tbuckley/cabot-search huggingface dataset:
Clinical relevance of a positive result in cerebrospinal fluid (CSF) by flow cytometry (FCM) in patients with diffuse large B-cell lymphoma (DLBCL).
Authors: R. Alvarez, J. Dupuis, A. Plonquet, C. Christov, C. Copie-Bergman, I. Gaillard, T. EL Gnaoui, K. Belhadj, F. Hemery, C. Haioun
Journal: Journal of Clinical Oncology (2010)

8089 Background: Central nervous system (CNS) relapse is an uncommon but serious complication of non-Hodgkin lymphoma and usually occurs early in the disease course, suggesting subclinical disease at diagnosis. Several studies have demonstrated the superiority of FCM analysis of CSF, as compared to conventional cytology (CC), in detecting occult leptomeningeal disease in heterogeneous groups of aggressive lymphoma. Nevertheless, the clinical relevance of a positive FCM is still to be determined in DLBCL. Methods: We reviewed CSF samples from 114 patients (pts) with DLBCL (15% being transformed follicular lymphoma), analyzed both by FCM and CC, between 2005 and 2009. Ninety-three samples were from newly diagnosed (ND) pts and 21 from pts in relapse. The R-IPI in ND was very good (2%), good (42%) and poor (56%). First-line treatments included R-CHOP (n=81) and R- ACVBP (n=9) regimens with methotrexate intrathecal prophylaxis, and pts in relapse received several types of salvage treatments. A FCM+ did not influence treatment strategies. Results: Seventeen samples of the 114 were FCM+, versus 1 sample CC+ (this being also FCM+). In order not to overestimate the risk of CNS relapse, we excluded from the analysis pts with signs at presentation suggesting leptomeningeal disease (n=13). Therefore, within ND pts without neurological signs (n=86), 9 (10%) were FCM+, versus 4 FCM+ (27%) in the 15 pts in relapse. In the first group, 1/9 (11%) developed CNS relapse versus 0/4 (0%) in the second group. Within all pts without neurological signs (n=101), 4 (4%) relapsed in the CNS, with a median time to relapse of 5.2 months. In those, only 1/4 (25%) was FCM+ prior to relapse. Clinical features that showed an association with CNS relapse were: more than one extranodal site (ENS) of disease and the conjunction of elevated LDH and ENS>1 (p=0.04 and p=0.018, respectively). Conclusions: FCM gives far more positive results than CC, when analyzing CSF of pts with DLBCL (17/114 FCM+, versus 1/114 CC+). However, a positive FCM result did not translate into an increased relapse rate in the CNS, in this population. Therefore, FCM failed to have a predictive value in the occurrence of CNS relapse in DLBCL. No significant financial relationships to disclose.
Perioperative blood transfusions and cancer recurrence.
Authors: H S Wu, A G Little
Journal: Journal of Clinical Oncology (1988)

This collective review addresses the issue of transfusion-induced immunosuppression as it relates to patients undergoing cancer surgery. Patients receiving perioperative blood transfusions have a significantly worse prognosis than patients undergoing cancer surgery without a perioperative transfusion. It is thought that this is because transfusions produce a nonspecific immunosuppression by increasing the number and/or activity of suppressor T lymphocytes, decreasing the number of natural killer cells, and inducing anti-idiotypic antibodies. This risk, particularly when considered with the other risks of transfusion such as hepatitis or the acquired immunodeficiency syndrome (AIDS), suggests that criteria for transfusion of these patients should be stringent and related to an unequivocal need for replenishment of RBCs.
Insulin-like growth factor 1 receptor (IGF-1R): A potential therapeutic target for gastrointestinal stromal tumors (GIST)
Authors: A. K. Godwin, L. Rink, T. Chi, D. Flieder, J. Testa, C. L. Corless, M. C. Heinrich, B. L. Eisenberg, M. von Mehren
Journal: Journal of Clinical Oncology (2008)

