tbuckley/cabot-search huggingface dataset:
Effect of zoledronic acid on tartrate-resistant acid phosphatase isoform 5b (TRAP-5b) and other bone markers in lung cancer patients with bone metastasis.
Authors: W. Zhang, G. Rabinowits, A. J. Janckila, L. Yam, F. J. Hendler, D. A. Laber, C. Li, G. H. Kloecker
Journal: Journal of Clinical Oncology (2010)

e18118 Background: Between 19 to 44% of patients with lung cancer eventually develop bone metastasis. Zoledronic acid (ZA), a bisphosphonate, can prevent skeletal-related complications in patients with bone metastases. Bone metabolic markers could play an important role in the prediction and diagnosis of bone metastasis. There are no guidelines in the use of these markers to monitor treatment efficacy. This study reports the final results on a previously reported study, in which we evaluate bone metabolic markers as indicators of a biochemical response to ZA in lung cancer patients. Methods: Lung cancer patients with bone metastasis received monthly ZA for 6 months. Baseline serum bone resorption and formation markers were tested during chemotherapy, before and after ZA treatment, and every two weeks for the first 6 weeks, and then monthly until either progression of bone metastasis or for a total of 6 months. Resorption markers included N-terminal telopeptide (NTx), tartrate-resistant acid phosphatase 5b (TRAP-5b), C-terminal telopeptides of type-I-collagen (ICTP) and deoxypyridinoline (DPD). Bone specific alkaline phosphatase (bALP) was the only formation marker included. Data were analyzed using linear mixed-effects model and paired t-test. Results: 28 participants were enrolled between 7/05 and 6/09. 13 of 28 study participants could not be evaluated: 7-because of sample deterioration; 5-participant non-compliance, 1-withdrew. Two weeks after ZA treatment, mean NTx decreased by 37.3% (95% CI [3.041, 11.339], p = 0.003); mean TRAP-5b by 44.9% (95% CI [0.524, 3.816], p = 0.014), and mean bALP by 12.9% (95% CI [0.386, 6.528], p = 0.031).These markers remained significantly decreased during monthly ZA, up to 6 months. ICTP and DPD levels did not correlate with ZA treatment. During chemotherapy without ZA the levels of TRAP-5b remained stable. Conclusions: TRAP-5b, NTx, and bALP levels decreased significantly with ZA treatment in lung cancer patients with bone metastasis. This suggests that TRAP-5b levels are another effective way to monitor bisphosphonate treatment of bone metastases. Chemotherapy alone did not affect the levels of TRAP-5b. No significant financial relationships to disclose.
Survival analysis of PETCAM: A multicenter randomized controlled trial of PET/CT versus no PET/CT for patients with resectable liver colorectal adenocarcinoma metastases.
Authors: Carol-anne Moulton, Mark Norman Levine, Calvin Law, Richard Hart, Leyo Ruo, Chu-Shu Gu, Aaron Hendler, Karen Y. Gulenchyn, Masoom A. Haider, Michael Marcaccio, Ved Tandan, Douglas Quan, Diederick Jalink, Robin Fairfull Smith, Shelly Luu, Paul David Greig, Mohamed Husien, Terri Finch, Jim A Julian, Steven Gallinger
Journal: Journal of Clinical Oncology (2012)

390 Background: An increasing proportion of patients with liver CAM are undergoing hepatic resection with curative intent. Detection of occult metastastic disease is important in this setting, and PET/CT is used to identify patients with either inoperable, or limited resectable extrahepatic disease not identified with conventional imaging. We recently reported the results related to the primary objective of PETCAM, a randomized trial for patients with resectable liver CAM, where 7.6% had a change in management based on PET/CT (ASCO 2011). As a secondary objective, we examined whether patients undergoing PET/CT derived a survival benefit, as they may be considered to be better selected. Methods: PETCAM was a multicenter trial with 404 subjects randomized 2:1 to receive PET/CT or