Long-Term Follow-Up of Oligometastases Patients Treated with Hypofractionated, Stereotactic Radiation Therapy (HSRT) on a Prospective Study

Abstract

To analyze the long-term follow up of patients treated with HSRT for oligometastases from non-breast malignancies. From 2001-2006, 82 non-breast cancer patients with 1-5 radiographically apparent metastatic lesions were enrolled on a prospective study of HSRT. The eligibility requirements included age ≥ 18 y, KPS ≥ 70, and metastases to 1-3 organ sites. Net GTV represents the sum of each lesion’s contoured GTV, and was grouped into five categories (<20, 20-40, 40-60, 60-80, and >100cc). A stereotactic x-ray was used. The PTV was generated with a volumetric GTV expansion of 10 mm in the craniocaudal direction and 7 mm in other directions, and was covered by the 80% isodose line. FFDM was defined from date of enrollment until death, an event (i.e. widespread distant metastasis not amenable to local therapy), or last radiographic study. Lesion local recurrence was scored as an event if pathologically confirmed or if increased by ≥20% using RECIST criteria. Prognostic variables were assessed using Cox regression analysis, and FFDM and OS rates were calculated using Kaplan-Meier survival analysis. The mean age was 61 ± 11 y with a male to female ratio of 46/36. The most common histologies were adenocarcinoma (61%), squamous cell carcinoma (9%), and sarcoma (9%). The most common metastatic sites were liver (50%), lung (48%), thoracic lymph nodes (18%), and bone (5%). 61 had 1 involved organ and 18 had 1 lesion treated. 50 Gy in 10 fractions (52/82 patients) was the preferred schedule. The mean and median net GTV were 32 and 55 ml respectively (range 0.3-422). Other analyzed variables included prior curative-intent local therapy (35%), previously had >5 metastatic lesions (20%), and systemic therapy at some point after diagnosis of metastatic disease (74%). The median follow-up was 1.7 y (and 13.4 y for 4 of 82 patients alive at last follow-up). Eleven patients lived >5 years, and 6 lived >10 years. The 5-year OS, FFDM, and LC rates were 13.4%, 13.6%, and 62.2%, and the 10-y OS, FFDM, and LC rates were 7.3%, 12.3%, and 61.0%, respectively. On both univariate (UV) and multivariate (MV) analysis, net GTV was the only variable significant for OS (MV p=0.034, HR 1.36). GTV also proved to be significant on UV and MV (p=0.039, HR 2.31) for lesion LC. Having more than one organ involved with metastasis was not significant on UV (p=0.49) but was significant on MV analysis (p=0.020) for local control. Analysis for FFDM showed that net GTV was not a significant factor. On MV analysis, systemic therapy during metastatic diagnosis was significantly associated with FFDM (p=0.046, HR 0.47). Select non-breast cancer patients with limited metastasis treated with HSRT are long-term survivors. Net GTV is a significant factor for tumor control and survival. By 5 years, only 1 in 8 patients treated remained free from distant metastasis. Further research is needed to help better select patients most likely to benefit from local therapy for metastatic disease.