tbuckley/cabot-search huggingface dataset:
The effect of PSA frequency and duration on PSA doubling time (PSADT) calculations in men with biochemically recurrent prostate cancer (BRPC) after definitive local therapy.
Authors: Channing Judith Paller, Sherlly Xie, Dare Olatoye, Samuel R. Denmeade, Mario A. Eisenberger, Emmanuel S. Antonarakis, Michael Anthony Carducci, Gary L. Rosner
Journal: Journal of Clinical Oncology (2012)

4559 Background: The prognostic nature of PSADT in men with BRPC makes it an attractive intermediate endpoint for assessing novel therapies in these patients. Although a number of investigational agents appear to favorably modulate PSADT, slowing in PSADT has also been observed in placebo-treated men. We aimed to determine whether PSADT calculations could be influenced by the frequency and duration of PSA measurements. Methods: We performed a retrospective analysis of men with BRPC who chose to defer hormonal therapy. Eligible men were those with PSA values ≥0.2 ng/mL and at least 6 values taken on average 3 mo apart, and whose local prostate cancer therapy was completed ≥1 year prior. To examine the influence of PSA frequency and duration on PSADT, we calculated median PSADT using different subsets of available PSA values (e.g. each vs every other; and first 3 vs. remaining PSA values). Results: After a median follow-up of 58 mo (range, 6-185 mo), 213 men with BRPC had ≥6 PSA values and 127 men had ≥9 PSA values for analysis. Men (77% white, 23% black/other) had a median age of 61 y with Gleason score distribution as follows (≤6: 30%; 7: 40%; ≥8: 18%; NOS: 12%). For men with ≥6 data points: PSADT calculated using earlier values ranged from 13.2 to 16.6 mo, compared to 16.6 to 17.8 mo, respectively, for the remaining values (within-patient change range: 0.6-1.2 mo). For men with ≥9 data points: PSADT calculated using earlier values ranged from 15.3 to 19.9 mo compared to 22.1 to 22.3 mo, respectively, for the remaining values (within-patient change range: 3.5 to 4.5 mo). When we examined the frequency of PSADT by using every other value, we found little difference (22.3 vs 22.1 mo). Conclusions: These data show that PSADT appears to increase even in the absence of therapy, and may be influenced by duration of PSA follow up. This finding explains PSADT slowing on placebo arms and calls into question the utility of PSADT as a surrogate endpoint. Placebo-controlled trials and the use of standard clinical endpoints are recommended to screen novel agents in men with BRPC to mitigate bias because of natural PSADT variability.
Attrition bias: Does the benefit of targeted agents (TA) increase the more we search for a selection biomarker? Meta-regression analysis of randomized clinical trials (RCTs) in advanced non-small cell lung and colorectal cancer (NSCLC/CRC).
Authors: D. Giannarelli, M. Milella, F. Loupakis, F. Cuppone, V. Vaccaro, I. Sperduti, P. Carlini, A. Falcone, F. Cognetti, E. Bria
Journal: Journal of Clinical Oncology (2011)

6056 Background: The efficacy of TA in molecularly selected patients (pts) is often based on retrospective analyses neither prospectively balanced nor adequately powered. The ‘attrition bias’ generated by the lack of information in a substantial proportion of pts may have a role in determining the magnitude of benefit of a TA in a specific patient population. Methods: Using a literature-based meta-analysis approach to evaluate the magnitude of benefit from the addition of Anti-EGFR antibodies (Ab) to standard chemotherapy for unselected advanced CRC pts or EGFR-TKI vs chemotherapy for unselected advanced NSCLC pts, we explored whether 1) the rate of pts analyzed (AN-Pts%) for KRAS (advanced CRC) or EGFR mutation (advanced NSCLC) or 2) the rate of mutant pts (M+Pts%) may influence the results of RCTs, thus generating an attrition bias. Regressions between AN-Pts% and M+Pts% (K-RAS and EGFR), respectively, upon Log Hazard Ratios (HR for PFS/OS) were determined. Results: Six CRC (3,722 pts) and 3 NSCLC (2,992 pts) RCTs were gathered. A statistically significant decrease in the HR for PFS (hence, an increased magnitude of benefit) was observed as the AN-Pts% increased (see table); when the M+Pts% was considered, the direction of the difference (benefit vs detriment) depended on the nature of the mutation analyzed (sensitizing/EGFR vs resistance-inducing/KRAS) (Table). A significant correlation between the K-RAS AN-Pts% (Z=-2.88, p=0.003) and M+Pts% (Z=+2.13, p=0.03) was also found for OS in the CRC trial sample. Conclusions: The attrition rate in the context of retrospective analyses investigating the efficacy of TA in molecularly selected subgroup of pts has a significant impact on the observed magnitude of the benefit, strongly calling for prospective trials in target-enriched populations. Disease Regression (Z-value [p]) bewteen LogHR(PFS) and: K-RAS M+Pts(%) AN-Pts% EGFR CRC -3.17 (0.001) +1.04 (0.24) - NSCLC -3.24 (0.0012) - -3.15 (0.0016)
Noncirrhotic complete obliterative portal vein thrombosis: Novel management using trans‐splenic transjugular intrahepatic portosystemic shunt with portal vein recanalization
Authors: Joseph Ralph Kallini, Ahmed Gabr, Laura Kulik, Daniel Ganger, Robert Lewandowski, Bartley Thornburg, Riad Salem
Journal: Hepatology (2015)

