Average Equivalent Uniform Dose Research Articles

Clinical and radiobiological evaluation of a method for planning target volume generation dependent on organ-at-risk exclusions in magnetic resonance imaging-based prostate radiotherapy.

Background and purposeDue to a smaller target volume when delineating prostate on magnetic resonance imaging (MRI), margins may be too tight as compared to computed tomography (CT) delineation, potentially reducing tumor control probability (TCP) in prostate radiotherapy. This study evaluated a clinically implemented MRI-based target expansion method to provide adequate margins yet limit organ-at-risk (OAR) dose as compared to CT-based delineation.Methods and materialsPatients in this study were treated to 79.2 Gy in 44 fractions via intensity modulated radiotherapy using an MRI-based expansion method, which excluded OARs when performing a 5 mm isotropic (except 4 mm posterior) expansion from gross tumor volume to clinical target volume (CTV), followed by an isotropic 5 mm expansion to generate the planning target volume (PTV). Ten cases were re-planned using CT-delineated prostate with CTV-to-PTV expansion of isotropic 8 mm, except for a 5 mm posterior expansion, with comparison of PTV volumes, TCP and normal tissue complication probability (NTCP) to the MRI-based method. Under IRB approved protocol, we retrospectively evaluated 51 patients treated with the MRI-based method for acute bladder and rectal toxicity with CTC-AE version 4.0 used for scoring.ResultsMRI-based PTV volume differed by 4% compared to CT-based PTV volume. Radiobiological calculated TCP of the MRI-based method was found comparable to CT-based methods with an average equivalent uniform dose of 80.5 Gy and 80.1 Gy respectively. Statistically significant decrease in bladder NTCP (toxicity Grade 2 and above for 5% complications within 5 years post radiotherapy) was observed in the MRI-based method. Outcomes data collected showed 65% and 100% of patients studied experienced Grade 0/1 bladder and rectal acute toxicity respectively. Grade 2 bladder toxicity was indicated in the remaining 35% of patients studied with no Grade 3 toxicity reported.ConclusionsResults showed comparable PTV volume with MRI-based method, and NTCP was reduced while maintaining TCP. Clinically, bladder and rectal toxicities were observed to be minimal.

A dosimetric evaluation of IGART strategies for cervix cancer treatment

PurposeImage guided adaptive radiotherapy (IGART) strategies can be used to include the temporal aspects of radiotherapy treatment. A dosimetric evaluation of on- and off-line adaptive strategies are done in this study. MethodsA library of equivalent uniform dose (EUD)-based Intensity Modulated Radiotherapy Treatment plans with incrementally increasing clinical target volume (CTV)-to-planning target volume (PTV) margins were developed for 10 patients. Utilizing daily computed tomography (CT) images an on-line strategy using a margin-of-the-day (MOD) concept that selects the best plan from the library was employed. This was compared to an off-line strategy with full analysis of accumulated dose between fractions where dosimetric deviations from the treatment intent triggered plan adaptation. A fixed margin treatment approach was used as benchmark. ResultsUsing fixed margins of <15mm lead to under-dosages of more than 5Gy in total delivered dose. The average CTV EUD for the off-line and on-line strategy was 50.0±5.0Gy and 50.4±2.0Gy respectively and OAR doses were comparable. ConclusionA fixed margin treatment approach yields a significant probability of CTV under-dosage. Using EUD dose metrics CTV coverage can be restored in both the off-line and on-line adaptive strategies at acceptable OAR dose levels. Considering the workload and time on the treatment machine, the off-line strategy proves to be sufficient and more practical.

SU‐F‐T‐388: Comparison of Biophysical Indices in Hippocampal‐Avoidance Whole Brain VMAT and IMRT Radiation Therapy Treatment Plans

Purpose:To compare biophysical indices of Volumetric Modulated Arc Therapy (VMAT) and Intensity Modulated Radiation Therapy (IMRT) treatment plans for whole brain radiation therapy following the NRG‐CC001 protocol.Methods:In this retrospective study, a total of fifteen patients were planned with Varian Eclipse Treatment Planning System using VMAT (RapidArc) and IMRT techniques. The planning target volume (PTV) was defined as the whole brain volume excluding a uniform three‐dimensional 5mm expansion of the hippocampus volume. Prescribed doses in all plans were 30 Gy delivered over 10 fractions normalized to a minimum of 95% of the target volume receiving 100% of the prescribed dose. The NRG Oncology protocol guidelines were followed for contouring and dose‐volume constraints. A single radiation oncologist evaluated all treatment plans. Calculations of statistical significance were performed using Student's paired t‐test.Results:All VMAT and IMRT plans met the NRG‐CC001 protocol dose‐volume criteria. The average equivalent uniform dose (EUD) for the PTV for VMAT vs. IMRT was respectively (19.05±0.33 Gy vs. 19.38±0.47 Gy) for α/β of 2 Gy and (19.47±0.30 Gy vs. 19.84±0.42 Gy) for α/β of 10 Gy. For the PTV, the average mean and maximum doses were 2% and 5% lower in VMAT plans than in IMRT plans, respectively. The average EUD and the normal tissue complication probability (NTCP) for the hippocampus in VMAT vs. IMRT plans were (15.28±1.35 Gy vs. 15.65±0.99 Gy, p=0.18) and (0.305±0.012 Gy vs. 0.308±0.008 Gy, p=0.192), respectively. The average EUD and NTCP for the optic chiasm were both 2% higher in VMAT than in IMRT plans.Conclusion:Though statistically insignificant, VMAT plans indicate a lower hippocampus EUD than IMRT plans. Also, a small variation in NTCP was found between plans.

