bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surrogate role of kinetic of perioperative circulating cancer cells (CTCs) in patients with liver metastases (M) of colorectal cancer (CRC).
Authors: Teijeira Lucia , Viudez Antonio , Antelo Maria L , Tarifa Antonio , Zazpe Cruz , Herrera Javier , Hernandez Irene , Vera Ruth 
Published: March 2020

e21086 Background: Kinetic behavior of perioperative CTCs in pts with liver CRC M has been little explored. The aim of this study was to quantified CTCs performance before/just performed and 3 months after radical liver surgery (LS) in pts with CRC M and analyzed the surrogate role of CTCs determinations in DFS and OS. Methods: 7.5 ml of blood were drawn in CellSave tubes. CTCs were isolated and enumerated before/just perfomed and 3 months after radical LS. CTCs were immunomagnetically separated and fluorescently labeled using the CellSearch System (Veridex®/Immunicon Corp.) Results: From February 2009 to December 2011, 35 pts were included. Median age was 61 (45-77); 53.7 % men. Kras status: 66.7% wild-type and 33.3% mutated; 48.6% with synchronous disease. Fong-Criteria (FC) distribution: 31.4% pts with 1 FC, 37.1% pts with 2 FC and 31.4% pts with 3 FC, of whom 60% received neoadjuvant (90% fluoropirimidines-based; 33.3% cetuximab-based; 38% bevacizumab-based) and 77.1% adjuvant treatment. PR and SD were observed in 60% and 40% of pts, respectively. In 70.7% of cases, limited LS were done (68.3% R0, median metastases resected:3) Of the 17 pts analysed, pCR were observed in 2 (12%) with 7 other pts (41%) with major pathological response. With a median of follow-up of 20 months (media 21.3; 95% CI:17.3-41.4) progression disease occurred in 13 pts (55.6% with liver progression), and 5 pts died. Median CTCs was 1 before (0-2: 76%; ≥3: 24%) and just performed surgery (0-2: 65%; ³3: 35%) and 0 in the 3 months determination (0-2: 94.1%; ³3: 5.9%). In the presurgery analysis, DFS was 15 months for the CTCs ≥3 group and 33 months for <3 CTCs (HR: 0.95; 95% CI:0.34-2.64) while in the postsurgery analysis, DFS was 13 months in CTCs ≥3 group and 33 months for <3 CTCs (HR: 1.11; 95% CI:0.37-3.29) CTCs ≥3 group after surgery, OS was 33 months, not having reached in the other groups. Conclusions: There is a marked difference in DFS in favor of pts with CTCs levels 0-2 before and just performed surgery. Our study shows a slight increase in CTCs quantification after LS, instead a significant CTCs decrease was observed after adjuvant therapy. Role of radical LS in kinetic of CTCs should continue to be analysed in future studies.
Development of a novel RT-PCR assay for the detection of EML4-ALK fusion products in FFPE speciments.
