tbuckley/cabot-search huggingface dataset:
What is the added value of actual tumor measurements (TM) in predicting overall survival (OS)? The North Central Cancer Treatment Group (NCCTG) findings
Authors: M. E. Campbell, S. J. Mandrekar, S. L. Hillman, R. M. Goldberg, A. A. Adjei, H. C. Pitot, K. M. Rowland, A. Grothey, J. C. Buckner, D. J. Sargent
Journal: Journal of Clinical Oncology (2008)

6520 Background: Categorical tumor response (TR), via the Response Evaluation Criteria in Solid Tumors (RECIST) or previously the WHO criteria, is the historical standard for assessing anti-tumor activity in cancer clinical trials (CCTs). We investigated whether area under the curve (AUC) metrics based on actual TM improve prediction of patient (pt) prognosis compared to categorical TR. Methods: Pts with measurable disease from 3 NCCTG CCTs, N0026 (First line Pemetrexed plus Gemcitabine in advanced lung, n=123), N9741 (First line IFL, FOLFOX4, or IROX in advanced colorectal (ACRC), n=1,128), and N9841 (2nd line IFL or FOLFOX in ACRC, n=341), were included. Average AUC (A-AUC) was computed using TM at each assessment including baseline, divided by time on study. Average change from baseline AUC (B-AUC) was computed using TM at each assessment divided by baseline TM, divided by time on study. The prognostic value of A-AUC and B-AUC versus categorical response, at 12 weeks (w) and over the entire course of therapy, was assessed using the concordance index (c-index, a measure of predictive accuracy that ranges from 0.5–1) in Cox models for OS. Results: Both A-AUC and B-AUC were associated with OS (p < 0.0001) but improved prediction for OS only modestly when added to Best Response (BR) or response at 12w (see table). Response at 12w was also associated with OS (p<0.0001) and showed a slight increase in the c-index over BR alone, suggesting that response at 12w is as predictive as BR for OS. Conclusions: In these 3 large CCTs, actual TM added minimal benefit to categorical TR for predicting subsequent survival. Following tumors beyond 12 w did not significantly improve OS prediction. Categorical 12w TR should be further explored as a more rapid, yet simple endpoint for phase II CCTs. Concordance Index (c) between Tumor Assessment Metrics and OS, by Study Entire Course of Treatment N0026 N9741 N9841 Best Response (BR) 0.60 0.63 0.65 Best Response & A-AUC 0.68 0.66 0.69 Best Response & B- AUC 0.61 0.65 0.66 12 Week Assessment Response (TR) 0.64 0.65 0.66 Response & A-AUC 0.70 0.66 0.69 Response & B-AUC 0.65 0.65 0.66 No significant financial relationships to disclose.
An open-label, phase I study of cetuximab to assess the safety, efficacy and pharmacokinetics (PK) of different cetuximab regimens in patients with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer (mCRC)
Authors: Y. Humblet, M. Peeters, H. Bleiberg, R. Stupp, C. Sessa, A. Roth, J. Nippgen, A. Nolting, P. Stuart, G. Giaccone
Journal: Journal of Clinical Oncology (2005)

