tbuckley/cabot-search huggingface dataset:
Symptomatic brain metastases from renal cell carcinoma during treatment with sunitinib or sorafenib.
Authors: J. M. Larkin, V. Hess, L. M. Pickering, T. Ferguson, R. Forrest, M. E. Gore
Journal: Journal of Clinical Oncology (2010)

e15023 Background: The kinase inhibitors (KIs) sunitinib and sorafenib have transformed the management of advanced renal cell carcinoma (RCC). Brain metastases may occur less commonly during treatment with these agents than with immunotherapy. Few data are reported describing outcomes of patients developing symptomatic brain metastases during KI therapy. Methods: Patients with advanced RCC that developed symptomatic brain metastases whilst on treatment with sorafenib or sunitinib were identified and their characteristics and outcomes summarised. Patients with a history of brain metastases at baseline were excluded. Results: Twenty one patients developing symptomatic brain metastases during treatment with sorafenib (n=5) or sunitinib (n=16) were identified out of 294 patients (21/294=7%) treated with either drug between 2003 and 2009 (216 sunitinib, 104 sorafenib, 26 both). Only 1 patient had undergone brain imaging prior to the initiation of therapy. All patients had undergone nephrectomy, median age was 58 (range 46 to 68) and 67% of patients were male. Median number of lines of prior therapy was 1 (range 0 to 4), the median Heng prognostic score was 1 (range 0 to 3) and the median ECOG PS was 1 (range 0 to 1). The median time from diagnosis of metastatic disease to starting KI therapy was 16 months (range 3 to 70) and the median time from starting KI therapy to brain metastases was 4 months (range 1 to 44). The median overall survival from starting KI therapy was 11 months (95% CI 5 to 17 months) and from the development of brain metastases 5 months (95% CI 2 to 8 months). At the time of diagnosis of brain metastases, disease status outside the brain was progressive disease in 6 patients (29%), stable disease in 11 patients (52%) and partial response in 2 patients (10%). Conclusions: The development of symptomatic brain metastases is a rare but significant problem in advanced RCC during therapy with sorafenib or sunitinib. At the time of diagnosis of brain metastases, most patients had disease control outside the brain, suggesting that the brain may be a sanctuary site in these individuals. Median overall survival was short and there is consequently a major need for prospective study of novel therapeutic approaches. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer, Novartis, Pfizer Bayer, GlaxoSmithKline, Novartis, Pfizer Bayer, Novartis, Pfizer Bayer, Novartis, Pfizer
High Frequency and Poor Outcome of Ph-like Acute Lymphoblastic Leukemia in Adults
Authors: Kathryn G. Roberts, Debbie Payne-Turner, Kelly McCastlain, Zhaohui Gu, Ilaria Iacobucci, Richard C. Harvey, I-Ming Chen, Marcus Valentine, Deqing Pei, Yongjin Li, Jinghui Zhang, Cheng Cheng, Alessandro Rambaldi, Orietta Spinelli, Jerald P. Radich, Mark D. Minden, Anthony V Moorman, Bella Patel, Adele K. Fielding, Jacob M. Rowe, Selina Luger, Jessica Kohlschmidt, Krzysztof Mrózek, Guido Marcucci, Clara D. Bloomfield, Wendy Stock, Hagop M. Kantarjian, Marina Konopleva, Elisabeth Paietta, Cheryl L Willman, Charles G. Mullighan
Journal: Blood (2015)
Chemotherapy for bladder cancer: A United Kingdom practice survey
Authors: P. Egan, B. Venugopal, R. J. Jones
Journal: Journal of Clinical Oncology (2008)

