Introduction

Head and neck cancer is the sixth most common cancer worldwide¹. Surgery is one of the treatments of choice for this condition but results in defects following resection that require major reconstructions to restore function and cosmetics². Since the introduction of microsurgery, radical resections with free-flap reconstruction (FFRR) for head and neck tumors have gained popularity among surgeons in the specialty³. This allowed the reconstruction of large defects in a single procedure reducing recovery time, length of hospital stay and costs, as opposed to two-stage reconstruction techniques⁴.

Originally, FFRR in head and neck tumors was considered feasible only in the young population because of the associated comorbidities in the elderly, and to prolonged operative time and complications associated with surgery⁵. Since their introduction in the 1970s, microsurgical flaps for reconstruction and cosmetic repair of large defects have been gradually improving to reach a success rate > 95% in high-volume centers, thanks to technological and technical advances and to perioperative support, even in elderly patients^6,7.

The aim of this study was to evaluate the surgical outcomes of FFRR and to analyze the risk factors for vascular pedicle thrombosis in patients aged 70 years and older.

Material and methods

We conducted a retrospective, observational and comparative study of prospectively gathered data. Patients undergoing tumor resection plus neck dissection (either prophylactic or therapeutic) and microsurgical flap reconstruction (command procedure) for primary head and neck cancer between 2000 and 2020 were included. Those patients undergoing pedicled flap reconstruction or oncologic resection due to tumor relapse were excluded. The patients were divided into two groups: G1: ≥ 70 years, and G2: < 70 years. All the procedures (resection and reconstruction) were performed by the same head and neck surgeons (NAM and JMFV). The flap underwent strict clinical monitoring in all the patients and, when feasible, the vascular pedicle was checked with Doppler ultrasound at 24 and 48 hours postoperatively.

The variables analyzed included age, sex, smoking habits, alcohol consumption, preoperative risk grade ≥ III of the American Society of Anesthesiologists (ASA) physical status classification, incidence of HPV (human papillomavirus), operative time, type of flap used for reconstruction, clear margins (R0 resection), flap viability at 48 hours postoperatively, length of hospital stay, risk factors for flap vascular pedicle thrombosis, cancer stage ≥ III, postoperative complications (according to the Clavien-Dindo classification)⁸, preoperative and postoperative chemotherapy and radiotherapy, and 30-day mortality. Neoadjuvant or adjuvant therapy was indicated by the oncology department of our institution following the NCCN (National Comprehensive Cancer Network) clinical practice guidelines in oncology for head and neck cancer⁹.

All the statistical calculations were performed using SPSS Statistics V22.0 software package. The potential variables associated with thrombosis underwent logistic regression analysis to evaluate predictors of this complication.

Results

Of a total of 280 radical resections performed in our center, 178 patients with FFRR were included: 61 corresponded to group 1 (G1) and 117 to group 2 (G2). The demographic variables and risk factors are described in Table 1. Both groups were homogeneous in terms of BMI, alcohol consumption, smoking habits, neoadjuvant treatment received and incidence of HPV. The incidence of ASA grade ≥ III was significantly higher in G1 (G1:80% - G2: 35%; p = 0.005).

Table 1 Demographic variables. Comparison between G1: 70 years or older and G2: < 70 years 

Microvascular reconstruction was performed using 113 parascapular flaps (44%), 45 radial forearm flaps (25%), 16 peroneal flaps (9%) and 4 jejunal flaps (2%). The rate of complications grade I-II of the Clavien- Dindo classification was 49% (G1: 42% vs. G2: 54%; p = NS), and 33% corresponded to grade III-IV (G1: 35% vs. G2: 28%; p = 0.07). Flap failure was similar in both groups: 4 patients in G1 (5.6%) vs. 7 patients in G2 (6%), (p = NS). Seven flap failures were due to vascular pedicle thrombosis (5 venous thrombosis and 2 arterial thrombosis). Vascular pedicle thrombosis occurred mostly in peroneal flaps (4.57%) and in one scapular flap (3.43%). The remaining flap failures were due to 2 arterial erosions in patients who had previously undergone radiotherapy, 1 vascular pedicle torsion and 1 hematoma. The perioperative variables are analyzed in Table 2. Seven postoperative deaths occurred, 2 in G1 (3%) and 5 in G2 (4%), (p = NS).

