bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain metastasis-free survival in patients with HER2-positive metastatic breast cancer.
Authors: Berghoff A. , Bago-Horvath Z. , Dubsky P. C. , Rudas M. , Pluschnig U. , Rottenfusser A. , Gnant M. , Steger G. G. , Zielinski C. , Bartsch R. 
Published: February 2017

41 Background: Brain metastases (BM) are diagnosed in up to 40% of patients with HER2-positive metastatic breast cancer (MBC). Since the introduction of trastuzumab in 1999, a rising incidence of BM was reported. We aimed to identify factors that prolong BM free survival (BMFS) in all HER2-positive patients (pts) treated for MBC at the Medical University of Vienna from 1999-2009. Methods: BMFS was defined as primary study endpoint and measured as the interval from diagnosis of metastatic disease until diagnosis of brain metastases. 201 pts with HER2-positive MBC were identified from a breast cancer database. 82 pts (40.8%) were diagnosed with BM; 13 pts were excluded from this analysis as brain was the first site of disease progression. Complete data sets of 69 pts with pathologically verified HER2-positive MBC were available. HER2 status was analyzed by immunohistochemistry and reanalyzed by FISH if a score of 2= was gained. BMFS was estimated by using the Kaplan-Meier product-limit method; factors significantly associated with BMFS in the univariate analysis were included into a Cox proportional hazard model. Results: Median BMFS was 25 months (m; 95%CI 13.37-36.63 m). Trastuzumab-based treatment significantly prolonged median BMFS (29 vs. 11 m; p<0.01); BMFS was further improved by trastuzumab treatment in multiple lines (30 vs. 17 m; p=0.045). Co-positivity for estrogen receptor (ER) and HER2 predicted for longer BMFS (30 vs. 15 m; p<0.05). Further variables such as prior exposure to capecitabine, presence of visceral metastasis, presence of lung metastasis, stage IV disease at primary diagnosis, as well as disease free interval from adjuvant therapy were not significantly associated with BMFS. In the Cox regression model, positive ER status (HR 2.03; 95%CI 1.22-3.36; p<0.05) and trastuzumab-based treatment (HR 2.72; 95%CI 1.20-6.17; p=0.017) remained independent predictors for longer BMFS. Conclusions: Trastuzumab-based therapy significantly prolongs BMFS in HER2-positive pts with MBC, probably due to improved systemic disease control. In line with known better survival outcome, ER/HER2 co-positive disease appears to be a less aggressive subtype of HER2-positive breast cancer associated with longer BMFS.
Quantitative nuclease protection assay (qNPA) for gene expression analysis on breast cancer core biopsies.
Authors: Evangelist M. C. , Snider J. , Krushkal J. , Qu Y. , Kulkarni A. , Kerns B. , Seligmann B. , Sachdev J. C. 
Published: February 2017

49 Background: qNPA employs in situ hybridization of detection probes to cross linked mRNA, making it ideal for formalin fixed paraffin embedded (FFPE) tissue. It has been shown to measure gene expression in archived lymphoid and lung cancer tissue. We assessed the feasibility of qNPA to measure differentially expressed genes in pretreatment FFPE core breast biopsies among pathologic responders (pR) and nonresponders (pNR) to preoperative chemotherapy. Methods: We included preoperative breast cancer patients treated at our institution from 2003-09 with FFPE core biopsies. mRNA expression of 170 genes, representing oncogenic pathways or associated with anthracycline and taxane response was measured by qNPA (HTG, Tucson, AZ). Data was normalized to 3 housekeeper genes and average of 3 biologic replicates reported. Seven genes below detection in > 50% samples were excluded. Expression values of 163 unique genes were analyzed for pR vs pNR with dChip software. Empirical FDR was estimated using 1,000 permutations of sample labels. Results: Treatment and response: Sample failure: 6/57 (10%). pR vs pNR did not separate on hierarchical clustering. FLJ12650 and IGFBP2 showed lower expression in pR vs pNR with fold changes of 4.09 and 2.40, respectively (p < 0.01; median FDR: 1/163). FLJ12650 was significant (p < 0.01, median FDR: 0/163) when patients receiving anthracycline ± taxane were analyzed (groups 1-3) and showed a trend (p < 0.05) in group 1 alone. Conclusions: qNPA for limited available FFPE tissue from core biopsies is feasible with acceptable sample failure rates. Small sample size and number of analyzed genes limited definitive conclusion about informative genes in our study. Our FLJ12650 results, a gene coding for membrane Na+/K+ ATPase interacting protein, are consistent with previous findings of overexpression in pNR to anthracyclines + taxanes (Hess et al, JCO 2006, Vol 24; 4236) using fresh tissue. Future qNPA validation of predictive markers, identified by whole transcriptome analysis in a homogenous cohort may provide more definitive results. [Table: see text]
Impact of chemotherapy timing on local-regional failures in patients with breast cancer undergoing breast-conserving therapy.
Authors: Mittendorf E. A. , Buchholz T. A. , Tucker S. L. , Meric-Bernstam F. , Kuerer H. M. , Gonzalez-Angulo A. M. , Bedrosian I. , Babiera G. , Yi M. , Ross M. I. , Hortobagyi G. N. , Hunt K. 
Published: February 2017

