Radiation therapy vault shielding calculational methods when IMRT and TBI procedures contribute.

The additional intensity modulated radiation therapy (IMRT) and total body irradiation (TBI) to conventional treatment clinical treatment procedures can significantly increase the contribution of accelerator head leakage radiation. Previously recommended procedures by the National Council on Radiation Protection and Measurements (NCRP) for vault design, specifically calculations of primary and secondary barrier thicknesses, are not valid when leakage radiation significantly exceeds direct radiation. Use factor distributions are also influenced by IMRT and TBI procedures. Methods are proposed to extend the NCRP barrier design formulas to resolve these problems. The medical accelerator (weekly) workload is separately determined for the direct, leakage, and scatter radiation components. Applications of the formulas to the calculation of primary and secondary barriers are discussed. The addition of IMRT to the shielding design is explored as a function of the fraction patients receiving IMRT and the MU to dose ratio. Secondary barrier thicknesses could be increased by as much as 1 TVL.

Angiotensin II-receptor blockers: clinical relevance and therapeutic role.

The limitations of angiotensin-converting-enzyme (ACE) inhibitors and the role of angiotensin II-receptor blockers (ARBs) in the treatment of hypertension, heart failure, and diabetic nephropathy are discussed. Although ACE inhibitors are generally well tolerated, two important class-related adverse effects are cough, which is common, and angioedema, which is rare but serious. Cough and angioedema appear to be less frequent with ARBs than with ACE inhibitors. ARBs seem to be as capable as ACE inhibitors of producing renal dysfunction. ARBs may offer more complete inhibition of angiotensin II than ACE inhibitors. The mechanism of action is based on selective binding to angiotensin type 1 receptors. Many clinical studies have shown that ARBs lower blood pressure as effectively as other antihypertensive agents, including ACE inhibitors. ARBs do not appear to have a greater clinical effect than ACE inhibitors in patients with heart failure. Some studies of combination ARB and ACE inhibitor therapy for heart failure indicate advantages of the combination over therapy with either class. ARBs may exert renal protective effects in diabetic nephropathy. ARBs offer an alternative to ACE inhibitors in the management of hypertension, especially for ACE-inhibitor-intolerant patients. ACE inhibitors remain the drugs of choice for patients with heart failure, left ventricular dysfunction after MI, and diabetic nephropathy; ARBs offer these patients an alternative when ACE inhibitor therapy is not tolerated.

The role of the renin-angiotensin-aldosterone system in the management of heart failure.

Numerous clinical trials have highlighted the role of the renin-angiotensin-aldosterone (RAA) system in the development and progression of heart failure. Over 30 randomized, controlled trials have evaluated the effects of angiotensin-converting enzyme (ACE) inhibitors on morbidity and mortality in over 7,000 patients with heart failure. Cumulative evidence from these trials shows that these agents significantly reduce mortality and hospitalizations, slow disease progression, and improve exercise tolerance and New York Heart Association class. The Heart Failure Society of America guidelines recommend ACE inhibitors as standard therapy for patients with left ventricular systolic dysfunction. The angiotensin receptor blockers and spironolactone offer alternative and perhaps complimentary mechanisms by which the RAA system may be therapeutically manipulated. The role of these therapies in treating heart failure is discussed.

Scatter fractions from linear accelerators with x-ray energies from 6 to 24 MV.

Computation of shielding requirements for a linear accelerator must take into account the amount of radiation scattered from the patient to areas outside the primary beam. Currently, the most frequently used data are from NCRP 49 that only includes data for x-ray energies up to 6 MV and angles from 30 degrees to 135 degrees. In this work we have determined by Monte Carlo simulation the scattered fractions of dose for a wide range of energies and angles of clinical significance including 6, 10, 18, and 24 MV and scattering angles from 10 degrees to 150 degrees. Calculations were made for a 400 cm2 circular field size impinging onto a spherical phantom. Scattered fractions of dose were determined at 1 m from the phantom. Angles from 10 degrees to 30 degrees are of concern for higher energies where the scatter is primarily in the forward direction. An error in scatter fraction may result in too little secondary shielding near the junction with the primary barrier. The Monte Carlo code ITS (Version 3.0) developed at Sandia National Laboratory and NIST was used to simulate scatter from the patient to the barrier. Of significance was the variation of calculated scattered dose with depth of measurement within the barrier indicating that accurate values may be difficult to obtain. Mean energies of scatter x-ray spectra are presented.

Scattered fractions of dose from 6,10,18, and 25 MV linear accelerator x rays in radiotherapy facilities.

