The objective of this study was to examine the quality of life (QOL) of patients who underwent salvage nasopharyngectomy for residual or recurrent nasopharyngeal carcinoma and to justify the value of the procedure.
The objective of this study was to examine the quality of life (QOL) of patients who underwent salvage nasopharyngectomy for residual or recurrent nasopharyngeal carcinoma and to justify the value of the procedure.
A self-reported, health-related QOL questionnaire was used to assess the QOL of patients after salvage nasopharyngectomy. The effects of potential complications after surgery also were evaluated.
Between 2003 and 2011, 185 patients underwent salvage nasopharyngectomy using the maxillary swing approach. Curative resection was achieved in 80% of patients. There were no significant changes in mean global health system scores after surgery, except after palliative resection requiring postoperative adjuvant chemoradiation. Social functioning scores were the lowest of the 5 functioning scales in all patient groups. Palatal fistula significantly affected social eating and weight loss, and osteoradionecrosis caused more pain and nasal discharge, severely affecting the social life of patients.
The QOL of patients after maxillary swing salvage nasopharyngectomy was good. The current results indicated that attention must be paid to the factors that adversely affect QOL after surgery, such as palliative resection, and complications like trismus, palatal fistula and osteoradionecrosis. Cancer 2012. © 2011 American Cancer Society.
Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia.1 The primary treatment for NPC is radiotherapy with or without chemotherapy, depending on the disease stage at presentation. For tumors that persist or recur after previous treatment, further irradiation is associated with a higher incidence of complications and less satisfactory treatment outcome.2-4 Surgical resection becomes a logical treatment option.
Maxillary swing nasopharyngectomy has been the treatment of choice for recurrent NPC in our center.5 Because the approach allows a wide exposure of the nasopharyngeal region for complete tumor resection, it achieves better local tumor control and a better disease-specific survival rate,6-9 although transoral robotic surgery (TORS) has been used recently as an alternative for selected patients who have small and favorably located tumors.10
In the literature, there are only a few studies11-14 on the quality of life QOL of patients with NPC after radiotherapy. We previously reported the preliminary results on the QOL of patients after salvage surgery.15 The current study represents a prospective, longitudinal study on the QOL of patients after salvage nasopharyngectomy in the past decade at our center.
The study was conducted using a self-reported, health-related QOL questionnaire to evaluate the QOL of patients with NPC who underwent nasopharyngectomy for recurrent NPC after chemoradiotherapy. We have performed salvage surgeries for patients with residual or recurrent NPC in the Division of Head and Neck Surgery, Department of Surgery at the University of Hong Kong Queen Mary Hospital from January 2003 to January 2011. The data forming the basis of the current study were composed of information from a prospective, longitudinal study of 185 consecutive patients. The inclusion criterion was that the patient had undergone salvage nasopharyngectomy for residual or recurrent NPC. Those who required simultaneous neck dissection for metastatic lymph node disease, those who had undergone nasopharyngectomy for other types of malignancy, and those who were unable to complete the questionnaire because of illiteracy were excluded from this study. The maxillary swing approach was used for all patients. If subsequent histologic examination of the resected specimen revealed positive margins, then the patient would be assessed by the oncologists and would receive further adjuvant chemoradiation if feasible. Assessment was made before surgery and 6 months after the completion of treatment. Eligible patients completed the questionnaires by themselves at the outpatient clinic. The completed questionnaires were returned to the research nurse for subsequent data entry.
Clinical data, including age, sex, smoking and drinking habits, medical history, type of surgery, and duration of follow-up, were recorded. The presence of a postoperative palatal fistula was documented. Moreover, the distance between the upper and lower incisors (the interincisor distance) was measured during follow-up. An interincisor distance <25 mm was defined clinically as severe trismus. The development of osteoradionecrosis (ORN) of the skull base was diagnosed by endoscopic and radiologic investigations. Regular nasal endoscopy, magnetic resonance imaging (MRI) of the nasopharynx, as well as plasma Epstein-Barr virus (EBV)-DNA testing were used to detect possible tumor recurrence after surgery.
