tbuckley/cabot-search huggingface dataset:
New overexpressed genes related to cell proliferation stimulation and apoptosis inhibition of plasma cells of multiple myeloma
Authors: M. M. Ortega, A. F. Cunha, D. M. Albuquerque, G. L. Costa, A. F. Sagarra, C. A. De Souza, I. Lorand-Metze, F. F. Costa, C. S. Lima
Journal: Journal of Clinical Oncology (2008)

8598 Background: The molecular mechanisms involved in multiple myeloma (MM) are not completely clarified. Serial analysis of gene expression (SAGE) is a powerful tool that allows analysis of overall gene expression pattern. The aim of this study was identified the global gene expression in malignant plasma cells (MPC) of MM. Methods: MPC were obtained from bone marrow (BM) of MM IgG patients using the CD138-antibody in a magnetic column. Normal plasma cells (NPC) were obtained by differentiation of BM B cells from a healthy individual. Libraries were performed with I-SAGE kit and were compared. To investigate the reliability of the MPC profile, 16 genes were studied by quantitative real-time polymerase chain reaction (qPCR) in the sample used to generate the library and in other 13 MM IgG patients’ samples. Results: A total of 84 965 tags from MPC SAGE and 77 080 tags from NPC SAGE profiles were generated, representing 24 601 and 25 527 unique tags, respectively. In comparison of the unique tags, 476 tags were found differentially-expressed at significant levels (fold≥ 5; P< 0.01). qPCR confirmed the gene expression measured by SAGE in 14 out of 16 (87.5%) analyzed genes. The genes differentially-expressed were clustered to their main function evidencing a cluster of overexpressed genes in MPC, related to cell proliferation and differentiation (FOSB, DUSP1, LATS2), apoptosis inhibition (IER3, TEGT, MCL1), proteasome-ubiquitines, chemokine and chemokine receptor (RGS2, CCL5, S100A9, S100A4), and transcriptional and translational process (CFOS, CJUN, EGR1, RHOB). In contrast, MPC underexpressed cell signaling (TCL1A), B cell differentiation (CD19, CD40), cytokine and cytokine receptor production (FCER2, IL6-ST), chemokine production (CCL17, CCL2), transcriptional process (PRDM2, RNAse1), and apoptosis stimulation (BMF, GSR). SAGE permitted the detection of genes involved in the stimulation of cell proliferation (LATS2, S100A4, S100A9, EGR1, RHOB) and the apoptosis inhibition (BMF, GSR), not previously described in MM, and also unknown sequences, which probably constitute novel genes. Conclusions: These findings contribute to clarify the MM pathology, as well as to highlight specific targets for new therapies. Financial support: FAPESP No significant financial relationships to disclose.
Randomized phase II window study of two schedules of irinotecan (CPT-11) and vincristine (VCR) in rhabdomyosarcoma (RMS) at first relapse/disease progression
Authors: L. Mascarenhas, E. R. Lyden, P. P. Breitfeld, S. S. Donaldson, C. N. Paidas, D. M. Parham, W. H. Meyer, D. S. Hawkins
Journal: Journal of Clinical Oncology (2008)

10013 Background: Patients with RMS have a poor prognosis at first relapse/disease progression. CPT-11 has significant and schedule-dependent preclinical activity in RMS, and prolonged exposure results in increased efficacy. Methods: Patients with biopsy proven RMS, < 21 years of age at original diagnosis and unfavorable prognosis at first relapse/progression were eligible. Entry criteria were: life expectancy ≥ 2 months, performance status ≤ 2, adequate organ function and written informed consent. Patients were randomized to one of two schedules of CPT-11/VCR: Regimen 1A: CPT-11, 20 mg/m2 intravenously (IV) daily × 5d × 2w on weeks 1 and 4, VCR 1.5 mg/m2 IV on day 1 of weeks 1, 2, 4 and 5; Regimen 1B: CPT-11, 50 mg/m2 IV daily × 5d on weeks 1 and 4, VCR identical to IA. Disease response at week 6 was assessed using RECIST. Secondary endpoints included toxicity, progression free survival (PFS) and survival (OS). The study was powered to detect a 25% improvement in response to IA when compared to IB (α=0.1, 1-β=0.9, 1-sided test). Those with responsive/stable disease continued to receive 44 weeks of standard multi-agent chemotherapy (doxorubicin, cyclophosphamide, etoposide, ifosfamide) in combination with their assigned CPT- 11/VCR regimen. Results: 92 patients were randomized (IA-45, IB-47). Response in 86 evaluable patients was: 1A - 4 CR, 6 PR, 11 SD, 19 PD (overall response 25%) 1B - 0 CR, 17 PR, 14 SD, 15 PD (overall response 37%) (p=0.23). The 1-year PFS on IA was 32% (95% CI: 18%, 47%) and for IB was 36% (95% CI: 22%, 50%). The 1-year OS for IA was 47% (95% CI: 30%, 62%) and 1B was 56% (95% CI: 40%, 69%). There were no unexpected toxicities or significant differences in toxicity between the two regimens. Conclusions: There was no difference in the response rates between the two CPT-11/VCR regimens. The shorter, more convenient CPT-11/VCR regimen is now being investigated in frontline Children’s Oncology Group RMS clinical trials. No significant financial relationships to disclose.
Impact of multicentricity/multifocality on contralateral events and survival in invasive breast carcinoma
Authors: H. F. Kennecke, R. Yerushalmi, R. Woods, C. Speers, K. A. Gelmon
Journal: Journal of Clinical Oncology (2008)

