bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation of FOXA1 expression with Oncotype Dx recurrence scores
Authors: Ademuyiwa F. O. , Thorat M. , Nakshatri H. , Badve S. 
Published: August 2020

11058 Background: Oncotype Dx assay (ODX) is a diagnostic assay that predicts the benefit of chemotherapy and assesses the likelihood of breast cancer (BC) recurrence in patients with estrogen receptor (ER) positive BC. The forkhead-box A1 (FOXA1) transcription factor is linked to ER regulated gene transcription and its expression is associated with ER positive luminal A type BC. Since higher FOXA1 expression is associated with ER positive luminal A BC, we investigated whether FOXA1 expression levels show a correlation with ODX recurrence scores in BC patients. Methods: 120 cases of BC from IU and affiliated hospitals had ODX performed on tumor blocks. 78 patient tumor blocks with ODX recurrence score have been analyzed for FOXA1 using IHC. FOXA1 expression was measured using intensity X percentage scoring. The correlation of FOXA1 scores and ODX recurrence scores with each other and with other variables was examined. Other variables included age, progesterone receptor (PR) status, tumor size, grade, histological type, and race. All p values are two-sided and have been adjusted for multiple comparisons using Bonferroni-Holm's method. Results: Twenty-one of 78 cases analyzed were < 50 years. ODX recurrence scores were low, intermediate, and high in 55.1%, 32.1%, and 12.8% of cases, respectively. Ductal carcinomas accounted for 73.1% of tumors, while 11.5% were lobular. Fifty percent of tumors were histologic grade II, 37% and 13% were grade I and III, respectively. PR was negative in 9 cases. Caucasians accounted for 78.2% of cases vs 7.7% African-Americans. FOXA1 expression correlated negatively with ODX recurrence score (p=.003), and histologic type (p=.024). ODX recurrence score also correlated negatively with PR (p=.034) with 78% of the PR negative cases having a high or intermediate ODX score. The correlation between FOXA1 expression and ODX recurrence score remained significant after adjusting for multiple comparisons and controlling for confounders such as histological type, grade, and PR. Conclusions: We demonstrate that FOXA1 expression has an inverse correlation with ODX recurrence scores. FOXA1 expression can potentially be used as a prognostic marker in low risk ER positive BC patients who lack access to ODX assays. This observation needs to be confirmed with a larger sample size. No significant financial relationships to disclose.
FL-DNA approach for noninvasive early diagnosis of colorectal cancer in FOBT-screened patients
Authors: Calistri D. , Rengucci C. , Casadei-Gardini A. , Scarpi E. , Zoli W. , Falcini F. , Milandri C. , Amadori D. , Silvestrini R. 
Published: August 2020

11062 Background: A promising approach for the early diagnosis of colorectal cancer (CRC) is the evaluation of genomic DNA integrity (FL-DNA) extracted from stool. Pilot and confirmatory studies carried out by our group have shown that, thanks to its diagnostic accuracy, this molecular assay could be a useful tool for the non-invasive, early diagnosis of CRC. The aim of the present study was to verify whether the FL-DNA method could represent a valid alternative to the fecal occult blood test (FOBT) or whether it could be used alongside FOBT in screening programs to unmask false FOBT positives and spare patients from unnecessary colonoscopy. For this purpose, stool samples were collected from all individuals participating in the FOBT (OC-Sensor, Alpha Wassermann) Regional Screening Program run by the Cancer Prevention Unit of Morgagni-Pierantoni Hospital in Forli. Methods: The program recruited subjects of either sex aged 50 to 69 years. Of the 560 individuals with FOBT-positive stool subjected to colonoscopy, 26 were diagnosed with adenocarcinoma, 264 with high-grade adenoma and 54 with low-grade adenoma. More than one third (216) of the group had only benign disease (hemorrhoids, diverticulitis, inflammation, etc), hyperplastic polyps or nothing. The integrity of fecal DNA was analyzed blindly by the FL-DNA test on the same specimen used for the occult blood determination. Results: Using a cut-off of 10 ng, the molecular analysis detected over 90% of the colorectal cancers and about 50% of the high- and low-grade adenomas. In particular, diagnostic accuracy was similar for lesions of any localization, level of dysplasia and histopathological characteristic, and higher for lesions > 2 cm and multiple lesions. The test also confirmed its capacity to identify colorectal cancer in asymptomatic individuals. Conclusions: FL-DNA represents a valid alternative to or support for approaches currently used in screening programs. A more in depth DNA stool evaluation in negative FOBT individuals could reveal the test's usefulness in unmasking colorectal tumors and adenomas missed by FOBT. No significant financial relationships to disclose.
Evaluation of a gene signature to predict single agent dacetuzumab (SGN-40) activity in patients with DLBCL
Authors: Advani R. , Burington B. , Shi X. , de Vos S. , Ansell S. , Forero-Torres A. , Ebens A. , Whiting N. , Dornan D. 
Published: August 2020

