tbuckley/cabot-search huggingface dataset:
Catumaxomab treatment of peritoneal carcinomatosis from EpCAM-positive cancer: Identification of biomarkers with relevance for improved efficacy and survival.
Authors: M. A. Ströhlein, M. M. Heiss
Journal: Journal of Clinical Oncology (2011)

e13003 Background: Catumaxomab (anti-EpCAM x anti-CD3) treatment of patients with peritoneal carcinomatosis of EpCAM-positive cancers was shown to be clinically effective in phase I and II studies and was approved in the EU for the treatment of malignant ascites. The aim of this hypothesis-generating study was to identify predictive or prognostic biomarkers with relevance for disease control and overall survival. Methods: A pooled population of 34 patients with peritoneal carcinomatosis in an investigative and a phase I/II study of catumaxomab treatment was assessed for age, Karnofsky Index, relative (RLC) and absolute (ALC) lymphocyte count, relative (RGC) and absolute granulocyte (AGC) count, T-cell subsets, NK cells, and monocytes before catumaxomab therapy. Disease control was defined by stable disease, partial response or complete response (RECIST v1.0) >3 months and overall survival >6 months. The following statistical methods were used: logistic regression, Kaplan-Meier curves, log-rank tests, and multivariate regression analysis. Results: Disease control after catumaxomab therapy was associated with RLC (p=0.005), AGC (p=0.005), and Karnofsky Index (p=0.043; logistic regression). Overall survival showed a positive correlation with Karnofsky Index (p=0.024) and RLC (p=0.03) in multivariate regression analysis. Patients with high RLC (>15%) showed an increased overall survival (mean 14.5 vs 7.1 months; p=0.04) vs patients with RLC ≤15%. Conclusions: RLC and Karnofsky Index were identified as potential prognostic parameters for superior disease control and overall survival after catumaxomab treatment. RLC may be used as a biomarker to indicate a suitable immune status for catumaxomab therapy. The predictive impact has to be confirmed in further studies.
Prognostic Factors for Outcome of Nonmyeloablative Allogeneic Stem Cell Transplantation (NST) in Poor-Risk Chronic Lymphocytic Leukemia (CLL): Final Results from a Prospective Multicenter Trial (GCLLSG CLL3X study)
Authors: Peter Dreger, Stephan Stilgenbauer, Sebastian Boettcher, Matthias Ritgen, Sascha Dietrich, Donald Bunjes, Dietrich Wilhelm Beelen, Sandra Cohen, Ute Hegenbart, Joerg Schubert, Michael Stadler, Bertram Glass, Andreas Burchert, Lutz Uharek, Michael Hallek, Michael Kneba, Norbert Schmitz, Hartmut Döhner
Journal: Blood (2008)
The Utility of Positron Emission Tomography (PET) with 18Fluorodeoxyglucose (18F-FDG) Compared to Standard Procedures in Detecting Bone Marrow Infiltration in Diffuse Large B-Cell Lymphoma in Developing Countries.
Authors: Marcelo Bellesso, Renata Oliveira Costa, Flavia Dias Xavier, José Claudio Meneguetti, Felipe Vieira Rodrigues Maciel, Daniel Salas Steinbaun, Abrahao Elias Hallack-Neto, Dalton Alencar Fisher Chamone, Juliana Pereira
Journal: Blood (2009)
Leaning upon international directives for optimization: Anemia—Results of the French Lidoanemia-2 Survey.
Authors: Vincent Launay-Vacher, Nicolas Janus, Lisa Ludwig, Gilbert Deray, Florian Scotte
Journal: Journal of Clinical Oncology (2015)

180 Background: Anemia in cancer patients is common. The LIDOANEMIA-1 survey [Scotté F. MASCC 2015] reported that French clinicians do not follow EORTC guidelines. We aimed at improving EORTC guidelines dissemination among French physicians (FP). This second survey aimed at assessing the impact of our initiative on physicians’ behavior. Methods: Declarative survey conducted in France. The intervention consisted of having physicians watch a short video summarizing EORTC guidelines and their main messages for clinical practice. Evaluation of the impact of the intervention was performed with a 4-question web-based form FP filled in after seeing the video. Results: 319 FP answered the survey. Results are showed in the Table regarding the 4 main items: anemia diagnosis, Hb cut-off for considering RBC transfusion or ESA initiation, and Target Hb level on treatment. Among FP who were not following the guidelines, 67.7, 38.2, 50.8 and 65.2% declared they will follow them after the intervention, respectively for anemia diagnosis, Hb cut-off for considering RBC transfusion or ESA initiation, and Target Hb level on treatment. After the intervention, the expected proportion of FP who will follow EORTC guidelines is 93.2, 69.4, 82.6, and 89.4%, respectively for each item evaluated. Conclusions: Dissemination of guidelines is key to improve patient care. We tested a simple mean of presentation of EORTC guidelines in anemia management in cancer patients which significantly increased the proportion of FP who declare they will follow the guidelines. However, a non-negligible proportion of them does not agree and will not follow them, especially for the Hb cut-off for considering RBC transfusion. [Table: see text]
Phase I clinical evaluation of AZD2171, a highly potent VEGF receptor tyrosine kinase inhibitor, in patients with advanced tumors
Authors: J. Drevs, M. Medinger, K. Mross, U. Zirrgiebel, R. Strecker, C. Unger, T. A. Puchalski, N. Fernandes, J. Roberston, P. Siegert
Journal: Journal of Clinical Oncology (2005)

