bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship of K-ras mutations and EGFR gene copy number to outcome in patients treated with Erlotinib on National Cancer Institute of Canada Clinical Trials Group trial study PA.3
Authors: Moore M. J. , da Cunha Santos G. , Kamel-Reid S. , Chin K. , Tu D. , Parulekar W. , Ludkovski O. , Squire J. , Richardson F. , Tsao M. 
Published: March 2020

4521 Background: The National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) PA.3 study compared treatment with the EGFR tyrosine kinase inhibitor erlotinib to placebo in patients with advanced stage pancreatic carcinoma who were receiving gemcitabine. This study demonstrated a significant advantage in survival [HR=0.82; P<0.04] and in progression free survival [HR=0.77; P<0.004] for patients who received erlotinib [Moore MJ et al, J Clin Oncol 2007]. While high-level expression of EGFR is common in pancreatic cancer, EGFR protein expression level as evaluated by immunohistochemistry did not predict which patients might benefit from erlotinib. In non- small cell lung cancer (NSCLC) where erlotinib has shown a survival benefit; the use of EGFR copy number measured by FISH is a better predictive factor for benefit, and patients whose tumor had a K-ras mutation do not respond nor benefit. Methods: The NCIC-CTG PA.3 trial had a sample size of 569 and NCIC.CTG has collected 280 archival formalin-fixed and paraffin embedded tumor biopsy or primary resection specimens from patients randomized on study. Many were fine needle aspirates and a total of 181 had sufficient tissue to allow molecular analysis. We performed a K-ras mutation analysis by PCR of exon 2 followed by sequencing, with negative results being validated by DHPLC. EGFR gene copy number was analysed by fluorescent in situ hybridization. Both methods were performed on all tumor samples adequate for analysis. Results: Overall 146 cases were suitable for K-ras mutation analysis and preliminary results have identified K-ras mutation in 90 patients [76%] and wild type KRAS in 29 patients; the remainder are pending. A total of 118 cases are suitable for EGFR FISH analysis, results have been obtained in 73 patients, and the remaining cases are pending. The correlations between K-ras mutational status and EGFR copy number, and outcomes [survival and disease control] in patients randomized to both erlotinib and placebo will be presented. [Table: see text]
p53 adapted neoadjuvant therapy for esophageal cancer: Pilot study
Authors: Kandioler D. , Hejna M. , Zwrtek R. , Kappel S. , Bichler C. , Wrba F. , Ba-Ssalamah A. , Zielinski C. , Jakesz R. , Zacherl J. ,   p53 Research Group Study
Published: March 2020

4535 Background: Randomized trials could not yet prove clinical efficacy of neoadjuvant chemotherapy for esophageal cancer. A survival benefit could be shown for treatment responders only. Using platinum based regimen, yet about 20 % of patients can achieve pathological complete remission which translates in reported 3-year survival rates of 64% in this group. Factors identifying this subgroup of responders and selecting optimal drugs for non responders could dramatically enhance treatment efficacy. Several studies suggest that mutations in the p53 gene may induce drug resistance especially for agents whose effect is based on apoptosis induction, like Cisplatin. Methods: In order to test the hypothesis that the p53 genotype is predictive for chemotherapy response, a prospective study was conducted. Thirty-eight patients with potentially respectable esophageal cancer were evaluated for the relation between p53 genotype and response to two different neoadjuvant treatments. P53 gene mutations were assessed by complete direct sequencing of DNA extracted from diagnostic biopsies. Response to neoadjuvant chemotherapy was assessed pathohistologically in the surgical specimen. Results: 20 squamous cell carcinoma and 18 adenocarcinoma were included. Overall the p53 mutation rate was 58% (22/38), with 66 % for squamous cell and 53% for adenocarcinomas, respectively. 30 patients received CIS/5FU (cisplatin 80mg/m2 d1 5-FU 1,000mg/m2 d 1–5, q21,2 cycles), 8 received docetaxel (75mg/m2, q21,2 cycles). The overall response rate was 48% (18/38). Patients with p53 mutation did not respond to CIS/5-FU (0/16), while all mutant patients responded to docetaxel (6/6). The overall response to p53 adapted neoadjuvant therapy was 94%. P53 adapted treatment was associated with a significant survival advantage (p=0,042) after a median follow up of 15,4 months. Conclusions: A prospective randomized trial was initiated to test the interaction between the predictive marker p53 and response to CIS/5-FU and Docetaxel, respectively. [Table: see text] No significant financial relationships to disclose.
Survivin expression in esophageal cancer: Association with histomorphological response to neoadjuvant therapy and prognosis
Authors: Vallboehmer D. , Kuhn E. , Brabender J. , Metzger R. , Warnecke-Eberz U. , Baldus S. E. , Drebber U. , Hölscher A. H. , Schneider P. M. 
Published: March 2020

