tbuckley/cabot-search huggingface dataset:
Rehabilitation assessments of pediatric sarcoma survivors
Authors: P. J. Mansky, L. Gerber, K. Hoffman, E. Augustine, U. Chaudhry, B. Parks, M. Bernad, L. Wiener, S. M. Steinberg, C. Mackall
Journal: Journal of Clinical Oncology (2004)

8528 Background: Improved diagnosis and comprehensive treatment of childhood cancers has increased the overall survival rate. This study assesses physical impairments, functional limitations, health status and behaviors; and vocational and occupational histories of adult survivors of pediatric sarcomas. Methods: Physical impairment assessment: Joint range of motion (ROM); manual muscle testing (MMT); hand grip strength (HGS). Functional limitations: Assessment of motor and process skills (AMPS); 6-minute walk (6MWT); and human activity performance (HAP) questionnaire. Health status and behaviors: Leisure satisfaction measure (LSM); SF-36; sickness impact profile (SIP). Vocational and occupational histories: The Goldberg Scale (GS). Statistics: Standardized measures compared patients with norms. The results were evaluated by Wilcoxon signed rank two-sided p-values, unadjusted for multiple comparisons. Results: 32 survivors were diagnosed at median age 15.4 years (male:female=17:15, Ewing's sarcoma in 24/32). ROM of 22 subjects tested was >40% reduced in 12/13 with lower extremity (LE) lesions. HGS equaled matched norms. 28 /32 performed the 6MWT. 3/4 non-ambulatory subjects were LE amputees. Velocity in 9 was <90% predicted. HAP maximum score/maximum adjusted scores were lower than matched norms (p=0.015 and p=0.043 respectively). Motor and process scores for performance of routine daily tasks were lower than normal matched controls (p<0.0001). SF36 physical competency subscale trended lower (p=0.065), mental competency scores trended higher (p=0.058) than normal, respectively. Overall LSM was higher than the control group (p<0.001). Preliminary GS evaluation suggests higher work satisfaction. Conclusion: Survivors of childhood sarcoma have residual impairment of strength and motion, more likely of the lower extremity. Performance(mobility and daily routines), was reduced. Leisure satisfaction and self-reported mental competency higher than matched normal subjects, despite significant physical limitations, may reflect an augmented sense of well-being. Vocational drive and occupational behaviors were above average compared to people with disabilities. No significant financial relationships to disclose.
Lymphodepletion with high-dose interleukin-2 (IL-2) and granulocyte macrophage-colony stimulating factor (GM-CSF) in metastatic melanoma patients: An interim analysis
Authors: S. L. Ketchum, B. Cole, K. Margolin, D. McDermott, T. Crocenzi, J. Roberts, N. Crosby, K. Meehan, J. Fisher, M. S. Ernstoff
Journal: Journal of Clinical Oncology (2006)

8034 Background: Lymphocyte depletion followed by homeostatic recovery has been shown to break tumor-specific tolerance. We have initiated a clinical trial of chemotherapy-induced lymphodepletion followed by high-dose (HD) IL-2 + GM-CSF in metastatic melanoma (MM) patients (pts). Methods: Pts with PS 0–1, normal organ function and with measurable MM were treated with intravenous cyclophosphamide 60 mg/kg (day 1–2), fludarabine 25 mg/m 2 (day 3–7) followed by two 5-day (d) courses of intravenous HD bolus IL-2 600,000 IU/kg (d 8–12 and 21–25) and daily subcutaneous administration of GM-CSF 250 mcg/m2 (d 8 until granulocyte recovery). Results: 8 pts are presently evaluable in this first stage of accrual to confirm safety and immunomodulation. A mean of 25/28 IL-2 doses were delivered. All pts experienced transient myelosuppression with ANC &lt; 500 cells/mm3 for a median of 7d (range 5–11d) and platelets &lt;50,000/mm3 for a median of 5.5 days (range 0–7d). Pts exhibited reversible capillary leak associated with high-dose IL-2. With the exception of myelosuppression, no grade 4 toxicities occurred. All pts experienced neutropenic fever and 2 developed line infections. CD4+/CD25high/CD62L+ T cells rebounded by d 14, peaked around d 28 and returned to baseline by d 85. CD8+/CD28- T cells recovered to levels lower than baseline for the first 28d but then showed persistent elevation through d 113. Skewing of T-cell populations based on TCR Î² chain expression was observed. One pt achieved complete response, 2 achieved partial responses, and 5 progressed. Conclusions: Lymphodepletion followed by high-dose IL-2 can be safely administered, affects immune reconstitution, and has activity in MM that may be useful as a platform for enhancing immunotherapeutic strategies. The trial continues to accrue in order to better estimate antitumor activity and immunomodulation. No significant financial relationships to disclose.