3002 Background: AZD2171 is a highly potent and orally available inhibitor of VEGF receptor tyrosine kinase activity, and has shown antitumor activity in a wide range of tumor xenograft models. This Phase I trial was designed to assess the safety, tolerability and pharmacokinetics (PK) of ascending doses of AZD2171 in patients with advanced tumors with liver metastases. Methods: Eligibility criteria included solid tumors refractory to standard therapies and a WHO performance status of 0–2. Patients received a single oral dose of AZD2171 (0.5–60 mg) followed by a 7-day washout period, before continuing daily oral therapy at the same initial dose for 28 days. Further 28-day cycles were administered until a withdrawal criterion was met. Results: As of Sep 10, 2004, 36 patients (19–75 years) have received treatment with AZD2171 (0.5, 1, 2.5, 5, 10, 20, 30, 45 or 60 mg; n = 3, 3, 3, 3, 4, 3, 5, 4 and 8, respectively). AZD2171 was generally well tolerated at doses ≤45 mg/day. Overall, the most common adverse events were fatigue (n = 13), nausea (n = 13), diarrhea (n = 10) and vomiting (n = 10). Three patients in the 60 mg cohort each experienced one serious adverse event possibly related to AZD2171: grade 4 cerebral hemorrhage, grade 4 hypoglycemia and grade 3 hypertension. Following a single dose, the terminal phase half-life ranged from 12.5–35.4 hours. Steady-state plasma concentrations predicted by single-dose PK did not support time-dependent changes in PK. Across the entire dosing range, plasma concentrations increased linearly following single and multiple doses. Biomarker observations included acute increases in VEGF that were not dose dependent, and dose- and time-dependent reductions in soluble VEGFR-2 levels. Early clinical response data are encouraging, with two unconfirmed partial responses in the ongoing 60 mg cohort and three minor responses at lower doses. Moreover, DCE-MRI assessment showed decreases of >40% in iAUC at consecutive visits in 2/3 patients receiving 20 mg and in 3/4 patients receiving 45 mg, indicating reduced tumor blood flow and permeability. Conclusions: In this ongoing Phase I study, continuous once-daily treatment with AZD2171 is generally well tolerated at doses ≤45 mg. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca
The relationship between adherence to adjuvant hormonal therapy and survival among low-income, insured women with primary breast cancer
Authors: G. G. Kimmick, F. Camacho, W. Hwang, R. T. Anderson
Journal: Journal of Clinical Oncology (2009)

e11522 Background: Clinical trials and meta-analyses show that adjuvant hormonal therapy for hormone receptor positive breast cancer significantly decreases risk of death. We explored the relationship between adherence to adjuvant hormonal therapy and death in a low-income, Medicaid-insured population. Methods: Using a Medicaid claims-tumor registry linked database and National Death Index data (NDI), we evaluated adherence to adjuvant hormonal therapy [defined as &gt;80% Medication Possession Ratio (MPR)] and mean six-year overall and cancer-specific survival by local versus regional stage for all female breast cancer diagnosed in years 2000–2002, in North Carolina. The Kaplan-Meier and Cox Proportional Hazards models were used to determine the role of adherence on cancer-specific survival. Models were adjusted for age, race, Charlson comorbidity score, number of prescription medications, type of surgery, use of radiation therapy, prior chemotherapy, hormone receptor status (positive or unknown). Results: The final sample consisted of 1,042 cases [ages range 29–97 years (mean 65.9 years; 56% Caucasian; mean Charlson comorbidity score 4.1 (SD 2.9); 680 local and 362 regional stage], of which 732 filled a prescription for adjuvant hormonal therapy within the year after breast cancer diagnosis. Filling a prescription for adjuvant hormonal therapy, versus not, was not significantly associated with cancer-related death: HR 1.04 (95% CI 0.66 - 1.64) overall; HR 0.75 (95% CI 0.39 - 1.43) for local stage and HR 1.01 (95% CI 0.51 - 2.00) for regional stage. However, adherence in the highest quartile (MPR&gt;95) is associated with an increase in mortality risk. Conclusions: In this low income insured group of breast cancer patients, no statistically significant association was found between death rates and use of adjuvant hormonal therapy. However, an unexpected association between very high adherence and increase in mortality was found. This may reflect methodological limitations of claims data involving bias and unidentified patient risk. More research is needed to explore reasons for higher mortality among low-income women with high medication adherence. [Table: see text]
Association of the expression of CD133 in locally advanced rectal cancer with tumor regression and survival after neoadjuvant radiochemotherapy.
Authors: Thilo Sprenger, Lena Conradi, Tim Beissbarth, Josef Rüschoff, B. Michael Ghadimi, Claus Rödel, Heinz Becker, Franz Rödel, Torsten Liersch
Journal: Journal of Clinical Oncology (2012)

