ß-Endorphin mediates radiation therapy fatigue.

Fatigue is a common adverse effect of external beam radiation therapy in cancer patients. Mechanisms causing radiation fatigue remain unclear, although linkage to skin irradiation has been suggested. ß-Endorphin, an endogenous opioid, is synthesized in skin following genotoxic ultraviolet irradiation and acts systemically, producing addiction. Exogenous opiates with the same receptor activity as ß-endorphin can cause fatigue. Using rodent models of radiation therapy, exposing tails and sparing vital organs, we tested whether skin-derived ß-endorphin contributes to radiation-induced fatigue. Over a 6-week radiation regimen, plasma ß-endorphin increased in rats, paralleled by opiate phenotypes (elevated pain thresholds, Straub tail) and fatigue-like behavior, which was reversed in animals treated by the opiate antagonist naloxone. Mechanistically, all these phenotypes were blocked by opiate antagonist treatment and were undetected in either ß-endorphin knockout mice or mice lacking keratinocyte p53 expression. These findings implicate skin-derived ß-endorphin in systemic effects of radiation therapy. Opioid antagonism may warrant testing in humans as treatment or prevention of radiation-induced fatigue.

Electronic intracavitary brachytherapy quality management based on risk analysis: The report of AAPM TG 182.

PURPOSE: The purpose of this study was to provide guidance on quality management for electronic brachytherapy. MATERIALS AND METHODS: The task group used the risk-assessment approach of Task Group 100 of the American Association of Physicists in Medicine. Because the quality management program for a device is intimately tied to the procedure in which it is used, the task group first designed quality interventions for intracavitary brachytherapy for both commercial electronic brachytherapy units in the setting of accelerated partial-breast irradiation. To demonstrate the methodology to extend an existing risk analysis for a different application, the task group modified the analysis for the case of post-hysterectomy, vaginal cuff irradiation for one of the devices. RESULTS: The analysis illustrated how the TG-100 methodology can lead to interventions to reduce risks and improve quality for each unit and procedure addressed. CONCLUSION: This report provides a model to guide facilities establishing a quality management program for electronic brachytherapy.

Measurement of the neutron leakage from a dedicated intraoperative radiation therapy electron linear accelerator and a conventional linear accelerator for 9, 12, 15(16), and 18(20) MeV electron energies.

The issue of neutron leakage has recently been raised in connection with dedicated electron-only linear accelerators used for intraoperative radiation therapy (IORT). In particular, concern has been expressed about the degree of neutron production at energies of 10 MeV and higher due to the need for additional, perhaps permanent, shielding in the room in which the device is operated. In particular, three mobile linear accelerators available commercially offer electron energies at or above the neutron threshold, one at 9 MeV, one at 10 MeV, and the third at 12 MeV. To investigate this problem, neutron leakage has been measured around the head of two types of electron accelerators at a distance of 1 m from the target at azimuthal angles of 0 degrees, 45 degrees, 90 degrees, 135 degrees, and 180 degrees. The first is a dedicated electron-only (nonmobile) machine with electron energies of 6 (not used here), 9, 12, 15, and 18 MeV and the second a conventional machine with electron energies of 6 (also not used here), 9, 12, 16, and 20 MeV. Measurements were made using neutron bubble detectors and track-etch detectors. For electron beams from a conventional accelerator, the neutron leakage in the forward direction in Sv/Gy is 2.1 x 10(-5) at 12 MeV, 1.3 x 10(-4) at 16 MeV, and 4.2 x 10(-4) at 20 MeV, assuming a quality factor (RBE) of 10. For azimuthal angles > 0 degrees, the leakage is almost angle independent [2 x 10(-6) at 12 MeV; (0.7-1.6) x 10(-5) at 16 MeV, and (1.6-2.9) x 10(-5) at 20 MeV]. For the electron-only machine, the neutron leakage was lower than for the conventional linac, but also independent of azimuthal angle for angles > 0 degrees: {[0 degrees: 7.7 x 10(-6) at 12 MeV; 3.0 x 10(-5) at 15 MeV; 1.0 x 10(-4) at 18 MeV]; [other angles: (2.6-5.9) x 10(-7) at 12 MeV; (1.4-2.2) x 10(-6) at 15 MeV; (2.7-4.7) x 10(-6) at 18 MeV]}. Using the upper limit of 6 x 10(-7) Sv/Gy at 12 MeV for the IORT machine for azimuthal angles > 0 degrees and assuming a workload of 200 Gy/wk and an inverse square factor of 10, the neutron dose equivalent is calculated to be 0.012 mSv/wk. For the primary beam at 12 MeV (0 degrees), the 10 x higher dose would be compensated by the attenuation of a primary beam stopper in a mobile linear accelerator. These neutron radiation levels are below regulatory values (National Council on Radiation Protection and Measurements, "Limitation of exposure to ionizing radiation," NCRP Report No. 116, NCRP Bethesda, MD, 1993).

