- Open Access
Quality of life and salivary output in patients with head-and-neck cancer five years after radiotherapy
© Braam et al; licensee BioMed Central Ltd. 2007
- Received: 30 October 2006
- Accepted: 05 January 2007
- Published: 05 January 2007
To describe long-term changes in time of quality of life (QOL) and the relation with parotid salivary output in patients with head-and-neck cancer treated with radiotherapy.
Forty-four patients completed the EORTC-QLQ-C30(+3) and the EORTC-QLQ-H&N35 questionnaires before treatment, 6 weeks, 6 months, 12 months, and at least 3.5 years after treatment. At the same time points, stimulated bilateral parotid flow rates were measured.
There was a deterioration of most QOL items after radiotherapy compared with baseline, with gradual improvement during 5 years follow-up. The specific xerostomia-related items showed improvement in time, but did not return to baseline. Global QOL did not alter significantly in time, although 41% of patients complained of moderate or severe xerostomia at 5 years follow-up. Five years after radiotherapy the mean cumulated parotid flow ratio returned to baseline but 20% of patients had a flow ratio <25%. The change in time of xerostomia was significantly related with the change in flow ratio (p = 0.01).
Most of the xerostomia-related QOL scores improved in time after radiotherapy without altering the global QOL, which remained high. The recovery of the dry mouth feeling was significantly correlated with the recovery in parotid flow ratio.
- Parotid Gland
- Flow Ratio
- Salivary Flow Rate
- Parotid Saliva
- Sticky Saliva
Patients with head-and-neck cancer have to cope with many aspects of their life-threatening disease. They have to deal with the diagnosis and the treatment as well as with the impact on physical, psychological and social functioning. Radiotherapy (RT) is a treatment modality, sometimes combined with surgery that can give considerable acute and long-term side effects to the oral cavity. One of the effects is a dry mouth (xerostomia), due to irradiation of the salivary glands. Furthermore, chewing and swallowing difficulties, impaired taste or an increased incidence of dental caries or oral candidiasis can occur [1, 2].
Quality of life (QOL) questionnaires have been utilized for several years in the follow-up of patients with head-and-neck cancer, and impaired QOL has been reported until years after RT [3, 4]. Up to 12 months after RT the xerostomia-related QOL scores follow the general pattern of salivary flow rates [5, 6]. The long-term relationship between the individual's perception of a dry mouth, the QOL and the objective parotid salivary output however, has not been determined.
We performed a prospective study in patients with head-and-neck cancer receiving RT. The first aim of the study was to assess the long-term change in time of the QOL. The second aim was to investigate the relationship between change in time of the subjective outcome and the objective parotid flow measurements. We also analyzed the relationship between the change in time of the subjective outcome and the mean parotid dose (Dpar), and the mean submandibular dose (Dsubm). Earlier we presented the short-term and long-term parotid flow data of this study group [7, 8]. In this paper, we present results after a minimum follow-up of 3.5 years.
From July 1996 till October 1998, patients with head-and-neck cancer that received primary or postoperative RT with curative intent were included in the study. Other inclusion criteria were no previous RT or surgery of the parotid glands, no history of suffering from malignancies or other diseases of the parotid glands and WHO 0–1. Patients with evidence of (p)N2c-N3 (TNM staging system 1997) or distant metastases, were excluded. All patients treated with induction or concomitant chemotherapy were excluded, because this might influence the parotid function . No patient used medication known to affect the function of the salivary glands.
Patient and tumor characteristics (n = 44)
Mean age (range)
Mean follow-up time (range)
since end of radiotherapy
Floor of mouth/oral cavity
Nose (nasal cavity)
Local + regional
Stage (TNM staging system 1997)
Patients completed a questionnaire before treatment and 6 weeks, 6 months, 12 months, and at least 3.5 years (mean 56 months, range 44–72 months) after treatment. The questionnaire consisted of the EORTC QLQ-C30(+3) and QLQ-H&N35.
The EORTC QLQ-C30 is a widely used questionnaire and contains QOL issues relevant to a broad range of cancer patients. It includes five functional scales, three symptom scales, a global QOL scale and six single items . Version 30(+3) contains two additional items on role functioning and one additional item on overall health. The EORTC QLQ-C30(+3) is meant to be used in conjunction with a tumor specific module.
