Independent quality assurance of a helical tomotherapy machine using the dose magnifying glass.

PURPOSE: Helical tomotherapy is a complex delivery technique, integrating CT image guidance and intensity modulated radiotherapy in a single system. The integration of the CT detector ring on the gantry not only allows patient position verification but is also often used to perform various QA procedures. This convenience lacks the rigor of a machine-independent QA process. METHODS: In this article, a Si strip detector, known as the Dose Magnifying Glass (DMG), was used to perform machine-independent QA measurements of the multileaf collimator alignment, leaf open time threshold, and leaf fluence output factor (LFOF). RESULTS: The DMG measurements showed good agreements with EDR2 film for the MLC alignment test while the CT detector agrees well with DMG measurements for leaf open time threshold and LFOF measurements. The leaf open time threshold was found to be approximately 20 ms. The LFOF measured with the DMG agreed within error with the CT detector measured LFOF. CONCLUSIONS: The DMG with its 0.2 mm spatial resolution coupled to TERA ASIC allowed real-time high temporal resolution measurements of the tomotherapy leaf movement. In conclusion, DMG was shown to be a suitable tool for machine-independent QA of a tomotherapy unit.

EBT2 radiochromic film for quality assurance of complex IMRT treatments of the prostate: micro-collimated IMRT, RapidArc, and TomoTherapy.

In response to the clinical need for a dosimetry system with both high resolution and minimal angular dependence, this study demonstrates the utility of Gafchromic EBT2 radiochromic dosimetry film for the quality assurance of micro-collimated IMRT, RapidArc and TomoTherapy treatments. Firstly, preliminary measurements indicated that the dose response of EBT2 film does not appreciably vary with either the angle of incidence of the radiation beam or the depth in water at which the film is placed. Secondly, prostate treatment plans designed for delivery using static-beam IMRT (collimated using the BrainLab m3 microMLC), RapidArc and TomoTherapy were investigated by comparing dose planes obtained from treatment planning calculations with EBT2 film measurements. For all treatment plans, the proportion of dose points agreeing with the film measurements to within γ (3%,3 mm) was found to be above 95%, with all points agreeing within 5%. The film images provided sufficient information to verify that the treatments could be delivered with an acceptable level of accuracy, while also providing additional information on low-level dose variations that were not predicted by the treatment planning systems. This information included: the location and extent of dose from inter-leaf leakage (in the RapidArc plan) and helical field junctioning (in the TomoTherapy plan), as well as the existence of small regions where the treatment planning system under-predicted the dose from very small treatment segments (in the micro-collimated IMRT plan).

On the impact of functional imaging accuracy on selective boosting IMRT.

In order to quantify the impact of loss of functional imaging sensitivity and specificity on tumor control and normal tissue toxicity for selective boosting IMRT four selective boosting scenarios were designed: SB91-81 (EUD=91Gy for the high-risk tumor subvolume and EUD=81Gy for a remaining low-risk PTV (rPTV)), SB80-74, SB90-70, and risk-adaptive optimization. For each sensitivity loss level the loss in tumor control probability (DeltaTCP) was calculated. For each specificity loss level, the increase in rectal and bladder toxicity was quantified using the radiobiological indices (equivalent uniform dose (EUD) and normal tissue complication probability (NTCP)) as well as %-volumes irradiated. The impact of loss in sensitivity on local tumor control was maximal when the prescription dose level for rPTV had the lowest value. The SB90-70 plan had a DeltaTCP=29.6%, the SB91-81 plan had a DeltaTCP=9.5%, while for risk-adaptive optimization a DeltaTCP=4.7% was found. Independent of planning technique loss in functional imaging specificity appears to have a minimal impact on the expected normal tissue toxicity, since an increase in rectal or bladder toxicity as a function of loss in specificity was not observed. Additionally, all plans fulfilled the rectum and the bladder sparing criteria found in the literature for late rectal bleeding and genitourinary complications. Our study shows that the choice of a low-risk classification for the rPTV in selective boosting IMRT may lead to a significant loss in TCP. Furthermore, for the example considered in which normal tissue complications can be limited through the use of a tissue expander it appears that the therapeutic ratio can be improved using a functional imaging technique with a high sensitivity and limited specificity; while for cases were this is not possible, an optimal balance between sensitivity and specificity has to be found.

Dose escalated, hypofractionated radiotherapy using helical tomotherapy for inoperable non-small cell lung cancer: preliminary results of a risk-stratified phase I dose escalation study.