Kallini, Joseph Ralph M.D.; Gabr, Ahmed M.D.; Kulik, Laura M.D.; Ganger, Daniel M.D.; Lewandowski, Robert M.D.; Thornburg, Bartley M.D.; Salem, Riad M.D., M.B.A. Author Information
Development and validation of a staging system for HPV-related oropharyngeal cancer by the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S): a multicentre cohort study
Authors: Brian O'Sullivan, Shao Hui Huang, Jie Su, Adam S Garden, Erich M Sturgis, Kristina Dahlstrom, Nancy Lee, Nadeem Riaz, Xin Pei, Shlomo A Koyfman, David Adelstein, Brian B Burkey, Jeppe Friborg, Claus A Kristensen, Anita B Gothelf, Frank Hoebers, Bernd Kremer, Ernst-Jan Speel, Daniel W Bowles, David Raben, Sana D Karam, Eugene Yu, Wei Xu
Journal: The Lancet Oncology (2016)
Masculinization of Female Infants Associated with Norethindrone Acetate
Authors: E FINE, H M LEVIN, E L MCCONNELL
Journal: JAMA (1963)

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Morphologic and Biologic Correlation of Lesions Obtained in Hepatic Carcinogenesis in A × C Rats Given 0.025 Percent <italic>N</italic>-2-Fluorenyl-diacetamide<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref>
Authors: Melvin D. Reuber, Harlan I. Firminger
Journal: JNCI Journal of the National Cancer Institute (1963)

A high correlation was found between the morphological interpretation and biological behavior of hepatic lesions induced by carcinogen feeding to rats. Inbred A × C male or female rats were fed 0.025 percent N-2-fluorenyldiacetamide in a semisynthetic diet for 2, 2½, 3, and 4 months; laparotomy, liver biopsy, and transplantation were carried out every 6 to 8 weeks. Autologous and isologous transplants of normal and cirrhotic liver and areas and nodules of hyperplasia (with a single exception) did not grow. A few “small hepatomas,” morphologically comparable to “carcinoma in situ” and measuring 5 mm or less in diameter, also failed to grow. Hepatomas that grew measured a minimum of 7 to 9 mm in diameter. Almost all primary hepatomas 1 cm or more in diameter grew autologously and isologously in transplant. Such well-developed hepatomas occurred only in animals given carcinogen for 3 or 4 months. To determine the transplantability the animals with transplants were followed for a number of months. The time of appearance of palpable growth, the rate of growth of the transplanted tumors, and the metastases were partly dependent on the morphologic pattern. Subsequent transplants of both well and poorly differentiated tumors appeared earlier in the second through the eighth generations. Pulmonary metastases were present in 26 percent of animals bearing successful transplants; 10 percent of these metastatic tumors were well differentiated and 90 percent were poorly differentiated. Curiously, well-differentiated hepatomas, 7 mm or greater in diameter, from rats given carcinogen for 4 months were more successfully transplanted isologously than those from rats given carcinogen in the diet for 3 months. As might be expected, autologous transplants of well-developed hepatomas appeared earlier and grew more rapidly than the corresponding isologous transplants. All homologous subcutaneous transplants in Sprague-Dawley rats and heterologous intracerebral transplants in Hauschka mice failed to grow within 8 to 12 months.
Depletion of Normal and Malignant B cells with a CD37-specific SMIP molecule
Authors: C. Cerveny, L. Grosmaire, E. Espling, R. Bader, C. Nilsson, P. Baum, A. Wahl, J. Ledbetter, M. Hayden-Ledbetter
Journal: Journal of Clinical Oncology (2007)

