tbuckley/cabot-search huggingface dataset:
Malignant pleural effusions in lymphoproliferative disorders: A clinico-pathologic study
Authors: S. Ahmed, A. K. Siddiqui, R. Rimawih, R. K. Shahid, L. J. Rossoff, C. P. Sison, K. R. Rai
Journal: Journal of Clinical Oncology (2004)

6080 Objective: To facilitate the diagnosis of malignant involvement of pleura by examining various clinical and cyto-chemical characteristics of pleural effusions in patients with lymphoproliferative disorders and to identify factors that predict mortality in these patients Methods:Clinical data of 86 eligible patients with lymphoproliferative disorders who were hospitalized from 1993 to 2002 on 91 occasions and underwent thoracentesis were reviewed. Cytological examination was performed in all specimens whereas flow cytometry and/or DNA study was performed in 40 (44%) specimens. A logistic regression analysis was carried out to determine prognostic variables that predict malignant involvement of pleura and hospital mortality. Results: Median age was 70 years (4–92) and M:F was 44:42. Of 86 patients, 60% had non-Hodgkin lymphoma, 23% had CLL, 9% had multiple myeloma, and 7% had Hodgkin's disease. 19% had a secondary malignancy. 74% patients had advanced disease, 50% had prior chemotherapy and 10% were in remission. Of 91 cases of pleural effusions, 48% were bilateral and 88% were exudates. 48 (53%) cases of pleural effusions were due to malignant involvement of pleura. Among various variables examined with respect to their correlation with malignant pleural effusion or hospital mortality, symptomatic pleural effusion (odds ratio 10.3, 95% CI; 1.7–98.3), pleural fluid mesothelial cells % <5 (odd ratio 8.0, 95%CI; 1.4–58.2), pleural fluid: serum LDH >1 (odd ratio 6.4, 95%CI; 1.2–45.6) and pleural fluid lymphocytes % >50 (odd ratio 6.4, 95% CI: 1.2–50) were significantly correlated with malignant pleural effusion whereas secondary cancer (odd ratio 11.9, 95% CI; 2.3–88.8), pleural fluid: serum LDH >1, (odd ratio 10.9, 95% CI; 2.6–64.9), and pneumonia (odd ratio 6.4, 95% CI; 1.7–28.6) were significantly correlated with hospital mortality in multivariate analysis Conclusions: Our results reveal that many clinical and cyto-chemical markers have discriminatory values in identifying malignant effusion in patients with lymphoproliferative disorders. A high pleural fluid to serum LDH level correlates with malignant pleural involvement and mortality. No significant financial relationships to disclose.
Prognostic factors in early stage head and neck squamous cell carcinoma (HNSCC) patients in a prospective clinical trial
Authors: E. S. Kim, J. Lee, L. Feng, S. Lippman, G. Shenouda, I. Hodson, E. Vokes, F. Khuri, W. K. Hong
Journal: Journal of Clinical Oncology (2004)

5515 Background: HNSCC is the 5th most common cancer in the United States. A majority abuse tobacco which leads to higher relapse rates and second primary tumors (SPT). Methods: We reported results of a randomized chemoprevention study (FRK ASCO 2003) in which pts received isotretinoin or placebo. This analysis focuses on the placebo group and prognostic characteristics related to prior therapy, site of disease, stage, and smoking status. Results: From 1991 to 1999, 600 pts were enrolled into the placebo arm: stage I (n=389), II (211); primary tumor of larynx (L; 343), oral cavity (OC; 187), pharynx (P; 70); prior therapy of radiation (RT; 353), surgery (S; 158), both (86); and smoking status of current (220), former (296), never (84). The median follow-up is 6 years and 5-year survival is 0.83 (0.80, 0.87). We compared the above pts in statistical models to identify prognostic markers, which may impact recurrence, smoking-related (sm) SPT development, disease-free (DFS), and overall survival (OS). Smoking status was found to be associated with site: OC primaries with more nonsmokers, L with more former smokers, and P with more current smokers. Site of disease was associated with stage as more L pts presented in stage I and P stage II. Treatment related with site of disease: L received more RT, OC received more S, and P received more of both. Treatment also related with stage: more single therapy for stage I and combination for II.Significant observations included worse recurrence-free and sm-DFS for OC as compared to L (P=0.0003 and 0.007, respectively), worse recurrence-free survival in pts with prior RT as compared to S (P=0.007) which was also marginally significant for survival (P=0.06); and higher sm-SPT survival for P primaries as compared to L (p=0.02). After adjusting by stage, site, and smoking status, sm-SPT survival and OS for current smokers was worse (p=0.04, p=0.008). Conclusion: Smoking status did not predict recurrence but current smoking status was the most significant predictor for poor survival. Further studies are needed to investigate the interaction between smoking and primary treatment modality early stage HNSCC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca Pfizer Pfizer AstraZeneca; Aventis Trial was funded by NCI-PO1 grant; this is a subset analysis of the trial
FLT-PET analysis of early response to everolimus in newly diagnosed glioblastoma patients enrolled on NCCTG N057K.
Authors: J. N. Sarkaria, P. J. Peller, E. Galanis, M. S. Jacobson, W. Wu, K. A. Jaeckle, J. C. Buckner
Journal: Journal of Clinical Oncology (2011)

