tbuckley/cabot-search huggingface dataset:
Immunomagnetic platform technology (IMPT) for the diagnosis of leptomeningeal metastasis in solid tumors (LMST).
Authors: L. Nayak, M. Fleisher, R. Gonzalez-Espinoza, A. S. Reiner, K. Panageas, O. Lin, C. Liu, L. M. DeAngelis, A. M. Omuro
Journal: Journal of Clinical Oncology (2010)

2032 Background: Establishing an early diagnosis of LMST may be difficult, as MRI findings can be equivocal and CSF cytology has low sensitivity (50% on a first spinal tap, increasing to 90% with repeat samples). IMPT based on the anti-EpCAM antibody (Veridex LLC, Warren, NJ) is a widely available tool for capturing and quantifying circulating tumor cells (CTC) in the blood of pts with solid tumors. We hypothesize that IMPT can be used in the diagnosis of LMST through identification of CSF CTC. Methods: Pts undergoing a spinal tap for suspicion of LMST were eligible. All pts had an initial MRI evaluation. CSF was analyzed by conventional cytology, and additional 7.5 mL were used to capture and quantify CSF CTC using anti-EpCAM antibody covered ferroparticles, through a modification of previously described methods (CellTracks Autoprep, Immunicon). Positive CTC was defined as ≥ 1 cell/7.5 mL (0.13/mL). A definitive diagnosis of LMST was defined as any positive CSF cytology or unequivocal MRI findings (leptomeningeal enhancement with subarachnoid nodules, enhancement/clumping of nerve roots or enhancement in basal cisterns) observed within 1 month of the spinal tap. Results: Forty-eight pts were included: NSCLC (n = 19), breast (15), gliomas (4), carcinoid tumor (3), ovarian (2), other (5). Fifteen pts met criteria for LMST within one month of the tap. CSF cytology was positive in 10 pts, MRI was positive in 11, and CSF CTCs were found in 16 (median: 13.3 cells/mL, range 0.13 to 42.8). Thus, initial cytology achieved a sensitivity of 67% (95% CI 42, 85), initial MRI 73% (95% CI 48, 89), and CTC 100% (95% CI 80, 100). One pt with 0.27/mL CTCs had breast cancer brain metastases and hydrocephalus, but no evidence of LMD after a 2-m follow-up. This pt has been treated with bevacizumab, known to mask MRI leptomeningeal enhancement. Conclusions: IMPT allows for an earlier diagnosis of LMST, outperforming CSF cytology and MRI, and identifying 100% of pts developing overt LMST within one month of the tap. Additional follow- up is needed for evaluation of the one false-positive pt. Caution should be exerted in pts with primary tumors with low expression of EpCAM, and confirmatory studies in a population enriched for such histologies is needed. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Schering-Plough
Relationship between volume of bone irradiated during pelvic radiation therapy (RT) for rectal cancer and complete blood counts (CBC).
Authors: Ovidiu Marina, Dan Ionascu, Daniel P McAree, Derek Schulze, Aamod Dekhne, Michelle Wallace, Inga S. Grills, Hong Ye, John M. Robertson
Journal: Journal of Clinical Oncology (2013)

551 Background: CBCs decrease during standard 3D-conformal pelvic RT for rectal cancer. We evaluated RT plans and CBCs to determine if this decrease is due to RT or only concurrent chemotherapy. Methods: Pelvic bones were contoured for 69 patients who had CT-based treatment plans and CBCs 3 months pre and during RT. CBCs included white blood cells (WBC), hemoglobin (Hgb) and platelets (PLT). The pelvic bones included the bilateral femoral heads and innominate bones, sacrum and L5. Dose volume histograms (DVH) for the pelvic bones were encoded as volumes (Vol) receiving 10 (V10) to 50 Gy (V50) in cc, and percent (Perc) (P10 to P50). The paired t-test was used to compare CBCs pre and during RT. CBCs were analyzed with a repeated measures general linear model for uneven time intervals (R 2.15.1). Results: Median age was 60 y, with 40 men (58%) and preoperative RT in 32 (46%). The median RT dose was 50.4 Gy (range 25.2-60.4 Gy), with all but 2 patients receiving ≥45 Gy. Among 677 CBCs, there were 675 WBC, 677 Hgb, and 672 PLT. The average WBC pre and during RT were 7.7 vs 5.4 bil/L (p&lt;0.001), Hgb 12.9 vs 12.5 g/dL (p=0.005), and PLT 271 vs 227 bil/L (p&lt;0.001). A statistical model with variables for time, the 3-week chemotherapy cycle, the pre-RT average CBC, and 1st and 2nd-order interactions of time with Vol and Perc was constructed. All Vol and Perc for all bones as one structure were significant predictors of the PLT timecourse during RT, with the first-order time-dose interaction encoding a decrease over time, and the second-order time-dose interaction a recovery towards the end of RT. For WBC, V40 and P40 were most predictive (p&lt;0.001), with P40 more so. There were no time-dependent interactions for Hgb. All models had a significant effect of pre RT average CBC and the 3-week chemo cycle. Conclusions: Whereas chemotherapy acts systemically, RT affects a circumscribed area. As such, bone marrow outside the RT field can compensate for lost hematopoiesis over time. Pelvic bone RT dose correlates with PLT and WBC (circulation half-life 1-3 d) but not Hgb (half-life 120 d) supporting an effect of RT in decreased CBC during treatment. Research of approaches that minimize bone marrow dose during pelvic radiotherapy is warranted.
Evaluation of a team-based clinical pharmacist in cancer chemotherapy.
Authors: S. Suzuki, M. Tahara, T. Kobayashi, Y. Yajima, H. Ishiki, J. Sugiyama, K. Endo, K. Izumi
Journal: Journal of Clinical Oncology (2011)

