tbuckley/cabot-search huggingface dataset:
PAM50 intrinsic subtyping and pathologic responses to neoadjuvant trastuzumab-based chemotherapy in HER2-positive breast cancer.
Authors: P. Gomez Pardo, A. Prat, G. Bianchini, M. Pickl, A. Belousov, A. Koehler, V. Semiglazov, W. Eiermann, S. Tjulandin, M. Biakhov, A. Lluch, M. Zambetti, F. Vázquez-Mazón, L. Gianni, J. Baselga
Journal: Journal of Clinical Oncology (2011)

554 Background: Gene expression profiling can be used to predict the likelihood of achieving a pathological complete response (pCR) to neoadjuvant chemotherapy (CT) in patients with primary breast cancer. We report a retrospective exploratory analysis to evaluate the utility of the PAM50 subtype assay in predicting pCR in women enrolled in the NeOAdjuvant Herceptin (NOAH) trial, which recruited 334 patients. Methods: Formalin-fixed paraffin-embedded core biopsies were collected from 156 patients randomized to receive doxorubicin/paclitaxel (AT) followed by CMF (Group 1; HER2-positive/negative), or the same regimen with trastuzumab (H) (AT+H→CMF+H; Group 2; HER2-positive). Total RNA was amplified, labeled, and hybridized onto Affymetrix 2.0 Plus microarrays. The PAM50 microarray-based assay was applied to 43 genes. The PAM50 Risk Of Relapse score based on subtype and Proliferation (RORP) was evaluated as a continuous variable and as low/medium/high-risk groups using previously reported cutoffs. pCR was defined by the absence of residual invasive tumor in the breast and axillary lymph nodes. Univariate logistic regression was used to evaluate the association of each signature with pCR. Results: Overall pCR rates were 21.5% (20/93) and 44.4% (28/63) in Groups 1 and 2, respectively (p<0.005). In Group 1, non-LumA tumors showed higher pCR rates than LumA tumors (27% vs. 0%, p<0.005). Low, medium and high RORP groups showed 0%, 19% and 37% pCR rates (p=0.02). In Group 2, all subtypes were identified and HER2-enriched tumors showed a non-significant increase in pCR rates compared to non-HER2-enriched tumors (53% vs. 34%). Low, medium and high RORP groups showed 17%, 36% and 75% pCR rates (p=0.01). In Group 2 the odds ratio for achieving a pCR in the high-risk RORP group was 15.0 compared to the low-risk group (p=0.029). Conclusions: HER2-positive tumors predicted to have a high risk of relapse by the PAM50 assay benefited substantially from H-based CT. Similar findings are observed in HER2-positive/negative tumors treated with CT only. The role of PAM50 and/or other genomics assays in predicting pCR and survival during treatment with anti-HER2 agents warrants further investigation.
Radiofrequency ablation (RFA) combined with chemotherapy for unresectable colorectal liver metastases (CRC LM): Long-term survival results of a randomized phase II study of the EORTC-NCRI CCSG-ALM Intergroup 40004 (CLOCC).
Authors: Theo Ruers, Cornelis J. A. Punt, Frits van Coevorden, Jean-Pierre Pierie, Inne Borel Rinkes, Jonathan A. Ledermann, Graeme John Poston, Wolf O. Bechstein, Marie-Ange Lentz, Murielle E. Mauer, Eric Van Cutsem, Manfred P. Lutz, Bernard Nordlinger
Journal: Journal of Clinical Oncology (2015)

