Clinical outcomes of melanoma brain metastases treated with stereotactic radiation and anti-PD-1 therapy.

BACKGROUND: The anti-programmed death-1 (anti-PD-1) therapy nivolumab has significant clinical activity in patients with metastatic melanoma. However, little is known about the safety and outcomes in patients receiving anti-PD-1 therapy and stereotactic radiation for the treatment of brain metastases (BMs). PATIENTS AND METHODS: Data were analyzed retrospectively from two prospective nivolumab protocols enrolling 160 patients with advanced resected and unresectable melanoma at a single institution. Patients were included if BMs were diagnosed and treated with stereotactic radiation within 6 months of receiving nivolumab. The primary end point of this study was neurotoxicity; secondary end points included BM control and survival. RESULTS: Twenty-six patients with a total of 73 BMs treated over 30 sessions were identified. Radiation was administered before, during and after nivolumab in 33 lesions (45%), 5 lesions (7%), and 35 lesions (48%), respectively. All BMs were treated with stereotactic radiosurgery (SRS) in a single session except 12 BMs treated with fractionated stereotactic radiation therapy, nine of which were in the postoperative setting. One patient experienced grade 2 headaches following SRS with symptomatic relief with steroid treatment. No other treatment-related neurologic toxicities or scalp reactions were reported. Eight (11%) local BM failures with a ≥20% increase in volume were noted. Of these lesions, hemorrhage was noted in 4, and edema was noted in 7. Kaplan-Meier estimates for local BM control following radiation at 6 and 12 months were 91% and 85%, respectively. Median overall survival (OS) from the date of stereotactic radiation and nivolumab initiation was 11.8 and 12.0 months, respectively, in patients receiving nivolumab for unresected disease (median OS was not reached in patients treated in the resected setting). CONCLUSIONS: In our series, stereotactic radiation to melanoma BMs is well tolerated in patients who received nivolumab. BM control and OS appear prolonged compared with standard current treatment. Prospective evaluation is warranted.

Beyond the conventional role of external-beam radiation therapy for skeletal metastases: new technologies and stereotactic directions.

BACKGROUND: Radiation therapy is a common and effective treatment modality in the management of skeletal metastases. Recent advances in technology permitting delivery of an ablative radiation dose with an image-guided stereotactic approach improve the therapeutic threshold. METHODS: The authors reviewed the literature on conventional external-beam radiation therapy and summarized the emerging data about image-guided stereotactic body radiation therapy (SBRT) for vertebral oligometastasis. RESULTS: Pain control can be achieved effectively with conventional external-beam radiation therapy and may be further improved with image-guided spinal SBRT. Image-guided SBRT allows delivery of an ablative radiation dose with minimal toxicity, may potentially improve local tumor control, and may enhance clinical outcomes for histologies that are considered radioresistant. However, further understanding of long-term normal tissue toxicity is lacking. CONCLUSIONS: Radiotherapy options are expanding for patients with skeletal metastases. Image-guided spinal SBRT can deliver a safe ablative radiation dose to improve pain control and potentially local tumor control. Randomized clinical trials are ongoing to assess clinical benefits and outcome with spinal SBRT.

Overview of diagnosis and management of metastatic disease to bone.

BACKGROUND: Bone metastases occur frequently in patients with advanced cancer and are a serious complication of cancer. The decision to treat is often individualized, based on each patient's clinical presentation, life expectancy, and quality of life. METHODS: We reviewed the current literature pertaining to management of metastatic disease to bone, and the medical, radiotherapeutic, and surgical treatment options for management of bone metastasis are discussed. RESULTS: Current management of skeletal metastasis includes analgesia, systemic therapy, radiation therapy, and surgery. We propose treatment algorithms for management of vertebral and nonvertebral bone metastases and suggest individualized interventions based on clinical presentation. CONCLUSIONS: Management of bone metastases is complex and requires a multidisciplinary approach. The goal of treatment is often palliative, and intervention and treatment regimens should be individualized based on the specific clinical presentation of each patient.

Long-term follow-up of Dupuytren disease after injection of triamcinolone acetonide in Chinese patients in Taiwan.

Injection of triamcinolone acetonide is a non-operative treatment for early-stage Dupuytren disease in Caucasians, but its effectiveness in non-Caucasians is unclear. We report averaged 5-year follow-up results of 37 patients (49 affected hands) with early-stage Dupuytren disease for patients in Taiwan (non-Caucasian) who received a single dose of 5 mg triamcinolone acetonide injection into nodules monthly for 3 months. Using ultrasound, we recorded no progression of sizes of the modules following injection after 6 months. After an average 5-year follow-up, two patients with three hands (6%) experienced reactivation of the treated nodules. None required surgical intervention. Ultrasound examination showed that sizes of the treated Dupuytren nodules decreased significantly by 40% 6 months after injection and 56% at the final follow-up. We conclude that in these Chinese patients in Taiwan with early Dupuytren nodules, triamcinolone acetonide injection was effective in reducing the size of the Dupuytren nodules and maintaining long-term durable control of the nodular growth. LEVEL OF EVIDENCE: III.