11063 Background: Dacetuzumab (SGN-40) is a humanized IgG1 monoclonal antibody that binds to CD40, mediates effector cell functions, and activates downstream apoptosis signaling pathways. Dacetuzumab has shown single-agent activity in relapsed/refractory DLBCL in phase I and phase II trials, with multiple objective responses and 1/3 of patients demonstrating tumor shrinkage, defined as a decrease in tumor volume (SPD) of at least 10%. We previously reported a 14-gene signature (ASH 2008 #1593) that was strongly associated with dacetuzumab sensitivity in DLBCL cell lines. Here, we report an initial evaluation of the gene signature as a classifier of patients likely to demonstrate tumor shrinkage after dacetuzumab therapy. Methods: The original 14 microarray probes were chosen for high correlation with in vitro dacetuzumab sensitivity (IC25) in 31 NHL cell line models. Matching qRT-PCR probes were developed and confirmed to correlate with the microarray probes in paired cell line samples. In this retrospective analysis, archived paraffin blocks from a 26 patient subset of the phase I and II trials, with a diagnosis of DLBCL and available tumor measurements, were assayed by qRT-PCR. Results: Overall, 42% of patients (11/26) exhibited decreased SPD of at least 10%. Of those who were marker +, 10 out of 13 (78%) had 10% or better decreases in SPD, whereas only 1 of 13 patients who were marker - demonstrated tumor shrinkage (8%). The overall accuracy for predicting tumor shrinkage was 85% (one-sided P=0.002, by permutation test). Among the 14 genes contributing to the multivariate signature, CD22 and VNN2 were the most strongly down-regulated in specimens from patients without at least a 10% decrease in SPD (P=0.14 and P=0.10, respectively), while IGF1R and CTSC were the most strongly up-regulated (P=0.05 and P=0.08, respectively). Conclusions: A 14-gene signature appears to predict tumor shrinkage in DLBCL patients receiving dacetuzumab in single-agent clinical trials (P=0.002). A larger clinical data set will be analyzed to further evaluate the correlation of this gene signature with objective clinical response rates.. [Table: see text]
Circulating tumor cells (CTCs) and endothelial cells (CECs) in primary lung cancer
Authors: Tanaka F. , Yoneda K. , Hashimoto M. , Takuwa T. , Matsumoto S. , Okumura Y. , Kondo N. , Hasegawa S. , Fukuoka K. , Nakano T. 
Published: August 2020

11066 Background: Circulating tumor cell (CTC), a surrogate of distant metastasis, and circulating endothelia cell (CEC), a surrogate of angiogenesis, are potentially useful in the diagnosis of malignant tumors, but clinical significance of CTC/CEC in primary lung cancer (LC) remains unclear. Methods: A total of 342 cases who presented at our institute from August 2007 through December 2008 were included in the study. CTC/CEC in the peripheral blood (7.5mL/4.0mL) were captured and quantitatively evaluated with the “CellSearch” system without knowledge of clinical characteristics of each case. Results: In 42 (30.7%) of 137 LC cases, CTC in the peripheral blood was positive (CTC-count, more than 1 cell/7.5mL), and the maximum CTC-count was 62 cells. In 11 (18.3%) of 145 cases with non-malignant (NM) diseases, CTC was also positive; however, in NM cases, CTC-count was 1 (cell/7.5mL) in most CTC-positive cases and the maximun CTC-count was 2. Among LC cases, the incidence of case with CTC-positive (CTC-count, 1 or more) was highest in small cell carcinoma cases (7/10, 70.0%), followed by squamous cell carcinoma (9/22, 40.9%) and adenocarcinoma (23/94, 24.5%) cases; the incidence of CTC-positive case was significantly higher in stage IV cases (68.6%; p<0.001), but it should be noted that CTC was positive in 17.4% of stage I cases and 15.4% of stage II cases. The mean CEC number (/4.0mL) was significantly higher in LC cases than in NM cases (97.5 versus 52.5, respectively; p=0.023), Among LC cases, the mean CEC significantly increased along with tumor progression (mean CEC for stage I, II, III, and IV cases: 58.7, 57.9, 83.4, and 178.4, respectively; p=0.002). Conclusions: CTC and CEC are useful clinical markers in LC, and its clinical value should be validated in future clinical trials. [Table: see text] No significant financial relationships to disclose.
Microfluidic device for circulating tumor cell sorting, characterization, and culture
Authors: Saliba A. , Saias L. , Bidard F. , Mathiot C. , Saada V. , Farace F. , Vielh P. , Pierga J. , Viovy J. 
Published: August 2020

