancer METHODS: The National Cancer Database (NCDB) was queried for women diagnosed between 2010 and 2017 with stage I-III breast cancer who underwent neoadjuvant chemotherapy and either 21-gene recurrence score (RS) or 70-gene signature (GS). Logistic multivariable analysis (MVA) was performed to identify variables associated with pCR. RESULTS: A total of 3009 patients met our inclusion criteria. The median follow up was 48.0 months (interquartile range 32.2-66.7 months). On logistic MVA for all patients, those with a high risk from GS (adjusted odds ratio [aOR] 3.23, 95% confidence interval [CI] 1.49-8.13, p = 0.006) or with RS ≥ 31 (aOR 1.99, 95% CI 1.41-2.82, p < 0.001) were more likely to have pCR. When compared to RS ≥ 31, a high risk from GS was not associated with pCR (aOR 1.01, 95% CI 0.75-1.37, p = 0.94). However, among those with favorable hormone receptor status, similar findings were noted, except that those with a high risk group from GS were less likely to have pCR compared to those with RS ≥ 31 (aOR 0.65, 95% CI 0.43-0.96, p = 0.03). When analyses were repeated using a high risk group from RS defined as RS ≥ 26 among those with favorable hormone receptor status, RS ≥ 26 was not associated with pCR when compared to the high risk from GS (aOR 0.74, 0.50-1.07, p = 0.12). CONCLUSIONS: To our knowledge, this is the largest study using a nationwide oncology database suggesting that high recurrence risk groups in both assays were associated with pCR. Among those with favorable hormone receptor status, RS ≥ 31 may be a more selective prognostic marker for pCR.

Ontologies in radiation oncology.

Ontologies are a formal, computer-compatible method for representing scientific knowledge about a given domain. They provide a standardized vocabulary, taxonomy and set of relations between concepts. When formatted in a standard way, they can be read and reasoned upon by computers as well as by humans. At the 2019 International Conference on the Use of Computers in Radiation Therapy, there was a session devoted to ontologies in radiation therapy. This paper is a compilation of the material presented, and is meant as an introduction to the subject. This is done by means of a didactic introduction to the topic followed by a series of applications in radiation therapy. The goal of this article is to provide the medical physicist and related professionals with sufficient background that they can understand their construction as well as their practical uses.

An ontology for representing hematologic malignancies: the cancer cell ontology.

BACKGROUND: Within the cancer domain, ontologies play an important role in the integration and annotation of data in order to support numerous biomedical tools and applications. This work seeks to leverage existing standards in immunophenotyping cell types found in hematologic malignancies to provide an ontological representation of them to aid in data annotation and analysis for patient data. RESULTS: We have developed the Cancer Cell Ontology according to OBO Foundry principles as an extension of the Cell Ontology. We define classes in Cancer Cell Ontology by using a genus-differentia approach using logical axioms capturing the expression of cellular surface markers in order to represent types of hematologic malignancies. By adopting conventions used in the Cell Ontology, we have created human and computer-readable definitions for 300 classes of blood cancers, based on the EGIL classification system for leukemias, and relying upon additional classification approaches for multiple myelomas and other hematologic malignancies. CONCLUSION: We have demonstrated a proof of concept for leveraging the built-in logical axioms of the ontology in order to classify patient surface marker data into appropriate diagnostic categories. We plan to integrate our ontology into existing tools for flow cytometry data analysis to facilitate the automated diagnosis of hematologic malignancies.

OSCI: standardized stem cell ontology representation and use cases for stem cell investigation.