3501 Background: This study evaluates the benefit of combining systemic chemotherapy (CT) with local tumor destruction by RFA in patients with unresectable CRC LM up to 9 lesions and without extrahepatic disease. Overall survival (OS) at 30 months and progression free survival (PFS) results were reported (Ann Oncol. 23(10): 2619-26, 2012). We now report on OS results, after a long term median follow-up of 9.7 years. Methods: Between 2002 and 2007, 119 pts were randomized between CT alone (59) or RFA+CT (60). In both arms, CT consisted of 6 months FOLFOX (oxaliplatin 85mg/m2 and LV5FU2) plus, since October 2005, bevacizumab. In the CT arm resection was allowed when unresectable disease was converted by CT to resectable disease. Primary objective was a 30-months OS rate > 38% for the combined treatment group. OS and PFS were secondary endpoints. Results: In the RFA+CT arm, 56 pts (93.3%) received RFA which was combined with resection in 27 pts (45%), 1 pt had all metastases resected (ineligible), 2 pts were not treated at all, in 1 pt no local treatment data were available. 51 patients (85%) in the RFA+CT arm received CT compared to all 59 in the CT arm. 6 pts in the CT arm eventually underwent hepatic resection. The primary endpoint was met, 30-months OS rate was 61.7% (95% CI: 48.2-73.9) for combined treatment. However, 30-month OS for systemic treatment only was 57.6% (95% CI: 44.1-70.4), higher than anticipated. At a median follow-up of 9.7 years, 92 deaths were reported, 53 in the CT arm and 39 in the RFA+CT arm. Causes of death in the CT arm were progressive disease (49 pts), and unknown for 4 pts, and in the RFA+CT arm, progressive disease (35 pts), other causes (2 pts) and unknown (2 pts). There was a significant difference in OS in favor of the RFA+CT arm (HR = 0.58, 95% CI: 0.38-0.88, p = 0.01). Observed median OS was 45.6 months (95% CI: 30.3 – 67.8) in the RFA+CT arm vs. 40.5 months (95% CI: 27.5 - 47.7) in the CT arm. Conclusions: This is the first study that prospectively investigated the efficacy of RFA +CT in pts with unresectable CRC LM. In this phase II trial, RFA+CT was associated with improved long-term OS compared to CT alone. Clinical trial information: NCT00043004.
Viable malignant cells after primary chemotherapy for disseminated non-seminomatous germ-cell tumors (NSGCT): An international validation study
Authors: K. Fizazi, A. Dunant, J. Oldenburg, I. Chen, R. Salvioni, J. T. Hartmann, G. Daugaard, A. Flechon, J. Bouzy, G. Fromont
Journal: Journal of Clinical Oncology (2005)

4521 Background: Our international group previously identified prognostic factors in patients (pts) with NSGCT and post-chemotherapy viable malignant cells (J Clin Oncol 2001, 19: 2647–57). We attempted to validate these prognostic factors in an independent set of pts. Methods: A series of 84 pts with post-chemotherapy viable NSGCT treated in 13 European and American institutions was collected. Tumor markers had normalized before resection. Pathologic samples were centrally reviewed. Pts with only teratoma in their residual masses were excluded. Results: With a median follow-up of 5.4 years, the 5-year progression-free survival (PFS) rate was 65% and the 5-year overall survival (OS) rate was 72%. The factors found in our previous study also predicted a favorable PFS in this series: a complete resection (p= 0.001), less than 10% of viable malignant cells (p=0.06) and a good International Germ Cell Consensus Classification (IGCCC) group (p=0.04). As in the initial study, pts (n= 61) were assigned to one of 3 risk groups of a prognostic index: no risk factor (favorable group), 1 risk factor (intermediate group) and 2–3 risk factors (poor-risk group). The 5-year PFS rate was 92%, 78%, and 42%, respectively (p=0.002) (versus 90%, 76%, and 41% in our original study). The 5-year OS rate was 90%, 86%, and 52%, respectively (p= 0.009) (versus 100%, 83% and 51% in our original study). There was no apparent benefit of using post-operative chemotherapy versus surveillance, although this data should be taken with caution due to the limited power and the lack of randomization. Conclusions: This study validates our prognostic index. Given the excellent outcome of pts in the favorable group (those with a complete resection, <10% viable malignant cells, and a favorable IGCCC group), we propose 1) that these patients be spared from having post-operative chemotherapy and 2) an international prospective study to validate this strategy. No significant financial relationships to disclose.
Regulation of β1-Integrin by Mir-134 in Mesenchymal Stromal Cells – Implications for Mesenchymal Stromal Cell Adherence and Hematopoietic Stem Cell Interaction
Authors: Friedrich Stölzel, David M. Poitz, Laleh S. Arabanian, Jens Friedrichs, Denitsa Docheva, Matthias Schieker, Fernando A. Fierro, Uwe Platzbecker, Ruth H. Strasser, Martin Bornhäuser, Carsten Werner, Gerhard Ehninger, Thomas Illmer
Journal: Blood (2012)
Effect of ciprofloxacin on the systemic exposure to erlotinib
Authors: H. Kletzl, E. Zwanziger, C. Kirkpatrick, E. Luedin
Journal: Journal of Clinical Oncology (2008)

