Inoperable or incompletely resected craniofacial osteosarcoma treated by particle radiotherapy.

Background: To report survival of craniofacial osteosarcoma patients treated by particle radiotherapy. Methods: Between January 2010 and December 2021, 51 patients with primary (N = 35) or recurrent (N = 16) inoperable or incompletely resected craniofacial osteosarcoma were treated. In most cases, intracranial infiltration (59%) and macroscopic tumor on MRI/CT (75%) were present. Thirteen had a secondary osteosarcoma (25%). Treatment concepts included combined ion beam radiotherapy (CIBRT, N = 18), protons only (N = 3), carbon ions only (N = 12), IMRT with a carbon ion boost (N = 5), and carbon ion re-irradiation (N = 13). Eighty percent (N = 41) received additionally chemotherapy, most frequently EURAMOS-1 (47%) or EURO-B.O.S.S. (18%). Results: The median age was 38, and all patients finished treatment predominantly as outpatients (N = 44). Information on overall survival was available for N = 49 patients. The median follow-up of the survivors was 55 months. For the whole cohort 1-, 2-, 3-, and 5-year overall survival (OS) was 82.8%, 60.4%, 55.2%, and 51.7%, respectively. Those treated by CIBRT (N = 17) demonstrated a superior OS with 92.9% after 1 and 2 years and 83.6% after 3 and 5 years. The median clinical target volume (CTV) was 192.7 and 95.2 cc for the primary and boost plan, respectively. CIBRT, primary diagnosis, age ≤40a, and no macroscopic residual tumor were associated with improved survival in univariate analysis (p = 0.006, p = 0.004, p = 0.002, p = 0.026, respectively), while any foregoing resection compared to biopsy was not identified as a prognostic factor. CIBRT and no macroscopic residual tumor were confirmed as independent predictors of OS on multivariate analysis (HR = 0.107, 95% CI = [0.014, 0.797], p = 0.029 and HR = 0.130, 95% CI = [0.023, 0.724], p = 0.020, respectively). No acute toxicity > grade III was observed. Conclusion: CIBRT shows promising results for patients with inoperable or incompletely resected craniofacial osteosarcoma.

Synergistic effects of dendritic cell targeting and laser-microporation on enhancing epicutaneous skin vaccination efficacy.

Due to its unique immunological properties, the skin is an attractive target tissue for allergen-specific immunotherapy. In our current work, we combined a dendritic cell targeting approach with epicutaneous immunization using an ablative fractional laser to generate defined micropores in the upper layers of the skin. By coupling the major birch pollen allergen Bet v 1 to mannan from S. cerevisiae via mild periodate oxidation we generated hypoallergenic Bet-mannan neoglycoconjugates, which efficiently targeted CD14+ dendritic cells and Langerhans cells in human skin explants. Mannan conjugation resulted in sustained release from the skin and retention in secondary lymphoid organs, whereas unconjugated antigen showed fast renal clearance. In a mouse model, Bet-mannan neoglycoconjugates applied via laser-microporated skin synergistically elicited potent humoral and cellular immune responses, superior to intradermal injection. The induced antibody responses displayed IgE-blocking capacity, highlighting the therapeutic potential of the approach. Moreover, application via micropores, but not by intradermal injection, resulted in a mixed TH1/TH17-biased immune response. Our data clearly show that applying mannan-neoglycoconjugates to an organ rich in dendritic cells using laser-microporation is superior to intradermal injection. Due to their low IgE binding capacity and biodegradability, mannan neoglycoconjugates therefore represent an attractive formulation for allergen-specific epicutaneous immunotherapy.

Long-term outcome of total knee replacement in patients with rheumatoid arthritis.

OBJECTIVES: We analysed the long-term clinical and radiological results of 68 consecutive total knee replacements in 50 patients with rheumatoid arthritis. METHODS: At a mean follow-up of 11.2+/-1.2 years (range, 9.7-13.7) all revisions were included. Thirty-seven knees in 28 patients still alive were followed retrospectively clinically and radiologically, all other patients who died without revision were censored at time of the last clinical follow-up and no patient was lost to follow-up. Revision was necessary in 13 knees (19%, one revised twice), including an overall deep infection rate of 1.47%. RESULTS: The survival rate was 81.6+/-0.05% at 12 years with any revision or removal of the prosthesis as an end point. There was no significant difference in survival between cemented, uncemented or hybrid fixation (log rank, 0.2544). The average Knee Society Scores were 77.2 points clinical (range, 40-95 points) and 75.3 points functional (range, 30-100 points), respectively, at final follow-up. The body mass index (BMI) was 25.9 at surgery and 25.3 at follow-up (n.s.). There was no correlation between BMI, age, side, gender and revision frequency. No arthroplasty was at risk for removal or revision at follow-up. CONCLUSIONS: The study shows good 10-12-year clinical and radiological results for the PCA knee replacement in patients with rheumatoid arthritis without preference for the method of fixation or patient weight.