tbuckley/cabot-search huggingface dataset:
Five-year follow-up results of imatinib 400 mg in late chronic phase chronic myeloid leukemia (CML) patients
Authors: I. Iacobucci, F. Palandri, M. Amabile, A. Poerio, S. Soverini, F. Castagnetti, N. Testoni, G. Rosti, M. Baccarani, G. Martinelli, F. Palandri
Journal: Journal of Clinical Oncology (2007)

7041 Background: Imatinib (IM) is the drug of choice for the treatment of Ph+ CML, where a complete cytogenetic response (CCgR) is achieved in more than 80% of early chronic phase (ECP) patients, with a 6-year survival of 89%. Methods: We monitored the hematologic, cytogenetic and molecular response to imatinib in a cohort of 295 patients with Ph+ CML in late chronic phase (LCP) who were enrolled in a national prospective study of the GIMEMA CML Working Party, with focus on the rate of major molecular response and on progression-free survival and overall survival of complete cytogenetic responders. Patients were monitored for cytogenetic and molecular response every 6 months. Cytogenetics was performed on bone marrow cells with conventional methods. Molecular response was assessed on peripheral blood samples by quantitative PCR (RQ-PCR) using TaqMan methodology and expressing the results as a ratio of BCR-ABL to ABL x100. The duration of chronic phase prior to IM treatment ranged from 1 to 202 months (median 38). Treatment was IM 400 mg daily through all the study period, with a few dose increase to 600 or 800 mg. Results: 158 patients (54%) achieved a CCgR in 3 to 62 months (median 6) after the first IM dose and 124 of them (78%) are still in continuous CCgR after 5 years whereas 34 patients lost the CCgR, 23 of them within 24 months after the CCgR achievement. For the 158 patients the 5-year survival free from progression to accelerated or blastic phase is 95% and overall survival is 91%. 114 patients were evaluable for molecular response and 68% of them were in major molecular response with a BCR-ABL/ABL ratio lower than 0.05. Conclusions: We showed that for the complete cytogenetic responders progression-free and overall survival are likely to be as good as for ECP patients, suggesting that the quality of the cytogenetic response is prognostically more important than the chronic phase duration before IM start. Supported by European LeukemiaNet, COFIN 2003, AIL, AIRC. No significant financial relationships to disclose.
EGFR, HER2, and phospho-Akt are not predictive factors for response to first-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC)
Authors: L. Toschi, G. Metro, E. Magrini, S. Bartolini, C. Ligorio, G. Finocchiaro, A. Pession, A. Cancellieri, G. Tallini, F. Cappuzzo
Journal: Journal of Clinical Oncology (2006)

7111 Background: Response to Epidermal Growth Factor Receptor tyrosine kinase inhibitor (EGFR-TKI) therapy is significantly associated with increased EGFR gene copy number, increased EGFR expression or presence of activating EGFR gene mutations. In presence of EGFR, increased HER2 gene copy number, as well as activation of the anti-apoptotic protein Akt demonstrated to increase EGFR-TKI sensitivity in both clinical and preclinical models. Aim of the present study was to assess whether these biomarkers also associate with response to first-line chemotherapy. Methods: Patients with advanced NSCLC with full clinical data and with tumor tissue available were selected for this analysis. Specimens were evaluated for EGFR and HER2 gene copy number by FISH, EGFR and p-AKT protein expression by immunohistochemistry. RECIST criteria were used to assess response to chemotherapy. Results: A total of 144 NSCLC were included in this analysis. Patient characteristics included: male/female: 95/49; PS 0/1/2: 112/29/3; stage III/IV: 44/100; adenocarcinomas plus bronchioloalveolar/squamous/other: 86/35/23; never/former/current smokers: 26/69/49. The majority of patients were treated with first-line platinum-based chemotherapy (115/79.9%). Response to chemotherapy was not associated with any clinical characteristic. A trend towards better response was observed in non-adenocarcinoma histologies (p = 0.08) and in smokers (p = 0.20). Response and time to disease progression (TTP) were not influenced by EGFR/HER2 FISH status, nor P-Akt/EGFR expression. In EGFR FISH positive response rate was 36.4% and TTP was 6.4 months, versus 28.7% and 7.3 months in EGFR FISH negative (p = 0.4 for both). Conclusions: Biomarkers useful for selection of patients candidate for TKI therapy are not predictive for response to first-line chemotherapy in NSCLC. No significant financial relationships to disclose.
Non-Svr to peginterferon Alfa-2a therapy and ribavirin is strongly predicted by baseline factors and week 8 on-treatment viral load in Hcv genotype (gt) 1 patients: New insights from cart analysis of the chariot study
Authors: S. K. Roberts, P. Ferenci, M. Yoshihara, D. H. Crawford, W. Sieverf, G. W. McCaughan, W. Cheng, M. Weltman, W. D. Rawlinson, P. I. McCloud, B. Rizkalla, G. J. Dore
Journal: Hepatology (2010)
Predictive factors of survival in amyotrophic lateral sclerosis patients with respiratory dysfunction
Authors: Inês Neves, Hans Dabo, Inês Belchior, Anabela Marinho, Tiago Pinto, Miguel Gonçalves, João Carlos Winck
Journal: European Respiratory Journal (2012)

