tbuckley/cabot-search huggingface dataset:
Predictors of employment (empl) outcomes in outpatients (pts) with common solid tumors: A secondary analysis from E2Z02 (ECOG's SOAPP study).
Authors: A. Tevaarwerk, J. Lee, M. C. Sesto, K. A. Buhr, C. S. Cleeland, J. Manola, L. I. Wagner, V. T. Chang, M. Fisch
Journal: Journal of Clinical Oncology (2010)

9118 Background: After cancer (Ca) diagnosis, nearly 25% of survivors do not return to work. We hypothesized that receiving an increasing number of treatment modalities (TM) (e.g. radiotherapy, chemotherapy) would be a risk factor for change in empl. Methods: E2Z02 prospectively enrolled pts with breast, prostate, colon or lung Ca irrespective of therapy or stage. Pts and oncologists answered questionnaires regarding Ca symptoms. Change in empl was assessed by “Has your empl status changed due to illness?” [Answer = Yes/No]; level of empl by “What is your current empl status?” [Answer = full-time; part-time; not in the workforce]. TMs were counted as 0 (no medical or radiotherapy), 1 (either/or) or 2 (both). Other variables included stage (nonmetastatic vs metastatic), Ca type (breast, prostate, colon, lung), therapy status (off vs ongoing), gender, age (≤ 45, >45 yrs) and ECOG PS (0, 1, 2-4). We excluded pts > 65 yo as likely to be retired. A multivariate logistic regression model was performed for each empl outcome (change in empl, level of empl) with the above as explanatory variables. Results: E2Z02 accrued 3,123 pts between 3/06-5/08 at academic (n=7) and community (n=32) medical oncology clinics. Characteristics of the pts analyzed (n=1976): median age 55 yrs, nonmetastatic (65%), female (77%), white (84%), breast Ca (59%) and PS 0 (61%). After adjusting for other explanatory variables, number of TMs was not a statistically significant predictor for change in empl status. Stage, therapy status, age, and PS were significant predictors (p < 0.0001, <0.0001, 0.0036, and <0.05 respectively). Number of TMs did not predict for level of empl. Ca type, stage, therapy status, gender, PS and age were significant predictors (p <0.05, 0.0006, 0.0211, 0.0273, <0.05, 0.0522). Conclusions: In this population, metastatic disease, age > 45, ongoing therapy, and PS 2-4 predicted for change in empl status and level; lung Ca and male gender also predicted for a decreased level of empl. Further analyses are ongoing to explore associated symptoms. These findings define a group of survivors who should receive targeted interventions to improve empl outcomes. No significant financial relationships to disclose.
A comparison of two HER2 FISH methods to measure HER2 amplification and predict clinical outcome
Authors: L. G. Dressler, G. Broadwater, D. Berry, C. Cirrincione, D. Cowan, L. Harris, D. Moore, H. Muss, D. Hayes, M. Ellis
Journal: Journal of Clinical Oncology (2004)