3063 Background: CD37 is a member of the tetraspanin family expressed at high levels by normal mature B cells and by most B cell malignancies. Previously, an antibody to CD37 has been labeled with 131 I and tested in clinical trials for therapy of NHL. Treatment with 131 I-MB-1, resulted in durable tumor remissions in patients lasting from 4 to 11 months (Press OW, Eary JF, Badger CC, et al. Treatment of refractory non-Hodgkin’s lymphoma with radiolabeled MB-1 (anti-CD37) antibody. J Clin Oncol. 1989;7:1027–1038). Here we assess the functional properties and therapeutic potential of a small modular immunopharmaceutical (SMIP) targeting CD37. Methods: Growth arrest and apoptosis of B lymphoma cell lines was assessed. ADCC activity was evaluated using BJAB targets and human peripheral blood mononuclear cells (PBMC) effectors. Drug-drug interactions were assessed by the Combination Index method. In vivo studies were performed utilizing established human B cell tumor xenografts in nude mice. Results: A CD37-directed SMIP drug candidate mediated growth arrest, apoptosis and ADCC, but not CDC, towards B lymphoma cell lines. The protein showed significant anti-tumor activity in a mouse xenograft model, and selectively depleted normal human B cells in short term cultures of PBMC. When combined with rituximab, the molecule increased apoptosis, C1q binding, and C’ dependent target cell death in vitro, and increased anti-tumor activity in vivo in a xenograft model. Conclusions: In vitro and in vivo characterization of the CD37-targeted SMIP drug suggest a potent capacity to eliminate target cells through combined effects of direct target cell signaling and effector cell recruitment. CD37-mediated growth was synergistic with standard chemotherapies in vitro and showed additive in vivo activity with CD20-targeted therapy. On the basis of these data CD37-directed SMIP therapy is being developed for clinical evaluation against B cell malignancies. No significant financial relationships to disclose.
Overall survival (OS) in metastatic breast cancer (MBC): Are we using the right endpoint in the right way?
Authors: Jacques Raphael, Sunil Verma
Journal: Journal of Clinical Oncology (2014)

142 Background: OS has been historically considered the most important clinical endpoint in MBC trials; however survival could be influenced by treatment after progression in an era of effective subsequent-line agents. Methods: We conducted a search strategy using PubMed for randomized phase 3 trials published in the last 2 decades (1994-2014) evaluating survival outcome in MBC. We investigated the frequency of trials reporting post progression outcome and response/resistance to treatment beyond progression. Results: 110 trials met our eligibility criteria: 69 (63%) evaluated chemotherapy regimens (group A), 27 (25%) evaluated targeted therapy (group B) and 14 (13%) focused on endocrine treatment (group C). The majority of the trials had OS as a primary or secondary endpoint (97% (66/69), 100% (27/27) and 86% (12/14) of the trials in group A, B and C respectively). An OS benefit was demonstrated in approximately 22% of the trials in each group. Post progression survival (PPS) and its effect on OS was reported and discussed in only 1% (1/69), 4% (1/27) and 7% (1/14) of the trials for group A, B and C respectively. Less than 10% of the trials in group A and B reported response data and duration of response after progression on trial therapy. In addition, post progression treatment resistance was only reported in group A in 3% (2/69) of the trials. Furthermore, the number of lines of treatment used post progression was reported in only 14% (10/69), 11% (3/27) and 14% (2/14) of the trials in group A, B and C respectively. Conclusions: A clear paucity of post progression treatment information is noted in the majority of the phase 3 trials for MBC. We do know that OS is directly affected by treatments used after progression. In order to assess the true clinical benefit of a new drug and a complete evaluation of overall survival outcome, a detailed collection of post progression treatment information is required and should be mandated in MBC clinical studies.
Circulating endothelial cells are a potential biomarker for patients with renal cell carcinoma (RCC) with and without von Hippel Lindau (VHL) syndrome
Authors: R. S. Bhatt, A. Norden-Zfoni, A. O’Neill, A. J. Zurita, H. Wu, D. Prox, M. B. Atkins, J. V. Heymach
Journal: Journal of Clinical Oncology (2008)

