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Objectives:  There is limited research on suicide risk screening (SRS) among head and neck cancer (HNC) patients, a population at increased risk for suicide. To address this gap, this single-site mixed methods study assessed oncology professionals' perspectives about the feasibility, acceptability, and appropriateness of an electronic SRS program that was implemented as a part of routine care for HNC patients., Methods: Staff who assisted with SRS implementation completed (e.g., nurses, medical assistants, advanced practice providers, physicians, social workers) a one-time survey ( N  = 29) and interview ( N  = 25). Quantitative outcomes were assessed using previously validated feasibility, acceptability, and appropriateness measures. Additional qualitative data were collected to provide context for interpreting the scores., Results:  Nurses and medical assistants, who were directly responsible for implementing SRS, reported low feasibility, acceptability, and appropriateness, compared with other team members (e.g., physicians, social workers, advanced practice providers). Team members identified potential improvements needed to optimize SRS, such as hiring additional staff, improving staff training, providing different modalities for screening completion among individuals with disabilities, and revising the patient-reported outcomes to improve suicide risk prediction., Conclusion:  Staff perspectives about implementing SRS as a part of routine cancer care for HNC patients varied widely. Before screening can be implemented on a larger scale for HNC and other cancer patients, additional implementation strategies may be needed that optimize workflow and reduce staff burden, such as staff training, multiple modalities for completion, and refined tools for identifying which patients are at greatest risk for suicide., Competing Interests: D.E.R. is on the Board of Directors for NanoString Technologies, Inc., (Thieme. All rights reserved.)

Background: Survival following melanoma and chronic lymphocytic leukemia (CLL) have both been individually associated with previous history of non-melanoma skin cancers (specifically keratinocyte carcinomas [KC]). Furthermore, melanoma and CLL have been reported to occur within the same patients. The survival experience of patients with both cancers is understudied, and the role of history of KC is unknown. Additional research is needed to tease apart the independent associations between KC and CLL survival, KC and melanoma survival, and the co-occurrence of all three cancers., Methods: A retrospective cohort study was conducted among patients who were diagnosed with melanoma and/or CLL at a comprehensive cancer center between 2008 and 2020. Multivariable Cox regression models were used to examine the association between history of KC and survival following melanoma and/or CLL with careful consideration of calendar year of diagnosis, treatment regimens and other risk factors. A nested case-control study comparing patients with both CLL and melanoma to those with only CLL or only melanoma was conducted to compare blood parameters across the three groups., Results: A time-dependent association was observed between history of KC and favorable melanoma survival within 4 years following diagnosis and poorer survival post 7 years after melanoma diagnosis. History of KC was not significantly associated with survival following the diagnosis of CLL, after adjustment for clinical factors including historical/concurrent melanoma. Patients with co-occurring melanoma and CLL tended to be diagnosed with melanoma first and had elevated blood parameters including white blood cell and lymphocyte counts as compared with patients who were diagnosed with only melanoma., Conclusions: History of KC was an independent predictor of survival following melanoma but not of CLL. Additional studies are needed to determine if blood parameters obtained at the time of melanoma diagnosis could be used as a cost-effective way to identify those at high risk of asymptomatic CLL for the promotion of earlier CLL diagnosis., (© 2023. The Author(s).)

Background: COVID-19 infection severity differs by race and ethnicity, but its long-term effect on cancer-related outcomes is unknown. Therefore, information on COVID-19 history is critical to ascertain among new cancer patients in order to advance research on its impact on cancer outcomes and potentially related health disparities., Methods: A cross-sectional study was conducted among 16,025 new patients seeking care at Moffitt Cancer Center (MCC) between 2021 and 2022. Patient self-reported histories of COVID-19 infection and other pre-existing health conditions were obtained from electronic questionnaires administered to all new MCC patients. Associations between demographics and COVID-19 infection and hospitalization were examined., Results: A total of 1,971 patients (12.3%) reported ever having COVID-19. Self-reported COVID-19 history was significantly more prevalent in Hispanic vs. non-Hispanic patients (OR = 1.24, 1.05-1.45) and less prevalent in Asian versus White patients (OR = 0.49, 95% 0.33-0.70). Among patients who ever had COVID-19, 10.6% reported a COVID-19-related hospitalization. Males had higher odds of a COVID-19 related hospitalization than females (OR = 1.50, 95% CI = 1.09-2.05), as did Black/African American patients (OR = 2.11, 95% CI = 1.18-3.60) and patients of races other than Black/African American and Asian (OR = 2.61, 95% CI = 1.43-4.54) compared to White patients. Hispanic patients also experienced higher odds of hospitalization (OR = 2.06, 95% CI-1.29- 3.23) compared with non-Hispanic patients of all races in a sensitivity analysis that combined race/ethnicity. Pre-existing lung and breathing problems were associated with higher odds of being hospitalized with COVID-19 (OR = 2.38, 95% CI = 1.61-3.48), but these and other health conditions did not explain the observed associations between race and COVID-19 hospitalization., Conclusions: Higher rates of COVID-19 hospitalization were observed among patients identifying as Black/African American or Hispanic independent of pre-existing health conditions. Future studies evaluating long-term effects of COVID-19 should carefully examine potential racial/ethnic disparities in cancer outcomes., (© 2023. The Author(s).)

Background: Randomized clinical trials of novel treatments for solid tumors normally measure disease progression using the Response Evaluation Criteria in Solid Tumors. However, novel, scalable approaches to estimate disease progression using real-world data are needed to advance cancer outcomes research. The purpose of this narrative review is to summarize examples from the existing literature on approaches to estimate real-world disease progression and their relative strengths and limitations, using lung cancer as a case study., Methods: A narrative literature review was conducted in PubMed to identify articles that used approaches to estimate real-world disease progression in lung cancer patients. Data abstracted included data source, approach used to estimate real-world progression, and comparison to a selected gold standard (if applicable)., Results: A total of 40 articles were identified from 2008 to 2022. Five approaches to estimate real-world disease progression were identified including manual abstraction of medical records, natural language processing of clinical notes and/or radiology reports, treatment-based algorithms, changes in tumor volume, and delta radiomics-based approaches. The accuracy of these progression approaches were assessed using different methods, including correlations between real-world endpoints and overall survival for manual abstraction (Spearman rank ρ = 0.61-0.84) and area under the curve for natural language processing approaches (area under the curve = 0.86-0.96)., Conclusions: Real-world disease progression has been measured in several observational studies of lung cancer. However, comparing the accuracy of methods across studies is challenging, in part, because of the lack of a gold standard and the different methods used to evaluate accuracy. Concerted efforts are needed to define a gold standard and quality metrics for real-world data., (© The Author(s) 2023. Published by Oxford University Press.)

