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Background: Suspicious F-18 fluciclovine PET/CT findings for osseous metastases from prostate cancer (PC) were targeted for core needle biopsy. We correlated the maximum standardized uptake value (SUVmax) of biopsied lesions, with biopsy results, other diagnostic outcomes, and blood and tissue molecular analysis (TMA)., Material and Methods: Patients with castrate resistant prostate cancer (CRPC) were recruited from a university oncology clinic. SUVmax, histology, blood, and TMA were correlated., Results: Fifteen patients were enrolled and 12 underwent bone biopsies. Fifty percent of bone biopsies demonstrated malignancy. Higher SUVmax was associated with positive biopsies for adenocarcinoma (P = .003), and lesions with SUVmax ≥ 5.1 were all positive for malignancy. Significant correlation between blood and somatic TMA (P = .002) was also found., Conclusion: Higher uptake of F-18 fluciclovine was associated with higher predictive value for osseous metastasis on biopsy. There was a significant correlation between blood and TMA., (© The Author(s) 2023. Published by Oxford University Press.)

Introduction: Pemigatinib is a selective small-molecule inhibitor of the fibroblast growth factor receptor (FGFR) 1-3. FGFR is associated with increased cell division, proliferation, and survival. Inhibition of this receptor is an effective treatment against tumors driven by activated fusions in FGFR2., Areas Covered: The drug was first evaluated in patients with advanced solid tumors and demonstrated a manageable safety profile, with the most common adverse events being oscillations in blood phosphate levels, fatigue, gastrointestinal symptoms, and skin and ocular toxicities. Pemigatinib was further evaluated in a phase II cohort study of patients with previously treated locally advanced or metastatic cholangiocarcinoma harboring FGFR2 genomic alterations. After a median follow-up of 17.8 months, the objective response rate in patients with tumors harboring FGFR2 fusions or rearrangements was 35.5% (95% CI, 26.5-45.4). Based on these results, the FDA granted accelerated approval on 17 April 2020, to pemigatinib, for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or another rearrangement. Articles selected for this review were based on reported studies indexed in PubMed (2010-2023)., Expert Opinion: Future perspectives in the treatment of FGFR2 fused cholangiocarcinoma include the evaluation of pemigatinib in previously untreated patients and possible active combinations or sequencing strategies with other drugs.

Introduction: The Leukemia Inhibitory Factor (LIF) is a member of the interleukin-6 (IL-6) cytokine family. Known to induce differentiation of myeloid leukemia cells, evidence has accumulated supporting its role in cancer evolution through regulating cell differentiation, renewal, and survival. LIF has recently emerged as a biomarker and therapeutic target for pancreatic ductal adenocarcinoma (PDAC). The first in-human clinical trial has shown promising safety profile and has suggested a potential role for LIF inhibitor in combination regimen., Areas Covered: Herein, we summarize, discuss, and give an expert opinion on the role of LIF in PDAC promotion, and its potential role as a biomarker and target of anti-cancer therapy. We conducted an exhaustive PubMed search for English-language articles published from 1 January 1970, to 1 August 2022., Expert Opinion: PDAC carries a devastating prognosis for patients, highlighting the need for advancing drug development. The results of the phase 1 trial with MSC-1 demonstrated tolerability and safety but modest efficacy. Future research should focus on investigating LIF targets in combination with current standard-of-care chemotherapy, and immunotherapy can be a promising approach. Further, larger multicenter clinical trials are needed to define the use of LIF as a new biomarker in PDAC patients.

Introduction: The treatment landscape of biliary cancers is rapidly changing. Inhibitors against the actionable targets FGFR and IDH1 are now being included in the treatment guidelines of multiple countries for patients with advanced cholangiocarcinoma. However, there remains an unmet need in identifying the mechanisms of resistance and treatment strategies involving possible tumor sequencing., Areas Covered: In this review article, we address clinical trials evaluating FGFR, IDH, BRAF and HER2 inhibitors in advanced cholangiocarcinoma. We also review the mechanisms of resistance described thus far and approaches to overcome them. Articles selected for this review were based on reported studies indexed in PubMed (2010-2022)., Expert Opinion: Precision medicine in biliary cancers has already been incorporated into the treatment landscape of the disease in many countries. Fusions of FGFR2 and mutations in IDH1 are the first drivers with targetable treatments approved in these cancers. HER2 and BRAF would be the next drivers with possible tumor-agnostic or cholangiocarcinoma-specific approvals. The advent of ctDNA could improve the accessibility of sequencing and recruitment in these clinical trials. However, limitations of detecting fusions should be considered and addressed in these platforms.

