Standard Intensity-modulated Radiotherapy Research Articles

Sparing of the hippocampus, limbic circuit and neural stem cell compartment during partial brain radiotherapy for glioma: A dosimetric feasibility study

The aim of this study was to assess the feasibility of sparing contralateral or bilateral neural stem cell (NSC) compartment, hippocampus and limbic circuit during partial brain radiotherapy (PBRT). Treatment plans were generated for five hemispheric high-grade gliomas, five hemispheric low-grade gliomas and two brainstem gliomas (12 patients). For each, standard intensity-modulated radiotherapy (IMRT) plans were generated, as well as IMRT plans which spared contralateral (hemispheric cases) or bilateral (brainstem cases) limbic circuit, hippocampus, and NSC. Biologically equivalent dose for late effects (BED(late effects)) was generated for limbic circuit, hippocampus and NSC. Per cent relative reduction in mean physical dose and BED was calculated for each plan (standard vs. sparing). We were able to reduce physical dose and BED(late effects) to these critical structures by 23.5-56.8% and 23.6-66%, respectively. It is possible to spare contralateral limbic circuit, NSC and hippocampus during PBRT for both high- and low-grade gliomas using IMRT, and to spare the hippocampus bilaterally during PBRT for brainstem low-grade gliomas. This approach may reduce late cognitive sequelae of cranial radiotherapy.

Clinician's guide to prostate IMRT plan assessment and optimisation

Intensity-modulated radiotherapy (IMRT) offers dosimetric benefit for irregularly shaped treatment volumes compared to three-dimensional conformal approaches. Some groups advocate IMRT as the standard of care for prostate radiotherapy. For clinicians, assessment of an IMRT plan can introduce new opportunities and challenges. Although a standard IMRT plan may be deemed acceptable by meeting pre-set dose constraints, further optimisation may yield a superior treatment plan by further reducing dose to critical structures or improving target volume homogeneity. The aim of this article is to present aspects of IMRT planning relevant to clinicians to aid in plan critiquing.

A VMAT planning solution for prostate patients using a commercial treatment planning system

Volumetric modulated arc therapy (VMAT) is a rotational delivery technique which offers the potential of improved dose distributions and shorter treatment times when compared to fixed-beam intensity-modulated radiation therapy (IMRT). This note describes the use of an existing treatment planning system (Philips Pinnacle3 v.8.0), supplemented by in-house software, to produce a single-arc VMAT prostate plan. While a number of planning systems for the Elekta VMAT platform are commercially available, the use of an in-house solution has allowed more detailed investigations of VMAT planning, as well as greater control over the optimization process. The solution presented here begins with a static step-and-shoot IMRT approach to provide initial segment shapes, which are then modified and sequenced into 60 equally spaced control points in a 360° arc. Dose–volume histogram comparisons demonstrate that this VMAT planning method offers multiple dose level target coverage comparable to that from a standard IMRT approach. The VMAT plans also show superior sparing of critical structures such as the rectum and bladder. Delivery times are reduced with the VMAT method, and the results of dosimetric verification, resilience and repeatability tests indicate that the solution is robust.

Poster — Thur Eve — 52: Head and Neck IMRT Complexity Characterization and Prediction of Deliverability Using the Modulation Complexity Score

Intensity modulated radiation therapy (IMRT) is often referred to as being highly complex, but the definition of complexity can be varied. A single metric, the modulation complexity score (MCS), has previously been developed to quantify IMRT complexity. The purpose of this study is to evaluate the use of MCS in the characterization of segmentation complexity and beam deliverability in the context of head and neck IMRT. Fifty treatment plans were evaluated by calculating the MCS per beam. Patient‐specific measurements were obtained as part of the standard IMRT QA process using a diode array and retrospective analysis was completed using various gamma analysis criteria. The MCS, as well as single beam parameters (e.g. number of MU or control points), were compared to dosimetric results. 375 individual treatment beams were analyzed, with an average MCS of 0.245 (range: −0.338 – 0.754) and 125 MU on average (range: 32 to 295). All beams had >90% of diodes passing the standard gamma analysis (3%/3mm) with an average of 98%. There was a linear relationship between the number of MU and the MCS score (r2=0.75). The relationship between pass rate and complexity (characterized by MCS or MU) is not simple, however it may be possible to predict good dosimetric results based on the plan complexity. In conjunction with the ability to compile complexity statistics for specific treatment sites or protocols, MCS could impact the radiation therapy process at many points, including during planning, plan evaluation and QA.

