tbuckley/cabot-search huggingface dataset:
Are there geographic differences in the outcome of patients (pts) with metastatic renal cell carcinoma (mRCC) treated with sunitinib (su)?
Authors: Daniel Keizman, Maya Ish-Shalom, Natalie Maimon, Maya Gottfried, Roberto Pili, Hans J. Hammers, Mario A. Eisenberger, Victoria J. Sinibaldi, Ben Boursi, Rony Weitzen, Henry Hayat, Avivit Peer, Avivit Neumann, Svetlana Kovel, Avishay Sella, Wilmosh Mermershtain, Keren Rouvinov, Raanan Berger, Michael Anthony Carducci
Journal: Journal of Clinical Oncology (2013)

e15598 Background: Geographic differences in the outcome of pts have been described in various cancers. The VEGFR inhibitor su is a standard treatment (tx) for mRCC. The effect of geographic differences on the outcome of su tx in mRCC is poorly defined. Aims: To study the effect of geographic differences on outcome of su tx in mRCC. Methods: We performed an international multicentre retrospective study of unselected cohort of 275 mRCC pts, who were treated with su from 2004 to 2012 in 7 centers across the US and Middle East (ME; Israel). Clinicopathologic and prognostic factors, and tx outcome were compared between US (n=133) and ME (n=142) pts. Chi-square and Fisher's exact tests were used to compare categorical variables, and two-sample t-test was used to compare continuous endpoints. Progression free survival (PFS) and overall survival (OS) were determined by Cox regression. Results: Median age was 61 (US) vs 65 (ME, p=0.01). The groups were balanced regarding gender, Heng risk, past nephrectomy, RCC histology, presence of ≥ 2 metastatic sites, lung/liver/bone metastasis, use of angiotensin system inhibitors (ASI), prior cytokines/ targeted txt, su induced HTN, and su dose reduction/tx interruption secondary to side effects. The incidence of active smokers (28% vs 15%, p=0.01), bisphosphonates users (23% vs 13%, p=0.03) and pts with pre-tx neutrophil to lymphocyte ratio (NLR) ≤ 3 (63% vs 49%, p=0.04) was higher among ME pts. In US vs ME pts, objective response was partial response/stable disease 77% (n=102) vs 79% (n=112), and progressive disease at first imaging evaluation within the first 3 months (mos) 23% (n=31) vs 21% (n=30) (p=0.77, OR 1.1). Median PFS was 8 vs 12 mos (HR=1.8, p&lt;0.0001), and median OS 21 vs 22 mos (HR=0.94, p=0.9) in US vs ME pts. Factors associated with PFS in multivariate analysis of the entire cohort (n=275) were geographic location (US vs ME), Heng risk, RCC histology, su induced HTN, ASI use, pre-tx NLR, and smoking status. Conclusions: Geographic differences in clinicopathologic factors and PFS of pts with mRCC treated with su may exist. This should be further investigated, and if validated, applied in clinical practice and clinical trials.
Costs and utilization of oncology health care services at the end of life.
Authors: B. Chastek, C. R. Harley, J. D. Kallich, L. N. Newcomer, C. J. Paoli, A. Teitelbaum
Journal: Journal of Clinical Oncology (2011)

