The first changes that are induced by radiation are increased vascular permeability and exudation of proteinaceous material in the alveolar space [4]. Capillary endothelial cells are very sensitive to ionizing radiation, and their damages are manifested by detachment of cells from their basement membrane, which is followed by blood flow turbulence and thrombosis formation. Following endothelial cell injury, capillary permeation increases, fibrin-rich exudate leaks into the alveoli, and a hyaline membrane is formed, which impairs gas exchange. Ionizing radiation can also damage alveolar cells, which are manifested by depletion of type I pneumocytes and hyperplasia of type II pneumocytes, in the context of the alveolar epithelium regeneration process [5]. On the other hand, type II pneumocytes are also known to be damaged by radiation therapy, resulting in release of surfactant into the alveolar space and detachment of the pneumocytes from their basement membrane [6]. Later, the alveolar exudate clears, fibroblasts migrate into the alveolar walls, and the alveolar septa are thickened.

Although pathologic changes in lung tissue occur in the initial 24–48 h after radiation, those changes are undetectable both clinically and radiologically. Radiation pneumonitis occurs typically within 6 months after a course of radiation with a peak onset at 1–3 months but may be seen as early as 1 week, especially in patients receiving high total dose [7]. In some cases, no symptoms are present, and the diagnosis is made by imaging alone (Fig. 10.1).

Dyspnea is the most common symptom, occurring in as many as 90% of cases. Dyspnea is frequently accompanied by a dry cough, which occurs in about 50–60% of cases. A low-grade fever is occasionally reported, which can be more pronounced in severe cases. Some patients complain of chest pain with breathing, malaise, and weight loss. Sensation of chest fullness usually develops 1–3 months after completion of radiation therapy.

Radiation pneumonitis is a diagnosis of exclusion. Physical findings are usually not prominent, but occasionally moist crackles, a pleural friction rub, or evidence of consolidation may be present. There is no specific lab test to predict the development of RP. Some patients might have a mild polymorphonuclear leukocytosis, elevated ESR, serum LDH, and CRP, but these findings are nonspecific.

Chest X-ray and computed tomography are the most commonly used modalities for assessing RP. The most common finding on CXR in early phases is perivascular haziness, which often progresses to patchy alveolar-filling densities [20]. Pleural effusions or atelectases are also sometimes seen. These changes occur shortly after completion of radiation therapy, peak at 6 months, and become stable by 12 months. One of the most characteristic features of radiation pneumonitis and fibrosis is that these radiologic changes are confined to the outlines of the field of radiation (Fig. 10.1). However, the use of oblique beam angles and the development of newer irradiation techniques such as three-dimensional conformal radiation therapy and intensity-modulated radiation therapy can result in an unusual distribution of these findings [21].

Computed tomography (CT) is more sensitive than chest radiograph in detecting subtle lung injury following radiation treatment but is not required to make the diagnosis of RP. The most common findings on CT are ground-glass opacities in the acute phase and traction bronchiectasis, volume loss, and consolidation in the late phase [22].

Pulmonary function test (PFT) in patients with radiation pneumonitis usually reveals a reduction in lung volumes and diffusing capacity of the lungs for carbon monoxide (DLCO), but these changes are nonspecific [23].

Bronchoalveolar lavage and transbronchial biopsy are not useful in the diagnosis of radiation pneumonitis but can be used to exclude other causes of pulmonary infiltrates.

Common Toxicity Criteria for Adverse Effect (CTCAE) (Table 10.1) [24] and Radiation Therapy Oncology Group (RTOG) (Table 10.2) [25] have defined five grades for radiation-induced pneumonitis with some differences.