tbuckley/cabot-search huggingface dataset:
Prognostic value of anemia in untreated metastatic prostate cancer: a multivariate analysis of SWOG 8894
Authors: L. B. Bland, C. M. Tangen, I. M. Thompson, E. D. Crawford, T. M. Beer
Journal: Journal of Clinical Oncology (2004)

4574 Background: The association of anemia with shorter survival in untreated metastatic prostate cancer may simply reflect extent of disease. We examined the prognostic value of anemia in a multivariate analysis that included disease extent and other demographic covariates in patients starting hormonal therapy for metastatic prostate cancer. Methods: Pre-treatment hemoglobin (HGB) and complete covariate information were available for 957 patients. The multivariate association of covariates with anemia (HGB < 12 g/dL) was evaluated with a logistic regression model. The associations between HGB and survival (S) and progression-free survival (PFS) were evaluated using a proportional hazards model and included indicators for quartiles of HGB and baseline covariates. PSA normalization (PSAN=PSA ≤ 4 ng/ml) was evaluated with a logistic model. Results: Quartiles of HGB were: Q1: ≤ 10.1, Q2: 10.2–12.0, Q3: 12.1–13.4, Q4: > 13.4 g/dL. In a multivariate model, anemia (≤ 12 g/dl) was significantly associated (p< 0.02) with being African American, PS 2–3 (vs. 0–1), extensive disease, and higher PSA; inversely associated with prior therapy with curative intent and with Gleason score 6–7 (vs. ≤5); and not associated with age or bone pain. Higher HGB was significantly associated with longer S and PFS and higher likelihood of PSAN with hormonal therapy, and longer time to non-prostate cancer death. After adjusting for potential confounders, higher HGB remained a significant predictor (p<0.01) of S, PFS, and PSAN. Conclusions: In this untreated metastatic prostate cancer population, anemia (HGB<12 g/dL) is seen in 50% of patients at study entry and is associated with shorter survival, shorter progression-free survival, and lower likelihood of PSA normalization with hormonal therapy after adjustment for disease status and other covariates. No significant financial relationships to disclose.
CNS leukemia: problem of diagnosis, treatment, and outcome.
Authors: P G Steinherz
Journal: Journal of Clinical Oncology (1995)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1995.13.2.310 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 7844591 CNS leukemia: problem of diagnosis, treatment, and outcome. P G SteinherzxP G SteinherzSearch for articles by this author https://doi.org/10.1200/JCO.1995.13.2.310 First Page PDF © 1995 by American Society of Clinical Oncology
Cellular localization of thrombin in prostate: Implications for thrombin targeted therapy in prostate cancer
Authors: M. Kohli, J. Huang, G. Palapattu, R. Dennis, J. Yao, T. Lester, W. Ricke
Journal: Journal of Clinical Oncology (2006)

14527 Background: Tumor and coagulation interaction is complex and heterogeneous. Expression of an intact repertoire of coagulation proteins is not detected in all tumor types. Thrombin, a key coagulation protein, which has been observed to promote tumorigenesis in experimental models, is not expressed on breast, colon and squamous lung cancer cells, but has been detected on small cell lung, melanoma and renal cancer epithelium. In prostate cancer, expression of its receptor, protease activated receptor-1 (PAR-1) has been previously reported but thrombin expression on epithelium not determined. Therefore, we evaluated thrombin and prothrombin expression in prostate specimens. Methods: Quantitative real-time PCR was performed for (pro)thrombin mRNA expression in fresh prostate cancer tissue lysates obtained from localized disease (n = 9 prostatectomy specimens) and advanced disease (n = 7 channel trans-urethral prostate resection specimens). Prothrombin and thrombin protein immunohistochemistry was performed on anonymized prostate tissue micro arrays which included benign (n = 117), prostate intra-epithelial neoplasia (PIN; n = 26) and prostate cancer (n = 112) cores. Results: (Pro)thrombin mRNA expression (normalized to 18s mRNA) was detected in all cancer tissue lysates. Mean intensity of expression in advanced cancer specimens was 20.3 compared to 14.0 for local stage specimens (p = 0.09; Wilcoxon rank sum test). Spatially, expression of thrombin was detected in stroma, benign and malignant epithelium (see Table) and on vascular endothelium. Prothrombin localization was similar to thrombin expression. Conclusions: Thrombin’s tumorigenic effects via PAR-1 activation provide novel therapeutic targets in tumors expressing thrombin-PAR1 axis. The current study confirms thrombin expression on prostate epithelium and taken with previous results of PAR1 epithelial expression, provides a rationale for exploring specific thrombin inhibitors and/or PAR inhibitors in prostate cancer. [Table: see text] No significant financial relationships to disclose.