To improve local control for inoperable non-small cell lung cancer (NSCLC), a phase I dose escalation study for locally advanced and medically inoperable patients was devised to escalate tumor dose while limiting the dose to organs at risk including the esophagus, spinal cord, and residual lung. Helical tomotherapy provided image-guided IMRT, delivered in a 5-week hypofractionated schedule to minimize the effect of accelerated repopulation. Forty-six patients judged not to be surgical candidates with Stage I-IV NSCLC were treated. Concurrent chemotherapy was not allowed. Radiotherapy was delivered via helical tomotherapy and limited to the primary site and clinically proven or suspicious nodal regions without elective nodal irradiation. Patients were placed in 1 of 5 dose bins, all treated for 25 fractions, with dose per fraction ranging from 2.28 to 3.22 Gy. The bin doses of 57 to 80.5 Gy result in 2 Gy/fraction normalized tissue dose (NTD) equivalents of 60 to 100 Gy. In each bin, the starting dose was determined by the relative normalized tissue mean dose modeled to cause < 20% Grade 2 pneumonitis. Dose constraints included spinal cord maximum NTD of 50 Gy, esophageal maximum NTD < 64 Gy to < or = 0.5 cc volume, and esophageal effective volume of 30%. No grade 3 RTOG acute pneumonitis (NCI-CTC v.3) or esophageal toxicities (CTCAE v.3.0 and RTOG) were observed at median follow-up of 8.1 months. Pneumonitis rates were 70% grade 1 and 13% grade 2. Multivariate analysis identified lung NTD(mean) (p=0.012) and administration of adjuvant chemotherapy following radiotherapy (p=0.015) to be independent risk factors for grade 2 pneumonitis. Only seven patients (15%) required narcotic analgesics (RTOG grade 2 toxicity) for esophagitis, with only 2.3% average weight loss during treatment. Best in-field gross response rates were 17% complete response, 43% partial response, 26% stable disease, and 6.5% in-field thoracic progression. The out-of-field thoracic failure rate was 13%, and distal failure rate was 28%. The median survival was 18 months with 2-year overall survival of 46.8% +/- 9.7% for this cohort, 50% of whom were stage IIIB and 30% stage IIIA. Dose escalation can be safely achieved in NSCLC with lower than expected rates of pneumonitis and esophagitis using hypofractionated image-guided IMRT. The maximum tolerated dose has yet to be reached.

Time series prediction of lung cancer patients' breathing pattern based on nonlinear dynamics.

This study focuses on predicting breathing pattern, which is crucial to deal with system latency in the treatments of moving lung tumors. Predicting respiratory motion in real-time is challenging, due to the inherent chaotic nature of breathing patterns, i.e. sensitive dependence on initial conditions. In this work, nonlinear prediction methods are used to predict the short-term evolution of the respiratory system for 62 patients, whose breathing time series was acquired using respiratory position management (RPM) system. Single step and N-point multi step prediction are performed for sampling rates of 5 Hz and 10 Hz. We compare the employed non-linear prediction methods with respect to prediction accuracy to Adaptive Infinite Impulse Response (IIR) prediction filters. A Local Average Model (LAM) and local linear models (LLMs) combined with a set of linear regularization techniques to solve ill-posed regression problems are implemented. For all sampling frequencies both single step and N-point multi step prediction results obtained using LAM and LLM with regularization methods perform better than IIR prediction filters for the selected sample patients. Moreover, since the simple LAM model performs as well as the more complicated LLM models in our patient sample, its use for non-linear prediction is recommended.

Semi-automatic cone beam CT segmentation of in vivo pre-clinical subcutaneous tumours provides an efficient non-invasive alternative for tumour volume measurements.