6067 Background: With rising health care costs in the US, clearly defined end of life (EOL) cancer costs are needed to help health administrators proactively manage this important care. Objective: Examine EOL healthcare resource utilization and costs among oncology patients in a US commercial insurance population. Methods: A retrospective claims database was used to analyze oncology EOL health care costs. Included patients had: a medical claim with a cancer diagnosis from 7/1/2002 to 12/31/2009, death on or before 12/31/2009, continuous enrollment with both medical and pharmacy benefits from cancer diagnosis until death, ≥180 follow-up days from diagnosis to death, and active cancer in the last 6 months before death (MBD). Death was captured from facility discharge codes and SSN death files. Costs were determined by summing paid amounts on all services utilized within the last 6 MBD: acute cancer-related inpatient (IP) stays, cancer-related hospice care, chemotherapy and related care (defined as ESAs and G-CSFs), radiation, cancer-related office or emergency room visits, cancer-related outpatient (OP) services and other services with a cancer diagnosis. Results: 28,530 patients met inclusion criteria. Mean total cancer-related costs over the last 6 MBD were $74,212 (SD: $112,740; acute IP: $40,702 [55%]; OP: $30,254 [41%]; hospice $3,256 [4%]). Conclusions: Oncology costs increase in the last 6 MBD with a sharp rise in cost as patients approach the last MBD. OP services and chemotherapy contribute little to overall cost during the last month of life. And even though hospice costs increase nearly 100-fold over the last 6 MBD, IP costs are the major contributor to the overall rise in total cost. Health care administrators should focus on IP care as the target for rising costs in oncology EoL care. Mean total cost Mean IP cost Mean hospice cost Mean OP service cost Mean OP chemo cost 6th MBD $7,834 $1,785 [23%] $28 [0%] $3,849 [49%] $2,172 [28%] 5th MBD $9,230 $3,269 [35%] $61 [1%] $3,751 [41%] $2,149 [23%] 4th MBD $10,051 $4,087 [41%] $95 [1%] $3,762 [37%] $2,107 [21%] 3rd MBD $10,362 $4,646 [45%] $173 [2%] $3,692 [35%] $1,852 [18%] 2nd MBD $11,469 $6,356 [55%] $435 [4%] $3,242 [28%] $1,437 [13%] Last MBD $25,261 $20,559 [81%] $2464 [10%] $1,632 [6%] $606 [3%]
Physician preferences and knowledge gaps regarding the care of childhood cancer survivors: A survey of the American Academy of Family Physicians (AAFP).
Authors: T. O. Henderson, P. C. Nathan, M. Kigin, F. J. Hlubocky, K. Wroblewski, T. V. Stewart, J. M. Galliher, K. C. Oeffinger, C. Daugherty
Journal: Journal of Clinical Oncology (2011)

9128 Background: Little is known about primary care physicians’ attitudes and knowledge regarding the health and long term follow-up (LTFU) of childhood cancer survivors (CCS). We sought to obtain family physicians’ (FPs) self-reported preferences and knowledge regarding this population. Methods: Following a pre-notification letter, surveys with a $2 bill were mailed to 1520 physicians from the AAFP membership directory in November 2010. A second mailing to non-responders is ongoing. Results: To date, 529 FPs have responded (35% response rate). Respondents have practiced a median of 25 years and see a median of 80 patients/week. In the last five years, 63% had seen at least one CCS in their practice; about half (54%) report almost never receiving a treatment summary. Among 3 specific cancer types, respondents’ discomfort in caring for CCS (1 = very uncomfortable; 7 = very comfortable) was greatest for osteosarcoma survivors (3.2 ± 1.7), less with ALL survivors (3.3 ± 1.7), and least with Hodgkin lymphoma (HL) survivors (mean ± SD 3.6 ± 1.7). The majority (82%) prefer to care for CCS in consultation with a cancer center based physician and/or LTFU clinic. A vignette of a 29-year-old female treated for HL with mantle radiation at age 16 was provided, participants were asked a series of follow-up monitoring questions. Concordance of responses to the Children’s Oncology Group LTFU Guidelines was: breast cancer surveillance, 18%; cardiac surveillance; 10%, and thyroid surveillance, 71%. Only 3% were concordant with all three of these questions. Concordance with breast cancer and cardiac questions was associated with reported familiarity with guidelines (OR=3.49, 95% CI 1.79-6.78; OR=3.73, 95% CI 1.73-8.04, respectively). In describing what would be most useful to care for CCS (1=not at all useful; 5=very useful), among 11 options, FPs reported the most preferred were access to LTFU guidelines (4.7 ± 0.6) and a patient-specific care plan (4.7 ± 0.6). Conclusions: While the majority of FPs are willing to follow CCS, they express some discomfort with this care, appear unfamiliar with the available LTFU guidelines and prefer to follow patients in collaboration with a cancer center.
Implementation of a prospective screening tool for breast cancer clinical trial eligibility at an NCI designated cancer center.
Authors: K. H. Lethert, S. K. Cheng, D. J. Nauman, D. M. Dilts, A. Sandler, S. Y. Chui
Journal: Journal of Clinical Oncology (2011)

