Megavoltage Photon Irradiation Research Articles

Dependence of surface dose on atomic number in megavoltage photon beams.

Surface dose in megavoltage photon radiotherapy has a significant clinical impact on the skin-sparing effect. In previously published works, it was established that the presence of medium atomic number (Z) absorbers, such as tin, decreases the surface dose. It was concluded that high-Z absorbers, such as lead, increase the surface dose, relative to medium-Z absorbers, due to the increased contributions from photoelectrons and electron-positron pairs. The purpose of this investigation is to revisit these conclusions in the context of photon beams from modern linacs. A metric estimating the relative intensity of charged particles emitted in the forward direction, , was proposed using cross-sections for the photon interactions. The values were calculated for various absorbers using energy spectra of 6 and 10 MV photon beams from a Varian TrueBeam linac. Monte Carlo (MC) simulations were performed using TOPAS MC code to calculate the surface dose for various absorbers. Surface dose measurements were performed with 6 and 10 MV photon beams with tin and lead absorbers. The values were found to decrease as a function of Z for both 6 and 10 MV photon beams indicating that the surface dose from electrons emitted in the forward direction consistently decreases with increasing Z. With the increasing Z of the absorbers, both experimental and MC-calculated surface dose decreased without exhibiting a minimum at medium-Z absorbers. The surface dose for lead and tin was determined to be within 1% of each other for both 6 and 10 MV photon beams using MC simulations and experimental measurements. Therefore, no statistically significant difference in surface dose was found between the tin and lead absorbers disproving the presence of any minima in the surface dose versus the Z curve as has been reported in the literature. Surface dose for modern photon beams can be reduced using both medium and high Z absorbers since a consistent decrease in surface dose was found with increasing absorber Z.

Tumor Regression with 5-Aminolevulinic Acid (5-ALA)-Mediated Radiodynamic Therapy (RDT) Using Different Megavoltage Energies

5-aminolevulinic acid (5-ALA) accumulates in target tumor cells, where it is metabolized to a photosensitizer - protoporphyrin IX (PpIX). Cherenkov light induced by high-energy photon beams effectively activates the PpIX due to the Soret band. The activated photosensitizers lead to cellular toxicities to kill malignant tumor cells by converting surrounding tissue oxygens into singlet oxygens. Radiodynamic therapy (RDT) utilizes cellular damage caused by both radiation dose and activated photosensitizer. The emission of Cherenkov light was observed higher with higher energy irradiation in phantom and ex-vivo tissues. Therefore, using an in-vivo mouse model, this study aimed to investigate the efficacy and energy dependency of RDT combined with 5-ALA and different ranges of megavoltage photon irradiation. In order to investigate individual and synergistic effects of 5-ALA administration and radiation treatment, the tumors (n = 344) were randomized into eight groups: control (untreated), 5-ALA only, 6-, 15-, and 45-MV conventional radiation treatment (RT) only, 6-, 15-, and 45-MV RDT. 4 Gy in a single fraction was delivered to the tumors using three different energy photons for RT only and RDT groups. 5-ALA was systemically injected into 5-ALA only and RDT groups at 100 mg/kg by tail-vein 4 hours before irradiation for endogenous PpIX accumulation in the tumor. Tumor growth was measured using a 1.5 T MR scanner on the day of treatment (prior to the treatment), 3, 7, and 14 days post-treatment. Two-way repeated ANOVA with Bonferroni correction was used to compare each treatment group to determine the statistically significant difference in tumor growth. A total of 45 MV RDT resulted in the most significant decrease in tumor growth by 58.8 ± 3.4 %, 58.0 ± 3.0 %, and 55.0 ± 3.0 % compared to 5-ALA, 45 MV RT, and control group on 7 days post-treatment (P<0.001), respectively. Moreover, a synergistic effect of 45 MV RDT causes a 47.1-54.1 % additional decrease in tumor growth toward the effective treatment outcome. Compared to the different energies, 45 MV RDT resulted in a 52.2 ± 3.1 % and 19.7 ± 7.2 % decrease in tumor growth compared to 6 MV RDT and 15 MV RDT on 7 days post-treatment, respectively (P<0.001), whereas the conventional RT was not. Radiodynamic therapy using 5-ALA administration and 45MV photon beam irradiation resulted in the most significant tumor growth control. A photon energy dependency was observed in radiodynamic therapy. 45MV photon beams showed greater in activating PpIX, improving the synergistic effects of radiation dose and activated photosensitizer than the other energies. The preliminary results provide a foundation for new innovative treatment strategies that have the potential to improve cancer treatment.

