Melanoma: Lymph Node Radiation After Lymphadenectomy Did Not Improve Survival

MedicalResearch.com Interview with:
Michael A Henderson
MBBS BMedSc MD FRACS
Professor of Surgery, University of Melbourne
Deputy Director Division of Cancer Surgery
Head Skin and Melanoma Service
Division of Cancer Surgery
Peter MacCallum Cancer Centre
East Melbourne Victoria  Australia

Medical Research: What is the background for this study? What are the main findings?

Dr. Henderson:  A number of retrospective reviews of adjuvant radiotherapy after lymphadenectomy for patients at high risk of further lymph node field relapse had all suggested that the risk of lymph node field relapse was reduced but there was controversy about whether there was any impact on survival. In addition many clinicians were concerned about the side effects of radiotherapy and in the absence of a proven survival benefit were reluctant to recommend it. Previously a phase 2 trial of adjuvant radiotherapy conducted by one of our co-authors Prof Bryan Burmiester confirmed that the morbidity of lymph node field radiotherapy was limited and the risks of recurrence was reduced. On that basis the current ANZMTG TROG randomised multicentre trial was initiated.

In summary this final report updates information on overall survival, lymph node field relapse etc and provides information for the first time on long term toxicity of treatment, quality of life and lymphedema. Adjuvant lymph node field radiotherapy for patients at high risk of further lymph node field relapse reduces the risk of further lymph node field relapse by 50% but it has no effect on survival. Although radiotherapy toxicity was common (3 in 4 patients), mostly involving skin and subcutaneous tissue it was mild-to-moderate in severity and had little impact upon the patient’s quality of life as measured by the FACT-G quality of life tool. Specific regional symptoms were more common in the radiated group. Limb volume measurements confirmed a significant but modest increase for patients receiving inguinal radiation (15%) but not for axillary radiation.

In the design of this trial, a decision was made to allow patients in the observation arm who developed an isolated lymph node field relapse to be salvaged by surgery and or radiotherapy. There were only two patients in the radiotherapy arm who developed an isolated lymph node field relapse and both died of metastatic disease. In the observation arm 26 patients developed an isolated lymph node field relapse and the majority (23) achieved lymph node field control with a combination of surgery and or radiotherapy. The five-year survival FROM development of a lymph node field relapse in this group was 34% which is comparable to the overall survival of the entire cohort (42% five-year overall survival). This information whilst a subset analysis suggests that if it would be reasonable in some patients to consider a policy of observation only, reserving further surgery and or radiotherapy for a second relapse.

Medical Research: What should clinicians and patients take away from your report?

Dr. Henderson: At this author’s institution, the Peter MacCallum Cancer Centre in Melbourne Australia, we do not now routinely recommend adjuvant radiotherapy after lymphadenectomy. Increasingly our preference is to recommend that patients consider participating in one of the new generation of adjuvant therapy trials. The extraordinary success of immune checkpoint inhibitors and targeted therapies in advanced disease gives great hope for an effect in the adjuvant setting. It should be remembered that patients at high risk of further lymph node field relapse after lymphadenectomy are also at high risk of developing metastatic disease and dying of melanoma (42% five-year overall survival was seen in this study).

This study provides information to allow patients and clinicians to understand the benefits and risks of adjuvant radiotherapy and make a decision in the absence of a survival benefit as to whether they will undergo radiotherapy. This study suggests that for those patients not entering an adjuvant study observation is a realistic option. The lymph node field relapse rate is of course higher in patients avoiding radiotherapy but the majority who do develop an isolated lymph node field relapse can achieve lymph node field control with a survival comparable to patients in the adjuvant radiotherapy arm with a combination of surgery and radiotherapy.

For some patients (and clinicians) the prospect of lymph node field relapse is unacceptable regardless of the inconvenience of treatment and possible side effects. This study provides patients and clinicians with information on the effectiveness of treatment and likely side effects to aid in the decision process. For other patients where participation in an adjuvant trial is not possible e.g. the elderly or unwell and a large tumor burden (extensive extra nodal extension of tumor) radiotherapy may be considered and balanced against anticipated side effects and morbidity.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Henderson: This study was conceived and undertaken during a time when there were no effective systemic treatments for melanoma. The spectacular success of targeted therapies and immune checkpoint inhibitors has dramatically changed the treatment options for patients with advanced melanoma and increasingly is likely to offer options for adjuvant therapy of patients at high risk of both lymph node field relapse and distant relapse. The details of these treatments is currently under intense investigation. The major benefit therefore of this study was to identify a group of patients at high risk of lymph node field relapse and describe their clinical course. This study has confirmed that adjuvant lymph node field radiotherapy does not impact on survival and it is reasonable to consider a policy of close observation. The long term toxicity of radiotherapy is modest and patents quality of life is acceptable regardless of whether they received adjuvant radiotherapy or not.

For the future the challenge will be to integrate all the therapeutic options to maximise outcomes with minimal morbidity.

Citation:

Adjuvant lymph-node field radiotherapy versus observation only in patients with melanoma at high risk of further lymph-node field relapse after lymphadenectomy (ANZMTG 01.02/TROG 02.01): 6-year follow-up of a phase 3, randomised controlled trial

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Michael A Henderson, & MBBS BMedSc MD FRACS (2015). Melanoma: Lymph Node Radiation After Lymphadenectomy Did Not Improve Survival 

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