Natural History Of Cancer Research Articles

Calibrating Natural History of Cancer Models in the Presence of Data Incompatibility: Problems and Solutions

The calibration of cancer natural history models is often challenged by a lack of representative calibration targets, forcing modellers to rely on potentially incompatible datasets. Using a microsimulation colorectal cancer model as an example, the purposes of this paper are to (1) highlight the reasons for uncertainty in calibration targets, (2) illustrate practical and generalisable approaches for dealing with incompatibility in calibration targets, and (3) discuss the importance of future research in the area of incorporating uncertainty in calibration. The low quality of data and differences in populations, outcome definitions, and healthcare systems may result in incompatibility between the model and the data. Acknowledging reasons for data incompatibility allows assessment of the risk of incompatibility before calibrating the model. Only a few approaches are available to address data incompatibility, for instance addressing biases in calibration targets and their adjustment, relaxing the goodness-of-fit metric, and validation of the calibration targets to the data not used in the calibration. However, these approaches lack explicit comparison and validation, and so more research is needed to describe the nature and causes of indirect uncertainty (i.e. uncertainty that cannot be expressed in absolute quantitative forms) and identify methods for managing this uncertainty in healthcare modelling.

Autophagy and ncRNAs: Dangerous Liaisons in the Crosstalk between the Tumor and Its Microenvironment.

Simple SummaryTumor cells communicate with the stromal cells within the tumor microenvironment (TME) to create a conducive environment for tumor growth. One major avenue for mediating crosstalk between various cell types in the TME involves exchanges of molecular payloads in the form of extracellular vesicles/exosomes. Autophagy is a fundamental mechanism to maintain intracellular homeostasis but recent reports suggest that secretory autophagy plays an important role in promoting secretion of exosomes that are packaged with non-coding RNAs (ncRNAs) and other biomolecules from the donor cell. Uptake of exosomal autophagy-modulating ncRNAs by recipient cells may further perpetuate tumor progression.Autophagy is a fundamental cellular homeostasis mechanism known to play multifaceted roles in the natural history of cancers over time. It has recently been shown that autophagy also mediates the crosstalk between the tumor and its microenvironment by promoting the export of molecular payloads such as non-coding RNA (ncRNAs) via LC3-dependent Extracellular Vesicle loading and secretion (LDELS). In turn, the dynamic exchange of exosomal ncRNAs regulate autophagic responses in the recipient cells within the tumor microenvironment (TME), for both tumor and stromal cells. Autophagy-dependent phenotypic changes in the recipient cells further enhance tumor growth and metastasis, through diverse biological processes, including nutrient supplementation, immune evasion, angiogenesis, and therapeutic resistance. In this review, we discuss how the feedforward autophagy-ncRNA axis orchestrates vital communications between various cell types within the TME ecosystem to promote cancer progression.

Optimizing the Design of a Repeated Fecal Immunochemical Test Bowel Cancer Screening Programme With a Limited Endoscopy Capacity From a Health Economic Perspective

ObjectivesIn 2016, it was announced that the fecal immunochemical test (FIT) would replace the guaiac fecal occult blood test in the UK Bowel Cancer Screening Programme. England has limited endoscopy capacity. This study informed decision making by determining the most cost-effective FIT screening strategy (age range, frequency, and FIT threshold) under a constrained endoscopy capacity. MethodsAn economic model with a colorectal cancer natural history component was used to model 60 221 screening strategies with first screening at age 50 to 60 years, screening interval of 1 to 6 years, 3+ screening episodes, and FIT integer threshold of 20 to 180 μg hemoglobin/g feces. Screening strategies requiring the same endoscopy capacity were compared to determine the characteristics of the most cost-effective strategies. ResultsWith 50 000 annual screening referral colonoscopies, the 20 most cost-effective strategies had a starting age of 50 to 53 years, 2-yearly screening, 7 or 8 rounds of screening, and FIT threshold of 127 to 166. Compared with a 2-yearly screening interval, screening less frequently (3-, 4-, 5-, or 6-yearly) with a more sensitive FIT was less cost-effective. ConclusionsThe UK Bowel Cancer Screening Programme should use a 2-yearly FIT screening interval. When endoscopy capacity increases, the screening starting age should be reduced first followed by reducing the FIT threshold. These findings are relevant for other colorectal cancer screening programs with constrained endoscopy capacity.