Measurement of the leakage radiation from linear accelerators in the backward direction for 4, 6, 10, 15, and 18 MV x-ray energies.

The x-ray leakage from the housing of a therapy x-ray source is regulated to be <0.1% of the useful beam exposure at 1 m from the source. It is to be expected that the machine leakage in the backward direction would be less because the gantry and stand contain significant amounts of additional metal to attenuate the x rays. A reduction in head leakage in this direction will have a direct effect on the thickness of the shielding wall behind the linear accelerator. However, no reports have been published to date on measurements in this area. The x-ray leakage in the backward direction has been measured from linacs having energies of 4, 6, 10, 15, and 18 MV using a 100 cm ionization chamber and Al2O3 dosimeters. The leakage was measured at nine different positions over the rear wall using a 3 x 3 matrix with a 1-m separation between adjacent horizontal and vertical points with either the leftmost or rightmost column aligned with the target and isocenter. In general, the leakage is less than the canonical value, but the exact value depends on energy, gantry angle, and measurement position. There is significantly greater attenuation directly behind the gantry stand for all energies. Leakage at 10 MV for some positions exceeded 0.1%. Additionally, neutron leakage measurements were made for 10, 15, and 18 MV x-ray beams using track-etch detectors. The average neutron leakage was less than 0.1% except for 18 MV, where neutron leakage was more than 0.1% of the useful beam at some positions.

Tenth value layers for 60Co gamma rays and for 4, 6, 10, 15, and 18 MV x rays in concrete for beams of cone angles between 0 degrees and 14 degrees calculated by Monte Carlo simulation.

The calculation of shielding barrier thicknesses for radiation therapy facilities according to the NCRP formalism is based on the use of broad beams (that is, the maximum possible field sizes). However, in practice, treatment fields used in radiation therapy are, on average, less than half the maximum size. Indeed, many contemporary treatment techniques call for reduced field sizes to reduce co-morbidity and the risk of second cancers. Therefore, published tenth value layers (TVLs) for shielding materials do not apply to these very small fields. There is, hence, a need to determine the TVLs for various beam modalities as a function of field size. The attenuation of (60)Co gamma rays and photons of 4, 6, 10, 15, and 18 MV bremsstrahlung x ray beams by concrete has been studied using the Monte Carlo technique (MCNP version 4C2) for beams of half-opening angles of 0 degrees , 3 degrees , 6 degrees , 9 degrees , 12 degrees , and 14 degrees . The distance between the x-ray source and the distal surface of the shielding wall was fixed at 600 cm, a distance that is typical for modern radiation therapy rooms. The maximum concrete thickness varied between 76.5 cm and 151.5 cm for (60)Co and 18 MV x rays, respectively. Detectors were placed at 630 cm, 700 cm, and 800 cm from the source. TVLs have been determined down to the third TVL. Energy spectra for 4, 6, 10, 15, and 18 MV x rays for 10 x 10 cm(2) and 40 x 40 cm(2) field sizes were used to generate depth dose curves in water that were compared with experimentally measured values.

Intraoperative radiation therapy using mobile electron linear accelerators: report of AAPM Radiation Therapy Committee Task Group No. 72.

