bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of kidney function on the outcome of metastatic renal cell carcinoma patients treated with vascular endothelial growth factor‐targeted therapy
Authors: Macfarlane Robyn , Heng Daniel Y. C. , Xie Wanling , Knox Jennifer J. , McDermott David F. , Rini Brian I. , Kollmannsberger Christian , Choueiri Toni K. 
Published: June 2011

AbstractBACKGROUND:A study was undertaken to investigate the effect of baseline renal function on treatment outcome in patients treated with vascular endothelial growth factor (VEGF)‐targeted therapy for metastatic renal cell carcinoma (mRCC).METHODS:Retrospective data from 6 North American cancer centers (3 US and 3 Canadian) were pooled to identify patients with mRCC treated with VEGF‐targeted therapy. Patient characteristics, response rate, time to treatment failure, and overall survival were collected. The Modification of Diet in Renal Disease formula was used at therapy initiation for calculation of glomerular filtration rate (GFR).RESULTS:Five hundred twenty‐nine patients with mRCC who received sunitinib (n = 323), sorafenib (n = 165), or bevacizumab (n = 41) were included in this analysis. Patient characteristics included: 74% male, median age 61 years, and median GFR 60.1 mL/min/1.73 m2 (range, 6.5‐174.2). On univariate analysis, patients with a GFR <60 (n = 262) were more likely to have had a previous nephrectomy (P < .0001) and to be older (P < .0001), but were less likely to have poor prognostic features such as anemia (P = .041), hypercalcemia (P = .008), neutrophilia (P = .039), thrombocytosis (P < .0001), short diagnosis to treatment interval (P = .007), and low Karnofsky performance status (P = .051). GFR <60, when adjusted for poor risk factors, did not have an impact on type of objective response (odds ratio, 1.31; 95% confidence interval [CI], 0.74‐2.32; P = .359), time to treatment failure (hazard ratio [HR], 0.97; 95% CI, 0.79‐1.19; P = .772), or overall survival (HR, 0.90; 95% CI, 0.69‐1.17; P = .439).CONCLUSIONS:Renal function at therapy initiation does not adversely affect the efficacy of VEGF‐targeted therapy in mRCC. Clinicians should not avoid treating patients with impaired baseline renal function. Cancer 2011;. © 2011 American Cancer Society.
Genetic variants of the nonhomologous end joining gene LIG4 and severe radiation pneumonitis in nonsmall cell lung cancer patients treated with definitive radiotherapy
Authors: Yin Ming , Liao Zhongxing , Liu Zhensheng , Wang Li‐E , O'Reilly Michael , Gomez Daniel , Li Minghuan , Komaki Ritsuko , Wei Qingyi 
Published: June 2011

AbstractBACKGROUND:Nonhomologous end joining (NHEJ) is a pathway that repairs DNA double‐strand breaks (DSBs) to maintain genomic stability in response to irradiation. The authors hypothesized that single nucleotide polymorphisms (SNPs) in NHEJ repair genes may affect clinical outcomes in patients with nonsmall cell lung cancer (NSCLC) who receive definitive radio(chemo)therapy.METHODS:The authors genotyped 5 potentially functional SNPs—x‐ray repair complementing defective repair in Chinese hamster cells 4 (XRCC4) reference SNP (rs) number rs6869366 (−1394 guanine to thymine [−1394G→T] change) and rs28360071 (intron 3, deletion/insertion), XRCC5 rs3835 (guanine to adenine [G→A] change at nucleotide 2408), XRCC6 rs2267437 (−1310 cytosine to guanine [C→G) change], and DNA ligase IV (LIG4) rs1805388 (threonine‐to‐isoleucine change at codon 9 [T9I])—and estimated their associations with severe radiation pneumonitis (RP) (grade ≥3) in 195 patients with NSCLC.RESULTS:A predictive role in radiation pneumonitis (RP) development was observed for the LIG4 SNP rs1805388 (adjusted hazard ratio, 2.08; 95% confidence interval, 1.04‐4.12; P = .037 for the CT/TT genotype vs the CC genotype). In addition, men with the TT genotype of the XRCC4 rs6869366 SNP and women with AG + AA genotypes of the XRCC5 rs3835 SNP also were at increased risk of developing severe RP.CONCLUSIONS:The current results indicated that NHEJ genetic polymorphisms, particularly LIG4 rs1805388, may modulate the risk of RP in patients with NSCLC who receive definitive radio(chemo)therapy. Large studies will be needed to confirm these findings. Cancer 2011;. © 2011 American Cancer Society.
Early stage squamous cell cancer of the oral tongue—clinicopathologic features affecting outcome
Authors: Ganly Ian , Patel Snehal , Shah Jatin 
Published: June 2011

