tbuckley/cabot-search huggingface dataset:
Utility of routine cardiac ejection fraction (EF) measurement prior to anthracycline-based chemotherapy (ABC) in patients with diffuse large b-cell lymphoma (DLBCL).
Authors: A. L. Conrad, V. L. McHugh, J. D. Gundrum, R. S. Go
Journal: Journal of Clinical Oncology (2010)

6101 Background: Routine EF measurement in DLBCL patients prior to ABC is recommended by the National Comprehensive Cancer Network and an eligibility criterion for most DLBCL trials sponsored by US cancer cooperative groups. The utility of this practice is unknown. Objectives: We determined the frequency of the following events in newly diagnosed DLBCL patients: a) EF measurement prior to ABC; b) finding of asymptomatic LV dysfunction; and c) modification in treatment strategy as a result of EF measurement. Methods: A list of DLBCL patients seen and treated at our institution from January 2000-September 2009 was obtained from our Cancer Registry. EF of < 50% was considered low. Congestive heart failure (CHF) risk factors were collected. Results: We identified 197 eligible patients. The median age was 71 years (range, 29-97) and 54% were men. EF was measured in 128 (65%) patients before treatment, including 15 with prior CHF. The reasons why EF was not measured in the remaining patients included: clinician assessed patient as low risk to develop CHF (n = 32), patient opted palliative care (n = 3), ABC not recommended due to poor performance status (n = 15), ABC not standard therapy (n = 12) or prior CHF (n = 7). The group considered to be low risk was younger (median 47 vs. 72 years; p < 0.001) and had fewer CHF risk factors (median 1 vs. 2; p < 0.001).Among patients without prior CHF and had EF assessed (n = 113), asymptomatic LV dysfunction was detected in 4 (4%) with EF ranging from 41%-48%. Four patients were not treated despite normal EF due to severe aortic stenosis, older age, and anticipated toxicities of ABC. On the contrary, all of the 4 patients with asymptomatic LV dysfunction received ABC. No patient in this group (0 of 113) had a modification of treatment strategy as a result of EF measurement. CHF developed in 19% and 6% of patients who did and did not have EF measured before ABC, respectively (p = 0.085). Conclusions: At our institution, EF measurement before ABC is a common though not uniform practice. Rarely, mild asymptomatic LV dysfunction was detected but did not affect treatment decision. Our findings challenge the utility of routine EF measurement on DLBCL patients prior to ABC. No significant financial relationships to disclose.
A phase Ib dose-escalation study of the safety, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of the humanized monoclonal antibody (huMAb) anti-EGFL7 (MEGF0444A) in combination with bevacizumab with or without paclitaxel in patients with advanced solid tumors.
Authors: L. Naumovski, M. S. Gordon, P. N. Munster, P. Hegde, J. Fredrickson, S. Bai, R. P. Funke, I. Chang, G. S. Chandler, D. S. Chen, L. S. Rosen
Journal: Journal of Clinical Oncology (2011)

2514 Background: Epidermal growth factor-like domain 7 (EGFL7), is a vascular-restricted, tumor selective, extracellular matrix protein that forms perivascular tracks and promotes endothelial cell adhesion and survival, especially under stress. Anti-EGFL7 (MEGF0444A) is a huMAb that inhibits these activities of EGFL7. In combination with an anti-VEGF antibody, anti-EGFL7 significantly enhances the anti-tumor activity of anti-VEGF in multiple murine tumor models. Methods: A standard 3+3 dose escalation design was used to study safety, PK, PD and anti-tumor activity in 40 patients (pts) with advanced solid tumors. In Arm A, MEGF0444A was given IV at doses of 2, 5 or 10 mg/kg followed by bevacizumab IV at 10 mg/kg on Days 1 and 15 of each 28-day cycle. Pts in Arm B also received paclitaxel (90 mg/m2) on Days 1, 8 and 15 of each 28 day cycle. PD biomarkers including circulating progenitor cells (CPC) and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) were assessed. Results: The combination of MEGF0444A and bevacizumab, with or without paclitaxel, was well tolerated without exacerbation of bevacizumab-related adverse events. MEGF0444A demonstrated linear PK typical of IgG1 monoclonal antibodies. Responses were observed in multiple tumor types in both arms of the on-going Phase Ib. Maximal changes in CPC and DCE-MRI measurements occurred at the 5 mg/kg dose level, consistent with anti-angiogenic effects. Conclusions: MEGF0444A has demonstrated favorable PK properties and is well tolerated in combination with bevacizumab and bevacizumab/paclitaxel. Activity of the combinations has been observed based upon clinical responses, changes in CPCs and DCE-MRI. Study data supports a Phase II dose of 5 mg/kg q2 wks (flat dose equivalent, 400mg q2 or 600mg q3 wks). Further studies of MEGF0444A in combination with chemotherapy and bevacizumab are planned.
Changes in HER2 overexpression between primary tumor and autologous metastases: Correlations with clinical and biological features
Authors: A. Fabi, A. Di Benedetto, G. Metro, E. Melucci, P. Papaldo, P. Vici, C. Nisticò, M. Russillo, F. Cognetti, M. Mottolese
Journal: Journal of Clinical Oncology (2008)

