tbuckley/cabot-search huggingface dataset:
Final results on phase II study of a weekly schedule of ixabepilone in patients with metastatic castrate-refractory prostate cancer (E3803): A trial of the Eastern Cooperative Oncology Group.
Authors: G. Liu, Y. Chen, R. S. DiPaola, M. A. Carducci, G. Wilding
Journal: Journal of Clinical Oncology (2011)

4529 Background: BMS-247550 (ixabepilone) is an epothilone B analogue with activity in taxane-resistent cancer cell lines. Here we report the activity and toxicity of ixabepilone, administered using a weekly schedule, in men with metastatic castrate-resistant prostate cancer (CRPC). Methods: Patients with metastatic CRPC were treated with ixabepilone at 20 mg/m2 IV weekly x 3, in 4 week cycles. This noncomparative study stratified patients to either a chemonaive (CN), prior-taxane (Tax) only, or two prior cytotoxic (TCx) chemotherapy arm. The trial was designed with 91% power to detect a PSA response of 50% vs 25% for the CN stratum and 90% power to detect a PSA response of 30% vs 10% for the Tax and TCx strata. Results: In total, 124 pts were enrolled of which 111 were eligible (35 CN, 42 Tax, and 34 TCx) for the primary response determination in this study. PSA responses were seen in 12 (34.3%), 12 (28.6%), and 8 (23.5%) pts with the partial objective response in 5/22 pts (22.7%), 2/25 pts (8.0%), and 0/25 (0.0%) for the CN, Tax, and TCx arms respectively. Significant (grade 3/4) neutropenia was seen in 6 (15.4%), 7 (14.6%), and 9 (25.0%), and grade 3/4 sensory neuropathy in 8 (20.5%), 13 (27.1%), and 11 (30.6%) for CN, Tax, and TCx respectively. Grade 3/4 thrombocytopenia was infrequent and seen in only one pt on the TCx arm. Conclusions: Ixabepilone was found to have an acceptable toxicity profile when administered using a weekly schedule with less myelosuppression compared with prior studies using the q3wk schedule. Single agent activity was observed and met prespecified activity levels for the Tax and TCx arm.
Risk factors for postoperative complications of a randomized clinical trial: Laparoscopic versus open surgery with D3 lymphadenectomy for stage II/III colon cancer (JCOG0404).
Authors: Yusuke Nishizawa, Masaaki Ito, Norio Saito, Hiroshi Katayama, Junki Mizusawa, Takashi Yamaguchi, Tadahiko Masaki, Yosuke Fukunaga, Kohei Murata, Tomonori Akagi, Masafumi Inomata, Seigo Kitano
Journal: Journal of Clinical Oncology (2015)

717 Background: A randomized controlled trial to confirm the non-inferiority of laparoscopic surgery to open surgery for clinical stage II/III colon cancers in terms of overall survival was conducted. In this ancillary study, we explored the risk factors for postoperative complications of laparoscopic surgery and open surgery. Methods: Eligibility criteria included colon cancer; tumor located in the cecum, ascending, sigmoid, or rectosigmoid colon; T3 or T4 without involvement of other organs; N0-2; and M0. Postoperative complications which were observed from the end of the operation to discharge were graded according to the CTCAE 3.0. Multivariate analysis was performed using logistic regression model. Results: Between October 2004 and March 2009, a total of 1,057 patients from 30 Japanese centers were registered. By per-protocol set, 524 patients underwent open surgery (OPEN) and 533 patients underwent laparoscopic surgery (LAP). Proportion of any grade (G) complication was 18.3% (OPEN 22.3%, LAP 14.3%), G2–G3 was 12.9% (OPEN 13.9%, LAP 11.8%), G3 was 5.3% (OPEN 6.9%, LAP 3.8%) and G4 was none. Postoperative complications (G2-G3) included leakage (OPEN 2.1%, LAP 1.9%), ileus (OPEN:1.5%, LAP:0.9%), and wound complication (OPEN: 0.2%, LAP: none). Multivariate analysis revealed that risk factors for postoperative complications were operation times 240 min or more (p=0.0019, odds ratio [OR] 2.01 [95% CI: 1.30-3.13]) and open surgery (p=0.0001, OR 2.05 [95% CI: 1.41-2.98]). Conclusions: Operation times more than 240 min and open surgery were considered to be the risk factors for postoperative complications for clinical stage II/III colon cancers. Clinical trial information: C000000105.
Prominin-1/CD133 Is Involved in the Lineage Decision As Well As a in the Sensitivity to Molecular Therapy in Ph+ Acute Lymphatic Leukemia.
Authors: Anna T. Metodieva, Heike Pfeifer, Afsar Mian, Anja Vogel, Hubert Serve, Oliver G. Ottmann, Martin Ruthardt
Journal: Blood (2012)
Personalized medicine as a model of care to improve patient outcomes, communication, and reduce cost.
Authors: Sherri Z. Millis, John M Davis, Stephanie Marie Ratliff, Melissa Lorraine Ray, Wendy M Schroeder, Tim Townsend, Janine R LoBello, Michael J. Demeure, Edgar Donald Staren
Journal: Journal of Clinical Oncology (2016)