586 Background: Bilateral breast cancer (BBC) has a cumulative incidence of 7- 20%. Earlier studies suggested that multicentricity is a risk factor for BBC. The aim of the study was to compare the incidence of contralateral breast cancer (CBC) in multifocal/multicenter (M/M) and unifocal (U) disease and to assess the impact of adjuvant hormone (HT) or chemotherapy (CT) systemic treatment on outcome. Methods: Women referred to the British Columbia Cancer Agency between 1989 and 2005 with newly diagnosed breast cancer, pT1–3, pN0–3, c or pM0 were classified as U or M/M disease. Patients with synchronous breast cancer were excluded. M/M disease was defined as two or more discrete invasive lesions anywhere in the same breast. Age, histology, T and N stage, ER, lymphovascular invasion, adjuvant hormone or chemotherapy, and LCIS or DCIS were recorded. The primary endpoint was metachronous free survival (MFS), defined as absence of contralateral breast cancer or death by any cause. Kaplan-Meier (KM) plots were created for MFS and overall survival (OS). Multivariate analysis was performed using a Cox proportional hazards model. Results: 25,321 women met inclusion criteria (23,767 U; 1554 M/M). Median follow-up was 6.8 years. CBC was documented in 3.8% of the U cases and 3% of M/M disease. KM plots were similar for both groups (MFS: p=0.97; OS: p=0.58). In multivariate analysis M/M was not an independent predictor of MFS (RR=1.041, 95%CI: [0.920, 1.178], p=0.52). Both HT and CT use were found to be associated with improved MFS (HT: RR=0.65, 95% CI: 0.61, 0.7; CT: RR=0.74, 95%CI: 0.68, 0.80). Conclusions: In this large study, M/M breast cancer does not increase the risk of metachronous contralateral breast cancer and is not an adverse prognostic factor. This may be due to systemic adjuvant treatment. Knowing the risk of contralateral cancer may help clinicians and patients tailor the optimal risk reduction approach. No significant financial relationships to disclose.
Lenalidomide in solid tumor patients with inflammatory cancer cachexia: A multicenter, randomized, double-blind, proof-of-concept study of fixed dose or CRP-response-guided dose or placebo.
Authors: F. Strasser, R. Oberholzer, D. Blum, M. Joerger, C. Driessen, S. deWolf-Linder, S. R. Haile, R. von Moos, N. Zerkiebel, A. Jatoi, R. Woelky, K. Fearon, T. Cerny
Journal: Journal of Clinical Oncology (2011)