Authors: Papadopoulou Eirini , Murray Samuel , Nasioulas George 
Published: March 2020

e21087 Background: EML4-ALK is a fusion-type protein tyrosine kinase identified recently in a subset of human lung carcinomas and seems to be a promising candidate for a therapeutic target as well as for a diagnostic molecular marker in NSCLC. To date, several EML4-ALK variants have been identified in lung cancer samples. Three methods have been used for the detection of these fusions, including IHC, FISH, and RT-PCR, which is the only method that can distinguish between different variants. Existing RT-PCR methods, are designed to amplify large cDNA fragments and are inadequate for the analysis of formalin-fixed paraffin-embedded (FFPE) tissues which produce cDNA fragments of limited size. Thus, we designed an RT-PCR assay that can detect all published EML4-ALK variants and is suitable for use with this commonly available material. Methods: Synthetic DNA fragments for each variant were cloned using the pCR2.1 cloning vector and used as positive controls. Specific primers that enhance specifically EML4-ALK transcripts 1, 2, 3a, 3b, 4, 5a, 5b, 6, 7, "4", and "5" were designed. Detection of all EML4-ALK fusions was achieved using RT-PCR. DNA sequencing analysis was performed to confirm the specificity of the obtained PCR products. The sensitivity of the method was calculated by adding to 1μg RNA serial dilutions of the synthetic DNA fragments. It was found that up to 22 copies of the translocation can be detected per μg of RNA. The study included FFPE specimens from NSCLC patients without EGFR and K-RAS mutations. Pathological review was obtained for all samples and macro-dissection was used to ensure a tumor cell content of >75%. We are currently increasing our sample size of Greek patients and are in collaboration with other centers to further understand the clinical impact of the variant spectrum. Results: Three control EML4-ALK FISH positive samples were positively subtyped using RT-PCR and sequencing. None of the 96 FFPE specimens tested so far was positive for the EML4-ALK fusion. Conclusions: We designed a robust multiplex RT-PCR assay that permits the sensitive detection of all published EML4-ALK variants. It’s suitable for use with commonly available materials such as FFPE specimens, cytological specimens and other aspirates.
Association of core needle biopsies with increase in metastatic dissemination of breast cancer.
Authors: Giacomantonio Carman A. , Dean Cheryl A. , Mathenge Edward G. , Black Amber A. , Schulte Wendy , Pink Desmond B. , Marcato Paola , Lee Patrick W. , Zijlstra Andries , Lewis John D. 
Published: March 2020

e21090 Background: Given the reported association between incisional procedures performed on cancer patients and subsequent increases in metastasis, as well as the established inverse relationship between metastasis and patient survival, this study establishes the extent to which incisional core needle biopsies (CNB) affects tumor growth and metastatic dissemination in two distinct breast cancer animal models. Methods: Using the chick embryo system (CES) and murine breast cancer model (MuBC)the impact of CNB on cancer metastases was evaluated. Human MDA-MB-231 and MDA-MB-435 cancer cells were used in the xenograft / CES, and murine 4T1 Breast cancer cells for the syngeneic MuBC . In each model, tumors were biopsied in half of the animals while the other half were left undisturbed (CES:n=40, MuBC:n=40). The impact of CNB on tumor growth, necrosis and metastases was assessed. Metastases levels in the CES was determined by quantitative PCR for human alu sequence DNA in chick tissue extracts. Metastatic burden in the MuBC model was evaluated by microscopic quantification of metastatic areas in sectioned and H-E stained mouse organs. Results: When biopsied and un-biopsied groups were compared, both models showed significant difference in pulmonary metastasis. MDA-MB-435 CES (p=0.025) and 4T1 MuBC (p=0.026). MDA-MB-231 CES showed no significant change in lung metastases in the CES but did however show increased Chorioallantoic Membrane (CAM) metastasis (p=0.018) and both cell lines showed statistically significant alteration in Liver metastasis, (MDA-MB-231 CES (p=0.006); MDA-MB-435 CES (p=0.004)). Interestingly only MDA-MB-435 (CES) tumor growth was significantly increased after CNB (p=0.002). Conclusions: These results offer the first experimental evidence that core needle biopsies result in an increased risk of metastatic dissemination and affect metastatic tropic behavior. They also reinforce the concept of a multi-step metastatic pathway and suggest involvement of extrinsic factors that influence the extravastion and intravasation steps. The clinical implications are considerable and follow-up studies examining potential mechanisms and countermeasures are urgently required
Frequency of Hsa-miR9 aberrant methylation in metastatic breast cancers.