Impact of Spot Size and Beam-Shaping Devices on the Treatment Plan Quality for Pencil Beam Scanning Proton Therapy

This study aimed to assess the clinical impact of spot size and the addition of apertures and range compensators on the treatment quality of pencil beam scanning (PBS) proton therapy and to define when PBS could improve on passive scattering proton therapy (PSPT). The patient cohort included 14 pediatric patients treated with PSPT. Six PBS plans were created and optimized for each patient using 3 spot sizes (∼12-, 5.4-, and 2.5-mm median sigma at isocenter for 90- to 230-MeV range) and adding apertures and compensators to plans with the 2 larger spots. Conformity and homogeneity indices, dose-volume histogram parameters, equivalent uniform dose (EUD), normal tissue complication probability (NTCP), and integral dose were quantified and compared with the respective PSPT plans. The results clearly indicated that PBS with the largest spots does not necessarily offer a dosimetric or clinical advantage over PSPT. With comparable target coverage, the mean dose (Dmean) to healthy organs was on average 6.3% larger than PSPT when using this spot size. However, adding apertures to plans with large spots improved the treatment quality by decreasing the average Dmean and EUD by up to 8.6% and 3.2% of the prescribed dose, respectively. Decreasing the spot size further improved all plans, lowering the average Dmean and EUD by up to 11.6% and 10.9% compared with PSPT, respectively, and eliminated the need for beam-shaping devices. The NTCP decreased with spot size and addition of apertures, with maximum reduction of 5.4% relative to PSPT. The added benefit of using PBS strongly depends on the delivery configurations. Facilities limited to large spot sizes (>∼8 mm median sigma at isocenter) are recommended to use apertures to reduce treatment-related toxicities, at least for complex and/or small tumors.

SU‐F‐BRD‐12: When Does Pencil Beam Scanning Become Superior to Passive Scattered Proton Therapy for Pediatric Head and Neck Cancers?

Purpose:To investigate the dosimetric benefits of pencil beam scanning (PBS) compared with passive scattered (PS) proton therapy for treatment of pediatric head&amp;neck patients as a function of the PBS spot size and explore the advantages of using apertures in PBS.Methods:Ten pediatric patients with head&amp;neck cancers treated by PS proton therapy at our institution were retrospectively selected. The histologies included rhabdomyosarcoma, ependymoma, astrocytoma, craniopharyngioma and germinoma. The prescribed dose ranged from 36 to 54 Gy(RBE). Five PBS plans were created for each patient using variable spot size (average sigma at isocenter) and choice of beam specific apertures: (1) 10mm spots, (2) 10mm spots with apertures, (3) 6mm spots, (4) 6mm spots with apertures, and (5) 3mm spots. The plans were optimized for intensity modulated proton therapy (IMPT) with no single beam uniformity constraints. Dose volume indices as well as equivalent uniform dose (EUD) were compared between PS and PBS plans.Results:Although target coverage was clinically adequate for all cases, the plans with largest (10mm) spots provide inferior quality compared with PS in terms of dose to organs‐at‐risk (OAR). However, adding apertures to these plans ensured lower OAR dose than PS. The average EUD difference between PBS and PS plans over all patients and organs at risk were (1) 2.5%, (2) −5.1%, (3) ‐5%, (4) −7.8%, and (5) −9.5%. As the spot size decreased, more conformal plans were achieved that offered similar target coverage but lower dose to the neighboring healthy organs, while alleviating the need for using apertures.Conclusion:The application of PBS does not always translate to better plan qualities compared to PS depending on the available beam spot size. We recommend that institutions with spot size larger than ∼6mm at isocenter consider using apertures to guarantee clinically comparable or superior dosimetric efficacy to PS treatments.

