Figure. Overall survival (OS) after total laryngectomy for a dysfunctional larynx. NA indicates not applicable.
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Theunissen EAR, Timmermans AJ, Zuur CL, et al. Total Laryngectomy for a Dysfunctional Larynx After (Chemo)Radiotherapy. Arch Otolaryngol Head Neck Surg. 2012;138(6):548–555. doi:10.1001/archoto.2012.862
Author Affiliations: Departments of Head and Neck Oncology (Drs Theunissen, Timmermans, Zuur, Hilgers, and van den Brekel), Surgery and Radiation Oncology (Dr Hamming-Vrieze), and Medical Oncology (Dr de Boer), The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam; and Department of Otorhinolaryngology, Academic Medical Center (Drs Zuur, Hilgers, and van den Brekel), and Institute for Phonetic Sciences (Drs Hilgers and van den Brekel), University of Amsterdam.
Objective To evaluate the functional outcomes after total laryngectomy (TLE) for a dysfunctional larynx in patients with head and neck cancer that is in complete remission after (chemo)radiotherapy.
Design Retrospective cohort study.
Setting Tertiary comprehensive cancer center.
Patients The study included 25 patients from a cohort of 217 consecutive patients with TLE who were treated between January 2000 and July 2010. The inclusion criteria for this subgroup analysis were complete remission and functional problems for which TLE was considered to be the only resolution. Quality of life assessment was carried out using the European Organization for Research and Treatment of Cancer Quality of Life C30 and Head and Neck Module 35 questionnaires and an additional study-specific questionnaire covering functional aspects, such as swallowing and dyspnea, in more detail.
Intervention Total laryngectomy.
Main Outcome Measures Morbidity, mortality, and functional outcomes.
Results The indication for TLE was chronic aspiration with or without recurrent pneumonia (n = 15 [60%]), debilitating dyspnea (n = 8 [32%]), and persistent profuse hemorrhage (radiation ulcer) (n = 2 [8%]). After TLE, 14 of the 25 patients (56%) had 20 major postoperative complications, including 11 pharyngocutaneous fistulas, requiring additional treatment. Tube feeding and recurrent pneumonia incidence had decreased from 80% and 28% to 29% and 0%, respectively, 2 years after surgery. Prosthetic voice rehabilitation was possible in 19 patients (76%). Two years after surgery, 10 of 14 patients (71%) still reported TLE-related pulmonary problems despite the consistent use of a heat and moisture exchanger. The 5-year overall survival rate was 35%.
Conclusions Total laryngectomy for a dysfunctional larynx tends to have a high complication rate. However, in this study, the initial functional problems (aspiration, recurrent pneumonia, and dyspnea) did not recur. Tube feeding was significantly reduced, and the quality of life of the surviving patients appeared to be reasonable.
Radiotherapy (RT), either as a single-modality treatment or as an adjuvant to surgery, plays a central role in the curative treatment of head and neck cancer.1 In advanced head and neck cancer, in the last 2 decades RT increasingly has been combined with chemotherapy (CT) (mainly cisplatin based), which either has been added as induction before radiation or has been administered concurrently. This treatment has led to improvements in locoregional control and overall survival in many head and neck cancer sites, especially in oropharyngeal cancer, with improvement between 8% and 15%.2 Nowadays, therefore, organ preservation cisplatin-based chemoradiation therapy (CRT) has become the treatment of choice for anatomically and functionally inoperable advanced-stage cancer of the head and neck, probably with the exception of stage IV laryngeal cancer.3,4
However, one of the challenges organ preservation treatment has created is that although more cases of cancer seem to be curable, the function of the target organ is not always preserved. Also, although RT as a single-treatment modality can result in serious adverse effects and complications, the addition of CRT has caused them to become more prominent and more serious.5
According to the National Cancer Institute's Common Terminology Criteria for Adverse Events,6 the most severe (grade 3-4) adverse effects due to CRT for laryngeal and pharyngeal carcinoma are stridor, severe (throat) pain, swallowing difficulty (dysphagia and/or aspiration), neurotoxic reactions, renal failure, and airway compromise. Dysphagia and aspiration can become so severe that permanent tube feeding is often required, and airway compromise due to laryngeal edema can become so problematic that permanent tracheotomy is unavoidable. These complications can become life threatening and severely compromising for the quality of life (QoL) of patients. In an attempt to reduce these adverse effects by reoxygenating damaged tissues, the use of hyperbaric oxygen therapy (HBO) has been recommended, but the results of HBO are rather limited and, to our knowledge, have never been substantiated in randomized trials.7 In some instances, despite complete remission, removal of the dysfunctional organ, eg, total laryngectomy (TLE), is the only resolution for controlling severely disabling and potentially life-threatening aspiration and for restoring at least some QoL for patients.