The EORTC QLQ-H&N35 is a module used for the assessment of health-related QOL in patients with head-and-neck cancer . It contains seven symptom scales and six symptom items. It is designed to be used together with the core QLQ-C30 and has been validated in 622 head-and-neck cancer patients from 12 countries .
After transformation all items and scales range in score from 0 to 100. High scores for a functional or global QOL scale represent good functioning, or a high QOL, whereas a high score for a symptom scale or single item represents a high level of symptomatology or problems .
Parotid flow rates were measured at the same time points as the QOL measurements. No oral stimulus was permitted for 60 min before saliva collection. Stimulated parotid saliva was simultaneously collected separately from left and right parotid gland using Lashley cups. These cups were placed over the orifice of the Stenson's duct. Stimulation was achieved by applying three drops of a 5% acid solution to the mobile part of the tongue every 30 seconds and collection was carried out for 10 min. The volume of the saliva was measured in tubes by weight. It was assumed that the density of the parotid saliva was 1 g/ml. The flow rate was expressed for each separate gland in milliliters per minute (ml/min). The left and right parotid flow rates were added together and converted into the percentage of baseline flow rates (flow ratio). A complication was defined as cumulated stimulated parotid flow rate of <25% of the pre-RT flow rate.
Mean scores of the scales and single items of questionnaire for patients with cancer of the head- and-neck treated with radiotherapy with or without surgery. A significant outcome presents a significant change in time towards improvement starting 6 weeks after RT.
p < 0.01
Nausea and vomiting
p < 0.01
p < 0.01
p < 0.05
Symptom scales-single items†
p < 0.01
p < 0.01
p < 0.01
p < 0.01
p < 0.01
Open mouth (trismus)
p = 0.01
p < 0.01
p < 0.01
p < 0.01
A deterioration of almost all scales and items in QLQ-H&N35 was noted after RT and generally no effect was seen in the QLQ-C30(+3) questionnaire (table 2). Most items improved in time but not all reached baseline values (figure 2). The specific xerostomia related items dry mouth and sticky saliva showed deterioration 6 weeks after RT, which continued for dry mouth till 6 months. Thereafter both items showed an improvement but at 5 years after RT their values remained higher than baseline. We investigated the relation between the change in time of the various parameters starting after RT and not the relation at specific time points. At 12 months follow-up, 49% of the patients complained of a moderate or severe dry mouth, which slightly improved to 41% of the patients at 5 years. The functional scales of the QLQ-C30(+3) showed no significant alteration after RT. The mean scores before RT were already relatively high and showed only slight differences in time, but no significant change caused by RT. The global QOL was also not significantly altered in time in spite of the remaining dry mouth complaints.
Parotid flow measurements
Percentage of patients divided into three groups by the flow ratio at different time points (n = 44).
Relationship between subjective and objective parameters
Global QOL, dry mouth, sticky saliva and flow ratio
We investigated the relationship between the change in time of the subjective outcome of the questionnaire and the change in time of the objective stimulated parotid flow ratio. As objective explanatory variable we used the sum of the left and right parotid flow ratio. No significant relation was found between the change in global QOL and the change in flow ratio (p = 0.60). A significant relation between the flow ratio and dry mouth was found (p = 0.01). We found no evidence that the reduction of problems with sticky saliva could be explained by parotid flow (p = 0.79), adjusting for time revealed a significant time effect (p = 0.003). In other words, the improvement of problems with sticky saliva could be explained by time and was not due to the improvement of the parotid flow.
Global QOL, dry mouth, sticky saliva and mean dose
No clear relation was found between the change in time of the dry mouth item and Dpar or Dsubm. We found no significant relation between the change in time of the global QOL or sticky saliva and the mean dose to the various salivary glands. We also did not find a combined relationship.
This is the first long-term prospective study of the QOL combined with parotid salivary output of patients with head-and-neck malignancies treated with RT. We found a deterioration of most of the QOL items after completion of radiotherapy compared with baseline, with improvement during 5 years follow-up, even after 12 months. The specific xerostomia-related items improved, but did not return to baseline. Global QOL did not alter significantly in time, despite the fact that 41% of patients complained of a dry mouth at 5 years follow-up. Similar to the partial recovery of the dry mouth, the stimulated parotid flow rates gradually improved after radiotherapy, even after 12 months. We have presented this recovery in more detail previously . This improvement of the dry mouth was significantly related with the improvement of the parotid flow ratio (p = 0.01).