e12501 Background: 18F-fluorodeoxyuridine (FLT) PET is potentially useful for imaging tumor proliferation. In this study, serial FLT PET imaging was used to evaluate tumor response during everolimus therapy in glioblastoma patients enrolled on N057K and treated at Mayo Clinic Rochester. Methods: Newly diagnosed GBM patients enrolled on this sub-study received a baseline (pre-Rx) FLT PET scan, 2 doses of everolimus (70 mg orally once weekly, and a second (post-Rx) FLT PET scan within 24 hours of the second everolimus dose. Patients continued to receive weekly RAD001 during conventional TMZ-based chemo-radiotherapy followed by maintenance RAD001 therapy until progression. Maximum standardized uptake values (SUV) within the tumor were calculated for each scan and the relative change in SUV (Δ-SUV) was calculated for each patient. Results: Between February and December of 2010, 4 patients were accrued to the imaging sub-study of N057K. The patient characteristics, imaging results, and follow-up for these patients are shown in the table. Pre-treatment SUV ranged from 4.5 to 0.8. The low baseline SUV for patient #4 (SUV = 0.8) precluded a meaningful evaluation of Δ-SUV in this patient. For the remaining 3 patients, the relative Δ-SUV ranged from -27% to -10%. The Δ-SUV observed in patient #2 reaches the EORTC criteria for a partial metabolic response. Ongoing IHC studies are evaluating PTEN status and mTOR signaling activity in diagnostic tissue samples from these patients. Conclusions: These results demonstrate the feasibility of using serial FLT PET imaging to evaluate drug-induced changes in tumor proliferation following one week of everolimus therapy. Additional accrual and follow-up on this study will provide a greater understanding of rates of initial response to everolimus therapy. FLT PET imaging results and follow-up for patients treated with everolimus. Patient Age/sex MGMT Pre-Rx SUV Post-Rx SUV D-SUV Disease status #1 61 yo F U 4.5 3.3 -27% Stable at 10 mo #2 68 yo M NA 3 2.7 -10% Stable at 2 mo #3 47 yo M M 1.4 1.2 -14% Stable at 11 mo #4 59 yo M NA 0.8 0.5 NA Progress at 6 mo Abbreviations: U, unmethylated; M, methylated; NA, not available.
Evaluation of the prognostic significance of human kallikrein 8 protein expression levels in advanced ovarian cancer by using automated quantitative protein analysis
Authors: P. Kountourakis, A. Psyrri, A. Scorilas, S. Markakis, D. Kowalski, R. L. Camp, E. P. Diamandis, M. A. Dimopoulos
Journal: Journal of Clinical Oncology (2007)

