RESUMO
PURPOSE: To determine the safety of an approach to immunologically enhance local treatment of hepatocellular cancer (HCC) by combining nonlethal radiation, local regional therapy with intratumoral injection, and systemic administration of a potent Toll-like receptor (TLR) immune adjuvant. METHODS: Patients with HCC not eligible for liver transplant or surgery were subject to: 1) 3 fractions of 2-Gy focal nonlethal radiation to increase tumor antigen expression, 2) intra-/peri-tumoral (IT) injection of the TLR3 agonist, polyinosinic-polycytidylic acid polylysine carboxymethylcellulose (poly-ICLC), to induce an immunologic "danger" response in the tumor microenvironment with local regional therapy, and 3) systemic boosting of immunity with intramuscular poly-ICLC. Primary end points were safety and tolerability; secondary end points were progression-free survival (PFS) and overall survival (OS) at 6 months, 1 year, and 2 years. RESULTS: Eighteen patients with HCC not eligible for surgery or liver transplant were treated. Aside from 1 embolization-related severe adverse event, all events were ≤grade II. PFS was 66% at 6 months, 39% at 12 months, and 28% at 24 months. Overall 1-year survival was 69%, and 2-year survival 38%. In patients <60 years old, 2-year survival was 62.5% vs. 11.1% in patients aged >60 years (P<0.05). Several patients had prolonged PFS and OS. CONCLUSION: Intra-tumoral injection of the TLR3 agonist poly-ICLC in patients with HCC is safe and tolerable when combined with local nonlethal radiation and local regional treatment. Further work is in progress to evaluate if this approach improves survival compared to local regional treatment alone and characterize changes in anticancer immunity.
RESUMO
Surgical resection has had control rates of 53% to 77% in the treatment of extra-abdominal desmoid tumors. Surgical excision combined with external beam radiation therapy (EBRT) has had local control rates of up to 83% in some series. The purpose of this study was to evaluate the effectiveness of resection combined with radiotherapy (brachytherapy, EBRT, or both) in the treatment of extra-abdominal desmoid tumors. We retrospectively reviewed the charts of 24 consecutive patients (27 histologically confirmed extra-abdominal desmoid tumors). Patients were included in the study if they had a lesion that was potentially resectable with a wide margin, allowing for limb salvage, and if they did not have a contraindication to radiotherapy. Limb functioning was assessed with the Musculoskeletal Tumor Society (MSTS) scoring system. Seventeen patients (7 men, 10 women) with 19 tumors met the inclusion criteria. Mean age at diagnosis was 23.4 years. Follow-up (mean, 4.28 years) involved serial clinical examinations and magnetic resonance imaging of tumor sites. After surgery, the tumors were treated with brachytherapy (n = 6), EBRT (n = 10), or both (n = 3). Two of the 17 tumors in patients with negative margins of resection recurred locally (local control rate, 88.2%). Mean MSTS score was 29/30 (96.7%). The role of surgery, radiotherapy, chemotherapy, hormone therapy, and other treatments for extra-abdominal desmoid tumors is not well defined. When wide-margin resection and radiotherapy can be performed with limb preservation surgery, local control and complication rates compare favorably with those of other reported methods of treatment. Given the results and limitations of our study, we cannot make a definitive recommendation as to which modality--brachytherapy or EBRT--should be used in the treatment of extra-abdominal desmoid tumors.
