General Anesthetics in CAncer REsection Surgery (GA-CARES) Trial: Pragmatic Randomized Trial of Propofol vs Volatile Inhalation Anesthesia Wade Coomer, 1Donald
1 BS ,
Sanjeev Ponnappan,
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Most patients undergoing major surgery for cancer require general anesthesia
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In contrast with propofol, volatile anesthetics depress NK cell activity both in vitro as well as in breast cancer patients5 and may therefore induce immunosuppression
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Volatile agents have been shown to upregulate HIF-1,6 which might promote tumor metastasis, whereas propofol downregulates HIF-16
The investigators hypothesize that patients who have their anesthesia maintained with TIVA will have better outcomes of survival compared to those receiving VA
References 1.
Pasin L, Landoni G, Cabrini L, et al. Propofol and survival: a meta-analysis of randomized clinical trials. Acta Anaesthesiol Scand 2015;59:17-24.
2.
Eschwege P, Dumas F, Blanchet P, et al. Haematogenous dissemination of prostatic epithelial cells during radical prostatectomy. Lancet 1995;346:1528-30. van der Bij GJ, Oosterling SJ, Beelen RH, Meijer S, Coffey JC, van Egmond M. The perioperative period is an underutilized window of therapeutic opportunity in patients with colorectal cancer. Ann Surg 2009;249:727-34. Yamaguchi K, Takagi Y, Aoki S, Futamura M, Saji S. Significant detection of circulating cancer cells in the blood by reverse transcriptase-polymerase chain reaction during colorectal cancer resection. Ann Surg 2000;232:58-65.
4.
Samuel Demaria,
5 MD ,
Elliot Bennett-Guerrero,
6 MD
5.
Buckley A, McQuaid S, Johnson P, Buggy DJ. Effect of anaesthetic technique on the natural killer cell anti-tumour activity of serum from women undergoing breast cancer surgery: a pilot study. Br J Anaesth 2014;113 Suppl 1:i56-62.
6.
Huang H, Benzonana LL, Zhao H, et al. Prostate cancer cell malignancy via modulation of HIF-1alpha pathway with isoflurane and propofol alone and in combination. Br J Cancer 2014;111:1338-49.
7.
Chang C, Wu M, Chien Y, et al. Anesthesia and Long-Term Oncological Outcomes: A Systematic Review and Meta-analysis. Anesthesia & Analgesia 2020; 132:623-634.
Multi-center study planning to enroll 2,000 adult patients across 5 participating locations undergoing any one of 8 procedures for resection of known or suspected cancer: • Lobectomy or pneumonectomy • Esophagectomy • Radical (total) cystectomy • Pancreatectomy for adenocarcinoma • Partial hepatectomy
Results •
Results still pending
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As of August 14, 2021, enrollment for the GA-CARES trial has reached 1563 out of the desired 2000 subjects
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Previously published meta-analysis of 17 retrospective cohort studies has shown patients who received propofol-based TIVA were associated with significantly better overall survival (p = .008) but no significant difference in recurrence-free survival (p = .137)7 compared to patients who received volatile agent
• Hyperthermic intraperitoneal chemotherapy (HIPEC) • Gastrectomy (total or subtotal) • Cholecystectomy or bile duct resection for known or suspected cancer
Figure 3. Forest plot of overall survival. HRs are presented as propofol-based total intravenous anesthesia in comparison to volatile anesthesia. CI, confidence interval; HR, hazard ratio; IV, inverse variance method; TIVA, total intravenous anesthesia; VA, volatile anesthesia. From Chang et al.7
However, there is no conclusive evidence regarding the optimal choice of anesthetic maintenance and its effects on outcomes following cancer surgery
Hypothesis
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The safety profile and effectiveness of both anesthetic techniques have been well studied and found to be comparable peri-operatively1 Prior studies suggest that patients can be “seeded” with their own cancer cells during surgery,2-4 implicating the activated immune system, e.g., natural killer (NK) cells, in response to circulating cancer cells
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Tim Quinn,
4 MD ,
Methods
In adults, general anesthesia is almost always induced using propofol but is maintained during the operation with either total intravenous anesthesia (TIVA) using propofol or inhalation of a volatile agent (VA) (i.e., gasses such as sevoflurane or desflurane)
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Jacob Nadler,
3 MD ,
and Barbara Zucker School of Medicine at Hofstra/Northwell 2Long Island Jewish Medical Center 3University of Rochester 4Roswell Park Center 5Icahn School of Medicine at Mt. Sinai 6Stony Brook University
Introduction •
1,2 MD ,
Figure 1. Map of New York State showing locations of 5 sites participating in GA-CARES trial
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Figure 2. Illustrative diagram of a lung lobectomy
After written informed consent is obtained, patients are randomized (1:1) to either TIVA with propofol or volatile inhalational anesthetic Pragmatic trial: no changes to routine care other than randomization to receiving either TIVA vs. volatile agent for maintenance of general anesthesia Intraoperative data is extracted from the anesthesia record and long-term follow-up data is collected from the New York Cancer Registry Primary Endpoint(s)
Figure 4. Forest plot of recurrence-free survival of TIVA vs. VA. From Chang et al.7
Future Directions •
The results of this study in conjunction with 2 other ongoing randomized clinical trials will help to definitively answer whether propofol should be used routinely in cancer surgery
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There may also be implications of using propofol-based anesthesia over volatile agents in other kinds of surgeries
Secondary Endpoint(s)
• Overall survival with • Recurrence free survival minimum 2-year follow-up • Postoperative hospital length of stay