e16535 Background: In Japan, pharmacists have both a dispensing and clinical role. This study was designed to evaluate the benefit of a team-based clinical pharmacist in cancer chemotherapy. Methods: Subjects include head and neck cancer inpatients who received cancer chemotherapy in May 2010 (Group A) and who received cancer chemotherapy in August 2010 (Group B). A retrospective study was performed using patient records. In group A, a pharmacist was responsible for both dispensing and clinical pharmacy interventions. In group B, a pharmacy resident, who as a team-based clinical pharmacist, provided interventions with three physicians. Endpoint of this study were (1) To determine the number of pharmacist interventions that reduces the number of adverse reactions in cancer chemotherapy, (2) To determine the number of monitoring for adverse events in patients with cancer chemotherapy, (3) To determine the number of times the pharmacist verify patient drug adherence, and (4) To determine the duration of hospitalization. Results: There were 34 patients in group A and 29 in group B, with no significant differences in age, performance status, type of cancer, and chemotherapy regimens between the two groups. (1) There were 35 pharmacist interventions to reduce the adverse drug events in cancer chemotherapy patients compared to 0 pharmacist interventions in group B. Of the 35 interventions, 14 interventions were about use of opioids in pain control and 10 interventions were about cancer chemotherapy. (2) In group B, there were a total of 311 adverse events monitored, compared to 156 adverse events monitored in group A. (3) The number of verifications by pharmacists with patient adherence in cancer chemotherapy was 127 in group B, compared to 62 verifications in group A. In group B, pharmacists found 92% (11/12) of patients as noncompliant, and pharmacists found 18% (2/11) of patients as noncompliant in group A. (4) There is no statistical significance in the difference of duration in hospitalization between the two groups. Conclusions: This is the first retrospective study which shows the benefits of a team-based clinical pharmacist on cancer chemotherapy in Japan. A team-based pharmacist could contribute to reduce the adverse drug events in patients.
Randomized phase 2, first line, of 5-FU, folinic acid, gemcitabine (FFG) versus FOLFOX-4 in patients (pts) with metastatic colorectal carcinoma (mCRC). Work in progress
Authors: S. Madajewicz, W.-T. Chen, D. Waterhouse, D. Higby, C. Leichman, P. Ritch, M. Khan, S. Malik, P. Hentschel, S. Nicol
Journal: Journal of Clinical Oncology (2005)