6052 Background: Enrollment of breast cancer patients (pts) in clinical trials (CTs) remains suboptimal for many cancer centers. Prospective screening logs assist with pt demographic characterization to augment CT enrollment and design. Methods: We implemented a comprehensive pt screening log for prospective review of every new and established pt visit at the OHSU Knight Cancer Institute Breast Cancer Clinic from September 2009 to September 2010. Pt data collection and screening for CT eligibility was conducted on a real-time basis. Results: 563 pts were seen over 1,904 pt visits. Pt demographics: median age=57; Caucasian=86%; early-stage=83%, metastatic=17%; ER-positive=80%; HER2-positive=19%; triple-negative=12%. 41% of pts were newly diagnosed early-stage; and 17% were new or established metastatic disease. These pts represent the majority of pts targeted by CTs. 12.9% of these “Target pts” enrolled on CT: 7.1% on first visit and 5.8% on subsequent visits through monitoring of the screening log (table). Pts initially identified as ineligible for CT, but later enrolled on subsequent visits accounted for 45% of CT enrollment. Currently 28% of our established pts are monitored for clinical status change that could lead to CT eligibility. In addition, screening logs have identified specific pt cohorts lacking CT opportunities. Our triple-negative population (12% of all pts) and untreated metastatic population with bone-only metastases (58% of metastatic pts) had no CTs available during the study period. Conclusions: The use of prospective screening logs to actively monitor pts for a clinical status change identified 45% of our breast cancer CT enrollment. Even in a busy practice, prospective screening logs are a feasible way to follow an evolving breast cancer population. They can improve identification of CT eligibility by providing detailed, intensive screening and monitoring. They also highlight pt populations lacking CT representation. Via these mechanisms, prospective screening logs can ideally increase subsequent CT enrollment. First visit Subsequent visits Overall Target pts (n, % total) 167 (51.4%) 158 (48.6%) 325 Enrolled (n, % total) 23 (7.1%) 19 (5.8%) 42 (12.9%)
Six single-nucleotide polymorphisms in apoptotic genes and chemotherapy outcome in lung cancer patients
Authors: L. F. Knöfel, G. Werle-Schneider, H. Dally, P. J. Müller, L. Edler, H. Bartsch, C. P. Heussel, M. Thomas, A. Risch
Journal: Journal of Clinical Oncology (2008)

3598 Background: Identification of genetic polymorphisms which influence chemotherapy outcome may help towards individually optimised therapy. We therefore investigated the influence of six single nucleotide polymorphisms (SNPs) in four apoptosis relevant genes on chemotherapy outcome in lung cancer patients. FAS: rs2234767, rs1800682, rs2234768, BAX: rs4645878, BCL- 2: rs2279115 and BCL-x: rs6121172. All SNPs were chosen on the basis of a known or suspected phenotypic effect. Methods: Using RECIST criteria response of 424 Caucasian primary lung cancer patients was assessed after the second cycle of chemotherapy. 97 of these patients were evaluated by clinically indicated CT. DNA isolated from peripheral blood lymphocytes obtained before start of chemotherapy was genotyped using PCR followed by fluorescence-based melting curve and restriction fragment length polymorphism analysis. Genotype frequencies were compared in responders (complete or partial remission) and non-responders (stable or progressive disease). For variant allele carriers, odds ratios (ORs) and 95% confidence intervals (CI) for the risk of being a non-responder were calculated by logistic regression for all lung cancer patients and in the subgroups SCLC (n=192) and NSCLC (n=232). For survival analyses the median follow-up time was 324 days. Results: In the group of all lung cancer patients as well as the subgroups none of the polymorphisms above modified response statistically significant. For all lung cancer patients rs2234768 showed a non-significantly better chemotherapy response (OR 0.65; CI 0.41–1.04). This effect was more pronounced in SCLC patients (OR 0.37; CI 0.14–1.02) than in NSCLC patients (OR 0.72 CI 0.4–1.3). Rs2236767 showed improved response in SCLC (OR 0.45; CI 0.19–1.11) but reduced response in NSCLC (OR 1.29; CI 0.70–2.39). Conclusions: Our data suggest an effect of rs2234768 and rs2234767 on chemotherapy response in lung cancer patients. In contrast to its supposed effect rs2234768 variant allele carriers had better chemotherapy response. Interestingly, rs2236767 may exert its effects depending on lung cancer histology. Funded in part by the Deutsche Krebshilfe and an DKFZ- intramural grant to L.F.K. No significant financial relationships to disclose.
The role of NeuroD1 in the upregulation of SMYD3 by HBx.
Authors: Junyao Xu, Qingqi Hong, Chuanchao He, Jie Wang
Journal: Journal of Clinical Oncology (2012)

