Chest and thorax: Symptoms and toxicities

Presentation/diagnosis

Radiation pneumonitis is considered to occur in two phases. Acute radiation pneumonitis occurs 4 to 12 weeks following the completion of radiation therapy. Subacute radiation pneumonitis occurs secondary to fibrosis mediated by tissue growth factor-beta (TGF-beta) and develops after 3 to 6 months. Both presentations consist of a nonproductive cough (a result of bronchial mucosal injury in the acute setting and fibrosis in the subacute setting), dyspnea on exertion, pleuritic chest pain, and fever (more common in the acute setting and severe cases). Physical exam findings may include pleural rub or crackles on pulmonary auscultation, dullness to percussion secondary to pleural effusion, tachypnea, and/or pulmonary hypertension. Of note, in the palliative setting, the differential diagnosis for a pleural effusion often includes malignant effusion. To help differentiate radiation-induced pleural effusion and malignant effusion, one can expect the radiation-induced effusion to remain stable or decrease with time.

Diagnosis of radiation pneumonitis requires a combination of clinical and radiographic findings. These include timing and characteristic qualities of symptoms, radiation dose, correlative radiographic findings, and exclusion of other diagnoses. Conditions that are part of the differential diagnosis due to similar presentations include viral or bacterial pneumonia; drug-induced pneumonitis; progression of malignant disease; thromboembolic disease; tracheoesophageal fistula; or exacerbation of heart failure, chronic obstructive pulmonary disease (COPD), or interstitial disease. The use of radiographic imaging can help narrow the differential diagnosis. Computer tomography (CT) chest with or without contrast may demonstrate perivascular haziness or ground-glass attenuation within the acute setting, and coarse reticular, dense opacities, and/or volume loss in the subacute and chronic setting ( Fig. 31.1 A). These characteristics do not respect anatomical boundaries. Definitive diagnosis is based on comparing dosimetric information of irradiation plans with diagnostic CT images during the symptomatic period (see Fig. 31.1 B). In the palliative setting, the “straight line effect” can appear on chest CT corresponding with a sharp drop-off of radiation dose that is less commonly seen with increased beam distribution.

Nonspecific changes include reductions in total lung capacity, forced vital capacity, residual lung volume, diffusing capacity for carbon monoxide, and lung compliance as measured on pulmonary function testing. Bronchoscopy and bronchoal veolar lavage, more likely to be performed to examine infection or disease progression, would typically demonstrate increased leukocyte count (lymphocyte predominant), increase in total cell count and intercellular adhesion molecule 1 (ICAM-1). Lymphadenopathy does not correspond with radiation pneumonitis, and, if new, may more likely reflect disease progression or infection.

CTCAE v5.0 Criteria grading of pneumonitis is outlined in Table 31.1 .

Prevalence

With standard fractionation of radiation therapy, radiation pneumonitis requiring oxygen or more occurs in roughly 3% to 8% of patients. Radiation pneumonitis requiring corticosteroids may occur in up 10% to 20% of patients, with the risk increased with adjuvant use of immunotherapy. Risk of radiation pneumonitis depends on the particular regimen, intensity modulated radiation therapy (IMRT) versus three-dimensional conformal radiation therapy (3DCRT), mean lung dose, V20, the volume of lung treated, and concurrent systemic therapy use. In the palliative setting, the rate of pneumonitis is considered to be 1% to 2%.

Underlying interstitial lung disease is a known risk factor for radiation pneumonitis. The risk of radiation pneumonitis and its correlation with underlying COPD is incompletely understood. Some retrospective studies demonstrate a correlation between COPD and radiation pneumonitis, while some show those with COPD prior to initiation of radiation develop less severe disease. These analyses are understandably limited by the increased likelihood of resulting symptomatology and treatment requirement in patients with pre-existing pulmonary deficits.

Management

Standard of care for symptomatic radiation pneumonitis includes supportive care and glucocorticoid therapy. Supportive care includes treatment of symptoms: supplemental oxygen, underlying comorbidities, and antitussive medications. In patients with minimal symptoms and existing relevant comorbidities, inhaled glucocorticoids have been suggested, as the use of oral glucocorticoids in some patients may lead to clinically relevant hyperglycemia, weight gain, insomnia, osteoporosis, myopathy, and cognitive disorders ( Table 31.2 ).