The Success Story of Targeted Therapy In Chronic Myeloid Leukemia: A Population-Based Study of 3,173 Patients Diagnosed In Sweden 1973–2008
Authors: Magnus Bjorkholm, Lotta Ohm, Sandra Eloranta, Åsa Rangert Derolf, Malin Hultcrantz, Jan Sjöberg, Therese Andersson, Martin Hoglund, Johan Richter, Ola Landgren, Sigurdur Y. Kristinsson, Paul W. Dickman
Journal: Blood (2010)
A randomized phase II study of gemcitabine plus S-1 versus gemcitabine alone in patients with unresectable pancreatic cancer.
Authors: Y. Omuro, T. Ikari, H. Ishii, M. Ozaka, M. Suyama, Y. Matsumura, T. Itoi, N. Egawa, S. Yano, K. Hanada, Y. Kimura, T. Ukita, Y. Ishida, M. Tani, S. Ohoka, Y. Hirose, S. Hijioka, R. Watanabe, T. Ikeda, T. Nakajima
Journal: Journal of Clinical Oncology (2011)

4029 Background: Combination chemotherapy with gemcitabine (GEM) and S-1 has been reported to be promising treatment for advanced pancreatic cancer. In order to evaluate its efficacy and safety, we conducted a multicenter randomized phase II study in patients (pts) with unresectable pancreatic cancer, comparing the combination of GEM and S-1 (GS) with GEM alone (G). Methods: Eligible pts had histologically or cytologically confirmed locally advanced or metastatic pancreatic adenocarcinoma with measurable lesion. Other main inclusion criteria were an age between 20 and 80 years, no prior anticancer treatment, well preserved function of major organs and Eastern Cooperative Oncology Group (ECOG) PS of 0-2. Pts were randomly assigned to receive either GS or G. GS regimen consists of intravenous GEM 1,000 mg/m2 over 30 minutes on days 1 and 8, combined with oral S-1 80 mg/m2 twice daily on days 1-14, repeated every 3 weeks. On the other hand, G includes intravenous GEM 1,000 mg/m2on days 1, 8 and 15, repeated every 4 weeks. These therapies were continued until disease progression. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR; complete response, partial response, and stable disease), progression-free survival (PFS), overall survival (OS), and safety. Results: Between Jun. 2007 and Aug. 2010, 117 pts from 16 institutions were registered. Patient characteristics in GS and G were: median age; 64.1 and 62.4 years, PS 0; 83% and 77%, locally advanced; 23% and 24%, respectively. ORR of GS was 22.6%, whereas that of G was 3.4%. This difference was statistically significant (p = 0.0029). DCR was 60.4% in GS and 44.1% in G. Median PFS was 8.0 months in GS and 4.9 month in G. This was also statistically significant (p=0.02). Moreover, median OS of GS was significantly likely to be longer than that of G (13.0 months vs. 7.9 months; p = 0.04). The major grade 3-4 adverse events were neutropenia (24.5% in GS and 5.1% in G), thrombocytopenia (13.2% in GS and 5.1% in G), and skin rash (9.4% in GS). Conclusions: Our study showed the possibility that GS could be a first line therapy for unresectable pancreatic cancer. Larger randomized phase III study is warranted.
