We attempted to investigate the incidence, the treatment modalities used and the outcome of Osteosarcoma (OS) patients treated at the two major Pediatric Oncology Hospitals in Singapore. A comprehensive list of patients with OS treated at the National University Hospital and KK Women’s and Children’s Hospital Singapore between April 1980 and May 2006 was generated. During the study interval, patients received neoadjuvant chemotherapy followed by definitive surgery consisting of either limb salvage or amputation followed by adjuvant chemotherapy. Chemotherapy was as per the European Osteosarcoma Intergroup (EOI) and as per the Memorial Sloan-Kettering Cancer Center’s (MSKCC) T12 protocols. Treatment of subsequent relapses consisted of various combinations of Methotrexate, ifosfamide, etoposide, other, and/or surgery.

Of the total 49 patients with OS, 30% presented with metastatic OS. Median age of diagnosis of OS was 12.4 years. For the cohort, two and five-year overall survival were 71% and 55% respectively. The two-year overall survival was 73% for patients who were treated as per the MSKCC protocol. At last follow-up, median 4.3 years (range, 0.3 – 21.6 years), 25 were alive with no evidence of disease and 16 were dead of disease.

Survival from OS in Singapore appears to be improving. Rarity and complexity of OS makes it crucial for patients to seek a centralized multi-disciplinary Musculoskeletal Oncology team involving surgeons and Pediatric Oncologists dedicated to the care of these young patients with the intent to cure.

Childhood long-term survivors now experience significant late effects from the primary cancer itself or from therapy. Cisplatin, an alkylating agent used in treatment for osteosarcoma, has been associated with irreversible high-frequency sensorineural hearing loss. There were 27 osteosarcoma patients treated at Department of Pediatrics, National University Hospital from 1997 to 2005. Twelve of these were long-term survivors, i.e. survived more than 2 years from initial diagnosis.

Pre-chemotherapy audiogram was performed in 50% (n=6) of patients and the audiogram results were not available in the remainder (n=6, 50%) as it was either not done or records were not available. Prior to year 2003, Cisplatin was administered at a dose of 100mg/ m2/course (EOI regimen) in 50% of cases, and after year 2003, 120mg/m2/course (T12 regimen) in 45%. Median cumulative dose of cisplatin was 550mg/m2 (cumulative dose range, 240 – 800 mg/m2). Out of 12 patients, 7 patients (58%) experienced cisplatin induced ototoxicity. According to NCI Toxicity Criteria, Grade I ototoxicty was observed in two cases (30%), grade 2 toxicity in five cases (70%), and bilateral sensorineural hearing loss was noted in six of the survivors. One long term survivor required a hearing aid. Six of them had and renal tubulopathy (NCI Toxicity Grade 2) was noted simultaneously in 35% of cases (n=4).

The incidence of cisplatin induced ototoxicity is high in our small series of long-term survivors of osteosarcoma. Baseline pre-chemotherapy testing, close monitoring during treatment and further follow-up are essential for this subset of patients receiving high doses of cisplatin.

The study was funded by Singapore Cancer Syndicate (POU-097)

Childhood cancer survival has increased dramatically over the last 30 years. Childhood Cancer Survivor Study- SG was established to evaluate the outcome and toxicities experienced by long term childhood cancer survivors in Singapore. There were 429 cases of hematological malignancies (HM) and 342 cases of solid tumors (ST) diagnosed and treated at National University Hospital (NUH) Singapore from May 1981 to December 2007.

There were seven long term survivors for Osteosarcoma (OS) out of 26 patients seen during the study period. Median age at diagnosis was 13.8 (range, 6.4–15.8 years) and median follow-up was 7.9 (range, 2.6 – 13.2 years). Cumulative doses of chemotherapy received included: cisplatin (240 – 800 mg/m2); doxorubicin 150 – 450 mg/m2); methotrexate (16 – 144 Grams/m2); ifosfamide (27–80 mg/m2); and etoposide (1000 – 3300 mg/ m2). According to the NCI Criteria for Toxicity (CTC version 2.0), three patients experiences grade 2 sensorineural hearing loss; three cases of grade 1 cardiomyopathy; three cases of grade 1 renal tubulopathy; and six cases of post surgical complications (infection-3, length discrepancy-3, poor fitting prosthesis-2).

Many of the patients did not have baseline pre-treatment evaluations such as audiograms, renal function, echocardiograms and similar proportion were not adequately followed-up post treatment. This is the first analysis and report in the country on treatment related outcome and toxicity in long-term survivors of childhood cancers such as osteosarcoma and other solid tumors. Authors recommend that future treatment protocols for childhood cancer in Singapore should incorporate pre- and post-treatment evaluations and close follow-up of young survivors with establishment of a multi-disciplinary late effects clinic.

Ten adults were studied two to seven years after resection of a fibula for use as a free vascularised bone graft. Six had no symptoms in the donor leg, four had some aching, weakness or paraesthesia and three had definite weakness of the long toe flexors and extensors. All knees and ankles were clinically and radiologically stable, but the distal fibular remnant was osteoporotic in nine patients. Gait analysis of the donor leg and the contralateral normal leg showed definite differences, which could be attributed to weakness of the deep muscles caused by loss of their normal origin and to the change in load transmission through the fibula.

Seven patients with segmental defects of both bones of the forearm had reconstruction operations using a vascularised fibular graft to bridge the radius. Reasonable forearm rotation was preserved with full elbow movements and satisfactory hand function.

We describe a new method of reconstruction after resection of tumours of the proximal tibia by grafting and arthrodesis of the knee. Two separate vascularised bone grafts from the ipsilateral limb were used, one a gastrocnemius-pedicled femoral graft and the other a pedicled fibular graft. An anatomical study of the gastrocnemius-pedicled femoral graft was made. The method was shown to be practical and reproducible. One patient with osteosarcoma has a successful result with no recurrence at two-and-a-half years.

Three women with osteoarthritis of the knee presented after sudden worsening of their symptoms. In each case this was found to be due to a stress fracture of the tibia. With treatment by rest and reduced activity, the fracture healed uneventfully in all three patients.

Five cases of congenital pseudarthrosis of the tibia successfully treated by a free vascularised fibular graft are described. Follow-up ranged from 5 to 34 months with a mean of 17.5 months. The technique, which includes radical excision of abnormal bone and soft tissue around the pseudarthrosis, also permits primary bone lengthening, and correction of deformity. The early results indicate that satisfactory bony union is achieved in a relatively short period of time.

An operation is described in which a microvascular technique was used to transfer a living fibula, with its vascular pedicle intact, to replace the lower end of the radius after massive resection for giant-cell tumour. Angiography carried out six weeks later showed that the grafted bone was viable. Six months after operation the transplanted fibula showed no osteoporosis or bone resorption and bony union at the junction of host and graft.