Biomedical subjects

Jake Van Dyk

Publications and source records attributed to Jake Van Dyk.

At least 19 recordsLinked to original sources

PubMed2006

A treatment planning study comparing whole breast radiation therapy against conformal, IMRT and tomotherapy for accelerated partial breast irradiation.

PURPOSE AND BACKGROUND: Conventional early breast cancer treatment consists of a lumpectomy followed by whole breast radiation therapy. Accelerated partial breast irradiation (APBI) is an investigational approach to post-lumpectomy radiation for early breast cancer. The purpose of this study is to compare four external beam APBI techniques, including tomotherapy, with conventional whole breast irradiation for their radiation conformity index, dose homogeneity index, and dose to organs at risk. METHODS AND MATERIALS: Small-field tangents, three-dimensional conformal radiation therapy, intensity-modulated radiation therapy and helical tomotherapy were compared for each of 15 patients (7 right, 8 left). One radiation conformity and two dose homogeneity indices were used to evaluate the dose to the target. The mean dose to organs at risk was also evaluated. RESULTS: All proposed APBI techniques improved the conformity index significantly over whole breast tangents while maintaining dose homogeneity and without a significant increase in dose to organs at risk. CONCLUSION: The four-field IMRT plan produced the best dosimetric results; however this technique would require appropriate respiratory motion management. An alternative would be to use a four-field conformal technique that is less sensitive to the effects of respiratory motion.

Breast Neoplasms↗

PubMed2006

Prostate contouring uncertainty in megavoltage computed tomography images acquired with a helical tomotherapy unit during image-guided radiation therapy.

PURPOSE: To evaluate the image-guidance capabilities of megavoltage computed tomography (MVCT), this article compares the interobserver and intraobserver contouring uncertainty in kilovoltage computed tomography (KVCT) used for radiotherapy planning with MVCT acquired with helical tomotherapy. METHODS AND MATERIALS: Five prostate-cancer patients were evaluated. Each patient underwent a KVCT and an MVCT study, a total of 10 CT studies. For interobserver variability analysis, four radiation oncologists, one physicist, and two radiation therapists (seven observers in total) contoured the prostate and seminal vesicles (SV) in the 10 studies. The intraobserver variability was assessed by asking all observers to repeat the contouring of 1 patient's KVCT and MVCT studies. Quantitative analysis of contour variations was performed by use of volumes and radial distances. RESULTS: The interobserver and intraobserver contouring uncertainty was larger in MVCT compared with KVCT. Observers consistently segmented larger volumes on MVCT where the ratio of average prostate and SV volumes was 1.1 and 1.2, respectively. On average (interobserver and intraobserver), the local delineation variability, in terms of standard deviations [Deltasigma = radical(sigma2MVCT-sigma2KVCT)], increased by 0.32 cm from KVCT to MVCT. CONCLUSIONS: Although MVCT was inferior to KVCT for prostate delineation, the application of MVCT in prostate radiotherapy remains useful.

Humans↗

PubMed2006

Partial volume rat lung irradiation: the protective/mitigating effects of Eukarion-189, a superoxide dismutase-catalase mimetic.

BACKGROUND AND PURPOSE: The purpose of the current study was to elucidate the protective/mitigating effects of a SOD-catalase mimetic, Eukarion-189 (EUK-189), on DNA damage in rat lung following irradiation. The particular focus of these studies was the efficacy of EUK-189 when given after irradiation (mitigation). PATIENTS AND METHODS: We exposed whole or lower lungs of female Sprague-Dawley rats to doses ranging from 10 to 20.5 Gray (Gy) of (60)Co gamma rays. Animals in the EUK-189 treated groups received 2 or 30 mg/kg intraperitoneally (i.p.) at various times postirradiation (PI). A micronucleus assay was used to examine DNA damage at various times up to 16 weeks PI. RESULTS: Our results indicated that EUK-189 administration after irradiation is effective at reducing micronucleus formation in lung fibroblasts at various times following radiation exposure. Treatment with EUK-189 in the first 3 days after thoracic irradiation did not, however, modify the dose required to cause severe morbidity at 2-3 months after irradiation. CONCLUSIONS: The protection produced when Eukarion-189 was given shortly after irradiation suggests that DNA damage observed in the lung may be caused by chronic production of ROS induced by a chronic inflammatory response initiated by the radiation treatment. We speculate that our failure to observe protection against severe morbidity at 2-3 months may be because our treatment regime only blocked the initial wave of ROS production and that treatment needs to be more prolonged to suppress the effects of a chronic inflammatory response.

