Radiation Pneumonitis

Radiation pneumonitis is an inflammatory lung reaction that follows irradiation of lung tissue, most often in thoracic radiotherapy for lung, breast, oesophageal cancer and lymphoma. Symptomatic disease occurs in 5 to 20 percent of patients after lung cancer radiotherapy, and in 1 to 5 percent after breast radiotherapy. It usually appears 1 to 6 months (peak 2 to 3 months) after radiotherapy completion.

Injury is dose, volume and fractionation dependent. Risk rises when mean lung dose exceeds 20 Gy, V20 (volume of lung receiving 20 Gy or more) exceeds 30 to 35 percent, concurrent chemotherapy is given, or in patients with pre-existing interstitial lung disease or emphysema, or poor lung function. Radiation damages pneumocytes and endothelium, releasing cytokines (TGF-beta, IL-1, TNF-alpha) that drive alveolitis.

The late phase, 6 to 24 months later, is radiation fibrosis, which is irreversible. Rarely a bilateral lymphocytic alveolitis occurs outside the radiation field (sporadic pneumonitis). Fatality is under 2 percent.

• Dry cough, exertional dyspnoea, low grade fever, pleuritic chest pain, and fatigue.
• Hypoxaemia; fine crackles, sometimes a friction rub over the irradiated area.
• Severe disease: respiratory failure, ARDS-type picture.
• Fibrotic phase: persistent dyspnoea, volume loss, traction bronchiectasis, clubbing uncommon.
• Recall pneumonitis after chemotherapy or immunotherapy.
• Red flags: SpO2 under 90 percent, fever over 38.5 degrees C with purulent sputum (infection), haemoptysis, rapid progression.

• Timing 4 to 12 weeks after radiotherapy plus compatible symptoms and a radiation field opacity.
• Chest radiograph: ground glass or consolidation conforming to the radiation portal rather than anatomical boundaries.
• CT chest: ground glass opacity or consolidation with a geometric straight edge matching the field; later volume loss, traction bronchiectasis, and fibrosis.
• Spirometry and DLCO: restrictive pattern with fall in DLCO of 15 percent or more.
• Oxygen saturation at rest and on exertion; arterial blood gas for respiratory failure.
• Bronchoscopy with lavage (lymphocytosis, exclusion of infection and tumour recurrence) when the picture is unclear; viral, bacterial and fungal cultures, and cytology.
• Blood tests: inflammatory markers, brain natriuretic peptide to exclude cardiac failure.
• Exclude infection, cancer progression, lymphangitic carcinomatosis, pulmonary embolism, drug pneumonitis (bleomycin, immune checkpoint inhibitors), cardiac failure, and aspiration.

• Mild (grade 1, asymptomatic radiographic change): observe, no treatment.
• Symptomatic (grade 2): prednisolone 1 mg/kg orally once daily (usual 40 to 60 mg) for 2 to 4 weeks until symptoms improve, then taper by 10 mg every 2 weeks, reaching zero over 6 to 12 weeks; a faster taper causes relapse.
• Cover: omeprazole 20 mg once daily, calcium 1000 mg with vitamin D 800 IU daily, co-trimoxazole 480 mg once daily for pneumocystis prophylaxis when steroids at 20 mg or more continue beyond 4 weeks, blood glucose monitoring.
• Cough: codeine linctus 15 mg orally every 6 hours, or dextromethorphan 15 mg every 6 hours, for up to 2 weeks; inhaled budesonide 400 micrograms twice daily for residual cough.
• Severe (grades 3 to 4, hypoxaemia): hospital admission, oxygen to SpO2 92 percent or more; methylprednisolone 1 to 2 mg/kg intravenously once daily (or 500 mg for 3 days in life threatening cases), then prednisolone taper; ventilatory support as needed; treat infection concurrently when suspected, piperacillin tazobactam 4.5 g intravenously every 6 hours for 7 days; steroid refractory disease may be treated with mycophenolate 500 mg orally twice daily increasing to 1 g twice daily or azathioprine 1 to 2 mg/kg daily as steroid sparing agents.
• Withhold concurrent chemotherapy or immunotherapy until pneumonitis resolves; permanently stop immune checkpoint inhibitors in grade 3 to 4 pneumonitis.
• Fibrosis: pulmonary rehabilitation, long term oxygen when resting PaO2 is under 7.3 kPa, and vaccination (annual influenza, pneumococcal).
• Follow up: clinical review every 2 to 4 weeks during steroid taper; CT and spirometry at 3 months and 6 months; early relapse on taper is managed by returning to the previous effective dose for 2 weeks.
• Prevention: radiotherapy dose volume planning (mean lung dose below 20 Gy, V20 under 30 percent), intensity modulated or proton planning, smoking cessation, and delaying radiotherapy in active infection.