Mucosal and Esophageal Toxicites of Radiation Therapy

Oral and esophageal mucosal injuries are inevitable postradiation changes, encountered with daily radiation therapy. Mucositis has remained a morbid side effect of radiation therapy since its first clinical use as an agent effective against cancer. Mucosal injury is generally the first change that is observed as the radiation beam enters human tissues. Alimentary mucositis (AM) is the recommended term to describe cancer therapy–associated mucosal injury of the alimentary tract (mouth to anus). This unifying term acknowledges the similarities along the entire gastrointestinal (GI) tract while allowing for regional differences that require discussion of oral and GI mucositis separately at times, based on pathophysiological responses, clinical characteristics, and management options. In almost all patients, AM is associated with considerable pain and thus can significantly impair quality of life and, in neutropenic patients, mucositis represents a clinically significant risk factor for sepsis. Furthermore, in some patients, AM becomes a dose‐limiting toxicity, slowing or preventing continuation of selected cancer therapies, including accelerated fractionation and hyperfractionation in radiotherapy and interventions that combine chemotherapy and radiotherapy.

The major determinants of mucosal injury are total dose of radiation, daily radiation dose, and concurrent chemotherapy, in addition to an individual’s inherent sensitivity to radiation. The incidence of AM is governed by these previously mentioned factors. Lower grade reactions are extremely common in nearly all patients receiving radiation with an incidence of almost 80% to 100%, with almost a third of these patients experiencing severe mucosal injury. ^,

Clinically, mucositis usually begins with mucosal congestion and erythema, which progresses through white, elevated, desquamative patches that are painful to contact pressure. Following this, the patches may coalesce and, eventually, there is development of painful, contiguous, pseudomembranous lesions ( Fig. 26.1 ) with associated dysphagia and decreased oral intake. The nonkeratinized mucosa in the oral cavity and GI tract is at the highest risk of being affected by the radiation-related reaction. Mucosal lesions usually heal within 2 to 3 weeks. The clinical course of AM may sometimes be complicated by local infection, particularly in immunosuppressed patients. Fungal infections such as candidiasis, and viral infections, such as herpes simplex virus (HSV) can sometimes be superimposed on oral mucositis, complicating its course by delaying healing.

The sequence of events that occurs during radiation therapy for head and neck cancer reflects the different kinetics of the cell populations involved :

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  Week 1: The first week is characterized by slight focal hyperemia and edema caused by dilatation of capillaries in sensitive patients. Sensitivity may be associated with alcohol or tobacco use, chemotherapy, infection (oral candidiasis, HSV), or immunosuppression (such as HIV).

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  Week 2: The second week is characterized by increasing pain and loss of desire to eat. Sense of taste is altered; bitter and acid flavors are most changed, with less change with salty and sweet tastes. Erythema and edema increase, and early desquamative mucositis occurs. Basal cell division has been affected; this layer is being denuded, and vasculoconnective tissue damage becomes apparent. Mucositis is patchy during this time.

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  Week 3: The third week is characterized by mucositis and swelling with depletion of gland secretions leading to difficulty in swallowing. Mucositis plaques are confluent. Impairment of taste acuity occurs during the third week of a multifraction radiotherapy regime.

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  Week 4: The fourth week is characterized by further progression of signs previously seen signs. Confluent mucositis sloughs, resulting in denuded lamina propria. Mucosa becomes covered by fibrin and polymorphonuclear leukocytes.

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  Week 5: Maximal radiation damage becomes apparent by the fifth week. There is extreme sensitivity to touch, temperature, and grainy food. Recovery of epithelial layer may begin during therapy.

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  Posttherapy : After therapy concludes basal cells migrate into the area and proliferate. In 2 to 4 weeks, complete resolution is observed.

Defining the epidemiology of mucositis has been confounded historically by a number of variables, including underreporting, differences in terminology used to describe it, differences in assessment techniques and scales, and the correlation between mucositis and other clinically important sequelae. Multiple scoring systems for AM have been devised over the years with the goal of providing a uniform system which is objective, validated, and reproducible across all clinical situations and applications. The two most commonly used scoring systems in the field of radiation oncology include the ones formulated by the National Cancer Institute (Common Terminology Criteria for Adverse Events - CTCAE), and the Radiation Therapy Oncology Group (RTOG) scales for the purpose of uniform reporting throughout the globe. ^, Regardless of the scale used, increasing evidence confirms the importance of training and standardization for improving the accuracy and consistency of mucositis assessment.

The RTOG and NCI–CTCAE scoring systems for mucositis and esophagitis, are given in Tables 26.1 and 26.2 .