Quality of life and salivary output in patients with head-and-neck cancer five years after radiotherapy

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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

Early to late sparing of radiation damage to the parotid gland by adrenergic and muscarinic receptor agonists

Damage to salivary glands after radiotherapeutic treatment of head and neck tumours can severely impair the quality of life of the patients. In the current study we have investigated the early-to-late pathogenesis of the parotid gland after radiation. Also the ability to ameliorate the damage using pretreatment with adrenergic or muscarinic receptor agonists is studied. Rats were locally irradiated with or without i.p. pretreatment with phenylephrine (α-adrenoceptor agonist, 5 mg kg−1), isoproterenol (β-adrenoceptor agonist, 5 mg kg−1), pilocarpine (4 mg kg−1), methacholine (3.75 mg kg−1) (muscarinic receptor agonists) or methacholine plus phenylephrine. Parotid salivary flow rate, amylase secretion, the number of cells and gland histology were monitored sequentially up to 240 days postirradiation. The effects were described in 4 distinct phases. The first phase (0–10 days) was characterised by a rapid decline in flow rate without changes in amylase secretion or acinar cell number. The second phase (10–60 days) consists of a decrease in amylase secretion and is paralleled by acinar cell loss. Flow rate, amylase secretion and acinar cell numbers do not change in the third phase (60–120 days). The fourth phase (120–240 days) is determined by a further deterioration of gland function but an increase in acinar cell number, albeit with poor tissue morphology. All drug pretreatments used could reduce radiation effects in phase I and II. The protective effects were lost during phase IV, with the exception of methacholine plus phenylephrine pretreatment. The latter combination of drugs ameliorated radiation-damage throughout the entire follow-up time. The data show that combined pre-irradiation stimulation of muscarinic acetylcholine receptors with methacholine plus α-adrenoceptors with phenylephrine can reduce both early and late damage, possibly involving the PLC/PIP2 second messenger pathways. This opens perspectives for the development of clinical applicable methods for long-term sparing of parotid glands subjected to radiotherapy of head and neck cancer patients. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Radiation induced DNA damage and damage repair in three human tumour cell lines

Three human tumour cell lines (HX142, RT112 and MGH-U1) with different radiosensitivities were tested for differences in the rate and/or extent of DNA unwinding in alkali as well as for differences in the induction of DNA double strand breaks by means of the pulsed field gel electrophoresis, after X-irradiation. Unlike that which has been found using the non-denaturing filter elution technique (NDE, McMillan et al., 1990), no differences in initial DNA damage (the extent of alkaline unwinding and the induction of double strand breaks) were found for the three cell lines. These data suggest that rather than a different number of DNA lesions per Da per Gy between these cell lines, structural differences in chromatin structure (related to radiosensitivity) might impair the detectability of lesions in some assays like the NDE. The nature of such structure differences remains unclear. However, the differences did not affect alkaline unwinding profiles, as all three cell lines showed identical rates of DNA unwinding after exposure to X-rays. Furthermore, the three cell lines did not show significant differences in the kinetics of DNA strand break rejoining nor in the amounts of damage remaining after 24 h repair. The results obtained in this study, together with other findings, suggest that the three cell lines may differ in their 'presentation' of DNA damage

A comparison of mean parotid gland dose with measures of parotid gland function after radiotherapy for head-and-neck cancer:Implications for future trials

Purpose: To determine the most adequate parameter to measure the consequences of reducing the parotid gland dose. Methods and Materials: One hundred eight patients treated with radiotherapy for various malignancies of the head and neck were prospectively evaluated using three methods. Parotid gland function was objectively determined by measuring stimulated parotid flow using Lashley cups and scintigraphy. To assess xerostomia-related quality of life, the head-and-neck cancer module European Organization for Research and Treatment of Cancer QLQ (Quality of Life Questionnaire) H&N35 was used. Measurements took place before radiotherapy and 6 weeks and 12 months after the completion of radiotherapy. Complication was defined for each method using cutoff values. The correlation between these complications and the mean parotid gland dose was investigated to find the best measure for parotid gland function. Results: For both flow and scintigraphy data, the best definition for objective parotid gland toxicity seemed to be reduction of stimulated parotid flow to Conclusions: Stimulated flow measurements using Lashley cups, with a complication defined as flo

Preservation of the rat parotid gland function after radiation by prophylactic pilocarpine treatment:Radiation dose dependency and compensatory mechanisms

Purpose: To study the ability of a prophylactic pilocarpine administration to preserve the rat parotid gland function after unilateral irradiation with graded doses of X-rays. Methods: The right parotid gland of male albino Wistar rats was irradiated with single doses of X-rays (10-30 Gy, at 1.5 Gy min(-1)). Pilocarpine (4 mg/kg) was administered intraperitoneally, 1 hour prior to irradiation. Saliva samples of both left and right parotid gland were collected by means of miniaturized Lashley cups 4 days before and 3, 7, 10, and 30 days after irradiation. The parotid salivary flow rate (mu l/min) was used as a parameter for the assessment of parotid gland function. Results: Our data confirm that a single prophylactic treatment of pilocarpine can attenuate radiation-induced loss of gland function. Surprisingly, the effect of pilocarpine was not restricted to the irradiated gland only. Pilocarpine also enhanced the how rate in the contralateral, nonirradiated gland. The latter effect was found for all doses above 10 Gy and became apparent around 7 days after the radiation treatment. The effectiveness of pilocarpine to attenuate function loss in the irradiated gland decreased with increasing dose and was lost after single doses of 30 Gy. Conclusions: Our data provide direct evidence that increasing the compensatory potential of the nondamaged gland, at least in part, underlies the "radioprotective effect" of pilocarpine in case of unilateral radiation. The ability of pilocarpine to ameliorate the early radiation-induced impairment of the parotid gland function in the irradiated gland may therefore be dependent on the remaining number of functional cells, and thus on the volume of the gland that lies within the radiation portal. (C) 1999 Elsevier Science Inc

Preservation of the rat parotid gland function after radiation by prophylactic pilocarpine treatment: Radiation dose dependency and compensatory mechanisms

Purpose: To study the ability of a prophylactic pilocarpine administration to preserve the rat parotid gland function after unilateral irradiation with graded doses of X-rays. Methods: The right parotid gland of male albino Wistar rats was irradiated with single doses of X-rays (10-30 Gy, at 1.5 Gy min(-1)). Pilocarpine (4 mg/kg) was administered intraperitoneally, 1 hour prior to irradiation. Saliva samples of both left and right parotid gland were collected by means of miniaturized Lashley cups 4 days before and 3, 7, 10, and 30 days after irradiation. The parotid salivary flow rate (mu l/min) was used as a parameter for the assessment of parotid gland function. Results: Our data confirm that a single prophylactic treatment of pilocarpine can attenuate radiation-induced loss of gland function. Surprisingly, the effect of pilocarpine was not restricted to the irradiated gland only. Pilocarpine also enhanced the how rate in the contralateral, nonirradiated gland. The latter effect was found for all doses above 10 Gy and became apparent around 7 days after the radiation treatment. The effectiveness of pilocarpine to attenuate function loss in the irradiated gland decreased with increasing dose and was lost after single doses of 30 Gy. Conclusions: Our data provide direct evidence that increasing the compensatory potential of the nondamaged gland, at least in part, underlies the "radioprotective effect" of pilocarpine in case of unilateral radiation. The ability of pilocarpine to ameliorate the early radiation-induced impairment of the parotid gland function in the irradiated gland may therefore be dependent on the remaining number of functional cells, and thus on the volume of the gland that lies within the radiation portal. (C) 1999 Elsevier Science Inc