tbuckley/cabot-search huggingface dataset:
Predictive factors of residual tumor for the patients with non-curative resection after endoscopic submucosal dissection for early gastric cancer.
Authors: Hideki Sunagawa, Takahiro Kinoshita, Akio Kaito, Kazuhiro Kaneko
Journal: Journal of Clinical Oncology (2017)

32 Background: Endoscopic submucosal dissection (ESD) is commonly performed for the patients who diagnosed with early gastric cancer. Although additional gastrectomy is recommended for the patients with non-curative ESD in the points of potential risk of residual tumor, many cases have neither lymph node (LN) metastasis nor local residual tumor in surgical specimens. Clinically, it can be difficult to decide whether to perform additional surgery according to patients’ conditions. This study aimed to analyze the clinicopathological features of patients who underwent additional gastrectomy as well as to detect the predictive factors for residual tumor after non-curative ESD. Methods: The patients who underwent additional gastrectomy after non-curative ESD in our institution from January 2005 to August 2016 were retrospectively reviewed. The incidence rates of LN metastasis or local residual tumor were calculated, and furthermore the predictive factors for these outcomes were estimated. Results: 211 patients were enrolled in this study. Pathological examination after additional surgery revealed LN metastasis in 18 patients (8.5%) and local residual tumor in 26 patients (12.3%). Multivariable analysis revealed that lymphatic invasion ( p&lt; 0.0001, odds ratio = 15.6), vascular invasion ( p= 0.042, odds ratio = 3.92) and macroscopic findings (flat/elevated type) ( p= 0.03, odds ratio = 3.53) are predictors for lymph node metastasis. All of the patients without LN metastasis revealed no lymphovascular invasion. Positive vertical margin ( p= 0.0045, odds ratio = 4.17) and horizontal margin ( p= 0.0002, odds ratio = 6.6) were predictors for local residual tumor. Conclusions: The risk of residual tumor can be estimated based on histopathology of ESD. Patients without lymphovascular invasion appear to be a low risk subpopulation for LN metastasis.
Lymphatic Drainages to the Paravertebral and Pararenal Lymph Nodes in Breast Cancer Patients
Authors: Mirela Roman, Romain Barbieux, Olivier Leduc, Pierre Bourgeois
Journal: Clinical Nuclear Medicine (2017)

An efficient evaluation of the lymphatic drainage from the breasts (thoracic wall) and/or the upper limbs is essential in the management of patients with breast cancer (BC) and/or BC-related lymphedema. Lymphoscintigraphy was performed in 2 patients with lymphedema. Lymphatic drainage was observed from the upper limb or breast to the posterior paravertebral and/or pararenal lymph nodes. The cases demonstrate lymphatic drainage pathways toward unusual and mostly unrecognized lymph nodes, which may be at risk for further evolution of BC and may be important for the physical treatment of BC-related lymphedema.
Discordance between HER2-phenotype on circulating tumor cells and primary tumor in women with advanced breast cancer.
Authors: Amelie Schramm, Thomas W. P. Friedl, Fabienne Schochter, Jens Bodo Huober, Lisa Maria Wiesmueller, Brigitte Kathrin Rack, Marianna Alunni-Fabbroni, Peter A. Fasching, Florin-Andrei Taran, Andreas D. Hartkopf, Andreas Schneeweiss, Volkmar Mueller, Bahriye Aktas, Klaus Pantel, Natalia Krawczyk, Wolfgang Janni, Tanja N. Fehm
Journal: Journal of Clinical Oncology (2015)

