Machine Learning Applications in Head and Neck Radiation Oncology: Lessons From Open-Source Radiomics Challenges

Radiomics leverages existing image datasets to provide non-visible data extraction via image post-processing, with the aim of identifying prognostic, and predictive imaging features at a sub-region of interest level. However, the application of radiomics is hampered by several challenges such as lack of image acquisition/analysis method standardization, impeding generalizability. As of yet, radiomics remains intriguing, but not clinically validated. We aimed to test the feasibility of a non-custom-constructed platform for disseminating existing large, standardized databases across institutions for promoting radiomics studies. Hence, University of Texas MD Anderson Cancer Center organized two public radiomics challenges in head and neck radiation oncology domain. This was done in conjunction with MICCAI 2016 satellite symposium using Kaggle-in-Class, a machine-learning and predictive analytics platform. We drew on clinical data matched to radiomics data derived from diagnostic contrast-enhanced computed tomography (CECT) images in a dataset of 315 patients with oropharyngeal cancer. Contestants were tasked to develop models for (i) classifying patients according to their human papillomavirus status, or (ii) predicting local tumor recurrence, following radiotherapy. Data were split into training, and test sets. Seventeen teams from various professional domains participated in one or both of the challenges. This review paper was based on the contestants' feedback; provided by 8 contestants only (47%). Six contestants (75%) incorporated extracted radiomics features into their predictive model building, either alone (n = 5; 62.5%), as was the case with the winner of the “HPV” challenge, or in conjunction with matched clinical attributes (n = 2; 25%). Only 23% of contestants, notably, including the winner of the “local recurrence” challenge, built their model relying solely on clinical data. In addition to the value of the integration of machine learning into clinical decision-making, our experience sheds light on challenges in sharing and directing existing datasets toward clinical applications of radiomics, including hyper-dimensionality of the clinical/imaging data attributes. Our experience may help guide researchers to create a framework for sharing and reuse of already published data that we believe will ultimately accelerate the pace of clinical applications of radiomics; both in challenge or clinical settings

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Long-term patient reported outcomes following radiation therapy for oropharyngeal cancer: cross-sectional assessment of a prospective symptom survey in patients ≥65 years old

Abstract Background Given the potential for older patients to experience exaggerated toxicity and symptoms, this study was performed to characterize patient reported outcomes in older patients following definitive radiation therapy (RT) for oropharyngeal cancer (OPC). Methods Cancer-free head and neck cancer survivors (>6 months since treatment completion) were eligible for participation in a questionnaire-based study. Participants completed the MD Anderson Symptom Inventory-Head and Neck module (MDASI-HN). Those patients ≥65 years old at treatment for OPC with definitive RT were included. Individual and overall symptom severity and clinical variables were analyzed. Results Of the 79 participants analyzed, 82% were male, 95% white, 41% T3/4 disease, 39% RT alone, 27% induction chemotherapy, 52% concurrent, and 18% both, and 96% IMRT. Median age at RT was 71 yrs. (range: 65–85); median time from RT to MDASI-HN was 46 mos. (2/3 > 24 mos.). The top 5 MDASI-HN items rated most severe in terms of mean (±SD) ratings (0–10 scale) were dry mouth (3.48 ± 2.95), taste (2.81 ± 3.29), swallowing (2.59 ± 2.96), mucus in mouth/throat (2.04 ± 2.68), and choking (1.30 ± 2.38) reported at moderate-severe levels (≥5) by 35, 29, 29, 18, and 13%, respectively. Thirty-nine % reported none (0) or no more than mild (1–4) symptoms across all 22 MDASI-HN symptoms items, and 38% had at least one item rated as severe (≥7). Hierarchical cluster analysis resulted in 3 patient groups: 1) ~65% with ranging from none to moderate symptom burden, 2) ~35% with moderate-severe ratings for a subset of classically RT-related symptoms (e.g. dry mouth, mucus, swallowing) and 3) 2 pts. with severe ratings of most items. Conclusions The overall long-term symptom burden seen in this older OPC cohort treated with modern standard therapy was largely favorable, yet a higher symptom group (~35%) with a distinct pattern of mostly local and classically RT-related symptoms was identified

Additional file 3: Table S3. of Long-term patient reported outcomes following radiation therapy for oropharyngeal cancer: cross-sectional assessment of a prospective symptom survey in patients ≥65 years old

Results of univariate and multivariate analysis comparing MDASI-HN symptom item composite and Top 5 MDASI-HN items by mean composite with clinical variables of interest. (DOCX 16 kb

Machine Learning Applications in Head and Neck Radiation Oncology: Lessons From Open-Source Radiomics Challenges

{Radiomics leverages existing image datasets to provide non-visible data extraction via image post-processing, with the aim of identifying prognostic and predictive imaging features at a sub-region of interest level. However, the application of radiomics is hampered by several challenges such as lack of image acquisition/analysis method standardization, impeding generalizability. As of yet, radiomics remains intriguing, but not clinically validated. We aimed to test the feasibility of a non-custom-constructed platform for disseminating existing large, standardized databases across institutions for promoting radiomics studies. Hence, University of Texas MD Anderson Cancer Center organized two public radiomics challenges in head and neck radiation oncology domain. This was done in conjunction with MICCAI 2016 satellite symposium using Kaggle-in-Class, a machine-learning and predictive analytics platform. We drew on clinical data matched to radiomics data derived from diagnostic contrast-enhanced computed tomography images in a dataset of 315 patients with oropharyngeal cancer. Contestants were tasked to develop models for (i) classifying patients according to their human papillomavirus status, or (ii) predicting local tumor recurrence, following radiotherapy. Data were split into training, and test sets. Seventeen teams from various professional domains participated in one or both of the challenges. This review paper was based on the contestants’ feedback; provided by 8 contestants only (47%). Six contestants (75%) incorporated extracted radiomics features into their predictive model building, either alone (n=5; 62.5%), as was the case with the winner of the “HPV” challenge, or in conjunction with matched clinical attributes (n=2; 25%). Only 23% of contestants, notably, including the winner of the “local recurrence” challenge, built their model relying solely on clinical data. In addition to the value of the integration of machine learning into clinical decision-making, our experience sheds light on challenges in sharing and directing existing datasets towards clinical applications of radiomics, including hyper-dimensionality of the clinical/imaging data attributes. Our experience may help guide researchers to create a framework for sharing and reuse of already published data that we believe will ultimately accelerate the pace of clinical applications of radiomics; both in challenge or clinical settings

Additional file 1: Table S1. of Long-term patient reported outcomes following radiation therapy for oropharyngeal cancer: cross-sectional assessment of a prospective symptom survey in patients ≥65 years old

Proportions of patients reporting moderate to severe (≥5) rating for the 22 MDASI-HN symptom items by clinical subgroups of interest. (DOCX 20 kb

Risk of COVID-19 after natural infection or vaccinationResearch in context

Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health

Risk of COVID-19 after natural infection or vaccinationResearch in context

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health