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Under the conditions of plane deformation, by using the Wiener-Hopf method, we perform the numerical analysis of a narrow small-scale process zone in the elastic body subjected to shear near the tip of an interface crack whose faces are in contact with friction. The process zone originates at the crack tip and makes a certain angle with the interface of the media. It is modeled by the straight line of discontinuities of displacements and consists of two segments. In the segment adjacent to the crack tip, which models the region of destruction of the material, both normal and tangential displacements have discontinuities. At the same time, in the second segment, only the normal component of displacements suffers discontinuities. The angle between the process zone and the interface of the media is determined from the condition of maximum of circumferential tensile stresses. We determine the sizes of the entire process zone and the region of destruction, the crack-tip opening displacements, and maximum opening displacement of the initial process zone. We also investigate the influence of the friction coefficient on the parameters of the process zone. By using the deformation criterion of fracture, we analyze the role played by the zone of destruction in the onset of crack propagation. It is shown that the crack starts as a result of the relative shear of its faces near the tip. The comparison of the obtained results with the data of other researchers is presented. [ABSTRACT FROM AUTHOR]

We consider a symmetric problem of development of plastic strips from the corner point of the interface of isotropic rigidly coupled media. Plastic strips are modeled by the lines of discontinuity of tangential displacements. The exact solution of the corresponding problem of the theory of elasticity is constructed by the Wiener-Hopf method. On the basis of this solution, we determine the length and the direction of propagation of plastic strips. [ABSTRACT FROM AUTHOR]

Purpose: Germline genetic testing (GT) is recommended for men with prostate cancer (PC), but testing through traditional models is limited. The ProGen study examined a novel model aimed at providing access to GT while promoting education and informed consent., Methods: Men with potentially lethal PC (metastatic, localized with a Gleason score of ≥8, persistent prostate-specific antigen after local therapy), diagnosis age ≤55 years, previous malignancy, and family history suggestive of a pathogenic variant (PV) and/or at oncologist's discretion were randomly assigned 3:1 to video education (VE) or in-person genetic counseling (GC). Participants had 67 genes analyzed (Ambry), with results disclosed via telephone by a genetic counselor. Outcomes included GT consent, GT completion, PV prevalence, and survey measures of satisfaction, psychological impact, genetics knowledge, and family communication. Two-sided Fisher's exact tests were used for between-arm comparisons., Results: Over a 2-year period, 662 participants at three sites were randomly assigned and pretest VE (n = 498) or GC (n = 164) was completed by 604 participants (VE, 93.1%; GC, 88.8%), of whom 596 participants (VE, 98.9%; GC, 97.9%) consented to GT and 591 participants completed GT (VE, 99.3%; GC, 98.6%). These differences were not statistically significant although subtle differences in satisfaction and psychological impact were. Notably, 84 PVs were identified in 78 participants (13.2%), with BRCA1/2 PV comprising 32% of participants with a positive result ( BRCA2 n = 21, BRCA1 n = 4)., Conclusion: Both VE and traditional GC yielded high GT uptake without significant differences in outcome measures of completion, GT uptake, genetics knowledge, and family communication. The increased demand for GT with limited genetics resources supports consideration of pretest VE for patients with PC.

Background: Cancer family history is a vital part of cancer genetic counseling (GC) and genetic testing (GT), but increasing indications for germline cancer GT necessitate less labor-intensive models of collection. We evaluated the impact of GC on patient pedigrees generated by an electronic cancer family history questionnaire (eCFHQ)., Methods: An Institutional Review Board-approved review of pedigrees collected through an eCFHQ was conducted. Paired pre-GC and post-GC pedigrees (n=1,113 each group) were analyzed independently by cancer genetic counselors for changes in patient-reported clinical history and to determine whether the pedigrees met NCCN GT criteria. Discrepancy in meeting NCCN GT criteria between pre-GC and post-GC pedigrees was the outcome variable of logistic regressions, with patient and family history characteristics as covariates., Results: Overall, 780 (70%) patients had cancer (affected), 869 (78%) were female, and the median age was 57 years (interquartile range, 45-66 years; range, 21-91 years). Of the 1,113 pairs of pre-GC and post-GC pedigrees analyzed, 85 (8%) were blank, 933 (84%) were not discrepant, and 95 (9%) were discrepant in meeting any NCCN GT criteria. Of the discrepant pedigrees, n=79 (83%) became eligible for testing by at least one of the NCCN GT criteria after GC. Patients with discrepant pedigrees were more likely to report no or unknown history of GT (odds ratio [OR], 4.54; 95% CI, 1.66-18.70; P=.01, and OR, 18.47; 95% CI, 5.04-88.73; P<.0001, respectively) and belonged to racially and/or ethnically underrepresented groups (OR, 1.91; 95% CI, 1.08-3.25; P=.02)., Conclusions: For most patients (84%), a standalone eCFHQ was sufficient to determine whether NCCN GT criteria were met. More research is needed on the performance of the eCFHQ in diverse patient populations.

