The primary objective of this study was to investigate the quality of life (QOL) of patients with oral squamous cell carcinoma (OSCC) undergoing curative neoadjuvant chemoradiotherapy followed by radical tumour resection and simultaneous oral cavity reconstruction, using two validated questionnaires. A secondary objective was to assess clinical variables predicting post-treatment dysfunction in chewing, saliva, and swallowing. Thirty-five patients with locally advanced OSCC who underwent preoperative chemoradiotherapy were recruited prospectively. All patients completed both the University of Washington Quality of Life version 4 questionnaire (UW-QOL) and the Functional Assessment of Cancer Therapy–Head & Neck version 4 questionnaire (FACT-H&N). UW-QOL and FACT-H&N items were associated with clinical variables. Nearly three-quarters of OSCC patients perceived good to excellent levels of overall QOL after preoperative chemoradiotherapy. Chewing difficulties, decreased salivary function, and swallowing dysfunction were the most frequent complaints of OSCC patients. Items related to food intake were significantly worse in OSCC patients older than 60 years and those with T4 tumours, as well as those without alcohol intake. Chewing, saliva, and swallowing are the most significant issues in patients with OSCC undergoing preoperative chemoradiotherapy. The results of this study may help guide treatment decisions for OSCC patients based on more accurate expectations of adverse effects of cancer treatment.
With an estimated 90,000 new cases and approximately 40,000 deaths annually in Europe, oral squamous cell carcinoma (OSCC) represents a major health issue . To date, surgery followed by postoperative radiotherapy or chemoradiotherapy has been considered the mainstay of curative treatment for patients with locally advanced OSCC in most institutions . However, accumulating evidence suggests that neoadjuvant chemoradiotherapy followed by surgery represents an effective alternative option in the management of patients with locally advanced OSCC . The neoadjuvant therapy protocol may facilitate tumour down-staging, thus leading to higher curative resection rates, as well as the elimination of distant micrometastases .
In the last few years, patient-reported outcomes such as quality of life (QOL) have been used increasingly to complement disease-related clinical measures in the assessment of the risk–benefit profiles of cancer treatment regimens . QOL is of particular concern for patients with locally advanced OSCC who experience the adverse effects of multimodal treatment including surgery and radiation or chemoradiotherapy and the late negative sequelae, such as problems with nutritional intake, speaking, and breathing, as well as psychological issues related to functional impairments and facial disfigurement .
Surgery for advanced OSCC results in a loss of structural integrity in the head and neck region, while functional and aesthetic impairments after tumour surgery depend on the extent of the resection, the tumour site, and the type of reconstruction . Radiation-induced side effects have a multifaceted pathogenesis involving inflammation, oedema, hyposalivation, and fibrosis, with subsequent neuromuscular disorders . Concomitant chemoradiation has shown synergistic and additive effects and may increase adverse effects due to the enhancement of radiation-induced fibrosis of the musculature . To date, few studies have analyzed QOL outcomes with an emphasis on oral functions in patients with OSCC undergoing neoadjuvant chemoradiotherapy followed by radical tumour resection .
The primary objective of this study was to investigate the QOL of patients with locally advanced OSCC undergoing preoperative chemoradiotherapy followed by surgery with simultaneous oral cavity reconstruction, using both the University of Washington Quality of Life version 4 questionnaire (UW-QOL) and the Functional Assessment of Cancer Therapy–Head & Neck version 4 questionnaire (FACT-H&N). Based on these questionnaires, a secondary objective was to assess patient- and treatment-related factors predicting difficulties in chewing, decreased salivary function, and swallowing dysfunction.
Materials and methods
Patients and treatment
A prospective study was conducted including 35 patients with primary locally advanced OSCC undergoing curative neoadjuvant chemoradiotherapy followed by radical tumour resection and simultaneous oral cavity reconstruction at the Medical University of Vienna between 2005 and 2009. Patients eligible for participation in the study had to fulfil the following inclusion criteria: (1) biopsy-proven primary OSCC, (2) clinical TNM stage III or IV, (3) no evidence of distant metastatic disease (M0), (4) no history of other cancer in the head and neck region, (5) reconstruction at the time of surgical resection with either a microvascular free flap or pedicled regional flap, (6) clear resection margins, (7) no evidence of tumour recurrence at the time of recruitment, with a minimum of 1 year disease-free survival, and (8) ability to understand the written and spoken German language.
