Prediction of pancreatic cancer in patients with new onset hyperglycemia: A modified ENDPAC model.

BACKGROUND/OBJECTIVES: The Enriching New-Onset Diabetes for Pancreatic Cancer (ENDPAC) model relies primarily on fasting glucose values. Health systems have increasingly shifted practice towards use of glycated hemoglobin (HbA1c) measurement. We modified the ENDPAC model using patients with new onset hyperglycemia. METHODS: Four cohorts of patients 50-84 years of age with HbA1c results ≥6.2-6.5 % in 2011-2018 were identified. A combine cohort was formed. A widened eligibility criterion was applied to form additional four individual cohorts and one combined cohort. The primary outcome was the diagnosis of pancreatic cancer within 3 years after the first elevated HbA1c testing. The performance of the modified ENDPAC model was evaluated by AUC, sensitivity, positive predictive value, cases detected, and total number of patients screened. RESULTS: The individual and combined cohorts consisted of 39,001-79,060 and 69,334-92,818 patients, respectively (mean age 63.5-65.0 years). The three-year PC incidence rates were 0.47%-0.54 %. The AUC measures were in the range of 0.75-0.77 for the individual cohorts and 0.75 for the combined cohorts. When the four individual cohorts were combined, more PC cases can be identified (149 by the combined vs. 113-116 by individual cohorts when risk score was 5+). Performance measures were compromised in nonwhites. Asian and Pacific islanders had lower sensitivity compared to other racial and ethnic groups (29 % vs. 50-60 %) when risk score was 5+. CONCLUSIONS: The modified ENDPAC model targets a broader population and thus identifies more high-risk patients for cancer screening. The differential performance needs to be considered when the model is applied to non-white population.

NCI SEER-Linked Virtual Tissue Repository Pilot.

BACKGROUND: The Surveillance, Epidemiology, and End Results (SEER) Program with the National Cancer Institute tested whether population-based cancer registries can serve as honest brokers to acquire tissue and data in the SEER-Linked Virtual Tissue Repository (VTR) Pilot. METHODS: We collected formalin-fixed, paraffin-embedded tissue and clinical data from patients with pancreatic ductal adenocarcinoma (PDAC) and breast cancer (BC) for two studies comparing cancer cases with highly unusual survival (≥5 years for PDAC and ≤30 months for BC) to pair-matched controls with usual survival (≤2 years for PDAC and ≥5 years for BC). Success was defined as the ability for registries to acquire tissue and data on cancer cases with highly unusual outcomes. RESULTS: Of 98 PDAC and 103 BC matched cases eligible for tissue collection, sources of attrition for tissue collection were tissue being unavailable, control paired with failed case, second control that was not requested, tumor necrosis ≥20%, and low tumor cellularity. In total, tissue meeting the study criteria was obtained for 70 (71%) PDAC and 74 (72%) BC matched cases. For patients with tissue received, clinical data completeness ranged from 59% for CA-19-9 after treatment to >95% for margin status, whether radiation therapy and chemotherapy were administered, and comorbidities. CONCLUSIONS: The VTR Pilot demonstrated the feasibility of using SEER cancer registries as honest brokers to provide tissue and clinical data for secondary use in research. Studies using this program should oversample by 45% to 50% to obtain sufficient sample size and targeted population representation and involve subspecialty matter expert pathologists for tissue selection.

Keratin 17 modulates the immune topography of pancreatic cancer.

BACKGROUND: The immune microenvironment impacts tumor growth, invasion, metastasis, and patient survival and may provide opportunities for therapeutic intervention in pancreatic ductal adenocarcinoma (PDAC). Although never studied as a potential modulator of the immune response in most cancers, Keratin 17 (K17), a biomarker of the most aggressive (basal) molecular subtype of PDAC, is intimately involved in the histogenesis of the immune response in psoriasis, basal cell carcinoma, and cervical squamous cell carcinoma. Thus, we hypothesized that K17 expression could also impact the immune cell response in PDAC, and that uncovering this relationship could provide insight to guide the development of immunotherapeutic opportunities to extend patient survival. METHODS: Multiplex immunohistochemistry (mIHC) and automated image analysis based on novel computational imaging technology were used to decipher the abundance and spatial distribution of T cells, macrophages, and tumor cells, relative to K17 expression in 235 PDACs. RESULTS: K17 expression had profound effects on the exclusion of intratumoral CD8+ T cells and was also associated with decreased numbers of peritumoral CD8+ T cells, CD16+ macrophages, and CD163+ macrophages (p < 0.0001). The differences in the intratumor and peritumoral CD8+ T cell abundance were not impacted by neoadjuvant therapy, tumor stage, grade, lymph node status, histologic subtype, nor KRAS, p53, SMAD4, or CDKN2A mutations. CONCLUSIONS: Thus, K17 expression correlates with major differences in the immune microenvironment that are independent of any tested clinicopathologic or tumor intrinsic variables, suggesting that targeting K17-mediated immune effects on the immune system could restore the innate immunologic response to PDAC and might provide novel opportunities to restore immunotherapeutic approaches for this most deadly form of cancer.

