Only few patients with osteosarcoma relapse with solitary skeletal lesions as only sign of recurrence. We used the COSS database to learn more about these rare occurrences.

This report covers all patients with high-grade osteosarcoma of the limbs or axial skeleton registered into the COSS database between 1980 and 2003 who developed 1st recurrences as solitary osseous lesions distant from the primary tumour before 01/2005. Patient-, tumour-, and treatment-related variables and outcomes were evaluated.

38 patients (27 male, 11 female) developed solitary osseous recurrences a median of 2.1 years (range:.5 – 14.3) from primary diagnosis. Primary sites had been limbs in 36 and axial in 2, relapses involved axial sites (24), limbs (10), or craniofacial bones (4). Treatment for osseous recurrence included surgery in 28 patients, radiotherapy in 10, and chemotherapy in 27. After a median follow-up of 1.9 years (range:.1–21.2) from 1st recurrence for all 38 patients and 5.5 years (.3–21.2) for 16 survivors (10 of these in continuous 2nd surgical remission), 2- & 5-year overall and event-free survival probabilities were 55% & 34% and 34% & 27%, respectively. A long interval to recurrence (> 1.5 years) predicted for better outcomes (p< .01). For those 21 patients achieving a 2nd complete surgical remission, 2- & 5-year overall and event-free survival probabilities were 81% & 61% and 52% & 49%, respectively, while only 1/17 patients failing to achieve a 2nd complete surgical remission survived beyond 5 years (p< .001) after additional radiotherapy. 14/16 survivors had also received 2nd-line chemotherapy.

1st solitary skeletal recurrences of osteosarcoma seem to have a favourable outcome provided treatment includes complete surgery as part of multimodal therapy. Some presumed bone metastases may rather represent second primary osteosarcomas.

The COSS studies that form the basis of this report were supported by Deutsche Krebshilfe.

Background: The incidence of osteosarcoma varies considerably with age and preschool children are extremely rarely affected. This study was conducted to investigate presentation, treatment, and outcome in very young children with osteosarcoma.

Patients and methods: The authors retrospectively analyzed the data of 2706 consecutive COSS patients with newly diagnosed high-grade osteosacroma of bone and identified 28 patients (1.0%) aged less than five years at diagnosis. Demographic, diagnostic, tumor, and treatment related variables; response and survival data of these 28 were analyzed.

Results: Of the 28 (male, N=16; female, N=12) toddlers, 27 presented with high-grade central osteosarcoma of an extremity (femur, N= 12; humerus, N=10; tibia, N=5) and one with a secondary osteosarcoma of the orbit. The size of primary extremity tumors was large (≥ 1/3 of the involved bone) in 20/27 evaluable patients. Primary metastases were detected in 4 children. All patients received multiagent chemotherapy, and 13/20 analyzed tumors responded well (> 90% necrosis) to neoadjuvant chemotherapy. Limb sparing surgery was performed in 11, ablative procedures were performed in 14, and no local surgery was performed in two patients with extremity tumors. With a median follow-up of 3.8 years (6.2 years for survivors), 13 patients were alive (CR1, N=12; CR3, N=1). Four patients never achieved a complete remission and 12 developed recurrences (local, N=3; metastatic, N=8; site unknown, N=1); and 15 of these 16 patients died. Five-year overall and event free survival probabilities were 50% (SE 10%) and 46% (SE 10%). Better survival was correlated with good response to chemotherapy.

Conclusions: Osteosarcoma is extremely rare in pre-school children. These young patients often have large tumors which may require mutilating resections. Prognosis may be poorer than in older patients.

The experience of radiotherapy (RT) in the local treatment of osteosarcoma (OS) is limited. Data of 100 patients with RT for OS from the international COSS-Registry (1980–2007) were analysed. Survival and local control rates at five years were calculated. Univariate and multivariate analyses were performed.

The COSS-registry includes 3500 patients with histo-logically proven OS. A total of 175 patients were irradiated over the period of 1980 to 2007, 100 patients were eligible. Median age was 18 (3–66) years. Indication for RT was a primary tumor in 66, a local recurrence in 11 and metastases in 23 patients. 94 Patients got external photontherapy, 2 pats. protontherapy, 2 pats. neutrontherapy, and 2 pats. intraoperative RT. Seventeen patients received a samarium-153-EDTMP therapy. Median dose for external RT was 55.8 Gy All patients were treated with chemotherapy in accordance to different COSS-protocols.

Median follow-up is 1.5 (0.2–23) years. Overall survival rates at 5 years for the whole group, for treatment of primary tumours, local recurrence, and metastases are 36 %, 55%, 15%, and 0% respectively. Local control rate for combined surgery and RT is significantly better than for RT alone (48% vs. 22%, p=0.002). Local control for treatment of primary tumours, local recurrence, and metastases are 40%, 17%, and 0% respectively. Prognostic factors for survival are indication for RT, RT plus surgery vs. RT alone and localisation. Prognostic factors for local control are indication for RT, and RT plus surgery vs. RT alone.

Radiotherapy is an important option for local treatment of unresectable OS, after intralesional resection, or symptomatic metastases. Survival prognosis of these patients is poor. Combination of surgery, radiotherapy, and chemotherapy can be curative. Prognostic factors were identified.

The development of local recurrence after multimodal treatment of osteosarcoma is associated with a very poor prognosis. The importance of clear surgical margins has been demonstrated in multiple studies, however up to date there are no studies defining which margin width is safe from an oncological perspective. The purpose of this retrospective analysis was to evaluate whether margin width or other surgical and tumour-related factors influence the development of local recurrence in osteosarcoma patients.

The files of 1867 consecutive patients with high-grade central osteosarcoma of the extremities, the pelvic bones and the shoulder girdle, who had achieved a complete surgical remission during combined-modality therapy on neoadjuvant Cooperative Osteosarcoma Study Group (COSS) protocols between 1986 and 2005, were reviewed. Of those, the data required were available for 1369 patients, who were the subject of this analysis. Eighty of these patients developed a local recurrence during the course of their illness.

The median surgical margin width amounted to 45 mm (range, 0 to 140 mm) in the local recurrence (LR) group and 50 mm (range, 0 to 350 mm) in the non-local recurrence (NLR) group (p=0.106). No statistically significant difference between the two groups was found regarding tumour size (mean, 10.38 cm and 9.53 cm respectively, p=0.169), T-status (p=0.225) and presence of pathological fracture (p=0.231). However infiltration of the soft tissue beyond the periosteum was documented in 58.8% of the patients with local recurrence and only in 36.9% of the rest (p=0.003). Furthermore, in 50% of the LR group the biopsy had been performed in a centre other than the one performing the definitive tumour resection, compared to 30.2% of the NRL group (p=0.001).

In conclusion, the absolute metric width of surgical margins does not define oncological safety. Local recurrence is more likely to develop in patients with soft tissue infiltration beyond the periosteum or those biopsied in a centre other than the one performing the tumour resection.