tbuckley/cabot-search huggingface dataset:
Analysis of CTLA4 expression on T regulatory cells in patients with advanced stage melanoma in the setting of high dose IL-2 (HDIL-2).
Authors: Maggie L. Diller, Cabell E. Eysmans, David H. Lawson, Keith A. Delman, Ragini Reiney Kudchadkar, Mandy Ford
Journal: Journal of Clinical Oncology (2015)

9043 Background: HDIL-2 is associated with long-term remissions in stage IV melanoma, but in less than 10% of patients. Combination therapy with HDIL-2 and agents immunomodulating CTLA-4 have been undertaken. We investigated the effect of HDIL-2 on CTLA4 expression on T cell subsets in patients with melanoma. Methods: Peripheral blood was collected at baseline and serially post-treatment at 24, 48, 72, and 96 hours from 6 patients with advanced stage melanoma undergoing HDIL-2. All patients were treatment naïve with regard to anti-CTLA4 therapy. PBMCs were isolated and restimulated ex vivo for 4 hours using PMA/ionomycin. Fluorophore conjugated anti-CTLA4 antibody was added at time of restimulation and incubated with cells for 4 hours. Intracellular and extracellular cytokine staining was then performed and co-signaling molecule expression was quantified via flow cytometry and measured on a continuous scale. Statistical analysis was performed using paired t tests via Prism 6.0e software. Results: HDIL-2 resulted in increased frequencies of T regulatory cells (Treg; CD25+FoxP3+CD4+) on day 4 of therapy (24% +/- 12% on day 4 compared to 12% +/- 7% at baseline; p = 0.03; 95% CI [1.5,22]). Importantly, CTLA4 expression on Treg cells was increased on day 4 post-treatment relative to baseline (51% +/- 19% on day 4 compared to 35% +/- 19% at baseline; p = 0.02; 95% CI [2.5,28]). CTLA4 expression was not statistically different within other CD4+ T cell compartments or within the CD8+ T cell compartments. Conclusions: These results demonstrate that HDIL-2 is associated with an increase in the expression of CTLA4 onTreg cells in patients with advanced melanoma. HDIL-2 effect on the Treg population provides a potential rationale for the lack of efficacy of HDIL-2 in most patients and implies potential synergy between HDIL-2 and CTLA4 blockade. Together, these findings provide justification for testing the combination of HDIL-2 and anti-CTLA4 therapy in patients with advanced melanoma and that timing of anti-CTLA4 therapy with HDIL2 will be crucial.
Prognostic significance of circulating secreted protein acidic and rich in cysteine (SPARC) in malignant pleural mesothelioma (MPM).
Authors: Steven Chuan-Hao Kao, Michaela Kirschner, Mark P. Molloy, Stephen John Clarke, Sjaak A. Burgers, Catharina M. Korse, Daan van de Broek, Nico Van Zandwijk, Glen Reid
Journal: Journal of Clinical Oncology (2014)

7580 Background: Supervised proteomic analyses (discovery with isobaric tag for relative and absolute quantitation [iTRAQ] and validation with enzyme-linked immunosorbent assay [ELISA]) using 12 MPM patients from two phase II studies identified circulating SPARC as a promising prognostic marker, with high SPARC level associated with poor survival (p<0.01). We aimed to determine the independent prognostic significance of circulating SPARC in an independent cohort of MPM patients. Methods: Serum samples from MPM patients treated at the Netherlands Cancer Institute between 1995 and 2011 were included in this validation study. The samples were collected at the time of diagnosis and stored at -80°C, with clinical data collected prospectively. SPARC concentration was measured using the SEA791Hu ELISA kit (USCN Life Science Inc) according to the manufacturer’s instruction. The primary end point of the study was overall survival (OS) from the date of sample collection, determined by the Kaplan-Meier method. The independent prognostic value of SPARC (categorised into high vs. low according to median concentration) was examined using Cox regression analysis, incorporating known prognostic factors in a multivariate model, including age (<60 vs. ≥60 years), gender (male vs. female), stage (I-II vs. III-IV) and histological subtype (epithelial vs. non-epithelial). Results: A total of 97 patients were included: median age 60 years; 85% male; 50% stage I-II; and 75% epithelial subtype. Treatment received included: 67% chemotherapy; 22% radical surgery; and 18% supportive care alone. The median OS was 13.5 months (92 patients deceased). The median SPARC concentration was 1745µg/ml. In the multivariate analyses, male gender (median OS: 10.8 vs. 22.4 months; p=0.05), stage III-IV (median OS: 10.1 vs. 17 months; p=0.05) and high SPARC level (median OS: 9.3 vs.19 months; p=0.05) were independently associated with poor OS. Conclusions: This validation study is the first to demonstrate the prognostic role of circulating SPARC in MPM, with high SPARC level being an independent predictor of poor OS.
Population-based analysis of time to palliative chemotherapy (TPC) and survival in advanced non-small cell lung cancer (NSCLC).
Authors: Krista Noonan, King Mong Tong, Sophie Sun, Barbara L. Melosky, Nevin Murray, Janessa J. Laskin, Cheryl Ho
Journal: Journal of Clinical Oncology (2014)