11068 Background: Circulating tumor cell (CTC) analysis is a promising approach to further characterize the tumor biology and the metastatic process, but has immediate clinical applications such as early predictive markers of response to chemotherapy. However, the devices that are used currently for CTC detection have a poor sensitivity. Microfluidic techniques offer new exciting perspectives in the field of cell sorting for CTC analysis. Methods: We propose here a new microfluidic system and strategy allowing the sorting of cells, their study by confoncal fluorescent microscopy and/or their subsequent culture. The core of our system is a self-organized array of superparamagnetic particles in a microchannel, allowing for the formation of a perfectly periodic and robust array. The superparamagnetic particles are coated with specific antibodies against surface antigens, in order to capture cells according to specific biomarkers. This original cell-separation microchip was integrated into a fully automated platform combining state-of-the-art microfluidic technologies, microvalves and nanofluidic pneumatic pumps. Results: Using B and T lymphocytes mixtures as a model biological system, the capture yield was better than 90%, and the specificity better than 97%. Captured cells were fully viable and were cultured in situ in the magnetic array. In clinics, immunophenotyping of circulating malignant B cells was performed using fluorescent confocal microscopy, and was successfully compared to flow cytometry data for each sample. Results on breast cancer cells will be presented at the meeting. Conclusions: This new system is a promising approach for efficient CTC sorting, analysis and culture in a completely integrated manner. No significant financial relationships to disclose.
Phase I evaluation of lapatinib (L) and epirubicin (E) in patients (pts) with anthracycline (anth)-naive metastatic breast cancer (MBC)
Authors: O'Connor R. A. , Kennedy M. J. , McDermott S. R. , Tryfanopoulos D. , McCreery C. , Collins D. , Martynyuk O. , Gethins R. , Moulton B. , Crown J. 
Published: August 2020

1107 Background: HER-2 alteration confers enhanced anth sensitivity in MBC, although HER-2 is not a target for anth. Topoisomerase 2A (Topo) is a target for anth. Topo amplification has been reported to occur only with HER-2 amplification, in approximately 1/3 of HER-2 amplified BC, providing a rationale for anth + trastuzumab(H) therapy in MBC with co-ampified HER-2/Topo. T+anth is cardiotoxic. L may have similar single agent activity, but less cardiotoxicity than H. L competes with anth for p-glycoprotein and might enhance its activity. The cardiac safety of L + anth needed to be established. Methods: We conducted a phase I evaluation of fixed dose lapatinib (1250 mg/day) with escalating doses of epirubicin (Epi-planned dose levels I-IV :75/80/90/100 mg/m2 ) in pts with HER-2±, anth-naive metastatic BC. Epirubicin was administered q3 weeks. A minimum of 3 (if no dose-limiting toxicity) and a maximum of 6 pts were treated per dose level. Ejection fractions were performed at base line and after every second cycle; BNP and troponin after every cycle. Results: 9 pts were treated, 3 level I, 6 level II. Dose level I was declared the maximum tolerated dose following two occurrences of dose-limiting toxicity in level II. 1 pt experienced febrile neutropenia,1 had > 20% decrease in LVEF. To date there have been 3 PRs by RECIST out of 8 evaluable patients which represents a response rate of 37.5%. Conclusions: Using classic phase I criteria, the combination of L 1250 mg together with Epi 75 mg/m2 combination is relatively well tolerated and suitable for further investigation in a phase II study of HER-2+veTopo+ve MBC patients. We will conduct such a study in pts with HER-2+Topo+ metastatic BC. [Table: see text]
Unknown primary cancer (UPC): Accuracy of tissue of origin prediction by molecular profiling
Authors: Greco F. A. , Spigel D. R. , Yardley D. A. , Erlander M. , Ma X. , Hainsworth J. D. 
Published: August 2020