Keratin 17 is a prognostic and predictive biomarker in pancreatic ductal adenocarcinoma.

OBJECTIVES: To determine the role of keratin 17 (K17) as a predictive biomarker for response to chemotherapy by defining thresholds of K17 expression based on immunohistochemical tests that could be used to optimize therapeutic intervention for patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: We profiled K17 expression, a hallmark of the basal molecular subtype of PDAC, by immunohistochemistry in 2 cohorts of formalin-fixed, paraffin-embedded PDACs (n = 305). We determined a K17 threshold of expression to optimize prognostic stratification according to the lowest Akaike information criterion and explored the potential relationship between K17 and chemoresistance by multivariate predictive analyses. RESULTS: Patients with advanced-stage, low K17 PDACs treated using 5-fluorouracil (5-FU)-based chemotherapeutic regimens had 3-fold longer survival than corresponding cases treated with gemcitabine-based chemotherapy. By contrast, PDACs with high K17 did not respond to either regimen. The predictive value of K17 was independent of tumor mutation status and other clinicopathologic variables. CONCLUSIONS: The detection of K17 in 10% or greater of PDAC cells identified patients with shortest survival. Among patients with low K17 PDACs, 5-FU-based treatment was more likely than gemcitabine-based therapies to extend survival.

Keratin 17 modulates the immune topography of pancreatic cancer.

Background: The immune microenvironment impacts tumor growth, invasion, metastasis, and patient survival and may provide opportunities for therapeutic intervention in pancreatic ductal adenocarcinoma (PDAC). Although never studied as a potential modulator of the immune response in most cancers, Keratin 17 (K17), a biomarker of the most aggressive (basal) molecular subtype of PDAC, is intimately involved in the histogenesis of the immune response in psoriasis, basal cell carcinoma, and cervical squamous cell carcinoma. Thus, we hypothesized that K17 expression could also impact the immune cell response in PDAC, and that uncovering this relationship could provide insight to guide the development of immunotherapeutic opportunities to extend patient survival. Methods: Multiplex immunohistochemistry (mIHC) and automated image analysis based on novel computational imaging technology were used to decipher the abundance and spatial distribution of T cells, macrophages, and tumor cells, relative to K17 expression in 235 PDACs. Results: K17 expression had profound effects on the exclusion of intratumoral CD8 + T cells and was also associated with decreased numbers of peritumoral CD8 + T cells, CD16 + macrophages, and CD163 + macrophages (p < 0.0001). The differences in the intratumor and peritumoral CD8 + T cell abundance were not impacted by neoadjuvant therapy, tumor stage, grade, lymph node status, histologic subtype, nor KRAS, p53, SMAD4, or CDKN2A mutations. Conclusions: Thus, K17 expression correlates with major differences in the immune microenvironment that are independent of any tested clinicopathologic or tumor intrinsic variables, suggesting that targeting K17-mediated immune effects on the immune system could restore the innate immunologic response to PDAC and might provide novel opportunities to restore immunotherapeutic approaches for this most deadly form of cancer.

Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma.

The relevance of KRAS mutation alleles to clinical outcome remains inconclusive in pancreatic adenocarcinoma (PDAC). We conducted a retrospective study of 803 patients with PDAC (42% with metastatic disease) at MD Anderson Cancer Center. Overall survival (OS) analysis demonstrated that KRAS mutation status and subtypes were prognostic (p < 0.001). Relative to patients with KRAS wildtype tumors (median OS 38 months), patients with KRASG12R had a similar OS (median 34 months), while patients with KRASQ61 and KRASG12D mutated tumors had shorter OS (median 20 months [HR: 1.9, 95% CI 1.2-3.0, p = 0.006] and 22 months [HR: 1.7, 95% CI 1.3-2.3, p < 0.001], respectively). There was enrichment of KRASG12D mutation in metastatic tumors (34% vs 24%, OR: 1.7, 95% CI 1.2-2.4, p = 0.001) and enrichment of KRASG12R in well and moderately differentiated tumors (14% vs 9%, OR: 1.7, 95% CI 1.05-2.99, p = 0.04). Similar findings were observed in the external validation cohort (PanCAN's Know Your Tumor® dataset, n = 408).