566 Background: Controversy exists regarding the optimal assay to measure HER2 status. We previously reported that breast cancer patients with HER2 amplified tumors benefit from dose intense doxorubicin-based therapy (Muss, NEJM, 1994). In the current study, we directly compare HER2 status, using the FDA-approved PathVysion (PV) FISH kit, and the new Tricolor (TC) FISH system (both from Vysis, Inc), which, in addition to the HER2 and chromosome 17 (CEP17) probe, contains a third probe against the TOPO2 gene, a target of doxorubicin therapy. Because the TC system involves different assay conditions, it was important to determine if this affected HER2 status and predicting outcome. Methods: The PV and TC methods were performed on two sections from the same tumor block from 408 stage II breast cancer patients registered to CALGB 8541 (dose-intensive CAF therapy; cyclophosphamide, doxorubicin and 5FU, Cancer and Leukemia Group B). Three different measures were performed: HER2 amplification status, using the ratio of HER2:CEP17 signals, where a ratio >=2.00 defined a case as amplified, per kit instructions; HER2 amplification status based only on the HER2 signal, where >=4 signals defined a case as amplified; and polyploidy of chromosome 17, where >=3 signals defined polyploidy. Results: There was no significant difference between the two kits in assigning a case as HER2 amplified or not amplified using the ratio definition (McNemar's exact test, p=.18; kappa=0.862). Of the 14 discordant cases, most had ratios near the cutpoint (e.g. 1.71 by PV vs 2.03 by TC). Using the HER2 signal alone (not normalized to CEP 17), we found significant differences between the two kits, with TC giving a higher frequency of amplification (McNemar's test, p=.02). The TC system also identified a higher frequency of chromosome 17 polyploidy. Using the ratio definition, both kits predicted outcome similarly (K-M plots nearly superimposable). Conclusion: Using the chromosome 17 probe to normalize HER2 amplification status yields the most consistent results for HER2 measurement and predicting clinical outcome in a comparison between the PathVysion kit and the new Tricolor probe FISH system. No significant financial relationships to disclose.
Age and Prognosis in Pediatric AML
Authors: Pernille Wendtland Edslev, Jonas Abrahamsson, Niels Clausen, Erik Forestier, Göran Gustafsson, Jesper Heldrup, Liisa Hovi, Kirsi Jahnukainen, Gudmundur Jonmundsson, Josefine Palle, Bem Zeller, Henrik Hasle
Journal: Blood (2008)
Acetaldehyde/ethanol breath test for identifying people at high risk of upper aerodigestive tract cancer.
Authors: Ikuo Aoyama, Mihoko Tsurumaki, Yukie Nakai, Shinya Ohashi, Manabu Muto
Journal: Journal of Clinical Oncology (2015)

18 Background: Alcohol drinking increases the risk of upper aerodigestive tract cancer, and acetaldehyde (a metabolite of alcohol) is a definite carcinogen for this type of cancer. Acetaldehyde is formed mainly by the oxidation of ethanol by alcohol dehydrogenase 1B (ADH1B) and is eliminated by aldehyde dehydrogenase 2 (ALDH2) in the liver. About 50% of Asian people have the ALDH2*2 variant allele, which encodes an inactive enzyme. Those with the ALDH2*2 allele and an alcohol drinking habit are at definite risk of esophageal and head and neck cancers. Genetic testing is the most reliable method for identifying the ALDH2 genotype, but it is not practical for mass screening because of the cost and time. Therefore, we have established a simple method to identify the ALDH2 genotype by analyzing breath samples. Methods: One hundred seven consecutive healthy Japanese volunteers participated in this study. After providing informed consent, participants drank 100 ml of 0.5% ethanol in a single gulp. Breath samples were collected with originally developed simple gasbags before the alcohol was consumed, and 1, 2, and 5 minutes later. The concentrations of acetaldehyde and ethanol in the bag were measured by high-sensitivity gas chromatography. The ALDH2 and ADH1B genotypes of all participants were confirmed using blood DNA. The relationships between acetaldehyde level and genotypes were determined. Results: The frequencies of ALDH2*1/*1, ALDH2*1/*2, and ALDH2*2/*2 were 46.7%, 43.9%, and 9.3%, respectively. The breath acetaldehyde levels at 1 minute after alcohol ingestion were 89.2 (18.1–399.0) ppb in those with ALDH2*1/*1, 346.3 (78.4–1218.4) ppb in those with ALDH2*1/*2, and 537.1 (213.2–1353.8) ppb in those with ALDH2*2/*2. The breath acetaldehyde level was significantly higher in the ALDH2*2 carrier group regardless of the ADH1B genotype (P&lt;0.001). Setting the cutoff for the acetaldehyde/ethanol ratio at 22.3×10 –3 to include ALDH2*2 carriers yielded an accuracy for the detection of ALDH2*2 carriers of 96.3% (95% CI: 91.5–96.9%), sensitivity of 100%, and specificity of 92%. Conclusions: Our breath test may be a convenient screening tool for identifying those at high risk of upper aerodigestive tract cancer.
The oncogene elongation factor 1 alpha-2 mRNA expression in epithelial ovarian cancer
Authors: S. Sharma, D. Driscoll, K. Odusni
Journal: Journal of Clinical Oncology (2005)