Response to phosphoinositol-3-kinase inhibition in ER-positive breast cancer cell lines after acquired resistance to estrogen deprivation.
Authors: C. Sanchez, C. Phommaly, R. Crowder, M. J. Ellis
Journal: Journal of Clinical Oncology (2010)

e13646 Background: We have recently shown that acquired resistance to aromatase inhibitors can, in some instances, be reversed by the therapeutic use of lower dose estradiol suggesting a cyclical approach to endocrine treatment for advanced disease (Ellis, M. JAMA 302:774, 2009). We have also demonstrated that simultaneous inhibition of phosphoinositol-3-kinase (PI3K) and ER activates cell death through apoptosis, which is reversed by the addition of estradiol, revealing a tight link between sensitivity to endocrine therapy and to PI3 kinase inhibition (synthetic lethality) (Crowder, R. Cancer Res 69:3955, 2009). Consistent with this concept we have shown that long term estrogen deprived (LTED) cells are coresistant to both classes of agent. We therefore studied whether re-exposing an LTED cell line to estradiol could restore sensitivity to PI3 kinase inhibition. Methods: ER+ MCF7 cells were cultured in phenol-red free media containing charcoal-stripped serum without supplemental estradiol for 12 months to create variants that proliferated in an estradiol independent manner (LTED). LTED cells were then exposed to estradiol for 4 months. After a period of pronounced cytotoxicity, consistent with the therapeutic effects of estradiol, the LTED cells recovered (LTED-R). The LTED-R cells were treated with a panel of clinical PI3K inhibitors plus or minus estradiol withdrawal. We measured the apoptotic response by TUNEL flow cytometry. Results: LTED-R cells acutely deprived of estradiol are re-sensitized to PI3K inhibition induced apoptosis. The level of synthetic lethality in LTED-R cells was similar to that achieved with parental MCF7 cells. Conclusions: This experimental model suggests that the efficacy of the cyclical approach to endocrine therapy with aromatase inhibitor-induced estrogen deprivation followed by estradiol therapy may in increased by adding a PI3 kinase inhibitor every time there is a switch back to estrogen deprivation in order to enhance tumor regression. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis
Human Colon Adenocarcinoma Cells. III. In Vitro Organoid Expression and Carcinoembryonic Antigen Kinetics in Hollow Fiber Culture&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: L P Rutzky, J T Tomita, M A Calenoff, B D Kahan
Journal: JNCI Journal of the National Cancer Institute (1979)

Cell line LS174T was established in our laboratory from a primary human colon adenocarcinoma and was serially cultured for 4 years. Following 1 month of culture in perfused hollow fiber matrices, organoid growth reminiscent of the patient's original tumor was observed. The cellular organization was predominantly glandular with mucin located within gland lumina and cells. Glands had irregular brush borders, well-developed junctional complexes, and intracytoplasmic lumina lined with microvilli, features found in adenocarcinoma tissue. Alternate-day determinations of carcinoembryonic antigen (CEA) revealed biphasic kinetics in the extracapillary fluids of the hollow fiber system but not in identically treated monolayer cultures. The initial rate of CEA release was similar to that of monolayer cultures. A significantly accelerated secondary CEA release phase was observed in 10,000- and 50,000-molecular weight (MW)-exclusion fiber cultures (P less than or equal to 0.001 and P = 0.05, respectively). Totals of 43.8 micrograms and 112.6 micrograms CEA were released into the extracapillary fluids of 10,000- and 50,000-MW-exclusion fiber cultures, respectively, which were onefold and 2.3-fold increases, respectively, over monolayer supernatant yields. Most CEA was released during the final days of the secondary phase. In monolayer cultures, maximum CEA release occurred during the stationary phase of growth.