Interestingly, although there are many series published on salvage TLE for residual and/or recurrent disease, there is rarely any literature discussing TLE for a dysfunctional larynx in patients with head and neck cancer that is in complete remission after (C)RT. Therefore, the aim of this study was to obtain more insight in the clinical outcomes and QoL aspects among this increasing subgroup of patients with TLE. Consequently, we performed a retrospective analysis of all relevant clinical and functional characteristics of 25 patients who underwent TLE for a dysfunctional larynx.
The study patients were selected from a cohort of 217 consecutive cases of TLE performed at The Netherlands Cancer Institute, Amsterdam, over a period of slightly more than 10 years (January 2000 to June 2010). Primary TLE was performed in 84 patients (39%); salvage TLE was performed in 108 patients (50%) with residual or recurrent cancer after (C)RT; and TLE was performed in 25 patients (11%) with a dysfunctional larynx after (C)RT. The latter 25 patients were all in complete remission based on imaging results, findings of examination with the patient under general anesthesia, and pathologic findings, but they had serious, often life-threatening adverse effects, such as inspiratory dyspnea, intolerable dysphagia, and/or recurrent aspiration pneumonia, after (C)RT, and TLE was considered to be the only resolution. One treatment choice was narrow-field TLE; however, in view of the clinical and pathologic findings in all of these patients and the relatively high chance of a sampling error in the biopsy specimens, narrow-field TLE would result in irradical resection in case of false-negative biopsy results. Therefore, wide-field TLE was performed in all cases. There were 20 male and 5 female patients, with a mean age of 63 years (age range, 48-77 years) at the time of TLE. The index tumor was laryngeal cancer in 14 patients (6 glottic, 8 supraglottic), hypopharyngeal cancer in 4 patients, cervical esophageal cancer in 1 patient, oropharyngeal cancer in 4 patients, and nasopharyngeal cancer in 2 patients. Table 1 shows all the relevant pre-TLE data. The study was approved by the institutional review board. Informed consent was obtained from the 11 patients who participated in the QoL part of the study.
Fourteen patients had received RT as a single-modality treatment and 11 had been treated with concurrent CRT. In the majority of the patients, the RT protocol consisted of 46 Gy in 23 fractions to the primary tumor and the bilateral aspect of the neck, with a boost to the tumor-bearing areas (additional 24 Gy in 12 fractions), to a total dose of 70 Gy in 7 weeks. Different RT schedules were used in 3 cases of laryngeal cancer: (1) hyperfractionation and accelerated fractionation consisting of 70 Gy in 40 fractions; (2) hypofractionation consisting of 60 Gy in 25 fractions in 5 weeks; and (3) a total dose of 68 Gy in 34 fractions. In the esophageal cancer case, the total dose was 60 Gy in 30 fractions. In the patients who underwent CRT, the RT schedule was similar to that in the RT-only group, with the exception of 1 patient (with T3N2c supraglottic carcinoma) who was treated according to the accelerated Danish Head and Neck Cancer study schedule.8 The concurrent CT regimen consisted of intravenous cisplatin therapy (100 mg/m2) on days 1, 22, and 43 of the RT, with the exception of the patient who was treated with the accelerated fractionation schedule. This patient received daily concomitant intravenous cisplatin therapy (6 mg/m2) for 5 weeks. In 3 patients, the larynx was previously irradiated because of head and neck cancer. The dose delivered to the larynx was approximately 70 Gy in all 3 patients (Table 2).