Authors: Parrella Paola , Florescu Anca , Copetti Massimiliano , Murgo Roberto , Valori Vanna Maria , Castelvetere Marina , Latiano Tiziana Pia , D'Addetta Carmela , Fazio Vito Michele , Maiello Evaristo 
Published: March 2020

e21092 Background: MicroRNAs (miRNAs) are a recently discovered class of very small non-coding RNAs involved in the regulation of gene expression by interfereing with mRNA translation. It has been shown that human miR-9 expression levels are reduced in breast cancer samples due to the aberrant methylation of its promoter region . Methods: We analyzed74breast cancer cases treated by surgery at the IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy. Pathological assessment included evaluation of histological type, grade and stage. Estrogen receptor (ER), progesterone receptor (PgR), Ki-67 labeling index and Her2 amplification were also evaluated. Six of the 74 patients showed metastases at the diagnosis, and 8 patients developed metastases during the follow up. The median follow up time for the patients cohort was 44 months (range 28-57+). All metastatic patients (n=14) died from the disease. Genomic DNA extracted from 6 normal breast tissues obtained by reductive mammoplasty, and tumour samples was subjected to bisulphite treatment and the converted DNA was used as a template for MSP using primers specific for the methylated hsa-miR9 sequence. Results: Methylation at the hsa-miR9 promoter region was detected in 33 of 74 (44%) breast tumours and none of the 6 normal breast tissues (p=0.02). Interestingly, hsa-miR9 methylation was significantly more frequent in patients with syncronous or metachronous distant metastases (8 of 14, 57%) as compared with patients free from metastases (11 of 33, 32%) (p=0.02 χ2 Test). In particular, methylation was detected in all 5 tumours showing only bone metastases (100%), whereas methylation was less frequent (33%) in the group characterized by the the presence of visceral metastases (P=0.03 χ2 Test). Conclusions: Our results suggest that hsa-miR9 methylation in breast cancer is associated with tumour metastatic behaviour and might represent a novel biomarker for monitoring breast cancer patients.
Systems biology in personalized medicine in oncology: A case study in non-small cell lung cancer.
Authors: Bianconi Fortunato , Perruccio Katia , Ludovini Vienna , Baldelli Elisa , Bellezza Guido , Flacco Antonella , Ragusa Mark , Valigi Paolo , Crinò Lucio 
Published: March 2020

e21096 Background: Systems biology together with translational oncology is a new approach to discover sensitive pathways in specific cancers. In this study, we propose a computational modeling technique to investigate the possible effects various alterations, such as protein overexpression, gene amplification or mutations, may have on signaling, through of the EGFR and IGF1R pathways, in non-small cell lung cancer (NSCLC). Methods: EGFR and IGF1R pathways and the downstream MAPK and PIK3 networks have been reproduced through a mathematical model. One hundred-twenty five tumors from surgical NSCLC patients were evaluated for EGFR and IGF1R protein expression, by immunohistochemistry (IHC) and gene amplification, by fluorescence in situ hybridization (FISH). KRAS mutations (exons 2 and 3) were evaluated by direct sequencing Results: To correlate EGFR and IGF1R expression levels, and KRAS mutations to tumor cell proliferation, we focused on the ERK signaling pathway, which plays a central role in several steps of cancer development including proliferation and cancer cell migration. The mathematical model predicts a relationship between a simultaneous high expression level of both receptors and a modification on ERK time behavior, implying a stronger attitude for cell proliferation. Furthermore KRAS activating mutations predict high level of active ERK and high probability to have cell proliferation. Cell growth can be closely related to disease progression and act, in survival analysis, as DFS estimator. Patients with concomitant IGF1R/EGFR FISH/IHC positivity had a worse DFS ( p=0.005). KRAS mutations have a statistically significant shorter DFS (p<0.001) as well Conclusions: We propose a Systems Biology approach, combined with Translational Oncology methodologies, to understand the interaction between EGFR, IGF1R and KRAS pathways in NSCLC. Computational model predictions confirm clinical evidences of survival analysis. Future work will validate our model with experiments on various NSCLC cell cultures and further investigate the response to drug administration. We thank AIRC and Fondazione Cassa di Risparmio for supporting the study.
Importance of the biologic effective dose in achieving local control of adrenal tumors treated with stereotactic radiosurgery.