A portable primary-standard level graphite calorimeter for absolute dosimetry in clinical pencil beam scanning proton beams

Objective. To report the use of a portable primary standard level graphite calorimeter for direct dose determination in clinical pencil beam scanning proton beams, which forms part of the recommendations of the proposed Institute of Physics and Engineering in Medicine (IPEM) Code of Practice (CoP) for proton therapy dosimetry. Approach. The primary standard proton calorimeter (PSPC) was developed at the National Physical Laboratory (NPL) and measurements were performed at four clinical proton therapy facilities that use pencil beam scanning for beam delivery. Correction factors for the presence of impurities and vacuum gaps were calculated and applied, as well as dose conversion factors to obtain dose to water. Measurements were performed in the middle of 10 × 10 × 10 cm3 homogeneous dose volumes, centred at 10.0, 15.0 and 25.0 g·cm−2 depth in water. The absorbed dose to water determined with the calorimeter was compared to the dose obtained using PTW Roos-type ionisation chambers calibrated in terms of absorbed dose to water in 60Co applying the recommendations in the IAEA TRS-398 CoP. Main results. The relative dose difference between the two protocols varied between 0.4% and 2.1% depending on the facility. The reported overall uncertainty in the determination of absorbed dose to water using the calorimeter is 0.9% (k = 1), which corresponds to a significant reduction of uncertainty in comparison with the TRS-398 CoP (currently with an uncertainty equal or larger than 2.0% (k = 1) for proton beams). Significance. The establishment of a purpose-built primary standard and associated CoP will considerably reduce the uncertainty of the absorbed dose to water determination and ensure improved accuracy and consistency in the dose delivered to patients treated with proton therapy and bring proton reference dosimetry uncertainty in line with megavoltage photon radiotherapy.

Radiation therapy for primary orbital and ocular adnexal lymphoma

ObjectiveTo report the efficacy and toxicity of External beam Radiotherapy (EBRT) as a sole treatment for MALT and Follicular Primary Orbital and Ocular adnexal Lymphoma (POOAL) MethodsRetrospective review of all POOAL patients treated with EBRT utilizing megavoltage photon or electron beam radiotherapy between 2003 and 2015. Patient demographics, tumour extent and pathology, radiotherapy techniques, and treatment outcomes were reviewed. The actuarial rates of tumour control and radiation toxicities were calculated using Kaplan-Meier estimates. ResultsThis study included 167 tumours, of which MALT lymphoma involved 149 (89 %). The conjunctiva and orbit were equally involved as the predominant site (48 %). Megavoltage photon radiotherapy was used in 60 % of predominantly orbital lymphoma and Electron beam with lens shielding in 77 % of the conjunctival lymphoma. The majority (95 %) were treated with a total dose of 25 Gy in 10 fractions. Local control rate was 98 % (CI: 93–100 %) at 5 years. The long-term RT toxicities included dry eye in 27 eyes (16 %) and cataract in 22 (13 %). None of the patients developed significant structural or functional radiation toxicity. ConclusionExternal Beam Radiotherapy, with lens shielding whenever indicated, at a dose of 20–30 Gy delivered over 10–20 fractions is an efficacious and safe primary treatment option for POOAL lymphoma, with excellent local control and low incidence of late manageable ocular toxicities.

Spinal cord re-treatments using photon and proton based radiotherapy: LQ-derived tolerance doses

Re-treatment, using megavoltage photon radiotherapy, can benefit carefully selected patients with new or recurrent tumours. Such re-treatments may involve the further exposure of tissues such as the brain or spinal cord.A time-dependent model has been developed, which incorporates data from all published radiobiological experiments concerned with the in vivo re-irradiation of the spinal cord using photons. It allows an estimation of the increasing recovery in tissue tolerance with elapsed time after the initial treatment course. In accordance with the experimental evidence, the recovery rate depends on the biological effective dose (BED) of the initial treatment. Various degrees of conservatism have been introduced in the model to allow for potential changes in CNS tissue tolerance due to patient age, chemotherapy, surgery etc.An estimation of the re-treatment dose-fractionation schedule is made easier by the use of a downloadable Graphical User Interface (GUI). Worked examples of its use are given forconventional photon (X-ray) based treatments, and also for protons, where relative biological effectiveness (RBE) considerations must be respected within the BED estimates. The model provides boundary conditions for clinical practice. The responsible clinician can choose to usemore ‘forgiving’ BED values and from this to calculate the re-irradiation dose-fractionation schedule.For protons, greater care is required sincethe inter-relationship between linear energy transfer (LET) and RBE can lead to significant over-dosage relative to accepted CNS tolerance doses, especially with the use of scanned proton beams. LET and RBE factors are important in order to deliver safe and effective re-treatment doses.

