The preclinical safety of RPR 106541, a novel 17-thiosteroid, was

Hemoglobin based oxygen-carrying solutions (HBOCs) as hemoglobin replacement therapeutics are being tested for clinical use. Some of these products are associated with elevations in both systemic and pulmonary vascular resistances but their effect on the distribution of blood flow to major organs in larger animals have not been extensively described. We tested two formulations of o-raffinose cross-linked human hemoglobin, Hemolink (frozen Hemolink-1 and refrigerated Hemolink-2) and compared them to Pentaspan, a colloid volume expander in extensive clinical use. Cardiovascular measurements and the distribution of blood flow (radionuclide-labeled microspheres) to the major organs were determined in Beagle dogs (n=5 per group). After baseline measurements, either Hemolink-1, or Hemolink-2, or Pentaspan was exchange transfused in an isovolemic manner (resulting in hematocrit reduction to approximately 20-25%); measurements were made 30, 60, 120 and 180 min post-exchange. There was no significant difference in cardiac output, mean arterial pressures and systemic or pulmonary vascular resistance after exchange in any of the three groups. Myocardial blood flow increased in all three groups post-exchange but the increase was more sustained in the Hemolink groups. Endocardial/epicardial flow ratios were also maintained after exchange in all groups. Thus, Hemolink is ideally suited for volume replacement when used in conjunction with acute normovolemic hemodilution because under these circumstances, the adverse hemodynamic effects are alleviated while extra hemoglobin is added to the blood.

Hemoglobin based oxygen-carrying solutions (HBOCs) as hemoglobin replacement therapeutics are being tested for clinical use. Some of these products are associated with elevations in both systemic and pulmonary vascular resistances but their effect on the distribution of blood flow to major organs in larger animals have not been extensively described. We tested two formulations of o-raffinose cross-linked human hemoglobin, Hemolink (frozen-Hemolink-1 and refrigerated Hemolink-2) and compared them to Pentaspan, a colloid volume expander in extensive clinical use. Cardiovascular measurements and the distribution of blood flow (radionuclide-labeled microspheres) to the major organs were determined in Beagle dogs (n = 5 per group). After baseline measurements, either Hemolink-1, Hemolink-2, or Pentaspan was exchange transfused in an isovolemic manner (resulting in hematocrit reduction to approximately 20-25%); measurements were made 30, 60, 120 and 180 min post-exchange. There was no significant difference in cardiac output, mean arterial pressures and systemic or pulmonary vascular resistances after exchange in any of the three groups. Myocardial blood flow increased in all three groups post-exchange but the increase was more sustained in the Hemolink groups. Endocardial/epicardial flow ratios were also maintained after exchange in all groups. Thus, Hemolink is ideally suited for volume replacement when used in conjunction with acute normovolemic hemodilution because under these circumstances, the adverse hemodynamic effects are alleviated while extra hemoglobin is added to the blood.

Purpose: To evaluate the dosimetric potential of respiratory‐gated volumetric‐modulated arc therapy (VMAT) to reduce the dose to normal lung when treating early stage non‐small cell lung cancer (NSCLC) with stereotactic body radiation therapy (SBRT). Methods: Seven early‐stage NSCLC patients were retrospectively planned with gated and un‐gated VMAT using Smart Arc (Pinnacle v9.0, Philips Medical Systems, Cleveland, USA). The average 4D‐CT of each patient was used as the planning CT for the un‐gated VMAT plans. A subset average CT that minimized the motion within a 30% gating window was used as the planning CT for the gated VMAT plans. Each VMAT plan consisted of one arc to minimize the delivery time. All plans were prescribed 54 Gy in 3 fractions and all dosimetric parameters satisfied the requirements of our in‐house lung SBRT protocol. In order to avoid dosimetry bias between the gated and un‐gated plans, a Pinnacle host script was generated and used to optimize all 14 plans. Dosimetric parameters such as D(2cm), V(20), and the total normal lung volume receiving 50% of the prescription dose were compared. Results: There was a significant decrease in all dosimetric parameters considered in this study. D(2cm) decreased from (53.960 +/− 2.680)% to (51.703 +/− 1.907)% (p<.05). V(20) decreased from (6.629 +/− 1.565)% to (5.213 +/−1.387)% (p<.005) and the total normal lung receiving 50% of the prescription dose decreased from (254.465 +/− 62.853) cm̂3 to (177.068 +/− 45.947) cm̂3 (p<0.004). Conclusions: Respiratory‐gated VMAT has the potential to reduce the dose to normal lung when treating early‐stage NSCLC with SBRT to moving targets with motion greater than 10 mm.

Purpose: To quantify the interplay effect for various IMRT techniques used to deliver Stereotactic‐Body Radiation Therapy (SBRT) to early‐stage lung cancer. Methods: Five lung cancer patients who received SBRT were retrospectively planned (54Gy/3fx) on the average 4D‐CT dataset with eight different IMRT techniques: three fixed‐beam IMRT plans (simple step‐and‐shoot (S/S), complex S/S, and sliding‐window (S/W)), Tomotherapy plans using three different beam sizes (1cm, 2.5cm, and 5cm), and two Volumetric‐Modulated Arc Therapy (VMAT) plans (one planned with Rapid Arc (Eclipse v8.9, Varian Medical Systems, Palo Alto, USA) and one planned with Smart Arc (Pinnacle v9.0, Philips Medical Systems, Cleveland, USA)). All treatment plans were calculated on a CT of the ArcCHECK phantom by Sun Nuclear (Gland, Switzerland) that was mounted on the QUASAR™ Programmable Respiratory Motion Platform (Modus Medical Devices Inc., London, Ontario). Each plan was delivered under the following motion conditions: 1) Static mode; 2) Sinusoidal mode (4s period) with S/I motion ranging from 5mm–20mm peak‐to‐peak in 5 mm increments; 3) Real‐patient waveforms ranging from 5mm–30mm peak‐to‐peak. A standard 3%/3mm gamma analysis compared each delivery to their corresponding calculated plan. Results: All methods were acceptable on average (>90% points pass) up to 15mm peak‐to‐peak motion except for the Rapid Arc plan, which had a significantly less pass rate (75.6+/−3.9%) than all other techniques (p<.02). Tomotherapy plans using either a 2.5cm beam (98.7+/−2.1%) or 5cm beam (96.8+/−3.5%) were still acceptable for motion up to 20 mm peak‐to‐peak. For irregular motion greater than 15mm, only the VMAT techniques failed ((74.9+/−16.6)% for Rapid Arc and (89.3+/−8.9)% for Smart Arc on average. Conclusions: Interplay effect in SBRT delivery was dependent on the IMRT technique for peak‐to‐peak motions greater than 15 mm. Tomotherapy was the least sensitive for motion up to 20mm. Rapid Arc was the most sensitive for motion greater than 15mm peak‐to‐peak.