tbuckley/cabot-search huggingface dataset:
Genomic profiling of intrahepatic cholangiocarcinoma: Refining prognostic determinants and identifying therapeutic targets.
Authors: Timothy M. Pawlik, Darrell R. Borger, Yuhree Kim, David Cosgrove, Sorin Alexandrescu, Ryan Thomas Groeschl, Vikram Deshpande, James M. Lindberg, Cristina Ferrone, Christine Sempoux, Irinel Popescu, Todd W. Bauer, T. Clark Gamblin, Jean Francois Gigot, Robert Anders, Andrew X. Zhu
Journal: Journal of Clinical Oncology (2014)

210 Background: The molecular alterations that drive tumorigenesis in intrahepatic cholangiocarcinoma (ICC) remain poorly defined. We sought to define the incidence and prognostic significance of mutations associated with ICC among patients undergoing surgical resection. Methods: 138 patients who underwent resection at 6 centers in the United States and Europe were included in the cohort. Mutational profiling was performed using nucleic acids that were extracted from resected ICC tumor specimens; mutations were identified using a multiplexed mutational profiling platform. The frequency of mutations was ascertained and the impact on outcome determined. Results: Most patients had a solitary tumor (82%) and median tumor size was 6.0cm. Most patients had R0 resection (89%); 19% patients had N1 disease, while 15% had microscopic vascular invasion. A minority received adjuvant therapy (30%). The majority (55%) of patients had no genetic mutation identified. Among the 62 (45%) patients with a genetic mutation, only a small number of gene mutations were identified with a frequency of &gt;5%: IDH1 (17.4%), KRAS (8.7%), BRAF (5.8%), PIK3CA (5.1%). In contrast, other genetic mutations were identified in very low frequency: IDH2 (3.6%), NRAS (3.6%), TP53 (2.2%), MAP2K1 (1.5%), CTNNB1 (0.7%), and PTEN (0.7%). Approximately 7% of IDH1-mutant tumors were associated with a concurrent PIK3CA gene mutation, and to a much lower extent, a mutation in MAP2K1 (2%). No concurrent mutations in IDH1 and KRAS were noted. Compared with ICC tumors that had no identified mutation, IDH1-mutant tumors were more often bilateral (OR 3.46), while KRAS-mutant tumors were more likely to be associated with perineural invasion (OR 5.72)(both P&lt;0.05). While clinicopathological features such as tumor number and nodal status were associated with survival, no specific mutation was associated with prognosis. Conclusions: Most patients with resected ICC had no somatic mutation identified on multiplexed mutational profiling. IDH1 and KRAS were the most common mutations noted. While certain mutations were associated with ICC clinicopathological features, mutational status did not seemingly impact long-term prognosis.
Can systemic inflammation at diagnosis predict benefit from primary resection in metastatic colorectal cancer (mCRC)?
Authors: Ben Tran, Hui-Li Wong, Jayesh Desai, Jeanne Tie, Kathryn Maree Field, Suzanne Kosmider, Susie Bae, Shu Fen Wong, Peter Gibbs
Journal: Journal of Clinical Oncology (2013)

