LTX-315 is an oncolytic peptide that elicits both local and systemic immune responses upon intratumoral injection. In the present pilot trial, we treated patients with metastatic soft tissue sarcoma with the combination of LTX-315 and adoptive T-cell therapy using in vitro expanded tumor-infiltrating lymphocytes. Six heavily pretreated patients were included in the trial and treated with LTX-315 of which four patients proceeded to adoptive T-cell therapy. Overall, the treatment was considered safe with only expected and manageable toxicity. The best overall clinical response was stable disease for 208 days, and in this patient, we detected tumor-reactive T cells in the blood that lasted until disease progression. In three patients T-cell reactivity against in silico predicted neoantigens was demonstrated. Additionally, de novo T-cell clones were generated and expanded in the blood following LTX-315 injections. In conclusion, this pilot study provides proof that it is feasible to combine LTX-315 and adoptive T-cell therapy, and that this treatment can induce systemic immune responses that resulted in stabilization of the disease in sarcoma patients with otherwise progressive disease. Further optimization of the treatment protocol is warranted to increase clinical activity. ClinicalTrials.gov Identifier: NCT03725605

Patients suffering from a pathological fracture or painful bony lesion because of metastatic bone disease often benefit from a total joint replacement. However, these are large operations in patients who are often weak. We examined the patient survival and complication rates after total joint replacement as the treatment for bone metastasis or hematological diseases of the extremities. 130 patients (mean age 64 (30-85) years, 76 females) received 140 joint replacements due to skeletal metastases (n = 114) or hematological disease (n = 16) during the period 2003-2008. 21 replaced joints were located in the upper extremities and 119 in the lower extremities. Clinical and survival data were extracted from patient files and various registers. The probability of patient survival was 51% (95% CI: 42-59) after 6 months, 39% (CI: 31-48) after 12 months, and 29% (CI: 21-37) after 24 months. The following surgical complications were seen (8 of which led to additional surgery): 2-5 hip dislocations (n = 8), deep infection (n = 3), peroneal palsy (n = 2), a shoulder prosthesis penetrating the skin (n = 1), and disassembly of an elbow prosthesis (n = 1). The probability of avoiding all kinds of surgery related to the implanted prosthesis was 94% (CI: 89-99) after 1 year and 92% (CI: 85-98) after 2 years. Joint replacement operations because of metastatic bone disease do not appear to have given a poorer rate of patient survival than other types of surgical treatment, and the reoperation rate was low.

Purpose. To assess the metastatic pattern of the histological subtype myxoid liposarcoma (MLS) with no or few round cells.Methods. Forty-five patients (F/M = 27/18, mean age 49 (range 17–85) years) were diagnosed with MLS at two Danish sarcoma centres in the period 1995–2004. A retrospective review of patients' files combined with an extraction of survival data from the Danish Centralised Civil Register was performed.Results. Seven patients had distant metastases during the observation period. Two patients had metastases at the time of diagnosis, while metastases occurred within 2.5 years in four patients, and in one patient 11.9 years after primary diagnosis. All metastases occurred at extrapulmonary sites. The first local relapse occurred within 3 years after surgery in six patients, in one patient after 4.0 years, and in one patient 7.7 years after surgery. The 5- and 10-year overall survival was 80% and 69%, respectively. Both the 5- and 10-year distant metastases-free survival was, respectively, 86%. The 5- and 10-year local relapse-free survival was, respectively, 83% and 80%.Conclusions. Patients with MLS had only extra-pulmonary metastases, and no lung metastases were found. Most local relapses and distant metastases occurred within the first 2-3 years after surgery.

To assess the prognostic value of primary tumor metabolic activity in patients with high-grade bone sarcomas (BS) or soft tissue sarcomas (STS) using F-18 FDG PET/CT. A single-site, retrospective study including 92 patients with high-grade BS or STS. Pretreatment F-18 FDG PET/CT scan was performed. Clinical data were registered. Accuracy of maximum standardized uptake value of primary tumor (SUVmax) and tumor-to-background (T/B) uptake ratio as prognostic variables and identification of cut-off values to group patients were determined. Kaplan-Meier survival estimates and log-rank test were used to compare survival distributions. Prognostic variables were assessed using Cox proportional hazards regression analysis. Forty-one of 92 patients died during follow-up (45%). Average survival was 6.5 years (95% CI 5.8-7.3 years) and probability of 5-year survival was 52%. Accuracy of SUVmax and T/B uptake ratio as prognostic variables in all patients and during subgroup analysis of patients with STS was significant. No significant results for AUCs were registered in patients with BS. Surgery was independently prognostic for survival throughout multivariate regression analysis of all patients (P = 0.001, HR 3.84) and subgroup analysis (BS: P = 0.02, HR 11.62; STS: P = 0.005, HR 4.13). SUVmax was significant as prognostic variable in all patients (P = 0.02, HR 3.66) and in patients with STS (P = 0.007, HR 3.75). No significant results were demonstrated for T/B uptake ratio. Estimation of primary tumor metabolic activity with pretherapeutic SUVmax using F-18 FDG PET/CT demonstrates independent properties beyond histologic grading for prediction of survival in patients with high-grade STS, but not with high-grade BS.