Quality of life in patients after resection of pt3 lateral tongue carcinoma: Microvascular reconstruction versus primary closure

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1 ORIGINAL ARTICLE Quality of life in patients after resection of pt3 lateral tongue carcinoma: Microvascular reconstruction versus primary closure Martin Canis, MD, 1 * Bernhard G. Weiss, MD, 1 Friedrich Ihler, MD, 1 Eva Hummers Pradier, MD, 2 Christoph Matthias, MD, 1 Hendrik A. Wolff, MD 3 1 Department of Otorhinolaryngology, Head and Neck Surgery, University of G ottingen, Germany, 2 Department of General Practice/Family Medicine, University of G ottingen, Germany, 3 Department of Radiation Oncology, University of G ottingen, Germany. Accepted 12 September 2014 Published online 16 June 2015 in Wiley Online Library (wileyonlinelibrary.com). DOI /hed ABSTRACT: Background. Controversy exists regarding the functional advantages of free flap reconstruction after partial glossectomy as compared to primary closure. Methods. Forty patients were included in this retrospective analysis after resection of pt3 lateral tongue carcinomas. Twenty patients received a free forearm flap and 20 patients had a primary closure. All patients had adjuvant chemoradiation, were free of disease at least 1 year after therapy, and completed the German versions of the European Organization for Research and Treatment of Cancer (EORTC) questionnaires Quality of Life Questionnaire-Core 30-questions (QLQ-C30) and Quality of Life Questionnaire-Core 30 Head and Neck 35-questions (QLQ-H&N35). Results. Mean time between surgery and quality of life (QOL) assessment was months. The average resection was 41.60% (reconstruction) of the oral tongue, and 39.1% (primary closure). After reconstruction, patients had significantly (p >.05) fewer problems with the swallowing, speech, and social eating subdomains of the EORTC QLQ-H&N35. All other items showed no significant differences. Conclusion. Our preliminary results suggest that free flaps might be useful when treating pt3 tongue cancer. VC 2015 Wiley Periodicals, Inc. Head Neck 38: 89 94, 2016 KEY WORDS: pt3 tongue carcinoma, free flap, primary closure, quality of life, partial glossectomy INTRODUCTION The relevance of health-related quality of life (HRQOL) has undergone a quantum shift since the beginning of the 21st century. According to the World Health Organization, HRQOL is the quality of life (QOL) relative to one s health or disease status and intended to be a major concern of policymakers, researchers, and health care practitioners. 1 Once regarded as a secondary outcome measure occasionally useful in addition to biological and clinical markers of disease, a major change has occurred within the last years with HRQOL issues now being at the forefront of public health policies. Head and neck squamous cell carcinoma severely affect patients health and well-being, whereas surgical treatment and radiotherapy improve the prognosis with regard to survival, they frequently result in impaired basic and social activities of daily life and can be disfiguring. 2 Therefore, assessing the impact of head and neck squamous cell carcinoma therapy on HRQOL is of utmost importance not only for the individual patient, but also to guide future therapeutic strategies. After resection of large tongue carcinomas, preservation and restoration of speech and swallowing function is one of the most important primary considerations with This article was published online 16 Jun An author was mistakenly added and has since been removed. This notice is included in the online and print versions to indicate that both have been corrected. *Corresponding author: M. Canis, University of G ottingen, Department of Otorhinolaryngology, Head and Neck Surgery, Robert-Koch-Str. 40, G ottingen, Germany. martin.canis@med.uni-goettingen.de regard to long-term HRQOL. 3 However, decision-making in terms of reconstructive surgery is challenging for both surgeon and patient because an individual prediction of postoperative function is hardly possible. Major factors that affect postoperative function and HRQOL depend on tumor stage and site, the extent of tissue resection, and the type of reconstruction. 4,5 For patients presenting with carcinoma of the lateral tongue, postoperative swallowing and speech performance is mostly affected by the extent of tissue loss, with function decreasing with an increasing percentage of resection. 