SU-EE-A1-06: A Comparative Study of Cobalt-60 Based Tomotherapy versus 6 MV Linac-Based Tomotherapy, IMRT, and 3DCRT for the Treatment Planning of Prostate and Head and Neck Cases

Purpose: Cobalt‐60 (Co‐60) based radiation therapy continues to play a significant role in a large number of countries due its simplicity and robustness. However, it has not been developed to accommodate modern techniques that provide intensity modulated radiation therapy(IMRT). In this paper we present the results of investigations of Co‐60 based tomotherapy. Particularly, we generate clinical plans for prostate and head and neck (H&N) anatomical regions and compare them with the plans obtained with 6MV based linac tomotherapy, standard 6MV IMRT, and 3D conformal radiation therapy (3DCRT) techniques. Method and Materials: The tomotherapy plans were obtained by modeling a MIMiC binary multileaf collimator attached to a Theratron‐780C Co‐60 unit and a 6MV linear accelerator. The EGSnrc/BEAMnrc Monte Carlo code was used to model the treatment units with the MIMiC collimator while EGSnrc/DOSXYZnrc code was used for calculating dose on prostate and H&N CT datasets. All heterogeneities and patient contours were considered. An in‐house inverse treatment planning program was then used to optimize all 2D tomotherapy plans. The IMRT and 3DCRT plans were generated in Eclipse treatment planning system based on our in‐house IMRT and 3DCRT clinical protocols for prostate and H&N treatment.Results: A quantitative analysis of the dose distributions and dose area histograms (DAHs) showed that the Co‐60 plans achieve the dose objectives for the targets and OARs. The dose distributions and DAHs for Co‐60 tomotherapy plans for both cases are very similar to those obtained with 6MV based tomotherapy and IMRT, and are much more conformal compared to 3DCRT plans. Conclusion: Our investigations confirm that Co‐60 tomotherapy is indeed capable of providing state‐of‐the‐art conformal dose delivery and could be used for the treatment of targets in both small and larger separation anatomical regions.

RapidArc Planning and Delivery in Patients With Locally Advanced Head-and-Neck Cancer Undergoing Chemoradiotherapy

Volumetric modulated arc therapy (RapidArc, Varian Medical Systems) permits the delivery of highly conformal dose distributions. We studied planning and delivery in patients who underwent RapidArc for locally advanced head-and-neck cancer (HNC). A total of 35 consecutive patients who completed RapidArc with concurrent chemotherapy for Stages III-IV tumors of the oro- and hypopharynx/larynx in our center were identified. All underwent bilateral neck irradiation and 21 patients had at least N2 disease. A simultaneous integrated boost (SIB) delivered 70 Gy (in 2 Gy/fraction) to the planning target volume (PTV)(boost) and elective nodal regions (PTV(elect)) received 57.75 Gy. A standard planning constraint set was used and constraints for parotid glands were individually adapted. Treatments were delivered using two arcs after all plans were verified in a solid water phantom using GafChromic External Beam Therapy films. RapidArc planning generally took 1.5-2 h, which was faster than with our previous seven-field intensity-modulated radiotherapy sliding window technique. Film dosimetry revealed that 0.6% of films exceeded a combination of dose differences ≥3% or distance to agreement ≥2 mm. More than 99% of both PTVs received ≥95% of the prescription dose. Average plan conformity index was 1.13 and mean dose to ipsilateral and contralateral parotid glands were 31.4 Gy and 26.1 Gy, respectively. The mean beam-on time was <3 min and mean number of monitor units was 426. RapidArc achieved excellent target coverage and normal tissue sparing, with delivery completed in less than 3 min. RA is currently our standard intensity-modulated radiotherapy approach for advanced HNC.

