Best of the Radiosurgery Society® Scientific Meeting 2014: stereotactic radiosurgery/stereotactic body radiotherapy treatment of extracranial and intracranial lesions.

The SRS/SBRT Scientific Meeting 2014, Minneapolis, MN, USA, 7-10 May 2014. The Radiosurgery Society(®), a professional medical society dedicated to advancing the field of stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT), held the international Radiosurgery Society Scientific Meeting, from 7-10 May 2014 in Minneapolis (MN, USA). This year's conference attracted over 400 attendants from around the world and featured over 100 presentations (46 oral) describing the role of SRS/SBRT for the treatment of intracranial and extracranial malignant and nonmalignant lesions. This article summarizes the meeting highlights for SRS/SBRT treatments, both intracranial and extracranial, in a concise review.

Anti-angiogenesis therapies: their potential in cancer management.

Angiogenesis plays an important role in normal animal growth and development. This process is also vital for the growth of tumors. Angiogenesis inhibitors have a different mechanism of action to traditional chemotherapy agents and radiation therapy. The angiogenesis inhibitors can act synergistically with conventional treatments and tend to have non-overlapping toxicities. There are four drugs which have a proven role in treating cancer patients. Bevacizumab is a humanized monoclonal antibody that binds to and neutralizes vascular endothelial growth factor (VEGF). Sunitinib and sorafenib inhibit multiple tyrosine kinase receptors that are important for angiogenesis. Thalidomide inhibits the activity of basic fibroblast growth factor-2 (bFGF). The licensed indications and the supporting evidence are discussed. Other drugs are currently being tested in clinical trials and the most promising of these drugs are discussed. Aflibercept, also known as VEGF-trap, is a recombinant fusion protein that binds to circulating VEGF. The vascular disrupting agents act by targeting established blood vessels. These exciting new treatments have the potential to transform the management of cancer.

A phase I trial of radioimmunotherapy with 131I-A5B7 anti-CEA antibody in combination with combretastatin-A4-phosphate in advanced gastrointestinal carcinomas.

PURPOSE: In preclinical models, radioimmunotherapy with (131)I-A5B7 anti-carcinoembryonic antigen (CEA) antibody ((131)I-A5B7) combined with the vascular disruptive agent combretastatin-A4-phosphate (CA4P) produced cures unlike either agent alone. We conducted a phase I trial determining the dose-limiting toxicity (DLT), maximum tolerated dose, efficacy, and mechanism of this combination in patients with gastrointestinal adenocarcinomas. EXPERIMENTAL DESIGN: Patients had CEA of 10 to 1,000 microg/L, QTc < or =450 ms, no cardiac arrhythmia/ischaemia, and adequate hematology/biochemistry. Tumor was suitable for blood flow analysis by dynamic contrast enhanced-magnetic resonance imaging (MRI). The starting dose was 1,800 MBq/m(2) of (131)I-A5B7 on day 1 and 45 mg/m(2) CA4P given 48 and 72 hours post-(131)I-A5B7, then weekly for up to seven weeks. RESULTS: Twelve patients were treated, with mean age of 63 years (range, 32-77). Two of six patients at the first dose level had DLTs (grade 4 neutropenia). The dose was reduced to 1,600 MBq/m(2), and CA4P escalated to 54 mg/m(2). Again, two of six patients had DLTs (neutropenia). Of ten assessable patients, three had stable disease and seven had progressive disease. Single-photon emission computed tomography confirmed tumor antibody uptake in all 10 patients. DCE-MRI confirmed falls in kinetic parameters (K(trans)/IAUGC(60)) in 9 of 12 patients. The change of both pharmacokinetic parameters reached a level expected to produce efficacy in one patient who had a minor response on computed tomography and a reduced serum tumor marker level. CONCLUSIONS: This is believed to be the first trial reporting the combination of radioimmunotherapy and vascular disruptive agent; each component was shown to function, and myelosuppression was dose-limiting. Optimal dose and timing of CA4P, and moderate improvements in the performance of radioimmunotherapy seem necessary for efficacy.

Linear quadratic modeling of increased late normal-tissue effects in special clinical situations.

PURPOSE: To extend linear quadratic theory to allow changes in normal-tissue radiation tolerance after exposure to cytotoxic chemotherapy, after surgery, and in elderly patients. METHODS: Examples of these situations are analyzed by use of the biologic effective dose (BED) concept. Changes in tolerance can be allowed for by: estimation of either the contribution of the additional factor as an equivalent BED or the equivalent dose in 2-Gy fractions or by the degree of radiosensitization by a mean dose-modifying factor (x). RESULTS: The estimated x value is 1.063 (95% confidence limits for the mean, 1.056 to 1.070) for subcutaneous fibrosis after cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy and radiotherapy in breast cancer. The point estimate of x is 1.18 for the additional risk of gastrointestinal late-radiation effects after abdominal surgery in lymphoma patients (or 10.62 Gy at 2 Gy per fraction). For shoulder fibrosis in patients older than 60 years after breast and nodal irradiation, x is estimated to be 1.033 (95% confidence limits for the mean, 1.028 to 1.0385). The equivalent BED values were CMF chemotherapy (6.48 Gy3), surgery (17.73 Gy3), and age (3.61 Gy3). CONCLUSIONS: The LQ model can, in principle, be extended to quantify reduced normal-tissue tolerance in special clinical situations.