tbuckley/cabot-search huggingface dataset:
The effect of connexin 36 deletion on chemotherapy-induced peripheral neuropathy (CIPN).
Authors: Adam Sterman, Regina Hanstein, David C. Spray
Journal: Journal of Clinical Oncology (2016)

1 Background: CIPN is a debilitating side effect and dose limiting toxicity of many chemotherapeutic agents. CIPN induces pathological changes in dorsal root ganglia (DRG), leading to increased cross-talk among the glia that surround sensory neurons (Satellite Glial Cells, SGC’s) and between sensory neurons and their adjacent SGCs via gap junctions. Since Connexin 36 (Cx36) is the main neuronal gap junction protein, we investigated CIPN in mice with deletion of Cx36. Methods: To induce CIPN, mice were given two i.p. oxaliplatin (oxa) injections 2 days apart. Controls received saline (sal). We used transgenic mice, which were either heterozygous for Cx36 or complete Cx36 knockouts (Cx36 Het or Cx36 KO), and littermate controls (Cx36 wildtype), 6-14 per group. Tactile sensitivity of the hindpaws was assessed prior to and every week after injections for 4 weeks using von Frey filaments. The number of paw withdrawals to 10 stimulations with each filament and pain thresholds (corresponding to filament that elicits 8/10 responses) were recorded. Results: Oxa-injected wildtype mice had higher response rates to filaments compared to sal-injected controls (p &lt; 0.05), and lower tactile thresholds (at 9 days: sal 6.0±0.0g vs. oxa 1.9±0.5g, p &lt; 0.0001), indicating hypersensitivity. Compared with wildtype, mice lacking Cx36 (Cx36 KO) displayed significantly less tactile hypersensitivity after oxa (tactile threshold at 9 days: WT 1.9±0.5g vs. KO 4.0±0.4g, p &lt; 0.01), whereas oxa induced tactile hypersensitivity occurred in a similar fashion in Cx36 Het mice (tactile threshold at 9 days: WT 1.9±0.5g vs. Het 1.5±0.1g). At 9 days, there were fewer responses to filaments in oxa-injected Cx36 KO mice compared to oxa-injected wildtype mice (p &lt; 0.05), but not in oxa-injected Cx36 Het mice. Conclusions: We found that oxaliplatin induces transient CIPN, represented by tactile hypersensitivity, in wildtype mice. Deletion of the gap junction protein Cx36, as displayed in the Cx36 KO mice, resulted in significantly less CIPN. This is the first report that a neuronal gap junction protein may modulate pain sensitivity, and points to a new molecule (Cx36) as a potential novel target for CIPN therapy.
Using individual quality-of-life information as a clinical tool in patients with advanced cancer.
Authors: Veronica B McInerney, Dympna Waldron, Eileen Mannion
Journal: Journal of Clinical Oncology (2015)

91 Background: Use of quality of life information as a tool to aide decision making in routine clinical practice is uncommon. The Schedule of Evaluation for Individual Quality of Life Direct Weighting (SEIQoL DW) is a measurement tool that captures the multidimensionality and uniqueness of the individual allowing him/her to define areas of importance to their quality of life and to demonstrate its measure of importance. It was hypothesised that routine quality of life measurement of patients followed by graphical presentation of this information to the clinician, may bridge views of clinicians and patients to improve quality of life outcome. Methods: A randomised controlled trial of 65 patients receiving chemotherapy for advanced cancer was conducted to measure differences in perception of quality of life over 4 time-points of patients in the intervention group whose quality of life was reported to the clinical team compared to patients in the control group whose quality of life information was not reported to the clinical team .The primary objective was to compare quality of life outcome and examine differences between groups. Results: Findings demonstrated improvement in quality of life of all patients from baseline to time point 4. (P = > 0.05). The top four cues nominated by patients as important to their quality of life were health (92%), social activity (64%), keeping active (58%) and family support (43%).Closer analysis of these individual cues showed interesting differences between the intervention and control group. Participants in the intervention group demonstrated a 51% improvement in perception of health functioning compared to 19% improvement in perception of health functioning in the control group (p = 0.014).Paradoxically there was a decline in patient perception of functioning in other cues (social activity, keeping active and family support) with no significant difference between groups. Conclusions: Review of Individual QoL assessments by the clinican had a clinically significant impact on the patients reported measurement of ‘health’ thus suggesting that utilisation of QoL measurements by the clinician positively impacts the patient.