A prospective comparison of Karnofsky (KPS) with ECOG performance status in patients with non-small cell lung cancer (NSCLC): A COMET group study investigating sensitivity and specificity issues important in clinical decision making
Authors: P. J. Hollen, R. J. Gralla, J. A. Stewart, C. Chin, G. A. Bizette, N. B. Leighl, P. G. Kuruvilla, J. M. Meharchand, H. Solow
Journal: Journal of Clinical Oncology (2005)

8134 Background: Performance status (PS) continues to be among the most accurate predictors of survival in all patients with lung cancer. Prior studies confirmed that both ECOG and KPS methods are useful and correlate fairly well with each other. However, new findings and practice patterns have necessitated investigation to determine if differences relevant to clinical decision making exist between the two methods. Two key factors have emerged: 1) suitability for chemotherapy is often based on PS (0 - 1 ECOG or 80 - 100 KPS), and 2) recent trials correlating single nucleotide polymorphisms (SNPs) with chemotherapy resistance and survival have found PS to be an important determinant for specific mutations. Methods: 75 patients with advanced NSCLC were prospectively evaluated at 9 COMET sites in Ontario. Both the ECOG and KPS methods, as well as the LCSS-QL (a validated QL instrument) were given prior to receiving initial docetaxel + platinum chemotherapy. Eligibility: PS 0 - 2 ECOG and KPS ≥ 60, Stage III-IV. Descriptive methods and linear regression were used to explore sensitivity and specificity. Results: Median age = 68 (range 46 - 81); men = 55%; median ECOG PS = 1 (11% - 0, 61% - 1, 28% - 2); median KPS = 80 (5% - 100, 28% - 90, 47% - 80, 12% - 70, 8% - 60). Correlation of the two PS methods was fairly high at 0.75 (Pearson r). While this was a positive result, of concern was the finding that the 21 patients with ECOG PS = 2 were as likely to be rated as having a KPS of 60 or 70 or 80, indicating a broad range of activity encompassed by the ECOG 2 category. In contrast, of those with KPS < 80, only 2 patients (3%) had ECOG PS ≤ 1. Sensitivity/specificity results for KPS are 0.86/0.87; for ECOG are 0.96/0.62. Conclusions: Both methods have a high degree of sensitivity; however, the greater specificity of the KPS indicates that it is a better choice 1) for decision making for suitability for chemotherapy (fewer inappropriate patients treated), and 2) for more accurately identifying which patients would benefit from having genomic studies performed to help determine individualized chemotherapy selection. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis Aventis Aventis Aventis Aventis
Phase I and Pharmacokinetic Study of the Camptothecin Analog DX-8951f Administered as a 30-Minute Infusion Every 3 Weeks in Patients With Advanced Cancer
Authors: Valérie Boige, Eric Raymond, Sandrine Faivre, Michel Gatineau, Kathleen Meely, S. Mekhaldi, Patricia Pautier, Michel Ducreux, Olivier Rixe, Jean-Pierre Armand
Journal: Journal of Clinical Oncology (2000)

PURPOSE: DX-8951f is a totally synthetic derivative of camptothecin with greater cytotoxicity and more potent topoisomerase I inhibition than SN-38, topotecan, and camptothecin in preclinical studies. This phase I study aimed to describe the toxicity and to determine the maximum-tolerated dose (MTD) and pharmacokinetics of DX-8951f given as a 30-minute intravenous infusion every 3 weeks. PATIENTS AND METHODS: Twelve patients with refractory solid malignancies were treated with DX-8951f at dose levels ranging from 4 to 7.1 mg/m 2 . All but one patient had received previous chemotherapy, and eight patients were considered heavily pretreated. Total DX-8951f plasma concentrations were assayed using high-performance liquid chromatography. RESULTS: Thirty-six cycles of DX-8951f were administered. Neutropenia was the dose-limiting toxicity, and it was dose-related, reversible, and noncumulative. Other toxicities included nausea and vomiting, alopecia, asthenia, fever, and anemia. Grade 1 or 2 diarrhea was observed in seven patients but was transient and resolved without requiring treatment. Pharmacokinetic analysis showed that DX-8951f had a half-life of 7.15 hours and a clearance rate of 1.65 L/h·m 2 . The DX-8951f area under the plasma-concentration curve increased linearly with the dose. We defined the MTD of DX-8951f administered as a 30-minute intravenous infusion every 3 weeks as 7.1 mg/m 2 . CONCLUSION: The dose-limiting toxicity of DX-8951f is neutropenia. The recommended dose for phase II studies is 5.33 mg/m 2 every 3 weeks in patients previously treated with chemotherapy.
