tbuckley/cabot-search huggingface dataset:
Resistance to imatinib among patients in chronic phase (CP) of chronic myelogenous leukemia (CML) in clinical practice
Authors: C. Davis, L. Sanders, I. Hirji, S. Oliveria, V. J. Willey, S. Phillips, M. Ulcickas Yood
Journal: Journal of Clinical Oncology (2008)

6595 Background: Imatinib has been shown to induce responses in most CP-CML patients, however resistance is still a concern. Results from IRIS suggest that resistance rates approach 4% per year. We report results from an observational study describing best response and resistance rates in patients with CP-CML within one year following initiation of imatinib 400 mg/day. Methods: Medical and pharmacy claims from HealthCore Integrated Research Database were used to identify patients with CML during 1/1/00–3/31/04. Chart reviews supplemented claims data to confirm and obtain data on CML diagnosis, phase, treatment, testing, test results, and clinical outcomes through 3/31/05. Patients with CP-CML treated with starting imatinib dose of 400 mg/day were identified and followed for one year after initiation of imatinib to determine resistance according to the National Comprehensive Cancer Network (NCCN) CML treatment guidelines. Results: From a total of 216 CML patients included in the overall cohort, 111 CP-CML patients were identified who started on imatinib 400 mg/day and were followed for at least one year. Observed overall best response was complete hematologic response (CHR) in 69.4% (77/111) and cytogenetic response (CyR) in 22.5% (25/111) of patients, of which 84% was major CyR (MCyR). Response could not be determined for 9 patients (8.1%). Observed resistance rate within the first year of imatinib treatment was 11.7% (13/111). Disease progression/loss of response was the reason for resistance in all 13 patients. Imatinib dose was increased in 11/13 (84.6%) of the resistant patients. Cytogenetic testing was performed on 66/111 patients (59.5%) and on 3/13 resistant patients (23.1%), which may account for the low CyR observed rates. Conclusions: Resistance rates in patients treated with 400mg/day of imatinib, not within a clinical trial setting, was greater than expected. For patients able to achieve and maintain a CHR, cytogenetic testing was not common. Cytogenetic testing at time points recommended in NCCN CML treatment guidelines may help physicians validate responses critical to effective patient management. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb
Abstract 19470: Presence of Anemia at Induction of Therapeutic Hypothermia as a Predictor of Neurological Outcome in Cardiac Arrest Survivors
Authors: Nishant Patel, Sanjeev U Nair, Raghu Manandhi, Harsha V Ganga, Justin B Lundbye
Journal: Circulation (2012)

Introduction: Therapeutic hypothermia (TH) has become an accepted practice to improve neurological outcome in survivors of cardiac arrest. Co-morbid factors that may impact neurological outcome in such patients are not well understood. Anemia has been shown to have a prognostic value in a wide variety of diseases. We investigated the effect of hematocrit on neurological outcome in cardiac arrest survivors undergoing TH. Methods: A retrospective analysis was performed on 196 consecutive cardiac arrest survivors who underwent TH with endovascular cooling in the cardiac intensive care unit at a tertiary care center between January 2007 and April 2012. Patients were divided into two groups based on anemia as per their hematocrit (Hct) value at induction of TH (Hct≤36 and Hct&gt;36). The primary endpoint was measured using the Pittsburgh cerebral performance category (CPC) scale and patients were assessed for a good (CPC 1 and 2) or poor (CPC 3-5) neurological outcome prior to discharge from hospital. Results: Of the 196 patients, 130 patients (66 %) had a Hct ≤ 36 and 66 patients (34 %) had a Hct &gt; 36. Forty two (32%) patients with Hct ≤ 36 and 25 patients (38%) with Hct&gt;36 had a good neurologic outcome (P=0.50) (Figure 1) . On multivariable analysis, initial/presenting rhythm (OR: 8.752; 95 % CI 2.60-29.40, P&lt; 0.001) and time to return of spontaneous circulation (OR: 0.942; 95 % CI 0.90-0.99, P=0.02) were independent predictors of neurologic outcome. Conclusion: Presence of anemia at induction of TH is not associated with neurological outcome in cardiac arrest survivors.
Evaluation of number of target lesions to analyze in time to progression by RECIST
Authors: M. Gonen, L. Schwartz, R. Ford
Journal: Journal of Clinical Oncology (2007)