5581 Background: Kallikreins, a subgroup of the serine protease enzyme family, are considered important prognostic biomarkers in cancer. Here, we sought to determine the prognostic value of kallikrein 8 (hkl8) in ovarian cancer using a novel method of compartmentalized in situ protein analysis. Materials and Methods: A tissue array composed of 150 advanced stage ovarian cancers, uniformly treated with surgical debulking followed by platinum-paclitaxel combination chemotherapy, was constructed. For evaluation of kallikrein 8 protein expression, we used an immunofluorescence-based method of automated in situ quantitative measurement of protein analysis (AQUA). Results: Mean follow-up time of the cohort was 34.35 months. One hundred twenty six of 150 cases had sufficient tissue for AQUA analysis. There was association between tumor mask hk8 protein expression levels and clinicopathological variables including grade (p=0.0011), residual disease (p=0.0063),clinical response to chemotherapy (p=0.0346). In univariate survival analysis there was a correlation between hk8 tumor mask expression and 5 years progression-free survival. Low hk8 expression correlated with better outcome (top vs. bottom quartile, p = 0.0319). In multivariate survival analysis, adjusting for well-characterized prognostic variables, tumor hkl8 expression level retained its prognostic significance for disease free survival (95%CI: 0.341–1.027, p=0.0468). Conclusions: Human Kallikrein 8 is an adverse prognostic factor in patients with ovarian cancer.The possibilities that hK8 may be suitable candidate as diagnostic, prognostic marker and therapeutic target merit further investigation. No significant financial relationships to disclose.
The utility and prognostic value of positron emission tomography with fluorine-18-fluoro-2-d-glucose (FDG–PET) on patients with Hodgkin and non-Hodgkin lymphoma.
Authors: B. Ozturk, M. Benekli, U. O. Akdemir, S. Buyukberber, U. Coskun, A. Uner, M. Unlu, D. Yamac, M. Kitapci, E. Yaman, Ramazan Yildiz, Umut Demirci, Ali O. Kaya, Ozlem Kapucu
Journal: Journal of Clinical Oncology (2010)

e18535 Background: 18F-FDG-PET is a functional imaging method and widely used for initial diagnosis, staging and response evaluation in the treatment of malignant lymphomas. We evaluated the FDG-PET for initial staging and post treatment evaluation of patients with HL and NHL. We also aimed to assess the prognostic value of FDG-PET in these patients. Methods: One hundred and five untreated patients with histologically proven malignant lymphoma were included the study. Statistical analysis was performed on 94 of these patients who have at least 12 months follow-up period. FDG-PET was performed on initial staging and after completion of primary chemotherapy. Treatment response in FDG-PET was correlated with PFS and OS. Cox regression analyses were performed to test the value of prognostic factors. Results: Ninety-four patients with HL (n=19) and NHL (n=75) (median age:52.5, range 20-80 years) were included the study. All initial PET-CT results were positive for lymphoma involvement. After completion of first line chemotherapy (R-CHOP or CHOP-like regimens for NHL, and ABVD for HL), PET-CT results were became negative in 75 (79.8%) of patients. Only 16% of PET negative patients relapsed and underwent RT or salvage CT ± HDT/ASCR. All PET-positive patients (20.2%) relapsed except for two patients with gastric DLBCL and HL with bone involvement. Median follow-up was 18 months. Estimated 1- and 2-year PFS rates were 88% and 78% for PET negative group, and 33% and 11% for PET positive group (p<0.00001). Estimated 1- and 2-year OS were not significantly different in the two groups (p=0.82). Multivariate Cox regression analysis showed that post-treatment PET was an independent prognostic factor for PFS. In patients with DLBCL (n=50), post-treatment PET negativity was associated with significant PFS advantage (p<0.0001) and was an independent prognostic factor. Conclusions: We concluded that post treatment FDG-PET is an accurate and independent predictor of PFS. True and early diagnosis of post treatment residual disease can be helpful for selection of the patients who require aggressive treatment modalities such as HDT/ASCR. No significant financial relationships to disclose.
Abstract #5652: Gefitinib and everolimus interact to produce synergistic effects that potentiate cytostasis and impede tumor growth in trastuzumab sensitive and resistant HER2 overexpressing breast cancer models
Authors: Wieslawa Dragowska, Ling Yan Wong, Yannick Franssen, Mohhamed Qadir, Jennifer Baker, Anita Kapanen, Dana Masin, Andrew Minchinton, Sharon Gorski, Karen Gelmon, Marcel Bally
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