3704 Background: FOLFOX-4 recently emerged as standard chemotherapy for mCRC. Over the last 4 years we have been reporting encouraging results with FFG and thus began a randomized trial of FFG v. FOLFOX (2005 ASCO/GI poster). Bevacizumab was added to both arms since. Methods: Fifty four out of 190 planned pts are evaluable now. Interim analysis will be after enrollment of 90 pts. Median age is 64, PS 0–1 and 50% of pts have at least 3 metastatic tumors. RECIST criteria is used for the evaluation of response. Bevacizumab 5mg/kg.b.w. is given IV q. 2 weeks. FFG as described before is given weekly x 6 q. 8 weeks: Folinic Acid 100mg/m2 IV/60min., 5-FU 450mg/m2 IVP and Gemcitabine 900mg/m2 IV/90min. FOLFOX-4 is given according to standard criteria. All pts in main institution have blood and/or tumor tissue analysis for circulating tumor cells (CTC), microarrays and pharmacogenomics. Twenty ml of blood are drawn into sodium heparinized tube. A novel cell adhesion matrix (CAM) is used to detect the presence of viable CTC and a population of CAM reactive leucocytes. Results: The overall response rate is 30% (1CR, 7PR) and 26% (1CR, 6PR) for FFG and FOLFOX respectively. The clinical benefit, CR+PR+SD, is seen in 60% of FFG and 52% of FOLFOX pts. It is too early to assess TTP and OS. Seventeen pts in FFG and 13 in FOLFOX developed grade 3–4 neutropenia, 3 and 2 respectively had grade 3 thrombocytopenia. Five pts in FOLFOX group were hospitalized (PE, TIA and stroke) with 2 deaths being analyzed. There were 2 hospital admissions for FFG pts unrelated to treatment. Two of 3 pts in FFG group showed 3–4 fold increase CAM reactive white cells and 10 fold decrease in viable CTC. Of these 3, one is CR and 2 are responding to treatment. Conclusions: These preliminary results, are encouraging for FFG in regards to less incidence of severe complications and ease of administration. Cell separation based on preferential adhesion of tumor cells to CAM coated surface seems to be rapid/ reliable method of assessing treatment response. Supported in part by grant from NIH R42 CA108247 and Eli Lilly Co Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Eli Lilly Eli Lilly Eli Lilly
A randomised phase II study evaluating the combination of carboplatin-based chemotherapy with pertuzumab (P) versus carboplatin-based therapy alone in patients with relapsed, platinum sensitive ovarian cancer
Authors: S. B. Kaye, C. J. Poole, M. Bidzinksi, L. Gianni, V. Gorbunova, E. Novikova, A. Strauss, V. A. McNally, G. Ross, I. Vergote
Journal: Journal of Clinical Oncology (2008)

5520 Background: Pertuzumab is a monoclonal antibody which specifically binds HER2 and prevents its dimerisation with either another HER2 molecule or other HER family receptors like HER1 or HER3. P has been shown to have activity as a single agent in relapsed ovarian cancer. In preclinical ovarian cancer models, P enhances the activity of platinum-based treatment. P was therefore evaluated in a randomized Phase II study. Methods: Eligibility criteria included: sensitive ovarian cancer (treatment-free interval >6 months), ECOG performance status 0 or 1, left ventricular ejection fraction (LVEF) >55%) and an histological specimen for the evaluation of potential biomarkers of response. Patients were randomised to receive either P at the standard dose of 840mg iv loading dose with 420mg iv 3-weekly maintenance (for 1 year), or no therapy in addition to carboplatin with (at the investigator's discretion) either paclitaxel or gemcitabine. The primary endpoint of the study was progression-free survival. Results: 152 Patients (Pts) were recruited. On a preliminary data review of 84 Pts; 44 received chemotherapy + P and 40 received chemotherapy alone. Tolerability has been good, with no marked increase in overall adverse events associated with P. Grade >3 neutropenia occurred in 30% vs. 38% of Pts on chemo + P vs. chemo alone. 1 Pt in the chemo + P arm experienced an asymptomatic fall in LVEF of >10% and to <50% and spontaneously recovered and continued therapy. 21 (25%) Pts overall have relapsed at the time of the preliminary review. Conclusions: The addition of P to carboplatin-based chemotherapy is well tolerated. The clinical efficacy data by treatment arm will be presented as well as subset evaluations based on biomarkers. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche Genentech™ BioOncology, Roche Roche Roche, Genentech
FOXP3+ regulatory immune cells in serial tumor biopsies from metastatic renal cell carcinoma patients during IL-2 based therapy
Authors: H. Jensen, F. Donskov, M. Nordsmark, N. Marcussen, H. von der Maase
Journal: Journal of Clinical Oncology (2008)

