Could methylated reprimo cell-free DNA serve as a novel tumor marker to assess response in locally advanced gastric cancer treated with preoperative chemotherapy?

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 101-101
Author(s):  
Bettina Gabriele Muller ◽  
Alejandra Alarcon ◽  
Jorge M Arancibia ◽  
Francisca Alfaro ◽  
Jose Antonio Sola ◽  
...  

101 Background: Gastric cancer (GC) is one of the leading causes of cancer death. Perioperative chemotherapy (CT) for locally advanced GC improves curative resection rates and survival compared to surgery alone. Response assessment is challenging and no tumor markers have been validated for this purpose. We conducted a pilot study to investigate the role of methylated Reprimo (RPRM) cell-free DNA (cfDNA) as tumor marker for assessment of response to preoperative CT in patients enrolled in the study GOCCHI 2009-01 (NCT01633203). Methods: Patients with locally advanced GC referred to receive preoperative CT with Epirubicin + Cisplatin + Capecitabine for 3 cycles were offered to enter the study. Patients had to have operable GC, with baseline CT showing a transmural tumor and/or regional lymphnode metastasis with no distant spread assessed by a multidisciplinary tumor board. After the approval of the amendment of the protocol to allow blood sampling for tumor marker measurement and only if informed consent had been given, blood samples were taken at day one of each cycle of preoperative CT. The status of methylated RPRM cfDNA was assessed by Methylight and the number of copies per mL was determined. Patients with at least 2 samples were analyzed. Results: Thirteen patients signed the informed consent form for this substudy, and 11 patients had blood samples available for analysis. Of these, 8 patients had detectable methylated RPRM cfDNA on Day 1 of the first cycle (i.e. baseline). Five patients showed decrease in methylated RPRM cfDNA, while 5 patients had increased levels of the tumor marker in subsequent measurements. In one patient, methylated RPRM cfDNA was not detected in either of two assessments. One patient with a marked increase in methylated RPRM cfDNA after two cycles of CT had metastatic disease at laparotomy. Correlation between pathological findings and changes in methylated RPRM cfDNA will be presented. Conclusions: Our findings suggest that methylated RPRM cfDNA could serve as a novel tumor marker to assess response in locally advanced GC treated with preoperative chemotherapy. Further validation of these preliminary results is warranted.

2015 ◽  
Vol 148 (4) ◽  
pp. S-568
Author(s):  
Alejandro H. Corvalan ◽  
Marcelo Garrido ◽  
María J. Maturana ◽  
Oscar Corsi ◽  
Gerardo Ledermann

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jaeseung Shin ◽  
Joon Seok Lim ◽  
Yong-Min Huh ◽  
Jie-Hyun Kim ◽  
Woo Jin Hyung ◽  
...  

AbstractThis study aims to evaluate the performance of a radiomic signature-based model for predicting recurrence-free survival (RFS) of locally advanced gastric cancer (LAGC) using preoperative contrast-enhanced CT. This retrospective study included a training cohort (349 patients) and an external validation cohort (61 patients) who underwent curative resection for LAGC in 2010 without neoadjuvant therapies. Available preoperative clinical factors, including conventional CT staging and endoscopic data, and 438 radiomic features from the preoperative CT were obtained. To predict RFS, a radiomic model was developed using penalized Cox regression with the least absolute shrinkage and selection operator with ten-fold cross-validation. Internal and external validations were performed using a bootstrapping method. With the final 410 patients (58.2 ± 13.0 years-old; 268 female), the radiomic model consisted of seven selected features. In both of the internal and the external validation, the integrated area under the receiver operating characteristic curve values of both the radiomic model (0.714, P < 0.001 [internal validation]; 0.652, P = 0.010 [external validation]) and the merged model (0.719, P < 0.001; 0.651, P = 0.014) were significantly higher than those of the clinical model (0.616; 0.594). The radiomics-based model on preoperative CT images may improve RFS prediction and high-risk stratification in the preoperative setting of LAGC.


PLoS ONE ◽  
2018 ◽  
Vol 13 (12) ◽  
pp. e0208508 ◽  
Author(s):  
M. Rohan Fernando ◽  
Chao Jiang ◽  
Gary D. Krzyzanowski ◽  
Tifany Somer-Shely ◽  
Wayne L. Ryan

2010 ◽  
Vol 28 (35) ◽  
pp. 5210-5218 ◽  
Author(s):  
Christoph Schuhmacher ◽  
Stephan Gretschel ◽  
Florian Lordick ◽  
Peter Reichardt ◽  
Werner Hohenberger ◽  
...  

