tbuckley/cabot-search huggingface dataset:
Identification of Material With Paternal HLA Antigen Immunoreactivity From Purported Circulating Immune Complexes in Patients With Gestational Trophoblastic Neoplasia&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: S J Lahey, G Steele, R Berkowitz, M L Rodrick, D S Ross, D P Goldstein, N Zamcheck, R E Wilson, J M Deasy
Journal: JNCI Journal of the National Cancer Institute (1984)

Circulating immune complex(es) (CIC) have been shown to rise progressively only when patients with hydatidiform molar pregnancy enter gonadotropin-documented remission. The CIC in 3 patients with gestational trophoblastic neoplasia (GTN)--1 with hydatidiform mole and 2 with choriocarcinoma--were characterized. Their clinical course was monitored by serial antigen-nonspecific polyethylene glycol (PEG) 6000-CIC assay and simultaneous human chorionic gonadotropin (HCG) assay from presentation until sustained gonadotropin-documented remission. As serial HCG progressively decreased to normal following surgical or chemotherapeutic reduction in tumor burden, PEG-CIC concurrently rose. Serum obtained at or near peak PEG-CIC levels was precipitated by 3.75% PEG 6000 and fractionated by column chromatography on Sephadex G-200 (exclusion limit, greater than 600,000 mol wt) in glycine-HCl and 1 M NaCl buffer at pH 2.8. None of the 5 elution fractions obtained from the 3 patients contained HCG or anti-HCG activity. However, in the hydatidiform molar patient, fractions 1 through 3 (mol wt greater than 67,000--and containing immunoglobulin) were shown to competitively inhibit complement-dependent antibody lysis on 1 of 4 paternal HLA haplotype (AW32) targets. In 2 of the 3 patients studied, low-molecular-weight fractions (not containing immunoglobulin) significantly inhibited reference anti-HLA binding of antisera directed against only 1 of 4 paternal HLA haplotypes. The immunospecificity of this inhibition was confirmed by criss-cross control assays in which elution fractions obtained from both of these patients were tested for inhibition of lymphocytolysis of both sets of paternal lymphocytes. None of these fractions were immunoreactive to maternal HLA haplotypes. Further analysis of serum from the hydatidiform molar patient revealed that no free complement-fixing antibody against paternal antigens could be found by conventional screening assays in unfractionated patient sera. Three of 4 paternal HLA antigens or non-complement-fixing anti-HLA immunoglobulin was detected in unfractionated pretreatment, treatment, and remission sera of the hydatidiform molar patient. Only in this patient's remission sera was unbound AW32 antigen or non-complement-fixing anti-AW32 antibody detected. These data demonstrate the successful characterization of at least 1 specific antigen fractionated from a tumor-associated immune complex. The implication that some patients with GTN may recognize and react to immunogenic paternal HLA antigens as part of their successful response to therapy for trophoblastic tumor is discussed.
A multicenter, randomized, double-blind, placebo-controlled trial of thalidomide plus dexamethasone versus dexamethasone alone as initial therapy for newly diagnosed multiple myeloma
Authors: S. V. Rajkumar, M. Hussein, J. Catalano, W. Jedrzejcak, S. Sirkovich, M. Olesnyckyj, Z. Yu, R. Knight, J. B. Zeldis, J. Blade
Journal: Journal of Clinical Oncology (2006)