OBJECTIVE: To evaluate the feasibility and accuracy of using cone beam CT (CBCT) scans obtained in radiation studies using the small-animal radiation research platform to perform semi-automatic tumour segmentation of pre-clinical tumour volumes. METHODS: Volume measurements were evaluated for different anatomical tumour sites, the flank, thigh and dorsum of the hind foot, for a variety of tumour cell lines. The estimated tumour volumes from CBCT and manual calliper measurements using different volume equations were compared with the "gold standard", measured by weighing the tumours following euthanasia and tumour resection. The correlation between tumour volumes estimated with the different methods, compared with the gold standard, was estimated by the Spearman's rank correlation coefficient, root-mean-square deviation and the coefficient of determination. RESULTS: The semi-automatic CBCT volume segmentation performed favourably compared with manual calliper measures for flank tumours ≤2 cm(3) and thigh tumours ≤1 cm(3). For tumours >2 cm(3) or foot tumours, the CBCT method was not able to accurately segment the tumour volumes and manual calliper measures were superior. CONCLUSION: We demonstrated that tumour volumes of flank and thigh tumours, obtained as a part of radiation studies using image-guided small-animal irradiators, can be estimated more efficiently and accurately using semi-automatic segmentation from CBCT scans. ADVANCES IN KNOWLEDGE: This is the first study evaluating tumour volume assessment of pre-clinical subcutaneous tumours in different anatomical sites using on-board CBCT imaging. We also compared the accuracy of the CBCT method to manual calliper measures, using various volume calculation equations.

Selective boosting of tumor subvolumes.

PURPOSE AND BACKGROUND: It is no longer considered mandatory to deliver a uniform dose to the tumor volume in radiotherapy. Non-uniform doses are unavoidable in brachytherapy and in stereotactic radiosurgery, with often good results. Deliberately non-uniform doses may increase tumor control probability (TCP) and enable steeper dose gradients outside the treated volume to be achieved. New methods of tumor imaging might show regions of specific activity or hypoxia which could be selectively targeted. This paper investigates by modeling the effect of boosting, by dose ratios up to 2, for a range of tumor subvolumes. METHODS AND MATERIALS: A standard linear-quadratic algorithm was used to define the dose-response curve for tumors of various volumes (numbers of clonogenic cells), radiosensitivity (SF(2)), assumed slope (gamma(50)) and dose for 50% tumor control (TCD(50)). Curves of tumor control probability (TCP) were constructed to show the increase of TCP, as a function of the ratio of boost dose to the TCD(50), above the baseline 50% TCP, for a set of different proportions of tumor volume boosted. RESULTS: Calculated values of TCP increased rapidly with both boost dose ratio and with proportion of volume boosted. The increase in TCP reached a plateau after boost dose ratios of 1.2-1.3, as has been noted before, except where very large proportions of tumor volume exceeding 90% were boosted. Quite large increases of TCP, to about 75%, could be achieved if the gamma(50) slope was steep, and especially in small tumors (having fewer cells). Radiosensitivity was not an independent factor because radiosensitive tumors had a low TCD(50) and this was the baseline dose considered as unity. CONCLUSION: There were few situations where a boost dose ratio exceeding 1.3 appeared to be worthwhile or necessary. Significant increases of TCP, up from 50% to 75%, might therefore be achieved for a small increase in risk of necrosis, where a substantial proportion of tumor volume (60-80%) could be boosted.

A high-precision system for conformal intracranial radiotherapy.

PURPOSE: Currently, optimally precise delivery of intracranial radiotherapy is possible with stereotactic radiosurgery and fractionated stereotactic radiotherapy. We report on an optimally precise optically guided system for three-dimensional (3D) conformal radiotherapy using multiple noncoplanar fixed fields. METHODS AND MATERIALS: The optically guided system detects infrared light emitting diodes (IRLEDs) attached to a custom bite plate linked to the patient's maxillary dentition. The IRLEDs are monitored by a commercially available stereo camera system, which is interfaced to a personal computer. An IRLED reference is established with the patient at the selected stereotactic isocenter, and the computer reports the patient's current position based on the location of the IRLEDs relative to this reference position. Using this readout from the computer, the patient may be dialed directly to the desired position in stereotactic space. The patient is localized on the first day and a reference file is established for 5 different couch positions. The patient's image data are then imported into a commercial convolution-based 3D radiotherapy planning system. The previously established isocenter and couch positions are then used as a template upon which to design a conformal 3D plan with maximum beam separation. RESULTS: The use of the optically guided system in conjunction with noncoplanar radiotherapy treatment planning using fixed fields allows the generation of highly conformal treatment plans that exhibit a high degree of dose homogeneity and a steep dose gradient. To date, this approach has been used to treat 28 patients. CONCLUSION: Because IRLED technology improves the accuracy of patient localization relative to the linac isocenter and allows real-time monitoring of patient position, one can choose treatment-field margins that only account for beam penumbra and image resolution without adding margin to account for larger and poorly defined setup uncertainty. This approach enhances the normal tissue sparing, high degree of conformality, and homogeneity characteristics possible with 3D conformal radiotherapy.