Data for computation of primary and secondary shielding barriers in radiotherapy facilities are presented in the National Council on Radiation Protection and Measurements Report 49, which covers primary barriers for accelerating voltages up to 10 MV and secondary barriers up to 6 MV. Inconsistencies in reported scattered fraction values found in the literature for megavoltage accelerators are due, in part, to differences in measurement techniques. A consistent approach was used to measure the scattered fractions of 6, 10, 18, and 25 MV photon dose. A reference ion chamber was placed on the symmetry axis of a cylindrical water phantom, approximating the human torso, 25.6 cm diameter, at the gantry isocenter. Measurements were made with a second ion chamber at 2m from the isocenter at angles ranging from 10 degrees through 150 degrees from the beam central axis with a field size of 20 cm x 20 cm at the isocenter. The dose measured at each angle is reported as a fraction of the reference chamber dose at the center of the phantom and as calculated to a reference chamber depth of d(max), also at the isocenter. The results of these measurements were compared with Monte Carlo calculations and show reasonable agreement. A comparison with previously published data was not as good due to the differences in measurement techniques. However, after some adjustments to correct for the differences, the comparison is very good. Scattered fractions beyond 30 degrees are highest for the lowest energy beam investigated. This indicates that the scattered fraction values reported in NCRP 49 for 6 MV are sufficient for use in conservative shielding calculations for the higher energy x rays beyond 30 degrees. For angles smaller than 30 degrees, the new data are more appropriate and show the scatter fractions are larger for higher MV x rays.

Investigation of neutron-induced damage in DNA by atomic force microscopy: experimental evidence of clustered DNA lesions.

Using atomic force microscopy (AFM), we have investigated neutron-induced DNA double-strand breaks in plasmids in aqueous solution. AFM permits direct measurement of individual DNA molecules with an accuracy of a few nanometers. Furthermore, the analysis of the DNA fragment size distribution is non-parametric, whereas other methods are dependent on the model. Neutron irradiation of DNA results in the generation of many short fragments, an observation not made for damage induced by low-LET radiation. These data provide clear experimental evidence for the existence of clustered DNA double-strand breaks and demonstrate that short DNA fragments may be produced by such radiations in the absence of a nucleosomal DNA structure.

Prolonged weakness after cisatracurium infusion: a case report.

OBJECTIVE: To present the first documented case report of myopathy persisting for >48 hrs in a patient treated with cisatracurium and concomitant high-dose corticosteroids. DESIGN: Anecdotal observations in one patient. SETTING: Medical-respiratory intensive care unit (ICU) at a tertiary care, university teaching hospital. PATIENT: A 45-yr-old female admitted status for post-bilateral total knee replacement complicated by aspiration pneumonitis and acute respiratory distress syndrome (ARDS). INTERVENTIONS: The patient required pressure control ventilation and sedation with midazolam and fentanyl infusions. On ICU day 2, the patient was placed on inverse ratio ventilation and paralyzed with cisatracurium. On ICU day 6, methylprednisolone 125 mg i.v. every 6 hrs was initiated for fibroproliferative ARDS. On ICU day 11, methylprednisolone was reduced to 60 mg i.v. every 6 hrs and tapered over several weeks. Cisatracurium infusion rates ranged from 6.3 to 10.5 microg/kg/min, with an average of 8.0 microg/kg/min. MEASUREMENTS AND MAIN RESULTS: Train-of-Four was assessed before initiation of therapy and every 4 hrs, thereafter. Train-of-Four values were maintained from 1 to 4 throughout therapy and a value of 4 was recorded when therapy was discontinued. On day 13, neuromuscular blocking agent therapy was discontinued, but severe proximal and distal muscle weakness was observed bilaterally. Creatinine kinase concentrations on 3 and 13 days after discontinuation of the paralytic agent were 181 and 96 units/L, respectively. On day 24, the patient moved her fingertips. On ICU day 30, the patient was weaned from the mechanical ventilator. The patient was transferred to the ward on day 33. Extensive rehabilitation with physical and occupational therapy was required for several months. CONCLUSION: Clinicians should remember that irrespective of chemical structural, neuromuscular blocking agents might produce prolonged paralysis in predisposed patients.

Treatment of female urethral carcinoma in medically inoperable patients using external beam irradiation and high dose rate intracavitary brachytherapy.