Phase III trial of a 3-weekly versus 5-weekly schedule of S-1 plus cisplatin (SP) combination chemotherapy for first-line treatment of advanced gastric cancer (AGC): SOS study.
Authors: Min-Hee Ryu, Eishi Baba, Kyung Hee Lee, Narikazu Boku, Young Iee Park, Ichinosuke Hyodo, Byung-Ho Nam, Taito Esaki, Baek-Yeol Ryoo, Eun-Kee Song, Sanghee Cho, Sung Sook Lee, Won Ki Kang, Sung Hyun Yang, Dae Young Zang, Dong Bok Shin, Sook Ryun Park, Katsunori Shinozaki, Toshimi Takano, Yoon-Koo Kang
Journal: Journal of Clinical Oncology (2013)

LBA4024 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Monday, June, 3, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Genomic-based signatures of chemosensitivity and ER/HER2 status in biologic replicate breast cancer samples
Authors: W. T. Barry, M. Datto, J. Geradts, T. Foster, J. Olson, P. K. Marcom, H. K. Dressman, J. R. Nevins, G. Ginsburg, A. Potti
Journal: Journal of Clinical Oncology (2008)

11068 Background: Genome-wide expression profiling has now been extensively used for research on breast cancer biology and led to many new insights regarding disease heterogeneity. However, clinical applications require an understanding of various technical considerations, including the extent to which a random sample provides a representative measure of the patient’s tumor. Using genome- scale expression data derived from cancer cell lines and tumor biopsies, we have developed signatures for predicting response to specific cytotoxic chemotherapies. Our objective in this study is to assess the concordance of chemosensitivity predictions and of microarray-based classifiers of ER and HER2 status in a series of multiple samples from individual breast cancer biopsies. Methods: Patients with multiple frozen cores were identified in the Duke Breast SPORE tissue repository. Cores were assessed for percent invasive cancer cellularity, primary tumor size, and standard biomarker assessments. RNA was hybridized to Affymetrix H133 Plus 2.0 microarrays, Gene expression based signatures were generated according to previously identified predictors of sensitivity to adriamycin and docetaxel (Potti et al, Nat Med, 2006). Predefined cutoffs of 0.60 are applied to each signature. Genomic predictors of hormone receptor status were applied to post- processed array data, and compared to single-patient measures from IHC/FISH. Results: Of 14 patients, 1 had quadruplicate samples, 12 had triplicate samples, and 1 had doublet samples. In an overall assignment of being most sensitive to adriamycin, most sensitive to docetaxel, or resistant to both agents, complete concordance was observed in 9 of 14 cases. Intra-class correlation coefficients for the adriamycin and docetaxel signatures were 86% and 92%, respectively. Genomic signatures of ER status showed complete concordance in 13 of 14 patients and >95% agreement with IHC. Genomic-predictors of HER2 status were inconsistent across biological replicates. Conclusions: For replicate frozen core samples, chemosensitivity signatures and ER status appear robust and reproducible. Since cores represent biologic replicates, discordant cases may due to true heterogeneity within cancers from the individual patients. No significant financial relationships to disclose.