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that causes severe respiratory dysfunction which is the major cause of death. Early management of respiratory symptoms may improve outcomes and survival.

Aim: Describe survival of patients with ALS and respiratory dysfunction and identify predictive factors of survival.

Methods: Retrospective analysis of patients with ALS evaluated in an outpatient setting. Ventilatory support data was screened. Kaplan-Meier survival analysis was performed and predictive factors were evaluated by Cox multivariate regression.

Results: 60 patients (25 females) with a median age of 64.5 years (range 34-80) were analyzed. At presentation, 33 patients (55%) had slow bulbar-onset and 27 (45%) rapid bulbar-onset. Non-invasive ventilation (NIV) was initiated in 52 patients (86.7%), with a mean vital capacity of 1698.0±768.0 L and 22.0±40.8 months after diagnosis. Mean duration of NIV was 19.6±23.7 months. Mechanical assisted cough was used in 23 patients (38.3%). Gastrostomy was performed in 21 patients (17 rapidly bulbar) and tracheostomy in 10 (9 rapidly bulbar) after a mean time of 13.6 ±17.0 months under NIV. The 5-year survival was 48%. The median overall survival and survival after respiratory muscle aids initiation was significantly higher in slowly bulbar patients compared with rapidly bulbar (p=0.03 and p<0.01, respectively). In multivariate analysis, predictive factors of survival were younger age, slow bulbar-onset, and early NIV initiation.

Conclusion: Survival may be prolonged in patients with ALS and respiratory dysfunction with early NIV initiation. Age and bulbar onset have significant negative impact on survival.
Risk partitioning model shows need to address time dependence of breast cancer recurrence.
Authors: L. Esserman, B. Chu, R. Chung, E. Ozanne, C. Yau, P. Tsing, F. L. Baehner, A. N. Tutt, D. H. Moore, C. Benz
Journal: Journal of Clinical Oncology (2010)

10605 Background: Outcomes absent adjuvant therapy provide insight and a basis for assessing incremental value of predictive and prognostic molecular signatures over standard variables. Methods: Of 562 adjuvant naive women from Guy's Hospital followed for > 21 years, 350 had tissue blocks, and ER, PR, HER2, and grade were reassessed by a single pathologist (RB). Recursive partitioning software (party) identified classification variables and optimal cut points that differentiated distant metastasis-free survival (DMFS). Additionally, 683 adjuvant-untreated node-negative breast cancer cases (447 ER+ and 236 ER-) annotated for DMFS were pooled from 4 different expression microarray public sources (van de Vijver 2002; Wang 2005; Minn 2007, Desmedt 2007); 478 did not recur within the first 5 years and were defined as the subgroup at risk for late recurrence. Results: HER2, HR status drive timing of recurrence. HER2+ and triple neg tumors (TN) risk is over by 5-7 years after diagnosis. HR+ recurrence risk is steady for 20 years. 60% of HR+, N-, Grade >2 cases are recurrence-free at 20 years. DMS is dominated by node positivity, followed by grade in HR+ cases. KM plots, for all subsets, show an asymptote, or mixed populations with many cured by surgery alone. Four gene based signatures (UCSF Celera Metastasis Score, Proliferative, UCSF HRneg, Caldas TN), driven by proliferation and immune function genes, are being tested for added value in predicting early vs late recurrence in HR and HER2 subsets. These 4 signatures were evaluated in silico in pooled datasets of 683 adjuvant naïve node- cases for ability to predict early and late recurrence. Early recurrence is predicted by proliferation signatures in HR+ cases and cytokine signatures in HR- breast cancers. Late recurrence in HR+ patients may be predicted by cytokine signatures. Validation in the Guy's set will be presented. Conclusions: Prognostic signatures are best evaluated in context of tumor subtype and timing of recurrence (early vs. late). Proliferation-related genes drive early metastatic events in HR+ but not HR- breast cancers, where cytokine or immune-related genes appear predictive early in HR- and HER2+ cases. Determinants of late metastatic events need further development. No significant financial relationships to disclose.
Use of statins and breast carcinoma: A case-control study
Authors: L. Dumasia, C. Lobocki, A. Couturier, C. Lebeis, A. Drelichman
Journal: Journal of Clinical Oncology (2006)

