Treatment Planning Techniques Research Articles

Cone Beam Computed Tomographic imaging in orthodontics.

Over the last 15 years, cone beam computed tomographic (CBCT) imaging has emerged as an important supplemental radiographic technique for orthodontic diagnosis and treatment planning, especially insituations which require an understanding of the complex anatomic relationships and surrounding structures of the maxillofacial skeleton. CBCT imaging provides unique features and advantages to enhance orthodontic practice over conventional extraoral radiographic imaging. While it is the responsibility of each practitioner to make a decision, in tandem with the patient/family, consensus-derived, evidence-based clinical guidelines are available to assist the clinician in the decision-making process. Specific recommendations provide selection guidance based on variables such as phase of treatment, clinically-assessed treatment difficulty, the presence of dental and/or skeletal modifying conditions, and pathology. CBCT imaging in orthodontics should always be considered wisely as children have conservatively, on average, a three to five times greater radiation risk compared with adults for the same exposure. The purpose of this paper is to provide an understanding of the operation of CBCT equipment as it relates to image quality and dose, highlight the benefits of the technique in orthodontic practice, and provide guidance on appropriate clinical use with respect to radiation dose and relative risk, particularly for the paediatric patient.

Comparison of treatment planning techniques in treatment of carcinoma of left breast: Second cancer perspective

AimTo compare the secondary cancer risk (SCR) between different planning techniques for treatment of Ca. Left-Breast patient. Materials and methodsFive treatment plans; 3DCRT tangential fields with physical wedge (PW), enhanced dynamic wedges (EDW), electronic compensator (EC), IMRT tangential fields (ITF) and Volumetric modulated arc (VMAT) plan (partial arcs) with 6MV photon beams were generated for a carcinoma of Left breast patient of age 40 to a prescription dose of 50Gy in 25 fractions. The SCR was estimated using the organ equivalent dose (OED) concept with a linear-exponential, a plateau, and a linear dose-response model for OARs. Also, the low dose-bath volume (5Gy) was calculated for all the plans. ResultsFor contra lateral breast the SCR relative to PW were (linear, plateau, linear-exponential) (−26.0%, −35.0%, −39.0%) for VMAT, (−50.0%,−50.0%,−51.0%) for ITF, (−48.0%, −49.0%,−49.0%) for EC and (−33.0%, −24% , −25.0%) for EDW respectively. The relative SCR (plateau) for heart and left lung were (−66.0% & −73.0%) for VMAT, (−20.0% & −6.0%) for ITF, (−24.0% & −18.0%) for EC and ( −17.0% & −14.0%)for EDW. In contrast, for skin the relative SCR (linear - exponential) were 78.0%, −8.0%, −13.0% and −10.0% for VMAT, ITF, EC and EDW respectively. The 5Gy low dose volume relative to PW for VMAT was 201.45%, whereas the same for ITF, EC and EDW were 17.0%, −7.33% and −4.3%. ConclusionCompared to all plans, VMAT plan showed high conformity for CTV and superior heart and left lung sparing. But SCR for skin and the low dose bath volume were significantly high in VMAT. ITF plan showed relatively better sparing for contra lateral breast and heart. EC plan shows moderately good sparing for OARs while scoring least SCR value for skin next to EDW. EDW and PW plans were similar but later had high SCR for contra lateral-breast. Planning techniques like ITF and VMAT can be strongly considered for left breast, provided better skin sparing techniques and less dose spillage can be achieved.

Development of a model web-based system to support a statewide quality consortium in radiation oncology

PurposeA database in which patient data are compiled allows analytic opportunities for continuous improvements in treatment quality and comparative effectiveness research. We describe the development of a novel, web-based system that supports the collection of complex radiation treatment planning information from centers that use diverse techniques, software, and hardware for radiation oncology care in a statewide quality collaborative, the Michigan Radiation Oncology Quality Consortium (MROQC). Methods and materialsThe MROQC database seeks to enable assessment of physician- and patient-reported outcomes and quality improvement as a function of treatment planning and delivery techniques for breast and lung cancer patients. We created tools to collect anonymized data based on all plans. ResultsThe MROQC system representing 24 institutions has been successfully deployed in the state of Michigan. Since 2012, dose-volume histogram and Digital Imaging and Communications in Medicine-radiation therapy plan data and information on simulation, planning, and delivery techniques have been collected. Audits indicated >90% accurate data submission and spurred refinements to data collection methodology. ConclusionsThis model web-based system captures detailed, high-quality radiation therapy dosimetry data along with patient- and physician-reported outcomes and clinical data for a radiation therapy collaborative quality initiative. The collaborative nature of the project has been integral to its success. Our methodology can be applied to setting up analogous consortiums and databases.

