Publications by authors named "Michael J Hall"

156 Publications

Melanocore uptake by keratinocytes occurs through phagocytosis and involves protease-activated receptor-2 internalization.

Traffic 2022 06 15;23(6):331-345. Epub 2022 May 15.

CEDOC-Chronic Diseases Research Center, NOVA Medical School (NMS), Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal.

In the skin epidermis, melanin is produced and stored within melanosomes in melanocytes, and then transferred to keratinocytes. Different models have been proposed to explain the melanin transfer mechanism, which differ essentially in how melanin is transferred-either in a membrane-bound melanosome or as a melanosome core, that is, melanocore. Here, we investigated the endocytic route followed by melanocores and melanosomes during internalization by keratinocytes, by comparing the uptake of melanocores isolated from the supernatant of melanocyte cultures, with melanosomes isolated from melanocytes. We show that inhibition of actin dynamics impairs the uptake of both melanocores and melanosomes. Moreover, depletion of critical proteins involved in actin-dependent uptake mechanisms, namely Rac1, CtBP1/BARS, Cdc42 or RhoA, together with inhibition of Rac1-dependent signaling pathways or macropinocytosis suggest that melanocores are internalized by phagocytosis, whereas melanosomes are internalized by macropinocytosis. Interestingly, we found that Rac1, Cdc42 and RhoA are differently activated by melanocore or melanosome stimulation, supporting the existence of two distinct routes of melanin internalization. Furthermore, we show that melanocore uptake induces protease-activated receptor-2 (PAR-2) internalization by keratinocytes to a higher extent than melanosomes. Because skin pigmentation was shown to be regulated by PAR-2 activation, our results further support the melanocore-based mechanism of melanin transfer and further refine this model, which can now be described as coupled melanocore exo/phagocytosis.
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http://dx.doi.org/10.1111/tra.12843DOI Listing
June 2022

Current methods to analyze lysosome morphology, positioning, motility and function.

Traffic 2022 05 24;23(5):238-269. Epub 2022 Apr 24.

Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.

Since the discovery of lysosomes more than 70 years ago, much has been learned about the functions of these organelles. Lysosomes were regarded as exclusively degradative organelles, but more recent research has shown that they play essential roles in several other cellular functions, such as nutrient sensing, intracellular signalling and metabolism. Methodological advances played a key part in generating our current knowledge about the biology of this multifaceted organelle. In this review, we cover current methods used to analyze lysosome morphology, positioning, motility and function. We highlight the principles behind these methods, the methodological strategies and their advantages and limitations. To extract accurate information and avoid misinterpretations, we discuss the best strategies to identify lysosomes and assess their characteristics and functions. With this review, we aim to stimulate an increase in the quantity and quality of research on lysosomes and further ground-breaking discoveries on an organelle that continues to surprise and excite cell biologists.
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http://dx.doi.org/10.1111/tra.12839DOI Listing
May 2022

Reconstructed human pigmented skin/epidermis models achieve epidermal pigmentation through melanocore transfer.

Pigment Cell Melanoma Res 2022 Jul 7;35(4):425-435. Epub 2022 Apr 7.

CEDOC - Chronic Diseases Research Centre, NOVA Medical School, NMS, Universidade NOVA de Lisboa, Lisboa, Portugal.

The skin acts as a barrier to environmental insults and provides many vital functions. One of these is to shield DNA from harmful ultraviolet radiation, which is achieved by skin pigmentation arising as melanin is produced and dispersed within the epidermal layer. This is a crucial defence against DNA damage, photo-ageing and skin cancer. The mechanisms and regulation of melanogenesis and melanin transfer involve extensive crosstalk between melanocytes and keratinocytes in the epidermis, as well as fibroblasts in the dermal layer. Although the predominant mechanism of melanin transfer continues to be debated and several plausible models have been proposed, we and others previously provided evidence for a coupled exo/phagocytosis model. Herein, we performed histology and immunohistochemistry analyses and demonstrated that a newly developed full-thickness three-dimensional reconstructed human pigmented skin model and an epidermis-only model exhibit dispersed pigment throughout keratinocytes in the epidermis. Transmission electron microscopy revealed melanocores between melanocytes and keratinocytes, suggesting that melanin is transferred through coupled exocytosis/phagocytosis of the melanosome core, or melanocore, similar to our previous observations in human skin biopsies. We, therefore, present evidence that our in vitro models of pigmented human skin show epidermal pigmentation comparable to human skin. These findings have a high value for studies of skin pigmentation mechanisms and pigmentary disorders, whilst reducing the reliance on animal models and human skin biopsies.
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http://dx.doi.org/10.1111/pcmr.13039DOI Listing
July 2022

Molecular Characterization of KRAS Wild-type Tumors in Patients with Pancreatic Adenocarcinoma.

Clin Cancer Res 2022 Jun;28(12):2704-2714

Caris Life Sciences, Phoenix, Arizona.

Purpose: KRAS mutation (MT) is a major oncogenic driver in pancreatic ductal adenocarcinoma (PDAC). A small subset of PDACs harbor KRAS wild-type (WT). We aim to characterize the molecular profiles of KRAS WT PDAC to uncover new pathogenic drivers and offer targeted treatments.

Experimental Design: Tumor tissue obtained from surgical or biopsy material was subjected to next-generation DNA/RNA sequencing, microsatellite instability (MSI) and mismatch repair status determination.