4536 Background: The poor prognosis associated with locally advanced esophageal cancer prompted an evaluation of combined modality treatments including neoadjuvant radiochemotherapy in combination with surgery. However, it has been well established that only patients with a complete pathological response to neoadjuvant therapy will have a significant survival benefit. Therefore, predictive markers to allow a tailored radiochemotherapy are needed. The aim of this study was to examine the association of the protein expression of survivin, an inhibitor of apoptosis, with histopathologic response to neoadjuvant radiochemotherapy and prognosis of patients with locally-advanced esophageal cancer. Methods: 59 patients with esophageal cancer (cT2–4, Nx, M0) received neoadjuvant radiochemotherapy (cisplatin, 5-FU, 36 Gy) followed by esophagectomy. Histomorphologic regression was defined as major response when resected specimens contained less than 10 % and as minor response when resected specimens contained more than 10 % of residual vital tumor cells. Pre- and post-therapeutic intratumoral protein expression of survivin was determined and correlated with clinicopathologic parameters. Results: The pre-therapeutic intratumoral survivin protein expression was not associated with any clinicopathologic factor, including histopathologic response and prognosis. Survivin protein expression was significantly reduced during neoadjuvant therapy, showing lower levels in post-therapeutic tumor samples (p<0.01). Higher postoperative survivin levels were significantly associated with a higher ypT-stage (p<0.009), a poorer histopathologic response (p<0.01) and a shorter overall survival (p<0.028). Conclusions: The intratumoral protein expression of survivin was significantly down-regulated during neoadjuvant therapy, whereas a higher survivin level after pre-operative therapy was significantly associated with a worse histopathologic response and prognosis. Therapeutic strategies which are able to reduce survivin expression or to block survivin mediated pathways might increase the histopathologic response rate and prognosis in the multimodal therapy of patients with locally-advanced esophageal cancer. No significant financial relationships to disclose.
Utility of 18-fluorodeoxyglucose positron emission tomography (FDG-PET) in the staging, radiotherapy planning and prognostication of anal cancer
Authors: de Winton E. , Heriot A. , Ng M. , Hicks R. , Hogg A. , Milner A. , Leong T. , Fay M. , MacKay J. , Ngan S. 
Published: March 2020

4559 Background: Accurate inguinal and pelvic nodal staging in anal cancer is important for prognosis and planning of (chemo)radiation fields. There is strong evidence for the impact of FDG-PET in staging and management of cancer, with early reports of an increasing role in outcome prognostication for a number of tumours. We aimed to determine the impact of FDG-PET on the nodal staging, radiotherapy planning and prognostication of patients with primary anal cancer. Methods: Sixty-two consecutive patients with anal cancer referred to a single tertiary oncology centre between August 1997 and November 2005 were staged with conventional imaging (CIm), computed tomography, magnetic resonance imaging and chest x-ray and by FDG-PET. The stage determined by CIm and the proposed management plan was prospectively recorded and changes in stage and management as a result of FDG-PET assessed. Patients were treated using uniform radiotherapy technique and dose. The accuracy of changes and prognostication of FDG-PET was validated by subsequent clinical follow-up. Kaplan-Meier survival analysis was used to assess survival for the cohort and by FDG-PET and CIm stage. Results: The TNM stage group was changed in 23% (14/62) as a result of FDG-PET (15% up-staged, 8% down-staged). Fourteen percent of T1 patients (3/22), 42% of T2 patients (10/24) and 38% of T3–4 patients (6/16), assessed using CIm, had a change in their N or M stage following FDG-PET. Sensitivity for nodal disease by FDG-PET and CIm was 92% and 72% respectively. The staging FDG-PET scan altered management intent in 3% (2/62), and altered radiotherapy fields in 13% (8/62). Estimated 5 year overall survival and progression free survival (PFS) for the cohort was 77.3% (95% CI 55.3%-90.4%) and 72.2% (95% CI 51.5%-86.4%) respectively. Estimated 5 year PFS for FDG-PET and CIm staged N2–3 disease was 70% (95% CI 42.8%-87.9%) and 55.3% (95% CI 23.3%-83.4%) respectively. Conclusions: FDG-PET shows increased sensitivity over CIm for staging nodal disease in anal cancer and changes treatment intent or radiotherapy fields in a significant proportion of patients. Improved 5 year PFS for FDG-PET staged N2–3 disease could be consistent with more accurate nodal staging and radiotherapy targeting. No significant financial relationships to disclose.
Tumor progression and chemoradiosensitivity in relation to the expression of apoptosis related proteins in esophageal squamous cell carcinoma
Authors: Tsujitani S. , Saito H. , Tatebe S. , Ikeguchi M. 
Published: March 2020