410 Background: In CRC, the tumor associated immune response can manifest as, (1) a good prognostic anti-tumor local (intra-tumoral) inflammatory response; or (2) a poor prognostic tumor promoting systemic inflammatory response. As suggested for renal cancer, the survival advantage associated with primary resection in mCRC patients (pts) might relate to modification of the tumor associated immune response, through reduction in tumor bulk and the resulting reduction in tumor promoting cytokines. We examine if systemic inflammation at diagnosis predicts benefit from primary resection in mCRC. Methods: A prospectively collected multi-disciplinary CRC database was used to explore clinicopathological data from pts diagnosed with de novo mCRC from Jan 2009 to Jul 2012. Evidence of systemic inflammation was defined as serum albumin (SA) &lt;35g/L or neutrophil-lymphocyte ratio (NLR) &gt;4 at diagnosis. Pts with primary resection &gt;42 days from diagnosis were excluded. Survival analyses utilised the Kaplan-Meier method and log-rank test. Results: Of 212 pts diagnosed with mCRC, 154 (72%) had de novo mCRC. 92 (60%) of these underwent primary resection, 62 (40%) had primary left in situ. SA was available in 141 pts, 71 (50%) had SA &lt;35g/L. NLR was available in all pts, 93 (60%) had NLR &gt;4. Primary resection was associated with superior overall survival (OS): median 32.5mo v 8.4mo (HR 0.29, p&lt;0.001). Systemic inflammation was associated with inferior OS using either SA &lt;35g/L (median 8.4mo v 19.8mo, HR 2.54, p&lt;0.001) or NLR &gt;4 (median 16.8 mo v 13.1 mo, HR 1.59, p=0.03). There was no difference in OS advantages associated with primary resection in pts with SA &lt;35g/L (HR 0.25, p&lt;0.001) compared to normal SA (HR 0.28, p&lt;0.001) at diagnosis; a non significant difference was observed for NLR ≤4 (HR 0.15, p&lt;0.001) compared to NLR &gt;4 (HR 0.42, p=0.001). Data regarding resolution of systemic inflammation following primary resection will be presented. Conclusions: Our study confirms the OS benefit from primary resection in mCRC and the adverse prognostic impact of systemic inflammation. Based on our current data, any benefit from primary tumour resection cannot be explained by an impact on the tumor associated immune response.
Measuring patient satisfaction in oncology.
Authors: Joseph Rodgers Steele, Ryan Kristopher Clarke, Stowe Shoemaker
Journal: Journal of Clinical Oncology (2012)

236 Background: Improving the patient experience has been an increasingly important quality improvement goal for most health care institutions; however, all patients are not equal. Within the oncology community exist a host of unique needs that must be identified, measured, and addressed. Commercially available questionnaires are too general and often non-diagnostic. The goal of our study was to develop a method to better identify, quantify, and address the needs of this population. Methods: Over 60 hours of in-depth qualitative interviews were conducted with a diverse population of patients (n=68), physicians (n=28), nurses. and technologists (n=33) at UT MD Anderson Cancer Center. A customized patient-experience questionnaire was created from the qualitative data obtained. A balanced incomplete block design was used so each patient answered only 60 questions, while the questionnaire contained over 85 questions. The questionnaire was administered via email to approximately 30,000 patients over one week time period. Results: A total of 4,179 patients completed the survey with average completion time of 24 minutes. A total of 6,909 opened the email invitation, 6,007 began the survey (a 69% completed/began response rate). Non-response bias was monitored via a short survey completed by 2,094 patients. Analysis revealed little difference between respondents and non-respondents. The survey results showed the following: (1) when relevant, a patient will complete a lengthy survey (2) a patient’s perception of their experience is directly related to how they perceive themselves (a number, customer, patient, or loved family member) (3) higher satisfaction is correlated with perception of a “unique” interaction or service (e.g. a visit with a sub-specialty oncologist versus one with a parking attendant). Conclusions: Proper survey techniques are necessary to identify, measure, and address the needs of oncology patients. Contrary to popular belief, patients are willing to complete lengthy questionnaires with little survey fatigue. Positive patient experiences correlate with patient perceptions of provider empathy, caring, and treatment similar to that of a “loved family member” as well as unique, health care services.
Near Real-Time Surveillance of U.S. Norovirus Outbreaks by the Norovirus Sentinel Testing and Tracking Network — United States, August 2009–July 2015
Authors: Minesh P. Shah, Mary E. Wikswo, Leslie Barclay, Anita Kambhampati, Kayoko Shioda, Umesh D. Parashar, Jan Vinjé, Aron J. Hall
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Norovirus is the leading cause of endemic and epidemic acute gastroenteritis in the United States (1). New variant strains of norovirus GII.4 emerge every 2-4 years (2-4) and are often associated with increased disease and health care visits (5-7). Since 2009, CDC has obtained epidemiologic data on norovirus outbreaks from state health departments through the National Outbreak Reporting System (NORS) (8) and laboratory data through CaliciNet (9). NORS is a web-based platform for reporting waterborne, foodborne, and enteric disease outbreaks of all etiologies, including norovirus, to CDC. CaliciNet, a nationwide electronic surveillance system of local and state public health and regulatory agency laboratories, collects genetic sequences of norovirus strains associated with gastroenteritis outbreaks. Because these two independent reporting systems contain complementary data, integration of NORS and CaliciNet records could provide valuable public health information about norovirus outbreaks. However, reporting lags and inconsistent identification codes in NORS and CaliciNet records have been an obstacle to developing an integrated surveillance system.
Phase II pharmacokinetic (PK) and pharmacodynamic (PD) study of OSI-7904L in previously untreated patients (pts) with advanced gastric or gastroesophageal junction cancer (G/GEJC)
Authors: S. J. Falk, A. Anthoney, M. Eatock, E. van Cutsem, J. Evans, J. Valle, J. Chick, D. Drolet, D. Ferry, J. Ajani
Journal: Journal of Clinical Oncology (2005)

