tbuckley/cabot-search huggingface dataset:
Final results of a phase II study of sunitinib as second-line therapy in malignant pleural mesothelioma (MPM).
Authors: A. K. Nowak, M. Millward, R. J. Francis, A. Hasani, A. A. van der Schaaf, T. Seguard, A. W. Musk, M. J. Byrne
Journal: Journal of Clinical Oncology (2010)

7036 Background: There is no standard second-line therapy for progressive MPM. Sunitinib is a multi-targeted tyrosine kinase inhibitor of rational targets in MPM including VEGFR and PDGFR. We tested the safety and efficacy of second-line sunitinib in MPM. Methods: Eligible consenting patients (pts) had progressive MPM during or after first-line platinum/antimetabolite, ECOG PS 0-1, adequate organ function, and measurable disease. Treatment: sunitinib 50 mg/day ×28d q6 weeks. Primary endpoint: objective response (OR) defined by either a). Modified RECIST Criteria (MRC) on CT scan or b) metabolic response on FDG-PET in pts without prior talc pleurodesis (J Nuc Med (48) 1449-58; 2007). Imaging was performed at baseline and after cycles 1, 2, and every 2 cycles thereafter; most PET imaging was during treatment break. Simon's 2 stage design: 2 responses in the first 23 pts and 5 responses in 51 assessable pts gave α = 0.05, β = 0.1 assuming an OR of 20% to be of interest. Results: From 05/06 to 12/09 53 eligible pts were accrued: 51 assessable for response on CT; 20 without pleurodesis assessable on FDG-PET. Demographics: M/F (44/9); median age 64 (range 45 - 81); histology epithelial/sarcomatoid/mixed/unknown (37:1:9:6). ECOG PS 0/1 (15:38). Prior platinum with pemetrexed/gemcitabine(79%/21%). Best MRC response: CR 0; PR 5 (10%); SD 33 (66%); PD 12 (24%). Metabolic response: 7/20 assessable (35%), 1 also with CT PR; 4 with CT minor response. Total protocol-defined response 11/51 (22%, 95% CI 11%-33%). Median OS was 6.7 months. Median TTP was 3.4 months. Total cycles given: 114 (median 2, range 1-6); 3 pts remain on S. Adverse events (number pts experiencing;%): Grade 3/4: thrombocytopenia (3;6%), neutropenia (2;4%); Grade 3: fatigue (11;21%,), anorexia (3;6%), nausea (2;4%). 15/53 required dose reduction. There was one possible treatment- related death from pulmonary infiltrates and respiratory failure, and one grade 4 pneumonitis. Four pts developed increasing pleural effusions or ascites without other radiologic evidence of PD. Conclusions: Sunitinib has modest activity in previously treated MPM; testing at a continuous lower dose may be warranted to ameliorate toxicity. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Australia
Recovery Of Myeloid Derived Suppressor Cell Subsets Following Allogeneic Hematopoietic Stem/Progenitor Cell Transplantation
Authors: Qingdong Guan, Anna Blankstein, Anjos Karla, Oleksandra Synova, Marie Tulloch, Angeline Giftakis, Bin Yang, Geoff D. E. Cuvelier, Zhikang Peng, Donna A. Wall
Journal: Blood (2013)
Long-term outcomes of survivors of autologous hematopoietic-cell transplantation for refractory and relapsed Hodgkin’s Disease
Authors: K. A. Goodman, V. Serrano, E. R. Riedel, S. Gulati, C. H. Moskowitz, J. Yahalom
Journal: Journal of Clinical Oncology (2006)