TPS239 Background: Cancer cachexia impacts physical functioning, appetite, tolerability and success of anticancer treatments of patients with advanced cancer. Currently, there is no standard treatment, which improves muscle and physical function. Recently, a new consensual definition, diagnosis and classification of cancer cachexia was published by others and our group (Fearon & Strasser et al, Lancet Oncology 2011), we confirmed (systematic literature review) inflammation as a key mechanism of cancer cachexia (Blum et al, CRHO 2011). One prior study reported an anti-cachexia effect of thalidomide (Gordon et al, Gut 2005), its derivate, lenalidomide, belongs to a new class of immunomodulatory drugs (IMiDs). To explore the potential of lenalidomide in patients with inflammatory cancer cachexia, we developed this trial. Methods: Patients with new diagnostic criteria for cancer cachexia, tumor-associated inflammation (average C-reactive protein ≥30mg/l, absence of infection), normal Mini Mental State Examination, no anticancer treatment or expected to be continued during the trial, are eligible. Patients are randomized (2:2:1) to 3 arms: A) Lenalidomide fixed dose 25mg, B) CRP-guided Lenalidomide dose (intrapatient dose escalation [5, 10, 15, 25mg] until CRP-response [≥50% reduction]), or C) placebo. All patients receive new standard cachexia management (Fearon EJC 2008; Strasser COSPC 2007) starting 2 weeks before baseline. Medication is administered double blinded. Treatment duration is 8 weeks. The binary, composite, primary endpoint is number of responders, having increase in hand grip strength ≥4kg and in muscle mass CT-scan L3/4 ≥2% at week 8. Additional endpoints include safety, survival, nutritional intake, symptoms (Functional Assessment Anorexia Cachexia Therapy), physical functioning (get-up-and-go, 10-step stair climb, ActivPal), inflammatory markers and cachexia genotypes. Interim analysis is planned after 9 patients in each active treatment arm to stop arms with <1 responder. Total sample size is 60 patients, we have randomized 7 patients.
The LIVESTRONG essential elements of survivorship care: Advancing quality survivorship care in clinical care settings.
Authors: Sarah R. Arvey, Ruth Rechis
Journal: Journal of Clinical Oncology (2012)

155 Background: The American College of Surgeons Commission on Cancer (COC) has set a 2015 deadline for oncology practices to comply with new patient-centered standards of care to maintain accreditation. Despite this mandate, there is not a strong evidence base on best practices, or guidance on how to implement quality survivorship care services. In September 2011, the Lance Armstrong Foundation (LAF) and the LIVESTRONG Survivorship Center of Excellence Network (Network) convened researchers, providers, advocates, and cancer survivors who identified and prioritized a list of 20 Essential Elements of survivorship care. LAF and the Network continued work to refine this list with input from stakeholders with the goal of disseminating a framework for survivorship care delivery and advancing a research agenda to strengthen the evidence base for implementing these elements as standard care. Methods: LAF and the Network have refined definitions of the Essential Elements through an iterative process and in late 2012 will facilitate a technology-mediated consensus-building process among a broad group of stakeholders. Results: Refinement of the Essential Elements included defining each element in such detail that “basic” and “enriched” levels of implementation are described to guide providers in real-world settings. This work outlines a research agenda aimed to strengthen the evidence-base of the Essential Elements’ effectiveness in improving survivors’ outcomes. In October 2012, the refined definitions will be disseminated to a broad stakeholder audience and subject to review. Details of this iterative process, resulting definitions, and open-forum feedback will be reported here. Conclusions: Once complete, the Essential Elements will represent a consensus-driven platform that provides the cancer care community with a blueprint for the development and implementation of high-quality survivorship care and research. Additionally, the finalized Essential Elements will further facilitate the broad adoption of the new COC standards including the provision of a treatment summary and survivorship care plans, palliative care, psychosocial distress screening, and care coordination.
Development of quality indicators for liver cancer care
Authors: T. Higashi, N. Kokudo, K. Hasegawa, T. Okusaka, T. Sobue
Journal: Journal of Clinical Oncology (2008)

17500 Background: Appropriate management of liver cancer can significantly prolong survival and enhance the quality of life of patients. Although evidence-based practice guidelines to promote standards of care have been published, no systematically-developed quality indicators (QI) to assess or monitor care for hepatocellular carcinoma have been reported. Methods: Using a formal method combining literature review and expert opinion, we developed a set of process QIs for the care of hepatocellular carcinoma. We first identified candidate QIs based on the current clinical practice guideline sponsored by the Japanese government as well as literature review. Each candidate QI described the patients targeted and the standard of care that these patients should receive. The QIs were designed to be implemented through review of medical records. Next, a multi-disciplinary panel of nine clinical experts, including surgeons, internists, and radiologists, examined the candidate QIs and selected a final set through two rounds of anonymous rating of validity, between which a face-to- face consensus meeting was held. Results: total of 34 candidate QIs were evaluated by the expert panel. The panel added two QIs pertaining to the post-operative provision of information to the patient. After major modification of four other QIs, 25 QIs were finally rated as valid. This final set of QIs comprised 13 on appropriate choice and indications for treatment (e.g. surgical resection for solitary hepatocellular carcinoma of 3–5cm diameter), 5 on pre-treatment work-up (e.g. dynamic studies before treatment), and 7 on follow-up/post-treatment care (e.g. image study after chemoembolization). Conclusions: We developed a set of QIs to assess the care of hepatocellular carcinoma patients. These QIs will facilitate quality improvement efforts in liver cancer care. No significant financial relationships to disclose.
Estrogen as a prognostic factor on liver metastasis from colorectal cancer.
Authors: Sen Zhang, Zhen Hua He, Xue Lei Zhang, Zhen Jie Wu, Jun Ouyang
Journal: Journal of Clinical Oncology (2012)