Helical Tomotherapy-Based STAT RT: Dosimetric Evaluation for Clinical Implementation of a Rapid Radiation Palliation Program

Helical tomotherapy–based STAT radiation therapy (RT) uses an efficient software algorithm for rapid intensity-modulated treatment planning, enabling conformal radiation treatment plans to be generated on megavoltage computed tomography (MVCT) scans for CT simulation, treatment planning, and treatment delivery in one session. We compared helical tomotherapy–based STAT RT dosimetry with standard linac-based 3D conformal plans and standard helical tomotherapy–based intensity-modulated radiation therapy (IMRT) dosimetry for palliative treatments of whole brain, a central obstructive lung mass, multilevel spine disease, and a hip metastasis. Specifically, we compared the conformality, homogeneity, and dose with regional organs at risk (OARs) for each plan as an initial step in the clinical implementation of a STAT RT rapid radiation palliation program. Hypothetical planning target volumes (PTVs) were contoured on an anthropomorphic phantom in the lung, spine, brain, and hip. Treatment plans were created using three planning techniques: 3D conformal on Pinnacle 3, helical tomotherapy, and helical tomotherapy–based STAT RT. Plan homogeneity, conformality, and dose to OARs were analyzed and compared. STAT RT and tomotherapy improved conformality indices for spine and lung plans (CI spine = 1.21, 1.17; CI lung = 1.20, 1.07, respectively) in comparison with standard palliative anteroposterior/posteroanterior (AP/PA) treatment plans (CI spine = 7.01, CI lung = 7.30), with better sparing of heart, esophagus, and spinal cord. For palliative whole-brain radiotherapy, STAT RT and tomotherapy reduced maximum and mean doses to the orbits and lens (maximum/mean lens dose: STAT RT = 2.94/2.65 Gy, tomotherapy = 3.13/2.80 Gy, Lateral opposed fields = 7.02/3.65 Gy), with an increased dose to the scalp (mean scalp dose: STAT RT = 16.19 Gy, tomotherapy = 15.61 Gy, lateral opposed fields = 14.01 Gy). For bony metastatic hip lesions, conformality with both tomotherapy techniques (CI = 1.01 each) is superior to AP/PA treatments (CI = 1.21), as expected. Helical tomotherapy–based STAT RT treatment planning provides clinically acceptable dosimetry, with conformality and homogeneity that is superior to standard linac-based 3D conformal planning and is only slightly inferior to standard helical tomotherapy IMRT dosimetry. STAT RT facilitates rapid treatment planning and delivery for palliative radiation of patients with metastatic disease, with relative sparing of adjacent OARs compared with standard 3D conformal plans.

Volumetric Modulated Arc Therapy: Planning and Evaluation for Prostate Cancer Cases

