Normal Tissue Dose Constraints Research Articles

The potential of shape-based treatment plan optimization for pancreatic IMRT treatments to spare organs at risk and allow for dose escalation to the tumor PTV.

316 Background: Due to the low dose tolerance of the organs at risk (OARs) in the abdomen the tumor dose for pancreatic cancer patient is restricted to 50-60 Gy in 1.8-2.0 Gy fractions when combined with chemotherapy. The goal of this study was to develop a system that can determine the minimal radiation dose to the OARs of each individual patient that is achievable while maintaining adequate tumor coverage. This could guide treatment planners to spare the OARs to the fullest extent. When the minimal doses to the OAR are achieved, the total plan can be upscaled until the normal tissue dose constraints are met, allowing for an increase in tumor dose without increased normal tissue toxicity. Methods: The minimal achievable dose to the OARs depends on its proximity to the planning target volume (PTV). The overlap volume histogram (OVH) was used to describe the spatial relation of each OAR to the PTV. A database of 33 patients, treated with IMRT, was queried to find the lowest achieved dose to an organ for any of the prior patients with less favorable PTV-OAR configurations than the current patient. This minimal dose must also be achievable for the OAR of the new patient. For 25 randomly chosen patients the lowest achievable dose to the liver and kidneys was predicted this way. Then the patients were replanned to verify if this dose could be achieved. The new plans were compared to the original clinical plans. Results: After replanning the predicted achievable dose to the liver was realized within 1 and 2 Gy for more than 86% and 96% of the patients respectively. For the kidneys these numbers were 83% and 96%. The average improvement in terms of mean dose was 1.4 Gy (range 0 – 4.6 Gy) for the liver and 1.7 Gy (range 0 – 6.3 Gy) for the kidneys. This would have allowed an increase in PTV dose of on average 5 Gy (range 0-13 Gy) based on the liver and 8.5 Gy (range 0-38 Gy) based on the kidneys compared to the original plan, without an increase in dose to the bowel, cord, and stomach. Conclusions: The lowest achievable dose to the OARs could accurately be predicted for pancreatic cancer patients within seconds. This can guide dosimetrists to spare the OARs or increase the PTV dose by 5 Gy without increased toxicity. [Table: see text]

Comparison of three-dimensional conformal irradiation techniques for prostate cancer using a low-energy (6 MV) photon beam

AbstractPurpose: To evaluate composite coplanar and non-coplanar three-dimensional conformal techniques (3D-CRT) for external-beam prostate radiotherapy using a low-energy (6 MV) photon beam.Methods and Materials: For treatment-planning purposes, three different planning target volumes (PTV) were defined for ten patients with prostate cancer and as follows: PTV1 (pelvis), PTV2 (prostate + seminal vesicles + 1 cm margin) and PTV3 (prostate + 1 cm margin). Conformal techniques of 2, 3, 4, 5 (coplanar) and 6 (non-coplanar) field techniques have been considered and combined to produce five different plan combinations (i.e. techniques A, B, C, D and E). Treatment plans were generated with a prescription dose of 75 Gy to PTV3, 65 Gy to PTV2 and 45 Gy to PTV1 and were assessed on the basis of 3D dose distributions and dose-volume histograms (DVHs). Normal tissue-dose constraints for the relevant organs at risk (OARs), that is, rectum, bladder and femoral heads, were also considered.Results: Findings show that all five treatment-plan combinations result in adequate PTV coverage and acceptable OAR irradiated volumes. The greatest rectal spacing in the high-dose region is achieved by technique C; all techniques achieve this, except for technique A, and give approximately the same fraction of volume (of rectum) that receives a dose of 50 Gy (V50) and 60 Gy (V60). When considering the bladder, techniques B, D and E give the best bladder sparing with small absolute differences, whereas technique A results in the lowest dose for femoral heads. Technique E appears to give the best compromise for all three considered OARs, provided the PTV is adequately covered.Conclusions: Even though the optimum photon-beam energy for conformal prostate radiotherapy is greater than 10 MV, our study shows that a good sparing of OAR can be achieved even with a lower-energy beam (6 MV) and the appropriate plan combination and that the dose to prostate can be as high as 75 Gy.