Optically guided intensity modulated radiotherapy.

BACKGROUND AND PURPOSE: Previously, we reported on development of an optically guided system for 3D conformal intracranial radiotherapy using multiple noncoplanar fixed fields. In this paper we report on the extension of our system for stereotactic fractionated radiotherapy to include intensity modulated static ports. METHODS AND MATERIALS: A 3D treatment plan with maximum beam separation is developed in the stereotactic space established by an optically guided system. Gantry angles are chosen such that each beam has a unique entrance and exit pathway, avoids the critical structures, and has a minimal beam's eye view projection. Once, a satisfactory treatment plan is found using this geometric approach an inverse treatment plan is developed using the beam portals established previously. The purpose of adding inverse planing is two fold, on the one hand it allows further reduction of margins around the PTV, while on the other hand it affords the possibility of conformal avoidance of critical structures that are close to or abut the PTV. RESULTS: The use of the optically guided system in conjunction with intensity modulated noncoplanar radiotherapy treatment planning using fixed fields allows the generation of highly conformal treatment plans that exhibit smaller 90, 70, and 50% of prescription dose isodose volumes, improved PITV ratios, comparable or improved EUD, smaller NTD(mean) for the critical structures, and an inhomogeneity index that is within generally accepted limits. CONCLUSION: Because optically guided technology improves the accuracy of patient localization relative to the linac isocenter and allows real-time monitoring of patient position, the planning target volume needs to be corrected only for the limitations of image resolution. Intensity modulated static beam radiotherapy planning then provides the user the ability to further reduce margins on the PTV and to conform very closely to this smaller target volume, and enhances the normal tissue sparing, and high degree of conformality possible with 3D conformal radiotherapy. In addition, since optically guided technology affords improved patient localization and online monitoring of patient position during treatment delivery it allows for safe and efficient delivery of intensity modulated radiotherapy.

On the calculation of mean restricted collision stopping powers.

An analytical method for the calculation of ratios of mean restricted collision stopping powers (L/rho)(g)m averaged over the charged particle spectra and the photon spectrum that is accurate to first order has been developed, and it has been explored whether a moderate change in the photon fluence spectrum with field size has an effect on the mean restricted collision stopping power ratio in high-Z materials. The results of this study indicate that for the case of a miniphantom, moderate changes in the photon fluence spectrum have only a weak effect on the ratios of mean restricted collision stopping powers.

Dosimetric characteristics of a double-focused miniature multileaf collimator.

The dosimetric characteristics of a double-focused miniature multileaf collimator (mMLC) attached to a Philips SL75/5 linear accelerator (linac) have been investigated. Output factors, percentage depth-dose, penumbra, leaf transmission, and leakage between the leaves were measured for the 6 MV x-ray beam on this accelerator. Because leakage both through and between the leaves is minimal, the linac jaws can be kept fixed while the mMLC leaf configuration is modified for different aperture shapes. This allows for accurate output prediction using the equivalent square formalism. Percent depth-dose measured for fields defined by the mMLC show little deviation from the percent depth-dose measured for fields defined by the machine jaws or Lipowitz metal blocks. Because the mMLC matches beam divergence in both directions, allows minimal beam transmission, and has a large source-to-collimator distance, the penumbra is sharper for fields defined by the mMLC than for fields defined by the linac jaws or Lipowitz metal blocks. Based on these data, dose calculations for mMLC-defined fields can be applied with no change in procedures from those used for fields defined using conventional methods.

Quality assurance of a helical tomotherapy machine.

Helical tomotherapy has been developed at the University of Wisconsin, and 'Hi-Art II' clinical machines are now commercially manufactured. At the core of each machine lies a ring-gantry-mounted short linear accelerator which generates x-rays that are collimated into a fan beam of intensity-modulated radiation by a binary multileaf, the modulation being variable with gantry angle. Patients are treated lying on a couch which is translated continuously through the bore of the machine as the gantry rotates. Highly conformal dose-distributions can be delivered using this technique, which is the therapy equivalent of spiral computed tomography. The approach requires synchrony of gantry rotation, couch translation, accelerator pulsing and the opening and closing of the leaves of the binary multileaf collimator used to modulate the radiation beam. In the course of clinically implementing helical tomotherapy, we have developed a quality assurance (QA) system for our machine. The system is analogous to that recommended for conventional clinical linear accelerator QA by AAPM Task Group 40 but contains some novel components, reflecting differences between the Hi-Art devices and conventional clinical accelerators. Here the design and dosimetric characteristics of Hi-Art machines are summarized and the QA system is set out along with experimental details of its implementation. Connections between this machine-based QA work, pre-treatment patient-specific delivery QA and fraction-by-fraction dose verification are discussed.