Predictive value of thymidylate synthase (<b><i>ts</i></b>) gene polymorphism for response to 5-FU in advanced colorectal cancer (CRC): Role of chromosome 18p allelic loss
Authors: A.-C. Dupont Gossart, J. Viguier, V. Boige, C. Miquel, M. Pocard, M. Ducreux, J.-C. Sabourin, F. Praz
Journal: Journal of Clinical Oncology (2004)

3603 Background: The variable number of tandem repeat of the TS promoter gene (mainly 2 or 3 28bp repeats) has been shown to influence response to 5-FU therapy. Because TS is located on chromosome 18p11.32, a region frequently lost in CRC, the impact of TS allelic imbalance needs to be taken into account to assess the predictive value of TS genotype for tumor response to 5-FU in advanced CRC. Methods: TS polymorphism was determined in both normal and tumor tissues obtained from 56 patients with advanced CRC (37 males, median age 54.5 yrs) treated with 5-FU as first line chemotherapy. In order to discriminate 2R/loss and 3R/loss TS genotypes from 2R/2R and 3R/3R, respectively, 18p allelic loss was analyzed in tumor tissues, using polymorphic markers located in the region of TS. Results: : In normal tissue, the distribution of TS genotype was: 2R/2R, 16% (n=9); 2R/3R, 47% (n=27); 3R/3R, 35% (n=20). Objective response rate (ORR) to 5-FU was 39%. The ORR was not different between the 3R/3R (50%), 2R/3R (37%), and 2R/2R (22%) genotypes. When TS polymorphism was studied in primary tumors (n=32), a better ORR was observed in patients with 3R/3R genotype (56%) compared to patients with 2R/3R and 2R/2R genotypes (22% and 0%, respectively; p=0.06). When loss of TS was considered, ORR was significantly better in patients with 3R/3R genotype (60%) compared to patients with either 3R/loss –2R/3R (35%) or 2R/2R –2R/loss (0%) genotypes (p=0.03). Conversely, ORR was not correlated to the TS genotype in metastasis (n=24), whatever loss of TS was considered or not. Conclusions: TS polymorphism in primary tumor may predict response to 5-FU in advanced CRC when loss of TS is considered. Specifically, the corrected 3R/3R TS genotype is associated with a better response to 5-FU first line chemotherapy. No significant financial relationships to disclose.
Adjuvant bevacizumab as treatment for melanoma patients at high risk of recurrence: Preplanned interim results for the AVAST-M trial.
Authors: Philippa Corrie, Andrea Marshall, Madusha Goonewardena, Janet A. Dunn, Mark R. Middleton, Paul D. Nathan, Martin Eric Gore, Neville Davidson, Steve Nicholson, Charles G. Kelly, Maria Marples, Sarah Danson, Ernest Marshall, Stephen Houston, Ruth E. Board, Ashita Marie Waterston, Jenny Nobes, Mark Harries, Jim Barber, Paul Lorigan
Journal: Journal of Clinical Oncology (2013)

LBA9000 Background: Bevacizumab (Bev) is a recombinant humanized monoclonal antibody to vascular endothelial growth factor (VEGF) shown to improve survival in several advanced solid tumors. Multiple adjuvant trials are underway, but trials that have reported in colon and triple-negative breast cancer did not meet their primary end points. Since VEGF is a relevant target in melanoma, AVAST-M aimed to evaluate the role of Bev in patients (pts) with resected melanoma at high risk of recurrence. Methods: AVAST-M is a randomized phase III trial evaluating single agent Bev (7.5mg/kg IV 3 weekly for 1 year) as adjuvant therapy following resection of AJCC stage IIB, IIC, and III cutaneous melanoma compared to standard observation (Obs). 1,320 pts were required to detect 8% differences in 5-year overall survival (OS) rate from 40% to 48%; 85% power, 5% alpha level. Primary endpoint is OS; secondary endpoints are disease free interval (DFI), distant-metastasis free interval (DMFI), safety, and quality of life (QoL). An associated translational study is ongoing. Results of the first pre-planned interim analysis (agreed by the IDSMC) are reported here. Results: Between July 2007 and March 2012, 1,343 pts were recruited. 