Territorial-based management of patients with cancer on active treatment following the Piacenza (north Italy) Model. Results of 4 consecutive years.

The natural history of cancer has radically changed in the last decade. The burden of travel from patient's residence to health care providers is an important issue that can influence access to diagnosis and treatment of cancer; however this issue is quite neglect by the medical community and by the national health system. In addition, community care in the oncology field is actually debated. In the district of Piacenza an innovative model to deliver onco-hematologic treatment near the residence of patients was initiated some years ago. The oncologic and hematologic treatments are delivered by specialized nurses under supervision of medical oncologists or hematologists at the 3 community hospital and at 1 house of health in the district of Piacenza. We conducted a retrospective study involving 1,339 cancer patients (CPs) managed and treated near their residence, CPs were on active medical treatment at the oncology and hematology department Azienda sanitaria (ASL) of Piacenza (North Italy). The electronic data base of the antiblastic drug unit (UFA) of the ASL Piacenza, provided: the number of patients treated each year, number of treatments and the accesses to the territorial medical structure each year. The kms saved to reach the nearest territorial structures instead of the oncologic unit of the city hospital, were registered and recorded. During a 4 years period, from January 2017 to December 2020, 1,339 CPs were treated near their residence, 278 in the year 2017, 347 in 2018, 354 in 2019 and 360 in 2020. The total accesses for treatment in 4 years were 10,003: 2,214 in the year 2017, 2,652 in 2018, 2,524 in 2019 and 2,613 in 2020. The mean distance saved for each patient was 937 kms in the year 2017, 891 in 2018, 879 in 2019, 920 in 2020, totally a mean of 3,627 kms in the 4 years. We believe that the results of our retrospective study highlight the possibility of treating cancer patients in territorial structures near their residence, with advantages for patients themselves, their caregivers and for the entire community.

Impact of Joint Lung Cancer Screening and Cessation Interventions Under the New Recommendations of the U.S. Preventive Services Task Force

IntroductionIn 2021, the U.S. Preventive Services Task Force (USPSTF) revised its lung cancer screening recommendations expanding its eligibility. As more smokers become eligible, cessation interventions at the point of screening could enhance the benefits. Here, we evaluate the effects of joint screening and cessation interventions under the new recommendations. MethodsA validated lung cancer natural history model was used to estimate lifetime number of low-dose computed tomography screens, percentage ever screened, lung cancer deaths, lung cancer deaths averted, and life-years gained for the 1960 U.S. birth cohort aged 45 to 90 years (4.5 million individuals). Screening occurred according to the USPSTF 2013 and 2021 recommendations with varying uptake (0%, 30%, 100%), with or without a cessation intervention at the point of screening with varying effectiveness (15%, 100%). ResultsScreening 30% of the eligible population according to the 2021 criteria with no cessation intervention (USPSTF 2021, 30% uptake, without cessation intervention) was estimated to result in 6845 lung cancer deaths averted and 103,725 life-years gained. These represent 28% and 34% increases, respectively, relative to screening according to the 2013 guidelines (USPSTF 2013, 30% uptake, without cessation intervention). Adding a cessation intervention at the time of the first screen with 15% effectiveness (USPSTF 2021, 30% uptake, with cessation intervention with 15% effectiveness) was estimated to result in 2422 additional lung cancer deaths averted (9267 total, ∼73% increase versus USPSTF 2013, 30% uptake, without cessation intervention) and 322,785 life-years gained (∼318% increase). Screening 100% of the eligible according to the 2021 guidelines with no cessation intervention (USPSTF 2021, 100% uptake, without cessation intervention) was estimated to result in 23,444 lung cancer deaths averted (∼337% increase versus USPSTF 2013, 30% uptake, without cessation intervention) and 354,330 life-years gained (∼359% increase). Adding a cessation intervention with 15% effectiveness (USPSTF 2021, 100% uptake, with cessation intervention with 15% effectiveness) would result in 31,998 lung cancer deaths averted (∼497% increase versus USPSTF 2013, 30% uptake, without cessation intervention) and 1,086,840 life-years gained (∼1309% increase). ConclusionsJoint screening and cessation interventions would result in considerable lung cancer deaths averted and life-years gained. Adding a one-time cessation intervention of modest effectiveness (15%) results in comparable life-years gained as increasing screening uptake from 30% to 100% because while cessation decreases mortality from many causes, screening only reduces lung cancer mortality. This simulation indicates that incorporating cessation programs into screening practice should be a priority as it can maximize overall benefits.