The finding of a moderate to severe dry mouth years after treatment and a normalized quality of life is consistent with other studies [4, 13–16]. It might be explained by adaptation of the patients to their disabilities, as I quote a patient: "doctor, I feel fine and I do not have a dry mouth" after which he took a sip of water out of a bottle he carried with him. It is known that the QOL varies according to gender and age and that gender and age have to be taken into consideration for analyses . But because of the relatively small number of patients in the present study, differentiation between men and women and age could not be studied. It should be remarked that at baseline most patients were preoperative with the tumor still in situ or just post-operative. Both situations may affect the QOL and related parameters and improvement in time. As all patients had this baseline situation, the analyses should be viewed in this perspective.
This study population consisted of 44 survivors derived from a larger group of patients. We only analyzed the group of surviving patients knowing that this is a favourable group and not representative of an average population. Analyses between survivors and non-survivors have been reported previously, and showed statistical difference between the flow ratio in favour of the survivors, but only at 6 weeks and 6 months and not at 12 months . This report shows that in patients who do survive, improvement over time can be seen.
There are various ways of recording parotid gland toxicity. Several head-and-neck cancer specific QOL questionnaires have been conducted and validated for subjective measurement [10–12, 18, 19]. We used the EORTC-QLQ-C30(+3) and the EORTC-H&N35 questionnaires which are well-validated and widely used. For objective methods salivary flow measurement using sialometry or scintigraphy have been reported [20–23]. The most adequate parameter to evaluate the function of the parotid gland is objective stimulated parotid flow measurement and consequently we used this method . Recently MRI, SPECT, and PET have been used to quantify the parotid gland radiation response, but they still have to prove their value [25–28].
Xerostomia-related QOL improved in time after radiotherapy without accompanying changes in global QOL. The global QOL remained high during time and no statistically significant changes were observed. The recovery of the dry mouth feeling was significantly related with the change in parotid flow ratio. Although the parotid flow rates recovered till baseline at 5 years follow-up, 41% of the patients complained of a moderate to severe dry mouth.
The authors wish to thank Dr. M. Schipper for her help with the statistical analysis. This research was supported by the Dutch Cancer Society (Grant UU 2001–2468).
- Cooper JS, Fu K, Marks J, Silverman S: Late effects of radiation therapy in the head and neck region. Int J Radiat Oncol Biol Phys 1995, 31: 1141-1164. 10.1016/0360-3016(94)00421-GView ArticlePubMedGoogle Scholar
- Valdez IH: Radiation-induced salivary dysfunction: clinical course and significance. Spec Care Dentist 1991, 11: 252-255.View ArticlePubMedGoogle Scholar
- Bjordal K, Kaasa S, Mastekaasa A: Quality of life in patients treated for head and neck cancer: a follow-up study 7 to 11 years after radiotherapy. Int J Radiat Oncol Biol Phys 1994, 28: 847-856.View ArticlePubMedGoogle Scholar
- Jensen AB, Hansen O, Jorgensen K, Bastholt L: Influence of late side-effects upon daily life after radiotherapy for laryngeal and pharyngeal cancer. Acta Oncol 1994, 33: 487-491.View ArticlePubMedGoogle Scholar
