It has been suggested that both the lack of alkaline phosphatases in the endothelium and the acidic conditions in the microenvironment prevent the activation of amifostine in the tumor, assuring a selective protection of normal tissues. Conversely, there is clinical evidence to support the use of amifostine. No difference after 2 years was observed in locoregional control or survival.
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To date, however, no trial has been powered sufficiently to detect small differences in survival. Another important issue is the toxicity of amifostine. Nausea and emesis are common side effects, but they generally are mild and can be controlled effectively with standard antiemetic medication. There is a risk of transient hypotension when amifostine is administered intravenously administered, but not when it is administered subcutaneously.
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The extent of the damage caused by RT depends both on the volume of tissue that is irradiated and on the dose of radiation that is delivered. A high dose is administered to a small part of the parotid and is positioned close to the tumor, while the rest of the gland receives a low dose or no dose at all. Patients who received that treatment have gained partial sparing of the salivary output from the parotid gland.
There also is evidence that reduction of xerostomia results in improved QoL. Lin and colleagues reported that both xerostomia and QoL scores improved significantly over time during the first year after IMRT. Data regarding the doses and irradiated volumes that permit preservation of the salivary flow after RT are emerging slowly. Usually, 3D dose distributions in parotid glands are compared with residual saliva production. It became clear that there is an exponential relation between saliva flow reduction and mean parotid dose for each gland, suggesting that it is essential to respect a certain threshold for mean parotid dose to preserve gland function.
However, the use of a mean dose as a threshold for the control of normal tissue tolerance is helpful only when an organ consists of independent functional units that are organized in parallel.
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In such an organ, irradiation of a small part results in less loss of function than in an organ that has a serial anatomic organization. In the latter case, damage to 1 substructure disables the entire organ eg, the spinal cord.
For the healthy parotid gland, it is generally assumed that a homogenous distribution of saliva production takes place over the entire volume. It was suggested that spatial information should be included in the comparison of different plans and that the mean dose concept has limited use for the prediction of late radiation damage. Similarly, it remains to be determined whether regional differences in gland radiosensitivity will prove to be equally important in humans as they appear to be in rats.
Before RT, all slices contributed equally; 7 months after an average dose of There was high interpatient variability in D50, and low doses 10—15 Gy also could induce serious loss of function, casting doubt on the utility of a general, standard, mean gland dose threshold. Probably, the mean parotid dose should be kept as low as possible. Colleagues Jha et al and Seikaly et al were the first to propose surgical transfer of 1 submandibular gland to the submental space, outside the proposed radiation field. Obviously, it is not always straightforward to predict which patients will need postoperative RT, and some patients may refuse further treatment.
Then again, in some patients, the submental space cannot be shielded because of its proximity to the disease.
These are important limitations, and, in the largest study to date, 17 of 60 patients However, all of the glands survived transfer and functioned well; the surgical technique had no complications and added an average of 45 minutes to the surgical protocol. A variety of artificial saliva substitutes have been developed to supplement the reduced production of saliva, although very few have been evaluated appropriately. Obviously, because saliva is a complex substance with many functions, it is difficult to replace; therefore, saliva substitutes rarely are effective, and some patients find regular sips of water equally useful.
Antimicrobial mouthwashes, such as chlorhexidine and hexitidine, play a central role in reducing the bacterial load and inhibiting cariogenesis. Studies have shown that, when there still is some residual salivary function, saliva stimulants produce greater relief than saliva substitutes. Pilocarpine obviously is contraindicated in patients who have asthma, acute iritis, or glaucoma and should be used with extreme caution in patients who have chronic obstructive pulmonary disease and cardiovascular disease.
Some work has been done with topical ie, oral application of pilocarpine, which seemed to produce results similar to those achieved with systemic delivery methods but with improved patient tolerance. Some promising preclinical results have been obtained by gene transfer, although clinical studies have yet to be initiated. Apparently, mobilized bone marrow cells may home to salivary glands and induce repair by secreting stimulatory factors, causing improved salivary gland function.
Therefore, further research, particularly regarding treatment, is urgently warranted. Volume , Issue The full text of this article hosted at iucr. Get A Copy. Hardcover , pages. More Details Original Title. Other Editions 3. Friend Reviews. To see what your friends thought of this book, please sign up. To ask other readers questions about Cured I - Lent , please sign up.
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