Myelodysplastic neoplasms (MDS) are a collection of hematopoietic disorders with widely variable prognoses and treatment options. Accurate pathologic diagnoses present challenges because of interobserver variability in interpreting morphology and quantifying dysplasia. We compared local clinical site diagnoses with central, adjudicated review from 918 participants enrolled in the ongoing National Heart, Lung, and Blood Institute National MDS Natural History Study, a prospective observational cohort study of participants with suspected MDS or MDS/myeloproliferative neoplasms (MPNs). Locally, 264 (29%) were diagnosed as having MDS, 15 (2%) MDS/MPN overlap, 62 (7%) idiopathic cytopenia of undetermined significance (ICUS), 0 (0%) acute myeloid leukemia (AML) with <30% blasts, and 577 (63%) as other. Approximately one-third of cases were reclassified after central review, with 266 (29%) diagnosed as MDS, 45 (5%) MDS/MPN overlap, 49 (5%) ICUS, 15 (2%) AML with <30%, and 543 (59%) as other. Site miscoding errors accounted for more than half (53%) of the local misdiagnoses, leaving a true misdiagnosis rate of 15% overall, 21% for MDS. Therapies were reported in 37% of patients, including 43% of patients with MDS, 49% of patients with MDS/MPN, and 86% of patients with AML with <30% blasts. Treatment rates were lower (25%) in cases with true discordance in diagnosis compared with those for whom local and central diagnoses agreed (40%), and receipt of inappropriate therapy occurred in 7% of misdiagnosed cases. Discordant diagnoses were frequent, which has implications for the accuracy of study-related and national registries and can lead to inappropriate therapy. This trial was registered at www.clinicaltrials.gov as #NCT05074550., (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Patient-reported data can improve quality of healthcare delivery and patient outcomes. Moffitt Cancer Center ("Moffitt") administers the Electronic Patient Questionnaire (EPQ) to collect data on demographics, including sexual orientation and gender identity (SOGI), medical history, cancer risk factors, and quality of life. Here we investigated differences in EPQ completion by demographic and cancer characteristics., Methods: An analysis including 146,142 new adult patients at Moffitt in 2009-2020 was conducted using scheduling, EPQ and cancer registry data. EPQ completion was described by calendar year and demographics. Logistic regression was used to estimate associations between demographic/cancer characteristics and EPQ completion. More recently collected information on SOGI were described., Results: Patient portal usage (81%) and EPQ completion rates (79%) were consistently high since 2014. Among patients in the cancer registry, females were more likely to complete the EPQ than males (odds ratio [OR] = 1.17, 95% confidence interval [CI] = 1.14-1.20). Patients ages 18-64 years were more likely to complete the EPQ than patients aged ≥65. Lower EPQ completion rates were observed among Black or African American patients (OR = 0.59, 95% CI = 0.56-0.63) as compared to Whites and among patients whose preferred language was Spanish (OR = 0.40, 95% CI = 0.36-0.44) or another language as compared to English. Furthermore, patients with localized (OR = 1.16, 95% CI = 1.12-1.19) or regional (OR = 1.16, 95% CI = 1.12-1.20) cancer were more likely to complete the EPQ compared to those with metastatic disease. Less than 3% of patients self-identified as being lesbian, gay, or bisexual and <0.1% self-identified as transgender, genderqueer, or other., Conclusions: EPQ completion rates differed across demographics highlighting opportunities for targeted process improvement. Healthcare organizations should evaluate data acquisition methods to identify potential disparities in data completeness that can impact quality of clinical care and generalizability of self-reported data., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: History of keratinocyte carcinoma (KC) has been associated with survival following the diagnosis of a second primary malignancy (SPM), with the direction of the association varying by cancer type. Research is needed to elucidate the role of other key factors in this association., Methods: A retrospective cohort study was conducted among patients newly diagnosed and/or treated at Moffitt Cancer Center in December 2008-April 2020 with breast cancer, lung cancer, melanoma, colon cancer, prostate cancer, and non-Hodgkin lymphoma/chronic lymphocytic leukemia (NHL/CLL) (n = 29,156). History of KC was obtained from new patient intake questionnaires. Age- and stage-adjusted hazard ratios (HR) and 95% confidence intervals (CI) were calculated to estimate the association between history of KC and survival following each cancer, stratified by demographic/clinical characteristics., Results: KC history was most prevalent in patients with melanoma (28.7%), CLL (19.8%) and lung cancer (16.1%). KC history was associated with better overall survival following prostate cancer (HR = 0.74, 95% CI = 0.55-0.99) and poorer overall survival following CLL (HR = 1.73, 95% CI = 1.10-2.71). Patients with a history of KC experienced better survival within the first four years of a melanoma diagnosis (HR = 0.79, 95% CI = 0.67-0.92); whereas poorer survival was observed for patients who survived 7 + years after a melanoma diagnosis (HR = 2.18, 95% CI = 1.17-4.05). Stratification by treatment and stage revealed directional differences in the associations between KC history and survival among patients with breast cancer and melanoma., Conclusions: KC history may be a predictor of survival following an SPM, possibly serving as a marker of immune function and/or DNA damage repair capacity., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: National Cancer Institute cancer centers (NCICCs) provide specialized cancer care including precision oncology and clinical treatment trials. While these centers can offer novel therapeutic options, less is known about when patients access these centers or at what timepoint in their disease course they receive specialized care. This is especially important since precision diagnostics and receipt of the optimal therapy upfront can impact patient outcomes and previous research suggests that access to these centers may vary by demographic characteristics. Here, we examine the timing of patients' presentation at Moffitt Cancer Center (MCC) relative to their initial diagnosis across several demographic characteristics., Methods: A retrospective cohort study was conducted among patients who presented to MCC with breast, colon, lung, melanoma, and prostate cancers between December 2008 and April 2020. Patient demographic and clinical characteristics were obtained from the Moffitt Cancer Registry. The association between patient characteristics and the timing of patient presentation to MCC relative to the patient's cancer diagnosis was examined using logistic regression., Results: Black patients (median days = 510) had a longer time between diagnosis and presentation to MCC compared to Whites (median days = 368). Black patients were also more likely to have received their initial cancer care outside of MCC compared to White patients (odds ratio [OR] and 95% confidence interval [CI] = 1.45 [1.32-1.60]). Furthermore, Hispanics were more likely to present to MCC at an advanced stage compared to non-Hispanic patients (OR [95% CI] = 1.28 [1.05-1.55])., Conclusions: We observed racial and ethnic differences in timing of receipt of care at MCC. Future studies should aim to identify contributing factors for the development of novel mitigation strategies and assess whether timing differences in referral to an NCICC correlate with long-term patient outcomes., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: There has been limited study of the implementation of suicide risk screening for patients with head and neck cancer (HNC) as a part of routine care. To address this gap, this study assessed oncology providers' and professionals' perspectives about barriers and facilitators of implementing a suicide risk screening among patients with HNC., Materials and Methods: All patients with HNC with an in-person visit completed a suicide risk screening on an electronic tablet. Patients reporting passive death wish were then screened for active suicidal ideation and referred for appropriate intervention. Interviews were conducted with 25 oncology providers and professionals who played a key role in implementation including nurses, medical assistants, patient access representatives, advanced practice providers, physicians, social workers, and informatics staff. The interview guide was based on the Consolidated Framework for Implementation Research. Interviews were transcribed and analyzed for themes., Results: Participants identified multilevel implementation barriers, such as intervention level (eg, patient difficulty with using a tablet), process level (eg, limited nursing engagement), organizational level (eg, limited clinic Wi-Fi connectivity), and individual level (eg, low clinician self-efficacy for interpreting and acting upon patient-reported outcome scores). Participants noted facilitators, such as effective care coordination across nursing and social work staff and the opportunity for patients to be screened multiple times. Participants recommended strengthening patient and clinician education and providing patients with other modalities for data entry (eg, desktop computer in the waiting room)., Conclusion: Participants identified important intervention modifications that may be needed to optimize suicide risk screening in cancer care settings.

Background: Patients with cancer require timely access to care so that healthcare providers can prepare an optimal treatment plan with significant implications for quality of life and mortality. The COVID-19 pandemic spurred rapid adoption of telemedicine in oncology, but study of patient experience of care with telemedicine in this population has been limited. We assessed overall patient experience of care with telemedicine at an NCI-designated Comprehensive Cancer Center during the COVID-19 pandemic and examined changes in patient experience over time., Patients and Methods: This was a retrospective study of outpatient oncology patients who received treatment at Moffitt Cancer Center. Press Ganey surveys were used to assess patient experience. Data from patients with appointments between April 1, 2020, and June 30, 2021, were analyzed. Patient experience was compared between telemedicine and in-person visits, and patient experience with telemedicine over time was described., Results: A total of 33,318 patients reported Press Ganey data for in-person visits, and 5,950 reported Press Ganey data for telemedicine visits. Relative to patients with in-person visits, more patients with telemedicine visits gave higher satisfaction ratings for access (62.5% vs 75.8%, respectively) and care provider concern (84.2% vs 90.7%, respectively) (P<.001). When adjusted for age, race/ethnicity, sex, insurance, and clinic type, telemedicine visits consistently outperformed in-person visits over time regarding access and care provider concern (P<.001). There were no significant changes over time in satisfaction with telemedicine visits regarding access, care provider concern, telemedicine technology, or overall assessment (P>.05)., Conclusions: In this study, a large oncology dataset showed that telemedicine resulted in better patient experience of care in terms of access and care provider concern compared with in-person visits. Patient experience of care with telemedicine visits did not change over time, suggesting that implementing telemedicine was effective.

Purpose: Electronic health record (EHR) data are widely used in precision medicine, quality improvement, disease surveillance, and population health management. However, a significant amount of EHR data are stored in unstructured formats including scanned documents external to the treatment facility presenting an informatics challenge for secondary use. Studies are needed to characterize the clinical information uniquely available in scanned outside documents (SODs) to understand to what extent the availability of such information affects the use of these real-world data for cancer research., Materials and Methods: Two independent EHR data abstractions capturing 30 variables commonly used in oncology research were conducted for 125 patients treated for advanced non-small-cell lung cancer at a comprehensive cancer center, with and without consideration of SODs. Completeness and concordance were compared between the two abstractions, overall, and by patient groups and variable types., Results: The overall completeness of the data with SODs was 77.6% as compared with 54.3% for the abstraction without SODs. The differences in completeness were driven by data related to biomarker tests, which were more likely to be uniquely available in SODs. Such data were prone to missingness among patients who were diagnosed externally., Conclusion: There were no major differences in completeness between the two abstractions by demographics, diagnosis, disease progression, performance status, or oral therapy use. However, biomarker data were more likely to be uniquely contained in the SODs. Our findings may help cancer centers prioritize the types of SOD data being abstracted for research or other secondary purposes.