AbstractBACKGROUND:The objective of this study was to report the authors' experience in the management of patients with early stage squamous cell cancer (SCC) of the oral tongue and determine clinicopathologic factors predictive of outcome.METHODS:Two hundred sixteen patients with early stage (cT1T2N0) SCC of the oral tongue were identified from a pre‐existing database of patients with oral cancer who were treated at Memorial Sloan‐Kettering Cancer Center from 1985 to 2005. Patient, tumor, and treatment characteristics were recorded. Overall survival (OS), disease‐specific survival (DSS), and recurrence free survival (RFS) were calculated using the Kaplan‐Meier method. Predictors of outcome were identified using multivariate analysis.RESULTS:With a median follow‐up of 80 months (range, 1‐186 months), the 5‐year DSS, OS, and RFS rates were 86%, 79%,and 70%, respectively. Local, neck, and distant recurrences occurred in 24 patients (11%), 40 patients (18%), and 5 patients (2%), respectively. Multivariate analysis identified occult neck metastases as the main independent predictor of OS, DSS, and RFS; patients who had occult metastases had a 5‐fold increased risk of dying of disease compared with patients who did not have occult metastases (5‐year DSS, 85.5% vs 48.5%; P = .001). A positive surgical margin was the main independent predictor for local RFS (91% vs 66% for a negative surgical margin; P = .0004), and depth of invasion was the main predictor for neck RFS (91% vs 73% for depth of invasion <2 mm and >2 mm, respectively; P = .02).CONCLUSIONS:In the authors' experience, patients with early stage oral tongue cancer have excellent outcomes. In the current study, the presence of occult metastases was the main predictor of survival outcome. Cancer 2012;. © 2011 American Cancer Society.
Conflict of interest in oncology publications
Authors: Kesselheim Aaron S. , Lee Joy L. , Avorn Jerry , Servi Amber , Shrank William H. , Choudhry Niteesh K. 
Published: June 2011

AbstractBACKGROUND:Disclosure of conflicts of interest in biomedical research is receiving increased attention. The authors sought to define current disclosure policies and how they relate to disclosure statements provided by authors in major oncology journals.METHODS:The authors identified all oncology journals listed in the Thomson Institute for Scientific Information and sought their policies on conflict‐of‐interest disclosure. For a subset of journals with an Impact Factor >2.0, they catalogued the number and type of articles and the details of the published disclosures in all papers from the 2 most recent issues.RESULTS:Disclosure policies were provided by 112 of 131 journals (85%); 99 (88%) of these requested that authors disclose conflicts of interest (mean Impact Factor for these journals: 4.6), whereas the remaining 13 (12%) did not (mean Impact Factor: 2.9). Ninety‐three journals (94%) required financial disclosure, and 42 (42%) also sought nonfinancial disclosures. For a subset of 52 higher‐impact journals (Impact Factor >2.0), we reviewed 1734 articles and identified published disclosures in 51 journals (98%). Many of these journals (31 of 51, 61%) included some disclosure statement in >90% of their articles. Among 27 journals that published editorials/commentaries, only 14 (52%) included disclosures with such articles. There was no publication of any nonfinancial conflicts of interest in any article reviewed.CONCLUSIONS:Disclosure policies and the very definition of conflict of interest varied considerably among journals. Although most journals had some policy in this area, a substantial proportion did not publish disclosure statements consistently, with deficiencies particularly among editorials and commentaries. Cancer 2012;. © 2011 American Cancer Society.
An integrated analysis of germline and somatic, genetic and epigenetic alterations at 9p21.3 in glioblastoma
Authors: Feng Junjie , Kim Seong‐Tae , Liu Wennuan , Kim Jin Woo , Zhang Zheng , Zhu Yi , Berens Michael , Sun Jielin , Xu Jianfeng 
Published: June 2011