Physician-Patient Relationship: Intervention Opportunities for Multiple Myeloma patients' Needs
Authors: Maria Felicia Pelagalli, Francesca Romana Dolcetti, Tommaso Caravita, Maria Cantonetti, Chiara Nozzoli, Mario Boccadoro, Luca Baldini, Felicetto Ferrara, Alessandro Corso, Rita Rizzi, Maria Teresa Petrucci
Journal: Blood (2010)
A randomized phase II study of carboplatin (C) and etoposide (E) with or without pan-BCL-2 antagonist obatoclax (Ob) in extensive-stage small cell lung cancer (ES-SCLC).
Authors: C. J. Langer, I. Albert, P. Kovacs, L. J. Blakely, G. Pajkos, P. Petrov, A. Somfay, A. Szczesna, P. Zatloukal, A. Kazarnowicz, M. M. Moezi, M. T. Schreeder, J. Schnyder, M. S. Berger
Journal: Journal of Clinical Oncology (2011)

7001 Background: Ob is a pan-BCL-2 antagonist that is synergistic in vitro with cisplatin and E. A phase I study concluded that a 3-hr Ob infusion in combination with C and E was favored over a 24-hr infusion (ASCO 2010, Ab e13531). Methods: Patients (pts) with chemotherapy-naive ES-SCLC, measurable disease, and PS 0-2 were randomized to receive six 21-day cycles of CE (C AUC 5 D1, and E 100 mg/m2 D1-3) or CEOb (CE plus Ob [30 mg as a 3-hr infusion D1-3]). 73 evaluable pts were planned for each arm. 1° endpoint was ORR (confirmed CR & PR); 2° endpoints included PFS and OS. After completing 6 cycles, responders received prophylactic cranial irradiation; pts on CEOb continued Ob as maintenance therapy. Results: 165 pts were randomized; 155 pts (77 CEOb; 78 CE) received treatment. The arms were well balanced for gender, PS, and metastatic sites; 21% in each arm had brain mets. CNS adverse events (AEs) (such as somnolence [46% all grades] and euphoric mood [31% all grades]) occurred during and shortly after the Ob infusion. The only Grade 3/4 non-heme AE with ≥ 5% increase in absolute frequency in the Ob arm was somnolence (8 vs 0%). Grade 3/4 febrile neutropenia was rare (5% both arms). Grade 3/4 hematologic lab data were similar for each arm (CEOb vs CE): anemia (8 vs 15%), neutropenia (61 vs 58%), and thrombocytopenia (17 vs 10%). 74% of the pts on the CEOb arm alive without progression after 6 cycles started maintenance therapy. Efficacy data, including death or progression during initial 6 cycles of chemotherapy (refractory rate) are summarized in the table below. Conclusions: The CEOb arm demonstrated a trend for improved ORR, PFS, 12 mo and overall survival (OS). Most importantly, consistent with its in vitro synergy, Ob markedly decreased the rate of refractoriness to the initial 6 cycles of chemotherapy by 36.5%. Pts with screening PS of 2 did poorly in either arm; OS in PS 0-1 pts will be evaluated in a phase III trial comparing CE to CEOb. Study arm ORR PFS 12-month survival OS OS (PS 0-1) Refractory rate (PS 0-1) CEOb 64.9% 6.0 mos* 45.5% 10.6 mos* 11.9 mos* 25.4% CE 53.8% 5.4 mos* 37.2% 9.9 mos* 10.1 mos* 40.0% One-sided p value 0.11 0.08 0.19 0.0506 0.052 0.05 Hazard ratio - 0.79 - 0.72 0.71 - * Median
Mammography use in women age 80 and older with breast cancer
Authors: S. H. Giordano, B. Badgwell, Z. Duan, I. Bedrosian, G. Hortobagyi, G. Babiera
Journal: Journal of Clinical Oncology (2007)