- Blanco AI, Chao KS, El Naqa I, Franklin GE, Zakarian K, Vicic M, Deasy JO: Dose-volume modeling of salivary function in patients with head-and-neck cancer receiving radiotherapy. Int J Radiat Oncol Biol Phys 2005, 62: 1055-1069. 10.1016/j.ijrobp.2004.12.076View ArticlePubMedGoogle Scholar
- Henson BS, Inglehart MR, Eisbruch A, Ship JA: Preserved salivary output and xerostomia-related quality of life in head and neck cancer patients receiving parotid-sparing radiotherapy. Oral Oncol 2001, 37: 84-93. 10.1016/S1368-8375(00)00063-4View ArticlePubMedGoogle Scholar
- Braam PM, Roesink JM, Moerland MA, Raaijmakers CP, Schipper M, Terhaard CH: Long-term parotid gland function after radiotherapy. Int J Radiat Oncol Biol Phys 2005, 62: 659-664. 10.1016/j.ijrobp.2004.12.015View ArticlePubMedGoogle Scholar
- Roesink JM, Moerland MA, Battermann JJ, Hordijk GJ, Terhaard CH: Quantitative dose-volume response analysis of changes in parotid gland function after radiotheraphy in the head-and-neck region. Int J Radiat Oncol Biol Phys 2001, 51: 938-946. 10.1016/S0360-3016(01)01717-5View ArticlePubMedGoogle Scholar
- Kosuda S, Satoh M, Yamamoto F, Uematsu M, Kusano S: Assessment of salivary gland dysfunction following chemoradiotherapy using quantitative salivary gland scintigraphy. Int J Radiat Oncol Biol Phys 1999, 45: 379-384. 10.1016/S0360-3016(99)00166-2View ArticlePubMedGoogle Scholar
- Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC: The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993, 85: 365-376. 10.1093/jnci/85.5.365View ArticlePubMedGoogle Scholar
- Bjordal K, Hammerlid E, Ahlner-Elmqvist M, de Graeff A, Boysen M, Evensen JF, Biorklund A, de Leeuw JR, Fayers PM, Jannert M, Westin T, Kaasa S: Quality of life in head and neck cancer patients: validation of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-H&N35. J Clin Oncol 1999, 17: 1008-1019.PubMedGoogle Scholar
- Bjordal K, de Graeff A, Fayers PM, Hammerlid E, van Pottelsberghe C, Curran D, Ahlner-Elmqvist M, Maher EJ, Meyza JW, Bredart A, Soderholm AL, Arraras JJ, Feine JS, Abendstein H, Morton RP, Pignon T, Huguenin P, Bottomly A, Kaasa S: A 12 country field study of the EORTC QLQ-C30 (version 3.0) and the head and neck cancer specific module (EORTC QLQ-H&N35) in head and neck patients. EORTC Quality of Life Group. Eur J Cancer 2000, 36: 1796-1807. 10.1016/S0959-8049(00)00186-6View ArticlePubMedGoogle Scholar
- de Graeff A, de Leeuw JR, Ros WJ, Hordijk GJ, Blijham GH, Winnubst JA: Long-term quality of life of patients with head and neck cancer. Laryngoscope 2000, 110: 98-106. 10.1097/00005537-200001000-00018View ArticlePubMedGoogle Scholar
- Hammerlid E, Silander E, Hornestam L, Sullivan M: Health-related quality of life three years after diagnosis of head and neck cancer–a longitudinal study. Head Neck 2001, 23: 113-125. 10.1002/1097-0347(200102)23:2<113::AID-HED1006>3.0.CO;2-WView ArticlePubMedGoogle Scholar
- Ringash J, Warde P, Lockwood G, O'Sullivan B, Waldron J, Cummings B: Postradiotherapy quality of life for head-and-neck cancer patients is independent of xerostomia. Int J Radiat Oncol Biol Phys 2005, 61: 1403-1407. 10.1016/j.ijrobp.2004.08.001View ArticlePubMedGoogle Scholar
- Wijers OB, Levendag PC, Braaksma MM, Boonzaaijer M, Visch LL, Schmitz PI: Patients with head and neck cancer cured by radiation therapy: a survey of the dry mouth syndrome in long-term survivors. Head Neck 2002, 24: 737-747. 10.1002/hed.10129View ArticlePubMedGoogle Scholar
- Hjermstad MJ, Fayers PM, Bjordal K, Kaasa S: Using reference data on quality of life–the importance of adjusting for age and gender, exemplified by the EORTC QLQ-C30 (+3). Eur J Cancer 1998, 34: 1381-1389. 10.1016/S0959-8049(98)00136-1View ArticlePubMedGoogle Scholar