e270 Background: Cancer treatment based on an individual’s tumor profiling has been associated with increased time to progression. Despite this, adoption has been impeded by various technical, financial, legislative, and ethical issues. Implementation of a personalized medicine program into a healthcare system with a goal of improving patient outcomes includes clinician and patient education, increased tumor profiling of patients, data sharing/analysis, expanded research, and billing/reimbursement practices. Methods: A personalized medicine program was implemented at a hospital system. Measures of physician practice included attendance at genomic medicine education sessions, utilization of genetic/genomic tests, enrollment of patients into clinical trials, modifications in billing practices, and submission of data for analysis. Reimbursement of off-label pharmaceutical agents as well as use of aggregate data to inform treatment and enrollment in biomarker-based clinical trials was recorded. Frequency of genetic and/or genomic tests relative to physician and patient education and access to research opportunities was also assessed. Early patient outcomes, overall costs of care, access to clinical trials, and changes in knowledge and communication are also being monitored. Results: Although analysis is ongoing, the initial assessment indicates an increased utilization of genetic and genomic tests, clarity in billing practices, improved reimbursement for off label therapies, and consumption of educational opportunities from clinicians to patients/caregivers. Analysis of the first year implementation will be reported, including evaluation of preliminary results relative to quality of life and survivorship. Conclusions: Preliminary analysis of data from implementation of a personalized medicine program indicates that utilizing relevant education, research, aggressive billing and reimbursement processes, and IT infrastructure, can provide patients with the individual therapies which reduce cost and improve survivorship.
Survival analysis of patients with/without lymph node examination after lung cancer resection.
Authors: R. U. Osarogiagbon, R. A. Ramirez, C. Wang, L. E. Miller, M. Ul-Haq, A. Farooq, J. W. Allen, D. Spencer, A. Berry, A. B. Weir, H. Cole, T. O'Brien
Journal: Journal of Clinical Oncology (2011)

7054 Background: Lymph node (LN) stage is the major prognostic factor in resectable lung cancer. Yet 16-18% of U.S. lung cancer resections have no examined LN (pNx). These patients are usually treated as though they were node negative, potentially misstating their true stage, prognosis, and benefit from adjuvant therapy. We compared the survival of patients in a Memphis cohort who had pNx to those without metastatic LN after examination of at least 1 LN (pN0). Methods: Retrospective review of all surgical resections in Memphis, TN, from 2004 to 2009, excluding patients with pre-operative therapy. Standard statistical methods were used for group comparisons. Results: Of 872 eligible patients, 12% were pNx. Group characteristics are compared in the table. Only 15% of the pN0 group had more than 10 LN examined. 5-year survival rates (pN0 v pNx) were: 56% v 41% (whole group); 64% v 47% (T1); 53% v 0% (T2); (p<0.05 for all comparisons). In multivariate analysis adjusting for type of resection, histology, and T category, pNx had a hazard ratio for death of 1.6 (confidence interval 1.1-2.3, p<0.02). Conclusions: After lung cancer resection, patients without LN examination have inferior long-term survival. A significant proportion probably have undiagnosed LN metastasis, because the surgeon did not remove involved hilar/mediastinal LN or the pathologist did not examine hilar/intrapulmonary nodes. Improvements in surgical LN harvesting and pathology examination practice are needed to eliminate this problem. Variable, N (%) pN0, N=771 pNx, N=101 P value Age, median (range) 68 (19-89) 70 (37-86) >0.05 Sex Female 332 (43) 51 (51) 0.16 Male 439 (57) 50 (50) Race Black 185 (24) 20 (20) 0.47 White 580 (75) 80 (79) Other 6 (1) 1 (1) Type of resection Pneumonectomy 51 (7) 0 (0) <0.0001 Lobe/bilobectomy 663 (86) 42 (42) Sublobar 57 (7) 59 (59) Histology Adeno 356 (46) 50 (50) 0.38 Squamous 332 (43) 36 (36) Other 83 (11) 14 (14) T Category 1 370 (48) 70 (69) 0.0007 2 278 (36) 21 (21) 3 96 (12) 7 (7) 4 25 (3) 2 (2) Median (range) tumor size, cm 2.5 (0.2-21) 2.0 (0.6-8) <0.0001 # LN examined, median (range) N1 3 (0-38) N2 2 (0-29) total 5 (1-45) Hazard ratio for death (CI) T1 1.0 1.7 (1.1, 2.5) 0.01 T2 2.0 (1.0, 3.8) 0.04 30-day mortality, % 4 4 0.99
Rates of CNS progression in patients with advanced NSCLC harboring somatic EGFR mutations and treated with gefitinib or erlotinib.
Authors: S. Heon, B. Y. Yeap, G. J. Britt, M. S. Rabin, D. M. Jackman, B. E. Johnson
Journal: Journal of Clinical Oncology (2010)