7517 Background: Thalidomide plus dexamethasone (Thal/Dex) yields superior response rates versus dexamethasone (Dex) but its impact as primary therapy for multiple myeloma (MM) is unknown. Methods: Patients (pts) with previously untreated, symptomatic MM were eligible and were randomized in this double-blind trial to Thal/Dex (Arm A) or placebo plus Dex (Arm B). Pts in Arm A received Thal 50 mg PO daily, escalated to 100 mg on day 15, and to 200 mg from day 1 of cycle 2; Dex 40 mg PO was given on days 1–4, 9–12, and 17–20. Pts in Arm B received placebo instead of Thal, and Dex as in Arm A. Cycles were 28 days long, repeated until progression or undue toxicity. The primary endpoint was time to progression (TTP) defined using EBMT criteria. All analyses were intent to treat. Planned sample size was 218 eligible pts in each arm. Full information for one-sided log rank test with significance level of 0.025 (allowing for 1interim analysis) to have 80% power to detect a 40% improvement in TTP (16.8 mo in Arm A vs. 12 mo in Arm B) would be achieved when 282 pts have progressed. A pre-planned interim analysis of the primary endpoint and safety was performed by an independent Data Monitoring Committee (DMC). P value &lt; 0.0015 at this interim analysis would indicate that Arm A is superior to Arm B based on an alpha-spending function of the O’Brien-Fleming type. The DMC recommended release of results. Results: 470 pts were enrolled: 235 randomized to Thal/Dex and 235 to placebo/Dex. Median follow-up was 25 months. Median age was 65 yrs. TTP was significantly superior with Thal/Dex vs placebo/Dex, median TTP 17.4 months (95% CI: 8.1 months-NE) vs 6.4 months (95% CI: 5.6–7.4 months), respectively, P &lt; 0.000065, crossing the upper boundary for superiority. DVT was higher with Thal/Dex vs placebo/Dex, 15.4% vs 4.3%, respectively. Median survival was not reached in either arm. Conclusions: Thal/Dex is significantly superior to Dex alone as first-line therapy for multiple myeloma. [Table: see text] [Table: see text]
Ifosfamide versus cyclophosphamide: Long term gonadal effects in 166 male survivors of childhood cancer
Authors: V. Ridola, A. S. Defachelles, C. Schmitt, O. Fawaz, J. C. Gentet, F. Aubier, J. Michon, C. Bergeron, C. Béhar, O. Oberlin
Journal: Journal of Clinical Oncology (2007)

9515 Background: Alkylating agents are associated with a risk of male gonadal damage, even in patients treated during childhood. The purpose of this work was to compare this risk after treatment by ifosfamide vs cyclophosphamide during childhood. Methods: Evaluation was based on basal FSH measurement known for its correlation with spermatogenesis. LH and testosterone were also measured in most of the patients. 159 males were evaluated after treatment of a soft tissue sarcoma (79), osteoasarcoma (39), ewing (10), lymphoma (28), other (3). 100 patients received ifosfamide as unique alkylating agent and the other 59 received cyclophosphamide as the other unique alkylating agent between 1973 and 2000. Median age at treatment was 11.2 years (0–18 yrs). Median interval after the end of the treatment was 10.7 years (4.1–20.2 yrs), median age at evaluation was 21.4 years (17.5–36.1 yrs). Median dose of ifosfamide was 54 g/m 2 (18- 114), median dose of cyclo was 8.3 g/m 2 (4.6–22). Age at treatment and at evaluation were similar in both groups. Results: All males but two (17.5 and 26.5 yrs) had normal testosterone levels. LH was elevated in 14% of the patients. FSH was above laboratory upper limit in 28 of the 59 males (47.5%) treated with cyclophosphamide and was within the normal range in 94 of 100 patients (94%) treated with ifosfamide. Eight patients treated with cyclophosphamide fathered children. The median dose of cyclo was 5.6 g/m 2 (4.8 - 10.8 g/m 2 ). Six patients who received 51 to 54 g/m 2 fathered children. The risk of abnormal FSH increased with the cumulative dose of cyclophosphamide: only 2/16 boys (12%) who received more than 12 g/m 2 had a normal dosage of FSH, while 29/43 (67%) of the boys who received lower doses of cyclo did so. Conclusions: These results show a low risk of gonadal dysfunction in men exposed to ifosfamide (median dose 54 g/m 2 ) compared to the results for males treated with cyclophosphamide. The risk of abnormal FSH increased with the cumulative dose of cyclophosphamide. No significant financial relationships to disclose.
Hepatocellular carcinoma presenting with lung metastasis: Clinical characteristics and prognostic factors
Authors: Y. Kojima, H. Ueno, T. Okusaka, C. Morizane, S. Kondo, A. Hagihara, S. Iwasa
Journal: Journal of Clinical Oncology (2009)

