tbuckley/cabot-search huggingface dataset:
Expression of cell cycle, angiogenesis and metastases associated factors in osteosarcoma - immunohistochemical analysis of tissue array in 35 patients
Authors: W. Chen, M. He, S. Aisner, J. Benevenia, F. Patterson, M. Hameed
Journal: Journal of Clinical Oncology (2007)

10036 Background: Osteosarcoma is the most common, non-haemopoietic primary malignant tumor of bone. A variety of biological markers have been investigated for their prognostic value with variable results. This study is aimed to assess the prognostic and biological value of biological markers involved in cell cycle checkpoint regulation (p53 family, p16, and PTEN), cell adhesion, motility and invasion (ezrin and beta catenin), angiogenesis (VEGF and PlGF) in tumor samples of osteosarcoma patients. Methods: Thirty-five patients were chosen for the study (ages 6–74 years, median age - 15 years). Among them, 32 were high-grade conventional intramedullary osteosarcoma, and 3 were Paget osteosarcomas. Eight patients presented with metastases. Immunohistochemical analysis was performed on a tissue array of tumor samples with standard protocol. Clinical outcome was measured as events (metastasis or death), chemo-response (stage), and survival by multivariate analysis. Analysis also included our previous reported results of p53, p63 and p73. Results: Staining was assessed based upon semi-quantitative manual scoring. Appropriate staining (nuclear or cytoplasmic) of &gt;5% in tumor cells was considered as positive for all markers. The percentage positivity for the markers is as follows: p53 =29%, p63 =37%, p73= 9%, p16 =60%, PTEN=83%, ezrin =77%, beta catenin =91%, VEGF= 86% and PlGF =54%. There was no association of marker expression with specific subtype or location. Statistical analysis revealed no significant association between the positivity of these markers with clinical outcomes. Expression of ezrin was observed in all eight patients with metastases, although this finding did not approach statistical significance (P = 0.15). There was significant association between ezrin and P63 (P &lt; 0.05). Conclusions: 1. Expression of p53 family proteins, p16, PTEN, ezrin, beta catenin, VEGF, and PlGF are not significant predictors of clinical outcome in osteosarcoma patients. 2. Ezrin may be essential for osteosarcoma metastases. 3. No significant association between VEGF, PlGF and metastases. 4. The positive association between ezrin and P63 is interesting and need to be evaluated further. No significant financial relationships to disclose.
Cost associated with distant, contralateral, and local-regional breast cancer recurrence in a vertically integrated health care system
Authors: D. Wiederkehr, S. Kaura, N. Mody-Patel, A. Ogbonnaya, L. Stern
Journal: Journal of Clinical Oncology (2008)

1141 Background: Breast cancer is associated with considerable health care resource utilization and patients who experience recurrent breast cancer require more costly care than patients who do not develop recurrent disease. Research has also shown that the cost associated with a distant recurrence is significantly greater than the cost associated with a contralateral or local-regional recurrence. Distant metastasis has also been shown to account for the greatest number of breast cancer recurrence events early in the course of the disease (2–3 years after surgery). In this study we evaluated the cost associated with breast cancer recurrence in postmenopausal women diagnosed with breast cancer between 1995 and 2005. Methods: Using data from the Henry Ford Health System, patients who were at least 45 year old at the time of diagnosis without a stage IV or unknown tumor were identified and included in the study. Patients had at least one year of continuous enrollment and received at least one of the following treatments: surgery, chemotherapy, radiation, or hormone therapy. Total health care costs incurred after distant, contralateral or local-regional recurrence were calculated up to one year after breast cancer or death and presented as mean cost per month. Results: A total of 1,649 women met the inclusion criteria. The mean age was 61 years, and most patients had surgery (99%). Other subsequent treatments included radiation (71%), chemotherapy (27%), and hormone therapy (51%). Stage I tumors were the most common (38%). Of the 232 patients who experienced a recurrence, distant (44%) was more common than contralateral (23%) or local-regional (34%). On average, patients with distant, contralateral, and local-regional recurrence incurred cost for approximately 7, 12, and 11 months, respectively. The mean cost per month associated with distant recurrence ($37,969) was significantly greater than contralateral ($10,934) or local-regional ($9,129) (P< 0.0001). Conclusions: Distant metastasis is the primary cause for breast cancer deaths. This study finds that in postmenopausal women, the greatest number of breast cancer recurrences was distant, and these are associated with significantly higher cost of care compared to local-regional or contralateral recurrence. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis
An international, randomized, placebo-controlled, double-blind phase III study (MONET1) of motesanib plus carboplatin/paclitaxel (C/P) in patients with advanced nonsquamous non-small cell lung cancer (NSCLC).
Authors: G. Scagliotti, I. Vynnychenko, Y. Ichinose, K. Park, K. Kubota, F. H. Blackhall, R. Pirker, R. Galiulin, T. Ciuleanu, O. Sydorenko, M. Dediu, Z. Papai-Szekely, N. Martinez Banaclocha, S. McCoy, B. Yao, Y. J. Hei, D. R. Spigel
Journal: Journal of Clinical Oncology (2011)

