A survey of prevention and treatment regimens for oral sequelae resulting from head and neck radiotherapy used in Dutch radiotherapy institutes.

Radiation treatment plays an important role in the management of head and neck cancer. Unfortunately several radiation-induced side effects may occur including mucositis, hyposalivation, radiation caries, trismus and osteoradionecrosis. It is generally accepted that most side effects can be prevented or reduced in severity. The purpose of this investigation was to make a survey of the prevention and treatment regimens for oral sequelae resulting from head and neck radiotherapy applied in all radiotherapy institutes in the Netherlands, and to evaluate the differences in these regimens. In all Dutch centers (n = 20) in which irradiation of head and neck cancer patients is performed, members of the staff responsible for prevention and treatment of oral side effects were interviewed. Questions referred to composition of the dental team, screening and care pre-irradiation, care during irradiation, and care post-irradiation. There appeared to be a great diversity in the preventive approach of the head and neck cancer patient in Dutch radiotherapy institutes. The most comprehensive counseling was performed by those centers in which a dental team was active, particularly when an oral hygienist was a member of such a team. The diversity is among others based on lack of well-defined guidelines in many centers, the spread of a relatively small patient group over a rather large number of centers, absence of a dental team in some centers, absence of an oral hygienist in some dental teams, and the observation that a rather large number of patients were not referred, or not timely referred to the dental team. There seems to be a need for the development of a general protocol for the prevention of oral complications applicable in all centers.     

Intensity-modulated radiation therapy in the treatment of head and neck cancer

Intensity-modulated radiation therapy (IMRT) is a new technical improvement of radiotherapy, in which computer-controlled treatment machines produce multiple beams of radiotherapy whose intensity is optimized to deliver a high dose of radiation to specified volumes, while reducing the dose to adjacent non-target organs. The potential benefits include the ability to deliver higher doses to the target with an improved safety than has previously been possible, and to reduce side effects and complications. Using IMRT to treat some head and neck cancers is especially attractive due to the close vicinity of the targets and many critical, dose-limiting and non-involved structures, and because of the lack of breathing-related motion. The main clinical uncertainties in the use of IMRT for head and neck cancer relate to uncertainties in the extent of radiation to the target areas. In addition, large volumes of adjacent, non-target tissue receive moderate to low radiation doses, raising concerns of increased risk of radiation-related carcinogenesis in young patients. Initial promising clinical data have emerged from IMRT treatment of several head and neck tumor sites.     

Organ-sparing radiation therapy for head and neck cancer

To improve locoregional tumor control and survival in patients with locally advanced head and neck cancer (HNC), therapy is intensified using altered fractionation radiation therapy or concomitant chemotherapy. However, intensification of therapy has been associated with increased acute and late toxic effects. The application of advanced radiation techniques, such as 3D conformal radiation therapy and intensity-modulated radiation therapy, is expected to improve the therapeutic index of radiation therapy for HNC by limiting the dose to critical organs and possibly increasing locoregional tumor control. To date, Review articles have covered the prevention and treatment of radiation-induced xerostomia and dysphagia, but few articles have discussed the prevention of hearing loss, brain necrosis, cranial nerve palsy and osteoradionecrosis of the mandible, which are all potential complications of radiation therapy for HNC. This Review describes the efforts to prevent therapy-related complications by presenting the state of the art evidence regarding advanced radiation therapy technology as an organ-sparing approach.     

Intensity-modulated radiation therapy for head and neck carcinoma

Intensity-modulated radiation therapy (IMRT) for head and neck tumors refers to a new approach that aims at increasing the radiation dose gradient between the target tissues and the surrounding normal tissues at risk, thus offering the prospect of increasing the locoregional control probability while decreasing the complication rate. As a prerequisite, IMRT requires a proper selection and delineation of target volumes. For the latter, recent data indicate the potential of functional imaging to complement anatomic imaging modalities. Nonrandomized clinical series in paranasal sinuses and pharyngolaryngeal carcinoma have shown that IMRT was able to achieve a very high rate of locoregional control with less morbidity, such as dry-eye syndrome, xerostomia, and swallowing dysfunction. The promising results of IMRT are likely to be achieved when many treatment conditions are met, for example, optimal selection and delineation of the target volumes and organs at risk, appropriate physical quality control of the irradiation, and accurate patient setup with the use of onboard imaging. Because of the complexity of the various tasks, it is thus likely that these conditions will only be met in institutions having large patient throughput and experience with IMRT. Therefore, patient referral to those institutions is recommended.     