TU-D-202-03: Clinical and Radiobiological Considerations

This section of the session will be an overview of the historical development of SBRT in terms of clinical implementation from the earliest efforts up to the present day as well as a presentation of selected aspects of the applied radiobiology of SBRT that appear to have clinical relevance. Learning Objectives: 1. Review key milestones in the evolution of SBRT from earliest clinical implementation to present day application. 2. Discuss viewpoints on available means of modeling tumor and normal tissue responses to SBRT-style radiation therapy regimens. 3. Present sources available to guide the clinical implementation of SBRT in terms of reasonable normal tissue dose constraints for different sites within the body.

Stereotactic Body Radiotherapy for Primary Management of Early-Stage, Low- to Intermediate-Risk Prostate Cancer: Report of the American Society for Therapeutic Radiology and Oncology Emerging Technology Committee

Stereotactic Body Radiotherapy for Primary Management of Early-Stage, Low- to Intermediate-Risk Prostate Cancer: Report of the American Society for Therapeutic Radiology and Oncology Emerging Technology Committee

Mature Results of an Individualized Radiation Dose Prescription Study Based on Normal Tissue Constraints in Stages I to III Non–Small-Cell Lung Cancer

We previously showed that individualized radiation dose escalation based on normal tissue constraints would allow safe administration of high radiation doses with low complication rate. Here, we report the mature results of a prospective, single-arm study that used this individualized tolerable dose approach. In total, 166 patients with stage III or medically inoperable stage I to II non-small-cell lung cancer, WHO performance status 0 to 2, a forced expiratory volume at 1 second and diffusing capacity of lungs for carbon monoxide >or= 30% were included. Patients were irradiated using an individualized prescribed total tumor dose (TTD) based on normal tissue dose constraints (mean lung dose, 19 Gy; maximal spinal cord dose, 54 Gy) up to a maximal TTD of 79.2 Gy in 1.8 Gy fractions twice daily. Only sequential chemoradiation was administered. The primary end point was overall survival (OS), and the secondary end point was toxicity according to Common Terminology Criteria of Adverse Events (CTCAE) v3.0. The median prescribed TTD was 64.8 Gy (standard deviation, +/- 11.4 Gy) delivered in 25 +/- 5.8 days. With a median follow-up of 31.6 months, the median OS was 21.0 months with a 1-year OS of 68.7% and a 2-year OS of 45.0%. Multivariable analysis showed that only a large gross tumor volume significantly decreased OS (P < .001). Both acute (grade 3, 21.1%; grade 4, 2.4%) and late toxicity (grade 3, 4.2%; grade 4, 1.8%) were acceptable. Individualized prescribed radical radiotherapy based on normal tissue constraints with sequential chemoradiation shows survival rates that come close to results of concurrent chemoradiation schedules, with acceptable acute and late toxicity. A prospective randomized study is warranted to further investigate its efficacy.

Decreasing Temporal Lobe Dose With Five-Field Intensity-Modulated Radiotherapy for Treatment of Pituitary Macroadenomas

To compare temporal lobe dose delivered by three pituitary macroadenoma irradiation techniques: three-field three-dimensional conformal radiotherapy (3D-CRT), three-field intensity-modulated radiotherapy (3F IMRT), and a proposed novel alternative of five-field IMRT (5F IMRT). Computed tomography-based external beam radiotherapy planning was performed for 15 pituitary macroadenoma patients treated at New York University between 2002 and 2007 using: 3D-CRT (two lateral, one midline superior anterior oblique [SAO] beams), 3F IMRT (same beam angles), and 5F IMRT (same beam angles with additional right SAO and left SAO beams). Prescription dose was 45 Gy. Target volumes were: gross tumor volume (GTV) = macroadenoma, clinical target volume (CTV) = GTV, and planning target volume = CTV + 0.5 cm. Structure contouring was performed by two radiation oncologists guided by an expert neuroradiologist. Five-field IMRT yielded significantly decreased temporal lobe dose delivery compared with 3D-CRT and 3F IMRT. Temporal lobe sparing with 5F IMRT was most pronounced at intermediate doses: mean V25Gy (% of total temporal lobe volume receiving ≥25 Gy) of 13% vs. 28% vs. 29% for right temporal lobe and 14% vs. 29% vs. 30% for left temporal lobe for 5F IMRT, 3D-CRT, and 3F IMRT, respectively (p < 10(-7) for 5F IMRT vs. 3D-CRT and 5F IMRT vs. 3F IMRT). Five-field IMRT plans did not compromise target coverage, exceed normal tissue dose constraints, or increase estimated brain integral dose. Five-field IMRT irradiation technique results in a statistically significant decrease in the dose to the temporal lobes and may thus help prevent neurocognitive sequelae in irradiated pituitary macroadenoma patients.