5034 Background: Approximately 50% of ovarian tumors have copy number increases in chromsome20q. The 20q ovarian amplicon has yet to be precisely mapped, but is known to include part of 20q12 and 20q13. Elongation Factor 1 alpha 2 gene (EEF1A2) maps to 20q13.3 and encodes protein elongation factor 1 alpha 2 (eEF1A2). eEF1A2 mRNA is not detectable in normal ovarian epithelium but may be aberrantly expressed in human ovarian tumors. This overexpression might lead to an inhibition of apoptosis, a process that could plausibly contribute to neoplastic progression. The aim of this study was to examine the expression of EEF1A2 in epithelial ovarian cancer (EOC), and correlate with clinico-pathologic characteristics. Methods: One step RT-PCR was performed with cDNA from various normal tissues, with mRNA from 91 epithelial ovarian tumor tissues. eEF1A2 specific PCR product was amplified using eEF1A2 specific primers. GAPDH specific PCR amplification was used as control. The χ2 test was used to analyze the distribution of eEF1A2 expression and clinico-pathologic variables (stage, residual tumor, recurrence, disease free interval, and overall survival). Survival probabilities were estimated by Kaplan-Meier method. Results: Low level eEF1A2 m-RNA expression was restricted only to the normal tissues of the heart, brain, and skeletal muscle. eEF1A2 was not seen in normal ovarian tissue. eEF1A2 m-RNA expression was demonstrated in 21/91 (23%) of the ovarian cancer specimens. The median follow-up for the patient population was 23 months. There was a correlation between eEF1A2 expression and recurrence risk (likelihood ratio 6.9; p=0.03). The difference in median survival for eEF1A2 positive and negative patients was not statistically significant. Kaplan-Meier analysis indicates eEF1A2 expression to be a non-significant predictor of overall survival. Conclusions: Our data demonstrates that eEF1A2 is expressed at moderate frequency in patients with EOC. eEF1A2 expression also appears to be associated with increased risk for recurrence of disease. This data provides a new potential prognostic marker and oncogene for EOC, and may lead to the study of eEF1A2 as a suitable target for anticancer targeted therapy. No significant financial relationships to disclose.
Carcinogenicity of Halo-Ethers&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: B. L. van Duuren, A. Sivak, B. M. Goldschmidt, C. Katz, S. Melchionne
Journal: JNCI Journal of the National Cancer Institute (1969)

Five halo-ethers, including compounds in which the chlorine atoms are α-,β- or γ- to the carbon-bearing ether oxygen atom, were tested for initiating, promoting, and carcinogenic activity on mouse skin. Two of the compounds were also tested (or carcinogenicity in rats by subcutaneous injection. Bis(chloromethyl)ether was carcinogenic by both routes of administration and also a potent initiating agent in two-stage carcinogenesis. Its monofunctional analog chloromethyl methyl ether was not carcinogenic for mouse skin but showed pronounced initiating activity in two-stage mouse skin carcinogenesis. The irritant action of this compound and its hydrolysis products had no tumor-promoting effect after a single application of benzo[a]pyrene on mouse skin. The other 3 compounds tested and found inactive were: octachlorodi-n-propyl ether, α,α-dichloromethyl methyl ether, and monochloroacetaldehyde diethyl acetal. Structureactivity relationships of these compounds are discussed.
Multiple marker analysis in breast tumors with long term follow-up using Tissue Microarray: Immunohistochemical evaluation of ER, PgR, MIB1, p27, p63, HMWCK, FITH, Her2/neu and p53
Authors: D. Di Vizio, A. Sboner, F. de Michelis, R. Micciolo, A. Lucenti, A. Ferro, R. Triolo, E. Galligioni, P. Dalla Palma, M. Barbareschi
Journal: Journal of Clinical Oncology (2005)