Authors: Rai Hema , Desai Amishi , Witten Matthew R. , Haas Jonathan A. , Schneider Jeffrey Gary 
Published: March 2020

e21114 Background: Adrenalectomy achieves long term survival in ~ 25% of patients with solitary adrenal metastasis (SAM). Stereotactic radiosurgery (SRS) represents a potential non-surgical alternative to this same endpoint, but reported local control rates vary from 45% to 96%. SRS delivers a range of biologic effective doses (BED) dependent upon fraction size, number and schedule. We herein review our experience with SRS for adrenal metastasis to evaluate the interaction between BED and local adrenal tumor control. Methods: The Winthrop SRS data base was queried to identify 14 patients undergoing SRS for malignant adrenal tumors from 2006 to 2011. Patients were characterized by their primary tumor site, stage at diagnosis and the time to adrenal involvement. BED was calculated for each patient. Local adrenal tumor control and durability of response were also recorded. Results: Calculated BEDs ranged from 4,667 cGy to13,000 cGy. Of the factors examined, BED was the single most important predictor of local adrenal tumor control. According to best adrenal tumor response, mean BEDs were: 10,053 cGy for radiographic regression of disease; 8,115 cGy for stable disease, and 6,667 cGy for progression of disease (p = 0.0465, by one-tail test). No solid tumor patient responded to SRS with BED < 8,800 cGy and no patient immediately progressed through SRS with BED > 6,667 cGy. Duration of adrenal tumor control also correlated with calculated mean BED which was: 9,676 cGy for never locally failing (n=6) and 7,600 cGy for ever locally failing tumors (n=5). However, eventual local treatment failure was seen in one of three patients receiving even the highest calculated BED (13,000 cGy). Conclusions: Because eventual local failures are observed with SRS even at the highest examined BED, adrenalectomy rather than SRS should remain the standard of care for patients with potentially curable SAM. SRS remains an acceptable alternative to adrenalectomy for palliation of symptomatic adrenal tumors or for the definitive treatment of SAM in non-surgical candidates. When given for these purposes, our data support the use of SRS regimens delivering a minimum BED of 8,800 cGy.
Role of FDG-PET as predictive biomarker of pathologic complete response (pCR) in locally advanced rectal cancer (LARC) treated with capecitabine-based neoadjuvant chemoradiation (NACR).
Authors: Pietrantonio Filippo , Di Bartolomeo Maria , Bampo Chiara , Valvo Francesca , Alessi Alessandra , Crippa Flavio , Biondani Pamela , Leo Ermanno , Milione Massimo , Dotti Katia F , Fantini Simona , Avuzzi Barbara , Formisano Barbara , Battaglia Luigi , Chiruzzi Chiara , De Braud Filippo G. 
Published: March 2020

e21118 Background: A favourable outcome is associated with pCR in LARC treated with NACR; pCR prediction through functional imaging may help the prospective evaluation of management strategies alternative to standard surgery. The aim of this prospective study was to identify whether FDG-PET activity and early/late response predicted independently pCR. Methods: Patients with histologically diagnosed cT3-4 and/or N+ primary rectal cancer were treated homogeneously with NACR (simultaneous boost technique radiotherapy 54 Gy on GTV/24 fractions plus capecitabine 1650 mg/mq/day) and total mesorectal excision 7-8 weeks later. FDG-PET uptake, expressed as maximum standardized uptake value, was obtained at baseline (SUV-1), at interim (2 weeks after treatment start: SUV-2) and 6 weeks after NARC completion (SUV-3) and was calculated as percentage difference (Δ-SUV). The role of SUV-1, SUV-2, SUV-3, Δ-SUV(1-2) and Δ-SUV(1-3) for pCR prediction was assessed using logistic regression analysis; ROC analysis was performed to identify the optimal thresholds. Results: The study enrolled 30 pts (median age 59 yrs; 12M:18F) treated from January 2009 to November 2011 at Istituto Nazionale Tumori of Milan. All underwent FDG-PET at baseline and post-NACR and 80% consented to an interim assessment; one patient was excluded due to surgery refusal. pCR rate was 28%. Among all parameters, only post-NACR SUV (mean 4 +/- 1.7 for pCR vs 8.7 +/-5.8 for non-pCR; P=0.001 by Mann-Whitney test) showed significant association with pCR at univariate analysis (P=0.03). At multivariate analysis including baseline SUV, post-NACR SUV, Δ-SUV, age (≤ or >65 yrs), sex (F or M) and pre-treatment stage (N- or N+/cT3 or cT4), only female sex and post-NACR SUV predicted independently pCR (both P=0.01). With ROC analysis, a post-NACR SUV threshold <5.5 had 88% sensitivity and 81% specificity, with 83% overall accuracy. Conclusions: The SUV cut-off of 5.5, explained by inflammatory modifications, could limit the applicability in clinical practice assuming values ≤2.5 for negativity. However, FDG-PET SUV post-NACR may serve as useful predictive biomarker in LARC.