On the use of virtual simulation in radiotherapy of the intact breast.

In this paper a method of breast cancer treatment planning using virtual simulation implemented at the Department of Human Oncology at the University of Wisconsin is described. All patients in this procedure are placed in a custom vacuum mold in treatment position with both arms up to avoid collision with the CT scanner aperture. For all patients a CT scan of 5-mm-slice thickness is acquired. The ipsilateral and contralateral breast, the ipsilateral lung and the heart are delineated and a three-dimensional plan is generated that tries to minimize the dose to the ipsilateral lung and heart while ensuring adequate coverage of the affected breast. Digitally reconstructed radiographs are used to verify the patient setup on the treatment machine.

A dosimetric analysis of tomotherapy based intensity modulated radiation therapy with and without bone marrow sparing in gynecologic malignancies.

Whole pelvic radiotherapy with concurrent chemotherapy is the standard of care for locally advanced cervical carcinoma. Published literature reports that the pelvic bone marrow (BM) dosimetric parameters of V10 > 90% and V20 > 80% are associated with higher rates of hematologic toxicities using this approach. Here, we investigate the ability of Tomotherapy based intensity modulated radiation therapy (IMRT) to reduce dose to pelvic BM while evaluating dose distribution to critical structures and planning target volume (PTV) coverage. Ten patients were selected for analysis. Normal structures, whole pelvic BM, PTV contours, and IMRT objects were standardized. Two whole pelvis Tomotherapy plans were created for each patient, one standard plan, and one with the addition of a BM sparing (BMS) constraint (V10 <85%, V20 < 80%). Data were calculated from multiple points with regard to BM dose, normal structure dose, and PTV coverage. Differences in dose distributions between the two sets of plans were analyzed using a paired t-test. The addition of a BMS planning constraint resulted in significant decreases in pelvic BM dose at the following dosimetric points: V5, V10, V15, V20, V30, V40, V50, and mean dose (p < 0.05 for all points). There were no significant differences in dose to small bowel, bladder or rectum, with the exception of one data point (small bowel V30, p = 0.004) between the two sets of plans. There was no sacrifice of PTV coverage or loss of homogeneity with the addition of a BMS planning constraint. BMS-IMRT significantly reduces radiation dose to the pelvic BM while maintaining the ability to spare dose to the small bowel, bladder and rectum. The planning constraints were met without violation of study criteria, and without sacrifice of PTV coverage. Further investigation is warranted to determine if rates of hematologic toxicity improve with utilization of Tomotherapy based BMS-IMRT.

Distribution of brain metastases: implications for non-uniform dose prescriptions.

OBJECTIVES: The aim of this study was to determine the disease-specific distribution of brain metastases and, using radiobiological modelling, estimate how these anatomical tendencies might be exploited when delivering prophylactic whole-brain radiotherapy for small cell lung cancer in complete remission. METHODS: Disease-specific brain metastasis atlases were created by mapping brain metastases to a standard image set from a database of patients who were to receive external beam radiation therapy. The specific diseases investigated included lung (both small cell and non-small cell), breast, renal and gynaecological cancers as well as melanoma. Radiobiological modelling was used to estimate how much improvement, in terms of the metastasis-free rate at 3 years, might be possible with non-uniform dose distributions if there are spatial biases in the incidence of micrometastases from small cell lung cancer. RESULTS: For lung and breast cancer, there was an increased probability of cerebellar metastases compared with what would be predicted based solely on brain volume. This trend was not evident for renal cancer, gynaecological malignancies or melanoma. CONCLUSION: Radiobiological models suggest that if there is a non-uniform distribution of microscopic brain metastases in patients with small cell lung cancer, higher population-based metastasis-free rates might be achievable with non-uniform irradiation compared with the same integral whole-brain dose delivered as a uniform prescription.

Time series analyses of breathing patterns of lung cancer patients using nonlinear dynamical system theory.

