Radiotherapy

Background

In contrast to treatment of childhood LCH, radiotherapy is still a feasible and effective treatment option for adult patients with LCH. It has a long tradition and the first successful radiation of LCH was described in 1930 by Sosman. Since then, the effectiveness of radiotherapy in LCH has been shown in a large number of publications, but all studies reported in literature have a retrospective nature and in general the number of patients is not large. [Atalar et al 2010; Gaundong Mbéthé et al 2010; Brady et al 2008; Greenberger et al 1979; Heyd et al 2000].

Indications

Radiotherapy indications should respect the age of patients, the possibility of radiogenic malignancies, and the semi-benign character of disease. This kind of treatment should be considered as a palliative measure only when it is clearly warranted by the presence of disease progression or when location and extent of disease threaten the function of critical organs.

Table 6: Possible indications for the use of radiotherapy in adults
Recommendation
Grade *
Isolated “unresectable” lesion:
  • if a resection would significantly compromise anatomic function, e.g. odontoid peg, CNS
C2
Recurrent or progressive lesion:
  • In multifocal or multisystem disease only in case of minor response to standard systemic therapy.
C2
Adjuvant treatment following marginal or incomplete resection:
  • especially in single system bone disease with soft tissue involvement
C2

* Grades of recommendation see here.

Response

Most literature data concerning radiotherapy in adult LCH deal with uni- or multifocal osseous single-system disease. Summarizing the results in these bone lesions, the local control rates ranged from 75-100%, complete remission from 79-100%, respectively. There is not much data in the literature on radiotherapy in non-osseous single-system disease, mostly presented as single case reports. Nevertheless, in most cases a complete remission is reported. Bony lesions are the predominantly irradiated manifestations also in multi-system disease. Local control rates ranged from 75% to 100%, complete remission rates were up to 85%. Thus in case of minor responsiveness to standard systemic therapy Radiotherapy may be considered as an additive treatment in multifocal or multisystem disease.

Radiotherapy technique and dose

Osseous and visceral lesions should be treated with megavolte equipment (Linear accelerator), whereas superficial x-rays or fast electrons are used for cutaneous or subcutaneous lesions. In external beam radiotherapy, individually optimized radiation set-up and shielding using a modern three-dimensional conformal radiotherapy technique should be used to minimize the volume of not affected tissue neighboring the disease lesion. An adequate margin of 1-2 cm of normal tissue around the treated lesion should be included, but in bony lesions the whole bone must not to be included [Micke/Seegenschmiedt 2002].

The dose recommendation for radiotherapy is still controversial, because the optimal dose is not well defined, and an exact dose-effect relationship has not been established. There is a wide dose range of applied total doses from 1,4 Gy up to 45 Gy. In general, a dose range from 10 to 20 Gy is recommended in adults but a dose range from 12-14 Gy should sufficient for local control. Such total doses should be delivered in fractions of 1-2 Gy per day to avoid a possibly limited capacity for tissue repair mechanisms in larger single doses [Brady et al 2008; Cassady 1987]). (Grade C2 *)

Side effects

Acute side effects of radiotherapy depend on the localization of the irradiated body site. As the applied total dose rarely exceeds 20 Gy, both acute and subacute side effects are rare. Most literature data do not provide any information about acute side effects of radiotherapy. Late side effects of radiotherapy are also rare due to the low applied dose range. The only risk, which should be mentioned, is the extremely low one of radiation-induced carcinogenesis. [Greenberger et al 1979] reported a rate of 3.9% for induction of malignant tumors, but this data should be interpreted with care, because many children were treated in this collective. Even though the doses applied for local control in adult LCH are low, several publications in the literature describe the induction of leukemia, osteosarcoma, teratoma, malignant meningioma, thyroid and liver tumors (but it must be considered that most studies also treated children, who bear a much larger risk of cancer induction, and there is a well-known tendency of patients with LCH to develop malignancies independently of therapies.

Conclusion

Finally, the radiation treatment technique has substantially improved during the last decade becoming a precise and normal tissue sparing instrument. Nevertheless, the indication for radiotherapy for a palliative treatment in LCH has to be accurately set up with and the potential benefits of radiation treatment must be carefully weighed against its possible risks. The exact target cells or structures affected by radiotherapy in LCH remain unclear. Low doses of radiotherapy not reaching a normal cell-killing level have been shown to heal the disease, resulting in theories, that either radiotherapy suppresses an inflammatory process and so reduces the de novo- fraction of Langerhans cells, or that Langerhans cells themselves are a very sensitive population to irradiation [Greenberger et al 1979].

Recommended indications for the use of radiotherapy in adults with LCH are listened in table 6.

* Grades of recommendation see here.