Radiotherapy in the Modern Era in the Management of Langerhans Cell Histiocytosis

Rupen Garg, BS; Qinyu Chen, MHS; Yin Zhang, PhD; Ariel E. Marciscano, MD; Jing Zeng, MD; Robert J. Arceci, MD, PhD; and Stephanie A. Terezakis, MD
Published: Sunday, Mar 12, 2017
Rupen Garg, BS
Rupen Garg, BS
 

EXPERT'S PERSPECTIVE:

Bradford Hoppe,
MD, MPH

Bradford Hoppe, MD, MPH
Associate Professor, University of Florida Proton Therapy Institute

Why is this article contemporary?

One concern for utilizing radiotherapy (RT) is the potential for toxicity, especially the late sequelae including musculoskeletal growth abnormalities and second malignancies that have been reported. Considering there are no clearly defined roles for conformal radiation techniques such as intensity-modulated radiation therapy (IMRT) in treating LCH, this study retrospectively reviewed 16 patients with histologically confirmed Langerhans cell histiocytosis (LCH) treated with radiation therapy between July 1983 and October 2013 at the Johns Hopkins Hospital. With regards to local control and overall survival, both conformal and conventional radiotherapy techniques provided excellent results in the management of LCH. These results also showed that conformal radiotherapy techniques employ significantly lower radiation dose to critical normal structures, such as temporal lobes, hippocampus, lens and hypothalamus/pituitary axis, compared to conventional techniques.

By utilizing modern and contemporary radiotherapy approaches, the reduction in critical structures can be achieved without sacrificing excellent clinical outcomes. Ultimately, this approach appears to improve the therapeutic ratio for children and young adults with this disease. Approximately 60% of LCH patients present in the head and neck where excess radiation dose could have significant long-term sequelae.

Younger patients are more vulnerable and radiosensitive than adults, and thus, this population merits more consideration for sparing of normal organs. These results support the use of contemporary, conformal radiation techniques. IMRT should be considered in pediatric and young adult patients receiving RT for LCH particularly given the long-term survival of these patients. Future research could evaluate using proton therapy to reduce the radiation dose further to the critical structures.

Abstract

Objective

Radiotherapy has been shown to be effective in treating Langerhans cell histiocytosis (LCH) with no clearly defined role for conformal radiation techniques such as intensity-modulated radiotherapy (IMRT). The goal of this study was to evaluate clinical outcomes and radiation dose to critical normal structures in patients treated for LCH with conventional and conformal radiotherapy techniques.

Methods

Sixteen patients (mean age 27.4 years, range 1-48 years) with 21 lesions treated with radiotherapy for LCH were retrospectively reviewed. The 6 IMRT-treated patients were replanned using conventional techniques and mean radiation doses to critical structures were compared using dose volume histograms (DVHs).

Results

After a median follow-up of 46.6 months (range, 3.0-341.9 months), 15 of 16 patients were alive with stable disease. Local control was 88% with IMRT and 90% with conventional radiotherapy at 5 years. One patient died after 28.5 years of follow- up due to progression of disease. All patients tolerated treatment with mild, acute toxicities. No late toxicities were reported at last follow-up. The median dose was 18 Gy (range, 7.5-4 Gy). DVH analysis showed that IMRT delivered less mean radiation dose to critical normal structures including the parotid glands, cochleae, temporal lobes, and hippocampi compared to conventional radiotherapy techniques. Mean ipsilateral parotid dose for skull-based lesions was 17 ± 0.9 Gy for IMRT and 21 ± 1.3 Gy for conventional techniques (P = 0.016). Mean temporal lobe dose was reduced in all 6 IMRT plans by up to 29% compared to conventional techniques (P = 0.021).

Conclusions

IMRT reduces the mean radiation dose delivered to critical normal structures and should be considered in LCH treatment when radiotherapy is indicated, particularly given the expected, long-term survival of these patients.
Introduction Langerhans cell histiocytosis (LCH) is a rare disorder characterized by proliferation of myeloid dendritic cells expressing the antigens CD1a and CD207.1 The accumulation of LCH cells results in single or multiple osteolytic bone lesions in 80% of cases, but other organ systems may also be involved including the skin, lymph nodes, lungs, liver, bone marrow, spleen, or central nervous system.2 While the exact incidence of LCH is unknown, it is estimated that the annual incidence of LCH is 5 to 6 cases per million children.3 It is predominantly a disease of childhood with a peak incidence in children 1 to 3 years of age.4,5,6 However, LCH may also be seen in adults.7,8


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