SU-E-T-629: Feasibility Study of Treating Multiple Brain Tumors with Large Number of Noncoplanar IMRT Beams

Purpose: To study the feasibility of treating multiple brain tumors withlarge number of noncoplanar IMRT beams. Methods: Thirty beams are selected from 390 deliverable beams separated by six degree in 4pi space. Beam selection optimization is based on a column generation algorithm. MLC leaf size is 2 mm. Dose matrices are calculated with collapsed cone convolution & superposition method in a 2 mm by 2mm by 2 mm grid. Twelve brain tumors of various shapes, sizes and locations are used to generate four plans treating 3, 6, 9 and 12 tumors. The radiation dose was 20 Gy prescribed to the 100% isodose line. Dose Volume Histograms for tumor and brain were compared. Results: All results are based on a 2 mm by 2 mm by 2 mm CT grid. For 3, 6, 9 and 12 tumor plans, minimum tumor doses are all 20 Gy. Mean tumor dose are 20.0, 20.1, 20.1 and 20.1 Gy. Maximum tumor dose are 23.3, 23.6, 25.4 and 25.4 Gy. Mean ventricles dose are 0.7, 1.7, 2.4 and 3.1 Gy.Mean subventricular zone dose are 0.8, 1.3, 2.2 and 3.2 Gy. Average Equivalent uniform dose (gEUD) values for tumor are 20.1, 20.1, 20.2 and 20.2 Gy. The conformity index (CI) values are close to 1 for all 4 plans. The gradient index (GI) values are 2.50, 2.05, 2.09 and 2.19. Conclusion: Compared with published Gamma Knife treatment studies, noncoplanar IMRT treatment plan is superior in terms of dose conformity. Due to maximum limit of beams per plan, Gamma knife has to treat multiple tumors separately in different plans. Noncoplanar IMRT plans theoretically can be delivered in a single plan on any modern linac with an automated couch and image guidance. This warrants further study of using noncoplanar IMRT as a viable treatment solution for multiple brain tumors.

Radiobiological impact of planning techniques for prostate cancer in terms of tumor control probability and normal tissue complication probability.

Background:The radiobiological models describe the effects of the radiation treatment on cancer and healthy cells, and the radiobiological effects are generally characterized by the tumor control probability (TCP) and normal tissue complication probability (NTCP).Aim:The purpose of this study was to assess the radiobiological impact of RapidArc planning techniques for prostate cancer in terms of TCP and normal NTCP.Subjects and Methods:A computed tomography data set of ten cases involving low-risk prostate cancer was selected for this retrospective study. For each case, two RapidArc plans were created in Eclipse treatment planning system. The double arc (DA) plan was created using two full arcs and the single arc (SA) plan was created using one full arc. All treatment plans were calculated with anisotropic analytical algorithm. Radiobiological modeling response evaluation was performed by calculating Niemierko's equivalent uniform dose (EUD)-based Tumor TCP and NTCP values.Results:For prostate tumor, the average EUD in the SA plans was slightly higher than in the DA plans (78.10 Gy vs. 77.77 Gy; P = 0.01), but the average TCP was comparable (98.3% vs. 98.3%; P = 0.01). In comparison to the DA plans, the SA plans produced higher average EUD to bladder (40.71 Gy vs. 40.46 Gy; P = 0.03) and femoral heads (10.39 Gy vs. 9.40 Gy; P = 0.03), whereas both techniques produced NTCP well below 0.1% for bladder (P = 0.14) and femoral heads (P = 0.26). In contrast, the SA plans produced higher average NTCP compared to the DA plans (2.2% vs. 1.9%; P = 0.01). Furthermore, the EUD to rectum was slightly higher in the SA plans (62.88 Gy vs. 62.22 Gy; P = 0.01).Conclusion:The SA and DA techniques produced similar TCP for low-risk prostate cancer. The NTCP for femoral heads and bladder was comparable in the SA and DA plans; however, the SA technique resulted in higher NTCP for rectum in comparison with the DA technique.

TU‐A‐108‐08: Comparison of Full Intensity Modulated and Single Field Uniform Dose Proton Beam Scanning Lung Treatments