Mammography Screening and Research Evidence: The Swedish Contribution.

Sweden has made a contribution to mammography screening research considerably disproportionate to its size. With 0.13% of the world's population, Sweden contributed almost half of the randomized trial evidence on mammography screening. In addition to the fundamental efficacy of screening in preventing deaths from breast cancer, Swedish researchers have produced a considerable volume of research evaluating mammography screening in the routine healthcare services setting and illuminating issues of breast cancer progression and natural history. The basic result that screening prevents deaths from breast cancer has informed policy and led to substantial preservation of life internationally.

Cost-effectiveness analysis of the 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines for the management of abnormal cervical cancer screening tests and cancer precursors

The guidelines for managing abnormal cervical cancer screening tests changed from a results-based approach in 2012 to a risk-based approach in 2019. We estimated the cost-effectiveness of the 2019 management guidelines and the changes in resource utilization moving from 2012 to 2019 guidelines. We utilized a previously published model of cervical cancer natural history and screening to estimate and compare the lifetime costs and the number of screens, colposcopies, precancer treatments, cancer cases, and cancer deaths associated with the 2012 vs 2019 management guidelines. We assessed these guidelines under the scenarios of observed screening practice and perfect screening adherence to 3-year cytology starting at age 21, with a switch to either 3-year or 5-year cytology plus human papillomavirus cotesting at age 30. In addition, we estimated the lifetime costs and life years to determine the cost-effectiveness of shifting to the 2019 management guidelines. Under the assumptions of both observed screening practice and perfect screening adherence with a strategy of 3-year cytology at ages 21 to 29 and switching to 3-year cotesting at age 30, the management of the screening tests according to the 2019 guidelines was less costly and more effective than the 2012 guidelines. For 3-year cytology screening at ages 21 to 29 and switching to 5-year cotesting at age 30, the 2019 guidelines were more cost-effective at a willingness-to-pay threshold of $100,000 per life year gained. Across all scenarios, the 2019 management guidelines were associated with fewer colposcopies and cancer deaths. Our model-based analysis suggests that the 2019 guidelines are more effective overall and also more cost-effective than the 2012 guidelines, supporting the principle of "equal management of equal risks."

Molecular Insights into Oral Malignancy.

Squamous cell carcinoma constitutes around 95% of malignancies in the oral cavity. The 5-year overall survival has not substantially improved for oral cancers over the last few decades, despite several advances in diagnosis, imaging, and treatment modalities. With progressive improvement in knowledge of the molecular pathways, cancer therapy can now be individualized. Understanding the genetic processes and natural history of cancer has the scope to enhance the clinical outcomes. There has been a significant improvement in our understanding of oncogenesis, advances in molecular detection methods, and novel biomarkers for oral cancers in the past decade. Indicators of genomic instability, the existence of expression regulators such as miRNA, and several genes and protein markers can predict which premalignant lesions are likely to turn into cancer. The molecular biomarkers in oncology are fast evolving. Still, integrating novel molecular tests into clinical practice will require a better understanding of the genetic pathways that lead to malignancy. Our article investigates the most recent concepts and knowledge on oral carcinogenesis, malignant transformation, and molecular markers for oral cancers.

Place de l’imagerie moléculaire dans la prise en charge du cancer de la prostate

In the management of prostate cancer in recent years, innovative therapies have appeared requiring precise and reliable disease detection. In 2021, new generation imaging (PET/CT, multiparametric MRI, PET/MRI) have their place at all stages of the prostate cancer natural history to help target the lesion(s) and guide therapy and improve the results obtained. PSMA PET/CT is currently the leader in this type of imaging with a complete offer during the disease: both from diagnosis, to recurrence or in the oligo-metastatic and metastatic stage resistant to castration with a pivotal role in the PSMA theranostic approach. However, multiparametric MRI also has many detection advantages when the prostate is left in place, which suggests the potential major benefit of hybrid PSMA PET/MRI imaging.