183 Background: SET and MYND Domain-Containing Protein 3 (SMYD3) is frequently overexpressed in hepatocellular carcinoma (HCC) exhibiting increased malignant phenotypes. It has also been known that the hepatitis B virus x protein (HBx) is strongly associated with HCC development and progression. Although overexpression of both proteins is related to HCC, the relationship between the two has not been well studied. Methods: Immunohistochemical staining was used to detect the expression of HBx and SMYD3 in HCC tumor tissues. HBx gene transfection, RNAi, and histone methyltransferase(H3-K4) activity assay were performed to reveal the transcrpitionally activation of HBx on functional SMYD3 gene expression. Chromatin immunoprecipitation (ChIP), Co-immunoprecipitation (Co-IP), Electrophoretic mobility shift assay (EMSA) were applied to investigate the underlying mechanism. Dual-luciferase reporter assay was used to search for the HBx responsive cis-element of SMYD3 gene. Results: Immunohistochemistry identified the positive correlation between HBx and SMYD3 expression in 42 HCC tissues. Up-regulation of HBx on SMYD3 expression was validated through experiments involving overexpression or knock-down of HBx in different HCC cell lines. And up-regulated SMYD3 is functionally active as histone methyltransferase. Next we found that HBx transcriptionally regulated SMYD3 gene expression by interacting with RNA polymerase IIand altering its binding site to a proximal promoter region(SD2) from a distant promoter region(SD6) of SMYD3. Truncated and mutant reporter assays revealed that the cis-element mapped in -178~-203bp in SMYD3 promotor is responsive for HBx-transactivation. And this 25bp cis-element contains a E-box 3 unit, which is a binding site for the transcriptional factor Neurogenic differentiation 1(NeuroD1). EMSA and Chip showed that HBx increased NeuroD1 binding to SMYD3 proximal promotor, however transcient expression of antisense NeuroD1 abolished HBx-induced SMYD3 expression. Conclusions: HBx transcriptionally up-regulates SMYD3 and that this process is mediated by NeuroD1 through binding to the E-box 3 site of SMYD3 promotor.
A study of the recurrence score by the 21-gene signature assay as a predictor of clinical response to neoadjuvant exemestane for 24 weeks in estrogen-receptor-positive breast cancer.
Authors: N. Masuda, M. Toi, T. Ueno, T. Yamanaka, S. Saji, K. Kuroi, N. Sato, H. Takei, Y. Yamamoto, S. Ohno, H. Yamashita, K. Hisamatsu, K. Aogi, H. Iwata, S. Saji, H. Sasano
Journal: Journal of Clinical Oncology (2011)

558 Background: Exemestane (EXE) is a steroidal aromatase inhibitor, one of the key drugs for postmenopausal ER-positive breast cancer patients (pts). We have reported that 24 wks neoadjuvant treatment of EXE has shown attractive response with sufficient safety and tolerability from multicenter phase II trial (JFMC34-0601; Toi M, et al. Cancer Science, 2011). The additional translational investigations were performed to find biomarkers that might be recommended for individualizing treatment in the neoadjuvant setting. This exploratory study was conducted to investigate the clinical usefulness of the 21-gene signature (OncotypeDX) for prediction of response to neo-EXE therapy. Methods: We tested whether the Recurrence Score (RS) by the 21-gene signature determined on core biopsy specimen at baseline would correlate with clinical objective response rate (ORR) in pts who were enrolled in the JFMC34-0601 trial. Postmenopausal pts over 55-yrs-old were eligible with confirmed Stage II or IIIA invasive breast cancer and ER-positive status. Results: Of 116 pts registered between 2006 and 2008, RS was obtained for 64 pts with adequate sufficient tissue. The median age and tumor size were 64 yrs (range, 56-77) and 27 mm (15-58). There were 47/15/2 pts for stage IIA/IIB/III and 2/50/12 pts for HER2-positive/negative/equivocal. The numbers of pts in the low, intermediate, or high RS groups were 32 (50%), 17 (27%), and 15 (23%), respectively. ORR to neo-EXE therapy was 59% (95%CI, 40–76%), 59% (33–82%), and 20% (4–48%) for pts in the low, intermediate, and high RS groups, respectively. There was a significant difference for ORR between the low and the high RS groups (P=0.015, Fisher exact test). In a multivariate logistic regression model, the continuous RS provided significant predictive power that was independent of age and tumor size (P=0.019, likelihood ratio test). Conclusions: This is the first report that the 21-gene signature has value in predicting a response to neo-EXE therapy in postmenopausal pts with ER-positive breast cancer, and provides preliminary evidence for the clinical usefulness of the neoadjuvant treatment selection.
Measuring adherence to 2012 Choosing Wisely recommendations: SEER Registry linked with health plan data.
Authors: Karma L. Kreizenbeck, Catherine R. Fedorenko, Erin E. Hughes, Joshua Shoemaker, Oscar Lucas, Rakesh T Chauhan, Scott David Ramsey
Journal: Journal of Clinical Oncology (2014)