Intraoperative radiation therapy (IORT) has been customarily performed either in a shielded operating suite located in the operating room (OR) or in a shielded treatment room located within the Department of Radiation Oncology. In both cases, this cancer treatment modality uses stationary linear accelerators. With the development of new technology, mobile linear accelerators have recently become available for IORT. Mobility offers flexibility in treatment location and is leading to a renewed interest in IORT. These mobile accelerator units, which can be transported any day of use to almost any location within a hospital setting, are assembled in a nondedicated environment and used to deliver IORT. Numerous aspects of the design of these new units differ from that of conventional linear accelerators. The scope of this Task Group (TG-72) will focus on items that particularly apply to mobile IORT electron systems. More specifically, the charges to this Task Group are to (i) identify the key differences between stationary and mobile electron linear accelerators used for IORT, (ii) describe and recommend the implementation of an IORT program within the OR environment, (iii) present and discuss radiation protection issues and consequences of working within a nondedicated radiotherapy environment, (iv) describe and recommend the acceptance and machine commissioning of items that are specific to mobile electron linear accelerators, and (v) design and recommend an efficient quality assurance program for mobile systems.

Long term stability of a 50 kV X-ray unit for stereotactic irradiation.

A low-energy (50 kV) X-ray tube used for the stereotactic irradiation of intracranial lesions has been in use since 1999. The unit is calibrated prior to every procedure and during periodic quality assurance (QA) tests. The unit uses an internal and an external scintillation detector to monitor dose as well as a conventional timer. The records of these calibrations were reviewed to see whether a change in the output had occurred over that period. Using time as the reference, it was found that both the internal radiation monitor (IRM) and the beam output, determined with a parallel plate ionization chamber, dropped by variable amounts over the given period. The beam output dropped significantly more than the IRM, while the external radiation monitor (ERM) showed no significant deviation from its initial value. The beam output dropped to about 90% of its initial value after about 200 days but remained relatively constant thereafter. The IRM dropped steadily to about 96% to 97% of its initial value at 1000 days, but recovered to about 98% after that. Calibration prior to each procedure is strongly recommended.

Review of the energy check of an electron-only linear accelerator over a 6 year period: sensitivity of the technique to energy shift.

The calibration and monthly QA of an electron-only linear accelerator dedicated to intra-operative radiation therapy has been reviewed. Since this machine is calibrated prior to every procedure, there was no necessity to adjust the output calibration at any time except, perhaps, when the magnetron is changed, provided the machine output is reasonably stable. This gives a unique opportunity to study the dose output of the machine per monitor unit, variation in the timer error, flatness and symmetry of the beam and the energy check as a function of time. The results show that, although the dose per monitor unit varied within +/- 2%, the timer error within +/- 0.005 MU and the asymmetry within 1-2%, none of these parameters showed any systematic change with time. On the other hand, the energy check showed a linear drift with time for 6, 9, and 12 MeV (2.1, 3.5, and 2.5%, respectively, over 5 years), while at 15 and 18 MeV, the energy check was relatively constant. It is further shown that based on annual calibrations and RPC TLD checks, the energy of each beam is constant and that therefore the energy check is an exquisitely sensitive one. The consistency of the independent checks is demonstrated.

Clinical physics, applicator choice, technique, and equipment for electron intraoperative radiation therapy.

IORT has been a widely used modality since the 1980s. The initial euphoria experienced at the beginning, however, has subsided, with the result that most centers still practicing IORT are academic institutions. The reason for the reduction in IORT performed at community hospitals is partly related to the method of treatment--namely, transporting the patient from the OR to the radiation therapy department. The advent of mobile linear accelerators, which require little or no shielding and can therefore be used in most OR rooms, is likely to reiginite interest in this modality. There are currently six new centers in the United States that practice IORT with a mobile linear accelerator and more than that in Europe.

Measurement of TVLs in lead for 4, 6 and 10 MV bremsstrahlung x-ray beams at scattering angles between 30 degrees and 135 degrees.