- Eisbruch A, Kim HM, Terrell JE, Marsh LH, Dawson LA, Ship JA: Xerostomia and its predictors following parotid-sparing irradiation of head-and-neck cancer. Int J Radiat Oncol Biol Phys 2001, 50: 695-704. 10.1016/S0360-3016(01)01512-7View ArticlePubMedGoogle Scholar
- Trotti A, Johnson DJ, Gwede C, Casey L, Sauder B, Cantor A, Pearlman J: Development of a head and neck companion module for the quality of life-radiation therapy instrument (QOL-RTI). Int J Radiat Oncol Biol Phys 1998, 42: 257-261. 10.1016/S0360-3016(98)00224-7View ArticlePubMedGoogle Scholar
- Wolff A, Herscovici D, Rosenberg M: A simple technique for the determination of salivary gland hypofunction. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002, 94: 175-178.View ArticlePubMedGoogle Scholar
- Fox PC, van der Ven PH, Sonies BC, Weiffenbach JM, Baum BJ: Xerostomia: evaluation of a symptom with increasing significance. J Am Dent Assoc 1985, 110: 519-525.View ArticlePubMedGoogle Scholar
- Klutmann S, Bohuslavizki KH, Kroger S, Bleckmann C, Brenner W, Mester J, Clausen M: Quantitative salivary gland scintigraphy. J Nucl Med Technol 1999, 27: 20-26.PubMedGoogle Scholar
- Loutfi I, Nair MK, Ebrahim AK: Salivary gland scintigraphy: the use of semiquantitative analysis for uptake and clearance. J Nucl Med Technol 2003, 31: 81-85.PubMedGoogle Scholar
- Roesink JM, Schipper M, Busschers W, Raaijmakers CP, Terhaard CH: A comparison of mean parotid gland dose with measures of parotid gland function after radiotherapy for head-and-neck cancer: implications for future trials. Int J Radiat Oncol Biol Phys 2005, 63: 1006-1009. 10.1016/j.ijrobp.2005.04.023View ArticlePubMedGoogle Scholar
- Bussels B, Maes A, Flamen P, Lambin P, Erven K, Hermans R, Nuyts S, Weltens C, Cecere S, Lesaffre E, van den Bogaert W: Dose-response relationships within the parotid gland after radiotherapy for head and neck cancer. Radiother Oncol 2004, 73: 297-306. 10.1016/j.radonc.2004.09.015View ArticlePubMedGoogle Scholar
- Buus S, Grau C, Munk OL, Rodell A, Jensen K, Mouridsen K, Keiding S: Individual radiation response of parotid glands investigated by dynamic (11)C-methionine PET. Radiother Oncol 2006, 78: 262-269. 10.1016/j.radonc.2006.02.013View ArticlePubMedGoogle Scholar
- Morimoto Y, Ono K, Tanaka T, Kito S, Inoue H, Shinohara Y, Yokota M, Inenaga K, Ohba T: The functional evaluation of salivary glands using dynamic MR sialography following citric acid stimulation: a preliminary study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005, 100: 357-364. 10.1016/j.tripleo.2004.11.053View ArticlePubMedGoogle Scholar
- van Acker F, Flamen P, Lambin P, Maes A, Kutcher GJ, Weltens C, Hermans R, Baetens J, Dupont P, Rijnders A, Maes A, van den Bogaert W, Mortelmans L: The utility of SPECT in determining the relationship between radiation dose and salivary gland dysfunction after radiotherapy. Nucl Med Commun 2001, 22: 225-231. 10.1097/00006231-200102000-00015View ArticlePubMedGoogle Scholar
- Parliament MB, Scrimger RA, Anderson SG, Kurien EC, Thompson HK, Field GC, Hanson J: Preservation of oral health-related quality of life and salivary flow rates after inverse-planned intensity- modulated radiotherapy (IMRT) for head-and-neck cancer. Int J Radiat Oncol Biol Phys 2004, 58: 663-673. 10.1016/S0360-3016(03)01571-2View ArticlePubMedGoogle Scholar
- Jellema AP, Doornaert P, Slotman BJ, Rene LC, Langendijk JA: Does radiation dose to the salivary glands and oral cavity predict patient-rated xerostomia and sticky saliva in head and neck cancer patients treated with curative radiotherapy? Radiother Oncol 2005, 77: 164-171. 10.1016/j.radonc.2005.10.002View ArticlePubMedGoogle Scholar
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