16078 Background: Chemotherapy has an established role in the treatment of locally advanced (LABC) and metastatic bladder cancer (MBC). Chemotherapy regimens vary, in particular, there is no agreed standard of care for second line treatment of metastatic disease. To aid future study design, we conducted a current practice survey. Methods: A written questionnaire was mailed to 110 UK urological oncologists requesting anonymous replies in pre-paid envelopes. Results: Of the 61 questionnaires returned, 8 denied treating bladder cancer. These were excluded from further analyses. In first line MBC, 45/53 [85%] preferred gemcitabine/cisplatin (GC), with considerable variation in schedule. Methotrexate/vinblastine/doxorubicin/cisplatin (MVAC) was the next preferred regimen (7/53[13%]). In patients unsuitable for cisplatin, 39/51 [76%] reported using gemcitabine/carboplatin (GCarbo). Other options were gemcitabine alone (5/51[10%]) and methotrexate/carboplatin/vinblastine (CMV) (2/51[4%]). In second line MBC, 10/43 [23%] respondents reported using GC, 7/43 [16%] used GCarbo, 6/43 [14%] used paclitaxel/carboplatin (PC) and 6/43 [14%] used MVAC. In the absence of formulary restrictions, 16/34 [47%] clinicians would choose paclitaxel alone or in combination with platinum as their preferred choice of second line regimen. 25/26 [96%] clinicians reported 3 weekly PC as an acceptable control arm for a randomised controlled trial of second line chemotherapy. The most popular neoadjuvant regimen for LABC was GC (42/49[86%]). 4/49 [8%] of clinicians used MVAC based regimens. In the adjuvant setting, 29/34 [85%] clinicians chose GC and the remainder CMV or MVAC. Conclusions: In UK clinical practice, chemotherapy treatment of bladder cancer is largely uniform. Standard of care for neoadjuvant, adjuvant and 1st line for MBC consists of gemcitabine/platinum doublet. Second line treatment of MBC, however, is more variable and this is an area which needs further clinical study. These data will inform the design of future trials in treatment of MBC. No significant financial relationships to disclose.
Supervised exercise for cancer survivors during and after active therapy.
Authors: Mark Allen O’Rourke, Regina A Franco, Dawn W. Blackhurst, Jennifer C. Trilk, Matthew F. Hudson, William Larry Gluck
Journal: Journal of Clinical Oncology (2012)

121 Background: Supervised exercise for cancer survivors can reduce symptoms and improve physical conditioning. This program evaluation reports the benefits of a nurse-supervised exercise program for cancer survivor participants both during and after active cancer therapy. Methods: The treating oncologist referred participants to the oncology rehabilitation program, called Moving On, either during or at the completion of active therapy. Participants enrolled in a 12-week program of supervised exercise for one hour, three days per week. Baseline and follow up evaluation included a patient reported fatigue score, on a scale from 1 to 10 (with higher scores indicating more fatigue), and the 6-minute walk test (6MWT), in feet. Results: In calendar 2011, 152 participants enrolled in the program and 91 completed all 12 weeks (completers). Participants were 71% female, 86% Caucasian, 14% African American, 68% enrolled on completion of active therapy, and 32% enrolled during active therapy. More than half were older than 60 years. More than half had cancer diagnoses other than breast cancer. A consistent decrease in fatigue and increase in exercise capacity was seen in subgroup analysis by gender, race, age, status on cancer therapy or after completion of therapy, and diagnosis. Conclusions: In this diverse group of cancer survivors, a program of 12 weeks of nurse-supervised exercise was feasible, substantially reduced fatigue, and increased exercise capacity. It is noteworthy that participants, both on active therapy and after, older and younger, and across diagnosis groups, experienced the benefits of the program. [Table: see text]
Clinical significance of cellular and acellular mucin pools in rectal carcinoma following preoperative chemoradiotherapy.
Authors: Javier A. Cienfuegos, Fernando Rotellar, Jorge Baixauli, Iosu Sola, Jorge Arredondo, Carlos Pastor, Jose Luis Hernandez-Lizoain
Journal: Journal of Clinical Oncology (2015)

718 Background: Currently, the standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (CRT) followed by surgery. Pathological findings in post-treated specimens remain the most significant prognostic factor. The presence of mucin pools and their prognostic significance is a controversial issue. Methods: The aim of this study was to analyze the incidence of cellular and acellular mucin pools and their clinical significance in 446 consecutive prospectively collected specimens from patients with stages II/III treated with preoperative CRT and surgery. Results: Mucin pools were present in 182 specimens (40.8%); 66 (14.7%) were acellular, and viable tumor cells were identified in 116 (26.0%). If acellular mucin is considered as a type of response and not residual tumor, the complete pathological response rate was 12.8% (57 of 446). With a median follow-up of 79.0 months, the 5- and 10-year disease-free survivals for patients with acellular and cellular mucin pools, were 81.8% and 63.4%, respectively (p &lt; 0.0225). The presence of cells in the colloid response to treatment was associated with a 2.5-fold increase in the possibility of dying of rectal cancer (HR = 2.5 [1.1 − 5.76], p= 0.028 univariant Cox regression analysis). Conclusions: Thus, our results suggest that cellular mucin pools are an indicator of an aggressive phenotype and harbingers of a worse prognosis.
NABTT 2111: A phase I trial of BMS-247550 for patients with recurrent high-grade gliomas
Authors: D. Peerebom, T. Batchelor, G. Lesser, S. Phuphanich, T. Mikkelsen, K. Carson, S. Desideri, J. Fisher, S. Grossman
Journal: Journal of Clinical Oncology (2005)

