ANTI-TUMOUR TREATMENTRadiation therapy following lymph node dissection in melanoma patients: treatment, outcome and complications
Introduction
Increased awareness and surveillance have resulted in earlier diagnosis of melanoma. Consequently, the melanoma patient is now diagnosed at an earlier stage of disease.1 Nevertheless, some melanoma patients still present or recur with loco-regional metastases (Stage III A.J.C.C.). Surgical excision of the primary tumour and/or lymph node dissection remains the standard of care for these patients.
Only 25–50% of the patients with regional lymph node metastases survive more than five years after a therapeutic lymph node dissection and 34–50% of the patients recur loco-regionally.[2], [3], [4], [5], [6], [7], [8], [9] Most of these melanoma patients die as a consequence of distant metastases, usually in less than two years after lymph node dissection. Loco-regional recurrences are often difficult to treat and might be accompanied with a substantial morbidity, such as ulceration and disfigurement. Therefore, prevention of loco-regional failure could improve the quality of life, even if it does not increase the long-term survival.10
Adjuvant radiation treatment to the dissected nodal basin has been suggested and investigated in an attempt to gain regional control after lymph node dissection.[11], [12], [13], [14], [15], [16], [17], [18], [19] However, the potential benefits of adjuvant radiation after therapeutic lymph node dissection for stage III melanoma patients must be weighed against the morbidity and side effects of radiation treatment.
Although early retrospective data suggested less sensitivity of melanoma to radiation, it is now well documented that regardless of the fractionation schedule, melanoma cells are radioresponsive if adequate doses of radiation are delivered.[20], [21], [22], [23] Despite this well documented radioresponsivity, routine irradiation is often avoided because there is still a belief that radiotherapy is ineffective for melanoma as well as an concern regarding short and long-term radiation induced morbidity.24 Adjuvant radiotherapy for lymph node metastases is nowadays generally reserved for melanoma patients with a high risk for regional recurrence after therapeutic lymph node dissection. High-risk features include extranodal growth (ENG) pattern, large lymph nodes, the involvement of multiple pathological lymph nodes, clinically palpable adenopathy and the anatomical site of involved lymph nodes.[3], [4], [5], [6], [7], [25], [26]
The relevant literature concerning the use of adjuvant radiotherapy after therapeutic lymph node dissection for stage III melanoma patients is reviewed. Different aspects of the treatment, the five-year loco-regional, disease-free and survival rates and the complications of the radiation are discussed.
Section snippets
Treatment
There is a belief among radiation oncologists that larger fraction size with lower total dose, so called “hypofractionation”, improves the therapeutic impact of radiation for melanoma. However, the optimal fractionation scheme for malignant melanoma remains controversial. Historically melanoma has been thought of as a relatively radioresistant tumour with a low α/β ratio, but several studies have shown that melanoma is radioresponsive. Besides that, the historical basis of this belief has been
Loco-regional control, disease-free survival and overall survival
Nine studies investigated the effect of adjuvant radiotherapy after therapeutic lymph node dissection and were reviewed with respect to the five-year loco-regional control (with and without radiotherapy), the disease-free and survival rates and presented in Table 1. Almost all the studies were retrospective, the predominant location was the neck and head region (seven studies) or axilla (two studies). No studies with respect to only inguinal irradiation were found. In six studies the
Risk factors
Risk factors for melanoma stage III patients for disease recurrence after lymph node dissection, distant metastases of melanoma and, as a consequence, overall survival is presented in Table 2.
Extranodal extension and multiple involved nodes were mentioned in almost all the studies. Adjuvant irradiation was recommended when extracapsular extension was noted histologically and different studies found the presence of extranodal extension a significant predictor of nodal basin failure. Multiple
Complications
The complications of adjuvant radiotherapy after lymph node dissection are summarised in Table 3. Edema was mentioned in almost all the studies besides fibrosis and skin desquamation, which may be encountered after irradiation treatment. Edema is also a potential complication after lymph node dissection, however given the retrospective nature of the studies, it was not possible to categorise complications as specifically related to surgery or radiation.
Complications of postoperative
Discussion and conclusions
Adjuvant radiotherapy after lymph node dissection for metastases of melanoma may improve loco-regional control without improving overall survival. The most important indications for adjuvant radiotherapy after lymph node dissection are (1) extranodal disease, (2) multiple involved nodes or (3) large involved nodes. The complications seem manageable and consist mainly of fibrosis and edema.
Melanomas have traditionally been regarded as extremely radioresistant tumours. The origin of this dogma is
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