Dosimetry Effects Caused by Unilateral and Bilateral Hip Prostheses: A Monte Carlo Case Study in Megavoltage Photon Radiotherapy for Computed Tomography Data without Metal Artifacts.

Background:Hip prostheses (HPs) are routinely used in hip augmentation to replace painful or dysfunctional hip joints. However, high-density and high-atomic-number (Z) inserts may cause dose perturbations in the target volume and interface regions.Aim:To evaluate the dosimetric influence of various HPs during megavoltage conformal radiotherapy (RT) of the prostate using Monte Carlo (MC) simulations.Materials and Methods:BEAMnrc and DOSXYZnrc MC user-codes were respectively used to simulate the linac head and to calculate 3D absorbed dose distributions in a computed tomography (CT)-based phantom. A novel technique was used to synthetically introduce HPs into the raw patient CT dataset. The prosthesis materials evaluated were stainless steel (SS316L), titanium (Ti6Al4V), and ultra-high-molecular-weight polyethylene (UHMWPE). Four, five, and six conformal photon fields of 6–20 MV were used.Results:The absorbed dose within and beyond metallic prostheses dropped significantly due to beam attenuation. For bilateral HPs, the target dose reduction ranged up to 23% and 17% for SS316L and Ti6Al4V, respectively. For unilateral HP, the respective dose reductions were 19% and 12%. Dose enhancement was always <1% for UHMWPE. The 6-field plan produced the best target coverage. Up to 38% dose increase was found at the bone–SS316L proximal interface.Conclusions:The novel technique used enabled the complete exclusion of metal artifacts in the CT dataset. High-energy plans with more oblique beams can help minimize dose attenuation through HPs. Shadowing and interface effects are density dependent and greatest for SS316L, while UHMWPE poses negligible dose perturbation.

O9. Dosimetry effects caused by bilateral and unilateral hip prostheses: A Monte Carlo study in megavoltage photon radiotherapy

Introduction Hip prostheses (HPs) are used in hip augmentation to replace diseased hip joints. However, high-density and high-atomic-number inserts may cause dose perturbations in the target volume and in tissue-HP interface regions. This study evaluates the dosimetric effect of various HPs during prostate radiotherapy using Monte Carlo (MC) simulations. Materials and Methods BEAMnrc and DOSXYZnrc MC user-codes were respectively used to model an Elekta Precise linac head and to calculate absorbed dose distributions in a CT-based phantom. Unilateral and bilateral HP contours were delineated in the pelvis CT dataset using MCSHOW and then converted into stainless steel (SS316L), titanium (Ti6Al4V) and ultra-high-molecular-weight polyethylene (UHMWPE) using an IDL code. Four, five and six conformal photon field plans of 6, 10, 15 and 20 MV were used. Results The dose within and beyond the metallic inhomogeneity drops significantly due to beam attenuation. For bilateral prostheses, the maximum isocenter dose reduction was 23%, 17% and <1% for SS316L, Ti6Al4V and UHMWPE, respectively. For unilateral HP, the respective dose reductions were 19%, 12% and <1%. The 6-field plan produced the best target coverage and least dose perturbation. Up to 38% dose enhancement was found at the bone-steel proximal interface due to radiation backscattered from the metal surface. Backscatter perturbation was more pronounced than forward scatter. Conclusions Our software enabled the addition of HPs in the CT dataset of a patient without HPs, allowing simulations to be performed without metal artefacts. Plans with more oblique beam portals can compensate for dose attenuated in fields passing through HPs. Shadowing and interface effects are density-dependent and greatest for SS316L. The attenuation effect of metallic HPs can be minimized (to below 5%) by using a 6-field plan at high energies. However, non-coplanar beams may be necessary to avoid HPs whilst giving sufficient target dose. Hip prostheses (HPs) are used in hip augmentation to replace diseased hip joints. However, high-density and high-atomic-number inserts may cause dose perturbations in the target volume and in tissue-HP interface regions. This study evaluates the dosimetric effect of various HPs during prostate radiotherapy using Monte Carlo (MC) simulations. BEAMnrc and DOSXYZnrc MC user-codes were respectively used to model an Elekta Precise linac head and to calculate absorbed dose distributions in a CT-based phantom. Unilateral and bilateral HP contours were delineated in the pelvis CT dataset using MCSHOW and then converted into stainless steel (SS316L), titanium (Ti6Al4V) and ultra-high-molecular-weight polyethylene (UHMWPE) using an IDL code. Four, five and six conformal photon field plans of 6, 10, 15 and 20 MV were used. The dose within and beyond the metallic inhomogeneity drops significantly due to beam attenuation. For bilateral prostheses, the maximum isocenter dose reduction was 23%, 17% and <1% for SS316L, Ti6Al4V and UHMWPE, respectively. For unilateral HP, the respective dose reductions were 19%, 12% and <1%. The 6-field plan produced the best target coverage and least dose perturbation. Up to 38% dose enhancement was found at the bone-steel proximal interface due to radiation backscattered from the metal surface. Backscatter perturbation was more pronounced than forward scatter. Our software enabled the addition of HPs in the CT dataset of a patient without HPs, allowing simulations to be performed without metal artefacts. Plans with more oblique beam portals can compensate for dose attenuated in fields passing through HPs. Shadowing and interface effects are density-dependent and greatest for SS316L. The attenuation effect of metallic HPs can be minimized (to below 5%) by using a 6-field plan at high energies. However, non-coplanar beams may be necessary to avoid HPs whilst giving sufficient target dose.