Of the 11 patients who were still alive at the start of this analysis, the QoL assessment was carried out using the European Organization for Research and Treatment of Cancer Quality of Life C30 and Head and Neck Module 35 (EORTC QLQ-C30/H&N35) questionnaires.9,10 The questionnaires were administered at the end of 2010. Also, to obtain more detailed information about functional aspects, such as swallowing and dyspnea, an additional study-specific questionnaire was administered based on earlier research in The Netherlands Cancer Institute.11
The data were entered in a database of SPSS version 15 (SPSS Inc). The statistics were mainly descriptive. The EORTC scale and item scores were linearly transformed to a scale of 0 to 100. The scores were calculated according to the EORTC QLQ-C30 Scoring Manual.12 For overall survival, a Kaplan-Meier curve was plotted.
Patient, tumor, and treatment characteristics are shown in Tables 1 and 2. The median time between (C)RT and TLE was 4 years (range, 1-20 years). In 13 patients (52%), there was clinically relevant comorbidity, including cardiovascular disease, chronic obstructive pulmonary disease, cerebrovascular disease, and diabetes mellitus. Thyroid-stimulating hormone values were available for 19 of the 25 patients (76%), and 8 of the 19 patients (42%) had hypothyroidism.
At the time of TLE, 13 patients (52%) had a body mass index (BMI) of less than 18 (calculated as weight in kilograms divided by height in meters squared). Before the TLE, the patients were classified according to the American Society of Anesthesiologists (ASA). Three patients (12%) were classified as ASA 1, 12 (48%) as ASA 2, and 10 (40%) as ASA 3. Twenty-three patients (92%) were cigarette smokers before the treatment of the index tumor (median [range], 35 [10-76] pack-years), and 12 (48%) of them were still smoking at the time of the TLE. Twenty-three patients (92%) had a history of alcohol use, and 14 (56%) of them still were using alcohol at the time of surgery. Six patients (24%) had been treated with HBO in attempt to prevent TLE.
The decisive indication for TLE was chronic aspiration with recurrent pneumonia in 12 patients (48%), persistent profuse hemorrhage of a radiation ulcer in the base of tongue/vallecula despite arterial embolization in 2 patients (8%), aspiration problems without recurrent pneumonia in 3 patients (12%), and debilitating dyspnea in 8 patients (32%). The indications were often overlapping, and, in total, 20 patients (80%) were dependent on tube feeding and 13 patients (52%) had a tracheotomy before surgery. Most indications were semielective. Therefore, the clinical condition of all patients, except the 2 with acute TLEs for intractable hemorrhage, was optimized as well as possible, but in most cases, stabilizing the malnutrition and correcting the hypothyroidism were the best outcomes that could be achieved.
Of the 12 patients with recurrent pneumonia, 2 with nasopharyngeal carcinoma were severely aspirating 20 and 8 years after CRT because of constrictor pharyngeal muscle dysfunction and a lack of laryngeal elevation; they had also had several life-threatening episodes of pneumonia before the TLE decision. At the time of TLE, all patients were in complete remission, which was confirmed by postoperative pathologic findings revealing that no recurrent or residual tumor was present in any of the laryngectomy specimens. In 1 of the specimens (4%), overt chondroradionecrosis was found. In 2 specimens (8%), no histologic abnormalities were seen. The other 22 specimens (88%) showed typical post-RT soft-tissue alterations such as reactive and degenerative changes, fibrosis, and/or necrosis.