To develop an optimization method using volumetric modulated arc therapy (VMAT) and evaluate VMAT plans relative to the standard intensity-modulated radiotherapy (IMRT) approach in prostate cancer. A single gantry rotation was modeled using 177 equispaced beams. Multileaf collimator apertures and dose rates were optimized with respect to gantry angle subject to dose-volume-based objectives. Our VMAT implementation used conjugate gradient descent to optimize dose rate, and stochastic sampling to find optimal multileaf collimator leaf positions. A treatment planning study of 11 prostate cancer patients with a prescription dose of 86.4 Gy was performed to compare VMAT with a standard five-field IMRT approach. Plan evaluation statistics included the percentage of planning target volume (PTV) receiving 95% of prescribed dose (V95), dose to 95% of PTV (D95), mean PTV dose, tumor control probability, and dosimetric endpoints of normal organs, whereas monitor unit (MU) and delivery time were used to assess delivery efficiency. Patient-averaged PTV V95, D95, mean dose, and tumor control probability in VMAT plans were 96%, 82.6 Gy, 88.5 Gy, and 0.920, respectively, vs. 97%, 84.0 Gy, 88.9 Gy, and 0.929 in IMRT plans. All critical structure dose requirements were met. The VMAT plans presented better rectal wall sparing, with a reduction of 1.5% in normal tissue complication probability. An advantage of VMAT plans was that the average number of MUs (290 MU) was less than for IMRT plans (642 MU). The VMAT technique can reduce beam on time by up to 55% while maintaining dosimetric quality comparable to that of the standard IMRT approach.

Single-Arc IMRT?

The idea of delivering intensity-modulated radiation therapy (IMRT) with a multileaf collimator in a continuous dynamic mode during a single rotation of the gantry has recently gained momentum both in research and industry. In this note we investigate the potential of this Single-Arc IMRT technique at a conceptual level. We consider the original theoretical example case from Brahme et al that got the field of IMRT started. Using analytical methods, we derive deliverable intensity ‘landscapes’ for Single-Arc as well as standard IMRT and Tomotherapy. We find that Tomotherapy provides the greatest flexibility in shaping intensity landscapes and that it allows one to deliver IMRT in a way that comes close to the ideal case in the transverse plane. Single-Arc and standard IMRT make compromises in different areas. Only in relatively simple cases that do not require substantial intensity modulation will Single-Arc be dosimetrically comparable to Tomotherapy. Compared with standard IMRT, Single-Arc could be dosimetrically superior in certain cases if one is willing to accept the spreading of low dose values over large volumes of normal tissue. In terms of treatment planning, Single-Arc poses a more challenging optimization problem than Tomotherapy or standard IMRT. We conclude that Single-Arc holds potential as an efficient IMRT technique especially for relatively simple cases. In very complex cases, Single-Arc may unduly compromise the quality of the dose distribution, if one tries to keep the treatment time below 2 min or so. As with all IMRT techniques, it is important to explore the tradeoff between plan quality and the efficiency of its delivery carefully for each individual case.

Investigation of the reliability, accuracy, and efficiency of gated IMRT delivery with a commercial linear accelerator

This work reports an investigation on the reliability, accuracy, and efficiency of gated intensity modulated radiation therapy (IMRT) delivery with a commercial linear accelerator. The dosimetry measurements of segmented multileaf collimated IMRT (SMLC-IMRT) were performed by using radiographic films and a two-dimensional diode array. Testing involved a series of IMRT fields from actual patients combined with some manually generated fields. To examine the delivery time, dosimetry plans of standard beamlet IMRT, direct-aperture-optimized (DAO) IMRT, compensator IMRT, and three-dimensional conformal radiotherapy with wedges were delivered with and without gating. The results demonstrated that the gated SMLC-IMRT can be reliably and accurately delivered on this type of accelerators, as long as extremely high interruption frequencies and very low number of monitor units per segment are avoided. Beam flatness exceeded 5% and monitor linearity deviated more than 3% for the gated operation with 2.5 s breathing cycle and 20% duty cycle with segment sizes less than 10 MU. Gating does not change multi leaf collimator (MLC) positioning accuracy. The DAO IMRT is preferred for gated delivery because of its short delivery time.