A review of clinicopathologic characteristics, therapy, and outcomes of 22 patients with aggressive B-cell lymphoma.
Authors: Jaglal Michael , Peker Deniz , Bello Celeste M. , Shah Bijal D. , Sokol Lubomir , Zhang Ling , Sotomayor Eduardo M. , Tao Jianguo , Cultrera Jennifer L. 
Published: March 2020

e21123 Background: B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma (BL) or Burkitt like lymphoma is a high grade lymphoma that is associated with a high proliferation index and a complex karyotype mostly involving MYC and BCL-2 genes, so called “double hit” as well as BCL-6 or CYCLIND1 genes, so called “triple hit”. This high grade lymphoma shows an aggressive behavior for which the most appropriate therapeutic approach is yet to be established. Methods: This was a single center retrospective review of pts with a confirmed diagnosis of B cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL from 2006 to 2011. The definitive diagnosis in all cases was based on morphological and phenotypic features, and genetic abnormalities involving MYC, BCL-2, BCL-6, and or CYCLIND1. Clinicopathological data was extracted including age, gender, primary disease location, phenotypic subtype, genetic abnormalities by FISH, IPI scores, treatment regimens and survival data . Descriptive statistical analyses were utilized. Kaplan-Meier method was used to estimate OS and log rank test was used to compare the groups. All data were analyzed using SPSS version 20.0 statistical software. Results: 22 pts with &quot;Double or Triple Hit&quot; lymphomas were identified between 2006 and 2011. The age range at diagnosis was 33-87 years with median age of 66. 16 of 22 pts (73%) were ≥ 60 years old. Male to female ratio was 1.75 :1 (14:8). The median ECOG PS was 1. No pts had HIV. A majority of pts presented with extranodal disease 17 with only 5 pts presenting with nodal disease. The median survival of the entire cohort was 9 months with ranges 32 to 2 months. 16 of 22 pts (73%) are currently alive. In the cohort of pts that are currently alive, 10 was treated with RCHOP and 6 with RHyperCVAD. Pts who presented with CNS disease had a worse prognosis when compared to the entire cohort with a median overall survival of 6.5 months (p=0.016). Conclusions: RCHOP was the most utilized treatment regimen in the cohort of alive patients. CNS disease is associated with worse prognosis in patients with &quot;Double or Triple Hit&quot; lymphomas.
Prognostic significance of MAGE-A10 and NY-ESO-1 cancer-testis antigen in breast cancer.