Changes in incidence of infant cancer: Analysis of SEER data 1992-2007.
Authors: G. A. Pereira, K. B. Ribeiro, C. Rodriguez-Galindo, L. G. Spector, A. L. Frazier
Journal: Journal of Clinical Oncology (2011)

9542 Background: Changes in the incidence of infant cancers may provide clues to key perinatal exposures that lead to malignant transformations in the vulnerable fetus. An increase in infant cancers from 1970-1990s has been previously reported, but trends over the last several decades have not been examined. Methods: Data reported to 13 registries of the National Cancer Institute’s Surveillance, Epidemiology and End Results Program (SEER-13) between 1992-2007 were used to assess incidence and trend of common primary cancers diagnosed in children between birth and one year of age (n=2153). Frequency, age-adjusted incidence rates and joinpoint regression results, including annual percent change (APC) in incidence rates (and 95% confidence intervals [95% CI]) were calculated using SEER*Stat, version 6.6.2 and Joinpoint Regression Program, version 3.4.3. Results: Between 1992-2007, the annual incidence rate of infant cancers was 234 cases/1,000,000; a non-significant increase in incidence rate was observed for infant cancers overall (APC 0.9%; 95% CI: -0.2%-2.1%). Notable trends were observed for several specific neoplasms including: soft tissue sarcomas (STS) (APC 8.1%; 95% CI: 4.3%, 12.1%), leukemias (APC 2.4%; 95% CI: 0.0%, 4.9%), and ependymomas and choroid plexus tumors (APC 8.7%; 95% CI: 2.4%, 15.4%). Extracranial and extragonadal germ cell tumors decreased among Hispanics (APC -2.7; 95% CI: -8.0%, -3.0%). The increase in STS was noted particularly in males (APC 10.3%; 95% CI: 5.1%, 15.7%) and in non-Hispanics (APC 8.9%; 95% CI: 5.4%, 12.5%) and was mainly attributable to an increase in incidence of fibrosarcoma, peripheral nerve and other fibrous sarcomas (APC 10.2%; 95%CI: 4.4%, 16.3%). Conclusions: The apparent increase in certain infant cancers over the last 16 years, specifically fibrosarcomas, ependymomas and choroid plexus tumors, warrants replication in other datasets; possible relationships to environmental causes should be explored.
Prevalence of detectable HBV DNA in cancer patients with resolved HBV infection (HBsAg (-) HBcAb (+) and its evolution after cytotoxic chemotherapy.
Authors: Taral Ramesh Shah, Huo Xiang Zheng, Pouyan Gohari, Maxim Shulimovich, Yiwu Huang, Yiqing Xu
Journal: Journal of Clinical Oncology (2014)

194 Background: Reactivation of hepatitis B virus (HBV) has been widely reported in HBsAg+ cancer patients undergoing chemotherapy, mainly in patients with lymphoma and breast cancer who received Rituximab and Adriamycin based chemotherapy. Reactivation of HBV has also been reported in a few patients who had previous exposure and resolved HBV infection (HBsAg-, HBcAb+). However there is no consensus as to whether prophylactic antiviral therapy should be used for this group, or whether the presence HBsAb plays a further protective role. Methods: We retrospectively and prospectively identified cancer patients undergoing chemotherapy who have HBsAg-, HBcAb+ status. Their HBV DNA levels and serial liver functions were followed. We aimed to evaluate the prevalence of detectable HBV DNA and HBV seroconversion rate after chemotherapy. Results: Between 11/2011 to 6/2013, 124 patients were screened and 51 (41%) had pretreatment HBsAg-, HBcAb+ status. Forty two (82%) patients were of Asian descent; 18 (35%) were males and 33 (65%) were females. Median age was 60 years with a range of 28 to 84 years. Forty seven patients (92%) received chemotherapy for solid malignancies while 4 (8%) received rituximab. Only one patient (2%) had detectable HBV DNA prior to treatment and received baraclude for prophylaxis. Fifteen patients (29%) had HBsAg-, HBcAb+, HBsAb- status, 36 (71%) had HBsAg-, HBcAb+, HBsAb+ status. Serial LFTs were followed over a median chemotherapy duration of 4 months (1 to 18 months). 2 had transient increase; 13 showed persistent but stable elevation related to tumor in the liver; 4 patients were tested for HBV DNA at LFT elevation and were negative. No patient had persistent or worsening LFT related to HBV reactivation. Conclusions: The prevalence of HBsAg-,HBcAb+ cancer patients is very high in South Brooklyn, NY, predominantly in Asian patients. Prevalence of detectable baseline HBV DNA is extremely low, even in isolated HbcAb positive patients and there was no seroconversion of HBV during chemotherapy, irrespective of HBsAb status. Prophylactic antiviral therapy is unnecessary.