3632 Background: Cetuximab (Erbitux) is an IgG1 monoclonal antibody that targets the human EGFR. Cetuximab has been shown to be active in patients with advanced CRC refractory to irinotecan-based chemotherapy, both as a single agent and when combined with irinotecan. Methods: The purpose of this study was to characterize the safety, efficacy and PK of cetuximab following the approved regimen (Group A) (initial dose of 400 mg/m2, followed by weekly doses of 250 mg/m2) and two exploratory regimens (weekly doses of 250 mg/m2 (Group B) or 350 mg/m2 (Group C) respectively not preceded by a higher initial dose) in patients with EGFR-expressing, refractory mCRC. Skin biopsies were taken to correlate biological activity with the different schedules. Results: 49 patients were enrolled on a sequential basis and evaluated for safety and efficacy, and 45 patients were evaluated for PK. PK parameters for Group A were in good agreement with historical data. Dose-related, predictable increases in Cmax and AUCτ were observed following weekly doses of 250 and 350 mg/m2. The PK parameters t1/2, CLss and Vss were similar across all treatment groups, indicating that they were independent of the dose. The ECOG performance status (PS) was not balanced across the groups (ECOG 2: A:35%/B11%/C:0). One patient, in group B, achieved a complete response. The objective response rates were 7.1%/22.2%/17.7% for arms A/B/C respectively. The disease control rates were 7.1%/27.8%/23.5%. Median survival was greater in group B (8.3 months) than in group A (3.6 months). The median survival time for group C was not yet been reached. Cetuximab therapy was well tolerated and the majority of the adverse events were due to the underlying disease or were consistent with the known safety profile of cetuximab. No Grade 3/4 skin toxicity occurred. Conclusions: The PK and safety profiles of the standard cetuximab regimen and 2 exploratory cetuximab regimens were within expectation. The differences between Groups A and B can be attributed to differences in PS. Evaluation of skin biopsies is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck KGaA AstraZeneca, Bristol-Myers Squibb, H3, Merck, Merck KGaA, Pfizer, Pharmachemic, Roche, Threshold AstraZeneca, Aventis, Bristol-Myers Squibb, Pfizer, Roche, Sanofi AstraZeneca, Roche Sanofi Aventis, Sanofi
Primary analysis of a phase 1b multicenter trial to evaluate safety and efficacy of talimogene laherparepvec (T-VEC) and ipilimumab (ipi) in previously untreated, unresected stage IIIB-IV melanoma.
Authors: Igor Puzanov, Mohammed M. Milhem, Robert Hans Ingemar Andtbacka, David R. Minor, Omid Hamid, Ai Li, Michael Chastain, Kevin Gorski, Abraham Anderson, Ari M. Vanderwalde, Jeffrey Chou, Howard Kaufman
Journal: Journal of Clinical Oncology (2014)

9029^ Background: T-VEC, an HSV-1 derived oncolytic immunotherapy designed to induce systemic antitumor immunity, showed a ≥ 6 mos higher durable response rate vs GM-CSF in a phase 3 melanoma trial (Andtbacka et al. ASCO 2013). This phase 1b/2 study will determine the safety and efficacy of T-VEC as a priming regimen when added to ipi. Methods: Phase 1b studied the safety of T-VEC+ipi. Objective response rate (ORR) was also evaluated with tumor assessments q12w. Blood was collected pre- and post-treatment (tx) for correlative studies. Key criteria: unresected Stage IIIB-IV melanoma, no prior systemic tx, measurable disease, and ≥1 injectable cutaneous, subcutaneous or nodal lesion. T-VEC was given intralesionally at ≤ 4 mL of 106 PFU/mL at wk 1, then 108 PFU/mL at wk 4 and then q2w. Ipi 3 mg/kg q3w was given as 4 infusions starting wk 6. Tx continued until DLT, intolerance, all injectable tumors disappeared, or disease progression (PD) per Immune Related Response Criteria. DLT was any grade (gr) ≥ 4 adverse event (AE) or gr ≥ 3 immune-related AE within the first 6 wks of ipi tx. Results: Of 19 patients (pts) enrolled: 42% men, 42% ≥ 65 yrs, 58% Stage IV M1b/c; 18 pts received T-VEC+ipi. No DLTs were reported. Gr 3/4 AEs occurred in 32%. 2 pts had possible immune-related gr 3/4 AEs: 1 pt had gr 3 hypophysitis (attributed to ipi) and gr 3 adrenal insufficiency and gr 3 diarrhea (both attributed to combination), and 1 pt had gr 4 amylase+lipase attributed to ipi. PD (CNS metastases) led to one gr 5 AE. By 15 Oct 13 (data cutoff), median tx duration of T-VEC was 13.3 wks. Of 17 pts with investigator assessed response, ORR was 41% (24% CR, 18% PR); 35% had SD. Median time to response was 2.9 mos. By flow cytometry, activated CD8 T cells significantly increased from baseline 1.8x after T-VEC alone and 2.9x during T-VEC+ipi tx. Conclusions: T-VEC+ipi appears to be tolerable with no DLTs. In consideration with published reports, these data, although preliminary, suggest higher CR and OR rates than either agent alone and earlier responses after ipi initiation during T-VEC+ipi than with ipi alone. Additional immunophenotyping and phase 2 (ipi vs T-VEC+ipi) are ongoing. Clinical trial information: NCT01740297.
IMPALA, a randomized phase III study in patients with metastatic colorectal carcinoma: Immunomodulatory maintenance therapy with TLR-9 agonist MGN1703.
Authors: David Cunningham, Alfredo Zurlo, Ramon Salazar, Michel Ducreux, Tom Samuel Waddell, Alexander Stein, Christophe Tournigand, Werner Scheithauer, Alberto F. Sobrero, Eric Van Cutsem, Dirk Arnold
Journal: Journal of Clinical Oncology (2015)