11071 Background: It is yet controversial to what degree the primary tumor is representative of metastases in terms of HER2 status. A hypothetic reason for trastuzumab failure in metastatic breast cancer (MBC) patients (pts), whose HER2 positivity had been determined on primary breast cancer (PBC), may be due to the potential change of HER2 status during disease progression. In this study we analyzed HER2 expression in PBC concomitantly to the first site of disease recurrence correlating HER2 modifications with conventional prognostic factors. Methods: We stained by immunohistochemistry tissue microarrays (TMA) constructed from surgical specimens of 80 PBC (67 ductal and 13 lobular) with known HER2 status and of the corresponding 80 metastases/breast recurrences (11 visceral and 25 non visceral diseases, 44 breast recurrences) with unknown HER2 status. Pts median age was 52 yrs (26–82) and hormonal receptors (HR) were positive in 42 (52.5%) tumors. Fifty-six (70%) and 42 (52.5%) pts had undergone adjuvant chemo and hormonal therapy respectively. No patients received trastuzumab alone or in combination therapy before progression of disease. Results: Discordance in HER2 overexpression between PBC and MBC was found in 12 of 80 cases (15%). In particular, HER2 was negative (0/1+) in the PBC and positive (2+/3+) in the MBC in 8 (10%) pts while HER2 was positive (2+/3+) in the PBC and negative (0/1+) in the MBC in 4 (5%) pts (p=0.04). HR positive PBC showed a slightly higher difference in HER2 expression between PBC and MBC than HR negative PBC (17% vs 13%, p=0.12). HER-2 status modification was not influenced by the type of metastatic site (visceral vs no visceral, p=0.43). In PBC and MBC with HER2 protein discordance, the gene amplification status is under evaluation. Conclusions: Our results, obtained on TMA constructed to allow us to concomitantly stain by IHC PBC and MBC, confirmed that HER2 status may vary from PBC to metachronous MBC. Therefore, in HER2 negative early breast cancers, showing progressive disease, HER2 measurement is recommended, when feasible, also in metastatic specimens, especially in local recurrence and HR positivity, since a high proportion of these pts may show changes in HER2 overexpression. No significant financial relationships to disclose.
Clinical implications of tumor cavitation following therapy with angiogenesis inhibitors in non-small cell lung cancer (NSCLC) patients
Authors: A. Onn, C. H. Martinez, R. S. Herbst, J. R. Riddle, G. R. Blumenschein, D. J. Stewart, E. M. Marom
Journal: Journal of Clinical Oncology (2007)

18034 Background: Angiogenesis inhibitors are being tested in patients with advanced cancer. We sought to determine the formation of tumor cavitation in NSCLC patients treated with antiangiogenic agents at MD Anderson Cancer Center. Methods: Retrospective analysis of all NSCLC cases treated with antiangiogenic agents in our institution between 6/1998 and 6/2005. Clinical data were retrieved from medical records, and chest-imaging findings were documented. Results: One hundred and twenty four patients were treated in 10 different trials. Twelve patients (9.7%, 6 men, 6 women, median age 56 years; cell type adenocarcinoma in 9 and squamous cell cancer in 3) developed tumor cavitation during the trial (median time to event 2 months). All patients had advanced lung cancer and failed previous chemotherapy. Tumor cavitation was found in 4 of 10 trials: 7/39 patients treated with bevacizumab (5 were treated in combination with erlotinib), 3/17 with ZD6474, and 2/23 with BAY43–9006. Median progression-free survival was similar between patients with (6 months) or without (4 months) cavitation. Stable disease was noted in 50% of patients who did and in 52% of patients who did not develop cavitation. Cavitation occurred in the primary tumor or metastases. Imaging characteristics did not significantly differ between tumors with or without cavitation: being proximal to subsegmental artery (66% vs 52%), having well-demarcated margins (66% vs 56%), and soft-tissue density (90% vs 85%). The frequency of adverse events (mild rash, neuropathy) of any grade was similar in patients with (42%) or without (51%) cavitation. One patient with cavitation developed hemoptysis and died. Conclusions: Development of tumor cavitation is not rare in lung cancer patients treated with antiangiogenic agents, but the clinical implications are minimal in most cases. No significant financial relationships to disclose.
Impact of positive pleural lavage cytology on survival in patients undergoing lung resection for non-small cell lung cancer: An international multicenter study
Authors: E. Lim, R. Clough, P. Goldstraw
Journal: Journal of Clinical Oncology (2009)