19047 Background: Erlotinib is a potent oral tyrosine kinase inhibitor (TKI) of the epidermal growth factor receptor (EGFR) and has been shown to increase overall survival and PFS in non-small cell lung cancer (NSCLC) and pancreatic cancer. Erlotinib is metabolized primarily by CYP3A4, and to a lesser extent by CYP1A2 and the pulmonary isoform CYP1A1. Although DDI studies have been conducted with CYP3A4 inhibitors, the interaction potential with ciprofloxacin, a quinolone antibiotic which inhibits both CYP3A4 and CYP1A2, has not yet been investigated. Therefore a phase I study was conducted to assess the effect of ciprofloxacin on the pharmacokinetics (PK) of erlotinib. Methods: Single-centre, open-label, one-sequence, two-period cross-over study in male and female healthy volunteers. Subjects received a single dose of 100 mg erlotinib po on Day 1, and 750 mg ciprofloxacin bid for 6 days (Day 13–18) plus a single dose of 100 mg erlotinib po on Day 15. Adverse events, physical examinations, clinical laboratory tests, vital signs, ECG and PK were assessed. Results: 28 subjects (age 19–53 years) were enrolled from May-Aug 2006. Erlotinib was well tolerated alone and together with ciprofloxacin. No deaths, SAEs or withdrawals due to AEs occurred. Erlotinib was absorbed with a median tmax of 3–3.5 h. Plasma concentrations of erlotinib increased when given with ciprofloxacin. The exposure to erlotinib (AUC0-∞) was 10300 ± 4020 ng.h/mL (mean ± SD) when given as single agent vs. 14000 ± 4890 ng.h/mL after concomitant ciprofloxacin administration. The corresponding maximum plasma concentration (Cmax) was 576 ± 312 ng/mL and 617 ± 215 ng/mL, respectively. The geometric mean ratio (90% CI) of erlotinib vs. erlotinib plus ciprofloxacin was 1.39 (1.24, 1.56) for AUC0-∞ and 1.17 (0.98, 1.40) for Cmax. For the active metabolite OSI-420, the mean ratio was 1.62 (1.40, 1.87) for AUC0-last and 1.48 (1.20, 1.82) for Cmax. Conclusions: The systemic exposure to erlotinib and its metabolite increases when erlotinib is co-administered with the CYP3A4/CYP1A2 inhibitor ciprofloxacin. Considering the interpatient variability this might not be clinically relevant. However, caution should be used and dose reduction considered when erlotinib is given together with potent CYP3A4/CYP1A2 inhibitors. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Hoffmann-La Roche
30-day readmission among gastrointestinal cancer patients in Texas.
Authors: Joanna-Grace Manzano, Ruili Luo, Linda S. Elting, Maria Suarez-Almazor
Journal: Journal of Clinical Oncology (2013)

121 Background: 30 day readmission has become an important metric in healthcare delivery. Policymakers have started to factor in readmission rates in their recommendations on reimbursement algorithms. It is unclear whether these methods are applicable to cancer patients. More studies are needed in order to understand readmission in the context of cancer patients. A few studies have found that the elderly and those with gastrointestinal (GI) malignancies are at risk. Methods: We conducted a retrospective cohort study using linked Texas Cancer Registry and Medicare claims data to describe the patterns of 30 day unplanned readmission among GI cancer patients in Texas. Only short stays to acute care hospitals were included in the study. Claims data were analyzed for a period of 2 years from the date of cancer diagnosis. Modified Poisson regression model was used to identify factors associated with the outcome. Results: 30,199 patients aged 66 and above were included in our study. The incidence of unplanned readmission in our cohort was 15%. The top 10 reasons for readmission were fluid and electrolyte disorders, secondary malignancies, complications of surgical procedures and medical care, congestive heart failure, intestinal obstruction, pneumonia, sepsis, GI hemorrhage, urinary tract infections, and complications of device, implant or graft. After multivariate analysis, age &gt;80 (OR 0.79, 0.73-0.85), regional (1.19, 1.11-1.27) and distant disease (1.16, 1.07-1.25), living in less affluent neighborhoods (1.10, 1.01-1.19), and increasing comorbidity index (p&lt;0.0001) were associated with 30 day readmission. Esophageal cancer carried the highest risk for 30 day readmission (1.53, 1.38-1.70). Conclusions: Most of the top reasons for readmission appear to be cancer-related. This means that most of these readmissions are likely not preventable. This should be taken into consideration by policymakers when making recommendations. There are, however, some that may be amenable to outpatient management. This further underlines the importance of primary care involvement in the management of cancer patients. Risk factors identified can help risk–stratify patients who may need early follow up post-discharge, in order to prevent early readmission.
Assessment of clinical trials in oncology: An evaluation of 40,696 trials on ClinicalTrials.gov.
Authors: B. R. Hirsch, R. M. Califf, A. Tasneem, K. Chiswell, J. Bolte, K. A. Schulman, A. P. Abernethy
Journal: Journal of Clinical Oncology (2011)