All patients received multimodal treatment consisting of neoadjuvant chemoradiotherapy and surgery as described previously . In brief, chemotherapy consisted of mitomycin C (15 mg/m 2 , an intravenous bolus injection on day 1) and 5-fluorouracil (750 mg/m 2 /day, continuous infusions on days 1–5). Concurrent radiotherapy was delivered over 5 weeks for a cumulative dose of 50 Gy (25 fractions of 2 Gy per day). Surgical resection with simultaneous oral cavity reconstruction (microvascular free flaps or regional pedicled flaps) was performed 4–8 weeks after the finalization of radiotherapy. Patients were followed up for at least 5 years (at 3-month intervals during the first 2 years and at 6-month intervals for the next 3 years) or until death. The pathological response to neoadjuvant chemoradiotherapy was assessed in surgical specimens as described previously , according to the percentage of vital residual tumour cells in relation to the tumour bed: no vital tumour cells, <5% of vital tumour cells, 5–50% of vital tumour cells, and >50% of vital tumour cells (regression grades (RG) 1, 2, 3, and 4, respectively).
Eligible patients were recruited prospectively and were asked to complete the questionnaires while waiting to be seen in the outpatient clinic during their follow-up visit at 1 year post-treatment. The study was explained in detail by two investigators (A.H. and C. P.) and written informed consent for participation in the study was obtained from all patients. In order to measure patient QOL the following surveys were used: the UW-QOL version 4, the FACT-H&N version 4, and an in-house questionnaire . For all patients, clinical information was obtained from their medical history, physical examination, radiology reports, and medical records found in the Vienna General Hospital Patient Information System (AKIM).
The UW-QOL version 4 questionnaire in the German language used in this study was retrieved from www.headandneckcancer.co.uk/For+professionals/Quality+of+Life+(QOL)/UW-QOLv4+Translations.aspx (Fig. S1A; the UW-QOL version 4 questionnaire in English is given in Fig. S1B). The UW-QOL questionnaire consists of four different sections. The first section measures QOL over the past 7 days by addressing 12 items related to the patient’s physical and social–emotional function. The items chewing, swallowing, speech, taste, saliva, and appearance comprise the physical UW-QOL subscale, while the items pain, activity, recreation, mood, shoulder function, and anxiety comprise the social–emotional UW-QOL subscale . The item-specific questions have three to six possible response options that are scaled evenly from 0 (worst) to 100 (best). Consequently the questions with six possible responses are scored as 0, 20, 40, 60, 80, and 100, those with five responses as 0, 25, 50, 75, and 100, those with four responses as 0, 30, 70, and 100, and those with three responses as 0, 50, and 100. In the second section of the instrument (UW-QOL importance rating), patients are asked to choose up to three items that affected them the most in the past 7 days. The most important item chosen receives 1 point, while the items not chosen receive 0 points. The third section of the questionnaire includes three global questions, ranked from 0 (worst) to 100 (best). The patients are asked about (1) current health-related quality of life (HR-QOL) compared to 1 month before developing cancer (scored as 0, 25, 50, 75, and 100), (2) HR-QOL during the past 7 days (scored as 0, 20, 40, 60, 80, and 100), and (3) overall quality of life (Overall-QOL) during the past 7 days (scored as 0, 20, 40, 60, 80, and 100). In the fourth section of the questionnaire, participants are asked to describe their QOL using their own words or drawings.
The FACT-H&N version 4 questionnaire in the German language was the second validated questionnaire used in this study (Fig. S2A; the FACT-H&N version 4 questionnaire in English is given in Fig. S2B). The FACT-H&N questionnaire is a multidimensional, self-reporting questionnaire consisting of five subscales: physical well-being (PWB; with seven items), social/family well-being (SWB; with seven items), emotional well-being (EWB; with six items), functional well-being (FWB; with seven items), and a head and neck cancer-specific subscale (FACT-HNC; with 12 items). The FACT-HNC subscale addresses 12 specific concerns of patients during the past 7 days, such as the ability to eat, dryness of the mouth, breathing difficulties, voice quality, eating assessment, face and neck appearance, swallowing, tobacco and alcohol use, ability to communicate, ability to eat solid food, and pain in the mouth, throat, or neck. Each FACT-H&N item includes five statements scored from 0 representing ‘not at all’ to 4 representing ‘very much’. All items are summed to provide a score for each FACT-H&N subscale. Unweighted total scores were calculated for FACT-General (FACT-G), FACT-H&N, and FACT-H&N Trial Outcome Index (TOI). The FACT-G total score was calculated by adding the PWB, SWB, EWB, and FWB subscale scores. The FACT-H&N total score was calculated by adding FACT-G and FACT-HNC scores. The FACT-H&N TOI summary score was calculated by adding the PWB, FWB, and HNC subscale scores. For the FACT-H&N questionnaire, higher scores reflect better QOL.
In addition, an in-house questionnaire was composed to gather the following information: sex, date of birth, family status, children, household, educational level, smoking status before surgical treatment and at the time of the survey, alcohol consumption before surgical treatment and at the time of the survey, and psychological assistance (Fig. S3).
