tbuckley/cabot-search huggingface dataset:
Cancer testis antigen expression and immune responses by prostate cancer patients: Implications for prognosis and immunotherapy
Authors: L. von Boehmer, P. Wild, L. Keller, T. Hermanns, M. Provenzano, G. Sais, E. Jaeger, F. Stenner, H. Moch, A. Knuth
Journal: Journal of Clinical Oncology (2009)

e16101 Background: Prostate cancer (PC) is the most frequent malignancy in men and it continues to be one of the most common fatal cancers. Treatment options in advanced castration-resistant prostate cancer (CRPC) are limited. Cancer testis (CT) antigens are expressed in a variety of human cancers, but not in normal tissues except for MHC deficient spermatogonia, and represent promising targets for immunotherapy. Little is known about CT antigen expression in relation to disease progression. The aim of this study was to investigate which CT antigens are expressed and immunogenic and hence represent promising targets for patients with prostate cancer and correlate these findings with clinicopathological characteristics. Methods: To determine the expression of 6 CT antigens in prostate cancer immunohistochemistry was performed on tissue micro arrays. We investigated 6 CT antigens (NY-ESO.1, MAGE-C1, MAGE-C2, GAGE, MAGE-A1 and MAGE-A4) in benign hyperplasia (n=45), early (n=388) and late stage (n=71) prostate cancer. To determine the occurrence of spontaneous antibodies against cancer testis antigens, ELISA and Western blot was performed for NY-ESO-1, MAGE-C1 and MAGE-C2 with sera from prostate cancer patients. Results: CT antigens are increasingly expressed in late stage prostate cancers. As an exception we found MAGE-C2 to be expressed early in the course of disease, frequently inducing MAGE-C2 specific antibodies. In later stage metastatic prostate cancer patients NY-ESO-1 is more often expressed, inducing NY-ESO-1 specific antibodies. Conclusions: Cancer testis (CT) antigens are prognostic markers, frequently inducing immune responses and may be suitable for immunotherapeutic intervention in patients with prostate cancer. No significant financial relationships to disclose.
Phase I-II studies of oral tegafur (ftorafur).
Authors: F J Ansfield, G J Kallas, J P Singson
Journal: Journal of Clinical Oncology (1983)

A total of 65 patients with advanced colorectal or breast cancer were given oral tegafur in the phase I study. Of these, 28 patients had accurately measurable lesions and were entered into the phase II study. Patients with liver metastasis, compromised bone marrow, or a decreased oral intake to less than 50% of their normal intake were given a poor-risk schedule consisting of 0.75 g/m2/day divided into 4 doses/day X 28 day unless early toxicity developed. In the absence of any of the above deficits, patients were given a good-risk schedule of 1.25 g/m2/day X 21 days if no toxicity appeared. The courses were followed by a 2-3-wk rest period depending upon the speed to recovery from all reactions and then repeated. Compared with 5-FU, nausea and vomiting occurred more frequently with tegafur while hematologic toxicity was less common and less severe. The paucity of significant hematologic toxicity permitted courses of this drug to be given safely on an outpatient basis even to the point of slight reaction for optimal dosing. No serious reactions occurred in any of the 65 patients. The clinical results showed partial regressions in 6 of 21 colorectal cancer patients and 3 of 7 breast cancer patients. Six of the 9 responses occurred in patients who had previous 5-FU trials. The average duration of regression in the colorectal cancer patients on oral tegafur was 9 mo with a significantly increased survival of the responders.
Melatonin as adjuvant care with and without chemotherapy: A systematic review and meta-analysis.
Authors: D. Seely, P. Wu, H. Fritz, D. A. Kennedy, A. J. Seely, E. Mills
Journal: Journal of Clinical Oncology (2010)