7543 Background: Gefitinib and erlotinib can penetrate into the CNS and elicit intracranial responses. However, there is incomplete data about their impact on the development and control of CNS metastases. The experience at DFCI was reviewed to determine the risk of CNS progression in patients with somatic EGFR mutations and advanced NSCLC treated initially with gefitinib or erlotinib. Methods: We identified patients with stage IIIB or IV NSCLC with somatic EGFR mutations treated with gefitinib or erlotinib as their initial therapy for advanced NSCLC between 1/01 and 2/09. The cumulative risk of brain relapse was calculated using death as a competing risk. Results: Of the 100 eligible patients, 19 had brain metastases (BM) at the time of diagnosis of advanced NSCLC; 17 of them received CNS therapy before initiating gefitinib or erlotinib. To date, 83 patients have progressed after a median potential follow-up of 41.3 months. The median progression-free survival for the entire cohort was 13.2 months. 28 patients developed CNS progression, 8 of whom had a history of previously treated BM. Carcinomatous meningitis occurred in 8 patients; 4 of them had synchronous BM. The brain was the initial site of relapse in 10 patients, and the sole site of initial failure in 5 of these. The 1- and 2-year actuarial rates of CNS progression were 7% and 19%, respectively. The risk of brain relapse was lower in those 81 patients without initial CNS involvement compared with 19 patients with pre-existing brain disease (6% vs 11% at 1 yr, 13% vs 49% at 2 yrs). The median overall survival from EGFR TKI initiation was 33.6 months (95% CI, 25.3-40.3 months). No difference in survival was noted between patients with and without CNS progression (30.3 vs 39.1 months, p = 0.49). Conclusions: Patients with somatic EGFR mutations initially treated with gefitinib or erlotinib for advanced NSCLC appear to have a lower risk of CNS progression compared with published 2-year rates of brain relapse of 20% to 40% in unselected historical controls receiving chemotherapy. Distinguishing between biological differences and therapeutic effect on brain failure patterns will be important to further guide first-line therapy in the post IPASS trial era. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Boehringer Ingelheim, Genentech, GlaxoSmithKline, KEW Group Diagnostics, Millennium, Pfizer Celgene Roche Genzyme
Prolonged Use of Lenalidomide (≥12 Cycles) for Multiple Myeloma (MM) Is Frequently Affected by Dose-Limiting Thrombocytopenia but Is Associated with Improved Quality of Response and Survival.
Authors: Elizabeth Yeboah, Esther Masih-Khan, Christine Massey, Donna E. Reece, Suzanne Trudel, Vishal Kukreti, Peter Anglin, Christine Chen
Journal: Blood (2009)
Improving quality and safety of oncology patient care: Standardization of the post-clinic message triage process.
Authors: Caitlin C. Donohue, Marina Kaymakcalan, Aymen Elfiky, Carole Kathleen Dalby, Julie M. Bryar, Joseph O. Jacobson
Journal: Journal of Clinical Oncology (2013)