10507 Background: Most GISTs possess a gain-of-function mutation in c-KIT or PDGFRα, which are targets of imatinib mesylate. However, wild type (WT) GIST and pediatric GIST lack mutations in either gene. These GISTs tend to be less responsive to imatinib-based therapies and have a poor prognosis. Overexpression of IGF-1R has been identified in many tumor types and inhibitors are currently being studied clinically. We identified amplification of IGF1R in a SNP analysis of GIST tumors and thus studied its potential as a therapeutic target in WT and mutant GIST. Methods: Expression of IGF-1R and downstream effectors in clinical GIST samples were examined using immunoblots and immunohistochemistry. Copy number changes of the IGF1R gene were examined by genomic qPCR and FISH. The role of IGF-1R in GIST signaling and viability were analyzed using NVP-AEW541 (Novartis, Basel, Switzerland), a specific inhibitor of IGF-1R, alone and in combination with imatinib, or via siRNA silencing of IGF1R. Results: IGF-1R was dramatically overexpressed and IGF1R amplification was detected at a significantly higher frequency in majority of WT GISTs and pediatric GIST when compared with mutant GISTs (P=0.000002 and P=0.0163, respectively). Inhibition of IGF-1R activity with NVP- AEW541 or down regulation of expression using siIGF1R led to cytotoxicity and induced apoptosis in both imatinib sensitive and resistant GIST cells via AKT and MAPK signaling. Combination of NVP-AEW541 and imatinib in GIST cell lines induced a strong cytotoxicity response. Conclusions: Our results reveal for the first time that the IGF1R gene is amplified and the protein is overexpressed in WT and pediatric GISTs. Our results demonstrate that the aberrant expression of IGF-1R may be associated with oncogenesis in a subset of GISTs that lack c-KIT or PDGFRα mutations and suggest an alternative or complementary therapeutic regimen in the clinical management of GIST, especially in tumors that respond less favorably to imatinib-based therapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis, Pfizer, MedImmune, Human Genome Sciences, Johnson & Johnson, Transgenomic Inc. MolecularMD Novartis, Pfizer Novartis, Pfizer
Alterations in molecular networks of metastatic colorectal carcinoma reveal organ-specific signatures: Implications for targeted therapy of metastatic disease
Authors: M. Pierobon, V. Calvert, M. Lipsky, K. Sheehan, R. Speer, E. Mammano, C. Belluco, J. Wulfkuhle, D. Nitti, L. Liotta, E. Petricoin
Journal: Journal of Clinical Oncology (2006)

3532 Background: Proteomic analysis of aberrant protein kinase activity is poised to provide crucial knowledge that could drive molecular-targeted therapeutics and personalized medicine. Many cancers are detected at late stages when metastasis has already occurred. Knowledge about the molecular derangements in the metastatic lesion is crucial for the rational selection of therapeutics. Very little is known about the signaling networks in the metastatic microenvironment. We employed reverse phase protein microarrays coupled to laser capture microdissection for a multiplexed phosphoproteomic fingerprint of colorectal metastatic disease to begin to understand the molecular functional changes that occur upon metastasis. Methods: 68 frozen cases of patient-matched colorectal cancer and hepatic metastasis, 15 cases of pulmonary metastasis, and 27 cases of hepatic metastasis of other primary cancers including breast, melanoma, pancreatic, ovarian, and stomach cancers (all taken at the same time at surgery), were subjected to laser capture microdissection. Procured tumor epithelia (20,000 cells per sample), were lysed and subjected to reverse phase protein microarray analysis. Using this technique, we measured the phosphorylation state of 75 kinase substrates. Molecular network analysis was performed using commercially available software. Results: Our results indicate that, unlike analysis of gene microarray data, we observe a significant difference between the molecular networks of activated kinase substrates within the metastatic lesion compared to the patient-matched primary tumor. In fact, despite overall patient-specific heterogeneity of the portraits, organ specific signatures that were independent of the primary origin of the tumor were identified. Conculsions: Effective treatment in the new era of personalized targeted therapeutics will require the ability to understand the functional activation of cellular signaling pathways since these are the drug targets themselves. Our results indicate that treatment of metastatic disease, and patient stratification for matching with the appropriate therapy may be organ-specific and not predicated upon the primary site of the disease. No significant financial relationships to disclose.
P-031 A novel reinforcement method for the surface of gastrointestinal metal stent: gas plasma treatment
Authors: I.K. Yoo, H.J. Chun, S.H. Kim, J.M. Lee, H.S. Choi, E.S. Kim, B. Keum, Y.T. Jeen, H.S. Lee, C.D. Kim
Journal: Annals of Oncology (2015)
Availability of therapeutic trials based on cancer site and stage
Authors: E. M. Basch, E. B. Elkin, E. Siegel, F. Xu, D. Schrag
Journal: Journal of Clinical Oncology (2004)