no PET/CT once they were assessed by a hepatobiliary surgeon to have resectable CAM. Subjects were followed over 4 years for overall survival (OS). As well as the intervention, we considered the SUV, Fong Score and other baseline factors as predictors for OS. Results: After a median 2.8 years of follow-up, 107 of the 404 (26%) study subjects had died. The 270 PET/CT subjects [and the 245 of these who underwent surgery] showed no statistically significant survival advantage over the 134 No PET/CT subjects [123 who underwent surgery] with a hazard ratio (HR) of 0.85, 95% confidence interval (CI): 0.57 to 1.3; p=0.41 [HR=0.81, 95% CI: 0.52 to 1.3; p=0.34]. Fong score was a strong predictor of OS for all patients (HR=1.4, 95% CI: 1.1 to 1.6), and for those who had surgery (HR=1.4, 95% CI, 1.1 to 1.7). In the PET/CT arm, SUV is strongly predictive of OS [HR per unit SUV increase =1.11, 95% CI: 1.05 to 1.18; p=0.0007. Conclusions: The addition of PET/CT had no effect on improving overall survival for patients who did or did not have hepatic resection for CAM. SUV is strongly predictive of survival for patients who had PET/CT, and Fong score is predictive of survival for all patients. The overall role of PET/CT in patients with resectable CAM appears limited and should be reevaluated in the current era of comparative effectiveness research and health care cost containment.
Predicting overall survival (OS) in patients (pts) with metastatic colorectal cancer (mCRC) treated with chemotherapy (CT): The British Columbia Cancer Agency (BCCA) mCRC score.
Authors: Leo Chen, Gillian Gresham, Winson Y. Cheung, Hagen F. Kennecke, Daniel John Renouf
Journal: Journal of Clinical Oncology (2013)

3624 Background: The prognosis of individual pts with mCRC can be highly variable. Our objective was to develop a scoring system to improve the prognostication of mCRC pts at baseline assessment. We also further explored the impact of palliative resection (PR) of the primary tumor on OS. Methods: Pts diagnosed with mCRC from 2006 to 2008, referred to 1 of 5 regional cancer centers in British Columbia were retrospectively reviewed. Pts with prior early stage CRC who relapsed with mCRC were excluded. Multivariate stepwise selection was performed using significant variables from univariate analysis. Patients were assigned a composite risk score (range 0-15) based on their baseline variables, and then separated into quartiles for OS using cut-point analysis and Kaplan Meier methods. A secondary propensity score matched analysis was performed to obtain hazard ratios (HR) for death in order to control for baseline differences between pts who underwent PR and those who did not. Results: A total of 505 mCRC pts were included: median age 63 (range 22-86), 58% male, 75% ECOG 0-1, 58% colon primary, 34% &gt;1 metastatic site, and 46% smokers. In this cohort, 81% of the population underwent PR. ECOG 2-3, no primary resection, colon primary, &gt;1 metastatic site, CEA level &gt;4 ng/ml, male gender, and smoker were significant in the multivariate model and subsequently assigned a score. Median OS varied significantly depending on the composite risk score (table). After ECOG PS, PR of the primary was the second strongest prognostic factor (HR 2.3, 95%CI 1.6-3.3). To further explore this, a propensity score matched analysis was performed adjusting for age, gender, ECOG and receipt of chemotherapy. Prognosis continued to be more favorable in the PR group with a median OS of 17 vs. 7.9 months (HR 0.66, 95% CI 0.50-0.86, p=0.0019). Conclusions: In this population based analysis, the BCCA mCRC score was a simple and effective method to improve prognostication for mCRC pts. PR of the primary was associated with significantly longer OS. [Table: see text]
Change in International mRCC Database Consortium (IMDC) prognostic category and implications for efficacy of second-line targeted therapy.