163 Background: Due to the rapidly increasing complexity of the treatment and management landscape of genitourinary oncology patients,the high volume of patient calls within our practice has raised safety concerns among providers about follow-through on issues and coordination of care. Survey data revealed that more than 20% of providers and staff (n=19) were unsatisfied with the existing message triage process and indicated that it was not the most efficient and timely way to respond to clinical messages. Patient survey data (n=94) and analysis of messages showed 80% of messages were related to direct patient care issues. The aim of this project was to analyze and streamline the message triage process with the goal of creating a standardized approach to respond to clinical messages in a timely and efficient manner. Methods: A multidisciplinary team constructed a process map, administered surveys, conducted cause-and-effect analyses, orchestrated brainstorming sessions, and used a priority/pay-off matrix to devise and implement an intervention using a standardized message template. Results: Baseline data showed that 18% of emails contained the necessary components to provide direction on who held responsibility for answering a message. Three Plan-Do-Study-Act (PDSA) cycles were conducted: (1) Education provided to administrative staff; (2) Implementation of email template; and (3) Subsequent modification in response to PDSA 2. After 3 weeks, 85% of emails contained the necessary components. Compared to a baseline of 79%, 96% of providers and staff prefer the new process. Conclusions: The interventions implemented using three sequential PDSA cycles resulted in an improved process for triaging clinical calls in conjunction with enhancing provider satisfaction. Additional steps are planned to further standardize the email notification template. [Table: see text]
Impact of Prior Second-Generation Tyrosine Kinase Inhibitors on the Outcome of Hematopoietic Stem Cell Transplantation for Chronic Myeloid Leukemia
Authors: Deau Benedicte, Bachy Emmanuel, Raus Nicole, Nicolini Franck-emmanuel, Rea Delphine, Reman Oumedaly, Maillard Natacha, Shanti Ame, Fegueux Nathalie, Coiteux Valerie, Gardembas Martine, Charbonnier Aude, Huyn Anne, Cahn Jean Yves, Buzyn Agnes
Journal: Blood (2010)
A pilot study comparing the role of positron-emission (PET) and computed tomography (CT) fusion scan (PET-CT) and contrast-enhanced magnetic resonance imaging (MRI) in the staging of locoregionally nasopharyngeal carcinoma (NPC)
Authors: B. Ma, A. King, B. Zee, S. Leung, A. T. C. Chan
Journal: Journal of Clinical Oncology (2005)

5562 Background: MRI is widely used for NPC staging, but the role of PET-CT in staging is unknown. Objective: This pilot study compared disease stage from “conventional” imaging vs “PET-CT”. Method: Pts enrolled in a trial involving radiotherapy (RT) entered this parallel study. Eligible pts had non-metastatic UICC (6th Edition) stage III-IV NPC based on “conventional” imaging: endoscopy, physical exam, MRI (nasopharynx, NP, neck), chest X-ray, bone scan, abdominal ultrasound. Pts had PET-CT before RT. Radiologists independently assessed MRI & PET-CT, assigned tumor (T) nodal (N) & overall (O) stage. Investigators = blinded to pt’s identity. FDG-PET uptake= expressed as maximum standard uptake value (SUVmax); lesions with SUVmax ≥ 2.0 =malignant. Result: Data of 30 pts were analyzed (22 males/ mean age 48 years). Mean SUVmaxT=10 (range 4.2–21), mean SUVmaxN= 27 (range 2.1–77); no distant metastasis detected on PET-CT. MRI stage (=no. of pts): T2a=0, T2b=0, T3=22, T4=8; N0=3, N1=9, N2=12, N3=6, O-III = 17, O-IVa=7, O-IVb=6. PET-CT stages(=no. of pts): T2a=5, T2b=5, T3=14, T4=6, N0=4, N1=5, N2=15, N3=6, O-III=18, O-IVa = 5, O-IVb = 7. Table 1 outlined the no. of pts with matched T, N, O stages, no. of pts whose MRI stages were up-/down-staged by PET-CT. Conclusion: PET-CT did not detect any distant metastasis missed by conventional imaging. Preliminary findings suggest MRI remains the standard in assessing T-stage. Although PET-CT may detect small N3 & N2 nodes, false-positives due to inflammatory causes cannot be excluded. Further investigation is warranted. No significant financial relationships to disclose.
Exposure-response analysis as evidence for anti-tumor activity of everolimus in the treatment of patients with subependymal giant-cell astrocytoma (SEGA) associated with tuberous sclerosis (TS).
Authors: N. Mehrotra, E. Pfuma, C. Garnett, Q. Liu, B. Booth, N. A. Rahman, A. H. Shahlaee, K. Liu
Journal: Journal of Clinical Oncology (2011)

