tbuckley/cabot-search huggingface dataset:
Usefulness of the patient self-administered cancer family history questionnaire in identification of gynecological cancer patients suspected of Lynch syndrome: KCOG-G1302 study.
Authors: Ryutaro Nishikawa, Kumiko Oseto, Hiroshi Nishikawa, Atsushi Arakawa, Kentaro Kai, Kaei Nasu, Mina Morii-Kashima, Hiroshi Tsubamoto, Kimihiko Ito, Naoto Furukawa
Journal: Journal of Clinical Oncology (2015)

1518 Background: Detailed family history collection is necessary to detect gynecological cancer patients suspected of Lynch syndrome (LS). However, clinicians have little time for family history interviews. In addition, there is a lack of genetic counselors in Japan. Therefore, information from medical records on the first visit (MR) is insufficient to determine if a patient may be at risk of LS. We showed that using the self-administered cancer family history questionnaire (SACFHQ) improves identification of patients suspected of LS. Methods: We recruited endometrial or ovarian cancer patients already diagnosed or newly diagnosed from research participating institutions. After consent was obtained, participants completed the questionnaire. By referring to the cancer family history obtained from MR and SACFHQ, we referred to cases that met the Amsterdam criteria II(AMSII), the SGO20-25% criteria (SGO20-25%), ACOG’s clinical bulletin 2014 criteria (ACOG2014). Results: There was a total of 493 participants. 38 patients were excluded by exclusion criteria. Finally, 455 were eligible. Median age at diagnosis was 56 (range21-84). 243 participants were endometrial cancer patients, and 213 were ovarian cancer, including peritoneal and tubal cancer. 12 cases had either synchronous/metachronous endometrial and colorectal cancer. 4 cases had either synchronous/metachronous ovarian and colorectal cancer. Among these 16 cases, endometrial or ovarian cancer was sentinel in 8 cases. By using MR, 0/455 (0%), 4/455 (0.9%), and 170/455 (37%) cases met AMSII, SGO20-25%, ACOG2014 criteria, respectively. By using SACFHQ, 6/455 (1.3%), 9/455 (2.0%), and 217/455 (48%) cases met AMSII, SGO20-25%, ACOG2014 criteria, respectively. All 6 cases that met AMSII were endometrial cancer patients. 8 of 9 patients who met SGO20-25% were endometrial cancer patients, and one patient was ovarian cancer. Conclusions: Family cancer history obtained from MR was shown to be insufficient to identify individuals at risk of LS. SACFHQ improves identification of gynecological cancer patients suspected of LS. Clinical trial information: 000013192.
Abstract 022: Exploring the 24 Hour Day: using Isotemporal Substitution to Model the Cardiometabolic Benefits of Sleep Duration in Older Women
Authors: Kelsie M Full, Jacqueline Kerr, Atul Malhotra, Linda Gallo, John Bellettiere, Elva Arredondo, Katie L Stone, Oleg Zaslavsky, Cora E Lewis, Xiaochen Lin, Andrea Z LaCroix
Journal: Circulation (2019)

Background: Sleep, sedentary behavior (SB), and physical activity (PA) are independently associated with cardiometabolic health, but few studies have examined the interrelationships between 24 hour activity and cardiometabolic risk factors. Extending sleep may be a feasible cardiometabolic risk reduction strategy; however, research is needed to understand how replacing time in SB and/or PA with sleep impacts cardiometabolic risk. Methods: Women’s Health Initiative participants in the OPACH Study (N=3329; mean age=78.5±6) wore ActiGraph GT3X+ accelerometers 24 hours/day for up to 7 days. Sleep duration was derived using a validated protocol. Adjusted regression models estimated the relationship between sleep duration and cardiometabolic markers. Separately for shorter (&lt;8 hours) and longer (≥8 hours) sleepers, isotemporal substitution models estimated the change in cardiometabolic risk markers associated with reallocating time in daytime activity (SB, light PA (LIPA), moderate to vigorous (MVPA)) to or from sleep. Results: Longer sleep duration was significantly associated with higher insulin, HOMA-IR, total cholesterol, triglycerides, and Reynolds Risk Score (RRS) (all p &lt; 0.05). For shorter sleepers, reallocating 33 minutes of MVPA to sleep was associated with significantly higher values of insulin, HOMA-IR, triglycerides, waist circumference, and RRS (0.9%-11.4%) (Figure 1). Replacing 91 minutes of SB time with sleep was associated with significantly lower waist circumference (-1%). In longer sleepers, reallocating 74 minutes from sleep to LIPA was associated with significantly lower values of insulin, HOMA-IR, trigylcerides, and waist circumference (-1.4% - -12.3%). Conclusions: This is one of the first isotemporal analysis to include objectively measured sleep duration. Results illuminate possible cardiometabolic risks and benefits of reallocating time to or from sleep duration.
A phase II trial in progress: Pamiparib, an investigational PARP inhibitor, in patients with metastatic castration-resistant prostate cancer and a circulating tumor cell homologous recombination deficiency (HRD) phenotype or <i>BRCA</i> defects.
Authors: Simon Chowdhury, Joaquin Mateo, Mitchell Gross, Andrew J. Armstrong, Marcia Cruz-Correa, Josep M. Piulats, Jean-Yves Blay, Delcia Rivas, Luis Quintero, Henry Castro, Andong Nkobena, Mitch Raponi, Robert Pelham, Mark Andrew Landers, Robert B. Montgomery
Journal: Journal of Clinical Oncology (2019)