BACKGROUND: Stem cells and stem cell lines are widely used in biomedical research. The Cell Ontology (CL) and Cell Line Ontology (CLO) are two community-based OBO Foundry ontologies in the domains of in vivo cells and in vitro cell line cells, respectively. RESULTS: To support standardized stem cell investigations, we have developed an Ontology for Stem Cell Investigations (OSCI). OSCI imports stem cell and cell line terms from CL and CLO, and investigation-related terms from existing ontologies. A novel focus of OSCI is its application in representing metadata types associated with various stem cell investigations. We also applied OSCI to systematically categorize experimental variables in an induced pluripotent stem cell line cell study related to bipolar disorder. In addition, we used a semi-automated literature mining approach to identify over 200 stem cell gene markers. The relations between these genes and stem cells are modeled and represented in OSCI. CONCLUSIONS: OSCI standardizes stem cells found in vivo and in vitro and in various stem cell investigation processes and entities. The presented use cases demonstrate the utility of OSCI in iPSC studies and literature mining related to bipolar disorder.

Adjuvant chemotherapy followed by concurrent chemoradiation is associated with improved survival for resected stage I-II pancreatic cancer.

BACKGROUND: This National Cancer Database (NCDB) analysis evaluates the clinical outcomes of postoperative chemotherapy followed by concurrent chemoradiation (C + CRT) compared to concurrent chemoradiation (CRT) alone or adjuvant chemotherapy alone (C) for resected pancreatic cancer. METHODS: The NCDB was queried for primary stage I-II, cT1-3N0-1M0, resected pancreatic adenocarcinoma treated with adjuvant C, CRT, or C + CRT (2004-2015). Patients treated with C + CRT were compared with those treated with C (cohort C) and CRT (cohort CRT). Baseline patient, tumor, and treatment characteristics were examined. Kaplan-Meier analysis, multivariable Cox proportional hazards method, forest plot, and propensity score matching were used. RESULTS: Among 5667 patients, median follow-up was 34.7, 45.2, and 39.7 months for the C, CRT, and C + CRT cohorts, respectively. By multivariable analysis for all patients, C and CRT had worse OS compared to C + CRT. Treatment interactions were seen among pathologically node-positive disease. C + CRT was favored in 1-3 and 4+ positive lymph node diseases when compared to C or CRT alone, but none of the treatment options were significantly favored in node negative disease. Using propensity score matching, 2152 patients for cohort C and 1774 patients for cohort CRT were matched. C + CRT remained significant for improved OS for both cohort C (median OS 23.3 vs 20.0 months) and cohort CRT (median OS 23.4 vs 20.8 months). CONCLUSION: This NCDB study using propensity score matched analysis suggests an OS benefit for C + CRT compared to C or CRT alone following surgical resection of pancreatic cancer, particularly for patients with pathologically positive lymph nodes.

Long-term outcomes of interventions for radiation-induced xerostomia: A review.

Xerostomia, or dry mouth, is a significant problem affecting quality of life in patients treated with radiation therapy for head and neck cancer. Strategies for reduction of xerostomia burden vary widely, with options including: sialagogue medications, saliva substitutes, acupuncture, vitamins, hyperbaric oxygen, submandibular gland transfer, and acupuncture or associated treatments. In this review, we sought to evaluate long-term outcomes of patients treated with various interventions for radiation-induced xerostomia. A literature search was performed using the terms "xerostomia" and "radiation" or "radiotherapy"; all prospective clinical trials were evaluated, and only studies that reported 1 year follow up were included. The search results yielded 2193 studies, 1977 of which were in English. Of those, 304 were clinical trials or clinical studies. After abstract review, 23 trials were included in the review evaluating the following treatment modalities: pilocarpine (three); cevimeline (one); amifostine (eleven); submandibular gland transfer (five); acupuncture like transcutaneous electrical nerve stimulation (ALTENS) (one); hyperbaric oxygen (one); and acupuncture (one). Pilocarpine, cevimeline, and amifostine have been shown in some studies to improve xerostomia outcomes, at the cost of toxicity. ALTENS has similar efficacy with fewer side effects. Submandibular gland transfer is effective but requires an elective surgery, and thus may not always be appropriate or practical. The use of intensity-modulated radiation therapy, in addition to dose de-escalation in select patients, may result in fewer patients with late xerostomia, reducing the need for additional interventions.