Dosimetric characteristics of brass mesh as bolus under megavoltage photon irradiation.

This article presents a set of dosimetric measurements describing the properties of brass mesh (Whiting and Davis, Attleboro Falls, MA) under megavoltage photon irradiation conditions, with particular relevance to its use in breast radiotherapy. The effectiveness of brass mesh as a bolus material was investigated using 6-, 15- and 6-MV flattening filter-free photon beams. The effect on dose build-up at the entrance surface, build-down at the beam-exit surface, dose with surface entrance obliquity, beam profiles, penumbra and percentage depth doses were investigated. One layer of the brass mesh produces a build-up effect equivalent to 1.1 mm of water at 6 MV and 1.9 mm at 15 MV. The brass generates a backscattered component of dose, if the photon beam exits through it. Percentage depth-dose curves are largely unaffected by the mesh and are shown to be equivalent to plain-field data. Beam penumbra and profiles are unchanged by the brass except within the first millimetre (mm) of phantom, where a periodic pattern of dose enhancement is seen. The data presented demonstrate that one layer of brass mesh provides a similar dose build-up effect equivalent to only a few millimetres of water. However, backscatter from the high atomic number (Z) mesh, at the beam exit, contributes appreciably to the overall dose surface enhancement. This dosimetric consequence cannot be neglected and indeed should be considered and accounted for, when determining the bolus effect of the brass mesh in the case of tangential breast irradiation. Advance in knowledge: This article provides dosimetric data necessary for the introduction of brass mesh bolus into the clinical setting for external-beam breast radiotherapy.

Monte Carlo calculation based on hydrogen composition of the tissue for MV photon radiotherapy.

The purpose of this study was to demonstrate that Monte Carlo treatment planning systems require tissue characterization (density and composition) as a function of CT number. A discrete set of tissue classes with a specific composition is introduced. In the current work we demonstrate that, for megavoltage photon radiotherapy, only the hydrogen content of the different tissues is of interest. This conclusion might have an impact on MRI‐based dose calculations and on MVCT calibration using tissue substitutes. A stoichiometric calibration was performed, grouping tissues with similar atomic composition into 15 dosimetrically equivalent subsets. To demonstrate the importance of hydrogen, a new scheme was derived, with correct hydrogen content, complemented by oxygen (all elements differing from hydrogen are replaced by oxygen). Mass attenuation coefficients and mass stopping powers for this scheme were calculated and compared to the original scheme. Twenty‐five CyberKnife treatment plans were recalculated by an in‐house developed Monte Carlo system using tissue density and hydrogen content derived from the CT images. The results were compared to Monte Carlo simulations using the original stoichiometric calibration. Between 300 keV and 3 MeV, the relative difference of mass attenuation coefficients is under 1% within all subsets. Between 10 keV and 20 MeV, the relative difference of mass stopping powers goes up to 5% in hard bone and remains below 2% for all other tissue subsets. Dose‐volume histograms (DVHs) of the treatment plans present no visual difference between the two schemes. Relative differences of dose indexes D98,D95,D50,D05,D02, and Dmean were analyzed and a distribution centered around zero and of standard deviation below 2% (3σ) was established. On the other hand, once the hydrogen content is slightly modified, important dose differences are obtained. Monte Carlo dose planning in the field of megavoltage photon radiotherapy is fully achievable using only hydrogen content of tissues, a conclusion that might impact MRI dose calculation, but can also help selecting the optimal tissue substitutes when calibrating MVCT devices.PACS numbers: 87.55.D‐, 87.55.dk, 87.55.K‐, 87.57.Q‐

Impact of the introduction of weekly radiotherapy quality assurance meetings at one UK cancer centre.