e17700 Background: The time interval between surgery and adjuvant chemotherapy has been shown not to be associated with inferior survival in NSCLC patients (pts). Whether there is an association between TPC and survival in advanced NSCLC has not yet been evaluated. Methods: The British Columbia Cancer Agency (BCCA) provides comprehensive cancer care to a population of 4.5 million. All cases of stage 3b/4 NSCLC diagnosed in BC, Canada, from January to December, 2009 were identified using the BC Cancer Registry. TPC was defined as the time from diagnosis (dx) to palliative chemotherapy (PC). Logistic regression was used to evaluate factors associated with TPC of greater than 8 wks. The effect of delayed TPC and overall survival (OS) was assessed by Cox proportional hazards modeling. Results: Of the 1374 pts with advanced NSCLC identified, 748 (54%) were assessed by medical oncology (MO), and 415 (55%) received PC. The median TPC was 8 weeks (wks) (range, 1-112 wks). The only factors associated with a TPC greater than 8 wks were older age and radiation oncology consult (RO). ECOG >2 was associated with a poorer OS (HR 1.74, CI 1.4-2.2). A TPC of >8 wks was associated with a better OS (HR 0.65, CI 0.52-0.81). Conclusions: Only half of advanced NSCLC pts saw a MO, and only half received PC. More than half of pts started PC > 8 wks after diagnosis. Delayed TPC was associated with an improved OS in advanced NSCLC. This may be a function of biology of disease, with more aggressive phenotypes receiving upfront chemotherapy. TPC 1-8 wks n = 210 (51%) TPC>8 wks n = 205 (49%) p-value Sex Male Female 109 (52) 101 (48) 106 (52) 99 (48) 0.52 Age, range 63, 29-87 65, 40-87 0.01 ECOG 0-2 3-4 123 (59) 87 (42) 127 (62) 78 (38) 0.27 Geographic site Rural Urban Unknown 40 (19) 169 (81) 1 (1) 48 (23) 156 (76) 1 (1) 0.55 Histology Non-squamous Squamous Not otherwise specified 138 (66) 41 (20) 31 (15) 123 (60) 51 (25) 31 (15) 0.39 RO 164 (78) 181 (88) 0.01 Radiation (RT) 153 (73) 161 (79) 0.18 Dx to referral 8 (0-205) 15 (0-213) <0.0001 Referral to MO 14 (0-287) 25 (0-462) <0.0001 Referral to RO 15 (0-1034) 15 (0-1209) 0.34 Dx to radiation 49 (2-1050) 58 (1-1234) 0.14 Dx to CT 39 (5-56) 92 (57-692) <0.0001 RO to RT 12 (0-1034) 12 (0-445) 0.17 MO to chemo 14 (0-56) 33 (0-650) <0.0001
Growth index, assessed with Ki-67 and ssDNA labeling, is a significant prognosticator for patients who underwent curative resection for hepatocellular carcinoma
Authors: S. Morinaga, T. Yoshikawa, Y. Noguchi, Y. Yamamoto, Y. Rino, T. Imada, Y. Takanashi, M. Akaike, Y. Sugimasa, S. Takemiya
Journal: Journal of Clinical Oncology (2004)

