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William R. Kennedy, Todd A. DeWees, Sahaja Acharya, Mustafaa Mahmood, Nels C. Knutson, S. Murty Goddu, James A. Kavanaugh, Timothy J. Mitchell, Keith M. Rich, Albert H. Kim, Eric C. Leuthardt, Joshua L. Dowling, Gavin P. Dunn, Michael R. Chicoine, Stephanie M. Perkins, Jiayi Huang, Christina I. Tsien, Clifford G. Robinson, and Christopher D. Abraham

radiosurgery (SRS), including prescription dose escalation, adding a small margin around the target, and the use of whole-brain radiation therapy (WBRT) in conjunction with SRS. However, there are potential drawbacks to each of these methods, which limit their widespread use. Escalation of the prescription dose, while having a positive correlation with improved LC, is associated with increased rates of radiation necrosis (RN). 10 The addition of a small margin also improves LC, but this method is limited near critical structures. Finally, adding WBRT prior to SRS also

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Eugene S. Flamm, Harold P. Adams Jr., David W. Beck, Richard S. Pinto, John R. Marler, Michael D. Walker, John C. Godersky, Christopher M. Loftus, José Biller, David J. Boarini, Chris O'Dell, Karla Banwart, and Gail Kongable

the small number of patients studied and because the dose of nicardipine administered was very low. 24 Before a randomized clinical trial could be initiated, it was necessary to determine a safe, potentially optimal dose of the drug in patients with recent SAH. Therefore, we have carried out a dose-escalation study to determine the maximally tolerated dose of nicardipine and the possible therapeutic response to such a dose. Our results are presented in this communication. Clinical Material and Methods Patients between the ages of 18 and 75 years, who were

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Kyung Hwan Kim, Doo-Sik Kong, Kyung Rae Cho, Min Ho Lee, Jung-Won Choi, Ho Jun Seol, Sung Tae Kim, Do-Hyun Nam, and Jung-Il Lee

G amma Knife radiosurgery (GKS) has become an increasingly utilized treatment option in the management of patients with brain metastases (BM). 15 While single-fraction treatment of small lesions was effective in both controlling tumors and sparing normal tissue, the ability to safely deliver an adequate dose in a single fraction to larger tumors was limited. 14 As shown in the Radiation Therapy Oncology Group (RTOG) 90–05 dose escalation study, dose limits of 24, 18, and 15 Gy were established for previously irradiated lesions measuring < 2, 2–3, and 3–4 cm in

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Gary K. Steinberg, Teresa E. Bell, and Midori A. Yenari

lateral sclerosis, and Huntington's disease 3, 11, 26 and found tolerable side effects at a variety of doses. Common side effects included dizziness, dysarthria, and ataxia at lower doses and hallucinations and fatigue at higher doses. A recent dose-escalation study of DX in acute stroke patients 1 showed similar side effects. At higher doses, however, reversible hypotension, depressed respirations, and stupor were seen in a few patients. Other NMDA antagonists administered to patients include the competitive antagonist, CGS19755, which has a similar side

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Tracy E. Alpert, Chung T. Chung, Lisa T. Mitchell, Charles J. Hodge, Craig T. Montgomery, Jeffrey A. Bogart, Daniel Y-J. Kim, Danel A. Bassano, and Seung S. Hahn

showing the distribution of GKS dose escalation from 70 to 95 Gy for the study population. Fig. 2. Gamma knife surgery plans for one-shot compared with two-shot treatment showing the 10-Gy (outer) and 50% isodose lines (inner) and dose—volume histograms of the pons. Follow-Up Evaluation and Statistical Analysis Patients underwent routine follow up performed by the Gamma Knife team, and pain, facial sensation, medication usage, and neurological examinations were recorded. Pain was assessed using the BNI Pain Scale 16 before and after GKS

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Markus M. Fitzek, Allan F. Thornton, James D. Rabinov, Michael H. Lev, Francisco S. Pardo, John E. Munzenrider, Paul Okunieff, Marc Bussière, Ilana Braun, Fred H. Hochberg, E. Tessa Hedley-Whyte, Norbert J. Liebsch, and Griffith R. Harsh IV

-CGE target volume in all but one case suggests that this dose, delivered in accelerated fractionation, is sufficient for very high rates of tumor control. The prolongation of the median survival time shown here may represent the longer time needed for solid tumor to regrow in more peripheral areas containing a lower density of malignant cells; these cells become clinically determinant when control of tumor in more central areas is achieved. 5, 18 A variety of other methods of dose escalation have been explored during the last decade, most notably brachytherapy and

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Stefania Morbidini-Gaffney, Chung-Taik Chung, Tracy Erin Alpert, Nancy Newman, Seung Shin Hahn, Hemangini Shah, Lisa Mitchell, Daniel Bassano, Aneela Darbar, Saeed Ahmed Bajwa, and Charles Hodge

common side effect. 1,16,20,22 A number of authors have attempted dose escalation to 90 Gy by using a single 4-mm collimator setting targeted to the root entry zone in an attempt to further improve pain relief; they have reported this dose to be safe and effective. 8 Another way to improve pain relief, such as increasing the treatment volume, was attempted in a single prospective, randomized trial. This trial failed to reveal a benefit for two isocenters compared with one isocenter. 4 Two to 4% of patients with MS suffer from TN. 3 Trigeminal neuralgia that occurs

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Minh Tam Truong, Gregory Grillone, Christine Tschoe, Lawrence Chin, Lisa Ann Kachnic, and Scharukh Jalisi

local control of HNC continues to be a therapeutic challenge. Rationale for Radiotherapy Dose Escalation in HNC The optimal radiation dose to effectively control HNC has been limited by the normal tissue tolerance of adjacent organs, rather than reaching the tumoricidal dose required for complete sterilization of the cancer. Methods to improve the therapeutic ratio include dose escalation by SRS or brachytherapy (catheters surgically placed into the tumor and loaded with radiation sources). Integration of a planned radiation boost following conventional EBRT has

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Edward H. Oldfield, Johanna J. Loomba, Stephen J. Monteith, R. Webster Crowley, Ricky Medel, Daryl R. Gress, Neal F. Kassell, Aaron S. Dumont, and Craig Sherman

therapeutic agent for the prevention and reversal of cerebral vasospasm after SAH, 6 , 15 , 16 prevention of reperfusion injury associated with myocardial infarction, 3 , 4 , 13 , 19 elicitation of therapeutic angiogenesis, 2 treatment of pulmonary hypertension, 14 and enhanced preservation of tissues for transplantation. 11 , 12 Several of these potential clinical therapies will require systemic delivery of nitrite over hours or days. A previous dose-escalating Phase I study examined the safety and pharmacokinetics of a 48-hour intravenous infusion of nitrite in

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Timothy D. Solberg, Nzhde Agazaryan, Bryan W. Goss, Magnus Dahlbom, and Steve P. Lee

J Radiat Oncol Biol Phys 55: 99–109, 2003 22. Nutting CM , Corbishley CM , Sanchez-Nieto B , et al : Potential improvements in the therapeutic ratio of prostate cancer irradiation: dose escalation of pathologically identified tumour nodules using intensity modulated radiotherapy. Br J Radiol 75 : 151 – 161 , 2002 Nutting CM, Corbishley CM, Sanchez-Nieto B, et al: Potential improvements in the therapeutic ratio of prostate cancer irradiation: dose escalation of pathologically identified tumour nodules using