e15604 Background: The efficacy of systemic chemotherapy for hepatocellular carcinoma (HCC) has been limited, but sorafenib has changed the strategy treating for metastatic HCC. The lung is one of the most common metastatic sites for HCC. Therefore, we focused on clinical features and prognostic factors of HCC patients (pts) with lung metastasis in this study. Methods: Between January 2000 and April 2008, 1,117 HCC pts were admitted into our division. During this period, extrahepatic metastasis was detected in 286 pts, and the initial metastatic site was lung in 130 pts. The relationships between the characteristics of these pts at the time of lung metastasis detection and prognosis were examined. Results: There were 107 males and 23 females. Median age was 64 years. The Child-Pugh classification was A in 84 pts, B in 32 pts. HCV Ab was positive in 57 pts, HBs Ag was positive in 46 pts, and both were negative in 27 pts. The median survival time of all pts was 298 days. Univariate analysis revealed 12 of the 20 variables evaluated to be significantly associated with survival time: number of lung metastasis, presence of intrahepatic HCC, maximum size of intrahepatic HCC, presence of tumor thrombus, AFP, PIVKA II, albumin, prothrombin time, ALP, presence of ascites, Child-Pugh classification, and previous history of hepatic resection. Multivariate analysis using the Cox proportional hazards model demonstrated a lower number (≤5) of lung metastases (p&lt;0.0001), the absence of intrahepatic HCC (p=0.0002), and the absence of ascites (p=0.0339) to be independent favorable prognostic factors. Conclusions: These results may provide useful reference data for determining treatment strategies and planning further clinical trials involving HCC patients with lung metastasis. No significant financial relationships to disclose.
Abstract 14728: Assessment of Myocardial Wall Thickness and T1 Mapping is Highly Reproducible in Multi-Center Trials: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Eunice Yang, Marcelo S Nacif, Chia-Ying Liu, Sirisha Donekal, Bharath A Venkatesh, Martin R Prince, Joao A Lima, David A Bluemke
Journal: Circulation (2012)

BACKGROUND: Myocardial wall thickness and extracellular volume in subclinical heart disease may be associated with alterations in myocardial tissue composition. The reproducibility of these paramet...
A phase I trial of GMX1777, an inhibitor of nicotinamide phosphoribosyl transferase (NAMPRT), given as a 24-hour infusion
Authors: M. J. Pishvaian, J. L. Marshall, J. J. Hwang, S. Malik, A. R. He, J. F. Deeken, C. B. Kelso, I. Cotarla, M. S. Berger
Journal: Journal of Clinical Oncology (2009)

3581 Background: GMX1777 is a pro-drug which converts to GMX1778, a potent and specific small molecule inhibitor of NAMPRT, the rate-limiting enzyme in NAD+ synthesis. NAMPRT activity is increased in tumor cells dependent on the glycolytic pathway. The aims of this first-in-man study were to define a dose of GMX1777 administered by 24-hr infusion with acceptable safety for phase II studies, and to determine the pharmacokinetic (PK) parameters of both GMX1777 and GMX1778. Methods: GMX1777 was administered at ascending doses as a 24 hour IV infusion q21 days to successive cohorts of patients with advanced malignancies. Single patient cohorts were utilized until a toxicity &gt;Grade (Gr) 1 was observed during cycle (C) 1; then a standard 3+3 dose escalation schema was used. PK samples were drawn during C1. Results: 19 patients (11 males; median age 57) received doses of 60, 120, 160, 200 or 140 mg/m 2 over 24 hours. 49 doses were administered. There were no toxicities &gt;Gr 1 during C1 at 60 mg/m 2 ; however Gr 2 toxicities were observed at 120 mg/m 2 and the cohort was expanded to 3 patients. Gr 4 GI hemorrhage and Gr 4 thrombocytopenia occurred at 200 mg/m 2 , leading to expansion of the 160 mg/m 2 cohort. 3/6 patients at 160 mg/m 2 had erythematous symmetrical Gr 3 rash occur during C2–5. Six patients enrolled at 140 mg/m 2 had no Gr 3 rash and 140 mg/m 2 was determined to be the MTD. Preliminary data indicate that the most common (&gt;30%) adverse events of all grades were nausea (89%), diarrhea (79%), fatigue (68%), vomiting (58%), anorexia (42%), pruritis (42%), thrombocytopenia (42%), rash (37%), anemia (32%), constipation (32%), dyspnea (32%), and insomnia (32%). Lab findings include lymphopenia. Two patients had stable disease for &gt; 4 cycles (6 &amp; 4 mos), and 3 additional patients had SD for ≥ 3 mos. Preliminary PK data document rapid conversion of GMX1777 to GMX1778 at all dose levels. Conclusions: The MTD for GMX1777 administered as a 24 hour infusion q21 days is 140 mg/m 2 . Thrombocytopenia, GI hemorrhage, and skin rash (the last occurring after multiple cycles) were encountered at higher doses. Single-agent GMX1777 exhibited moderate clinical activity, suggesting that inhibition of NAMPRT should be explored in other schedules or in combination with other agents. [Table: see text]
Immune-Related and Inflammatory Conditions Likely Play a Role in the Development of Lymphoplasmacytic Lymphoma/Waldenström’s Macroglobulinemia
Authors: Sigurdur Y Kristinsson, Magnus Bjorkholm, Jill Koshiol, Lynn R. Goldin, Mary L. McMaster, Ingemar Turesson, Ola Landgren
Journal: Blood (2008)
Impact of dermatologic toxicities on quality of life in patients receiving anticancer therapies.
Authors: S. E. Rosenbaum, Y. Balagula, S. W. Dusza, J. Hensley, M. Agulnik, J. Brieva, M. E. Lacouture
Journal: Journal of Clinical Oncology (2010)

