Current 5-year survival after complete resection of pulmonary metastases is ≈ 30%, and many patients develop pulmonary recurrences. Obviously new treatment options are needed for this indication. Isolated lung perfusion (ILuP) is an experimental technique to deliver high-dose chemotherapy to the lung without systemic exposure. Recently, a phase I trial of ILuP combining 45 mg melphalan followed by pulmonary metastasectomy for resectable lung metastases proved to be feasible and safe.

The current 3-center phase II study (including University Hospital Antwerp/P. van Schil and Anthonius Hospital Nieuwegein/F. Schramel) allows patients with resectable lung metastases from colorectal cancer, soft tissue- and osteosarcoma to be treated with ILuP prior to metastasecomy.

At Leiden University Medical Center we treated 8 patients: 4 with colorectal cancer (age 54–59 y), 2 osteosarcoma (19–20 y), 1 sarcoma NOS of bone (38 y) and 1 sarcoma NOS (56 y) of soft tissue. The number of metastases was 1–2 and one patient had resection of 9 metastases. The procedure was uncomplicated in 7 cases and 1 patient had reversible pulmonary edema. Hospital admission duration was 6–8 days in the uncomplicated group and 14 days in the one patient with a complication. No long term toxicity was observed with extensive follow-up including lung function tests. With a median follow-up of 7 months (range 2–16), only the patient with 9 metastases had a recurrence and died of disease.

Our single center prelimininary data show that ILuP is feasible and does not lead to irreversible or severe toxicity. Compared to retrospective data with metastasectomy alone, perfusion did not add toxicity. Follow-up is too short to draw any conclusions on efficacy.

Giant cell tumour of bone (GCT) is a primary osteolytic neoplasm, histopathologically characterized by osteoclast-like giant cells and clinically characterized by local bone destruction and high recurrence rates. There is a need to identify risk factors for recurrence. In order to reduce the recurrence rate we initiated an international, multicenter, randomised phase II trial with adjuvantzoledronic acid as compared to standard care for high risk GCT patients.

One hundred and sixteen GCT patients, treated at the LUMC from 1971 to 2006, with a minimal follow-up of a year, were retrospectively analysed for the following risk factors for local recurrence: GCT grade III and tumour involvement into soft tissue caused by ingrowth or fracture. Resection was used as treatment in 21 patients (group A), intralesional surgery with cement or adjuvant in 24 (group B) and intralesional surgery with cementation and adjuvant in 71 patients (group C).

GCT recurred in 5% (1/21) in group A. Risk factors were found in 90% of patients without recurrence (18/20). Group B shows a recurrence of 25% (6/24). Risk factors were found in 83% (5/6) of recurring GCTs, compared with 28% in patients without recurrence. In group C, a recurrence rate of 23% (16/71) was found. Risk factors were present in 94% (15/16) of recurrences, compared to 36% (20/55) in patients without recurrence.

Soft tissue involvement and GCT grade 3 and up are risk factors for recurrence in GCT. Recurrence rates are lowest when resection is used. Risk factors may influence the choice of treatment. High risk patients may benefit from resection or systemic treatment with adjuvant therapy.

Resection of pulmonary metastases has previously been reported to improve outcome in high grade osteosarcoma (OS) patients with pulmonary metastases. In this study factors influencing survival in OS patients with pulmonary metastases were determined.

One hundred ninety seven patients with OS treated at our institution between 1990 and 2008 under the age of 40 were included. Excluded were patients with insufficient follow-up data (n=12) and irresectable primary tumour (n=11). Of the 174 remaining patients, 26 patients had pulmonary metastases at diagnosis and 62 developed pulmonary metastases during follow-up. Twenty-two of 88 patients (25%) also had extra-pulmonary metastases. Almost all patients with primary non-metastatic OS who experienced a relapse within 310 days (first tertile) died of disease, whereas patients with a relapse free interval of more than 310 days (second and third tertiles) have a significantly better overall survival at about 20% (p=0.02).

In total, 56 (63.6%) of 88 patients with pulmonary metastases were treated by metastasectomy. The main reason not to perform metastasectomy was irresect-ability by number and site. Patients with irresectable pulmonary metastases had higher numbers of pulmonary nodules (mean of six vs. three nodules) and more frequent bilateral involvement than patients eligible for surgery (p-values respectively 0.002 and 0.06). Independent risk factors determining survival after metastasectomy in multivariate analysis were male sex (p=0.05), higher numbers of pulmonary nodules (p=0.03) and necrotic metastases (p=0.04). Patients undergoing repeated metastasectomies had a similar chance of survival as patients who underwent metastasectomy once.

This well-defined cohort of patients with extensive follow-up data enabled us to identify important risk factors determining survival in OS patients with pulmonary metastases. Risk factors determining poor survival after pulmonary metastasectomy were male sex, higher numbers of pulmonary nodules and resection of vital metastases. Furthermore, we demonstrate that even after repeated metastasectomies, curation can be achieved.