In 9 patients (36%), the pharynx could be closed primarily, and in 16 patients (64%), reconstruction was required; 13 pectoralis major (PM) flaps and 3 microvascular flaps (2 free radial forearm flaps and 1 anterolateral thigh flap) were used for closure. Fourteen patients (56%) had a total of 20 major postoperative complications. There were 11 cases of pharyngocutaneous fistulas requiring additional interventions; 2 cases of wound infection without fistula formation, which were treated conservatively; and 1 case of bilateral permanent hypoglossal nerve damage. Other major complications in these 14 patients were postoperative hemorrhage (n = 1), which had to be controlled surgically; pneumonia (n = 2); carotid blowout (n = 2) (managed with ligation and PM flap reconstruction); and perioperative cerebrovascular accident (n = 1).
In the 9 primary closed cases, 3 patients developed a pharyngocutaneous fistula, which required 3 surgical interventions in 2 patients. The median total healing time was 10 weeks. Of the 13 patients with PM flap reconstruction, 5 developed a pharyngocutaneous fistula. In 2 of these 5 patients, the fistula healed spontaneously, 1 needed a second intervention with an additional PM flap, and 2 died with a persistent fistula. The median total healing time in the 3 spontaneously healing cases was 4 weeks (Table 3). All 3 patients who underwent reconstruction with a microvascular flap developed a pharyngocutaneous fistula, and 1 patient required an additional PM flap; the median healing time of these patients was 7 weeks. The use of a PM flap did not significantly improve healing time (P = .59). There were no statistically significant correlations between the complications and the comorbidity factors assessed (eg, BMI <18, hypothyroidism, and ASA <1) (P > .10 in all cases). Two patients (8%) died shortly after surgery: one developed a sudden nocturnal metabolic encephalopathy due to hypoglycemia despite 15 days of stable glucose blood values with insulin and antidiabetic medications (BMI, 26-30), and the other (BMI <18) had a cerebrovascular accident during his emergency TLE for persistent profuse hemorrhage. After surgery, the latter patient developed a nonhealing pharyngocutaneous fistula and pneumonia and subsequently died.
After discharge from the hospital, there were a total of 27 readmissions in 14 patients (56%). The median time between discharge and first readmission was 5.5 weeks (range, 0-36 weeks). The reasons for readmission were pulmonary infection requiring intravenous antibiotics (8 times in 6 patients); neck abscess requiring drainage (3 times in 2 patients); stenosis of the pharyngoesophageal segment requiring dilatation (2 times in 2 patients); hypopharyngeal hemorrhage requiring embolization (2 times in 1 patient); suspicion of tumor recurrence requiring examination with the patient under general anesthesia (3 times in 3 patients); trismus requiring surgical intervention (1 time in 1 patient); and osteoradionecrosis of the mandible requiring repeated sequestrectomy (3 times in 1 patient). Finally, there were 5 readmissions for voice prosthesis (VP) problems in 2 patients (eg, a too-wide tracheoesophageal fistula, leakage, and replacements). In 4 patients, there were overlapping indications.
The median survival was 30.0 months (95% CI, 17.0-NA [not applicable]). The 5-year overall survival rate was 35% (Figure). At the time of the final analysis (November 2011), 15 patients (60%) had died. Four patients developed recurrent cancer: 1 regional recurrence in the neck (at 4 months), 1 stoma recurrence in the patient with esophageal cancer (at 12 months), 1 local recurrence in a patient with oropharyngeal cancer (at 24 months), and 1 case of lung metastases (at 1 month). Three other patients developed a second primary cancer in the lung (at 7, 14, and 18 months, respectively). All patients with recurrent disease, metastases, or a second primary cancer died of their disease. Of the other 8 patients, 2 died after surgery and 6 died of other causes, eg, kidney failure or pulmonary decompensation.
