tbuckley/cabot-search huggingface dataset:
Gastrointestinal cancer risk in Irish hereditary breast ovarian cancer families.
Authors: Tomas G Lyons, Darragh S Gogarty, Michael P. Farrell, Naoise Maria Dorman, Andrew J Green, David J. Gallagher
Journal: Journal of Clinical Oncology (2013)

e12565 Background: Colorectal and breast cancer are linked in certain predisposition syndromes such as Cowden and Peutz-Jegers syndrome. Breast cancer risk also appears increased in certain Lynch Syndrome kindreds. Original reports suggested an increased risk of gastrointestinal malignancies in BRCA1 or 2 mutation carriers. Two large studies in Ashkenazi Jewish populations subsequently contradicted this evidence, although only the three founder mutations were included in these studies. We report the Irish experience of colorectal and gastro-oesophageal (GE) cancer in Irish hereditary breast ovarian cancer (HBOC) families. Methods: 104 HBOC families at two tertiary referral centres were reviewed for the presence of early onset gastrointestinal (GI) malignancies. The medical records of individuals with GI cancer were reviewed to determine carrier status. Clinical data including age at diagnosis, stage, treatment and outcome were extracted. Median age of diagnosis and outcome were compared among BRCA1/2 mutation carriers and non-carriers. Results: We identified 33 individuals with GI malignancies in 102 HBOC families (22 with colorectal, 11 with gastric). Definitive carrier status was available on 8 individuals. An additional 7 individuals were obligate carriers. Age at diagnosis ranged from 27-84 years (median=60). Median age of colorectal cancer diagnosis among carriers was 54 compared with 61 among non-carriers. Median age of gastric cancer diagnosis among carriers was 66 compared with 53 among non-carriers. Conclusions: Early onset colorectal cancer occurs in certain HBOC families and may be related to mutation status. No genotype-phenotype association was identified in this study. An additional 60 Irish HBOC families are being screened for GI malignancies and updated data will be presented at the meeting.
Regional analysis of a cohort compassionate-use program (CUP) and early access program (EAP) with cabazitaxel (Cbz) plus prednisone (P; Cbz + P) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel (D).
Authors: Zafar Malik, Giuseppe di Lorenzo, Sergio Bracarda, Alexandros Ardavanis, Mert Basaran, Phillip Parente, Wito de Schultz, Fred Saad, Inge van Oort, Winald R. Gerritsen, Luis M. Antón Aparicio, Geoffrey Matus, Simon Hitier, Axel Heidenreich, Amit Bahl
Journal: Journal of Clinical Oncology (2014)

242 Background: Cbz is an established second-line treatment for pts with mCRPC, having demonstrated an overall survival benefit (with P) vs mitoxantrone with P in the Phase III TROPIC trial. The global CUP (CABAZ_C_05005) and EAP (NCT01254279) (both funded by Sanofi) aimed to provide access to Cbz + P before commercial availability and to document safety in a real-world population. We present a regional analysis of interim data from the CUP and EAP. Methods: Expected total enrolment is 1,450 pts. Pts received Cbz 25 mg/m 2 IV Q3W + P 10 mg QD until disease progression (PD), death, unacceptable toxicity or physician/pt decision. Granulocyte colony-stimulating factor (G-CSF) was administered per ASCO guidelines. The cut-off date for this analysis was 30 May 2012. Results: Globally, 1,301 pts have been included from eight regions (Eastern Europe [EE], Western Europe [WE], Northern Europe [NE] and Southern Europe [SE]; Asia [As]; Canada [Ca]; Latin America [LA]; and Australia [Aus]). Key data by region are shown in the Table. Median age varied from 65 years (Ca) to 70 years (Aus, LA, SE). In pts who progressed after last D line, time from last D dose to last PD ranged from 2.3 months (EE, LA) to 6.6 months (Ca). G-CSF use (therapeutic or prophylactic) at Cycle 1 varied widely between regions, from 23% (WE) to 79% (As). Between 11% (LA) and 30% (NE) of patients received ≥10 cycles of Cbz. Conclusions: In this extensive, real-world CUP/EAP cohort of mCRPC pts, substantial regional variation was observed for baseline and on-treatment parameters, including time from last D dose to last PD and G-CSF use. The low proportion of patients receiving ≥10 cycles in LA, Ca and WE may result from a limit of 10 cycles of therapy in some centers. Clinical trial information: NCT01254279. [Table: see text]
病院外での心停止後、自発的循環が回復(ROSC)した患者でのアドレナリン濃度と蘇生後症候群との関係
Authors: Nishikawa K, Nagao K, Kikushima K, Watanabe K, Tachibana E, Mukohyama T, Tominaga Y, Tada K, Chiba N, Ishii M, Kasai A, Soga T, Matsuzaki M, Ikeda H, Tateda Y, Yagi T
Journal: Circulation (2007)
The Morbidity and Mortality Conference (MMC) in Oncology: A patient safety and root cause analysis (RCA)-driven approach at the Cleveland Clinic Taussig Cancer Institute (TCI).
Authors: Lindsey Martin Goodman, Machelle Moeller, Amy E. Guthrie, Marc A. Earl, Nathan A. Pennell, Timothy D. Gilligan, James Stevenson
Journal: Journal of Clinical Oncology (2014)