4084 Backgroud: The growth of tumor depends on the degree of imbalance between cell production and cell loss. Knowledge of such biological difference is of importance to understand aggressiveness of the cancer and to the management of cancer patients. This study was conducted to clarify a possible role of the modified prognosticator, Growth Index (GI), in patients who underwent curative resection for hepatocellular carcinoma (HCC). GI (%) was defined as a difference between a Ki-67 labeling index (%) and a single-stranded DNA (ssDNA) labeling index (%). Methods: HCC tissue specimens were obtained from 40 HCC patients (27 men and 13 women, range 45–80 years old) who underwent curative resection between April 1998 and March 2001. Immunohistochemical staining was perfomed using the avidin-biotin-peroxidase-complex method on formalin-fixed paraffin-embedded-tissues. Results: Ki-67 labeling index ranged from 0.20% to 29.10%, and ssDNA labeling index ranged from 0.22% to 4.20%. The GI ranged from -1.90% to 28.65% with a median of 3.73. GI was related with histologic grade (P = 0.014 by Kruskal-Wallis), pathologic T stage (P = 0.026 by Kruskal-Wallis), and intrahepatic metastasis (P = 0.048 by Mann-Whitney). The cumulative survival was poorer in patients with higher GI (≥ 3.73%, a median value) than those with lower GI (P = 0.014 by log-rank test). The univariate analysis demonstrated that GI, histologic grade, pathologic T stage, vascular invasion, intrahepatic metastasis, and age were significant factors affecting survival. The Cox multivariate analysis indicated that GI (P = 0.003) is an independent prognosticator along with intrahepatic metastasis (P = 0.003) and age (P = 0.018). Conclusions: Higher values of GI were significantly associated with histologically aggressive features of HCC, and GI was a significant independent prognosticator in HCC patients after curative resection. Assessing GI is feasible on routine paraffin sections and may provide additional prognostic information in those post-operative patients. No significant financial relationships to disclose.
Clinical relevance of HER-2 expression in node-negative breast cancer patients
Authors: J. M. Sun, W. Han, D. W. Kim, T. Y. Kim, I. A. E. Park, D. Y. Noh, D. S. Heo, Y. J. Bang, K. J. Choe, N. K. Kim
Journal: Journal of Clinical Oncology (2004)

598 Background: Adjuvant chemotherapy of node-negative breast cancer is generally being determined according to the St. Gallen classification. HER-2 expression, widely investigated in breast cancer but with controversy, is not a component of St. Gallen classification. This study was conducted to analyze clinical relevance of HER-2 expression in node-negative breast cancer. Methods: We retrospectively analyzed 906 node-negative breast cancer patients who were operated between 1995 and 2000. HER-2 protein overexpression was evaluated by immunohistochemistry. We grouped patients by tumor size (>2cm, ≤2cm), histologic grade (3, 1or2), age (<35yrs, ≥35yrs), ER status, PgR status and HER-2 expression. Then we analyzed prognostic value of these variables for disease-free survival (DFS) in all patients. In addition, prognostic value of HER-2 expression was analyzed in average/high risk group by St. Gallen classification. Results: In univariate analysis, tumor size, ER, PgR status, and HER-2 expression were prognostic factors for DFS. In multivariate analysis, only HER-2 expression was an independent prognostic factor for DFS. In average/high risk group by St. Gallen classification, HER-2 expression was a significant discriminant of prognosis. Data are summarized in the table below. Six-year relapse rate was 20.1% for HER-2 positive patients and 11.6% for HER-2 negative patients in average/high risk group. (P=0.0065). Conclusions: HER-2 expression was an independent prognostic factor for DFS in node-negative breast cancer. Furthermore, HER-2 expression in average/high risk group identified a subgroup of node-negative breast cancer patients with the worst prognosis, who were candidates for intensive adjuvant therapy. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Seoul National University Seoul National University
Response rate and outcome of a novel first line therapy for advanced head and neck carcinomas: Chemo-radiochemotherapy (CRC)
Authors: R. Knecht, H. Tesch, M. Baghi, M. Hambek, N. Zamboglou, W. Gstöttner
Journal: Journal of Clinical Oncology (2004)