9039 Background: The guidelines for screening mammography use in patients age 80 years and older are not clear. The purpose of this study was to determine the effect of mammography use on stage and tumor size at breast cancer diagnosis. Methods: The study is a retrospective cohort using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. We evaluated 14,976 women aged 80 and older diagnosed with breast cancer between 1996–2002. Patients were divided into three cohorts based on screening mammography use in the 60 months prior to diagnosis: nonusers, non-regular users (1–2 mammograms), and regular users (3+). The effects of screening on tumor stage (0-I vs. II-IV) and size were determined by logistic regression and multivariate analysis of variance. Results: Regular mammography use for the age groups 80–84, 85–89, and &gt;= 90 was 29%, 19%, and 9%, respectively. Among regular users of mammography, 26% presented with stage II or greater cancer while 64% of non-users presented with stage II or greater disease. On multivariate analysis, non-users were 4.7 (95% CI 4.26–5.14) times more likely to present with high-stage cancer. Non-users, non-regular users, and regular users had an adjusted mean tumor size of 5.08 (4.44–5.72), 3.26 (2.57–3.95), and 2.77 (2.02–3.51), respectively. Conclusions: Regular screening mammography among women aged 80 years and older is associated with earlier stage at presentation and smaller tumor size compared to mammography nonusers. Health care providers should consider discussing potential benefits of screening mammography with their older patients particularly for those without significant comorbidity. No significant financial relationships to disclose.
The role of HER2/neu, estrogen, and progesterone receptor status in the risk and survival of breast cancer leptomeningeal metastasis
Authors: J. Grewal, M. D. Groves, B. N. Bekele, W. A. Yung
Journal: Journal of Clinical Oncology (2007)

11512 Background: Leptomeningeal metastasis (LM) is a dreaded complication of breast cancer with a median survival of approximately 4 months from the time of LM diagnosis. HER2/neu (HER2), estrogen (ER), and progesterone (PR) receptor status are routinely used to determine prognosis and guide treatment. There is emerging data regarding the influence of these receptors on the risk and prognosis of parenchymal brain metastasis. However, the role of these receptors in LM is unknown. We performed a retrospective analysis of 61 patients with breast cancer to determine the risk and survival of LM as a function of receptor status. Methods: Of patients with breast cancer evaluated in our department for possible LM between 2003 and 2006, those requiring CSF analysis were included in this study. Of these 61 patients, 27 were diagnosed with LM and 34 were found to be negative for LM, based on analysis of CSF and MRI. Information regarding HER2 receptor status was unavailable in 3 patients (1 with LM) due to technical issues with the assay. ER, PR, and survival data were available for all patients. Odds ratio of developing LM was calculated based on each receptor status. The Fisher exact test was used to determine significance. For the 27 patients with LM, receptor status was used to stratify survival from the time of LM diagnosis using Kaplan-Meyer analysis; significance was evaluated using the log-rank test. Results: The odds ratios of developing LM in patients with positive HER2, ER, and PR were 1.89, 0.32, and 0. 825, respectively. P values were 0.378, 0.056, and 0.799. In the 27 patients with LM, survival from the time of LM diagnosis was not significantly different when stratified by receptor status; p values were 0.983, 0.317, and 0.625 respectively. Conclusions: Our retrospective analysis suggests that HER2/neu-positive and ER-negative breast cancer may be associated with a higher risk of LM, although this approached statistical significance only for ER. For patients with confirmed LM, there were no significant differences in survival based on receptor status, although there was a trend favoring ER-positive disease. Larger studies are needed to clarify the role of these receptors in the risk and prognosis of breast cancer LM. No significant financial relationships to disclose.