WE‐D‐213A‐02: Establishing a Stereotactic Body Radiation Therapy (SBRT) Clinical Program, Part 2: Clinical and Radiobiological Considerations

Stereotactic Body Radiation Therapy (SBRT) has emerged as an important form of cancer therapy with broad application across a spectrum of tumor types in the primary and metastatic settings. The capability of safely administering a very high dose of therapeutic radiation to discrete extracranial tumor sites has raised new questions about the radiobiology of high dose per fraction treatment. Accumulating clinical experiences are yielding new insights into practical aspects of tumor and normal tissue responses to high dose per fraction treatment.The current practice of SBRT has evolved to some extent from knowledge gained from principles learned from the practice of cranial stereotactic radiosurgery (SRS). For the integration of SBRT into clinical practice, medical physicists and radiation oncologists are advised to collaborate closely to establish clear guidelines for normal tissue dose constraints and tumor dose prescription practices that are suitable to their own clinical environment. Published literature relevant to this objective will be discussed. A consistent strategy for contouring sensitive organs is encouraged. The technological challenges introduced by the high dose and high precision paradigm of SBRT are presented and the vital relationship between physicist and physician in this context cannot be overemphasized.The radiobiological issues that have been parsed by this new paradigm of treatment will be explored, including understanding of conventional, hypofractionated and single dose treatments, radiobiological modeling, and the concepts of equivalent doses. Future trends in SBRT will be discussed. Clinical outcomes after SBRT in a variety of setting will be summarized.Learning Objectives:1. Review and understand the major issues related to the use SBRT for, including key strategies for uniform contouring and determination of organ tolerances.2. Review and understand the common clinically observed normal tissue responses to SBRT and the inferences to be drawn regarding the practical radiobiology of high dose per fraction therapy3. Discuss these new paradigms of fractionation as they relate to conventional regimes, including hypofractionation and single dose treatments and their radiobiological threshold effects.4. Review potential future application of SBRT

Obtaining Normal Tissue Constraints Using Intensity Modulated Radiotherapy (IMRT) in Patients with Oral Cavity, Oropharnygeal, and Laryngeal Carcinoma

The purpose of this study was to evaluate normal tissue dose constraints while maintaining planning target volume (PTV) prescription without reducing PTV margins. Sixteen patients with oral cavity carcinoma (group I), 27 patients with oropharyngeal carcinoma (group II), and 28 patients with laryngeal carcinoma (group III) were reviewed. Parotid constraints were a mean dose to either parotid < 26 Gy (PP1), 50% of either parotid < 30 Gy (PP2), or 20 cc of total parotid < 20 Gy (PP3). Treatment was intensity modulated radiation therapy (IMRT) with simultaneous integrated boost (SIB). All patients met constraints for cord and brain stem. The mandibular constraints were met in 66%, 29%, and 57% of patients with oral, oropharyngeal, and laryngeal cancers, respectively. Mean dose of 26 Gy (PP1) was achieved in 44%, 41%, and 38% of oral, oropharyngeal, and laryngeal patients. PP2 (parotid constraint of 30 Gy to less than 50% of one parotid) was the easiest to achieve (group I, II, and III: 82%, 76%, and 78%, respectively). PP3 (20 cc of total parotid < 20 Gy) was difficult, and was achieved in 25%, 17%, and 35% of oral, oropharyngeal, and laryngeal patients, respectively. Mean parotid dose of 26 Gy was met 40% of the time. However, a combination of constraints allowed for sparing of the parotid based on different criteria and was met in high numbers. This was accomplished without reducing PTV-parotid overlap. What dose constraint best correlates with subjective and objective functional outcomes remains a focus for future study.