AbstractBACKGROUND:Glioblastoma multiforme (GBM) is the most prevalent and deadly brain tumor. A variety of germline and somatic, genetic and epigenetic alterations at 9p21.3, which encode CDKN2A/CDKN2B tumor suppressor genes, have been isolatedly reported to be associated with GBM risk and prognosis.METHODS:To obtain a comprehensive view of these events, we leveraged the wide‐spectrum GBM data available from The Cancer Genome Atlas project and performed an integrated analysis by systematically evaluating 9p21.3‐related germline single‐nucleotide polymorphisms, somatic copy number alterations (CNAs), DNA methylation, and microRNAs (miRNAs) with regard to CDKN2A/CDKN2B expression and patient prognosis in GBM.RESULTS:Our multivariate analysis indicated that expression of CDKN2A and CDKN2B was both strongly affected by CNAs (P = 1.00 × 10−4 and 2.37 × 10−14). The miRNAs hsa‐mir‐126, hsa‐mir‐517a, and hsa‐mir‐125b exhibited significant negative correlations with CDKN2A expression (P = 0.003, 0.041, and 0.050). Survival analysis showed that complete 9p21.3 loss and low CDKN2B expression were associated with worse prognosis for both tumor progression/recurrence‐free survival (P = .041 and .019) and patient overall survival (P = .043 and .021) after adjustment for age and treatment, and that higher methylation at cg17449661 predicted poorer overall survival (P = .048).CONCLUSION:Representing one of the first attempts to systematically integrate various levels of alterations associated with the often complex cancer genomes and phenotypes, our study provided a holistic view and a mechanistic explanation over the functional connections of multiple 9p21.3‐related events in GBM, as well as clinically useful biomarker information for predicting disease outcomes. Cancer 2012;. © 2011 American Cancer Society.
Serum cell‐free DNA in renal cell carcinoma
Authors: de Martino Michela , Klatte Tobias , Haitel Andrea , Marberger Michael 
Published: June 2011

AbstractBACKGROUND:Currently, there are no established diagnostic and prognostic serum markers for renal cell carcinoma (RCC). The objective of this study was to evaluate the putative significance of serum cell‐free DNA.METHODS:Preoperative serum samples from 200 consecutive patients with sporadic, solid renal tumors were analyzed (157 patients with RCC and 43 patients with benign renal tumors). Quantitative real‐time polymerase chain reaction was used to assess total cell‐free DNA (ring finger protein 185 [RNF185]) and CpG island methylation of Ras association domain family member 1A (RASSF1A) von Hippel‐Lindau (VHL), prostaglandin‐endoperoxidase synthase 2 (PTGS2), and P16 (cyclin‐dependent kinase inhibitor 2A). Associations with RCC, pathologic variables, and disease‐specific survival were evaluated.RESULTS:Total cell‐free DNA levels and CpG island methylation of RASSF1A and VHL were highly diagnostic for RCC with an area under the receiver operating characteristic curve of 0.755, 0.705, and 0.694, respectively. VHL methylation was detected more frequently in patients with clear cell RCC than in those with other subtypes (P = .007). Total cell‐free DNA levels were higher in patients with metastatic RCC (P < .001) and necrotic RCC (P = .003) and were associated with poorer disease‐specific survival (P < .001). In multivariate analysis, the tumor stage, size, grade, and necrosis (SSIGN) score (P < .001) and categorized total cell‐free DNA levels (P = .028) were retained as independent prognostic factors.CONCLUSIONS:The current results indicated that cell‐free DNA represents a novel serum‐based diagnostic and prognostic biomarker for RCC. Total serum cell‐free DNA levels and CpG island methylation of RASSF1A and VHL may be useful diagnostic biomarkers for RCC. VHL methylation of cell‐free DNA is suggestive of clear cell RCC. Total serum cell‐free DNA may be a useful prognostic biomarker that may assist in tailoring postoperative surveillance and therapy. External prospective validation of these data will be required. Cancer 2012;. © 2011 American Cancer Society.
Identification of potential prognostic biomarkers in patients with untreated, advanced pancreatic cancer from a phase 3 trial (Cancer and Leukemia Group B 80303)
Authors: Roberts Andrew S. , Campa Michael J. , Gottlin Elizabeth B. , Jiang Chen , Owzar Kouros , Kindler Hedy L. , Venook Alan P. , Goldberg Richard M. , O'Reilly Eileen M. , Patz Edward F. 
Published: June 2011