6 For tissue resection, primary closure, 7 local flaps, 8 pedicled flaps, 9 or microvascular free tissue transfer 10 has been propagated and published. However, there is no evidence proving the functional advantages of any one method over the others in terms of HRQOL. 11 For therapeutic decision-making in patients with pt3 tongue carcinoma, we investigated speech and swallowingrelated QOL after partial glossectomy, microvascular tongue reconstruction, or primary closure of the defect and adjuvant chemoradiation. We compared patients who had undergone primary closure versus those who had received free forearm flap reconstruction at least 1 year earlier. The present study was exploratory and findings were regarded as preliminary. PATIENTS AND METHODS Patients The study was carried out as a retrospective chart analysis between January 2009 and July 2012 and approved HEAD & NECK DOI /HED JANUARY

2 CANIS ET AL. by the institutional review board (reference number 19/ 11/13An). All procedures were conducted in 1 single tertiary center by 2 experienced surgeons. A total of 40 consecutive patients with previously untreated locally advanced squamous cell carcinoma of the tongue and pt3, cn0 2, and cm0 disease were treated with curative intent at the Department for Otorhinolaryngology Head and Neck Surgery of the G ottingen University Medical Center. All tumors were staged according to the current classification of the Union for International Cancer Control and the American Joint Committee on Cancer. 12 Inclusion criteria were: pt3 tongue carcinoma, primary tumor resection, and patients who were alive and free of disease at least 1 year after surgery. We included 20 consecutive patients after resection of a pt3 lateral tongue carcinoma and microvascular reconstruction and 20 consecutive patients after resection of a pt3 carcinoma of the lateral tongue and primary closure of the defect. Exclusion criteria for this study were: nonsquamous cell carcinomas, simultaneously second primary tumor, simultaneous distant metastases, and cn3 neck disease. Treatment of primary tumors Preoperative examination consisted of microscopic and rigid or flexible endoscopic examination of the oral cavity, the oropharynx/hypopharynx, and the larynx on the alert patient, followed by ultrasonography of the neck for lymph node evaluation and local staging. CT or MRI of the neck was undertaken unless the patient presented with satisfactory imaging performed at the referring hospital. Further standard preoperative investigations included a CT scan of the chest and ultrasonography of the abdomen. At the beginning of the planned surgery, with the patient under general anesthesia, a panendoscopy was performed to exclude any second primary tumor in the upper aerodigestive tract before tumor resection. Enoral laser microsurgery was undertaken with the CO 2 -laser in continuous superpulse mode. Resection was performed using the technique previously described by Steiner and Ambrosch. 13 Histopathological examination of the resection margins proved to be a complete (R0) resection. In patients undergoing a reconstruction procedure, tissue defects were reconstructed by a free radial forearm transplant, whereas, in control patients, the defects were closed by suture. No patient declined to participate in this study. Adjuvant chemoradiotherapy Adjuvant chemoradiotherapy was performed in all patients. In all cases, intensity-modulated external-beam radiotherapy was given 5 times per week with daily concomitant cisplatinum-based chemotherapy. The primary tumor and all lymph node areas with histopathologically proven invasion of the capsule were treated daily with 2.08 Gy up to a cumulative dose of 62.4 Gy. Histopathologically diseased lymph nodes without invasion of the capsule received 1.92 Gy daily up to a cumulative dose of 57.6 Gy. On both sides of the neck, including the supraclavicular region, all lymph node areas without proven invasion were covered with 1.8 Gy daily up to a cumulative dose of 54 Gy. Evaluation of health-related quality of life All patients completed the German versions of the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) 14 and the EORTC Head and Neck Life Questionnaire (QLQ-H&N35). 