Results: Of the 2,483 patients (male 53.7%, median age 66 years) studied, 266 tumors (10.7%) were KRAS WT. The most frequently mutated gene in KRAS WT PDAC was TP53 (44.5%), followed by BRAF (13.0%). Multiple mutations within the DNA-damage repair (BRCA2, ATM, BAP1, RAD50, FANCE, PALB2), chromatin remodeling (ARID1A, PBRM1, ARID2, KMT2D, KMT2C, SMARCA4, SETD2), and cell-cycle control pathways (CDKN2A, CCND1, CCNE1) were detected frequently. There was no statistically significant difference in PD-L1 expression between KRAS WT (15.8%) and MT (17%) tumors. However, KRAS WT PDAC were more likely to be MSI-high (4.7% vs. 0.7%; P < 0.05), tumor mutational burden-high (4.5% vs. 1%; P < 0.05), and exhibit increased infiltration of CD8+ T cells, natural killer cells, and myeloid dendritic cells. KRAS WT PDACs exhibited gene fusions of BRAF (6.6%), FGFR2 (5.2%), ALK (2.6%), RET (1.3%), and NRG1 (1.3%), as well as amplification of FGF3 (3%), ERBB2 (2.2%), FGFR3 (1.8%), NTRK (1.8%), and MET (1.3%). Real-world evidence reveals a survival advantage of KRAS WT patients in overall cohorts as well as in patients treated with gemcitabine/nab-paclitaxel or 5-FU/oxaliplatin.

Conclusions: KRAS WT PDAC represents 10.7% of PDAC and is enriched with targetable alterations, including immuno-oncologic markers. Identification of KRAS WT patients in clinical practice may expand therapeutic options in a clinically meaningful manner.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-3581DOI Listing
June 2022

The Role of Medical Mistrust in Concerns about Tumor Genomic Profiling among Black and African American Cancer Patients.

Int J Environ Res Public Health 2022 02 23;19(5). Epub 2022 Feb 23.

Fox Chase Cancer Center, Cancer Prevention and Control Program, Department of Clinical Genetics, 333 Cottman Avenue, Philadelphia, PA 19111, USA.

Tumor genomic profiling (TGP) is used in oncology practice to optimize cancer treatment and improve survival rates. However, TGP is underutilized among Black and African American (AA) patients, creating potential disparities in cancer treatment outcomes. Cost, accuracy, and privacy are barriers to genetic testing, but medical mistrust (MM) may also influence how Black and AA cancer patients perceive TGP. From December 2019 to February 2020, 112 Black and AA adults from two outpatient oncology sites in Philadelphia, PA without a known history of having TGP testing conducted completed a cross-sectional survey. Items queried included sociodemographic characteristics, clinical factors, patient-oncologist relationship quality, medical mistrust, and concerns about TGP. A k-means cluster analysis revealed two distinct psychographic clusters: high (MM-H) versus low (MM-L) medical mistrust. Clusters were not associated with any sociodemographic or clinical factors, except for age (MM-H patients older than MM-L patients, = 0.006). Eleven TGP concerns were assessed; MM-H patients expressed greater concerns than MM-L patients, including distrust of the government, insurance carriers, and pharmaceutical companies. TGP concerns varied significantly based on level of medical mistrust, irrespective of sociodemographic characteristics. Targeted communications addressing TGP concerns may mitigate disparities in TGP uptake among those with medical mistrust.
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http://dx.doi.org/10.3390/ijerph19052598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909390PMC
February 2022

The Role of the Fused Ring in Bicyclic Triazolium Organocatalysts: Kinetic, X-ray, and DFT Insights.

J Org Chem 2022 Mar 1;87(6):4241-4253. Epub 2022 Mar 1.

Department of Chemistry, Durham University, South Road, Durham DH1 3LE, U.K.

Bicyclic triazolium scaffolds are widely employed in -heterocyclic carbene (NHC) organocatalysis. While the incorporation of a fused ring was initially for synthetic utility in accessing chiral, modular triazolyl scaffolds, recent results highlight the potential for impact upon reaction outcome with the underpinning origins unclear. The common first step to all triazolium-catalyzed transformations is C(3)-H deprotonation to form the triazolylidene NHC. Herein, we report an analysis of the impact of size of the fused (5-, 6-, and 7-membered, = 1, 2, and 3, respectively) ring on the C(3) proton transfer reactions of a series of bicyclic triazolium salts. Rate constants for the deuteroxide-catalyzed C(3)-H/D-exchange of triazolium salts, , were significantly influenced by the size of the adjacent fused ring, with the kinetic acidity trend, or protofugalities, following the order ( = 1) > ( = 2) ≈ ( = 3). Detailed analyses of X-ray diffraction (XRD) data for 20 triazolium salts (including 16 new structures) and of computational data for the corresponding triazolylidene NHCs provide insight on structural effects of alteration of fused ring size. In particular, changes in internal triazolyl NCN angle and positioning of the most proximal CH with variation in fused ring size are proposed to influence the experimental protofugality order.
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http://dx.doi.org/10.1021/acs.joc.1c03073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8938951PMC
March 2022

Adverse Events Reported by Patients With Cancer After Administration of a 2-Dose mRNA COVID-19 Vaccine.

J Natl Compr Canc Netw 2022 02;20(2):160-166

9Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania.

Background: Most safety and efficacy trials of the SARS-CoV-2 vaccines excluded patients with cancer, yet these patients are more likely than healthy individuals to contract SARS-CoV-2 and more likely to become seriously ill after infection. Our objective was to record short-term adverse reactions to the COVID-19 vaccine in patients with cancer, to compare the magnitude and duration of these reactions with those of patients without cancer, and to determine whether adverse reactions are related to active cancer therapy.

Patients And Methods: A prospective, single-institution observational study was performed at an NCI-designated Comprehensive Cancer Center. All study participants received 2 doses of the Pfizer BNT162b2 vaccine separated by approximately 3 weeks. A report of adverse reactions to dose 1 of the vaccine was completed upon return to the clinic for dose 2. Participants completed an identical survey either online or by telephone 2 weeks after the second vaccine dose.

Results: The cohort of 1,753 patients included 67.5% who had a history of cancer and 12.0% who were receiving active cancer treatment. Local pain at the injection site was the most frequently reported symptom for all respondents and did not distinguish patients with cancer from those without cancer after either dose 1 (39.3% vs 43.9%; P=.07) or dose 2 (42.5% vs 40.3%; P=.45). Among patients with cancer, those receiving active treatment were less likely to report pain at the injection site after dose 1 compared with those not receiving active treatment (30.0% vs 41.4%; P=.002). The onset and duration of adverse events was otherwise unrelated to active cancer treatment.

