A new study published in Physics and Imaging in Radiation Oncology shows that combining intensity modulated proton therapy with breath hold may offer the strongest organ-sparing potential for patients with mediastinal lymphoma.
The article, “Improved organs-of-interest dose reduction potential with intensity modulated proton therapy and breath-hold in mediastinal lymphoma,” evaluated whether IMPT with breath hold could reduce dose to organs of interest compared with other commonly used radiotherapy approaches.
Why This Study Matters
Radiotherapy remains an important curative treatment for mediastinal lymphoma, including Hodgkin lymphoma, diffuse large B-cell lymphoma, and primary mediastinal B-cell lymphoma.
Many patients are young and have high long-term survival rates. This makes late treatment-related toxicity a central issue. Survivors may face increased risks of cardiac disease, lung cancer, breast cancer, and other second malignancies years after treatment.
Because of this, reducing dose to the heart, lungs, and breasts is especially important.
Modern radiotherapy techniques such as deep inspiration breath hold and proton therapy are designed to limit unnecessary dose to healthy tissues. However, direct comparative data between multiple techniques have been limited.
Study Design
This retrospective in silico planning study included 58 patients with mediastinal lymphoma treated between 2019 and May 2024.
Each patient had both 4D-CT and breath-hold CT available. Four radiotherapy plans were created for every patient:
- VMAT in free breathing
- VMAT with breath hold
- IMPT in free breathing
- IMPT with breath hold
The authors compared dose-volume histogram metrics and estimated normal tissue complication probabilities for late effects, including acute coronary events, secondary lung cancer, and secondary breast cancer.
An absolute dose difference of at least 1 Gy was considered clinically relevant when determining the optimal technique for each patient.
Key Findings
IMPT with breath hold achieved the lowest average mean heart dose.
The average mean heart dose was 5.4 Gy with IMPT breath hold, compared with 8.0 Gy for VMAT free breathing, 6.3 Gy for VMAT breath hold, and 5.8 Gy for IMPT free breathing.
IMPT with breath hold also achieved the lowest average mean lung dose.
The average mean lung dose was 6.7 Gy with IMPT breath hold, compared with 9.2 Gy for VMAT free breathing, 7.5 Gy for VMAT breath hold, and 7.3 Gy for IMPT free breathing.
For breast dose, IMPT techniques performed better than VMAT. Average bilateral mean breast dose was 2.1 Gy with IMPT compared with 3.2 Gy with VMAT.
Estimated Late Toxicity Risk
The study also estimated normal tissue complication probability for important late effects.
IMPT with breath hold reduced the median estimated risk of acute coronary events to 17.9%, compared with 19.9% for VMAT free breathing, 18.5% for VMAT breath hold, and 18.6% for IMPT free breathing.
For secondary lung cancer, the estimated risk was also lowest with IMPT breath hold at 8.0%, compared with 12.9% for VMAT free breathing, 10.3% for VMAT breath hold, and 8.9% for IMPT free breathing.
For secondary breast cancer, both IMPT techniques reduced the estimated risk compared with VMAT.
What the Figure Shows
The figure on page 5 illustrates which technique was optimal for each patient based on organ dose.
For mean heart dose, IMPT breath hold was optimal in 35% of patients and IMPT free breathing in 26%.
For mean lung dose, IMPT breath hold was optimal in 59% of patients and IMPT free breathing in 19%.
For bilateral mean breast dose, IMPT breath hold was optimal in 38% of female patients and IMPT free breathing in 28%.
When all endpoints were considered together, IMPT breath hold was the optimal overall technique in 47% of patients, IMPT free breathing in 22%, and VMAT breath hold in 28%. This means that IMPT techniques were optimal for at least 69% of patients.
Clinical Interpretation
The results suggest that breath hold and proton therapy may have complementary effects.
Breath hold can change thoracic anatomy by increasing the distance between target volumes and organs at risk, while also reducing respiratory motion. IMPT can reduce unnecessary dose through proton beam characteristics, particularly by limiting exit dose.
Together, IMPT and breath hold provided the most favorable average organ sparing in this study.
However, the optimal technique was not identical for every patient. Some patients benefited most from IMPT breath hold, others from IMPT free breathing or VMAT breath hold.
This highlights the importance of individualized plan comparison rather than assuming one technique is best for all patients.
Limitations
The study was retrospective and based on treatment planning comparisons rather than clinical outcome data.
Although all plans met clinical requirements, in silico planning may still be influenced by inter-planner variability and technique-selection bias.
The authors also note that treatment planning is time-consuming, especially when multiple plans are needed for model-based selection. Future decision-support tools may help identify which patients are most likely to benefit from IMPT, breath hold, or both.
Clinical Takeaway
For patients with mediastinal lymphoma, reducing radiation dose to the heart, lungs, and breasts is essential because many are young and may live for decades after treatment.
This study shows that IMPT with breath hold provides the strongest average dose reduction to key organs of interest compared with VMAT free breathing, VMAT breath hold, and IMPT free breathing.
IMPT breath hold may therefore be an important strategy for reducing the risk of late treatment-related effects in selected mediastinal lymphoma patients.
The next step is to better define which patients benefit most and to develop predictive tools that support individualized technique selection.
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