TPS328 Background: Men with metastatic castration-resistant prostate cancer (mCRPC) who have a BRCA1/2 mutation ( BRCA1/2 mut ) or mutations in other HRD genes have a poor prognosis. The EPIC liquid biopsy test is a novel assay that can identify circulating tumor cells (CTC) with HRD associated phenotypes. Preliminary studies have shown that these men may respond to treatment with a PARP inhibitor. Pamiparib is an investigational PARP1/2 inhibitor that has shown brain penetration and potent PARP–DNA complex trapping in nonclinical studies. In early phase clinical studies (NCT02361723; NCT03333915), pamiparib was generally well tolerated and showed preliminary antitumor activity; 60 mg orally twice daily (BID) was established as the recommended investigational dose. Methods: This open-label, global, phase 2 study (NCT03712930) will evaluate antitumor activity and safety of pamiparib in mCRPC pts with CTC-HRD, assessed by the EPIC CTC-HRD assay, or deleterious germline/somatic BRCA1/2 mut status. Patients must have progressed on/after ≥1 androgen receptor-targeted therapy, have received ≥1 taxane-based therapy, and have prostate-specific antigen (PSA) progression per PCWG3 criteria. Four cohorts of patients will receive pamiparib 60 mg BID in 28-day cycles. Cohort 1 will include ~50 pts with CTC-HRD + +/- BRCA1/2 mut mCRPC with measurable metastatic disease; Cohort 2 will include ~30 pts with CTC-HRD + +/- BRCA1/2 mut mCRPC with bone-only disease; Cohorts 3 &amp; 4 will include ~20 pts with CTC-HRD -/unknown + BRCA1/2 mut mCRPC with measurable metastatic disease (Cohort 3), or bone-only disease (Cohort 4). Disease status will be assessed every 8 wks for 24 wks, then every 12 wks; PSA levels will be tested every 4 wks. Co-primary endpoints are radiographic ORR assessed by IRC (pts with measurable disease) and confirmed PSA response rate per PCWG3 criteria (pts +/- measurable disease). Secondary endpoints include ORR, time to PSA response/progression, duration of PSA response, time to symptomatic skeletal event, radiographic progression-free survival, overall survival, and safety. Clinical trial information: NCT03712930.
Evaluation of circulating tumor DNA (ctDNA) with respect to germline alterations in metastatic castrate resistant prostate cancer patients.
Authors: Peter Steinwald, Lynne Chapman, Bryce Raymon Christensen, Leta Ko, James Vu, Joshua Schiff, Lahiru Ranasinghe, Marcus Marie Moses, Patrick Cotogno, Charlotte Manogue, Jodi Lyn Layton, Brian E. Lewis, A. Oliver Sartor, Elisa Ledet
Journal: Journal of Clinical Oncology (2019)

