Background: Most stage I-IIA classical Hodgkin lymphoma (cHL) patients are cured with limited chemotherapy followed by radiotherapy (RT), with a risk of late toxicity from RT. The dose to normal tissue can be minimized with proton therapy (PT) due to the finite range in tissue and the rapid dose-drop beyond that. This study reports preliminary results of the PRO-Hodgkin study.
Method: The first 19 patients included (median age 31 (19-53)) are analysed. They received 2-4 cycles of ABVD followed by involved-node/site PT to 29.75 Gy (RBE; relative biological effectiveness)/17 fractions for patients with risk factors, and 20 Gy (RBE)/10 fractions for those without risk factors. Planning CT in deep inspiration breath hold was recommended; if not feasible, a 4DCT was performed to ensure motion amplitudes within 5 mm. Patients were typically treated by pencil beam scanning with two anterior oblique fields, sometimes with a complementary posterior field. All treatment plans were robustly optimized.
Results: All patients were in complete remission at end of therapy. Acute toxicity was generally limited and similar to photon treatment, except slightly more skin reaction, which occurred in all patients (1 grade 3, 1 grade 2 and 17 grade 1). Surprisingly 4 patients (age 26-45), previously healthy and non-smokers, presented with skin hyperesthesia radiating from the neck or the scapula/chest wall area towards the axilla and upper arm, starting weeks or a few months after RT. The symptoms mostly resolved within a month, but one patient had symptoms gradually improving for 4 months. None of the patients had skin rash during symptoms and none had motor affection. Analysis of the dose plans showed that the brachial nerve plexus was frequently located in or close to the target, and often had a modest overdosage (max 5% over the prescribed dose). Thoracic nerve roots and the spinal cord were usually located in the dose drop-off. Even assuming slightly higher RBE towards the end of the proton range, the dose to spinal cord/peripheral nerves was well within tolerance.
Conclusion: PT was generally well tolerated, except for an unexpected, transient neurological toxicity in 4 out of 19 patients. This could not be explained by an overdosage, and the potential mechanism has not yet been identified. Radiation- induced inflammation and cytokine release could be a possible cause. Further analyses are warranted and neurological toxicity will be reported for future patients.