Although health care delivery is becoming increasingly digitized, driven by the pursuit of improved access, equity, efficiency, and effectiveness, progress does not appear to be equally distributed across therapeutic areas. Oncology is renowned for leading innovation in research and in care; digital pathology, digital radiology, real-world data, next-generation sequencing, patient-reported outcomes, and precision approaches driven by complex data and biomarkers are hallmarks of the field. However, remote patient monitoring, decentralized approaches to care and research, "hospital at home," and machine learning techniques have yet to be broadly deployed to improve cancer care. In response, the Digital Medicine Society and Moffitt Cancer Center convened a multistakeholder roundtable discussion to bring together leading experts in cancer care and digital innovation. This viewpoint highlights the findings from these discussions, in which experts agreed that digital innovation is lagging in oncology relative to other therapeutic areas. It reports that this lag is most likely attributed to poor articulation of the challenges in cancer care and research best suited to digital solutions, lack of incentives and support, and missing standardized infrastructure to implement digital innovations. It concludes with suggestions for actions needed to bring the promise of digitization to cancer care to improve lives., (©Smit Patel, Jennifer C Goldsack, Grace Cordovano, Andrea Downing, Karen K Fields, Cindy Geoghegan, Upinder Grewal, Jorge Nieva, Nikunj Patel, Dana E Rollison, Archana Sah, Maya Said, Isabel Van De Keere, Amanda Way, Dana L Wolff-Hughes, William A Wood, Edmondo J Robinson. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 04.01.2023.)

Importance: While the health care community advocates broadly for climate change policy, medical professionals can look within care practices to assess their contribution to carbon dioxide (CO2) emissions, and provide solutions wherever possible. Telemedicine can help in mitigating climate change by providing care from a distance., Objective: To assess the carbon savings achieved from telemedicine visits., Design, Setting, and Participants: This cross-sectional study of telemedicine visits was conducted at a single-institution National Cancer Institute (NCI)-designated comprehensive cancer center. Eligible patients were aged 18 years and above, completed telemedicine visits from April 1, 2020, to June 20, 2021, and had a Florida mailing address documented in their electronic medical record. Groups were divided between those within driving time of 60 minutes (1-way) to the cancer center vs those living beyond 60 minutes of drive time. Data were analyzed between April 2020 and June 2021., Main Outcomes and Measures: Carbon emission savings from telemedicine, measured in total and average per-visit savings., Results: A total 49 329 telemedicine visits with 23 228 patients were conducted from April 1, 2020, to June 30, 2021. A total 21 489 visits were for patients with driving time of 60 minutes or less (median [IQR] age, 62.0 [52.0-71.0] years; 12 334 [57.4%] female; 1685 [7.8%] Black, 1500 [7.0%] Hispanic, 16 010 [74.5%] non-Hispanic White), while 27 840 visits were for patients with driving time greater than 60 minutes (median [IQR] age, 67.0 [57.0-74.0] years; 14 372 [51.6%] female; 1056 [3.8%] Black, 1364 [5.0%] Hispanic, 22 457 [80.7%] non-Hispanic White). For patients living within a driving time of 60 minutes from the cancer center, 424 471 kg CO2 emissions were saved (mean [SD] emissions savings, 19.8 [9.4] kg CO2 per visit) due to telemedicine-equivalent to 91.5 passenger vehicles driven for 1 year. For patients whose driving distance was greater than 60 minutes, 2 744 248 kg CO2 emissions were saved (mean emissions savings, 98.6 [54.8] kg CO2 per visit)-equivalent to 591 passenger vehicles driven for 1 year., Conclusions and Relevance: Using a large data set, this cross-sectional analysis highlighted the carbon emissions savings due to telemedicine in oncology. This has important implications in reducing health care-related carbon footprint.

Cancer surveillance at the population level is a highly labor-intensive process, with certified tumor registrars (CTRs) manually reviewing medical charts of cancer patients and entering information into local databases that are centrally merged and curated at state and national levels. Registries face considerable challenges in terms of constrained budgets, staffing shortages, and keeping pace with the evolving national and international data standards that are essential to cancer registration. Advanced informatics methods are needed to increase automation, reduce manual efforts, and to help address some of these challenges. The Cancer Informatics Advisory Group (CIAG) to the North American Association of Central Cancer Registries (NAACCR) board was established in 2019 to advise of external informatics activities and initiatives for long-term strategic planning. Reviewed here by the CIAG are current informatics initiatives that were either born out of the cancer registry field or have implications for expansion to cancer surveillance programs in the future. Several areas of notable activity are presented, including an overview of informatics initiatives and descriptions of 12 specific informatics projects with implications for cancer registries. Recommendations are also provided to the registry community for the continued tracking and impact of the projects and initiatives., (© 2022 National Cancer Registrars Association.)

Background: Cutaneous human papillomaviruses (cuHPV) and polyomaviruses (HPyV) have been implicated in skin cancers; however, interpretation of findings across studies is complicated by limited understanding of the natural history of these infections across normal tissue types., Methods: In total, 675 eyebrow hair (EBH) and skin swab (SSW) samples were collected from 71 skin cancer screening patients every 6 months over 2 years and measured for presence of β-HPV, γ-HPV, and HPyV. Incidence, persistence, and clearance of cuHPV/HPyV were estimated, and risk factors associated with infection were examined., Results: Prevalence, incidence, and persistence of β-HPV, γ-HPV, and HPyV were consistently higher in SSW than in EBH, with types 5, 24, 49, 76 and Merkel cell polyomavirus (MCPyV) having incidence rates greater than 20 per 1000 person-months. Prevalent γ-HPV EBH infections persisted more often in women (P = .024), incident β-HPV EBH infections persisted less often among individuals with history of blistering sunburn (P = .019), and prevalent MCPyV SSW infections persisted more often in those with a history of skin cancer (P = .033)., Conclusions: Incidence and persistence of cuHPV/HPyV were observed in SSW and EBH; however, none of the risk factors examined were commonly associated with cuHPV/HPyV infections across normal tissue types., Competing Interests: Potential conflicts of interest. D. E. R. serves on the board of directors for NanoString Technologies, Inc. T. W. serves on advisory boards for MSD (Merck) Sharp & Dohme. A. R. G. reports grants from Merck & Co, Inc and personal fees (Advisory Board Member) from Merck & Co, Inc, during the conduct of the study. V. K. S. is a compensated consultant for Merck. All other authors report no conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Information in pathology reports is critical for cancer care. Natural language processing (NLP) systems used to extract information from pathology reports are often narrow in scope or require extensive tuning. Consequently, there is growing interest in automated deep learning approaches. A powerful new NLP algorithm, bidirectional encoder representations from transformers (BERT), was published in late 2018. BERT set new performance standards on tasks as diverse as question answering, named entity recognition, speech recognition, and more., Objective: The aim of this study is to develop a BERT-based system to automatically extract detailed tumor site and histology information from free-text oncological pathology reports., Methods: We pursued three specific aims: extract accurate tumor site and histology descriptions from free-text pathology reports, accommodate the diverse terminology used to indicate the same pathology, and provide accurate standardized tumor site and histology codes for use by downstream applications. We first trained a base language model to comprehend the technical language in pathology reports. This involved unsupervised learning on a training corpus of 275,605 electronic pathology reports from 164,531 unique patients that included 121 million words. Next, we trained a question-and-answer (Q&A) model that connects a Q&A layer to the base pathology language model to answer pathology questions. Our Q&A system was designed to search for the answers to two predefined questions in each pathology report: What organ contains the tumor? and What is the kind of tumor or carcinoma? This involved supervised training on 8197 pathology reports, each with ground truth answers to these 2 questions determined by certified tumor registrars. The data set included 214 tumor sites and 193 histologies. The tumor site and histology phrases extracted by the Q&A model were used to predict International Classification of Diseases for Oncology, Third Edition (ICD-O-3), site and histology codes. This involved fine-tuning two additional BERT models: one to predict site codes and another to predict histology codes. Our final system includes a network of 3 BERT-based models. We call this CancerBERT network (caBERTnet). We evaluated caBERTnet using a sequestered test data set of 2050 pathology reports with ground truth answers determined by certified tumor registrars., Results: caBERTnet's accuracies for predicting group-level site and histology codes were 93.53% (1895/2026) and 97.6% (1993/2042), respectively. The top 5 accuracies for predicting fine-grained ICD-O-3 site and histology codes with 5 or more samples each in the training data set were 92.95% (1794/1930) and 96.01% (1853/1930), respectively., Conclusions: We have developed an NLP system that outperforms existing algorithms at predicting ICD-O-3 codes across an extensive range of tumor sites and histologies. Our new system could help reduce treatment delays, increase enrollment in clinical trials of new therapies, and improve patient outcomes., (©Joseph Ross Mitchell, Phillip Szepietowski, Rachel Howard, Phillip Reisman, Jennie D Jones, Patricia Lewis, Brooke L Fridley, Dana E Rollison. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 23.03.2022.)