Purpose: To determine differences in motion interplay effects between single‐field uniform dose (SFUD) and intensity modulated proton therapy (IMPT) treatments for lung patients. Methods: SFUD and IMPT treatment plans were generated for 10 lung cancer patients. The spot spacing was set to 0.7σ for all treatment plans and all plans used 2 fields delivered to the planning target volume (PTV). Treatment plans required that at least 95% of the PTV and 99% of the ICTV received the prescription dose. The ICTV was defined as the IGTV+8mm and covered the CTV in all 10 phases of the 4DCT. SFUD plans require each field homogeneously, within a given tolerance, cover the PTV, whilst IMPT has no such constraint. Monte Carlo simulations were performed using the detailed timing structure of the proton fields and the patient 4DCT for 2.5Gy(RBE) and 12Gy(RBE) fractions using 2 different spot sizes (σ ∼8–17mm and ∼2–4mm). Simulations were performed on the different phases of the patient 4DCT. The 4D dose distribution was generated via deformable image registration, using the 50% phase as the reference. Degradation in the dose distributions due to motion and interplay effects was quantified via equivalent uniform dose (EUD), V95 and dose homogeneity. Results: All values are quoted as percentages of the dose per fraction. For 2.5Gy(RBE) fractions, the average EUD loss due to interplay is 3.7+/−3.6% and 4.4+/−3.3% for IMPT and SFUD respectively for the larger spot size. For the smaller spot size, the average EUD loss for IMPT and SFUD treatments is 12.2+/−10.5% and 15.1+/−12.2% respectively. The average EUD loss for 12Gy(RBE) fractions is within 1% of the 2.5Gy(RBE) values. No significant differences between the SFUD and IMPT plans were observed for V95 and target dose homogeneity. Conclusion: No significant difference in motion effects was observed between SFUD and IMPT treatments. This project was supported by the National Cancer Institute Grant No. R01 CA111590

Temporal compartmental dosing effects for robotic prostate stereotactic body radiotherapy

The rate of dose accumulation within a given area of a target volume tends to vary significantly for non-isocentric delivery systems such as Cyberknife stereotactic body radiotherapy. In this study, we investigated whether intra-target temporal dose distributions produce significant variations in the biological equivalent dose. For the study, time courses of ten patients were reconstructed and calculation of a biologically equivalent uniform dose (EUD) was performed using a formula derived from the linear quadratic model (α/β = 3 for prostate cancer cells). The calculated EUD values obtained for the actual patient treatments were then compared with theoretical EUD values for delivering the same physical dose distribution except that the whole target being irradiated continuously (e.g. large-field ‘dose-bathing’ type of delivery). For all the case, the EUDs for the actual treatment delivery were found to correlate strongly with the EUDs for the large-field delivery: a linear correlation coefficient of R2 = 0.98 was obtained and the average EUD for the actual Cyberknife delivery was somewhat higher (5.0 ± 4.7%) than that for the large-field delivery. However, no statistical significance was detected between the two types of delivery (p = 0.21). We concluded that non-isocentric small-field Cyberknife delivery produced consistent biological dosing that tracked well with the constant-dose-rate, large-field-type delivery for prostate stereotactic body radiotherapy.

A Comparison of Treatment Plans using Linac-Based Intensity-Modulated Radiation Therapy and Helical Tomotherapy for Maxillary Sinus Carcinoma

This study evaluated whether helical tomotherapy (TOMO) planning could achieve better isodose distribution for the maxillary sinus while concomitantly sparing the adjacent _critical normal organs than linac-based step-and-shoot IMRT (s-IMRT) planning. TOMO and s-IMRT were established for 10 patients with maxillary sinus cancer. The prescription (66 Gy, 30 fractions) was used to cover the planning target volume (PTV) with a 95% isodose line. Each plan was independently optimized using the CORVUS planning system and Tomotherapy Hi-Art system. The treatment plans were compared using dose volume histogram (DVH), a dose homogeneity index (DHI) of the PTV, and equivalent uniform dose (EUD) and DVH of organs at risk (OARs). The TOMO plans demonstrated better dose homogeneity compared to the s-IMRT plans. The average V95% of the TOMO plans was similar to that of the s-IMRT (92.92% vs. 95.07%, respectively), but the average V107% was 0% for TOMO compared with 18.74% for s-IMRT. The average maximum dose reduction was 7 Gy, and DHI increased by 8% for PTV1 in TOMO compared with s-IMRT (79 Gy vs. 71 Gy and, 89% vs. 97%, respectively). The average EUD reduction for the optic nerve was 17%. In summary, planning with TOMO was superior to s-IMRT planning with respect to dose homogeneity within the PTV and sparing of the optic nerve.