AbstractBACKGROUND:Patients with advanced stage adenocarcinoma of the pancreas have a poor prognosis. The identification of prognostic and/or predictive biomarkers may help stratify patients so that therapy can be individualized.METHODS:Serum samples from patients enrolled in the Cancer and Leukemia Group B 80303 phase 3 trial, “Randomized Study of Gemcitabine With Versus Without Bevacizumab in Patients With Locally Advanced or Metastatic Adenocarcinoma of the Pancreas” were used to discover novel biomarkers. For the discovery phase, 40 sera were selected based on length of survival and type of therapy, and subjected to liquid chromatography coupled to tandem mass spectrometry analysis (LC‐MS‐MS). The top features (proteins) were then further selected for validation by enzyme‐linked immunosorbent assay (ELISA).RESULTS:Quantification by nano–LC‐MS‐MS resulted in 1452 peptides mapping to 156 proteins across all 40 samples, 92 of which had 2 or more peptides. After curation of the data, the authors selected 1 putative prognostic protein, alpha 1‐antichymotrypsin (AACT), and 2 putative predictive proteins, histidine‐rich glycoprotein (HRG) and complement factor H (CFH), for validation by ELISA. AACT was found to be negatively correlated with overall survival (τ = −0.30 [−0.38, −0.22]; P < .00001). There was no evidence for interaction with bevacizumab and HRG, but there was some evidence for a weak positive correlation of HRG with overall survival (τ = 0.11 [0.03, 0.19]; P < .01). CFH was found to be neither a predictive nor a prognostic factor for overall survival.CONCLUSIONS:AACT may be a useful prognostic marker in patients with advanced stage pancreatic carcinoma, although additional validation studies are needed. Cancer 2011;. © 2011 American Cancer Society.
A scoring system to predict the risk of death during induction with anthracycline plus cytarabine‐based chemotherapy in patients with de novo acute myeloid leukemia
Authors: Valcárcel David , Montesinos Pau , Sánchez‐Ortega Isabel , Brunet Salut , Esteve Jordi , Martínez‐Cuadrón David , Ribera José M. , Tormo Mar , Bueno Javier , Duarte Rafael , Llorente Andrés , Torres Juan Pio , Guardia Ramón , Sanz Miguel A. , Sierra and Jorge ,   on behalf of the CETLAM Group
Published: June 2011

