Morgan JE, Breau RL, Suen JY, Hanna EY. Surgical Wound Complications After Intensive Chemoradiotherapy for Advanced Squamous Cell Carcinoma of the Head and Neck. Arch Otolaryngol Head Neck Surg. 2007;133(1):10–14. doi:10.1001/archotol.133.1.10
To define the rate of complications from surgery following intensive chemoradiotherapy in patients with advanced squamous cell carcinoma of the head and neck.
The medical records of 131 consecutive patients treated with a combination of chemotherapy and radiation therapy for head and neck squamous cell carcinoma from 1995 through 2002 were reviewed. Thirty-eight patients underwent 50 surgical procedures. Thirty-seven neck dissections were performed either for persistent disease, initial neck stage N2 or greater, recurrent disease, or electively as part of salvage surgery for the primary site. Thirteen salvage operations were performed for persistent or recurrent disease at the primary site.
Academic tertiary care referral center.
A total of 131 consecutive patients treated with a combination of chemotherapy and radiation therapy for head and neck squamous cell carcinoma (mean age at diagnosis, 53 years).
Main Outcome Measure
Rate of complications from surgery.
Wound complications occurred in 4 (11%) of 38 patients and 5 (10%) of 50 procedures. Major wound complications occurred in 3 (8%) of 38 patients. Minor wound complications occurred in 2 patients (5%).
Surgery can be safely performed after intensive chemoradiotherapy.
The upper aerodigestive tract contains the anatomic structures that allow breathing, swallowing, and talking. One or more of these 3 important functions are usually altered by the presence of squamous cell carcinoma, especially when it reaches advanced stages. In the past, the primary treatment option for these lesions was complete surgical excision, which often left patients with dramatic alterations in their ability to breathe, swallow, or talk. Over the last few decades, attempts have been made to maintain these functions in patients by preserving all or part of the structures involved with cancer. These attempts have included conservative surgery (eg, partial laryngectomy), radiation therapy, and various combinations of chemotherapy and radiation therapy. Several recent studies1- 11 have supported the role of concurrent chemotherapy and radiation therapy as the primary treatment for organ preservation of advanced squamous cell carcinoma of the upper aerodigestive tract. An integral aspect of this treatment strategy is salvage surgery for persistent or recurrent disease.12 The existing literature describes complication rates from surgery following chemoradiotherapy from 24% to 61%.13- 17 The purpose of the present study was to define the rate of complications from surgery following intensive chemoradiotherapy by documenting the experience with a group of patients at the authors' institution.
The medical records of 131 consecutive patients treated with a combination of chemotherapy and radiation therapy for head and neck squamous cell carcinoma from 1995 through 2002 were reviewed. This study was approved by the institutional review board of the University of Arkansas for Medical Sciences, Little Rock. The mean follow-up time for these patients was 32 months. Patients who underwent surgery after receiving definitive chemoradiotherapy were evaluated retrospectively by reviewing their inpatient and outpatient records. Information gathered included age, sex, tumor site, TNM stage, chemotherapy regimen, dosage of radiotherapy, date and type of salvage surgery and/or neck dissection, and wound complications. Demographic and tumor data for the patients who underwent surgery is summarized in Table 1. Major wound complications were defined as pharyngocutaneous fistulas and those complications requiring further operative intervention. Minor wound complications were defined as skin flap necrosis, seroma, or wound infection. All patients received intravenous preoperative antibiotic prophylaxis and 7 days of oral postoperative antibiotics. Most patients received cefazolin sodium preoperatively and cephalexin hydrochloride for 7 days postoperatively, while patients allergic to penicillins received clindamycin hydrochloride both preoperatively and postoperatively.
Three patients underwent a sequential regimen of chemotherapy followed by radiation therapy during the early portion of this case series. They received 2 cycles of monthly cisplatinum and 5-fluorouracil followed by 69 to 72 Gy at 1.8 Gy/d, 5 days per week. Twenty-three patients received concurrent chemoradiotherapy consisting of 3 to 4 monthly cycles of cisplatinum and 5-fluorouracil with radiation therapy. Twelve patients received 2 cycles of monthly induction chemotherapy (cisplatinum and 5-fluorouracil) followed by radiation therapy, concurrent with at least 2 cycles of cisplatinum. Patients who received induction chemotherapy with a partial response (50%-99% reduction in tumor volume) or a complete response (no clinical evidence of tumor) proceeded with concurrent chemoradiotherapy. All patients received at least 2 cycles of chemotherapy. The mean dose of radiotherapy was 6960 cGy, with a range from 5940 to 7250 cGy. In 10 patients, the radiotherapy dose could not be determined from the records available.