191 Background: MMC has been traditionally viewed as an educational tool. However, negative associations with MMC include emphasis on individual error and assigning blame, with little attention to improving patient safety and quality of care. MMC at the TCI has been designed to provide an opportunity to discuss MMC cases in an open, non-judgmental setting. Methods: Since September 2013, a monthly MMC, open to all caregivers, not just physicians, has been held as part of CME certified oncology grand rounds. Two cases are discussed per session and are obtained from nursing, pharmacy, and physician recommendation through the hospital Safety Event Reporting System or direct communication. Fellows investigate and present cases with patient and provider information de-identified to assure the discussion occurs in a blame-free setting. RCA is performed to determine action items. Process and safety improvements are recommended where applicable. Ongoing follow-up and improvement tracking is reported at future MMCs. The MMC governance committee, composed of the TCI quality officer, quality director, fellow representative, and a multi-disciplinary group of providers, meets quarterly to review cases and follow up action items under the guidance of the TCI MMC charter. The MMC governance committee reports to the TCI Quality Steering Committee. Results: Cases reviewed to date include chemotherapy dosing/administration errors (23%), hospital acquired medical complications (31%), communication breakdown between caregivers (15%), and end of life care (31%). An average of 3.5 action items has resulted from each case with 75% addressed within 90 days. Physician attendance is 59% higher and 23% more physicians report that they are very likely to change their practice behaviors from MMC than other grand rounds presentations. Conclusions: A patient safety driven MMC, delivered in an open setting, can be an effective tool to improve quality of care and caregiver communication in a large academic cancer center. High provider attendance and survey feedback reflects engagement in the process and will be essential to sustaining a meaningful and productive MMC.
Daily rounds on inpatient oncology floor by inpatient hospitalist oncologist and reduced length of stay.
Authors: Sabeen Fatima Mekan, Dan Loen, George Raptis, Daniel R. Budman
Journal: Journal of Clinical Oncology (2014)

228 Background: Hospitalist services have expanded recently resulting in improved patient care and reduced length of stay compared with traditional inpatient services. Methods: We implemented an inpatient oncology hospitalist service with consistent daily rounding by the same team on all patients on the oncology floor in July 2012 and compared the impact on inpatient length of stay (LOS), inpatient mortality, cost saving, 30 day readmission rate and patient satisfaction scores before and after. Data was collected from hospital administration from patient medical and billing records. Results: The changes had an immediate effect on LOS which reduced from 7.30 days to 6.38 days over the next 6 months and further trended down to 6.20 over the next 11 months. Total number of discharges increased from 839 from Jan-Jun 2012 to 947 in Jan-Jun 2013. Decrease in LOS occurred in almost all groups including patients with and without cancer. However, the greatest reduction occurred in patients who were admitted with primary diagnosis related to complications of their cancer from 11.2 days to 9.0 days from Jan-Jun 2012 to Jan-Jun 2013. Inpatient mortality decreased from 37 to 30 from Jan-Jun 2012 to Jan-Jun 2013 and discharges to hospice increased from 42 to 65 patients. The 30 day readmission rate increased slightly from 196 to 222 patients. The most common admission diagnoses remained relatively constant. The payer mix of the patients, administrative structure and staffing on the floor remained unchanged during this time period. Patient satisfaction measured by the overall Press-Ganey scores remained unchanged. Conclusions: Daily consistent rounding of inpatient hospitalist service had a significant positive impact on all patients especially patients admitted with oncologic diagnoses. It also resulted in decrease in inpatient mortality and increased the number of discharges to hospice without significant increase in readmission rate.
The DASH Study: A phase 1b study of dalantercept plus sorafenib in advanced hepatocellular carcinoma.
Authors: Ghassan K. Abou-Alfa, Rebecca A. Miksad, Martin Gutierrez, Mohamedtaki Abdulaziz Tejani, Manish Sharma, Weijing Sun, Charles A. Henderson, Ari David Baron, Olugbenga Olanrele Olowokure, R. Scott Pearsall, Dawn Wilson, Chris Korth, Matthew L. Sherman, Shuchi Sumant Pandya
Journal: Journal of Clinical Oncology (2015)