4588 To study apoptosis related protein expression and their impact on patient’s survival time and sensitivity to postoperative chemoradiotherapy (CRT), we examined the expression of RB, mutant p53, MDM2 and Bax proteins using immunohistochemistry in 115 (CRT; 42) surgically resected esophageal squamous cell carcinoma (ESCC). We also investigated the survivin mRNA expression with quantitative analysis by real-time RT-PCR in 57 (CRT; 30) patients with ESCC. CRT contained 40–60 Gy radiation and continuous infusion of 5-FU (300mg/sqm, day1–5qw). Expression of RB, mutant p53, MDM2, Bax proteins and survivin mRNA were detected in 65%, 46%, 33%, 37% and 32% of patients, respectively. Patients with RB(+), MDM2(-), Bax(+) or survivin(-) tumor had significantly better survival rates than those with RB(-), MDM2(+), Bax(-) or survivin(+) tumor, respectively. However, there was no significant difference in survival between patients with and without mutant p53 expression. In patients not treated with CRT, those with RB(+) or survivin(-) tumor survived significantly longer than those with RB(-) or survivin(+) tumor, respectively. In patients treated with CRT, the expression of Bax protein and survivin mRNA was prognostic indicator. The 5-year survival rates of patients with Bax(+) and survivin(-) tumors were 65% and 39%, significantly superior to 21% and 0% of those with Bax(-) and survivin(+) tumors (P<0.05 and P<0.01, respectively). These results indicate that the expression levels of apoptosis related proteins are important for predicting the prognosis of ESCC patients. Furthermore, CRT may be effective in patients with Bax(+) or survivin(-) tumors. Further investigations are required for clarifying the relationship between the efficacy of postoperative CRT and apoptosis promoting status of ESCC. No significant financial relationships to disclose.
Preoperative level of VEGF and IL-6 are associated with lymph node invasion and stage in gastric cancer
Authors: OH S. , Kwon H. , Yoo H. , Lee S. , Kim S. , Kim S. , Jang J. , Kim M. , Jeong J. , Kim K. , Kim H. 
Published: March 2020

4626 Introduction: Angiogenesis plays an important role in growth, progression, and metastasis of tumors, and various cytokines are associated with the spread of cancer cell. In this study, we evaluate the role of VEGF and IL-6 in predicting the spread of gastric cancer. Methods: Preoperative one hundred twenty seven gastric cancer patients and 88 healthy subjects’ specimens were examined. The association of VEGF and IL-6 level with clinical and pathological findings was evaluated Results: Serum VEGF and IL-6 level in gastric cancer patients were higher than those in control (P<0.001, P=0.006, respectively). VEGF and IL-6 level were associated with presence of LN metastasis (P=0.003, P=0.041, respectively). IL-6 level was correlated with stage (P=0.012) and depth of invasion (P=0.018). VEGF level was correlated with invasion of lympho-vascular structure (P=0.021). VEGF and IL-6 level was not related to differentiation, size or CEA level. Conclusions: Serum VEGF and IL-6 levels in gastric cancer patients are higher than those in control. Preoperative VEGF and IL-6 levels could be a predictive marker of tumor invasion and LN metastasis. No significant financial relationships to disclose.
Intraperitoneal(IP) 5’-fluoro-2’deoxyuridine(FUDR): Safety and outcome when administered prior to adjuvant chemoradiotherapy(chemoRT) following R0 resection for gastric adenocarcinoma
Authors: Cohen D. J. , Ryan T. , Newman E. , Iqbal S. , Liu M. , Utate M. , Moore S. , Potmesil M. , Hochster H. , Muggia F. M. 
Published: March 2020

