Tools for optimal tissue sparing in concomitant chemoradiation of advanced head and neck cancer: Subcutaneous amifostine and computed tomography-based target delineation

Abstract

Organ preservation in patients with head and neck cancer can be achieved using concomitant chemoradiation protocols. Critical tissues can be spared using highly conformal radiation therapy techniques and/or radiation protectors. With three-dimensional conformal radiation therapy (3DCRT) tight target definitions of the primary tumor and neck nodal levels are mandatory. In 2000, a clinical trial for advanced-stage head and neck squamous cell carcinoma was initiated in Rotterdam, The Netherlands. Patients are treated with paclitaxel administered concomitantly with 3DCRT and randomized to receive subcutaneous (SC) amifostine or no amifostine. Those in the radioprotectant arm received amifostine 500 mg SC before each radiation therapy (RT) fraction. This article presents early findings on toxicity. Acute toxicity is evaluated according to Radiation Therapy Oncology Group criteria. Xerostomia was scored subjectively and by whole saliva measurements. Neck nodal levels were delineated in accordance with previously published computed tomography (CT)-based guidelines developed in Rotterdam. Forty-one patients are the subject of this report. In patients treated with amifostine, mucositis and dysphagia took longer to resolve than with conventional RT schedules. No difference in objective and subjective evaluation of xerostomia was seen between treatment arms. So far in this ongoing study, no advantage of SC amifostine has been detected. This might be because of the toxicity of the concomitant treatment itself, the dose of amifostine, the route of administration, or the insufficient sparing of critical structures by 3DCRT. These early findings and the ongoing development of better tissue-sparing techniques with more accurate CT-based target delineation protocols and intensity-modulated radiation therapy (IMRT) are discussed.

Differentiating purging and nonpurging bulimia nervosa and binge eating disorder

“…Single‐institution studies recently showed that this technique is comparable to other radiotherapy modalities in NPC, with marked incidence and severity decreases of acute and long‐term toxicities, particularly xerostomia 48. Imaging‐based radiotherapy planning and amifostine are important to xerostomia prevention in head and neck radiotherapy,49 and they should be considered when managing NPC in children 50…”

Comparative Study of Mucositis in Patients of Head and Neck Cancer Treated by External Radiotherapy with or Without Amifostine.

“…Less evidence has been published to support the cytoprotective effects of subcutaneous amifostine during combined modality treatment with radiochemotherapy. A preliminary analysis of an ongoing Phase II trial reported that when amifostine 500 mg was administered subcutaneously before radiotherapy in patients who also received weekly paclitaxel, higher mean doses of radiotherapy were required to elicit Grade 3/4 mucositis in the amifostine group than in the control group 25 .…”

Amifostine is a Nephro-Protectant in Patients Receiving Treatment with Cisplatin- Myth, Mystery or Matter-of-Fact?

“…Trials that did compare amifostine with placebo or other therapies found it difficult to measure the subjective nature of mucositis and its end points. 4,5,[16][17][18][19][20] For this reason, it was concluded by the ASCO panel that blinded, placebo-control trials would be necessary for proper assessment of the efficacy of amifostine in reducing radiation induced mucositis. 4…”