1563 Background: BMS-247550 is a semi-synthetic analog of epothilone B, a novel non-taxane microtubule-stablizing agent. A phase I trial of this agent in patients with recurrent high-grade glioma is in progress Methods: Patients (pts) receive BMS-247550 on a 1-hour infusion, daily x 5 every 3 weeks. Cohorts of 3 pts are treated at each dose level starting at 5 mg/m2/day. Pts are stratified into groups A and B according to the use or non-use, respectively, of cytochrome P450 enzyme-inducing anticonvulsants. Dose escalation for each group occurs separately using the continual reassessment method (CRM) to calculate each dose level. The MTD is reached when the CRM assigns two consecutive dose levels within 10% of the previous level. Pharmacokinetic sampling (PKs) occurs on days 1–5 of cycle 1. Results: Twenty-nine pts have been enrolled: median age 54 years (range 22–75); 21 (72%) male; 12 in group A. All had received radiation and 25 (data on 3 missing) had received prior chemotherapy. Four dose levels (5, 6, 7, 7.7 mg/m2) have been tested in group A with no dose-limiting toxicities (DLT). Six dose levels (5, 7.5, 6, 6.6, 7, 6.8 mg/m2) have been tested in group B with 1 treatment-related death (sepsis/typhlitis) at 7.5 mg/m2,and 2 DLTs (grade 4 ANC and grade 3 febrile neutropenia) at 7 mg/m2. Data for the 6.8mg/m2 are currently under review, however 1 DLT (grade 3 arthralgia) has been observed. Other grade 3 treatment-related toxicities: anemia, abdominal cramping, arthralgias, neuropathic pain, and fatigue. Of 23 pts evaluable for response, 5 had stable disease and 18 have progressed. PKs are being assessed. Conclusions: To date, BMS-247550 has not shown new toxicities in glioma pts with the possible exception of typhlitis for which BMS-247550 could not be excluded as the cause. The most severe toxicity has been hematological. Dose escalation in group B is near completion, and the MTD will be close to that (6 mg/m2) established in non-CNS pts. Dose escalation continues on group A and the MTD will be ≥ 7.7 mg/m2. Because BMS 247550 is a substrate for the P450 system, pharmacodynamic differences between the groups A and B may emerge. No significant financial relationships to disclose.
Pilot trial of a Wilms tumor-1 (WT1) peptide vaccine in patients with thoracic and myeloid neoplasms
Authors: A. B. Brown, L. M. Krug, P. Maslak, L. P. James, T. Dao, L. Tyson, S. M. Chanel, S. Bekele, D. A. Scheinberg
Journal: Journal of Clinical Oncology (2008)