6015 Background: The reasons that enrollment in cancer clinical trials falls short of the ideal have not been well specified. We sought to determine the extent to which patients diagnosed with one of several common cancers in 2001 had a therapeutic trial open to them, based on their stage at diagnosis and region of residence. Methods: Population-based cohorts were identified using incidence data from the Surveillance, Epidemiology, and End Results (SEER) program, including cases of colorectal, prostate, breast, ovarian, and non-small cell lung cancer located in the states of Connecticut and Iowa and metropolitan San Francisco and Detroit. Cohorts were stratified by tumor stage and county of residence to determine the therapeutic trials for which patients might have been eligible using websites of regional cancer centers, cooperative groups, and the NCI PDQ database. For each stage and region-specific cohort, we calculated the ratio of available studies (RAS) per 10,000 prevalent cases of cancer. For stages I, II and III disease, we relied on disease incidence data from SEER. To estimate the prevalence of advanced disease, we used incidence and stage-specific survival data. Results: There were available therapeutic trials for most patients presenting with prostate, breast, lung, or ovarian cancer in the SEER regions of Connecticut, Iowa, San Francisco, and Detroit (Table). Early stage colon cancer, primarily a surgical disease, was the only notable exception. Most enrollment opportunities were through cooperative group studies, with less than 10% accounted for by industry-sponsored or institution-specific research. Conclusion: Lack of appropriate clinical trials does not appear to be an explanation for low enrollment rates for these common cancer types. No significant financial relationships to disclose.
Phase II trial of copper depletion as angiosuppressive treatment in newly diagnosed Glioblastoma Multiforme: Final report
Authors: S. Brem, S. A. Grossman, K. A. Carson, P. New, S. Phuphanich, J. B. Alavi, T. Mikkelsen, R. Priet
Journal: Journal of Clinical Oncology (2004)

1530 Background: Penicillamine is an oral agent used to treat intracerebral copper overload in Wilson's disease. Copper is a known regulator of angiogenesis; copper reduction inhibits experimental glioma growth and invasiveness. This study examined the feasibility, safety, and efficacy of copper deficiency in human glioblastoma multiforme. Methods: Forty eligible patients with newly diagnosed glioblastoma began concurrent radiation therapy (6000 cGy) in conjunction with a low copper diet and gradual dose escalation of penicillamine. Serum copper was measured at baseline and monthly. The primary endpoint was overall survival compared to controls in the NABTT database. Results: Twenty-five males and 15 females were enrolled between March 1999 and April 2000. The median age was 54 years, the mean KPS was 88, and 83% received surgical debulking. The mean baseline serum copper level was 138.6 ± 31.6 μg/dL and generally fell to the target range of 50–70 μg/dL (57.5 ± 27.5) after two months. Hypocupremia was found to be well tolerated for months. Significant toxicities such as myelosuppression, elevated liver function values, and skin rash were rapidly reversed by copper repletion. The median survival was 11.3 months and the median progression-free survival was 7.1 months. Prolonged survival was related to age and extent of surgical resection, but not hypocupremia. Conclusions: Although serum copper was effectively reduced by diet and penicillamine in patients with newly diagnosed glioblastoma multiforme who also received radiation, this antiangiogenesis strategy did not improve survival. No significant financial relationships to disclose.
A multicenter, open-label phase II trial of dovitinib, an FGFR1 inhibitor, in FGFR1 amplified and non-amplified metastatic breast cancer.
Authors: F. Andre, T. D. Bachelot, M. Campone, F. Dalenc, J. M. Perez-Garcia, S. A. Hurvitz, N. C. Turner, H. S. Rugo, M. M. Shi, Y. Zhang, A. C. M. Kay, A. J. Yovine, J. Baselga
Journal: Journal of Clinical Oncology (2011)