Dosimetric Parameters in Partial Breast Irradiation Through Brachytherapy

The objective of this work is to evaluate biological models and dose homogeneity in a new partial breast irradiation method, the MammoSite RTS. The study is based on 11 patients who received the therapy. For each patient, we determined the dose volume distribution delivered to the breast. Based on these data, we estimate some important biological parameters. Eleven patients with early-stage, invasive, ductal breast cancer were treated using MammoSite RTS brachytherapy, which delivers radiation through a balloon placed in the lumpectomy bed. The radiation was provided by an Iridium-192 source, and 340 cGy were delivered per fraction twice daily. We calculated some commonly used dosimetric parameters, and evaluated the biological parameters tumor control probability (TCP) and normal tissue complication probability (NTCP). We also looked for correlations among these parameters. The average equivalent uniform dose (EUD), NTCP, and TCP were 43.66 Gy, 47.95%, and 91.78%, respectively. The coefficient of variation (CV) among the patients was very low for all 3 parameters. Two dose homogeneity indices (DHI and the S-index) are strongly correlated ( r = −0.815). The area under the dose-volume histogram (DVH) and the treatment volume (TXV) also showed a strong correlation ( r = 0.995, p < 0.0001). A simplified logit Poisson–EUD model is suitable for determining NTCP and TCP. Other factors such as the area under the DVH and dose homogeneity indices are also useful in planning radiotherapy treatments for early breast cancer.

Evaluation of linear accelerator performance standards using an outcome oriented approach

Radiation therapy, along with other branches of medicine, is moving towards a firmer basis in evidence to optimally utilize resources. As new treatment technology and strategies place greater demands on quality assurance resources, the need to objectively evaluate equipment and process performance standards from the perspective of predicted clinical impact becomes more urgent. This study evaluates the appropriateness of recommended quality control tolerance and action levels for linear accelerators based on the calculated dosimetric impact of suboptimal equipment performance. A method is described to quantify the dosimetric changes, as reflected by the changes in the outcome surrogate, equivalent uniform dose (EUD), of machine performance deviations from the optimal, specifically in the range of tolerance and action levels promulgated by the Canadian Association of Provincial Cancer Agencies (CAPCA). Linear accelerator performance deviations were simulated for the treatment of prostate, breast, lung, and brain using 3D conformal techniques, and the impact evaluated in terms of the changes in the EUD of the target volumes and two principal organs at risk (OARs) per site. The eight key performance characteristics examined are: Output constancy, beam flatness, gantry angle, collimator angle, field size indicator, laser alignment (three directions) and, by inference, the optical distance indicator. Currently accepted CAPCA tolerance levels for these eight performance characteristics are shown to maintain average EUD deviations to within 2% for the targets and 2 Gy for the OARs. However, within the 2% or 2 Gy range, the recommended tolerance levels are found to have markedly different effects on the EUDs of the structures of interest.

The Influence of Changes in Tumor Hypoxia on Dose-Painting Treatment Plans Based on 18F-FMISO Positron Emission Tomography

To evaluate how changes in tumor hypoxia, according to serial fluorine-18-labeled fluoro-misonidazole (18F-FMISO) positron emission tomography (PET) imaging, affect the efficacy of intensity-modulated radiotherapy (IMRT) dose painting. Seven patients with head and neck cancers were imaged twice with FMISO PET, separated by 3 days, before radiotherapy. Intensity-modulated radiotherapy plans were designed, on the basis of the first FMISO scan, to deliver a boost dose of 14 Gy to the hypoxic volume, in addition to the 70-Gy prescription dose. The same plans were then applied to hypoxic volumes from the second FMISO scan, and the efficacy of dose painting evaluated by assessing coverage of the hypoxic volumes using Dmax, Dmin, Dmean, D95, and equivalent uniform dose (EUD). Similar hypoxic volumes were observed in the serial scans for 3 patients but dissimilar ones for the other 4. There was reduced coverage of hypoxic volumes of the second FMISO scan relative to that of the first scan (e.g., the average EUD decreased from 87 Gy to 80 Gy). The decrease was dependent on the similarity of the hypoxic volumes of the two scans (e.g., the average EUD decrease was approximately 4 Gy for patients with similar hypoxic volumes and approximately 12 Gy for patients with dissimilar ones). The changes in spatial distribution of tumor hypoxia, as detected in serial FMISO PET imaging, compromised the coverage of hypoxic tumor volumes achievable by dose-painting IMRT. However, dose painting always increased the EUD of the hypoxic volumes.

Comparison of three accelerated partial breast irradiation techniques: Treatment effectiveness based upon biological models