Positron Emission Tomography-Guided, Focal-Dose Escalation Using Intensity-Modulated Radiotherapy for Head and Neck Cancer

To assess the feasibility of intensity-modulated radiotherapy (IMRT) using positron emission tomography (PET)-guided dose escalation, and to determine the maximum tolerated dose in head and neck cancer. A Phase I clinical trial was designed to escalate the dose limited to the [(18)-F]fluoro-2-deoxy-D-glucose positron emission tomography ((18)F-FDG-PET)-delineated subvolume within the gross tumor volume. Positron emission tomography scanning was performed in the treatment position. Intensity-modulated radiotherapy with an upfront simultaneously integrated boost was employed. Two dose levels were planned: 25 Gy (level I) and 30 Gy (level II), delivered in 10 fractions. Standard IMRT was applied for the remaining 22 fractions of 2.16 Gy. Between 2003 and 2005, 41 patients were enrolled, with 23 at dose level I, and 18 at dose level II; 39 patients completed the planned therapy. The median follow-up for surviving patients was 14 months. Two cases of dose-limiting toxicity occurred at dose level I (Grade 4 dermitis and Grade 4 dysphagia). One treatment-related death at dose level II halted the study. Complete response was observed in 18 of 21 (86%) and 13 of 16 (81%) evaluated patients at dose levels I and II (p < 0.7), respectively, with actuarial 1-year local control at 85% and 87% (p = n.s.), and 1-year overall survival at 82% and 54% (p = 0.06), at dose levels I and II, respectively. In 4 of 9 patients, the site of relapse was in the boosted (18)F-FDG-PET-delineated region. For head and neck cancer, PET-guided dose escalation appears to be well-tolerated. The maximum tolerated dose was not reached at the investigated dose levels.

IMRT boost dose planning on dominant intraprostatic lesions: Gold marker-based three-dimensional fusion of CT with dynamic contrast-enhanced and 1H-spectroscopic MRI

To demonstrate the theoretical feasibility of integrating two functional prostate magnetic resonance imaging (MRI) techniques (dynamic contrast-enhanced MRI [DCE-MRI] and 1H-spectroscopic MRI [MRSI]) into inverse treatment planning for definition and potential irradiation of a dominant intraprostatic lesion (DIL) as a biologic target volume for high-dose intraprostatic boosting with intensity-modulated radiotherapy (IMRT). In 5 patients, four gold markers were implanted. An endorectal balloon was inserted for both CT and MRI. A DIL volume was defined by DCE-MRI and MRSI using different prostate cancer-specific physiologic (DCE-MRI) and metabolic (MRSI) parameters. CT-MRI registration was performed automatically by matching three-dimensional gold marker surface models with the iterative closest point method. DIL-IMRT plans, consisting of whole prostate irradiation to 70 Gy and a DIL boost to 90 Gy, and standard IMRT plans, in which the whole prostate was irradiated to 78 Gy were generated. The tumor control probability and rectal wall normal tissue complication probability were calculated and compared between the two IMRT approaches. Combined DCE-MRI and MRSI yielded a clearly defined single DIL volume (range, 1.1-6.5 cm3) in all patients. In this small, selected patient population, no differences in tumor control probability were found. A decrease in the rectal wall normal tissue complication probability was observed in favor of the DIL-IMRT plan versus the plan with IMRT to 78 Gy. Combined DCE-MRI and MRSI functional image-guided high-dose intraprostatic DIL-IMRT planned as a boost to 90 Gy is theoretically feasible. The preliminary results have indicated that DIL-IMRT may improve the therapeutic ratio by decreasing the normal tissue complication probability with an unchanged tumor control probability. A larger patient population, with more variations in the number, size, and localization of the DIL, and a feasible mechanism for treatment implementation has to be studied to extend these preliminary tumor control and toxicity estimates.