Isodose-based methodology for minimizing the morbidity and mortality of thoracic hypofractionated radiotherapy

Background and purpose Help identify and define potential normal tissue dose constraints to minimize the mortality and morbidity of hypofractionated lung radiotherapy. Materials and methods A method to generate isodose-based constraints and visually evaluate treatment plans, based on the published peer reviewed literature and the linear quadratic model, is presented. The radiobiological analysis assumes that the linear quadratic model is valid up to 28 Gy per fraction, the α/β ratio is 2 for the spinal cord and brachial plexus, 4 for pneumonitis, 4 or 10 for acute skin reactions depending on treatment length, and 3 for late complications in other normal tissues. A review of the literature was necessary to identify possible endpoints and normal tissue constraints for thoracic hypofractionated lung radiotherapy. Results Preliminary normal tissue constraints to reduce mortality and morbidity were defined for organs at risk based upon hypofractionated lung radiotherapy publications. A modified dose nomenclature was introduced to facilitate the comparison of hypofractionated doses. Potential side effects from hypofractionated lung radiotherapy such as aortic dissection, neuropathy, and fatal organ perforation rarely seen in conventional treatments were identified. The isodose-based method for treatment plan analysis and normal tissue dose constraint simplification was illustrated. Conclusions The radiobiological analysis based on the LQ method, biologically equivalent dose nomenclature, and isodose-based method proposed in this study simplifies normal tissue dose constraints and treatment plan evaluation. This may also be applied to extrathoracic hypofractionated radiotherapy. Prospective validation of these preliminary thoracic normal tissue dose constraints for hypofractionated lung radiotherapy is necessary.

Accrediting radiation technique in a multicentre trial of chemoradiation for pancreatic cancer

Before a multicentre trial of 3-D conformal radiotherapy to treat cancer of the pancreas, participating clinicians were asked to complete an accreditation exercise. This involved planning two test cases according to the study protocol, then returning hard copies of the plans and dosimetric data for review. Any radiation technique that achieved the specified constraints was allowed. Eighteen treatment plans were assessed. Seven plans were prescribed incorrect doses and two of the planning target volumes did not comply with protocol guidelines. All plans met predefined normal tissue dose constraints. The identified errors were attributable to unforeseen ambiguities in protocol documentation. They were addressed by feedback and corresponding amendments to protocol documentation. Summary radiobiological measures including total weighted normal tissue equivalent uniform dose varied significantly between centres. This accreditation exercise successfully identified significant potential sources of protocol violations, which were then easily corrected. We believe that this process should be applied to all clinical trials involving radiotherapy. Due to the limitations of data analysis with hard-copy information only, it is recommended that complete planning datasets from treatment-planning systems be collected through a digital submission process.

Dosimetry and Acute Toxicity in IG-IMRT using a Consensus Prostate Bed CTV Following Prostatectomy

Recently published institutional guidelines for anatomic boundaries of the prostate bed clinical target volume (CTV) have raised concerns regarding the feasibility of high-dose delivery to the planning target volume (PTV) while respecting rectal and bladder dose-volume constraints. This study describes the prospective use of daily image guided intensity modulated radiation therapy (IG-IMRT), and reports the preliminary measures of acute toxicity in this group of patients. Between August 2007 and March 2008, 25 patients were enrolled on a prospective research ethics board approved clinical trial. All were CT-simulated with a full bladder and empty rectum, immobilized in a customized vacuum device. Seven field step-and-shoot IMRT plans were generated, prescribing 6600cGy in 33 fractions to the ICRU reference point. Dose planning objectives were as follows, in the order of priority: PTV D99 ≥ 5400cGy, posterior half of rectal wall (PostRW) 1cm3 ≤ 5500cGy, rectal wall 1cm3 ≤ 6600cGy, bladder wall 2 cm3 ≤ 6730cGy, penile bulb 0.5 cm3 ≤ 6600cGy, femur 1 cm3 ≤ 5500cGy and PTV V95 ≥ 95%. Dosimetry endpoints were measured using dose-volume histograms. Patient-reported acute radiation-induced toxicity was assessed weekly during treatment, and graded using the CTCAE v3.0 toxicity scale. PTV D99 ≥ 5400cGy was achievable in all cases with a mean dose of 5827cGy. PTV coverage was compromised to achieve the PostRW constraint, resulting an average V95 of 95.3% (range, 92 - 99% and SD = 2.0). Among the 25 patients, 60% had PTV V95 ≥ 95%. Dose constraints for other normal tissue were met. Grade 2 GU and GI toxicities were experienced by 8% and 32% of patients, respectively. One patient reported grade 3 GU toxicity due to voiding more frequently than once per hour, which resolved during the course of treatment. For patients who reported experiencing GI 2 toxicity, 4 of them required the use of medication for symptom management. The use of IG-IMRT technique is feasible in delivering high-dose to the PTV with minimal compromise to coverage while respecting normal tissue dose constraints. Preliminary acute toxicity data is considered acceptable. Ongoing investigation will continue to evaluate biochemical control and late toxicity.