Conclusions: When patients with cancer were compared with those without cancer, few differences in reported adverse events were noted. Active cancer treatment had little impact on adverse event profiles.
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http://dx.doi.org/10.6004/jnccn.2021.7113DOI Listing
February 2022

Structural Diversity of Perylenequinones Is Driven by Their Redox Behavior.

J Org Chem 2022 03 25;87(5):2697-2710. Epub 2022 Jan 25.

Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina 27402, United States.

Hypocrellins and hypomycins are two subclasses of fungal perylenequinones with unique structural, biological, and photochemical properties. With the growing interest in these naturally occurring photosensitizers, more studies were warranted to better understand the structural relationships between these two subclasses of perylenequinones. In this study, the long-postulated biosynthetic precursor () of class B fungal perylenequinones was isolated and characterized from a -like sp. (strain MSX60519). Furthermore, the electrochemical and chemical redox behaviors of hypocrellins and hypomycins were investigated under aerobic and anaerobic conditions. These studies served to define the structural relationship within hypocrellins (-), which was further supported by X-ray crystallography, and between hypocrellins and hypomycins (-). Chemical reductions of hypocrellins under anaerobic conditions identified the origin of hypomycin A (), hypomycin C (), and hypomycin E (), which in turn served to confirm and revise the absolute configurations of and . Hypocrellins were shown to undergo reversible reduction and reoxidation under aerobic conditions, while in an anaerobic environment and longer time scale, the fully reduced form can, to some extent, undergo an intramolecular ring closing metathesis. This may impart a means of reductive pathway for self-protection against these phototoxins and explain the chemical diversity observed in the fungal metabolites.
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http://dx.doi.org/10.1021/acs.joc.1c02639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8898278PMC
March 2022

Association of Organizational Context, Collaborative Practice Models, and Burnout Among Physician Assistants in Oncology.

JCO Oncol Pract 2022 Jan 21:OP2100627. Epub 2022 Jan 21.

Fox Chase Cancer Center, Philadelphia, PA.

Purpose: Despite an increase in the number of physician assistants (PAs) in the oncology workforce, their potential to meet anticipated demand for oncology services may be hindered by high rates of burnout. The aim of this study was to examine the association between organizational context (OC) and burnout among oncology PAs to better understand factors associated with burnout.

Methods: A national survey of oncology PAs was conducted to explore relationships between burnout and the OC in which the PA practiced. The Areas of Worklife Survey (AWS) assessed OC by examining six key workplace qualities (workload, control, reward, community, fairness, and values). Burnout was assessed using the Maslach Burnout Inventory.

Results: PAs demonstrating burnout scored significantly lower across all domains of the AWS than those without burnout ( < .001 for each AWS subscale). The median score for each domain of the AWS and burnout (No Yes) were as follows: workload (3.33 2.67), control (3.67 3.00), reward (4.00 3.67), community (4.00 3.67), fairness (3.33 2.67), and values (4.00 3.33). Multivariable analysis found that mismatches between the PA and their work environment in workload (odds ratio [OR] = 1.99; 95% CI, 1.32 to 3.02; = .001), reward (OR = 1.89, 95% CI, 1.18 to 3.02; = .008), and values (OR = 2.25; 95% CI, 1.31 to 3.88; = .003) were more likely to report burnout. Differences in burnout in the context of workload were not explained by patient volume, practice structure, or professional autonomy.

Conclusion: Workload, reward, and values were associated with greater odds of burnout, with workload being the most common mismatch in job fit. Sustainable workloads and consistency in rewards (financial, institutional, and social) for oncology PAs should be an employer's focus to help mitigate their risk of burnout.
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http://dx.doi.org/10.1200/OP.21.00627DOI Listing
January 2022

Therapeutic implications of germline vulnerabilities in DNA repair for precision oncology.

Cancer Treat Rev 2022 Mar 5;104:102337. Epub 2022 Jan 5.

Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, PA, United States; Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA, United States. Electronic address:

DNA repair vulnerabilities are present in a significant proportion of cancers. Specifically, germline alterations in DNA repair not only increase cancer risk but are associated with treatment response and clinical outcomes. The therapeutic landscape of cancer has rapidly evolved with the FDA approval of therapies that specifically target DNA repair vulnerabilities. The clinical success of synthetic lethality between BRCA deficiency and poly(ADP-ribose) polymerase (PARP) inhibition has been truly revolutionary. Defective mismatch repair has been validated as a predictor of response to immune checkpoint blockade associated with durable responses and long-term benefit in many cancer patients. Advances in next generation sequencing technologies and their decreasing cost have supported increased genetic profiling of tumors coupled with germline testing of cancer risk genes in patients. The clinical adoption of panel testing for germline assessment in high-risk individuals has generated a plethora of genetic data, particularly on DNA repair genes. Here, we highlight the therapeutic relevance of germline aberrations in DNA repair to identify patients eligible for precision treatments such as PARP inhibitors (PARPis), immune checkpoint blockade, chemotherapy, radiation therapy and combined treatment. We also discuss emerging mechanisms that regulate DNA repair.
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http://dx.doi.org/10.1016/j.ctrv.2021.102337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9016579PMC
March 2022

Risk assessment and genetic counseling for Lynch syndrome - Practice resource of the National Society of Genetic Counselors and the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer.

J Genet Couns 2022 06 9;31(3):568-583. Epub 2022 Jan 9.

Dana-Farber Cancer Institute, Harvard Medical School, and Brigham and Women's Hospital, Boston, Massachusetts, USA.

Identifying individuals who have Lynch syndrome involves a complex diagnostic workup that includes taking a detailed family history and a combination of various tests such as immunohistochemistry and/or molecular which may be germline and/or somatic. The National Society of Genetic Counselors and the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer have come together to publish this practice resource for the evaluation of Lynch syndrome. The purpose of this practice resource was to provide guidance and a testing algorithm for Lynch syndrome as well as recommendations on when to offer testing. This practice resource does not replace a consultation with a genetics professional. This practice resource includes explanations in support of this and a summary of background data. While this practice resource is not intended to serve as a review of Lynch syndrome, it includes a discussion of background information and cites a number of key publications which should be reviewed for a more in-depth understanding. This practice resource is intended for genetic counselors, geneticists, gastroenterologists, surgeons, medical oncologists, obstetricians and gynecologists, nurses, and other healthcare providers who evaluate patients for Lynch syndrome.
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http://dx.doi.org/10.1002/jgc4.1546DOI Listing
June 2022

Cascade Genetic Testing for Hereditary Cancer Risk: An Underutilized Tool for Cancer Prevention.