e19538 Background: Cancer patients undergoing treatment are at risk for developing dermatological toxicities (dT). These untoward events are associated with symptoms of pruritus and pain, and may affect consistent dosing of antineoplastic therapy. Despite these implications, the effect of therapy- induced dT on quality of life (QoL) has not been ascertained. In this study we investigate the relationship between cancer treatment type and patient reported dermatologic QoL. Methods: Medical records of patients seen in the dermatology referral clinic for cancer patients at Northwestern University between 9/2007 and 9/2008 were searched for completion of the Skindex, a dermatology-specific QoL questionnaire. All charts of patients who had completed the Skindex were then searched by ICD-9 code and keyword for a diagnosis of cancer, and stratified using keywords that included generic and trade names of targeted and cytotoxic agents, stem cell transplant and radiation. Skindex scores range from 0 (best QoL) to 96 (worst QoL) and measure 3 domains: symptoms, emotions and functioning. The total Skindex score and the scores of each domain were analyzed for 3 patient groups: those receiving cytotoxic agents (CA), those on targeted agents (TA), and those on combination therapy (CT) (any combination of CA, TA, radiotherapy or therapeutic transplant). Descriptive statistics (means, medians, range) were used to describe scores by group. Results: A total of 367 patients were included in the analysis; 253 females (69%), 114 males (31%). Of these, 121 (33%) were treated with CT, 141 (38.4%) with CA, and 105 (28.6%) with TA. Differences in mean scores were evaluated by one way ANOVA. Mean QoL score was 31.6 (CA), 38.2 (CT) and 38.1 (TA) (p = 0.06). Lower emotional domain scores for CA (16.6) were observed as compared to CT (20.6) and TA (19.6) (p<0.05). No significant intergroup differences were observed for the symptoms (p = 0.28) and functioning domains (p = 0.14). Conclusions: During treatment, cancer patients' dT-related QoL is negatively impacted, with CT and TA having a greater impact on emotions than CA. Total impact on QoL was similar in CA, CT, and TA treated patients. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, ImClone Systems, Onyx Amgen, Bayer, Bristol-Myers Squibb, ImClone Systems, Onyx Hana Biosciences
Radiochemotherapy followed by gemcitabine and capecitabine in extrahepatic bile duct cancer (EBDC): A phase I/II-trial
Authors: K. Schoppmeyer, M. W. Wiedmann, A. Liebmann, S. Miethe, J. Mossner, K. Caca, H. Witzigmann, G. Hildebrandt
Journal: Journal of Clinical Oncology (2006)

14087 Background: The 5-year survival rate of patients with resected EBDC is less than 30%. Phase II trials demonstrated that advanced EBDC responds to both chemotherapy with gemcitabine and capecitabine and to radiotherapy. Our objective was to define a feasible and effective postoperative therapy in patients with EBDC. Methods: Patients were eligible after surgery for EBDC. Surgery included resection of lymph node positive cancer, incomplete resections and diagnostic laparotomy in unresectable tumors. Patients received a fractionated radiotherapy with 49.6 Gy accompanied by gemcitabine 100 mg/m 2 weekly × 5. After a two week rest patients were treated with gemcitabine (1000 mg/m 2 IV D1+8 q3w) and capecitabine (1500 mg/m 2 PO D1–14 q3w) on a 3-week cycle. Treatment continued for 6 cycles in nonmeasurable disease or until disease progression or intolerable toxicity. Primary endpoint was toxicity; secondary endpoints were response rate in measurable disease and overall survival. Results: 18 Patients (resectable/unresectable disease 7/11) were enrolled. Radiotherapy was completed in all patients and a total of 66 cycles of chemotherapy were applied. Anemia, fatigue, and nausea were the most common mild adverse events in 16, 14, and 16 patients, respectively. Grade 3 and 4 toxicity was rare after resection but frequent in unresectable disease and consisted of fatigue, nausea, duodenal ulcer, cachexia and cholangitis in 1, 2, 2, 4, and 4 patients, respectively. We observed a 50% disease stabilization rate in patients with measurable disease. Median overall survival was 7.9 months in patients with unresectable tumors. Median overall survival in patients after resection has not been reached after a median follow-up of 19.5 months. Conclusions: Radiochemotherapy with gemcitabine followed by gemcitabine and capecitabine is an active regimen with manageable toxicity after resection of EBDC but has significant toxicity in unresectable disease. No significant financial relationships to disclose.
Pharmacogenetics begins to deliver on its promises
Authors: Alain Li-Wan-Po
Journal: BMJ (2015)

