Influence of irradiation and oncologic surgery on head and neck microsurgical reconstructions

Oral Oncology 48 (2012) 367–371

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Influence of irradiation and oncologic surgery on head and neck microsurgical reconstructions Thomas Mücke a,⇑, Andrea Rau a, Jochen Weitz a, Andreas Ljubic a, Nils Rohleder a, Klaus-Dietrich Wolff a, David A. Mitchell b, Marco R. Kesting a a b

Department of Oral and Maxillofacial Surgery, Technische Universität München, Klinikum Rechts der Isar, Germany Department of Oral and Maxillofacial Surgery, Mid Yorkshire Hospitals NHS Trust, Aberford Road, West Yorks WF1 4DG, UK

a r t i c l e

i n f o

Article history: Received 30 September 2011 Received in revised form 14 November 2011 Accepted 21 November 2011 Available online 11 December 2011 Keywords: Microvascular free flaps Radiation therapy Neck dissection Flap surgery Outcome Microsurgery

s u m m a r y Despite the refinement of microsurgical techniques, microsurgical free flap transfer in patients with a history of previous radiotherapy, neck dissection or free flaps remains a challenge in oncologic reconstructive surgery. Previous studies on the prognostic factors for postoperative complications have been largely retrospective and shown conflicting results. Our aim was to design a prospective study to identify negative outcome predictors of free flap surgery in previously treated oral cancer patients. Prospective study including all patients who required microsurgical free flap transfer for reconstruction of the oral cavity between July of 2007 and June of 2010 with subset analysis of those cases in whom previous surgical or nonsurgical oncological treatment for head and neck cancer had been carried out. A total of 360 free flaps were performed in 358 patients, of whom 61 had previous neck dissection and 58 had undergone radiation therapy. Operation time was significantly found to be longer in irradiated patients. The need for microsurgical revision, postoperative wound infection and free flap loss were significantly associated with the ASA score and a previous neck dissection. Wound infection was seen significantly more often after radiotherapy. Previous neck dissections and radiotherapy as well as the ASA score are significant negative predictors for success in free flap transfer. For patients with prior oncologic treatments in their medical history, we recommend detailed preoperative assessment of the vascular status and an intensified postoperative care to reduce complication rates to improve outcome in oncologic reconstructive surgery. Ó 2011 Elsevier Ltd. All rights reserved.

Introduction Reconstructive surgery in the treatment of cancer of the head and neck region has been improved over the recent decades by the routine use of free flap reconstruction and refining microvascular techniques.1 Simultaneously radiotherapy and chemotherapy have developed with both combination techniques and techniques aimed at maximizing dose to the tumor and minimizing damage to surrounding tissue. Unfortunately while Intensity Modulated Radiotherapy can reduce toxic doses to surrounding tissue the addition of chemotherapy in a variety of forms creates even greater damage in an unpredictable fashion to surrounding tissue resulting in substantially increased scarring and fibrosis. Reoperation is the only viable form of salvage in patients who do not respond to this treatment or who develop a further new cancer.2 Reconstruction in ⇑ Corresponding author. Address: Department of Oral and Maxillofacial Surgery, Klinikum Rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675 München, Germany. Tel.: +49 89 4140 2921; fax: +49 89 4140 4993. E-mail address: [email protected] (T. Mücke). 1368-8375/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.oraloncology.2011.11.013

an irradiated area of the head and neck results in an increased level of difficulty especially if previous neck dissection has been performed.3,4 Previous operations whether ablative or reconstructive also result in scarring, disruption of normal anatomy and therefore may affect the outcome of microvascular free flap reconstructive surgery of the head and neck in this group of patients. Counter intuitively several retrospective studies have failed to demonstrate a significant influence of irradiation or previous ablative or reconstructive surgery on the success of microvascular reconstruction.5–7 Head and neck cancer patients, especially patients suffering from oral squamous cell carcinomas often have a history of tobacco and alcohol abuse, associated with cardiovascular and pulmonary diseases.8 Reconstruction of defects are complex, time consuming, cost intensive, and potentially associated with high rates of morbidity and mortality.9,10 The range of surgical possibilities in previously operated, irradiated, and highly co-morbid patients remains unclear and is mostly based on the surgical experience of the treating oncological team. It is self evident that successful surgery is not only dependent on the extent of the tumor, but is also dependent