6554 Background: With improvements in survival among refractory/relapsed Hodgkin’s Lymphoma (HL) patients after high-dose chemo-radiotherapy and autologous hematopoietic-cell transplant (AHCT), it is important to evaluate risk of late complications in this heavily treated population. Methods: From 1985–1998, 218 refractory/relapsed HL patients were treated on high dose chemo-radiotherapy and AHCT salvage protocols. 153 (70%) surviving ≥2 years after AHCT were analyzed. All received either radiotherapy with initial therapy or total lymphoid irradiation and involved field boost with the conditioning regimen (43%). Information from surviving patients was obtained through a self-administered questionnaire. The NDI was queried to determine vital status and cause of death. Primary endpoint was non-HL mortality, defined as mortality due to cardiac causes, infection or second malignancy (SM). Competing risk methods were used to calculate cause-specific mortality rates and examine its predictors. All events were calculated from 2 years post-AHCT to date of death/last follow-up. Results: Median follow-up time was 11 years. There have been 51 deaths, 32 due to HL and 19 due to other causes. Eleven deaths were due to SM: AML (3), MDS (2), NHL (2), NSCLC (2), gastric and colon cancer. There were 8 non-SM deaths: cardiac toxicity (4), infection, aplastic anemia, suicide, unknown causes (1 each). The 10 and 15-year overall survival (OS) rates are 64% and 57%, respectively. The 10-year cumulative incidence of death from HL and from non-HL causes were 22% and 13.5% ( table ). By univariate analysis, increased risk of death due to SM was associated only with higher age at AHCT (p=0.02). Conclusions: While HL initially accounts for the majority of deaths among patients surviving high-dose therapy, the HL mortality rate plateaus and risk of death from non-HL mortality increases after 5 years. Yet, even at 15-years, SM risk does not exceed that observed in patients treated with standard regimens. [Table: see text] No significant financial relationships to disclose.
Improved methods and standards for telomerase assay: Quantitative histopathology using antibody staining
Authors: John P. Jakupciak, Nathan D. Gallant, Matthew L. Becker, Alex Tona, Donald H. Atha
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4983 

Clinical studies show a direct association between telomerase activity and cells that are cancerous. The enzyme telomerase has been demonstrated to be expressed in 85-90% of all human cancers, but not in normal tissues. Clinical assays for telomerase in easily obtained body fluids would have great utility as non-invasive, cost-effective methods for the early detection of cancer. However, the use of telomerase as a biomarker has been hindered because of a lack of high-throughput methods essential for large cohort studies that are required to statistically validate telomerase as a biomarker for cancer. In addition, a critical problem has been the lack of universal controls or reference standards. Standards and reference materials would significantly expedite the acceptance and translation of biomarkers, such as telomerase, for expanded diagnostic use. To this end we are developing a direct imaging method using a standard protein chip and antibody staining for the presence of telomerase. A direct histological method has been shown to be a valuable tool to quantify other cancer biomarkers (Xiao and Barker, 2004, Nucleic Acids Research, 32, e28). In the current study we have used confocal microscopy and fluorescent-labeled telomerase antibodies to directly quantify telomerase in cultured human lung tumor A549 cells and human fibroblast IMR90 cells as a control. These measurements were compared to telomerase activity measured by TRAP/PCR and hTERT mRNA by RT-PCR, as described previously (Jakupciak et al., 2005, Clinical Chemistry, 51:1443). The sensitivity was determined for both assays, including the minimal number of determinations and the minimal number of cells required for accurate analyses. Although the measurement of telomerase by antibody staining will not determine whether the telomerase is active, it will be a valuable tool to determine its presence in individual cells where heterogeneity is problem for accurate diagnosis. In addition, the telomerase protein chip would serve as a reference to quantify telomerase concentration at a molecular level. This combination of measurement of telomerase by tissue staining, TRAP/PCR activity and mRNA expression will provide a more complete quantification of telomerase levels in tissues at various stages of cancer.
Study of mortality associated with febrile neutropenia among children with cancer
Authors: S. K. Basu, I. D. Fernandez, S. G. Fisher, B. L. Asselin, G. H. Lyman
Journal: Journal of Clinical Oncology (2004)