Authors: Ian D. Davis, Wanling Xie, Carmel Jo Pezaro, Frede Donskov, Connor Wells, Neeraj Agarwal, Sandhya Srinivas, Takeshi Yuasa, Benoit Beuselinck, Lori Wood, D. Scott Ernst, Ravindran Kanesvaran, Jennifer J. Knox, Allan J. Pantuck, Sadia Saleem, Ajjai Shivaram Alva, Brian I. Rini, Jae-Lyun Lee, Toni K. Choueiri, Daniel Yick Chin Heng
Journal: Journal of Clinical Oncology (2016)

534 Background: Currently no predictive markers exist for choosing second-line targeted therapy (2L) in metastatic renal cell carcinoma (mRCC). A change in IMDC prognostic group when calculated at first-line therapy (1L) and 2L and its association with 2L efficacy was examined. Methods: The IMDC database was interrogated for patients who received 1L VEGF inhibitors (VEGFi) and then 2L with VEGFi or an mTOR inhibitor (mTORi). IMDC prognostic categories (Favorable, F; Intermediate, I; Poor, P) were defined prior to each line of therapy. Overall survival (OS), time to treatment failure (TTF) and response to 1L or 2L were assessed in relation to change in IMDC prognostic risk category. Results: Data for 1516 patients were analyzed; 89% had clear cell histology. Prognostic risk categories at 1L were F: 21.7%; I: 59.5%; P: 18.8%. 60.3% of patients remained in the same risk category at start of 2L; 9.0% improved (3% I→F; 6% P→I); 30.7% deteriorated (14% F → I or P; 16% I → P). Improvement in prognostic risk category was associated with better response and longer duration of 1L. Patients who improved prognostic risk (I → F or P → I), or maintained I or F grouping, had longer TTF if they remained on VEGFi for 2L compared to those who switched to mTORi (p &lt; 0.05). In contrast, patients whose risk category deteriorated (F → I or P) may be more likely to benefit from switching to mTORi. Conclusions: Changes in IMDC prognostic category may predict the subsequent clinical course of patients with aRCC and provide a rational basis for selection of subsequent therapy. [Table: see text]
PT1a,bN0M0 breast carcinoma characteristics and management: The French ODISSEE cohort.
Authors: F. Dalenc, F. M. Penault-Llorca, M. Cohen, G. Houvenaeghel, J. Piat, P. Liegeois, L. Puyuelo, J. Suchaud, M. E. H. Zouai, S. Beauclair, Y. Belkacemi
Journal: Journal of Clinical Oncology (2011)

e11084 Background: Breast cancer (BC) patients with tumor ≤ 10 mm without lymph node metastasis are increasing due to early diagnosis by mammographic screening. Although most of these tumors have favorable issue, controversy surrounds the prognosis of these patients with locoregional therapy only and the need for adjuvant systemic therapy. The objective of the prospective ODISSEE study was to describe the disease management in daily practice and outcome of these patients over a 10-year follow-up period. Methods: This ongoing prospective French cohort collects baseline clinical, pathologic, treatment and outcome data in routine visits. Centralized pathological analysis of tumors is ongoing. From May 2009 to March 2010, 618 women with infiltrating, unifocal pT1a,bN0M0 BC who underwent surgery were recruited by 116 centers. Preliminary results are described below. Results: Median age at diagnosis was 61 years. 569 were ECOG 0 (93%) and 519 diagnosed from imagery (84%). 592 (96%) patients underwent conservative surgery with sentinel node biopsy in 547 (88.5%) and axillary dissection in 90 (15%). Median tumor size was 8 mm (range [0–10] mm) with 114 (18%) pT1a / 504 (82%) pT1b. 450 (73%) are pN0(i-) / 17 (3%) pN0(i+). SBR : 326 (53%) grade I , 237 (38%) grade II , 50 (8%) grade III. 60 patients had positive surgical margins (11%) with 9 second surgery (2%). 556 (91%) were ER+, 456 (74%) were PR+ (562 (91%) were ER+ and/or PR+), 33 (5,6%) were HER2+ (IHC2+ and ISH+ or IHC3+) and 32 (5%) were triple negative. Adjuvant treatment consisted of radiotherapy (RT) for 553 patients (95%), chemotherapy (CT) for 42 (7%), hormone therapy (HT) for 406 (70%) and trastuzumab for 20 (3%), as shown in the table. Conclusions: The ODISSEE cohort patients with pT1a,bN0M0 BC were mainly SBR I or II with pT1b HR+/HER2- tumor. Majority had conservative surgery followed by radiotherapy. Less than 50% of triple-negative patients (5%) received adjuvant therapy and 62.5% of HER2+ patients (5.6%) received trastuzumab. % of patients HR-/HER2- (n=31) HR+/HER2- (n=502) HER2+ (n=32) RT alone 51.6% 22.2% 9.7% RT + HT - 72.7% 19.4% RT + CT 38.7% 0.2% 3.2% RT + CT + HT - 1.2% - Trastuzumab - - 62.5%
Adjuvant and neoadjuvant chemotherapy in muscle-invasive bladder cancer: A systematic review and meta-analysis.