JCO Precis Oncol 2021 11;5:1387-1396

Department of Clinical Genetics, Fox Chase Cancer Center. Philadelphia, PA.

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http://dx.doi.org/10.1200/PO.21.00163DOI Listing
November 2021

Community oncologists' perceptions and utilization of large-panel genomic tumor testing.

BMC Cancer 2021 Nov 25;21(1):1273. Epub 2021 Nov 25.

Center for Outcomes Research and Evaluation, Maine Medical Center Research Institute, Portland, ME, USA.

Purpose: Large-panel genomic tumor testing (GTT) is an emerging technology with great promise but uncertain clinical value. Previous research has documented variability in academic oncologists' perceptions and use of GTT, but little is known about community oncologists' perceptions of GTT and how perceptions relate to clinicians' intentions to use GTT.

Methods: Community oncology physicians (N = 58) participating in a statewide initiative aimed at improving access to large-panel GTT completed surveys assessing their confidence in using GTT, attitudes regarding the value of GTT, perceptions of barriers to GTT implementation, and future intentions to use GTTs. Descriptive and multivariable regression analyses were conducted to characterize these perceptions and to explore the relationships between them.

Results: There was substantial variability in clinicians' perceptions of GTT. Clinicians generally had moderate confidence in their ability to use GTT, but lower confidence in patients' ability to understand test results and access targeted treatment. Clinicians had positive attitudes regarding the value of GTT. Clinicians' future intentions to use GTT were associated with greater confidence in using GTT and greater perceived barriers to implementing GTT, but not with attitudes about the value of GTT.

Conclusions: Community oncologists' perceptions of large-panel genomic tumor testing are variable, and their future intentions to use GTT are associated with both their confidence in and perceived barriers to its use, but not with their attitudes towards GTT. More research is needed to understand other factors that determine how oncologists perceive and use GTT in clinical practice.
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http://dx.doi.org/10.1186/s12885-021-08985-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8620967PMC
November 2021

Molecular characteristics and clinical outcomes of patients with Neurofibromin 1-altered metastatic colorectal cancer.

Oncogene 2022 01 2;41(2):260-267. Epub 2021 Nov 2.

Division of Medical Oncology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.

Loss-of-function alterations of Neurofibromin 1 (NF1) activate RAS, a driver of colorectal cancer. However, the clinical implications of NF1 alterations are largely unknown. We performed a comprehensive molecular profiling of NF1-mutant colorectal cancer using data from 8150 patients included in a dataset of commercial CLIA-certified laboratory (Caris Life Sciences). In addition, NF1 expression levels were tested for associations with clinical outcomes using data from 431 patients in the CALGB/SWOG 80405 trial. In the Caris dataset, 2.2% of patients had pathogenic or presumed pathogenic NF1 mutations. NF1-mutant tumors more frequently harbored PIK3CA (25.0% vs. 16.7%) and PTEN mutations (24.0% vs. 4.2%) than wild type tumors. Gene set enrichment analysis revealed that MAPK and PI3K pathway signatures were enriched in NF1-mutant tumors. In the CALGB/SWOG 80405 cohort, low NF1 expression was associated with poor prognosis, and high NF1 expression was associated with better efficacy of cetuximab than bevacizumab. Together, we revealed concurrent genetic alterations in the PI3K pathways in NF1-mutant tumors, suggesting the need to simultaneously block MAPK and PI3K pathways in treatment. The potential of NF1 alteration as a novel biomarker for targeted therapy was highlighted, warranting further investigations in clinical settings.
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http://dx.doi.org/10.1038/s41388-021-02074-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8738154PMC
January 2022

Molecular differences between lymph nodes and distant metastases compared with primaries in colorectal cancer patients.

NPJ Precis Oncol 2021 Oct 27;5(1):95. Epub 2021 Oct 27.

Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Lymph nodes (LNs) and distant metastases can arise from independent subclones of the primary tumor. Herein, we characterized the molecular landscape and the differences between LNs, distant metastases and primary colorectal cancers (CRCs). Samples were analyzed using next generation sequencing (NGS, MiSeq on 47 genes, NextSeq on 592 genes) and immunohistochemistry. Tumor mutational burden (TMB) was calculated based on somatic nonsynonymous missense mutations, and microsatellite instability (MSI) was evaluated by NGS of known MSI loci. In total, 11,871 samples were examined, comprising primaries (N = 5862), distant (N = 5605) and LNs metastases (N = 404). The most frequently mutated genes in LNs were TP53 (72%), APC (61%), KRAS (39%), ARID1A (20%), PIK3CA (12%). LNs showed a higher mean TMB (13 mut/MB) vs distant metastases (9 mut/MB, p < 0.0001). TMB-high (≥17mut/MB) and MSI-H (8.8% and 6.9% vs 3.7%, p < 0.001 and p = 0.017, respectively) classifications were more frequent in primaries and LNs vs distant metastases (9.5% and 8.8% vs 4.2%, p < 0.001 and p = 0.001, respectively). TMB-high is significantly more common in LNs vs distant metastases and primaries (P < 0.0001), regardless MSI-H status. Overall, LNs showed significantly different rates of mutations in APC, KRAS, PI3KCA, KDM6A, and BRIP1 (p < 0.01) vs primaries, while presenting a distinct molecular profile compared to distant metastases. Our cohort of 30 paired samples confirmed the molecular heterogeneity between primaries, LNs, and distant metastases. Our data support the hypothesis that lymphatic and distant metastases harbor different mutational landscape. Our findings are hypothesis generating and need to be examined in prospective studies.
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http://dx.doi.org/10.1038/s41698-021-00230-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551277PMC
October 2021

NCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 1.2021.