Reducing the dosimetric impact of positional errors in field junctions for craniospinal irradiation using VMAT

AimTo improve treatment plan robustness with respect to small shifts in patient position during the VMAT treatment by ensuring a linear ramp-like dose profile in treatment field overlap regions. BackgroundCraniospinal irradiation (CSI) is considered technically challenging because the target size exceeds the maximal field size, which necessitates using abutted or overlapping treatment fields. Volumetric modulated arc therapy (VMAT) is increasingly being examined for CSI, as it offers both better dose homogeneity and better dose conformance while also offering a possibility to create field junctions which are more robust towards small shifts in patient position during the treatment. Materials and methodsA VMAT treatment plan with three isocenters was made for a test case patient. Three groups of overlapping arc field pairs were used; one for the cranial and two for the spinal part. In order to assure a ramp-like dose profile in the field overlap region, the upper spinal part was optimised first, with dose prescription explicitly enforcing a ramp-like dose profile. The cranial and lower spinal part were done afterwards, taking into account the dose contribution of the upper spinal fields. ResultsUsing simple geometrical reasoning, we demonstrated that hot- and cold spots which arise from small displacement of one treatment field relative to the other treatment field can be reduced by taking two precautions: (a) widening the field overlap region, and (b) reducing the field gradient across the overlap region. The function with the smallest maximal gradient is a linear ramp. We present a treatment planning technique which yields the desired dose profile of the two contributing fields, and minimises dosimetric dependence on minor positional errors in patient set-up.

Optimization of dental implant treatment

Aim ― Modern dentistry cannot exist without dental implantation. The lifetime of the installed implants depends on condition of the bone and on the quality of the treatment planning and surgery technique. Usually, complications during the implant treatment are related to the inability to accurately predict the condition and location of intraosseous structure that entails the selection of the wrong type of implant and installation position. Methods ― This work is devoted to the bone-implant system investigation aiming on the optimization of dental prostheses installation. The objective of this study was to develop the implant treatment planning technique. Modern non-invasive methods such as computer tomography (CT) and 3D-scanning as well as numerical calculations and 3D-prototyping allow optimizing all of dental prosthetics stages. Results ― In this work, complex methodology of dental prosthesis installation is presented. Patient-specific dental templates developed in this work are easy to create and very accurate. Conclusion ― CT processing method, numerical modeling and 3D prototyping techniques allowed us to develop a methodology of dental prosthesis installation. An integrated approach to the planning of implant surgery can significantly reduce the risk of complications in the first few days after treatment, and throughout the period of operation of the prosthesis.

Treatment Plan Technique and Quality for Single Isocenter Stereotactic Ablative Radiation Therapy of Multiple Lung Lesions With Volumetric Modulated Arc Therapy or Intensity Modulated Radiosurgery

Treatment Plan Technique and Quality for Single Isocenter Stereotactic Ablative Radiation Therapy of Multiple Lung Lesions With Volumetric Modulated Arc Therapy or Intensity Modulated Radiosurgery

Treatment Plan Technique and Quality for Single-Isocenter Stereotactic Ablative Radiotherapy of Multiple Lung Lesions with Volumetric-Modulated Arc Therapy or Intensity-Modulated Radiosurgery.