The dosimetric effects of tissue heterogeneities in intensity-modulated radiation therapy (IMRT) of the head and neck

The dosimetric effects of bone and air heterogeneities in head and neck IMRT treatments were quantified. An anthropomorphic RANDO phantom was CT-scanned with 16 thermoluminescent dosimeter (TLD) chips placed in and around the target volume. A standard IMRT plan generated with CORVUS was used to irradiate the phantom five times. On average, measured dose was 5.1% higher than calculated dose. Measurements were higher by 7.1% near the heterogeneities and by 2.6% in tissue. The dose difference between measurement and calculation was outside the 95% measurement confidence interval for six TLDs. Using CORVUS' heterogeneity correction algorithm, the average difference between measured and calculated doses decreased by 1.8% near the heterogeneities and by 0.7% in tissue. Furthermore, dose differences lying outside the 95% confidence interval were eliminated for five of the six TLDs. TLD doses recalculated by Pinnacle3's convolution/superposition algorithm were consistently higher than CORVUS doses, a trend that matched our measured results. These results indicate that the dosimetric effects of air cavities are larger than those of bone heterogeneities, thereby leading to a higher delivered dose compared to CORVUS calculations. More sophisticated algorithms such as convolution/superposition or Monte Carlo should be used for accurate tailoring of IMRT dose in head and neck tumours.

Dysphagia and aspiration after chemoradiotherapy for head-and-neck cancer: Which anatomic structures are affected and can they be spared by IMRT?

To identify the anatomic structures whose damage or malfunction cause late dysphagia and aspiration after intensive chemotherapy and radiotherapy (RT) for head-and-neck cancer, and to explore whether they can be spared by intensity-modulated RT (IMRT) without compromising target RT. A total of 26 patients receiving RT concurrent with gemcitabine, a regimen associated with a high rate of late dysphagia and aspiration, underwent prospective evaluation of swallowing with videofluoroscopy (VF), direct endoscopy, and CT. To assess whether the VF abnormalities were regimen specific, they were compared with the VF findings of 6 patients presenting with dysphagia after RT concurrent with high-dose intra-arterial cisplatin. The anatomic structures whose malfunction was likely to cause each of the VF abnormalities common to both regimens were determined by literature review. Pre- and posttherapy CT scans were reviewed for evidence of posttherapy damage to each of these structures, and those demonstrating posttherapy changes were deemed dysphagia/aspiration-related structures (DARS). Standard three-dimensional (3D) RT, standard IMRT (stIMRT), and dysphagia-optimized IMRT (doIMRT) plans in which sparing of the DARS was included in the optimization cost function, were produced for each of 20 consecutive patients with advanced head-and-neck cancer. The posttherapy VF abnormalities common to both regimens included weakness of the posterior motion of the base of tongue, prolonged pharyngeal transit time, lack of coordination between the swallowing phases, reduced elevation of the larynx, and reduced laryngeal closure and epiglottic inversion, contributing to a high rate of aspiration. The anatomic structures whose malfunction was the likely cause of each of these abnormalities, and that also demonstrated anatomic changes after RT concurrent with gemcitabine doses associated with dysphagia and aspiration, were the pharyngeal constrictor muscles (median thickness near midline 2.5 mm before therapy vs. 7 mm after therapy; p = 0.001), the supraglottic larynx (median thickness, 2 mm before therapy vs. 4 mm after therapy; p < 0.001), and, similarly, the glottic larynx. The constrictors and the glottic and supraglottic larynx were, therefore, deemed the DARS. The lowest maximal dose delivered to a stricture volume was 50 Gy. Reducing the volumes of the DARS receiving > or =50 Gy (V(50)) was, therefore, a planning and evaluation goal. Compared with the 3D plans, stIMRT reduced the V(50) of the pharyngeal constrictors by 10% on average (range, 0-36%, p < 0.001), and doIMRT reduced these volumes further, by an additional 10% on average (range, 0-38%; p <0.001). The V(50) of the larynx (glottic + supraglottic) was reduced marginally by stIMRT compared with 3D (by 7% on average, range, 0-56%; p = 0.054), and doIMRT reduced these volumes by an additional 11%, on average (range, 0-41%; p = 0.002). doIMRT reduced laryngeal V(50) compared with 3D, by 18% on average (range 0-61%; p = 0.001). Certain target delineation rules facilitated sparing of the DARS by IMRT. The maximal DARS doses were not reduced by IMRT because of their partial overlap with the targets. stIMRT and doIMRT did not differ in target doses, parotid gland mean dose, spinal cord, or nonspecified tissue maximal dose. The structures whose damage may cause dysphagia and aspiration after intensive chemotherapy and RT are the pharyngeal constrictors and the glottic and supraglottic larynx. Compared with 3D-RT, moderate sparing of these structures was achieved by stIMRT, and an additional benefit, whose extent varied among the patients, was gained by doIMRT, without compromising target doses. Clinical validation is required to determine whether the dosimetric gains are translated into clinical ones.

