Oncolytic viruses represent a unique type of agents that combine self-amplification, lytic and immunostimulatory properties against tumors. A local and locoregional clinical benefit has been demonstrated upon intratumoral injections of an oncolytic herpes virus in melanoma patients, leading to its approval in USA and Europe for patients without visceral disease (up to stage IVM1a). However, in order to debulk and change the local immunosuppressive environment of tumors that cannot be injected directly, oncolyitc viruses need to be administered systemically. Among different viruses, adenovirus has been extensively used in clinical trials but with few evidences of activity upon systemic administration. Preclinical efficacy of a single intravenous administration of our oncolytic adenovirus ICOVIR5, an adenovirus type 5 responsive to the pRB pathway commonly deregulated in tumors, led us to use this virus in a dose-escalation phase I trial in metastatic melanoma patients. The results in 12 patients, treated with a single infusion of a dose up to 1E13 viral particles, show that ICOVIR5 can reach melanoma metastases upon a single intravenous administration but fails to induce tumor regressions. These results support the systemic administration of armed oncolytic viruses to treat disseminated cancer.
Adjuvant therapy in elderly patients with colorectal cancer is controversial due to the high risk for competing events among these patients. In order to effectively select older patients for adjuvant therapy, we have to weigh the risk of cancer-related mortality and the potential survival benefits with treatment against the patient's life expectancy, irrespective of cancer. This prospective study focused on the prognostic value of geriatric assessment for survival using a competing-risk analysis approach, providing an important contribution on the treatment decision-making process and helping clinicians to identify elderly patients who might benefit from adjuvant chemotherapy among those who will not.
In this trial, local control and survival rates after SBRT were very good. Treatment with SBRT had no significant impact on lung function at 36 months. These findings provide further support for the use of SBRT as a radical treatment for NSCLC. Lung toxicity is minimal, even in patients with poor pulmonary function before treatment.
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