Local Recurrence After Radiation Therapy for Langerhans Cell Histiocytosis: Risk Stratification by Site of Disease

Abstract

Langerhans cell histiocytosis (LCH) is a rare disease characterized by histiocytic proliferation. While treatment guidelines have been developed for systemic therapy, little evidence exists to guide localized treatment options. We intended to characterize the efficacy and safety of radiation therapy (RT) in a contemporary cohort and to explore if there are sites at higher risk for local recurrence. From 1990-2015, 325 patients had a pathological diagnosis of LCH at our center. After excluding 105 patients who were referred only for confirmation of pathology and an additional 34 patients with concurrent malignancy, 40 patients with 47 irradiated lesions were identified and comprised the study population. Per recommended guidelines, patients were grouped by single/multisystem involvement (SS/MS) and risk organ involvement (RO; liver, spleen, hematopoietic system, brain if age >18, lung if age <18 years). The primary endpoint was freedom from local failure (FFLF), defined as local progression or recurrence of disease. The log-rank test and Kaplan-Meier method were used to assess FFLF. Treatment toxicities were evaluated using CTCAE v 4.0. Median age at RT was 35 years (range 1.5 – 67). Twelve patients had multisystem involvement, and of those patients 5 had disease in high-risk organs. The following sites were irradiated: bone (32), brain (6), skin (3), lymph node (3), thyroid (2), and nasopharynx (1). Median dose was 11.4 Gy (7.5 – 50.4, interquartile 10.4-20), and 15 of 37 (41%) reported treatment techniques were IMRT, IGRT, or 3DCRT. RT was combined with surgery for 13 lesions and with chemotherapy for 10. At a median follow-up of 44 months (range 6 – 199), local recurrence, or progression was noted in 5 of 47 (10.6%) lesions. There were no local failures of 32 bone lesions evaluated, while the 3-year FFLF in the 15 non-bone lesions was 63% (95% CI 31 – 83%; P = 0.001). In particular, skin lesions had a higher likelihood of local failure (2/3; 3-year FFLF 0%) than non-skin lesions (P < 0.001). Local failures also occurred in 2 of 6 brain lesions and 1 of 3 lymph node lesions. No other patient, tumor, or treatment characteristics, including RO and SS/MS status, had a statistically significant association with FFLF. No acute adverse events (greater than grade 2) were identified. Late adverse events included grade 3 chronic headache in one patient, grade 2 hypopituitarism in two patients, and minor bone growth asymmetry in one pediatric patient. Radiotherapy is a safe and effective measure for providing local control of LCH, with low rates of local failure and few adverse events. While bone lesions are well controlled with low doses of radiation, we are concerned about control of disease in the skin and the brain. These sites may require additional treatment modalities or higher doses of radiation. Further characterization of the disparate outcomes for LCH lesions may guide future management decisions.