Systemic Chemotherapy and Surgical Cytoreduction for Poorly Differentiated and Signet Ring Cell Adenocarcinomas of the Appendix
Ann Oncol. 2011 Jun 8;[Epub Ahead of Print], CH Lieu, LA Lambert, RA Wolff, C Eng, N Zhang, S Wen, S Rafeeq, M Taggart, K Fournier, R Royal, P Mansfield, MJ Overman
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This single-center retrospective study found that systemic chemotherapy is a viable option for treating metastatic poorly differentiated and signet ring cell adenocarcinomas of the appendix and that complete cytoreduction correlates with improved survival.
SUMMARY
OncologySTAT Editorial Team
Appendiceal adenocarcinomas are a rare and histologically diverse group of cancers; patient prognosis varies significantly by tumor biology. Most of these tumors are slow growing and do not develop extraperitoneal metastases, and the standard treatment is complete cytoreductive surgery (CRS), followed by hyperthermic intraperitoneal chemotherapy. Tumors with poorly differentiated or signet ring cell histology, however, tend to be more aggressive, with studies suggesting worse outcomes for patients with these tumor histologies. As treatment response in patients with poorly differentiated and/or signet ring cell tumor histology has not been evaluated, Lieu et al conducted a single-center retrospective study to examine the effects of CRS and systemic chemotherapy on survival in this subset of patients with appendiceal adenocarcinoma.
The study included patients who were treated for appendiceal adenocarcinoma at MD Anderson Cancer Center (Houston, TX) between September 1992 and January 2010 and who were identified as having either poor tumor differentiation or signet ring cell histology. Study patients (n = 142; median age, 52 years) were histologically grouped for analysis into those with poorly differentiated adenocarcinomas with/without focal signet ring cells (n = 114 [80%]), those with signet ring cell adenocarcinomas (n = 19 [13%]), and those with well- or moderately differentiated adenocarcinomas with focal signet ring cells (n = 9 [6%]). Patients’ medical records were reviewed for patient and tumor characteristics, treatment history, treatment response, laboratory tumor markers, disease progression, and survival. Patients with peritoneal metastases who underwent CRS were divided into those with no visible remaining disease following CRS (complete cytoreduction score of 0 [CC-0]) and those with visible remaining disease ≤ 2.5 mm (CC-1). For systemic chemotherapy evaluation, patients had to have visible radiographic disease prior to chemotherapy, to receive at least one cycle of chemotherapy, and to undergo follow-up radiographic evaluation; only patients with radiographic improvement were considered to have a response to chemotherapy.
Study endpoints were progression-free survival (PFS), relapse-free survival (RFS), and overall survival (OS) by Kaplan–Meier method. OS for the overall study population was calculated from date of diagnosis to death. For the chemotherapy and CRS subgroups, PFS and OS were calculated from the date of initial chemotherapy and the date of CRS, respectively.
Median follow-up was 4.5 years. All patients with metastatic disease at presentation (n = 123) had peritoneal disease; 12 (10%) also had extraperitoneal disease. Of patients with metastatic disease, 78 underwent first-line systemic chemotherapy with radiographic follow-up; the overall radiographic response rate was 44%. In the chemotherapy cohort, median PFS was 6.9 months (95% CI, 5.3–9.2), and median OS was 1.7 years (95% CI, 1.4–2.3). In a multivariate analysis of this subset, achieving a chemotherapy response correlated with improved PFS (hazard ratio [HR], 0.49; 95% CI, 0.27–0.89; P = .02), and achieving a complete CRS correlated with improved OS (HR, 0.26; 95% CI, 0.10–0.66; P = .004).
Of patients with metastatic disease, 26 had complete CRS (15 with CC-0; 11 with CC-1). In the CRS cohort, median RFS after resection was 1.2 years (95% CI, 1.05–7.08), and median OS was 4.2 years (95% CI > 2.55). In a multivariate analysis of this cohort, achieving a CC-0 resection correlated with both improved RFS (HR, 0.07; 95% CI, 0.01–0.53; P = .01) and improved OS (HR, 0.02; 95% CI, 0–0.37; P = .01).
This single-center retrospective study suggests that systemic chemotherapy is a viable treatment option for patients with metastatic poorly differentiated and/or signet ring cell appendiceal adenocarcinoma. In addition, CRS may offer survival benefits for those patients in whom complete CRS (no visible remaining disease) is considered feasible.
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