Background and purpose Accelerated partial breast irradiation (APBI) is being studied in a phase III randomized trial as an alternative to whole breast irradiation (WBI) for early stage breast cancer patients. There are three methods for APBI: multi-catheter brachytherapy (MCT), MammoSite ® brachytherapy (MST), or 3D conformal (3DCRT). There is a paucity of data comparing among methods. Using a linear–quadratic (LQ) model, we evaluated the anticipated efficacy among the APBI methods for equivalent uniform dose (EUD), Tumor Control Probability (TCP), and Normal Tissue Complication Probability (NTCP). Materials and methods Treatment plans from five patients treated by each APBI modality were retrospectively selected. Dose-volume-histograms (DVH) for planning target volume (PTV), breast, and lung were generated. The LQ parameters α = 0.3 Gy −1 and α/ β = 10 Gy were used for calculations. The values of EUD, TCP, and NTCP were calculated based on DVHs. Results The average EUD (normalized to 3.4 Gy BID) for the MCT, MST, and 3DCRT APBI was 35, 37.2, and 37.6 Gy. When normalized to 2 Gy fractionation these become, 42.2, 46.4, and 46.9 Gy. Average TCP for MCT, MST, and 3DCRT PBI was 94.8%, 99.1%, and 99.2%. The NTCP values for breast and lung were low for all three methods. Conclusions The EUD for PTV and TCP were most similar in MST and 3DCRT APBI and were lower in MCT APBI. This questions the equivalence of the three APBI modalities that are currently being evaluated in the NSABP-B39/RTOG 0413 protocol.

Intensity-modulated radiation therapy (IMRT) dosimetry of the head and neck: A comparison of treatment plans using linear accelerator–based IMRT and helical tomotherapy

To date, most intensity-modulated radiation therapy (IMRT) delivery has occurred using linear accelerators (linacs), although helical tomotherapy has become commercially available. To quantify the dosimetric difference, we compared linac-based and helical tomotherapy-based treatment plans for IMRT of the oropharynx. We compared the dosimetry findings of 10 patients who had oropharyngeal carcinoma. Five patients each had cancers in the base of the tongue and tonsil. Each plan was independently optimized using either the CORVUS planning system (Nomos Corporation, Sewickly, PA), commissioned for a Varian 2300 CD linear accelerator (Varian Medical Systems, Palo Alto, CA) with 1-cm multileaf collimator leaves, or helical tomotherapy. The resulting treatment plans were evaluated by comparing the dose-volume histograms, equivalent uniform dose (EUD), dose uniformity, and normal tissue complication probabilities. Helical tomotherapy plans showed improvement of critical structure avoidance and target dose uniformity for all patients. The average equivalent uniform dose reduction for organs at risk (OARs) surrounding the base of tongue and the tonsil were 17.4% and 27.14% respectively. An 80% reduction in normal tissue complication probabilities for the parotid glands was observed in the tomotherapy plans relative to the linac-based plans. The standard deviation of the planning target volume dose was reduced by 71%. In our clinic, we use the combined dose-volume histograms for each class of plans as a reference goal for helical tomotherapy treatment planning optimization. Helical tomotherapy provides improved dose homogeneity and normal structure dose compared with linac-based IMRT in the treatment of oropharyngeal carcinoma resulting in a reduced risk for complications from focal hotspots within the planning target volume and for the adjacent parotid glands.

Multiple fields may offer better esophagus sparing without increased probability of lung toxicity in optimized IMRT of lung tumors

To evaluate whether increasing numbers of intensity-modulated radiation therapy (IMRT) fields enhance lung-tumor dose without additional predicted toxicity for difficult planning geometries. Data from 8 previous three dimensional conformal radiation therapy (3D-CRT) patients with tumors located in various regions of each lung, but with planning target volumes (PTVs) overlapping part of the esophagus, were used as input. Four optimized-beamlet IMRT plans (1 plan that used the 3D-CRT beam arrangement and 3 plans with 3, 5, or 7 axial, but predominantly one-sided, fields) were compared. For IMRT, the equivalent uniform dose (EUD) in the whole PTV was optimized simultaneously with that in a reduced PTV exclusive of the esophagus. Normal-tissue complication probability-based costlets were used for the esophagus, heart, and lung. Overall, IMRT plans (optimized by use of EUD to judiciously allow relaxed PTV dose homogeneity) result in better minimum PTV isodose surface coverage and better average EUD values than does conformal planning; dose generally increases with the number of fields. Even 7-field plans do not significantly alter normal-lung mean-dose values or lung volumes that receive more than 13, 20, or 30 Gy. Optimized many-field IMRT plans can lead to escalated lung-tumor dose in the special case of esophagus overlapping PTV, without unacceptable alteration in the dose distribution to normal lung.

Online image-guided intensity-modulated radiotherapy for prostate cancer: How much improvement can we expect? A theoretical assessment of clinical benefits and potential dose escalation by improving precision and accuracy of radiation delivery