Individualized Radical Radiotherapy of Non–Small-Cell Lung Cancer Based on Normal Tissue Dose Constraints: A Feasibility Study

Local recurrence is a major problem after (chemo-)radiation for non-small-cell lung cancer. We hypothesized that for each individual patient, the highest therapeutic ratio could be achieved by increasing total tumor dose (TTD) to the limits of normal tissues, delivered within 5 weeks. We report first results of a prospective feasibility trial. Twenty-eight patients with medically inoperable or locally advanced non-small-cell lung cancer, World Health Organization performance score of 0-1, and reasonable lung function (forced expiratory volume in 1 second > 50%) were analyzed. All patients underwent irradiation using an individualized prescribed TTD based on normal tissue dose constraints (mean lung dose, 19 Gy; maximal spinal cord dose, 54 Gy) up to a maximal TTD of 79.2 Gy in 1.8-Gy fractions twice daily. No concurrent chemoradiation was administered. Toxicity was scored using the Common Terminology Criteria for Adverse Events criteria. An (18)F-fluoro-2-deoxy-glucose-positron emission tomography-computed tomography scan was performed to evaluate (metabolic) response 3 months after treatment. Mean delivered dose was 63.0 +/- 9.8 Gy. The TTD was most often limited by the mean lung dose (32.1%) or spinal cord (28.6%). Acute toxicity generally was mild; only 1 patient experienced Grade 3 cough and 1 patient experienced Grade 3 dysphagia. One patient (3.6%) died of pneumonitis. For late toxicity, 2 patients (7.7%) had Grade 3 cough or dyspnea; none had severe dysphagia. Complete metabolic response was obtained in 44% (11 of 26 patients). With a median follow-up of 13 months, median overall survival was 19.6 months, with a 1-year survival rate of 57.1%. Individualized maximal tolerable dose irradiation based on normal tissue dose constraints is feasible, and initial results are promising.

Radiation Dose Prescription for Non–Small-Cell Lung Cancer According to Normal Tissue Dose Constraints: An In Silico Clinical Trial

Local tumor recurrence remains a major problem in patients with inoperable non-small-cell lung cancer undergoing radiotherapy. We investigated the theoretical gain in the estimated tumor control probability (TCP) using an individualized maximal tolerable dose (MTD) prescription, for both conventional and accelerated fractionation schemes. For 64 non-small-cell lung cancer patients, five treatment plans were compared, dependent on the normal tissue dose constraints for the lung and spinal cord. The first two used a classic fractionation (2 Gy/d, 5 d/wk) to a total dose of 60 Gy (QD(classic)) or determined by the individualized MTD (QD(MTD)). The third scheme assumed a hypofractionated schedule of 2.75-Gy fractions (QD(hypofr)). The fourth and fifth assumed hyperfractionation and acceleration (1.8 Gy twice daily, either BID(classic) or BID(MTD)). The TCPs for the groups of patients were estimated. The mean biologic equivalent dose in 2-Gy fractions for tumor, corrected for accelerated repopulation was significantly greater for the BID(MTD) scheme (62.1 Gy) than for any other scheme (QD(classic), 47.5 Gy; QD(MTD), 52.0 Gy; QD(hypofr), 56.9 Gy; and BID(classic), 56.9 Gy; p < 0.001). Although both dose-escalation (QD(MTD)) and hypofractionation (QD(hypofr)) resulted in an increase in the mean estimated TCP of 5.6% (p < 0.001) and 14.6% (p < 0.001), respectively, compared with QD(classic), the combination of escalation and acceleration (BID(MTD)) improved the mean estimated TCP by 26.4% (p < 0.001). The results of this planning study showed a large gain in the estimated TCP using an MTD scheme with 1.8-Gy fractions BID compared with other fractionation schedules. Clinical studies implementing this concept are ongoing.

