Purpose: Standard treatments have modest effect against pancreatic cancer, and current research focuses on agents targeting molecular pathways involved in tumor growth and angiogenesis. This study investigated the interactions between ZD6474, an inhibitor of tyrosine kinase activities of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor (EGFR), gemcitabine, and ionizing radiation in human pancreatic cancer cells and analyzed the molecular mechanisms underlying this combination. Experimental Design: ZD6474, ionizing radiation, and gemcitabine, alone or in combination, were given in vitro to MIA PaCa-2, PANC-1, and Capan-1cells and in vivo to MIA PaCa-2 tumor xenografts. The effects of treatments were studied by the evaluation of cytotoxicity, apoptosis, cell cycle, EGFR and Akt phosphorylation, modulation of gene expression of enzymes related to gemcitabine activity (deoxycytidine kinase and ribonucleotide reductase), as well as vascular endothelial growth factor immunohistochemistry and microvessel count. Results: In vitro, ZD6474 dose dependently inhibited cell growth, induced apoptosis, and synergistically enhanced the cytotoxic activity of gemcitabine and ionizing radiation. Moreover, ZD6474 inhibited phosphorylation of EGFR and Akt and triggered cell apoptosis. PCR analysis showed that ZD6474 increased the ratio between gene expression of deoxycytidine kinase and ribonucleotide reductase. In vivo, ZD6474 showed significant antitumor activity alone and in combination with radiotherapy and gemcitabine, and the combination of all three modalities enhanced MIA PaCA-2 tumor growth inhibition compared with gemcitabine alone. Conclusions: ZD6474 decreases EGFR and Akt phosphorylation, enhances apoptosis, favorably modulates gene expression in cancer cells, and acts synergistically with gemcitabine and radiotherapy to inhibit tumor growth. These findings support the investigation of this combination in the clinical setting.Pancreatic cancer is a highly malignant illness that has steadily increased in incidence over recent decades, and it is now the fourth leading cause of death from cancer in the Western world. Despite this, there has been little improvement in prognosis over the past 20 years (1). Due to the delay of clinical symptoms, pancreatic cancer is usually detected at an advanced stage, and survival ranges between 4 and 6 months after diagnosis. Moreover, because of its aggressive biological behavior, this malignancy has a grim prognosis even following surgical resection, and the 5-year survival for all stages of the disease remains below 4% (2). Therefore, pancreatic cancer represents a clinical challenge and novel therapeutic approaches are warranted.Several studies showed that pancreatic cancer is characterized by dysregulation of molecular mechanisms involved in cell proliferation, invasiveness, and angiogenesis (3). Epidermal growth factor receptor (EGFR) is a key driver of cell proliferation, and

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Background/Aim: To assess predictors of local control (LC) for stereotactic ablative radiotherapy (SAbR) in pulmonary oligometastatic disease (OMD) from gastrointestinal (GI) malignancies. Patients and Methods: Patients with pulmonary OMD treated with SAbR from January 2016 to December 2018 were included in this observational analysis. Primary endpoint was LC. Uni-and multivariate analyses to assess variable correlations were conducted. Results: Thirty-seven patients and 59 lung metastases were evaluated. The delivered dose was 30-60 Gy in 3-8 fractions. After a median follow-up of 23.0 months (range=6.3-50.4 months), LC rate at 1/2 years was 89.7%/85.0%, and increased to 96.0%/91.0% for lesions treated with a biologically effective dose (BED 10 ) ≥100 Gy (p=0.03). RECIST response at 6 months was predictive for LC (p=0.002). Conclusion: SAbR is an effective option for pulmonary OMD from GI malignancies. A BED 10 ≥100 Gy and radiological response at 6 months can affect LC.Oligometastasis, a term first introduced in 1995, refers to a limited metastatic state with a small number of lesions and involved organs (1). The notion of oligometastatic disease (OMD) has dramatically changed the concept and therapeutic approach to metastatic cancer (2). Even if systemic therapy remains essential, these patients seem to benefit from local therapy (e.g. surgery and radiation therapy), and multimodality approach is considered potentially able to improve oncological outcomes in selected OMD cases (3). Lung parenchyma represents a common site for oligometastatic seeding. Notably, in a series of 575 patients and 708 lung metastasectomies, 35.6% resulted from gastrointestinal (GI) tumors (4). Surgery represents a mainstay of treatment for lung oligometastasis, resulting in long-term disease control and survival (5). More recently, stereotactic ablative radiotherapy (SAbR), also referred to as stereotactic body radiotherapy (SBRT), has emerged as a consistent alternative to surgery, with reported promising local control and acceptable toxicity (6)(7)(8)(9)(10)(11)(12)(13)(14)(15).Based on this background, we aimed at performing a novel analysis of the efficacy of using SAbR in a cohort of pulmonary OMD from GI malignancies. Factors potentially affecting LC were analyzed. Patients and MethodsStudy design. Patients treated with SAbR for lung OMD from GI cancers between January 2016 and December 2018 were included in this analysis. Each case was discussed by the institutional multidisciplinary tumor board including dedicated Radiation Oncologists, Medical Oncologists, Thoracic and General Surgeons, Pathologists and Diagnostic Radiologists. Indications for SAbR were as follows: oligometastasis and oligorecurrence, treatment of all pulmonary lesions (≤5 lung lesions); oligoprogression and oligopersistence, treatment only of progressive/active lesions after chemotherapy (≤5 lung lesions). In the latter case, the treatment goal was to obtain local control and prevent or delay any change in systemic therapy (CST). All treated patients ga...

A 58-year old man, affected by metastatic thyroid carcinoma, experienced a progressive bilateral visual impairment. Ophthalmic examination revealed the presence of a choroidal mass with an associated exudative retinal detachment in both eyes. Twelve years before, a diagnosis of metastatic thyroid carcinoma had been established and the patient had been subject to several therapeutic procedures.In May 2007, he received a radiotherapy treatment to the left eye with an episcleral plaque and bilateral bulbar injection of bevacizumab. The patient had a rapid and stable visual acuity recovery. Twenty months after treatment, the lesion treated with radiotherapy was still stable whereas the contra-lateral lesion had evolved and determined a vitreal hemorrhage.