The QOL instrument was developed and translated by the European Organization for Research and Treatment of Cancer (EORTC).16-18 The questionnaire has 2 parts: the core questionnaire (Quality-of-Life Questionnaire [QLQ]-C30, version 3), which applies to all patients with cancers, and the disease-specific questionnaire (QLQ-H&N35, Hong Kong version), which is designed specifically for patients with cancer of the head and neck region. The raw scores obtained from the EORTC questionnaires were converted to scores ranging from 0 to 100 using linear transformation according to the scoring procedures.19 For this study, we used the traditional Chinese version of questionnaires, which have been validated as useful in assessing the QOL of Chinese patients with cancer.20, 21
The QLQ-C30 includes 30 questions comprising both multi-item scales and single-item measures. The 5 functional scales are physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning. The 3 symptom scales are fatigue, nausea and vomiting, and pain. There is a global QOL scale. The 6 single-item measures are dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties. A high score for a scale represents a higher response level. Thus, a high score for a functional scale represents a high or healthy level of functioning, a high score for the global QOL scale represents a high QOL, but a high score for a symptom scale or item represents a high level of symptoms (problems).
The QLQ-H&N35 comprises 35 questions incorporating 7 multi-item scales and 11 single items. The multi-item scales are pain, swallowing, senses, speech, social eating, social contact, and sexuality. The single items are teeth, opening mouth, dry mouth, sticky saliva, coughing, felt ill, pain killers, nutritional supplements, feeding tube, weight loss, and weight gain. For all items and scales, high scores indicate more problems. There are no function scales in which high scores would mean better functioning.
The transformed raw scores were analyzed with respect to the scales and items of the EORTC questionnaires. Possible significant factors affecting the QOL measurement were tested. They included the presence of severe trismus (an interincisor distance <25 mm), the presence of a postoperative fistula, and the presence of ORN of the skull base after surgery.
We used SPSS statistical software (version 18.0; SPSS Inc., Chicago, Ill) in the analyses. Univariate analysis of the median scores between the 6 factors was performed using the Mann-Whitney U test, and covariables were adjusted using the multiple regression model. The level of significance was set at 5% in all comparisons, and all statistical testing was 2-sided.
The study complied with the latest version of the Declaration of Helsinki (52nd World Medical Association General Assembly; Edinburgh, Scotland; October 2000) and was approved by the ethics committee of the institutional review board of the University of Hong Kong. We obtained permission to use the QOL questionnaires from the EORTC.
During the study period, we performed 185 salvage surgeries for patients with recurrent NPC after previous chemoradiation. The sociodemographic characteristics of the participants are provided in Table 1. Their ages ranged from 24 years to 81 years (mean ± standard deviation, 50.2 ± 11.4 years). Among them, 81.6% of patients were men. Most of patients were married and had received formal education. The majority of patients were employed (full time, 55.7%; part time, 5.4%). The use of cigarettes or alcohol was not common. Recurrent NPC was the sole illness in 83.8% of patients. It is worth noting that a significant proportion of patients (42.7%) were taking over-the-counter herbal medicine before surgery, because they believed that this may suppress the tumor growth as well as improve their general well being. This practice was not observed in patients with other head and neck malignancies in the locality.
|Variables||No. of Patients (%)|
|No formal education||2 (1.1)|
|Primary level||38 (20.5)|
|Secondary level||119 (64.3)|
|Full time||103 (55.7)|
|Part time||10 (5.4)|
|Former smoker||13 (7.0)|
|Social drinker||21 (11.4)|
|Former drinker||20 (10.8)|
|No medical illness||155 (83.8)|
|Diabetes mellitus||15 (8.2)|
|Use of herbal medicine|
|Regular consumption||79 (42.7)|
|No consumption||106 (57.3)|
|Mean time to recurrence after initial chemoradiation, mo||22.4|
|Preoperative RT-related complications|
|Severe trismus||8 (4.3)|
Table 2 lists the types of treatment received. All patients underwent nasopharyngectomy using the maxillary swing approach. A subgroup of patients who had positive margins in their final paraffin resection specimens were reassessed by the oncologists, and they received further adjuvant treatment if possible. Among them, 30 patients eventually received either chemotherapy or chemoradiation after surgery. Table 3 lists the major outcome variables after surgery. All patients achieved macroscopic clearance of their tumors. The resection margins were positive for malignancy in 37 patients (20%), and further resection was impossible because of the involvement of important structures, such as the skull base or the petrosal internal carotid artery. At the time of assessment, the majority of patients (84.8%) were alive with no evidence of tumor recurrence. Eight patients (4.3%) developed postoperative fistulas, and 25 patients (13.5%) had severe trismus. Thirty patients (16.2%) developed clinical and radiologic evidence of ORN involving the skull base.
|Treatment Variable||No. of Patients (%)|
|Type of resection|
|Maxillary swing nasopharyngectomy||185 (100)|
|Radiotherapy and chemotherapy||10 (5.4)|
|Outcome Variable||No. of Patients (%)|
|Status of resection margins|
|Negative margins||148 (80)|
|Positive margins||37 (20)|
|Disease status at the time of assessment|
|Alive, no disease||162 (84.8)|
|Alive, with disease||21 (11)|
The reliability of the questionnaire used in this study was calculated using the Cronbach α-coefficient, and α coefficients ≥.70 were sought as evidence of adequate scale reliability for use at the level of group comparison. The internal reliability coefficients of the QLQ-C30 and QLQ-H&N35 instruments were .88 and .79, respectively.