Authors: F. M. Carcano, L. V. Santos, S. V. Serrano, J. P. S. N. Lima
Journal: Journal of Clinical Oncology (2011)

e15192 Background: The standard curative management of muscle invasive bladder carcinoma (MIBC) has been the combination of neoadjuvant chemotherapy and radical cystectomy, neo-adjuvant chemotherapy (NC) based on platinum has consistently shown benefit. However the role of adjuvant chemotherapy (AC) has been extensively debated, with contradictory results in randomized trials. A systematic review was sought to elucidate this confounding scenario. Methods: Randomized controlled trials (RCT) and meta-analysis (MA) testing AC or NC in MIBC patients were searched in MEDLINE, EMBASE, and CENTRAL databases, ESMO and ASCO meeting proceedings. Meta-analysis was performed using random-effects model and interaction test were used to compare subgroups. The outcome of interest was overall survival (OS). Sensitive analyses were run to identify any difference according the type of chemotherapy (gemcitabine-platinum versus other platinum-based) and the therapy timing (AC versus NC). Pertinent interaction test were calculated. Results: Two AC studies (333 patients) and two individual patient data MA (one NC: 3005 patients, one AC: 498 patients) were included. OS meta-analysis combining NC+AC demonstrated a robust benefit in survival (HR = 0.70; 95% CI 0.52-0.94; P < 0.02). The sensitive analysis according therapy timing showed similar positive results irrespective to moment of chemotherapy initiation (interaction test P=0.37). Sensitive analysis suggests that addition of taxane (paclitaxel) to AC may lead to even more positive results (interaction test, P=0.02) Conclusions: AC can be considered a valid option for MIBC patients radically operated. The most appropriate time for curative chemotherapy remains an open issue and must be discussed with patients in a multidisciplinary setting. Inclusion of paclitaxel to platin-based regimens might bring extra OS benefit and demands further confirmation.
Randomized phase II study of erlotinib (E) alone or combined with fulvestrant (F) in previously treated patients with advanced non-small cell lung cancer (NSCLC).
Authors: E. B. Garon, S. M. Dubinett, W. Hosmer, K. L. Reckamp, F. F. Kabbinavar, L. Goodglick, D. C. Marquez-Garban, L. P. Stabile, J. Siegfried, R. J. Pietras
Journal: Journal of Clinical Oncology (2010)

TPS295 Background: Estrogen receptors (ERs) and aromatase are expressed in most NSCLC specimens. Preclinical data shows that estrogens stimulate NSCLC growth, while the pure antiestrogen fulvestrant (F) blocks NSCLC progression, adding to the effects of EGFR inhibitors (Weinberg et al. Cancer Res, 2005; Siegfried et al. Semin Oncol, 2009). Increased risk of death from NSCLC occurs in patients randomly assigned to receive exogenous estrogens (Chlebowski et al. Lancet, 2009), and retrospective studies show a reduced risk of death from lung cancer in breast cancer patients who received antiestrogen therapy (Rapiti et al. SABCS Abstract 35, 2009). Methods: This phase II clinical study evaluates whether fulvestrant (F) adds to the antitumor efficacy of erlotinib (E). Patients are randomized in a 2:1 ratio to receive E (150 mg PO qd) ± F (500 mg IM q2wk × 3, then q4wk), as 500 mg F has demonstrated clinical benefit in other estrogen target organs compared to the standard 250 mg (Di Leo A. SABCS Abstract 25, 2009). Response rate at 2 months is the primary endpoint, and secondary endpoints include correlation between