PURPOSE: We developed and present our experience with high dose rate brachytherapy for treatment of carcinoma of the urethra in medically inoperable women. MATERIALS AND METHODS: Since 1991, 4 women with localized urethral cancer, medically unable to undergo resection or interstitial implantation, were treated with external beam and high dose rate intracavitary implantation rather than external beam irradiation alone. The fractionated implants were delivered with a high dose rate remote afterloader using a shielded vaginal applicator and modified urethral catheter. The urethral catheter was inserted through the lumen of a 20F Foley tube to improve depth dose. Homogeneous dose distribution was achieved and customized to the individual patient. RESULTS: All high dose rate brachytherapy treatments were given at the clinic without use of sedation or anesthesia. Treatment was well tolerated, and all patients maintained voluntary urinary function and local control at 12 to 55 months after therapy. Chronic morbidity due to urethral, bladder, vaginal or rectal injury, including urethral stenosis, necrosis or fistula, was not noted. Isodose distributions were compared among this technique, interstitial implantation and external beam radiotherapy alone. CONCLUSIONS: Although we prefer interstitial implantation as the boost technique for women with urethral cancer, high dose rate brachytherapy is a reasonable option for medically inoperable patients. This outpatient treatment is well tolerated, preserves voluntary urinary function and enhances quality of life.

Effects of beam spoiler on radiation dose for head and neck irradiation with 10-MV photon beam.

PURPOSE: To determine the effects of a lucite beam spoiler on the dose distribution to points inside and outside the primary beam for head and neck irradiation with a 10-MV photon beam. METHODS AND MATERIALS: Build-up and depth-dose measurements were performed with a parallel-plate ionization chamber for 5 x 5, 10 x 10, and 15 x 15-cm field sizes using lucite spoilers with two different thicknesses at two different lucite-to-skin distances (LSD) for a 10-MV x-ray beam. Corrections were applied to account for finite chamber size. Beam profiles and isodose curves were obtained at several depths using film dosimetry. Beam uniformity was determined from uniformity indices. Peripheral doses (PD) were measured at the surface and at 1.5- and 2.5-cm depths using film dosimetry and a parallel-plate ionization chamber. Measurement points were positioned at the edge of a 10 x 10-cm field and at distances extending to 5.0 cm away. The treatment planning data for the 10-MV x-ray beam were modified to account for the effects of the beam spoiler when treating head and neck patients. RESULTS: The spoiler increased the surface and build-up dose and shifted the depth of maximum dose toward the surface. With a 10-MV x-ray beam and a 1.2-cm-thick lucite at 15 cm LSD, a build-up dose similar to a 6-MV x-ray beam was achieved. The beam uniformity was altered at shallow depths. The peripheral dose was enhanced particularly at the surface and at the points close to the beam edge. The effects of the beam spoiler on beam profile and PD were reduced with increasing depths. CONCLUSION: The lucite spoiler allowed use of a 10-MV x-ray beam for head and neck treatment by yielding a build-up dose similar to that of a 6-MV x-ray beam while maintaining skin sparing. The increase in PD was at superficial depths and was reduced at points away from the edge; therefore, it is clinically nonsignificant. Spoiling the 10-MV x-ray beam resulted in treatment plans that maintained dose homogeneity without the consequence of increased skin reaction or treatment volume underdose for regions near the skin surface.

Correlating angiograms with CT/MRI scans for radiosurgery.

A mathematical solution is described to reconstruct 3-D objects in the stereotactic space from angiographic, not necessarily perpendicular 2-D projections. The mathematical calculation requires 6 markers, whose coordinates should be known within the stereotactic frame reference system. This method was developed to improve the planning in stereotactic radiosurgery of AVM. An AVM nidus can be geometrically described as delineated on plane film angiography. This approach provides a more accurate determination of the lesion shape, size, angulation and position when using information from stereotactic planar angiograms. Further more this technique supports a stereotactically accurate projection of the surface volume model of the AVM nidus on to the corresponding CT and MRI scans images.

Optimization of dose distribution for LINAC based radiosurgery using elliptical collimators.

The use of non-circular collimators is considered on all or some of the arcs used for radiosurgery on a linear accelerator in order to obtain conformal dose distribution for non-spherical lesions using a single isocenter. An extension of software to allow for use of non-circular collimators and a mathematical optimization based on prescribed doses on the lesion surface and on points in normal tissue (critical structures) are presented. Tests of the optimization method on simulated cases indicate that several boosts from selected positions along the arcs, superimposed on an optimized arc configuration allows one to obtain a highly conformal dose distribution with simple elliptical inserts. The optimization method can be applied to any type of collimation and is particularly effective with variable dose-rate machines.

Dosimetric parameters of a modified set of wedges for use with asymmetric fields of a 6 MV linear accelerator.

A set of standard wedge filters has been modified for use with half-collimated beams of a 6 MV linear accelerator. The position of the standard size wedge filter has been shifted as far to one side of the wedge plate to ensure optimum half-collimated field coverage (up to 20 x 30 cm) required in certain clinical situations. Dosimetric parameters were normalized at 1.5 cm depth and at an off-axis reference point (3.5 cm from the central axis of the collimator at 100 cm SSD. The shapes of the wedged profile and isodose curves of the modified wedges remained similar to those of standard wedges. Data presented include wedge transmission factors, wedge angles, beam profiles, and isodose distributions. The clinical advantages of using modified wedge filters (larger field size, larger transmission, and smaller weight) over standard large wedges is discussed.