Purpose: When treating esophageal cancer with radiation therapy, it is critical to limit the dose to surrounding structures, such as the lung and/or heart, as much as possible. Proton radiation therapy allows a reduced radiation dose to both the heart and lungs, potentially reducing the risk of cardiopulmonary toxicity. Here, we report disease control, survival, and toxicity outcomes among patients with esophageal cancer treated with proton radiation therapy and concurrent chemotherapy (chemoradiation therapy; CRT) with or without surgery., Materials and Methods: We enrolled 17 patients with thoracic esophageal carcinoma on a prospective registry between 2010 and 2021. Patients received proton therapy to a median dose of 50.4-GyRBE (range, 50.4-64.8) in 1.8-Gy fractions.Acute and late toxicities were graded per the Common Terminology Criteria for Adverse Events, version 4.0 (US National Cancer Institute, Bethesda, Maryland). In addition, disease control, patterns of failure, and survival outcomes were collected., Results: Nine patients received preoperative CRT, and 8 received definitive CRT. Overall, 88% of patients had adenocarcinoma, and 12% had squamous cell carcinoma. With a median follow-up of 2.1 years (range, 0.5-9.4), the 3-year local progression-free, disease-free, and overall survival rates were 85%, 66%, and 55%, respectively. Two patients (1 with adenocarcinoma and 1 with squamous cell carcinoma) recurred at the primary site after refusing surgery after a complete clinical response to CRT. The most common acute nonhematologic and hematologic toxicities, respectively, were grades 1 to 3 esophagitis and grades 1 to 4 leukopenia, both affecting 82% of patients. No acute cardiopulmonary toxicities were observed in the absence of surgical resection. Reagarding surgical complications, 3 postoperative cardiopulmonary complications occurred as follows: 1 grade 1 pleural effusion, 1 grade 3 pleural effusion, and 1 grade 2 anastomotic leak. Two severe late CRT toxicities occurred: 1 grade 5 tracheoesophageal fistula and 1 grade 3 esophageal stenosis requiring a feeding tube., Conclusion: Proton radiation therapy is a safe, effective treatment for esophageal cancer with increasing evidence supporting its role in reducing cardiopulmonary toxicity., Competing Interests: Conflicts of Interest: Bradford Hoppe, MD, MPH, and Perry Johnson, PhD, are Associate Editors of the International Journal of Particle Therapy. All other authors have no relevant conflicts of interest to disclose., (©Copyright 2022 The Author(s).)