592 Background: Statin drugs, which enzymatically inhibit HMG CoA reductase, are used in the treatment of hypercholesterolemia. In vitro, statins have been shown to induce apoptosis and inhibit growth in breast cancer cell lines. Although controversial, recent clinical data has indicated that statins may have a chemopreventive effect against breast cancer. Our objective was to determine whether the long-term intake of statins (at least four years) demonstrates a protective effect against breast cancer as a primary endpoint. Methods: We conducted a retrospective, case-control study of female patients from a community-based hospital and medical center located in southeastern Michigan. Cases included patients diagnosed with invasive breast carcinoma between 1995–2005, as identified through the tumor registry. Controls were family practice patients (age &gt; 35 years) randomly selected from a database generated for this same time-period. Patients completed a mailed questionnaire with information pertaining to their use of statins and other medications, as well as other breast cancer risk factors. Subjects (N = 521) and controls (N = 521) were case matched by age, race, and body mass index (BMI). Results: The mean age of patients was 62.9 (range 35–101 yrs.) with an average BMI of 27.5. Reported usage of statins for four or more years prior to diagnosis was 5.5% in breast cancer subjects and 6.9% in case-matched controls. Compared to nonusers, women who had been on statin therapy for four or more years prior to diagnosis were not found to have a decreased risk of breast cancer (odds ratio 0.78: 95% CI 0.47 - 1.31). Similarly, there was no difference in risk for nonusers versus those taking statins for &lt;1 yr., 1–4 yrs., or ≥ 4 yrs. However, nulliparity, positive family history, report of any benign breast biopsy, and ≥ 5-year use of oral contraceptives (before age 30) were significantly associated with the occurrence of breast cancer (p &lt; 0.002, Chi-square test). Conclusion: Although statins have been shown to inhibit growth in breast cancer cell lines in vitro, its effect in vivo has remained inconclusive. Our study did not demonstrate a significant protective effect against breast carcinoma in women who had ever taken statins, or those who had taken the drug for a minimum of four years. No significant financial relationships to disclose.
Outpatient management in febrile neutropenia with an intermediary risk of complications: Limitative clinical factors.
Authors: I. Borget, S. Antoun, P. Bonnet, B. Gachot, E. Chachaty, M. Di Palma, M. Merad
Journal: Journal of Clinical Oncology (2010)