508 Background: Amplification of the FGFR1 gene occurs in ≈ 10% of breast cancers (BC), correlates with FGFR1 overexpression, and is mainly observed in ER+/Her2− BCs. Preclinical (pc) studies suggest that FGFR1 is a candidate therapeutic target in BC. Dovitinib (TKI258) is a tyrosine kinase inhibitor that targets FGFR, VEGFR, and PDGFR. In pc models, dovitinib demonstrated potent antitumor activities in FGFR1−amplified tumor cell lines. Methods: A 2-stage, phase 2 study to determine the efficacy and safety of dovitinib in 4 groups (gps) of metastatic BC patients (pts): (gp 1: FGFR1+, HR+), (gp 2: FGFR1+, HR−) (gp 3: FGFR1−, HR+), (gp 4: FGFR1−, HR−). Pt selection was performed according to FISH/CISH for FGFR1 (cut-off ≥ 6 gene copies). Dovitinib (500 mg) was administered once daily on a 5-day on/ 2-day off schedule. The primary endpoint was RECIST best overall response rate in pts with measurable disease per external radiology review. Results: As of January 2011, 81 pts were treated, with data for 77 pts available (gp 1 = 21, gp 3 = 34, gp 4 = 22). Prior therapy in the metastatic setting: a median of 2 chemotherapy lines (all pts) and 2 endocrine therapy lines (HR+ pts). 58% of pts had liver metastases (gp1: 81%; gps 3,4: 50%). Most common adverse events included: vomiting (75%; grade 3 [g3]: 6%), diarrhea (72%; g3: 6%), nausea (62%; g3: 5%), and asthenia (61%; g3: 17%). Median exposure was 1.7 (range, 0-8.2) months (mos), including 8 pts who received > 4 mos of therapy. For pts with measurable disease at baseline: gp 1, 2 (13%) had unconfirmed partial responses, and 7 (44%) pts had stable disease ≥ 4 mos (SD4); gps 3 and 4, SD4 was respectively noted in 8 (29%) and 2 (11%) pts. Conclusions: This is the first trial reporting efficacy of an FGFR1 inhibitor in pts with FGFR1−amplified BCs. Dovitinib showed antitumor activity in this heavily pretreated BC population with extensive visceral involvement. Activity was observed in HR+ pts with FGFR1−amplified disease with disease stabilization observed in other subgroups. FGFR1 is likely a relevant target in BC and FGFR1 amplification may define a molecular segment of dovitinib-sensitive disease. Further evaluation of dovitinib in pts with HR+ BC is planned.
Improving screening mammography return rates in overdue women: A randomized study of signed reminder letters from family physicians.
Authors: Elisa K. Chan, Christine Wilson, Scott Tyldesley, Anky Lai, Janette Sam, Ritinder Harry, Alan Nichol
Journal: Journal of Clinical Oncology (2014)

1 Background: For asymptomatic women aged 50 to 74 with an average risk for developing breast cancer, screening mammography (SM) is recommended every 2 years in British Columbia (BC). The Screening Mammography Program of BC (SMP) uses a schedule of multiple postcard reminders, which achieves an on-time (within 30 months) participation rate of 54% among those aged 50 to 69. The purpose of this study was to determine whether the SM return rate of overdue women could be improved by a reminder letter signed by their family physicians. Methods: Eligible women met the following criteria: prior normal SM, age 52 to 74, overdue by 30 to 48 months from their last SM and had agreed to being contacted for research by the SMP. All family physicians in BC were invited to participate. Consenting physicians signed the study letters, which encouraged SM, for all of the overdue women in their practice. Women were randomized to receive a postcard reminder or a postcard reminder and the signed family physician reminder letter. Six months after the mailing, the SMP database was queried to determine the SM return rate. Results: In BC, 822 physicians participated in the study and 5,385 women with signed letters were randomized. SMP sent a postcard to 2,689 women and a postcard and letter to 2,696 women. The age, number of prior SMs and time overdue were not statistically different between the arms. Within 6 months, 600 women (22.3%) in the postcard arm returned, while 894 women (33.2%) in the postcard and letter arm returned (odds ratio 1.7, p &lt; 0.0001). The maximum difference between the SM return rates was observed at 4 months. On multivariable analysis, women who had &gt;1 previous SM were more likely to return compared to those who only had 1 previous SM (odds ratio 2.2, p &lt; 0.0001). Women who were 30 to 36 months overdue were more likely to return compared to those who were 42 to 48 months overdue (odds ratio 2.4, p &lt; 0.0001). Conclusions: A signed family physician reminder letter is a simple and effective intervention to improve screening mammography return rates in overdue women.
Usefulness of PET/CT in the diagnosis of distant metastases of potentially operable gastric adenocarcinoma
Authors: R. Gallego, D. Fuster, A. Ginés, J. Ortín, J. R. Ayuso, D. Momblan, P. Arguis, C. Conill, F. Pons, J. Maurel
Journal: Journal of Clinical Oncology (2009)