Background and Purpose: The study objective was to determine whether longitudinal changes in patient-reported outcomes (PROs) were associated with survival among early-stage, non-small cell lung cancer (NSCLC) patients undergoing stereotactic body radiation therapy (SBRT)., Materials and Methods: Data were obtained from January 2015 through March 2020. We ran a joint probability model to assess the relationship between time-to-death, and longitudinal PRO measurements. PROs were measured through the Edmonton Symptom Assessment Scale (ESAS). We controlled for other covariates likely to affect symptom burden and survival including stage, tumor diameter, comorbidities, gender, race/ethnicity, relationship status, age, and smoking status., Results: The sample included 510 early-stage NSCLC patients undergoing SBRT. The median age was 73.8 (range: 46.3-94.6). The survival component of the joint model demonstrates that longitudinal changes in ESAS scores are significantly associated with worse survival (HR: 1.04; 95% CI: 1.02-1.05). This finding suggests a one-unit increase in ESAS score increased probability of death by 4%. Other factors significantly associated with worse survival included older age (HR: 1.04; 95% CI: 1.03-1.05), larger tumor diameter (HR: 1.21; 95% CI: 1.01-1.46), male gender (HR: 1.87; 95% CI: 1.36-2.57), and current smoking status (HR: 2.39; 95% CI: 1.25-4.56)., Conclusion: PROs are increasingly being collected as a part of routine care delivery to improve symptom management. Healthcare systems can integrate these data with other real-world data to predict patient outcomes, such as survival. Capturing longitudinal PROs-in addition to PROs at diagnosis-may add prognostic value for estimating survival among early-stage NSCLC patients undergoing SBRT., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Treatment outcomes of advanced non-small cell lung cancer (NSCLC) have substantially improved with immune checkpoint inhibitors (ICI), although only approximately 19% of patients respond to immunotherapy alone, increasing to 58% with the addition of chemotherapy. The gut microbiome has been recognized as a modulator of ICI response via its priming effect on the host immune response. Antibiotics as well as chemotherapy reduce gut microbial diversity, hence altering composition and function of the gut microbiome. Since the gut microbiome may modify ICI efficacy, we conducted a retrospective study evaluating the effects of prior antibiotic or chemotherapy use on NSCLC patient response to ICI., Methods: We retrospectively evaluated 256 NSCLC patients treated between 2011-2017 at Moffitt Cancer Center with ICI ± chemotherapy, examining the associations between prior antibiotic or chemotherapy use, overall response rate and survival. Relative risk regression using a log-link with combinatorial expectation maximization algorithm was performed to analyze differences in response between patients treated with antibiotics or chemotherapy versus patients who didn't receive antibiotics or chemotherapy. Cox proportional hazards models were constructed to evaluate associations between risk factors and overall survival., Results: Only 46 (18% of 256) patients used antibiotics prior to and/or during ICI treatment, and 146 (57%) had prior chemotherapy. Antibiotic users were 8% more likely to have worse overall response rate (RR:1.08; CI:0.93-1.26; p = 0.321), as well as a 35% worse overall survival (HR:1.35; CI:0.91-2.02; p = 0.145), although results were not statistically significant. However, prior use of chemotherapy was significantly associated with poor ICI response (RR:1.24; CI:1.05-1.47; p = 0.013) and worse overall survival (HR:1.47; CI:1.07-2.03; p = 0.018)., Conclusions: Patients receiving antibiotics prior to and/or during ICI therapy might experience worse treatment outcomes and survival than unexposed patients, although these associations were not statistically significant and hence warrant further prospective study. Prior chemotherapy significantly reduced ICI response and overall survival. Antibiotic or chemotherapy exposure may negatively impact ICI response, perhaps through disruption of the eubiotic gut microbiome., (© 2022. The Author(s).)

Ultraviolet radiation exposure (UVR) is a risk factor for cutaneous squamous cell carcinoma (cuSCC) and has been shown to be positively associated with circulating immunosuppressive regulatory T cells ("Tregs"). However, the risk of cuSCC in association with circulating Tregs has not been studied. The aim of this study was to determine whether circulating Treg levels are associated with cuSCC development, particularly in the context of high UVR. Blood and spectrophotometer-based UVR measurements were obtained on 327 immunocompetent individuals undergoing routine skin cancer screenings at baseline and followed for up to 4 years for incident cuSCC development within a prospective cohort study. Proportions of phenotypically distinct Tregs, especially CCR4 hi and CLA + cells which are associated with activation and homing, respectively, were measured by flow cytometry. Tregs in cuSCC tumors were assessed using immunohistochemistry and graded for solar elastosis, a measure of cumulative UVR damage. Of several Treg phenotypes examined, higher levels of circulating CCR4 hi Tregs at baseline were significantly associated with increased risk of subsequent cuSCC; those with higher levels of both CCR4 hi and UVR were four times more likely to develop cuSCC compared to those with lower levels of both (Hazard Ratio = 4.11, 95% CI = 1.22-13.90). Within cuSCC tumors, CCR4 hi Tregs were positively associated with solar elastosis. Results show that a higher proportion of CCR4 hi peripheral Tregs predicts incident cuSCC up to 4 years, especially among highly UV-exposed individuals. Research of the underpinning biology of Tregs in UVR-associated skin damage may possibly reveal novel opportunities for screening, prevention, and treatment., Competing Interests: DER and PE-B filled a provisional Patent titled “Methods of detecting risk of a cancer,” application serial #63/041,676 filed on 6/19/2020. DER serves on the Board of Directors for NanoString Technologies, Inc. PE-B and the Moffitt Cancer Center and Research Institute received payment from licensing unrelated technology to Celgene Corporation and have an appropriate conflict-of-interest management plan. AA is currently employed by AstraZeneca. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Rollison, Messina, Cherpelis, Fenske, Schell, Adeegbe, Zhao, Amorrortu, Akuffo, Hesterberg and Epling-Burnette.)

Cutaneous human papillomavirus (cuHPV) infections may be novel targets for skin cancer prevention and treatment, but critical information regarding the development of virus-positive skin cancers following cuHPV infection has been lacking. In this study, baseline cuHPV infection was measured by serology and viral DNA detection in eyebrow hairs (EBH) and forearm skin swabs (SSW) among 1,008 individuals undergoing routine skin cancer screening exams and followed for incidence of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cuSCC). Baseline β-HPV detection, particularly in SSW, significantly predicted cuSCC (HR = 4.32; 95% confidence interval, 1.00-18.66), whereas serologic evidence of past β-HPV infection was not associated with cuSCC. Less than 5% of baseline β-HPV types detected in SSW were present in subsequent cuSCC tumors, and cuHPV detected in SSW with higher mean fluorescence intensity values were more likely to be present in cuSCC compared with those with lower levels ( P < 0.001). β-HPV-positive cuSCC occurred more often in areas of highly sun-damaged skin than did β-HPV-negative cuSCC. Overall, no clear patterns were observed between baseline β-HPV detection and subsequent development of BCC, or between baseline γ-HPV detection and either cuSCC or BCC. Collectively, these results demonstrate that β-HPV detection in SSW is a significant predictor of cuSCC risk, although evidence suggests only a small subset of cuSCC is etiologically linked to β-HPV infection. SIGNIFICANCE: β-HPV positivity may be a useful biomarker for identifying individuals who could benefit from increased screening or novel cutaneous squamous cell carcinoma prevention strategies., (©2021 American Association for Cancer Research.)

Background: A positive association between Merkel cell polyomavirus (MCPyV) infection and cutaneous squamous cell carcinoma (cuSCC) has been observed in at least one previous case-control study. To evaluate this association in a prospective context, we investigated infections with human polyomaviruses (HPyV), including MCPyV, as predictors of keratinocyte carcinomas, including cuSCC and basal cell carcinoma (BCC), among a cohort of immunocompetent individuals enrolled in the Viruses in Skin Cancer (VIRUSCAN) Study., Methods: Associations between markers of baseline HPyV infection (serum antibodies and viral DNA in eyebrow hairs and skin swabs) and incident keratinocyte carcinomas were modeled using Cox proportional hazards regression. Proportions of baseline HPyV infections that were concordant with a subsequent tumor positive for the same HPyV type were assessed., Results: No significant associations were observed between baseline markers of MCPyV or other HPyV infections and cuSCC or BCC. Less than 4.5% of baseline MCPyV infections were also detected in subsequently developed keratinocyte carcinoma tumors., Conclusions: HPyV infection was not a predictor of keratinocyte carcinoma risk in this prospective cohort., Impact: Cancer-associated infections represent attractive targets for cancer prevention; however, HPyV infections have limited potential as novel targets for cuSCC prevention., (©2021 American Association for Cancer Research.)