5559 Background: Concurrent radiochemotherapy has become a standard procedure for treatment of advanced head and neck cancer.A recent publication(N Engl J Med 2003;349:2091–8)has shown that concurrent radiochemotherapy is superior to sequential radiochemotherapy for locoregional control in carcinomas of the larynx. The aim of our ongoing study(Phase II) is to answer the question if the addition of induction chemotherapy (TPF) to this form of concurrent radiochemotherapy is able to enhance the response rate and the outcome of patients with advanced disease of the pharynx and larynx. Methods: Patients(42/42) with carcinomas of the larynx and pharynx(stage III/IV)were either treated with concurrent radiochemotherapy(RC) at 70Gy(2Gy per day,7weeks)with cisplatin 100mg/m2 administered on days 1,22,43 of the radiation course or induction chemotherapy(IC)consisting of docetaxel 75mg/m2/d1, Cisplatin 100mg/m2 /d1 and 5-Fluorouracil 1000mg/m2/d1–4(TPF) followed by the same radiochemotherapy-CRC-. .Response rate was confirmed by magnetic resonance imaging and surgical biopsies based on WHO-guidelines. Results: Post-IC we observed 22 complete responses(CR),16 partial resonses(PR),2 stable diseases(SD)and 2 progressive diseases(PD).Reversible neutropenia up to grade 4 was the most common toxicity.After full therapy we observed an overall response rate(ORR) of 37/42 with CRC and an ORR of 32/42 RC.The mucosal and renal toxicities in patients treated with CRC were more frequent as the toxicities in patients treated with RC .The rate of recurrences and distant metastases was lower with CRC compared with RC.Because of the short median follow up of 18 months this difference does not reach a significant level. Conclusions: TPF induction chemotherapy may enhance the response rate of concurrent radiochemotherapy in advanced carcinomas of the pharynx and larynx. No significant financial relationships to disclose.
A Phase II Study Evaluating the Combination of Nivolumab (Nivo) or Ipilimumab (Ipi) with Azacitidine in Pts with Previously Treated or Untreated Myelodysplastic Syndromes (MDS)
Authors: Guillermo Garcia-Manero, Naval G. Daver, Guillermo Montalban-Bravo, Elias J. Jabbour, Courtney D. DiNardo, Steven M. Kornblau, Prithviraj Bose, Yesid Alvarado, Maro Ohanian, Gautam Borthakur, Jorge E. Cortes, Kiran Naqvi, Naveen Pemmaraju, Xuelin Huang, Graciela M. Nogueras-Gonzalez, Carlos E Bueso-Ramos, Yvonne Gasior, Virginia R Bayer, Sherry Pierce, Hui Yang, Simona Colla, Hagop M. Kantarjian
Journal: Blood (2016)
Relapse rate of patients with low-risk gestational trophoblastic tumor treated in a single institution
Authors: H. Matsui
Journal: Journal of Clinical Oncology (2004)

8191 Background: To determine the factors for relapse in patients with low-risk gestational trophoblastic tumor (GTT) treated with single-agent chemotherapy. Methods: Between 1974 and 2000, 272 consecutive patients with low-risk GTT were initially treated with methotrexate (MTX), actinomycin D (Act-D) or etoposide chemotherapy. The primary remission rate, change of chemotherapy because of drug resistance or toxicity, and relapse rate were compared. Results: Overall survival rate and primary remission rate for 272 patients were 100% and 75.7%, respectively. Primary remission rate was significantly higher in patients given etoposide than those given conventional MTX (p<0.0001) or MTX-folic acid (MTX-CF) (p=0.0005). Twenty-four (8.8%) patients required a change of chemotherapy because of drug resistance. The frequency of drug resistance was significantly higher in patients treated with MTX-CF than those treated with etoposide (p=0.006). Although maternal age, presence of metastasis, high pretreatment hCG titer, and planned hysterectomy did not influence the development of drug resistance, the new FIGO scores were significantly higher in patients who developed drug resistance. Relapse rate increased significantly in patients who had high FIGO scores and who required change of chemotherapy due to drug resistance. Conclusions: All patients with low-risk GTT eventually attained complete remission, even though some developed drug resistance to the first-line chemotherapy. The relapse rate was significantly higher in patients with drug resistance than those with primary remission. Chemotherapy regimen that induces little drug resistance is desirable from the viewpoint of long-term prognosis. No significant financial relationships to disclose.
Weekly oxaliplatin, fluorouracil and folinic acid (OXALF) as first-line chemotherapy for elderly patients with advanced gastric cancer (AGC)
Authors: D. Santini, F. Graziano, V. Catalano, M. Di Seri, E. Testa, G. Catalano, S. Spalletta, B. Vincenzi, S. Cascinu, G. Tonini
Journal: Journal of Clinical Oncology (2004)

