Induced Leukopenia In Head And Neck Cancer Patients Treated With Proton Or Photon Radiotherapy

Abstract

Leukopenia and lymphopenia are associated with worse overall survival in many cancers. Proton therapy was shown to reduce the risk of severe lymphopenia in esophageal cancer patients treated with neoadjuvant chemoradiation by 50% compared to photon IMRT. The hypothesis of our study was that proton therapy can also reduce the induced leukopenia of head and neck cancer (HNC) patients treated with chemoradiation compared to photon radiotherapy. We retrospectively compared the absolute and relative (compared to baseline) leukocyte counts of 40 consenting HNC patients treated with definitive photon (n = 20) and proton radiotherapy (n = 20) at baseline and throughout the treatment course. The majority of patients presented with nasopharyngeal carcinomas (80%), tumors of the nasal cavity (10%) or other HNC tumors (10%). The histological distribution was comparable between both groups. All patients received a total radiation dose of 70 Gy and concurrent cisplatin chemotherapy with the majority of patients receiving 40mg/m2 of weekly cisplatin (90%) and a minority of patients receiving three-weekly 100mg/m2 cisplatin (10%). Patients treated with other/additional systemic therapies, as well as patients receiving immunostimulatory agents (e.g. G-CSF) were excluded. There were no significant differences between the leukocyte counts of both groups at baseline and within the first 4 weeks of treatment. However, from the fifth week onward the proton therapy group presented with significantly higher leukocyte counts compared to the photon therapy group for both relative (p = 0.004) and absolute leukocyte counts (p = 0.017). This difference was most pronounced in the last treatment week and the following week where the photon patients presented with a relative mean reduction of leukocytes to 55% and 53% of the baseline leukocytes, respectively. In comparison, the proton patients presented with 77% and 81% of baseline leukocytes, respectively. In addition, the photon patients experienced a prolonged delay of leukocyte recovery, reaching 79% of baseline four weeks post-treatment, compared to 94% in the proton patients. Proton therapy is associated with a significant reduction of leukopenia during and following chemoradiation of HNC patients. The clinical implications in terms of outcome or infection-rate will need to be confirmed in future prospective clinical trials.