Background: Surveys play a vital role in cancer research. During the COVID-19 pandemic, the use of electronic surveys is crucial to improve understanding of the patient experience. However, response rates to electronic surveys are often lower compared with those of paper surveys., Objective: The aim of this study was to determine the best approach to improve response rates for an electronic survey administered to patients at a cancer center during the COVID-19 pandemic., Methods: We contacted 2750 patients seen at Moffitt Cancer Center in the prior 5 years via email to complete a survey regarding their experience during the COVID-19 pandemic, with patients randomly assigned to a series of variations of prenotifications (ie, postcard, letter) or incentives (ie, small gift, modest gift card). In total, eight combinations were evaluated. Qualitative interviews were conducted to understand the level of patient understanding and burden with the survey, and quantitative analysis was used to evaluate the response rates between conditions., Results: A total of 262 (9.5%) patients completed the survey and 9 participated in a qualitative interview. Interviews revealed minimal barriers in understanding or burden, which resulted in minor survey design changes. Compared to sending an email only, sending a postcard or letter prior to the email improved response rates from 3.7% to 9.8%. Similarly, inclusion of an incentive significantly increased the response rate from 5.4% to 16.7%, especially among racial (3.0% to 12.2%) and ethnic (6.4% to 21.0%) minorities, as well as among patients with low socioeconomic status (3.1% to 14.9%)., Conclusions: Strategies to promote effective response rates include prenotification postcards or letters as well as monetary incentives. This work can inform future survey development to increase response rates for electronic surveys, particularly among hard-to-reach populations., (©Cassandra A Hathaway, Melody N Chavez, Mika Kadono, Dana Ketcher, Dana E Rollison, Erin M Siegel, Anita R Peoples, Cornelia M Ulrich, Frank J Penedo, Shelley S Tworoger, Brian D Gonzalez. Originally published in JMIR Cancer (https://cancer.jmir.org), 06.08.2021.)

Background: The MinION sequencer belongs to the third generation of sequencing technology that allows for the generation of ultra-long reads, representing a potentially more effective approach to characterize entire viral genome sequences than other time-consuming and low-throughput methodologies., Methods: We report the use of the MinION nanopore sequencer to sequence the full-length genome of human papillomavirus (HPV)-ICB2 (7441 bp), which was previously characterized in our laboratory. Three independent MinION libraries were prepared and sequenced using either three consecutive 12 -h runs (Protocol A) or a single run of 48 h starting from a pool of three barcoded DNA libraries (Protocol B). A fully automated bioinformatics pipeline was developed for the reconstruction of the viral genome., Results: Protocols A and B generated 9,354,933 and 3,255,879 reads, respectively. Read length N50 values ranged between 6976 and 7360 nucleotides over the four sequencing runs. Bioinformatics analysis showed that both protocols allowed for the reconstruction of the whole viral genome, with pairwise percentages of identity to HPV-ICB2 of 100 % for protocol A and 99.98 % for protocol B., Conclusion: Our results show that the use of the MinION nanopore sequencer represents an effective strategy for whole-genome sequencing of HPVs with a minimal error rate., (Copyright © 2021. Published by Elsevier B.V.)

Next-generation sequencing (NGS) is rapidly expanding into routine oncology practice. Genetic variations in both the cancer and inherited genomes are informative for hereditary cancer risk, prognosis, and treatment strategies. Herein, we focus on the clinical perspective of integrating NGS results into patient care to assist with therapeutic decision making. Five key considerations are addressed for operationalization of NGS testing and application of results to patient care as follows: (1) NGS test ordering and workflow design; (2) result reporting, curation, and storage; (3) clinical consultation services that provide test interpretations and identify opportunities for molecularly guided therapy; (4) presentation of genetic information within the electronic health record; and (5) education of providers and patients. Several of these key considerations center on informatics tools that support NGS test ordering and referencing back to the results for therapeutic purposes. Clinical decision support tools embedded within the electronic health record can assist with NGS test utilization and identifying opportunities for targeted therapy including clinical trial eligibility. Challenges for project and change management in operationalizing NGS-supported, evidence-based patient care in the context of current information technology systems with appropriate clinical data standards are discussed, and solutions for overcoming barriers are provided., Competing Interests: The following represents disclosure information provided by the authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center. Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments). J. Kevin Hicks Consulting or Advisory Role: Quest Diagnostics, 23andMe Research Funding: OneOmeKaren K. Fields Stock and Other Ownership Interests: Pfizer, AbbVie Honoraria: NCCN, NACCME, Pacific Group on Business, HMP, MJH Healthcare Holdings LLC Consulting or Advisory Role: United Health Group Speakers' Bureau: Genentech/Roche Travel, Accommodations, Expenses: Genentech/Roche, CBI, Discern Health, Tapestry, NACCME, Cigna Health Care, FLASCOJhanelle E. Gray Consulting or Advisory Role: Bristol Myers Squibb, EMD Serono, Inivata, Merck Sharp & Dohme, Axiom Healthcare Strategies, Novartis, AstraZeneca, Blueprint Medicines, Lilly, Sanofi, Janssen Scientific Affairs Research Funding: Array BioPharma, Merck, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Genentech/Roche, G1 Therapeutics, Novartis, Pfizer, Ludwig Institute for Cancer Research Travel, Accommodations, Expenses: Bristol Myers Squibb, Merck Sharp & Dohme, Inivata, Merck, EMD Serono, NovartisBryan McIver Honoraria: Eisai, Loxo/Lilly, Blueprint Medicines, Exelixis Consulting or Advisory Role: Eisai, Loxo/Lilly, Exelixis Speakers' Bureau: Loxo/LillyMandy F. O'Leary Stock and Other Ownership Interests: Bristol Myers SquibbRanda M. Perkins Stock and Other Ownership Interests: Progyny Other Relationship: Centene Open Payments Link: https://openpaymentsdata.cms.gov/physician/263299Jamie K. Teer Patents, Royalties, Other Intellectual Property: Patent application: Large Data Set Negative Information Storage ModelJoseph Markowitz Stock and Other Ownership Interests: Intel, Aflac, CVS, Amdocs, Consolidated Edison Honoraria: Springer Consulting or Advisory Role: Idera, Newlink Genetics, Array Biopharma Research Funding: Reata Pharmaceuticals, Macrogenics, Morphogenesis, Genoptix, Idera, Jackson Laboratory for Genomic Medicine, Merck Other Relationship: SpringerDana E. Rollison Leadership: NanoString Technologies Stock and Other Ownership Interests: NanoString Technologies Patents, Royalties, Other Intellectual Property: I am a co-inventor on a provisional patent application filed in July of 2020. The patent pertains to the use of spectrophotometer-measured UV radiation exposure in combination with regulatory T-cells measured in circulation to predict risk of subsequent skin cancer Travel, Accommodations, Expenses: Caserta Analytics Inc (not a healthcare company specifically, but they do business with healthcare companies), NanoString Technologies No other potential conflicts of interest were reported., (© 2021 by American Society of Clinical Oncology.)

Glioma is an aggressive primary tumor of the brain with a poorly understood etiology. We studied the association of 4 human polyomaviruses (HPyV)-JC virus (JCV), BK virus (BKV), human polyomavirus 6 (HPyV6), and Merkel cell polyomavirus (MCPyV) with glioma risk within the Cancer Prevention Study II in the US (CPS-II) and the Janus Serum Bank in Norway. Cohort participants subsequently diagnosed with glioma from the CPS-II (n = 37) and Janus Serum Bank (n = 323), a median of 6.9 and 15.4 years after blood collection, respectively, were matched to individual controls on age, sex, and date of blood draw. Serum antibodies to the major viral capsid protein (VP1) were used to establish infection history for each polyomavirus. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. In the Janus Serum Bank, MCPyV infection was associated with a higher risk of glioma overall (OR: 1.56; 95% CI 1.10, 2.19). A modest, nonsignificant positive association with MCPyV infection was also observed in CPS-II (OR: 1.29; 95% CI 0.54, 3.08). In both cohorts, glioma risk was not significantly related to infection with JCV, BKV or HPyV6. The present study suggests that MCPyV infection may increase glioma risk.