6549 Background: RECIST criteria were designed to evaluated tumor shrinkage and response to therapy by measurement of multiple target lesions, evaluation of non target and new lesions. There is considerable controversy surrounding the optimal number of lesions to assess response, with RECIST requiring the measurement of up to 10 target lesions. These guidelines were set up to evaluate the endpoint of best overall response. Increasingly, time to progression has become an important endpoint in oncology trials. We evaluated the optimal number of lesions to measure to accurately and reproducibly assess time to progression. Methods: We evaluated target lesions metastases in 105 patients enrolled on a Phase III clinical trial. All patients underwent CT at baseline and standard follow up scans until progression. Target lesions were measured unidimensionally and response was assessed according to RECIST by 2 independent Radiologists. A total of 519 target lesions were assessed. Response was calculated according to the rules of target lesions (up to 10) by RECIST, utilizing the 2 largest lesions and randomly selecting 2 target lesions. Results: Using the 2 largest lesions, time to progression was concordant in 83% of cases. The 2 Radiologists determined the two same largest lesions in 89% of cases. Since the determination of the largest or the same target lesions is not always possible or performed, a random selection of 2 target lesions demonstrated a 76% concordance in the time to progression. Conclusions: Measurement of time to progression may have a greater degree of variability than measurement of best overall response and therefore measurement of minimal selected lesions will lead to a great variability in response assessment. No significant financial relationships to disclose.
The men’s cycle plus docetaxel (Doc) in prostate cancer patients with rising PSAs in the non-castrate state
Authors: S. F. Slovin, M. A. Carducci, K. W. Beekman, R. Pili, C. Eicher, W. K. Kelly, M. J. Morris, D. Shaffer, M. Eisenberger, H. I. Scher
Journal: Journal of Clinical Oncology (2005)

4564 Background: Continuous androgen ablation is standard for patients (pts) with rising PSAs following definitive local therapy or untreated metastatic disease. We have shown that androgen ablation followed by intermittent testosterone administration is feasible and can induce successive declines in PSA peaks and troughs (ASCO 2004). This trial tests the hypothesis that Doc given to proliferating cells followed by androgen withdrawal will give a greater response than Doc administered to non-proliferating cells. Methods: Sixty pts with a rising PSA with or without radiographic metastases, and ≤ 6 months of prior hormone exposure were eligible. Pts received six 4-week cycles consisting of monthly Leuprolide and Doc given on Day 1 of week 1 followed by application of topical Androgel for 7 days prior to initiation of the subsequent cycle. The primary endpoint was the proportion of pts at 6 and 18 months after the start of therapy who achieved the following: PSA ≤ 0.05ng/ml following RRP, PSA ≤0.5 ng/ml following RT, or PSA ≤ 2.0 ng/ml for pts with untreated metastatic disease. Results: Of 60 pts accrued, 22 had a rising PSA alone and 38 had radiographic metastases. Of the pts with a rising PSA alone, 4 of 9 (44%) evaluable patients achieved the primary endpoint at 6 months. Of the pts with radiographic metastases, 9 of 24 evaluable pts (38%) have reached the primary endpoint at 6 months. No pts progressed while on treatment and successive declines in PSA peaks and troughs were seen. Toxicities for all evaluable pts included grade 3/ 4 neutropenia in 91% (30 of 33), and grade 3/ 4 hyperglycemia in 18% (6 of 33). One pt was removed from study for grade 3 mental status changes. Conclusions: Rapid hormonal cycling with Doc results in successive declines in PSA peaks and troughs. PSA troughs of ≤0.05 ng/ml following prostatectomy or ≤0.5 ng/ml following radiation can be achieved. This unique approach may facilitate a higher proportion of pts who achieve an undectectable PSA. The increased incidence of neutropenia may be related to decrease clearance of docetaxel in the setting of non-castrate testosterone levels (Baker, SD; ASCO, 2005). PSA outcomes at 18 months and impact on survival are pending. Supported by Aventis, CA-05816 and PepsiCo. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis
A × C Rat Prostate Adenocarcinoma: Initial Characterization of Testosterone Regulation of Hormone Receptors of Cultured Cancer Cells and Derived Tumors&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: S A Shain, R W Boesel, S S Kalter, R L Heberling
Journal: JNCI Journal of the National Cancer Institute (1981)