Consensus guidelines for hereditary breast and ovarian cancer include management recommendations for pathogenic/likely pathogenic (P/LP) variants in ATM , CHEK2 , PALB2, and other DNA damage repair (DDR) genes beyond BRCA1 or BRCA2 . We report on clinical management decisions across three academic medical centers resulting from P/LP findings in DDR genes in breast/ovarian cancer patients. Among 2184 patients, 156 (7.1%) carried a P/LP variant in a DDR gene. Clinical follow-up information was available for 101/156 (64.7%) patients. Genetic test result-based management recommendations were made for 57.8% ( n = 59) of patients and for 64.7% ( n = 66) of patients' family members. Most recommendations were made for moderate-to-high risk genes and were consistent with guidelines. Sixty-six percent of patients ( n = 39/59) implemented recommendations. This study suggests that P/LP variants in DDR genes beyond BRCA1 and BRCA2 can change clinical management recommendations for patients and their family members, facilitate identification of new at-risk carriers, and impact treatment decisions. Additional efforts are needed to improve the implementation rates of genetic-testing-based management recommendations for patients and their family members.

Two major molecular pathways of colorectal carcinogenesis, chromosomal instability (CIN) and microsatellite instability (MSI), are considered to be mutually exclusive. Distinguishing CIN from MSI-high tumors has considerable therapeutic implications, because patients with MSI-high tumors can derive considerable benefit from immune checkpoint inhibitors, and tumors that evolved through the CIN pathway do not respond to these agents. Familial adenomatous polyposis (FAP) is a genetic syndrome that is defined by a mutation in the APC gene and is thought to lead to carcinogenesis through the CIN pathway. Here, we report a case of a young woman with FAP who was treated for medulloblastoma as a child and developed advanced MSI-high colon cancer as a young adult. Her response to second-line immunotherapy enabled resection of her colon cancer, and she is free of disease >10 months after surgery. This case highlights the potential for overlap between the CIN and MSI carcinogenic pathways and associated therapeutic implications.

Objective: Germline genetic testing is crucial to the care of ovarian cancer patients, and as part of the guideline-based care for ovarian cancer patient's adherence to this recommendation has been low. We sought to determine whether embedding a genetic counselor (GC) within a medical and gynecologic oncology clinic would increase testing rates and improve the timeliness of testing., Methods: Prospective cohort study of 358 ovarian cancer patients seen by medical and gynecologic oncologists between 2013 and 2015. Rates of referrals, completion of counseling, and genetic testing and timeliness of counseling were abstracted before and after a GC was embedded in the clinic in 2014. An additional year of data (2015) was collected to evaluate sustainability of the intervention., Results: Between 2013 and 2015, 88-92% of women were referred for genetic testing, but in 2013 only 66% completed counseling and 61% were tested. After a GC was embedded in the clinic in 2014, more than 80% of referred women completed counseling and germline genetic testing. Time to genetic counseling also decreased from a median of 107 to 40 days, irrespective of age and cancer family history (p < 0.01)., Conclusions: Embedding a GC into the workflow for ovarian cancer patients is an effective way of improving access to genetic counseling, testing rates, and the timeliness of testing., Competing Interests: Declaration of Competing Interest Dr. Judy E. Garber has the following COI: personal fees from Helix Genetics, Novartis Oncology, GTx, Aleta BioTherepeutics, H3 Biomedicine, Inc., Kronos Bio, American Society of Clinical Oncology (ASCO), James P. Wilmot Foundation, Inc., Diane Helis Henry Medical Research Foundation, and Adrienne Helis Melvin Medical Research Foundation, and other from Myriad Genetics, Astrazeneca, Ambry Genetics, Invitae Genetics, GV20 Therapeutics, American Association for Cancer Research, Breast Cancer Research Foundation, Konica Minolta, and Facing Our Risk of Cancer Empowered, outside the submitted work. Dr. Ursula Matulonis has the following COI: personal fees from Astrazeneca, Myriad Genetics, Clovis, Merck, Eli Lilly, Mersana, Geneos, Fuji Film, Cerulean, Immunogen, Novartis, and 2× Oncology, outside the submitted work. Ms. Kipnis reports personal fees from Invitae outside the submitted work. All other authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)