4627 Background: ChemoRT after surgery for locally advanced gastric cancer improves overall and relapse-free survival (OS and RFS) compared to observation (NEJM 2000,345:725–30). However, loco-regional recurrences (>50%) remain high and we hypothesized that adding IP FUDR would further improve outcome. Methods: Patients (pts) ECOG performance status (PS) 0–2, gastric/gastroesphogeal(GEJ) adenocarcinoma stage Ib-IV (M0) undergoing R0 resection were eligible, and had insertion of IP catheters at surgery. IP FUDR(3gm/dose/day) was given on protocol days 1, 2, 3 and 15, 16, 17 prior to 5-FU/LV and external beam RT (45Gy) as in cited study. Simon 2-stage optimum design was used to demonstrate safety. Endpoints also included were loco-regional recurrence and survival. Results: 28 pts with gastric/GEJ adenocarcinoma (25/3) were enrolled from 2002 to 2006 at 2 institutions: median age 59.5 years (range 39–81), M /F (21/7). R0 gastric resection was performed with dissection of median 22 (range 8–102) lymph nodes(LN’s). 22/28 pts were lymph node positive. Full dose IP FUDR was completed in 20/28 pts. 4 pts required dose reduction (1 for grade(gr) 2 hepatic enzyme elevation, 2 gr 2 neutropenia, 1 gr 4 neutropenia), 3 discontinued therapy (1 gr 3 abdominal pain, 1 GI abscess, and 1 bleeding arterial pseudoaneurysm). One pt received no IP treatment due to catheter failure. 24/28 pts completed chemoRT and had toxicity comparable to that previously reported in the Intergroup 0116 trial. At 26 month median follow up (range 2.8–43.4), of the 26 pts evaluable for response, 16 pts are NED, 6 alive with disease, 3 dead of disease, and 1 dead from other cause. 5 recurrences were intra-abdominal, 1 local, 2 distant, and 1 at multiple sites. At present analysis, the median RFS is 32.5 months. Conclusions: IP FUDR prior to chemoRT after R0 gastric cancer resection is well tolerated. A randomized study to test its role in reducing regional recurrence and improving outcome is warranted. (FDA Orphan Products grant# FD-R-2150–04) No significant financial relationships to disclose.
Mobilized circulating endothelial progenitor cells after the first cycle of chemotherapy with prophylactic G-CSF can be used as a predictive biomarker and patient selection marker for anti-angiogenesis combination treatment
Authors: Shin S. , Jeung H. , Ahn J. , Choi H. , Cho B. , Rha S. , Yoo N. , Roh J. , Chung H. , Chung H. 
Published: March 2020

4638 Background: We investigated whether the level of circulating endothelial progenitor cells (CEPs) and endothelial cells (CECs) could be used as surrogate predictors of clinical outcome in patients receiving taxotere-based chemotherapy for advanced gastric cancer. Methods: Peripheral blood mononuclear cells were obtained in 49 gastric cancer patients who received taxotere combined with 5-FU and leucovorine (FLT regimen) after chemotherapy and prophylactic G-CSF treatment. To categorize the endothelial cells, immunofluorescent staining for specific endothelial cell markers (CD34, vWF, P1H12, CD31) was used. The changes of CEPs and CECs and their clinical significance on the response prediction and prognosis were analyzed. Results: After the first cycle of chemotherapy, the numbers of CD34+/vWF+, CD34+, vWF+, P1H12+ and CD31+ cells of 49 patients were 19.5 (2.7% of PBMCs), 20.1 (2.7%), 30.0 (4.8%), 12.9 (2.7%) and 214.3 (26.5%) cells/ml, respectively. The number of CD34+/vWF+ and CD34+ cells after the first and second cycle of chemotherapy were found to be higher in non-responders than responders (the first cycle: P=.012 and P=.008, the second cycle: P=.027 and P=.013, respectively). Moreover, the level of CD31+ cells after the second cycle of chemotherapy were significantly decreased compared with the first cycle in the patients who showed response (P=.026). In non-responders, however, the level of CD34+ cells was significantly increased after the second cycle of chemotherapy (P=.034). The level of CD34+ cells significantly related to the median time to progression (TTP) (6.1 and 4.0 months in CD34low and CD34high, respectively, cutoff level: 5.8, P=.046). Conclusion: CD34+/vWF+ and CD34+ cells can be used as a biomarker for prediction and prognosis in taxotere-based chemotherapy. CEP after the first cycle of chemotherapy can be a selection marker for addition of anti-angiogenic treatment after chemotherapy. No significant financial relationships to disclose.
Risk factors for low-grade neuroendocrine carcinoma (LGNET): Hospital-based case-control study in US
Authors: Hassan M. , Dagohoy C. , Leary C. , Li D. , Yao J. C. 
Published: March 2020