SIFT: a method to verify the IMRT fluence delivered during patient treatment using an electronic portal imaging device.

Radiotherapy patients are increasingly treated with intensity-modulated radiotherapy (IMRT) and high tumor doses. As part of our quality control program to ensure accurate dose delivery, a new method was investigated that enables the verification of the IMRT fluence delivered during patient treatment using an electronic portal imaging device (EPID), irrespective of changes in patient geometry. Each IMRT treatment field is split into a static field and a modulated field, which are delivered in sequence. Images are acquired for both fields using an EPID. The portal dose image obtained for the static field is used to determine changes in patient geometry between the planning CT scan and the time of treatment delivery. With knowledge of these changes, the delivered IMRT fluence can be verified using the portal dose image of the modulated field. This method, called split IMRT field technique (SIFT), was validated first for several phantom geometries, followed by clinical implementation for a number of patients treated with IMRT. The split IMRT field technique allows for an accurate verification of the delivered IMRT fluence (generally within 1% [standard deviation]), even if large interfraction changes in patient geometry occur. For interfraction radiological path length changes of 10 cm, deliberately introduced errors in the delivered fluence could still be detected to within 1% accuracy. Application of SIFT requires only a minor increase in treatment time relative to the standard IMRT delivery. A new technique to verify the delivered IMRT fluence from EPID images, which is independent of changes in the patient geometry, has been developed. SIFT has been clinically implemented for daily verification of IMRT treatment delivery.

Optimization in intensity modulated radiation therapy

Intensity modulated radiation therapy(IMRT) uses nonuniform intensity distributions to conform high dose to a tumor and low dose to surrounding sensitive structures. Because of the large number of beams (5–11) and the wide range of intensities, treatment planning is typically an inverse problem in which the intensity distributions are optimized. Three areas addressed in this thesis are plan complexity, beam directions, and dose–volume constraints. Inverse treatment planning is flexible and can deliver complex dose distributions that are sometimes not warranted. The first goal of this thesis is to demonstrate simple alternatives to inverse planning that use just enough degrees of freedom for the problem so that the solution is not overly sensitive to a slight change in dose constraints and patient geometry. With the addition of simple beam direction optimization, a suitable IMRT plan can be created while maintaining clinical practicality. The second goal of the thesis is to introduce and analyze a new algorithm which systematically analyzes and selects beam directions in the fewest number of beams possible. In IMRT, the optimization of beam directions is complicated due to the interdependence with beam intensities. Our beam direction algorithm has the capability of achieving plans that are better than standard IMRT techniques, often with a fewer number of beams. The third goal of this thesis is to propose a new formulation of the inverse treatment planningoptimization problems that include dose–volume constraints which are known to destroy convexity. This is compared to a formulation that has been addressed in the literature. We solve both formulations with a new technique based on direct search optimization with a systematic search region reduction. This is compared to a standard fast simulated annealing technique. The results of using the new formulation show a direct correspondence between the minimum objective function values and the resulting dose distributions and dose–volume histograms. The research of this thesis is performed using examples of lung, prostate, and brain stem radiotherapy. We provide evidence that dose–volume based formulations of inverse treatment planningoptimization for IMRT have the ability to achieve optimal plans that are clinically relevant.