82 Background: Debate continues as to whether BCT after neoadjuvant chemotherapy (chemo) can achieve long-term local control rates similar to those experienced by patients undergoing surgery first, especially in those presenting with large tumors. This study was performed to evaluate long-term results of BCT for patients undergoing surgery first versus chemotherapy. Methods: 2,984 patients underwent BCT with whole breast irradiation from 1987 to 2005. Clinicopathologic and outcomes data were reviewed and comparisons made between surgery first and chemotherapy patients. Results: 2,331 (78%) patients underwent surgery first; 653 (22%) received chemotherapy first. Overall, chemotherapy patients had more adverse clinicopathologic features (Table). 5 and 10-yr local-regional recurrence (LRR)-free survival rates were 97% (95% CI: 96%-98%) and 94% (93%-95%) for surgery first patients. Chemotherapy downstaged patients presenting with clinical stage II/III disease (608/653; 93%) allowing for BCT, and pathologic findings revealed stage II/III disease in only 305/653 (46%) (p<.001). 5 and 10-yr LRR-free survival rates were 93% (91%-95%) and 90% (87%-93%) after chemotherapy. After adjusting for clinical stage at presentation, there were no differences in LRR between surgery first and chemotherapy patients. On multivariate analysis, age<50, clinical stage III, grade 3, ER neg status, associated DCIS on final pathology, and close/positive margins were associated with LRR. Conclusions: LRR after BCT is driven by biologic factors and not the timing of chemotherapy. Chemotherapy downstages a significant number of patients with stage II/III disease allowing appropriately selected patients to achieve high rates of local-regional control with BCT. [Table: see text]
Can locoregional treatment of the primary tumor improve outcomes for women with stage IV breast cancer at diagnosis?
Authors: Nguyen D. H. A. , Truong P. T. , Lesperance M. , Alexander C. , Walter C. V. , Hayashi E. , Christie J. , Olivotto I. A. 
Published: February 2017

89 Background: To determine whether locoregional treatment (LRT) of the primary tumor improves outcomes in patients with stage IV breast cancer at diagnosis. Methods: The study cohort comprised 733 women referred from 1996 to 2005 to a population-based cancer institution with clinical or pathologic M1 breast cancer at diagnosis. Patient, tumor, and treatment characteristics were compared between women who were treated with (n=378) and without LRT (n=355) of the primary tumor. Five-year Kaplan-Meier overall survival (OS) and locoregional progression-free survival (LRPFS) were compared between groups. Multivariable analysis to control for potential confounding factors was performed using Cox regression modeling. Results: LRT consisted of surgery alone in 67%, radiotherapy alone in 22%, and both in 11% of patients. LRT use was significantly associated with age <50 years, ECOG performance status 0-1, T1-2 tumors, and N0-1 disease, (all p<0.05). Subjects with less metastatic disease burden and those asymptomatic from the M1 disease were more likely to undergo LRT (p<0.001). Systemic therapy was used in 92% and 85% of patients treated with vs. without LRT, respectively. Five-year OS rates in the LRT and no LRT cohorts were 21% vs 14% (p<0.001). The 5-year LRPFS rates were 72% vs 46% (p<0.001). Among 378 patients who underwent LRT, 5-year OS rates were higher in patients with age <50, ECOG 0-1, ER positive disease, clear surgical margins, single M1 subsite, bone only metastases, and 1-3 metastatic lesions (all p<0.003). Type of LRT (surgery vs radiotherapy vs both) and type of surgery (lumpectomy vs mastectomy) were not associated with 5-year OS (all p>0.05). On multivariable analysis, LRT was associated with improved OS (hazard ratio 0.78, 95% confidence interval 0.64-0.94, p=0.009). Conclusions: LRT of the primary disease was associated with improved survival in women with stage IV breast cancer at diagnosis. Among subjects treated with LRT, the most favorable survival rates were observed in patients with young age, good performance status, ER-positive disease, clear resection margins and in those with distant disease limited to one subsite, bone only, or fewer than 4 metastatic lesions.
Use of perioperative therapy in gastric cancer: A retrospective comparison of ECF and chemoradiation.
Authors: Siripurapu V. , Watson J. C. , Hoffman J. P. 
Published: February 2017