Those promises include safer and smarter use of drugs

Pharmacogenetics promises the safer use of drugs through personalised prescribing that is informed by the genetic make-up of the individual, cancer tumour, or invading micro-organism. Although the first inherited molecular marker for a severe drug induced toxic effect was identified over half a century ago, until recently, few such markers were routinely used by prescribers. Even pharmacogenetics pioneers were beginning to wonder whether it was all hype. However, rapid progress is being made, and an increasing number of drugs have been licensed for use with a companion genetic test, both to improve the chances of success and to reduce the risk of severe side effects. This progress is typified in a linked article reporting that genetic testing helped to reduce patients’ risk of a rare but serious adverse reaction to allopurinol.1

Abnormal reactions to foods and chemicals have been recorded since antiquity. Pythagoras, better known for his geometry, commented on hypersensitivity to the broad bean (favism); a reaction now known to be associated with hereditary deficiency in glucose-6-phosphate dehydrogenase (G6PD). Over 2000 years later, Charles Darwin observed that hair and skin colour was “correlated …
Cytogenetic responses to a 5-day dosing schedule of decitabine in patients (Pts) with myelodysplastic syndromes (MDS)
Authors: L. A. Godley, D. P. Steensma, M. R. Baer, J. L. Slack, R. Buckstein, J. S. Larsen, S. Arora, M. T. Cullen, H. M. Kantarjian
Journal: Journal of Clinical Oncology (2008)

7030 Background: Among pts with MDS, cytogenetic abnormalities predict transformation to acute myeloid leukemia or death. Cytogenetic responses suggest clonal suppression and may alter the natural progression of the disease. Decitabine is an efficient inhibitor of DNA methylation and has been approved for pts with MDS. In a Phase III MDS study, cytogenetic responses were observed in 38% of evaluable pts (Cancer 2006:106:1794). Further, in a Phase II single center MDS trial examining three unique dosing regimens, an overall cytogenetic response (IWG 2006: complete response [CR] + partial response [PR]) was observed in 51% of pts (Cancer 2007:109:265). A Phase II multicenter trial was recently conducted to evaluate a 5-day regimen for decitabine, and here we report the cytogenetic responses. Methods: Decitabine was given at 20 mg/m2 IV over 1 hour once daily for 5 days repeating every 4 weeks as outpatient therapy. Eligible pts were ≥18 years of age with MDS (de novo or secondary) of any FAB subtype and International Prognostic Scoring System score ≥ 0.5. Cytogenetics were evaluated locally. In order to be included in the cytogenetic analysis, pts must have had abnormal cytogenetics at baseline and adequate cytogenetic data available for at least one post-baseline visit. Cytogenetic response was determined by a central reviewer using IWG 2006 criteria. Results: As expected, one-half of the 99 pts in trial had abnormal cytogenetics at baseline. Chromosome alterations noted at baseline included: -Y, del (5q), del (20q), chromosome 7, +8, and complex (≥3 abnormalities) karyotype. 33 pts were evaluable for cytogenetic response. Overall, the cytogenetic response rate was 52% (17/33) with 11 CR and 6 PR. 53% (9/17) of these responders had poor risk cytogenetics at baseline. A prompt median time to cytogenetic response of 65 days (range 50–302 days) was observed. Of the 17 pts with a cytogenetic response, 76% (13) were associated with a clinical complete response (CR or marrow CR). Conclusions: In this multi-center study, the alternate 5-day dosing schedule of decitabine resulted in meaningful cytogenetic response in pts with MDS, including those with poor risk cytogenetics. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration MGI Pharma MGI Pharma MGI Pharma MGI Pharma MGI Pharma, Pharmion