Sparing of salivary gland function
The effect of amifostine or IMRT to preserve the parotid function after radiotherapy of the head and neck region measured by quantitative salivary gland scintigraphy☆

https://doi.org/10.1016/j.radonc.2008.07.016Get rights and content

Abstract

Purpose

In this retrospective study, two approaches to preserve the parotid function after radiotherapy (RT) were compared: application of the radioprotective agent amifostine during RT and parotid-sparing intensity-modulated radiotherapy (IMRT).

Patients and methods

Patients were qualified for this analysis if (1) both parotid glands received a radiation dose of ⩾50 Gy using conventional radiotherapy techniques (cRT) or if they received a parotid-sparing IMRT as alternative, if (2) salivary gland scintigraphies before and after RT were performed, and if (3) a normal parotid function was present before RT. Quantitative salivary gland scintigraphy was used to assess the parotid gland function.

Results

Altogether 275 salivary gland scintigraphies of 100 patients were analyzed. The mean relative tracer uptake (ΔU) of patients treated with cRT, cRT with amifostine and IMRT 1–12 months after RT was 0.59 (95%CI 0.54–0.65), 0.67 (95%CI 0.59–0.76), and 0.93 (95%CI 0.78–1.07), respectively. The mean relative ΔU 13–47 months after RT was 0.40 (95%CI 0.32–0.49), 0.60 (95%CI 0.48–0.71), and 0.92 (95%CI 0.56–1.28). At 1–12 months after RT, ANOVA testing with post-hoc comparison using the Bonferroni correction showed a significant difference between IMRT and cRT (p < 0.001) or IMRT and amifostine (p < 0.01). The difference between amifostine and cRT was not significant during the first year. At 13–47 months after RT, the difference between cRT and amifostine was significant (p = 0.02).

Conclusion

Our data suggest that both amifostine and IMRT are able to partially preserve the parotid function after radiotherapy. The effect of IMRT appeared to be much greater.

Section snippets

Patients and methods

This is a retrospective analysis of patients who received radiotherapy of the head and neck region at the University Hospitals Heidelberg, Hamburg and Mainz in Germany. The objective of this analysis was to compare the parotid function after conventional non-parotid sparing radiotherapy (cRT), cRT with amifostine, and parotid-sparing IMRT.

Patients were treated according to different protocols evaluating the parotid gland function after radiotherapy. All protocols included an assessment of the

Conventional radiotherapy with or without amifostine

The conventional (non-parotid-sparing) radiotherapy (cRT) usually consisted of three fields, two lateral opposed fields for the primary tumor and the upper neck, and one anterior field for the supraclavicular lymph nodes and lower neck (half beam technique). After a dose of about 30 Gy, the spinal cord was blocked in all three fields. The blocked areas at risk were treated with electrons of various energies depending on CT findings. Pre-treatment CT examinations and conventional simulation were

Parotid-sparing IMRT

Patients were immobilized using an individually manufactured head mask. CT and MRI were used as the basis for treatment planning, and the target point was defined stereotactically. The inverse treatment planning, dose calculation and visualization of the dose distribution were performed either by using the treatment planning system CMS XIO or by using the in-house developed KonRad treatment planning system in combination with the in-house developed 3D-treatment planning system VIRTUOS as

Quantitative salivary gland scintigraphy

The quantitative salivary scintigraphy was performed using a standard protocol [14], [23]. In short, salivary scintigraphy was performed after a 4 hour fasting. After intravenous injection of the tracer (technetium-99 m pertechnetate) sequential images of 1 min/frame were acquired for 30 min using a gamma camera. After 20 min, salivary flow was stimulated with 10 mL of diluted lemon juice administered to the dorsal tongue. Time–activity curves were calculated using manually drawn oval

Statistical analysis

Significance of differences in the distributions of the maximum tracer uptake between patients with cRT, cRT with amifostine, and IMRT were tested using multivariate analysis of variance (ANOVA) with post-hoc comparison using the Bonferroni correction. Differences in the distribution of the RTOG score were evaluated using the Kruskal–Wallis ANOVA with post-hoc comparison of mean ranks of all pairs of groups. The dose–response curve was adjusted with a maximum-likelihood fitting procedure using

Results

Altogether 275 salivary gland scintigraphies of 100 patients were analyzed for comparison of the three treatment groups. The patient and treatment characteristics in Table 1 show that the parotid dose of the non-spared glands was similar in all groups. Most of the patient and treatment characteristics were well balanced between the groups. An imbalance of the tumor site distribution was most probably due to the retrospective nature of this analysis but was unlikely to significantly bias the

Discussion

This retrospective analysis of combined data from three institutions suggested that both conventional radiotherapy with amifostine and parotid-sparing IMRT are able to partially preserve the parenchymal parotid function when compared to conventional radiotherapy alone. The effect of IMRT appeared to be much greater.

Our results concerning the parotid function preserving effect of amifostine are well in line with the results of a phase III trial reported by Brizel et al. [17]. In this randomized

Acknowledgement

The authors thank Prof. Dr. Winfried Alberti for his support.

References (41)

  • K. Mossman et al.

    Long-term effects of radiotherapy on taste and salivary function in man

    Int J Radiat Oncol Biol Phys

    (1982)
  • A.B. Jensen et al.