HER2-positive breast cancers frequently coexpress epidermal growth factor receptor (EGFR) and sustain elevated PI3K/Akt/mammalian target of rapamycin (mTOR) signaling. A combination of the EGFR inhibitor gefitinib and mTOR inhibitor everolimus was investigated to assess efficacy in HER2 overexpressing trastuzumab (TZ)-sensitive (MCF7-HER2 and SKBR3) and TZ-resistant (JIMT-1) breast cancer models. All cell lines were sensitive to gefitinib and everolimus as single agents. In combination, gefitinib and everolimus resulted in synergistic effects, as judged by the median effect methodology defined by Chou and Talalay, when cell growth was used as a measured endpoint. The combination did not increase cell death over the levels found when the drugs were used alone but was reflected by enhanced G1/G0 cell cycle arrest. Inhibition of cell growth by gefitinib and everolimus, alone and in combination, was associated with a rise in cell populations with cytoplasmic vesicles which positively stained with acidotropic dye monodansylcadaverine (MDC); a result linked to drug induced alterations in autophagy flux. These data suggest an involvement of cytoprotective autophagy in response to these drugs, whether used alone or in combination. An analysis of targeted molecular pathways indicates that the combination downregulated the mTOR pathway (as shown by western blot analysis of phosphorylated (P) p70S6K and P-S6 proteins) to a much greater extend than achieved by the agents when used alone. In vivo studies (MCF7-HER2 and JIMT-1 xenograft models) demonstrate that the combination of gefitinib and everolimus achieve significant (p 0.05) from those found in tumors from animals treated with the vehicle or single agents. In contrast, Ki67 tissue expression and protein levels of P-p70S6K, P-S6 and cyclin D1 were considerably lower in tumors from animals treated with the combination when compared to those from animals treated with the agents alone. These data demonstrate synergy and potentiation of the beneficial therapeutic effects of gefitinib and everolimus in HER2-positive breast cancers when the drugs are used in combination. Benefits include augmentation of cytostasis and attenuation of the mTOR pathway allowing more effective control over the tumor growth. Gefitinib and everolimus combinations should be investigated clinically in patients with HER2-positive breast cancers, including TZ-resistant phenotype.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5652.
Zoledronic acid and calcitriol in malignancies with bone involvement. A pilot trial
Authors: G. M. Palmieri, L. Schwartzberg, R.E. Imseis
Journal: Journal of Clinical Oncology (2004)

3185 Background: 1,25 dehydroxyvitamin D (calcitriol) has anticancer effects by stimulating cell differentiation and inhibiting proliferation and angiogenesis. Its major drawback is stimulation of osteoclasts with liberation of cancer growth factors from bone and hypercalcemia. Aminobisphosphonates inhibit osteoclasts and correct hypercalcemia of malignancies. We reported bone healing with calcitriol + pamidronate in 2 multiple myeloma patients (pts) (AmJMedSci, 1999). We are reporting ongoing findings during a 12 month (m) pilot trial with zoledronic acid (Z) + calcitriol (C) in 10 pts (5 women, 5 men), with bone metastases from various tumors (4 breast, 4 prostate, 2 myeloma). Methods: Patients on cancer therapy received Z, 4 mg i.v./m + C (Calcijex), 1 μg i.v., 2/week x 2 weeks, followed by C (Rocaltrol) 0.25 μg po/tid + Ca 1,500 mg/d. Chemistries, calciotropic factors, bone turnover markers, skeletal MRI and bone density by DEXA were determined at 1 - 3 m. Results: Two pts died of cancer in the first 2 m and 1 pt discontinued the protocol in the 11th m due to progression of cancer. Two pts completed 12 m of the study. Three pts completed 6 m and 2 pts, 3 m. Z + C were well tolerated. There was no severe hypercalcemia (>11.3 mg/dl) or hypercalciuria. Skeletal MRI at 3 m intervals showed no new lesions or progression of the lesions in 5 of 6 pts who had at least two MRI; two of them showed sclerosis suggesting healing of the lesions, and 1 pt showed progression of the lesions. Bone density increased in 5 of 5 pts at 6 m of treatment (hip 6.0%, lumbar spine 10.5%, whole body 2.6%). PTH fell in 7 of 7 pts by 62%. Serum C remained within the normal range in most pts and urinary NTX, a marker of bone resorption, fell in 6 of 6 pts by 60%. Conclusion: Ongoing data suggest: 1. Z + C were well tolerated. 2. Skeletal metastases did not progress in most pts and in 2 pts signs of bone healing were observed. 3. Bone density increased in multiple sites. 4. PTH and NTX fell by 60%. These results are encouraging and support the continuation and completion of this study. No significant financial relationships to disclose.
IFCT0002 phase III study comparing a preoperative (PRE) and a perioperative (PERI) chemotherapy with two different CT regimens in resectable non-small cell lung cancer (NSCLC): Early results
Authors: B. Milleron, E. Quoix, V. Westeel, M. Puyraveau, D. Braun, J. L. Breton, L. Bigay Game, J. L. Pujol, F. Morin, A. Depierre
Journal: Journal of Clinical Oncology (2007)