7519 Background: Pleural lavage cytology (PLC) is the instillation of saline into the chest during surgery for non-small cell lung cancer (NSCLC). The aims of this study were to collate multi-institutional individual patient data to determine independence as a prognostic marker and characterise impact of positive results on stage adjusted survival. Methods: We identified 31 publications from 22 centers/research groups that performed pleural lavage cytology during surgery for NSCLC and invited submission of individual patient data. Actuarial survival was calculated using Kaplan Meier methods and comparisons were performed using the log-rank test. Cox proportional hazards regression was utilised to ascertain the covariates associated with survival. Results: By 1 January 2008, submissions were received internationally from 11 centers with individual data from 8763 patients. In total, 511 (5.8%) patients had a positive pleural lavage cytology result, and this was shown to be an independent predictor of adverse survival associated with a hazard ratio of 1.465 (1.290 - 1.665; P&lt;0.001). On statistical modelling, the best adjustment for patients with a positive PLC result was a single increase in the T category assigned to the case, up to a maximum of T4. Correction for differences in survival were obtained in stage IB (P=0.315) and IIB (P=0.453), with a degree of correction in stage IIIA (P=0.07). Conclusions: Pleural lavage cytology should be considered in all patients with NSCLC suitable for resection. A positive result is an independent predictor of adverse survival and the impact on survival suggests that it may be appropriate to upstage patients by one T category. No significant financial relationships to disclose.
Evaluation of a New Chemotherapeutic Agent in Patients with "Advanced Refractory" Acute Leukemia. Studies of 6-Azauracil
Authors: EMIL J. FREIREICH, EMIL FREI, JAMES F. HOLLAND, DONALD PINKEL, OLEG SELAWRY, HARVEY ROTHBERG, FARID HAURANI, ROBERT TAYLOR, EDMUND A. GEHAN
Journal: Blood (1960)
Screening for lung cancer: Individualized benefit by risk indicators for the first round of screening
Authors: C. I. Henschke
Journal: Journal of Clinical Oncology (2005)

7064 Background: The I-ELCAP investigators at 35 institutions throughout the world have been performing CT screening for lung cancer to evaluate its usefulness and to determine the benefit of undergoing the first round of screening given a person’s individual risk indicators. Methods: Baseline screening has been performed on 27,701 high-risk men and women (age, smoking history) between 1993–2004. A lung cancer diagnosis was classified as a baseline screen-diagnosed case if the work-up was prompted by a positive result on the initial CT. Prevalence of lung cancer on baseline screening was determined by age (40–49, 50–74, 75+ years) and smoking history (1–29, 30–59, 60+ pack-years). Kaplan-Meier analysis was applied to resected cases of lung cancers of Stage I to determine lung cancer case-fatality rate. The benefit of a single round of screening was determined by the estimated probability of detecting a lung cancer, of it being of Stage I, of being cured of the cancer following its resection and not dying of non-lung cancer causes (e.g., cardiovascular, stroke) in the 10 years following that round of screening. Results: The benefit of screening ranged from 0.15% for those of age 40–49 with a history of less than 60 pack-years of smoking and increased to 0.76% for this age group with a 60+ pack-year smoking history. Similarly for those aged 50–74, it ranged from 0.88% to 2.0%, with the benefit increasing with increasing age and pack-years of smoking. The same trend was seen for those 75+ for whom it ranged from 1.3% to 2.1%. Conclusions: This approach provides the estimated probability that the first round of screening will save a person’s life based on the individual risk indicators. No significant financial relationships to disclose.
Bevacizumab (B) plus everolimus (E) in refractory metastatic colorectal cancer (mCRC)
Authors: K. E. Bullock, H. I. Hurwitz, H. E. Uronis, M. A. Morse, G. C. Blobe, S. D. Hsu, S. Y. Zafar, A. B. Nixon, L. A. Howard, J. C. Bendell
Journal: Journal of Clinical Oncology (2009)