The complexity of radiotherapy planning is increasing rapidly. Delivery and planning is subject to detailed quality assurance (QA) checks. The weakest link is often the oncologists' delineation of the clinical target volume (CTV). Weekly departmental meetings for radiotherapy QA (RTQA) were introduced into the Royal Wolverhampton Hospital, Wolverhampton, UK, in October 2011. This article describes the impact of this on patient care. CTVs for megavoltage photon radiotherapy courses for all radical, adjuvant and palliative treatments longer than five fractions (with the exception of two field tangential breast treatments not enrolled into clinical trials) were reviewed in the RTQA meeting. Audits were carried out in January 2012 (baseline) and September 2013, each over a 4-week period. Adherence to departmental contouring protocols was assessed and the number of major and minor alterations following peer review were determined. There was no statistically significant difference for major alterations between the two study groups; 8 alterations in 80 patients (10%) for the baseline audit vs 3 alterations from 72 patients (4.2%) in the second audit (p = 0.17). A trend towards a reduction in alterations following peer review was observed. There has, however, been a change in practice resulting in a reduction in variation in CTV definition within our centre and greater adherence to protocols. There is increasing confidence in the quality and constancy of care delivered. Introduction of a weekly QA meeting for target volume definition has facilitated consensus and adoption of departmental clinical guidelines within the unit. The weakest areas in radiotherapy are patient selection and definition of the CTV. Engagement in high-quality RTQA is paramount. This article describes the impact of this in one UK cancer centre.

TU‐E‐BRC‐05: First MR Images Obtained During Megavoltage Photon Irradiation From An Integrated Linac‐MR System

Purpose: To prove whether our hybrid linac‐MR design can sufficiently decrease mutual magnetic and radio frequency (RF) interferences to produce a MR image during linac‐irradiation that has similar geometric accuracy and image contrast to an MR image obtained without linac‐irradiation. Method and Materials: A hybrid prototype has been built consisting of a 6 MV linac mounted on the open end of a bi‐planar 0.2 T permanent‐magnet MR system. Both the linac waveguide and the MR system are mounted onto a single gantry that would rotate around a subject. The permanent magnet poles (82×82 cm2) are rigidly held apart to give 27.9cm pole‐to‐pole opening with flat gradients (40 mT/m max) running under a TMX NRC console (Canada). The linac components are comprised of salvaged magnetron‐based Varian 6 MV 600C decommissioned system. The distance from linac target to MR isocentre is 80 cm. Magnetic and RF shielding calculations were performed by finite element analysis and confirmed with appropriate measurements. Faraday cage shielding, typical of all MR installations, was also provided. The testing phantom was an acrylic rectangular cube, 15.95 × 15.95 × 25.4 mm with holes of diameters 2.52 mm, 3.45 mm and 4.78 mm drilled parallel to the length (25.4 mm) of rectangular cube. The cube was immersed in a 10 mM solution of within a plastic container 22.5 mm inner diameter. The container with the cube insert were placed inside an inductively tuned solenoid RF coil with an integrated pin‐diode transmit/receive switch. Results: Images (128×128) were obtained in about 38 secs using raw gradient echo sequences. Compared to no‐radiation, MR images during linac‐radiation had no geometric distortion but slightly reduced SNR. Conclusion: Our linac‐MR design produces MR images obtained during or without linac irradiation that are sufficiently similar to implement real‐time MR‐guided radiotherapy.

First MR images obtained during megavoltage photon irradiation from a prototype integrated linac‐MR system

The authors report the first magnetic resonance (MR) images produced by their prototype MR system integrated with a radiation therapy source. The prototype consists of a 6 MV linac mounted onto the open end of a biplanar 0.2 T permanent MR system which has 27.9 cm pole-to-pole opening with flat gradients (40 mT/m) running under a TMX NRC console. The distance from the magnet isocenter to the linac target is 80 cm. The authors' design has resolved the mutual interferences between the two devices such that the MR magnetic field does not interfere with the trajectory of the electron in the linac waveguide, and the radiofrequency (RF) signals from each system do not interfere with the operation of the other system. Magnetic and RF shielding calculations were performed and confirmed with appropriate measurements. The prototype is currently on a fixed gantry; however, in the very near future, the linac and MR magnet will rotate in unison such that the linac is always aimed through the opening in the biplanar magnet. MR imaging was found to be fully operational during linac irradiation and proven by imaging a phantom with conventional gradient echo sequences. Except for small changes in SNR, MR images produced during irradiation were visually and quantitatively very similar to those taken with the linac turned off. This prototype system provides proof of concept that the design has decreased the mutual interferences sufficiently to allow the development of real-time MR-guided radiotherapy. Low field-strength systems (0.2-0.5 T) have been used clinically as diagnostic tools. The task of the linac-MR system is, however, to provide MR guidance to the radiotherapy beam. Therefore, the 0.2 T field strength would provide adequate image quality for this purpose and, with the addition of fast imaging techniques, has the potential to provide 4D soft-tissue visualization not presently available in image-guided radiotherapy systems. The authors' initial design incorporates a permanent magnet; however, other types of magnets and field strengths could also be incorporated. Usable MR images were obtained during linac irradiation from the linac-MR prototype. The authors' prototype design can be used as the functional starting point in developing real-time MR guidance offering soft-tissue contrast that can be coupled with tumor tracking for real-time adaptive radiotherapy.