A × C rat prostate cancer cells were established in continuous culture. The polygonal epithelial cells had granular cytoplasm and well-defined cell margins, contained round to oval nuclei with prominent nucleoli, and were tumorigenic when inoculated into A × C male rats. The tumors produced by the injected prostate cancer cells grew as well-vascularized, solid, cribriform adenocarcinomas. The rat prostate cancer cells and derived tumors contained cytoplasmic and nuclear androgen receptors and prolactin receptors. Androgen regulation of prolactin receptor content and androgen receptor distribution in A × C rat prostate cancer cells were comparable to those of the normal ventral prostate gland. These studies suggest that the A × C rat prostate cancer cells and tumors may represent a unique model for studies of hormonal regulation of prostate cancer cell behavior.
Sphingosomal vincristine in CHOP is a promising new treatment for elderly, as well as poor prognosis patients with aggressive non-Hodgkin's lymphoma (NHL): Follow-up results of a phase II study
Authors: M. A. Rodriguez, N. H. Dang, L. Fayad, A. Goy, F. B. Hagemeister, P. McLaughlin, B. Pro, J. E. Romaguera, A. Younes, F. Cabanillas
Journal: Journal of Clinical Oncology (2004)

8080 Background: Individuals older than 60 years have a worse prognosis than younger patients with aggressive NHL. Vincristine is active in malignant lymphomas. Sphingosomal vincristine (SV) was well tolerated with 45% ORR in multiply relapsed aggressive NHL (ASH Abst. 412, 1999). Based on these data, a phase II study of CHOP with or without rituximab, and substituting SV for free vincristine, was undertaken in patients with previously untreated aggressive NHL. Methods: Patients were treated with standard dose CHOP that included SV 2.0 mg/m2 without dose capping ± rituximab 375 mg/m2, given every 21 days for 6 to 8 courses (ASH abst. 338, 2002). Results: Of 73 patients enrolled on study, 68 were evaluable for response. Median age was 63 (range 22–80), 37 pts (54%) were > 60. Overall, 24 pts (23 elderly) had an IPI score ≥ 3. Patients received a median of 6 study treatments (range 1–8). ORR was 92.6% (63/68 pts) with 55 pts achieving CR (80.1%), 7 CRu (10.3%), and 1 PR (1.5%). 3 pts had PD (4.4%) and 2 were not assessed for response (2.9%). ORR was similar in both elderly (>60) and younger pts (≤ 60): 91.9% and 93.5% respectively. The median PFS and OS have not been reached at a median follow up of 22 months. The probability of being progression free at 17 mos was 0.88 (5 relapses) for elderly pts and 0.86 (4 relapses) for pts ≤ 60. Overall survival probability was 0.98 (1 death) at 22 mos. Neuropathy was generally mild (Gr.1-2). Hematological toxicities were as follows: 56% Gr.3-4 neutropenia, 6% Gr.3 anemia, and 13% Gr.3-4 thrombocytopenia. Toxicites were comparable in both elderly and younger patients. Conclusions: CHOP plus rituximab regimen with sphingosomal vincristine substituted for free vincristine is a well tolerated therapy with only mild neurotoxicity. Remarkably, the activity in the elderly is comparable to that in younger patients. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration INEX
ILX651 administered daily for five days every 3 weeks (qdx5dq3w) in patients (pts) with inoperable locally advanced or metastatic melanoma: Phase II experience
Authors: D. F. McDermott, E. Hersh, J. Weber, J. Stephenson, C. C. Cunningham, S. Ebbinghaus, J. Thompson, S. O’Day, S. Weitman, L. Hammond
Journal: Journal of Clinical Oncology (2005)

