Hearing loss in survivors of childhood head and neck rhabdomyosarcoma: a long-term follow-up study.

OBJECTIVES: To determine the hearing status of survivors treated for head and neck rhabdomyosarcoma (HNRMS) at long-term follow-up. DESIGN: Cross-sectional long-term follow-up study. SETTING: Tertiary comprehensive cancer centre. PARTICIPANTS: Survivors treated for HNRMS during childhood in two concurrent cohorts; survivors in London had been treated with external beam radiotherapy (EBRT-based local therapy); survivors in Amsterdam were treated with AMORE (Ablative surgery, MOuld technique afterloading brachytherapy and surgical REconstruction) if feasible, otherwise EBRT (AMORE-based local therapy). MAIN OUTCOME MEASURES: We assessed hearing status of HNRMS survivors at long-term follow-up. Hearing thresholds were obtained by pure-tone audiometry. METHODS: We assessed the hearing thresholds, the number of patients with clinically relevant hearing loss and hearing impairment graded according to the Common Terminology Criteria for Adverse Events version 4.0 (CTCAEv4) and Boston criteria. Furthermore, we compared hearing loss between survivors treated with EBRT-based local therapy (London) and AMORE-based local therapy (Amsterdam). RESULTS: Seventy-three survivors were included (median follow-up 11 years). We found clinically relevant hearing loss at speech frequencies in 19% of survivors. Multivariable analysis showed that survivors treated with EBRT-based treatment and those with parameningeal tumours had significantly more hearing impairment, compared to survivors treated with AMORE-based treatment and non-parameningeal tumours. CONCLUSIONS: One in five survivors of HNRMS developed clinically relevant hearing loss. AMORE-based treatment resulted in less hearing loss compared to EBRT-based treatment. As hearing loss was highly prevalent and also occurred in survivors with orbital primaries, we recommend systematic audiological follow-up in all HNRMS survivors.

Hypoxia in head and neck cancer: how much, how important?

BACKGROUND: Hypoxia develops in tumors because of a less ordered, often chaotic, and leaky vascular supply compared with that in normal tissues. In preclinical models, hypoxia has been shown to be associated with treatment resistance and increased malignant potential. In the clinic, several reports show the presence and extent of tumor hypoxia as a negative prognostic indicator. This article reviews the biology and importance of hypoxia in head and neck cancer. METHODS: A review of literature was carried out and combined with our own experience on hypoxia measurements using exogenous and endogenous markers. RESULTS: Hypoxia can increase resistance to radiation and cytotoxic drugs and lead to malignant progression, affecting all treatment modalities, including surgery. Hypoxia measurements using electrodes, exogenous bioreductive markers, or endogenous markers show the presence of hypoxia in most head and neck cancers, and correlations with outcome, although limited, consistently indicate hypoxia as an important negative factor. Each hypoxia measurement method has disadvantages, and no "gold standard" yet exists. Distinctions among chronic, acute, and intermediate hypoxia need to be made, because their biology and relevance to treatment resistance differ. Reliable methods for measuring these different forms in the clinic are still lacking. Several methods to overcome hypoxia have been tested clinically, with radiosensitizers (nimorazole), hypoxic cytotoxins (tirapazamine), and carbogen showing some success. New treatments such as hypoxia-mediated gene therapy await proper clinical testing. CONCLUSIONS: The hypoxia problem in head and neck cancer needs to be addressed if improvements in current treatments are to be made. Increased knowledge of the molecular biology of intermediate, severe, and intermittent hypoxia is needed to assess their relevance and indicate strategies for overcoming their negative influence.

Scintigraphic assessment of salivary function and excretion response in radiation-induced injury of the major salivary glands.

BACKGROUND: Both loss of the secretory function and impairment of the excretion may play a role in radiation-induced injury of the major salivary glands after radiotherapy for head and neck malignancies. Therefore, quantitative 99mTc-pertechnetate (99mTc) salivary scintigraphy to assess trapping, secretion, and excretion, was used to analyze irradiation-induced changes in relation to the radiation dose and the time interval after radiotherapy. PATIENTS AND METHODS: Salivary scintigraphy was performed on 25 patients who had been irradiated to the neck and head for various malignancies with irradiation of the major salivary glands and in 6 nonirradiated patients. Excretion was induced by stimulation with carbachol (Carbacholum, Pharmachemie BV, Haarlem, The Netherlands). As a parameter for salivary glandular trapping and secretion, the cumulative 99mTc-pertechnetate glandular uptake in the first 12 minutes was used. Scintigraphic data were analyzed for each patient and for each individual gland at three radiation dose levels (range, 5-70 Gy), and at short (range, 2-7 months) and long (range, 10-50 months) intervals after radiotherapy. RESULTS: The excretion response to the stimulant carbachol was totally or partially disturbed in 84% of the irradiated patients. For individual glands, excretion was maintained in all glands irradiated with 25 Gy or less, in nearly half of the glands at doses of 25-45 Gy, and was almost invariably impaired at doses higher than 45 Gy, regardless of the time interval after radiotherapy. Although cumulative 99mTc glandular uptake tended to decrease at higher radiation dose levels (z = -3.059, P < 0.0022), at 45 Gy or more, cumulative 99mTc uptake was considerably higher in glands examined at a short postirradiation interval compared with glands examined after a long time interval (P = 0.0001). This tendency, seen for both parotid and submandibular glands, was not observed at doses lower than 45 Gy. CONCLUSION: These data suggest that in the first period after high dose irradiation, xerostomia is based predominantly on the failure of the gland to excrete saliva, whereas in the later period, a decreased trapping ability together with loss of secretory function play an additional role. Salivary scintigraphy using 99mTc-pertechnetate is a suitable method to assess radiation-induced salivary gland injury. The test is able to detect salivary glandular dysfunction in an early phase and may be useful to predict which patients will respond symptomatically to salivary stimulants.

Hyperbaric oxygen treatment of osteoradionecrosis of the mandible with repeated pathologic fracture. Report of a case.

Treatment of patients with osteoradionecrosis of the mandible with a pathologic fracture consists in almost all cases of a continuity resection of the mandible. This leads to functional and esthetic problems that can only be solved by often extensive surgery. In this case report we present a 38-year-old woman who developed osteoradionecrosis of the mandible with a pathologic fracture 1 1/2 years after combined surgical and radiation therapy of an adenocarcinoma of the right parotid gland. The patient had a subcondylar pathologic fracture together with osteolysis in the right mandibular body, normally an indication for partial resection of the mandible. Because of the absence of denuded bone, fistulation, and the poor quality of the surrounding soft tissues, a more conservative approach was chosen. Treatment consisted of hyperbaric oxygen and dental extractions with alveolectomy with the patient under local anesthesia. During follow-up, a second pathologic fracture occurred in the region of the right first and second molar. No additional treatment was given. Six and one-half years after the initial treatment and 5 1/2 years after the last fracture, the patient is free of complaints, the fractures have healed and both esthetic and functional results are good.