The Utility of Preoperative Tumor Markers in Peritoneal Carcinomatosis from Primary Appendiceal Adenocarcinoma: an Analysis from the US HIPEC Collaborative

Author(s):  
Nadege Fackche ◽  
Ryan K. Schmocker ◽  
Boateng Kubi ◽  
Jordan M. Cloyd ◽  
Ahmed Ahmed ◽  
...  
2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16280-e16280
Author(s):  
Zongyuan Li ◽  
Xiaolin Pu ◽  
Hua Jiang

e16280 Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) is the main treatment for peritoneal carcinomatosis (PC).However, It is still a major problem to predict the efficacy of HIPEC. Some studies have shown that peritoneal cancer index (PCI) can be used to predict the efficacy of HIPEC, but the invasiveness and inaccuracy are shortcomings. Therefore, we need a minimally invasive and accurate prediction biomarker. Many studies have confirmed that circulating tumor DNA (ctDNA) can accurately predict the efficacy and prognosis of various solid tumors. This study aimed to evaluate the predictive value of ctDNA from ascites and plasma for HIPEC. Methods: Eligible PC patients should be defintive diagnosed by pathology or cytology. Each patient was treated with HIPEC for 4 times, with an interval of 3 days each time. Plasma and ascites samples were collected before HIPEC and after the last HIPEC. All samples were detected by next generation sequencing (NGS). The molecular tumor burden index (mTBI) and main clone variant allele fraction (VAF) changes were used as the prediction indexes of efficacy. In addition, The changes of common tumor markers such as CEA during the same period were used as controls. Results: A total of 19 patients with PC were enrolled from November 2018 to January 2020. Firstly, the mTBI changes of 14 patients whom had plasma samples at two time points (baseline and postHIPEC)were analyzed. Among them, 3 patients had no gene mutation were detected in two time points. There were significant differences in mTBI before and after HIPEC in the remaining 11 patients (Wilcoxon, p = 0.026). the median Ascites progression free survival (PFS) was 3.35 months (95% CI: 2.34 – 5.13 months), and the median overall survival (OS) was 5.93 months (95% CI: 4.93 – 11.17 months). The mTBI decline was significantly positively correlated with ascites PFS (Spearman r = 0.673, p = 0.023) and moderately positively correlated with OS (Spearman r = 0.510, p = 0.109). The highest VAF in plasma samples was defined as the main clone mutation. The main clone VAF decline was moderately positively correlated with ascites PFS (Spearman r = 0.588, p = 0.057) and slightly positively correlated with OS (Spearman r = 0.386, p = 0.241). As the controls, We found that the common tumor markers decline was no correlated with ascites PFS(Spearman r = 0.091, p = 0.790) and OS (Spearman r = 0.287, p = 0.396). We further analyzed the correlation of VAF between ascites and plasma co-mutation genes in 12 patients. The VAF of co-mutated genes in plasma and ascites was positively correlated (Spearman r = 0.794, p = 0.001). Conclusions: Plasma ctDNA can be used as a biomarker for predicting the efficacy of HIPEC for peritoneal carcinomatosis, and its accuracy is significantly higher than comon tumor markers. However, a larger sample size study are needed to validate our results.


2019 ◽  
Vol 24 (1) ◽  
pp. 155-164 ◽  
Author(s):  
Nick C. Levinsky ◽  
Mackenzie C. Morris ◽  
Koffi Wima ◽  
Jeffrey J. Sussman ◽  
Syed A. Ahmad ◽  
...  

2017 ◽  
Vol 10 (2) ◽  
pp. 548-552 ◽  
Author(s):  
Celina Ang ◽  
Aryeh Stollman ◽  
Hongfa Zhu ◽  
Umut Sarpel ◽  
Bethann Scarborough ◽  
...  

We report the case of a patient with appendiceal adenocarcinoma with mucinous peritoneal carcinomatosis who was treated with trametinib upon identification of a GNAS R201H mutation by comprehensive genomic profiling. The molecular pathology of appendiceal neoplasms is reviewed, and the mechanistic basis underlying the clinical benefit as well as the subsequent course on trametinib that were observed in this patient are discussed.


2019 ◽  
Author(s):  
C Tauste Rubio ◽  
S Aguirre Gorospe ◽  
J Zabaleta Jurío ◽  
M Ruiz García ◽  
I Zabaleta Loinaz ◽  
...  

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14020-14020 ◽  
Author(s):  
E. Andreopoulou ◽  
F. Muggia ◽  
M. Safa ◽  
J. Escalon ◽  
A. Downey ◽  
...  

14020 Background: Mucinous peritoneal carcinomatosis is most commonly associated with primariy tumors of the appendix and colon. Typically, spread remains confined to the abdominal cavity. Imaging assessment of these mucinous lesions is difficult, and tumor markers (CEA and CA19.9) are often used as a surrogate for extent of disease. Patients (pts) often undergo surgical debulking, sometimes coupled with intraperitoneal (IP) drug delivery, but recurrence is common. Since mucin genes are regulated by EGFR, our two institutions initiated this study. Methods: Between Sept 2004 and Dec 2005, weekly cetuximab (loading 400 mg/m2 on first dose, followed by 250 mg/m2/week thereafter) was given to 20 pts (4 men, 16 women): 17 of appendiceal origin were entered a median 3 y (6 m-7 y) after diagnosis; 3 were unknown primaries 24, 23, and 2 m after diagnosis. Prior treatment included surgery (18), systemic (17), and intraoperative (4) or subsequent IP therapy (2). Results: Pts received a median of 12 doses (0–51) of cetuximab. No major objective responses were observed; transient > 25% decreases in CEA and CA19.9 were noted in 4/19 pts; markers were never elevated in 1. Stable disease was best response in 3 of 15 evaluable (5 too early). The most common toxicities, as expected, were skin rash, dryness, and nail fragility. Hypersensitivity reactions in 2 patients did not preclude repeated dosing with premedications. The median time to progression from the start of treatment was 3 m. Conclusions: Brisk accrual by two institutions in this rare clinical entity is noteworthy. In this heavily pretreated population, transient decrease in tumor markers and time on study with stable disease were encouraging, prompting plans for a future study of cetuximab with the addition of systemic irinotecan. [Table: see text]


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