11070 Background: Molecular profiling may be useful to identify the primary site and direct therapy for patients (pts) with UPC. Since most UPC pts never have a primary site identified, the accuracy of molecular profiling diagnoses are difficult to verify. We identified a group of UPC pts who had a primary site subsequently identified during their clinical course, and performed a 92-gene real time polymerase chain reaction (RT-PCR) assay (Arch Pathol Lab Med 130:465, 2006) on tissue from the initial diagnostic biopsy. We then compared the RT-PCR diagnosis with the subsequent clinical diagnosis. Methods: 38 of 501 UPC pts (7%) seen between 2000 and 2008 had their primary tumor subsequently identified during life. 24 of the 38 pts had tissue biopsies (excluding FNA cytology) and are the subject of this study. The RT-PCR assay was performed on unstained slides from the formalin-fixed, paraffin-embedded (FFPE) initial diagnostic biopsy, and the assay predictions were compared to the actual primary sites (found later). No clinical or pathologic data (other than sex, biopsy site, and 1 H&E stained slide) were used in the prediction of the primary site. Results: 16 of 24 assays were successful (8 had no tumor or RNA in the material). 11 of 16 predictions of the site of origin (68%) were correct, corresponding to the actual primary sites found 3–58 months (median 8.5 months) after the initial diagnosis of UPC. Primary sites correctly identified included breast 2, ovary/peritoneal 4, NSCLC 1, colorectal 2, gastric 1, melanoma 1. 3 predictions were inaccurate (colorectal, testicular, sarcoma) in patients with gastroesophageal, pancreas and NSCLC, respectively. 2 assays were unclassifiable. Conclusions: RT-PCR performed on FFPE initial diagnostic tissue was accurate in predicting the primary site of origin in 11 of 16 pts with UPC who eventually had their primary site identified clinically. These data provide a direct validation of the reliability of this RT-PCR assay in predicting the primary site in pts with UPC. When used in concert with clinical features and IHC stains, molecular profiling may provide the basis for more successful site-directed therapy for many of these pts. Prospective studies of RT-PCR in UPC are ongoing. [Table: see text]
Early assessment of response to aromatase inhibitor (AI) therapy
Authors: Linden H. M. , Kurland B. F. , Livingston R. B. , Ellis G. K. , Gadi V. K. , Specht J. M. , Gralow J. R. , Mankoff D. A. , Peterson L. M. , Schubert E. K. 
Published: August 2020

11075 Background: Early decline in proliferative index (Ki-67) predicts response to endocrine therapy. For estrogen receptor positive (ER+) tumors, a low Ki-67 two weeks into endocrine therapy also predicts response (Dowsett JNCI 2007). FDG PET is promising for evaluating early response to systemic therapy and has the advantage of being non-invasive and of providing simultaneous quantitative measures at multiple tumor sites in vivo. We tested the association between FDG PET SUV and Ki-67 after two weeks of aromatase inhibitor (AI) therapy, and their prediction of response. Methods: Patients undergoing AI therapy were eligible for enrollment in the imaging study, and underwent a two week “run-in” of AI monotherapy prior to continued monotherapy or the addition of chemotherapy. Patients underwent baseline FDG PET, and Ki-67 was measured in tumor biopsy specimens. Following two weeks of therapy FDG PET and biopsy were again performed. Patients on AI therapy only were followed for clinical response. Results: A total of 21 patients enrolled in the study. 16/21 (76%) of patients had a greater than 20% decline in FDG SUV, including 11 with analyzable serial biopsy, all with 2-week Ki67 ≤5%. Of the 5 patients who did not show greater than 20% decline in FDG SUV, all 3 with serial biopsy had 2-week Ki67 of ≥20%. Subsequent response to AI was evaluable at 4–6 months in 8 patients who underwent AI monotherapy (5 R, 3 PD). All 5 responders showed decline of at least 20% in FDG SUV (30% - 60% decline), and 2/3 with PD did not (no change, 3% decline, 29% decline). Conclusions: We observed substantial changes in Ki-67 and FDG SUV following 2 W of targeted therapy. Decline in FDG SUV in patients on single agent AI predicted response in almost all cases. Serial FDG PET appears promising as an early indicator of response to AI therapy. No significant financial relationships to disclose.
Use of CXCR4 as a prognostic marker for disease-specific survival and pattern of recurrence following resection of hepatic colorectal metastases
Authors: Yopp A. C. , Shia J. , Allen P. J. , DeMatteo R. P. , Jarnagin W. R. , Fong Y. , Blumgart L. , D'Angelica M. I. 
Published: August 2020