6095 Background: In 2007, it was mandated that all clinical trials must be registered with clinicaltrials.gov. A collaboration between the Food and Drug Administration (FDA) and Duke University, this study represents the first systematic assessment of the clinicaltrials.gov database. What is the portfolio of cancer studies? What insights can be gained about our contemporary research enterprise? Methods: MeSH terms and submitted conditions were classified by clinical sub-specialists to group studies by disease state. After isolating oncology trials, basic descriptive statistics profiled trial designs, patient populations, and interventions. Results: Of the 40,969 interventional studies registered after September 2007 with submitted conditions, 9,102 (22%) focused on oncology, the highest among all subspecialties. Of the interventions studied, 72% assessed medications. When compared to clinical trials in other diseases as shown in the table, more oncology trials are early phase (70% phase I or II in oncology vs 33% overall), single arm (65% vs 23%), and unblinded (88% vs 47%). In the subset of trials which reported actual accrual, oncology studies averaged 42 patients and non-oncology 60 patients. In terms of eligibility criteria, maximum age cut-offs were less frequent in oncology (25% vs 60%); the most common exclusion was age > 70 years. Oncology trials were more likely to have a data monitoring committee (DMC) (53% vs 38%), although less likely to provide information regarding the existence of a DMC (70% vs 85%). Conclusions: The clinicaltrials.gov database represents a unique opportunity to understand the scope of clinical trials in oncology. These data identify strengths and weaknesses in trial design and patient populations that need to be carefully addressed in an era of increasing focus on research design and comparative effectiveness research. Categories Oncology Other medicine specialties Trial phase Phase I 21.0% 13.5% Phase I/II 10.6% 3.6% Phase II 38.1% 15.8% Phase II/III 1.4% 2.9% Phase III 11.4% 16.2% Phase IV 2.7% 16.7% Intervention model Single arm 64.7% 23.1% Parallel 32.5% 61.5% Crossover/factorial 2.9% 15.4% Masking Open 87.5% 47.1% Single blind 3.5% 13.3% Double blind 9.0% 39.6%
Oral mucositis (OM) and outcomes of allogeneic (AL) hematopoietic stem cell transplantation (HSCT)
Authors: G. Oster, M. Vera-Llonch, C. Ford, I. Khazanov, S. Sonis
Journal: Journal of Clinical Oncology (2005)

6107 Background: OM is a common toxicity of conditioning regimens for HSCT that has been associated with adverse clinical and economic outcomes. Methods: A retrospective chart review study of 300 consecutive AL HSCT recipients is being undertaken at a single academic center. OM severity was assessed across 8 oropharyngeal sites using a validated scale which was scored as follows: no erythema/ulceration = 0; erythema only = I; ulceration one site = II; two sites = III; three sites= IV; and four or more sites = V. OM assessments began on the day of conditioning and continued bi-weekly to discharge. Outcomes included number of days of fever, total parenteral nutrition (TPN), and parenteral narcotic therapy, incidence of grade III (Common Toxicity Criteria) infection and graft-versus host-disease (GvHD), and inpatient days and charges. We report data here for the first 63 patients. Results: Mean age was 40 yrs. Most common diagnoses were acute (35%) and chronic (21%) myeloid leukemia. All patients received total body irradiation. 47% of grafts were from related donors. 62% of patients experienced OM ≥ grade II. Study findings are reported below. Conclusions: Ulcerative OM is associated with worse clinical and economic outcomes in AL HSCT. No significant financial relationships to disclose.
Utility or futility? Use of chemotherapy in end stage cancer patients admitted for symptom control
Authors: C. Simmons, M. Trudeau, A. Vyas, J. Sue, J. Fralick, M. Clemons
Journal: Journal of Clinical Oncology (2005)