Table 4 shows the functional outcomes of the TLE. Inspiratory stridor, present in 8 patients (32%) before TLE, did not recur after surgery. Recurrent penumonia, which occurred in 12 patients (48%) before TLE, also did not recur. Pulmonary problems related to TLE were seen frequently in more than half of the patients, despite the consistent use of a heat and moisture exchanger. Swallowing problems, which occurred in all but 1 patient (96%) before TLE, decreased considerably, with 4 of 14 patients (29%) having persistent dysphagia at 2 years. In concordance, tube feeding decreased from 80% prior to surgery to 29% at 2 years after TLE. Changes in diet consistencies are also shown in Table 4. With respect to the BMI of the patients, weight gain was reported in 62% of the patients, but precise weight data were not recorded.
Twenty-two patients (88%) underwent primary tracheoesophageal puncture, with immediate insertion of an 8-mm Provox VP, and 1 patient (4%) underwent a secondary tracheoesophageal puncture.13 In 3 of these 23 cases, the VP was removed because of poor voicing due to fibrosis of the neoglottis (n = 1) or unmanageable periprosthetic leakage (n = 2). One patient died early after surgery and never had the opportunity to use his VP. Two patients (8%) did not receive a VP because of the complexity of the surgery. Therefore, in total, 19 patients (76%) could be rehabilitated with a VP and 6 could not. With respect to TLE voice quality, the patients were grouped as having a good/reasonable voice or a moderate/poor voice, and, over time, there was an improvement in this respect, with most patients having a good/reasonable voice, as shown in Table 4.
At the start of the retrospective analysis, October 2010, a total of 11 patients (44%) were available for QoL assessment. The mean follow-up of this subgroup was 5 years (range [median], 1-10  years). Results of the EORTC QoL C-30/H&N35 questionnaires are shown in Table 5. The mean score for global health in general was 63, and the mean scores on the functional scales ranged from 66 to 85 (scale, 0-100; a higher score represents better QoL). On the symptom scales (a higher score means a higher level of symptoms), the highest scores on the EORTC QLQ-C-30 questionnaire were seen for fatigue, dyspnea, and insomnia (34, 24, and 24, respectively; scale, 0-100). On the H&N35 symptom scales (here a higher score also means a higher level of symptoms), most problems were seen in speech (score 60), followed by senses, eg, smell and taste (score 56), mouth opening (score 52), and sticky saliva (score 49).
On the additional study-specific questionnaire, the patients were asked to grade their current swallowing and dyspnea complaints (good, fair, moderate, or poor) and to compare their current complaints with those before surgery. Overall, most patients graded their current swallowing and dyspnea complaints as fair to good. In comparing their current complaints with complaints before TLE, roughly half of the patients reported an improvement and half a deterioration of the swallowing and dyspnea complaints. All patients considered their voice quality and sputum production to be worse than before TLE.
The main indications for TLE are advanced (stage IV) laryngeal and/or hypopharyngeal cancer and residual/recurrent disease after organ preservation (C)RT. Much less frequently, this surgical procedure is required for a dysfunctional larynx after organ preservation treatment. Our series of 25 patients, representing 11% of the total 10-year TLE cohort in a tertiary comprehensive head and neck cancer center, shows that the indication for TLE in this case is made relatively late. The mean time of 4 years between CRT and TLE certainly seems longer than that in most series of salvage laryngectomy. Most patients already had experienced several life-threatening complications, such as the need for a permanent tracheotomy in 13 patients and for permanent tube feeding in 20 patients, before the decision for TLE was made. The severe weight loss and the inherent loss of condition (with half of the patients having a BMI <18) also suggests that the indication for surgery in most cases was postponed for a long time. This is obviously not surprising, because all patients were in complete remission, and apparently both the patients and the health care professionals had to “grow” toward the belief that TLE was the only option left for resolving the patients' intolerable situations and for restoring of at least some QoL. In view of that, and taking into account the frequent presence of significant comorbidities, the results in this patient cohort seem acceptable. Of course, there were many complications and frequent readmissions that the patients had to deal with, and there were 2 postoperative fatalities, but, still, most patients recovered reasonably well. In hindsight, it could be said that the decision to perform a TLE should have been made earlier, while the patient was still in a better condition, but, as stated, it is obviously a difficult dilemma to sacrifice a “disease-free” organ only for functional reasons. Moreover, for 7 patients, an even longer delay would have meant that the tumor had recurred or that a second primary cancer had become apparent in the mean time, thereby overruling the indication for TLE. It could be interesting, though, to compare this cohort of the 25 patients considered to have a vital indication for the TLE with other patients who have had similar severe adverse effects of (C)RT but in whom the decision for TLE was not made because tracheotomy and/or gastrostomy had solved the main “vital issues.” Such a comparison was not in the scope of this study but is certainly worthwhile looking into in the near future.