e13562 Background: Melatonin has a large body of evidence from both preclinical assays and clinical trials to support its use in the treatment of multiple cancer types. A key concern on the part of medical oncologists; however, is the potential for natural health products like melatonin to interact with conventional therapies, especially chemotherapy.To explore the issue of potential patient benefit and interaction in further depth, we conducted a systematic review of the literature to find evidence of melatonin consumption in addition to chemotherapy in humans with cancer. Methods: We searched seven electronic databases from inception to January 2010. All randomized trials where melatonin was used as an adjunct to chemotherapy were included in the review and meta-analysis. Outcomes assessed included: survival, complete and partial response, alopecia, anemia, asthenia, cardiac symptoms, diarrhea, fever, leucopenia, nausea, vomiting, thrombocytopenia, and hypotension. Results: We found a total of 18 different studies comprising 20 separate clinical trials that fit our inclusion criteria. In all measures of tumour response, including survival, there were statistically significant improvements for those receiving melatonin. The summary OR for survival in all studies at one year was 4.02 (95% CI: 2.90, 5.59) for the groups randomized to melatonin. In a summary analysis of a subset of 15 trials where chemotherapy was provided to trial participants, the group receiving adjuvant melatonin had an improved odds ratio for survival of 3.42 (95% CI: 2.29, 5.12). In every measure of chemotherapy related adverse events except anemia and cardiotoxicity there were significant improvements for those receiving adjuvant melatonin. In no cases were any of the symptoms worsened by the inclusion of melatonin in patient care. Conclusions: Evidence from randomized clinical trials suggests that melatonin taken by cancer patients orally at night may improve patient survival, not interact negatively with a number of chemotherapy agents, and also may result in a reduction of chemotherapy related side effects. No significant financial relationships to disclose.
Clinical implications of serum levels of soluble CD30 in 70 adult anaplastic large-cell lymphoma patients.
Authors: P L Zinzani, S Pileri, M Bendandi, M Buzzi, E Sabattini, S Ascani, F Gherlinzoni, M Magagnoli, P Albertini, S Tura
Journal: Journal of Clinical Oncology (1998)

PURPOSE In the last few years, the search for new biologic markers in high-grade non-Hodgkin's lymphomas has provided important results. In particular, soluble CD30 (sCD30) levels were elevated in most patients with Hodgkin's disease (HD) and anaplastic large-cell lymphoma (ALCL). PATIENTS AND METHODS From September 1988 to October 1993, treatment was completed in 70 previously untreated patients with ALCL, of whom 38 had the common type (ALCL-CT) and 32 had the Hodgkin's-like subtype (ALCL-HL). Serum sCD30 levels were measured at the time of diagnosis and after induction polychemotherapy in all patients; in addition, the initial sCD30 levels were compared with those obtained from 50 stage-matched patients with HD. RESULTS Pretreatment levels of sCD30 were highly elevated in the stage-matched group of HD patients compared with healthy controls; median sCD30 levels in patients with ALCL-CT and ALCL-HL were 18 and seven times higher, respectively, than in patients with HD. The sCD30 level normalized on achievement of complete response (CR). The risk of lower relapse-free survival was associated with bulky disease, advanced stage, and high pretreatment sCD30 levels; the risk of lower overall survival was associated with advanced stage and pretreatment levels of sCD30 in both univariate and multivariate analysis. CONCLUSION The results of this study suggest that sCD30 is a specific prognostic indicator of the risk for lower complete response rate and relapse-free expectancy for patients with ALCL.
Community practice experience with gefitinib (ZD1839) as treatment for patients with advanced non-small-cell lung cancer (NSCLC) within an expanded access clinical program
Authors: T. J. Ervin, S. R. Toothaker
Journal: Journal of Clinical Oncology (2004)

7367 Background: Preclinical and clinical studies including IDEAL 1 and 2 showed that oral gefitinib (Iressa, ZD1839) is an effective treatment for advanced NSCLC. Because reported studies reflect referral oncology experience, we reviewed toxicity and outcome data on 100 patients entered into an expanded access clinical program within a community oncology program. Methods: Patients with histologically confirmed advanced NSCLC (Stages IIIB and IV) were maintained on 250 mg of gefitinib daily until they developed worsening performance status (PS), gefitinib related intolerance/ toxicity, disease progression or death. PS and drug toxicity were monitored at 4 weeks and then at 12-week intervals. Informed consent was obtained from all patients. Results: During September 2000 to April 2003, 100 patients were enrolled. Pretreatment characteristics included a higher percentage of males (54M, 46F) and older median age (68) than IDEAL 2. The PS of the patient population (ECOG 0/1/2: 8/44/48) was worse compared with IDEAL 2 (19/68/13). The disease control rate was lower (28%> 4 months) compared with IDEAL 2 (42%). Better PS was associated with longer average time to progression (155 days/110/69). Patients with adenocarcinoma had a significantly longer time to progression (156 days) when compared with other histologies (Squam: 94 days, Large-cell 92 days, Bronchoalv: 86 days). Those who developed a rash while on treatment also had a significantly longer time to progression (162 days) than those without (100 days). Within the group of patients with a rash, those with adenocarcinoma had a longer time to progression (196 days) when compared to the other histologies (Squam: 105 days, Bronchoalv: 96 days). Conclusions: Gefitinib use in the community was less efficacious than in the IDEAL 2 trial. Clinical predictors of response to gefitinib included better PS, adenocarcinoma histology, and development of rash while on treatment. No significant financial relationships to disclose.
Important serum markers in malignant lymphoma
Authors: S. Yavuz, M. Erkisi, I. Petekkaya, N. Basel
Journal: Journal of Clinical Oncology (2009)