254 Background: Circulating tumor-derived DNA (ctDNA) is an accessible method for characterizing tumoral alterations. We report ctDNA screenings of mCRPC patients (pts) who have had germline testing. Methods: Guardant360 (Guardant Health, Inc.) assesses ctDNA using sequencing to identify genomic alterations in 73 cancer-related genes. Alterations were categorized by type which included amplifications, deletions, frameshift mutations, insertions, missense mutations, splice mutations, truncations, and other. A total of 186 PCa pts in various stages of therapy had both ctDNA and germline DNA tested. Results: Of the 186 pts tested for germline mutations, 26 (14%) were germline positive. The most common germline mutation was BRCA2 with 12 (46%) pts, followed by ATM with 3 (11%). Of the total gene alterations were detected on ctDNA analysis of germline positive pts, with the most common genes being TP53 (n = 14/73, 19%), NF1 (n = 6/73, 8%), PIK3CA (n = 6/73, 8%), and BRCA2 (n = 5/73, 7%). Of the total gene alteration were detected on ctDNA analysis of germline negative pts, with the most common genes being TP53 (n = 94/588, 16%), AR (n = 90/588, 15%), EGFR (n = 31/588, 5%), and BRAF (n = 29/588, 5%). Germline negative pts showed had more amplifications (p = 0.008) while germline positive patients had more frameshift mutations (p = 0.025). Other alterations (deletion, missense, insertion, other, splicing, and truncating) were not significantly different. Missense mutations were the most prevalent type of gene alteration in germline negative (n = 306/609, 44%) and germline positive (n = 45/77, 48%), followed by amplifications (n = 210/609, 25% germline negative and n = 15/45, 18% germline positive). The median percent ctDNA values for missense mutations in germline negative and positive patients were 0.5% and 0.3% respectively. Of the germline positive pts, BRCA2 mutation was associated with the highest number of genes with alterations (n = 39), followed by RECQL4 (n = 8), ATM (n = 5), and MSH2 (n = 5). Conclusions: Germline positive pts had a higher number of frameshift mutations compared to germline negative pts. Additionally, pts with BRCA2 had the highest number of genes altered in ctDNA.
A Woman in Her 40s With Transient Neurological Symptoms, Migraine Headaches, and Hearing Loss
Authors: David A. Roshal, James P. Dunn, Duo Xu
Journal: JAMA Neurology (2019)

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F-actin dynamics regulates mammalian organ growth and cell fate maintenance
Authors: Arianna Pocaterra, Giulia Santinon, Patrizia Romani, Irene Brian, Andrea Dimitracopoulos, Andrea Ghisleni, Alejandro Carnicer-Lombarte, Mattia Forcato, Paola Braghetta, Marco Montagner, Francesca Galuppini, Mariaceleste Aragona, Gianmaria Pennelli, Silvio Bicciato, Nils Gauthier, Kristian Franze, Sirio Dupont
Journal: Journal of Hepatology (2019)
Venetoclax plus R- or G-CHOP in non-Hodgkin lymphoma: results from the CAVALLI phase 1b trial
Authors: Andrew D. Zelenetz, Gilles Salles, Kylie D. Mason, Carla Casulo, Steven Le Gouill, Laurie H. Sehn, Herve Tilly, Guillaume Cartron, Martine E. D. Chamuleau, Andre Goy, Constantine S. Tam, Pieternella J. Lugtenburg, Adam M. Petrich, Arijit Sinha, Divya Samineni, Sylvia Herter, Ellen Ingalla, Edith Szafer-Glusman, Christian Klein, Deepak Sampath, Martin Kornacker, Mehrdad Mobasher, Franck Morschhauser
Journal: Blood (2019)
3βHSD1 immunohistochemistry and <i>HSD3B1</i> genotype in prostate cancer.
Authors: JJ Haijing Zhang, Marlo Nicolas, Aimalie Hardaway, Kelsey Bohn, Daniel Hettel, Eric A. Klein, Nima Sharifi
Journal: Journal of Clinical Oncology (2019)

