Micaela M. Hernberg

Radical surgery is not feasible for all osteosarcoma patients. Overall survival for non-extremity osteosarcoma, as well as for patients with metastatic disease at diagnosis remains poor. For such patients, radical radiotherapy combined with chemotherapy may present an effective treatment approach. This report describes the results of conservative treatment for osteosarcoma patients not suitable for surgery. Seven out of 71 consecutive osteosarcoma patients were treated non-surgically at the Helsinki University Central Hospital either due to the inoperability of the tumour or the patient’s choice of therapy. Staging procedures and measurement of tumour size were performed using computed tomography and magnetic resonance imaging. Six patients were treated with chemo-radiotherapy, and one patient received radiotherapy alone. Five patients received computer-assisted dose-planned radiotherapy with curative intent (total dose 60–70.5 Gray), and two patients received radiotherapy as palliation. Radiotherapy relieved symptoms efficiently. Median time to local failure was 2.6 years (range 0.5–16.9+ years). Five year after treatment termination four patients were alive, and one of them remained disease-free. For selected patients not suitable for surgery, radiotherapy combined with chemotherapy provides an option to reduce symptoms caused by the primary tumour and improve quality of life. For some patients, this approach may (even) produce long-term remission.

The aim of this study was to investigate whether the profile of peripheral blood lymphocyte subsets of patients with high-risk malignant melanoma is associated with prognosis. Blood samples were systematically obtained from 31 patients with high-risk melanoma eligible for the Nordic Melanoma Cooperative Group adjuvant interferon study. The frequencies of peripheral blood lymphocyte subsets were monitored by flow cytometry using CD3, CD4, CD8, CD56, and CD69 monoclonal antibodies. Patients with low proportions of CD3+CD4+CD69+ cells and of CD3+CD56+ cells before treatment had an improved disease-free survival compared to those with high proportions [77.7 vs. 16.8 mo, hazard ratio (HR) 0.25, confidence interval (CI) 0.09-0.71, P=0.005 and 77.2 vs. 16.0 mo, HR: 0.25, CI 0.086-0.73, P=0.001, respectively]. Low pretreatment levels of these cell populations also correlated with a better overall survival (79.2 vs. 22.6 mo, HR: 0.17, CI 0.05-0.52, P=0.0005 and 78.2 vs. 21.4 mo, HR: 0.2, CI 0.07-0.59, P=0.001, respectively). In the multivariate analysis both the pretreatment proportion of CD3+CD4+CD69+ cells (P=0.01, HR: 0.21, CI 0.07-0.67) and CD3+CD56+ cells (P=0.01, HR: 0.22, CI 0.062-0.65) were independent prognostic factors for overall survival. Our data show that both the proportions of CD3+CD4+CD69+ cells and of CD3+CD56+ cells seem to have a prognostic potential in the natural course of melanoma. These results need to be confirmed in larger studies.

We have observed that an early increase in the CD4+/CD8+ ratio of metastatic melanoma patients during chemoimmunotherapy is the most favourable independent prognostic factor. In this study, 87 patients with metastatic melanoma were monitored for peripheral blood lymphocyte subsets (CD4+ and CD8+) before and during chemoimmunotherapy (dacarbazine, vinblastine, lomustine and bleomycin or dacarbazine alone plus interferon-alpha) to confirm our previous observation. Blood samples were systematically obtained from patients who received either of these chemoimmunotherapies. The frequencies of peripheral blood lymphocyte subsets were monitored by flow cytometry using monoclonal antibodies OKT4 (CD4+, T-helper cells) and OKT8 (CD8+, T-suppressor cells). The overall response rate was 46.5%, and the median overall survival was 9.3 months. Patients with pre-treatment CD4+ levels above the mean level, who later responded to therapy, had a median survival of 28.1 months vs. 10.2 months for responders with low pre-treatment CD4+ levels (P=0.053, log-rank test). Responders with decreasing CD8+ levels had a median survival of 27.8 months vs. 10.8 months for responders with increasing CD8+ levels (P=0.04, log-rank test). Similarly, responding patients with an increasing CD4+/CD8+ ratio had a median survival of 28.1 months vs. 10.5 months for those with decreasing ratios (P=0.002, log-rank test). Non-responders showed no difference in median survival irrespective of low or high pre-treatment CD4+ lymphocytes, increasing or decreasing CD8+ levels, or increasing or decreasing CD4+/CD8+ ratios. This follow-up study confirms that the monitoring of CD4+ and CD8+ lymphocytes may provide important predictive and prognostic information in metastatic melanoma patients receiving chemoimmunotherapy.