BRCA1 -mutated prostate cancer has been shown to be less responsive to poly (ADP-ribose) polymerase (PARP) inhibitors as compared to BRCA2 -mutated prostate cancer. The reason for this differential response is not clear. We hypothesized this differential sensitivity to PARP inhibitors may be explained by distinct genomic landscapes of BRCA1 versus BRCA2 co-segregating genes. In a large dataset of 7,707 men with advanced prostate cancer undergoing comprehensive genomic profiling (CGP) of cell-free DNA (cfDNA), 614 men harbored BRCA1 and/or BRCA2 alterations. Differences in the genomic landscape of co-segregating genes was investigated by Fisher's exact test and probabilistic graphical models (PGMs). Results demonstrated that BRCA1 was significantly associated with six other genes, while BRCA2 was not significantly associated with any gene. These findings suggest BRCA2 may be the main driver mutation, while BRCA1 mutations tend to co-segregate with mutations in other molecular pathways contributing to prostate cancer progression. These hypothesis-generating data may explain the differential response to PARP inhibition and guide towards the development of combinatorial drug regimens in those with BRCA1 mutation., Competing Interests: NA reports consultancy to Astellas, Astra Zeneca, Aveo, Bayer, Bristol Myers Squibb, Calithera, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Foundation Medicine, Genentech, Gilead, Janssen, Merck, MEI Pharma, Nektar, Novartis, Pfizer, Pharmacyclics, and Seattle Genetics; and additionally reports institutional research funding from Astra Zeneca, Bavarian Nordic, Bayer, Bristol Myers Squibb, Calithera, Celldex, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Glaxo Smith Kline, Immunomedics, Janssen, Medivation, Merck, Nektar, New Link Genetics, Novartis, Pfizer, Prometheus, Rexahn, Roche, Sanofi, Seattle Genetics, Takeda, and Tracon. LK is an employee and stockholder of Guardant Health. PB declares grants or contracts from Merck, Seagen, Blue Earth Diagnostics, Pfizer, and EMD Serono; consulting fees from Dendreon, Pfizer, Caris Life Sciences, Astellas, Eisai, Janssen, EMD Serono, Seattle Genetics, Bristol-Myers Squibb, Bayer, and Guardant Health; payments or honoraria from Caris Life Sciences, Bayer, and Pfizer; and participation on boards for Bristol-Myers Squibb, Seagen, Astellas, Eisai, Janssen, EMD Serono, Dendreon, Pfizer, Seattle Genetics, Bayer, and Guardant Health. MB declares consulting fees from Exelixis, Bayer, Bristol-Myers Squibb, Eisai, Pfizer, AstraZeneca, Janssen, Calithera Biosciences, Genomic Health, Nektar, EMD Serono, Seagen, and Sanofi and institutional research support from Merck, Xencor, Bayer, Bristol-Myers Squibb, Genentech/Roche, Seagen, Incyte, Nektar, AstraZeneca, Tricon Pharmaceuticals, Genome & Company, AAA, Peloton Therapeutics, and Pfizer for work performed outside the current study. EIH has received honoraria from Bayer, Sanofi, and Seattle Genetics; acted as a consultant/advisor for Astellas Pharma; is an Advisory Board and/or Speakers’ Bureau member for AstraZeneca, Bayer, Bristol-Myers Squibb, Sanofi; and has received paid travel from Astellas Pharma, Caris Life Sciences, Sanofi, and Seattle Genetics; in addition, her institution has received research funding from Astellas Pharma, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Caris Life Sciences, Celgene, Celldex, Corcept Therapeutics, Curementa, Dendreon, eFFECTOR Therapeutics, Esanik, Fortis Therapeutics, Genetech/Roche, GlaxoSmithKline, Ignyta, Inovio Pharmaceuticals, Medivation, Merck Sharp & Dohme, Merck, Millennium, Oncolys BioPharma, Plexxicon, Seattle Genetics, Synta, Tokai Pharmaceuticals, and Zenith Epigenetics. HB Consulting or Advisory Role: Endocyte, Celgene, Idera, Myovant Sciences Speakers' Bureau: Guardant Health. SP reports personal fees from F. Hoffman-La Roche outside the submitted work, as well as research funding to his institution from Eisai, Genentech, Roche, Exelixis, and Pfizer; and reports a consulting/advisory role for Novartis, Medivation, Astellas Pharma, Pfizer, Aveo, Myriad, Genentech, Exelixis, and Bristol-Myers Squibb. US reports consultancy to Astellas, Exelixis and Seattle Genetics and research funding to institute from Janssen, Exelixis and Astellas/Seattle Genetics. OS is a consultant for Advanced Accelerator Applications, Astellas, AstraZeneca, Bayer Blue Earth Diagnostics Inc., Bavarian, Nordic, Bristol, Myers, Squibb, Clarity, Pharmaceuticals, Clovis, Constellation, Dendreon, EMD, Serono, Fusion, Janssen, Myovant, Myriad, Noria, Therapeutics, Inc., Novartis, Noxopharm, Progenics, POINT, Biopharma, Pfizer, Sanofi, Tenebio, Telix, Theragnostics, Dendreon, Endocyte, Innocrin, Invitae, Merck, and SOTIO; research funding from Advanced Accelerator Applications, AstraZeneca, Bayer, Invitae, and Merck. BH reports receiving travel assistance from Flatiron Health, and served as a consultant for AstraZeneca, Value Analytics, National Kidney Foundation, and Prometic Life Sciences. MY is a stock holder or has received stock option awards from Fabric Genomics Inc. and has received consulting fees from Fabric Genomics Inc. BM has consulted for Janssen Oncology, Exelixis, Tempus, Peloton Therapeutics and Astellas. RN has consulted for Tempus. 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 © 2022 Swami, Zimmerman, Nussenzveig, Hernandez, Jo, Sayegh, Wesolowski, Kiedrowski, Barata, Lemmon, Bilen, Heath, Nandagopal, Babiker, Pal, Lilly, Maughan, Haaland, Yandell, Sartor and Agarwal.)