LBA7512 Background: This study evaluated whether motesanib (a selective oral inhibitor of VEGFR 1, 2 and 3; PDGFR and Kit) plus C/P improved overall survival (OS) compared with placebo + C/P in patients (pts) with nonsquamous NSCLC and in a subset of pts with adenocarcinoma. Methods: Pts had stage IIIB/IV or recurrent nonsquamous NSCLC and no prior systemic therapy for advanced NSCLC. The study initially enrolled all histologies but was amended to exclude pts with squamous NSCLC owing to a high rate of hemoptysis. Pts were randomized 1:1 to receive up to six 3-wk cycles of C (AUC 6 mg/mL·min) and P (200 mg/m 2 ) with either motesanib 125 mg QD (Arm A) or placebo QD (Arm B) orally continuously. The primary endpoint was OS; secondary endpoints included progression-free survival (PFS), adverse events (AEs), objective response rate (ORR) and association between placental growth factor (PLGF) change and OS. OS was evaluated using a stratified Cox model and 2-sided log-rank test (α=0.03 for nonsquamous pts and α=0.02 for adenocarcinoma pts). Results: 1090 pts with nonsquamous NSCLC were randomized (Arm A/B, n=541/549); 890 had adenocarcinoma (n=448/442). 61% were men; median age was 60 years (range 21–87); 83% had stage IV disease. At the time of analysis, 753 pts had died (608 pts with adenocarcinoma). Median follow-up was 10.6 mo. OS was not significantly improved in Arm A compared with Arm B (Table). In Arm A, PLGF analysis did not show an association with OS. The incidence of grade ≥3 AEs in Arms A/B was 73/59%. Grade ≥3 AEs occurring more frequently in Arm A than B included neutropenia (22/15%), diarrhea (9/1%), hypertension (7/1%) and cholecystitis (3/0%). The incidence of grade 5 AEs was 14/9% in Arms A/B. Conclusions: In pts with advanced nonsquamous NSCLC, treatment with motesanib + C/P did not significantly improve OS compared with C/P alone. [Table: see text]
The role of cancer Nurse coordinator in foregut malignancy: Workload and costing considerations in the Australian setting
Authors: F. M. Wade, N. Pavlakis, I. Receveur, S. Leibman, G. S. Smith
Journal: Journal of Clinical Oncology (2009)

e20559 Background: Foregut (esophageal and gastric) malignancy (FM) encompasses a number of diseases with poor outlook and complex and often morbid treatment. In keeping with world wide trends, the investigation and management of patients with FM is undertaken in the context of a multidisciplinary group consisting medical, nursing and paramedical specialists. Crucial to the delivery of co-ordinated and compassionate care is the Cancer Nurse Co-ordinator (CNC). Further, the CNC is pivotal in ensuring that benchmarks regarding intervals from diagnosis, to multidisciplinary assessment to treatment commencement are met. The aim of this study was to quantify the workload of the CNC in a newly established esophagogastric surgical unit. Methods: Clinical data and data regarding workload of the CNC in our unit was recorded prospectively. Results: Of 218 patients with newly diagnosed FM referred to our unit between November 2005 and December 2008 198 (91%) were seen by the CNC. The number of cancers arising from the esophagus or esophagogastric junction was 135 (62%), stomach 78 (36%) and small bowel 5 (2%). The interval between CNC referral and initial contact was 4 days (range -13 to 40 days) and 89 (45%) patients were seen at the initial consultation with the surgeon. The mean number of CNC contacts with individual patients was 18 (range 1–76), comprising 9 (range 0–42) face to face consultations, 9 (range 0–58) telephone contacts and 0.2 (range 0–14) email contacts. Referrals to other support services were made for 164 (83%) patients with an average of 1 referral made per patient. This workload was carried out over 29 hours per fortnight at $43 AUD per hour. The average cost per patient with FM cared for by the CNC was $491 AUD ($349 USD). Conclusions: The complex care of patients with FM is augmented by the presence of a specialist CNC. The resource requirement for CNC funding is a small proportion on the costs of overall patient treatment and represents a prudent use of finite health care resources. No significant financial relationships to disclose.
Gene and surface-antigen expression profilings concordantly identify alpha4-integrin/CD49d as a marker for unmutated (UM) bad prognosis B-cell chronic lymphocytic leukemia (B-CLL)
Authors: V. Gattei, D. Benedetti, D. Marconi, M. Dal Bo, A. Zucchetto, G. Del Poeta, A. Steffan, R. Bomben, R. Campanini, M. Degan
Journal: Journal of Clinical Oncology (2006)