Similarities in treatment (Tx) patterns and clinical outcomes (CO) in patients (pts) with metastatic colorectal cancer (mCRC) initially treated with FOLFOX/BV or FOLFIRI/BV: Results from ARIES, a bevacizumab (BV) observational study.
Authors: J. C. Bendell, T. S. Bekaii-Saab, A. L. Cohn, H. Hurwitz, M. Kozloff, H. Tezcan, S. Feng, E. D. Flick, A. Sing, A. Grothey
Journal: Journal of Clinical Oncology (2011)

480 Background: COs associated with varying Tx patterns in mCRC pts are poorly understood because patterns diverge from the randomized trials (RCT). The RCTs of BV (Avastin) plus chemotherapy (CT) in mCRC pts continued BV until progressive disease (PD), even if CT was stopped/changed. Some RCTs of BV+CT in mCRC show ∼50% of pts stopping Tx early for reasons other than PD with possible lessening of benefit. It is unclear if this is due to use of a particular CT regimen or other practice pattern. While the beneficial effect of post-PD BV Tx has been shown in ARIES (HR 0.52 BBP vs No BBP) [A Cohn, ASCO 2010], the effect of stopping BV or CT before PD is unclear. ARIES, a community based observational study with a large cohort of 1st line BV-treated mCRC pts, will assess the COs associated with different 1st line Tx patterns (BV and CT) based on real world practice. Methods: ARIES enrolled mCRC pts receiving first- or second-line CT+BV. No Tx regimens or assessments are protocol specified. Data are collected prospectively at baseline (BL) and quarterly. Analyses included first-line pts with PD. Tx patterns of pts initially treated with FOLFOX/BV or FOLFIRI/BV are described and preliminary COs (PFS and OS) are estimated from K-M curves. Tx duration is calculated from enrollment date. Results: As of 2/5/10, 1,548 first-line mCRC pts enrolled (median follow up = 21 m); 1,133 pts had PD. Of 1,133 pts with PD, most had FOLFOX/BV (63%) or FOLFIRI/BV (16%) as first CT. BL characteristics were similar, but the FOLFOX/BV group had more stage 4 pts (74%). Main reasons for stopping BV include AE, max benefit achieved and CT holiday. Tx patterns and COs are in the table. Conclusions: ARIES first-line mCRC pts treated with FOLFOX/BV or FOLFIRI/BV had similar Tx patterns and COs despite the common opinion that they may differ in tolerability and possibly effectiveness. Additional analyses will assess the impact of stopping BV and/or CT before PD. [Table: see text] [Table: see text]
SIRFLOX: Differences in site of first progression between mFOLFOX6 ± bevacizumab (bev) versus mFOLFOX6 ± bev + selective internal radiation therapy (SIRT) in first-line patients (pts) with metastatic colorectal cancer (mCRC).
