A Prospective Investigation of Definitive Targeted Therapy for Solid Malignancies With Oligometastases

Abstract

Purpose/Objective(s): This prospective Phase II hypothesis-generating study investigated the clinical outcome after definitive localized treatment for oligometastases. Materials/Methods: Between March 2006 and March 2011, 73 consecutive patients with oligometastatic carcinoma or sarcoma (defined as 4 or less active sites of disease), Karnofsky performance status of 70, and no life-threatening comorbidities were treated on an IRB-approved prospective protocol utilizing site-appropriate definitive local treatments such as radiation therapy with BED 45 Gy, surgery, or a combination. Locoregional disease included within the same procedure was counted as 1 site. Clinical outcomes were assessed. Results: Median OS was 35.1 months. Seventy-three patients with 113 definitively treated sites were evaluated. The median follow-up for survivors from first definitive treatment to most recent follow-up was 19.0 months (range 8.6-74.3). Thirteen patients were treated at initial presentation, 10 patients were recurrent with < 1 year disease-free interval, and 50 patients were recurrent with 1 year disease-free interval. Among the recurrent patients, median time from original diagnosis to beginning protocol treatment was 36.1 months. The primary cancer diagnoses were as follows: 17 breast, 17 colorectal, 15 lung, and 24 other (including 6 prostate, 4 melanoma, 2 esophageal, 2 renal, and 2 bladder). Forty patients received systemic therapy prior to protocol treatment. Sixty-five patients had 1-2 sites of active disease, and 8 patients had 3-4 sites of active disease. Sites of metastatic or recurrent disease were distributed as follows: 20 lung, 19 bone, 17 liver, 16 primary site, 13 regional lymph nodes, 11 distant lymph nodes, 5 brain, and 12 other. Of the 113 treated sites, 41 were treated with SBRT, 2 with SRS, 37 with conventionally fractionated EBRT, 15 with yttrium 90 spheres, 5 with surgery alone, and 13 with 2 or more targeted modalities (including 10 with surgery and EBRT). The pattern of first failure was as follows: 16 within targeted treatment volumes only, 8 progressed both within and outside the targeted treatment volumes, 30 progressed only outside of targeted treatment volumes, and 19 remain progression-free. Of the 113 sites treated, local control was 71% at last follow-up with 27 progressing within the treatment volumes at the time of first failure, and 6 additional sites subsequent to first failure. Twenty-three patients had died from their disease at the time of the data analysis. Kaplan-Meier estimated 1 and 2 year LC were 76.1% and 66.7%; PFS were 35.8% and 23.9%; CSS were 83.0% and 65.9%; and OS were 79.3% and 60.0%. Conclusions: Definitive treatment of oligometastases in a prospective, broadly identified population resulted in favorable LC, PFS, and OS, warranting further investigation. Author Disclosure: R.Y. Lei: None. S.P. Fryman: None. A.L. White: None. W.E. Daniel: None. A.G. Antell: None. M. Patel: None. D.L. Carter: None.