Background: Androgen deprivation therapy (ADT) for prostate cancer is associated with adverse effects, such as obesity and metabolic syndrome, which increase cardiovascular risk, the most common cause of non-cancer mortality in men diagnosed with prostate cancer. The Comprehensive Lifestyle Improvement Program for Prostate Cancer (CLIPP) was created to determine the feasibility of conducing a comprehensive lifestyle modification intervention in men on ADT for prostate cancer and determine its early efficacy in reducing obesity and metabolic syndrome., Methods: A single-arm, open-label clinical trial was conducted by recruiting 31 men diagnosed with prostate cancer and exposed to ADT within the last 5 years. A multicomponent lifestyle modification program was delivered weekly for 16 weeks by a trained health coach. This was followed by 8 weeks of passive follow-up resulting in a total trial duration of 24 weeks. Feasibility was determined by calculating study recruitment, retention, and adherence rates. Weight and components of metabolic syndrome (waist circumference, triglycerides (TG), high-density lipoprotein (HDL), serum glucose, and blood pressure (BP)) were measured at baseline, 12, and 24 weeks., Results: Recruitment, retention, and adherence rates were 47.1%, 90.3%, and 100%, respectively. Statistically significant improvements were noted between baseline and end of study measurements for weight (206.3 vs. 191.3 lbs, p < 0.001), waist (41.3 vs. 38.8 inches, p < 0.001), systolic BP (144.1 vs. 133.4 mm of Hg, p = 0.014), diastolic BP (83.3 vs. 76.2 mm of Hg, p = 0.0056), TG (146.0 vs. 113.8 mg/dl, p = 0.022), HDL (51.1 vs. 55.0 mg/dl, p = 0.012), and serum glucose (114.0 vs. 103.2 mg/dl, p = 0.013)., Conclusion: CLIPP demonstrates feasibility and early efficacy of a multicomponent lifestyle modification intervention toward addressing obesity as well as components of metabolic syndrome in men on ADT for prostate cancer. This study provides strong preliminary data to develop future clinical trials in this population., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Competing Interests: Hani M. Babiker Consulting or Advisory Role: Endocyte, Celgene, Idera, Myovant Sciences Speakers' Bureau: Guardant Health No other potential conflicts of interest were reported.Hani M. Babiker Consulting or Advisory Role: Endocyte, Celgene, Idera, Myovant Sciences Speakers' Bureau: Guardant Health No other potential conflicts of interest were reported.

Primary care physicians are in a favorable position to curb the growing burden of pancreatic ductal adenocarcinoma. This review aims to provide an overview of pancreatic ductal adenocarcinoma from a primary care perspective, with a specific focus on risk factors, selection of high-risk individuals for screening, patient presentation at the primary-care clinic, and the role of the internist in supportive care. Overall, the internist is an essential member of the multidisciplinary care team with respect to optimizing patients' quality of life across various stages of the pancreatic cancer., (Copyright © 2021. Published by Elsevier Inc.)

