Isabel Monteiro Grillo

Low Doses of Ionizing Radiation Promote Tumor Growth and Metastasis by Enhancing Angiogenesis

Radiotherapy is a widely used treatment option in cancer. However, recent evidence suggests that doses of ionizing radiation (IR) delivered inside the tumor target volume, during fractionated radiotherapy, can promote tumor invasion and metastasis. Furthermore, the tissues that surround the tumor area are also exposed to low doses of IR that are lower than those delivered inside the tumor mass, because external radiotherapy is delivered to the tumor through multiple radiation beams, in order to prevent damage of organs at risk. The biological effects of these low doses of IR on the healthy tissue surrounding the tumor area, and in particular on the vasculature remain largely to be determined. We found that doses of IR lower or equal to 0.8 Gy enhance endothelial cell migration without impinging on cell proliferation or survival. Moreover, we show that low-dose IR induces a rapid phosphorylation of several endothelial cell proteins, including the Vascular Endothelial Growth Factor (VEGF) Receptor-2 and induces VEGF production in hypoxia mimicking conditions. By activating the VEGF Receptor-2, low-dose IR enhances endothelial cell migration and prevents endothelial cell death promoted by an anti-angiogenic drug, bevacizumab. In addition, we observed that low-dose IR accelerates embryonic angiogenic sprouting during zebrafish development and promotes adult angiogenesis during zebrafish fin regeneration and in the murine Matrigel assay. Using murine experimental models of leukemia and orthotopic breast cancer, we show that low-dose IR promotes tumor growth and metastasis and that these effects were prevented by the administration of a VEGF receptor-tyrosine kinase inhibitor immediately before IR exposure. These findings demonstrate a new mechanism to the understanding of the potential pro-metastatic effect of IR and may provide a new rationale basis to the improvement of current radiotherapy protocols.

Endoluminal high dose rate brachytherapy in the treatment of primary and recurrent bronchogenic tree malignancies

INTRODUCTION Locally advanced tumours as the initial form of presentation of tumours in the bronchial tree are not a rare event. Bronchogenic recurrence is frequent in the natural history of some tumours. The choice of therapeutic options from the raft available depends on such variables as initial therapy, place of recurrence, symptoms and patients physical status. AIM To demonstrate the advantages of endoluminal brachytherapy (EBT) with high dose rate (HDR) in primary and recurrent tumour of the bronchial tree. MATERIAL AND METHODS A retrospective study of seven patients (pts) with primary tumours of the colon, trachea and lung. Tracheobronchial recurrence (trachea, two pts, bronchus, five pts) occurred between March 2003 and September 2004. Patients under- went EBT with HDR for primary or recurrent therapy in association with external radiotherapy, laser therapy and chemotherapy with palliative or curative intention. EBT with HDR doses of 5 to 7 Gy in 2 to 4 fractions at 1 cm from the source axis were given. Treatment included endoluminal application of Ir192 with a French 6 catheter. RESULTS There was symptomatic relief related to reduction of tumour in six of the seven patients treated. In one of the six patients studied, there was progression of the local disease between the second and third fractions of the treatment (obstruction of the trachea). In a mean follow up of 17 (2-40) months between EBT and this study, three patients are alive, one has no evidence of disease while two have had bronchial recurrence, four patients have died, one after massive haemoptysis and three due to disease progression. DISCUSSION AND CONCLUSIONS Patients undergoing brachytherapy for symptomatic primary tumours or endobronchial recurrence show good tolerance, important symptom relief and improved quality of life. Despite the small size of our sample, it is clear that EBT with HDR plays an important role in the palliative/ curative treatment of these patients.

Stevens Johnson Syndrome in a patient undergoing gynaecological brachytherapy: An association or an incident?

BACKGROUND Stevens Johnson Syndrome and Erythema Multiforme are hypersensitivity skin reactions generally arising in the context of multiple causes. Radiation therapy is considered to be one of these causes, although most reports are hindered by concomitant medications. AIM The aim of this paper was to present a case of Stevens Johnson Syndrome arising in a patient undergoing gynaecological brachytherapy with an unusual presentation. CASE We describe a case of a 56-year-old woman with endometrial cancer undergoing adjuvant gynaecological radiotherapy. While undergoing a gynaecological brachytherapy boost, she developed bilateral conjunctivitis that progressed to oral mucositis and pruritic erythema with sloughing of the skin on her arms and legs but not the torso or irradiated fields (namely the vaginal mucosa). CONCLUSION This case illustrates the association of RT/SJS; however, it also raises the question of patients undergoing RT being more susceptible to SJS as opposed to a direct cause of the disease.