TPS495 Background: The activin receptor-like kinase (ALK1) pathway is a novel target in angiogenesis that promotes blood vessel maturation and stabilization. ALK1 binds to the ligand bone morphogenetic protein 9 (BMP9) which is overexpressed in hepatocellular carcinoma (HCC) compared to normal hepatocytes. Dalantercept is an ALK1 receptor fusion protein that binds BMP9 and acts as a ligand trap. Sorafenib, a multi-kinase and vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR TKI), is the standard therapy for advanced HCC. In a preclinical model of HCC, simultaneous blockade of ALK1 and VEGF signaling with dalantercept and sorafenib resulted in additive tumor growth inhibition. In a completed Phase 1 study in thirty-seven subjects with solid tumors, dalantercept monotherapy demonstrated preliminary anti-tumor activity and a safety profile that was generally non-overlapping with VEGFR TKIs. Methods: An open label, multi-center, dose escalating, phase 1b study to evaluate dalantercept plus sorafenib in subjects with advanced HCC is ongoing. The primary endpoint includes the evaluation of the safety and tolerability of dalantercept plus sorafenib and determination of the recommended phase 2 dose levels of the combination. Secondary endpoints include assessments of the pharmacokinetic profile of the combination, preliminary activity including response rate using RECIST 1.1 and time to progression, and pharmacodynamic biomarkers in the serum and tissue including ALK1 and BMP9 expression. In the first two cohorts of 3-6 subjects each, the dalantercept dose levels will be 0.6 and 0.9 mg/kg, respectively, administered subcutaneously (SC) every 3 weeks in combination with sorafenib 400 mg PO once daily. In cohort three, 3-6 subjects will receive dalantercept dose level 0.9 mg/kg SC every 3 weeks with sorafenib 400 mg PO twice daily. Patient safety data through day 22 will be evaluated prior to escalation to the next cohort. An expansion cohort will enroll 10-20 subjects at or below the maximum tolerated dose level. Key eligibility criteria: histologically confirmed advanced HCC, Child-Pugh A liver disease, ECOG performance status of 0-1, and no prior systemic therapy in the advanced setting. Clinical trial information: NCT02024087.
Patient and caregiver well-being: Observation of changing dyad over time.
Authors: Timothy S Sannes, Susan K Mikulich-Gilbertson, Teresa L Simoneau, Mark L Laudenslager
Journal: Journal of Clinical Oncology (2015)

89 Background: Allogeneic hematopoietic stem cell transplant (Allo-HSCT) is a particularly stressful time for patient and caregivers alike. As such, well-being within patient-caregivers dyads is highly correlated in previous studies. It is less clear how this dyadic relationship changes over the course of treatment and recovery. Methods: In these secondary analyses of a randomized clinical trial of psychoeducational support (5 time points across 12 months), partial correlations, adjusting for group assignment and age, tested the relationship between individual mental and physical summary scores of patients and caregivers. 117 Allo-HSCT patient and caregivers provided baseline data, with available data used at each subsequent timepoint. Quality of life was measured with the Short-Form Health Survey; divided into mental (MCS) and physical summary (PCS) scores. Results: Patients were primarily men (69.6% male; Mage=49.36; SD=13.04); caregivers were primarily female (78%;Mage=53.26;SD=12.34). Patient and caregivers’ MCS were significantly correlated at baseline (r=.23;p&lt;.05) and 4 weeks after consenting to study participation, (r=.26;p&lt;.01), whereas patients’ PCS scores were significantly correlated with caregivers’ MCS at 3 months (r=.26;p&lt;.05). At 6 months, the relationship between patient PCS and caregiver MCS was no longer significant (p=.51), whereas the relationship between patient and caregiver MCS re-emerged at 6 months (r=.32; p&lt;.05). In evaluating 6 month completers (N=84), the trend between patient-caregivers well-being displayed the same significant pattern at each timepoint. Conclusions: These data replicate significant relationships of mental well-being within patient-caregiver dyads in Allo-HSCT. This relationship shifts over time, in which caregiver mental well-being becomes related to patients’ physical functioning. These data underscore the importance of this dyadic relationship and deserve follow-up statistical approaches (e.g., covariation). Extending these relationships to clinical endpoints remains an area for future investigation. Funding: NIHCA126971(MLL); T32AG044296(TS): DA034604(SMG) and PCORI CE-1304-6208(MLL). Clinical trial information: NCT00833898.
What is the optimal management of Gleason score 7 (GS7) prostate cancer (PC) at biopsy? A comparison of disease control for prostatectomy (RP) versus radiation therapy (RT).
Authors: John Morgan Watkins, Patricia L. Watkins, Tarek A. Dufan, Nadim Koleilat
Journal: Journal of Clinical Oncology (2014)

