Comparative Analysis of Second Malignancy Risk in Patients Treated with Proton Therapy versus Conventional Photon Therapy

Article Outline

• Background
• Purpose/Objective(s)
• Materials/Methods
• Results
• Conclusion
• Copyright

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Background 

Compared to photon radiation, proton radiation improves dose distribution to the target and decreases dose to adjacent normal tissues. The most common method of delivering proton radiation involves passive scattering. However, passive scattering produces secondary low-dose neutrons, which may induce late radiation-induced malignancies. The magnitude of second cancer risk in patients treated with proton radiation compared to photon radiation therapy has not been reported to date.

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Purpose/Objective(s) 

To quantify the risk of a second malignancy associated with the use of proton radiation therapy compared to photon radiation therapy.

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Materials/Methods 

Matched retrospective cohort study of 1,450 patients treated with proton radiation therapy from 1974-2001 at the Harvard Cyclotron in Cambridge, MA, and patients treated with photon therapy in the Surveillance, Epidemiology, and End Results (SEER) cancer registry. We matched patients by age at radiation treatment, year of treatment, cancer histology, and site of treatment. We restricted the study to patients with ≥1 year of follow-up. The primary endpoint was the risk of a second malignancy in any site after radiation therapy.

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Results 

We matched 503 Harvard Cyclotron proton patients with 1591 photon patients from the SEER registry. 6.4% of proton patients (32 patients) developed a second malignancy, while 12.8% of photon patients (203 patients) developed a second malignancy. The median duration of follow-up was 7.7 years in the proton cohort and 6.1 years in the photon cohort. The median age at treatment was 56 years in the proton cohort and 59 years in the photon cohort. After adjusting for gender and the age at treatment, treatment with photon therapy was significantly associated with an increased risk of a second malignancy (Adjusted Hazard Ratio 2.73, 95% CI 1.87 to 3.98, p < 0.0001).

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Conclusion 

The results of our preliminary analysis indicate that the use of proton radiation therapy is associated with a significantly lower risk of a second malignancy compared to photon radiation therapy. Additional analyses are required, and ongoing close surveillance of these patients is necessary, given the prolonged latency period for the development of second cancers.