The transformed scores of the QLQ-C30 and QLQ-H&N35 for all participants before and after surgery are provided in Table 4. Compared with the score before surgery, there was no significant change in the mean global health system score after maxillary swing nasopharyngectomy. However, the score was significantly lower among patients after combined surgery and chemoradiotherapy than among patients after surgery alone. Consistent with our previous study, social functioning had the lowest scores among the 5 functioning scales in all groups of patients. Fatigue and financial difficulties were common concerns of our participants. Furthermore, the symptoms of fatigue and appetite loss seemed to persist for a prolonged duration after the completion of surgery and chemoradiotherapy, significantly affect the QOL of this group of patients. In patients after maxillary swing nasopharyngectomy, social eating (42.1 ± 21.2), mouth opening (64.3 ± 14.1), and weight loss (34.3 ± 31.2) were common symptoms that significantly affected their QOL after surgery. Not surprisingly, similar symptoms also were observed in the group of patients who underwent both surgery and adjuvant treatment; in addition, they were more likely to feel ill than patients in the other groups.
|Score: Mean ± SD|
|EORTC Scale||Pre-Op||MS||Surgery and Adj Tx|
|Global health system||70.5 ± 25.6||67.3 ± 28.4||58.3 ± 16.7a|
|Physical functioning||83.6 ± 23.2||83.2 ± 18.6||76.2 ± 18.1|
|Role functioning||83.8 ± 20.4||86.5 ± 25.4||80.8 ± 22.3|
|Emotion functioning||80.5 ± 28.2||78.6 ± 20.2||74.0 ± 18.2|
|Cognitive functioning||85.2 ± 17.6||83.3 ± 20.1||78.6 ± 20.8|
|Social functioning||67.7 ± 28.9||65.8 ± 21.5||61.7 ± 19.1|
|Fatigue||24.3 ± 14.0||25.2 ± 18.2||41.3 ± 14.2a|
|Nausea and vomiting||6.4 ± 12.1||6.8 ± 14.3||21.3 ± 24.7|
|Pain||14.2 ± 20.9||16.4 ± 24.1||18.0 ± 28.8|
|Dyspnea||23.6 ± 18.4||25.2 ± 28.2||25.9 ± 26.4|
|Insomnia||22.8 ± 21.9||24.3 ± 34.9||23.1 ± 22.6|
|Appetite loss||16.1 ± 14.2||17.4 ± 22.6||34.0 ± 21.2a|
|Constipation||8.9 ± 13.4||7.6 ± 18.1||8.9 ± 21.6|
|Diarrhea||7.0 ± 13.6||8.1 ± 14.2||6.8 ± 19.8|
|Financial difficulties||34.2 ± 41.9||33.8 ± 35.4||40.8 ± 32.3|
|Pain||22.8 ± 14.9||25.3 ± 20.0||24.8 ± 18.7|
|Swallowing||20.3 ± 20.1||26.6 ± 22.4||27.6 ± 17.1|
|Senses||31.8 ± 12.1||33.9 ± 24.8||38.2 ± 21.3|
|Speech||29.3 ± 27.3||30.1 ± 28.1||30.8 ± 26.1|
|Social eating||26.2 ± 24.3||42.1 ± 21.2a||32.7 ± 31.2|
|Social contact||14.2 ± 18.9||16.4 ± 21.8||17.1 ± 34.9|
|Sexuality||28.9 ± 32.2||30.4 ± 41.4||33.2 ± 41.8|
|Teeth||34.9 ± 22.1||36.1 ± 24.6||35.9 ± 21.4|
|Opening mouth||46.0 ± 18.3||64.3 ± 14.1a||66.5 ± 23.2a|
|Dry mouth||56.4 ± 14.1||64.8 ± 18.5||62.1 ± 18.9|
|Sticky saliva||48.8 ± 28.4||51.2 ± 24.6||52.2 ± 33.1|
|Coughing||26.3 ± 21.2||28.1 ± 16.1||34.3 ± 28.5|
|Felt ill||14.3 ± 23.3||16.4 ± 22.8||24.8 ± 22.1a|
|Pain killers||22.8 ± 41.9||23.6 ± 32.8||24.4 ± 27.6|
|Nutrition supplements||22.8 ± 28.1||23.6 ± 19.8||22.8 ± 26.2|
|Feeding tube||3.3 ± 13.2||4.2 ± 14.7||5.8 ± 16.2|
|Weight loss||21.4 ± 43.8||34.3 ± 31.2a||52.4 ± 14.7a|
|Weight gain||11.2 ± 38.1||10.3 ± 37.7||7.9 ± 16.3|
|Appearance||18.4 ± 15.3||20.5 ± 18.2||21.3 ± 14.9|
With regard to the QLQ-C30 assessments (Table 5), we observed no significant differences in the presence of severe trismus or in postoperative palatal fistula formation. However, those patients who developed ORN of the skull base after surgery had significantly lower scores in the domains of emotional and social functioning.