10076 Background: The highly heterogeneous clinical courses of B-CLL can be foreseen by investigating IgVH gene mutations or expression of specific prognosticators. Gene and surface-antigen expression profilings (GEP and SEP) have been both employed for identifying molecules of prognostic relevance in B-CLL. Methods: i) GEP - Purified B-CLL cells from 19 UM and 38 mutated (M) cases were investigated for differential GEP by using a two-color Operon Human Genome Oligo Set 2.1 platform with normal B cells as common reference and by applying, after data pre-processing, the LIMMA (Linear Model for MicroArray) package with two combined cutoffs (Bayesian log-odds&gt;1; adjusted p value for false discovery rate &lt;10e−4); ii) SEP - B-CLL cells from 60 UM and 101 M cases were investigated for the expression of 36 surface markers by flow cytometry. Results: i) GEP - 77 probes (32 duplicates) were overexpressed in M B-CLLs (UM/M log-ratio range −0.79/−3.62; p range 6.72e−5/3.6e−10) and 81 probes (46 duplicates) in UM B-CLLs (UM/M log-ratio range 0.87/4.57; p range 9.49e−5/3.01e−12); the CD49d gene was overexpressed in UM cases with UM/M log-ratio of 3.21 (p=8.3e-10). ii) SEP - Six markers significantly discriminated UM to M B-CLLs (t-test, p&lt;10ed-3) and separated most UM (49/60) from M B-CLLs by hierarchical clustering; among them, CD49d was significantly overexpressed in UM cases (median % positive cells 71.2±36 vs. 10.0±31; p=2.1e−10). By applying standardized log-rank statistics in 95 pts, all with CD49d expression and survival data, 30% of positive cells was judged optimal cutoff for identifying two groups with different survivals, 41 CD49dhigh pts showing worse prognosis than 54 CD49dlow cases (p=7.4×10e−5). Similarly, 46 UM B-CLLs had shorter survival than 77 M cases (p=1.4×10e−5). By combining IgVH mutations and CD49d expression, 42 concordant M/CD49dlow pts had better prognosis than 25 concordant UM/CD49dhigh cases (p=1.8×10e−5); noteworthy, among 28 discordant cases, 16 with a M/CD49dhigh phenotype had survival similar to bad prognosis cases. Conclusions: CD49d is a novel prognosticator for B-CLL. Given its high expression level in bad prognosis subsets, CD49d may be a promising therapeutic target. No significant financial relationships to disclose.
The poor prognostic significance of deletions of derivative chromosome 9 in Chinese patients with chronic myelogenous leukemia
Authors: J. Li, W. Xu, W. Wu, S. Zhang, Y. Zhu
Journal: Journal of Clinical Oncology (2007)

17535 Background: Chronic myeloid leukemia (CML) is characterized by formation of the BCR/ABL fusion gene, usually as a consequence of the Philadelphia (Ph) translocation between chromosomes 9 and 22. Deletions of the derivative 9 chromosome [der(9)] in 10- 15% of CML patients with a standard Ph translocation and in &gt;30% of CML patients with a variant Ph translocation. Subsequent studies demonstrated that CML patients who carry a der(9) deletion progress more rapidly to blast crisis and have a shorter survival than those without a deletion. The characteristics of Chinese patients with each hematologic malignancy compared with those in other countries have not yet been clarified. This prompted us to perform molecular and cytogenetic analyses on Chinese patients with CML. Methods: To study the incidence and the prognostic significance of the derivative chromosome 9 [der(9)] deletions in on Chinese patients with CML, a series of 48 BCR/ABL positive Chinese CML blast crisis (CML-BC) patients were investigated using dual colour dual fusion BCR/ABL probe and fluorescence in situ hybridization (FISH). Results: Eight (16.7%) cases showed der(9) deletions, and the deletions were also existed in chromosome preparations made at diagnosis. The estimated median length of chronic phase for patients with der(9) deletions was 18 months (range 4–38 months) compared to 48 months (range 0–204 months) for patients without deletions. Kaplan-Meier analysis revealed a striking difference in length of chronic phase between with and without der(9) deletions, and this difference was highly significant by log-rank analysis. Der(9) deletions are not associated with increased karyotypic instability. There was no difference in the probability of the der(9) deletions between the cases transformed to acute nonlymphocytic leukemia (ANLL) and those to acute lymphoid leukemia (ALL). Conclusions: The results indicate that FISH technique could effectively detect the der(9) deletions. Der(9) deletions occur at the time of Ph translocation. CML patients with der(9) deletions have more rapid process and poorer prognosis. Deletion status is a powerful prognostic factor for patients with CML. Der(9) deletions might not lead to transformation to specific type in CML. No significant financial relationships to disclose.
JAK2 V617F mutation positives in the general population.
Authors: S. E. Bojesen, C. Nielsen, H. Birgens, B. G. Nordestgaard, L. Kjaer, H. Hasselbalch
Journal: Journal of Clinical Oncology (2010)