Measurements have been made of the transmission factors through lead for scattered radiation produced by 4, 6, and 10 MV bremsstrahlung x-ray beams incident on a polystyrene phantom; these measurements cover the range of scattering angles between 30 degrees and 135 degrees. The results show that the tenth value layer (TVL) for scattered radiation decreases sharply with increasing scattering angle and increases slightly with increasing beam energy, although at large scattering angles there is little energy dependence. TVLs range from 3.5 cm to 0.3 cm for 4 MV at scattering angles between 30 degrees and 135 degrees, from 3.8 cm to 0.6 cm for 6 MV, and from 4.2 cm to 0.7 cm for 10 MV, respectively, at scattering angles between 30 degrees and 120 degrees. Monte Carlo calculations, performed at 4 MV to simulate the transmission of scattered radiation, are in good agreement with the experimental measurements.

Outcomes in a multi-institutional cohort of patients treated with intraoperative radiation therapy for advanced or recurrent renal cell carcinoma.

PURPOSE/OBJECTIVE(S): This study aimed to analyze outcomes in a multi-institutional cohort of patients with advanced or recurrent renal cell carcinoma (RCC) who were treated with intraoperative radiation therapy (IORT). METHODS AND MATERIALS: Between 1985 and 2010, 98 patients received IORT for advanced or locally recurrent RCC at 9 institutions. The median follow-up time for surviving patients was 3.5 years. Overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were estimated with the Kaplan-Meier method. Chained imputation accounted for missing data, and multivariate Cox hazards regression tested significance. RESULTS: IORT was delivered during nephrectomy for advanced disease (28%) or during resection of locally recurrent RCC in the renal fossa (72%). Sixty-nine percent of the patients were male, and the median age was 58 years. At the time of primary resection, the T stages were as follows: 17% T1, 12% T2, 55% T3, and 16% T4. Eighty-seven percent of the patients had a visibly complete resection of tumor. Preoperative or postoperative external beam radiation therapy was administered to 27% and 35% of patients, respectively. The 5-year OS was 37% for advanced disease and 55% for locally recurrent disease. The respective 5-year DSS was 41% and 60%. The respective 5-year DFS was 39% and 52%. Initial nodal involvement (hazard ratio [HR] 2.9-3.6, P<.01), presence of sarcomatoid features (HR 3.7-6.9, P<.05), and higher IORT dose (HR 1.3, P<.001) were statistically significantly associated with decreased survival. Adjuvant systemic therapy was associated with decreased DSS (HR 2.4, P=.03). For locally recurrent tumors, positive margin status (HR 2.6, P=.01) was associated with decreased OS. CONCLUSIONS: We report the largest known cohort of patients with RCC managed by IORT and have identified several factors associated with survival. The outcomes for patients receiving IORT in the setting of local recurrence compare favorably to similar cohorts treated by local resection alone suggesting the potential for improved DFS with IORT.

Do angles of obliquity apply to 30 degrees scattered radiation from megavoltage beams?

The angle of obliquity is used in radiation shielding calculations to account for the longer path length x rays will see when obliquely incident on the protective barrier. According to the National Council on Radiation Protection and Measurements (NCRP), use of the angle of obliquity is explicitly assumed for primary radiation, so that an angle of obliquity for secondary radiation is never addressed. However, in the example section of the latest report, it specifically recommends against using an angle of obliquity for scattered radiation. To check this assumption, the existence or not of an angle of obliquity for scattered radiation has been investigated for bremsstrahlung x-ray beams of 4, 6, 10, 15, and 18 MV and for barriers consisting of concrete, lead, and steel using a Monte Carlo approach. The MCNP Monte Carlo code, v4.2C, has been used to generate scattered radiation at 30 degrees from a water phantom and incident on a secondary barrier at the same angle relative to the normal to the barrier. The barrier thickness was increased from zero to a thickness sufficient to reduce the fluence (f4 tally) to <10(-3). A transmission curve was created for each energy-barrier material combination by normalizing to zero thickness. The results for the first tenth-value layer (TVL) in concrete (5 energies) show an average angle of obliquity of 21.7 degrees +/- 5.6 degrees , and for the first two TVLs averaged 29.7 degrees +/- 3.9 degrees . The results for the first TVL in lead (3 energies) show an average angle of obliquity of 27.7 degrees +/- 4.0 degrees , and for the first two TVLs averaged 20.5 degrees +/- 5.8 degrees . There are no data in the NCRP reports for 30 degrees scattered radiation attenuated by steel with which to make a comparison.