Rates of prostate cancer relapsing from anti-androgen therapies are increasing in the United States and worldwide. It has been suggested that this is caused by variant and altered lineage marker expression within the tumor, allowing for lineage plasticity that then facilitates therapeutic resistance. The genomic landscape of castrate-resistant prostate cancer has been well-defined with the advent of next-generation sequencing, but the clinical applications of these findings as measured by patient outcomes remains poorly understood. Here, we report on a patient with recurrent, metastatic castrate-resistant prostate cancer and identified RB1 mutation with progressive symptomatology, who was treated with cyclophosphamide and dexamethasone after other standard treatment regimens failed. After completing 2 years of treatment, he experienced complete resolution of his symptoms. Disease remission was confirmed on multiple imaging modalities and through serial measurements of prostate-specific antigen levels that showed a reduction of 99%. Our patient's case supports ongoing research that genetic profiling can help elucidate key biological and molecular tumor components, which can then inform targeted, individualized treatment approaches in the management of recurrent, castrate-resistant prostate cancer., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Pexidartinib is approved for treatment of adults with symptomatic tenosynovial giant cell tumor. In vitro data showed pexidartinib's potential to inhibit and induce cytochrome P450 (CYP) 3A, inhibit CYP2C9, CYP2C19 and P-glycoprotein (P-gp). Herein, 2 open-label, single-sequence, crossover studies evaluated the drug-drug interaction potential of pexidartinib on CYP enzymes (CYP2C9, CYP2C19, and CYP3A) and P-gp. Thirty-two subjects received single oral doses of midazolam (CYP3A substrate) and tolbutamide (CYP2C9 substrate) alone and after single and multiple oral doses of pexidartinib. Twenty subjects received single oral doses of omeprazole (CYP2C19 substrate) and digoxin (P-gp substrate) alone or with pexidartinib. Analysis of variance was conducted to determine the effect of pexidartinib on various substrates' pharmacokinetics. No drug-drug interaction was concluded if the 90% confidence interval of the ratio of test to reference was within the range 80% to 125%. Coadministration of single and multiple doses of pexidartinib resulted in 21% and 52% decreases, respectively, in the area under the plasma concentration-time curve from time zero to the last measurable time point (AUC last ) of midazolam, whereas AUC last values of tolbutamide increased 15% and 36%, respectively. Omeprazole exposure decreased on concurrent administration with pexidartinib, the metabolite-to-parent ratio was similar following omeprazole administration alone vs coadministration with pexidartinib; pexidartinib did not affect CYP2C19-mediated metabolism. Maximum plasma concentrations of digoxin slightly increased (32%) with pexidartinib coadministration; no significant effect on digoxin AUC last . These results indicate that pexidartinib is a moderate inducer of CYP3A and a weak inhibitor of CYP2C9 and does not significantly affect CYP2C19-mediated metabolism or P-gp transport., (© 2020 Daiichi Sankyo, Inc. The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Background: Although androgen deprivation therapy (ADT) for prostate cancer demonstrates improved overall and disease-free survival, it is associated with adverse effects such as obesity and metabolic syndrome that increase risk of cardiometabolic disease and diabetes type 2. ADT also leads to fatigue, depression and erectile dysfunction, which reduce quality of life (QoL). Lifestyle modification has shown promise in reducing obesity, metabolic syndrome and diabetes type 2 in other disease types. However, there is a paucity of data regarding the utility of lifestyle modification in men receiving ADT for prostate cancer., Methods: The primary aim of the Comprehensive Lifestyle Improvement Program for Prostate Cancer-2 (CLIPP2) is to test the feasibility of conducting a 24-week lifestyle modification intervention in men on ADT for prostate cancer. Additionally, it will also determine the effect of this intervention on weight loss, cardiometabolic markers (secondary aim and markers of interest: serum glucose, insulin resistance, hemoglobin A1C and lipid panel), and QoL (tertiary aim). The intervention will be delivered weekly via telephone for the first 10 weeks and bi-weekly for the remaining 14 weeks. Questionnaires and serum samples will be collected at baseline, week 12, and week 24. Anthropometric measurements will be collected at baseline, week 6, week 12, week 18 and week 24., Results: We hypothesize that the CLIPP2 intervention will produce a 7% weight loss that will result in improved markers associated with cardiometabolic disease and type 2 diabetes in the study population., Conclusion: Results will provide insight into the role of lifestyle modification in addressing ADT adverse effects as well as provide preliminary data to inform the development of future lifestyle interventions in this area., Trial Registration: NCT04228055 Clinicaltrials. gov., (© 2021 Published by Elsevier Inc.)