56% were male; median age 56 years (range 18-88 years), 16% were stage IIB, 11% IIC, 15% IIIA, 36% IIIB, 20% IIIC, and 2% unknown stage. Ulceration status of the primary melanoma was: 38% present, 45% absent, 17% unknown. At the time of the interim analysis, 286 (21%) patients had died. Median follow-up for survival was 25 months. Median duration of Bev treatment in 671 treated pts was 51 weeks (dose intensity 86%). Main outcomes are shown in the table. Grade 3/4 adverse events were experienced in 101 (15%) Bev pts and 36 (5%) Obs pts. Conclusions: Interim analysis of this large, multicenter trial of melanoma patients at high risk of recurrence has shown that adjuvant Bev monotherapy is well tolerated and improved DFI. Longer follow-up is required to determine an impact on the primary endpoint of 5-year OS. Clinical trial information: 81261306. [Table: see text]
Cetuximab, capecitabine, and oxaliplatin (Cet-CapOx) with concurrent radiotherapy (RT) in advanced rectal cancer (RC): Results of a phase I/II trial
Authors: D. Arnold, M. Hipp, T. Liersch, K. Dellas, O. Koelbl, W. Hohenberger, F. Lordick, H. Sülberg, R. Sauer, C. Rödel
Journal: Journal of Clinical Oncology (2007)

4042 Background: CapOx given concurrently with neoadjuvant RT in rectal cancer is well tolerated and has achieved high rates of pathologic complete response (pCR) in phase II trials. Cetuximab is active in metastatic colorectal cancer. Synergy of cetuximab with RT resulted in improved survival (vs. RT alone) in head and neck cancer. This trial was to evaluate feasibility and efficacy of Cet-CapOx in RT of rectal cancer, with maximal tolerated dose as primary endpoint in phase I, and pCR as primary endpoint in phase II. Method: Patients (pts) had to have untreated, T3–4 and/or N+ disease per MRI or CT plus endoscopic ultrasound, M1 allowed, normal organ function. During conventionally fractionated RT (1.8 Gy for 28 days [d]), cetuximab was given in standard dose (400 mg/m 2 on d - 7, then 6 weekly doses of 250 mg/m 2 , to d35). CapOx was administered as in the phase II trial of our group (Rödel et al, J Clin Oncol 2007), with oxaliplatin (50 mg/m 2 d 1,8,22 and 29) plus capecitabine (d1–14 and d22–35) at 3 dose levels: 1,000, 1,300 and 1,650 mg/m 2 /day. Results: 60 pts were enrolled: Median age 62 [35–83] yrs., male 61%, T3/T4 83/17%, N+ 85%, M1 20%. 7/ 3/ 50 pts. were treated on levels 1/ 2/ 3: as only 1 pt. experienced DLT (diarrhea 4°) on level 1 and none on level 2, level 3 was chosen for phase II (n=50 pts.). Most common toxicity was CTC grade 3 diarrhea in 14% of pts. Full dose of all drugs and of RT was administered in &gt;90% of cycles. No grade 4 toxicity occurred. 53/60 pts underwent resection after completed chemoradiation without increase of perioperative complications when compared to historic controls of CapOx-RT alone. Radiologic downstaging (17 pts. evaluated so far) was seen in 35% for T category and in 67% for N category. Pathologic complete response (45 pts. evaluable) was observed in 9% of pts, another 38% had “good regression” (&gt;50% of tumor cells). Conclusion: CapOx can safely be combined with cetuximab without requiring dose reduction of chemo- or radiotherapy and leads to significant downstaging. However, the relatively low rate of pathologic responses underachieved the assumptions. [Table: see text]
KEYNOTE-012: A phase Ib study of pembrolizumab (MK-3475) in patients (pts) with metastatic triple-negative breast cancer (mTNBC)
Authors: L. Buisseret, J. Specht, E.C. Dees, R. Berger, S. Gupta, R. Geva, L. Pusztai, C.K. Gause, V. Karantza, R. Nanda
Journal: Annals of Oncology (2015)
VEGF, angiogenesis and adjuvant therapy outcomes in resected pancreatic cancer