11003 Background: In the DETECT study program, women with HER2-negative metastatic breast cancer (MBC) are screened for circulating tumor cells (CTCs) to evaluate eligibility for different DETECT treatment intervention trials based on presence and HER2 phenotype of CTCs. Here we present data on the association of CTC prevalence and positive HER2-status on CTCs with patient and tumor characteristics. Methods: As of January 2015, number of CTCS using the FDA-cleared CellSearch System (Janssen Diagnostics, LLC) and their HER2 status have been evaluated in 1052 women with HER2-negative MBC screened for the DETECT Study program. Patients were defined as CTC positive if at least 1 CTC was detected in 7.5 ml of peripheral blood, and the cutoff for HER2 positivity was the presence of at least 1 CTC with a strong (+++) immunocytochemical HER2 staining intensity. Results: Overall, CTCs were detected in 661 (62.8%) of the 1052 screened patients (median 7 CTCs, range 1 – 35078). CTC prevalence was associated with a higher proportion of pN2/pN3 tumors (28.0 vs. 20.2%; p = 0.021) and a higher proportion of lobular carcinomas (22.4 vs. 9.5%; p < 0.001) compared to CTC-negative patients. Among the 661 patients with CTCs, at least one HER2-positive CTC was found in 130 patients (19.7%), indicating a discordance between primary tumor and CTCs with regard to HER2-status. Patients with HER2-positive CTCs had less often G3 tumors (27.7 vs. 39.0%; p = 0.024), and more often lobular carcinomas (39.2 vs. 18.3%; p < 0.001) compared to patients with only HER2-negative CTCs. In addition, patients with triple-negative tumors were less likely to have HER2-positive CTCs than patients with HER2-negative but hormone-receptor positive tumors (6.6 vs. 22.8%; p < 0.001). Conclusions: Our data confirm discordance in HER2-status between primary tumor and CTCs in 19.7% of patients with HER2-negative MBC. Interestingly, presence of HER2-positive CTCs was associated with hormone-receptor positive tumors. Awareness of the HER2-phenotype of CTCs may have important implications for further personalized therapy options. Clinical trial information: NCT01619111/NCT02035813.
Plasma vascular endothelial growth factor level and cognitive changes in breast cancer patients.
Authors: Terence Ng, Yin Ting Cheung, Maung Shwe Ham Guo, Yuan Chuan Kee, Han Kiat Ho, Gilbert Fan, Wei Sean Yong, Preetha Madhukumar, Wei Seong Ooi, Wen Yee Chay, Raymond C.H. Ng, Quan Sing Ng, Soo Fan Ang, Soo Kien Lo, Yoon Sim Yap, Rebecca Alexandra Dent, Alexandre Chan
Journal: Journal of Clinical Oncology (2013)

e20566 Background: It is suggested that vascular endothelial growth factor (VEGF) induces neurogenesis in the brain and provides neuroprotectiveeffects. This study was designed to examine the relation between plasma VEGF level and cognitive functioning in breast cancer patients who have received chemotherapy. Methods: Early-stage breast cancer patients (stage I to III) who received anthracycline- and/or taxane-based chemotherapy were prospectively recruited at a single center. Perceived cognitive functioning (FACT-Cog) and computerized neuropsychological assessment (Headminder) were used to evaluate patients’ cognitive function at three time points: prior to chemotherapy (T1), at midpoint (T2), and end of chemotherapy (T3). Headminder evaluated four cognitive domains: Attention, Memory, Processing, and Response speed. Impairment in each domain were defined as a &gt;2.5 reduction of the Z score from baseline, as calculated by the reliable change index for repeated cognitive measurements. Plasma VEGF levels were analyzed at each time point using the multiplex immunoassay. Spearman Correlation (r s ) was utilized to correlate the change in plasma VEGF and neurocognitive functioning. Results: Thirty-six patients were recruited (median age: 51.5; Chinese: 80.6%; post-menopausal: 58.3%). Median plasma VEGF levels were T1: 19.2 pg/ml; T2: 26.5 pg/ml; T3: 21.9 pg/ml. Weak correlations were observed between the change in VEGF level and the change in FACT-Cog and Headminder scores for individual cognitive domain (Table). Conclusions: Results suggest a weak correlation between plasma VEGF level and cognitive functioning in the domains of attention, concentration, functional interferences, mental acuity and response speed. Larger sample size and longer follow up are required to further explore the findings. [Table: see text]
Neurocognitive functions in adults treated with radiation for primary brain tumors: A longitudinal study.
Authors: Kim Edelstein, Normand Laperriere, Lori J Bernstein, Rebecca Simpson, Caroline Chung, Barbara Ann Millar, Warren P. Mason
Journal: Journal of Clinical Oncology (2014)