The underlying requirements for successful implementation of any efficient tumour motion management strategy are regularity and reproducibility of a patient's breathing pattern. The physiological act of breathing is controlled by multiple nonlinear feedback and feed-forward couplings. It would therefore be appropriate to analyse the breathing pattern of lung cancer patients in the light of nonlinear dynamical system theory. The purpose of this paper is to analyse the one-dimensional respiratory time series of lung cancer patients based on nonlinear dynamics and delay coordinate state space embedding. It is very important to select a suitable pair of embedding dimension 'm' and time delay 'τ' when performing a state space reconstruction. Appropriate time delay and embedding dimension were obtained using well-established methods, namely mutual information and the false nearest neighbour method, respectively. Establishing stationarity and determinism in a given scalar time series is a prerequisite to demonstrating that the nonlinear dynamical system that gave rise to the scalar time series exhibits a sensitive dependence on initial conditions, i.e. is chaotic. Hence, once an appropriate state space embedding of the dynamical system has been reconstructed, we show that the time series of the nonlinear dynamical systems under study are both stationary and deterministic in nature. Once both criteria are established, we proceed to calculate the largest Lyapunov exponent (LLE), which is an invariant quantity under time delay embedding. The LLE for all 16 patients is positive, which along with stationarity and determinism establishes the fact that the time series of a lung cancer patient's breathing pattern is not random or irregular, but rather it is deterministic in nature albeit chaotic. These results indicate that chaotic characteristics exist in the respiratory waveform and techniques based on state space dynamics should be employed for tumour motion management.

Assessment of multiple task activation and reproducibility in patients with benign and low-grade neoplasm.

Twenty-four patients with proven benign and low-grade brain neoplasms each performed two iterations of four fMRI paradigms: language (word generation), primary and association auditory (text listening), upper limb fine motor control (alternating-limb bilateral finger tapping), and primary visual perception (reversing checkerboard). Activation clusters with varying thresholds were generated for each scan and used to calculate reproducibility parameters: Difference in the Center of Mass (COM) location, R(size), and R(overlap). The average difference in the COM, R(size), and R(overlap) values ranged from 1.70 +/- 0.53 mm -10.60 +/- 3.21 mm, 0.6 +/- 0.04-0.90 +/- 0.05 and 0.23 +/- 0.12 -1 +/- 0.16 respectively for all tasks. These values are within the range of, or higher than, previously published reports on fMRI test-retest precision. FMRI is indicated to be a noninvasive tool with acceptable reproducibility measures for assessing the localizations of multiple language and sensorimotor functions in patients scheduled for radiotherapy treatment.

Accurate accumulation of dose for improved understanding of radiation effects in normal tissue.

The actual distribution of radiation dose accumulated in normal tissues over the complete course of radiation therapy is, in general, poorly quantified. Differences in the patient anatomy between planning and treatment can occur gradually (e.g., tumor regression, resolution of edema) or relatively rapidly (e.g., bladder filling, breathing motion) and these undermine the accuracy of the planned dose distribution. Current efforts to maximize the therapeutic ratio require models that relate the true accumulated dose to clinical outcome. The needed accuracy can only be achieved through the development of robust methods that track the accumulation of dose within the various tissues in the body. Specific needs include the development of segmentation methods, tissue-mapping algorithms, uncertainty estimation, optimal schedules for image-based monitoring, and the development of informatics tools to support subsequent analysis. These developments will not only improve radiation outcomes modeling but will address the technical demands of the adaptive radiotherapy paradigm. The next 5 years need to see academia and industry bring these tools into the hands of the clinician and the clinical scientist.

On the possible increase in local tumour control probability for gliomas exhibiting low dose hyper-radiosensitivity using a pulsed schedule.

Using modelling, we have developed a treatment strategy for gliomas exhibiting low dose hyper-radiosensitivity (HRS) that employs both a reduced dose-rate and pulsed treatment dose delivery. The model exploits the low dose hypersensitivity observed in some glioma cell lines at low radiation doses. We show, based on in vitro data, that a pulsed delivery of external beam radiation therapy could yield significant increases in local control. We therefore propose a pulsed delivery scheme for the treatment of gliomas in which the daily treatment fraction is delivered using 0.20 Gy pulses, separated by three minutes for a time-averaged dose-rate of 0.0667 Gy/min. The dose per pulse of 0.2 Gy is near or below the transition dose observed in vitro for four of the five glioma cell lines we have studied. Using five established glioma cell lines our modelling demonstrates that our pulsed delivery scheme yields a substantial increase in tumour control probability (TCP).