Pancreatic Cancer Action Network's SPARK: A Cloud-Based Patient Health Data and Analytics Platform for Pancreatic Cancer.

PURPOSE: Pancreatic cancer currently holds the position of third deadliest cancer in the United States and the 5-year survival rate is among the lowest for major cancers at just 12%. Thus, continued research efforts to better understand the clinical and molecular underpinnings of pancreatic cancer are critical to developing both early detection methodologies as well as improved therapeutic options. This study introduces Pancreatic Cancer Action Network's (PanCAN's) SPARK, a cloud-based data and analytics platform that integrates patient health data from the PanCAN's research initiatives and aims to accelerate pancreatic cancer research by making real-world patient health data and analysis tools easier to access and use. MATERIALS AND METHODS: The SPARK platform integrates clinical, molecular, multiomic, imaging, and patient-reported data generated from PanCAN's research initiatives. The platform is built on a cloud-based infrastructure powered by Velsera. Cohort exploration and browser capabilities are built using Velsera ARIA, a specialized product for leveraging clinicogenomic data to build cohorts, query variant information, and drive downstream association analyses. Data science and analytic capabilities are also built into the platform allowing researchers to perform simple to complex analysis. RESULTS: Version 1 of the SPARK platform was released to pilot users, who represented diverse end users, including molecular biologists, clinicians, and bioinformaticians. Included in the pilot release of SPARK are deidentified clinical (including treatment and outcomes data), molecular, multiomic, and whole-slide pathology images for over 600 patients enrolled in PanCAN's Know Your Tumor molecular profiling service. CONCLUSION: The pilot release of the SPARK platform introduces qualified researchers to PanCAN real-world patient health data and analytical resources in a centralized location.

Association of Pancreatic Adenocarcinoma Location With DNA Damage Response Status and Response to Platinum-Based Therapy.

PURPOSE: Pancreatic adenocarcinoma is an aggressive disease with poor clinical outcomes. Primary pancreatic tumors originating from the head of the pancreas (H) have different prognostic implications than tumors arising from the body and tail (BT). This is thought to be largely due to anatomic differences, as molecular underpinnings of survival have not been fully explored. We hypothesized that differences in the primary site of H and BT tumors might account for differential molecular outcomes and response to chemotherapy. METHODS: Retrospective data from a single high-volume academic center were analyzed for hypothesis generation. A large-scale, real-world retrospective cohort of 2015 patients with next-generation sequencing (NGS) results were analyzed from a Real-World Evidence database. Progression-free survival (PFS) was evaluated from the initiation of first line of therapy for advanced disease until discontinuation because of progression. HR and P values were computed via Cox regression between first-line FOLFIRINOX and gemcitabine/nanoparticle albumin-bound (gem/nab) paclitaxel. Differences in frequencies of genomic alterations between H and BT were analyzed by Fisher's exact test. RESULTS: Genomic alterations in the DNA damage response (DDR) pathway (such as BRCA1, BRCA2, and PALB2) were enriched (unadjusted P value = .00244) in BT tumors (21.7% of 618) relative to H tumors (15.6% of 942) where BRCA2 was a top contributor within this pathway. Median PFS in BT tumors on first-line FOLFIRINOX was longer than first line gem/nab-paclitaxel (P = .006393); this difference was not identified in H tumors (P = .5546). CONCLUSION: DDR pathway alterations including BRCA1/BRCA2/PALB2 are known predictors of increased benefit from platinum-based chemotherapy. NGS testing for germline and somatic mutations remains important in pancreatic ductal adenocarcinoma, especially in BT tumors where DDR pathway alterations may be more common than in H tumors.

Impact of KRAS Mutations and Co-mutations on Clinical Outcomes in Pancreatic Ductal Adenocarcinoma.