7556 Background: ILX65, a synthetic pentapeptide derivative of dolastatin-15, has a unique mechanism of action. At low concentrations ILX651 inhibits microtubule nucleation or elongation which likely disrupts mitotic spindle formation and mitosis. Chemical modification gave ILX651 a potentially enhanced therapeutic window over previous dolastatins. Cardiovascular toxicity characteristic of the dolastatins was not seen in ILX651 phase I studies. Activity in melanoma was observed in the phase I setting, providing the impetus for further evaluation in this pt population. Methods: In this multi-institutional phase II study, ILX651 was administered at 28mg/m2 IV over 30 mins qdx5dq3w. Response rate was the primary endpoint. The study was designed: to assess the feasibility of increasing the dose if <3/10 DLTs occurred in C1 in the first 10 pts; with an early stopping rule in the event of no response in 25 pts. Pharmacokinetic blood draws were performed during C1. Eligibility criteria: ECOG PS 0–1; no prior systemic chemotherapy; no active ocular melanoma; adequate organ function. Results: Preliminary pt demographics (n=65): M/F=43/22; median age 59 (30–83); locally advanced/metastatic=2/63; ECOG 0/1=48/17; treatment naïve/prior biologics/vaccine=37/25/9; number of cycles=224+ (median 2; range 1–12+). At 34mg/m2, 3/10 pts had DLT (neutropenia; ANC). C1 ILX651 in 55 pts at 28mg/m2 was tolerable; G4 ANC occurred in 21 (38%) pts, 1 episode was complicated by fever. Other toxicities include fatigue, nausea, vomiting, and alopecia. One G3 bowel obstruction was possibly drug-related. One pt died on C1d7 cause unknown. To date 5 responses (4PR [1 unconfirmed], 1CR; RECIST) have been observed. At 28mg/m2, preliminary median PFS is 39 (range 7–256) and median overall survival is 271 (range 7–303) days. No drug-related sensory neuropathy, thrombocytopenia, or cardiovascular toxicity was noted. Conclusion: ILX651 is well-tolerated in this melanoma population. Follow-up of response and overall survival continue. Consideration should be given to further study of ILX651 in combination with other agents in the treatment of melanoma. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ilex Products Ilex Products Ilex Products Ilex Products
Recovery of polyclonal immunoglobulin serum levels to normal levels after autologous stem cell transplantation predicts disease free survival in patients with multiple myeloma
Authors: C. Joao, S. Geyer, S. Markovic, M. Gertz, M. Lacy, A. Dispenzieri, S. Kumar, S. Hayman, D. Gastineau, L. Porrata
Journal: Journal of Clinical Oncology (2006)

10088 Background: The ability of the immune system to recover its components after autologous stem cell transplantation (ASCT) is known to predict survival in patients with different types of neoplasms. Also, our previous work showed that polyclonal immunoglobulin can be used to improve T cell diversity and, consequently, T cell function in animal models. The aim of this retrospective study was to understand if the recovery of the polyclonal compartment of immunoglobulin in patients with multiple myeloma (MM) at day 100 (± 40d) after ASCT is a predictor factor for survival in MM patients who were subject to ASCT. Methods: From294 patients with IgG-MM subject to ASCT at the Mayo Clinic, Rochester, MN since October, 1993 until June, 2004, 143 patients were studied. The rational to select this group of patients was the fact that they had levels of serum IgM collected at day 100 ± 40 after ASCT recorded. Progression free survival (PFS) was assessed from the day of the transplant. PFS was studied using Kaplan-Meier curves and the univariate and multivariate analysis were done using age-adjusted proportional Cox. The prognostic variables in the multivariate model were: recovered of IgM at day 100, B2 microglobulin, age, conditioning regimen and disease status at the time of transplant. Results: There were 59 females in the study. The median age of the cohort was 58 y (33–75). The median follow up of the study was 26 mo (range, 2-111). PFS was significantly higher in the group who recovered normal serum levels of IgM at D100 compared to the pts who did not. This corresponds to a survival that is 1.5 longer in the group of patients who recovered normal levels of IgM at day100 after ASCT versus the patients who did not (median: 34 to 23 mo, respectively; p=0.05). By univariate analysis, those who did not recover normal serum levels polyclonal immunoglobulin by day 100 after ASCT had a risk of relapse 65% higher than the risk of the patients who recovered. Multivariate analysis suggests that recover the normal levels of polyclonal immunoglobulin after ASCT is an independent prognostic factor for PFS for MM patients after ASCT. Conclusions: These results suggest that polyclonal immunoglobulin is a major factor promoting immunity after ASCT. No significant financial relationships to disclose.
Inhibition Of JAK-STAT Pathway As a Therapeutic Option For Myelofibrosis Associated Pulmonary Hypertension
Authors: Ali Tabarroki, Daniel Lindner, Valeria Visconte, Li Zhang, Edy Hasrouni, Yvonne Parker, Heesun J. Rogers, Tracy Cinalli, Kristin Dodd, Gina Rupp, Hien Kim Duong, Alan E. Lichtin, Matt Kalaycio, Mikkael A. Sekeres, Anjali S. Advani, Betty K. Hamilton, Sudipto Mukherjee, Yogen Saunthararajah, Stavros E Mountantonakis, Gustavo A Heresi, Ramon V. Tiu
Journal: Blood (2013)
Determination of pelvic node status in patients with high-risk localized or locally advanced prostate cancer by [11c]choline PET-CT.
Authors: K. B. Contractor, A. Challapalli, R. Sharma, L. M. Kenny, L. Maher, M. Winkler, G. Hellawell, A. Al-Nahhas, E. Aboagye, S. Mangar
Journal: Journal of Clinical Oncology (2010)