SU-FF-T-398: The Implications of Monitor Unit and SSD Rounding Errors On Delivered Dose

Purpose: To investigate the individual and overall contributions of Monitor Unit and SSD rounding errors on delivered dose for different treatment regions. Method and Materials: Treatment planning computers are configured to calculate treatment monitor units (MUs) to at least one decimal place, but because the ion chambers in many linear accelerators can not measure radiation to this accuracy, treatment plan MUs are often rounded off to the nearest whole number. Further more, treatment planning systems can calculate radiation source-skin distances (SSDs) to millimeter accuracy, while the optical distance indicators (ODIs) on linear accelerators generally require rounding to the nearest half centimeter. Acceptable treatment plans were generated to obtain MUs and SSDs to at least one decimal places. Treatment MUs and SSDs from these plans were then rounded and put back into the plans to obtain the real world deliverable plans. The isodose distributions and Dose-Volume Histograms (DVHs) for individual and total contributions of these two rounding errors were then compared and analyzed for different treatment regions. Results: Our results show distortions of isodose distributions and Dose-Volume Histograms (DVH) as a result of the compounded rounding errors in MU calculations and ODI SSD readings. In particular, we found that normal tissue dose constraints, which appeared to be satisfied in the original computer plan, could be exceeded by up to 6% when rounding errors were taken into account, particularly in sites with relatively short radiation effective path-lengths, like the head and neck. The effects of MU rounding error appear to be greater than those ODI SSD rounding error and less significant for sites with long radiation effective path lengths such as lung tumors. Conclusions: This work indicates the potential overdose or underdose as a result of MU and SSD rounding errors.

Is There a Selection Bias in Radiotherapy Dose-Escalation Protocols?

To investigate the existence of a selection bias using a virtual radiotherapy dose-escalation trial. In dose-escalation trials, normal tissue constraints generally remain constant while the tumor dose is increased. Since tumor dose and normal tissue constraints are competing demands, a point will be reached at which the tumor dose cannot be increased without exceeding normal tissue constraints. In 9 patients with non-small-cell lung cancer, the tumor dose was escalated from 66 Gy to 78 Gy in 4-Gy dose levels using intensity-modulated radiotherapy planning, while the limiting normal tissue dose constraints remained constant. Dosimetric, radiobiologic, and other planning parameters were compared at the 66-Gy dose level for patients eligible for all dose levels and for those eligible only for lower dose levels. Seven of 9 patients were eligible for all dose levels (Group E). Two of 9 patients ("ineligible" or Group I) qualified only for lower total doses (95% confidence interval, 0.075-0.6, significant). In Group E, mean planning target volumes were smaller (132 vs. 404 cm(3), nonsignificant), monitor units per fraction were significantly lower (448 vs. 802, p = 0.0008), and the average composite score for plan quality was better than in Group I (0.012 vs. 0.068, nonsignificant). Average tumor-control probabilities were higher (0.33 vs. 0.23, nonsignificant), and normal tissue-complication probabilities were lower for Group E than for Group I. Patients eligible for higher dose levels had significantly superior estimated outcome parameters. A method to eliminate this source of error in the interpretation of dose-escalation trials is suggested.

Time trends in the maximal uptake of FDG on PET scan during thoracic radiotherapy. A prospective study in locally advanced non-small cell lung cancer (NSCLC) patients

Background and purpose 18F-fluoro-2-deoxy-glucose (FDG) uptake on PET scan is a prognostic factor for outcome in NSCLC. We investigated changes in FDG uptake during fractionated radiotherapy in relation to metabolic response with the ultimate aim to adapt treatment according to early response. Methods and materials Twenty-three patients, medically inoperable or with advanced NSCLC, underwent four repeated PET-CT scans before, during and after radiotherapy. Changes in maximal standardized uptake value (SUV max) were described. Patients were treated with accelerated radiotherapy with a total tumour-dose depending on normal tissue dose constraints. Results The most striking result was the large intra-individual heterogeneity in the evolution of SUV max. For the total group a non-significant increase in the first week ( p = 0.05), and a decrease in the second week ( p = 0.02) and after radiotherapy ( p < 0.01) was observed. Different time trends were shown for responders (no change during radiotherapy) and non-responders (48% increase during first week, p = 0.02 and 15% decrease in the second week, p = 0.04). Non-responders had a higher SUV max on all time points investigated. Conclusions Time trends in SUV max showed a large intra-individual heterogeneity and different patterns for metabolic responders and non-responders. These new findings may reflect intrinsic tumour characteristics and might finally be useful to adapt treatment.