2097 Background: Cranial radiation is associated with progressive declines in processing speed, attention, memory and executive functions, presumably due to deleterious effects on white matter growth in children and accelerated cognitive aging in older adults. However, little is known about the longitudinal effects of radiation in the adult brain tumor population. Methods: In this retrospective cohort study, we conducted neurocognitive assessments in 21 adults diagnosed with a primary brain tumor (12 male; mean age 44 years, range 21-66) within a year of radiation (baseline mean ± SD: 0.17 ± 0.36 years, range -0.15 to 1.1 years), and 3.05 ± 1.83 years later (range 0.51 to 6.77 years). Patients who required additional surgery, or developed tumor progression prior to neurocognitive follow up were excluded from analyses. Neurocognitive test scores were converted to scaled scores according to published criteria, and transformed to z-scores (mean 0, SD 15). Tests measuring the same construct were averaged to provide 4 cognitive domains: Speed, Attention, Memory, and Executive Functions. Results: At baseline, Memory, Attention, and Executive Function were below population norms, and Speed was within normal limits (one-sample t-tests, respective means ±SD: -0.66±0.84;-0.40±0.74; -0.70±1.12; -0.30±0.94; all p<0.05). At follow-up, only Attention was below average (-0.40±0.81). Moreover, there was no difference in performance at baseline compared to follow-up across domains, nor was there an interaction between time and domain (time x domain repeated measures ANOVA, all p>0.1). There was also no difference in the number of tests that were impaired (defined as one standard deviation below the population mean) at baseline compared to follow up. Conclusions: Adult brain tumor patients showed deficits in cognitive functions that did not appear to decline over time after radiation in the absence of tumor progression. Longitudinal assessments of neurocognitive functions following radiation treatment in a larger sample is warranted to identify factors contributing to neurocognitive decline across the lifespan in this population.
Predicting nonsentinel node status in breast cancer preoperatively by molecular characterization of core needle biopsies with multiparametric protein analyses
Authors: G. W. Sauer, N. Schneiderhahn-Marra, C. Kurzeder, K. Koretz, R. Kreienberg, T. Joos, H. Deissler
Journal: Journal of Clinical Oncology (2007)

21068 Background: Axillary lymph node dissection (ALND) still remains the standard treatment for breast cancer patients with sentinel lymph node (SLN) metastases. However, since only 40% to 60% of patients show additional lymph involvement, complete ALND offers no additional benefit for almost 50% of patients but carries a significant risk of axillary morbidity. In an attempt to achieve a more precise prediction for the individual patient a multivariable logistic-regression analysis of a large data set of eight histopathological variables has been published by the Memorial Sloan-Kettering Cancer Center (MSKCC) that predicts the likelihood of metastases in Non-SLNs with a ROC of 0,71. To achieve a more precise estimation of additional lymph node involvement preoperatively we analysed molecular markers of potential predictive value. Methods: Beside histopathological variables, fifty proteins of potential prognostic and predictive value were preoperatively quantified in lysates from 120 core needle biopsies with multiplex sandwich immunoassays. Biopsies, taken at the Breast Cancer Center of the University of Ulm Medical School, were classified as invasive mammary carcinomas. Variables which could be used to improve the accuracy of prediction of non-sentinel lymph node (NSLN) involvement were defined. Results: We demonstrated appropriate sensitivity, reproducibility, and robustness for this protein microarray technology to characterize proteins in core needle biopsies and generate reliable data sets. In an initial univariate data analysis (Mann Whitney test) six of the analysed parameters (TIMP2, p= 0,027; FasR, p = 0,0025; MIF, p= 0,030; FGF-2, p= 0,0020, PDGF AA/BB p= 0,027; RANTES p= 0,024) correlated with NSLN involvement beside known histopathological variables (i.e. tumor size, p= 0,006; grading, p = 0,0009). Conclusions: We defined molecular markers of diagnostic value to predict NSLN involvement. This might be an acceptable substitute to the known histopathological variables by the MSKCC nomogram to predict potential NSLN involvement preoperatively. No significant financial relationships to disclose.
A prospective, phase II trial of induction chemotherapy with docetaxel/cisplatin for Masaoka stage III/IV thymic epithelial tumors.
Authors: Silvia Park, Keunchil Park, Myung-ju Ahn, Jin Seok Ahn, Jong-Mu Sun, Hee Kyung Ahn, Su Jin Lee, Chi Hoon Maeng, Deok Won Hwang
Journal: Journal of Clinical Oncology (2012)