506 Background: Estrogen plays an important role in some cancer. However, previous studies about the influence of estrogen on colorectal cancer (CRC) have been conflicting, especially rare reports on liver metastasis. This study tries to explore the prognostic impact of estrogen on CRC with liver metastasis. Methods: Eighty six patients with CRC including 43 synchronous liver metastases were studied. Estrogen receptor-beta (ER-beta) were assayed by immunohistochemistry (IHC) in liver metastasis tissues, colorectal cancer tissues and normal tissues. And the serum estrogens were detected by radioimmunoassay (RIA) in 30 patients with CRC including 14 synchronous liver metastases. After follow-up, the relationship between ERβ, estrogen and survival time were analyzed. Results: The positive rates of ER-beta in liver metastases tissues, CRC tissues and normal tissues were 39.5% (17/43), 39.5% (34/86) and 62.8% (54/86), respectively; and significant differences were found between liver metastasis (P=0.012) or CRC (P=0.002) with normal tissues. The 1-, 2-, 3-and 5-year survival rates for ER-beta positive patients were 97%, 79%, 71% and 51%, respectively comparing with 82%, 59%, 55% and 40%, respectively for ER-beta negative patients (P=0.190). In contrast, the 1-, 2-, 3- and 5-year survival rates in liver metastasis group were 77%, 37%, 31% and 23%, respectively; and 93%, 64%, 57% and 57%, respectively for ER-beta positive patients comparing with 67%, 19%, 14% and 7%, respectively for ER-beta negative patients (P=0.004). Serum estrogen levels in patients with liver metastases were significantly lower than those without liver metastasis (P=0.012) and Pearson Correlation showed that there was a moderate positive correlation between level of serum estrogen and survival time (P=0.006). Conclusions: CRC liver metastasis patients with positive ER-beta have a better survival, which indicates estrogen is a protective factor for CRC liver metastasis patients. But more study is needed to show estrogen would be a protective factor for CRC patients.
Development and internal validation of a prognostic nomogram for overall survival in patients with advanced renal cell carcinoma (aRCC) treated with pazopanib (PAZ).
Authors: Michael W. Kattan, Debasis Chakrabarti, Kamalnayan Bhatt, Faisal Mehmud, Cora N. Sternberg, Robert John Motzer
Journal: Journal of Clinical Oncology (2013)

380 Background: PAZ, an oral multikinase inhibitor, demonstrated significant improvement in PFS over placebo in patients with aRCC in a randomized, phase III trial (J Clin Oncol 2009:29; 475). The purpose of this study was to develop and internally validate a prognostic nomogram based on the outcome data from phase III trial for predicting the probability of 12-month OS for treatment-naïve and cytokine-pretreated aRCC patients who received PAZ. Methods: Statistical modeling was performed on a dataset consisting of 281 patients from the PAZ arm of the phase III trial. Missing values were first imputed using multiple imputation with chained equations. A Cox proportional hazards regression model was fit using routinely available predictors thought to be prognostic based on clinical judgment. These predictors included the neutrophil count relative to ULN, platelet count relative to ULN, LDH relative to ULN, alkaline phosphatase relative to ULN, corrected calcium, albumin, hemoglobin, ECOG performance status, months from diagnosis to treatment, number of metastatic sites, and presence of lung, liver and bone metastases. Bootstrap-corrected estimates of discrimination and calibration in the small were calculated following 1,000 resamples. The Cox model was plotted as a nomogram. Results: A prognostic nomogram was developed and internally validated for predicting the probability of 12-month OS in aRCC patients based on a Cox regression model using 13 predictor variables. Calibration plots suggested reasonable correspondence between predicted probabilities and actual proportions of OS. The bootstrap-corrected concordance index, a measure of discrimination, was 0.70. When examining the nomogram, albumin appeared to have the greatest potential influence on predicted OS. Months from diagnosis to treatment and corrected calcium level seemed to be the next most potentially influential predictors. Conclusions: The nomogram predicts with reasonable accuracy and should facilitate treatment decision making for patients with advanced renal cell carcinoma. Validation in a separate dataset is planned.
Dynamics of bone mineral density during intermittent androgen deprivation for men with biochemical recurrence of prostate cancer.
Authors: E. Y. Yu, K. Kuo, R. Gulati, P. Y. Jiang, C. S. Higano
Journal: Journal of Clinical Oncology (2010)