277 Background: 3β-hydroxysteroid dehydrogenase (3βHSD1), encoded by HSD3B1, catalyzes intratumoral androgen synthesis from adrenal precursors. The HSD3B1(1245A&gt;C) germline variant encodes a more stable enzyme that promotes increased DHT synthesis and more rapid clinical progression in men treated with androgen deprivation therapy (ADT). 3βHSD1 localization and expression in prostate tissue has not been rigorously characterized. We hypothesized that HSD3B1 homozygous variant genotype is associated with elevated 3βHSD1 immunoreactivity compared with wild-type (WT) genotype. Methods: In a pilot study, HSD3B1 genotypes were obtained from prostatectomy tissues of 30 patients with prostate cancer (10 WT, 10 heterozygous, and 10 homozygous variant). Following prostatectomy, tumor tissue with adjacent benign prostate was formalin-fixed and paraffin-embedded. Immunostaining for 3βHSD1 using a validated mouse monoclonal antibody was performed. Human placenta was used as a positive control. Immunostaining patterns and histology was qualitatively assessed by a GU pathologist. Immunoreactivity was quantitatively assessed using ImagePro7. Results: Qualitative IHC scoring localizes 3βHSD1 to epithelial cells in prostatic glands and urothelium, with faint muscle and stromal staining. 3βHSD1 was immunoreactive in 100% of prostates in both benign and malignant regions. When stratified by HSD3B1 genotype, the mean density/intensity was significantly greater for HSD3B1 homozygous variant prostate (670.10u) compared to heterozygous (174.69u) and WT (176.19u) (p=0.044). (Density/Intensity) per square micron demonstrated higher mean values for homozygous variant (35.79)&gt; heterozygous (28.67) &gt;WT (22.56) (p=0.52). Conclusions: These pilot data demonstrate differential tissue expression of 3βHSD1 according to HSD3B1 genotype: importantly, homozygous variant HSD3B1 (1245A&gt;C) specimen showed the most robust 3βHSD1 expression compared to heterozygous and WT prostates. These results explore the potential for 3βHSD1 as a prostate biomarker to predict aggressive disease.
Differential Effects of TLR1/2 and TLR2/6 Signaling on Normal and Premalignant Hematopoietic Stem and Progenitor Cells
Authors: Darlene A. Monlish, Zev J. Greenberg, Sima T. Bhatt, Dagmar Ralphs, John L. Keller, Lauren Bendesky, Laura G. Schuettpelz
Journal: Blood (2018)
Health literacy is a barrier to shared decision making in early prostate cancer (PCA) among African American (AA) men.
Authors: William Martin-Doyle, Christopher Paul Filson, Susan Regan, Quoc-Dien Trinh, Sierra Williams, Viraj A. Master, Kerry L. Kilbridge
Journal: Journal of Clinical Oncology (2019)

84 Background: ASCO, AUA, ASTRO and SUO endorse shared decision making for men with localized PCa. We explored treatment decisions among providers and their AA patients (pts) in a prospective cohort study at Grady Memorial Hospital and the Atlanta Veterans Administration Hospital. Methods: Following their visit, 18 providers documented the PCa treatment options they had discussed with 124 newly diagnosed, early-stage, African American PCa pts. At a subsequent visit, prior to choosing their cancer treatment, pts were asked to name the options they had discussed with their provider. Demographics were collected. Health literacy was measured using the Rapid Estimate of Adult Literacy in Medicine (REALM). Numeracy, comprehension of common PCa terms, and anatomic knowledge were assessed using published methods (Kilbridge K, et al. J Clin Oncol 27:2015-2021, 2009). Chi-square, t-tests and multivariate logistic regression were used to identify variables associated with correct understanding of treatment choices. Results: Just 23.4% of pts correctly understood their treatment options. In univariate analysis, only health literacy was statistically significantly associated with comprehension of PCa treatment options (p &lt; 0.05). In a multivariate logistic model adjusting for age, education, income, numeracy, comprehension of common PCa terms, and anatomic knowledge; health literacy remained the only significant predictor of pts’ comprehension of their treatment choices (OR 3.8, 95% CI 1.2-11.9, p = 0.021). Even among the 49 pts with the highest level of health literacy, only 34.7% correctly understood their cancer treatment options (compared to 16.0% among low literacy patients). Conclusions: Successful shared decision making requires pts to understand their treatment choices. Information presented by healthcare providers may be overwhelming for newly diagnosed pts, particularly those with lower health literacy. Our study suggests that even pts with the highest level of health literacy may need additional support to understand their PCa treatment options.
A phase I/II study of proxalutamide (GT0918), a potent androgen receptor blocker, in patients with mCRPC progressed after both hormonal therapy and chemotherapy.
Authors: Nicholas J. Vogelzang, Richard Levin, David T. Chu, Nashat Y. Gabrail, Luke T. Nordquist, Mark N. Stein, Harish P. Dave, Phoebe Zhang, Karl Zhou
Journal: Journal of Clinical Oncology (2019)