112 Background: Gastric Cancer (GC) remains a major cause of cancer related morbidity and mortality in Western Countries with five year survival rates between 30%-40%. Preoperative therapy has been championed by groups extrapolating data from the Intergroup 0116 and the MAGIC trials, with a view to enhancing completion of therapy and improving survival in locally advanced tumors. Methods: Patients with preoperative treatment of GC were reviewed from our tumor registry. Stages were assigned by AJCC 7th edition. A comparison between the ECF regimen and non-ECF chemoradiation regimens was performed to view patterns of pathologic complete response (pCR), recurrence, toxicity and overall survival. Results: Forty-two patients were identified and stratified into two groups; Group 1 ECF treatment arm (n = 16) compared to group 2 non-ECF chemo-radiation arm (n = 26). No statistical difference was noted in age, ethnicity or stage stratification. All of Group 1 received their chemotherapy regimen after 2005. In contrast, 60% of Group 2 patients received their treatment pre-2005. Only 56% the ECF group completed their treatment course (19% received other postoperative therapy). Seventy percent of group 2 received adjuvant chemotherapy. A grade 2 or higher toxicity was noted in 16% of Group 1 compared to 60% in Group 2 (p = 0.035). Seven complications were noted in the group 1 compared to 10 in group 2 (p = NS). The differentiation of tumor between groups was not significant (p = 0.97). Length of stay was significant (Group 1:9 days, Group 2:12 days, p = 0.02). More nodes were retrieved from group 1 versus group 2 (20.2 versus 15.2, p = 0.03). Group 1 had 3 recurrences (19%) while Group 2 had 11 recurrences (42%, p = 0.94). In both groups 80% of recurrences were distant. Group 1 had a 19% pCR versus 23% in group 2 (p = 0.79). Two-year survival was 70% in both groups, with a median survival of 51 months for group 2. Median survival was not reached for group 1. Conclusions: No difference was noted in pCR, recurrences, or survival between these two regimens. If this can be confirmed in larger, prospective, randomized trials, use of radiation and its potential morbidity may be avoided. No significant financial relationships to disclose.
Pharmacokinetic and pharmacodynamic analysis of gastric cancer patients treated with telatinib.
Authors: Burd A. , Castillo J. , Whiteside M. , White M. , Ajani J. A. , Fattaey A. , Kunkel L. A. 
Published: February 2017

113 Background: The soluble form of the VEGFR2 receptor (sVEGFR2) neutralizes circulating VEGF, and functions as a negative feedback mechanism to enable partial inhibition of VEGF-stimulated endothelial cell migration and proliferation. In response to inhibition of VEGFR2 tyrosine kinase activity, up-regulation of VEGF expression and down-regulation of sVEGFR2 expression levels have been observed (Murukesh et al., 2010). Telatinib (tel) is a novel orally available kinase inhibitor that is highly selective for the VEGFR, PDGFR, and KIT tyrosine kinases at nanomolar concentrations with potent antiangiogenic activity. Correlation between telatinib exposure and reduction in plasma sVEGFR2 levels from baseline has previously been demonstrated in patient serum samples in phase I studies. Methods: TEL0805, a phase II study administered tel with capecitabine (X) and cisplatin (P) in previously untreated metastatic or unresectable gastric or GEJ adenocarcinoma pts. Patient serum samples were obtained on day -7, [6 plasma samples (pre-dose, and at 30 min, 1, 2, 3 and 4 hours)] and on day 1, [4 plasma samples (pre-dose and at 1, 2 and 3 hours)] and evaluated for the levels of telatinib and its M2 metabolite (M2). Additional serum samples were collected every 42 days and evaluated for VEGF and sVEGFR2 levels. Results: Measurement of tel and M2 levels confirmed previous pharmacokinetic findings and demonstrated no drug accumulation following continuous daily dosing. Baseline plasma sVEGFR2 levels have previously not been reported for advanced gastric cancer patients and displayed a wide range at disease presentation. Reduction in sVEGFR2 levels were noted for nearly all treated patients and correlated with the duration of stay on tel therapy. Conclusions: Telatinib continuous dosing is possible in combination with XP with little effect on tel exposure or accumulation. Reduction in sVEGFR2 levels may be useful in identifying patients who may benefit from tel treatment in this combination setting. [Table: see text]
Feasibility study of postoperative management based on ERAS of patients with gastrectomy.
Authors: Sugiyama Y. , Hirabayashi N. , Taomoto J. , Mimura T. , Yoshimitsu M. , Murakami S. , Saeki S. , Mukaida H. , Takiyama W. 
Published: February 2017