7104 Background: Thymic epithelial tumors (TETs), thymoma and thymic carcinoma, are the most common tumor of the anterior mediastinum. Initial complete resection is the most powerful prognostic indicator of survival. However, it is obviously related to stage. Here, we report the result of a prospective phase II study of neoadjuvant docetaxel/cisplatin in patients with locally advanced TETs. Methods: In this open-label, phase II, nonrandomized study, patients with histologically proven, Masaoka stage III/IV TETs at presentation were enrolled. Patients received docetaxel 75mg/m 2 I.V for 1 hr, followed by I.V cisplatin 75mg/m 2 over 1.5hr on day 1 of every 3 week. After 3 cycles of chemotherapy, subsequent surgical resection was performed, if resectable. Results: From March 2007 to July 2011, a total of 27 TETs patients were entered into the trial. The median age was 54 (range, 15-68), and Masaoka stage at presentation was III (n=8, 29.6%), IVA (n=17, 63.0%), and IVB (n=2, 7.4%). Histologic type by the WHO includes type B1 (n=2, 7.4%), B2 (n=3, 11.1%), B3 (n=5, 18.5%), and thymic carcinoma designated as type C (n=16, 59.3%). After completion of neoadjuvant chemotherapy, 17 (63.0%) achieved PR and 10 (37.0%) had SD. Nineteen patients (70.4%) underwent surgical resection, and 8 patients did not (surgeons’ decision, n=5; patients’ refusal, n=2; radiation therapy, n=1). Of the 19 patients undergoing surgical resection, 17 (89.5%) had complete resections and 2 (10.5%) did not. Major side effects of chemotherapy include grade 3 anorexia (n=1), nausea (n=2), diarrhea (n=3), alopecia (n=1). After completion of surgical resection, adjuvant therapy was performed as follows: radiotherapy (RT, n=8), chemotherapy (CTx, n=6), radiotherapy with chemotherapy (RT + CTx, n=2) and observation (n=3). Overall, 4yr OS and PFS was 79.4% and 40.6%. Patients with complete resection showed 93.8% of 4yr OS and 50.2% of 4yr PFS whereas patients without complete resection showed 47.6% of 4yr OS and 26.7% of 4yr PFS, respectively (OS, p=0.06; PFS, p=0.27). Conclusions: Neoadjuvant docetaxel/cisplatin was well tolerated and feasible, and improved the surgical respectability in patients with advanced TETs.
Factors associated with octreotide LAR use among elderly patients with carcinoid syndrome: A population-based analysis.
Authors: Ya-Chen T. Shih, Ying Xu, Colleen Leary, James C. Yao
Journal: Journal of Clinical Oncology (2012)

e14549 Background: Octreotide LAR is indicated for the treatment of carcinoid syndrome, diarrhea related to VIPoma, and may delay tumor growth in neuroendocrine tumors (NETs). The pattern of octreotide LAR use in clinical practice has not been well documented. Methods: Using the SEER-Medicare database, we identified patients diagnosed with NETs from July 1999 to Dec 2007. We then excluded those patients with poorly differentiated histology, under age 65 at diagnosis, enrolled in HMOs, and who did not have continuous Part A &amp; B enrollment within 12 months of diagnosis. We further identified patients with potential indication for octreotide LAR use as those having two or more claims indicating carcinoid syndrome, flushing, diarrhea, or malignant islet cell neoplasm within the first year of NETs diagnosis, with the first claim occurring within 6 months of diagnosis. HCPCS codes, J2352 and J2353, were used to identify octreotide LAR use. Multivariate logistic regression analysis was performed to ascertain factors associated with octreotide use; covariates included age, race, region, comorbidity score, urban/rural status, tumor characteristics, neighborhood socioeconomic status and year of diagnosis. Results: Of the 2000 NETs patients with potential indication for octreotide LAR use, 478 (23.9%) were started on octreotide LAR within 6 months of diagnosis. Multivariate analysis showed that older age (≥ 80) (OR=0.61, 95 CI=0.44 – 0.86), southern region (OR =0.67; 95% CI =0.44 – 1.00) and tumor of undetermined grade (OR=0.71, 95% CI=0.52 – 0.98) were associated with lower odds of octreotide use while the odds was positively associated with advanced stage and more recent diagnosis years. By primary site, no clear pattern was identified. Conclusions: Our analyses suggest only a small (&lt; 25%) fraction of patients with eligible diagnoses are receiving indicated therapy with octreotide LAR. Further studies and improved education are needed to improve the management of carcinoid syndrome.
The Feature of CD3γ, CD3δ and CD3ε Gene Expression in Benzene-Exposed and Benzene- Poisoned Workers
Authors: Bo Li, Jing Jing Fan, Jing Ru Wang, Yun Yu Chen, Shao Hua Chen, Li Jian Yang, Yu Wei, Wei Wei Liu, Jia Yu Chen, Yang Qiu Li
Journal: Blood (2011)
Phase II study of dabrafenib and trametinib following progression on BRAF inhibitor monotherapy in metastaticmelanoma: Exploration of clinical and molecular predictors of response.
Authors: Jennifer Leigh McQuade, Guo Chen, David J Panka, Alexandre Reuben, Roland L. Bassett, Aron Joon, Alexander J. F. Lazar, Michael T. Tetzlaff, Lauren Simpson, Rosalind Mouton, Sapna Pradyuman Patel, Isabella Claudia Glitza, Wen-Jen Hwu, Rodabe Navroze Amaria, Adi Diab, Patrick Hwu, Jennifer Ann Wargo, Ryan J. Sullivan, Kevin Kim, Michael A. Davies
Journal: Journal of Clinical Oncology (2015)