Reflecting on 20 years of breast cancer modeling in CISNET: Recommendations for future cancer systems modeling efforts.

Since 2000, the National Cancer Institute’s Cancer Intervention and Surveillance Modeling Network (CISNET) modeling teams have developed and applied microsimulation and statistical models of breast cancer. Here, we illustrate the use of collaborative breast cancer multilevel systems modeling in CISNET to demonstrate the flexibility of systems modeling to address important clinical and policy-relevant questions. Challenges and opportunities of future systems modeling are also summarized. The 6 CISNET breast cancer models embody the key features of systems modeling by incorporating numerous data sources and reflecting tumor, person, and health system factors that change over time and interact to affect the burden of breast cancer. Multidisciplinary modeling teams have explored alternative representations of breast cancer to reveal insights into breast cancer natural history, including the role of overdiagnosis and race differences in tumor characteristics. The models have been used to compare strategies for improving the balance of benefits and harms of breast cancer screening based on personal risk factors, including age, breast density, polygenic risk, and history of Down syndrome or a history of childhood cancer. The models have also provided evidence to support the delivery of care by simulating outcomes following clinical decisions about breast cancer treatment and estimating the relative impact of screening and treatment on the United States population. The insights provided by the CISNET breast cancer multilevel modeling efforts have informed policy and clinical guidelines. The 20 years of CISNET modeling experience has highlighted opportunities and challenges to expanding the impact of systems modeling. Moving forward, CISNET research will continue to use systems modeling to address cancer control issues, including modeling structural inequities affecting racial disparities in the burden of breast cancer. Future work will also leverage the lessons from team science, expand resource sharing, and foster the careers of early stage modeling scientists to ensure the sustainability of these efforts.

Application of proteome profiling in the clinical diagnosis of breast cancer

The early diagnosis, prognosis, and anticipation of breast cancer are crucial for proper treatment and patient survival. This disease imposes quite a severe health care encumbrance on women globally. Breast cancer classification has emphasized several global efforts, and analysis of the subtypes of the molecular basis of breast cancer has aimed to associate them with clinical outcomes and improve the current diagnostic routine. Since the last two decades, proteomics-based methods for studying breast cancer's natural history and treatment are gaining traction. In this review, some of the proteome profiling studies of tissues, plasma, serum and saliva conducted mainly by mass spectrometry-based approaches – including MALDI-TOF and SELDI-TOF are discussed. This review also emphasized tissue microarray studies and their role in identifying clinical tissues and markers in breast cancer.

BayCANN: Streamlining Bayesian Calibration With Artificial Neural Network Metamodeling.

Purpose: Bayesian calibration is generally superior to standard direct-search algorithms in that it estimates the full joint posterior distribution of the calibrated parameters. However, there are many barriers to using Bayesian calibration in health decision sciences stemming from the need to program complex models in probabilistic programming languages and the associated computational burden of applying Bayesian calibration. In this paper, we propose to use artificial neural networks (ANN) as one practical solution to these challenges.Methods: Bayesian Calibration using Artificial Neural Networks (BayCANN) involves (1) training an ANN metamodel on a sample of model inputs and outputs, and (2) then calibrating the trained ANN metamodel instead of the full model in a probabilistic programming language to obtain the posterior joint distribution of the calibrated parameters. We illustrate BayCANN using a colorectal cancer natural history model. We conduct a confirmatory simulation analysis by first obtaining parameter estimates from the literature and then using them to generate adenoma prevalence and cancer incidence targets. We compare the performance of BayCANN in recovering these “true” parameter values against performing a Bayesian calibration directly on the simulation model using an incremental mixture importance sampling (IMIS) algorithm.Results: We were able to apply BayCANN using only a dataset of the model inputs and outputs and minor modification of BayCANN's code. In this example, BayCANN was slightly more accurate in recovering the true posterior parameter estimates compared to IMIS. Obtaining the dataset of samples, and running BayCANN took 15 min compared to the IMIS which took 80 min. In applications involving computationally more expensive simulations (e.g., microsimulations), BayCANN may offer higher relative speed gains.Conclusions: BayCANN only uses a dataset of model inputs and outputs to obtain the calibrated joint parameter distributions. Thus, it can be adapted to models of various levels of complexity with minor or no change to its structure. In addition, BayCANN's efficiency can be especially useful in computationally expensive models. To facilitate BayCANN's wider adoption, we provide BayCANN's open-source implementation in R and Stan.