clinical response and expression of ERα, ERβ, EGF/HER-1 receptor and HER-2/neu biomarkers. Targeted enrollment is 102 patients. Eligibility:Men and pre- and postmenopausal women with advanced NSCLC and at least one prior chemotherapy regimen (unless patient refuses) are eligible. Patients must have sufficient available tissue for study of biologic correlates, including EGFR mutation analysis and gene copy number. Current Enrollment: To date, 30patients have been enrolled, with enrollment ongoing. The study was initially restricted to a single site pending a successful protocol-mandated safety evaluation, but the study will open in 16 TORI network sites throughout the United States by April 2010. Supported by NIH Lung Cancer SPORE P50-CA90388 and P50-CA90440, AstraZeneca, Genentech, Stiles Program. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Tragara Pharmaceuticals Genentech, Roche AstraZeneca, Genentech
High resolution oligonucleotide array-CGH to identify therapeutic targets in breast cancer
Authors: V. Lazar, F. André, C. Liedtke, B. Job, W. F. Symmans, A. Levy, S. Delaloge, P. Dessens, S. Michiels, L. Pusztai
Journal: Journal of Clinical Oncology (2008)

547 Background: We used high resolution oligonucleotide CGH arrays to assess DNA copy number changes in breast cancer (BC). The aim of the present study was to identify new therapeutic targets, specific indications for existing targeted therapies, and to develop predictor for efficacy of preoperative chemotherapy. Methods: DNA was extracted from 106 pre-treatment needle biopsies of stage II-III BC and hybridized to Agilent Human 4x44K CGH arrays (G4426A). All patients received preoperative chemotherapy. Data on gene expression (Affymetrix U133A) were available on 103 patients. P-values were adjusted for false discovery rate (FDR). Results: CGH-array presented an accuracy ranged between 96 and 99% to detect ERBB2 amplification. The average number of chromosomal aberrations was 76 (range 1 to 318). Among all observed aberrations, 11 and 37 distinct minimal common regions were gained or lost in more than 20% of samples respectively. FGFR1 gene presented a high level of amplification in 10% of samples. A correlation between DNA copy number and mRNA level was detected for 3,883 probesets. Some of these dysregulated genes are being investigated as therapeutic targets, including ERBB2 (adj p=10- 6), EGFR (adj p=0.004), PAK1 (adj p=0.00039), VEGFA (adj p=0.01), PARP1 (adj p=0.02), AURKA (aurora kinase A) (adj p=4.5e-5), AKT1 (adj p=0.003), PTEN (adj p=0.00095), APC (adj p=0.0036), CHEK (adj p=0.0048). Non-negative Matrix Factorization clustering of gene aberrations suggested 3 molecular classes in this data set. Class I was characterized by a high rate of triple-negative cancer (64%). One chromosomal region located in 6p21 was found to be significantly gained ( adj p<0.01) in triple-negative (n=35) as compared to nontriple-negative tumors. This region includes VEGFA gene that was gained in 34% of triple-negative tumors. Four chromosomal regions were commonly altered in tumors with pCR to paclitaxel-containing chemotherapy compared to cancers with lesser response (p<0.001, FDR 45%-59%). Conclusions: Genes with aberrant DNA copy numbers leading to dysregulated expression were identified. Some of these gene anomalies could be potentially targeted in different subsets of breast cancers. No significant financial relationships to disclose.
Statin use and the development of bone metastasis in breast cancer patients.