Proton radiation therapy for head and neck cancer

Due to the close spatial relationship of head and neck and skull base tumors to numerous normal anatomical structures, conventional photon radiation therapy can be associated with significant acute and long-term treatment-related toxicities. Superior dose localization properties of proton radiation therapy allow smaller volumes of normal tissues to be irradiated than is feasible with any photon technique. Intensity-modulated proton therapy (IMPT) is a powerful delivery technique which results in improved dose distribution as compared to that of intensity-modulated radiation therapy (IMRT). Initial clinical experience with proton radiation therapy in treatment of head and neck and skull base tumors is promising. Prospective multi-institutional trials are underway to define the role of proton radiation therapy, particularly IMPT, in the treatment of head and neck and skull base tumors.     

Intensity-modulated radiation therapy for head and neck cancer

Opinion statement Intensity-modulated radiation therapy (IMRT) involves the delivery of optimized nonuniform beam intensities to the patient. In the head and neck region, there are many critical structures in close proximity to the target, with little influence from internal organ motion. Because IMRT produces tightly conformal doses and steep-dose gradients next to normal tissues, it provides the potential for organ sparing and improved tumor control. The dosimetric superiority of head and neck IMRT over conventional techniques has been demonstrated. The initial results of clinical IMRT studies showed reduction in xerostomia with no compromise in locoregional control if caution and appropriate knowledge are exercised in target determination and delineation.     

Advances in radiation therapy for head and neck cancer

Radiation therapy either as a single modality or as part of multimodality plans remains an integral part of curative treatment for cancers of the head and neck. This paper traces the modernization of radiation therapy regarding tumors of the head and neck using examples of sites of malignancy where radiation therapy is the sole modality or where radiation therapy can be combined with surgery and chemotherapy for optimal results. As local-regional control rates have improved with the use of combined radiation therapy and surgery and aggressive hyperfractionation schemes for advanced primary tumors, distant metastases and second primary neoplasms are now accounting for a larger proportion of treatment failures. Until such time as more effective systemic therapy and cancer control mechanisms are developed to address these problems, radiation therapy will continue to play a major role in the overall management of patients with cancers of the head and neck.     

Intraoperative radiation therapy for recurrent head and neck cancer

Forty-seven patients with recurrent head and neck cancer in a previously irradiated field were treated with surgical resection and intraoperative radiation therapy (IORT). Recurrent disease occurred at a median of 18 months from primary treatment, and was at the primary tumor site in 31 and metastatic to regional lymph nodes in 16. Recurrences were squamous cell carcinomas in 42 and adenoid cystic in five. Surgical resection left microscopic residual disease in 41 and gross residual in six. All patients received IORT with a median of 20 Gy. Two-year actuarial survival is 54.9%, and 15 patients are alive and disease free with a median survival of 29 months. Two-year actuarial local control is 61.5%. A trend toward increased survival (P less than 0.09) and local recurrence control (P = 0.05) was noticed when treating microscopic residual disease as opposed to gross residual disease. Perioperative mortality was seen in 8.5% and there was no increase in morbidity secondary to IORT. The authors believe that surgical resection and IORT is an effective treatment modality for head and neck cancers recurrent in previously irradiated fields and is adaptable to tertiary care hospitals.     

Recent advances in radiation therapy for head and neck cancer

The most efficacious treatment method for head and neck cancer is not yet defined. However, there have been some improvements made in the radiotherapy of head and neck cancer that are encouraging. Both hyperfractionated radiation therapy and accelerated radiation therapy have improved the local control rates in numerous primary sites, and the results of more rigorous prospective randomized studies, if positive, will justify more routine use of these techniques. The use of neutrons for unresectable salivary gland tumors has clearly been established as the treatment of choice. Local control as well as cosmetic outcome is excellent, with the only disadvantage being that neutron therapy is not as widely used as photon radiation. The same is true for charged particle therapy, the greatest utility of which appears to be for relatively small tumors adjacent to critical structures such as the brain and spinal cord. We also believe that intraoperative radiation therapy shows great promise and may soon be more widely available for the treatment of head and neck cancers. However, we believe that the most exciting advancement in the treatment of head and neck cancer is the use of concomitant radiation therapy and chemotherapy, a topic that is discussed in detail in another article in this issue.     