J Natl Compr Canc Netw 2021 10 15;19(10):1122-1132. Epub 2021 Oct 15.

Dana-Farber/Brigham and Women's Cancer Center.

Identifying individuals with hereditary syndromes allows for timely cancer surveillance, opportunities for risk reduction, and syndrome-specific management. Establishing criteria for hereditary cancer risk assessment allows for the identification of individuals who are carriers of pathogenic genetic variants. The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal provides recommendations for the assessment and management of patients at risk for or diagnosed with high-risk colorectal cancer syndromes. The NCCN Genetic/Familial High-Risk Assessment: Colorectal panel meets annually to evaluate and update their recommendations based on their clinical expertise and new scientific data. These NCCN Guidelines Insights focus on familial adenomatous polyposis (FAP)/attenuated familial adenomatous polyposis (AFAP) syndrome and considerations for management of duodenal neoplasia.
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http://dx.doi.org/10.1164/jnccn.2021.0048DOI Listing
October 2021

Synthesis and Reactivity of 3,5-Diiodo-BODIPYs via a Concerted, Double Aromatic Finkelstein Reaction.

Org Lett 2021 Nov 11;23(21):8595-8599. Epub 2021 Oct 11.

Chemistry, School of Natural and Environmental Sciences, Newcastle University, Newcastle Upon Tyne, NE1 7RU, U.K.

3,5-Diiodo-8-aryl-BODIPYs are prepared from the corresponding 3,5-dichloro- and 3,5-dibromo- congeners via a double aromatic Finkelstein reaction with NaI in refluxing propionitrile, in yields from 51 to 100%. Rate enhancement is observed for 3,5-dibromo-BODIPYs (ArBr > ArCl) suggesting a concerted SAr mechanism for this transformation. Thus formed 3,5-diiodo-BODIPYs are examined as coupling partners in Migita-Kosugi-Stille, Mizoroki-Heck, Sonogashira, and Suzuki-Miyaura reactions, providing routes toward complex BODIPY architectures.
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http://dx.doi.org/10.1021/acs.orglett.1c03317DOI Listing
November 2021

Patients' Expectations of Benefits From Large-Panel Genomic Tumor Testing in Rural Community Oncology Practices.

JCO Precis Oncol 2021 29;5. Epub 2021 Sep 29.

Center for Outcomes Research and Evaluation, Maine Medical Center Research Institute, Portland, ME.

Large-panel genomic tumor testing (GTT) is an emerging technology that promises to make cancer treatment more precise. Because GTT is novel and complex, patients may have unrealistic expectations and limited knowledge of its benefits. These problems may limit the clinical value of GTT, but their prevalence and associated factors have not been explored.

Methods: Patients with cancer enrolled in a large initiative to disseminate GTT in community oncology practices completed surveys assessing their expectations, knowledge, and attitudes about GTT. The study sample (N = 1,139) consisted of patients with a range of cancer types (22% gynecologic, 14% lung, 10% colon, 10% breast, and 46% other malignancies) and cancer stages (4% stage I, 3% stage II, 15% stage III, and 74% stage IV). Mean age was 64 years (standard deviation = 11); 668 (59%) were women; 71% had no college degree; 57% came from households with less than $50,000 US dollars household income; and 73% lived in a rural area.

Results: Generally, patients had high expectations that they would benefit from GTT (M = 2.81 on 0-4 scale) and positive attitudes toward it (M = 2.98 on 0-4 scale). Patients also had relatively poor knowledge about GTT (48% correct answers on an objective test of GTT knowledge). Greater expectations for GTT were associated with lower knowledge (b = -0.46; < .001), more positive attitudes (b = 0.40; < .001), and lower education (b = -0.53; < .001).

Conclusion: This research suggests patients have high expectations that they will benefit from GTT, which is associated with low knowledge, positive attitudes, and low education. More research is needed to understand the concordance between expectations and actual clinical outcomes.
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http://dx.doi.org/10.1200/PO.21.00235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492376PMC
March 2022

Genetic risk assessment for hereditary renal cell carcinoma: Clinical consensus statement.

Cancer 2021 Nov 3;127(21):3957-3966. Epub 2021 Aug 3.

Massachusetts General Hospital Cancer Center, Boston, Massachusetts.

Background: Although renal cell carcinoma (RCC) is believed to have a strong hereditary component, there is a paucity of published guidelines for genetic risk assessment. A panel of experts was convened to gauge current opinions.

Methods: A North American multidisciplinary panel with expertise in hereditary RCC, including urologists, medical oncologists, clinical geneticists, genetic counselors, and patient advocates, was convened. Before the summit, a modified Delphi methodology was used to generate, review, and curate a set of consensus questions regarding RCC genetic risk assessment. Uniform consensus was defined as ≥85% agreement on particular questions.

Results: Thirty-three panelists, including urologists (n = 13), medical oncologists (n = 12), genetic counselors and clinical geneticists (n = 6), and patient advocates (n = 2), reviewed 53 curated consensus questions. Uniform consensus was achieved on 30 statements in specific areas that addressed for whom, what, when, and how genetic testing should be performed. Topics of consensus included the family history criteria, which should trigger further assessment, the need for risk assessment in those with bilateral or multifocal disease and/or specific histology, the utility of multigene panel testing, and acceptance of clinician-based counseling and testing by those who have experience with hereditary RCC.

Conclusions: In the first ever consensus panel on RCC genetic risk assessment, 30 consensus statements were reached. Areas that require further research and discussion were also identified, with a second future meeting planned. This consensus statement may provide further guidance for clinicians when considering RCC genetic risk assessment.

Lay Summary: The contribution of germline genetics to the development of renal cell carcinoma (RCC) has long been recognized. However, there is a paucity of guidelines to define how and when genetic risk assessment should be performed for patients with known or suspected hereditary RCC. Without guidelines, clinicians struggle to define who requires further evaluation, when risk assessment or testing should be done, which genes should be considered, and how counseling and/or testing should be performed. To this end, a multidisciplinary panel of national experts was convened to gauge current opinion on genetic risk assessment in RCC and to enumerate a set of recommendations to guide clinicians when evaluating individuals with suspected hereditary kidney cancer.
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http://dx.doi.org/10.1002/cncr.33679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8711633PMC
November 2021

Oncologists' Perceptions of Tumor Genomic Profiling and the Communication of Test Results and Risks.