PurposePatients with locally advanced gastric cancer benefit from combined pre- and postoperative chemotherapy, although fewer than 50% could receive postoperative chemotherapy. We examined the value of purely preoperative chemotherapy in a phase III trial with strict preoperative staging and surgical resection guidelines.Patients and MethodsPatients with locally advanced adenocarcinoma of the stomach or esophagogastric junction (AEG II and III) were randomly assigned to preoperative chemotherapy followed by surgery or to surgery alone. To detect with 80% power an improvement in median survival from 17 months with surgery alone to 24 months with neoadjuvant, 282 events were required.ResultsThis trial was stopped for poor accrual after 144 patients were randomly assigned (72:72); 52.8% patients had tumors located in the proximal third of the stomach, including AEG type II and III. The International Union Against Cancer R0 resection rate was 81.9% after neoadjuvant chemotherapy as compared with 66.7% with surgery alone (P = .036). The surgery-only group had more lymph node metastases than the neoadjuvant group (76.5% v 61.4%; P = .018). Postoperative complications were more frequent in the neoadjuvant arm (27.1% v 16.2%; P = .09). After a median follow-up of 4.4 years and 67 deaths, a survival benefit could not be shown (hazard ratio, 0.84; 95% CI, 0.52 to 1.35; P = .466).ConclusionThis trial showed a significantly increased R0 resection rate but failed to demonstrate a survival benefit. Possible explanations are low statistical power, a high rate of proximal gastric cancer including AEG and/or a better outcome than expected after radical surgery alone due to the high quality of surgery with resections of regional lymph nodes outside the perigastic area (celiac trunc, hepatic ligament, lymph node at a. lienalis; D2).


BMC Cancer ◽  
2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Wang-Yang Pu ◽  
Rong Zhang ◽  
Li Xiao ◽  
Yong-You Wu ◽  
Wei Gong ◽  
...  

2007 ◽  
Vol 22 (4) ◽  
pp. 287-294 ◽  
Author(s):  
H.W. Chang ◽  
K.H. Tsui ◽  
L.C. Shen ◽  
H.W. Huang ◽  
S.N. Wang ◽  
...  

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 136-136
Author(s):  
U. Pluschnig ◽  
J. Zacherl ◽  
S. Schoppmann ◽  
M. Raderer ◽  
G. Prager ◽  
...  

136 Background: Gastric cancer is a worldwide common malignant disease with a high mortality rate. Adjuvant chemotherapy did not result in a survival advantage in Caucasian populations. Therapeutic chemotherapy options consist of either monotherapy or of polychemotherapy and have been applied as neoadjuvant chemotherapy with combinations of epirubicin, cyclophosphamide and 5-fluorouracil or capecitabine as well as cisplatin or oxaliplatin. The aim of this retrospective analysis was to investigate the use of the EOX regimen in the neoadjuvant setting which had shown activity in advanced gastric cancer. Methods: 23 patients (pts) (median age: 70, range 36-85, years; 16 pts >65 years) with locally advanced adenocarcinoma of the upper GI-tract received 3 courses of preoperative chemotherapy with epirubicin 50 mg/m2, day1, oxaliplatin 130 mg/m2, day 1, and capecitabine 2,000 mg/m2, days 1-14, of a 3-week cycle. Toxicity was assessed by CTC (Common Toxicity Criteria) after every cycle. Progression free survival (PFS) was defined as time from surgery to disease progression assessed by PET-CT which was performed at diagnosis and after 3 cycles chemotherapy. Results: 20 pts completed all three planned cycles of preoperative chemotherapy, 2 pts received only 1 cycle because of rapid tumor progression and 1 pt. is currently still on treatment. 16 pts. underwent surgery with curative resection with 2 pCRs on pathological review. 6 pts. remained inoperable despite chemotherapy and 1 pt is currently scheduled for surgery. After surgery, 2 pts. died after a median of 9 months (8-10). 4 pts. died without surgery due to disease progression. After a median follow-up of eight months (range 5-26), median PFS and overall survival was not reached yet. In 2 pts., grade 3-4 toxicities including nausea, diarrhea and hand-foot syndrome and one non-life-threatening pulmonary embolism occurred. Conclusions: In summary, EOX is a well tolerated, safe, and efficacious neoadjuvant treatment in also elderly patients with locally advanced adenocarcinoma of the upper GI-tract. However, more studies with a larger population are needed to corroborate the current results of this promising treatment schedule. [Table: see text]


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