The aim of this study is to provide a practical approach to the planning technique and evaluation of plan quality for the multi-lesion, single-isocenter stereotactic ablative radiotherapy (SABR) of the lung. Eleven patients with two or more lung lesions underwent single-isocenter volumetric-modulated arc therapy (VMAT) radiosurgery or IMRS. All plans were normalized to the target maximum dose. For each plan, all targets were treated to the same dose. Plan conformity and dose gradient were maximized with dose-control tuning structures surrounding targets. For comparison, multi-isocenter plans were retrospectively created for four patients. Conformity index (CI), homogeneity index (HI), gradient index (GI), and gradient distance (GD) were calculated for each plan. V5, V10, and V20 of the lung and organs at risk (OARs) were collected. Treatment time and total monitor units (MUs) were also recorded. One patient had four lesions and the remainder had two lesions. Six patients received VMAT and five patients received intensity-modulated radiosurgery (IMRS). For those treated with VMAT, two patients received 3-arc VMAT and four received 2-arc VMAT. For those treated with IMRS, two patients were treated with 10 and 11 beams, respectively, and the rest received 12 beams. Prescription doses ranged from 30 to 54 Gy in three to five fractions. The median prescribed isodose line was 84% (range: 80–86%). The median maximum dose was 57.1 Gy (range: 35.7–65.1 Gy). The mean combined PTV was 49.57 cm3 (range: 14.90–87.38 cm3). For single-isocenter plans, the median CI was 1.15 (range: 0.97–1.53). The median HI was 1.19 (range: 1.16–1.28). The median GI was 4.60 (range: 4.16–7.37). The median maximum radiation dose (Dmax) to total lung was 55.6 Gy (range: 35.7–62.0 Gy). The median mean radiation dose to the lung (Dmean) was 4.2 Gy (range: 1.1–9.3 Gy). The median lung V5 was 18.7% (range: 3.8–41.3%). There was no significant difference in CI, HI, GI, GD, V5, V10, and V20 (lung, heart, trachea, esophagus, and spinal cord) between single-isocenter and multi-isocenter plans. This multi-lesion, single-isocenter lung SABR planning technique demonstrated excellent plan quality and clinical efficiency and is recommended for radiosurgical treatment of two or more lung targets for well-suited patients.

Chung-Ang University (CAU) protocol for orthognathic surgery: 3-dimensional treatment planning, navigation and key-hole technique for correcting facial asymmetry

Chung-Ang University (CAU) protocol for orthognathic surgery: 3-dimensional treatment planning, navigation and key-hole technique for correcting facial asymmetry

Brachytherapy: state‐of‐the‐art radiotherapy in prostate cancer

Brachytherapy: state‐of‐the‐art radiotherapy in prostate cancer

A forward planned treatment planning technique for non-small-cell lung cancer stereotactic ablative body radiotherapy based on a systematic review of literature

AbstractPurpose and MethodA systematic literature review of six computerised databases was undertaken in order to review and summarise a forward planned lung stereotactic ablative body radiotherapy (SABR) treatment planning (TP) technique as a starting point for clinical implementation in the author’s department based on current empirical research. The data were abstracted and content analysed to synthesise the findings based upon a SIGN quality checklist tool.FindingsA four-dimensional computed tomography scan should be performed upon which the internal target volume and organs at risk (OAR) are drawn. A set-up margin of 5 mm is applied to account for inter-fraction motion. The field arrangement consists of a combination of 7–13 coplanar and non-coplanar beams all evenly spaced. Beam modifiers are used to assist in the homogeneity of the beam, although a 20% planning target volume dose homogeneity is acceptable. The recommended fractionations by the UK SABR Consortium are 54 Gy in 3 fractions (standard), 55–60 Gy in 5 fractions (conservative) and 50–60 Gy in 8–10 fractions (very conservative). Conformity indices for both the target volume and OAR will be used to assess the planned distribution.ConclusionAn overview of a clinically acceptable forward planned lung SABR TP technique based on current literature as a starting point, with a view to inverse planning with support from the UK SABR Consortium mentoring scheme.

The concept and evolution of involved site radiation therapy for lymphoma

We describe the development of radiation therapy for lymphoma from extended field radiotherapy of the past to modern conformal treatment with involved site radiation therapy based on advanced imaging, three-dimensional treatment planning and advanced treatment delivery techniques. Today, radiation therapy is part of the multimodality treatment of lymphoma, and the irradiated tissue volume is much smaller than before, leading to highly significant reductions in the risks of long-term complications.

