Abstract 227P
Background
Appendix cancer is a rare disease, with marked differences in natural history and chemotherapy response by histologic subtypes. Goblet Cell Adenocarcinoma (GCA) is particularly understudied, with little data to guide clinical decision making or molecular data to direct drug development.
Methods
The Foundry platform was used to query electronic health records to identify patients with GCA of the appendix. Median Overall Survival (OS) was calculated from the date of initial diagnosis to death. A Cox-proportional hazards regression model was performed, considering multiple clinicopathologic variables. Clinical Targeted sequencing and whole exome sequencing (WES) profiles were analyzed.
Results
A total of 414 patients with GCA were identified with a median age of 57, median follow up of 57 months, and median OS of 95 months. 253 (64%) had stage IV disease and 309 (86%) had poorly differentiated tumors. Lymph Node (LN) involvement was noted in 143 (44%), while Lymphovascular Invasion (LVI) was noted in 241 (74%), Perineural Invasion was present in 275 (87%), and Signet Ring Cells (SRC) were observed in 183 (44%). On multivariable analysis, stage IV disease, LVI, and SRC were independently associated with OS (p<0.05) (Table). 40 patients received first-line chemotherapy at our institution, with radiological response in 12 (30%) and PFS of 11 months. 59 patients had cytoreductive surgery (CRS). Median OS was 32 months, mean peritoneal cancer index was 15 and complete cytoreduction (CCR=0/1) was achieved in 42 (71%). 116 tumors underwent somatic gene mutation testing, TP53 was mutated in 22 (27%). WES analysis of 15 tumors identified recurrent deletion at 19q, 19p, and 22q chromosomal regions in 8 (53%) cases, leading to loss of apoptosis-inducing genes, such as WTIP and PDCD2L. Table: 227P
| Variables | Univariable | Multivariable | ||
| HR | P value | HR | P value | |
| Lymph node involvement | 3.2 | <0.01 | 0.7 | 0.36 |
| Poorly differentiated | 2.6 | 0.01 | 1.1 | 0.84 |
| Lymphovascular invasion | 4.9 | <0.01 | 5.3 | <0.01* |
| Signet ring cells | 1.6 | <0.01 | 1.8 | 0.049* |
| Stage IV | 11.4 | <0.01 | 8.8 | <0.01* |
Conclusions
This study highlights the clinical features predicting survival in patients with GCA and suggests a new staging system is needed in GCA to better stratify patient outcomes.
Legal entity responsible for the study
The authors.
Funding
This work was supported by the Colonel Daniel Connelly Memorial Fund, the National Cancer Institute (grant No. K22 CA234406 to Dr Shen, Cancer Center Support grant No. P30 CA016672), the Cancer Prevention and Research Institute of Texas (CPRIT) (grant No. RR180035 to Dr Shen, who is a CPRIT Scholar in Cancer Research), and a Conquer Cancer Career Development Award (to Dr Shen).
Disclosure
All authors have declared no conflicts of interest.