Introduction: Fibroblast growth factor receptors (FGFR 1-4) are a highly conserved family of receptor tyrosine kinases, involved in several physiological processes. Genetic aberrations of FGFRs and their ligands, fibroblast growth factors (FGFs) are involved in several pathological processes including cancer. The FGF-FGFR axis has emerged as a treatment target in oncology. Because these aberrations drive cancer progression, the development of FGFR targeted therapies have been accelerated., Areas Covered: In this comprehensive review, we evaluate molecular pathology and targeted therapies to FGFRs. We reviewed the evidence for safety and efficacy from preclinical and clinical studies (phase I-III) of FGFR targeted therapies. We also discuss potential challenges in bringing these targeted therapies from bench to bedside and the potential opportunities., Expert Opinion: Despite the challenges of the clinical development of FGFR targeted therapies, two FGFR small-molecule inhibitors, namely Erdafitinib and Pemigatinib, are FDA approved for urothelial cancer and cholangiocarcinoma, respectively. Understanding and detection of FGFR genomic aberrations, protein overexpression and the development of isoform-specific inhibitors are factors in the clinical success of these therapies. An enhanced understanding of patient selection based on a gene signatures or biomarkers is key to success of FGFR targeted therapies.

Background: We theoretically derived a new quantitative metric reflecting the product of T1 signal intensity and contrast media concentration ( T1C ) using first principles for the signal provided by the gradient echo sequence. This metric can be used with conventional gadolinium contrast-enhanced magnetic resonance imaging (CE-MRI) exams. We used this metric to test our hypothesis that gadolinium enhancement changes with pancreatic ductal adenocarcinoma (PDA) treatment response, and that this metric may differentiate responders from non-responders., Methods: Out of 264 initially identified patients, a final total of 35 patients with PDA were included in a retrospective study of responders (n=24) and non-responders (n=11), which used changes in cancer antigen 19-9 (CA 19-9) and tumor size as reference standards. T1C was computed for the pancreatic mass in the arterial, portal venous, and delayed phases in pre-treatment and post-treatment MRIs. Changes in measurements and correlations with treatment response were assessed by repeated measures analysis of variance and paired t -tests., Results: In the treatment responder group, T1C significantly increased in the arterial, portal venous, and delayed phases (P=7.57e-5, P=3.25e-4, P=1.75e-4). In the non-responder group, T1C did not significantly change in any phase (P>0.58). Post-treatment T1C significantly differed between responders and non-responders (P=0.044) by repeated measures analysis of variance., Conclusions: T1C significantly increases in all phases of CE-MRI in responders to treatment, but does not change in non-responders. T1C correlates with treatment response, can be computed from clinical MRI exams, and may be useful as an additional metric to stratify patients undergoing treatment., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/apc-20-25). Dr. SV reports grants from NIH/NCI during the conduct of the study. HB serves as an unpaid Section Editor of Annals of Pancreatic Cancer from October 2019 to September 2021. The other authors have no conflicts of interest to declare.

Coronavirus disease 2019 (COVID-19) has caused significant morbidity and mortality and new cases are on the rise globally, yet malaria-endemic areas report statistically significant lower incidences. We identified potential shared targets for an immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by immune determinants' shared identities with P. falciparum using the Immune Epitope Database and Analysis Resource Immune 9.0 browser tool. Probable cross-reactivity is suggested through HLA-A∗02:01 and subsequent CD8 + T-cell activation. The apparent immunodominant epitope conservation between SARS-CoV-2 (N and open reading frame (ORF) 1ab) and P. falciparum thrombospondin-related anonymous protein (TRAP) may underlie the low COVID-19 incidence in the malaria-endemic zone by providing immunity against virus infection to those previously infected with Plasmodium . Additionally, we hypothesize that the shared epitopes which lie within antigens that aid in the establishment of the P. falciparum erythrocyte invasion may be an alternative route for SARS-CoV-2 via the erythrocyte CD147 receptor, although this remains to be proven., (© 2020 The Author(s).)