Public Health Genomics 2021 29;24(5-6):304-309. Epub 2021 Jul 29.

College of Public Health, Cancer Prevention and Control Program, Fox Chase Cancer Center, Temple University, Philadelphia, Pennsylvania, USA.

Tumor genomic profiling (TGP) identifies genetic targets for precision cancer treatments. The complexity of TGP can expose gaps in oncologists' skills, complicating test interpretation and patient communication. Research on oncologists' use and perceptions of TGP could inform practice patterns and training needs. To study this, a sample of oncologists was surveyed to assess TGP use, perceptions, and perceived skills in TGP interpretation/communication, especially in communication of hereditary risks. Genomic self-efficacy and TGP knowledge were also assessed. The goal sample (n = 50) was accrued from 12/2019 to 1/2020. Respondents were primarily medical oncologists (78%) with >10 (mean 17.7) years of practice experience. TGP use was moderate/high (median 50 [range 2-398]) tests/year. Most oncologists reported informal/no training in interpretation (72%) or communication (86%) of TGP results and risks. Genomic self-efficacy was high and was associated with higher use of TGP (p = 0.047). Perceptions of the benefits and limitations of TGP were mixed: heterogeneity was seen by years of experience, TGP use, and knowledge. Most participants agreed that additional training in TGP communication was needed, especially in communication of hereditary risks, and that an online training tool would be useful (86%). We conclude that oncologists are frequently using TGP despite having mixed views about its utility and not feeling prepared to communicate risks to patients. Oncologists receive little education in interpreting TGP or communicating its results and risks, and would value training in this area.
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http://dx.doi.org/10.1159/000517486DOI Listing
February 2022

Formation of Lipofuscin-Like Autofluorescent Granules in the Retinal Pigment Epithelium Requires Lysosome Dysfunction.

Invest Ophthalmol Vis Sci 2021 07;62(9):39

iNOVA4Health, CEDOC - Chronic Diseases Research Center, NOVA Medical School, Universidade Nova de Lisboa, Lisboa, Portugal.

Purpose: We aim to characterize the pathways required for autofluorescent granule (AFG) formation by RPE cells using cultured monolayers.

Methods: We fed RPE monolayers in culture with a single pulse of photoreceptor outer segments (POS). After 24 hours the cells started accumulating AFGs that were comparable to lipofuscin in vivo. Using this model, we used a variety of light and electron microscopical techniques, flow cytometry and Western blot to analyze the formation of AFGs. We also generated a mutant RPE line lacking cathepsin D by gene editing.

Results: AFGs seem to derive from incompletely digested POS-containing phagosomes and after 3 days are surrounded by a single membrane positive for lysosome markers. We show by various methods that lysosome-phagosome fusion is required for AFG formation, and that impairment of lysosomal pH or catalytic activity, particularly cathepsin D activity, enhances AF accumulation.

Conclusions: We conclude that lysosomal dysfunction results in incomplete POS degradation and enhanced AFG accumulation.
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http://dx.doi.org/10.1167/iovs.62.9.39DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322709PMC
July 2021

Changes in Burnout Among Oncology Physician Assistants Between 2015 and 2019.

JCO Oncol Pract 2022 01 22;18(1):e47-e59. Epub 2021 Jul 22.

Fox Chase Cancer Center, Philadelphia, PA.

Purpose: Burnout has significant implications for the individual provider, the oncology workforce, and the quality of care for patients with cancer. The primary aim of this study was to explore temporal changes in burnout among physician assistants (PAs) in oncology in 2019 compared with 2015.

Methods: Oncology PAs were surveyed to assess for burnout using the Maslach Burnout Inventory according to the same cross-sectional design of the study performed in 2015. Comparison between oncology PAs in 2015 and 2019 in the prevalence of burnout and personal and professional characteristics was performed.

Results: Two hundred thirty-four participants completed the full-length survey. The participants in 2015 and 2019 were similar in age (41.8 40.3 years), sex (88.8% 86.3% female), number of years as a PA in oncology (9.6 10), and percentage involved in academic practice (55.2% 59.2%). There was a significant increase in burnout in 2019 compared with 2015 with 48.7% of PAs reporting at least one symptom of burnout compared with 34.8% (odds ratio for burnout, 2019 2015 = 1.92 [95% CI, 1.40 to 2.65], < 0.001). The odds of burnout remained higher in 2019 compared with 2015 when adjusted for age, sex, relationship status, practice setting, subspecialty, practice type, and hours worked. Factors associated with burnout in both 2015 and 2019 include the percentage of time spent on patient care, collaborative physician relationship, number of hours worked, and satisfaction with compensation. No new factors associated with burnout emerged in 2019 that were not identified in 2015.

Conclusion: The rate of burnout of oncology PAs has significantly increased. Burnout in oncology PAs is multifactorial, and the increase cannot be easily explained. Additional research is needed to better define the drivers of PA burnout.
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http://dx.doi.org/10.1200/OP.21.00051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8757962PMC
January 2022

Expanding Germline Testing to All Patients With Esophagogastric Cancers-Easy to Do, Harder to Justify.

JAMA Netw Open 2021 07 1;4(7):e2114789. Epub 2021 Jul 1.

Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, Pennsylvania.

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http://dx.doi.org/10.1001/jamanetworkopen.2021.14789DOI Listing
July 2021

Updates in chemoprevention research for hereditary gastrointestinal and polyposis syndromes.

Authors:
Michael J Hall

Curr Treat Options Gastroenterol 2021 Mar 28;19(1):30-46. Epub 2020 Dec 28.

Fox Chase Cancer Center, Philadelphia, PA, USA.

Purpose Of Review: To critically examine recently published research in the area of chemoprevention in hereditary polyposis and gastrointestinal cancers, and to briefly review several ongoing chemoprevention trials testing novel agents in this population.