Animals↗

PubMed2006

Comparative planning evaluation of intensity-modulated radiotherapy techniques for complex lung cancer cases.

BACKGROUND AND PURPOSE: Lung cancer treatment can be one of the most challenging fields in radiotherapy. The aim of the present study was to compare different modalities of radiation delivery based on a balanced scoring scheme for target coverage and normal tissue avoidance. PATIENTS AND METHODS: Treatment plans were developed for 15 patients with stage III inoperable non-small cell lung cancer using 3D conformal technique and intensity-modulated radiotherapy (IMRT). Elective nodal irradiation was included for all cases to create the most challenging scenarios with large target volumes. A 2 cm margin was used around the gross tumour volume (GTV) to generate PTV2 and 1cm margin around elective nodes for PTV1 resulting in PTV1 volumes larger than 1000 cm(3) in 13 of the 15 patients. 3D conformal and IMRT plans were generated on a commercial treatment planning system (TheraPlan Plus, Nucletron) with various combinations of beam energies and gantry angles. A 'dose quality factor' (DQF) was introduced to correlate the plan quality with patient specific parameters. RESULTS: A good correlation was found between the quality of the plans and the overlap between PTV1 and lungs. The patient feature factor (PFF), which is a product of several pertinent characteristics, was introduced to facilitate the choice of a particular technique for a particular patient. CONCLUSIONS: This approach may allow the evaluation of different treatment options prior to actual planning, subject to validation in larger prospective data sets.

Carcinoma, Non-Small-Cell Lung↗

PubMed2006

Evaluation of image-guided radiation therapy (IGRT) technologies and their impact on the outcomes of hypofractionated prostate cancer treatments: a radiobiologic analysis.

PURPOSE: To quantify the mitigation of geometric uncertainties achieved with the application of various patient setup techniques during the delivery of hypofractionated prostate cancer treatments, using tumor control probability (TCP) and normal tissue complication probability. METHODS AND MATERIALS: Five prostate cancer patients with approximately 16 treatment CT studies, taken during the course of their radiation therapy (77 total), were analyzed. All patients were planned twice with an 18 MV six-field conformal technique, with 10- and 5-mm margin sizes, with various hypofractionation schedules (5 to 35 fractions). Subsequently, four clinically relevant patient setup techniques (laser guided and image guided) were simulated to deliver such schedules. RESULTS: As hypothesized, the impact of geometric uncertainties on clinical outcomes increased with more hypofractionated schedules. However, the absolute gain in TCP due to hypofractionation (up to 21.8% increase) was significantly higher compared with the losses due to geometric uncertainties (up to 8.6% decrease). CONCLUSIONS: The results of this study suggest that, although the impact of geometric uncertainties on the treatment outcomes increases as the number of fractions decrease, the reduction in TCP due to the uncertainties does not significantly offset the expected theoretical gain in TCP by hypofractionation.

Dose Fractionation, Radiation↗

PubMed2005

Impact of geometric uncertainties on evaluation of treatment techniques for prostate cancer.