8075 Background: Therapeutic options for patients with advanced cancer continue to increase. While chemotherapy (CT) may improve quality of life in certain metastatic cancers, little is known about its role in end stage cancer patients admitted for symptom control. The purpose of this study was to assess utilization of CT on an inpatient population at a single cancer centre, and to identify potential prognostic criteria. Methods: A retrospective chart review was undertaken of metastatic, non-hematological, cancer patients who received inpatient CT between July 2002 and July 2004. Patient demographics, symptoms, length of hospitalization, prior CT use and time to death were recorded. Results: 113 patients received inpatient CT. 37 were excluded with non-metastatic or curable disease. Of the remaining 76 patients, mean age was 60 yrs (range 30–85). Most common tumor sites were breast (37%), lung (21%), colorectal (10%) and prostate (7%). 53% of patients had received CT prior to admission; average number of lines of prior CT was 1.9 (range 1–6). The average length of hospitalization was 27 days (range 1–117). 57% of patients were eventually discharged home. 32% of patients subsequently received outpatient CT. 56/76 (74%) of patients had died at the time of analysis. The median number of days between inpatient CT and death was 39 (range 0–585). The presence of dyspnea, anorexia, confusion, visceral metastases, prior CT use, and supplemental oxygen at the time of admission were each predictive for shorter survival. Conclusions: The use of CT in end stage cancer patients admitted to hospital for symptom control has major implications for both patient quality of life and resource utilization. Only 32% of patients receiving CT as an inpatient go on to receive further outpatient CT. Factors have been identified that may assist physicians in deciding which patients have a particularly poor prognosis and for whom inpatient CT might not be appropriate. No significant financial relationships to disclose.
Luciferase-expressing MCF-7-luc-F5 human breast cancer cells used to monitor mammary fat pad tumor growth and metastasis in vivo in nude-beige mice
Authors: Darlene E. Jenkins, Yvette S. Hornig, Yoko A. Oei, Shang-Fan Yu, Joan M. Dusich, Tony Purchio
Journal: Cancer Research (2004)

5114  A clonal human tumor cell line expressing firefly luciferase, MCF-7-luc-F5, was developed from parental MCF-7 breast carcinoma cells and characterized for bioluminescence in vitro and in vivo. As few as twenty cells were detectable in vitro and average bioluminescence measured approximately 680 photons/sec/cell. Tumorigenesis of MCF-7-luc-F5 cells was assessed with and without estrogen supplement in vivo following injection of cells into the mammary fat pad of nude-beige mice. Continuous tumor growth was observed by weekly bioluminescent imaging in mice receiving a slow release (60 day) estrogen pellet implant (0.36 mg/pellet), while no tumor growth occurred in mice without estrogen supplement. Caliper measurements of tumor volume indicated similar results. A kinetic analysis of luciferase activity in vivo demonstrated that peak signals were evident approximately 12-15 minutes after injection of luciferin substrate and were maintained at a relatively stable level for at least another 20-25 minutes. Spontaneous metastasis from the primary mammary fat pad tumor to thoracic and axillary regions was observed in vivo in 50% of the animals. Subsequent ex vivo images and histology identified metastatic sites in lung, rib, or lymph nodes depending on the mouse. Standard drug treatment on primary and secondary tumor growth was also monitored by bioluminescent imaging.
Relationship of T lymphocytes, T regulatory cells, and B lymphocytes to clinical outcome in prostate cancer.
Authors: M. Trepel, A. Flammiger, L. Weisbach, T. Schlomm, H. Huland, S. Minner, P. Tennstaedt, C. Bokemeyer, G. Sauter
Journal: Journal of Clinical Oncology (2011)

4632 Background: Tumor-infiltrating lymphocytes are functionally important and correlate with clinical outcome in several tumor entities. In prostate cancer, systematic profiling of the number and subtype of lymphatic cells in the tumor tissue based on large patient cohorts are lacking. Methods: We explored the prognostic significance of the density of T and B lymphocytes in prostate cancer tissue in 3,261 prostate cancer tissue samples. The number of prostate cancer-infiltrating CD3-positive T cells, FOX-P3-positive T-regulatory cells (Tregs), and CD20-positive B cells per tissue spot in a tissue microarray format was determined by immunohistochemistry and was correlated with clinical and functional pathological data from the same patient cohort. Results: Patients with very low and very high numbers of CD3-positive T cells per tissue spot had a significantly shorter PSA recurrence-free survival compared to patients with intermediate numbers of T cells. The number of intraepithelial CD3-positive T cells and the number of CD20-positive B cells per tissue spot was not associated with other clinical and histopathological parameters. PSA recurrence-free survival was significantly reduced in patients with higher numbers of Tregs. Further, a higher number of intratumoral FOXP3+ Tregs was associated with a more advanced tumor stage and higher Ki67 labeling index. The tissue density of Tregs was unrelated to other clinical parameters such as spread to lymph nodes, preoperative PSA level, and Gleason score. Conclusions: Our study suggests for the first time that both the intratumoral absence or presence of T cells and T regulatory cells is functionally relevant and may have an impact on the clinical course in prostate cancer.