Osteosarcoma is the most common malignant bone tumour in children and young people. Approximately 40% patients respond poorly to highly toxic preoperative MAP (methotrexate adriamycin, cisplatin) chemotherapy with consequent inferior survival. The role of genetic polymorphisms in drug response and toxicity is reported in acute leukaemia and some solid tumours. Recent evidence in osteosarcoma suggests increased chemotherapy toxicity is associated with improved survival. The aim of this pilot study is to investigate the influence of drug target and metabolising gene polymorphisms on tumour response and chemotherapy toxicity in osteosarcoma.

Patients who have completed MAP chemotherapy are eligible. Chemotherapy toxicity (CTCAE grade) is collected from patient records. Tumour response is graded as good (> 90% necrosis) or poor (< 90% necrosis) in resection specimen. Peripheral blood DNA is typed for genome-wide single nucleotide polymorphisms (SNP) using the Illumina 610 Quad array and analysed using Bead Studio software. Standard PCR techniques are used to genotype the Thymidylate synthase (TS) gene (folate pathway) for the presence of 2 or 3 copies of a 28 base pair repeat (2R/3R) and a G/C SNP in the 3R allele.

52 patients have entered to date: 33 good responders, 12 poor and 7 unevaluable for response. Median age 18 years (range 10–51), males:females 1.3:1. Median follow up is 39 months (range 2–76) with 11 patients relapsing. 23 patients have TS genotype 2R/2R, nineteen 2R/3R, six 3R/3R, three 2R/4R and one 2R/7R. Neither TS repeat or G/C SNP genotype correlated with histological response or degree of methotrexate stomatitis. Interestingly, presence of the 2R allele was significantly related to relapse (p=0.01) but may reflect small patient numbers. Recurrent methotrexate stomatitis (> 2 episodes of CTCAE grade 2) was weakly correlated with no relapse (p=0.07). Analysis of SNP array data with emphasis on MAP pathway polymorphisms will be presented when complete.

Purpose: We report a series of patients with malignant tumours of the pelvis that had a tissue expander inserted in the pelvis to facilitate radical radiotherapy, and report functional outcomes following treatment.

Introduction: Surgery for malignant tumours affecting the pelvis is challenging. Some tumours are suitable for internal hemipelvectomy and reconstruction, some require hindquarter amputation and some are inoperable. Overall prognosis is poor with high morbidity and mortality rates. There may be a place for alternative treatment with the insertion of pelvic spacers to facilitate radical radiotherapy. This is indicated in patients who have an inoperable tumour, who decline amputation, or who had an internal hemipelvectomy with close margins and high risk of local recurrence.

Methods & Results: We performed a retrospective review of all patients who presented with a malignant tumour of the pelvis and who underwent an insertion of a pelvic spacer followed by local high dose radiotherapy. Available patients were followed up and evaluated using the Musculoskeletal Society Tumour Score (MSTS) and the Toronto Extremity Salvage Score (TESS). There were ten patients; 5 had Ewing’s sarcoma, 3 had osteosarcoma, 1 had spindle cell sarcoma and 1 had alveolar soft part sarcoma. 4 patients had metastases on presentation. The average age was 30 years (14 to 56 years), and average follow-up was 15 months (12 to 24 months). 4 patients died and 6 are still alive. There were no surgical complications. The average length of hospital stay was 6 days (2 to 10 days). Patients averaged an MSTS score of 63% and a TESS of 67%.

Conclusion: Radical radiotherapy after spacer insertion offers an alternative to morbid surgery and is associated with good functional outcomes.