PURPOSE: To assess the impact of patient repositioning and internal organ motion on prostate treatment plans using three-dimensional conformal and intensity-modulated radiotherapy. METHODS AND MATERIALS: Four-field, six-field, and simplified intensity-modulated arc therapy plans were generated for 5 prostate cancer patients. The planning target volume was created by adding a 1-cm margin to the clinical target volume. A convolution model was used to estimate the effect of random geometric uncertainties during treatment. Dose statistics, tumor control probabilities, and normal tissue complication probabilities were compared with and without the presence of uncertainty. The impact of systematic uncertainties was also investigated. RESULTS: Compared with the planned treatments, the delivered dose distribution with random geometric uncertainties displayed an increase in the apparent minimal dose to the prostate and seminal vesicles and a decrease in the rectal volume receiving a high dose. This increased the tumor control probabilities and decreased the normal tissue complication probabilities. Changes were seen in the percentage of prostate volume receiving 100% and 95% of the prescribed dose, and the minimal dose and tumor control probabilities for the target volume. In addition, the volume receiving at least 65 Gy, the minimal dose, and normal tissue complication probabilities changed considerably for the rectum. The simplified intensity-modulated arc therapy technique was the most sensitive to systematic errors, especially in the anterior-posterior and superior-inferior directions. CONCLUSION: Geometric uncertainties should be considered when evaluating treatment plans. Contrary to the widely held belief, increased conformation of the dose distribution is not always associated with increased sensitivity to random geometric uncertainties if a sufficient planning target volume margin is used. Systematic errors may have a variable effect, depending on the treatment technique used.

Algorithms↗

PubMed2005

Investigation of dose homogeneity for loose helical tomotherapy delivery in the context of breath-hold radiation therapy.

Loose helical delivery is a potential solution to account for respiration-driven tumour motion in helical tomotherapy (HT). In this approach, a treatment is divided into a set of interlaced 'loose' helices commencing at different gantry angles. Each loose helix covers the entire target length in one gantry rotation during a single breath-hold. The dosimetric characteristics of loose helical delivery were investigated by delivering a 6 MV photon beam in a HT-like manner. Multiple scenarios of conventional 'tight' HT and loose helical deliveries were modelled in treatment planning software, and carried out experimentally with Kodak EDR2 film. The advantage of loose helical delivery lies in its ability to produce a more homogeneous dose distribution by eliminating the 'thread' effect-an inherent characteristic of HT, which results in dose modulations away from the axis of gantry rotation. However, loose helical delivery was also subjected to undesirable dose modulations in the direction of couch motion (termed 'beating' effect), when the ratio between the number of beam projections per gantry rotation (n) and pitch factor (p) was a non-integer. The magnitude of dose modulations decreased with an increasing n/p ratio. The results suggest that for the current HT unit (n = 51), dose modulations could be kept under 5% by selecting a pitch factor smaller than 7. A pitch factor of this magnitude should be able to treat a target up to 30 cm in length. Loose helical delivery should increase the total session time only by a factor of 2, while the planning time should stay the same since the total number of beam projections remains unchanged. Considering its dosimetric advantage and clinical practicality, loose helical delivery is a promising solution for the future HT treatments of respiration-driven targets.

Body Burden↗

PubMed2005

Image-guided adaptive radiation therapy (IGART): Radiobiological and dose escalation considerations for localized carcinoma of the prostate.