Table 2 Perioperative variables 

Female sex was the only predictor of vascular flap thrombosis (p = 0.05) (Table 3). Vascular flap thrombosis was managed with Fogarty catheter thrombectomy in 1 case. Five patients required a new microsurgical flap (4 with parascapular flap and 1 with peroneal flap), and in 5 cases the complication was solved with a new pedicled pectoralis major flap. Table 3 analyzes the potential risk factors associated with the development of vascular pedicle thrombosis.

Table 3 Risk factors associated with flap pedicle thrombosis in patients undergoing commando procedures in cancers of the head and neck 

Discussion

We analyzed the safety and feasibility of radical resection of primary head and neck tumors with microsurgical flap reconstruction in patients aged 70 years or older. We found that: a) the procedure is safe and feasible in this age group; b) it has a similar incidence of major postoperative complications; c) in addition, female sex represents an independent risk factor for the development of flap pedicle thrombosis in patients undergoing FFRR.

In studies published 60 years ago, major surgeries were contraindicated in elder subjects^10,11. Such management was based on the greater number of comorbidities in these patients, prolonged anesthesia and higher incidence of postoperative morbidity and mortality^10,12. However, as life expectancy has increased as a result of better medical and surgical treatments, our understanding of perioperative physiology has improved, and these patients currently have postoperative outcomes similar to those of the general population¹³.

Resection of head and neck tumors with microvascular free flap reconstruction represents a major surgical procedure that requires prolonged anesthesia and is associated with complex postoperative complications, with risk of death¹⁴. Yet, many publications have addressed that these procedures are safe in elder patients^15-19. In 2013, Spyropoulou et al. published a retrospective study analyzing the safety of FFRR in head and neck tumors by comparing patients > 70 years (33 patients) with patients < 70 years (714 patients)²⁰. After a 3-month follow-up period, the authors did not find significant differences in flap failure, postoperative complications or reexploration. Yet, mortality rate within 15 days postoperatively was statistically higher in elder patients (6% vs. 0.28% p = 0.011)²⁰. Similarly, two other retrospective studies confirmed the safety of these procedures, without showing differences in overall complications, flap failure and donor site complications^14,21. In the same way, there were no differences in postoperative complications between the groups in our series, and we concluded that FFRR is a feasible and safe procedure in patients aged 70 years or older. The exact age to consider patients as “elderly” is a matter of controversy. Some authors propose a cutoff point of 50 years²², while others suggest an age > 80 years or even greater^15,23. However, these patients undoubtedly represent a particular challenge, as they present progressive physiologic multiorgan function decline, cognitive impairment, poor nutritional status and coexistence of multiple morbidities with direct negative impact on microsurgical reconstructions¹³. For this reason, different tools should be used to perform an exhaustive preoperative evaluation of the clinical status of those who will undergo these procedures. The different assessment scales include the Charlson comorbidity index²⁴, the Kaplan-Feinstein index²⁵ and the ASA score²⁶. In our institution we systematically use the ASA score for the preoperative evaluation of our patients.

The postoperative success rate of microvascular flaps is > 90%^27,28. However, because head and neck cancer patients generally present with multiple comorbidities, a low percentage of patients with flap failure require early surgical re-exploration. In these cases, early detection of this complication and of the potential contributing factors is essential to achieve a rapid solution²⁹. The most common cause of flap failure is venous thrombosis (58% of cases), followed by nonthrombotic events (46%) as pedicle compression or vascular spasm²⁹. A review of the literature performed in 2010 proposed different factors associated with the development of pedicle thrombosis: high ASA score, choice of vein where the anastomosis will be performed (higher risk of thrombosis in anastomosis to the external jugular system compared to the internal jugular system), advanced tumor stages, and strict postoperative flap monitoring³⁰. However, the most relevant risk factor is technical failure in flap preparation and in vascular anastomoses³⁰. In our series, only female sex was an independent risk factor for the development of vascular pedicle thrombosis in patients aged 70 years or older undergoing FFRR. A recent publication confirmed this finding, identifying female sex and other risk factors as significant predictors of free flap failure³¹. One of the most significant limitations of our study is its retrospective methodological design. Probably there may a selection bias, since those elder patients with multiple comorbidities in the preoperative assessments could not have been candidates to undergo this type of procedure and could have been excluded from the analysis. Furthermore, the analysis of all head and neck tumors is biased due to lack of differentiation of their anatomical location.

As a conclusion, free flap reconstruction after radical resection of head and neck tumors is a safe and feasible procedure in patients aged 70 years or older. Postoperative morbidity and mortality rate is similar to that of patients less of 70 years old.