Descriptive statistics were used to summarize the clinical characteristics of the study cohort. Variables assessed were age, sex, smoking, alcohol intake, primary tumour site, clinical T category, clinical N category, neck dissection, and reconstruction. Categorical data were described with absolute and relative frequencies. Continuous data were described with the mean, standard deviation (SD), and standard error (SE) due to the skewed distribution of the data. For the primary objective, the following scores were assessed: (1) UW HR-QOL score, (2) UW Overall-QOL score, and (3) FWB subscale item GF7 score (“I am content with the quality of my life right now”; Fig. S2B). For the secondary objective, UW-QOL items (chewing, saliva, swallowing) and FACT-H&N items (“My mouth is dry”, H&N2; “I can swallow naturally and easily”, H&N7; “I can eat solid foods”, H&N11) were compared between two or more groups using the Mann–Whitney U -test or Kruskal–Wallis test, as appropriate. The Spearman correlation coefficient was used to quantify the correlation between the UW-QOL and FACT-H&N scores. A two-sided P -value of <0.05 was considered statistically significant. IBM SPSS Statistics version 21.0 (IBM Corp., Armonk, NY, USA) was used for the statistical analysis. The institutional ethics committee approved the study.
Demographic and clinicopathological characteristics of the study cohort are presented in Table 1 . A total of 35 patients were recruited into this study. There were 19 male patients (mean age 60.4 (SD 6.4) years) and 16 female patients (mean age 61.2 (SD 14.2) years). The most frequently involved primary tumour site was the floor of the mouth ( n = 13, 37%). The majority of patients had a T4 tumour size ( n = 23, 66%) and N2 nodal involvement ( n = 21, 60%). Among those with T4 tumours, a segmental mandibulectomy was performed in eight cases (35%), while a solely soft tissue resection was performed in 15 cases (65%). All patients had a history of neck dissection, with an ipsilateral neck dissection carried out in 21 patients (60%) and a bilateral neck dissection in 14 patients (40%). For reconstruction after tumour resection, the following flaps were used: jejunum ( n = 11, 31%), radial forearm ( n = 7, 20%), iliac crest ( n = 6, 17%), pectoralis major ( n = 5, 14%), latissmus dorsi ( n = 4, 11%), and fibula ( n = 2, 6%). Twenty-four of the 35 patients (68%) achieved a pathological complete response (RG1 group), whereas nine patients (26%) were categorized as RG2, one patient (3%) as RG3, and one patient (3%) as RG4.
|Primary tumour site|
|Floor of the mouth||13 (37)|
|Retromolar trigone||10 (29)|
|Lower gum||6 (17)|
|Buccal mucosa||2 (6)|
|Clinical T category|
|Clinical N category|
|Radial forearm||7 (20)|
|Iliac crest||6 (17)|
|Pectoralis major||5 (14)|
|Latissimus dorsi||4 (11)|
According to the in-house questionnaire, 18 of the 35 patients (51%) were married and 26 (74%) had children. Four patients (11%) reported living alone in a one-person household. More than half of the patients had graduated from a vocational college ( n = 19, 54%), while nine (26%) had graduated from main school. Twenty-eight (80%) patients reported smoking at diagnosis, while nine (26%) reported that they still smoked at the time of the survey. Alcohol drinking at diagnosis was reported by 31 patients (89%), while 26 (74%) reported still consuming alcohol at the time of the survey. Five (14%) patients reported that they had received psychological support to manage the physical, mental, and emotional effects associated with cancer and its treatment.
Patient-reported QOL outcomes
All UW-QOL scores, including mean scores with SEs and the percentage of patients reporting the maximum score of 100 for each domain and global questions, are shown in Table 2 . When asked about HR-QOL compared to a month before they had cancer, a total of 24 patients (69%) reported an improved ( n = 14; 40%) or about equal well-being ( n = 10; 29%). Regarding HR-QOL during the past 7 days, 19 patients (54%) rated their health as ‘good,’ ‘very good,’ or ‘excellent’, while none rated it as ‘very poor’. Regarding Overall-QOL during the past 7 days, 26 patients (74%) reported a ‘good,’ ‘very good,’ or ‘excellent’ QOL, while none of the patients stated a very poor QOL. For the UW-QOL subscales, the mean (SE) scores were 78.8 (2.1) for social–emotional function and 67.55 (4.1) for physical function. Of the items included in the physical UW-QOL subscale, the lowest mean score was recorded for chewing (mean 52.8, SE 5), followed by swallowing, saliva, appearance, speech, and taste (the last being the highest scored item). Of the items included in the social–emotional UW-QOL subscale, activity showed the lowest mean score (mean 72.1, SE 3.8), followed by mood, recreation, anxiety, pain, and shoulder function (the last being the highest scored item). Regarding the items considered to be most important in the last 7 days (UW-QOL importance rating), swallowing was chosen as the top priority ( n = 16, 46%), followed by saliva ( n = 11, 31%) and chewing ( n = 10, 29%). Less highlighted items were shoulder function ( n = 2, 6%) and taste ( n = 2, 6%) ( Table 2 ).