8526 Background: Febrile neutropenia is a common occurrence in children with cancer. This study aims to evaluate risk factors for mortality in this population. Methods: This is a secondary analysis of longitudinal data from the University HealthSystem Consortium database which includes information from discharge data on all patients hospitalized at 115 academic centers across the U.S. from 1995 to 2002. All patients who were at most 21 years of age and had at least one diagnostic code each for neoplastic disease and febrile neutropenia were included in this study. Patients who were undergoing or had undergone bone marrow transplantation were excluded from the study. Only one observation per patient was selected randomly. Results: A total of 12446 patients were identified for the study. There were 7045 (57%) males and 5401 (43%) females. The median age was 8 years (range: 0 to 21 yrs). The length of stay was less than 5 days for 6799 (55%) patients and greater than 5 days for 5647 (45%) patients (range: 1 to 359 days, median: 5 days). 7233 patients (58%) had a hematological malignancy, 4652 (38%) had a solid tumor and 561 (4%) were coded as in-situ, benign or unspecified tumors. The mortality rate was 2.88%. On bivariate analysis, race (p=0.0046), length of stay (p<0.0001), age (p<0.0001) and histopathology (p<0.0001) were significantly associated with mortality. Using logistic regression, infancy (compared to child aged 1–12 years, OR=2.06), adolescence (age:13–21 years, OR=2.26), hematological malignancies (versus solid tumors, OR=1.48) and length of stay >5 days (OR=6.86) were significantly associated with increased risk of mortality after accounting for sex, race and year of discharge. Conclusions: Age, length of stay and histopathology were variables that were significantly associated with risk of mortality in this study. Further evaluation of the role of complications and comorbidities at the time of hospitalization may help in identifying high-risk patients who might benefit from targeted antibiotic therapy or prophylactic hematopoietic growth factor support. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen
Phase II trial of neoadjuvant exemestane [EXE] and celecoxib [CELE] in breast cancer: Results of biomarkers
Authors: C. L. Shapiro, S. P. Povoski, R. Jiminez, J. Dehart, S. Ottman, D. R. Shiels, L. Xiaobia, R. Brueggemeier
Journal: Journal of Clinical Oncology (2007)

11056 Background: Aromatase [CYP19] activity and expression is increased by prostaglandin E2, thus providing a rational for combining the COX-2 inhibitor, CELE, with an aromatase inhibitor. To evaluate the effects of these drugs on proliferation and other biomarkers, we conducted a neoadjuvant trial of EXE alone followed by the combination of EXE and CELE. The primary endpoint was the assessment of biomarkers and the secondary endpoint was toxicity. Methods: Clinical stages II/III, postmenopausal, estrogen [ER] and/or progesterone receptor [PR] positive, previously untreated, ECOG 0–1 were eligible. Excluded were inflammatory breast cancer, history of myocardial infarction, and documented allergy to aspirin, NSAIDs, or sulfonamides. After initial core biopsy pts received 8 weeks (wks) of EXE 25 mg daily. They then received a second core biopsy followed by 8 wks of EXE and CELE 400 mg twice daily. After 16 wks, pts had definitive surgery. Compliance was assessed by pill counts at study visists every 4 wks. At baseline, 8, and 16 wks, pts had tumor measurements by physical exam, mammogram, and ultrasound. A tissue microarray [TMA] was contructed and immunohistochemical [IHC] staining with commercially available antibodies for Ki-67, COX-2, HER-2, ER, and PR was performed. Two independent pathologists scored intensity and percentage of cells staining and were blinded to treatment and the timimg of specimen acquistion. Statistical analyses were performed using Wilcoxon signed-rank test Results: Twenty pts with a median age 62 (range 56–87) were enrolled. CELE was discontinued in 3 (15%) pts for grade 1 rash-1 pt; grade 1 creatinine elevation-1 pt; and grade 1 melena-1 pt. Three (15%) pts-partial response, 16 (80%)-stable disease, and 1 (5%)-progressive disease. None of the differences in biomarkers between 0 and 8 wks and 8 and 16 wks were significant. A trend toward decreasing mean Ki 67 was observed from 0 to 8 wks (20% vs 9%, p=0.19) and 8 to 16 wks (9% vs 7%, p=0.7) Conclusions: Neoadjuvant EXE followed by EXE/CELE was well tolerated with anti-tumor activity. Tumor cell proliferation decreased by about 50% during EXE, but small sample size precluded reaching statistical significance. Frozen tissue was collected and the results of CYP 19 mRNA expression will be presented. [Table: see text]
Breast cancer ErbB2 status in Asian women: A review of local literature
Authors: Y. Tan, S. Han, Y. Lu, C. H. Yip, P. Sunpaweravong, J. Jeong, P. B. Caguioa, S. Aggarwal, E. M. Yeoh, H. Moon
Journal: Journal of Clinical Oncology (2009)