3051 Background: The transcription factor, WT1, is overexpressed in several solid tumors and leukemias and has been targeted by investigators for immunotherapy. Using computer prediction analysis we designed analog peptides derived from WT-1 sequences by substituting amino acids at key HLA-A0201 binding positions. One peptide (WT-A1) was capable of stimulating CD8 T-cells for killing of HLA matched tumor cells. A modified version of the protein (WT1–122A1) created by adding flanking amino acids to the core sequence, generated CD4 responses as well. Two additional peptides were generated (WT1–427 & WT1–331) which were capable of recruiting CD4 T-cell response across multiple HLA-DR subtypes. These four peptides administered together with adjuvant Montanide and GM-CSF comprise the vaccine. Methods: The primary objective of the study is to test the safety, activity and immunogenicity of WT1 vaccine in 10 patients with mesothelioma (meso) or non-small cell lung cancer (NSCLC) expressing WT1 protein by immunohistochemistry, and 10 patients with acute myeloid leukemia (AML) or myelodysplastic syndrome with WT1 transcript measured by RQ-PCR. Patients receive up to 12 vaccinations over 9 months. Immune responses are evaluated by delayed-type hypersensitivity, CD4 T-cell proliferation, CD4 and CD8 T-cell interferon release, and WT1 peptide tetramer staining. Results: 12 patients (5 AML, 5 meso, 2 NSCLC) have been enrolled and 2 are currently active. 4 meso patients discontinued the vaccines after 3 or 6 doses because of progression. 1 meso patient has stable disease after 12 vaccinations. 3 AML patients relapsed on the vaccine (after 3rd, 6th, 8th dose) and had evidence of increasing WT-1 transcript. 3 of 10 patients tested developed a DTH skin reaction. 6 of 7 patients evaluated had a CD8 or CD4 immune response to the vaccinating peptides. One AML patient had grade 2 urticaria after the 5th vaccination and was removed from study. No other significant adverse events occurred. Conclusions: This analog WT1 peptide vaccine is well-tolerated and immune responses can be elicited. Future studies will incorporate this vaccine as adjuvant therapy in meso and AML. Supported by NIH PO1 23766, Innovive Pharmaceuticals, MARF, The Experimental Therapeutics Center and the Baker Street Foundation. No significant financial relationships to disclose.
HCT-CI Is Not a Useful Predictor for Non Relapse Mortality in Older Patients (&gt;60 years old) Receiving RIC Transplant for AML or MDS
Authors: Victor Noriega, Hugues de Lavallade, Victoria T Potter, Pramila Krishnamurthy, Judith C. W. Marsh, Stephen Devereux, Robert E. Marcus, Kavita Raj, Donal McLornan, Anjum Bashir Khan, Sangeeta Atwal, Robin M. Ireland, Deborah Yallop, Antonio Pagliuca, Ghulam J Mufti
Journal: Blood (2012)
Use of a multigene prognostic assay for selection of adjuvant chemotherapy in patients with stage II colon cancer: Impact on quality-adjusted life expectancy and costs.
Authors: N. J. Meropol, G. H. Lyman, R. Chien, J. C. Hornberger
Journal: Journal of Clinical Oncology (2011)

491 Background: Uncertainty exists regarding the use of adjuvant therapy in patients with stage II colon cancer. To assist decision making, we compared quality-adjusted life expectancy and costs associated with using a multigene recurrence score (RS) assay with the use of clinicopathological factors currently recommended in clinical guidelines. Methods: A state-transition (Markov) model was developed to assess outcomes associated with the use of the RS (Oncotype Dx gene expression assay) in adjuvant therapy decisions in stage II colon cancer (excluding T4 tumors and those with deficient DNA mismatch repair). RS test characteristics were based on results reported from a randomized controlled trial (QUASAR, Kerr et al. ASCO, 2009). Current rates of administering adjuvant chemotherapy (aCTX) as a function of age, lymphatic invasion, tumor stage, and number of lymph nodes examined was derived from the NCCN Colon/Rectum Cancer Outcomes study (Earle et al, J Surg Oncol, 2009). Effects of aCTX on recurrence risk were based on published data. Medicare fee schedules were used to estimate cost; toxicities, recurrence, and quality-of-life adjustments were obtained from published studies. Results: Treatment decisions based on RS and a patient's years of life remaining without cancer recurrence would reduce aCTX use by 17% compared with current treatment patterns, and increase quality-adjusted life expectancy by an average of 0.035 years. With lower use of aCTX, direct medical costs are expected to decrease by an average of $2,971 per patient. One-way sensitivity analysis predicts overall QALY improvement with the RS through a range of variables, with the results most sensitive to the disutility associated with aCTX use. Sensitivity analyses also show the assay to be cost-saving under a variety of conditions. Conclusions: Clinical use of a multigene RS to assess risk of recurrence in T3 stage II colon cancers with intact mismatch repair is likely to improve quality-adjusted life expectancy and be cost-saving from a societal perspective. Patient age and disutility associated with chemotherapy are important considerations in adjuvant treatment decisions. [Table: see text]
Hepatitis B screening prior to chemotherapy: A survey of practitioners' knowledge, beliefs, and screening practices.
Authors: R. Lee, C. M. Bell, L. K. Hicks
Journal: Journal of Clinical Oncology (2010)