e13546 Background: The evaluation of pelvic lymph node status has important therapeutic and prognostic significance in prostate cancer. Pelvic lymphadenectomy (PL) is considered the benchmark for staging the pelvis, though it is invasive, associated with morbidity, and is not able to sample all lymph node areas. While nodal status on MRI is based on size criteria (commonly involved nodes >1cm), functional imaging with positron emission tomography-computed tomography (PET-CT) may allow for detecting small volume nodal disease. The primary aim of this observational study is to assess the accuracy of [11C]choline PET-CT (CHO) relative to MRI in detecting pelvic lymph node status, by direct histological comparison of nodes removed at PL. Methods: 25 patients with high risk localized (PSA>20 or GS>8, or T3 disease) or locally advanced (N1) prostate cancer were enrolled. All patients were staged with pelvic MRI before having a dynamic pelvic CHO scan (mean injected radioactivity, 700MBq) and prior to PL. The mean tumor standardized uptake value at 55 min (SUVmean) was derived. The pathological status of lymph nodes removed at PL was used to assess the sensitivity/specificity of CHO relative to pelvic MRI. Results: Complete data was available for analysis in 23 of 25 patients. 8 (31%) were pathologically node positive (total nodes=26). The mean number of nodes removed at PL was 16 (SD ± 8). Pelvic lymph nodes were well visualized with good tumor-background ratio (SUVmean 3.7 x10-5 vs 10.2 m2/ml for primary tumor within the prostate). 75% of all positive nodes were <1cm diameter. While[11C]choline uptake was seen in all 8 patients, direct relationship with node positivity was observed in 7 patients (87.5%). CHO was more sensitive (88% vs. 43%) and specific (100% vs. 93%) than MRI in detecting nodal disease. Conclusions: CHO shows early promise as a noninvasive method of staging pelvic lymph nodes in prostate cancer. Functional imaging with CHO appears superior to MRI, especially in identifying sub-centimetre involved pelvic lymph nodes, and has the potential to assist targeted radiotherapy treatment for locally advanced prostate cancer. No significant financial relationships to disclose.
RET oncogene mutations in a large Korean kindred with familial medullary thyroid carcinoma
Authors: Y. Lee, H. Park, J. Jung, Y. Lim, S. Uchino
Journal: Journal of Clinical Oncology (2007)

6066 Background: Familial medullary thyroid carcinoma (FMTC) is related to germ-line mutations in the RET proto-oncogene. The mutations concern mainly cystein residues in exons 10 and 11, whereas noncystein mutations in exons 13–16 are rare. These mutations have been recorded in the different populations, but to date there is no corresponding study in Korean families. In this study, we identify the RET mutations in the Korean family with FMTC and propose therapeutic approach in managing the disorder. Methods: The large family consists of 4 generations with a total of 32 individuals. There was a history of MTC in five members of the family. The index case was a 67-yr- old woman who underwent total thyroidectomy and both modified radical neck dissection in our hospital at the age of 48. We analysed exons 10, 11, 13, 14, 15 and 16 in index patients using DNA sequencing. Twenty-nine subjects from the family were clinically assessed and subsequently molecularly analysed for the presence of RET gene mutations. Results: We have found a missense TGC?AGC mutation at codon 618 in Exon 10. This transversion leads to the substitution of cystein with serin. The mutation was detected in all five MTC patients as well as in 6 asymptomatic relatives. The mutation shows a wide clinical heterogenecity, as there are carrier patients with age of diagnosis ranging from 9 to 64 years. Conclusions: It is likely that the mutation causes FMTC, because no other mutation was found in RET. This study showed 100% accordance between presence of the disease and gene carrier status is reported. Total preventive thyroidectomy has been recommended in all carriers of RET genetic defects. No significant financial relationships to disclose.
Water Intake and Exchange and Hydration of Rats During Growth of Walker 256 Carcinoma
Authors: Seoras D. Morrison
Journal: JNCI Journal of the National Cancer Institute (1971)

The average fluid water intake of rats increased by 65% during growth of Walker 256 carcinoma. Only about one-third of this increase could be accounted for by increase in identifiable need for water, that is, by increase in water retention of the whole organism, particularly the tumor, and by increase in urinary water obligated to an increase in urinary solutes. There was no increase in water loss by nonurinary routes. The remainder of the increase in water intake represents an increase in turnover of free water and appears as an increased volume of a dilute urine.