Recent Findings: Four recent chemoprevention trials in patients with familial adenomatous polyposis (FAP) were identified and reviewed. In the FAPEST trial, the combination of erlotinib+sulindac (compared to placebo) met its primary outcome of decreased duodenal polyp burden. A secondary analysis of lower gastrointestinal tract outcomes also demonstrated significant benefits. Two randomized trials in FAP patients examining combination regimens (celecoxib+DFMO and sulindac+DFMO) failed to meet their primary endpoints. Benefits of further research into these combinations was suggested by efficacy signals seen in secondary and post-hoc analyses. Finally, a randomized trial found curcumin (vs placebo) to have no benefit in reducing colorectal polyp count or size in patients with FAP.

Summary: Progress in developing new and more effective preventive options for patients with hereditary gastrointestinal syndromes continues to be made through the efforts of investigators conducting chemoprevention research.
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http://dx.doi.org/10.1007/s11938-020-00306-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240460PMC
March 2021

Novel LRRK2 mutations and other rare, non-BAP1-related candidate tumor predisposition gene variants in high-risk cancer families with mesothelioma and other tumors.

Hum Mol Genet 2021 08;30(18):1750-1761

Cancer Epigenetics and Signaling Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.

There is irrefutable evidence that germline BRCA1-associated protein 1 gene (BAP1) mutations contribute to malignant mesothelioma (MM) susceptibility. However, BAP1 mutations are not found in all cases with evidence of familial MM or in other high-risk cancer families affected by various cancers, including MM. The goal of this study was to use whole genome sequencing (WGS) to determine the frequency and types of germline gene variants occurring in 12 MM patients who were selected from a series of 141 asbestos-exposed MM patients with a family history of cancer but without a germline BAP1 mutation. WGS was also performed on two MM cases, a proband and sibling, from a previously reported family with multiple cases of MM without the inheritance of a predisposing BAP1 mutation. Altogether, germline DNA sequencing variants were identified in 21 cancer-related genes in 10 of the 13 probands. Germline indel, splice site and missense mutations and two large deletions were identified. Among the 13 MM index cases, 6 (46%) exhibited one or more predicted pathogenic mutations. Affected genes encode proteins involved in DNA repair (ATM, ATR, BRCA2, BRIP1, CHEK2, MLH3, MUTYH, POLE, POLE4, POLQ and XRCC1), chromatin modification (ARID1B, DNMT3A, JARID2 and SETD1B) or other cellular pathways: leucine-rich repeat kinase 2 gene (LRRK2) (two cases) and MSH4. Notably, somatic truncating mutation or deletions of LRRK2 were occasionally found in MMs in The Cancer Genome Atlas, and the expression of LRRK2 was undetectable or downregulated in a majority of primary MMs and MM cell lines we examined, implying that loss of LRRK2 expression is a newly recognized tumor suppressor alteration in MM.
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http://dx.doi.org/10.1093/hmg/ddab138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411985PMC
August 2021

The Landscape of Alterations in DNA Damage Response Pathways in Colorectal Cancer.

Clin Cancer Res 2021 06 25;27(11):3234-3242. Epub 2021 Mar 25.

Division of Medical Oncology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.

Purpose: Defective DNA damage response (DDR) is a hallmark of cancer leading to genomic instability and is associated with chemosensitivity. Although the mismatch repair system has been extensively studied, the clinical implications of other mechanisms associated with DDR alterations in patients with colorectal cancer remain unclear. This study aimed to understand DDR pathways alterations and their association with common clinical features in patients with colorectal cancer.

Experimental Design: Next-generation sequencing and whole-transcriptome sequencing were conducted using formalin-fixed paraffin-embedded samples submitted to a commercial Clinical Laboratory Improvement Amendments-certified laboratory. Samples with pathogenic or presumed pathogenic mutations in 29 specific DDR-related genes were considered as DDR-mutant (DDR-MT) and the remaining samples as DDR-wild type (DDR-WT).

Results: Of 9,321 patients with colorectal cancer, 1,290 (13.8%) were DDR-MT. The frequency of DDR-MT was significantly higher in microsatellite instability-high (MSI-H) cases than in microsatellite stable cases (76.4% vs. 9.5%). The DDR-MT genotype was higher in the right-sided, -wild, -mutant, and CMS1 subgroups. However, these associations were primarily confounded by the distribution of MSI status. Compared with the DDR-WT tumors, the DDR-MT tumors had a higher mutational burden and gene expression levels in the immune-related pathway, which were independent of MSI status.

Conclusions: We characterized a distinct subgroup of patients with colorectal cancer with tumors harboring mutations in the DDR-related genes. These patients more commonly had MSI-H tumors and exhibited an activated immune signature regardless of their tumor's MSI status. These findings warrant further investigations to develop personalized treatment strategies in this significant subgroup of patients with colorectal cancer.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-3635DOI Listing
June 2021

Psychological distress in patients with metastatic cancer enrolling on phase I clinical trials.

J Cancer Surviv 2021 06 13;15(3):398-402. Epub 2021 Mar 13.

Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA.

Purpose: Psychological distress is common in patients with cancer and is associated with lower quality-of-life (QOL). Although distress among oncology outpatients undergoing standard therapy has been widely studied, few studies have evaluated distress among patients enrolling on Phase I therapeutic clinical trials. Thus, we aimed to characterize levels of distress and types of stressors in patients enrolling on Phase I clinical trials.

Methods: Participants completed the National Comprehensive Cancer Network Distress Thermometer (NCCN DT) and Problem list and measures of anxiety and depression at the time of Phase I clinical trial initiation.

Results: We enrolled 87 patients (95% with metastatic/incurable disease) who were initiating a Phase I clinical trial. Analyses revealed a high prevalence of distress (51%) and anxiety (28%). There were significant correlations between overall distress and practical problems (r = 0.31, p = 0.016), family problems (r = 0.35, p = 0.006), and emotional problems (r = 0.64, p < 0.001), but not physical problems (r = 0.17, p = 0.206).