The goal of this work was to evaluate the efficacy of various image-guided adaptive radiation therapy (IGART) techniques to deliver and escalate dose to the prostate in the presence of geometric uncertainties. Five prostate patients with 15-16 treatment CT studies each were retrospectively analyzed. All patients were planned with an 18 MV, six-field conformal technique with a 10 mm margin size and an initial prescription of 70 Gy in 35 fractions. The adaptive strategy employed in this work for patient-specific dose escalation was to increase the prescription dose in 2 Gy-per-fraction increments until the rectum normal tissue complication probability (NTCP) reached a level equal to that of the nominal plan NTCP (i.e., iso-NTCP dose escalation). The various target localization techniques simulated were: (1) daily laser-guided alignment to skin tattoo marks that represents treatment without image-guidance, (2) alignment to bony landmarks with daily portal images, and (3) alignment to the clinical target volume (CTV) with daily CT images. Techniques (1) and (3) were resimulated with a reduced margin size of 5 mm to investigate further dose escalation. When delivering the original clinical prescription dose of 70 Gy in 35 fractions, the "CTV registration" technique yielded the highest tumor control probability (TCP) most frequently, followed by the "bone registration" and "tattoo registration" techniques. However, the differences in TCP among the three techniques were minor when the margin size was 10 mm (< or = 1.1 %). Reducing the margin size to 5 mm significantly degraded the TCP values of the "tattoo registration" technique in two of the five patients, where a large difference was found compared to the other techniques (< or = 11.8 %). The "CTV registration" technique, however, did maintain similar TCP values compared to their 10 mm margin counterpart. In terms of normal tissue sparing, the technique producing the lowest NTCP varied from patient to patient. Reducing the margin size seemed the only sure way to reduce the NTCP significantly, irrespective of the IGART technique employed. In escalating the dose with the iso-NTCP constraint, the largest average gain in dose was observed with the "tattoo registration" technique, followed by the "CTV registration" and "bone registration" techniques. This is attributed to the fact that in three of the five patients, the "tattoo registration" technique yielded the lowest NTCP, hence a greater window of opportunity to escalate the dose was possible with this technique. However, the variation among the five patients was also largest with the "tattoo registration" technique where, in the case of one patient, the required dose actually needed to be below the original prescription dose of 70 Gy to satisfy the iso-NTCP constraint. This was not the case with the "CTV registration" technique where positive and similar dose escalation was allowed on all five patients. Based on these data, an attractive dose escalation strategy may be to implement the "CTV registration" technique (for consistent dosimetric coverage) for daily target localization in combination with a margin reduction (for increased normal tissue sparing).

Dose Fractionation, Radiation↗

PubMed2004

A multileaf collimator phantom for the quality assurance of radiation therapy planning systems and CT simulators.

PURPOSE: The evolution of three-dimensional conformal radiation treatment has led to the use of multileaf collimators (MLCs) in intensity-modulated radiation therapy (IMRT) and other treatment techniques to increase the conformity of the dose distribution. A new quality assurance (QA) phantom has been designed to check the handling of MLC settings in treatment planning and delivery. METHODS AND MATERIALS: The phantom consists of a Perspex block with stepped edges that can be rotated in all planes. The design allows for the assessment of several MLC and micro-MLC types from various manufacturers, and is therefore applicable to most radiation therapy institutions employing MLCs. The phantom is computed tomography (CT) scanned as is a patient, and QA assessments can be made of field edge display for a variety of shapes and orientations on both radiation treatment planning systems (RTPS) and computed tomography simulators. RESULTS: The dimensions of the phantom were verified to be physically correct within an uncertainty range of 0-0.7 mm. Errors in leaf position larger than 1 mm were easily identified by multiple observers. CONCLUSIONS: The MLC geometry phantom is a useful tool in the QA of radiation therapy with application to RTPS, CT simulators, and virtual simulation packages with MLC display capabilities.

Algorithms↗

PubMed2004

Planning evaluation of radiotherapy for complex lung cancer cases using helical tomotherapy.