Authors: Peter Gibbs, Volker Heinemann, Navesh K. Sharma, Michael P. N. Findlay, Jens Ricke, Marc Peeters, David Perez, Bridget Anne Robinson, Andrew Strickland, Tom Ferguson, Javier Rodriguez, Hendrik Kroening, Ido Wolf, Vinod Ganju, Euan Thomas Walpole, Eveline Boucher, Thomas E. Tichler, Val Gebski, Mark Van Buskirk, Guy A. Van Hazel
Journal: Journal of Clinical Oncology (2016)

637 Background: SIRFLOX, an international multi-centre open-label RCT in first-line pts with non-resectable, liver-only or liver-dominant mCRC, showed that compared to FOLFOX (± bev) chemotherapy alone [arm A] FOLFOX (± bev) plus SIRT using Y-90 resin microspheres [arm B] did not improve overall PFS (median 10.2 v 10.7 months arm A v B, HR: 0.93; 95% CI 0.77–1.12; p = 0.429). However, liver PFS by competing risk analysis was improved with the addition of SIRT (median 12.6 v 20.5 months in arm A v B, HR: 0.69; 95% CI 0.55–0.90; p = 0.002). The current analysis examines patterns of disease progression and potential impact on the primary study endpoint. Methods: Site and pattern (intra/extra-hepatic) of first progression, and whether progression was due to growth of existing lesions or the appearance of new lesions, was judged by an independent reader blinded to study arm. Results: From Oct 2006 to Apr 2013, 530 pts were randomised (arm A, n = 263; arm B, n = 267); 212 (40%) had extra-hepatic metastases at study entry; 292 (55%) were stratified to receive bev. As of 31 Jan 2015, the total number of patients with disease progression in arm A v B were 178 and 166, respectively. The site of first progression was more frequently in the liver (± other sites) in arm A v B (92.1% v 72.3%; p &lt; 0.001). Conversely, site of first progression was less frequent in the lung (± other sites) in arm A v B (19.1% v 42.8%; p &lt; 0.001). A higher proportion of first progression occurred in the liver alone in arm A v B (77.0% v 52.4%; p &lt; 0.001). Conversely, a lower proportion of first progression occurred only in non-liver sites, primarily lung, in arm A v B (7.9% v 47.7%; p &lt; 0.001). Of patients with first progression in the liver, a higher proportion occurred in existing liver lesions (± extrahepatic sites) in arm A v B (72.5% v48.2%; p &lt; 0.001). Conclusions: The addition of SIRT to FOLFOX chemotherapy alone (± bev) reduced the frequency at which first disease progression occurred in the liver. Where first progression did occur in the liver, the addition of SIRT led to this more frequently being due to the appearance of lesions not evident on baseline imaging. Clinical trial information: NCT00724503.
Significance of preoperative butyrylcholinesterase as an independent predictor of overall survival in patients with renal clear cell carcinoma treated with nephrectomy.
Authors: Takuya Koie, Hayato Yamamoto, Atsushi Imai, Shingo Hatakeyama, Takahiro Yoneyama, Yasuhiro Hashimoto, Chikara Ohyama
Journal: Journal of Clinical Oncology (2014)

458 Background: Prognostic factors for overall survival (OS) of the patients with clear cell renal cell carcinoma (cRCC) treated with nephrectomy are still not defined well. Butyrylcholinesterase (BChE) is an α-glycoprotein found in the nervous system and liver. Advanced cancer is a condition with mild to moderate inflammation and interacts with various degree of protein-energy malnutrition. In this study, we analyzed the potential preoperative prognostic significance of BChE in patients with cRCC undergoing nephrectomy. Methods: etween 1992 and 2013, we treated 551 patients with renal cell carcinoma. Of these 400 patients with cRCC who underwent radical or partial nephrectomy were enrolled. Serum BChE was routinely measured before operation in all patients. Covariates included age, gender, performance status (PS), preoperative laboratory data, clinical T stage, and distant metastasis status. Univariate analyses were performed using the Kaplan-Meier and log-rank methods. Multivariate analysis was performed using a Cox proportional hazard model. Univariate and multivariate analyses were performed to determine clinical factors that associated with OS. Results: Of these, 302 patients had an organ-confined disease (T1-2N0M0) and 56 patients had a distant metastasis (any T, any N, and M1). The median BChE level was 250U/L (normal range from 168 to 470U/L). The median follow-up period was 34 months. At the time of analysis, 26 patients (6.5%) had alive with recurrent cRCC and 38 patients (9.5%) had died from cRCC. The 3-year OS rate for our entire cohort of 400 patients was 88%. The 3-year OS rates were 89.3% and 77.7% in the BChE ≥100 and &lt;100U/L groups (p= 0.004). In the univariate analysis, PS, anemia, hypoalbuminemia, BChE, corrected calcium, C-reactive protein, and distant metastasis status were significantly associated with OS. Multivariate analysis revealed that BChE and distant metastasis status were significantly associated with OS. Conclusions: These data suggest a possible role of pre-operative BChE as an independent predictor of OS after nephrectomy for cRCC.