479 Background: CD133 has been described as a stem cell marker in colorectal cancer and is associated with higher tumorigenic potential and resistance to radiochemotherapy (RCT). In this study the expression of CD133 was evaluated in pre-treatment tumor biopsies and corresponding post-treatment surgical specimens of locally advanced rectal cancer patients undergoing multimodal therapy and was correlated to histopathological features and clinical follow-up. Methods: 97 patients with UICC II/III rectal cancer treated with preoperative 5-FU based RCT within the German Rectal Cancer Trials were investigated. Pre- and post-treatment CD133 expression levels were determined using immunhistochemistry and correlated with histopathologic parameters, tumor regression, tumor recurrence and disease-free survival (DFS). Results: As compared to pre-treatment biopsies we observed a significantly higher CD133 expression in post-treatment tumor specimens (p=0.01). There was, however, no correlation for both biopsies and tumor specimens between CD133 expression levels, pathological characteristics and survival. In matched analyses of corresponding biopsy/tumor pairs, patients with a decreased number of CD133 positive cells after preoperative RCT showed significantly lower post-treatment tumor stages (p=0.03) and higher histopathological tumor regression (p&lt;0.01). Moreover, these patients had a significantly improved DFS in uni- (p&lt;0.001) and multivariate analyses (p=0.001). Conclusions: CD133 expression displays a marker with prognostic and monitoring validity in rectal cancer patients. A decrease of the CD133 positive cell fraction in post-treatment tumor tissue is associated with a more favorable outcome after preoperative RCT.
Utilization and costs of epoetins and darbepoetin for treating platinum chemotherapy-induced anaemia
Authors: H. Malonne
Journal: Journal of Clinical Oncology (2005)

6110 Background: Supportive medications such as haematopoietic growth factors represent significant healthcare costs in oncology patients. Our objective was to examine the utilization and costs of erytropoiesis stimulating agents in patients treated with platinum-based chemotherapy. Methods: We conducted a retrospective analysis of anonymized medical and pharmacy claims of over 1.7 million members from the MLOZ (Union Nationale des Mutualités Libres), a public health fund, between January 1, 2002 and June 30, 2004. Patient cohorts, epoetin α (n=1177), β (n= 292) and darbepoetin α (n=157), were identified through (1) prescription invoice of these 3 drugs and (2) co-administration of platinum-based chemotherapy. Patients were excluded if they were (1) under dialysis, (2) switched from one drug to another or (3) invoiced (or prescribed) negative or zero amount of one of the 3 drugs. Since the cohorts where not normally distributed, utilization and costs of erythropoietic factors were expressed by median dose (1μg darbepoetin α = 200IU) and median amount (€) reimbursed per quarter. The between-group difference was analysed using the Kruskal-Wallis and the Mann-Whitney tests. Results: No significant difference was observed between epoetin α and β median administered dose per quarter or median reimbursed amount during the observation period. From the beginning of darbepoetin α reimbursement for anaemic patients receiving platinum-based chemotherapy (June 30, 2003) until the end of the study (June 30, 2004), a marked difference was observed between darbepoetin α and epoetin α or β quarterly doses and reimbursed amounts (see table). Conclusions: Compared with epoetins, patients treated with darbepoetin α received significantly higher doses of medication and consequently, incurred higher cost. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Janssen-Cilag
Natural history of T1N0M0 hepatocellular carcinoma: Large scale study in the United States.
Authors: Humaid Obaid Al-Shamsi, Reham Abdel-Wahab, Manal Hassan, Gehan Botrus, Ahmed S Shalaby, Robert A. Wolff, Ahmed Omar Kaseb
Journal: Journal of Clinical Oncology (2016)