With respect to complications, it can be concluded that since 11 of our study patients (44%) developed an orocutaneous fistula, our results are in line with those published for the Radiation Therapy Oncology Group trial 91-11.14 Meta-analysis of the risk factors that contribute to the development of a fistula after TLE has shown that these risk factors include prior tracheostomy, concurrent neck dissection, and preoperative radiotherapy.15 All patients in the present study had at least 1 of these risk factors, and more than half of them had a tracheotomy. It should be stressed that treatment of comorbity issues, such as substitution of thyroid-stimulating hormone in case of hypothyroidism (42% in our series), and preoperative improvement of the nutritional status (more than half of our patients had a BMI <18) remain imperative for the reduction of complications, even though we did not find significant correlations in this respect. However, the small number of patients does not allow adequate statistical analysis of the association of comorbidities and complications.
A possible strategy to reduce fistula rates after TLE is treatment with HBO. The efficacy of HBO has been suggested in only a few case reports and series.7 In our study, 6 patients were treated with HBO before TLE, but no differences were seen in the development of postoperative fistulas. Another fistula-preventive strategy is the insertion of nonirradiated, well-vascularized tissue; therefore, many authors have described the use of PM flap reconstruction in a salvage setting. Righini et al16 performed a study examining the use of the PM flap and noted a substantial reduction in fistula rate, from 50% to 23%. This difference, however, did not reach statistical significance. Patel and Keni17 concluded that the PM flap is a safe, reliable means of preventing pharyngocutaneous fistula at the time of salvage laryngectomy. In their study, 17 patients underwent a salvage laryngectomy; 10 were also treated with a PM flap reconstruction, and none of them developed a fistula. On the other hand, 4 of the 7 patients who did not receive a PM flap developed a fistula. Gil et al18 concluded that in a selected population of patients undergoing salvage TLE who were at high risk for fistula because they had already undergone prior CRT, PM flap reconstruction could be a valuable adjunct for decreasing the risk of complications, morbidity, and the potential need for revision surgery.
In the present study, a similar number of fistulas were seen after PM flap reconstruction or primary closure (38% and 33%, respectively). Also, all 3 patients who underwent a free-flap reconstruction developed a fistula after TLE. Healing time seemed somewhat shorter after PM flap reconstruction (4 and 10 weeks, respectively), but this difference was statistically not significant (P > .10) and does not allow any definite recommendations in this respect.
van der Putten et al19 found postoperative complications in 56% of the patients treated with salvage laryngectomy for residual or recurrent laryngeal carcinoma after prior treatment with (C)RT, a percentage that is identical to the 56% in the present study. In their study, the postoperative mortality rate was 3% (3 of 120 patients), and we observed a mortality rate of 8% (2 of 25 patients). The difference in mortality rate in both studies, however, is not significant (unpaired t test, P = .17). Overall survival in the series of van der Putten and colleagues was 50%, a percentage that is somewhat higher than the 35% in the present study, which also suggests that our patients were in poorer condition at the time of TLE. The results of the present study are also comparable to those of the rather similar retrospective study that was just published online by Hutcheson et al,20 who stated:
Salvage TL [total laryngectomy] may improve health status by significantly decreasing the rate of pneumonia and improve quality of life by restoring oral intake in patients with refractory laryngopharyngeal dysfunction after head and neck cancer treatment. TE [tracheoesophageal] voice restoration may enhance functional outcomes in select patients treated with elective TL for dysfunction.