CD34+AC133+VEGFR-2+ Cells Are Primitive Hematopoietic Progenitors, Not Functional Endothelial Progenitor Cells.
Authors: Jamie Case, Laura E. Mead, Hilary A. White, Mohammad R. Saadatzadeh, Mervin C. Yoder, Laura S. Haneline, David A. Ingram
Journal: Blood (2006)
Hemoglobin A1c and Mortality in Older Adults With and Without Diabetes: Results From the National Health and Nutrition Examination Surveys (1988–2011)
Authors: Priya Palta, Elbert S. Huang, Rita R. Kalyani, Sherita H. Golden, Hsin-Chieh Yeh
Journal: Diabetes Care (2017)

OBJECTIVE Hemoglobin A1c (HbA1c) level has been associated with increased mortality in middle-aged populations. The optimal intensity of glucose control in older adults with diabetes remains uncertain. We sought to estimate the risk of mortality by HbA1c levels among older adults with and without diabetes. RESEARCH DESIGN AND METHODS We analyzed data from adults aged ≥65 years (n = 7,333) from the Third National Health and Nutrition Examination Survey (NHANES III) (1998–1994) and Continuous NHANES (1999–2004) and their linked mortality data (through December 2011). Cox proportional hazards models were used to examine the relationship of HbA1c with the risk of all-cause and cause-specific (cardiovascular disease [CVD], cancer, and non-CVD/noncancer) mortality, separately for adults with diabetes and without diabetes. RESULTS Over a median follow-up of 8.9 years, 4,729 participants died (1,262 from CVD, 850 from cancer, and 2,617 from non-CVD/noncancer causes). Compared with those with diagnosed diabetes and an HbA1c &amp;lt;6.5%, the hazard ratio (HR) for all-cause mortality was significantly greater for adults with diabetes with an HbA1c &amp;gt;8.0%. HRs were 1.6 (95% CI 1.02, 2.6) and 1.8 (95% CI 1.3, 2.6) for HbA1c 8.0–8.9% and ≥9.0%, respectively (P for trend &amp;lt;0.001). Participants with undiagnosed diabetes and HbA1c &amp;gt;6.5% had a 1.3 (95% CI 1.03, 1.8) times greater risk of all-cause mortality compared with participants without diabetes and HbA1c 5.0–5.6%. CONCLUSIONS An HbA1c &amp;gt;8.0% was associated with increased risk of all-cause and cause-specific mortality in older adults with diabetes. Our results support the idea that better glycemic control is important for reducing mortality; however, in light of the conflicting evidence base, there is also a need for individualized glycemic targets for older adults with diabetes depending on their demographics, duration of diabetes, and existing comorbidities.
Evaluation of the UCSF cancer of the prostate risk assessment for prediction of biochemical recurrence (CAPRA) to predict which patients need dose escalation in intermediate-risk disease.