|EORTC Scale||Severe Trismus||Palatal Fistula||Osteoradionecrosis|
|No, of patients||160||25||177||8||155||30|
|Nausea and vomiting||5.6||4.2||6.8||9.1||13.2||14.8|
When the analysis was performed with the same factors using the QLQ-H&N35 measurements, weight loss and social eating were significantly worse when a postoperative fistula was present. The presence of ORN was associated with more pain and, hence, more consumption of analgesics as well as poorer social contact.
NPC is endemic in southern China and Southeast Asia,1 affecting 10 to 50 per 10,000 population.22 It is a radiosensitive tumor, which makes radiation therapy an important primary treatment modality.23, 24 For those who present with advanced disease, it was demonstrated that the addition of chemotherapy improved overall and progression-free survival.25, 26 Despite the advances in chemoradiation, locoregional failure occurs in 10% to 30% of patients with NPC. Surgical salvage for residual or recurrent tumor of the nasopharynx is a logical option after failure of chemoradiotherapy. Reports indicate that nasopharyngectomy achieves better local control and survival than reirradiation,27-30 and it also is associated with less post-treatment morbidities. In a recent review of our experience with maxillary swing nasopharyngectomy on 246 patients over the past 2 decades,9 negative resection margin status was 1 of the most important factors determining 5-year actuarial local disease control and 5-year disease-free survival. Although small and favorably located tumors can be resected successfully using endoscopic or transoral robotic surgery,10 the majority of recurrent tumors are characterized by widespread submucosal and deep paranasopharyngeal extension. The anterolateral approach of the maxillary swing operation provides better exposure to the region, allowing resection of the tumor with wider margins.
However, the side effects and potential complications associated with surgical procedures cannot be underestimated. Postoperative trismus and palatal fistula formation may disturb normal speech, eating, and swallowing functions. There are few reports in the literature studying the QOL of patients after salvage nasopharyngectomy.
We previously published the preliminary results of our retrospective, cross-sectional study on the QOL of patients after maxillary swing nasopharyngectomy for recurrent NPC.15 To overcome the limitations of our previous study, we have performed the current prospective, longitudinal study investigating potential changes in the QOL of patients after undergoing salvage surgery.
Our patients reflected the typical characteristics of patients with NPC; that is, it affects a younger population (mean age, 50.2 years) than other head and neck cancers; it is not usually associated with smoking or alcohol abuse; and the patients have a lower incidence of associated comorbidity. Compared with reference data from the EORTC QOL scores in the population of patients with head and neck cancer, we observed that most of scores for the QOL domains in our patients were good, and the global QOL scale score approached 70. There was no significant change in the global QOL score after maxillary swing nasopharyngectomy, except in those patients who had positive resection margins and required further adjuvant chemoradiotherapy. This represented a subgroup of patients who had locoregionally advanced, recurrent tumors. They had significantly lower mean global health scores and were more likely to perceive themselves as “ill” at the time of assessment compared with the patients who underwent surgery alone. This can be explained by the presence of persistent fatigue and appetite loss, trismus, and weight loss. Financial difficulty was also 1 of the most common concerns among our patients, although there was no significant worsening of the problem after surgery alone or surgery and chemoradiation. The majority of our patients were married, middle-aged men who were the income earners in their families, and unemployment as a result of their disease caused a considerable decrease in the family income. Fang et al11 observed that financial resources were important variables in determining a patient's ability to cope with cancer and treatment complications. Those patients who had higher economic status and stable employment tended to enjoy a better QOL. Ramsey et al31 demonstrated that lower income status among cancer survivors was associated with worse outcomes for reported pain, ambulation, and social and emotional status.