Purpose: The use of genomics within cancer research and clinical oncology practice has become commonplace. Efforts such as The Cancer Genome Atlas have characterized the cancer genome and suggested a wealth of targets for implementing precision medicine strategies for patients with cancer. The data produced from research studies and clinical care have many potential secondary uses beyond their originally intended purpose. Effective storage, query, retrieval, and visualization of these data are essential to create an infrastructure to enable new discoveries in cancer research., Methods: Moffitt Cancer Center implemented a molecular data warehouse to complement the extensive enterprise clinical data warehouse (Health and Research Informatics). Seven different sequencing experiment types were included in the warehouse, with data from institutional research studies and clinical sequencing., Results: The implementation of the molecular warehouse involved the close collaboration of many teams with different expertise and a use case-focused approach. Cornerstones of project success included project planning, open communication, institutional buy-in, piloting the implementation, implementing custom solutions to address specific problems, data quality improvement, and data governance, unique aspects of which are featured here. We describe our experience in selecting, configuring, and loading molecular data into the molecular data warehouse. Specifically, we developed solutions for heterogeneous genomic sequencing cohorts (many different platforms) and integration with our existing clinical data warehouse., Conclusion: The implementation was ultimately successful despite challenges encountered, many of which can be generalized to other research cancer centers., Competing Interests: Steven A. EschrichEmployment: CvergenxLeadership: CvergenXStock and Other Ownership Interests: CvergenXPatents, Royalties, Other Intellectual Property: Patents on RSI, radiation sensitivity technology, January 15, 2019, Timothy Yeatman, Gregory C. Bloom, Steven A. Eschrich: Methods and Systems for Predicting Cancer Outcome, US Patent No. 10181009; August 1, 2017, Robert J. Gillies, Steven A. Eschrich, Robert A. Gatenby, Philippe Lambin, Andre L. A. J. Dekker, Sandy A. Napel, Sylvia Plevritis, Daniel L. Rubin, Systems: Methods and Devices for Analyzing Quantitative Information Obtained From Radiological Images, US Patent No. 9721340; February 4, 2014, Timothy J. Yeatman, Jeff Xiwu Zhou, Gregory C. Bloom, Steven A. Eschrich: Artificial Neural Network Proteomic Tumor Classification, US Patent No. 8642349Travel, Accommodations, Expenses: CvergenXUncompensated Relationships: Cvergenx Jamie K. TeerPatents, Royalties, Other Intellectual Property: Patent application: Large Data Set Negative Information Storage Model Erin SiegelResearch Funding: Bristol Myers Squibb/Sanofi Chandan ChallaStock and Other Ownership Interests: GE Healthcare, Apple, Microsoft, Google, Milestone Pharmaceuticals, Elite Pharmaceuticals, Mereo BioPharma, Liquidia Technologies Rodrigo CarvajalPatents, Royalties, Other Intellectual Property: Moffitt Cancer Center has submitted a patent on the Negative Storage Model (NSM) on behalf of Rodrigo Carvajal Scott CukrasStock and Other Ownership Interests: AbbVie, Genprex, Rigel Melissa AvedonStock and Other Ownership Interests: Pfizer Aik Choon TanResearch Funding: Bristol Myers Squibb Amilcar BlakeEmployment: KEDPLASMA Jennifer GreenmanEmployment: Cancer Treatment Centers of AmericaLeadership: Cancer Treatment Centers of AmericaUncompensated Relationships: MyCareGorithm Dana RollisonLeadership: NanoString TechnologiesStock and Other Ownership Interests: NanoString TechnologiesPatents, Royalties, Other Intellectual Property: I am a co-inventor on a provisional patent application filed in July of 2020. The patent pertains to the use of spectrophotometer-measured ultraviolet radiation exposure in combination with regulatory T cells measured in circulation to predict risk of subsequent skin cancerTravel, Accommodations, Expenses: Caserta Analytics Inc (not a health care company specifically, but they do business with health care companies), NanoString TechnologiesNo other potential conflicts of interest were reported.

The complex interplay between ultraviolet radiation (UVR) and cutaneous viral infections in the context of cancer etiology is challenging to unravel, given the limited information on the independent association between UVR and cutaneous viral infections. Using multiple biomarkers of infection with 24 types of cutaneous human papillomavirus (HPV) and 4 types of polyomaviruses (HPyV), we investigated cross-sectional associations with recent UVR exposure, using skin pigmentation measured by spectrophotometer. Age- and sex-adjusted associations between UVR and viral seropositivity, viral DNA present in eyebrow hairs (EBH) and skin swabs (SSW) were estimated using logistic regression. Beta-HPV seropositivity was associated with viral DNA positivity in EBH (OR = 1.40, 95% CI = 1.05-1.88) and SSW (OR = 1.86, 95% CI = 1.25-2.74). Similar associations were observed for Merkel cell polyomavirus. Participants in the highest tertile of UVR exposure were more likely to be seropositive for beta-HPV (OR = 1.81, 95% CI = 1.16-2.38), and have beta-HPV DNA in EBH (OR = 1.57, 95% CI = 1.06-2.33) and SSW (OR = 2.22, 95% CI = 1.25-3.96), compared to participants with the lowest tertile of UVR exposure. UVR exposure was positively associated with three different markers of beta-HPV infection. Therefore, future studies of HPV associated KC development should address more directly the role of HPV and UVR exposure as potential co-carcinogens., (© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.)

Purpose: Deep learning (DL) algorithms have shown promising results for brain tumor segmentation in MRI. However, validation is required prior to routine clinical use. We report the first randomized and blinded comparison of DL and trained technician segmentations. Approach: We compiled a multi-institutional database of 741 pretreatment MRI exams. Each contained a postcontrast T1-weighted exam, a T2-weighted fluid-attenuated inversion recovery exam, and at least one technician-derived tumor segmentation. The database included 729 unique patients (470 males and 259 females). Of these exams, 641 were used for training the DL system, and 100 were reserved for testing. We developed a platform to enable qualitative, blinded, controlled assessment of lesion segmentations made by technicians and the DL method. On this platform, 20 neuroradiologists performed 400 side-by-side comparisons of segmentations on 100 test cases. They scored each segmentation between 0 (poor) and 10 (perfect). Agreement between segmentations from technicians and the DL method was also evaluated quantitatively using the Dice coefficient, which produces values between 0 (no overlap) and 1 (perfect overlap). Results: The neuroradiologists gave technician and DL segmentations mean scores of 6.97 and 7.31, respectively ( p < 0.00007 ). The DL method achieved a mean Dice coefficient of 0.87 on the test cases. Conclusions: This was the first objective comparison of automated and human segmentation using a blinded controlled assessment study. Our DL system learned to outperform its "human teachers" and produced output that was better, on average, than its training data., (© The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.)

Quality Assurance and Education are 2 areas of the Cancer Registry that go hand in hand. High-quality data can only be maintained through routine surveillance of data quality coupled with tailored continuing education of certified tumor registrars (CTRs). However, the magnitude of information a CTR is required to know, the rapid frequency with which standards change, and growing demands on the time of the CTRs can be roadblocks to maintaining quality in the Cancer Registry. Here we describe a robust approach to quality assurance in a high-volume hospital-based Cancer Registry, leveraging a repeated cycle of quality assessment and educational activities targeting identified opportunities for improvement. Establishing such an approach encourages the professional development of CTRs while simultaneously ensuring the highest quality data for use in population-based cancer surveillance, cancer research, and patient care.

Background: The detection of known human papillomaviruses (PVs) from targeted wet-lab approaches has traditionally used PCR-based methods coupled with Sanger sequencing. With the introduction of next-generation sequencing (NGS), these approaches can be revisited to integrate the sequencing power of NGS. Although computational tools have been developed for metagenomic approaches to search for known or novel viruses in NGS data, no appropriate tool is available for the classification and identification of novel viral sequences from data produced by amplicon-based methods., Results: We have developed PVAmpliconFinder, a data analysis workflow designed to rapidly identify and classify known and potentially new Papillomaviridae sequences from NGS amplicon sequencing with degenerate PV primers. Here, we describe the features of PVAmpliconFinder and its implementation using biological data obtained from amplicon sequencing of human skin swab specimens and oral rinses from healthy individuals., Conclusions: PVAmpliconFinder identified putative new HPV sequences, including one that was validated by wet-lab experiments. PVAmpliconFinder can be easily modified and applied to other viral families. PVAmpliconFinder addresses a gap by providing a solution for the analysis of NGS amplicon sequencing, increasingly used in clinical research. The PVAmpliconFinder workflow, along with its source code, is freely available on the GitHub platform: https://github.com/IARCbioinfo/PVAmpliconFinder.

Cancer Informatics for Cancer Centers (CI4CC) is a grassroots, nonprofit 501c3 organization intended to provide a focused national forum for engagement of senior cancer informatics leaders, primarily aimed at academic cancer centers anywhere in the world but with a special emphasis on the 70 National Cancer Institute-funded cancer centers. Although each of the participating cancer centers is structured differently, and leaders' titles vary, we know firsthand there are similarities in both the issues we face and the solutions we achieve. As a consortium, we have initiated a dedicated listserv, an open-initiatives program, and targeted biannual face-to-face meetings. These meetings are a place to review our priorities and initiatives, providing a forum for discussion of the strategic and pragmatic issues we, as informatics leaders, individually face at our respective institutions and cancer centers. Here we provide a brief history of the CI4CC organization and meeting highlights from the latest CI4CC meeting that took place in Napa, California from October 14-16, 2019. The focus of this meeting was "intersections between informatics, data science, and population science." We conclude with a discussion on "hot topics" on the horizon for cancer informatics.