9550 Background: On October 29, 2010 the US FDA granted accelerated approval for the use of everolimus in the treatment of patients with SEGA associated with TS not amenable to curative surgical resection. Data from a single-arm trial (N=28 patients) was submitted for patients treated with a starting dose of 3 mg/m2/day of everolimus and subsequently titrated to a target steady-state blood trough concentration (Cminss) of 5–15 ng/ml. An exposure-response analysis of the results was conducted to examine whether: Everolimus demonstrates activity in SEGA, and; therapeutic window (5-15 ng/ml) is appropriate. Methods: Exposure-response analysis focused on the relationship between average Cminss within a patient during 6 months (exposure) and percent reduction from baseline SEGA tumor volume at six months (response). The distribution of Cminss along with the % of patients within the 5–15 ng/ml target range was also examined to explore appropriateness of therapeutic window. Results: Exposure (Cminss) data were divided into quartiles (n=7 patients per quartile). An increased response was observed with increased average Cminss with no additional increase in response for Cminss ≥ 3 ng/ml. Increase in response with increase in exposure indicates that the drug elicited a pharmacological effect. The exposure-response relationship results support the lower limit of everolimus target trough concentration of 5 ng/ml, as clinical response was observed at 3 ng/ml. However, the upper limit of 15 ng/ml was not supported by these results. Only 21–44% of the patients were within the target range with most of the patients having Cminss <5 ng/ml. Only 6 patients demonstrated concentrations that exceeded 10 ng/ml. Consequently, the safety profile at higher exposures remains unknown. Furthermore, since no additional reduction in tumor volume was observed at Cminss ≥3 ng/ml, therapeutic window was revised to 5-10 ng/ml in the everolimus labeling. Conclusions: The observed exposure-response relationship provided supportive evidence for anti-tumor activity of everolimus in the treatment of SEGA and a rationale for 5-10 ng/ml therapeutic window.
Fractionated dose radiolabeled anti−prostate specific membrane antigen (PSMA) radioimmunotherapy (<sup>177</sup>Lu−J591) for progressive metastatic castration−resistant prostate cancer (mCRPC).
Authors: Jaspreet S. Batra, Beerinder S. Karir, Kavya Pinto-Chengot, Yuliya Jhanwar, Shankar Vallabhajosula, Paul J. Christos, Gillian Hodes, Linda Lam, Ana M. Molina, Himisha Beltran, David M. Nanus, Stanley J. Goldsmith, Neil Harrison Bander, Scott T. Tagawa
Journal: Journal of Clinical Oncology (2016)

205 Background: Phase I and II single dose 177 Lu−J591 studies have been published. Based on the theoretical advantages of dose fractionation on safety and efficacy, we initiated a phase I dose−escalation study of fractionated−dose 177 Lu−J591. Methods: Men with progressive mCRPC with normal neutrophil and platelet counts were enrolled. The initial portion was 3+3 dose−escalation, with 6 cohorts of 3−6 patients receiving 2 doses 177 Lu−J591, 2 weeks apart starting with 20 mCi/m 2 , escalating to 45 mCi/m 2 . After determining maximum tolerated dose (MTD), patients enrolled in 2 expansion cohorts at recommended phase II doses (RP2D). Planar imaging of 177 Lu−J591 at 6−8 days following the initial dose was performed. Pre− and post−treatment PSA was measured for all patients and the highest dose−level cohorts had CTC counts (CellSearch) measured before and after treatment. Results: 48 patients enrolled with median age 74 (55−95) ), median baseline PSA 45.38 (1.93−766.5), 37.5% with prior chemo. The RP2D’s of fractionated 177 Lu−J591 were 40 mCi/m 2 or 45 mCi/m 2 x2 with option for GCSF. Overall PSA decline ≥ 50% in 9 (18.8%), ≥ 30% in 14 (29.2%) and any PSA decline in 26 (54.2%); at RP2D doses (n = 32), 8 (25%) with ≥ 50%, 12 (37.5%) with ≥ 30%, and 20 (62.5%) with any PSA decline. Of 25 with available CTC counts, 14 declined, 8 remained stably favorable, and 3 increased. Of 12 with unfavorable baseline CTC counts, 8 (66.7%) became favorable at follow up, 2 decreased by 30% and 88% but remained ≥ 5, and 2 increased; 1 converted from &lt; 5 to ≥ 5. Thirty-five (72.9%) had grade 3/4 hematological toxicities; 19 (59.4%) with Gr 4 heme toxicity in RP2D cohorts, with 15 (16.9%) receiving at least 1 platelet transfusion, 6 receiving GCSF, and 0 with febrile neutropenia. Overall 4 had Gr 1 transaminitis and 14 (29.2%) had grade 1 infusion reactions (without pre−medication). Accurate targeting of 177 Lu−J591 at known sites of disease seen in 84.4%. Conclusions: Fractionated 177 Lu−J591 is well tolerated with predictable, reversible myelosuppression, achieving a higher cumulative dose than possible with a single dose. Both PSA and CTC count control was achieved. Clinical trial information: NCT00538668.