Authors: Gentry T King, Jeong H Yun, Young K Chae, Matias E Valsecchi
Journal: Journal of Clinical Oncology (2012)

536 Background: The Mevalonic Acid Pathway has been implicated in the promotion of a microenvironment suitable for establishment of bony metastasis from breast cancer. The statins, which act on this pathway, have been shown to have in-vitro anti-neoplastic activity against breast cancer. This study was designed to evaluate the association of statin use and development of bony metastasis in breast cancer patients. Methods: Medical records of patients treated for stage II-III breast cancer from 1999 to 2010 were retrospectively reviewed. Statin use was defined as medication use for at least 3 months in patients with no evidence of disease after initial diagnosis and treatment. The primary outcome was development of metastasis to bone. Secondary outcomes were overall survival, disease free survival and other sites of distant metastasis. Results: A total of 841 patients were included in the study of which 223 used statins. Both unadjusted and multivariate analysis adjusted for age, race, grade, stage , BRCA status, showed that patients on statins had a significantly lower incidence of metastasis to bone (OR 0.49, 95% CI 0.25-0.96, p=0.04). Adjusted analysis for other sites showed a trend towards decreased incidence of metastasis for statin users, but was not statistically significant (95% CI 0.39-1.08, p=0.10). Overall survival was increased in statin users with mean survival of 66.45 +/- 2.48 months versus non-users 58.78 +/ - 1.41 months (p=0.05). Statin users had significantly longer disease free survival with a mean of 63.65 +/- 2.49 months versus 53.96 +/- 1.42 months in non statin users (p=0.00). Conclusions: The use of statin drugs in patients with breast cancer was significantly associated with decreased incidence of metastasis to bone, but not to other distant sites. The role of statins in chemoprevention of bone metastasis should be further explored.
Stem Cell Graft Cellular Composition, Hematological and Immune Recovery in NHL Patients Mobilized with or without Plerixafor: A Prospective Comparison
Authors: Jaakko Valtola, Ville Varmavuo, Antti Ropponen, Marja Pyörälä, Anne Nihtinen, Anu Kutila, Kaija Vasala, Päivi Lehtonen, Karri Penttilä, Taru Kuittinen, Tapio Nousiainen, Jukka Pelkonen, Pekka Mäntymaa, Esa Jantunen
Journal: Blood (2014)
Known colorectal cancer susceptibility loci and survival after colorectal cancer diagnosis.
Authors: Amanda Phipps, Xabier Garcia-Albeniz, Carolyn Hutter, Emily White, Charles S. Fuchs, Hongmei Nan, Ulrike Peters, Polly A. Newcomb, Andrew T. Chan
Journal: Journal of Clinical Oncology (2012)

394 Background: Beyond clinicopathologic stage, there are few established markers of prognosis in colorectal cancer (CRC). Recent genome-wide association studies have identified 17 germline single nucleotide polymorphisms (SNPs) significantly associated with incident CRC. However, it is unclear if these CRC susceptibility SNPs influence survival after CRC diagnosis. Although the functionality of many of these SNPs remains unknown, a few, including rs4939827 in SMAD7, map to genes with plausible biological mechanisms associated with both cancer risk and prognosis. We examined 17 CRC susceptibility SNPs in relation to survival after CRC diagnosis. Methods: We genotyped 2,611 men and women enrolled in five prospective cohort studies who were diagnosed with invasive CRC during study follow-up: the Physicians’ Health Study (N=281), Health Professionals Follow-up Study (N=268), Nurses’ Health Study (N=367), Vitamins and Lifestyle Study (N=281), and the Women’s Health Initiative (N=1414). Analyses were limited to Caucasians with known vital status, cause of death, and survival time. We used Cox proportional hazards regression to assess associations between each SNP and CRC-specific and overall survival in study-specific models adjusted for age, sex, and stage; SNPs were modeled additively to reflect associations per copy of the minor allele. Study-specific results were combined via fixed-effects meta-analysis. Results: The G allele in rs4939827 was associated with poorer CRC-specific survival [hazard ratio (HR)=1.16, p=0.02] and overall survival (HR=1.13, p=0.03) in CRC patients. The A alleles in rs10795668 and in rs4925386 were associated with a 1.14-fold increased risk of overall mortality (both p-values=0.03) but not CRC-specific mortality. Other evaluated SNPs were not associated with survival. Conclusions: Genetic variation in rs4939827 (SMAD7) is associated with CRC-specific and overall survival. These results suggest that SMAD7 may have a role in CRC progression, and provide proof-of-principle that common germline variation may provide prognostic information beyond traditional considerations such as stage.