In vivo efficacy of melanoma internal radionuclide therapy with a 131I-labelled melanin-targeting heteroarylcarboxamide molecule.

The development of alternative therapies for melanoma treatment is of great interest as long-term tumour regression is not achieved with new targeted chemotherapies on selected patients. We previously demonstrated that radioiodinated heteroarylcarboxamide ([131I]ICF01012) induced a strong anti-tumoural effect by inhibiting both primary tumour growth and dissemination process in a B16BL6 melanoma model. In our study, we show that a single injection of [131I]ICF01012 (ranging from 14.8 to 22.2 MBq) was effective and associated with low and transient haematological toxicity. Concerning pigmented organs, cutaneous melanocytes and skin were undamaged. In 30% of treated animals, no histological alteration of retina was observed, and in the remaining 70%, damages were restricted to the optic nerve area. Using the Medical Internal Radiation Dose methodology, we determined that the absorbed dose in major organs is very low (<4 Gy) and that a delivery of 30 Gy to the tumour is sufficient for an effective anti-tumoural response. Molecular analyses of treated tumours showed a strong radiobiological effect with a decrease in proliferation, survival and pro-angiogenic-related markers and an increase in tumour suppressor gene expression, melanogenesis and anti-angiogenic markers. All these features are in accordance with a tumour cell death mechanism that mainly occurs by mitotic catastrophe and provide a better understanding of in vivo anti-tumoural effects of [131I] radionuclide. Our findings raise [131I]ICF01012 a good candidate for disseminated melanoma treatment and strongly support transfer of [131I]ICF01012 to clinical trial.

MRI tumor response and clinical outcomes after LINAC radiosurgery on 50 patients with recurrent malignant gliomas.

BACKGROUND: The place of radiosurgery (RS) as an option in the treatment of recurrent malignant glioma is still debated on in the absence of prospective randomized trials. OBJECTIVE: To assess the clinical outcome and MRI response after radiosurgery of recurrent malignant glioma. METHODS: We evaluated 50 consecutive patients treated in a single institution. Between 2001 and 2008, 34 glioblastoma (GBM) and 16 anaplastic oligodendroglioma (AO) patients were treated with linear accelerator (Linac) RS for recurrence. RESULTS: The median marginal dose was 15 Gy and the median gross tumor volume (GTV) was 6.64 ml. No patient had acute (< 3 months) neurological morbidity after RS. Ten patients (20%) were reoperated on after RS, histopathological findings included necrosis alone in 3 cases (6%). The median overall survival was 21.5 months for GBM and 57.9 months for AO. The median survival after RS was 9.5 months for GBM and 32.9 months for AO. The median progression-free survival after RS was 6.7 months for GBM and 18 months for AO. MRI volume modifications after RS showed a transitory reduction or stabilization of disease linked to significantly improved survival in 58.8% of patients with GBM, 81.1% of patients with AO. Pathological subtype (AO versus GBM), MRI response, KPS >70, marginal dose > 13 Gy, largest diameter of GTV < 25 mm and GTV < 7 ml were the main prognostic factors, associated with improved survival or PFS from RS. CONCLUSION: The magnitude of the survival increase compared to historical RPA classes may not be due to selection bias alone. Linac RS in selected patients with recurrent malignant glioma was well tolerated, effective and can be considered as one of several re-treatment options.