Lung cancer treatment is one of the most challenging fields in radiotherapy. The aim of the present study was to investigate what role helical tomotherapy (HT), a novel approach to the delivery of highly conformal dose distributions using intensity-modulated radiation fan beams, can play in difficult cases with large target volumes typical for many of these patients. Tomotherapy plans were developed for 15 patients with stage III inoperable non-small-cell lung cancer. While not necessarily clinically indicated, elective nodal irradiation was included for all cases to create the most challenging scenarios with large target volumes. A 2 cm margin was used around the gross tumour volume (GTV) to generate primary planning target volume (PTV2) and 1 cm margin around elective nodes for secondary planning target volume (PTV1) resulting in PTV1 volumes larger than 1000 cm3 in 13 of the 15 patients. Tomotherapy plans were created using an inverse treatment planning system (TomoTherapy Inc.) based on superposition/convolution dose calculation for a fan beam thickness of 25 mm and a pitch factor between 0.3 and 0.8. For comparison, plans were created using an intensity-modulated radiation therapy (IMRT) approach planned on a commercial treatment planning system (TheraplanPlus, Nucletron). Tomotherapy delivery times for the large target volumes were estimated to be between 4 and 19 min. Using a prescribed dose of 60 Gy to PTV2 and 46 Gy to PTV1, the mean lung dose was 23.8+/-4.6 Gy. A 'dose quality factor' was introduced to correlate the plan outcome with patient specific parameters. A good correlation was found between the quality of the HT plans and the IMRT plans with HT being slightly better in most cases. The overlap between lung and PTV was found to be a good indicator of plan quality for HT. The mean lung dose was found to increase by approximately 0.9 Gy per percent overlap volume. Helical tomotherapy planning resulted in highly conformal dose distributions. It allowed easy achievement of two different dose levels in the target simultaneously. As the overlap between PTV and lung volume is a major predictor of mean lung dose, future work will be directed to control of margins. Work is underway to investigate the possibility of breath-hold techniques for tomotherapy delivery to facilitate this aim.

Carcinoma, Non-Small-Cell Lung↗

PubMed2004

Radiation treatment of lung cancer--patterns of practice in Canada.

BACKGROUND AND PURPOSE: To assess the patterns of practice among Canadian radiation oncologists who treat lung cancers. PATIENTS AND METHODS: A questionnaire detailing different aspects of radiation treatment of lung cancer was mailed to all radiation oncologists treating lung cancer in Canada. Seventy-two percent (74/103) of radiation oncologists who treat lung cancer from all 34 Canadian cancer centres replied to the questionnaire. RESULTS: (a) Radiotherapy regimens in Canadian cancer centres are in accordance with several major randomised studies. There is still some variation in treatment practice that may be due to unresolved controversies or limited resources. The most frequently used prescription dose was 40Gy/15f/3w (where f stands for fractions and w stands for weeks) for small cell lung cancer (SCLC) and 60Gy/30f/6w for non-small cell lung cancer (NSCLC). If there were no resource constraints, 30% (22/74) and 20% (15/74) would prefer to use a different dose-fractionation scheme for SCLC and NSCLC, respectively; 95% (70/74) would prefer to use 3D-conformal or intensity-modulated radiotherapy. (b) Among the various modern technologies assessed by respondents, CT (computed tomography) simulator, multi-leaf collimator, on-line electronic portal imaging and PET (positron-emission tomography) scanning were rated the highest in terms of potential patient benefit. Discrepancy between demand and availability of technology was greatest for PET scanning. CONCLUSIONS: Canadian practice in the treatment of lung cancers shows some variations although it is consistent with the trends in the literature. The lack of some modern technologies and human resources is an ongoing concern, especially the lack of PET imaging equipment.

Adult↗

PubMed2004

Prediction of radiation pneumonitis by dose - volume histogram parameters in lung cancer--a systematic review.