686 Background: The tissue microarray (TMA) technique allows to assemble multiple tumor samples in the same paraffin block to evaluate multiple markers using immunohistochemistry. Methods: we have constructed TMAs of 293 breast carcinomas with complete follow-up (median 132 mos). Four tumor cores per sample (i.e.: 4 replica) were included in TMA blocks. We evaluated the expression of ER, PgR, Her2/neu (Herceptest), p53, MIB1, Bcl2, p27, p63, HMW cytokeratin (HMWCK), and FITH. The 4 different replica of each case were separately analysed by two pathologists. Her2/neu was evaluated according to FDA score. For all other markers we evaluated cellular compartimentalization, intensity (from 0 to 3) and percentage of reacting cells. Results: from the original 1172 cores in the TMAs, 78% were evaluable for each marker because of lack of cells or loss of cores during the TMA sections processing. The most relevant prognostic markers were Her2/neu and p53: they retained prognostic value even after adjusting for N status (p<0.01 for OS and DFS). MIB1 was of borderline prognostic significance. ER, PgR, Bcl2, p27, FITH, p63 and HMWCK did not provide prognostic information. Conclusions: Our results confirm that TMA may be a reliable tool in the evaluation of prognostic/predictive markers, with the advantage of sparing time and tissues. The most reliable prognostic marker was Her2/neu. These data further support that Her2/neu, beside being predictive of therapeutic response to Herceptin, is a reliable prognostic marker. Unexpected negative results for ER,PgR and Bcl2 are more difficult to explain, and further studies on larger TMA are necessary.Loss of p27 or FITH, and the identification of markers of the so-called “basal phenotype” (p63 and HMWCK) of breast carcinomas were not prognostic predictors in our series, in keeping with their known controversial prognostic role No significant financial relationships to disclose.
Rituximab with short duration chemotherapy followed by <sup>90</sup>Y ibritumomab tiuxetan as first-line treatment for patients with follicular lymphoma: Update of a Minnie Pearl Cancer Research Network phase II trial
Authors: D. L. Shipley, F. A. Greco, D. R. Spigel, D. Edwards, M. Mayfield, K. Yost, J. P. Allerton, J. D. Hainsworth
Journal: Journal of Clinical Oncology (2005)

6577 Background: First-line treatment with chemotherapy/rituximab combinations improves complete remission (CR) rates and lengthens remission duration in patients with follicular NHL. We previously demonstrated a high CR rate with short course chemotherapy plus rituximab (CHOP-R or CVP-R). In this phase II trial, we added 90Y ibritumomab tiuxetan following short course CHOP-R, in an attempt to further improve the CR rate. Methods: Eligibility criteria included: follicular NHL grades 1–3, stages II-IV, ECOG PS 0–2, adequate organ function, no CNS involvement, no HIV infection, informed consent. Patients with cardiac ejection fraction < 45% received CVP-R instead of CHOP-R. All patients received 4 weeks of rituximab (375mg/m2 weekly x 4) followed by 3 courses of CHOP-R (standard doses). After complete restaging, responding patients with bone marrow involvement < 25% received 90Y ibritumomab tiuxetan 5 weeks after the last dose of CHOP-R. Final restaging was performed 12 weeks after 90Y ibritumomab tiuxetan. Results: 42 patients entered the trial between 4/02 and 3/04. Patient characteristics: median age 57 years; stage IV, 60%; low or low-intermediate IPI risk category, 88%. 3 patients (7%) did not complete treatment (toxicity during CHOP-R, 2; HACA+, 1 patient). Following short course CHOP-R, 100% of patients responded (CR 28%, PR 72%). After 90Y ibritumomab tiuxetan, CR rate rose to 67%. After median follow-up of 20 months, actuarial 2-year PFS is 77%. No unexpected toxicity was seen during CHOP-R therapy. Grade 3/4 hematologic toxicity following 90Y ibritumomab tiuxetan included: neutropenia, 64% (grade 4, 16%); thrombocytopenia 47% (grade 4, 0%); platelet transfusions, 19%; neutropenia/fever, 0. No grade 3/4 non-hematologic toxicities occurred. Myelosuppression resolved within 12 weeks in all pts. Conclusions: Short duration CHOP-R followed by 90Y ibritumomab tiuxetan is highly active and well tolerated in patients with follicular NHL. Further follow-up is necessary to assess progression-free and overall survival. No significant financial relationships to disclose.
Decision-control preferences in patients with advanced cancer
Authors: A. B. Astrow, D. P. Narendra, J. R. Sood, M. T. Nolan, R. Thompson, D. P. Sulmasy
Journal: Journal of Clinical Oncology (2004)

