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Phase II study of patients with peritoneal carcinomatosis from gastric cancer treated with preoperative systemic chemotherapy followed by peritonectomy and intraperitoneal chemotherapy
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
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2013 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 4, 824-830 p.Article in journal (Refereed) Published
Abstract [en]

Background

The aim was to evaluate the feasibility and the effectiveness of neoadjuvant systemic chemotherapy followed by cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC) in patients with peritoneal carcinomatosis (PC) from gastric cancer.

Material and methods

Eighteen patients (median age 57 years, range 38-74) were scheduled for three months' neoadjuvant systemic chemotherapy followed by CRS + HIPEC + EPIC.

Results

At the time of surgery, the peritoneal tumor burden was extensive with tumor growth on the entire peritoneal cavity. Only eight patients received the entire treatment and OS was 14.3 months (range 6.1-34.3, 95% CI 6.6-20.3). Six patients had macroscopically radical (CC0) surgery and for this subgroup OS was 19.1 months (range 6.1-34.3, 95% CI 6.9-27.1). Postoperative 90-day mortality was 10% (one patient) and the perioperative grades II-IV adverse events (AE) rate was 62.5%.

Discussion

Neoadjuvant chemotherapy followed by CRS + HIPEC + EPIC does not seem to be associated with prolonged OS in patients with extensive PC growth from gastric cancer unless macroscopically radical surgery is achieved. However, morbidity from this treatment is considerable and it cannot be recommended for routine care until a prospective randomized trial has been performed.

Place, publisher, year, edition, pages
2013. Vol. 52, no 4, 824-830 p.
Keyword [en]
gastric cancer, peritoneal carcinomatosis, neoadjuvant chemotherapy, cytoreductive surgery, HIPEC
National Category
Surgery
Research subject
Surgery
Identifiers
URN: urn:nbn:se:uu:diva-181680DOI: 10.3109/0284186X.2012.702925ISI: 000317239200018PubMedID: 22974074OAI: oai:DiVA.org:uu-181680DiVA: diva2:557361
Available from: 2012-09-27 Created: 2012-09-27 Last updated: 2017-12-07Bibliographically approved
In thesis
1. Clinical and Experimental Studies in Peritoneal Metastases from Gastric Cancer
Open this publication in new window or tab >>Clinical and Experimental Studies in Peritoneal Metastases from Gastric Cancer
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Gastric cancer (GC) is one of leading causes of death in the world, and peritoneal metastases (PM) are a major site of recurrence. PM from GC implies a poor prognosis, with median overall survival (mOS) approximately 3 months and no survival at five years.

The aims of this thesis were to explore the incidence and evaluate prognostic factors for mOS of PM from GC in a defined population; to investigate the outcome of a new multimodal treatment; to analyse the treatment costs, and to investigate differences in drug sensitivity between individual patient samples and between various tumours.

The incidence of loco-regional advanced GC was 3.8 per 100,000 person-years. Synchronous loco-regional GC in combination with synchronous distant metastasis was a negative prognostic factor while chemotherapy and good performance status, and radiotherapy plus chemotherapy were positive prognostic factors . There were no significant differences in mOS for the group of patients included during the period 2000-2004 versus 2005-2009, and this lack of improvement in mOS during the past decade justifies new treatment approaches.

In a Phase II study of patients treated with neoadjuvant systemic chemotherapy followed by cytoreductive surgery + hyperthermic intraperitoneal chemotherapy, mOS was 14.3 months and for patients with macroscopically radical surgery mOS was 19.1 months. The mean overall cost of the loco-regional treatment was $145,700 compared to $59,300 with systemic chemotherapy treatment.

In an ex vivo chemo-sensitivity test, it was determined that GC samples were equivalent to colorectal cancer in chemo-sensitivity to standard drugs and targeted drugs, whereas ovarian cancer samples were more sensitive. The individual GC samples varied considerably in sensitivity to increasing concentrations of the drugs, arguing for individualized drug selection. The incidence of loco-regional advanced GC was more common than previously reported and there were no improvements in mOS over the past decade. The mOS for patients with neoadjuvant systemic chemotherapy followed by macroscopically radical cytoreductive surgery + hyperthermic intraperitoneal chemotherapy was better than in recent reports on treatment with systemic chemotherapy. Treatment of advanced GC patients is costly irrespective of treatment modality. The GC samples varied considerably between individuals in terms of sensitivity to increasing concentrations of the drugs and were comparable to colorectal cancer in chemo-sensitivity.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 70 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 886
Keyword
gastric cancer, peritoneal metastases, peritoneal carcinomatosis, epidemiology, prognostic factor, survival, neoadjuvant chemotherapy, cytoreductive surgery, HIPEC, health economy, costs, systemic chemotherapy, cultured tumor cells, fluorometric analysis, cancer drug tests, chemo-sensitivity, anti tumor drugs.
National Category
Surgery
Research subject
Surgery
Identifiers
urn:nbn:se:uu:diva-197776 (URN)978-91-554-8635-8 (ISBN)
Public defence
2013-05-18, Gustavianum, Auditorium minus, Akademigatan 3, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2013-04-26 Created: 2013-04-03 Last updated: 2013-08-30Bibliographically approved

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Hultman, BoGlimelius, BengtSundbom, MagnusNygren, PeterHaglund, UlfMahteme, Haile

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