BACKGROUND AND PURPOSE: To perform a systematic review of the predictive ability of various dose-volume histogram (DVH) parameters (V(dose), mean lung dose (MLD), and normal tissue complication probability (NTCP)) in the incidence of radiation pneumonitis (RP) caused by external-beam radiation therapy. METHODS AND MATERIALS: Studies assessing the relationship between CT-based DVH reduction parameters and RP rate in radically treated lung cancer were eligible for the review. Synonyms for RP, lung cancer, DVH and its associated parameters (NTCP, V(20), V(30), MLD) were combined in a search strategy involving electronic databases, secondary reference searching, and consultation with experts. Individual or group data were abstracted from the various reports to calculate operating characteristics and odds ratios for the different DVH metrics. RESULTS: A total of 12 published studies and two abstracts were identified. Eleven studies assessed V(dose), seven assessed MLD, and eight assessed NTCP. Nine studies exclusively analyzed the association between various DVH metrics and RP risk. Five studies also analyzed other patient, tumor, and treatment variables in conjunction with standard DVH metrics. A direct comparison between studies and the generation of summary statistics (i.e. meta-analysis) could not be achieved due to significant predictive and outcome variable heterogeneity. Most studies did show an association between DVH parameters and RP risk. However, overall accuracy, sensitivity, specificity, and positive predictive value were generally poor to fair for all three classes of DVH metrics. CONCLUSIONS: An association between DVH parameters and RP risk has been demonstrated in the literature. However, the ideal DVH metric with excellent operating characteristics, either alone or in a model with other predictive variables, for RP risk prediction has not yet been identified. Several recommendations for reporting and conduct of future research into the association between DVH metrics and RP risk are provided.

Carcinoma, Non-Small-Cell Lung↗

PubMed2004

Asymmetric fan beams (AFB) for improvement of the craniocaudal dose distribution in helical tomotherapy delivery.

Helical tomotherapy (HT) is a novel radiotherapy technique that utilizes intensity modulated fan beams that deliver highly conformal dose distributions in a helical beam trajectory. The most significant limitation in dose delivery with a constant fan beam thickness (FBT) is the penumbra width of the dose distribution in the craniocaudal direction, which is equivalent to the FBT. We propose to employ a half-blocked fan beam at start and stop location to reduce the penumbra width by half. By opening the jaw slowly during the helical delivery until the desired FBT is achieved it is possible to create a sharper edge in the superior and inferior direction from the target. The technique was studied using a tomotherapy beam model implemented on a commercial treatment planning system (Theraplan Plus V3.0). It was demonstrated that the dose distribution delivered using a 25 mm fan beam can be improved significantly, to reduce the dose to normal structures located superiorly and inferiorly of the target. Dosimetry for this technique is straightforward down to a FBT of 15 mm and implementation should be simple as no changes in couch movement are required compared to a standard HT delivery. We conclude that the use of asymmetric collimated fan beams for the start and stop of the helical tomotherapeutic dose delivery has the potential of significantly improving the dose distribution in helical tomotherapy.

Algorithms↗

PubMed2004

Limitations of a convolution method for modeling geometric uncertainties in radiation therapy: the radiobiological dose-per-fraction effect.

The convolution method can be used to model the effect of random geometric uncertainties into planned dose distributions used in radiation treatment planning. This is effectively done by linearly adding infinitesimally small doses, each with a particular geometric offset, over an assumed infinite number of fractions. However, this process inherently ignores the radiobiological dose-per-fraction effect since only the summed physical dose distribution is generated. The resultant potential error on predicted radiobiological outcome [quantified in this work with tumor control probability (TCP), equivalent uniform dose (EUD), normal tissue complication probability (NTCP), and generalized equivalent uniform dose (gEUD)] has yet to be thoroughly quantified. In this work, the results of a Monte Carlo simulation of geometric displacements are compared to those of the convolution method for random geometric uncertainties of 0, 1, 2, 3, 4, and 5 mm (standard deviation). The alpha/betaCTV ratios of 0.8, 1.5, 3, 5, and 10 Gy are used to represent the range of radiation responses for different tumors, whereas a single alpha/betaOAR ratio of 3 Gy is used to represent all the organs at risk (OAR). The analysis is performed on a four-field prostate treatment plan of 18 MV x rays. The fraction numbers are varied from 1-50, with isoeffective adjustments of the corresponding dose-per-fractions to maintain a constant tumor control, using the linear-quadratic cell survival model. The average differences in TCP and EUD of the target, and in NTCP and gEUD of the OAR calculated from the convolution and Monte Carlo methods reduced asymptotically as the total fraction number increased, with the differences reaching negligible levels beyond the treatment fraction number of > or =20. The convolution method generally overestimates the radiobiological indices, as compared to the Monte Carlo method, for the target volume, and underestimates those for the OAR. These effects are interconnected and attributed to assuming an infinite number of fractions inherent in the implementation of the convolution technique, irrespective of the uniqueness of each treatment schedule. Based on the fraction numbers analyzed (1-50), and the range of fraction numbers normally used clinically (> or =20), the convolution method can be used safely to estimate the effects of random geometric uncertainties on prostate treatment radiobiological outcomes, for both the target and the OAR. Although the results of this study is likely to apply to other clinical sites and treatment techniques other than the four-field, further validation similar to those done in this study may be necessary prior to clinical implementation.