The relevance of KRAS mutation alleles to clinical outcome remains inconclusive in pancreatic adenocarcinoma (PDAC). We conducted a retrospective study of 803 PDAC patients (42% with metastatic disease) at MD Anderson Cancer Center. Overall survival (OS) analysis demonstrated that KRAS mutation status and subtypes were prognostic (p<0.001). Relative to patients with KRAS wildtype tumors (median OS 38 months), patients with KRASG12R had a similar OS (median 34 months), while patients with KRASQ61 and KRASG12D mutated tumors had shorter OS (median 20 months [HR: 1.9, 95% CI 1.2-3.0, p=0.006] and 22 months [HR: 1.7, 95% CI 1.3-2.3, p<0.001], respectively). There was enrichment of KRASG12D mutation in metastatic tumors (34% vs 24%, OR: 1.7, 95% CI 1.2-2.4, p=0.001) and enrichment of KRASG12R in well and moderately differentiated tumors (14% vs 9%, OR: 1.7, 95% CI 1.05-2.99, p=0.04). Similar findings were observed in the external validation cohort (PanCAN's Know Your Tumor® dataset, n=408).

Pre-Diagnosis Pain in Patients With Pancreatic Cancer Signals the Need for Aggressive Symptom Management.

OBJECTIVE: This study assessed the impact of pancreatic cancer (PC) pain on associated symptoms, activities, and resource utilization from 2016 to 2020 in an online patient registry. PATIENTS AND METHODS: Responses from PC patient volunteers (N = 1978) were analyzed from online surveys in a cross-sectional study. Comparisons were performed between PC patient groups reporting, (1) the presence vs. absence of pre-diagnosis PC pain, (2) high (4-8) vs. low (0-3) pain intensity scores on an 11-point numerical rating scale (NRS), and (3) year of PC diagnosis (2010-2020). Descriptive statistics and all bivariate analyses were performed using Chi-square or Fisher's Exact tests. RESULTS: PC pain was the most frequently reported pre-diagnosis symptom (62%). Pre-diagnostic PC pain was reported more frequently by women, those with a younger age at diagnosis, and those with PC that spread to the liver and peritoneum. Those with pre-diagnostic PC pain vs. those without reported higher pain intensities (2.64 ± 2.54 vs.1.56 ± 2.01 NRS mean ± SD, respectively, P = .0039); increased frequencies of post-diagnosis symptoms of cramping after meals, feelings of indigestion, and weight loss (P = .02-.0001); and increased resource utilization in PC pain management: (ER visits N = 86 vs. N = 6, P = .018 and analgesic prescriptions, P < .03). The frequency of high pain intensity scores was not decreased over a recent 11-year span. CONCLUSIONS: PC pain continues to be a prominent PC symptom. Patients reporting pre-diagnosis PC pain experience increased GI metastasis, symptoms burden, and are often undertreated. Its mitigation may require novel treatments, more resources dedicated to ongoing pain management and surveillance to improve outcomes.

Management of Patients With Pancreatic Cancer Using the "Right Track" Model.

Pancreatic cancer is one of the few cancer types in the US with incidence and death rates continuing to rise. As the disease threatens to become the second leading cause of cancer-related deaths in the country, it is imperative to review the best practices currently available to extend and improve patient lives. To provide a roadmap for healthcare professionals detecting, diagnosing, and caring for patients with pancreatic cancer as a supplement to national guidelines focused on recommended treatment regimens, the Pancreatic Cancer Action Network (PanCAN)'s Scientific and Medical Affairs staff and expert Scientific and Medical Advisory Board have created a series of position statements. The statements are based upon scientific evidence and clinical observations published in the literature and research conducted through PanCAN's internal programs and initiatives. This review summarizes the rationale and sources for these position statements related to diagnosis, treatment, and care for pancreatic cancer and provides information about resources to make these recommendations accessible to patients and their medical teams. Pancreatic cancer is a complex and extremely challenging disease. Beyond treatment recommendations outlined in national guidelines, steps can be taken to help patients feel better and live longer. Under the framework of the "Right Track" model-right team, right tests, right treatments, data sharing-PanCAN's position statements can provide supplementary guidance to healthcare professionals for the short- and long-term management of patients with the disease.

Imaging of the Pancreas in New-Onset Diabetes: A Prospective Pilot Study.