Edge restenosis: impact of low dose irradiation on cell proliferation and ICAM-1 expression

BackgroundLow dose irradiation (LDI) of uninjured segments is the consequence of the suggestion of many authors to extend the irradiation area in vascular brachytherapy to minimize the edge effect. Atherosclerosis is a general disease and the uninjured segment close to the intervention area is often atherosclerotic as well, consisting of neointimal smooth muscle cells (SMC) and quiescent monocytes (MC). The current study imitates this complex situation in vitro and investigates the effect of LDI on proliferation of SMC and expression of intercellular adhesion molecule-1 (ICAM-1) in MC.MethodsPlaque tissue from advanced primary stenosing lesions of human coronary arteries (9 patients, age: 61 ± 7 years) was extracted by local or extensive thrombendarterectomy. SMC were isolated and identified by positive reaction with smooth muscle α-actin. MC were isolated from buffy coat leukocytes using the MACS cell isolation kit. For identification of MC flow-cytometry analysis of FITC-conjugated CD68 and CD14 (FACScan) was applied. SMC and MC were irradiated using megavoltage photon irradiation (CLINAC2300 C/D, VARIAN, USA) of 6 mV at a focus-surface distance of 100 cm and a dose rate of 6 Gy min-1 with single doses of 1 Gy, 4 Gy, and 10 Gy. The effect on proliferation of SMC was analysed at day 10, 15, and 20. Secondly, total RNA of MC was isolated 1 h, 2 h, 3 h, and 4 h after irradiation and 5 μg of RNA was used in standard Northern blot analysis with ICAM-1 cDNA-probes.ResultsBoth inhibitory and stimulatory effects were detected after irradiation of SMC with a dose of 1 Gy. At day 10 and 15 a significant antiproliferative effect was found; at day 20 after irradiation cell proliferation was significantly stimulated. Irradiation with 4 Gy and 10 Gy caused dose dependent inhibitory effects at day 10, 15, and 20. Expression of ICAM-1 in human MC was neihter inhibited nor stimulated by LDI.ConclusionThus, the stimulatory effect of LDI on SMC proliferation at day 20 days after irradiation may be the in vitro equivalent of a beginning edge effect. Extending the irradiation area in vascular brachytherapy in vivo may therefore merely postpone and not inhibit the edge effect. The data do not indicate that expression of ICAM-1 in quiescent MC is involved in the process.

Atypical and malignant meningiomas: an outcome report of seventeen cases.

Limited data are available concerning the outcome of patients with atypical and malignant meningiomas. We therefore analyzed the outcome of seventeen patients with meningiomas (9 atypical; 8 malignant) at Thomas Jefferson University Hospital between 1973 and 1996. Strict adherence to the 1993 WHO criteria for the typing of CNS tumors was maintained. The median potential follow-up period for all patients was 87 months. The age at diagnosis ranged from 22 to 72 (mean 51.8 years). There were 5 males and 12 females. The mean tumor diameter was 4.45 cm. Of the 16 cases where the extent of surgical resection was known, 4 were partial and 12 were complete resections. Six patients (35%) had dural or cortical invasion by tumor. Fifteen patients received postoperative megavoltage photon irradiation (mean 61 Gy). One of these fifteen pts. received an additional 20 Gy with Au-198 implantation and 1 received post-radiation chemotherapy for recurrent disease. The overall survival rate for all patients at 5 and 10 years were 87% and 58% respectively. The 5- and 10-year survival rates for atypical meningiomas were 87% and 58%; for malignant meningiomas the survival rates were 60% and 60% respectively. Five patients (30%) have died. Three of these 5 patients initially received less than 54 Gy to the tumor bed and have died of recurrent disease. Local disease progression was documented in 11 patients (65%) after surgery and in 3 patients (18%) after radiation. There was an improvement in performance status in 3 (18%) patients with a decline and no change seen in 1 (6%) and 13 (77%) respectively after receiving radiation. There appeared to be no difference in survival in patients as a function of dural or cortical invasion. Long term survival is possible for patients with atypical and malignant meningiomas treated with surgery and post-operative radiation. We are unable to distinguish a difference in outcome between these two pathological entities. Dural and cortical invasion were not associated with a decrease in survival. In addition, improved tumor control and survival may be associated with increased radiation dose.