Algorithms↗

PubMed2003

The impact of geometric uncertainty on hypofractionated external beam radiation therapy of prostate cancer.

PURPOSE: Recent publications indicate alpha/beta for prostate carcinoma could be lower than assumed. Therefore, hypofractionation might increase the therapeutic ratio. However, patient repositioning and organ motion may affect hypofractionated treatments more than conventional treatments. Our purpose is to evaluate the potential impact of geometric uncertainties on hypofractionated treatments. METHODS AND MATERIALS: Tumor control probability (TCP) and normal tissue complication probability (NTCP) are calculated for simulated conventional and hypofractionated treatments, assuming alpha/beta of 1.5 Gy for prostate and 3.0 Gy for rectum. A Monte Carlo simulation randomly samples systematic and random displacements and produces the cumulative dose distribution for the prostate and rectum. The limiting number of fractions and the impact of different alpha/beta values are also explored. RESULTS: A consistent but small reduction in TCP is seen with hypofractionation (generally <1%) as a result of geometric uncertainties. Escalated hypofractionation seems to allow large TCP gains ( approximately 20%) without increasing NTCP. Treatments of five fractions seem to affect outcome minimally. The alpha/beta value has a much greater impact on TCP than geometric uncertainties. CONCLUSION: The potential increased influence of geometric uncertainties on hypofractionation seems small. Limited knowledge of radiobiologic response is likely a greater obstacle to prostate hypofractionation than geometric uncertainties.

Algorithms↗

PubMed2003

Partial volume rat lung irradiation; assessment of early DNA damage in different lung regions and effect of radical scavengers.

PURPOSE: These studies were designed to examine radiation-induced in-field and out-of-field DNA damage in rat lung as a function of dose and various volumes of irradiation. They also determined whether superoxide dismutase (SOD) and nitro-L-arginine methyl ester (L-NAME) protected against this damage. METHODS AND MATERIALS: The whole lung, or various volumes of the lower or upper lungs of Sprague-Dawley rats were exposed to doses up to 20 Gy of 60Co gamma rays. Radiation-induced DNA damage was quantified in fibroblasts obtained at 18 h after irradiation from both irradiated and shielded lung regions using a micronucleus assay. The radioprotective role of SOD (CuZnSOD: 10 mg/kg body weight; MnSOD: 50-100mg/kg body weight) and L-NAME (0.2 mg/kg body weight.) in vivo was determined by injecting them into rats 30 min before or immediately after a dose of 10 Gy. RESULTS: Micronucleus formation was approximately linear with dose up to 15 Gy. When 70% of the lung volume was irradiated with 10 Gy, irradiated lower lung gave similar numbers of micronuclei (MN)/binucleate cell (BN) to that observed following whole lung irradiation (0.91 MN/BN), whereas the irradiated upper lung gave only 0.66 MN/BN. Following lower lung irradiation, the shielded upper lung (30% of lung volume) showed substantial (out-of-field) damage (0.43 MN/BN). When 30% of the lung was given 10 Gy, irradiated upper or lower lung showed similar amounts of in-field damage (0.43 MN/BN) but this was smaller than that seen following irradiation of 70% of the lung volume. For 30% lower lung irradiation, the shielded upper lung showed only a small out-of-field effect (0.1 MN/BN). For both volumes of irradiation there was a similar or smaller effect in the shielded lower lung after upper lung irradiation. Injection of SOD before or L-NAME after 10 Gy to the lower 70% lung volume resulted in a reduction in DNA damage both in-field and out-of-field but the percentage was much greater for out-of-field damage (50-60%) than for in-field damage (10-30%). Following whole lung irradiation (10 Gy) significantly greater DNA damage was observed in fibroblasts from the left lung than from the right lung (0.93 MN/BN vs. 0.82 MN/BN). Following whole lung irradiation there was no significant difference in DNA damage observed in fibroblasts from the lower lung and the upper lung. CONCLUSIONS: With partial lung irradiation the lower lung sustains more in-field DNA damage following irradiation than the upper lung, whereas out-of-field effects are observed primarily in the upper lung (i.e. following lower lung irradiation). Following whole lung irradiation the left lung sustains more damage than the right lung but there is no difference between the upper and lower lung. The protective effects of SOD and L-NAME suggest that inflammatory cytokines induced by the irradiation may be involved in the initiation of a reaction resulting in the production of reactive oxyradicals and nitric oxide that cause indirect DNA damage both in and out of the radiation field.

