Tobin Strom, MD

Javier F. Torres-Roca, MD

Louis B. Harrison, MD

IN A LARGE single-institution study reported in the Journal of the National Comprehensive Cancer Network, Tobin Strom, MD, and colleagues found that regional radiotherapy was associated with a reduced risk of regional recurrence in patients with node-positive cutaneous melanoma, including those with extracapsular extension or clinically detected nodal disease.¹ 

Dr. Strom and Javier F. Torres-Roca, MD, of the Department of Radiation Oncology at Moffitt Cancer Center, are the co–first authors of the published report. Louis B. Harrison, MD, also of Moffitt Cancer Center, is the corresponding author of the article. 

Study Details 

THE STUDY WAS A RETROSPECTIVE REVIEW of data from 699 patients at Moffitt Cancer Center, Tampa, Florida, diagnosed from 1998 through 2015 with node-positive cutaneous melanoma but no distant metastatic disease. After excluding patients with initial management of node-positive disease at outside institutions, satellite or in-transit metastasis only, unknown recurrence status, unclear treatment records, or < 12 months follow-up from the time of lymph node dissection, 410 patients remained in the analysis set. 

All 410 patients had American Joint Committee on Cancer (AJCC) stage III melanoma (any T, N1–3, M0) and no clinical, radiologic, or pathologic evidence of metastasis beyond the regional lymph nodes. Patients without a known primary (T0, N1b–3, M0) were included. 

The primary objectives of the study were to identify risk factors associated with regional recurrence and to determine whether a radiosensitivity index gene-expression signature could identify patients with a survival benefit associated with regional radiotherapy. 

Patients had a median age of 59 years, 67% were male, 39% had T3 and 33% T4 primary tumors, 57% had involved axillary lymph nodes, 57% had involved lymph nodes found on sentinel lymph node biopsy (AJCC N1a/N2a), and 66% had no extracapsular extension of involved lymph nodes. 

“Regional radiotherapy was associated with a reduced risk of regional recurrence among patients with [extracapsular extension] and clinically detected nodal disease.”

— Tobin Strom, MD; Javier F. Torres-Roca, MD; and colleagues

Tweet this quote

Patients received sentinel lymph node biopsy alone (n = 49) or followed by completion lymph node dissection (n = 270) or therapeutic lymph node dissection (n = 91). Most patients with a known primary received a wide excision with a 2-cm margin and a minimum margin of 1 cm in the head and neck. 

Postoperative regional radiotherapy to the involved nodal basin was administered to 83 patients (20.2%) at a median dose of 54 Gy (range = 30–60 Gy) in 27 fractions (range = 5–30). Receipt of regional radiotherapy was significantly more common in patients who were older, male, and had AJCC T4 and T0 primary tumors, head and neck primary tumors, more examined and involved nodes, AJCC N3 nodal disease, extracapsular extension, and larger nodes. Adjuvant therapy was received by 40% of patients not receiving radiotherapy and 38% of those receiving radiotherapy. 

A total of 42 patients (10%) had tumor samples available for gene-expression profiling (begun in 2006) to determine radiosensitivity index gene-expression signature. 

Impact of Regional Radiotherapy 

MEDIAN FOLLOW-UP was 69 months (range = 13–180 months). In total, 50 of 410 patients (12.2%) experienced a first recurrence in the regional lymph node basin, with the median time to regional failure of 11 months (range = 2–42 months). On univariate analysis, regional radiotherapy was associated with a reduced 5-year risk of regional recurrence vs no radiotherapy (P = .036), with regional control rates of 96.3% vs 91.7%, 95.0% vs 87.4%, and 95.0% vs 83.3% at 1, 2, and 5 years. 

On multivariate analysis, regional radiotherapy was an independent predictor of reduced risk for regional recurrence at 5 years (hazard ratio [HR] = 0.15, P < .001). Variables associated with an increased risk of regional recurrence included clinically detected lymph nodes (HR = 2.40, P = .004) and extracapsular extension (HR = 2.17, P =.01). In a subset analysis, regional radiotherapy was associated with a significantly reduced 5-year risk of regional recurrence among 175 patients with AJCC nodal N1b/N2b/N3 disease (1-, 2-, and 5-year control rates of 95.7% vs 85.3%, 94.1% vs 79.1%, and 94.1% vs 69.5%; P = .003) and among 141 with extracapsular extension (1-, 2-, and 5-year control rates of 98.4% vs 82.3%, 96.7% vs 75.5%, and 96.7% vs 62.2%; P < .001). 

Radiosensitivity Index 

IN THE SUBSET of 42 patients with radiosensitivity index gene-expression signature data, median radiosensitivity index gene-expression signature values were similar between 11 patients who received regional radiotherapy and 31 who did not (0.489 vs 0.476). A low radiosensitivity index score indicates a more sensitive tumor, whereas a high score indicates a less sensitive, more resistant tumor. Radiosensitivity index–low tumors were defined as those with a radiosensitivity index gene-expression signature < 0.3745 and radiosensitivity index–high tumors as those with a radiosensitivity index gene-expression signature ≥ 0.3745. 

Among patients receiving regional radiotherapy, overall survival was significantly better among the four with radiosensitivity index– low tumors vs seven with radiosensitivity index–high tumors, with 1-, 2-, and 5-year estimated survival rates of 100% vs 85.7%, 100% vs 14.3%, and 75.0% vs 0%; HR = 10.68, P = .009). Among the 33 who did not receive regional radiotherapy, there were no significant differences in survival rates for 12 with radiosensitivity index–low vs 19 with radiosensitivity index–high status, with 1-, 2-, and 5-year survival rates of 100% vs 84.2%, 91.7% vs 63.2%, and 56.3% vs 27.1% (P = .19). 

The investigators concluded: “Regional radiotherapy was associated with a reduced risk of regional recurrence among patients with [extracapsular extension] and clinically detected nodal disease. Gene expression data show promise for better predicting radiocurable patients in the future. In the era of increasingly effective systemic therapies, the value of improved regional control potentially takes on greater significance.” ■

DISCLOSURE: The study was supported in part by the DeBartolo Family’s contributions to the Total Cancer Care Initiative at the Moffitt Cancer Center. For full disclosures of the study authors, visit www.jnccn.org. 

REFERENCE 

1. Strom T, et al: Regional radiation therapy impacts outcome for node-positive cutaneous melanoma. J Natl Compr Canc Netw 15:473-482, 2017.