To quantify the theoretical benefit, in terms of improvement in precision and accuracy of treatment delivery and in dose increase, of using online image-guided intensity-modulated radiotherapy (IG-IMRT) performed with onboard cone-beam computed tomography (CT), in an ideal setting of no intrafraction motion/deformation, in the treatment of prostate cancer. Twenty-two prostate cancer patients treated with conventional radiotherapy underwent multiple serial CT scans (median 18 scans per patient) during their treatment. We assumed that these data sets were equivalent to image sets obtainable by an onboard cone-beam CT. Each patient treatment was simulated with conventional IMRT and online IG-IMRT separately. The conventional IMRT plan was generated on the basis of pretreatment CT, with a clinical target volume to planning target volume (CTV-to-PTV) margin of 1 cm, and the online IG-IMRT plan was created before each treatment fraction on the basis of the CT scan of the day, without CTV-to-PTV margin. The inverse planning process was similar for both conventional IMRT and online IG-IMRT. Treatment dose for each organ of interest was quantified, including patient daily setup error and internal organ motion/deformation. We used generalized equivalent uniform dose (EUD) to compare the two approaches. The generalized EUD (percentage) of each organ of interest was scaled relative to the prescription dose at treatment isocenter for evaluation and comparison. On the basis of bladder wall and rectal wall EUD, a dose-escalation coefficient was calculated, representing the potential increment of the treatment dose achievable with online IG-IMRT as compared with conventional IMRT. With respect to radiosensitive tumor, the average EUD for the target (prostate plus seminal vesicles) was 96.8% for conventional IMRT and 98.9% for online IG-IMRT, with standard deviations (SDs) of 5.6% and 0.7%, respectively (p < 0.0001). The average EUDs of bladder wall and rectal wall for conventional IMRT vs. online IG-IMRT were 70.1% vs. 47.3%, and 79.4% vs. 72.2%, respectively. On average, a target dose increase of 13% (SD = 9.7%) can be achieved with online IG-IMRT based on rectal wall EUDs and 53.3% (SD = 15.3%) based on bladder wall EUDs. However, the variation (SD = 9.7%) is fairly large among patients; 27% of patients had only minimal benefit (<5% of dose increment) from online IG-IMRT, and 32% had significant benefit (>15%-41% of dose increment). The ideal maximum dose increment achievable with online IG-IMRT is, on average, 13% with respect to the dose-limiting organ of rectum. However, there is a large interpatient variation, ranging <5%-41%. The results can be applied to calibrate other practical online image-guided techniques for prostate cancer radiotherapy, when intratreatment organ motion/deformation and machine delivery accuracy are considered.

Equivalent uniform dose predicts delayed hyperintensity on T1-weighted magnetic resonance imaging after combined proton and photon irradiation in paranasal sinus cancer

To determine the prognostic factors of delayed hyperintensity on T1-weighted Magnetic Resonance Imaging (MRI) after accelerated hyperfractionated radiotherapy with combined protons and photons in patients with locally advanced paranasal sinus cancer. Between July 1991 and December 2001, 105 patients with newly diagnosed non-metastatic paranasal sinus cancer received accelerated hyperfractionated radiotherapy using combined protons and photons. Fifty-three patients with minimum follow-up of 18 months and with local control were used for the study. There were 31 males and 22 female, with a median age of 49 years. All but two patients had locally advanced diseases; T3 in 13 and T4 in 37. Twelve patients had meningeal or brain extension. The primary site was maxillary and/or ethmoid sinus in 22, nasal cavity extended to the ethmoid in 19, sphenoid sinus in 9, and others in 3 patients. The median primary target volume was 79 cc (range 4.7-216). There were 13 squamous cell carcinoma, 19 carcinoma with neuroendocrine differentiation, 11 adenoid cystic carcinoma, 5 sarcoma, and 5 with other histologic types. Seventy-six percent of patients underwent surgical resection before radiation. Most patients with carcinoma with neuroendocrine differentiation received neoadjuvant cisplatin and etoposide chemotherapy. The median dose delivered to the primary target volume was 69.8 Cobalt-Gray-Equivalent (CGE) (range 60-80). Three accelerated hyperfractionated (BID) protocols were used: 1.6CGE BID in 29; 15–20 CGE with conventional daily fractionation (QD) then 1.8/1.4 CGE BID in 8; and 15-20 Gy QD then 1.8+1.5 CGE BID in 16 patients. Delayed brain changes were assessed clinically and radiographically with MRI. Two four- grade scales were developed to characterize MRI changes according to the extent and characteristics of Hyperintensity on T1-weighted and T2-weighted images. Dose Volume Histograms (DVHs) were generated for the frontal and temporal lobes. Equivalent Uniform Dose (EUD) value was calculated for each individual lobe. With a median clinical follow-up of 65 months (range 18-138), 8 patients developed seizures: uncal epilepsy in 4, petit mal in 2, and grand mal in 2 patients. Seven patients developed short-term memory difficulties. Two patients experienced personality changes. With a median 36 months follow-up after the development of first clinical symptoms, seizures were persistent in 4 patients but completely controlled in 4 others. Two patients experienced worsening of their short-term memory deficits. Fifty patients were available for delayed radiographic analysis. With a median radiographic follow-up of 54 months (range 10-132), 26 patients developed gadolinium-enhancement on T1-weighted images of the brain. Fifty-six percent of patients who developed contrast enhancement had a complete or partial clinical and radiographic response with steroids. EUD was calculated for 200 brain lobes, 62 of them with gadolinium-enhancement on T1-weighted images. The average EUD was 51.2 ± 5.0Gy versus 39.6 ± 10.0Gy for the lobes with and without any MRI change (p < 0.0001), respectively. On univariate analysis, primary target dose (p = 0.01), maximal dose (p < 0.0001), and EUD (p < 0.0001) (figure below) were predictive for contrast enhancement changes. Gender, surgery prior to irradiation, use of chemotherapy, age, hypertension, diabetes, anemia, and smoking were not predictive. On multivariate analysis, EUD was the most significant predictive of delayed contrast enhancement changes. EUD predicts delayed gadolinium-enhancement on T1-weighted magnetic resonance imaging after accelerated hyperfractionated radiotherapy with combined proton and photon irradiation in paranasal sinus cancer.