Of 131 patients, 38 (29%) underwent 50 surgical procedures. The types of procedures performed are listed in Table 2. Complications occurred in 4 (11%) of 38 patients and 5 (10%) of 50 procedures. Table 3 summarizes the complications at the primary site and the neck. Three patients experienced major complications, 2 of which were pharyngocutaneous fistula. One of those 2 patients also developed a separate minor wound infection. There were no documented cases of seroma or skin flap necrosis.
Of 133 patients, 13 (10%) required salvage surgery at the primary site for persistent or recurrent disease. Seven patients underwent simultaneous neck dissection, while 6 patients underwent resection at the primary site only. Complications at the primary site are summarized in Table 4. Three patients (23%) experienced complications. Two patients experienced major complications (15%), both of whom underwent resection at the primary site only. One patient developed a pharyngocutaneous fistula after a total laryngectomy, which was successfully closed using a sternocleidomastoid muscle flap. Another patient required a pectoralis major myocutaneous flap to repair a pharyngocutaneous fistula after a total laryngopharyngectomy. One of the patients with a pharyngocutaneous fistula also had separate development of a wound infection. Another patient had an isolated wound infection after a total laryngectomy, which resolved with conservative therapy. Overall, minor wound complications occurred in 2 patients, for a rate of 15%. The pharynx was entered in 10 of these salvage operations, giving a fistula rate of 20% of cases in which the pharynx was opened.
Of 131 patients, 32 (24%) underwent 37 neck dissections that were performed either for persistent disease (16 patients), initial stage N2 or greater (8 patients), recurrent disease (5 patients), or electively as part of salvage surgery for the primary site (3 patients). Six patients underwent bilateral neck dissections, 5 simultaneously. One patient underwent an ipsilateral neck dissection prior to definitive chemoradiotherapy at the primary site, followed by a contralateral neck dissection for recurrence after chemoradiotherapy. Her pretreatment neck dissection was not included in this analysis. Twenty-five patients underwent “isolated” neck dissections (without simultaneous resection of the primary site), while 7 patients underwent neck dissection simultaneously with primary site resection. There were no complications in these 7 patients. There was 1 documented complication (3%) in the 32 patients who underwent neck dissection. This patient developed a chylous fistula with associated carotid artery exposure. She was treated with a pectoralis major myocutaneous flap and recovered without complication. There were no cases of wound infection, seroma, or skin flap necrosis among patients who underwent neck dissection.
Table 5 classifies the procedures performed according to wound type. For clean wounds (neck dissection only) there was a 4% (1 of 25 patients) complication rate. The complication rate in clean-contaminated wounds (primary site resection with or without neck dissection) was 23% (3 of 13 patients).
Preoperative radiation therapy alone for advanced head and neck squamous cell carcinoma has been reported to increase surgical complications, with rates varying from 37% to 74%.18- 21 Sassler et al16 first reported on the combined effect of preoperative chemotherapy and radiation therapy on surgical complication rates in 1995. They reported an overall wound complication rate of 61% (11 of 18 patients), with 77% experiencing complications when surgery was performed within 1 year after receiving chemoradiotherapy. All of these patients received a sequential regimen of induction chemotherapy followed by radiation therapy. In 1997, Newman et al15 reported wound complications in 6 (35%) of 17 patients within the first 30 postoperative days. Two patients (12%) experienced major complications, and 4 patients (24%) experienced minor complications. All patients in that series received induction chemotherapy followed by concurrent chemoradiotherapy. In 1998, Lavertu et al14 reported a 46% overall complication rate in 33 patients who had received radiation therapy alone and the same rate of 46% in 26 patients who had received chemoradiotherapy. The major wound complication rate in that series was 12% for both groups of patients, while the minor wound complication rate was 33% for the radiation therapy group and 35% for the chemoradiotherapy group. In that study, minor complications included skin incision breakdown, granulation tissue at the tracheostoma, hypothyroidism, and partial small bowel obstruction. Minor complications in the present study consisted of skin flap necrosis, wound infection, and seroma. Our more limited definition of minor wound complication partially accounted for our lower overall and minor complication rates. If this study's criteria were applied to the study by Lavertu et al,14 their overall and minor complication rates would be 27% and 15%, respectively.