TPS791 Background: The potent TLR-9 agonist MGN1703, a synthetic DNA-based immunomodulator, was compared to placebo in metastatic colorectal cancer (mCRC) patients with disease control after standard induction chemotherapy +/- bevacizumab in the phase II IMPACT trial and showed a superior effect with a hazard ratio for the primary endpoint PFS on maintenance of 0.55 (p=0.041) by local investigator assessment and 0.56 (p=0.070) by independent radiological review. In the MGN1703 arm 3 objective responses were observed, two of them appearing as late as 9 months after the start of treatment. At time of study closure 4 MGN1703 patients were still without progressive disease and continued treatment by self-administration in a compassionate use setting. Exploratory Cox regression and ROC analyses suggested a potential predictive role at baseline for normal CEA, objective response to prior chemotherapy and presence of activated NKT-cells. Methods: The pivotal IMPALA study has been designed to confirm these data and started to enroll patients with smaller tumor burden after a good response to chemotherapy, as best candidates to receive a maintenance treatment with immunotherapy. IMPALA is a randomized, international, multicenter, open-label phase III trial that will include 540 patients from 120 centers with the collaboration of the AIO, TTD, and GERCOR cooperative groups and is currently recruiting patients. In this study mCRC patients with an objective tumor response following any first line induction therapy will be randomized to MGN1703 monotherapy maintenance or local standard of care. At time of relapse, patients will reintroduce the induction treatment whenever feasible, with those in the experimental arm continuing to receive MGN1703 in the weeks without chemotherapy. Patients will also be stratified by CEA level and activated NKT at baseline. The primary endpoint of the study will be overall survival. Secondary endpoints include PFS, response rates, safety, and QoL in selected centers. All patients will be evaluated for cytokines and chemokines in serum and the activation status of various immune cell populations. Clinical trial information: NCT02077868.
Integrated analyses of DNA copy number variations and gene expression in inflammatory breast cancer (IBC).
Authors: Mian Xie, Chao-sheng He, Shen-hai Wei
Journal: Journal of Clinical Oncology (2013)

28 Background: Inflammatory breast cancer (IBC) is an aggressive form of BC poorly defined at the molecular level. We aim to perform genome-wide analyses of copy number variation and gene expression to identify genes reproducibly associated with survival in IBC patients. Methods: We performed concurrent genome-wide microarray analyses of copy number variable regions (CNVRs) and gene expression in IBC patients. Fifty-six pairs of breast cancer and normal specimens from IBC patients were analyzed by using Affymetrix SNP 6.0 and Affymetrix U133 plus 2.0 microarrays. To investigate genomic alterations, we used an Affymetrix Genome-Wide Human SNP 6.0 array containing 1.8 million SNP and CNV probes in total. The microarray data were imported into the Partek Genomic Suite to perform CNV analysis. Ingenuity Pathway Analysis was carried out to describe gene-gene interaction networks and canonical pathways. Cox regression model was used to evaluate the association between expression of these CNV-driven genes and survival outcomes. Results: The genomic landscape of frequent copy number variable regions (CNVRs) in at least 35% of samples was revealed. Further statistical analysis for genes located in the CNVRs identified 387 genes differentially expressed between tumor and normal tissues (p &lt; 0.001). We demonstrated the concordance between copy number variations and gene expression changes by elevated Pearson correlation coefficients. Fisher’s exact test identified five canonical pathways that were significantly enriched among the 387 CNV-driven genes. Pathway analysis revealed two major dysregulated functions in IBC: survival regulation via Rac/PAK and PTEN/PI3K/AKT signaling pathway. Further validation using three independent cohorts demonstrated prediction of survival. Conclusions: We identified genes/pathways that may serve as prognostic markers for IBC patients by integrating gene expression profiles and copy number variations.
Different kinases acting on stathmin (oncoprotein, Op18) in human healthy and malignant hematopoietic stem cells
Authors: H. Lannert, T. Able, S. Leicht, R. Saffrich, V. Eckstein, M. Lenze, R. Hofmann, A. Lenze, T. Franz, A. D. Ho
Journal: Journal of Clinical Oncology (2007)