4042 Background: OSI-7904L is a liposomal TS inhibitor with increased plasma residence and superior preclinical antitumor activity compared to parent drug or 5-FU. Methods: A 2-stage Simon design was used to evaluate the activity of OSI-7904L in G/GEJC, administered at 12 mg/m2 over 30 min every 21 days. Eligibility criteria included pathologically confirmed G/GEJC, ECOG PS 0–2, no prior chemo for advanced disease and ≥1 measurable lesion per RECIST. Secondary endpoints were safety, time to progression (TTP), survival and PK/ PD endpoints (TS genotype, 2’-dU and homocysteine). Results: Fifty of 53 enrolled pts were treated. Median age was 64 years (range 35–82), 62% were male and 90% had ECOG PS 0/1. Primary site was gastric in 80% of pts and GEJ in 20%. Two-thirds of pts had recurrent or metastatic disease; main sites of metastases were liver and lymph node. To date, 215 cycles have been given, median of 4/pt (range 1–12+). Eleven pts required dose reductions, mainly for skin toxicity (8 pts). Reductions and/or prophylaxis with dexamethasone ameliorated symptoms, permitting further treatment. Seven pts had cycle delays. The ORR was 15% (95% CI 6.2 - 28.3) with 7 PRs in 47 evaluable pts. Twenty-three pts (49%) had SD including several minor responses. Median TTP was 17 weeks. G3/4 neutropenia (14%) and thrombocytopenia (4%) were uncommon. The main G3/4 nonhematological toxicities were skin-related 20%, fatigue 19%, mucositis/stomatitis 16% and diarrhea 9%. PK data showed high interpatient variability and significantly higher AUC in pts with G3/4 toxicity and/or dose reductions. Response did not correlate with AUC. Baseline homocysteine did not influence cycle 1 toxicity. TS genotype and 2’-dU elevations as well as tumor biopsies from a subset of pts are being analyzed. Conclusions: OSI-7904L is active in advanced G/GEJC with ORR and TTP comparable with other single agents. Safety profile was favorable and dexamethasone premedication increased tolerability. Study was funded by OSI Pharmaceuticals. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration OSI OSI OSI OSI OSI
Risk of lymphoma in women with breast implants: Analysis of clinical studies.
Authors: J. A. Largent, M. Oefelein, H. M. Kaplan, T. Okerson, P. Boyle
Journal: Journal of Clinical Oncology (2011)

