Radiation Therapy for Mesothelioma

Radiation therapy uses high-energy beams to kill cancer cells or slow their growth. In mesothelioma treatment, radiation plays a supporting role within multimodal therapy rather than serving as a standalone curative treatment. The diffuse, sheet-like growth pattern of mesothelioma along the pleural surfaces makes it exceptionally challenging to target with radiation without damaging surrounding vital organs, including the lungs, heart, esophagus, and spinal cord.¹

Despite these challenges, advances in radiation technology — particularly intensity-modulated radiation therapy (IMRT) — have expanded the role of radiation in mesothelioma management. IMRT uses computer-guided modulation of beam intensity to conform the radiation dose more precisely to tumor targets while minimizing exposure to adjacent healthy tissue. This has enabled higher therapeutic doses to be delivered with acceptable toxicity profiles.²

Radiation therapy for mesothelioma is used in three primary contexts: adjuvant therapy after surgery (to eliminate microscopic residual disease), neoadjuvant therapy before surgery (the SMART protocol), and palliative therapy to control pain and other symptoms in advanced disease. Each application has specific dosing, timing, and technique considerations that require expertise from radiation oncologists experienced in thoracic malignancies.³

The SMART (Surgery for Mesothelioma After Radiation Therapy) protocol, developed at the Princess Margaret Cancer Centre in Toronto, represents an innovative approach that delivers high-dose accelerated hemithoracic radiation prior to extrapleural pneumonectomy. Early results have shown promising improvements in local recurrence rates and survival compared to traditional surgery-first approaches.⁴

Types of Radiation Used for Mesothelioma

• Intensity-Modulated Radiation Therapy (IMRT): The most commonly used technique for mesothelioma. Computer-controlled linear accelerators deliver precise radiation doses that conform to the three-dimensional shape of the tumor while sparing nearby organs. IMRT can be used after pleurectomy/decortication when the lung remains in place.
• External Beam Radiation Therapy (EBRT): The broad category of radiation delivered from outside the body. Includes IMRT, 3D conformal radiation, and older techniques. All mesothelioma radiation is delivered externally.
• Hemithoracic Radiation: High-dose radiation delivered to the entire affected hemithorax (half of the chest). Used after extrapleural pneumonectomy when the lung has been removed, allowing higher doses without risk of radiation pneumonitis.
• Prophylactic Tract Irradiation: Low-dose radiation delivered to biopsy and surgical port sites to prevent tumor seeding along instrument tracts. Evidence on its effectiveness is mixed, and routine use is debated.⁵

Before beginning radiation therapy, patients undergo treatment planning that includes:

• CT simulation: A dedicated CT scan performed in treatment position to map the target volume and surrounding anatomy
• Target delineation: Radiation oncologists outline the gross tumor volume (GTV), clinical target volume (CTV), and planning target volume (PTV) on CT images
• Dose planning: Medical physicists design a treatment plan that delivers the prescribed dose to the target while respecting dose limits for organs at risk (lungs, heart, liver, kidneys, spinal cord)
• Pulmonary function testing: Essential to assess baseline lung function, especially if radiation will be delivered to the hemithorax with the remaining lung

Adjuvant Radiation (After Surgery)

Adjuvant radiation is delivered after surgical resection to eliminate microscopic residual disease at surgical margins and reduce local recurrence. The approach differs based on the type of surgery performed:

• After extrapleural pneumonectomy (EPP): Hemithoracic radiation (45–54 Gy) can be delivered to the entire affected hemithorax because the lung has been removed, reducing the risk of radiation pneumonitis
• After pleurectomy/decortication (P/D): IMRT is used to treat the pleural surfaces while sparing the remaining lung. This is technically more challenging but achievable with modern IMRT planning

SMART Protocol (Neoadjuvant Radiation)

The SMART protocol reverses the traditional sequence by delivering 25 Gy in 5 fractions of accelerated hemithoracic radiation over one week, followed by extrapleural pneumonectomy within the subsequent week. Potential advantages include:⁴

• Radiation delivered to intact tumor with better oxygenation (more radiosensitive)
• Sterilization of the surgical field may reduce intraoperative tumor cell spillage
• Accelerated hypofractionation completes treatment faster than conventional adjuvant courses
• Initial studies showed 3-year survival rates of 56–84% for epithelioid mesothelioma

Palliative Radiation

Palliative radiation is used to control symptoms in patients who are not surgical candidates or who have advanced disease:

• Pain control: Radiation can effectively reduce chest wall pain caused by tumor invasion
• Tract-site treatment: Low-dose radiation (21 Gy in 3 fractions is common) to biopsy or chest tube sites where tumor seeding has occurred
• Compression syndromes: Radiation can relieve superior vena cava obstruction or nerve compression caused by tumor growth

Side Effects

Common side effects of thoracic radiation for mesothelioma include:

• Fatigue (the most common side effect, often cumulative)
• Skin changes (redness, irritation, peeling in the treatment field)
• Esophagitis (difficulty swallowing if the esophagus is in the radiation field)
• Radiation pneumonitis (inflammation of lung tissue — risk is highest when the ipsilateral lung is present)
• Nausea (if the radiation field includes the upper abdomen)
• Cardiac toxicity (long-term risk with left-sided treatment)

Radiation therapy alone does not meaningfully improve survival in mesothelioma. However, when combined with surgery and chemotherapy in a multimodal approach, radiation contributes to improved local disease control and may extend survival. The SMART protocol has reported 3-year overall survival rates of 56 to 84 percent in selected patients with epithelioid mesothelioma, though these results come from single-institution studies with carefully selected patients.⁴

Palliative radiation is effective for symptom control, with response rates of 50 to 70 percent for pain relief. Quality of life improvements from effective symptom management should not be underestimated, even in the setting of advanced disease.¹

Patients undergoing radiation therapy for mesothelioma can take several steps to manage side effects and maintain quality of life:

• Skin care: Use gentle, fragrance-free moisturizers on irradiated skin; avoid sun exposure to treated areas
• Nutrition: Maintain adequate caloric and protein intake; soft or liquid foods may help if esophagitis develops
• Energy conservation: Plan activities around energy levels; fatigue typically peaks 2–3 weeks after treatment completion
• Breathing exercises: Pulmonary rehabilitation techniques to maintain lung function during and after treatment
• Follow-up imaging: Regular CT scans to monitor treatment response and detect recurrence