AbstractBACKGROUND:A prognostic index to predict induction death in adult patients receiving induction chemotherapy for de novo acute myeloid leukemia (AML) was developed.METHODS:The authors analyzed 570 patients (aged 16‐70 years) included in 2 multicenter trials of the CETLAM Group to develop a scoring system (study cohort). The scoring system was tested in 209 patients from an external single institution (validation cohort). Induction regimens consisted of anthracycline and cytarabine combination with or without etoposide. Induction death was defined as death in the first 42 days without evidence of leukemic resistance.RESULTS:The cumulative incidence of induction death was 11% in the study cohort and 18% in the validation cohort. Median age was 48 years in the study cohort and 56 years in the validation cohort (P < .001). Multivariate analysis in the study cohort showed the following adverse risk factors for induction death: leukocyte count >100 × 109/L, serum creatinine >1.2 mg/dL, and age ≥50 years. According to these factors, the authors developed a predictive score: low risk (no risk factors), intermediate risk (1 factor), and high risk (2 or 3 factors). The cumulative incidence of induction death in the 3 respective groups was 5%, 13%, and 26% (P < .001). The scoring system was applied in the validation cohort, resulting in cumulative incidence rates of induction death of 6%, 19%, and 32%, for the low‐risk, intermediate‐risk, and high‐risk categories, respectively (P < .001).CONCLUSIONS:By using this validated and simple scoring system, the risk of induction death in patients with AML can be predicted accurately. The score may be helpful to design risk‐adapted induction strategies. Cancer 2011;. © 2011 American Cancer Society.
Measuring response to BCR‐ABL inhibitors in chronic myeloid leukemia
Authors: Radich Jerald P. 
Published: June 2011

AbstractIn patients with chronic myeloid leukemia (CML), the hallmark Philadelphia chromosome is the marker of disease that can be detected by conventional metaphase cytogenetics, fluorescence in situ hybridization, or polymerase chain reaction. The current “gold standard” of treatment response is cytogenetic response. Cytogenetic response to imatinib is strongly associated with disease progression and survival. Various strategies aimed at improving cytogenetic response have been explored, such as escalation of imatinib and switching to the newer breakpoint cluster region/v‐abl Abelson murine leukemia viral oncogene (BCR‐ABL) inhibitors dasatinib and nilotinib. Data from recent randomized trials of dasatinib and nilotinib as first‐line therapy of newly diagnosed chronic‐phase CML suggest that these agents are more effective than imatinib in achieving 6‐month and 12‐month complete cytogenetic responses. However, it is still too early to know whether or not this early response will translate into a long‐term survival advantage. In addition, more sensitive assays to detect residual disease also may be associated with improved long‐term outcomes. The deepest measure of response—a complete molecular response—may help identify patients who can stop taking imatinib for the short term, although the long‐term consequences of this strategy remain unknown. Cancer 2011;. © 2011 American Cancer Society.
High‐dose cytarabine induction is well tolerated and active in patients with de novo acute myeloid leukemia older than 60 years
Authors: Arellano Martha , Winton Elliott , Pan Lin , Lima Lisa , Tighiouart Mourad , Bhalla Kapil , Heffner Leonard T. , Neely Jessica , Hutcherson Donald , McLemore Morgan , Langston Amelia , Khoury H. Jean 
Published: June 2011

AbstractBACKGROUND:High‐dose cytarabine (HiDAC) is safe and very effective in younger patients with acute myeloid leukemia (AML), but it generally is not well tolerated in the elderly.METHODS:The authors explored the safety and tolerability of a modified HiDAC induction regimen consisting of 6 daily doses of cytarabine at 2 g/m2 in combination with 3 daily doses of daunorubicin at 45 mg/m2 in 59 consecutive patients aged >60 years who had de novo AML diagnosed between July 1996 and February 2005.RESULTS:The median patient age was 68 years (range, 60‐86 years). The regimen was well tolerated. Infections were common and occurred in 39% of patients, but cerebellar toxicities occurred in only 7% of patients and were reversible. The day‐30 induction‐related mortality rate was 10%. Overall, 69% of patients achieved complete remissions (CR), and 80% received up to 3 consolidations with HiDAC. The median follow‐up for surviving patients was 53 months (range, 17‐114 months). The median overall survival was 15.3 months (range, 1‐114 months), and the relapse‐free survival was 13.8 months (range, 1‐113 months). Survival for patients who achieved CR was 27 months (range, 2‐114 months).CONCLUSIONS:The modified HiDAC regimen was well tolerated in patients aged >60 years with AML and was associated with low induction mortality and high rates of CR. Nevertheless, these high remissions still were associated with poor overall outcomes. Cancer 2011;. © 2011 American Cancer Society.
Phase 2 randomized study of p53 antisense oligonucleotide (cenersen) plus idarubicin with or without cytarabine in refractory and relapsed acute myeloid leukemia
Authors: Cortes Jorge , Kantarjian Hagop , Ball Edward D. , DiPersio John , Kolitz Jonathan E. , Fernandez Hugo F. , Goodman Mark , Borthakur Gautam , Baer Maria R. , Wetzler Meir 
Published: June 2011