178 Background: The ASCO Choosing Wisely campaign aims to reduce the use of interventions that lack evidence of benefit in cancer care. This project characterized adherence to the 2012 ASCO Choosing WiselyRecommendations by linking health plan claims data to a regional cancer registry in order to identify areas for research interventions to improve adherence. Methods: Surveillance, Epidemiology, and End Results (SEER) records for patients diagnosed with cancer in Western Washington state between 2007 and 2013 were linked with enrollment and claims from a large regional commercial insurance plan. Using claims and SEER records, algorithms were developed to characterize each Choosing Wisely measure. Results: For the 5 recommendations measured, adherence rates were as follows: (see Table). Conclusions: Using algorithms involving insurance claims and cancer registry records, we found variable adherence to the 2012 ASCO Choosing Wisely recommendations. While 100% adherence is not expected due to limitations of claims data, such records may be useful to identify areas for intervention and estimating potential savings from improved adherence. [Table: see text]
Outcome analyses after the first admission to an intensive care unit in patients with cancer enrolled into a phase I clinical trials program: When is the optimal time to trigger code status discussion?
Authors: S. Fu, D. S. Hong, A. Naing, J. J. Wheler, G. S. Falchook, S. Wen, A. Howard, D. Barber, J. L. Nates, K. J. Price, R. Kurzrock
Journal: Journal of Clinical Oncology (2011)

e13020 Background: This study assesses outcomes and prognostic variables of 212 patients with advanced cancer admitted to the intensive care unit (ICU) after becoming patients in the Phase I clinic at MD Anderson Cancer Center. Methods: Outcome analyses were conducted on 212 consecutive patients admitted to the MD Anderson Cancer Center ICU after being seen in the Phase I clinic starting on May 1, 2007. All data were obtained by review of patient electronic medical records. Results: The median survival of 212 Phase I cancer patients after the initial ICU admission was 3.2 weeks (95% CI: 2.5 – 4.9). Those who underwent cardiopulmonary resuscitation (CPR) succumbed within a median of 0.4 weeks. In multivariate analysis, patients who were admitted for surgical intervention did better than those admitted for medical intervention (median survival of 21.5 weeks versus 2.1 weeks, p < 0.0001). Conclusions: Phase I cancer patient outcomes after initial ICU admission for critical care were dismal, particularly when not for surgical intervention and/or when CPR was needed. Most, if not all, of these patients should be encouraged to have out-of-hospital DNR (do not resuscitate) orders.
Predictors of trust in the medical profession among cancer patients receiving palliative care: A preliminary study.
Authors: Kimberson Tanco, Wadih Rhondali, Minjeong Park, Diane D Liu, Eduardo Bruera
Journal: Journal of Clinical Oncology (2015)

60 Background: Trust influences health care through the willingness to seek and continue care, disclose sensitive information, adhere to treatment, and satisfaction with care. In a recent prospective study of patient perception of physician compassion, the degree of trust in the medical profession was found to be significantly associated with higher perception of compassion. In this secondary analysis, we explored the association between trust and other demographic and psychosocial factors. We also explored the performance of the single item Degree of Trust scale compared to the validated 5-item Trust in Medical Profession scale. Methods: A secondary analysis of prospectively collected data was performed. Trust scores completed by 100 patients were correlated with age, gender, ethnicity, educational level, anxiety, depression, hopefulness, and a 0 (best) – 10 (worst) Degree of Trust question. Results: Scores were 13, 11-14 [median, IQR; inversely scored] for Trust in Medical Profession and 2, 1-4 [median, IQR] for Degree of Trust with moderate correlation [r = 0.587, p &lt; 0.001]. On evaluating performance of Degree of Trust scale to the validated Trust in Medical Profession scale, a moderately high performance was found [Youden’s J = 0.73; Topleft = 0.21]. Older age [57, 49-65 (median, IQR), p = 0.02] lower depression scores [6,3-9 (median, IQR), p &lt; 0.01] and more hopefulness [22,20-25 (median, IQR), p = 0.01] were associated with higher levels of trust. Conclusions: Trust was associated with older age, less depressed and more hopeful patients. A single 0-10 item trust scale was found to perform adequately compared to a multiple item questionnaire.