Adjuvant radiation following surgery for soft-tissue sarcomas of the extremities did not lead to a survival benefit and seemed to be associated with some degree of long-term limb complications, according to a presentation at the 2014 Society of Surgical Oncology (SSO) Cancer Symposium in Phoenix.1
Follow-up data from a 146-patient trial that compared limb-sparing surgery alone vs surgery plus adjuvant external-beam radiation showed a 20-year survival rate of 64% (95% confidence interval [CI] = 52%–75%) for patients who received surgery alone and 71% (95 CI = 59%–81%) for patients who underwent the combination therapy (P = .22), reported Joal Beane, MD, of the National Cancer Institute in Bethesda, Maryland, and colleagues.
Uncertain Link
“The ability of radiation therapy to improve local control following surgery has made it a cornerstone in the multimodality treatment of common cancers, like primary breast and rectal cancer. However, the link between improved local control and overall survival remains uncertain,” Dr. Beane said.
Despite its widespread use in soft-tissue sarcoma of the extremity, the pairing of radiation and surgery has never turned in exceptional results for survival. For instance, in a 1982 prospective study that compared limb-sparing surgery plus external-beam radiation therapy to amputation, disease-free survival and overall survival were similar between the two study arms.2
Dr. Beane’s group evaluated long-term data from a 1983–1991 trial that reported better local control with limb-sparing surgery and external-beam radiation therapy vs surgery alone, but still no differences in survival outcomes.3 The limited data available on long-term impact of radiation therapy on limb function may offset the modality’s benefit in local control, Dr. Beane explained.
Study Details
In the original trial, the external-beam radiation therapy protocol consisted of 4,500 cGy delivered to a wide field, 1,800-cGy boost to the tumor bed, and 180-cGy fractions given 5 days a week for 6 to 7 weeks. Patients with high-grade soft-tissue sarcomas also received concurrent adjuvant chemotherapy with doxorubicin and cyclophosphamide.
Dr. Beane’s group analyzed patient-reported quality of life using a phone-based questionnaire that included queries on severity of pain, need for pain medication more than three times a week, need for wound care, degree of limb edema, and impact of limb disability.
Since the original publication of the trial results in 1998, 55 patients died, 76 were confirmed living, and 19 were lost to follow-up. The overall median follow-up time was 17.9 years for both study arms.
The lack of a survival benefit with radiation in the overall study was also true when patients with high-grade and low-grade lesions were considered separately (P = .59 and .14, respectively).
Quality of Life
With regard to quality of life, among the 76 patients who were confirmed living, 54 completed the phone interviews. Results for variables related to pain favored limb-sparing surgery alone, but did not reach statistical significance when compared with dual-modality treatment.
The majority of patients in either group did not require any wound care (79% for surgery alone and 73% for surgery plus radiotherapy). However, one patient in the surgery group had a pathologic fracture and required three orthopedic surgeries to correct the problem, while two patients in the combination treatment group required amputation.
One amputation was secondary to nonunion of a pathologic fracture and the other was due to chronic wound complications and osteomyelitis, Dr. Beane stated.
In terms of limb edema, most patients in the two study arms did not require treatment (63% and 50%), although two patients in the external-beam radiation group did need to be hospitalized for treatment of limb edema (P = .21).
Most patients in both groups had no deficits in their limbs from the treatment regimens (85% and 88%,
P = .84). While the majority of patients did not suffer from long-term limb complications, Dr. Beane emphasized that “the use of adjuvant therapy should be selective in patients with a low risk of recurrence.”
Practicing-Changing?
Dr. Beane noted that the study had many limitations including the small sample size and the fact that it was a retrospective analysis of limb function. In addition, the authors did not look at the effect of chemotherapy on long-term complications.
Finally, the study was done before the advent of three-dimensional radiation therapy and intensity-modulated radiation therapy. Both modalities require more complex planning, which could lead to improvements in outcomes.
SSO Plenary Session moderator Ronald J. Weigel, MD, PhD, of the Unviersity of Iowa Carver College of Medicine, asked how the results would apply in clinical practice, given that radiation therapy in these patients is now standard.
“I don’t think [radiation] treatment should be withheld,” Dr. Beane replied. “I think we need to be critical about when it’s administered, using some of the nonograms … that predict the 3- and 5-year local recurrence in patients who don’t have external-beam radiation therapy. I think [with this study], we are trying to highlight that these [tools] should be used more frequently to better select patients who would benefit from radiation therapy.” ■
Disclosure: Dr. Beane reported no potential conflicts of interest.
References
1. Beane JD, Yang JC, White D, et al: Efficacy of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity: 20-year follow-up of a randomized prospective trial. 2014 SSO Cancer Symposium. Abstract 4. Presented March 14, 2014.
2. Rosenberg SA, Tepper J, Glatstein E, et al: The treatment of soft-tissue sarcomas of the extremities: Prospective randomized evaluations of (1) limb-sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy. Ann Surg 196:305-315, 1982.
3. Yang JC, Chang AE, Baker AR, et al: Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas
of the extremity. J Clin Oncol 16:197-203, 1998.