Three- Versus Five-Fraction Regimens of Stereotactic Body Radiotherapy for Peripheral Early-Stage Non-Small-Cell Lung Cancer: A Two-Institution Propensity Score-Matched Analysis.

PURPOSE: To evaluate differences in outcomes of early-stage peripheral non-small-cell lung cancer (NSCLC) treated with either 3- or 5-fraction stereotactic body radiotherapy (SBRT) at 2 institutions. PATIENTS AND METHODS: Patients diagnosed with peripherally located early-stage NSCLC who received either a median dose of 60 Gy (interquartile range [IQR], 60-60, biologically effective dose, 151-151) in 3 fractions or a median dose of 50 Gy (IQR, 50-50, biologically effective dose, 94-94) in 5 fractions were included in this study. All data were retrospectively collected and reviewed in an institutional review board-approved database. RESULTS: A total of 192 lesions in 192 patients were identified: 94 received 3-fraction SBRT and 98 received 5-fraction SBRT. Patients in the 5-fraction cohort had significantly smaller tumors (P = .0021). Larger tumor size was associated with worse overall survival (hazard ratio, 1.40, P = .0013) for all patients. A single grade 3 toxicity was reported in each cohort. A propensity score-matched cohort of 94 patients was constructed with a median follow-up of 29.3 months (IQR, 17.3-44.6) for the 3-fraction cohort and 31.0 months (IQR, 17.0-48.5) for the 5-fraction cohort (P = .84). There were no statistically significant differences between these 2 cohorts in overall survival (P = .33), progression-free survival (P = .40), local failure (P = .86), and nodal or distant failure (P = .57) at 2 years. CONCLUSION: The 3- and 5-fraction SBRT regimens for early-stage peripheral NSCLC had comparable clinical outcomes. Both regimens were well tolerated. A large tumor size was an adverse prognostic factor for worse survival.

Comparison of Single- and Three-fraction Schedules of Stereotactic Body Radiation Therapy for Peripheral Early-stage Non-Small-cell Lung Cancer.

BACKGROUND: To compare the clinical outcomes of patients with early-stage non-small-cell lung cancer (NSCLC) who had undergone either single-fraction (SF) or three-fraction (TF) stereotactic body radiation therapy (SBRT) at a single institution during over 8-year period. PATIENTS AND METHODS: Patients with peripherally located early-stage NSCLC who had undergone SBRT from February 2007 to November 2015 were included in the present study. SBRT was delivered without heterogeneity correction. Data were retrospectively reviewed and collected in an institutional review board-approved database. R software (version 3.3.2) was used for statistical analysis. RESULTS: Of 159 total lung tumors, 65 lesions received 30 Gy (median, 30 Gy) in 1 fraction, and 94 lesions received 48 to 60 Gy (median, 60 Gy) in 3 fractions. Patients with a Karnofsky performance status < 80 were more common in the SF-SBRT cohort (P = .050). After a median follow-up of 22.2 and 26.2 months for the SF-SBRT and TF-SBRT cohorts, respectively (P = .29), no statistically significant difference was found in overall survival (P = .86), progression-free survival (P = .95), local failure (P = .95), nodal failure (P = .91), and distant failure (P = .49) at 24 months. At 1 and 2 years, the overall survival rates were 86.1% and 63.2% for the SF-SBRT cohort and 80.8% and 61.6% for the TF-SBRT cohort, respectively. At 1 and 2 years, the local control rates were 95.1% and 87.8% for the SF-SBRT cohort and 92.7% and 86.2% for the TF-SBRT cohort, respectively. Both regimens were well tolerated. CONCLUSION: Despite more patients with poor performance status in the SF-SBRT cohort, the SF- and TF-SBRT regimens showed no differences in clinical outcomes. SF-SBRT is now our standard approach.