The combination of financial constraints, cancer-related fatigue, and irradiation-induced oral symptoms makes this vulnerable group of patients particularly prone to difficulties in social and interpersonal adjustments, which, in turn, may explain why social functioning scores were the lowest among the 5 functioning scales in all groups of patients. Some patients avoid eating in restaurants, visiting friends and relatives, and participating in social functions; others even resign themselves to a solitary, reclusive life. Similarly, Hammerlid et al32 observed that social functioning and role functioning were worse after the completion of treatment among patients with NPC and that the 3 major concerns were difficulty in enjoying meals, feeling ill, and dryness of mouth.
Based on the results from our previous work and the current study, dry mouth and sticky saliva were common symptoms among our group of patients. However, because there was no significant change in the severity of these symptoms before and after surgery, previous radiotherapy rather than the surgery itself is more likely to be responsible for these conditions. Conversely, together with the effect of previous radiotherapy, scarring at the pterygoid region after nasopharyngectomy causes a variable degree of postoperative trismus. It drastically limits the patient's choice of food, and most of patients can tolerate only food pastes or purees. Mastication, swallowing, and speech functions are greatly affected by the combined effects of xerostomia, sticky saliva, and trismus.33-35 Our early experience indicated that the risk of developing severe postoperative trismus, which is defined as an interincisor distance <2.5cm, was up to 71%.15 In attempt to tackle this problem, mouth-opening exercises are started as early as 1 week after surgery under the guidance of our speech therapists. The most commonly used treatment is using a stack of tongue depressors between the teeth to push the mouth open over time.36 Another, more effective way is to use the Therabite Jaw Motion Rehabilitation System (Atos Medical, West Allis, Wis), which is a patient-operated device for passive stretching of the jaw. After adopting such aggressive therapy, the incidence of severe postoperative trismus dropped to 13.5%. Once the condition is well established, hyperbaric oxygen,37 oral medications like pentoxifylline,38 and surgical procedures like masticatory muscle myotomy and coronoidotomy39, 40 have been described in the literature. However, when trismus is prevented early, these measures rarely are necessary.
Palatal fistula formation is a major complication after maxillary swing nasopharyngectomy. Our current study indicates that it adversely affects patients' swallowing function, leading to more significant weight loss after surgery. Furthermore, because of the fistula, nasal regurgitation of fluid occurs during swallowing. The recurrent leakage of food and fluid from the nose causes embarrassment and inconvenience during social eating. Over the years, we have modified the incision over the soft tissue on the hard palate from the originally described midline position to a curved incision along the lingual border of the teeth on the upper alveolus.41 The line of osteotomy no longer overlaps with the soft tissue incision (Fig. 1), thereby effectively reducing the rate of fistula formation from 24% according to our previous report to 4.3% in the current series. Some of our patients had secondary breakdown of the palatal wound because of infection. Close monitoring with more frequent nasal washout as well as early administration of antibiotics should infection occur may further reduce the fistula rate. Once a fistula develops, it can be repaired using local mucosal flaps (Fig. 2).
ORN of the skull base may develop after, or can be exacerbated by, surgical resection of tumors at the nasopharynx. The effect of previous radiotherapy, together with exposed bone after nasopharyngectomy and subsequent infection, is responsible for the condition. Thirty patients (16.2%) in our series had clinical and radiologic evidence of ORN to a variable degree, resulting in disturbing symptoms, such as foul-smelling nasal discharge, trismus, and headache. Our study demonstrated that the presence of postoperative ORN was associated with significantly more pain and increased consumption of analgesics. The social life of the patients also was affected, which may be explained by the presence of persistent headache and the foul-smelling nasal discharge. Resurfacing the raw bone after surgery with soft tissue flaps rather than inferior turbinate mucosal grafts may reduce the rate and severity of ORN, and small defects can be repaired with posterior-based nasal septal mucosal flaps. For large defects or those with evidence of pre-existing ORN, the necrotic bone, if present, should be debrided as much as possible, and the wound should be repaired with vascularized tissue, such as the temporalis muscle flap or even a microvascular-free flap.
With the recent development and popularization of TORS, its application has been extended to the resection of tumors of the nasopharynx. We have been using this approach for a selected group of patients with small and favorably located, recurrent NPC. However, in the current study, the number of patients was too small to make any meaningful comparison with the results after maxillary swing operation. Further study on the QOL of patients after TORS nasopharyngectomy is necessary.
In conclusion, our current results indicate that the QOL is good for patients after salvage nasopharyngectomy using the maxillary swing approach. Attention should be paid to achieving curative resection as much as possible and, at the same time, avoiding complications like trismus, palatal fistula, and ORN after surgery.
No specific funding was disclosed.
The authors made no disclosures.