INTRODUCTION: The aim of this study was to assess the feasibility of cross-sectional imaging for detection of pancreatic cancer (PDAC) in patients with new-onset hyperglycemia and diabetes (NOD). METHODS: We conducted a prospective pilot study from November 2018 to March 2020 within an integrated health system. Patients aged 50-85 years with newly elevated glycemic parameters without a history of diabetes were invited to complete a 3-phase contrast-enhanced computed tomography pancreas protocol scan while participating in the Prospective Study to Establish a NOD Cohort. Abnormal pancreatic findings, incidental extrapancreatic findings, and subsequent clinical evaluation were identified. Variability in clinical reporting between medical centers based on descriptors of pancreatic duct and parenchyma was assessed. RESULTS: A total of 130 of 147 participants (88.4%) consented to imaging; 93 scans were completed (before COVID-19 stay-at-home order). The median age was 62.4 years (interquartile range 56.3-68.8), 37.6% women; Hispanic (39.8%), White (29.0%), Black (14.0%), and Asian (13.3%). One (1.1%) case of PDAC (stage IV) was diagnosed, 12 of 93 participants (12.9%) had additional pancreatic findings: 5 fatty infiltration, 3 cysts, 2 atrophy, 1 divisum, and 1 calcification. There were 57 extrapancreatic findings among 52 of 93 (56%) unique patients; 12 of 57 (21.1%) prompted clinical evaluation with 2 additional malignancies diagnosed (nonsmall cell lung and renal oncocytoma). Reports from 1 participating medical center more frequently provided description of pancreatic parenchyma and ducts (92.9% vs 18.4%), P < 0.0001. DISCUSSION: High proportion of incidental findings and variability in clinical reports are challenges to be addressed for a successful NOD-based early detection strategy for PDAC.

Early Detection Initiative: A randomized controlled trial of algorithm-based screening in patients with new onset hyperglycemia and diabetes for early detection of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is the only leading cause of cancer death without an early detection strategy. In retrospective studies, 0.5-1% of subjects >50 years of age who newly develop biochemically-defined diabetes have been diagnosed with PDAC within 3 years of meeting new onset hyperglycemia and diabetes (NOD) criteria. The Enriching New-onset Diabetes for Pancreatic Cancer (ENDPAC) algorithm further risk stratifies NOD subjects based on age and changes in weight and diabetes parameters. We present the methodology for the Early Detection Initiative (EDI), a randomized controlled trial of algorithm-based screening in patients with NOD for early detection of PDAC. We hypothesize that study interventions (risk stratification with ENDPAC and imaging with Computerized Tomography (CT) scan) in NOD will identify earlier stage PDAC. EDI uses a modified Zelen's design with post-randomization consent. Eligible subjects will be identified through passive surveillance of electronic medical records and eligible study participants randomized 1:1 to the Intervention or Observation arm. The sample size is 12,500 subjects. The ENDPAC score will be calculated only in those randomized to the Intervention arm, with 50% (n = 3125) expected to have a high ENDPAC score. Consenting subjects in the high ENDPAC group will undergo CT imaging for PDAC detection and an estimate of potential harm. The effectiveness and efficacy evaluation will compare proportions of late stage PDAC between Intervention and Observation arm per randomization assignment or per protocol, respectively, with a planned interim analysis. The study is designed to improve the detection of sporadic PDAC when surgical intervention is possible.

Leveraging patient-reported outcomes (PROs) in patients with pancreatic cancer: The Pancreatic Cancer Action Network (PanCAN) online patient registry experience.

BACKGROUND: The Pancreatic Cancer Action Network (PanCAN) Patient Registry is an online, pancreatic cancer-specific, global registry enabling patients to self-report sociodemographics, disease/management characteristics, and patient-reported outcomes (PROs). We sought to describe the creation, user experience, and research potential of the PanCAN Registry. METHODS: We obtained data to describe (1) the creation of the Registry (questionnaire development, marketing efforts, and regulatory considerations); (2) the user experience (user characteristics and interactions with the registry following inception); and (3) the research potential of the registry (comparing PROs and treatment patterns by age [±65 years] and treatment site [community or academic] for users with de novo metastatic disease). RESULTS: The Registry was conceived as part of PanCAN's strategic plan for a personalized therapy initiative. PanCAN staff and disease expert consultants developed questionnaires hosted on an electronic PRO platform. Users had the option to include their data in research efforts, and the Registry platform received institutional review board approval. From 7/2015 to 12/2020, 2187 patients visited the registry and 1697 (77.6%) completed at least one survey (median age = 64 years [range: 24-90], 47.9% women, 88.7% White, 34.0% metastatic disease). Among patients with metastatic disease (N = 567), 46.0% were ≥65 years old and 67.5% received treatment at community sites. Patients ≥65 years reported feeling less hopeful about the treatment plan (12.4% vs. 24.3%, p = 0.003), and patients treated at community sites reported more frequent treatment breaks of >2 weeks (58.2% vs. 28.1%, p < 0.001). CONCLUSIONS: Our findings demonstrate the feasibility, usability, and research potential of an online PRO registry for patients with cancer. This description of the PanCAN Registry should inform future registry-building efforts to facilitate standardized PRO reporting and provide a valuable research database. CLINICAL TRIAL REGISTRATION NUMBER: Not applicable.