127 Background: Although the usefulness of the postoperative management based on Enhanced Recovery After Surgery (ERAS) program of patents with colectomy is shown, there are a few papers concerning ERAS program for gastric cancer patients. The aim of the present study was to examined whether a new postoperative management based on ERAS was feasible for pts with gastrectomy. Methods: From September 2009 to April 2010, we have adopted the new clinical pathway (CP) based on ERAS and oral rehydration therapy (ORT) for 30 consecutive gastric cancer patients who underwent curative gastrectomy. These pts began a oral rehydration solution (ORS) on the first postoperative day, and after the volume of ORS got 1,000 ml, we stopped intravenous transfusion. The incidence of adverse events, postoperative pt's activity score, which pt's daily activity was evaluated with, and total infusion volume of these pts were compared with 30 pts with the previous CP that were enrolled as a control group. Results: There were no significant differences in the clinical and operative factors between the two groups. The post operative patient's activity score of ERAS group was significantly higher up to 7th postoperative day (POD). Total infusion volume was significantly little besides, in most cases, infusion therapy was substituted for ORT with OS-1 within 2 POD. There was no difference in the hospitalized days, and the incidence of adverse events were statistically no significance between two groups. Conclusions: Our CP based on ERAS and ORT is feasible for patients with gastrectomy. No significant financial relationships to disclose.
Neoadjuvant radio chemotherapy in esophageal squamous cell carcinoma: Early results analysis of a 5-year experience.
Authors: Lima da Costa E. J. , Santos Sousa H. , Bouca-Machado T. , Caldeira B. , Paredes C. , Pinto-de-Sousa J. , Gouveia A. , Sousa Rodrigues J. , Costa-Maia J. ,   Unidade de Patologia Esofago-Gastro-Duodenal do Servico de Cirurgia Geral do Hospital de S. Joao
Published: February 2017

141 Background: Optimized survival in oesophageal squamous cell carcinoma (OSCC) depends on complete surgical resection: prognostic impact of well-standardized techniques and per operative management in experienced groups has proven to be a key aspect. Multimodal treatment (MT) options are still controversial but particularly important in locally advanced disease apparently allowing better resectability. We perform an early evaluation of a MT protocol in locally advanced OSCC. Methods: Survival and clinical response analysis of a cohort of pts selected between 01/01/2002 and 31/12/2007. Criteria: Locally advanced OSCC (T3/4); No distant metastases; Negative bronchoscopy; Age under 76y; No other known cancer; Surgical feasibility. Pts underwent a 5 week MT: Chemo – taxotere 20 mg/m2 IV, cysplatin 20 mg/m2 IV, 5-FU 425 mg/m2 iv (days 1,8,14,22 and 29); Radio- 40 Gy (days 1-5, 8-12, 14-19, 22-26 and 29-34) followed by surgery within 4 weeks. Results: 57 pts (38% of all admitted) 8 fem and 49 male, aged < 50y = 11, 51-65y = 30 and > 65y = 16. Response: Complete pathological remission = 13; Partial clinical response with downstaging = 15; Minimal / no clinical response = 14; Disease progression / no surgery: 15. From the 42 pts operated, an “en bloc” osophagectomy with extended lymphadenectomy was possible in 36. The overall mean follow-up for resected pts was 16.9 months (CI 95%: 10.9-22.8). The median survival was 18 months for resected patients (CI 95%: 8.7-27.3) in contrast with 7 for all candidates to MT. There was a statistically significant difference in the survival of the 4 groups divided according to their response to MT, with clear advantage of the complete pathological remission achievers. Conclusions: Short follow-up and series size does not allow definite conclusions. It seems nevertheless that only the group of full pathological remission and probably those that obtain a downstaging of their disease benefit from MT. Histopathological or molecular markers are required to identify target pts for neoadjuvant radio chemotherapy. No significant financial relationships to disclose.
The potential role of somatostatin analogues in the treatment of gastrointestinal (GI) cancers.
Authors: Hasskarl J. , Kaufmann M. , Schmid H. , Metz D. C. 
Published: February 2017