Authors: A. A. Khorana, Y. C. Hu, C. K. Ryan, R. A. Komorowski, G. Hostetter, S. A. Ahrendt
Journal: Journal of Clinical Oncology (2005)

4032 Background: Angiogenesis is important for pancreatic cancer progression, but its role in predicting response to therapy is not known. We investigated the association of various angiogenic factors and intratumoral microvessel density (IMD) with adjuvant therapy and survival in resected pancreatic cancer. Methods: Tissue cores from a multi-institutional retrospective series of resected patients were used to build a pancreatic cancer tissue microarray. Vascular endothelial growth factor (VEGF), platelet-derived endothelial cell growth factor (PD-ECGF), CD31 (for IMD) and DPC4 expression were determined using immunohistochemistry. Their association with clinical variables was assessed using Fisher’s or Wilcoxon’s test and quantified using hazard ratios. Survival probabilities were estimated using the method of Kaplan and Meier. Results: Expression of VEGF and PD-ECGF, both proangiogenic factors, was observed in 70(56%) and 75(59%) of 124 tumors, respectively. Expression of DPC4, an angiogenesis inhibitor, was observed in 59 of 124(48%) tumors. VEGF expression correlated significantly with increased IMD(p=0.03), as did loss of anti-angiogenic DPC4(p=0.05). PD-ECGF expression did not correlate with IMD. Use of adjuvant therapy was associated with increased survival in patients with VEGF-positive tumors (18.8[treated] versus 11.2[untreated] months; HR 0.38, 95%CI, 0.19–0.76; p=0.005), but not in patients with VEGF-negative tumors. Similarly, improved survival was observed in patients with high IMD (16.3[treated] versus 11.2[untreated] months; HR 0.44, 95%CI, 0.23–0.87; p=0.02) and in patients with loss of DPC4 (20.3[treated] versus 11.2[untreated] months; HR 0.31, 95%CI, 0.14–0.67; p=0.002), but not in those with low IMD or normal DPC4 expression. Conclusions: VEGF (stimulator) and DPC4 (inhibitor) are important regulators of pancreatic tumor angiogenesis. Increased angiogenesis, VEGF and loss of DPC4 are all predictive of benefit from adjuvant therapy, suggesting that adjuvant therapy may have both anti-angiogenic and cytotoxic effects. Addition of anti-VEGF agents to adjuvant regimens may further improve outcomes. No significant financial relationships to disclose.
Use of intratumoral mRNA expression of genes involved in angiogenesis and HIF1 pathway to predict outcome to VEGFR tyrosine kinase inhibitor (TKI) in patients enrolled in CONFIRM1 and CONFIRM2
Authors: P. M. Wilson, D. Yang, M. M. Shi, W. Zhang, C. Jacques, J. C. Barrett, K. Daneneberg, T. Trarbach, G. Folprecht, G. Meinhardt, H. J. Lenz
Journal: Journal of Clinical Oncology (2008)

4002 Background: Recent clinical trials (CONFIRM 1 and CONFIRM2) have shown that pts with mCRC with high serum LDH benefited from PTK787/ZK 222584 (PTK/ZK), a VEGFR TKI. We tested the hypothesis that pts with high intratumoral mRNA levels of genes involved with hypoxia (hypoxia inducible factor (HIF 1a) and lactate dehydrogenase A (LDHA) and glycolysis (glucose transporter 1 (Glut-1) and genes involved in angiogenesis such as vascular endothelial growth factor A (VEGF) and its receptors (VEGFR1 and VEGF2) will predict outcome in pts enrolled in CONFIRM1 and CONFIRM2. Methods: 191 formalin fixed paraffin embedded (FFPE) tumor samples from pts enrolled in CONFIRM 1 and CONFIRM2 were analyzed. 