1588 Background: Large studies suggest the overall rate of lymphoma in women with breast implants is no greater than in the general population although recent clinical reports suggest a potential association between breast implants and the rare non-Hodgkin lymphoma: anaplastic large cell lymphoma (ALCL) of the breast. Methods: Observed cases of lymphoma reported in Allergan-sponsored breast implant clinical studies were compared to the numbers of cases expected based on incidence rates of lymphoma among women in the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) program, using standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). Results: In these clinical studies, a combined total of 28 observed cases of lymphoma were reported among 89,382 patients with 204,682 person-years of follow-up compared with 43 expected cases [SIR==0·65 (95% CI: 0·43-0·94) P==0·02]. SIRs were calculated stratifying by baseline cancer history: the risk was not significantly elevated either among women without a prior history of cancer [SIR ==0·70 (95% CI: 0·41-1·13) P==0·17], or women with a prior cancer history [SIR==0·79 (95% CI: 0·39-1·41) P==0·52]. SIRs were calculated by implant shell type and, again, there was no evidence of an increased risk either for textured shell implants [SIR==0·70 (95% CI: 0·40-1·13) P==0·16] or smooth shell implants [SIR==0·63 (95% CI: 0·33-1·10) P==0·12]. SEER reported 12 cases of primary breast ALCL in women between 1996-2007 without a previous history of cancer, producing an average annual incidence of 4·28 (95% CI: 3·51-5·05) per 100 million women in the United States – these women may or may not have had breast implants. In clinical studies, three ALCL cases were reported in women with breast implants and a history of breast cancer, yielding a crude incidence rate of 1·46 (95% CI: 0·30-4·3) per 100,000 patient-years. Conclusions: Large, carefully conducted clinical studies, based on over 89,000 subjects with over 200,000 person-years of follow-up, suggest no evidence of an increased risk of lymphoma among women who have received breast implants.
Impact of FDA guideline changes on treatment patterns and cost among cancer patients with anemia who do not respond to erythropoietin stimulating agents (ESAs).
Authors: Allicia C. Girvan, Yiu-Keung Lau, Gerhardt Pohl, Pamela Landsman-Blumberg, Nianwen Shi, Helen Varker, Lee Bowman
Journal: Journal of Clinical Oncology (2013)

97 Background: Due to emerging evidence in 2007, the FDA issued warnings in the labeling of ESAs regarding use among cancer patients. Subsequently, ASCO/ASH clinical practice guidelines were also updated to recommend discontinuation of ESAs in patients who fail to respond within 6-8 weeks. Methods: Patients with breast, head and neck, cervical, non-small cell lung cancer, or multiple myeloma initiating ESAs during 1/1/2003 - 7/1/2011 were identified from EMRs in the ACORN Data Warehouse (ACORN, Memphis TN). The study included those with at least 6-8 weeks of ESA use with documented hemoglobin (Hb) values. Following the ASCO/ASH guidelines, patients were defined as non-responders if Hb increased &lt; 1g/dL between baseline (≤ 28 days before ESA initiation) and response determination date (Hb assessment closest to day 56). Non-responders were further classified as continuers or discontinuers based on the presence of ESA treatment following determination of non-response. ESA use, adverse events, and costs were assessed using Chi-square test for comparisons. Results: A total of 1,198 patients were classified as non-responders (591 in pre-2007 and 607 in post-2007). ESA continuation rate was lower for post-2007 compared to pre-2007 (75% vs. 90%, p &lt; 0.0001). Conclusions: The percentage of patients continuing ESA treatment in the absence of Hb response has decreased since 2007, yet still remains high despite guideline recommendations. It is not clear from these data whether the increased risks and cost burden in these patients were offset by other positive outcomes. [Table: see text]
Patient-generated online survivorship care plans for adult survivors of childhood cancer: Feasibility and patient preferences.
Authors: Dava Szalda, Marilyn M. Schapira, Lisa Schwartz, Esther Kim, Carolyn Vachani, James M. Metz, Christine E. Hill-Kayser
Journal: Journal of Clinical Oncology (2016)