The QoL interviews taken from 11 patients to compare their QoL before and after TLE show an acceptable overall QoL of 63 on a scale of 0 to 100. These results are comparable to the results of Hanna et al,21 who compared the QoL of patients treated with CRT or TLE and found mean scores of overall QoL of 63.6 and 65.8, respectively. van der Putten et al19 studied functional outcomes, including speech. Within 1 year after TLE, 87% of the patients were able to speak with a VP; in our study population, acceptable voice was achieved in 86% of the patients after 5 years.
The limitations of this retrospective study include the small number of patients and the heterogeneity of the study population. A case-control study comparing the present patient cohort with the salvage TLE subgroup could have given additional information. Such a study is planned as part of the analysis of the total 10-year TLE cohort at our institution (The Netherlands Cancer Institute). However, we believe that the present results are already clinically important and can guide future counseling of patients for informed consent. The patients should understand that the surgery is not without major risks. Furthermore, some patients will still have dysphagia after TLE, and although debilitating and life-threatening aspiration is “cured” by the TLE, the patients should also be informed of this potential remaining dysphagia issue, even though 16 of the 25 patients (62%) in our study showed an increase in body weight. In this patient population, there are not many alternatives for treatment. Laryngotracheal separation (ie, separation of the esophagus and trachea with a permanent tracheostomy) is mostly performed in patients with intractable aspiration due to neurologic disease.22 After CRT, laryngotracheal separation most likely is also complication prone and often has the added disadvantage of leaving behind an organ in which cancer is still suspected.
In conclusion, this study showed that TLE for a dysfunctional larynx after (C)RT is accompanied by a relatively high incidence of major complications (56%) and mortality (8%). However, the main eliciting functional problems (aspiration, recurrent pneumonia, and dyspnea) did not recur. Dysphagia requiring pre-TLE tube feeding was not completely eliminated in 20 of the 25 patients (80%), however, leaving 4 of 24 patients (29%) dependent on tube feeding. The QoL of the patients who survived appeared to be reasonable.
Correspondence: Charlotte L. Zuur, MD, PhD, Department of Head and Neck Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands (email@example.com).
Submitted for Publication: December 13, 2011; final revision received March 29, 2012; accepted April 11, 2012.
Author Contributions: Drs Theunissen and Timmermans contributed equally to the work and the writing of the manuscript. Drs Theunissen, Timmermans, Zuur, and Hilgers had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Theunissen, Zuur, de Boer, Hilgers, and van den Brekel. Acquisition of data: Theunissen, Timmermans, Zuur, Hamming-Vrieze, and Hilgers. Analysis and interpretation of data: Theunissen, Zuur, Hamming-Vrieze, de Boer, and Hilgers. Drafting of the manuscript: Theunissen, Timmermans, Zuur, de Boer, and Hilgers. Critical revision of the manuscript for important intellectual content: Zuur, Hamming-Vrieze, de Boer, and van den Brekel. Statistical analysis: Theunissen, Timmermans, and Zuur. Obtained funding: Hilgers. Administrative, technical, and material support: Theunissen, Timmermans, Zuur, de Boer, and Hilgers. Study supervision: Zuur, Hamming-Vrieze, de Boer, Hilgers, and van den Brekel.
Financial Disclosure: None reported.
Previous Presentation: This study was presented in part at the annual meeting of the Dutch ENT Society; November 18, 2011; Groningen, the Netherlands.
Additional Contributions: Harm van Tinteren, PhD, is acknowledged for his statistical assistance.
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