Considering cases in which the pharynx was opened, Sassler et al16 had a fistula rate of 50% (7 of 14 patients). Newman et al15 opened the pharynx in 5 patients, one of whom developed a fistula (20%).15 Lavertu et al14 reported 1 fistula in 23 patients in whom the pharynx was opened, for a rate of 4%. The present study's rate of 20% (2 of 10 patients) falls reasonably among these values.
As expected, neck dissections had a lower complication rate than salvage surgery at the primary site (3% vs 23%). There are few studies that have assessed complication rates from isolated neck dissection. Conley22 described a neck dissection complication rate of 5%, while Bland et al23 described a complication rate of 38% in 132 neck dissections. Of the 50 complications in that series, 47 were localized to the neck, with most being either skin flap necrosis, wound infections, or seromas. None of the patients had received either chemotherapy or radiation therapy.23 In 1998, Boyd et al17 described 28 patients with N2/N3 neck disease who underwent neck dissection following radiation therapy alone, 4 (14%) of whom experienced wound complications. Reviewing patients who had been previously treated with either radiation therapy alone or chemoradiotherapy, Davidson et al13 reported systemic and/or wound complications in 13 (38%) of 34 patients and 15 (37%) of 41 neck dissections. The difference in complications between the radiation therapy alone group and the chemoradiotherapy group did not achieve statistical significance. When the complications were divided into wound complications and systemic complications, wound complications occurred in 8 (24%) of 34 patients and 9 (22%) of 41 neck dissections. No distinction was made in that study between major and minor wound complications.
Organ preservation protocols were developed to help patients with head and neck cancer better maintain their ability to breathe, swallow, and talk, without compromising oncologic control of disease. In that light, achieving the following 2 goals will help even more patients with head and neck cancer maintain these vital functions: (1) improved pretreatment risk stratification and (2) improved posttreatment tumor assessment. While few patients in this series required salvage surgery (29%) and the complication rate in those patients was low (10%), the ideal situation would be to initially avoid chemoradiotherapy in patients who will not respond to it, while providing chemoradiotherapy only to those who will respond. By doing so, much unnecessary morbidity, cost, and definitive treatment delay could be avoided. Further research in tumor genetics needs to be accomplished to obtain this valuable foreknowledge. Improved posttreatment tumor assessment is needed to determine which patients actually need surgery after chemoradiotherapy. Not all patients who undergo salvage surgery for persistent clinical disease or advanced nodal stage have cancer in their surgical specimens. Unnecessary cost and morbidity could be avoided by only operating on those patients who will have pathologically positive surgical specimens. Further refinement of minimally invasive biopsy techniques and advanced imaging modalities such as positron emission tomography and combined computed tomographic–positron emission tomography are needed to differentiate between the patient who needs salvage surgery and the patient who does not.
In conclusion, the findings from this study concur with those from other studies,13- 15 showing acceptable rates of surgical wound complications following organ preservation protocols using intense doses of chemotherapy and radiation therapy.
Correspondence: Justin E. Morgan, MD, 5532 Spoked Wheel Dr, Colorado Springs, CO 80918 (Morganjk99@msn.com).
Submitted for Publication: June 21, 2006; final revision received July 31, 2006; accepted September 4, 2006.
Author Contributions: Dr Morgan had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Hanna. Acquisition of data: Morgan, Breau, Suen, and Hanna. Analysis and interpretation of data: Morgan and Hanna. Drafting of the manuscript: Morgan. Critical revision of the manuscript for important intellectual content: Morgan and Hanna. Administrative, technical, and material support: Hanna. Study supervision: Breau, Suen, and Hanna.
Acknowledgment: We thank Jenny Badley, RNP, for her tireless work in caring for the patients with head and neck cancer and assisting with the data collection of this study.
Financial Disclosure: None reported.