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Long-term data clarify role of adjuvant radiotherapy after lymphadenectomy for melanoma
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Adjuvant radiation to the lymph-node field after lymphadenectomy significantly reduced the rate of lymph-node field relapse without an OS improvement for patients with melanoma at high risk for relapse, according to results of a multicenter, randomized controlled study.
Because the study was designed before the availability of many targeted therapies, the researchers recommend patients for whom lymph-node field control is a major issue enroll on an adjuvant systemic trial if available. Further, observation also may be an acceptable strategy for certain patients, researchers noted.
Michael A. Henderson, MD, FRACS, associate professor of surgery in the department of surgery at University of Melbourne and a surgeon as part of the head, skin and melanoma service at Peter MacCallum Cancer Centre in Melbourne, Australia, and colleagues first published data from this study in 2012. The current report updates the follow-up analyses of lymph-node field relapse, RFS and OS, and also includes data on late toxic effects, lymphedema and quality of life for the first time.
Michael A. Henderson
“This study was conceived and undertaken during a time when there were no effective systemic treatments for melanoma,” Henderson told HemOnc Today. “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 for both lymph-node field relapse and distant relapse.
“The details of these treatments is currently under intense investigation,” Henderson added. “The major benefit therefore of this study was to identify a group of patients at high risk for lymph-node field relapse and describe their clinical course.”
Researchers evaluated data from 109 patients assigned adjuvant radiotherapy (48 Gy in 20 fractions over a maximum of 30 days) and 108 patients assigned observation.
After a median follow-up of 6.08 years, relapses occurred in 21% of the radiotherapy group compared with 36% of the observation group (adjusted HR = 0.52; 95% CI, 0.31-0.88).
Patients in the observation arm more frequently had first relapses in the lymph-node field than patients in the adjuvant radiation arm (HR = 0.52; 95% CI, 0.31-0.88). However, researchers observed no significant difference in OS (HR = 1.27; 95% CI, 0.89-1.79) or RFS (HR = 0.89; 95% CI, 0.65-1.22) between the two groups.
The researchers reported that minor, long-term toxic effects from radiotherapy — such as pain and fibrosis of the skin or subcutaneous tissue — commonly occurred. Twenty-two percent of patients assigned radiotherapy experienced grade 3 to grade 4 toxic effects, and grade 3 effects mainly affected skin (10%) and subcutaneous tissue (7%).
Researchers observed a significant increase in lower limb volumes following adjuvant radiotherapy compared with observation over 5 years (mean volume ratio, 15% vs. 7.7%; difference, 7.3%; 95% CI, 1.5-13.1).
Results of quality-of-life assessments demonstrated improvements in both cohorts after lymphadenectomy, although improvements occurred more slowly in the adjuvant radiotherapy arm. With the exception of social well-being, which remained high throughout, the other domains and overall score improved over the first 18 months before stabilizing at similar levels.
“This study has confirmed that adjuvant lymph-node field radiotherapy does not impact survival and it is reasonable to consider a policy of close observation,” Henderson said. “The long-term toxicity of radiotherapy is modest and patients’ quality of life is acceptable regardless of whether they received adjuvant radiotherapy. For the future, the challenge will be to integrate all the therapeutic options to maximize outcomes with minimal morbidity.”
However, because quality-of-life data were incomplete following distant relapse, those findings only apply to the period before distant relapse.
“At the Peter MacCallum Cancer Centre, we do not routinely recommend adjuvant radiotherapy after lymphadenectomy,” Henderson said. “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.”
Henderson added that the results of this study can provide information so patients and clinicians understand the benefits and risks of adjuvant radiotherapy and can make a decision to undergo radiotherapy or observation.
“For some patients (and clinicians), the prospect of lymph-node field relapse is unacceptable, regardless of the inconvenience of treatment and possible side effects,” Henderson said. “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 — eg, the elderly or unwell and those with extensive extra nodal extension of tumor — radiotherapy may be considered and balanced against anticipated side effects and morbidity.” – by Anthony SanFilippo
For more information:
Michael A. Henderson, MD, FRACS, can be reached at Peter MacCallum Cancer Centre, 2 St. Andrews Pl, East Melbourne VIC 3002, Australia; email: michael.henderson@petermac.org.
Disclosure: Henderson reports no relevant financial disclosures. One other researcher reported personal fees and non-financial support from Bristol-Myers Squibb, GlaxoSmithKline and Provectus.
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