250 Background: Optimal therapy for Gleason score 7 (GS7) prostate cancer (PC) remains to be defined, with consensus guidelines identifying both prostatectomy (RP) and radiation therapy (RT) as acceptable. The present investigation seeks to compare outcomes between these treatment approaches. Methods: Patients were retrospectively identified for inclusion by clinically localized disease, GS7, and a prostate-specific antigen (PSA) less than 30 at diagnosis. Comparison of demographic, tumor, staging, and outcome variables was performed. Disease recurrence was defined as per contemporary society guidelines. Kaplan-Meier method employed for disease control estimates. Results: Between 2003 and 2010, 267 patients were diagnosed with GS7 prostate cancer, of whom 207 were eligible for the current analysis (120 RP/87 RT). Excepting older age for RT patients (median age 73 vs. 62), the groups were well-balanced. For RP patients, 82 patients (60%) had at least one high-risk feature, of whom only four (5%) received adjuvant RT. For RT patients, 71 of patients (82%) received hormone therapy (median duration 6 months), and 48% (42) underwent external beam RT alone, 41% (36) brachytherapy (BT) alone, and 10% (9) external beam RT plus BT boost. At a median follow-up of 62.2 months (range, 13.1-136.6; with no difference between treatment groups), 64 patients had PSA relapse (51 RP/13 RT) and 15 had died (five of or with disease). Five-year disease-free and disease-specific survivals for RP versus RT were 55.4% versus 82.6% (p&lt;0.0001) and 97.6% versus 98.8% (p=NS), respectively. Conclusions: For GS7 prostate cancer patients, RT is associated with superior disease-free survival at 5 years when compared with RP alone. Whether this difference remains in the setting of appropriately employed adjuvant RT remains to be determined. No difference in survival endpoints was detected, though there were few events at 5 years.
St. Joseph Mercy Oakland Pink Ribbon Mammogram Program designed to address health-care disparities.
Authors: Rachel Norianne Sell, Mitchel Muhleman, Amy Kirby
Journal: Journal of Clinical Oncology (2015)

11 Background: Despite ongoing national efforts to promote state-mandated health care, such as the Affordable Health Care Act, many regions still struggle with high rates of uninsured and under-insured residents. Over 500,000 people have enrolled in the Healthy Michigan Plan, but premium payments are often prohibitively higher than the penalties for failing to obtain insurance. In Oakland County, 15% of adults remain uninsured and only 66.4% receive access to mammography screening. Developed in 2009, the St Joseph Mercy Oakland Pink Ribbon Mammogram Program takes a unique approach to addressing this issue, providing free breast cancer screening for women in Oakland County. Methods: Since its inception six years ago, the SJMO Pink Ribbon Program has served 806 Oakland County uninsured and under-insured women. This was made possible through the coordination of funding from the Pink Ribbon Trailblazers, a local grass-roots organization led by a breast cancer survivor, and St Joseph Mercy Oakland Hospital. Our program is unique, as women not only receive a free screening mammogram, but also a personalized breast cancer risk assessment and a clinical breast exam by a breast surgeon. The program also covers diagnostic mammogram and ultrasound if necessary. Women who need biopsy meet with the oncology financial navigator. Most women are enrolled in either the State of Michigan Title XV program/BCCCP, or Mercy Support, a charitable financial assistance program through the hospital. Women diagnosed with breast cancer either continue in Mercy Support or are enrolled in Medicaid. Results: We have found that despite the recent Affordable Health Care Act, demand for our program continues to increase annually. There continues to be a need for local communities to address health care disparities amongst lower income populations in Oakland County and throughout the nation. Conclusions: The purpose of this article is to describe the way that a local charitable organization, physician, and the hospital can come together to fund and provide continuity of care from screening, diagnosis, to treatment for low income women.
Integrated whole exome and RNA sequencing to reveal distinct genomic and transcriptomic landscape of upper tract urothelial carcinoma.
Authors: Bishoy Faltas, Rohan Bareja, Himisha Beltran, Joanna Cyrta, Manoj Ponadka Rai, Scott T. Tagawa, David M. Nanus, Juan Miguel Mosquera, Andrea Sboner, Douglas Scherr, Olivier Elemento, Brian D. Robinson, Mark A. Rubin
Journal: Journal of Clinical Oncology (2016)