416 Background: Prognostic modeling of hepatocellular carcinoma (HCC) is complex due to preexisting cirrhosis in most cases. Tumor features and factors related to functional hepatic reserve must be taken into account when considering treatment options or counseling patients about their survival. The key prognostic factors may vary at different stages of the disease especially for early stage. Methods: From 1992 to 2011 total of 397 HCC patients with T 1 N 0 M 0 were referred to MD Anderson Cancer Center for treatment. Detailed clinical-pathologic information were retrieved from medical records. Univariate analysis was done using the c 2 or Fisher’s exact test for categorical variables. Kaplan-Meier used to estimate the median overall survival (OS). Multivariate cox regression analysis was performed to estimate the hazard ratio (HR) and 95% confidence interval (CI). Results: The male to female ratio was3:1. The mean age ± standard deviation was 65.04 ± 12.5, 57.2% were non-viral related, 59.7% had cirrhosis, and 9.3% had poorly differentiated tumor (PDT). Median OS (95% CI) was 28.5 months (23.6 – 33.4). First line therapy is summarized in table 1. Surgical intervention was similar to systemic therapy with 76% reduction in mortality compared to non-treated group. Restricted analysis among cirrhotic patients showed similar results. PDT was associated with significant poor prognosis compared to well-differentiated tumor, HR (95% CI) was 2.42 (1.36-4.28) after adjustment for demographic, epidemiological, and clinical factors. Conclusions: Our results indicate that T 1 N 0 M 0 HCC patients have similar outcome with systemic therapy and surgery which could be beneficial for patients with underlying cirrhosis and high risk of postsurgical complications. [Table: see text]
Impact of chromosomal copy number variation on outcome in metastatic clear cell renal cell carcinoma patients treated with antiangiogenic agents.
Authors: Eric Jonasch, Suresh Thakur, Kanishka Sircar, Pheroze Tamboli, Nizar M. Tannir, Federico A. Monzon
Journal: Journal of Clinical Oncology (2013)

393 Background: Antiangiogenic agents (AA) are used to treat metastatic clear cell renal cell carcinoma (ccRCC). Currently there are no biomarkers of therapeutic efficacy with these agents. We have previously shown that chromosome copy number variation (CNV) is associated with poor (14q loss) or more favorable outcomes (5q31-ter gain) in nonmetastatic patients. The purpose of the current study was the impact of CNV on response, progression free survival (PFS) and on overall survival (OS) after AA in patients with metastatic ccRCC. Methods: We obtained archival FFPE or frozen tumor specimens from patients with mRCC treated with sorafenib (after tumor removal), bevacizumab or sunitinib (neoadjuvant treatment). DNA was analyzed with Affymetrix 250K Nsp SNP microarrays. We identified the presence of genomic imbalances and loss of heterozygosity (LOH) to obtain “virtual karyotypes”. We then compared CNV to outcome using Wilcoxon-Gehan statistical analysis. Results: A total of 83 patients were used to analyze CNV after treatment with AA: 22 sorafenib, 29 sunitinib, 31 bevacizumab. Gain of 8q (p = 0.036) and loss of 16q (p = 0.0031), 20p (p = 0.038) or 20q (p = 0.022) were associated with a shorter OS, whereas gain of 1q (p = 0.037) and 5q (p = 0.019) were associated with longer OS in this patient cohort. When 14q loss was combined with 8q gain, median OS was further decreased (p 0.01). Surprisingly, when assessed as a group, no specific CNV was associated with PFS. However, when compared separately, 5q gain was predictive for better PFS in sorafenib or bevacizumab treated patients (p = 0.006), but no such effect was seen in the sunitinib treated cohort. Conclusions: Our results show that chromosomal imbalances are associated with divergent clinical outcome in metastatic ccRCC patients treated with AA, and are predominantly prognostic. Dissecting out driver tumor suppressor or tumor activating genes within these chromosomal regions will guide our understanding of what defines a particularly lethal phenotype. The possibility exists that specific CNV profiles predict for response to therapy, but a larger sample size is required to validate this possibility.
Neoadjuvant (NA) oxaliplatin (FOLFOX4) followed by chemoradiation (CRT) in locally advanced rectal cancer: Intermediate results
Authors: F. A. Calvo, J. Serrano, M. Gomez-Espi, P. Garcia-Alfonso, R. Garcia, E. Lozano, D. de la Mata, J. A. Arranz, R. Herranz, G. Perez-Manga
Journal: Journal of Clinical Oncology (2005)