    Influence of late side-effects upon daily life after radiotherapy for laryngeal and pharyngeal cancer

    Acta Oncol

    (1994)
  • J.S. Cooper et al.

    Late effects of radiation therapy in the head and neck region

    Int J Radiat Oncol Biol Phys

    (1995)
  • K. Bjordal et al.

    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)
  • A.P. Jellema et al.

    Impact of radiation-induced xerostomia on quality of life after primary radiotherapy among patients with head and neck cancer

    Int J Radiat Oncol Biol Phys

    (2007)
  • C. Dawes

    Circadian rhythms in the flow rate and composition of unstimulated and stimulated human submandibular saliva

    J Physiol

    (1975)
  • J.L. Roh et al.

    Xerostomia following radiotherapy of the head and neck affects vocal function

    J Clin Oncol

    (2005)
  • B.C. Jham et al.

    Oral health status of 207 head and neck cancer patients before, during and after radiotherapy

    Clin Oral Investig

    (2007)
  • K.E. Ohrn et al.

    Oral status during radiotherapy and chemotherapy: a descriptive study of patient experiences and the occurrence of oral complications

    Support Care Cancer

    (2001)
  • A.M. Kielbassa et al.

    Radiation-related damage to dentition

    Lancet Oncol

    (2006)
  • J.M. Balogh et al.

    Osteoradionecrosis of the mandible: a review

    J Otolaryngol

    (1989)
  • A. Eisbruch et al.

    The prevention and treatment of radiotherapy-induced xerostomia

    Semin Radiat Oncol

    (2003)
  • B. Bussels et al.

    Recurrences after conformal parotid-sparing radiotherapy for head and neck cancer

    Radiother Oncol

    (2004)
  • M.W. Munter et al.

    Evaluation of salivary gland function after treatment of head-and-neck tumors with intensity-modulated radiotherapy by quantitative pertechnetate scintigraphy

    Int J Radiat Oncol Biol Phys

    (2004)
  • K.S. Chao et al.

    Patterns of failure in patients receiving definitive and postoperative IMRT for head-and-neck cancer

    Int J Radiat Oncol Biol Phys

    (2003)
  • L.A. Dawson et al.

    Patterns of local-regional recurrence following parotid-sparing conformal and segmental intensity-modulated radiotherapy for head and neck cancer

    Int J Radiat Oncol Biol Phys

    (2000)
  • D.M. Brizel et al.

    Phase III randomized trial of amifostine as a radioprotector in head and neck cancer

    J Clin Oncol

    (2000)
  • T. Wasserman et al.

    Effect of amifostine on patient assessed clinical benefit in irradiated head and neck cancer

    Int J Radiat Oncol Biol Phys

    (2000)
  • A. Eisbruch et al.

    How should we measure and report radiotherapy-induced xerostomia?

    Semin Radiat Oncol

    (2003)
  • D. Rades et al.

    Serious adverse effects of amifostine during radiotherapy in head and neck cancer patients

    Radiother Oncol

    (2004)

    • Cited by (42)

    • Radiation Therapy and Soft Tissue Response

      2021, Plastic Surgery - Principles and Practice

    • Double blind randomized prospective trial of bethanechol in the prevention of radiation-induced salivary gland dysfunction in head and neck cancer patients

      2015, Radiotherapy and Oncology

    • Underlying protective mechanism of a1-adrenoceptor activation against irradiation-induced damage in rat submandibular gland

      2013, Archives of Oral Biology

    • Contemporary Radiotherapy in Head and Neck Cancer. Balancing Chance for Cure with Risk for Complication

      2013, Surgical Oncology Clinics of North America
      Citation Excerpt :

      Lower doses to the parotids allow for better recovery of salivary function and less xerostomia.36 Quantitative scintigraphy studies have found IMRT considerably more effective than amifostine in protection of salivary gland function.37,38 Two small phase III trials from Hong Kong randomized subjects with nasopharyngeal cancer to IMRT or conventional RT.

    • Volumetric modulated arc therapy for nasopharyngeal carcinoma: A dosimetric comparison with TomoTherapy and step-and-shoot IMRT

      2012, Radiotherapy and Oncology

    • Does hyperbaric oxygen treatment have the potential to increase salivary flow rate and reduce xerostomia in previously irradiated head and neck cancer patients? A pilot study

      2011, Oral Oncology
      Citation Excerpt :

      Spontaneous oral mucosal pain and difficulties in chewing, swallowing and speech have a major impact on quality of life in these patients.2 Different approaches have been applied to prevent radiation-induced salivary gland hypofunction and xerostomia, such as optimisation of radiation techniques, e.g. intensity-modulated radiation therapy and administration of cytoprotective agents, e.g. amifostine.3 Furthermore, stimulation of a residual capacity in radiation-damaged salivary gland tissue has been attempted by administration of cholinergic muscarinic agonists; e.g. pilocarpine and bethanecol,4–6 masticatory and gustatory stimulation7 and acupuncture,8–10 or by the use of lubricating agents when saliva secretion cannot be stimulated.

    View all citing articles on Scopus
    ☆

    This work was supported by grants of the “Forschungsförderung of the University of Heidelberg” and “Hamburger Krebsgesellschaft”.

    View full text
    Copyright © 2008 Elsevier Ireland Ltd. All rights reserved.