Adherence to US Preventative Services Task Force (USPSTF) cancer screening guidelines remains considerably lower than the recommendation of the Healthy People 2020 initiative. Patient populations recommended for screening are not screened at an appropriate rate, and populations not recommended for screening are inappropriately screened. Closer adherence to guidelines should improve outcomes and reduce costs, estimated to reach $158 billion/year by 2020. We evaluated whether a use of low-cost educational health maintenance (HM) card by medical residents at a university hospital could impact education and adherence to updated cancer screening guidelines. We also analyzed savings to the healthcare system. Adherence to cervical, breast, and colorectal cancer screening guidelines, defined as percentage that was screened (or not screened) in accordance with the USPSTF guidelines, in clinic visits from December 2012 (n = 336) was compared to those from December 2013 (n = 306) after a quality improvement intervention. Post-intervention, adherence to screening guidelines increased by 40.8% (p < 0.01) for cervical, 33.2% (p < 0.01) for breast, and 20.5% (p < 0.01) for colorectal cancer in average-risk patients. Inappropriate screening was reduced by 26.8% (p < 0.01) for cervical and 32.8% (p < 0.01) for breast cancer. A non-significant 1.1% decrease (p = 0.829) was observed for colorectal cancer. The annual potential savings from avoiding inappropriate screenings were $998,316 (95% CI; $644,484-$1,352,148). We showed a significant absolute increase in USPSTF knowledge of 28.3% irrespective of the house staff level that remained high at 2 years from the educational intervention. The low-cost HM card increased appropriate knowledgeable cancer screening adherence while reducing unnecessary testing and producing substantial savings to the healthcare system.

Whole exome sequencing (WES) of matched tumor-normal pairs in rare tumors has the potential to identify genome-wide mutations and copy number alterations (CNAs). We evaluated 27 rare cancer patients with tumor-normal matching by WES and tumor-only next generation sequencing (NGS) as a comparator. Our goal was to: 1) identify known and novel variants and CNAs in rare cancers with comparison to common cancers; 2) examine differences between germline and somatic variants and how that functionally impacts rare tumors; 3) detect and characterize alleles in biologically relevant genes-pathways that may be of clinical importance but not represented in classical cancer genes. We identified 3343 germline single nucleotide variants (SNVs) and small indel variants-1670 in oncogenes and 1673 in tumor suppressor genes-generating an average of 124 germline variants/case. The number of somatic SNVs and small indels detected in all cases was 523:306 in oncogenes and 217 in tumor suppressor genes. Of the germline variants, six were identified to be pathogenic or likely pathogenic. In the 27 analyzed rare cancer cases, CNAs are variable depending on tumor type, germline pathogenic variants are more common. Cell fate pathway mutations (e.g., Hippo, Notch, Wnt) dominate pathogenesis and double hit (mutation + CNV) represent ~18% cases.

Matched-targeted and immune checkpoint therapies have improved survival in cancer patients, but tumor heterogeneity contributes to drug resistance. Our study categorized gene mutations from next generation sequencing (NGS) into three core processes. This annotation helps decipher complex biologic interactions to guide therapy. We collected NGS data on 145 patients who have failed standard therapy (2016 to 2018). One hundred and forty two patients had data for tissue (Caris MI/X) and plasma cell-free circulating tumor DNA (Guardant360) platforms. The mutated genes were categorized into cell fate (CF), cell survival (CS), and genome maintenance (GM). Comparative analysis was performed for concordance and discordance, unclassified mutations, trends in TP53 alterations, and PD-L1 expression. Two gene mutation maps were generated to compare each NGS platform. Mutated genes predominantly matched to CS with concordance between Guardant360 (64.4%) and Caris (51.5%). TP53 alterations comprised a significant proportion of the mutation pool in Caris and Guardant360, 14.7% and 13.1%, respectively. Twenty-six potentially actionable gene alterations were detected from matching ctDNA to Caris unclassified alterations. The CS core cellular process was the most prevalent in our study population. Clinical trials are warranted to investigate biomarkers for the three core cellular processes in advanced cancer patients to define the next best therapies.

Purpose: An accurate clinical and radiological staging is the pyramid of treatment decisions in locally advanced rectal cancer (LARC). Guidelines recommended neoadjuvant chemoradiation therapy (CRT) followed by surgical resection for fit patients with LARC. Determining the aggressiveness of intervention while avoiding needless morbidity according to patient risk remains an unmet pre-operative decision-making need. With newer magnetic resonance imaging (MRI) techniques and image acquisition available at our Cancer Center, we seek to retrospectively review the correlation between pre- and post-CRT MRI response to the surgical pathological stage in order to aide multidisciplinary team decision making., Methods: Our Cancer Center Rectal Cancer Registry between 2011 and 2015 included 57 patients with LARC, 20 completed standard CRT with surgery, and of those 10 had repeated MRI after CRT., Results: Our retrospective case series revealed that 90% of the patients had a downstage tumor response on surgical specimen compared to radiological evaluation after CRT, and furthermore, all patients who were re-staged with MRI prior to surgery correlated with the gold standard pathological stage (p = 0.02)., Conclusions: Post-CRT MRI could potentially aide decision making to further avoid 20% of patients with a complete pathological response from a morbid surgery, whereas 10% of patients with an upstaged disease state may require a more aggressive neoadjuvant or planned surgical intervention. We concluded that future multidisciplinary oncology care treatment decision making would benefit from a repeat MRI after neoadjuvant CRT of LARC.