e22225 Background: In this study, 78 patients with new diagnosed, 21 patients with relapsed malignant lymphoma who applied to Cukurova University Hospital between March 2006 - 2008, and 36 age and sex matched healthy control group were evaluated and have been followed up. Methods: The aim of this study was to investigate if; any acute phase reactants or lymphocyte markers in peripheral blood have any predictive role concerning the treatment response, or disease progression. Results: Peripheral blood CD20 (+) lymphocyte levels were slightly higher in new diagnosed patients (12.09±13.79), than the control group (11.25 ±4. 79) but, much lower in relapsed patients (7.30±9.51, P= 0.038). After the chemotherapy (CT), CD20 (+) cell percentage decreased significantly only in new diagnosed patients (p&lt;0.001). Pretreatment CD20 (+) cell levels were higher in responding patients than no responders (15. 42 ± 13.30 versus, 6.72 ± 5.24 p= 0.052). Peripheral blood CD 4 (+) cell levels were below the healthy control group (p= 0.01) and remained low after the CT. Interestingly, CD8 (+) cell levels increased in responders, after the CT (p= 0.046) in both patient groups. CD 56(+) lymphocyte levels were higher only in new diagnosed patients than healthy group (p= 0.05). Its level increased further after the CT (p= 0.044). Serum TNF α levels were higher in patient groups than control (p&lt;0.001). Its level decreased following CT (p= 0.002). CRP levels were higher in both patient groups and remained high following the CT (p&lt;0.001), regardless of the response status. Ferritin levels were also higher in patients groups (p&lt;0.001). Pre-treatment serum ferritin levels were lower in responders, than no responders (236.65 ± 242.17 ng/ml versus 718.77 ± 645.24 ng/ml, p= 0.02). Serum prealbumine levels were lower in lymphoma patients than the healthy controls (p&lt; 0.001). Its level was increased after treatment, especially in patients with recurrent disease (21.15± 5.89 versus 26.60 ± 7.29 mg/dl, p= 0.019). Conclusions: In conclusion, it was decided that; during the different stages of lymphoma progression, several mutations may occur, in the different components of the host immune system. Some of the immune responses would continue in spite of complete clinical remission, as some others would predict the response. No significant financial relationships to disclose.
The prognostic significance of tryptophanyl-tRNA synthetase (trpRS) in colorectal cancer
Authors: H. Birgisson, A. Ghanipour, K. Jirström, F. Pontén, L. Påhlman, B. Glimelius
Journal: Journal of Clinical Oncology (2008)

4137 Background: Tryptophanyl-tRNA synthetase (trpRS) is an aminoacyl-tRNA synthetase involved in protein synthesis, regulation of transcription and translation of RNA and an inhibitor of angiogenesis. TrpRS has in the Swedish Human Protein Atlas program (www.proteinatlas.org) been identified as a possible prognostic marker for colorectal cancer (CRC). The aim of this study was to analyze the correlation of trpRS to the prognosis of patients treated for CRC. Methods: Immunohistochemistry (IHC) on tissue microarray (TMA) was done with a polyclonal, monospecific IgG tryptophanyl-tRNA synthetase (trpRS) antibody, on 320 consecutive patients with colorectal cancer, diagnosed 2000–2003. Staining intensity and fraction of positive tumor cells were recorded. Cox multivariate model including age, stage, differentiation and lymphatic and vascular vessel invasion was used to calculate hazard ratio and 95% confidence interval for overall and disease-free survival. Results: Patients with tumours that showed increased levels of trpRS protein expression had better survival compared to patients with low expression levels. Multivariate analyses revealed significantly better overall survival (HR 0.53; 95%CI 0.30–0.92) and disease-free survival (HR 0.41; 0.22–0.74) for patients with high expression compared to low expression. No recurrences were seen in stage II when more than 12 lymph node were analysed in patients with high trpRS (n=28) compared to 9 recurrences in patients with low expression (n=66) (p=0.026). Conclusion: Low IHC expression of TrpRS in tumor biopsies correlates to increased risk for recurrence and worse survival in patients with CRC. This can be related to its anti-angiogenic properties and could aid in the future selection of new drugs in the treatment of CRC. No significant financial relationships to disclose.
Abstract 12775: Sixty is the New Ninety: Ten Year Experience of the In-Hospital 24X7 Interventional Cardiology Team
Authors: M. Fuad Jan, Jaswant Basraon, Suhail Allaqaband, Maharaj Singh, Sara Walczak, Tanvir Bajwa
Journal: Circulation (2015)

