Systemic chemotherapy and surgical cytoreduction for poorly differentiated and signet ring cell adenocarcinomas of the appendix

Lieu, Christopher H.; Lambert, Laura; Wolff, Robert A.; Eng, Cathy; Zhang, N.; Wen, Sijin; Rafeeq, Safia; Taggart, Melissa W.; Fournier, Keith F.; Royal, Richard E.; Mansfield, Paul F.; Overman, Michael J.

doi:10.1093/annonc/mdr279

Cited by 99 publications

(81 citation statements)

References 16 publications

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“…Although this study did not control for receipt of preoperative or postoperative systemic chemotherapy, considering the low rates of response and the excellent outcomes with cytoreductive surgery and HIPEC, we see a very limited role for systemic treatment in this setting. High grade disease, on the other hand, had much poorer outcomes, and such cases should be considered for systemic preoperative and/or postoperative chemotherapy 23,24,25 .…”

Section: Discussionmentioning

confidence: 99%

A Multicenter Randomized Trial to Evaluate Hematologic Toxicities after Hyperthermic Intraperitoneal Chemotherapy with Oxaliplatin or Mitomycin in Patients with Appendiceal Tumors

Levine

Votanopoulos

Shen

et al. 2018

Journal of the American College of Surgeons

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Background Appendiceal cancer is a rare disease, which has proven difficult to study in prospective trials. Cytoreductive surgery with HIPEC is an established therapy for peritoneal dissemination from appendiceal cancer. The optimal chemotherapeutic agent to use in the HIPEC is not clear. Mitomycin has long been the utilized, however our previous phase I experience, and European retrospective studies suggest oxaliplatin as an alternative. Therefore, we initiated a multicenter randomized trial to compare mitomycin to oxaliplatin HIPEC for appendiceal cancer. Study Design Patients with mucinous appendiceal neoplasms with evidence of peritoneal dissemination underwent cytoreductive surgery and HIPEC using a closed technique for 120 minutes. Patients were randomized intraoperatively to HIPEC using mitomycin(40mg) or oxaliplatin(200mg/M2). Follow up included daily blood counts and toxicity assessments. Results 121 analytic patients were accrued to the trial over 6 years at 3 sites. The cases were 57% female, with an average age of 55.3 years(range 22-82). The disease was low grade in 77% and high grade in 23%. There were no significant differences in hemoglobin or platelet counts. The WBC was significantly lower in the mitomycin group between postoperative days 5-10. Overall and disease free survival at 3 years were similar at 83.7% and 66.8% for mitomycin and 86.9% and 64.8% for oxaliplatin. Conclusions This represents the first completed prospective randomized trial for cancer of the appendix, and shows that multicenter trials for this disease are feasible. Both mitomycin and oxaliplatin are associated with minor hematologic toxicity. However, mitomycin has slightly higher hematologic toxicity and lower QOL than oxaliplatin in HIPEC. Consequently, oxaliplatin may be preferred in patients with leukopenia and mitomycin preferred in patients with thrombocytopenia due to prior chemotherapy.

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Section: Discussionmentioning

confidence: 99%

A Multicenter Randomized Trial to Evaluate Hematologic Toxicities after Hyperthermic Intraperitoneal Chemotherapy with Oxaliplatin or Mitomycin in Patients with Appendiceal Tumors

Levine

Votanopoulos

Shen

et al. 2018

Journal of the American College of Surgeons

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“…This is in agreement with prior reports demonstrating that even for HGA lesions, long-term survival is possible if a complete cytoreduction is obtained. 10–12 …”

Section: Discussionmentioning

confidence: 99%

Peritoneal Surface Disease (PSD) from Appendiceal Cancer Treated with Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC): Overview of 481 Cases

et al. 2014

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Background Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) used to treat peritoneal surface disease (PSD) from appendiceal cancer have shown variability in survival outcomes. The primary goal of this study was to determine predictors of surgical morbidity and overall survival. The secondary goal was to describe the impact of nodal status on survival after CRS/HIPEC for PSD from low-grade appendiceal (LGA) and high-grade appendiceal (HGA) primary lesions. Methods A retrospective analysis of 1,069 procedures from a prospective database was performed. Patient characteristics, tumor grade, nodal status, performance status, resection status, morbidity, mortality, and survival were reviewed. Results The study identified 481 CRS/HIPEC procedures: 317 (77.3 %) for LGA and 93 (22.7 %) for HGA lesions. The median follow-up period was 44.4 months, and the 30-day major morbidity and mortality rates were respectively 27.8 and 2.7 %. Major morbidity was jointly predicted by incomplete cytoreduction (p = 0.0037), involved nodes (p < 0.0001), and comorbidities (p = 0.003). Multivariate negative predictors of survival included positive nodal status (p = 0.003), incomplete cytoreduction (p < 0.0001), and preoperative chemotherapy (p = 0.04) in LGA patients and incomplete cytoreduction (p = 0.0003) and preoperative chemotherapy (p = 0.0064) in HGA patients. After complete cytoreduction, median survival was worse for patients with positive nodes than for those with negative nodes in LGA (85 months vs not reached [82 % alive at 90 months]; p = 0.002) and HGA (30 vs 153 months; p < 0.0001). Conclusions Positive nodes are associated with decreased survival not only for HGA patients but also for LGA patients even after complete cytoreduction. Nodal status further stratifies histologic grade as a prognostic indicator of survival. Patients with node-negative HGA primary lesions who receive a complete cytoreduction may experience survival comparable with that for LGA patients.

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“…Th e utility of systemic chemotherapy for metastatic appendiceal adenocarcinoma is controversial because particularly mucinous adenocarcinomas have been considered refractory to intravenous 5-fl uorouracil chemotherapy, although there are studies that suggest the opposite (Shaphiro et al 2010;Lieu et al 2012). …”

Section: Discussionmentioning

confidence: 99%

Infiltrating mucinous appendicular carcinoma during pregnancy. A case report and review of the literature

Chiverto

Cabezas

Pérez-Medina

et al. 2015

Journal of Obstetrics and Gynaecology

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Systemic chemotherapy and surgical cytoreduction for poorly differentiated and signet ring cell adenocarcinomas of the appendix

Cited by 99 publications

References 16 publications

A Multicenter Randomized Trial to Evaluate Hematologic Toxicities after Hyperthermic Intraperitoneal Chemotherapy with Oxaliplatin or Mitomycin in Patients with Appendiceal Tumors

A Multicenter Randomized Trial to Evaluate Hematologic Toxicities after Hyperthermic Intraperitoneal Chemotherapy with Oxaliplatin or Mitomycin in Patients with Appendiceal Tumors

Peritoneal Surface Disease (PSD) from Appendiceal Cancer Treated with Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC): Overview of 481 Cases

Infiltrating mucinous appendicular carcinoma during pregnancy. A case report and review of the literature

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