Background: Only 15-20% of pancreatic ductal adenocarcinoma (PDAC) patients are upfront surgical candidates at presentation, and for this cohort of patients, the 5-year survival is a mere 20% despite adjuvant therapy. Previous data indicate that in clinical practice most of these cases are "borderline-resectable," and there is currently no mature data on perioperative treatment., Methods: We performed a retrospective electronic chart review of patients with "borderline-resectable"PDAC treated at an academic comprehensive cancer center, dividing them into groups based on surgery alone, surgery plus neoadjuvant, adjuvant, or neoadjuvant plus adjuvant perioperative treatment groups. The objectives were to determine the median overall survival (mOS), progression-free survival (PFS) and disease-free survival (DFS). Statistical analysis was performed to assess the association of demographic, tumor traits, and interventions with OS, PFS and DFS., Results: Only surgery followed by adjuvant therapy showed an increase in mOS [hazard ratio (HR) 0.22; 95% CI, 0.09-0.51; P<0.001), after adjustment for radiation (yes vs. no), resection margins (R0 vs. R1 or R2), and tumor location (head vs. body or tail). Patients who received adjuvant therapy after surgery had 2.1 times greater odds to be alive at 24 months after diagnosis than those who had surgery alone (P=0.015). PFS and DFS were not statistically significantly different among treatment groups after adjustment. Those whose disease was located in the head of the pancreas had a significantly improved OS (HR =0.27; 95% CI, 0.11-0.64; P=0.003), PFS (HR =0.40; 95% CI, 0.17-0.94; P=0.035), and DFS (HR =0.30; 95% CI, 0.13-0.67; P=0.004). Negative margins led to a significant improvement in PFS (HR =0.30; 95% CI, 0.16-0.57; P<0.001) and DFS (HR =0.30; 95% CI, 0.16-0.57; P<0.001). Those who received radiation had a non-significantly improved OS, PFS, and DFS (P>0.05)., Conclusions: Our study corroborated that patients treated with adjuvant therapy after surgical resection had an mOS benefit as reported on prior phase III clinical trials. Patients with "borderline-resectable" pancreatic cancer are encouraged to participate in a clinical trial or clinically be treated with adjuvant therapy until more mature results from the ongoing perioperative prospective study are available., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Objectives : To estimate the pancreatic cancer risk among subjects exposed versus not exposed to proton pump inhibitors. Methods : The authors searched PubMed, EMBASE, Scopus, Cochrane Library, and clinicaltrials.gov to identify relevant studies. The authors quantified pancreatic cancer risk among subjects exposed versus not exposed to PPIs, expressed as the pooled (adjusted) odds ratio (OR/aOR) and 95% confidence interval (95%CI) in overall and sensitivity analyses. Results : One randomized trial, two cohort, four case-control, and five nested case-control studies with 700,178 subjects (73,985 cases; 626,193 controls) were retained. PPI exposure was associated with pancreatic cancer risk (OR = 1.75, 95%CI = 1.12-2.72, I 2  = 99%); confirmed in sensitivity analyses for high-quality studies, observational studies, case-control studies, studies with pancreatic cancer as the primary outcome, and in sensitivity analyses for diabetes and obesity but not for pancreatitis and smoking. This association was independent of the duration and Defined Daily Dose of PPI exposure. Rabeprazole had a singular significant association with pancreatic cancer (OR = 5.40, 95%CI = 1.98-14.703, I 2  = 87.9%). Conclusion : The class of PPIs is associated with a 1.75-fold increase in pancreatic cancer risk, confirmed in sensitivity analyses.