AbstractBACKGROUND:The p53 antisense oligonucleotide cenersen has been shown to sensitize acute myeloid leukemia (AML) stem cells to DNA damaging agents.METHODS:To determine whether cenersen merits testing in larger efficacy studies, an exploratory study of cenersen in combination with idarubicin either alone or with 1 of 2 doses of cytarabine was performed in first‐salvage AML patients. Patients who either had failed to respond to a single induction course or had responded to induction but relapsed within 12 months were enrolled. Stopping rules based on an expected 14% complete response (CR) rate were applied to each treatment arm.RESULTS:Fifty‐three patients were treated, and none of the arms was terminated for lack of activity. Nearly all patients received a single course unless they responded. Ten of the 53 (19%) patients responded (8 CR and 2 CR with incomplete platelet recovery). There was a positive trend for a better response rate with increasing intensity of chemotherapy in the patients refractory to front‐line treatment compared with those who had relapsed previously. One‐third (17/53) of the patients received cenersen inhibitors (acetaminophen and/or high dose antioxidants) during treatment, and none of these responded to treatment. No unique toxicity was attributed to cenersen.CONCLUSION:The results of this study suggested that the combination of cenersen with chemotherapy may have clinical efficacy, and additional studies are warranted to explore its full potential. Cancer 2011;. © 2011 American Cancer Society.
Long‐term outcomes of BRCA1/BRCA2 testing: risk reduction and surveillance
Authors: Schwartz Marc D. , Isaacs Claudine , Graves Kristi D. , Poggi Elizabeth , Peshkin Beth N. , Gell Christy , Finch Clinton , Kelly Scott , Taylor Kathryn L. , Perley Lauren 
Published: June 2011

AbstractBACKGROUND:For BRCA1/BRCA2 gene testing to benefit public health, mutation carriers must initiate appropriate risk management strategies. There has been little research examining the long‐term use and prospective predictors of the full range of risk management behaviors among women who have undergone BRCA1/2 testing. We evaluated long‐term uptake and predictors of risk‐reducing mastectomy (RRM), risk‐reducing bilateral salpingo‐oophorectomy (RRBSO), chemoprevention, and cancer screening among women at a mean of 5.3 years after testing.METHODS:The study participants comprised 465 women who underwent BRCA1/2 testing. Prior to genetic counseling, we measured family/personal cancer history, sociodemographics, perceived risk, cancer‐specific distress, and general distress. We contacted patients at a mean of 5.3 years after testing to measure use of RRM, RRBSO, chemoprevention, and breast and ovarian cancer screening.RESULTS:Among participants with intact breasts and/or ovaries at the time of testing, BRCA1/2 carriers were significantly more likely to obtain RRM (37%) and RRBSO (65%) compared with women who received uninformative (RRM, 6.8%; RRBSO, 13.3%) or negative (RRM, 0%; RRBSO, 1.9%) results. Among carriers, precounseling anxiety was associated with subsequent uptake of RRM. RRO was predicted by age. Carriers were also more likely have used breast cancer chemoprevention and have undergone magnetic resonance imaging screening.CONCLUSION:This prospective evaluation of the uptake and predictors of long‐term management outcomes provides a clearer picture of decision making in this population. At a mean of 5.3 years after testing, more than 80% of carriers had obtained RRM, RRBSO, or both, suggesting that BRCA1/2 testing is likely to have a favorable effect on breast and ovarian cancer outcomes. Cancer 2011;. © 2011 American Cancer Society.