5096 Background: Interleukin-2 (IL-2) based therapy is currently the only curative treatment for patients with metastatic renal cell carcinoma (mRCC). However, administration of IL-2 increases the frequency of circulating FOXP3+ regulatory immune cells, potentially compromising an effective anti-tumor immune response. The present study investigated the impact of IL-2 based therapy on FOXP3+ regulatory immune cells in repeated tumor tissue biopsies from patients with mRCC. Methods: Baseline and on-treatment tumor core biopsies were prospectively obtained from 48 patients treated with IL-2 based immunotherapy. Follow-up was at least five years. Immunohistochemical expression of FOXP3 was evaluated using Clone CM299b, Biocare Medical, 1:50. The number of cells/mm2 was estimated using stereological counting technique and correlated with other immune cell subtypes (continuous values) and overall survival (dichotomized by the upper quartile). Results: A significant increase in intratumoral FOXP3+ immune cells was observed when comparing baseline (median 15/mm2, range 0–123) and on-treatment biopsies (median 70/mm2, range 7 - 388), p<0.001. The relative increase in individual patients was median 5 fold, range 0.1 - 230, p<0.001. No association between the absolute numbers of FOXP3+ and objective response was observed. FOXP3+ cells were positively correlated to CD3+, CD4+, CD8+ and CD57+ tumor-infiltrating immune cells at baseline, and to CD4+, CD8+ and CD66b+ during treatment (all comparisons: p<0.05). All patients achieving high numbers of on-treatment FOXP3+ intratumoral regulatory immune cells (>175/mm2) (N=12) were dead within 21 months, whereas patients with low numbers of on-treatment FOXP3+ cells (N=36) had a 5 year survival rate of 22%, (HR 2.2, CI 1.1–4.5, p=0.02). Conclusion: This is the first report of intratumoral FOXP3+ regulatory immune cells in mRCC patients treated with interleukin-2. Intratumoral FOXP3+ regulatory immune cells were significantly increased by IL-2 based immunotherapy. High numbers of on-treatment FOXP3+ were correlated with poor prognosis in patients with mRCC. No significant financial relationships to disclose.
Disruption of MYD88 Pathway Signaling Leads to Loss of Constitutive IRAK1, NF-κβ and JAK/STAT Signaling and Induces Apoptosis of Cells Expressing the MYD88 L265P Mutation in Waldenstrom's Macroglobulinemia
Authors: Guang Yang, Yangsheng Zhou, Xia Liu, Yang Cao, Zachary Hunter, Steven P Treon
Journal: Blood (2011)
Cognitive function in cancer survivors: Analysis of the 1999-2002 National Health and Nutrition Examination Survey.
Authors: AnnaLynn Williams, Michelle Christine Janelsins, Edwin van Wijngaarden
Journal: Journal of Clinical Oncology (2016)

193 Background: Cancer and its treatment may affect cognitive function in up to 35% of survivors months after treatment. While short-term treatment-related cognitive changes are well recognized, only limited research is available in older, long-term survivors of cancer. Methods: Using NHANES data from 1999 through 2002, 408 cancer survivors and 2,639 non-cancer participants age 60 and above were identified. Cognitive function of these groups were compared on self-reported problems with memory or confusion and using the Digit Symbol Substitution Test (DSST), a test of processing speed, attention, and learning and working memory involving executive functions domains. Results: Cancer survivors were on average 72.8 years old and 11.5 years from diagnosis. After adjustment for covariates, cancer survivors scored, on average, 1.99 points lower on the DSST compared to non-cancer survivors (ß=-1.99, 95%CI -3.94, -0.05). Cancer survivors also had 17% higher odds of self-reporting problems with memory or confusion (OR 1.17, 95%CI 0.89, 1.53). Similar results were observed among survivors ≥ 5 years from diagnosis (ß =-2.38, 95%CI -4.57, -0.18, OR1.41, 95%CI 0.99, 2.02). Results suggest that age modifies the association between cancer diagnosis and DSST score (p=0.11) with a larger effect size in the younger group (between 60 and 75 years). Among those younger than 75, cancer survivors performed 3.25 points lower on the DSST compared to non-cancer survivors (ß =-3.25; 95%CI -5.88, -0.62). However, this difference was only 0.18 points lower among those 75 or older (ß =-0.18; 95%CI -2.94, 2.57). Conclusions: This is the only study to examine domain specific cognitive deficits in a large, nationally representative, older population of long-term cancer survivors and the first to report deficits in processing speed, attention, and learning and working memory domains. These domains are thought to be important for social and executive functioning and quality of life. Characterizing affected domains and subpopulations will help to develop and test effective interventions and may influence treatment practices in older cancer patients.
Correlation of Symptom Assessment with Genotyping Analysis of Saliva Samples in a Large Cohort of Myeloproliferative Neoplasm Patients
Authors: Huong (Marie) Nguyen, David A. Hinds, Kimberly E. Barnholt, Amy K. Kiefer, Chuong B. Do, Nicholas Eriksson, Joanna L. Mountain, Uta Francke, Joyce A. Tung, Ross L. Levine, James L. Zehnder, Jason Gotlib, Ruben A. Mesa
Journal: Blood (2012)
A miRNA assay for the classification of benign and neoplastic lesions in pancreatic fine needle aspirates.
Authors: A. E. Schwarzbach, A. Adai, M. Lloyd, B. F. Andruss
Journal: Journal of Clinical Oncology (2011)