Background: Accumulating evidence suggests that cutaneous viral infections are risk factors for the development of keratinocyte carcinomas. The Viruses in Skin Cancer (VIRUSCAN) Study, a prospective cohort study, was established in 2014 to investigate the risk of keratinocyte carcinoma associated with cutaneous human papillomavirus and polyomavirus infection and the possible interaction with ultraviolet radiation exposure (UVR)., Methods/results: VIRUSCAN incorporates repeated measures of viral infection using multiple markers of infection and quantitative measures of UVR using a spectrophotometer. Participants were recruited between July 14, 2014 and August 31, 2017 at the University of South Florida Dermatology Clinic in Tampa, FL. After excluding 124 individuals with prevalent keratinocyte carcinomas at baseline, 1,179 participants (53.2% women, 46.8% men, all ages 60 years and older) were followed for up to 4 years with routine skin exams occurring every 6 to 12 months. Here, we present the VIRUSCAN Study design, methods, and baseline characteristics, including demographics, sun exposure behavior, quantitative UVR exposure measurements, and cutaneous viral prevalence, for the full study cohort., Conclusions: The VIRUSCAN Study will provide critical temporal evidence needed to assess the causality of the role cutaneous viral infections play in the development of keratinocyte carcinomas, as well as the potential interaction between cutaneous viral infections and UVR exposure., Impact: Study findings will be valuable in future development of novel keratinocyte carcinoma prevention strategies., (©2019 American Association for Cancer Research.)

Myelodysplastic syndromes (MDS), a spectrum of heterogeneous hematopoietic stem cell diseases, vary in clinical severity, response to therapy, and propensity toward progression to acute myeloid leukemia. These are acquired clonal disorders resulting from somatic mutations within the hematopoietic stem or progenitor cell population. Understanding the natural history and the risk of developing leukemia and other adverse outcomes is dependent on access to well-annotated biospecimens linked to robust clinical and molecular data. To facilitate the acquisition and distribution of MDS biospecimens to the wider scientific community and support scientific discovery in this disease, the National MDS Natural History study was initiated by the National Heart, Lung, and Blood Institute (NHLBI) and is being conducted in collaboration with community hospitals and academic medical centers supported by the National Cancer Institute (NCI). The study will recruit up to 2000 MDS patients or overlapping myeloproliferative neoplasms (MDS/MPN) and up to 500 cases of idiopathic cytopenia of undetermined significance (ICUS). The National MDS Natural History Study (NCT02775383) will offer the world's largest disease-focused tissue biobank linked to longitudinal clinical and molecular data in MDS. Here, we report on the study design features and describe the vanguard phase of 200 cases. The study assembles a comprehensive clinical database, quality of life results, laboratory data, histopathology slides and images, genetic information, hematopoietic and germline tissues representing high-quality biospecimens and data from diverse centers across the United States. These resources will be available to the scientific community for investigator-initiated research.

Cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) are keratinocyte carcinomas, the most frequently diagnosed cancers in fair-skinned populations. Ultraviolet radiation (UVR) is the main driving carcinogen for these tumors, but immunosuppression, pigmentary factors, and aging are also risk factors. Scientific discoveries have improved the understanding of the role of human papillomaviruses (HPV) in cSCC as well as the skin microbiome and a compromised immune system in the development of both cSCC and BCC. Genomic analyses have uncovered genetic risk variants, high-risk susceptibility genes, and somatic events that underlie common pathways important in keratinocyte carcinoma tumorigenesis and tumor characteristics that have enabled development of prediction models for early identification of high-risk individuals. Advances in chemoprevention in high-risk individuals and progress in targeted and immune-based treatment approaches have the potential to decrease the morbidity and mortality associated with these tumors. As the incidence and prevalence of keratinocyte carcinoma continue to increase, strategies for prevention, including effective sun-protective behavior, educational interventions, and reduction of tanning bed access and usage, are essential. Gaps in our knowledge requiring additional research to reduce the high morbidity and costs associated with keratinocyte carcinoma include better understanding of factors leading to more aggressive tumors, the roles of microbiome and HPV infection, prediction of response to therapies including immune checkpoint blockade, and how to tailor both prevention and treatment to individual risk factors and needs., (©2018 American Association for Cancer Research.)

Evidence suggests that beta human papillomaviruses (HPVs), together with ultraviolet radiation, contribute to the development of cutaneous squamous cell carcinoma. Beta HPVs appear to be not the main drivers of carcinogenesis but rather facilitators of the accumulation of ultraviolet-induced DNA mutations. Beta HPVs are promoters of skin carcinogenesis, although they are dispensable for the maintenance of the malignant phenotype. Therefore, beta HPV represents a target for skin cancer prevention, especially in high-risk populations., (Copyright © 2019 American Society for Microbiology.)

We report the complete genome characterization of a novel human papillomavirus (HPV) (ICB2) isolated from a skin swab. The L1 region of HPV ICB2 shares 87.9% nucleotide similarity with its closest relative, HPV37, and thus constitutes a novel human betapapillomavirus.

Background: Findings from previous studies of cutaneous human papillomavirus (cuHPV) infection and keratinocyte carcinomas have varied due to several factors, including use of different sample types for cuHPV DNA detection. Elucidating the relationship between cuHPV infection in eyebrow hairs (EBHs) and skin swabs (SSWs) is critical for advancing the design of future studies., Methods: DNA corresponding to 46 β-HPV and 52 γ-HPV types was measured in EBHs and SSWs obtained from 370 individuals undergoing routine skin cancer screening examinations., Results: Prevalence of β-HPV/γ-HPV was 92%/84% and 73%/43% in SSWs and EBHs, respectively, with 71%/39% of patients testing positive for β-HPV/γ-HPV in both sample types. Number of cuHPV types detected and degree of infection were correlated across SSWs and EBHs. When the EBH was positive for a given β-HPV/γ-HPV type, the SSW was positive for that same type 81%/72% of the time., Conclusions: Testing SSWs captures more cuHPV infection than EBHs, with EBH infections usually representing a subset of SSW infections. The importance of optimizing sensitivity of cuHPV infection detection using SSWs vs specificity using EBHs (or a combination of the 2) will be ascertained in an ongoing cohort study investigating cuHPV associations with subsequent keratinocyte carcinomas., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

The cutaneous human papillomavirus (HPV), mostly from β- and γ-HPV genus, is ubiquitously distributed throughout the human body and may be part of the commensal flora. The association of β-HPVs and cutaneous squamous cell carcinoma (cSCC) development was initially reported in patients with the rare genetic disorder Epidermodysplasia verruciformis. Likewise, immunosuppressed organ transplant recipients have an increased susceptibility to β-HPV infections in the skin as well as to cSCC development. Although ultraviolet radiation (UVR) is the main risk factor of cSCC, experimental data points toward β-HPVs as co-carcinogens, which appear to be required solely at early stages of skin carcinogenesis by facilitating the accumulation of UVR-induced DNA mutations. Several epidemiological studies relying on different biomarkers of β-HPV infections have also been conducted in immunocompetent individuals to access their association with cSCC development. Additionally, in vivo and in vitro studies are presenting cumulative evidence that E6 and E7 proteins from specific β-HPVs exhibit transforming activities and may collaborate with different environmental factors in promoting carcinogenesis. Nevertheless, further research is crucial to better understand the pathological implications of the broad distribution of these HPVs., (© 2019 S. Karger AG, Basel.)

UV radiation (UVR) causing DNA damage is a well-documented risk factor for nonmelanoma skin cancer. Although poorly understood, UVR may also indirectly contribute to carcinogenesis by promoting immune evasion. To our knowledge, we report the first epidemiological study designed to investigate the association between quantitative measures of UVR, obtained using a spectrophotometer, and circulating T regulatory (Treg) cells. In addition to total Treg cells, the proportion of functionally distinct Treg cell subsets defined by CD45RA and CD27 phenotypic markers, graded expression of FOXP3 and CD25, and those expressing cutaneous lymphocyte-associated Ag and the chemokine receptor CCR4 were enumerated in 350 individuals undergoing routine skin cancer screening exams and determined not to have prevalent skin cancer. No associations were identified for UVR exposure or the overall proportion of circulating Treg cells; however, Treg cell subpopulations with an activation-associated phenotype, CD45RA - /CD27 - , and those expressing cutaneous homing receptors were significantly positively associated with UVR. These subpopulations of Treg cells also differed by age, sex, and race. After stratification by natural skin tone, and adjusting for age and sex, we found that spectrophotometer-based measures of UVR exposure, but not self-reported measures of past sun exposure, were positively correlated with the highest levels of these Treg cell subpopulations, particularly among lighter-skinned individuals. Findings from this large epidemiologic study highlight the diversity of human Treg cell subpopulations associated with UVR, thus raising questions about the specific coordinated expression of CD45RA, CD27, CCR4, and cutaneous lymphocyte-associated Ag on Treg cells and the possibility that UVR contributes to nonmelanoma skin cancer carcinogenesis through Treg cell-mediated immune evasion., (Copyright © 2018 by The American Association of Immunologists, Inc.)