Impact of disruptions and recovery for established cervical screening programs across a range of high-income country program designs, using COVID-19 as an example: A modelled analysis

COVID-19 has disrupted cervical screening in several countries, due to a range of policy-, health-service and participant-related factors. Using three well-established models of cervical cancer natural history adapted to simulate screening across four countries, we compared the impact of a range of standardised screening disruption scenarios in four countries that vary in their cervical cancer prevention programs. All scenarios assumed a 6- or 12-month disruption followed by a rapid catch-up of missed screens. Cervical screening disruptions could increase cervical cancer cases by up to 5–6%. In all settings, more than 60% of the excess cancer burden due to disruptions are likely to have occurred in women aged less than 50 years in 2020, including settings where women in their 30s have previously been offered HPV vaccination. Approximately 15–30% of cancers predicted to result from disruptions could be prevented by maintaining colposcopy and precancer treatment services during any disruption period. Disruptions to primary screening had greater adverse effects in situations where women due to attend for screening in 2020 had cytology (vs. HPV) as their previous primary test. Rapid catch-up would dramatically increase demand for HPV tests in 2021, which it may not be feasible to meet because of competing demands on the testing machines and reagents due to COVID tests. These findings can inform future prioritisation strategies for catch-up that balance potential constraints on resourcing with clinical need.

Documentation of goals of care (GOC) by medical oncologists is associated with improved oncology patient end-of-life (EOL) care outcomes.

1507 Background: Documenting GOC is integral to patient care and quality performance but has been underutilized by oncologists due to many barriers. As oncologists play a key role in initiating GOC discussions, we implemented a clinical initiative to improve their GOC documentation and evaluated the impact of such documentation on patient care during the EOL (last 30 days of life). Methods: We launched the initiative among 270 medical oncologists in an academic cancer center in 4/2020. A newly formulated GOC note to ease documentation was embedded in oncology outpatient and inpatient notes. Oncologists completed components in the GOC note that applied to their communication about GOC with the patient: 1) cancer natural history, 2) patient goals, and 3) EOL discussion: patient resuscitation preferences and, when pertinent, receptivity to hospice referral. GOC notes were pulled to a centralized location in the electronic health record (EHR) that displays documents relevant to patients’ values, goals and preferences. A dashboard allowed continual monitoring of documentation performance. We evaluated the association between GOC notes and outcomes of patient care at EOL. We further analyzed the impact of EOL discussion on EOL care. Results: The GOC note completion rate steadily rose after implementation. GOC notes were present in EHR for 46% of 10,006 patients who were either seen in outpatient clinic or discharged from hospital during the 1st week of January 2021. Among 1790 patients who died between 7/1/20 and 12/31/20 and had either at least an outpatient visit or hospitalization during EOL, the median days from first GOC note and first EOL discussion to the patient’s death were 71 days and 24 days, respectively. Linear regression analysis demonstrated that patients who had GOC note 60 days before death spent less time as inpatient during EOL (0.4 day less/patient, from 8.1 to 7.7, P = 0.01). When EOL discussion was documented 30 days before death, patients also spent less time in the hospital (1.2 days less/patient, from 9.7 to 8.5, P < 0.001) and in the ICU (0.3 days less/patient, from 1.7 to 1.4 ICU days, P = 0.04), and were 4% less likely to receive chemotherapy (from 38% to 34%, P = 0.004) at EOL. During the same period, among 1,009 patients with hospital admission in the last 30 days of life, those with a prior documented EOL discussion had shorter inpatient stay (7.7 vs 13.1 days, P < 0.001) and were more likely to be discharged to hospice (34% vs 22%, P = 0.003). Conclusions: During the COVID-19 pandemic, we successfully implemented GOC documentation by medical oncologists that is easily visible by the full care team. Documentation of GOC including EOL discussion was associated with fewer days in the hospital and ICU, increased hospice referral, and lower likelihood of receiving chemotherapy during patients’ last 30 days of life.