Irradiation protection from hypersensitivity

A 71-year-old man with metastatic carcinoma of the prostate was admitted for investigation of severe lower back pain. Spinal-cord compression at the level of the tenth thoracic vertebra (T10) was suspected clinically and multiple areas of vertebral bone metastases were seen on technetium bone scan. He was treated with bed rest, high-dose dexamethasone (4 mg four times a day) and a course of radiotherapy (5 MeV, 2000 cGy in 5 fractions over one week to his thoracic spine as a single posterior field, 8 15 cm), followed by radiotherapy to the lumbar spine (5 MeV, 2000 cGy in 5 fractions over 5 days as a single posterior field, 8 15 cm) as a site of known bony disease. On completion of radiotherapy, the dose of steroids was reduced and stopped, he was mobilised and started on cyproterone acetate (100 mg three times a day). A widespread maculopopular rash developed 2 weeks after completing radiotherapy. The rash covered most of his body except the areas (on both the front and back of his trunk) which had received a dose of radiotherapy (figure). He was treated with piriton and calamine lotion for the mild itch and discomfort associated with the rash. He had no known drug allergies, his medication before appearance of the rash included cyproterone acetate, goserelin, dexamethasone, subcutaneous heparin, codanthrusate, paracetamol, cimetidine, lactulose, and fybogel. He had recently received a blood transfusion. The rash was thought to be a result of cutaneous hypersensitivity although no cause was found, and it slowly faded. Our hypothesis is that skin within the radiation treatment field received a dose of radiotherapy (2000 cGy posteriorly and 600 cGy anteriorly) sufficient to result in local suppression of an otherwise generalised rash. Although the treatment was given as a single posterior field to both sites, a significant dose (approximately 600 cGy) would exit through the anterior surface of the patient at this energy. There are several possible explanations for this observation. Photon irradiation may have resulted in an altered response to an allergen or internal factors, or a cell population was affected in either a functional way (receptor alterations, cytokine production, intercellular or extracellular signals) or by depopulation. We were unable to take skin biopsies in this case which may have helped to elucideate the mechanism of this observed phenomenon. It is known that Langerhans cells have a role in both contact and atopic dermatitis, and that they exhibit multiple cell-surface receptors (allowing antigen recognition) and secrete a variety of cytokines (providing a mechanism for the observed ‘dermatitis’). Whilst there is no data on the sensitivity of Langerhans cells to megavoltage photon irradiation (as used in this case). Grenz rays (which are much less penetrating) delivered to the skin of people with contact hypersensitivity to nickel resulted in almost total suppression of allergic contact dermatitis in treated skin. Biopsies of skin showed pronounced reduction in numbers of Langerhans cells in the irradiated area as demonstrated by the monoclonal antibody OKT6.

Arteriovenous malformations of the brain: Outcome of conventional radiotherapy in the management of 33 cases

Thirty three patients with inoperable arteriovenous malformations of the brain received conventionally fractionated megavoltage photon radiotherapy. The dose varied between 30.00 wand 50.00 Gy with a median of 40.00 Gy. Treatment was not associated with any significant morbidity. Follow-up ranged from 16 months to 148 months, with a median of 79 months. The projected 5-year survival is 92% and rebleed-free survival 78%. There was a trend of increased bleed-free survival for doses greater than 46.00 Gy.

The role of radiotherapy in the management of intracranial meningiomas: the royal marsden hospital experience with 186 patients