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on the general medical condition of the patient, as postoperative complications are generally increased with additional diseases.8,9,11 It is intuitive that preoperative assessment of this complex group of patients is important but without a clear idea of the negative predictors of outcome it is hard to plan investigations with the maximum efficiency. Previous studies on prognostic factors for postoperative complications have mainly been retrospective analyses of medical or surgical complications5,6,11–13 and their results are conflicting, generating the need for this prospective study. The purpose of the present study was to perform a prospective evaluation of patients undergoing microsurgical reconstruction to evaluate the outcome of head and neck reconstructions in a previously treated neck (either by operation or irradiation) to identify negative outcome predictors for wound healing and free flap failure. We also determined whether microsurgical complications or postoperative medical complications had the more profound influence on morbidity and mortality outcomes. Patients and methods Study design and patient recruitment Any patient who required reconstructive surgery within the oral cavity with microvascular free flaps was eligible. Patients receiving preoperative neoadjuvant radiation therapy were not included in this study as the protocols available are not comparable in doses and effect on the irradiated tissue.14 A prospective study was initiated from July of 2007 to June 2010. All patients were prospectively subdivided into four different groups: (1) untreated patients, (2) patients previously undergone neck dissection, (3) irradiated patients, (4) treated by microsurgical free flap reconstruction. The groups (2–4) were included if the treatment was performed before more than 12 months. Postoperative care Our standard regimen was to keep the patient sedated for one night on the intensive care unit and afterwards transfer on the surgical ward. Data analysis Recorded parameters included: age, sex, preoperative medical history, American society of Anesthesiologists classification of preoperative status,15 diagnosis, stage of disease, defect localization, type of microvascular free flap, choice of recipient vessels, flap success, rate and number of operative revisions, primary or secondary reconstruction, type of previous treatment (radiation or surgery), type of previous neck dissection (if any), microvascular complications, the total operative time, wound healing disturbances subdivided into dehiscence and infection at the neck, region of reconstruction, or donor site, stay on intensive care unit, and length of hospital stay. Infection was defined as a purulent discharge at the wounds. Descriptive statistics for quantitative variables are given as the mean ± standard deviation. The data were analyzed with the ‘‘Statistical Package for the Social Sciences’’ (SPSS for Windows, release 18.0.0. 2010, SPSS Inc., Chicago, IL, USA). Figures are generated with SPSS and MicrosoftÒ Office Excel (Microsoft Excel for Windows, release 11.0, 2003, Microsoft Corporation, Redmond, WA, USA). Multiple linear regression analyses were used to determine factors independently associated with the dependent variable flap success, wound healing disturbances, or microsurgical revision.