6599 Background: The JAK2 V617F mutation is a somatic mutation in the JAK2 gene resulting in cell autonomuos overproduction of myeloid cells. The mutation is present in virtually all patients with polycythaemia vera and in about half of those with essential thrombocythaemia and primary myelofibrosis. However, its prevalence and clinical significance in the general population is unknown. We tested the hypotheses that the presence of the JAK2 V617F mutation in the general population is associated with early death, any cancer, haematological cancer, myeloproliferative neoplasm and thrombotic events. Methods: We screened for the presence of the mutation in participants (n = 10,507) of the Copenhagen City Heart Study with up to 17.6 years (mean = 12.5 years) of follow-up. Endpoints were collected in the Danish health registries. Hazard ratios of all endpoints were calculated by Cox proportional hazards regression analysis. Differences in cumulative incidence (per 10,000 person-years) of all endpoints were tested using log-rank statistics. Results: The 18 (0.2%) mutation positives vs. mutation negatives had a lower cumulative survival (log-rank, p = 0.00003) corresponding to an age- and sex-adjusted hazard ratio of early death of 2.87 (95% confidence interval: 1.78-4.64). Corresponding hazard ratios for any cancer, all haematological cancers and myeloproliferative neoplasms were 3.72 (1.72-8.01), 57.0 (14.9-218) and 161 (12-2197), respectively. Despite the huge risk estimates, 5 of the 18 did not develop any kind of cancer including myeloproliferative neoplasms during follow-up. Conclusions: JAK2 V617F mutation positives from the general population have increased mortality and morbidity, especialy from myeloproliferative neoplasms. No significant financial relationships to disclose.
Impact of number of resected and involved lymph nodes (LN) at the time of surgical resection on the survival of non-small cell lung cancer (NSCLC)
Authors: H. Saji, M. Tsuboi, K. Miyajima, Y. Shimada, T. Ohira, N. Ikeda
Journal: Journal of Clinical Oncology (2009)

7514 Background: Total number of lymph-nodes has recently proven prognostic in early breast and colorectal cancer. In this study we retrospectively evaluated the prognostic impact of the number of resected and involved lymph-nodes on the survival of stage I-III NSCLC. Methods: A series of 928 consecutive NSCLC pts who underwent complete lobectomy, bilobectomy or pneumonectomy with lymph-nodes dissection from 1/2000 to 11/2007 at Tokyo Medical University was eligible. Log rank and Cox proportional hazard model was used to estimate survival rates and relative risks. Results: Demographics are as follows: median age: 65.0 (22–87yrs), sex: 547 males and 381 females, median follow-up time: 2.5 yrs, clinical stage: 765 stage I, 84 stage II and 76 stage III, histology: 684 adenocarcinoma, 182 squamous cell carcinoma, and 62 others, operation: 870 lobectomy, 42 bilobectomy and 16 pneumonectomy, mean number of resected LN: 15 (1–49), mean number of involved LN: 0.9 (0–22). We observed a statistically significant increasing trend in overall survival (OS) between 0–3 and 4 and more of number of involved LN (P&lt;0.001). Although a significant increasing in OS of 0–9 of number of resected LN cases compared with 10 and more was observed in all stages (P=0.024), no significant differentiation was observed in clinical stage I cases. Conclusions: This data suggests that there is a significant decrease in OS with 10 and more number of resected LN examined at surgery in NSCLC pts. However, there is no significant different in stage I pts, which implies that selected LN sampling is enough in clinical stage I cases. Further study such as LN dissection vs LN sampling in clinical stage I will be needed. No significant financial relationships to disclose.
Preliminary results of a phase II trial of gefitinib in progressive metastatic neuroendocrine tumors (NET): A Phase II Consortium (P2C) study
Authors: T. J. Hobday, M. Mahoney, C. Erlichman, R. Lloyd, G. Kim, D. Mulkerin, J. Picus, T. Fitch, R. Donehower
Journal: Journal of Clinical Oncology (2005)