Fractionated stereotactic radiation therapy for extracranial head and neck tumors

BACKGROUND: This study is to report the clinical experiences of fractionated stereotactic radiation therapy (FSRT) for extracranial head and neck tumors. METHODS AND MATERIALS: Between the period of July 1995 and November 1998, 48 patients with extracranial head and neck tumors were given FSRT as a boost and sole modality. Individualized treatment planning was performed using XKnife-3 system with relocatable Gill-Thomas-Cosman frame. In 24 patients, FSRT was applied as a boost technique following the 2-dimensional conventional external radiation therapy (ERT); in 24 patients FSRT was the sole radiotherapy modality. The primary diseases in the boost group consisted of nasopharynx cancer (19), lacrimal gland adenoid cystic carcinoma (3), orbital lymphoma (1), and skull-base recurrence of maxillary sinus adenoid cystic carcinoma (1). The primary diseases in the sole modality group consisted of recurrent nasopharynx cancer (12), orbital pseudotumor (4), skull-base recurrence of maxillary sinus, submandibular gland, and hypopharynx cancers (3), orbital rhabdomyosarcoma (2), orbital lymphoma (1), orbital metastasis of neuroblastoma (1), and nasal cavity melanoma (1). The fractionation schedule was to give 5 treatments per one week and the fractional doses were 2.0-3 Gy depending on the treatment aim and the FSRT volume. The FSRT doses varied depending on the nature of the primary diseases. RESULTS: The local tumor response in nasopharynx cancer patients was excellent compared to retrospective data without occurrence of unexpectedly severe complication. FSRT to other regions was well tolerated by the patients and resulted in good to excellent local tumor responses with no unacceptable side effects as expected by the authors. CONCLUSION: Based on the current observations, FSRT is a very effective and safe modality in the treatment of extracranial head and neck tumors.     

Vestibular apparatus disorders after external radiation therapy for head and neck cancers.

External irradiation of different head and neck cancers may involve parts of the ear. The vestibular function of 25 patients in which the inner ear was comprised in the irradiated volume was investigated by electronystagmography (ENG). Doses administered to the vestibular system ranged between 2800 and 5120 cGy. Five patients suffered subjective vertigo or dizziness. Eleven patients (three out of five with vertigo) showed vestibular abnormalities to ENG (44% of the total). Altered responses to specific tests were as follow: six patients to the bithermal caloric stimulation, two to the pendular-sinusoidal test and the other three to both of them. Patients were evaluated 3 and 6 months after the ending of the radiation therapy course. At the first evaluation, abnormalities to caloric test were noted in three patients (12%) and to sinusoidal rotatory test in one patient (4%). At the second evaluation, rates of abnormal response increased to 36% and 20%, respectively. Vestibular disorders seemed to be scantly related to the total radiation dose. Data of literature are discussed in order to identify possible implications on treatment planning.     

Clinical and histopathological evaluation of sucralfate in prevention of oral mucositis induced by radiation therapy in patients with head and neck malignancies

Forty-four patients with head and neck malignancies were included in a prospective, randomized, double-blind, placebo-controlled study for evaluation of sucralfate in prevention of oral mucositis induced by radiation therapy. Patients were randomized to receive oral suspensions of either sucralfate (n = 23) or placebo (n = 21) in six daily doses of 1 g. The primary tumors were treated with portals covering at least one-third of the oral mucosa to a minimum dose of 60 Gy. Drug therapy was not associated with significant adverse effects and compliance was satisfactory. Daily inspection of the oral mucosa and questionnaires for oral mucositis-related items demonstrated reduction in oral mucositis scores and oral pain scores and biopsies obtained from the buccal mucosa demonstrated reduction in evidence of altered vascular calibration, altered vascular permeability and leukocyte emigration with sucralfate. Clinical and histopathological demonstration of reduction in oral mucositis with sucralfate suggests that sucralfate might be recommended in the prevention of oral mucositis induced by radiation therapy in patients with head and neck malignancies.     

Advances in radiation therapy of head and neck cancer

Head and neck cancer is the fifth most common cancer in the USA. Although there have been major improvements in surgical and radiation techniques, the overall survival has not changed significantly in the last decade. The major changes occurring in recent years have been in the ability to preserve organs and to improve quality of life. The advances in radiation therapy include 3D conformal radiotherapy, intensity-modulated radiotherapy and, more recently, imaging-guided radiotherapy. In advanced head and neck cancer the addition of chemotherapy to radiation has concomitantly improved survival and facilitated higher rates of organ preservation. Clinical trials are needed to develop better strategies customized to subgroups defined by individual biological risk and imaging findings.     

Advances in radiation therapy of head and neck cancer

Head and neck cancer is the fifth most common cancer in the USA. Although there have been major improvements in surgical and radiation techniques, the overall survival has not changed significantly in the last decade. The major changes occurring in recent years have been in the ability to preserve organs and to improve quality of life. The advances in radiation therapy include 3D conformal radiotherapy, intensity-modulated radiotherapy and, more recently, imaging-guided radiotherapy. In advanced head and neck cancer the addition of chemotherapy to radiation has concomitantly improved survival and facilitated higher rates of organ preservation. Clinical trials are needed to develop better strategies customized to subgroups defined by individual biological risk and imaging findings.