95% confidence intervals (95% CI) are also given. Differences were considered to be statistically significant for a two-sided p-value of less than 0.05. Results General characteristics From July 2007 to June 2010, 360 free flaps were performed in 358 consecutive patients in this study. Two patients had had simultaneous free flaps in one surgery. There were 212 men (59.2%) and 146 woman (40.8%), with a mean age of 59.7 ± 13.4 years (range, to years). The ASA scores of patients were categorized 1 in 178 (49.7%), 2 in 92 (25.7%), 3 in 87 (24.3%), and 4 in 1 (0.3%) patients. The reason for microsurgical reconstructions were oral squamous cell carcinoma in 278 patients (77.7%), osteonecrosis in 27 cases (7.5%), sarcomas of the head and neck in 25 patients (7.0%), trauma in 16 patients (4.5%), mucoepidermoid carcinoma in 7 cases (1.9%), and adenoid cystic carcinoma in 5 cases (1.4%). Defects involved the mandible in 109 (30.4%), anterior and lateral floor of the mouth in 89 (24.9%), the upper jaw in 64 (16.8%), the buccal mucosa in 31 (8.7%), and the oropharynx in 5 (1.4%) patients. The microvascular free flaps used for reconstruction were the radial forearm flap in 154 (43%), fibula flap in 80 (22.3%), anterolateral thigh flap in 74 (20.7%), soleus perforator flap in 19 (5.3%), iliac crest flap in 18 (5%), ulnaris forearm flap in 4 (1.1%), lateral arm and gracilis flap in each 2 (0.6%), parascapular, latissimus dorsi, radial forearm combined with a fibula flap, and radialis forearm combined with a iliac crest flap in each one patient (0.3%). The vessels used for anastomosis at the neck region are illustrated in Fig. 1. In 61 patients (17%) previous oncological neck dissection was performed and 58 patients (16.2%) underwent preoperative radiotherapy involving the oral cavity and the neck. Forty three patients (12.0%) had at least one previous free flap to the oral cavity. Intensity-modulated radiation therapy was mainly used for patients treated by adjuvant radiotherapy or neutron irradiation in adenoid cystic carcinomas.16,17 An average of 64.6 Gy (range 54–96 Gy) was administered. In the multiple regression analysis a longer time of operation was found in patients with previously radiation therapy (p = 0.022, 95% CI, 0.99–1.00). There was no association between the time of operation and previously performed neck dissection (p = 0.15, 95% CI, 0.99–1.01). In the presented cohort, a microvascular revision was performed in 51 (14.2%) cases, a total of 327 microvascular free flaps (91.3%) were performed successfully. The mean stay of patients on intensive care unit was 1.53 ± 1.48 days (range 0–16), the mean stay on standard ward was 16.1 ± 0.5 days (range 6–100). Complications and infection was detected in 22.0% (n = 79) of patients. Negative outcome predictors of free flap surgery Predictors potentially contributing to an increased complication rate are presented in Tables 1–3. Microsurgical revision In the multiple regression analysis the ASA score (p = 0.002) was found to be a strong predictor for the need to perform a postoperative revision of microanastomoses. A higher rate of necessary revisions was noted in patients with anastomoses at the superior thyroid vein (p = 0.04) as recipient vein for the microvascular free flap compared to the other locations (internal jugular, retromandibular, facial), whereas no significant difference was found to be associated with an increased risk in arterial anastomosis (Table 1). In relation to the influence of previous treatments, only neck

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Figure 1 Type of arterial and venous anastomosis used for microsurgical anastomosis at the head and neck. The superior thyroid vein was found to have a statistically significant association with an increased need for microvascular revisions.

dissections before free flap reconstruction (p = 0.013) were found to be significantly influencing the need for revision (Table 1).

Infection Partial flap failure and wound dehiscence due to wound infections were the most common complications. Factors influencing the development of wound infection are the ASA score of the patient (p = 0.002), time of operation (p = 0.049), previously performed neck dissection (p < 0.0001), radiotherapy of the head and neck (p = 0.025), and the need for microsurgical revisions (p < 0.0001) (Table 2).

Free flap loss Factors influencing the development of free flap failure are the ASA score of the patient (p = 0.012), previous neck dissection (p = 0.001), microvascular revisions (p < 0.0001), and wound infections at the neck and the defect site (p < 0.0001). Neither patient dependent factors nor surgical factors were found to be associated with free flap failure (Table 3). Discussion This study reveals the relations between wound infection, microvascular revisions, and free flap failure in a complex patient

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Table 1 Significant outcome predictors affecting the success and course after microvascular free flap surgery requiring microsurgical revision of anastomoses.

⁄

Variable

Odds ratio

95% CI

p

Age Gender ASA score

1.01 0.94 1.75

0.97–1.04 0.49–1.81 1.24–2.49

0.825 0.857 0.002*

Reason for reconstruction Type of free flap

0.98 0.925

0.86–1.13 0.76–1.13

0.810 0.450

Arterial anastomosis A. facialis A. lingualis

1.09 0.98

0.56–2.12 0.32–3.01

0.804 0.971

Venous anastomosis V. thyroidea sup. V. jugularis int. V.retromandibularis V. facialis Other Time of operation

3.24 1.95 1.23 1.98 1.10 1.00

1.06–9.94 0.66–5.80 0.38–3.99 0.67–5.88 0.11–10.93 0.99–1.01

0.040* 0.230 0.725 0.220 0.935 0.643

Previous neck dissection Previous radiotherapy Previous microvascular free flap

2.36 1.52 1.20

1.2–4.7 0.73–3.18 0.50–2.86

0.013* 0.264 0.685

p < 0.05.