4641 Background: There has been an increase in the diagnosed incidence of LGNET in US over the last 2 decades. Little is known about the etiology of LGNET. In this hospital-based, case-control study we evaluated the association of cigarette smoking, alcohol consumption, diabetes mellitus (DM) and family history of cancers with LGNET of different sites. Method: Cases were patients with LGNET referred to The University of Texas M.D. Anderson Cancer Center between 12/1999 and 9/2005. Controls were selected from healthy individuals who accompanied patients with other cancers. Logistic regression was applied to estimate the adjusted odds ratio (AOR) and 95% confidence interval (CI) for potential risk factors and demographic characteristics. Result: We identified 951 LGNET patients with primary sites including appendix (n=102, 10.7%), small bowel (n=234, 24.6%), lung (n=149, 15.7%), pancreas (n=166, 17.5%), stomach (n=55, 5.8%), rectum (n=56, 5.9%), and others (n=189, 19.2%). Cases were compared to 924 controls. Majority of subjects were white-race (cases, 79.7%; controls, 89.5%). Gender distribution was similar in LGNET patients with 1:1 ratio. DM was associated with pancreatic and gastric primary sites; AOR and 95% CI were 2.5 (1.6–3.9) and 4.5 (2.2–9.3) respectively. Ever cigarette smoking was associated with lung carcinoid (OR=1.3; 95%CI, 1.01–1.9) especially among heavy smokers (20 cigarettes per day), (OR=1.7; 95%CI, 1.01–2.9). Ever or heavy alcohol consumption (= 60 ml ethanol/day) was not significantly related to LGNET of any site. The significantly elevated risk for carcinoid tumors extended to participants with a family history of breast, colon, esophageal, pancreas, prostate, and renal cancers after adjustment for demographic and environmental risk factors (P<.05). Conclusion: Smoking, DM, and family history may increase the risk of LGNET of various sites. Determining environmental and genetic factors related to LGNET may lead to development of surveillance and prevention strategies for high-risk individuals. No significant financial relationships to disclose.
Value of PSA measured in middle age in predicting diagnosis of advanced prostate cancer in an unscreened population
Authors: Ulmert D. , Serio A. , Vickers A. , Eastham J. , Scardino P. , Berglund G. , Björk T. , Lilja H. 
Published: March 2020

5006 Background: The association between PSA-levels in blood and prostate cancer (PCa) is currently under intense debate as many benign conditions also affect blood levels. We recently reported that PSA-levels in blood predicted very strongly later PC-diagnosis at any stage in a large representative population-based cohort in Malmö, Sweden (MPM) where the rate of PSA-testing is very low. Now, we studied predictors of stages =T3 or metastatic (M+) PCa at the time of cancer diagnosis. Material: Among archived bloods from 22,439 men (aged =50 or 60) during 1974–86, 192/549 men diagnosed with PCa until Dec 31, 1999, were eligible cases with =T3 or M+ at time of diagnosis. Median delay from baseline to diagnosis was 17 years among cases aged =50 (n=161) and 10 years among men aged 60 (n=31). Conditional logistic regression between cases and controls nested within our study cohort determined association and interaction between analyte levels, time to diagnosis, and age. Results: There was strong evidence that plasma levels of all PSA-forms and kallikrein 2 (hK2) associate with case status (p<0.01), and even a small elevation in total PSA (tPSA) markedly increased the risk of subsequent event. A tPSA of 2.1 - 3.0 ng/ml raised the odds of subsequent event 22-fold compared to a tPSA =0.5 ng/ml and men with tPSA =2 ng/ml had a predicted probability of advanced prostate cancer of 12% - three times the population mean. AUC for a model with tPSA alone, compared to tPSA+cPSA+%fPSA+hK2 were higher in men aged 60 (AUC increase of 0.054) compared to men aged =50 (AUC increase of 0.030). This is consistent with the results of interaction analysis showing that the association between hK2-level and cases status grows stronger as the interval between date of venipuncture and diagnosis decreases. Similarly, the effect of %fPSA on case status was dependent on age suggesting that the association between %fPSA and case status is stronger in older compared to younger men. Conclusion: Very strong associations exist between levels of all PSA-forms and hK2 measured at middle age and decade(s) before diagnosis of advanced stages of prostate cancer. There is an urgent need to validate these data in independent study cohorts as they could contribute important arguments in the revision of current PC- screening guidelines. No significant financial relationships to disclose.