6147 Background: Hepatitis B virus (HBV) reactivation is a recognized risk of chemotherapy which can be reduced with lamivudine. However, HBV carriers may be unrecognized. Some authors and Associations recommend HBV screening for all patients undergoing chemotherapy. We explored the knowledge, beliefs and practices of Canadian oncologists and hematologists regarding HBV screening prior to chemotherapy. Methods: A novel questionnaire was mailed to all oncologists and hematologists practicing in British Columbia, Alberta, Manitoba, Ontario, Nova Scotia, Newfoundland, and Prince Edward Island. Results: Eligible practitioners were identified (508), of whom 308 (61%) responded. Only respondents who administered chemotherapy were included in the analysis (n = 242). Most respondents (77%) practiced in a university setting, 47% treated mainly solid tumors, and 39% treated mainly hematologic malignancy. Half of respondents (54%) agreed that “hepatitis B screening prior to chemotherapy is important”; however, only 22% of respondents screened all patients prior to chemotherapy; 38% reported screening high-risk patients only, and 40% reported rarely or never testing for HBV. Almost half (44%) of respondents had seen at least one case of HBV reactivation. Prior experience with HBV reactivation and a predominantly hematologic practice were independently associated with agreeing that HBV screening is important (p = 0.008 and p < 0.001 respectively). Screening for HBV (all or high-risk patients) was independently associated with prior experience with HBV reactivation and having a predominantly hematologic practice (p < 0.001 and p = 0.006 respectively). Most respondents accurately estimated the prevalence of HBV in Canada. However, most respondents underestimated the risk of reactivation in HBV carriers. Conclusions: A minority of Canadian oncologists and hematologists routinely screened all patients for HBV prior to chemotherapy. Screening for HBV was independently associated with prior experience with HBV reactivation and a practitioner treating mainly hematologic malignancy. Low HBV screening rates could be related to respondents' tendency to underestimate the risks of HBV reactivation. No significant financial relationships to disclose.
The influence of spirituality and religiosity on the personal use and practice patterns with complementary and alternative medicine (CAM): A national survey of US oncologists.
Authors: Richard T. Lee, Catherine Powers-James, Adriana L. Alvarez, Kathrin Milbury, Francoise Adan, Gabriel Lopez, Lorenzo Cohen, Marvin Delgado-Guay, Olufunmilayo I. Olopade, Farr A Curlin
Journal: Journal of Clinical Oncology (2016)

248 Background: Although cancer patients frequently use CAM, it is uncertain how oncologists’ spirituality and religiosity impact their decisions to use or recommend CAM with their patients. Methods: A US probability sample of 1,000 ASCO members was contacted by mail and email to complete a survey regarding clinical approaches to herb and supplement (HS) use by cancer patients. Results: Of 927 deliverable surveys, 423 surveys were returned for a response rate of 46%. Respondents were mostly men (72%), Caucasian (76%), with a median age of 48. Approximately 16% reported no religion, 19% Jewish, 24% Catholic, 28% Christian, and 13% other religions. Eighteen percent reported attending religious services at least once a week including 15% who attend several times per week. Twenty-eight percent reported high theological pluralism (skepticism regarding whether one religion is the only true religion). Fifty-eight percent self-described themselves as very or moderately spiritual. Univariate analyses indicated significant correlations with self-reported spirituality and religious service attendance and the likelihood of personal CAM use, recommending any CAM, and recommending HS. In multivariate analyses, predictors of personal CAM use were: female gender (OR = 5.6, CI 0.09-0.37), non-Caucasian (OR = 3.0, CI 0.16-0.70), educated in HS (OR = 2.6, CI 1.37-5.08), attending religious services less than monthly (OR = 3.0, CI 0.17-0.65), and self –reported high or moderate spirituality (OR = 3.2, CI 1.5-6.6). Physician predictors for sometimes or often recommending HS were male gender (OR = 1.85, CI 0.92-3.75) and self–reported low spirituality (OR = 2.9, CI, 0.15-0.77). Recommending CAM was associated with female gender (OR = 2.6, CI 0.15-0.97), educated in HS (OR = 3.4, CI 1.46-7.78), and self–reported high or moderate spirituality (OR = 2.8, CI 1.26-6.31). No correlations were found with religious affiliation. Conclusions: This is the first study to identify self-reported spirituality as a significant factor among US oncologists’ decision to use CAM and recommend CAM to patients, and further studies are needed to explore this potential influence.