15 The QLQ-C30 questionnaire is widely used in conjunction with the QLQ-H&N35 to assess HRQOL in clinical studies of patients with head and neck cancer and has demonstrated adequate psychometric properties. Patients were surveyed at least 12 months after completion of all therapeutic procedures. The EORTC QLQ-C30 consists of a global health status/ global QOL scale, 5 functional scales, and symptom or single-item scales. The H&N35 contains 18 symptom or single-item scales. High values for the functional and general QOL scales indicate high functionality and QOL, whereas high values in the symptom scales indicate strong symptoms or impairment. Value differences of 10 are usually considered clinically relevant. 15 Statistical methods Statistical analyses were carried out by SigmaPlot 2004 for Windows version 9.01 (Systat Software, Chicago, IL). To detect significant differences between groups with free flap and primary closure, the t test was used to compare measurements if the data was normally distributed, as assessed by the Shapiro Wilk normality test. If no normal distribution was found, the Mann Whitney rank sum test was used instead. For categorical variables, the chi-square test or Fisher s exact test were performed. Throughout all tests, a p value of a <.05 was considered to be statistically significant. RESULTS Patients and health-related quality of life scores We included 20 patients after resection of a pt3 lateral tongue carcinoma and microvascular reconstruction. Patient s characteristics are shown in Table 1. Mean follow-up since completion of all treatment was months, months within the reconstruction group and months within the primary closure group. Postoperative N classifications of both groups are given in Table 1. The mean time between surgery and HRQOL assessment was months, in the reconstruction group and in the primary closure group. The average resection volume in the reconstruction group was cm, within the primary closure group cm. This comprises an average 41.60% reduction of the entire tongue volume 16 in the reconstruction group, and 39.1% in the primary closure group. The EORTC QLQ-C30 and the EORTC QLQ-H&N35 scales and items are shown in Table 2. Mean values of QOL questionnaires after reconstruction and primary closure are also shown in Figures 1 and 2. After reconstruction with free radialis forearm flaps, patients had significantly (p <.05) less difficulty (on 3 of 33 scales) within the swallowing, speech, and social eating 90 HEAD & NECK DOI /HED JANUARY 2016

3 QUALITY OF LIFE AFTER TONGUE RECONSTRUCTION TABLE 1. Sample characteristics. Reconstruction (n 5 20) Primary closure (n 5 20) p value Sex Male 18 90% 17 85% Female 2 10% 3 5% 1.000* Age, y Median Range Time from diagnosis until surgery, mo Median Range Resection volume cm Mean SD Neck dissection Levels I III % % Level IV 13 65% 11 55%.871 Level V 9 45% 10 50% Levels I V 4 20% 5 25% Marital status Single 6 30% 4 20%.715 Married 14 70% 16 80% Habit Cigarette smoking 16 80% 18 90%.661 Alcohol 8 40% 9 45% pn 0 0 0% 0 0% % 4 20% 2a 6 30% 4 20% 2b 7 35% 7 35% * Fisher s exact test. Mann Whitney rank sum test. Chi-square test. subdomain of the EORTC QLQ-H&N35 compared with patients after primary closure. The 3 scales (swallowing, speech, and social eating) that differed significantly between the groups also showed clinically meaningful mean differences (greater than 10 points), favoring the reconstruction group. All other items within the EORTC QLQ-C30 and the EORTC QLQ- H&N35 questionnaires showed no statistically significant or clinically relevant differences. Postoperative complications and functional results Within the reconstruction group, 1 patient experienced partial necrosis of the free flap and needed revision of the venous anastomosis under general anesthesia; 1 patient had postoperative bleeding of the donor site requiring revision under plexus anesthesia. Ten patients needed a temporary tracheotomy because of swelling. Their tracheostoma was closed before chemoradiotherapy in 6 cases and after chemoradiotherapy in 4 cases. Within the primary closure group, 1 patient developed cervical hematoma after neck dissection and 1 patient experienced postoperative bleeding in the oral cavity. Temporary tracheostomy was needed in 2 patients because of swelling that were closed after adjuvant treatment. Both had to be managed in the operating room. Two patients needed a temporary tracheotomy postoperatively because of swelling of the tongue with dyspnea. In both groups, no patient died because of bleeding, aspiration, and/or airway obstruction. Postoperatively, all patients needed nasogastric feeding tubes for a mean duration of 14.3 days (range, 7 36 days) in the reconstruction group and 11.7 days (range, 5 28 days) in the primary closure group. In each group, 1 patient required a temporary gastrostomy tube because of impaired swallowing function. After a gradual improvement, these were removed 4 months later in the reconstruction group and after 8 months after primary closure. Nasogastric feeding tubes and gastrostomy tubes were removed only when the patients were able to eat a normal diet without any clinical and radiologic signs of aspiration. DISCUSSION Partial glossectomy has a vast influence on a patient s HRQOL because swallowing and speech performance is mostly affected by the extent of tissue loss. 4,5 Moreover, scarring of the tongue can tie the tongue down to the remaining floor of the mouth, thereby further decreasing function. 17 Therefore, numerous authors have proposed reconstruction of soft tissue after partial glossectomy in order to maintain mobility of the remaining tongue. 18 Reconstruction enables the surgeon to achieve oncologic safety because of wider tumor resection, while minimizing voids and allowing for better speech and mastication. Many types of free and pedicled flaps have been HEAD & NECK DOI /HED JANUARY

4 CANIS ET AL. TABLE 2. Results of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30-questions and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Head and Neck 35-questions quality of life questionnaires. All patients (n 5 40) Reconstruction (n 5 20) Primary closure (n 5 20) Mean SD Mean SD Mean SD EORTC QLQ-C30 Global health status/qol Physical functioning Role functioning Emotional functioning Cognitive functioning Social functioning Fatigue Nausea and vomiting Pain Dyspnea Insomnia Appetite loss Constipation Diarrhea Financial difficulties EORTC QLQ-H&N35 Pain Swallowing * Senses Speech * Social eating * Social contact Sexuality Teeth Open mouth Dry mouth Sticky saliva Cough Feeling ill Pain killers Nutritional supplements Feeding tube Weight loss Weight gain Abbreviations: EORTC QLQ-C30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30-questions; QOL, quality of life; EORTC QLQ-H&N35, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Head and Neck 35-questions. * p <.05 for comparison of reconstruction group versus primary closure group. Scores range from 0 100; a high score for the functioning scale and the global QOL scale represents a better level of functioning, whereas a high score for a symptom scale or a single-item scale represents a high level of symptoms or problems. described for tongue reconstruction, including free radial forearm 10,19 and anterolateral thigh flaps, 20 or pedicled supraclavicular artery island 21 and myocutaneous pectoralis major flap. 9 On the other hand, some authors recommend reconstruction of the tongue by free flap only in cases where the void is larger than 50% of the tongue. 10 Therefore, it is still not clear if free flap reconstruction improves HRQOL, and there is considerable debate about functional advantages of free flap reconstruction, as compared with pedicled flaps or primary closure. In HRQOL investigations, the time of evaluation is a crucial factor and studies have demonstrated some variability within the first 12 months after treatment. 22 Some studies 23,24 suggested some stability of scores 1 year after treatment; however, others suggested variability over the course of long-term follow-up. 25 HRQOL can be reliably surveyed as a long-term outcome quality indicator in patients with disease-free head and neck cancer. Different studies 3,26 investigated HRQOL combining a general questionnaire with a disease-specific instrument. Within the present study, we used the same approach with a general questionnaire applicable to all patients with cancer (the EORTC QLQ-C30) as well as a specific questionnaire (the EORTC QLQ-H&N35). The EORTC QLQ- H&N35 is designed for use in association with the EORTC QLQ-C30 questionnaire by patients with head and neck cancer regardless of the tumor site, stage, or treatment regimen. The radial forearm flap continues to be the workhorse in reconstruction of substantial defects in the oral cavity. 18 It is a thin, soft tissue transplant with consistent anatomy, however, variable in size and shape. Further advantages are large-caliber vessels for microvascular anastomosis and low donor site morbidity. The results of Brown et al 27 support the use of free flaps for glossectomies larger than one quarter of the tongue in order to prevent scarring and contracture of the resection site. Hartl et al 11 investigated correlations between HRQOL and the 92 HEAD & NECK DOI /HED JANUARY 2016