2059: Biologically Targeted Therapy for High Grade Gliomas Using Inverse-Planned Intensity Modulated Radiotherapy and Diffusion Tensor Imaging

To examine the role of Diffusion Tensor Imaging (DTI) in implementing biologically targeted radiotherapy, using IMRT to deliver synchronous dose boosts to the GTV and adjacent areas of abnormality on DTI. In this dosimetry study of seven patients, IMRT based synchronous boost therapy was compared to standard conformal radiotherapy (CRT). CRT plans were prepared using a 2.5cm CTV margin added to the GTV, and a 0.5cm margin for the planning target volume. A dose of 60Gy in 30 fractions was specified to the PTV. For IMRT synchronous boost plans, a class solution was used to determine doses to the GTV, DTI abnormality and PTV, for a fixed 30 fraction schedule. Multiple normal tissue complication probability models were applied to each plan, specifically to assess the effect of biological dose transformation, and exclusion of the GTV from the volume of brain at risk of radionecrosis. Morphology analysis was used to assess the eccentricity of treatment volumes. Small (GTV<20cc, PTV<380cc) and medium sized (GTV<100cc, PTV<750cc) tumours could be boosted to achieve doses of 80Gy and 74Gy to the GTV respectively, without violating specified normal tissue dose constraints. In 6 of 7 cases, the estimated NTCP for the IMRT boost plan was lower than that of the standard CRT plan. Excluding the GTV from the NTCP calculation resulted in a 32% mean reduction in estimated NTCP. Morphology analysis demonstrated that adequate spatial conformation to the treatment volumes could be achieved without the need for specialist hardware such as micro-multileaf collimators. Dose inhomogeneity was observed in the outer concentric boost volumes, but at a level that compares favourably with previously published clinical studies. DTI based planning is a feasible technique for the implementation of IMRT based biologically targeted therapy.

2128: Optimizing the Cardiac and Pulmonary Dose in Treatment Planning for Distal Esophageal Cancer: Does IMRT Always Produce the Best Plan?

For distal esophageal cancer, intensity-modulated radiation therapy (IMRT) offers the potential to decrease radiation dose to the heart and lungs while covering the large target volume. However, even with IMRT, it can be difficult to achieve all tumor dosimetric goals and critical normal tissue dose constraints while maintaining dose homogeneity. A recent study from MD Anderson demonstrated that full course IMRT reduced lung dose over a range of dosimetric parameters, but did not significantly lower cardiac dose.

Promising Early Local Control of Malignant Pleural Mesothelioma Following Postoperative Intensity Modulated Radiotherapy (IMRT) to the Chest

Malignant pleural mesothelioma often recurs locally in spite of aggressive resection by extrapleural pneumonectomy and conventional radiotherapy. This may be due to failure to recognize the extent of clinical target volume (CTV) or suboptimal dose delivery to a target that abuts the heart, esophagus, liver, lung, kidney, and spinal cord. We report how these geometric/dosimetric constraints were overcome by exploiting intensity-modulated radiotherapy in the first cohort patient. Twenty-eight patients who had undergone extrapleural pneumonectomy were treated with intensity-modulated radiotherapy. The CTV included the surgically violated inner chest wall, insertion of diaphragm, pleural reflections, and deep margin of the incision. CTV delineation was facilitated by intraoperative radio-opaque marking. Motion was assessed. CTV doses were 45-50 Gy with boosts taken to 60 Gy. Despite the large, irregular CTV (median, 4151 cc; range, 2667-7286 cc), an average of 97% of the CTV was covered to the target dose (range, 92%-100%). Respiratory motion was minimal because of immobility of the prosthetic diaphragm. Normal tissue dose constraints were met. The commonest effects were nausea/vomiting (89%) and dyspnea (80%). Esophagitis was absent (59% of patients) or mild (34% grade 1/2). At median follow-up of 9 months (range, 5-27 months), local control within the contoured target was 100%. One-year survival, disease-specific survival, and disease-free survival are 65%, 91%, and 88%, respectively. Intensity-modulated radiotherapy after extrapleural pneumonectomy is tolerable and seems effective, at least at this early point. As local control improves, systemic metastases become more common, and it may be appropriate to add novel agents to further improve the therapeutic ratio.