Table 2 Significant outcome predictors affecting the success and course after microvascular free flap surgery causing wound infection.

⁄

Variable

Odds ratio

95% CI

Age Gender ASA score

0.98 0.69 2.14

0.95–1.01 0.34–1.41 1.31–3.49

p 0.101 0.303 0.002*

Reason for reconstruction Type of free flap Time of operation

0.96 1.11 1.01

0.83–1.12 0.93–1.30 1.00–1.01

0.589 0.243 0.049*

Previous neck dissection Previous radiotherapy Previous microvascular free flap Microvascular revision

5.86 2.26 0.62 7.43

2.35–14.60 1.11–4.61 0.23–1.68 3.94–14.02

<0.0001* 0.025* 0.344 <0.0001*

p < 0.05.

Table 3 Significant outcome predictors affecting the success and course after microvascular free flap surgery causing flap loss.

⁄

Variable

Odds ratio

95% CI

Age Gender ASA score

1.02 0.72 0.49

0.98–1.06 0.32–1.60 0.27–0.85

0.291 0.418 0.012*

Reason for reconstruction Type of free flap

0.92 0.98

0.73–1.17 0.78–1.21

0.515 0.816

Arterial anastomosis A. facialis A. lingualis

0.86 0.74

0.37–1.99 0.20–2.70

0.727 0.651

Venous anastomosis V. thyroidea sup. V. jugularis int. V. retromandibularis V. facialis Other Time of operation

0.51 1.07 0.58 0.56 0.79 1.01

0.12–2.17 0.24–4.67 0.15–2.31 0.14–2.16 0.29–2.12 0.99–1.01

0.363 0.932 0.444 0.396 0.637 0.321

Previous neck dissection Previous radiotherapy Previous microvascular free flap Microvascular revision Wound infection

0.28 0.74 1.20 0.13 0.05

0.13–0.28 0.27–2.05 0.50–2.86 0.60–0.29 0.02–0.14

0.001* 0.563 0.685 <0.0001* <0.0001*

p < 0.05.

p

cohort who may require microsurgical reconstruction as part of head and neck oncologic salvage or rehabilitative surgery. The influence of previously performed treatments such as radiotherapy and neck dissection in the history of the patient has been found to be of significance in the outcome of microvascular free flap surgery, as they were strongly correlated with complications in the postoperative course of the patient. The influence of radiotherapy of patients on the vessels in the head and neck has been well investigated and becomes obvious in the clinical situation.5,6,9,12,18 The scarring and fibrosis of the generally poor quality tissue found in post irradiation sites is associated with a longer time of operation as also found in this study.11 It is worth noting that it is generally more experienced surgeons who perform surgery on patients who underwent previous radiotherapy, the time of operation was found to be significantly longer and the associated complications, especially wound infections and the need for microsurgical revision, was found to be significantly higher. The overall success rate in the literature was not found to be lower than in patients without previously performed irradiation therapy,5,6,9,12,19 and only a few studies have found a significant difference in these patients.11,18 In the present study age was not found to be a significant indicator of free flap complications, the ASA score has been identified in all categories to be a significant predictor of medical complications. These findings were already reported in the literature in patients without previous treatments.13,20–22 The general medical condition in patients selected for radiotherapy (as opposed to surgery when the cure rates are comparable) is generally considered to be reduced.23,24 The complication rate may therefore reflect the overall poor physiological condition of patients who underwent radiotherapy rather than the problems caused by radiation of the recipient vessels at the head and neck. The ASA score is generally supposed to influence the outcome of free flap surgery as a prognostic factor for the overall outcome.25,26 Is also represents an important score for preoperative risk assessment for the development of postoperative morbidity.26 In contrast, there was found no association between the ASA score and the disease-free survival or overall mortality.27 The occurrence of metastatic diseases to the neck were also not correlated with the ASA score, reflecting its independent role in patients general and not disease specific assessment.27 For further scoring, the Acute Physiology and Chronic Health Evaluation (APACHE II) score was evaluated for predicting early postoperative surgical complications.28 In a large study, a strong correlation between APACHE II scores with total flap loss and with other immediate complications was found in patients managed postoperatively in the critical care unit.28 Although it has been proven to be a useful scoring system, its use is rather common in head and neck oncology practice than the ASA score.13,20–22,25–28 Interestingly, in patients with previously performed neck dissection a strong correlation with free flap loss, wound infection, and microsurgical revision was detected. This finding is in accordance with the literature, and is thought to be due to inadvertent vascular injury and ligation of potential recipient vessels during the previous surgery. It is important to keep this factor in mind as it was one of the strongest factors associated with the need for microsurgical revision, free flap loss, and wound infection in this study. A preventative strategy would be for neck dissections for head and neck cancer only to be performed by those familiar with microvascular reconstructive techniques even if those techniques are not being planned during that particular operation. Preoperative planning by using computed tomographic angiography in these patients could be beneficial to assess the vascular status of the neck and potentially reduce postoperative complications and costs.9,11 Some authors routinely advocate the contralateral neck vessels for microsurgical reconstruction,29,30 but the surgical