e19511 Background: Febrile neutropenia (FN) is a severe chemotherapy side effect. According to the MASCC score, hospitalization and outpatient management are respectively recommended for high-risk (HR) and low-risk (LR) patients. We have identified patients with intermediate-risk (IR) not requiring systematic hospitalization and for whom the MASCC alone may be insufficient to determine the management strategy (hospitalization or outpatient). In this study, we identified additionnal prognosis factors which help distinction between HR and IR episodes. Methods: Prospective study about consecutive FN in solid tumor patients consulting at the emergency unit of the Gustave Roussy Institute. Collected data included demographic, clinical, biological, therapeutic and economic features, MASCC score and complications. A logistic regression was performed to identify prognosis factors. Results: 137 FN were recorded for 128 patients. Twenty-six FN (18%) were managed at home (MASCC≥20). One hundred and eleven (82%) FN led to hospitalization (MASCC<20 or > 20 with clinical symptoms). Symptoms grade allowed distinction into 2 subgroups: HR (n=37) vs. IR (n=74). In IR group, 10 patients were >70 years, 41 had metastasis, 9 received third-line chemotherapy and 45 had 1-2 WHO status. Main symptoms were fever>C‘>39°C (n=19), mucitis (n=15), diarrhea (n=7), urinary symptoms (n=4), cough without anomaly in x-ray chest (n=7) and CRP>100 (n=28). MASCC was between 16 and 26 (23/74 with MASCC<21). No complications were observed in IR patients. According to the logistical analysis, FN with a 3-4 status for diarrhea or mucitis, urinary symptoms, MASCC<21 or fever>C‘>39°C must be hospitalized. Conversely, age>70 years, metastasis, shiver, chemotherapy line>3, CRP>100, presence of cough or moderate clinical symptoms (1-2) have not emerged as HR factors. In this study, 11/23 and 37/51 episodes without HR factors and a MASCC respectively <21 and ≥21 would beneficiate of an outpatient management, leading to a reduction of 58% of hospitalization costs (4486€/episode). Conclusions: This study defined an IR group, for which the MASCC additional to prognosis factors allow to determine if the hospitalization is required. No significant financial relationships to disclose.
Analysis of HER1 and HER2 status in CNS metastases from patients (pts) with breast carcinoma (BC)
Authors: G. Viale, B. Del Curto, E. Orvieto, E. Maiorano
Journal: Journal of Clinical Oncology (2008)

1041 Background: HER2-positive disease is a recognised risk factor for metastatic spread of BC to the CNS but the role of HER1 is unclear. This study was undertaken to establish the prevalence of HER1 immunoreactivity and gene amplification in CNS metastases from BC pts, and to assess the correlation between the HER1 and HER2 status of these metastases. Methods: Surgically removed, formalin-fixed, paraffin-embedded CNS metastases from 55 pts with BC were investigated. HER2 status was assessed using immunohistochemistry (IHC; HercepTest) and fluorescence in situ hybridisation (FISH; PathVysion). HER1 status was investigated using IHC (31G7 monoclonal antibody) and FISH (LSI EGFR SpectrumOrange/CEP7 SpectrumGreen Probe). IHC results for both HER1 and HER2 were evaluated in accordance with FDA recommendations for reporting HER2 immunostaining. For each FISH assay, ≥60 non-overlapping nuclei of tumour cells in ≥2 randomly selected fields were assessed for the absolute number of HER1 and HER2 gene signals, and the number of centromeric signals for chromosomes 7 and 17. Results: IHC and FISH results are shown in the table. HER1 immunoreactivity (1–3+) was detected in 9 (31%) HER2-positive (FISH+) and 11 (42%) HER2-negative cases (p=NS, Fisher's exact test). The 2 HER1-amplified tumours did not show co-amplification of the HER2 gene. Chromosome 7 polysomy (mean count >3 centromeric signals/cell) was identified in 6 (11%) cases: 1 was FISH+ and IHC 3+; 4 also showed chromosome 17 polysomy. Conclusions: This study did not show any correlation between HER1 and HER2 status in CNS metastases from pts with BC. Furthermore, the 2 HER1-amplified tumours did not show co-amplification of the HER2 gene. Thus, HER1 does not co-express with HER2 and is unlikely to play a role in CNS metastases in BC. Our data also suggest that chromosome 7 polysomy may be correlated with chromosome 17 polysomy. IHC FISH 3+ 2+ 1+ 0 + - HER1 6 (11%) 3 (5%) 11 (20%) 35 (64%) 2 (4%) 53 (96%) HER2 27 (49%) 3 (5%) 17 (31%) 8 (15%) 29 (53%) 26 (47%) No significant financial relationships to disclose.
Second primary malignancies after chronic lymphocytic leukemia
Authors: J. M. Flynn, L. A. Andritsos, T. S. Lin, J. C. Byrd, J. A. Jones
Journal: Journal of Clinical Oncology (2008)