Introduction: Expeditious reperfusion in acute ST-elevation myocardial infarction (STEMI) with goal door-to-balloon time (DBT) &amp;lt 90 minutes (ACC/AHA guidelines) is of utmost importance. The innovative 7-day 24-hour (24x7) in-hospital cardiac catheterization laboratory (CCL) program (24-hour in-hospital availability of an interventional cardiologist and dedicated lab staff) has been previously described by our institution. Here we present our 10-year experience on sustained gains of the program. Hypothesis: From a systems point, there is room for improvement in DBT as an integral process metric for measuring cardiovascular quality. Methods: A cohort of 1233 consecutive non-transfer STEMI patients [69.9% males (n=863), median age 61 years] presenting within 12 hours of symptom onset, formed the study population. Patients were studied for DBT, survival benefit and major adverse cardiovascular events (MACE, i.e., reinfarction, stroke, and cardiogenic shock) after primary percutaneous coronary intervention (PPCI). Using a precise protocol to allow quick entry into the CCL (door-to-CCL time) PPCI was used as the choice reperfusion strategy. Results: Median DBT was 50 minutes (interquartile range 39-67) with 91.65% of patients reperfused within the 90-minute goal. Of note, majority of the patients (66.59% n= 821) were reperfused within 60 minutes and approximately 10% of patients within 30 minutes. DBT &amp;lt 60 minutes compared with DBT &amp;gt 60 minutes was associated with statistically significant less in-hospital mortality (3.87 % vs. 7.66 %, p= 0.004), 1-year mortality (7.23 % vs. 12.99%, p= 0.0009) and MACE (10.7% vs. 16.01%, p= 0.0076) {(Figure 1).} Conclusions: A committed in-hospital 24x7 interventional cardiology team continues to succeed in breaking time inertia in achieving a new standard of 60 minutes. It decreases MACE and mortality in STEMI (in-hospital and 1-year) and thus justifies continued efforts to improve reperfusion times.
A nomogram to predict subsequent brain metastasis in metastatic breast cancer (MBC) patients
Authors: N. K. Ibrahim, B. Abdulkarim, F. Huguet, Z. Gabos, L. Hsu, O. Marpeau, S. Uzan, L. Pusztai, E. A. Strom, G. N. Hortobagyi, R. Rouzier
Journal: Journal of Clinical Oncology (2008)

1040 Background: The development of brain metastases (BrM) is usually a terminal event in the clinical course of breast cancer patients with metastatic disease other than brain (MDOB). We hypothesized that occurrence of BrM can be predicted in patients with MDOB, thus allowing preventive treatment such as prophylactic radiation. Methods: Patients with MBC treated between 2000 and February 2007 at M. D. Anderson Cancer Center were included in this retrospective analysis. We tested 20 variables and developed a multivariate model to predict occurrence of subsequent BrM and created a nomogram that could be used for individual prediction. The model was cross-validated by bootstrapping and tested in two independent cohorts consisting of 128 patients with MDOB treated at the Cross Center Institute, Edmonton, Canada, and 91 patients with BrM treated at Hopital Tenon, France. Results: Among 2,136 patients with metastatic breast cancer, 362 subsequently developed BrM. Young age, histologic characteristics, number of metastatic lymph nodes, short disease-free survival, and number of metastatic sites were significantly and independently associated with subsequent BrM. The Nomogram will be presented at the meeting. For each parameter, points are determined on a specific scale, added, and the probability of BrM is read along the Total Points scale. The cross-validation showed that the mean error was 0.8%. In the validation set, BrM probabilities were well predicted with less than 5% difference between the predicted and observed proportions for each quartile. Conclusions: We developed a robust tool to predict subsequent BrM in patients with metastatic breast cancer. A prospective randomized study is in progress to confirm these results and test the effect of prophylactic treatment. No significant financial relationships to disclose.
Starlyte phase II study of coltuximab ravtansine (CoR, SAR3419) single agent: Clinical activity and safety in patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL; NCT01472887).
Authors: Marek Trneny, Gregor Verhoef, Martin JS Dyer, Dina Ben Yehuda, Caterina Patti, Miguel Canales, Andrés López, Farrukh Awan, Paul Montgomery, Andrea Janikova, Anna Maria Barbui, Kazimierz Sulek, Maria José Terol, John A. Radford, Laure Siraudin, Laurence Hatteville, Sandrine Schwab, Corina Oprea, Alessandro M. Gianni
Journal: Journal of Clinical Oncology (2014)