8069 Background: Many argue that when patients with advanced cancer face medical decisions, the chief value that clinicians must respect is patient autonomy, and when patients cannot speak for themselves, decisions should be based on substituted judgments about patients' autonomous wishes. Others have suggested that the decision making process is more complex. Methods: We interviewed 130 patients with a ≥ 50% 2-year expected mortality (47 with advanced gastrointestinal or lung cancer, 52 with Class III-IV heart failure, and 31 with amyotrophic lateral sclerosis) at 2 teaching hospitals using a modified Decision Control Preferences Scale. We assessed the extent to which patients would involve others in medical decisions along 3 dimensions: patient-physician, patient-family, and physician-family, considering their present state and a hypothetical unconscious state. Results: A plurality of all patients (44%), presuming they were conscious, wanted to share decision making with their families. However, compared with the others, cancer patients were more likely to prefer decision making independent of their family (64% vs. 42%, P = .01). Overall, presuming they were conscious, most patients (52%) wanted to share decision making with their physicians. However, compared with others, patients with cancer preferred decision making independent of their physicians (43% vs. 29%, P = .07). Comparing decision control preferences for the unconscious with the conscious state, patients were significantly more likely to prefer that their physicians should decide based on the patient's best interest rather than on their autonomous preferences (P < .001). For the hypothetical unconscious state, few patients (19%) weigh the physician's views more than their families'. A plurality (48% overall, 53% cancer) prefer equal family/physician input. Conclusions: A plurality of patients preferred shared decision-making; a minority preferred autonomous decision-making. However, when capable, patients with cancer were more likely than others to prefer autonomous decision making. The pattern of preferences for the hypothetical unconscious state is more complicated than might be predicted by the autonomy model. No significant financial relationships to disclose.
Research in academic medical centers: Two threats to sustainable support
Authors: Arthur S. Levine, Robert J. Alpern, Nancy C. Andrews, Karen Antman, Jeffrey R. Balser, Jeremy M. Berg, Pamela B. Davis, J. Gregory Fitz, Robert N. Golden, Lee Goldman, J. Larry Jameson, Vivian S. Lee, Kenneth S. Polonsky, Marsha D. Rappley, E. Albert Reece, Paul B. Rothman, Debra A. Schwinn, Larry J. Shapiro, Allen M. Spiegel
Journal: Science Translational Medicine (2015)

Reductions in federal support and clinical revenue jeopardize biomedical research and, in turn, clinical medicine.
Trimetrexate in malignant mesothelioma: A Cancer and Leukemia Group B Phase II study.
Authors: N J Vogelzang, L B Weissman, J E Herndon, K H Antman, M R Cooper, J M Corson, M R Green
Journal: Journal of Clinical Oncology (1994)