Authors: Badovinac Crnjevic Tanja , Jakic Razumovic Jasminka , Spagnoli Giulio C , Podolski Paula , Saric Nera , Basic Koretic Martina , Juretic Antonio 
Published: March 2020

e21126 Background: Cancer testis antigens (CTAs) are expressed in a variety of malignant tumors. In normal adult tissues CTA expression is restricted predominantly to germs cells of the adult testis and placenta. Based on their tumor-restricted expression pattern, CTAs are regarded as valuable targets for cancer immunotherapy. The prognostic significance of CTAs in breast cancer has not been analyzed previously. Methods: To evaluate the potential prognostic significance of two member of this family, MAGE-A10 and NY-ESO-1 antigens, we examined their expression in breast cancer patients who underwent curative surgery at our hospital between 2002 and 2003. Paraffin embedded tumor sections were collected retrospectively from 165 breast cancer patients and immunohistochemical staining for MAGE-A10 and NY-ESO-1 was performed. Impact of MAGE-A10 and NY-ESO-1 expression on disease free survival (DFS) and overall survival (OS) was analyzed by the Kaplan-Meier method using 8-year follow up data. Results: MAGE-A10 expression (score ≥2+) was detected in 105/164 (64%) and NY-ESO-1 expression (score ≥2+) was observed in 14/164 (8.5%) patients. 8-year DFS for MAGE-A10 positive patients was 69% and 73% for MAGE-A10 negative (p=0.452). 8-year OS for MAGE-A10 positive patients was 80% and 90% for MAGE-A10 negative (p=0.134). For NY-ESO-1 positive patients 8-year DFS was 67% and 70% for NY-ESO-1 negative patients (p=0.837). 8-year OS for NY-ESO-1 positive patients was 83% and 84% for NY-ESO-1 negative patients. (p=0.991) Conclusions: To our knowledge this is the first study analyzing prognostic significance CTAs in breast cancer. In this retrospective study we did not show statistically significant correlation between MAGE-A10 and NY-ESO-1 expression and clinical outcome. Additional studies are warranted to determine weather this antigens might have prognostic value in breast cancer patients.
Study evaluating possible causes of the normal variant 18F-FDG uptake in the thoracic spinal cord in patients without CNS malignancy.
Authors: Bhatt Geetika , Li Xiao-Feng , Sharma Vivek R. , Bhatt Aashish D. , Cambon Alex , Rai Shesh , Civelek Ali Cahid 
Published: March 2020

e21144 Background: Focal increased lower thoracic spinal cord 18F-FDG uptake is not infrequently observed and may be confused for spinal cord metastases. The cause of this physiological uptake is indeterminate though various theories have been postulated. We hypothesized that there may be a correlation between the thoracic (T11-T12) spinal uptake and lower limb movements or to bowel FDG activity. In the absence of paired FDG PET studies in same patients with and without leg movements we correlated the FDG uptake of the lower thoracic cord in ambulatory to that in bedridden patients. Methods: Sixty-three consecutive patients (12 bedridden) with 18F- FDG PET-CT with no known evidence of spinal cord or bony spine metastases were included. The SUV max/avg values of the liver, Thoracic: T11-T12 and Cervical: C3-C5 spinal cord segments and the bowel FDG activities of the ambulatory and bedridden patients were determined and compared. Statistical analysis was performed to evaluate various factors predictive of increased spinal cord FDG uptake. Results: Median age was 54 years (18- 93). Primary tumor histology was lung (21.8%), breast (9.3%), melanoma (15.6 %) and lymphomas (21.8%). The mean SUV max/avg values were liver (2.89/2.43); Thoracic cord (2.46/1.89); Cervical cord (2.25/1.82) and Bowel (4.4/2.9). Visible 18F-FDG thoracic spinal uptake was seen in 28%. Our analysis showed no significant correlation between the ambulatory status (p=0.219) or bowel FDG activity (p=0.210) and T11-T12 cord uptake. Conclusions: Although of no significance in this study, there might be a correlation between limb movements (amongst other factors) and physiological FDG uptake in the lower T-spine which warrants further dual studies in the same patient with and without leg motion. This may also help in differentiating normal variant spinal cord uptake from spinal cord metastatic lesions. [Table: see text]