Authors: Daniel Taussky, Vimal Krishnan, Jean-Paul Bahary, Thu-Van Nguyen-Huynh
Journal: Journal of Clinical Oncology (2013)

54 Background: The University of California, San Francisco (UCSF) Cancer of the Prostate Risk Assessment (CAPRA) is a validated preoperative index which predicts recurrence free survival and the risk of adverse pathological features after prostatectomy. We analyzed the value of the CAPRA score to predict which patients might benefit from dose escalation in a randomized dose-escalation trial for intermediate risk patients. Methods: We analyzed 119 patients with intermediate risk prostate cancer (Gleason ≤ 6 and PSA 10-20 or Gleason 7 and PSA &lt;10). Patients were randomized between external beam radiotherapy (EBRT) doses of either 70.2 Gy or 79.2 Gy (1.8 Gy per day). All patients had a follow up of at least 2 years. Biochemical failure (BF) was defined with the Phoenix definition. Difference between CAPRA groups was calculated using Kaplan-Meier method. Results: Twenty percent (24/119) had BF. Median time to BF was 60.5 months (1-102) and median follow up for patients without failure was 66 months (25-102). A CAPRA score of 0-2 (risk of recurrence 5y post prostatectomy &lt;10%) was present in 16%, a score of 3-5 (5y risk 18-26%) in 72% and CAPRA 6 (5y risk 37%) in 12%. Stratified according to the 3 CAPRA groups 0%, 20% and 50% ofpatients had a recurrence. The difference between the 3 groups was significant (p=0.019). When stratified according to treatment arm, differences remained significant (p=0.025). None of the patients with a CAPRA 0-2 had biochemical recurrence, even with 70.2 Gy only. When analyzing only patients with a CAPRA score of 3-5, patients in the treatment arm with 79.2 Gy, had less BF with 15% compared to 26% in the arm with 70.2 Gy (p=0.187). The 2 survival curves start to split at 5y of follow-up. Conclusions: The CAPRA score seems to be a promising, clinically easily applicable tool to predict for patients who might benefit from dose escalation. Patients with a CAPRA score of 0-2 do not seem to benefit from dose escalation, but there is a trend for a benefit in patients with a CAPRA 3-5. Clinical trial information: NCT00033631.
Measuring value in bundled payments for head and neck cancer.
Authors: Seohyun Lee, Tracy E. Spinks, Alexis B. Guzman, Randal S. Weber, Ehab Y. Hanna, Amy Clark Hessel, Beth Michelle Beadle, Kate A. Hutcheson, James Incalcaterra, Nancy M. Wood, Delrose Jones, Thomas W. Feeley
Journal: Journal of Clinical Oncology (2016)

11 Background: Value, defined as outcomes relative to costs, cannot be improved without rigorous long-term measurement. To assess value within a bundled payment pilot for head and neck cancer, we aim to generate timely, patient-centered outcomes and robust, near-real time financial tracking (Porter and Teisberg, Redefining health care. Creating value-based competition on results; Harvard Business School Press, 2006). Methods: Clinical and quality experts created an outcome measure set for head and neck cancer, using a three-tiered outcomes hierarchy from Michael Porter of Harvard Business School as a framework. Process measures were identified to evaluate compliance with standards of care. Data sources were verified and patient-reported outcomes were collected via a patient portal. A REDCap database was created to aggregate all longitudinal outcomes. The project managers and financial leaders identified key financial metrics to be tracked for enrolled patients. Outcomes and financial data were built into a dashboard to deliver timely, actionable information on value. Patients will be tracked for 2 years post-treatment completion. Results: 22 outcome measures and 6 process measures are being collected for all enrolled patients. Financial indicators, such as cumulative costs and fee-for-service payment vs. bundled payment, are being tracked for each patient. Currently, most outcomes and financial data are extracted manually. Implementation of a new electronic health record (EHR) should alleviate much of this administrative burden (Table). Conclusions: The project demonstrates the feasibility of value measurement for bundled payment. With provider and patient input, the outcome measures direct attention to what is important to patients and is actionable by clinicians. Additionally, near real-time financial tracking offers insights into the financial implications of this alternative payment model for cancer care. With automation via the EHR, this value measurement methodology can be scaled for other disease sites and additional payers. [Table: see text]