5 QUALITY OF LIFE AFTER TONGUE RECONSTRUCTION FIGURE 1. Mean values of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30- questions (EORTC-QLQ-C30) questionnaire after reconstruction and primary closure. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] FIGURE 2. Mean values of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Head and Neck 35-questions (EORTC-QLQ-C30-H&N35) questionnaire after reconstruction and primary closure. *p <.05 for comparison of reconstruction group versus primary closure group. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] extent of surgical resection in patients who had undergone free flap tongue reconstruction after resection of T4a tongue carcinoma. Using the EORTC H&N35 questionnaire, the authors demonstrated that the volume of resection is a major predictor of swallowing-related and aspiration-related QOL after tongue resection and free flap reconstruction. However, reconstruction did not seem to palliate effects of soft-tissue loss, especially in tongue base resection. In our study, significantly better scores in the EORTC H&N35 swallowing, speech, and social eating subdomains were found after free flap reconstruction. The difference may be due to the necessity of extended resections of the base of the tongue, as all patients studied by Hartl et al 11 had been diagnosed pt4a tongue carcinoma after a near total tongue resection. However, in the Hartl et al 11 study, no direct comparison was made to patients without any reconstructive measures, an option that might have been associated with even worse HRQOL. McConnel et al 7 found that primary closure resulted in better speech and swallowing than did regional or free flap reconstruction, comparing equivalent tumor sites and resection volumes. The authors concluded that soft tissue reconstruction, resulting in an amotile segment, may impair the driving force of the remaining tongue. In contradiction, the preliminary results of the present study may suggest that free flap reconstruction enables improved functional outcome as measured by the swallowing, speech, and social eating subdomains of the EORTC H&N35 questionnaire. These 3 scales differed significantly between the groups and were also the only scales that showed improvements in a clinically meaningful way with value differences larger than 10 points. The difference between studies might be explained by the larger resections in our study (median reduction of the oral tongue by 41.60% and 39.1%) compared to a reduction of 10% to 20% of the oral tongue in the publication of McConnel et al. 7 Even though we did not find better overall HRQOL, according to the EORTC QLQ-C30 questionnaire, our findings imply that tongue reconstruction with free flaps may be beneficial in the treatment of patients with tongue cancer whose tumor resection exceeds 30% to 40% of the entire oral tongue. In cases with a resection of less than 20% to 30%, primary closure might be equivalent to reconstruction (or even better, considering the publication of McConnel et al 7 ) in terms of HRQOL and, thus, the treatment of choice. However, because of the nonrandomized design, the small sample of patients, the exploratory nature of the analyses, and the absence of objective speech or swallowing assessments, all conclusions are preliminary and have to be proven by further investigations. CONCLUSION Controversy still exists regarding the functional advantages of free flap reconstruction after partial glossectomy as compared to primary closure. Even though we did not find better overall HRQOL within the EORTC QLQ-C30 questionnaire, 1 year after resection about 40% of the patients with oral tongue cancer had significantly better outcomes in the swallowing, speech, and social eating subdomains of the EORTC QLQ-H&N35 questionnaire after reconstruction with a free forearm flap compared to primary closure. These findings suggest that tongue reconstruction with free flaps might be useful when treating pt3 tongue cancer. Because of the preliminary character of the findings, future research must prove if reconstruction of tongue defects is beneficial for the functional outcome of patients with pt3 lateral tongue cancer. HEAD & NECK DOI /HED JANUARY

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