5098 Background: VHL is a primary cause of inherited RCC and 60% of sporadic clear cell RCCs have mutations in the VHL gene. RCCs often remain asymptomatic for long intervals. Diagnosis during presymptomatic screening has the potential to improve overall outcome. Circulating endothelial cells (CECs) are a potential biomarker for monitoring angiogenesis. Mature CECs are thought to be shed from existing vessels while circulating endothelial progenitors (CEPs) are thought to be derived from bone marrow. We sought to assess the potential of CECs and CEPs as markers of RCC in pts with VHL and sporadic RCC. Methods: Batch analysis of PBMCs obtained from consenting pts with sporadic or VHL associated RCC, VHL (without RCC), and normal volunteers (NV) was performed FACS analysis was performed using a panel for four antibodies including CD45, CD31, CD146, and CD133. CECs were defined as CD45-, CD31+ and CD146+, and CD133-. CEPs had the same phenotype but were CD133+. Results: RCC pts have higher CECs, CEPs and CEP/CEC ratio as compared to NV (p<0.05 for each comparison). Additionally, these 3 parameters were similar in NV and pts with VHL without RCC. However pts with VHL and RCC had significantly higher CEP/CEC ratio and CEP values than pts with VHL without RCC. (p<0.05 for each comparison) (Table). Conclusions: CECs are a potential biomarker for RCC in pts with sporadic RCC. These data suggests that CEPs and CEP/CEC ratio may represent a screen that may allow for the early detection of RCC in VHL pts. Larger studies will be needed to validate these findings. Supported by VHL Family Alliance (Joyce Graff Director) the DF/HCC Kidney Cancer SPORE P50CA101942, and the ASCO YIA. Average CEC (cells/ul) Average CEP (cells/ul) Average CEP/CEC RCC (n=10) * 2.36 2.08 1.97 NV (n=17) 0.45 0.21 0.61 VHL (without RCC) (n=13) 0.54 0.19 0.67 VHL (with RCC) (n=6) 3.16 2.91 2.76 * includes pts with VHL and RCC (n=6) and pts with sporadic RCC (n=4). No significant financial relationships to disclose.
Choice of chemotherapy (CT) for advanced/metastatic lung carcinoma, WHO types I - III - IV (NSCLC)
Authors: R. Bollina, G. Beretta, P. Belloni, D. Toniolo, C. Cozzi, S. Brigida, G. A. Beretta
Journal: Journal of Clinical Oncology (2006)

17132 For NSCLC optimal CT has not been established so far, while many equivalent moderately active schemes are used. The present 40-month study randomized 71 consecutively accrued patients (pts) with parametrable disease between platinum(P)-based three-weekly combinations and non-P monoCT (weekly gemcitabine, vinorelbine or taxane). 68 evaluable pts characteristic were well balanced between treatments: median age 67 years (r. 40–82y), median P Status &lt; 2 WHO scale (r. 0–2),male predominant 82.3%, ratio of IIIb/IV = 1.34 and squamous/non squamous histotype = 1.19, pathologies 26% (only mild to moderate, not contraindicating CT). Objective/subjective response (RECIST/MILAN criteria, JNCI 92:180; P.ASCO 19:642a) after poliCT (PCT) or monoCT (MCT) are reported in the descriptive table . Tolerance was good for both treatment, MCT resulting less deeply toxic and more easily accepted by the majority of pts. This study is still ongoing to achieve the total pts accrual in order to explore statistical significant in the principal determinant subgroup, to determine the subjective response to CT, and to confirm a possible difference in survival. The role of a programmed second line CT vs supportive care alone, and the impact of adding new biomolecular therapies (combined with CT) are the short-term challenges of the second part of this prospective study for advanced NSCLC. [Table: see text] No significant financial relationships to disclose.
Phase 1 Study Of Single Agent CC-292, a Highly Selective Bruton's Tyrosine Kinase (BTK) Inhibitor, In Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)
Authors: Jennifer R. Brown, Wael A. Harb, Brian T. Hill, Janice Gabrilove, Jeff P. Sharman, Marshall T. Schreeder, Paul M. Barr, James M. Foran, Thomas P. Miller, Jan A. Burger, Kevin R. Kelly, Daruka Mahadevan, Shuo Ma, Evelyn Barnett, Jeffrey Marine, Pilar Nava-Parada, Ada Azaryan, Jay Mei, Thomas J. Kipps
Journal: Blood (2013)
Quantitative Tumor Cell Content of Bone Marrow and Blood as a Predictor of Outcome in Stage IV Neuroblastoma: A Children’s Cancer Group Study
Authors: Robert C. Seeger, C. Patrick Reynolds, Richard Gallego, Daniel O. Stram, Robert B. Gerbing, Katherine K. Matthay
Journal: Journal of Clinical Oncology (2000)