17527 Background: Stathmin/Op18 is a cytosolic phosphoprotein which regulates the dynamics of microtubules. This regulation is important in mitosis during cell division and in the migration of cells in modification of the cytoskeleton. The process of tumor proliferation and metastasis is characterized by high rates of mitosis and migration into distant tissues. Stathmin itself is regulated by kinases through phosphorylation of mainly 4 different serin sides. In this study, we investigated stathmin- and its kinases expression in native hematopoietic CD34+ stem cells (HSCs) from bone marrow (BM) in comparison to mobilized peripheral blood stem cells (mPBSCs) from G-CSF stimulated donors and leukemic CD34+ cells from patients with AML. Methods: Mononuclear cells were isolated by a standard Ficoll-Hypaque gradient separation method from the different blood sources. An Auto-MACS (Miltenyi) and FACS Vantage SE cell sorter (Becton Dickinson) was used to highly enrich (&gt;99%) CD34+ cells fractions. In comparative proteome analysis, we detected the protein expression of stathmin in mPBSCs, AML CD34+ cells, and in native HSCs from BM. We performed microarray-based gene expression profiles of these cells and focused on kinases regulating stathmin’s activity. Furthermore, we monitored stathmin and its relevant kinases by FACS analyses of the enriched cell fractions and by fluorescence microscopy of bone marrow smears and cytospins. Results: In this study, we have shown in comparative proteome analysis (Q-TOF-MS/MS) that stathmin is expressed in G-CSF mobilized hematopoietic stem cells for the first time and in AML cells. In microarray analysis we indentified up- and down-regulated kinases: MAPK, PAK1, PKC beta/zeta, MEKK3 and CDKs. Accordingly, we demonstrated in FACS analyses and in immunofluorescence microscopy the high intracellular expression of PKCzeta in AML cells and MEKK3 as well PAK1 in mPBSCs. Conclusions: Our findings show that G-CSF stimulates Stathmin expression in mPBSCs and plays a key role in migration into peripheral blood. Furthermore, we show the different expression of kinases acting on stathmin in mPBSCs and AML cells. Consequently, stathmin and its relevant kinases promise to become a future target in therapies of malignant processes. No significant financial relationships to disclose.
The Quantitation of Mixtures of Hemoglobin Derivatives by Photoelectric Spectrophotometry
Journal: JAMA (1952)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Effects of Maternal Age and Birth Order on the Risk of Mongolism and Leukemia
Authors: Stark, Charles R., Mantel, Nathan
Journal: JNCI Journal of the National Cancer Institute (1966)

Journal Article Effects of Maternal Age and Birth Order on the Risk of Mongolism and Leukemia Get access Charles R. Stark, Charles R. Stark Epidemiology Branch, National Cancer Institute,4Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Nathan Mantel Nathan Mantel Epidemiology Branch, National Cancer Institute,4Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 37, Issue 5, November 1966, Pages 687–698, https://doi.org/10.1093/jnci/37.5.687 Published: 01 November 1966 Article history Received: 26 April 1966 Published: 01 November 1966
Melphalan/prednisone/lenalidomide (MPR) versus high-dose melphalan and autologous transplantation (MEL200) plus lenalidomide maintenance or no maintenance in newly diagnosed multiple myeloma (MM) patients.
Authors: Mario Boccadoro, Federica Cavallo, Francesca Maria Gay, Francesco Di Raimondo, Arnon Nagler, Vittorio Montefusco, Francesca Patriarca, Paola Tacchetti, Tommasina Guglielmelli, Pellegrino Musto, Luca Baldini, Claudia Crippa, Marina Ruggeri, Fabiana Gentilini, Maide Cavalli, Dina Ben Yehuda, Tommaso Caravita, Giovannino Ciccone, Izhar Hardan, Antonio Palumbo
Journal: Journal of Clinical Oncology (2013)