4080 Background: For patients (pts) with mCRC, no standard therapy exists after progression on 5-FU, oxaliplatin, irinotecan, bevacizumab, and/or cetuximab/panitumumab. Preclinical data demonstrate combined VEGF and mTOR inhibition has greater anti-angiogenic and anti-tumor activity than either monotherapy. B inhibits VEGF; E inhibits mTOR. Phase I data in patients demonstrated B + E was safe and activity was seen in several pts with refractory mCRC. Methods: 25 pts with refractory mCRC were enrolled in an expanded cohort of B + E. Doses: B 10 mg/kg q2 wks; E 10 mg PO QD. Blood, skin, and tumor biopsies pre- and on-treatment were collected for markers of response and resistance. Results: At this time, 19 pts (10M: 9F) are evaluable for toxicity; 17 for efficacy. Median age 57 years (range 35–78). Median number prior regimens 3. All pts had prior B exposure; 17 pts had progressive disease on prior B-based therapy. There was one Grade (Gr) 4 adverse event (AE) of hypokalemia. Grade 3 AE related to treatment were bowel perforation/fistula, (n=2), hyperglycemia (3), hypokalemia (3), hypertension (2), fatigue (1), alk phos elevation (1; lab only), hypoalbuminemia (1), and volume depletion (1). Other events of interest were: Gr1–2 mucositis (n=10), Gr1 hyperlipidemia (11). Of 17 pts evaluable for response, 4 pts had SD as best response (median 24 wks, range 17–31+ wks); there were 3 minor responses in pts who had progressed on B (median 16 wks, range 16–27 wks). No CR or PR were seen. Biomarker data is pending. Conclusions: B+E has activity in refractory mCRC in pts who had progressed on a B-based regimen, suggesting B+E may overcome resistance to B. Patient accrual is continuing and updated data will be presented. [Table: see text]
The impact of breast cancer morphology on the prediction of a <i>BRCA1</i> mutation
Authors: D. Gadzicki, A. Schubert, S. Milde, U. Lehmann, C. Fischer, D. Steinemann, H. Lück, H. Kreipe, B. Schlegelberger
Journal: Journal of Clinical Oncology (2008)

22125 Background: Since tailored therapeutic strategies are currently being developed, it would be useful to know at the time of diagnosis whether a BRCA1 or BRCA2 mutation is causatively related to an individual breast cancer. The aim of this study was to determine in an unselected hospital-based series of breast cancer patients, whether morphological features can improve the prediction of a BRCA1 mutation. Methods: In a retrospective approach, histopathological results of tumours from 897 women previously diagnosed with breast cancer were re-evaluated regarding the age at diagnosis, subtype of cancer, tumour grade, estrogen (ER), progesterone (PR) and the Her2/neu receptor status as well as the p53 and Ki67 status. 142 tumours fulfilled the morphologic criteria indicative of a BRCA1 mutation. Out of 59 women who were willing to participate in this study, 26 concomitantly showed a positive family history. Results: Pathogenic BRCA1 germline mutations were detected in seven out of the 18 women (39%). None of these women carried a BRCA2 mutation. All BRCA1-associated tumours were of high grade, of invasive-ductal subtype, PR and Her2/neu-negative, 91% were negative for ER. 60% of the tumours showed a high expression of p53 and 60% showed a high expression of Ki67. In particular, there was a highly significant difference between BRCA1-associated tumours and other familial tumours with respect to grading (p=0.001 for G3), ER negativity (p=0.0075), Ki67 ≥ 65% (p=0.0039) and “triple (ER-, PR-, Her2/neu-) negativity” (p=0.0019). Conclusions: This study more clearly defines the histopathological criteria, i.e. triple negative, high expression of Ki67 and p53, that may help to improve the prediction of a BRCA1 mutation in breast cancer patients. No significant financial relationships to disclose.
Pharmacoepidemiology of myelotoxicity (TOX) with temozolomide (TMZ) in malignant glioma patients
Authors: T. S. Armstrong, Y. Cao, E. Vera, M. E. Scheurer, R. Manning, M. F. Okcu, M. Bondy, M. R. Gilbert
Journal: Journal of Clinical Oncology (2008)