311 Temozolomide (TMZ) combined with radiotherapy (RT) versus radiotherapy (RT) alone in newly diagnosed glioblastoma multiforme (GBM): A randomized phase III study

Purpose: To date, most intensity-modulated radiation therapy (IMRT) delivery has occurred using linear accelerators (linacs), although helical tomotherapy has become commercially available. To quantify the dosimetric difference, we compared linac-based and helical tomotherapy–based treatment plans for IMRT of the oropharynx.Methods and Materials: We compared the dosimetry findings of 10 patients who had oropharyngeal carcinoma. Five patients each had cancers in the base of the tongue and tonsil. Each plan was independently optimized using either the CORVUS planning system (Nomos Corporation, Sewickly, PA), commissioned for a Varian 2300 CD linear accelerator (Varian Medical Systems, Palo Alto, CA) with 1-cm multileaf collimator leaves, or helical tomotherapy. The resulting treatment plans were evaluated by comparing the dose–volume histograms, equivalent uniform dose (EUD), dose uniformity, and normal tissue complication probabilities.Results: Helical tomotherapy plans showed improvement of critical structure avoidance and target dose uniformity for all patients. The average equivalent uniform dose reduction for organs at risk (OARs) surrounding the base of tongue and the tonsil were 17.4% and 27.14% respectively. An 80% reduction in normal tissue complication probabilities for the parotid glands was observed in the tomotherapy plans relative to the linac-based plans. The standard deviation of the planning target volume dose was reduced by 71%. In our clinic, we use the combined dose–volume histograms for each class of plans as a reference goal for helical tomotherapy treatment planning optimization.Conclusions: Helical tomotherapy provides improved dose homogeneity and normal structure dose compared with linac-based IMRT in the treatment of oropharyngeal carcinoma resulting in a reduced risk for complications from focal hotspots within the planning target volume and for the adjacent parotid glands.

Optimization of planar high-dose-rate implants

Purpose: Brachytherapy has long been used to deliver localized radiation to the breast and other cancer sites. For interstitial implants, proper source positioning is critical in obtaining satisfactory dose distributions. The present work examines techniques for optimizing source guide placement in high-dose-rate (HDR) biplanar implants, and examines the effects of suboptimal catheter placement. Methods and Materials: Control of individual dwell times in HDR implants allows a high degree of dose uniformity in planes parallel to the implant planes. Biplanar HDR implants can be considered optimized when the dose at the implant center is equal to the dose at the symmetric target boundaries. It is shown that this optimal dose uniformity is achieved when the interplanar separation is related to the target thickness T through the direct proportionality, s = T/√2. To quantify the significance of source positioning, the average dose and a related quantity, equivalent uniform dose (EUD), were calculated inside the treatment volume for two conditions of suboptimal catheter geometry. In one case, the interplanar spacing was varied from 1 cm up to the target thickness T, while a second study examined the effects of off-center placement of the implant planes. Results: Both the average dose and EUD were minimized when the interplanar spacing satisfied the relationship s = T/ √2. EUD, however, was significantly smaller than the average dose, indicating a reduced relative cell killing in the high dose regions near the dwell points. It was also noted that in contrast to the average dose, the EUD is a relatively weak function of catheter misplacement, suggesting that the biological consequences of suboptimal implant geometry may be less significant than is indicated by the increase in average dose. Conclusion: A concise formula can be used to determine the interplanar separation needed for optimal dose uniformity in Manchester-type implants. Deviations from optimal source geometry result in an increase in the average dose inside the treatment volume, but the weaker dependence of the EUD suggests that the surviving fraction of cells may not be not strongly affected by suboptimal source geometry.