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time, potential morbidity of dissection of the opposite neck, and elevated risk of kinking or compression of the vein is increased.11 As part of the preoperative assessment of the vascular status, preoperative computed tomographic angiography was integrated into daily reconstructive practice based on the presented data. If patients underwent bilateral neck dissection or developed wound healing disturbances without the clear identification of healthy vessels of the external carotid artery in the oncological follow up radiological examination, computed tomographic angiography is performed to assess potential recipient arteries and veins for microsurgical reconstruction. The role of infection is of particular interest in patients after complex surgical operations.1 Complex ablation and reconstruction of the head and neck with marked distortion of the anatomy makes radiologic evaluation very difficult and the detection of potentially dangerous infections much harder. In addition, in patients with previous radiotherapy infections are common and associated with free flap failure31 taking the whole procedure of functional and esthetic rehabilitation at risk.1,9,12 Most studies evaluating microsurgical reconstructive surgery at the head and neck in patients are limited by the fact that the patients are surveyed in a retrospective manner. Only large, controlled, prospectively designed studies can resolve clinical questions completely. In the present study, the patients and their data were analyzed and evaluated in a prospective manner. To the best of our knowledge, this is the first study evaluating the outcome of patients after microsurgical free flap surgery in a prospective survey. Conclusion Patients with a history of head and neck cancer who have undergone neck dissection or radiotherapy and who have the need for complex microsurgical reconstruction are at increased risk for postoperative complications. Previously performed neck dissections are particularly associated with the risk of microsurgical revision, free flap loss, and wound infection in the postoperative course. Irradiated patients, microsurgical revision, and long operation time are also significant risk factors for postoperative wound infections. The ASA score of the patient was also found to be a significant factor for the development of postoperative complications. We conclude, that a history of neck dissection and irradiation in patients requiring microvascular reconstructive procedures has an increased for preoperative assessment of the vascular status and special postoperative care of patients in order minimize complications. Conflict of interest statement The authors declare that no potential conflict of interest exists. References 1. Mücke T, Wolff KD, Wagenpfeil S, Mitchell DA, Hölzle F. Immediate microsurgical reconstruction after tumor ablation predicts survival among patients with head and neck carcinoma. Ann Surg Oncol 2010;17(1):287–95. 2. Mücke T, Wagenpfeil S, Kesting MR, Hölzle F, Wolff KD. Recurrence interval affects survival after local relapse of oral cancer. Oral Oncol 2009;45(8):687–91. 3. Klug C, Berzaczy D, Reinbacher H, Voracek M, Rath T, Millesi W, et al. Influence of previous radiotherapy on free tissue transfer in the head and neck region: evaluation of 455 cases. The Laryngoscope 2006;116(7):1162–7. 4. Schultze-Mosgau S, Grabenbauer GG, Radespiel-Troger M, Wiltfang J, Ries J, Neukam FW, et al. Vascularization in the transition area between free grafted soft tissues and pre-irradiated graft bed tissues following preoperative radiotherapy in the head and neck region. Head Neck 2002;24(1):42–51. 5. Bengtson BP, Schusterman MA, Baldwin BJ, Miller MJ, Reece GP, Kroll SS, et al. Influence of prior radiotherapy on the development of postoperative complications and success of free tissue transfers in head and neck cancer reconstruction. Am J Surg 1993;166(4):326–30.

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