e22164 Background: Breast cancer incidence is increasing throughout Asia. However, the characteristics of Asian breast cancer are not always well understood due to the limited availability of local data and their inadequate inclusion in global literature databases. Effective breast cancer treatment in this region requires a better understanding of Asian breast cancer biology, including ErbB2 status. Methods: We performed a literature search in seven Asian countries on breast cancer studies in which tumour ErbB2 overexpression was assessed. The keywords erbB2 OR HER2 OR ErbB-2 OR HER-2 AND breast cancer AND (country) were used to search PubMed, international and local conference abstracts and local-language journals from the year 2000 onwards. Where available, we selected up to five representative studies from each country on the basis of population size, multi-institution patient populations, institution reputation and journal impact factor. We excluded studies containing only mRNA, serum, or cell line data or those conducted on biased populations or in western countries on Asian populations. Results: ErbB2 data from 26 Asian breast cancer studies are summarized in the table . The mean or median age of the study populations ranged from 46–56 years, with one exception. In most studies that evaluated tumour ErbB2 and hormone status, ErbB2 over-expression correlated negatively with ER positivity. Conclusions: The larger studies in particular confirm that the proportion of ErbB2-positive breast cancer in Asia is generally similar to the 20–30% reported for western women. Definitions of ErbB2 positivity using IHC vary between institutions and FISH is not routinely performed in several Asian countries. This may contribute to the fact that reliable, representative data on breast tumour ErbB2 status is scarce in Malaysia, the Philippines, India and Thailand. The increased availability of accurate ErbB2 testing and data would aid improved treatment of ErbB2-positive breast cancer in these countries. [Table: see text] [Table: see text]
Evaluation of the effiacy of posaconazole as antifungal prophylaxis in patients with acute leukemia
Authors: M. G. Kiehl, M. Wernicke, S. Klebe, W. Stein, K. Kokowski, W. Steinborn
Journal: Journal of Clinical Oncology (2008)

20687 Background: The incidence of proven or probable invasive fungal infections (IFIs) in immunocompromised patients with hematologic malignancies, especially patients with acute leukemia receiving intensive induction or consolidation is very high. In these patients invasive fungal infections are difficult-to-treat and often fatal. Posaconazol (POS), an extended spectrum triazol, has shown to be effective in the prophylaxis of invasive aspergillosis in these high-risk patients. Methods: We retrospectively compared the incidence of IFIs in patients with acute myeloid leukemia and acute lymphoblastic leukaemia receiving induction chemotherapy (n=28), consolidation chemotherapy (n=8), second line chemotherapy (n=1) or allogeneic stem cell transplantation (n=3) treated in our department of hematology before and after initiation of POS prophylaxis. Patients of the POS group received oral POS suspension (400 mg twice daily) starting day one after chemotherapy. Occurrence was assessed by clinical signs, symptoms and CT-scan. Results: A total of 40 cases were enrolled in this analysis. In the POS group (n=23) two cases (8,7%) with probable IFIs could be observed. Prophylaxis were interrupted in two cases because of vomiting. Before POS prophylaxis 5 of 12 patients (42%) developed proven or probable IFI during induction chemotherapy. Two of these 5 patients died (1 patient cerebral bleeding, 1 patient persistent leukaemia). The other 3 patients received further treatment using voriconazol as secondary prophylaxis. Conclusions: Prophylaxis with POS in patients with hematologic malignancies receiving high-dose chemotherapy for acute leukemia is feasible, well-tolerated and cost effective. We observed a clear reduction of probable invasive aspergillosis using POS prophylaxis as well as a clear reduction in iv antimycotic drugs. Further pharmacoeconomics analysis of POS prophylaxis in these high-risk patients in a single center setting will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Schering-Plough Schering-Plough
Organotypic slice cultures of human gastric cancer (GC) and esophagogastric junction adenocarcinoma (AEG): A new technology to study treatment response, resistance, and tumor heterogeneity.
Authors: Justus Koerfer, Sonja Kallendrusch, Felicitas Merz, Christoph Kubick, Woubet Kassahun, Guido Schumacher, Christian Moebius, Nikolaus Gassler, Christian Eckmann, Alfred Koerfer, Arved Weimann, Volker Wiechmann, Daniela Geister, Achim Aigner, Ingo Bechmann, Florian Lordick
Journal: Journal of Clinical Oncology (2015)

