In the present study, we have evaluated the efficacy and toxicity of repeated brain metastases (BM) stereotactic radiosurgery (SRS2) following local failure of a prior radiosurgical procedure (SRS1). Between December 1996 and August 2015, 30 patients with 36 BM underwent SRS2 with a median dose of 18Gy. All BM were located outside critical structures. Following SRS2, local control at 6 months and one year were respectively 82.9% (IC 95%: 67.6–91.9) and 67.8% (IC 95%: 51–81). On multivariate analysis, planning target volume (PTV) < 3cc (HR: 0.19 (0.1–0.52)) and whole brain radiotherapy (WBRT) prior to SRS2 (HR: 0.25 (0.1–0.64)) were significantly associated with a better local control. One- and two-year overall survival rates after SRS2 were respectively 65.5% (IC 95%: 47.3–80%) and 27.6% (IC 95%: 14.7–45.7). Median overall survival following SRS2 was 14.2 months (range 1–106). Nineteen (63%) patients died from progressive systemic disease. Three (10%) patients died from out-field progressive brain disease and 8 (27%) in-field. Concerning toxicities, edema, radionecrosis, and hemorrhages were identified in 5 (12.8%), 4 (10.2%), and 5 (12.8%) patients respectively. No toxicity resulted in a neurological deficit. On univariate analysis, toxicities were significantly associated with PTV > 7cc (p = 0.02) and all patients had a WBRT before SRS2. A second course of SRS for locally recurrent brain metastases showed encouraging rates of local control. This treatment led to acceptable toxicities, especially for brain metastases smaller than 7cc, in our selected cohort of patients with BM located outside critical structures. Further studies are needed.

Radiation-induced endothelial/vascular injury is a major complicating factor in radiotherapy and a leading cause of morbidity and mortality in nuclear or radiological catastrophes. Exposure of tissue to ionizing radiation (IR) leads to the release of oxygen radicals and proteases that result in loss of endothelial barrier function and leukocyte dysfunction leading to tissue injury and organ damage. Microvascular endothelial cells are particularly sensitive to IR and radiation-induced alterations in endothelial cell function are thought to be a critical factor in organ damage through endothelial cell activation, enhanced leukocyte-endothelial cell interactions, increased barrier permeability and initiation of apoptotic pathways. These radiation-induced inflammatory responses are important in early and late radiation pathologies in various organs. A better understanding of mechanisms of radiation-induced endothelium dysfunction is therefore vital, as radiobiological response of endothelium is of major importance for medical management and therapeutic development for radiation injuries. In this review, we summarize the current knowledge of cellular and molecular mechanisms of radiation-induced endothelium damage and their impact on early and late radiation injury. Furthermore, we review established and emerging in vivo and in vitro models that have been developed to study the mechanisms of radiation-induced endothelium damage and to design, develop and rapidly screen therapeutics for treatment of radiation-induced vascular damage. Currently there are no specific therapeutics available to protect against radiation-induced loss of endothelial barrier function, leukocyte dysfunction and resulting organ damage. Developing therapeutics to prevent endothelium dysfunction and normal tissue damage during radiotherapy can serve as the urgently needed medical countermeasures.

Background The rate of toxic deaths related to induction chemotherapy in the treatment of locally advanced head and neck cancers is unacceptable and calls into question this therapeutic strategy, which is however highly effective in terms of rate and speed of response. The purpose of the study was to investigate predictive factors of toxicity of induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (TPF) in locally advanced head and neck cancers (LAHNC). Methods Between June 2009 and December 2017, 113 patients treated consecutively with TPF were included retrospectively. Patients were receiving induction chemotherapy for either an inoperable cancer or laryngeal preservation. For inoperable cancer, induction chemotherapy was proposed to patients presenting either a large tumor with strong symptoms (dyspnea, dysphagia, pain) or a tumor with rapid progression. Risk factors were chosen among the initial patient and tumour characteristics and chemotherapy modalities. Results Eighty-nine patients (79%) were male; the median age was 58 years [32–71]. Sixty-nine (61%) patients were treated for inoperable cancer and 44 (39%) for laryngeal preservation. 45% had stage IVa cancer, 28% stage III and 25% stage IVb. Sixty percent of patients had a partial response after TPF, 22% had a complete response, 12% were stable, 5% were progressing, and 1% had a discordant response. Thirty-four patients (30%) received enteral feeding during induction chemotherapy with TPF. The possibility of oral feeding without a tube was predictive of a better response (p = 0.003). Seven (6%) patients died during TPF. There was an increased risk of death with preexisting liver dysfunction (liver dysmorphia on imaging or decrease prothrombin rate) (p = 0.032). There was an increased risk of grade ≥ 3 infection if an enteral feeding occurred during the period of induction chemotherapy (p = 0.03). Conclusions TPF induction chemotherapy had an 82% objective response rate with 6% toxic deaths. Nutritional status and the presence of hepatic dysfunction are significant risk factors to be taken into account in therapeutic decisions.

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