Correction: Data Sharing Goals for Nonprofit Funders of Clinical Trials.

[This corrects the article DOI: 10.2196/23011.].

Potential Cost-Effectiveness of Risk-Based Pancreatic Cancer Screening in Patients With New-Onset Diabetes.

BACKGROUND: There are no established methods for pancreatic cancer (PAC) screening, but the NCI and the Pancreatic Cancer Action Network (PanCAN) are investigating risk-based screening strategies in patients with new-onset diabetes (NOD), a group with elevated PAC risk. Preliminary estimates of the cost-effectiveness of these strategies can provide insights about potential value and inform supplemental data collection. Using data from the Enriching New-Onset Diabetes for Pancreatic Cancer (END-PAC) risk model validation study, we assessed the potential value of CT screening for PAC in those determined to be at elevated risk, as is being done in a planned PanCAN Early Detection Initiative trial. METHODS: We created an integrated decision tree and Markov state-transition model to assess the cost-effectiveness of PAC screening in patients aged ≥50 years with NOD using CT imaging versus no screening. PAC prevalence, sensitivity, and specificity were derived from the END-PAC validation study. PAC stage distribution in the no-screening strategy and PAC survival were derived from the SEER program. Background mortality for patients with diabetes, screening and cancer care expenditure, and health state utilities were derived from the literature. Life-years (LYs), quality-adjusted LYs (QALYs), and costs were tracked over a lifetime horizon and discounted at 3% per year. Results are presented in 2020 US dollars, and we took a limited US healthcare perspective. RESULTS: In the base case, screening resulted in 0.0055 more LYs, 0.0045 more QALYs, and $293 in additional expenditures for a cost per QALY gained of $65,076. In probabilistic analyses, screening resulted in a cost per QALY gained of <$50,000 and <$100,000 in 34% and 99% of simulations, respectively. In the threshold analysis, >25% of screen-detected PAC cases needed to be resectable for the cost per QALY gained with screening to be <$100,000. CONCLUSIONS: We found that risk-based PAC screening in patients with NOD is likely to be cost-effective in the United States if even a modest fraction (>25%) of screen-detected patients with PAC are resectable. Future studies should reassess the value of this intervention once clinical trial data become available.

Estimated Projection of US Cancer Incidence and Death to 2040.

Importance: Coping with the current and future burden of cancer requires an in-depth understanding of trends in cancer incidences and deaths. Estimated projections of cancer incidences and deaths will be important to guide future research funding allocations, health care planning, and health policy efforts. Objective: To estimate cancer incidences and deaths in the United States to the year 2040. Design and Setting: This cross-sectional study's estimated projection analysis used population growth projections and current population-based cancer incidence and death rates to calculate the changes in incidences and deaths to the year 2040. Cancer-specific incidences and deaths in the US were estimated for the most common cancer types. Demographic cancer-specific delay-adjusted incidence rates from the Surveillance, Epidemiology, and End Results Program were combined with US Census Bureau population growth projections (2016) and average annual percentage changes in incidence and death rates. Statistical analyses were performed from July 2020 to February 2021. Main Outcomes and Measures: Total cancer incidences and deaths to the year 2040. Results: This study estimated that the most common cancers in 2040 will be breast (364 000 cases) with melanoma (219 000 cases) becoming the second most common cancer; lung, third (208 000 cases); colorectal remaining fourth (147 000 cases); and prostate cancer dropping to the fourteenth most common cancer (66 000 cases). Lung cancer (63 000 deaths) was estimated to continue as the leading cause of cancer-related death in 2040, with pancreatic cancer (46 000 deaths) and liver and intrahepatic bile duct cancer (41 000 deaths) surpassing colorectal cancer (34 000 deaths) to become the second and third most common causes of cancer-related death, respectively. Breast cancer (30 000 deaths) was estimated to decrease to the fifth most common cause of cancer death. Conclusions and Relevance: These findings suggest that there will be marked changes in the landscape of cancer incidence and deaths by 2040.