85 patients from CONFIRM1 (42 pts treated with FOLFOX, 43 pts with FOLFOX/PTK) and 106 from CONFIRM2 (54 pts treated with FOLFOX, 52 with FOLFOX/PTK). FFPE tissues were dissected using laser-captured microdissection and analyzed for gene expression using a quantitative real-time RT-PCR method. Relative mRNA levels are expressed as ratios between the target gene and internal reference gene (beta-actin). Results: LDHA (p=0.024), Glut1 (p=0.045) and VEGFR1 (p=0.012) mRNA levels predicted response in pts treated with FOLFOX/PTK/ZK in CONFIRM1 but not in pts treated with FOLFOX. There was a significant interaction for VEGFR1 and Glut1 to predict PTK activity (p=0.031 and p=0.036). HIF1a gene expression predicted response in pts treated with FOLFOX/PTK in CONFIRM2 (p=0.049). HIF1a mRNA levels were significantly associated with PFS in CONFIRM1 and 2. There was significant interaction for VEGFR2 showing benefit for patients treated with PTK in CONFIRM1 (p=0.001). VEGFR2 was significantly associated with OS in CONFIRM1 with VEGF mRNA levels showing significant interaction for pts receiving PTK in CONFIRM1. LDHA and Glut1 were significantly associated with OS in pts treated in CONFIRM 2 when receiving PTK. Conclusions: These results suggest that mRNA levels of genes involved in angiogenesis and in the HIF pathway may predict outcome to VEGFR TKI. These are the first data suggesting genes associated with specific PTK effect. Further studies are warranted to validate these exploratory findings. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer Schering Pharma AG, Novartis, Response Genetics Bristol-Myers Squibb, Genentech, ImClone, Merck, Pfizer, Response Genetics,Inc Novartis, Response Genectics,Inc Genentech, Merck, Pfizer, Roche, sanofi-aventis Dhont Family Foundation, NCI, NIH, Novartis
Cetuximab and cisplatin/5-FU (CF) versus CF in first-line metastatic squamous cell carcinoma of the esophagus (MESCC): A randomized phase II study of the Arbeitsgemeinschaft Internistische Onkologie (AIO)
Authors: F. Lordick, S. Lorenzen, S. Al-Batran, R. Hofheinz, P. C. Thuss-Patience, R. Porschen, N. Röthling, T. Schuster, C. Peschel
Journal: Journal of Clinical Oncology (2008)

4546 Background: Combining the EGFR antibody cetuximab with chemotherapy has shown increased efficacy compared with chemotherapy alone in various types of cancer. This trial was conducted to assess the activity of cetuximab in combination with CF in MESCC. Methods: Patients (pts) with prior treatment for metastatic disease received cetuximab (400 mg/m2 at first infusion followed by weekly 250 mg/m2) in combination with CF (100 mg/m² d1 plus 5-FU 1000 mg/m² d1–5 every 29d) or CF alone. The primary endpoint was tumor response (RECIST). Patients who progressed on CF were allowed to crossover to CF+cetuximab or cetuximab alone. Results: 66 pts with MESCC were included (median age 61y, range 40–76y; ECOG PS 0/1: 33/33). Two pts died and 2 pts had a deterioration of their PS before therapy started and were excluded from analyses. In 62 pts (CF 30, cetuximab and CF 32), the median duration of treatment was 11 wks for CF and 16 wks for cetuximab+CF. Of 5 pts who crossed over to cetuximab after disease progression with CF, 3 showed disease control, including 2 PRs (1 on cetuximab alone; 1 on cetuximab+CF) and 1 SD (cetuximab alone). With a median follow-up of 21.5 mo, median PFS was 3.6 [1.0–6.2] vs 5.7 [3.4–8.0] mo and median overall survival 5.5 [1.9–9.1] vs 9.5 [8.4–10.6] mo for CF vs cetuximab+CF. Median survival was 9.3 mo in pts with grade 2/3 skin reactions and 7.0 mo in pts with grade 1 or no skin reactions. Conclusions: Cetuximab can be combined safely with standard doses of CF. Although this study was not powered to demonstrate a significant difference in survival, results suggest that the addition of cetuximab may increase the efficacy of standard CF chemotherapy in MESCC. Tumor response and adverse events (grade 3/4) CF (%) Cetuximab+CF (%) Overall response rate [95%CI] 13 [4–31] 19 [7–36] Disease control rate [95%CI] 57 [37–75] 75 [57–89] Leukopenia 10 19 Thrombocytopenia 7 0 Nausea 3 13 Emesis 0 3 Diarrhea 0 16 Sensory neuropathy 0 6 Skin rash 0 6 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Merck Serono Merck Serono