Role of radiotherapy in melanoma management

Abstract

Background: In melanoma, radiotherapy has generally been considered as a palliative treatment option indicated only for advanced cases or disseminated disease. In the 70s of the previous century, the technological advances in radiotherapy, linked to rapid development of computer sciences, resulted in restored interest for radiotherapy in melanoma management. Although a fundamental lack of well designed prospective and/or randomized clinical trials critically influenced the integration of radiotherapy into treatment strategies in melanoma, radiotherapy was recently recognized as an indispensable part in the multidisciplinary management of patients with melanoma. Altogether, approximately 23% of melanoma patients should receive at least one course of radiotherapy during the course of the disease. In this review, radiobiological properties of melanoma that govern the decisions for the fractionation patterns used in the treatment of this disease are described. Moreover, the indications for irradiation and the results of pertinent clinical studies from the literature, creating a rationale for the use of radiotherapy in the management of this disease, are reviewed and a brief description of radiotherapy techniques is given.

Conclusions: Basic treatment modality in melanoma is surgery. However, whenever surgery is not radical or there are adverse prognostic factors identified on histopathological examination of resected tissue specimen, it needs to be supplemented. Also, in patients with unresectable disease or in those not being suitable for major surgery or who refuse proposed surgical intervention, other effective mode(s) of therapy need to be implemented. From this perspective, supported by clinical experiences and literature results, radiotherapy is a valuable option: it is effective and safe, in curative and palliative setting.

Keywords: fractionation; indications; melanoma; radiobiology; radiotherapy; toxicity.

FIGURE 1

Dose-response curve for melanoma cells. High intrinsic capacity of melanoma cells for repair of sublethal DNA damages caused by irradiation is graphically presented by a distinctly broad shoulder in the low-dose portion of the logarithmic cell survival curve. Accordingly, the ability of melanoma cell to overcome sublethal DNA injuries suggests increased sensitivity to large doses per fraction (hypofractionation).

FIGURE 2

Stereotactic radiosurgery. This radiotherapy technique is characterized with maximal accuracy and is used for focal irradiation of small brain lesions (usually up to 3 tumors of 3.5 cm maximal diameter). After rigid fixation of the head with specific frame, several small beams coming from various directions are focused on one spot inside of the target, creating a steep dose gradient on periphery of the target. Tumor doses in the range of 16–25 Gy are prescribed on 80% isodose encompassing the lesion, whereas 1–2 mm from the edge of the target, the dose drops to 20–30% of its prescribed value. Local control is in the range of 90% and the prevailing cause of death is progression of extracranial disease. In January 2009, a 59-year-old male with melanoma, diagnosed 4 years earlier, presented with 4 metastatic lesions in the brain. On PET-CT, two additional metastases were identified elsewhere in the body, occupying the third lumbar vertebra and the musculature of the posterior abdominal wall. T1-weighted post-contrast MRIs revealed a lesion of 30x20 mm (long arrow) in the right temporoparietal region, a smaller one in the left half of the pons (short arrow), a 6 mm lesion in the left frontal lobe (thick arrow) and a 7 mm lesion in the left cerebellar hemisphere (arrowhead) (Figure 2A). The patient was treated with surgical resection of the large temporoparietal metastasis, whole brain irradiation (10 × 3 Gy), temozolamide and stereotactic radiosurgery of other three (smaller) brain metastases with the irradiation doses to 80% isodose of 20 Gy (the lesion in the frontal lobe) and 18 Gy (the lesions in the pons and cerebellum). Four months after the procedure, the size of all three irradiated tumors was reduced and no new lesion was identified in the brain (Figure 2B). In September 2009, disease progression was recorded after detecting a metastasis in the spinal cord which was treated with surgery, postoperative irradiation and chemotherapy. No progression of treated brain metastases occurred so far (January 2010, 11 months after stereotactic radiosurgery).