e15598 Background: 1) To evaluate the usefulness of Positron Emission Tomography with combined 18F-Fluorodeoxyglucose with Computed Tomography (PET/CT) in the diagnosis of distant metastases in patients with gastric adenocarcinoma (GAC) compared to spiral double contrast thoracoabdominal Computed Tomography (CT); 2) To establish the utility of PET/CT in the detection of peritoneal carcinomatosis compared to laparoscopy. Methods: Thirty prospective patients (22 men, 8 women; mean age 67±11) who underwent endoscopic ultrasound and were classified as T2–3N1 or T3Nx GAC were included in this study. Whole body images were obtained 1 hour after injection of 370 MBq of 18F-Fluorodeoxyglucose. CT was performed within 2 weeks of PET/CT. Laparoscopy was performed without remarkable incidences. All findings were confirmed by histopathology examination and/or by at least 6 months follow- up. Results: Distant metastases were found in 9/30 cases: carcinomatosis (3), retroperitoneal (3) or mediastinal (2) pathological lymph nodes and one case of bone metastases (1). PET/CT diagnosed unsuspected distant metastases by CT in 4/9 patients (retroperitoneal (1) or mediastinal (2) pathological lymph nodes and 1 case of bone metastasis in the spine). In 1/3 patients with histopathological confirmed diagnosis of peritoneal carcinomatosis by laparoscopic findings was negative by PET/CT, and considered as a false negative case. On the other hand, 3 patients with initially positive peritoneal carcinomatosis by invasive laparoscopy were finally diagnosed as benign lesions. These lesions did not show significant uptake in PET/CT and were considered as true negative cases. Conclusions: 1) PET/CT is useful in the diagnosis of distant metastases in patients with GAC 2) Further studies are needed to establish the role of PET/CT to detect peritoneal carcinomatosis. No significant financial relationships to disclose.
Phase II open-label study of weekly taxoprexin (TXP) as first-line treatment in patients with metastatic cutaneous and mucosal malignant melanoma
Authors: J. Homsi, A. Y. Bedikian, K. B. Kim, N. E. Papadopoulos, W. Hwu, S. L. Mahoney, M. Davies, P. Hwu
Journal: Journal of Clinical Oncology (2008)

9056 Background: Taxoprexin (TXP) is a covalent conjugate of paclitaxel and the fatty acid docosahexanoic acid. Due to its unique pharmacokinetics, it can expose melanoma cells to a high concentration of paclitaxel for a prolonged period. TXP administered every 3 weeks is active against metastatic melanoma. Since paclitaxel has a better response rate and tolerability in weekly administration in other solid tumors, this phase II study investigates the response rate and safety of weekly TXP in metastatic melanoma. Methods: Chemo-naive (Prior immunotherapy or vaccine therapy allowed) patients with metastatic cutaneous or mucosal melanoma were enrolled. Patients with controlled brain metastases were allowed. TXP (500mg/m2 by 1-hour intravenous infusion) was administered weekly for 5 weeks every 6 week cycle until progression. Responses were assessed every 6 weeks using the Response Evaluation Criteria in Solid Tumors (RECIST). Toxicity was assessed weekly. Results: Thirty patients (65% males) were enrolled. Median age was 67 years (range 29–86) and 53% had M1c disease. Median number of cycles was 2 (range 1–6). Twenty-six patients completed at least 1 cycle of chemotherapy and were evaluable for response; 3 discontinued the treatment due to toxicity (neutropenia, neuropathy, myalgia) and one died on the study (pneumonia and cerebrovascular disease). Three patients (12%) had partial response; one lasting for 119 days and two for 169 days. Eleven patients (42%) had stable disease with median duration of 85 days (78–266). Median time to disease progression was 68 days (range 42–274). Median time to treatment failure was 70 days (range 42–274). Median survival has not been reached at the time of this analysis. Eighteen patients are alive, 13 for more than 12 months. Most common grade 3 and 4 toxicities were neutropenia (10%) and musculoskeletal pain (10%). Most common side effects (all grades) were fatigue (73%), skin rash (70%), and diarrhea (60%). Conclusions: Weekly TXP is an active and well tolerated single agent therapy in patients with metastatic melanoma. Its efficacy is comparable to dacarbazine. Further evaluation of TXP in combination with other chemotherapy or targeted agents is warranted. No significant financial relationships to disclose.
Isoelectric Focusing of α-l-Fucosidase From Human Embryonal Carcinoma2
Authors: Lisa D. Laury Kielntop, Jack A. Alhadeff, Ivan Damjanov
Journal: JNCI Journal of the National Cancer Institute (1986)

Isoelectric focusing profiles of α-l-fucosidase recovered from human embryonal carcinoma (EC) and seminoma were compared with those of mouse germ cell tumor-derived stem cells and some human somatic cell neoplasms in an attempt to determine whether EC cells could be used as a source of human basic isoelectric forms of the enzyme previously identified in normal and malignant mouse embryonic cells. α-l-Fucosidase activity in all human tumors was associated with isoelectric forms in the isoelectric point (pi) range between approximately 4.5 and 7, corresponding to the range seen in normal human tissues. The basic isoelectric forms (pi values, 7.5–9.5) that predominate in the embryonic isoelectric focusing pattern in mouse were not found in human neoplasms. The present data illustrate another difference between human and mouse EC and show that mouse EC cells are not a complete replica of equivalent human tumor cells.