Potential for reduced toxicity and dose escalation in the treatment of inoperable non–small-cell lung cancer: A comparison of intensity-modulated radiation therapy (IMRT), 3D conformal radiation, and elective nodal irradiation

Purpose To systematically evaluate four different techniques of radiation therapy (RT) used to treat non–small-cell lung cancer and to determine their efficacy in meeting multiple normal-tissue constraints while maximizing tumor coverage and achieving dose escalation. Methods and materials Treatment planning was performed for 18 patients with Stage I to IIIB inoperable non–small-cell lung cancer using four different RT techniques to treat the primary lung tumor ± the hilar/mediastinal lymph nodes: ( 1) Intensity-modulated radiation therapy (IMRT), ( 2) Optimized three-dimensional conformal RT (3D-CRT) using multiple beam angles, ( 3) Limited 3D-CRT using only 2 to 3 beams, and ( 4) Traditional RT using elective nodal irradiation (ENI) to treat the mediastinum. All patients underwent virtual simulation, including a CT scan and 18fluorodeoxyglucose positron emission tomography scan, fused to the CT to create a composite tumor volume. For IMRT and 3D-CRT, the target included the primary tumor and regional nodes either ≥1.0 cm in short-axis dimension on CT or with increased uptake on PET. For ENI, the target included the primary tumor plus the ipsilateral hilum and mediastinum from the inferior head of the clavicle to at least 5.0 cm below the carina. The goal was to deliver 70 Gy to ≥99% of the planning target volume (PTV) in 35 daily fractions (46 Gy to electively treated mediastinum) while meeting multiple normal-tissue dose constraints. Heterogeneity correction was applied to all dose calculations (maximum allowable heterogeneity within PTV 30%). Pulmonary and esophageal constraints were as follows: lung V 20 ≤25%, mean lung dose ≤15 Gy, esophagus V 50 ≤25%, mean esophageal dose ≤25 Gy. At the completion of all planning, the four techniques were contrasted for their ability to achieve the set dose constraints and deliver tumoricidal RT doses. Results Requiring a minimum dose of 70 Gy within the PTV, we found that IMRT was associated with a greater degree of heterogeneity within the target and, correspondingly, higher mean doses and tumor control probabilities (TCPs), 7%–8% greater than 3D-CRT and 14%–16% greater than ENI. Comparing the treatment techniques in this manner, we found only minor differences between 3D-CRT and IMRT, but clearly greater risks of pulmonary and esophageal toxicity with ENI. The mean lung V 20 was 36% with ENI vs. 23%–25% with the three other techniques, whereas the average mean lung dose was approximately 21.5 Gy (ENI) vs. 15.5 Gy (others). Similarly, the mean esophagus V 50 was doubled with ENI, to 34% rather than 15%–18%. To account for differences in heterogeneity, we also compared the techniques giving each plan a tumor control probability equivalent to that of the optimized 3D-CRT plan delivering 70 Gy. Using this method, IMRT and 3D-CRT offered similar results in node-negative cases (mean lung and esophageal normal-tissue complication probability [NTCP] of approximately 10% and 2%–7%, respectively), but ENI was distinctly worse (mean NTCPs of 29% and 20%). In node-positive cases, however, IMRT reduced the lung V 20 and mean dose by approximately 15% and lung NTCP by 30%, compared to 3D-CRT. Compared to ENI, the reductions were 50% and >100%. Again, for node-positive cases, especially where the gross tumor volume was close to the esophagus, IMRT reduced the mean esophagus V 50 by 40% (vs. 3D-CRT) to 145% (vs. ENI). The esophageal NTCP was at least doubled converting from IMRT to 3D-CRT and tripled converting from IMRT to ENI. Finally, the total number of fractions for each plan was increased or decreased until all outlined normal-tissue constraints were reached/satisfied. While meeting all constraints, IMRT or 3D-CRT increased the deliverable dose in node-negative patients by >200% over ENI. In node-positive patients, IMRT increased the deliverable dose 25%–30% over 3D-CRT and 130%–140% over ENI. The use of 3D-CRT without IMRT increased the deliverable RT dose >80% over ENI. Using a limited number of 3D-CRT beams decreased the lung V 20, mean dose, and NTCP in node-positive patients. Conclusions The use of 3D-CRT, particularly with only 3 to 4 beam angles, has the ability to reduce normal-tissue toxicity, but has limited potential for dose escalation beyond the current standard in node-positive patients. IMRT is of limited additional value (compared to 3D-CRT) in node-negative cases, but is beneficial in node-positive cases and in cases with target volumes close to the esophagus. When meeting all normal-tissue constraints in node-positive patients, IMRT can deliver RT doses 25%–30% greater than 3D-CRT and 130%–140% greater than ENI. Whereas the possibility of dose escalation is severely limited with ENI, the potential for pulmonary and esophageal toxicity is clearly increased.