Cancer: New Needs, New Models. Is It Time for a Community Oncologist? Another Brick in the Wall.

Simple SummaryCommunity care activity in the oncology field does not exist. This unmet need contrasts with the increasing number of patients with a previous diagnosis of cancer.Over the last few decades, thanks to early detection, effective drugs, and personalized treatments, the natural history of cancer has radically changed. Thanks to these advances, we have observed how survival of cancer patients has increased, becoming an ever more important goal in cancer care. Effective clinical governance of survivorship care is essential to ensure a successful transition between active and post-treatment life, identifying optimization of healthcare outcomes and quality of life for patients as the primary objectives. For these reasons, potential intervention models must consider these differences to rationalize the available resources, including economic aspects. In this perspective, analyzing the different models proposed in the literature to manage this type of patients, we focus on the possible role of the so-called “community oncologist”. As a trained health professional, also focused on longevity, he could represent the right management solution in all those “intermediate” clinical conditions that arise between the hospital specialist, frequently overworked, and the general practitioner, often biased by the lack of specific expertise.

The Value of Real-World Data in Understanding Prostate Cancer Risk and Improving Clinical Care: Examples from Swedish Registries.

Simple SummaryReal-world data (RWD), i.e., data reflecting normal clinical practice collected outside the constraints of randomised controlled trials, provide important insights into our understanding of prostate cancer and its management. Clinical cancer registries are an important source of RWD. Depending on their scope and the potential linkage to other data sources, registry-based data can be utilised to address a variety of questions including risk factors, healthcare utilisation, treatment effectiveness, adverse effects, disparities in healthcare access, quality of care and healthcare economics. This review describes the various registry-based RWD sources for prostate cancer research in Sweden (namely the National Prostate Cancer Register, the Prostate Cancer data Base Sweden (PCBaSe) and the Patient-overview Prostate Cancer) and documents their utility for better understanding prostate cancer aetiology and improving clinical care.Real-world data (RWD), that is, data from sources other than controlled clinical trials, play an increasingly important role in medical research. The development of quality clinical registers, increasing access to administrative data sources, growing computing power and data linkage capacities have contributed to greater availability of RWD. Evidence derived from RWD increases our understanding of prostate cancer (PCa) aetiology, natural history and effective management. While randomised controlled trials offer the best level of evidence for establishing the efficacy of medical interventions and making causal inferences, studies using RWD offer complementary evidence about the effectiveness, long-term outcomes and safety of interventions in real-world settings. RWD provide the only means of addressing questions about risk factors and exposures that cannot be “controlled”, or when assessing rare outcomes. This review provides examples of the value of RWD for generating evidence about PCa, focusing on studies using data from a quality clinical register, namely the National Prostate Cancer Register (NPCR) Sweden, with longitudinal data on advanced PCa in Patient-overview Prostate Cancer (PPC) and data linkages to other sources in Prostate Cancer data Base Sweden (PCBaSe).

Cardiac Metastatic Involvement in Lung Cancer – Cardiac Metastatic Involvement

Lung cancer is the second most common solid tumour and the first in mortality worldwide. Important progress has been reached in recent years in this pathology, focusing its treatment on histology, molecular biology and clinical presentation. Cardiac metastatic involvement consists in a severe clinical entity with increasing incidence due to better radiological techniques and longer survival of lung cancer. It requires special care and attention from many specialists. Clinical review about cardiac involvement secondary to lung cancer is provided, focused on its epidemiology, clinical presentation, diagnoses and treatment. Better understanding about cancer natural history is needed to offer the best treatment and care. Condensed abstract Cardiac metastatic involvement consists in a severe clinical entity with increasing incidence due to better radiological techniques and longer survival of lung cancer. It requires special care and attention from many specialists. Clinical review about cardiac involvement secondary to lung cancer is provided, focused on its epidemiology, clinical presentation, diagnoses and treatment.

COVID-19 impact in radiotherapy practice in an oncology hub: a screenshot from Lombardy, Italy.