379 Background: Upper tract urothelial carcinoma (UTUC) represents up to 10% of all urothelial carcinoma (UC). UTUC is a lethal malignancy, with nearly one half the patients dying within 5 years. Our objective was to understand the biological differences between UTUC and bladder UC.Methods: Fresh frozen chemotherapy-naïve primary tumors from nephroureterectomy cases and corresponding germline samples underwent whole exome sequencing (WES) and RNA sequencing (RNAseq). The Cancer Genome Atlas (TCGA) WES and RNAseq raw data was reanalyzed through our in-house bioinformatic pipeline to compare the mutational and transcriptomic landscape of UTUC to bladder UC. We evaluated the expression values for a set of 40 housekeeping genes between the two different datasets to exclude batch effects. We used gene set Enrichment Analysis (GSEA) to identify differentially enriched pathways in UTUC.Results: 17 tumors underwent WES, 20 RNAseq, with 11 analyzed for both WES and RNAseq. UTUC samples harbored several recurrent mutations including PIK3CA (4/17), FGFR3 (2/17), MLL2 (4/17), MLL3 (2/17), ATM 2/17). Three KRAS mutations were discovered in two patients (G12D, G12V and Q61H), which were confirmed by targeted sequencing. Frequent copy number alterations included CDKN2A/B deletions (3/17), BG4ALT3, SEMG1 and USP6 amplifications (2/17 each). GSEA analysis revealed significant enrichment of the KRAS signaling in UTUC whereas bladder UC showed an enrichment of genes involved in mTOR and E2F signaling. There were significant differences in the expression of several key DNA damage repair (DDR) pathway genes between the two entities including TP53, RAD51 and ERCC4 despite infrequent or absent mutations in these genes (q value 0.03 for DDR gene set). MSH5, a gene associated with cisplatin-resistance was the most highly ranked DDR overexpressed gene in UTUC compared to bladder UC (enrichment score = 0.8).Conclusions: This study generates a detailed genomic and transcriptomic profile of UTUC. RNAseq demonstrated a distinct pattern of DDR pathway expression in UTUC independent of genomic alterations; these findings may have important implications for platinum-based chemotherapy.
Obesity as a risk factor for cancer in adult urban Nigerians.
Authors: S. N. Akarolo-Anthony, C. A. Adebamowo
Journal: Journal of Clinical Oncology (2011)

e12020 Background: Developing countries are undergoing epidemiological transitions with increasing prevalence of non-communicable diseases (NCD) including cancers. In many African countries increasing prevalence of obesity makes this the second commonest risk factor for cancers after infections. In this study, we evaluated the prevalence of BMI in an urbanized Nigerian population. Methods: 1059 workers at a government office in Nigeria answered an interviewed administered questionnaire and had anthropometric characteristics measured in a study of body size, dietary energy intake and physical activity in fall of 2010. Results: The mean age (SD) of participants was 41.5 (9.3) years and mean BMI (SD) was 27.0 (4.9). 36% of our study population are overweight and 25% are obese. We found the mean BMI (SD) and proportion overweight/obese for age groups ≤20 years, 21-30, 31-40, 41-50, 51-60 and >60 years to be 21.7 (2.4) years, 10% / 0%; 24.0(3.5), 34% / 4.5%; 27.3(5.3), 32% / 32%; 27.7 (4.7), 42% / 31%; 27.5 (4.9), 39% / 28%; and 26.2 (3.7) 56% / 13%. Conclusions: Our result shows that the BMI of urbanized Nigerian adults increases with age. As obesity is a modifiable risk factor for NCD, adults should be encouraged to engage in lifestyle activities that will prevent obesity as a modality to reduce cancer incidence in Africa.