Artificial Intelligence and Early Detection of Pancreatic Cancer: 2020 Summative Review.

ABSTRACT: Despite considerable research efforts, pancreatic cancer is associated with a dire prognosis and a 5-year survival rate of only 10%. Early symptoms of the disease are mostly nonspecific. The premise of improved survival through early detection is that more individuals will benefit from potentially curative treatment. Artificial intelligence (AI) methodology has emerged as a successful tool for risk stratification and identification in general health care. In response to the maturity of AI, Kenner Family Research Fund conducted the 2020 AI and Early Detection of Pancreatic Cancer Virtual Summit (www.pdac-virtualsummit.org) in conjunction with the American Pancreatic Association, with a focus on the potential of AI to advance early detection efforts in this disease. This comprehensive presummit article was prepared based on information provided by each of the interdisciplinary participants on one of the 5 following topics: Progress, Problems, and Prospects for Early Detection; AI and Machine Learning; AI and Pancreatic Cancer-Current Efforts; Collaborative Opportunities; and Moving Forward-Reflections from Government, Industry, and Advocacy. The outcome from the robust Summit conversations, to be presented in a future white paper, indicate that significant progress must be the result of strategic collaboration among investigators and institutions from multidisciplinary backgrounds, supported by committed funders.

Data Sharing Goals for Nonprofit Funders of Clinical Trials.

Sharing clinical trial data can provide value to research participants and communities by accelerating the development of new knowledge and therapies as investigators merge data sets to conduct new analyses, reproduce published findings to raise standards for original research, and learn from the work of others to generate new research questions. Nonprofit funders, including disease advocacy and patient-focused organizations, play a pivotal role in the promotion and implementation of data sharing policies. Funders are uniquely positioned to promote and support a culture of data sharing by serving as trusted liaisons between potential research participants and investigators who wish to access these participants' networks for clinical trial recruitment. In short, nonprofit funders can drive policies and influence research culture. The purpose of this paper is to detail a set of aspirational goals and forward thinking, collaborative data sharing solutions for nonprofit funders to fold into existing funding policies. The goals of this paper convey the complexity of the opportunities and challenges facing nonprofit funders and the appropriate prioritization of data sharing within their organizations and may serve as a starting point for a data sharing toolkit for nonprofit funders of clinical trials to provide the clarity of mission and mechanisms to enforce the data sharing practices their communities already expect are happening.

Targeting the NTRK Fusion Gene in Pancreatic Acinar Cell Carcinoma: A Case Report and Review of the Literature.

Pancreatic acinar cell carcinoma (PACC) is a rare pancreatic exocrine malignancy. Compared with the more common pancreatic ductal adenocarcinoma (PDAC), PACC is more common in younger White men, has earlier stages and a lower mean age (56 vs 70 years) at the time of presentation, and has a better prognosis. In addition to differences in demographic, histologic, and clinical characteristics, PACC has a genomic profile distinct from PDAC, with only rare mutations in TP53, KRAS, and p16 that are commonly found in PDAC. This case report presents a man aged 81 years who presented with a pancreatic body mass with peripancreatic lymph node enlargement. Biopsy of the mass showed acinar cell carcinoma. The patient underwent upfront surgical resection, followed by one cycle of adjuvant gemcitabine, with stoppage of therapy due to poor tolerance. Lower-dose gemcitabine was reintroduced after disease progression 6 months later. Nab-paclitaxel was added to gemcitabine after 6 cycles because of a continued increase in the size of peripancreatic lymph nodes. Combination chemotherapy was stopped after 4 cycles because of further disease progression with new liver metastasis. Molecular testing showed the presence of an SEL1L-NTRK1 fusion. Targeted therapy was started with the oral neurotrophic tropomyosin receptor kinase (NTRK) inhibitor larotrectinib at a dosage of 100 mg twice daily. At the time of writing, the patient has been on therapy for 13 months with an exceptional radiographic response and has not experienced any grade 3 adverse effects. To our knowledge, this is the first clinical report of an NTRK gene fusion in a patient with PACC. This case study highlights the significance of tumor molecular profiling in patients with pancreatic tumors, especially rare histologies.