150 Background: Somatostatin receptors (sstr) are expressed in various normal and malignant tissues, including non-neuroendocrine GI solid tumors. Gastric cancer (GC) cells mainly express sstr2 and sstr5, colorectal cancer (CRC) cells predominantly express sstr1 followed by sstr5 and sstr2, and hepatocellular carcinoma (HCC) cells express mainly sstr5 as well as sstr1,2,3. Somatostatin analogues (SAs) may have direct and indirect antitumor activity. Octreotide and lanreotide primarily target sstr2, whereas the new agent pasireotide has high affinity for sstr1,2,3 and sstr5. Methods: Published data evaluating the antitumor properties of SAs in GI tumors were reviewed. Results: The table lists the results of clinical studies in which SAs were evaluated as antitumor therapies in GI cancers. Conclusions: Although octreotide and lanreotide are efficacious in the treatment of symptoms of neuroendocrine tumors, these agents have demonstrated mixed results in the antitumor treatment of non-neuroendocrine GI tumors. Data suggesting potential favorable outcomes with SAs alone or in combination with other agents have been seen in solid tumors with predominant sstr2 expression such as GC. Novel SAs such as pasireotide may have improved antitumor effects in non-neuroendocrine solid tumors expressing multiple sstr compared with octreotide and lanreotide. [Table: see text] [Table: see text]
Evaluation of the neutrophil-lymphocyte ratio as a predictor of survival after liver transplantation for hepatocellular carcinoma.
Authors: Limaye A. R. , Cabrera R. 
Published: February 2017

170 Background: The Milan criteria are utilized to predict outcomes in patients with hepatocellular carcinoma (HCC) who undergo liver transplantation (LT). Though the survival of these patients has significantly improved since the adoption of these criteria, the risk of recurrence after LT is as high as 20 percent. One limitation of the Milan criteria is the lack of any estimation of tumor biology. The neutrophil-lymphocyte ratio (NLR) has been proposed as a peripheral surrogate for tumor biology. The predictive power of the NLR has been demonstrated for several solid tumors, and early evidence points to a role in HCC. We hypothesize that the NLR is predictive of overall survival and recurrence-free survival in patients with HCC who undergo LT. Methods: This is a retrospective analysis of adult patients undergoing LT for HCC between 2000 and 2008 at our institution. We defined an elevated NLR as a ratio of five or greater. Results: We identified 160 patients who underwent LT for HCC, 28 of whom had an elevated NLR. Seventeen subjects experienced recurrent HCC during the study period. The cumulative survival for subjects with an elevated NLR (1-year cumulative survival 70% ± 0.08, 3-year cumulative survival 48% ± 0.09, 5-year cumulative survival 38% ± 0.11) was significantly lower than for subjects with a normal NLR (1-year survival 80% ± 0.04, 3-year survival 75% ± 0.04, 5-year survival 68% ± 0.06). On univariate analysis, seven factors (including an elevated NLR) predicted decreased overall and recurrence-free survival. However, after multivariate analysis, only three factors (including elevated NLR) remained significant as predictors of overall survival. Additionally, multivariate analysis revealed that an elevated NLR was the only significant independent predictor of recurrence-free survival. Conclusions: Preoperative NLR is a powerful independent predictor of overall survival and recurrence-free survival in patients undergoing LT for HCC. Measurement of NLR could serve as a useful and easily obtained adjunct to the MELD score and Milan criteria when evaluating this patient population and determining which patients will gain the most survival benefit from transplant. No significant financial relationships to disclose.