Intraoperative high-dose rate interstitial irradiation of hepatic metastases from colorectal carcinoma. Results of a phase I-II trial.

BACKGROUND: Resection of liver metastases from colorectal carcinoma can be curative. Unresectable but liver-confined metastases might be ablated by high-dose radiation with a similar curative result. METHODS: At Georgetown University Hospital, 22 patients with unresectable hepatic metastases from colorectal carcinoma underwent 24 interstitial irradiation procedures at laparotomy in a Phase I-II study. A single dose was administered with a high-dose rate iridium-192 afterloader. Dose to the tumor periphery was 20 Gy, 25 Gy, and 30 Gy in 13, 9, and 2 procedures, respectively. RESULTS: No acute or chronic radiation toxicity has occurred at a median follow-up of 11 months. Median actuarial local control at irradiated sites was 8 months, with 26% actuarial local control at 26 months by computed tomography (CT) or magnetic resonance imaging (MRI) scanning. In the two patients undergoing two procedures each, a second biopsy of previously irradiated areas demonstrated tumor eradication. CONCLUSIONS: This innovative, radical approach to unresectable colorectal hepatic metastases proved safe. Additional study is needed to determine whether interstitial irradiation is as effective as surgical resection, or whether it alters the natural history of the disease or longevity.

A stereotactic brain implant technique with high activity I-125 seeds using a conventional brachytherapy treatment planning system.

A stereotactic brain implant program with removable high-activity I-125 seeds has recently been implemented for the treatment of malignant brain tumors. A Brown-Roberts-Wells (BRW) stereotactic frame with an NIH arc system and a guide template is used to introduce parallel catheters precisely into the tumor volume (Fig. 1). CT scans of patients with the BRW frame in place are used to determine the position of the catheters and the location of seeds in each catheter. The positions of the catheters are determined with respect to a "reference line" which represents the direction of approach in the central plane of the tumor. The seed coordinates are expressed in the catheter coordinate system with the X-axis along the catheter direction and the Y-Z plane parallel to the surface of the guide block. The Y-Z plane is orthogonal to x-axis. An AECL Theratronics Theraplane treatment planning system (SEED program) is used to obtain dose distributions based on seed coordinates. This treatment planning system does not require special purpose software for brachytherapy treatment planning. High-activity I-125 seeds (nominal 10-15 mCi/seed) are after-loaded into the inner catheters of double coaxial silicone (Gutin) catheters according to a preplanned scheme. The physical aspects of the brain implant program, treatment planning technique, and radiation safety measures are described.

Digital image processing of radiation therapy portal films.

Digital image processing has the potential to enhance and improve several functions of a modern radiation oncology department. These functions may include improving perception of information for low contrast films, electronic transfer of images to remote facilities and back, and reducing storage space requirements for archiving once treatment is finished. This paper gives an overview of the digitization process and of image processing fundamentals. The clinical evaluation of digitized portal films is also discussed. The authors conclude that digitizing low contrast radiation therapy portal films is feasible with present technology and will produce images acceptable for routine clinical use in most instances. The role of image enhancement is less well established and remains investigational.

Intraoperative interstitial radiation therapy for hepatic metastases from colorectal carcinomas.

Liver metastases from colorectal carcinomas occur frequently. While surgical resection offers the only hope for long-term cure, unsuspected bilobar metastases or extrahepatic metastatic disease may be found at laparotomy, precluding hepatic resection for cure. In this setting intraoperative interstitial hepatic irradiation using the Gamma Med II (Mick Radio-Nuclear Instruments, Bronx, New York) remote afterloading irradiator and an Iridium-192 source permits delivery of a tumoricidal dose to liver tumor(s) with a limited radiation dose to adjacent normal liver. Six patients underwent laparotomy for potential resection of hepatic metastases in a shielded operating room equipped with remote anesthesia monitoring capability and were found to be unresectable. An upper hand retractor facilitated liver exposure during the exploratory and subsequent radiation phases of the procedure. Intraoperative interstitial radiation therapy was performed in each patient. No significant complications occurred on follow-up from 2 to 9 months. Hepatic tumor regression or stabilization occurred on sonography and/or CT scan in each case with a median follow-up of 5 months. The technique offers the potential to ablate discrete tumor nodules within the liver. Ongoing clinical trials will determine the role of intraoperative interstitial radiation in the treatment of hepatic metastases.