Objective:During 2020, medical clinical activities were dramatically modified by the coronavirus disease 2019 (COVID-19) emergency. We aim to evaluate the impact of COVID-19 on radiotherapy (RT) practice in a hub cancer center.Methods:Retrospective data collection of patients with suspected COVID-19 infection, identified by pathognomonic symptoms feedback at triage realized at the entrance to RT division. Inclusion criteria were diagnosis of oncologic disease, COVID-19–related symptoms, and signed written informed consent.Results:Between 1 March and 30 June 2020, 1,006 patients accessed our RT division for RT simulation or treatment. Forty-four patients matched inclusion criteria (4.4% of all patients): 29 women and 15 men. Seventeen patients had metastatic disease. Twenty-one patients reported fever, 6 presented dyspnea, 4 complained of ageusia and anosmia, and 3 developed conjunctivitis. Thirty-six patients underwent nasal swab, with 7 positive results. From our cohort, 4 cases of pneumonia were diagnosed with computed tomography scan imaging: 3 were related to COVID-19 infection, while the fourth was evaluated as an RT adverse event. From the entire series, 4 patients died: 3 during hospitalization in intensive care unit of complications of COVID-19 and 1 of other causes neither COVID-19 nor cancer-related.Conclusions:Cancer hub allows for safe RT practice continuation while minimizing the spread of contagion in this frail patient population. A challenge for the future will be to understand pandemic consequences in cancer natural history and manage its clinical impact.

Obstructive sleep apnea and cancer: a complex relationship.

Obstructive sleep apnea (OSA) has been recognized as a risk factor for cancer mainly through hypoxia, based on studies that did not distinguish among cancer types. The purpose of this review is to discuss the most recent data on epidemiology and pathophysiology of the OSA-cancer association. According to epidemiological studies, OSA may have different influences on each type of cancer, either increasing or decreasing its incidence and aggressiveness. Time spent with oxygen saturation below 90% appears the polysomnographic variable most strongly associated with unfavorable effects on cancer. Experimental studies support the role of hypoxia as an important risk factor for cancer growth and aggressiveness, especially when it shows an intermittent pattern. These effects are largely mediated by the hypoxia-inducible factor, which controls the synthesis of molecules with effects on inflammation, immune surveillance and cell proliferation. Sleep fragmentation participates in increasing cancer risk. Modulating effects of age remain controversial. Effects of OSA on cancer may largely vary among neoplastic diseases, both in their magnitude and direction. The worse risk associated with intermittent rather than persistent hypoxia, and the effects of OSA therapy on cancer natural history are still poorly known, and deserve new careful studies.

Abstract IA12: A prospective cohort study embedded into integrated health care systems in the US to study cancer etiology, prevention, and early detection

Abstract The Division of Cancer Epidemiology and Genetics is conducting a new prospective cohort study of 150,000-200,000 adults in the US to further investigate the etiology of cancer and its outcomes, which can inform new approaches in precision prevention and early detection. The new cohort will capitalize on recent developments that provide unprecedented opportunities to advance the field of cancer epidemiology and prevention, including 1) innovative technologies (e.g., tracking and sensor technologies to measure behavior and environment); 2) large-scale analyses of the genome, epigenome, transcriptome, proteome, metabolome, and microbiome; 3) molecular profiling of tumors and precursor lesions to study the natural history of cancer and its etiologic heterogeneity. This cohort will be conducted within a set of integrated health care systems (HCS), with electronic medical records (EMRs), a passive follow-up system that is both cost effective and thorough, and existing clinical infrastructure for specimen collection. Consented participants will complete an online questionnaire at baseline and periodically throughout the duration of follow-up. Passive follow-up via tumor registries and EMRs will provide outcome information for cancers and their precursors. Blood, urine, and saliva samples will be collected at baseline and repeatedly during follow-up in local clinics. Additional biologic specimens including fecal and tissue specimens will be collected. This state-of-the-art cohort will be built with an efficient, flexible, and integrated infrastructure that makes the most of modern interoperability standards in order to serve as a research workhorse for future generations of scientists in the intramural and extramural research community. Citation Format: Stephen Chanock, on behalf of the Cohort Executive Committee. A prospective cohort study embedded into integrated health care systems in the US to study cancer etiology, prevention, and early detection [abstract]. In: Proceedings of the AACR Special Conference on Modernizing Population Sciences in the Digital Age; 2019 Feb 19-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(9 Suppl):Abstract nr IA12.