In patients with moderate to severe symptoms, the patient should be treated with oral glucocorticoids (see Table 31.2 ). Moderate to severe symptoms include apparent dyspnea, changes from one’s baseline, and impaired respiratory function. During the steroid taper, if the patient has a return of pulmonary symptoms, consider returning to full dosing for 2 weeks, followed by the taper. Proton pump inhibitors or H2-receptor blockers should be prescribed for gastrointestinal prophylaxis. Trimethoprim-sulfamethoxazole may be prescribed for pneumocystis pneumonia prophylaxis.

Comments

The dose of radiation the lung receives directly correlates with the risk of radiation pneumonitis. To optimize the patient’s outcome, mean lung dose (MLD) and V20, defined as the total lung volume minus the planning target volume (normal lung) that receives more than 20 Gy, should be optimized. Accepted guidelines support maintaining the V20 ≤30% to 35% and MLD ≤20 Gy; this maintains a risk of pneumonitis ≤20%.

As we consider palliative treatment to the thorax, various radiation techniques include IMRT, stereotactic body radiation therapy (SBRT), and 3-dimensional conformal radiation therapy (3DCRT). With more specialized techniques of radiation therapy, we expect lower levels of radiation dose to the lung. For example, in palliative radiation to the thoracic spine, for the patient with underlying pulmonary disease or malignant pleural effusion with baseline poor pulmonary function, one may consider SBRT over 3DCRT to decrease the risk of radiation pneumonitis.

Presentation/diagnosis

Most patients experience symptoms of esophagitis, such as odynophagia, dysphagia, substernal discomfort, or sharp chest pain that may radiate to the back. These symptoms may occur in the acute setting within 2 to 3 weeks of the start of radiation, lasting up to 4 weeks after radiation completion. Esophagitis is due to radiation-induced effects on the basal epithelial layer and its continuous mucosal cell turnover. Continuous cell turnover in the setting of repeated DNA damage can cause epithelial thinning and can progress to denudation and ulceration.

Late effects of radiation esophagitis are less common in palliative radiation therapy due to the influence of dose per fraction, lower total dose to the esophagus, and a smaller field. Late symptoms include esophageal strictures, mechanical dysphagia secondary to stenosis or impaired esophageal motility, and odynophagia secondary to ulceration. Fibrosis of the esophageal wall mediates these long-term morbidities. In rare cases, chronic esophagitis can result in esophageal perforation, particularly after SBRT.

Diagnosis of esophagitis in a patient with the appropriate symptoms is made by upper endoscopy and biopsy. Endoscopy may demonstrate mucositis or ulceration in the short term, versus epithelial thickening, submucosal or muscularis fibrosis, cellular atypia, and chronic inflammation in the long term. When one is concerned about esophageal stricture, a barium swallow study can be performed to assess stricture location, length, and the diameter of the esophagus lumen.

CTCAE v5.0 Criteria grading of esophagitis is outlined in Table 31.3 .

Prevalence

Up to 15% of patients may experience esophagitis in the palliative setting. Risk factors that increase a patient’s risk for developing esophagitis include existing esophageal disease (gastroesophageal reflux disease, erosion) and concurrent chemotherapy.

Management

For the treatment of acute esophagitis, topical anesthetics such as viscous lidocaine, analgesic and antacid medications may be used. A combination solution is often prescribed for the convenience of the patient; this may include diphenhydramine, viscous lidocaine, nystatin, and hydrocortisone. Patients should be instructed to “swish and swallow.” Take 5 to 15 mL, swish for 1 to 2 minutes. This can be performed within 15 to 30 minutes prior to eating (often an exacerbating act of the patient’s pain) and can be completed every 4 hours. Prophylactic proton pump inhibitors may be prescribed; these help prevent candida infections due to the promotion of an alkalotic environment and can provide symptomatic relief. The combination of these medications inhibits the cytokine-mediated inflammatory reaction and disrupts yeast colonization, both often associated with chemotherapy or radiation therapy.

Dietary modifications are recommended to maintain adequate nutrition, including soft solids and high-calorie liquids to supplement intake. Eating small, frequent meals and avoiding triggering foods such as those that are spicy, very hot or very cold, acidic (coffee), or sharp (toast, chips) may be suggested. The patient should be counseled on tobacco cessation and may be advised to decrease alcohol consumption if this promotes painful episodes. In severe cases of esophagitis, IV hydration can be offered during the acute phase to minimize the risk of dehydration and resulting hospitalization.