8509 Background: The incorporation of new drugs into induction, consolidation, and maintenance therapy is changing the treatment paradigm of MM. Methods: At diagnosis, 402 pts (&lt; 65 years) were randomly assigned to receive six MPR cycles (N=202) or tandem MEL200 (N=200). After MPR or MEL200, pts were further randomized, within each group, for no maintenance (N=204) or lenalidomide maintenance (N=198). A 2x2 factorial randomized trial was designed. The primary end point was PFS. An enrolment of 170 pts/arm was required to demonstrate a 15% improvement of PFS at 2 years (2-sides a = 0.05, 1- β 80%). Results: After a median follow-up of 45 mos from diagnosis, the median PFS was 25 mos with MPR and 39 mos with MEL200 (p=.0002). Median PFS were 37.5 mos for maintenance and 25.7 mos for no maintenance (p=.0008). The 4-year OS from diagnosis was 71% with MPR and 72% with MEL200 (p=0.71), 76% for maintenance and 68% for no maintenance (p=.08). After a median follow-up of 32 mos from start of maintenance, the median PFS was for 41 mos for maintenance and 18 mos for no maintenance (p&lt;.0001). The 3-year OS from start of maintenance was 81% for maintenance and 72% for no maintenance (p=.04). Conclusions: MEL200 significantly prolonged PFS in comparison with MPR. Lenalidomide maintenance significantly reduced the risk of progression independently from the previous treatment. OS is similar between MPR and MEL200, with a trend for an improved OS in pts receiving lenalidomide as maintenance therapy. Clinical trial information: NCT00551928. [Table: see text]
Detecting bleomycin pulmonary toxicity: a continued conundrum.
Authors: R L Comis
Journal: Journal of Clinical Oncology (1990)

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.1990.8.5.765 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 1692087 Detecting bleomycin pulmonary toxicity: a continued conundrum. R L ComisxR L ComisSearch for articles by this author Show More Fox Chase Cancer Center, Philadelphia, PA. https://doi.org/10.1200/JCO.1990.8.5.765 First Page PDF © 1990 by American Society of Clinical Oncology
Evaluation of Bcl-2 expression in melanoma - A tissue microarray study
Authors: K. A. Divito, M. Dolled-Filhart, R. Camp, A. Berger, D. Rimm, H. Kluger
Journal: Journal of Clinical Oncology (2004)

7515 Background: Metastatic melanoma remains a highly chemotherapy-resistant disease, for which there is no cure. One of the few recent advances in treating metastatic melanoma is the addition of Bcl-2 antisense to dacarbazine as first line therapy, which increases response rates, median survival and disease free survival. Studies in the literature report a very wide range of frequencies of expression of the anti-apoptotic protein Bcl-2 in melanoma specimens (60% to 96%). Some reports have shown up regulation of Bcl-2 with increased disease aggression, while other groups have demonstrated an inverse relationship. These studies have included fewer than 100 patients; therefore we sought to re-address this issue using a large cohort of melanoma specimens. Methods: Tissue microarrays containing specimens from 282 melanoma patients with 20 year follow-up were employed and evaluated with our AQUA system for automated quantitative analysis. The system uses S100 to define pixels as melanoma (tumor mask) within the array spot, and then measures intensity of Bcl-2 expression using Cy5 conjugated antibodies within the mask. Scores were divided into quartiles, and correlated with clinical and pathological variables. Results: High Bcl-2 expression was associated with better outcome in the entire cohort and among the metastatic specimens only (P = 0.02 and P = 0.01, respectively). Bcl-2 expression was higher in primary than in metastatic specimens (P = 0.002) and in patients older than 50 years of age (P = 0.03). Among the primary specimens there was no association between Bcl-2 expression and Breslow depth and Clark level. Conclusions: High Bcl-2 expression is associated with better survival in melanoma and with earlier stage disease. The diverse results in the literature might be due to use of small cohorts or to variability in staining technique. Studies are needed to evaluate the association between Bcl-2 expression and response to Bcl-2 antisense. Patient selection based on Bcl-2 expression might improve response rates to Bcl-2 antisense. No significant financial relationships to disclose.