4558 Background: Androgen deprivation therapy (ADT) for prostate cancer leads to loss of bone mineral density (BMD) and increased fracture risk. We hypothesize that intermittent ADT (IADT) may attenuate BMD loss. Methods: Patients with rising PSA after surgery (RP) or radiation (RT) received IADT in a prospective clinical trial. After 9 months “on treatment” with leuprolide and flutamide, ADT was stopped and monthly PSA levels were measured during the “off treatment” interval until a threshold PSA (1 ng/mL for RP, 4 ng/mL for RT) was met. At that time, ADT was resumed in another cycle and patients were treated intermittently in this manner until castration resistance. Standardized average dual energy X-ray absorptiometry (DXA) scans of lumbar spine and left hip were performed at baseline and at each change in therapy. Men who completed at least one entire treatment cycle and who underwent at least 3 DXA scans were eligible for analysis. Results: Forty-eight of 100 patients met criteria. Mean spine BMD decreased 3.1% (p<0.0001) while mean hip BMD decreased 1.0% (p=0.005) during first “on treatment” interval. Significant gains were made in mean spine BMD of 1.8% (p=0.001) but not in the hip during first “off treatment” interval. Subsequent cycles of IADT also revealed attenuation of “on treatment” losses during “off treatment” intervals, though few achieved statistical significance (see table). Despite regained BMD during “off treatment” intervals, the net result for the first cycle was loss of 1.3% (p=0.08) at the spine and 1.0% (p=0.02) at the hip. Conclusions: ADT-induced loss of BMD is attenuated during the “off treatment” intervals of IADT. However, BMD does not return to baseline, sustaining only a smaller net loss. Cycle Lumbar spine Left hip N Mean BMDg/cm2 (% change) N Mean BMD g/cm2 (% change) 1 On 48 (−3.1) 48 (−1.0) Off 47 (1.8) 48 (−0.1) 2 On 38 (−0.7) 37 (0.4) Off 28 (1.2) 28 (0.2) 3 On 31 (0.1) 29 (−0.6) Off 24 (2.3) 23 (−0.1) 4 On 23 (−1.1) 20 (−0.4) Off 16 (0.4) 15 (−0.5) No significant financial relationships to disclose.
Access to palliative care before death among patients treated at a comprehensive cancer center.
Authors: David Hui, Sun Hyun Kim, Jung Hye Kwon, Kimberson Cochien Tanco, Tao Zhang, Jung Hun Kang, Wadih Rhondali, Gary B. Chisholm, Eduardo Bruera
Journal: Journal of Clinical Oncology (2012)

25 Background: Palliative care (PC) access is a critical component of quality cancer care. Previous studies on PC access have mostly examined the timing of PC referral. The proportion of patients who actually received PC is unclear. We determined the proportion of cancer patients who received PC at our comprehensive cancer center, and the predictors of PC referral. Methods: We reviewed the charts ofconsecutive patients with advanced cancer from the Houston region seen at MD Anderson Cancer Center and died between September 2009 and February 2010. We compared patients who received PC services with those who did not receive PC services before death using univariate and multivariate logistic regression. Results: A total of 366/816 (45%) decedents had a PC consultation. The median interval between PC consultation and death was 1.4 months (interquartile range (0.5-4.2) and the median number of medical team encounters before PC was 20 (6-45). In multivariate analysis, older age, being married, and specific cancer types (gynecology, lung and head and neck) were significantly associated with a PC referral (Table). Patients with hematologic malignancies had significantly fewer PC referrals (33%), the longest interval between advanced cancer diagnosis and PC consultation (median 16 months), the shortest interval between PC consultation and death (median 0.4 month), and one of the largest number of medical team encounters (median 38) before PC. Conclusions: We found that a majority of cancer patients at our cancer center did not access PC before they die. PC referral occurs late in the disease process with many missed opportunities for referral. Further effort is needed to improve quality of end-of-life care. [Table: see text]