54 Background: With improvements in pediatric cancer treatment, the number of childhood cancer survivors is growing rapidly. Survivorship care plans (SCPs) can provide survivors with necessary information and resources to engage in risk-based follow-up care. Online patient motivated SCPs are promising for adult survivors of childhood cancer with multiple care transitions and the need for self-management outside clinical encounters. Methods: An existing online SCP generator (OncoLife) was adapted to create Smart Adult Living After Childhood Cancer plans for survivors of pediatric Acute Lymphoblastic Lymphoma (ALL) and Hodgkin’s Lymphoma (HL) by incorporating Children’s Oncology Group Long Term Follow-Up Guidelines into existing information technology logic. Results: Adult survivors (n = 20) of pediatric ALL or HL, registered to be seen in radiation oncology or survivorship clinic at the University of Pennsylvania, created an online SCP and completed an online survey. Approximately 80% of patients contacted consented and completed SCP indicating high acceptability; two-thirds (66%) completed the survey. Participants were a median of 35.5 years of age and of 26.5 years since diagnosis. They were 50% female, majority Caucasian (90%), 70% ALL and 30% HL survivors. SCPs took an average of 9 minutes 46 seconds to complete. The majority (95%) of respondents found the SCP generator easy to use, would recommend it to others (85%), and were satisfied with the amount of information received (80%). Ninety percent stated they intended to discuss their SCP with a healthcare provider. Only a third (35%) of survivors stated they had previously received a formal SCP. Seventy percent (70%) stated a written or online plan was the best way to convey health information between visits. Preferences for use of online SCP included: 70% wanting a treatment summary to complete their SCP and 50% wanting personal information to be saved for later use. Conclusions: Online patient-motivated SCPs are a feasible and acceptable way to deliver information to adult survivors of pediatric cancer about long term health risks. Further research into optimal methods for creation, use and health benefits of SCPs is warranted.
Basal Glucose Can Be Controlled, but the Prandial Problem Persists—It’s the Next Target!
Authors: Matthew C. Riddle
Journal: Diabetes Care (2017)

Both basal and postprandial elevations contribute to the hyperglycemic exposure of diabetes, but current therapies are mainly effective in controlling the basal component. Inability to control postprandial hyperglycemia limits success in maintaining overall glycemic control beyond the first 5 to 10 years after diagnosis, and it is also related to the weight gain that is common during insulin therapy. The “prandial problem”—comprising abnormalities of glucose and other metabolites, weight gain, and risk of hypoglycemia—deserves more attention. Several approaches to prandial abnormalities have recently been studied, but the patient populations for which they are best suited and the best ways of using them remain incompletely defined. Encouragingly, several proof-of-concept studies suggest that short-acting glucagon-like peptide 1 agonists or the amylin agonist pramlintide can be very effective in controlling postprandial hyperglycemia in type 2 diabetes in specific settings. This article reviews these topics and proposes that a greater proportion of available resources be directed to basic and clinical research on the prandial problem.
Gender disparities in colorectal cancer screening.
Authors: S. Yager, W. Y. Cheung
Journal: Journal of Clinical Oncology (2011)

1544 Background: Prior research suggests that recurrence and survival from colorectal cancer are worse in men than in women, but the causes for this disparity are as yet unclear. Our aims were to 1) assess for gender differences in colorectal cancer screening (CRCS) as a potential cause for the male-female disparities in colorectal cancer outcomes and 2) examine the impact of income, education and insurance status on gender differences in CRCS. Methods: Screening-eligible patients were identified from the US California Health Interview Survey. Up-to-date CRCS was defined as a fecal occult blood test within the past 2 years, a flexible sigmoidoscopy within 5 years, or a colonoscopy within 10 years. Logistic regression models were constructed to evaluate the relationship between gender and CRCS while controlling for other clinical factors, such as age, race, smoking history, marital status and health services use. Stratified analyses based on ‘health care access’ as measured by self-reported income (low vs. high), education (< highschool vs. > highschool), and health insurance status (insured vs. uninsured) were performed to determine if gender differences were modified by these parameters. Results: In total, 11,260 men and 17,705 women were identified: mean age was 65 and 66 years, respectively, and 63% were White in both genders. In the entire cohort, only about two-thirds of men and women reported undergoing up-to-date CRCS. In multivariate analyses, advanced age, White race, urban residence, non-smokers, married and those who visited their physicians frequently were more likely to receive CRCS (all p<0.001). When compared to men, women had decreased odds of CRCS (OR 0.88, 95% CI 0.82-0.94, p<0.001), after adjusting for potential confounders. Stratified analyses indicated that gender disparities in CRCS persisted even among the insured, educated, and high income earners. Conclusions: Women are less likely to undergo CRCS when compared to men. Gender-specific interventions that raise awareness about preventive care may be more effective in optimizing CRCS than conventional strategies aimed at improving health care access. The observation that colorectal cancer outcomes are worse in men than in women is unlikely to be explained by gender disparities in CRCS.