One hundred and eighty-six patients with intracranial meningiomas were treated at the Royal Marsden Hospital between 1963 and 1983 with megavoltage photon irradiation ( 60Co gamma rays and 6–8 Mv. X rays). Survival parameters were measured from the time of referral for radiotherapy. The 10-year actuarial cause-specific survival was 67% for all cases and the actuarial disease-free survival was 61 %. Both malignant and also “aggressive benign” histologies were associated with poor long-term survival. Benign angioblastic meningioma was associated with lower actuarial cause specific and disease-free survival compared with other benign histological sub-groups. Prognosis was related to the extent of initial surgical resection. Of those who underwent subtotal or partial tumor resection with post-operative radiotherapy the 10-year actuarial cause-specific survival was 77%, and in inoperable patients treated by radiotherapy alone it was 46%. Radiotherapy alone resulted in improvement of neurological performance (Karnofsky) in 12 out of the 32 (38%) patients with inoperable disease. The 10-year survival of patients referred for irradiation following “complete” surgical resection was only 34% owing to the high incidence of adverse histological sub-types in this treatment sub-group. Based upon univariate analysis, performance status of less than 60 (Karnofsky) and also age greater than 50 years at the time of referral for radiotherapy were adverse prognostic factors. Multivariate analysis revealed that histological type, extent of surgical resection and performance status at the time of presentation for radiotherapy were independant prognostic variables. However age at the time of referral lost significance as an independant variable when analyzed using this method. Patients undergoing complete surgical resection for the typical benign non-aggressive meningioma do not require adjuvant irradiation. The results of this study support the role of radiotherapy for treatment of incompletely resected and inoperable meningioma of all 3 histological types (benign, “aggressive benign”, malignant).

Tumor heterogeneity, tumor size, and radioresistance

Mutant clonogenic cells, resistant to individual chemotherapeutic agents, are known to play a central role in clinical chemotherapy failure. The possibility that mutant cells, resistant to conventionally fractionated megavoltage photon radiotherapy, exist in human tumors is considered. Applying the mutation theory of Luria and Delbruck to describe the appearance of resistant cells, several conclusions follow: (a) the mean number of resistant cells in a tumor will be determined by the tumor size and the mutation rate; (b) a wide variation in radiosensitivity in tumors of the same histology is expected, because of a large variation in the number of resistant cells that they contain; (c) the presence of a resistant clone will not reduce the tumor-control probability until the tumor becomes sufficiently large; (d) initial response will not be a reliable predictor of long-term control; (e) clonogenic assays may not accurately predict treatment outcomes; (f) the mutation rate may be the most accurate predictor of tumor aggressiveness and resistance to various treatment modalities; (g) tumors with a low mutation rate, which may include seminoma, Hodgkin's disease and many pediatric tumors would be curable by either chemotherapy or radiation; (h) pleomorphic tumors with a high mutation rate, which may include glioblastoma multiforme, would be difficult to cure by any means. Clinical and experimental evidence is reviewed for the existence of radioresistant cell lines in human and animal tumors, and further experiments are proposed to test this hypothesis. Treatment strategies for targeting radioresistant clones are discussed.

Radiation therapy oncology group phase I–II study on fast neutron teletherapy for carcinoma of the bladder

From June 1977 through March 1981, the Radiation Therapy Oncology Group sponsored a Phase I-II study (RTOG 77-05) on the use of fast neutrons for treating carcinomas of the urinary bladder. Patients entered on the study had Stage B1 (grade III or IV histology) or Stage B2, C, or D1 (any grade histology) disease. Thirteen patients received preoperative mixed-beam (neutron/photon) irradiation to 50 photon Gy-equivalent, and in 12 of these a cystectomy was performed in 4 to 6 weeks. The incidence of pathologic downstaging to Po was 58% in the cystectomy specimens. The projected survival at 30 months is 32%. Twenty-six patients were treated definitively with mixed-beam irradiation consisting of 50 photon Gy-equivalent to the pelvis followed by a 20 photon Gy-equivalent boost to the bladder itself. Eighteen of 26 patients (69%) achieved tumor clearance at some time during their follow-up but 8/18 (44%) of these ultimately exhibited some component of local failure. The projected survival at 30 months for this group of patients is 34%. However, the subset of patients with Stage B or C disease had a projected survival at 30 months of 60%. Four patients received definitive neutron irradiation alone and 3/4 achieved tumor clearance at some time during their follow-up. Actuarial curves are presented for patient survival and duration of local control, and results are compared with comparably staged patients treated with megavoltage photon irradiation. Treatment-related morbidity is also discussed.

A modified radiotherapy technique in the treatment of medulloblastoma.

Craniospinal irradiation is a standard treatment technique in patients who receive surgery for medulloblastoma. In most centers megavoltage photon irradiation is used, resulting in significant irradiation exposure to critical organs. In order to overcome this difficulty, we recently modified the technique applied in our center, by using high energy electrons (20 MeV) for irradiation of the spinal cord. The reliability of this technique was checked by performing dosimetry in a specially constructed wax phantom. Attention was focused upon dose variations at the junction of fields. Furthermore, the influence of vertebrae on the absorbed dose distribution of high energy electrons is presented. This technique seems to be safe and reliable in selected patients (children and teenagers).