76 Background: GC and AEG have an unpredictable response to cytotoxic treatment and a poor prognosis. There is an urgent need for new research methods allowing for the determination of chemotherapy sensitivities, the analysis of resistance mechanisms and tumor heterogeneity. Here, we describe a novel technique extending our recent findings in other tumors (Gerlach et al. 2014; Merz et al. 2013), by which cancer specimens can be cultured in vitro and maintained in their natural micro-environment. Methods: Using a tissue chopper, fresh surgical and endoscopic tissue samples from GC and AEG were cut in 400 µm thick slices and cultivated in 6-well plates for up to 6 days. The slices were then fixed, embedded in paraffin and cut for routine histopathology and immunohistochemistry. Cytokeratin stains (CK8 and AE1/3) were used for determining tumor cellularity, ki-67 for proliferation, and cleaved caspase 3 staining for apoptosis. The slices were examined under naïve condition and following in-vitro exposure to 5-FU, cisplatin or docetaxel over a period of 2-4 days. Results: GC and AEG slice cultures from resection specimens (n=14) and endoscopic biopsies (n=17) revealed a good preservation of tissue morphology and tumor cell integrity during the culture period in most cases. The stroma and the tumor cellularity remained stable over at least 4 days, proving the viability of cancer in slice cultures. The amount of sampled tissue from endoscopic biopsies was identified as a critical determinant for the feasibility of slice cultures. During treatment of cultures with chemotherapy, a significant loss of tumor cellularity and an increase of apoptotic cells were observed, although a systematic and reproducible read-out still needs to be established. Conclusions: Slice cultures of GC and AEG were successfully established. They can be expected to provide a unique and powerful in vitro platform for the determination of sensitivities of a given tumor towards chemotherapy, to examine mechanisms of drug-resistance and to analyze tumor heterogeneity in patient samples.
How Italian oncologists cope with end-of-life care: A pilot study
Authors: E. Cortesi, S. Barni, B. Massidda, E. Aitini, G. Colucci, C. Gridelli, C. Iacono, V. Lorusso, M. Maltoni, P. Pronzato
Journal: Journal of Clinical Oncology (2008)

20554 Background: A very delicate but important moment for terminal patients (TP) and their families is the discussion of end-of- life issues. The topic is stimulating for the medical profession, patients and caregivers. Research literature guiding clinical practice is scarce. The way Italian oncologists cope with TP is explained, and in particular concerning end-of-life care. Methods: During 10 CME meetings concerning palliative care (PC) - Suffering Is Over (SIO) Project, held between March and November 2006, 238 oncologists completed a questionnaire adapted from an ESMO survey (Cherny and Catane, 2003), regarding their views towards TP. Certain questions specifically examined end-of-life problems. Results: The 238 oncologists completing the questionnaire were: male/female 56/44%, mean age 45.03 yrs (± 8.95) and mean years of experience in Oncology 16.19 (± 9.33). The majority (76%) were working in public or university hospitals. 44% Italian oncologists stated having received good training regarding PC during their professional career (vs 53% from ESMO survey); however, 77% still required a specialist consultation for pain management. According to 84% participants, oncologists should be expert in the management of the physical and psychological symptoms of TP. 90 % Italian oncologists were also responsible for the care of TP; 24% had never been involved in the coordination of encounters with the family of dying patients; 29% did not make decisions regarding the admittance of TP to a hospice. 32% Italian oncologists were asked by TP to help assisted suicide (90% of whom occasionally vs 94% ESMO). Differences between the Italian and the European surveys regards managing existential distress (41% vs 27% respectively), directly administering end-of-life care to TP (62% vs 43%), managing complications of chemotherapy (63% vs 91%) and discussing end-of-life care options with TP (40% vs 57%). Caring for TP and dying patients depressed 21% Italian doctors, and 19% felt emotionally burnt out by dealing with too many deaths. One third had to deal with the PC of only non-terminal patients. Conclusions: Interviewed oncologists considered the management of symptoms to be of prime importance. The request for elective death still remains infrequent in Italy. No significant financial relationships to disclose.
Rituximab Combined with Chemotherapy and Interferon in Follicular Lymphoma Patients: Final Analysis of the GELA-GOELAMS FL2000 Study with a 5-Year Follow-Up.
Authors: Gilles Andre Salles, Nicolas Mounier, Sophie de Guibert, Franck Morschhauser, Chantal Doyen, Jean-Francois Rossi, Corinne Haioun, Pauline Brice, Béatrice Mahé, Reda Bouabdallah, Bruno Audhuy, Christophe Ferme, Caroline Dartigeas, Pierre Feugier, Catherine Sebban, Luc Xerri, Charles Foussard
Journal: Blood (2007)