e20051 Background: The combination of dabrafenib (D) and trametinib (T) has demonstrated clinical responses in a subset of metastatic melanoma (MM) patients (pts) with BRAF V600 mutations after progression on BRAF inhibitor (BRAFi) monotherapy. We conducted a phase II study to identify clinical and molecular markers that predict response to D+T combination treatment in these pts. Methods: MM pts with BRAF V600 mutations that had progressed after BRAFi monotherapy were treated with D (150 mg twice daily) and T (2 mg daily). Treatment response was assessed by RECIST v1.1 every 2 cycles (8wks). Tumor samples were collected prior to starting D+T and were analyzed by next generation sequencing (NGS) for mutations, RT-PCR for BRAF splicing, and by IHC. Blood samples were collected at baseline (BL), C1D8, C1D15, C2D1, C4D1, and off-study. Level of mutant BRAF RNA in circulating tumor cells isolated with peripheral blood mononuclear cells was assessed by RT-PCR. Results: Twenty pts were evaluable for response. The overall response rate was 10%, disease control rate (DCR) was 45%, and median progression free survival (PFS) was 13 wks. PFS and DCR did not correlate significantly with age, gender, LDH, or stage. Pts with duration of prior BRAFi monotherapy > 6 months had better PFS (median 16 vs 8 wks, HR 0.29, p = 0.01) and DCR (73% vs. 11%, OR 21.3, p = 0.015). NGS and RT-PCR analysis on tumors with sufficient material for both analyses (n = 15) identified 5 pts (33%) with molecular changes predicted to reactivate the MAPK pathway (2 NRAS mutations, 2 BRAF amplifications, 2 BRAF splice variants, 1 MAP2K1 mutation). There was no significant difference in PFS (p = 0.36) or DCR (p = 0.73) between pts with and without such molecular events. Decreases in circulating BRAF V600 were detected by C1D8 in pts who achieved disease control (p = 0.06) or PFS > 13 wks (p = 0.06) compared to pts who did not. Conclusions: In pts who have progressed on BRAFi monotherapy, clinical benefit from D+T correlates with duration of prior BRAFi therapy, but not the presence of resistance mechanisms in the MAPK pathway. Changes in levels of circulating mutant BRAF may be an early predictor of clinical benefit. Clinical trial information: NCT01619774.
Oral vinorelbine and cisplatin with concomitant radiotherapy in stage III non-small cell lung cancer (NSCLC): COVeRT study.
Authors: Nimit Singhal, Kenneth B. Pittman, Christos Stelios Karapetis, Sonya Stephens, Martin Borg
Journal: Journal of Clinical Oncology (2012)

e17544 Background: Chemoradiation is standard of care for the treatment of stage III NSCLC. Vinorelbine has been widely used for the treatment in NSCLC and it has been established, either as single agent or in combination with platinum, as one of the standard reference treatments. Oral vinorelbine is a new formulation which has achieved comparable results to the IV vinorelbine. The present trial is evaluating combination of oral vinorelbine, cisplatin with radical radiation for management of stage III NSCLC. Methods: Patients with diagnosis of stage III NSCLC with PS 0-1 and adequate cardio-respiratory function. Primary objective: progression-free survival. Secondary objectives: response rate, overall survival and safety profile. Treatment - chemotherapy (2 cycles q 21 days): vinorelbine oral 50 mg/m 2 d1, d8. Cisplatin 100 mg/m 2 / cycle (given as either 20mg/m 2 D1-5 or 50mg/m 2 D1 and D8) - radiotherapy: 60 Gy in 30 fractions at 2 Gy/ fraction to the isocentre, treating all fields daily, 5 days a week over 6 weeks using 10 MV photons and 3-D CRT. Results: Since May 2008, 33 patients have been enrolled with 31 patients having completed treatment so far. The data is presented for these 25 patients. 16 were male with age ranging from 50-89. The median age was 66. 13 patients had stage IIIa. There were 11 squamous cell carcinoma and 10 adenocarcinoma. The side effects were generally mild and included Gr I, II nausea, constipation and esophagitis. Serious adverse events requiring admission included dehydration, fever with grade I neutropenia, atrial fibrillation and UTI in one patient each. One patient had tracheo-esophageal fistula resulting in death within 30 days of completing chemoRT and was attributed to treatment. The confirmed radiological response assessment is available for 22 patients with 1 CR, 13 PR, 7 SD and 1 PD giving a total response rate of 64%. Conclusions: Two cycles of chemotherapy with oral vinorelbine and cisplatin plus radical radiation appears to be well tolerated with significant activity in stage III NSCLC.