Head and neck cancer with microvascular reconstruction : prospective, randomized, blinded clinical study on effects of Dexamethasone on postoperative recovery, long-term quality of life, and mortality

Background Surgery is usually the primary treatment of Head and neck cancer (HNC). It causes significant morbidity and large surgical defects that usually require microvascular reconstruction to restore the tissue deficiency. Treatments of these very challenging areas are associated with psychological disruption of life. Unfortunately, the studies of long-term Health-related quality of life (HRQoL) after microvascular reconstruction surgery of HNC are scarce. Complications related to microvascular surgery are quite rare, but they can be devastating. Prolonged treatment periods often exacerbate complications and therefore delay adjuvant oncologic treatments. Glucocorticoids (GCs) are widely used perioperatively to diminish immediate postoperative complications such as PONV, pain and swelling, but the evidence of their safety is unclear. Complex surgery of HNC and postoperative complications may influence survival and patient’s high long-term mortality is common. Aim This thesis is focused on three main aims: first, to evaluate whether the perioperative use of dexamethasone in reconstructive HNC surgery is beneficial (Study I-II); second, to evaluate the long-term HRQoL compared with an age- and gender-standardized sample of the general population (Study III); and third, to investigate whether the use of perioperative dexamethasone affects short-term mortality in HNC patients and to analyze the predictors affecting long-term mortality (Study IV). Patients and Methods This study consisted of a prospective, double-blind randomized group of 93 HNC patients with a microvascular reconstruction operated at the Department of Oral and Maxillofacial Surgery and Department of Plastic Surgery in Helsinki University Hospital in Finland between December 2008 and February 2013. Patients were randomized into two groups, 51 patients received dexamethasone (DEX) and 42 served as a control group (NON-DEX). Patients in the study group received 10 mg dexamethasone intravenously (IV) every 8 h on the first day, every 12 h on the second day and once on the third day, total amount of dexamethasone being 60 mg. In studies I, II, and IV, the data was analyzed depending on randomization, in Study III, the data was analyzed for all patients independent of randomization using 15D questionnaire. Results Patients who received dexamethasone had significantly more major complications, especially surgical infections, and need for second surgery within three weeks. Dexamethasone use failed to diminish the amount of neck swelling, length of stay in the intensive care unit (ICU) or hospital, or duration of intubation or tracheostomy (Study I). The use of dexamethasone did not reduce postoperative nausea and vomiting (PONV) in five days. Patients in the DEX-group received less oxycodone in five days postoperatively and reported significantly less pain. Patients required significantly more insulin and lactate levels were higher (Study II). The long-term (4.9-years) HRQoL of operated HNC patients was significantly lower than at baseline. The most affected dimensions were “speech” and “usual activities” at the end of follow-up. The HRQoL was a significantly lower in HNC patients as compared with the general population (Study III). Perioperative use of dexamethasone was associated with higher short-term mortality in reconstructive HNC surgery. During the first year, more deaths occurred in the DEX group than in the NON-DEX group: at one month 4% vs 0%, at six months 14% vs 0% and at 12 months 22% vs 5%. HNC was the primary cause of death in most of the deceased. The most important long-term predictors of death were distant metastases, CCI 5-9, and the use of perioperative dexamethasone (Study IV). Conclusions The results of this thesis conclude that the perioperative use of dexamethasone is not recommended for reconstructive HNC patients requiring microvascular reconstruction. It is associated with major complications and higher short-term morbidity, and it does not seem to significantly enhance immediate post-operative recovery or shorten ICU or hospital stay. Long-term HRQoL was significantly reduced and speech and usual activities were the most affected dimensions up to 4.9-years after the operation in the whole patient cohort. There is more harm than benefit of the perioperative use of dexamethasone with reconstructive HNC patients.