4083 Background: Metastatic NET (including islet cell carcinoma (ICC) and carcinoid tumors) are progressive in nature despite their indolent behavior. Systemic treatment options are limited. Immunohistochemichal (IHC) data suggest these tumors frequently express the epidermal growth factor receptor (EGFR). This suggests that EGFR mediated signaling may contribute to the growth of NET. Gefitinib is a small-molecule inhibitor of the EGFR tyrosine kinase domain. Methods: We evaluated 6 month progression-free survival (PFS) in two separate cohorts (ie, carcinoid and ICC) and using two separate Phase II trial designs. PFS rates at 6 months of 30% (carcinoid) and 10% (ICC) were considered promising. Importantly, objective radiologic progression by RECIST criteria was required for study entry. Other eligibility criteria included: ECOG PS ≤ 2, ≤ 1 prior chemotherapy, and good organ function. Prior or concurrent octreotide and prior interferon were allowed. Results: 37 patients (pts) were enrolled: (22 carcinoid, 15 ICC). There were 16, 20, and 1 patients with PS of 0, 1, and 2 respectively. Median age was 56 yrs (range 36–79). 14 of 22 (64%) pts with carcinoid tumors and 2 of 15 (13%) pts with ICC were progression-free at 6 months. No objective responses have been observed. Grade 3–4 toxicity (i.e. at least possibly related to gefinitib) was observed in 3 carcinoid pts including diarrhea (1), nausea (1), duodenal ulcer (1), anorexia (1), dehydration (1), fatigue (1), and rash (1);and 3 ICC pts including fatigue (1), hyperglycemia (1), and rash (1). IHC markers of the EGFR pathway on tumor tissue will be presented. Conclusion: Gefitinib can produce prolonged disease stabilization in pts with prior documented objective progression of carcinoid tumors and ICC. Further accrual to this multicenter P2C trial is ongoing. Supported by NOI CM17104. No significant financial relationships to disclose.
Airflow Limitation and Endothelial Dysfunction. Unrelated and Independent Predictors of Atherosclerosis
Authors: Divay Chandra, Aman Gupta, Patrick J. Strollo, Carl R. Fuhrman, Joseph K. Leader, Jessica Bon, William A. Slivka, Ali Hakim Shoushtari, Jennifer Avolio, Kevin E. Kip, Steven Reis, Frank C. Sciurba
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Lower FEV1 is associated with increased prevalence of atherosclerosis; however, causal mechanisms remain elusive.Objectives: To determine if systemic endothelial dysfunction mediates the association between reduced FEV1 and increased atherosclerosis.Methods: Brachial artery endothelial function, pulmonary function, coronary artery calcium, and carotid plaque were assessed in 231 Pittsburgh SCCOR (Specialized Centers for Clinically Oriented Research) study participants; peripheral arterial endothelial function, pulmonary function, and coronary artery calcium were assessed in 328 HeartSCORE (Heart Strategies Concentrating on Risk Evaluation) study participants.Measurements and Main Results: Lower FEV1 was independently associated with increased atherosclerosis in both cohorts (per 25% lower % predicted FEV1: odds ratio [OR], 1.76; 95% confidence interval [CI], 1.30–2.40; P < 0.001 for carotid plaque in SCCOR participants) (per 25% lower % predicted FEV1: OR, 1.35; 95% CI, 1.02–1.77; P = 0.03 for coronary artery calcium in HeartSCORE participants). Similarly, reduced endothelial function was independently associated with increased atherosclerosis in both cohorts (per SD lower endothelial function: OR, 1.30; 95% CI, 1.01–1.67; P = 0.04 for carotid plaque in SCCOR participants) (per SD lower endothelial function: OR, 1.38; 95% CI, 1.09–1.76; P = 0.008 and OR, 1.41; 95% CI, 1.07–1.86; P = 0.01 for coronary artery calcium in SCCOR and HeartSCORE participants, respectively). However, there was no association between endothelial dysfunction and FEV1, FEV1/FVC, low-attenuation area/visual emphysema, and diffusing capacity in SCCOR participants, and between endothelial dysfunction and FEV1 or FEV1/FVC in HeartSCORE participants (all P > 0.05). Adjusting the association between FEV1 and atherosclerosis for endothelial dysfunction had no impact.Conclusions: Endothelial dysfunction does not mediate the association between airflow limitation and atherosclerosis. Instead, airflow limitation and endothelial dysfunction seem to be unrelated and mutually independent predictors of atherosclerosis.