PURPOSE: This study investigated the prognostic value of quantifying tumor cells in bone marrow and blood by immunocytology in children with high-risk, metastatic neuroblastoma. PATIENTS AND METHODS: Patients with stage IV neuroblastoma (N = 466) registered on Children’s Cancer Group study 3891 received five cycles of induction chemotherapy and were randomized either to myeloablative chemoradiotherapy with autologous purged bone marrow rescue or to nonmyeloablative chemotherapy. Subsequently, they were randomized to 13-cis-retinoic acid or no further treatment. Immunocytologic analyses of bone marrow and blood were performed at diagnosis, week 4, week 12, bone marrow collection, and end induction and were correlated with tumor biology, clinical variables, treatment regimen, and event-free survival (EFS). RESULTS: Immunocytology identified neuroblastoma cells in bone marrow of 81% at diagnosis, 55% at 4 weeks, 27% at 12 weeks, 19% at bone marrow collection, and 14% at end induction. Tumor cells were detected in blood of 58% at diagnosis and 5% at collection. There was an adverse effect on EFS of increasing tumor cell concentration in bone marrow at diagnosis (P = .04), at 12 weeks (P = .006), at bone marrow collection (P &lt; .001), and at end induction (P = .07). Positive blood immunocytology at diagnosis was associated with decreased EFS (P = .003). The prognostic impact of immunocytology was independent of morphologically detected bone marrow disease, MYCN status, and serum ferritin level in bivariate Cox analyses. CONCLUSION: Immunocytologic quantification of neuroblastoma cells in bone marrow and blood at diagnosis and in bone marrow during induction chemotherapy provides prognostic information that can identify patients with very high-risk disease who should be considered for experimental therapy that might improve outcome.
Sequential combination of systemic high-dose ara-C and asparaginase for the treatment of central nervous system leukemia and lymphoma.
Authors: S Amadori, G Papa, G Avvisati, M C Petti, M Motta, M Salvagnini, G Meloni, M Martelli, B Monarca, F Mandelli
Journal: Journal of Clinical Oncology (1984)

Eight patients with overt central nervous system (CNS) leukemia and lymphoma were treated with sequential administration of systemic high-dose cytosine arabinoside (HiDAC) and asparaginase (ASP) with no direct CNS therapy. Complete clearing of the cerebrospinal fluid (CSF) was achieved in six (86%) of seven patients with meningeal disease, generally after the first course of therapy. Two patients presented with evidence of extensive intracerebral disease; both responded with a greater than 50% regression of the tumor infiltrates. Concomitant extraneurologic localizations responded equally well to HiDAC/ASP: responses were seen in four of five patients, including complete remission in three of four patients who presented with marrow involvement. Toxicity was generally moderate and limited to myelosuppression (eight of eight patients), tolerable nausea and vomiting (eight of eight patients), mild hepatotoxicity (two of eight patients), and oral mucositis (one of eight patients). These results indicate that HiDAC/ASP is a tolerable and highly effective treatment modality for CNS leukemia and lymphoma and suggest its potential role for sanctuary chemoprophylaxis.
Tamoxifen and chemotherapy in the treatment of metastatic melanoma: are there other possible mechanisms explaining their potentiation?
Authors: G Gasparini
Journal: Journal of Clinical Oncology (1994)

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.1994.12.9.1994 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8083722 Tamoxifen and chemotherapy in the treatment of metastatic melanoma: are there other possible mechanisms explaining their potentiation? G GasparinixG GaspariniSearch for articles by this author https://doi.org/10.1200/JCO.1994.12.9.1994 PDF "Tamoxifen and chemotherapy in the treatment of metastatic melanoma: are there other possible mechanisms explaining their potentiation?." Journal of Clinical Oncology, 12(9), pp. 1994–1996© 1994 by American Society of Clinical Oncology