PURPOSE Folic acid antagonists are reported to have activity against mesothelioma. The Cancer and Leukemia Group B (CALGB) undertook this phase II study of the new antifolate, trimetrexate (TMTX), to evaluate its response rate and toxicity in chemotherapy-naive patients with malignant mesothelioma. PATIENTS AND METHODS Fifty-two patients were accrued to this protocol. Because of concerns about TMTX toxicity in patients with malignant effusions and/or hypoalbuminemia, the first 17 patients were treated at a dose of 6 mg/m2 daily for 5 days every 21 days. Because minimal toxicity was observed, the subsequent 35 patients were treated at a dose of 10 mg/m2. RESULTS Two of 17 patients (12%) in the 6-mg/m2 treatment group had a partial response (PR) and four of 34 eligible patients (12%) in the 10-mg/m2 treatment group had a PR or regression (R) of assessable disease. No patient achieved a complete response (CR). Median survival durations were 5.0 and 8.9 months in the 6- and 10-mg/m2 treatment groups, respectively, while the 2-year survival rates were identical at 18%. At the 10-mg/m2 dose, toxicity was tolerable, with one toxic death from sepsis and a 12% rate of grade 4 thrombocytopenia and granulocytopenia. CONCLUSION In this large trial, TMTX showed minor activity in the treatment of malignant mesothelioma. Myelosuppression was mild and dose-related. Future studies of higher doses of TMTX should be considered.
Inhibition of the AKT pathway with genistein combined polysaccharide (GCP) plus external beam radiation therapy (EBRT) in a prostate cancer (CaP) xenograft
Authors: W. S. Holland, D. Shih, R. Harse, S. Vijayakumar, R. Hackman, D. R. Gandara, R. W. Devere White, P. H. Gumerlock
Journal: Journal of Clinical Oncology (2005)

3135 Background: While EBRT is an effective treatment for primary CaP, many patients will fail biochemically within 5 years. Activation of the AKT pathway of survival has been identified in response to EBRT. Genistein, a primary component of GCP, is an isoflavone aglycone that acts as a protein kinase inhibitor. Single agent GCP inhibits CaP cell growth in vitro and in xenografts models. GCP-treated CaP cells have shown inhibition of the PI3-K/AKT pathway and our previous work showed near complete inhibition of colony formation after GCP + EBRT treatment. We hypothesized that combining a tyrosine kinase inhibitor, such as genistein, with EBRT would result in decreased activation of the AKT survival pathway and greater inhibition of tumor growth than EBRT alone. Methods: We examined the combination of GCP with EBRT in PC-3 xenografts. A clinically relevant dose of radiation (2 Gy) was used to determine either increased combined activity or antagonism by addition of GCP. PC-3 (5x106) cells were injected subcutaneously into Balb/c nu/nu mice. Tumors were treated with GCP alone, EBRT alone, GCP + EBRT, or were untreated. Animals receiving either GCP or GCP + EBRT therapy received daily oral doses of GCP (10% GCP in 0.1ml/10 kg body weight). Within 2 weeks after initial GCP treatment, animals in the EBRT and GCP + EBRT groups were irradiated locally at the tumor site (a single dose of 2Gy). Tumor volume was measured thrice weekly. Results: A reduction in tumor growth was seen in each of the single treatment groups GCP and EBRT (40%) versus untreated tumors up to 40 days. The combination of EBRT and GCP inhibited tumor growth (80%) versus untreated over the same time period. By day 70, 80% of GCP + EBRT-treated tumors showed a reduction in tumor volume with some tumors no longer measurable. Conclusion: 1) GCP + EBRT inhibited CaP tumor growth which was followed by tumor regressions in most animals. 2) These data support additional studies combining GCP with EBRT as a potential treatment for primary CaP. (Support: Amino Up Chemical Co., Ltd.) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amino Up Chemical Co., Ltd.