Analysis of Variance↗

PubMed2003

Dose-volume analysis of lung complications in the radiation treatment of malignant thymoma: a retrospective review.

BACKGROUND AND PURPOSE: Radiation pneumonitis and fibrosis are limiting factors in radiation treatment (RT) of thoracic tumors. The objectives of this study were to quantify the influence of irradiated lung volume and dose on lung response, and to evaluate the influence of other prognostic factors. MATERIAL AND METHODS: Treatment histories of 55 thymoma patients were evaluated retrospectively for radiation pneumonitis and fibrosis. Complications were scored as pneumonitis if observed within 6 months of completion of RT, and as fibrosis if observed after 6 months. Complications were classified as 'all pneumonitis' and 'all fibrosis' if a patient either showed symptoms (such as chronic cough and dyspnea) or radiographic changes in lung. The second group scored as 'symptomatic pneumonitis' and 'symptomatic fibrosis' consisted of patients that exhibited clinical symptoms. Dose-volume data were estimated using representative anatomies combined with available individual dose data. The Lyman NTCP model was used to assess the dependence of lung complication incidence on dose and volume. RESULTS: The derived values of the parameters governing dose-volume dependence for symptomatic complications agreed with currently accepted and recently published values within the margins of error. Dose-response curves for complications that included radiographic changes were less steep than for symptomatic complications. The volume dependence for symptomatic fibrosis was more pronounced compared to all fibrosis. A strong correlation was observed between developing pneumonitis and developing fibrosis. CONCLUSIONS: The long survival allowed the assessment of lung complication data in thymoma patients for both acute and late response. Mean dose in lung strongly correlated with lung complications that manifest clinically. The determination of the dose-volume dependence is affected by the choice of endpoints (i.e. whether complications are scored based on clinical symptoms or radiographic changes not accompanied by clinical symptoms).

Adolescent↗

PubMed2003

Dosimetric considerations for patients with HIP prostheses undergoing pelvic irradiation. Report of the AAPM Radiation Therapy Committee Task Group 63.

This document is the report of a task group of the Radiation Therapy Committee of the AAPM and has been prepared primarily to advise hospital physicists involved in external beam treatment of patients with pelvic malignancies who have high atomic number (Z) hip prostheses. The purpose of the report is to make the radiation oncology community aware of the problems arising from the presence of these devices in the radiation beam, to quantify the dose perturbations they cause, and, finally, to provide recommendations for treatment planning and delivery. Some of the data and recommendations are also applicable to patients having implanted high-Z prosthetic devices such as pins, humeral head replacements. The scientific understanding and methodology of clinical dosimetry for these situations is still incomplete. This report is intended to reflect the current state of scientific understanding and technical methodology in clinical dosimetry for radiation oncology patients with high-Z hip prostheses.

Advisory Committees↗