7519 Background: Recent trials have shown a survival benefit of CT in resectable NSCLC. The primary objective was to define the best timing of CT (all before surgery versus perioperative). Another objective was to compare two regimens, gemcitabine-cisplatin (GP) and paclitaxel-carboplatin (TC). Methods: Between May 2001 and Dec 2005, 528 patients (pts) with a stage IA-II resectable NSCLC were randomized to 4 parallel arms: A: 2 GP + 2 GP in responders, then surgery, B: 2 GP - surgery + 2 GP in responders, C: 2 TC + 2 TC in responders then surgery, D: 2 TC - surgery + 2 TC in responders (GP: Gemcitabine 1250 mg/m 2 /d1, 8 and cisplatin 75 mg/m 2 /d1 q3 wk; TC: Paclitaxel 200 mg/m 2 /d1 and carboplatin AUC 6, q3 wk). Results: Pathological tumor volume and pathological complete response rate did not differ with the number of preoperative cycles. Proportions of pts receiving cycles 3 and 4 were higher when all CT was given before surgery. There were several significant differences in the main toxicities between GP and TC. Conclusions: 1- GP and TC were effective and safe. 2- Results of pathological response suggested that 2 cycles might be as effective as 4 cycles. 3- Dose intensity was higher when all chemotherapy was given before surgery compared to both before and after surgery. No significant financial relationships to disclose. [Table: see text]
Phase III trial (EORTC 10994/BIG 00-01) assessing the value of p53 using a functional assay to predict sensitivity to a taxane versus nontaxane primary chemotherapy in breast cancer: Final analysis.
Authors: H. R. Bonnefoi, J. Bogaerts, M. Piccart, L. Mauriac, P. Fumoleau, J. Jassem, V. Becette, D. A. Cameron, J. Bergh, R. Iggo
Journal: Journal of Clinical Oncology (2010)

LBA503 Background: Predictive markers of response to chemotherapy are lacking. Preclinical data suggest that p53 mutated tumors are resistant to anthracyclines and sensitive to taxanes. However, clinical data are contradictory. Using a functional yeast assay to detect biologically important mutations, this study tested the hypothesis that docetaxel confers a greater advantage over anthracyclines in p53 mutated tumors (mut) than p53 wild type (wt). Methods: Patients (pts) with locally advanced/inflammatory or large operable tumors were randomized to either a standard anthracycline regimen (arm A) or a taxane-based treatment (arm B). In arm A pts received 6 cycles of FEC 100, or tailored FEC + G-CSF (Swedish cohort). In arm B docetaxel (T) 100mg/m 2 was given for 3 cycles, followed by 3 cycles of epirubicin 90mg/m 2 and T 75mg/m 2 q3 weeks (T-ET). After chemotherapy, pts underwent surgery followed by radiotherapy. Endocrine therapy and/or trastuzumab were given according to each center's policy. Fresh frozen tumor biopsies were mandatory before starting chemotherapy: frozen sections were examined centrally and the p53 test was done when the invasive tumor cell content was &gt; 20%. cDNA derived from tumor-extracted RNA was transfected into yeast (Flaman et al. PNAS 1995): tumors were deemed p53 wt when there were &lt; 20% red colonies (background) and p53 mut &gt; 20%. The three co-primary comparisons for the endpoint of progression-free survival (PFS) were between arms A and B in p53 mut, p53 wt, and the entire trial population, each at a p=0.02. The sample size gave sufficient power for an interaction test for outcomes between p53 mut and wt at p&lt;0.05. Results: From April 2001 to November 2006, 1,856 patients were included. A total of 386 pts (21%) were ineligible (including 292 pts with &lt;20% tumor cells and 67 without sample). No unexpected toxicity was observed. At the time of analysis 675 events were registered after a median follow-up time of 57 months. The results are summarized below. Conclusions: p53 is not a predictive factor of response or resistance to taxanes, although it is, as expected, prognostic (&lt;0.001). PFS is not statistically significantly different between FEC and T-ET arms at the 2% cutoff level. [Table: see text] [Table: see text]