8506 Background: CoR is an anti-CD19 antibody maytansinoid conjugate. CD19 is expressed in the majority of B cell lymphomas. Phase I program showed clinical activity in pts with both indolent and aggressive lymphomas. Methods: Pts withCD19+ R/R DLBCL after at least one standard treatment including rituximab and not candidate for transplantation were eligible. Primary refractory pts were excluded. Biopsy was required at baseline. CoR 55 mg/m² was administered weekly for 4 weeks then bi-weekly until disease progression or other study discontinuation criteria. The primary objective was to demonstrate an overall response rate (ORR) of at least 20% following Cheson 2007 criteria. Tumor assessments were done every 12 weeks. Secondary objectives were: safety, pharmacokinetics (PK), duration of response (DOR), progression free and overall survival (PFS, OS). Assessment of correlation between biomarkers (BM) status and disease outcome was an exploratory objective. Results: 41 pts were evaluable. Median age was 71 (39:85), 53.7% were male; 92.7% had ECOG performance status 0-1. 31.7% had received ≥ 3 prior regimens for DLBCL. The ORR was 43.9% (90% CI: 30.6% to 57.9%, p-value<0.0001) including 5 complete responses (12.2%). DOR, OS and PFS data are not mature (11 pts ongoing). The most common (>10%) all grades (gr) non-hematologic treatment-emergent adverse events (TEAEs) were nausea (23.0%), diarrhea (19.7%), fatigue and cough (18.0%), vomiting and decrease appetite (13.1%), asthenia, abdominal and back pain (11.5%). TEAEs led to treatment discontinuation in 4 pts. Only gr 1-2 eye disorders were reported, including 1 pt with unrelated gr 2 keratitis. Peripheral neuropathies were observed in 5 pts, all were gr 1-2. Hematological toxicity was moderate, with gr 3-4 neutropenia, thrombocytopenia and anemia in 26.4%, 9.9% and 6.6% pts respectively. PK assessment and investigations on BM expression are ongoing. Conclusions: CoR as single agent demonstrated significant activity in R/R DLBCL pts and reached its primary endpoint for ORR, with acceptable safety profile. Trial funded by Sanofi. Clinical trial information: NCT01472887.
A controlled prospective randomized placebo-controlled trial of Zoledronic acid in bony metastatic bladder cancer patients
Authors: M. S. Zaghloul, R. Boutrus, H. El-Hosieny, Y. A-Kader, I. El-Attar, M. Nazmy
Journal: Journal of Clinical Oncology (2008)

5033 Background: Bisphosphonates decreased the skeletal-related events (SRE) in metastatic breast cancer and multiple myeloma patients. Zoledronic acid succeeded in lowering SRE in metastatic bronchial and urologic cancer patients including prostate and renal cancer patients. Methods: Forty bony metastatic bladder cancer patients were treated with palliative radiotherapy. One week later, they were randomized into 2 arms. Arm 1(placebo) received 250 ml N saline over 15 minutes infusion and arm 2 (Zoledronic acid ) received 4 mg. Zoledronic acid was dissolved in the same amount of N saline and given in the same schedule for 6 months Results: Randomized patients were evenly distributed between the 2 arms with no statistical differences. Patients were followed up for a period of 58 to 756 days with a median of 183 days. All patients tolerated treatment nicely. None of the patients developed generalized bony pain, GIT, eye symptoms or local reaction at site of injection. Three patients in Zoledronic arm developed hypocalcaemia. Five patients in arm 1 and 7 patients in arm 2 developed mild elevated s. creatinine with no statistical difference. The mean SRE had reduced from 2.05 ± 1 in the placebo arm to 0.9± 0.9 in Zoledranic acid arm (P=0.001). Nine patients (45%) in zoledronic arm did not experience any new SRE compared to 2 (10%) in the placebo arm (p=0.011). The median time to first SRE was prolonged from 56 days in the placebo arm to 115 days in Zoledronic arm (0.0004). Zoledronic acid reduced the mean pain score from 4.37 in the placebo arm to 2.95 in treatment arm (P=0.015). The mean score was continuously better in Zoledronic patients than placebo patients. Multiple event analysis of SRE revealed that Zoledronic acid decreased the hazard by 58% with a hazard ratio of 0.413 P value of 0.008. The one-year overall survival rate was 30±10%in Zoledronic arm compared to 5± 4% in the placebo arm (0.02). No significant difference was noticed in distant metastasis (other than bone) in the 2 arms. Conclusions: Zoledronic acid decreased the SRE in bladder cancer patients. It improved the one-year overall survival rate of patients having bony metastasis either due to its antitumor effect or through improving patients' quality of life via decreasing SRE. No significant financial relationships to disclose.