11081 Background: Expression of the chemokine receptors CXCR4 and CCR7 has been associated with metastases and poor prognosis in primary tumors but their relevance in colorectal liver metastases (CLM) is unclear. This study examines the relationship between tumor chemokine receptor expression, pattern of recurrence and outcome after resection of hepatic metastases.Methods: Eighty patients with metastases from colon or rectal primary tumors who underwent a R0 partial hepatectomy from February 2002 to April 2004 were studied prospectively. Immunohistochemical staining was performed on the formalin-fixed, paraffin-embedded tissues of hepatic metastases using antibodies specific for CXCR4, CXCL12 and CCR7. The correlation between the CXCR4, CXCL12 and CCR7 expression and clinicopathological factors was evaluated.Results: Median follow-up was 42.9 months. Positive expression of CXCR4, CXCL12 and CCR7 was seen in 49 (61%), 23 (29%) and 48 (60%) of tumor specimens, respectively. Clinical risk score greater than 2 and high CXCR4 expression were associated with a shorter disease-specific survival (DSS) and a reduced recurrence-free survival (RFS) following partial hepatectomy for CLM (p<0.05) by multivariate analysis. CCR7 and CXCL12 expression, hepatic artery infusion pump chemotherapy, systemic chemotherapy and site of primary disease did not influence DSS or RFS. Fifty-three (68%) of the patients recurred; 11 with liver only recurrences, 25 with lung only recurrences and 18 with multiple sites of recurrences. High expression of CXCR4 is associated with widespread multiple sites of recurrence ( Table ).Conclusions: CXCR4 expression in colorectal hepatic metastases adds prognostic information with regards to DSS, RFS and patterns of recurrence and may play role in clinical decision making regarding chemotherapy and surgical interventions. CXCR4 expression may also provide additional prognostic information beyond the already validated clinical risk score. [Table: see text] No significant financial relationships to disclose.
Influence of inflammation-based prognostic score on mortality of patients undergoing chemotherapy for far advanced or recurrent unresectable colorectal cancer
Authors: Ishizuka M. , Nagata H. , Takagi K. , Kubota K. 
Published: August 2020

11084 Background: Recent studies have revealed that the Glasgow prognostic score (GPS), an inflammation-based prognostic score that includes only C-reactive protein (CRP) and albumin, is a useful tool for predicting postoperative outcome in cancer patients. However, few studies have investigated the GPS in patients undergoing chemotherapy for far advanced or recurrent unresectable colorectal cancer (AR-UCRC). Objective: To demonstrate the influence of the GPS for prognostication of patients undergoing chemotherapy for AR-UCRC. Methods: The GPS was calculated as follows: patients with both an elevated level of CRP (>1.0 mg/dl) and hypoalbuminemia (<3.5 g/dl) were allocated a score of 2, and patients showing one or none of these blood chemistry abnormalities were allocated a score of 1 or 0, respectively. Results: One hundred twelve patients who had undergone chemotherapy for AR-UCRC with regimens such as such as FOLFIRI (5-fluorouracil [5-FU]/l-leucovorin [LV]/irinotecan hydrochloride [CPT-11]) or FOLFOX (5-FU/LV/oxialiplatin [L-OHP]) were evaluated retrospectively. Kaplan-Meier analysis and log rank test revealed that GPS2 predicted a higher risk of mortality than GPS0 or 1 (P <0.0001). Univariate analyses revealed that the neutrophil ratio (P = 0.0411), CA19–9 (P = 0.0473), CRP (P = 0.0477), albumin (P = 0.0043) and GPS (0,1/2) (P < 0.0001) were associated with mortality. Multivariate analyses using these five factors revealed that only GPS (0,1/2) (odds ratio, 6.071; 95% C.I., 1.625–22.68; P = 0.0073) was an independent risk factor of mortality. Conclusions: GPS is considered the most important and independent predictor of mortality in patients undergoing chemotherapy for AR-UCRC. No significant financial relationships to disclose.