4237 Background: The weekly PLF regimen with routine filgrastim support showed high activity in elderly patients with AGC (Graziano et al, BJC, 2003). We investigated safety and efficacy of a similar weekly oxaliplatin-based regimen without filgrastim support. Methods: Chemotherapy-naive pts with AGC aged 70 or older were considered eligible for study entry. Inclusion criteria consisted of: ECOG performance status I or II, normal renal, liver, bone marrow functions and measurable disease. Frail elderly pts were excluded after baseline geriatric assessment. Pts received weekly oxaliplatin 40 mg/m2, fluorouracil 500 mg/m2 and folinic acid 250 mg/m2 (OXALF). All drugs were given intavenously on a day-1 schedule. After 8 weekly cycles, pts with complete response (CR), partial response (PR) and stable disease (SD) received six more weekly administrations. Results: 231 cycles were administered to 17 evaluable pts; median age was 75 years (70–81), M/F sex ratio was 12/5. 11 pts had two or more metastatic sites. According to intent-to-treat the overall response rate was 47% (CI: 27%–54%), with 2 CR, 6 PR, 7 SD and 2 progressions. In the whole group, time to disease progression and median survival were 5.9 months and 7.5 months respectively. Due to grade II toxicities, chemotherapy was delayed one or two weeks in 5 pts. No grade III-IV toxicities including peripheral neuropathy were reported in these patients and no toxic deaths occurred. Grade II nausea and fatigue resulted the commonest non-hematologic toxicity (respectively, 29% and 23.5% of pts). Other grade II non-hematologic toxicities were: diarrhea (11.7%), mucositis (5.8%) and transaminases increase (5.8%). No episodes of grade II neurological and hematologic toxicity were reported. Conclusions: Weekly OXALF chemotherapy showed palliative activity with favorable response rates and toxicity profile in elderly pts with AGC. More mature data will be presented during the meeting. No significant financial relationships to disclose.
Ibrutinib, a Bruton’s tyrosine kinase inhibitor used for treatment of lymphoproliferative disorders, eliminates both aeroallergen skin test and basophil activation test reactivity
Authors: Jennifer A. Regan, Yun Cao, Melanie C. Dispenza, Shuo Ma, Leo I. Gordon, Adam M. Petrich, Bruce S. Bochner
Journal: Journal of Allergy and Clinical Immunology (2017)
Efficacy of mepolizumab add-on therapy on health-related quality of life and markers of asthma control in severe eosinophilic asthma (MUSCA): a randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 3b trial
Authors: Geoffrey L Chupp, Eric S Bradford, Frank C Albers, Daniel J Bratton, Jie Wang-Jairaj, Linda M Nelsen, Jennifer L Trevor, Antoine Magnan, Anneke ten Brinke
Journal: The Lancet Respiratory Medicine (2017)
Combined Clinical Parameters and Multiparametric Magnetic Resonance Imaging for Advanced Risk Modeling of Prostate Cancer—Patient-tailored Risk Stratification Can Reduce Unnecessary Biopsies
Authors: Jan Philipp Radtke, Manuel Wiesenfarth, Claudia Kesch, Martin T. Freitag, Celine D. Alt, Kamil Celik, Florian Distler, Wilfried Roth, Kathrin Wieczorek, Christian Stock, Stefan Duensing, Matthias C. Roethke, Dogu Teber, Heinz-Peter Schlemmer, Markus Hohenfellner, David Bonekamp, Boris A. Hadaschik
Journal: European Urology (2017)
Comparison of serum HER2 and CA15–3 in monitoring clinical tumor response in patients with HER2 positive metastatic breast cancer (MBC)
Authors: S. Y. Kong, D. H. Lee, E. S. Lee, J. Ro
Journal: Journal of Clinical Oncology (2004)

9705 Background: HER2 extracellular domain shed from cell surface has been detected in serum (S) of normal individuals and patients (pts) with breast cancer. S HER2 was elevated in >40% of pts with MBC, which was associated with increased tumor volume and poor prognosis. CA15–3 is a conventional tumor marker and elevated in 50–60% of MBC. Therefore, we aimed to compare the S HER2 and CA15–3 in monitoring clinical response to therapy in patients with HER2 positive MBC. Methods: S samples of 37 pts with HER2 positive (measured by immunohistochemistry and fluorescent in situ hybridization) MBC were studied. The serial S HER2 and CA15–3 of 92 samples were measured by immunoassay using Bayer ADVIA Centaur. The correlation of S HER2 and CA15–3 were analyzed, and the changes of both tumor markers were compared with clinical responses (CR, PR, MR, SD, PD). Cutoff value of abnormal S HER2 was ≥15ng/ml and of CA15–3, >38 U/ml. Results: Median age was 46yrs (range 25–66 yrs). ER was positive in 46% and PR, in 27%. HER2 was 3+ in 27, 2+/FISH+ in 7, and 2+ in 4 pts. Twenty six pts received Herceptin mono- or with chemotherapy and 11 pts, other chemotherapy for MBC. S HER2 was elevated in 33 (89%) pts and CA15–3 in 23 (62%) pts prior to therapy. One patient did not show elevation of either marker. Positive correlation between S CA15–3 and HER2 was observed (r = 0.39, p = 0.008). The percent changes of S HER2 and CA15–3 from initial to follow-up according to clinical responses are shown in the Table. Conclusions: Current study suggests that S HER2 is more useful tumor marker than CA15–3 in HER2 positive MBC as it is more often elevated (89% vs 62%), while the variations of both markers during the courses of therapy are well concordant with clinical tumor responses. No significant financial relationships to disclose.