9548 Background: A benefit of temozolomide (TMZ) is that myelosuppression (TOX) is uncommon. Recently, several small series report significant TOX resulting in treatment delays or even death in malignant glioma (MG) patients. The ability to predict individual patient risk of TOX may allow for more individualized dosing and management. Methods: A retrospective review of all MG patients treated at M. D. Anderson Cancer Center between 12/97 and 12/04 was completed. Incidence of TOX during the first cycle of TMZ and association with clinical variables was assessed by univariate analysis. A clinical risk formula for each gender was then developed by logistic regression using those factors with an alpha of ≤0.25. Results: In 680 patients with complete data, women were more likely to experience Grade 3 or 4 TOX than men (18% vs 7% p=0.015). The clinical risk formula was then developed. Age remained in each clinical risk formula because of observable trends and clinical significance for males >40 and females 31–40. For males, other factors which increased risk included: Body Surface Area (BSA) ≥2; white blood count ≤6.5; not on steroids; and being on bowel medication (MED) or thyroid replacement (p=0.0001). For females, final factors are: no prior chemotherapy; creatinine ≥1; platelet count < 270,000; BSA < 2; not on anxiety or reflux MED; and being on bowel or pain MED (p<0.0001). The final variables are given a score of 1 if present and are added for a final score with associated risk of TOX. Based on the number of factors present, risk of TOX ranged from 0% for a score of 0–1 (males) and 0–3 (females) to as high as 33% (male score of 5) and 80% (female score of 7). Conclusions: TOX is uncommon with TMZ, but may be significant for those at risk. Use of a clinical model to predict risk may allow for individualized dosing and management. As has been previously reported (Scheurer et al, AACR 2008), a subset of these patients also had evaluation of polymorphisms (SNPs) in DNA repair and xenobiotic metabolism analyzed. Three SNPs were associated with risk for TOX., NQ01 and GSTP1 decreased risk by 70% and 72%, whereas alterations in MGMT resulted in a 2.4-fold increase in risk. The association between the clinical risk factors for TOX and genetic effects will be further explored in a larger sample. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Schering-Plough Schering-Plough
Interim Results of a Phase I/II Study of Ocrelizumab, a New Humanised Anti-CD20 Antibody in Patients with Relapsed/Refractory Follicular Non-Hodgkin’s Lymphoma.
Authors: Franck Morschhauser, Paula Marlton, Umberto Vitolo, Ola Linden, John Seymour, Michael Crump, Bertrand Coiffier, Alessandro Pulsoni, Andrew Belch, Erika Lerch, Eva Kimby, Kristina Arnljots, Elisabeth Wassner, Myriam Mendila
Journal: Blood (2007)
Impact of the radical prostatectomy surgical technique and surgeon experience on freedom from cancer recurrence
Authors: F. J. Bianco, J. A. Eastham, A. J. Vickers, A. M. Serio, J. Pontes, E. A. Kline, P. T. Scardino
Journal: Journal of Clinical Oncology (2006)

4569 Background: We have shown a direct relation between positive margin (PM), morbidity outcomes and surgeon volume, technique after radical prostatectomy (RP). Significant variation occurs even among high volume providers. Our aim was to analyze the surgeon effects on cancer control after RP. Methods: We evaluated 8196 consecutive cT1–3NxMx naive men who underwent RP by one of 76 surgeons within 4 institutions between 1987 and 2003. We calculated the 5-yr probability of recurrence (BCR, PSA elevation &gt;0.4 ng/ml × 2 or initiation of secondary therapy for a PSA rise) for each surgeon assuming a log-logistic survival distribution. A meta-analysis controlling for case mix: PSA, Gleason score, stage, PM and surgical expertise (i.e. cumulative number of surgeries performed) to evaluate for differences in BCR rates between surgeons was performed. We applied the I-square statistic to determine what proportion of the variation represented genuine differences v. chance alone. Results: 33 surgeons performed &gt; 40 RP with 17 surgeons having &gt; 100 procedures during the study period. BCR events were recorded in 1361 patients. The overall 5-yr freedom from BCR with 2524 patients remaining at risk was 80% (79%, 81%) . Extracapsular extension, seminal vesicle invasion, nodal metastasis, PM, Gleason score and PSA were independent predictors of BCR. The surgical volume also correlated independently with BCR. Importanntly we found significant variability on freedom from BCR between high volume surgeons. The I-squared statistic from the meta-analysis was 0.63. That is, approximately 63% of the difference in BCR rates among surgeons can be explained by genuine differences in surgical skill and approach, and approximately 37% is compatible with chance alone. For a sensitivity analysis, we repeated the analysis excluding surgeons who performed less than 100 procedures. In this sub-analysis, the I-squared statistic remained very significant at 0.48. Conclusions: Our data shows that in men treated by RP, the BCR outcomes of men are not exclusively determined by the biology and stage of prostate cancers (explained in most models), but to the surgical skill. Clinical trials evaluating BCR outcomes must prove equivalency among providers so that results are not biased by them. No significant financial relationships to disclose.