169 Background: GT0918 is a new chemical entity of androgen receptor (AR) blocker. A phase I/II study was conducted to identify dose-limiting toxicities (DLTs) and to assess safety, tolerability, and PK of GT0918 in pts with mCRPC who have progressed on standard of care (SoC) and experimental therapies in the United States. Methods: Patients (pts) with histologically confirmed mCRPC who had progressed after both hormonal therapy (abiraterone or/and enzalutamide) and chemotherapy (e.g., docetaxel) were eligible. GT0918 was administered once daily orally for 28 consecutive days, followed by a 7-day off-treatment period for PK analysis. The first 28-days on treatment (cycle 1) was defined as DLT period. Pts continued on receiving GT0918 thereafter until they experienced one of following events of intolerable toxicities, disease progression or withdrew consent. Results: 35 pts were enrolled to GT0918-US-1001 trial with 6 dose escalations of study drug defined in protocol: 50 mg (n = 3), 100 mg (n = 6), 200 mg (n = 6), 300 mg (n = 7), 400 mg (n = 7) and 500 mg (n = 6). All pts progressed on multiple lines of therapies including but limited to bicalutamide, abiraterone, enzalutamide, docetaxel, cabazitaxel, radium 223, sipuleucel T and pembrolizumab. No DLT was observed and MTD has not been reached. GT0918 related adverse events (AEs) were less than 10% and grade 1 or 2 as per CTCAE v4.03, including fatigue, nausea, dizziness, loss of appetite, back pain, hot flush, hypercholesterolemia, anemia, constipation, etc. Two events of grade 3 fatigue and one event of grade 4 elevated creatine kinase (CK) were reported. Stable disease by imaging scans at 24 weeks by dose group were; 1/50 mg, 1/100mg, and 4/400mg. Three pts on 500mg finished 3 cycles and continue on the treatment (as 10/15/18). PSA decreases were also seen among pts at 500mg dose level for 4 cycles. Conclusions: GT0918 administrated orally once a day is well tolerated and resulted in SD in late-stage pts. No DLT has occurred to date (at 500 mg) and dose escalation is planned to 600 mg or higher. Extended/Ph II trial will further evaluate safety and efficacy of GT0918 in mCRPC pts. Clinical trial information: NCT02826772.
Factors associated with potentially preventable oncology re-admissions (re-ADM).
Authors: Barry R. Meisenberg, Elizabeth Hahn, Madelaine Binner, David Edward Weng
Journal: Journal of Clinical Oncology (2015)

e17761 Background: 30 day re-ADM are associated with poor QOL and are being assessed as a measure of quality of care, with the consequence of possible financial penalties for hospitals. Previous work suggests 2-50% of re-ADM can be prevented with greater supportive care and communication. Methods: To determine potential preventability of re-ADM, 3 oncology specialists independently reviewed records from pts with re-ADM. To evaluate potential preventability, two reviewers applied criteria for standard care. A third reviewer evaluated the subset of re-ADM discordant between the 2 reviewers. Results: 72 non-planned 30 day re-ADM (69 pts) were identified (re-ADM rate of 23%) - 25 (35%) from skilled nursing facilities and 47 (65%) from home. 70 of 72 were re-ADM via the emergency department (ED). Of these ED re-ADM, 54 (77%) occurred during non-clinic hours. Both reviewers agreed that 18 (25%) were potentially preventable and that 29 (40%) were not likely preventable even with enhanced support. Of the remaining 25, a 3rdreviewer assessed 3 as potentially preventable, leading to a potential preventability rate of 21/ 72 (29%). Based on criteria proposed for this study, potential preventability causes among the 21 cases included: -Progressive symptoms in pts with late stage cancer who were not in hospice-16 -Insufficient communication between patient and clinic about progressive symptoms-15 -Complications of chemoRx in advanced disease pts.-5 - Lack of outpt service availability-5 -Febrile neutropenia re-ADM as candidates for outpt care- 4 Common causes of non-preventability (51 cases): -Progressive symptoms despite aggressive outpt supportive care -33 -Advanced symptoms of disease in pts not appropriate for hospice-22 -Complications of aggressive therapy in early stage disease-8 Conclusions: Re-ADM pts have high symptom burdens and are admitted via the ED during non-clinic times. Many re-ADM occurred despite intensive outpt care, with the majority occurring in patients where hospice care could have potentially prevented re-ADM. Determining potential preventability is highly subjective and relies upon assumptions about the appropriate level of active therapy, supportive care and communication that can be provided.