The purpose of this study was to determine whether chemotherapy delivered concurrently with external beam radiation therapy for loco-regionally advanced head and neck cancer affects the rate or severity of postoperative complications in patients who underwent salvage surgery for recurrent or persistent disease with simultaneous microvascular free flap reconstruction. The primary study group consisted of patients with head and neck malignancies that had undergone surgical salvage with microvascular free flap reconstruction for persistent or recurrent disease following definitive radiation or concomitant chemoradiation treatment. A group of demographically matched patients who underwent microvascular free flap reconstruction for non-malignant and malignant conditions who never received radiation were randomly selected to serve as a control group. The study cohort was divided according to radiation treatment. The overall success rate of flap reconstruction was 92%, with an overall complication rate of 23%. Concurrently administered chemotherapy did not appear to affect the type of or the complication rate. The results of this investigation indicate that microvascular free flap reconstruction of head and neck defects is highly predictable, results in relatively few major complications, and suggests that neither radiation alone nor concomitant chemoradiation has a statistically significant effect on overall flap survival or complication rate.
Contemporary emphasis on organ preservation utilizing chemoradiotherapy protocols for the treatment of laryngeal, hypopharyngeal, and oropharyngeal squamous cell carcinoma, as well as increasing enthusiasm for adjuvant, concomitant chemoradiation for surgically resectable, advanced stage oral squamous cell carcinoma underscores the evolving role and increased importance of free tissue transfer in irradiated fields. The addition of chemotherapy, which has been shown to improve survival in advanced head and neck cancer, intensifies the effect of radiation on the surrounding tissue and can impact wound healing.
More than 15 years have elapsed since the introduction of microvascular surgery to head and neck reconstruction and a number of studies with large series of patients demonstrate that in experienced hands the success rate is greater than 90%. Perioperative complication rates range from 9% to 85% depending on the definition of complication and the patient population. Surgical re-exploration for ischemic flaps occurs under 10% of the time and salvage rates have been reported to be between 50% and 70%. Mortality is generally not greater than any other major surgical procedure in age and performance matched patient populations, ranging from 0.5% to 6.5%.
Questions have arisen regarding the effect of radiation therapy on microvascular free tissue transfer, and the true effect on complications and flap survival is not definitively known. Numerous experimental and clinical investigations have come to divergent conclusions. Radiation therapy has the potential to damage small vessels and may adversely affect microvascular anastomoses. Specific vascular damage has been demonstrated in experimental models and includes diminished smooth muscle activity, endothelial cell dehiscence, and vessel wall fibrosis. In an experimental study in rabbits, K rag et al. showed that administering radiation to recipient vessels before surgery significantly increased free flap failure rates. In a clinical study, D eutsch et al. reported a higher complication rate in patients receiving preoperative or postoperative radiation, and concluded that the timing of the radiation did not affect complications. Other experimental studies performed in rats found that radiating recipient vessels before surgery did not adversely effect free flap viability. The preponderance of clinical evidence suggests that radiation therapy does not affect the rate or severity of local complications after free tissue transfers.
Concomitant chemoradiation is increasingly administered to patients with advanced stage head and neck squamous cell carcinoma and may or may not have an effect on reconstructive microvascular free tissue transfer. Although C hoi et al. found no correlation between complications and chemotherapy in a multivariant analysis, few studies have independently evaluated the effect of chemoradiation therapy on free flap complications. The purpose of this study is to determine whether chemotherapy delivered concurrently with external beam radiation therapy (XRT) for loco-regionally advanced head and neck cancer affects the rate or severity of postoperative complications in patients who underwent salvage surgery for recurrent or persistent disease with simultaneous microvascular free flap reconstruction.
Materials and methods
The records of 305 consecutive patients who underwent microvascular free flap reconstruction from 1995 to 2005 were reviewed retrospectively. Demographic variables were collected in addition to diagnosis, tumour site, stage, cancer therapy including radiation/chemotherapy and surgery, medical co-morbidities, flap donor and recipient site, postoperative complications and flap survival. The primary study group consisted of patients with malignant head and neck tumours that had undergone surgical salvage with microvascular free flap reconstruction for persistent or recurrent disease following definitive radiation or concomitant chemoradiation as part of their initial treatment modality. An additional group of demographically matched patients who underwent microvascular free flap reconstruction for a variety of problems and who never received radiation were randomly selected to serve as a control group. Patients with inadequate records, a history of osteoradionecrosis and those who received postoperative radiation therapy (re-irradiation) or chemotherapy were excluded from the study. For purposes of comparison, the study cohort was divided, according to radiation treatment: group 1 (control) no radiation; group 2 (XRT) radiation alone; group 3 (ChemoXRT) concomitant chemoradiation. Descriptive statistics were recorded and an analysis of variance was performed to identity differences between the three groups. Fisher’s exact test was used to evaluate the null hypothesis that the occurrence of a particular outcome measure was the same for all three patient groups. The primary outcome measures were type and rate of various postoperative complications. Study cohort characteristics are summarized in Table 1 . A new variable, ‘problem’ was created, which was true if there was partial or complete flap failure. Partial flap loss was defined as complete or partial necrosis of the skin paddle for the fibula osteocutaneous flap or partial necrosis for the anterolateral thigh flap. In order to determine if some combination of data could be found which improved the prediction of a complication, a logistic regression analysis was performed on a number of patient variables, such as sex, radiation status, infection and other complications, and reoperation.
|Group||No XRT ( n = 25)||XRT ( n = 21)||ChemoXRT ( n = 19)||Total ( n = 65)|
|Median age||56.7||55.7||54.6||55.7 (SD = 15)|
|Other malignant||3||1||0||4 (6%)|
|Oral cavity||22||16||3||41 (63%)|
|Salivary gland||3||2||2||7 (11%)|
|Radial forearm||10||9||7||26 (40%)|
|Anterolateral thigh||0||0||1||1 (2%)|
|Lat Dorsi||0||4||0||4 (6%)|
|Skin necrosis||0||1||2||3 (5%)|
|Wound infection||4||3||3||10 (15%)|
|Salivary fistula||0||2||1||3 (5%)|
|Partial flap failure||0||1||3||4 (6%)|
|Complete flap failure||2||2||1||5 (7%)|
XRT generally consisted of megavoltage photon and electron treatment delivered by means of a standard 3-field isocentric technique. Patients receiving chemotherapy were generally treated with cisplatin. All patients were reconstructed immediately with various microvascular free flaps using standard microinstrumentation. The microvascular anastomosis was performed under a surgical microscope of 10× power, utilizing microinstruments with a low closing pressure and 9-0 suture. The arterial anastomosis was generally performed in end-to-end fashion into a branch of the external carotid artery. The venous anastomosis was generally performed in end-to-side fashion into the internal jugular vein. No systemic heparin or colloid solution was administered routinely, although all patients were treated with aspirin to minimize platelet aggregation postoperatively. During the first 24 h postoperative period, patients were monitored with hourly flap checks using visual and hand-held Doppler examination. Any significant change in turgor, colour or Doppler signal prompted return to the operating room. Salvage reconstructive procedures were variable depending on the prognosis of the patient.