Background: The purpose of this study was to assess genital recurrence of human papillomavirus (HPV) genotypes included in the 9-valent vaccine and to investigate factors associated with recurrence among men in the HPV Infection in Men (HIM) Study., Methods: Men were followed every 6 months for a median of 3.7 years. HPV genotypes were detected using Roche linear array. Factors associated with type-specific HPV recurrence (infections occurring after a ≥12-month infection-free period) were assessed., Results: In type-specific analyses, 31% of prior prevalent and 20% of prior incident infections recurred. Among prevalent infections, HPV types 52, 45, 16, 58, and 6 and among incident infections, HPV types 58, 52, 18, 16, and 11 had the highest rates of recurrence. New sexual partners (male or female) and frequency of sexual intercourse with female partners were associated with HPV-6, -16, -31, and -58 infection recurrence. In grouped analyses, lifetime and new male sexual partners were associated with recurrence of prior incident infection with any of the 9 HPV types., Conclusions: Recurrence of genital HPV infections is relatively common among men and associated with high-risk sexual behavior. Further studies are needed to understand the role of HPV recurrence in the etiology of HPV-associated diseases.

With the advent of new molecular tools, the discovery of new papillomaviruses (PVs) has accelerated during the past decade, enabling the expansion of knowledge about the viral populations that inhabit the human body. Human PVs (HPVs) are etiologically linked to benign or malignant lesions of the skin and mucosa. The detection of HPV types can vary widely, depending mainly on the methodology and the quality of the biological sample. Next-generation sequencing is one of the most powerful tools, enabling the discovery of novel viruses in a wide range of biological material. Here, we report a novel protocol for the detection of known and unknown HPV types in human skin and oral gargle samples using improved PCR protocols combined with next-generation sequencing. We identified 105 putative new PV types in addition to 296 known types, thus providing important information about the viral distribution in the oral cavity and skin., (Copyright © 2018. Published by Elsevier Inc.)

The role of cutaneous viral infections in the development of non-melanoma skin cancer (NMSC), including cutaneous squamous cell carcinoma (SCC), among chronic lymphocytic leukemia (CLL) and blood and marrow transplant (BMT) patients is not established. CLL (n = 977) and BMT (n = 3587) patients treated at the Moffitt Cancer Center were included in a retrospective cohort study. Human papillomavirus (HPV) and human polyomavirus (HPyV) DNA were examined in a subset of incident SCC tumors. Five-year cumulative incidence of NMSC was 1.42% in both BMT (n = 31 NMSCs) and CLL (n = 18 NMSCs) cohorts. Of the nine SCC tumors examined from each cohort, 22.2% and 33.3% were positive for viral DNA in the transplant (HPV 65, MCV) and CLL (HPV 38, HPV 15, HPyV6) cohort, respectively. Enhanced skin cancer screening of BMT/CLL patients should be conducted to better capture incident NMSCs and examine the role of viral infections in these tumors.

Seroepidemiology of human papillomaviruses (HPV) among men is poorly understood. We examined the association between seropositivity to cutaneous HPV and 9-valent HPV (9vHPV) types. Six hundred men were randomly selected from the HPV Infection in Men (HIM) Study. Archived serum specimens were tested for antibodies against 9vHPV types [low-risk (6/11) and high-risk (16/18/31/33/45/52/58)], and 14 cutaneous types, including β-types 5/8/12/14/17/22/23/24/38/47, α-type-27, γ-type-4, µ-type-1, and ν-type-41, using a GST L1-based multiplex serology assay. Risk factor data were collected through questionnaires. Logistic regression was used to evaluate associations between mucosal and cutaneous HPV types. Approximately 21% of men were positive for ≥ 1 cutaneous HPV type, and ≥ 1 nine-valent HPV vaccine type at the same time. Men who were seropositive for any-cutaneous HPV were nearly twice as likely to be seropositive for 9vHPV (adjusted odds ratio (AOR) = 1.97, 95% confidence interval (CI): 1.30-2.99), high-risk (AOR = 1.83; 95% CI: 1.04-3.20), low-risk (AOR = 1.92; 95% CI: 1.16-3.18), and four-valent, 4vHPV, (AOR = 2.01; 95% CI: 1.25-3.21). Type-specific cutaneous HPV seropositivity (types: 8/14/17/23/38/27/4/1) was also positively associated with seropositivity to 9vHPV, high-risk, and low-risk categories. These data indicate that exposure to cutaneous HPV and 9vHPV types is common. Future longitudinal studies are needed to assess the temporality of these associations., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

A novel human papillomavirus (HPV ICB1) was fully characterized from a skin swab by using a sensitive degenerate PCR protocol combined with next-generation sequencing. The L1 open reading frame of HPV ICB1 shares 70.54% nucleotide homology with its closest relative, HPV164, and thus constitutes a novel human gammapapillomavirus., (Copyright © 2017 Brancaccio et al.)

Background: Cutaneous beta human papillomavirus (HPV) infection across cutaneous and mucosal tissues within individuals has not been examined., Methods: A subcohort of men (n = 87) participating in the HPV Infection in Men (HIM) study provided eyebrow hairs, forearm skin swabs, genital skin swabs, oral rinse samples, and anal swabs. Beta-HPV DNA in the 5 tissues was detected using a multiplex assay, and site-specific beta-HPV prevalence was examined., Results: Any beta-HPV was most prevalent in genital skin (81.6%), followed by forearm skin (64.4%), eyebrow hairs (60.9%), oral mucosa (35.6%), and anal mucosa (33.3%). Most prevalent beta-HPV types included HPV-38 (beta-2) in both genital skin (32.2%) and eyebrow hairs (16.1%), HPV-12 (beta-1) in forearm skin (23%) and oral mucosa (9.2%), and HPV-76 (beta-3) in anal mucosa (14.9%). Concordance of any beta-HPV infection was greater (31.0%) across the 3 keratinized tissue sites (genital skin, eyebrow hairs, forearm skin) than across the 2 mucosal sites (anal and oral mucosa, 6.9%)., Conclusions: Prevalence of beta-HPV varied by anatomic site of infection. Biological properties of beta-HPV types detected at mucosal sites and their role in disease pathogenesis should be examined., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

A new human gammapapillomavirus (HPV&#95;MTS2) genome was isolated and fully cloned from a skin swab. The L1 open reading frame of HPV&#95;MTS2 was 79% and 80% identical to those of its closest relatives, HPV type 149 (species Gamma-7 of the genus Gammapapillomavirus ) and HPV isolate Dysk2 (GenBank accession no. KX781281), respectively, thus qualifying it as a new HPV type., (Copyright © 2017 Dutta et al.)

The small double-stranded DNA polyomaviruses (PyVs) form a family of 73 species, whose natural hosts are primarily mammals and birds. So far, 13 PyVs have been isolated in humans, and some of them have clearly been associated with several diseases, including cancer. In this study, we describe the isolation of a novel PyV in human skin using a sensitive degenerate PCR protocol combined with next-generation sequencing. The new virus, named Lyon IARC PyV (LIPyV), has a circular genome of 5269 nucleotides. Phylogenetic analyses showed that LIPyV is related to the raccoon PyV identified in neuroglial tumours in free-ranging raccoons. Analysis of human specimens from cancer-free individuals showed that 9 skin swabs (9/445; 2.0%), 3 oral gargles (3/140; 2.1%), and one eyebrow hair sample (1/439; 0.2%) tested positive for LIPyV. Future biological and epidemiological studies are needed to confirm the human tropism and provide insights into its biological properties., (Copyright © 2017 Elsevier Inc. All rights reserved.)

We report the genetic characterization of a new papillomavirus (HPV&#95;MTS1) isolated and fully cloned from a skin swab. The L1 open reading frame of HPV&#95;MTS1 was 85% identical to its closest human papillomavirus (HPV) type 80, which belongs to the species beta-2 of the genus Betapapillomavirus , hence qualifying it as a new HPV type., (Copyright © 2017 Dutta et al.)

Risk of subsequent primary malignancies (SPMs) associated with lenalidomide therapy in multiple myeloma (MM) patients, outside the context of melphalan-based therapy is not established. We assessed the risk of SPMs in lenalidomide treated MM patients (n = 1653) at Moffitt Cancer Center (2004-2012) outside the context of melphalan-based induction therapy and post-melphalan maintenance therapy, via (1) cohort analysis and (2) nested case-control study. Incident SPMs (n = 51) were matched to controls (n = 102) on age at MM diagnosis, gender, follow-up time, and date of diagnosis. Incidence of SPM differed significantly (p = 0.0038) between MM patients treated with and without lenalidomide (5-year incidence estimates of 3.2 and 6.2%, respectively), although not significant after adjustment for age and year of diagnosis (HR = 0.82, 95%CI = 0.43-1.57). Lenalidomide treatment was inversely associated with SPM in the nested case-control analysis (OR = 0.03, 95%CI = 0.002-0.34). In this large cohort of MM patients, lenalidomide treatment was not associated with an increased risk of SPM.