3624 Background: To explore the contribution of induction FOLFOX4 and inmediate oral Tegafur sensitized preoperative CRT in ≥cT3 rectal cancer. Particular emphasis is given to the analysis of local effects of the NA treatment segment: tumor downstaging and pelvic normal tissue tolerance. Methods: From April/2001 to March/2003, 67 consecutive patients (p) diagnosed of ≥cT3 rectal cancer (90% EUS and 100% CT scan; 48% cN+, 10% cT4) were treated with NA FOLFOX4 (Oxaliplatin 85 mg/m2 as a 2 h infusion day 1, LV 200 mg/m2 as a 2 h infusion followed by bolus 5-FU 400 mg/m2 and a 22 hours infusion of 5-FU 600 mg/m2 day 1 for 2 consecutive days). Treatment was repeated every 2 weeks, 2 courses, inmediately followed by 4500–5040 cGy pelvic radiation with concurrent oral Tegafur 1200 mg/day. Surgery was programmed 4 to 6 weeks after. Transanal excission of post-CRT rectal wall cancer residue was done in 3 p (5%). Intraoperative presacral electron boost (1000–1250 cGy) was given to 47 p (76%). Adjuvant chemotherapy was electively administered to 76% of p (86% 5FU-LV and 10% FOLFOX4). Results: Median follow-up time was 30 months at the time of the analysis (November/04). NA FOLFOX4 was suspended or modified in 9 p (14%) and CRT was incomplete or delayed in 13 p (21%). Acumulated grade 3–4 registered toxic events were: 21% gastrointestinal, 16% cutaneous and 2% urologic. In 5 p (7%) pelvic surgery was cancelled (evidence of metastatic disease). Among the remaining 62 p, the surgical specimen showed a total T downstaging rate of 75% and N downstaging of 40%. Incidence of pT0 stage was 26% and pT1 13% (no pN+ findings in these categories). Actuarial 2-years local control, disease-free survival and overall survival were 95%, 88% and 93%, respectively (in pT0–1 downstaged patients no cancer-related events were registered). Conclusions: The data suggests that Oxaliplatin sensitive cancer cells are present in the primary rectal cancer lesion and envolved regional nodes. Downstaging effects compares favourably NA FOLFOX plus CRT to CRT alone. Long-term patients outcome seems to correlate with the efficacy observations identified in the NA treatment segment. No significant financial relationships to disclose.
The outcome differences between late and early relapses after orchiectomy (OE) in patients (pts) with stage I germ cell tumors (GCT).
Authors: M. Fedyanin, A. Tryakin, E. Burova, A. Bulanov, I. Pokataev, D. Kanagavel, T. Zakharova, K. Figurin, A. Garin, S. Tjulandin
Journal: Journal of Clinical Oncology (2011)

e15013 Background: Late relapses (>2 years) after completion of chemotherapy are rare and often platinum-resistant. There are limited data concerning late relapses in chemotherapy-naïve pts with stage I GCT. This retrospective analysis was performed to compare the outcome between pts with stage I GCT, who had late (≥2 years) and early (≥3 months and < 2 years) relapse after OE. Methods: We analyzed data of 1069 CT-naïve pts with advanced GCT of testis treated in our department from 1986 to 2008. All pts had cisplatin- and etoposide-based CT. We identified 169 (15.8%) pts with prior stage I disease, who had not received adjuvant treatment: 140 and 29 pts had early and late relapse, respectively. Among pts with late relapse pure seminoma was revealed in 14 pts, nonseminoma – in 15 pts. Median f.-up time for 169 pts was 35 (range, 2 - 218) months. Results: Pts with late relapse were older – 35 years (23-57), whereas pts with early relapse – 30 years (16-63) (p=0.0008) and also had more frequent pure seminoma in primary tumor: 14/29 (48,3%) vs. 46/140 (32,8%), p=0.08. At the time of disease progression both groups were very similar according to well-known prognostic factors incl. IGCCCG classification. The only difference between groups was larger size of retroperitoneal lymph nodes in late (9 cm) than in early relapse (4 cm, p<0.0001). The outcome in pts with late relapse was significantly worse than in pts with early relapse: complete response rate after induction CT was 20.7% (6/29) vs. 42.1% (59/140) (p=0.01), three-year PFS - 70% vs. 84% (p=0.05, HR 2.1, 95%CI 1.0-7.6) and three-year OS - 72% vs. 88% (p=0.04, HR=2.4 95% CI 1.05-10.25), respectively. In pts with pure seminoma this difference in OS was even more significant: 65% vs. 91% (p=0.04, HR=3.8, 95%CI=1.06-32.4). Conclusions: Late relapse following stage I GCT was associated with seminoma, older age and worse outcome after induction CT.