Conclusions: Patients may be better prepared to manage physical stressors but not practical, emotional, or family stressors at the time of Phase I trial enrollment.

Implications For Cancer Survivors: Phase I trial patients experience high levels of distress which may be due to the rigors of previous therapies therapy and related emotional and social stressors related to the poor prognosis of their advanced cancer diagnosis. Distress may go unidentified without screening which is not standard practice at the time of Phase I trial consideration. Future studies should evaluate strategies to routinely identify and intervene upon addressable stressors in patients participating in Phase I clinical trials.
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http://dx.doi.org/10.1007/s11764-021-01014-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955695PMC
June 2021

Pancreatic cancer in the era of COVID-19 pandemic: Which one is the lesser of two evils?

World J Clin Oncol 2021 Feb;12(2):54-60

Department of Surgery, Fox Chase Cancer Center, Philadelphia, PA 19111, United States.

Pancreatic adenocarcinoma remains one of the deadliest malignancies affecting the older population. We are experiencing a paradigm shift in the treatment of pancreatic cancer in the era of coronavirus disease 2019 (COVID-19) pandemic. Utilizing neoadjuvant treatment and further conducting a safe surgery while protecting patients in a controlled environment can improve oncological outcomes. On the other hand, an optimal oncologic procedure performed in a hazardous setting could shorten patient survival if recovery is complicated by COVID-19 infection. We believe that oncological treatment protocols must adapt to this new health threat, and pancreatic cancer is not unique in this regard. Although survival may not be as optimistic as most other malignancies, as caregivers and researchers, we are committed to innovating and reshaping the treatment algorithms to minimize morbidity and maximize survival as caregivers and researchers.
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http://dx.doi.org/10.5306/wjco.v12.i2.54DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918523PMC
February 2021

Germline Pathogenic Variants in the Ataxia Telangiectasia Mutated () Gene are Associated with High and Moderate Risks for Multiple Cancers.

Cancer Prev Res (Phila) 2021 04 28;14(4):433-440. Epub 2021 Jan 28.

Stanford University, Stanford, California.

Pathogenic variants (PVs) in are relatively common, but the scope and magnitude of risk remains uncertain. This study aimed to estimate PV cancer risks independent of family cancer history. This analysis included patients referred for hereditary cancer testing with a multi-gene panel ( = 627,742). Cancer risks for PV carriers ( = 4,607) were adjusted for family history using multivariable logistic regression and reported as ORs with 95% confidence intervals (CIs). Subanalyses of the c.7271T>G missense PV were conducted. Moderate-to-high risks for pancreatic (OR, 4.21; 95% CI, 3.24-5.47), prostate (OR, 2.58; 95% CI, 1.93-3.44), gastric (OR, 2.97; 95% CI, 1.66-5.31), and invasive ductal breast (OR, 2.03; 95% CI, 1.89-2.19) cancers were estimated for PV carriers. Notably, c.7271T>G was associated with higher invasive ductal breast cancer risk (OR, 3.76; 95% CI, 2.76-5.12) than other missense and truncating PVs. Low-to-moderate risks were seen for ductal carcinoma (OR, 1.80; 95% CI, 1.61-2.02), male breast cancer (OR, 1.72; 95% CI, 1.08-2.75), ovarian cancer (OR, 1.57; 95% CI, 1.35-1.83), colorectal cancer (OR, 1.49; 95% CI, 1.24-1.79), and melanoma (OR, 1.46; 95% CI, 1.18-1.81). PVs are associated with multiple cancer risks and, while professional society guidelines support that carriers are eligible for increased breast and pancreatic cancer screening, increased screening for prostate and gastric cancer may also be warranted. c.7271T>G is associated with high risk for breast cancer, with a 3- to 4-fold risk increase that supports consideration of strategies for prevention and/or early detection. PREVENTION RELEVANCE: This study estimated risks for multiple cancers associated with pathogenic variants independent of family history. These results indicate that some common variants may be associated with higher breast cancer risks than previously appreciated and increased screening for prostate and gastric cancer may be warranted for carriers of pathogenic variants.
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http://dx.doi.org/10.1158/1940-6207.CAPR-20-0448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026745PMC
April 2021

Feasibility of Fitness Tracker Usage to Assess Activity Level and Toxicities in Patients With Colorectal Cancer.

JCO Clin Cancer Inform 2021 01;5:125-133

Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA.

Purpose: Performance status (PS) is a subjective assessment of patients' overall health. Quantification of physical activity using a wearable tracker (Fitbit Charge [FC]) may provide an objective measure of patient's overall PS and treatment tolerance.

Materials And Methods: Patients with colorectal cancer were prospectively enrolled into two cohorts (medical and surgical) and asked to wear FC for 4 days at baseline (start of new chemotherapy [± 4 weeks] or prior to curative resection) and follow-up (4 weeks [± 2 weeks] after initial assessment in medical and postoperative discharge in surgical cohort). Primary end point was feasibility, defined as 75% of patients wearing FC for at least 12 hours/d, 3 of 4 assigned days. Mean steps per day (SPD) were correlated with toxicities of interest (postoperative complication or ≥ grade 3 toxicity). A cutoff of 5,000 SPD was selected to compare outcomes.

Results: Eighty patients were accrued over 3 years with 55% males and a median age of 59.5 years. Feasibility end point was met with 68 patients (85%) wearing FC more than predefined duration and majority (91%) finding its use acceptable. The mean SPD count for patients with PS 0 was 6,313, and for those with PS 1, it was 2,925 (122 and 54 active minutes, respectively) ( = .0003). Occurrence of toxicity of interest was lower among patients with SPD > 5,000 (7 of 33, 21%) compared with those with SPD < 5,000 (14 of 43, 32%), although not significant ( = .31).

Conclusion: Assessment of physical activity with FC is feasible in patients with colorectal cancer and well-accepted. SPD may serve as an adjunct to PS assessment and a possible tool to help predict toxicities, regardless of type of therapy. Future studies incorporating FC can standardize patient assessment and help identify vulnerable population.
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http://dx.doi.org/10.1200/CCI.20.00117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189607PMC
January 2021
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