9632 Background: An increased risk for second primary malignancies (SPM) has been associated with CLL. Immunocompromise secondary to not only CLL itself but also its treatment has been implicated. We sought to determine population-based estimates of the risk for secondary neoplasia according to age, surveillance time, gender and year of diagnosis. Methods: Data were obtained from the Surveillance, Epidemiology, and End-Results (SEER) database encompassing 1973 and 2004. Incident CLL cases surviving for at least 2 months were included. Risk of second malignancies was estimated as a standardized incidence ratio (SIR) comparing observed to expected new cases in the standard 2000 U.S. population. 95% confidence limits were calculated for each ratio. Cancer risk was assessed by age (<60 v. ≥60 years), gender, surveillance time and date of diagnosis. Date of diagnosis was considered by periods (A: prior to 1989; B: 1990 to 2000; and C: 2001 to 2004) which coincided with major changes in accepted treatment standards. Results: A total of 39,718 patients, encompassing 145,394 person years of surveillance were included. The mean age at diagnosis of CLL in the <60 group was 52.5 years and 75.6 years in the ≥ 60 group. The SIR for all solid tumors by time periods (A, B, C) were 1.16, 1.17 and 1.44 (p<0.05 for all). Among solid tumors, incident neoplasms of the lung, melanoma, colorectal, kidney and Hodgkin’s disease were all observed in excess. Cancers of the kidney (O/E=1.56), lip(O/E=2.20) and salivary glands(O/E=2.92) were seen in excess only in males. Cancers of the stomach(O/E=1.82), colorectal (O/E=1.26), bladder (O/E=1.54) and Kaposi’s sarcoma(O/E=12.78) were elevated only in females, age ≥ 60 years. Duration of surveillance did not significantly impact risk, with the exception of kidney cancer which was more likely identified in the first 2–11 months after CLL diagnosis. Conclusions: Second malignancies remain a significant source of morbidity in CLL. In our analysis, gender and age were the most significant factors influencing risk, while length of surveillance had little impact. Incidence rates did not vary per time period, however, future studies directed at determining effects of specific treatments and the underlying mechanisms of SPM are warranted. No significant financial relationships to disclose.
Programmed death-ligand 1 (PD-L1) characterization of circulating tumor cells (CTCs) and white blood cells (WBCs) in muscle invasive and metastatic bladder cancer patients.
Authors: Archana Anantharaman, Terence W. Friedlander, David Lu, Rachel Krupa, Gayatri Premasekharan, Jeffrey Hough, Matthew Edwards, Ryon Graf, Adam Jendrisak, Jessica Louw, Lyndsey Dugan, Dena C. Marrinucci, Ryan Vance Dittamore, Pamela Paris
Journal: Journal of Clinical Oncology (2016)

446 Background: Recent studies indicate that PD-1 and PD-L1 checkpoint inhibitors have activity in chemotherapy refractory patients with muscle invasive (MIBC) and metastatic (mBCa) bladder cancer. PD-L1 expression on tumor cells or lymphocytes may correlate with response to therapy. To identify potential patients who may benefit from PD-1/PD-L1 targeted immunotherapeutics, we utilized a non-invasive blood test to evaluate PD-L1 protein expression in CTCs and WBCs of bladder cancer patients. Methods: Whole blood from 20 patients with MIBC or mBCa were collected and shipped to Epic Sciences. All nucleated cells were plated onto glass slides and subjected to immunofluorescent (IF) staining and CTC identification using scanners and algorithmic analysis. CTCs, defined as traditional (CK+ CD45- w/ intact DAPI+ nuclei and morphologically distinct) or CK- (CK-, CD45-, DAPI+, intact and distinct) were identified. PD-L1 biomarker characterization was assessed by IF staining. UroVysion FISH testing was used to assess genomic abnormalities in a subset of patient samples. Additionally, WBCs (CD45+ cells) were assessed for PD-L1 expression, relative to healthy controls. Results: Eighty percent of patients had mBCa and 20% had MIBC, 70% percent were men, and themedian age was 67 years, (range 43 to 88). Traditional CTCs were detected in 11/20 (55%) patients. Seven out of 20 (35%) patients had PD-L1+ cells, 4 of these patients had exclusively CK-/PD-L1+ CTCs, a subset of which were confirmed as malignant via FISH. CK- CTCs were detected in 14/20 (70%) patients. Five patients had greater than 4-fold PD-L1 positivity in WBCs as compared to healthy donors. Conclusions: Patients with MIBC and mBCa patients have detectable, heterogeneous CTCs with a population of CK-/PD-L1+ CTCs. Utilization of a liquid biopsy to identify patients with PD-L1+ CTCs and PD-L1+ WBCs may enable patient selection or short term therapeutic monitoring for measuring therapeutic efficacy. Further work will investigate association of PD-L1+ CTCs and WBCs with clinical response to PD-1 checkpoint immunotherapy.