|UW-QOL||UW-QOL scores||UW-QOL importance rating|
|0||20||25||30||40||50||60||70||75||80||100||Mean||SE||Best score = 100, % of all patients||No. (%) of patients
choosing the domain
|Shoulder function||2||–||–||1||–||–||–||9||–||–||23||84.5||4.5||66||2 (6)||9|
|Health-related QOL compared to a month before had cancer|
|Much worse (score 0)||Somewhat worse (score 25)||About the same (score 50)||Somewhat better (score 75)||Much better (score 100)||Mean||SE||Best score = 100, % of all patients|
|Health-related QOL during the past 7 days|
|Very poor (score 0)||Poor (score 20)||Fair (score 40)||Good (score 60)||Very good (score 80)||Excellent (score 100)||Mean||SE||Best score = 100, % of all patients|
|Overall-QOL during the past 7 days|
|Very poor (score 0)||Poor (score 20)||Fair (score 40)||Good (score 60)||Very good (score 80)||Excellent (score 100)||Mean||SE||Best score = 100, % of all patients|
Mean and SE scores for each of the FACT-H&N subscales and summary scales are provided in Table 3 . Regarding the FWB subscale item GF7 quantifying the current level of satisfaction with QOL, the statement “I am content with the quality of my life right now” was reported as follows: the majority of patients ( n = 25, 71%) reported that they were ‘quite a bit’ or ‘very much’ satisfied with their current quality of life, six (17%) reported moderate satisfaction, while four (11%) reported being ‘a little bit’ or ‘not at all’ satisfied with their current quality of life. Regarding the SWB subscale item measuring the current level of sexual activity, the statement “I am satisfied with my sex life” was reported as follows: 14 (40%) patients reported being ‘quite a bit’ satisfied and seven (20%) as being ‘very much’ satisfied, while 14 (40%) patients did not answer the question at all, with the majority of them being women (64%). With respect to the HNC subscale item “I am unhappy with how my face and neck look”, most of the patients ( n = 26, 74%) reported ‘not at all’, ‘a little bit,’ or ‘somewhat’.
|FACT-H&N scores (range)||No. of items||Mean||SE|
|FACT subscale scores|
|PWB subscale score (0–28)||7||23.9||0.5|
|SWB subscale score (0–28)||7||23||1|
|EWB subscale score (0–24)||6||19.6||0.6|
|FWB subscale score (0–28)||7||19.8||1|
|HNC subscale score (0–48)||12||24.1||1.1|
|FACT summary scores a|
|FACT-G total score (0–108)||27||86.1||2.2|
|FACT-H&N total score (0–156)||39||110||3|
|FACT-H&N TOI total score (0–104)||26||68.2||2|
a FACT-G (Functional Assessment of Cancer Therapy–General) = PWB + SWB + EWB + FWB; FACT-H&N (Functional Assessment of Cancer Therapy–Head & Neck) = FACT-G + HNC; FACT-H&N TOI (FACT-H&N Trial Outcome Index) = PWB + FWB + HNC.
Table 4 shows the associations between UW-QOL and FACT-H&N items related to food intake and clinical variables of the 35 patients with oral cancer. There was a statistically significant association between patient age >60 years and difficulties eating solid food ( P = 0.016). The analysis showed that patients who reported no alcohol consumption at the time they completed the questionnaire had significantly worse chewing function ( P = 0.022) and more difficulties eating solid food ( P = 0.01). Patients with pre-treatment clinical stage T4 had significantly worse chewing function ( P = 0.043) and decreased salivary function ( P = 0.048) compared to patients with clinical stages T1/T2/T3. The FACT-H&N total score was significantly correlated with the UW Overall-QOL score ( r s = 0.398, P = 0.018) and the UW HR-QOL score ( r s = 0.496, P = 0.002) during the past 7 days.
|UW-QOL items||FACT-H&N items|
|Chewing||Swallowing||Saliva||I can swallow naturally and easily||My mouth is dry||I can eat solid food|
|Variable a||No. of
|Mean rank||P -value||Mean rank||P -value||Mean rank||P -value||Mean rank||P -value||Mean rank||P -value||Mean rank||P -value|
|Primary tumour site||0.29||0.71||0.24||0.64||0.36||0.81|
|Floor of the mouth||13||16.0||17.0||21.8||17.2||21.8||17.6|
|Clinical T category||0.043*||0.52||0.048*||0.10||0.44||0.09|
|Clinical N stage||0.87||0.70||0.18||0.07||0.10||0.69|
|Soft tissue flap||27||17.7||17.3||18.6||16.4||17.6||17.0|