10614 Background: Improved diagnosis of pancreatic ductal adenocarcinoma (PDAC) versus benign pancreatic lesions is an urgent clinical need. We previously reported a laboratory-developed test based on the differential expression of 2 miRNAs, miR-196a and miR-217, with a sensitivity and specificity of 95% in formalin-fixed, paraffin-embedded (FFPE) specimens with ≥60% tumor content. Here, we report the development and validation of a miRNA-based research test optimized for low % tumor specimens and un-enriched fine needle aspirates (FNA). Methods: RNA was extracted using methods developed and validated by the Asuragen Services Laboratory from frozen, FFPE or FNA pancreatic specimens. One to 3 endoscopic ultrasonography-guided FNAs were collected, stored, and shipped in RNARetain, an RNA stabilization solution formulated in 1 mL single-use vials. Expression levels of up to 12 miRNAs were interrogated using TaqMan qRT-PCR assays. Results: A set of 211 specimens, including 94 PDAC, 96 chronic pancreatitis, and 21 normal, was used to develop a miRNA classifier to discriminate benign and low tumor content PDAC specimens. Training on 95 FFPE specimens showed that expression analysis of miR-196a, -210, and -375 improved by 2- to 3-fold the detection rate of PDAC in specimens with 5-88% tumor. The classifier performance was further verified on 4 independent sets of specimens (n=116): frozen with high tumor content (80-100%), FFPE with high tumor content (60-95%), FFPE with low tumor content (10-60%), and FNA. The signature alongside the remaining 9 miRNAs, is now being evaluated in a multi-site prospective study using FNAs collected in RNARetain; 133 specimens have been analyzed to date and we will report the relative performance of the top miRNA classifiers. Conclusions: Benign lesions and PDAC can be accurately classified based on the expression level of a few miRNAs in specimens with 5-100% tumor and in FNA. Testing of pre-operative FNAs collected in RNARetain as part of routine clinical evaluation could in the future improve the differential diagnosis of PDAC and potentially reduce the rate of indeterminate or false negative calls.
Intraoperative open-cavity implant (IOCI) technique for accelerated partial breast irradiation (APBI) using HDR multicatheter brachytherapy for breast cancer patients with small breasts.
Authors: K. Sato, R. Shigenaga, T. Okawa, T. Shimo, M. Kato
Journal: Journal of Clinical Oncology (2010)

e11088 Background: Breast-conserving treatment (BCT) is comprised of lumpectomy followed by whole-breast irradiation (WBI). The efficacy of an accelerated partial breast irradiation (APBI) has been investigated compared with WBI. APBI starting just after surgery might give more benefit by intraoperative insertion of catheters. Although balloon catheter-based APBI is available in the US, it would not be adapted for Asian women with small breast. When the applicators are implanted during operation for the tumor, APBI can start just after surgery. The aim of this study is an assessment of the efficacy and safety of APBI using Intraoperative Open-cavity Implant (IOCI) technique. Methods: Patients (≥ 40 yrs) with invasive breast cancer (≤ 3 cm) were enrolled. Before the lumpectomy, the insertion of applicators and delivery doses were simulated with CT. After the confirmation of the free margin and negative SNs for metastasis using frozen section analysis, applicators were inserted. Dose distribution analysis, using dose-volume histograms, was achieved based on a postoperative CT. APBI was started the same day of the operation. APBI therapy delivered 32 Gy in 8 fractions over 5-6 days with coverage of 2 cm tumor margins. Results: From October 2008 to Jan 2010, 71 women were enrolled (SN + :13, < 40:7 for patients' request). The mean number of applicators was 7.2 (2-15). The mean planning target volume was 40.8 cm3 (6.5-137.1). All toxicities related to radiation therapy were mild. One patient had bleeding one month after the treatment. Infection: 1, fat necrosis:1, and Gr 1/2 dermatitis:11/4patients were observed. However, no ipsilateral breast recurrences and late severe toxicity have been observed to date. All patients could achieve good cosmetic results. Conclusions: This study is a small number of participants and short follow-up period and further research on APBI using IOCI technique is needed to establish clinical efficacy and safety. This technique is convenient, especially for working ladies. After confirmation of long-term safety, dose-escalation study (5Gy/fraction) will be conducted. No significant financial relationships to disclose.
High-Dose Mitoxantrone-Based Induction Therapy in Newly-Diagnosed AML. Results of 171 Patients Treated at NYMC between 1991–2003.
Authors: Karen Seiter, Delong Liu, Eric Feldman, Qiuhu Shi, Paul Baskind, Muhammad Arshad, Anila Qureshi, Tauseef Ahmed
Journal: Blood (2005)