WE-A-304-01: Strategies and Technologies for Cranial Radiosurgery Planning: MLC-Based Linac

The high fractional doses, stringent requirements for accuracy and precision, and surgical perspective characteristic of intracranial radiosurgery create considerations for treatment planning which are distinct from most other radiotherapy procedures. This session will introduce treatment planning techniques specific to two popular intracranial SRS modalities: Gamma Knife and MLC-based Linac. The basic treatment delivery characteristics of each device will be reviewed with a focus on how those characteristics determine the paradigm used for treatment planning. Basic techniques for treatment planning will be discussed, including considerations such as isodose selection, target and organ-at-risk definition, quality indices, and protection of critical structures. Future directions for SRS treatment planning will also be discussed. Learning Objectives: 1. Introduce the basic physical principles of intracranial radiosurgery and how they are realized in the treatment planning paradigms for Gamma Knife and Linac radiosurgery. 2. Demonstrate basic treatment planning techniques. 3. Discuss metrics for evaluating SRS treatment plan quality. 4. Discuss recent and future advances in SRS treatment planning. D. Schlesinger receives research support from Elekta, AB

WE-A-304-00: Stereotactic Radiosurgery

The high fractional doses, stringent requirements for accuracy and precision, and surgical perspective characteristic of intracranial radiosurgery create considerations for treatment planning which are distinct from most other radiotherapy procedures. This session will introduce treatment planning techniques specific to two popular intracranial SRS modalities: Gamma Knife and MLC-based Linac. The basic treatment delivery characteristics of each device will be reviewed with a focus on how those characteristics determine the paradigm used for treatment planning. Basic techniques for treatment planning will be discussed, including considerations such as isodose selection, target and organ-at-risk definition, quality indices, and protection of critical structures. Future directions for SRS treatment planning will also be discussed. Learning Objectives: 1. Introduce the basic physical principles of intracranial radiosurgery and how they are realized in the treatment planning paradigms for Gamma Knife and Linac radiosurgery. 2. Demonstrate basic treatment planning techniques. 3. Discuss metrics for evaluating SRS treatment plan quality. 4. Discuss recent and future advances in SRS treatment planning. D. Schlesinger receives research support from Elekta, AB

WE-A-304-02: Strategies and Technologies for Cranial Radiosurgery Planning: Gamma Knife

The high fractional doses, stringent requirements for accuracy and precision, and surgical perspective characteristic of intracranial radiosurgery create considerations for treatment planning which are distinct from most other radiotherapy procedures. This session will introduce treatment planning techniques specific to two popular intracranial SRS modalities: Gamma Knife and MLC-based Linac. The basic treatment delivery characteristics of each device will be reviewed with a focus on how those characteristics determine the paradigm used for treatment planning. Basic techniques for treatment planning will be discussed, including considerations such as isodose selection, target and organ-at-risk definition, quality indices, and protection of critical structures. Future directions for SRS treatment planning will also be discussed. Learning Objectives: 1. Introduce the basic physical principles of intracranial radiosurgery and how they are realized in the treatment planning paradigms for Gamma Knife and Linac radiosurgery. 2. Demonstrate basic treatment planning techniques. 3. Discuss metrics for evaluating SRS treatment plan quality. 4. Discuss recent and future advances in SRS treatment planning. D. Schlesinger receives research support from Elekta, AB

SU‐C‐213‐04: Application of Depth Sensing and 3D‐Printing Technique for Total Body Irradiation (TBI) Patient Measurement and Treatment Planning

Purpose:To develop and validate an innovative method of using depth sensing cameras and 3D printing techniques for Total Body Irradiation (TBI) treatment planning and compensator fabrication.Methods:A tablet with motion tracking cameras and integrated depth sensing was used to scan a RANDOTM phantom arranged in a TBI treatment booth to detect and store the 3D surface in a point cloud (PC) format. The accuracy of the detected surface was evaluated by comparison to extracted measurements from CT scan images. The thickness, source to surface distance and off‐axis distance of the phantom at different body section was measured for TBI treatment planning. A 2D map containing a detailed compensator design was calculated to achieve uniform dose distribution throughout the phantom. The compensator was fabricated using a 3D printer, silicone molding and tungsten powder. In vivo dosimetry measurements were performed using optically stimulated luminescent detectors (OSLDs).Results:The whole scan of the anthropomorphic phantom took approximately 30 seconds. The mean error for thickness measurements at each section of phantom compare to CT was 0.44 ± 0.268 cm. These errors resulted in approximately 2% dose error calculation and 0.4 mm tungsten thickness deviation for the compensator design. The accuracy of 3D compensator printing was within 0.2 mm. In vivo measurements for an end‐to‐end test showed the overall dose difference was within 3%.Conclusion:Motion cameras and depth sensing techniques proved to be an accurate and efficient tool for TBI patient measurement and treatment planning. 3D printing technique improved the efficiency and accuracy of the compensator production and ensured a more accurate treatment delivery.

SU‐E‐T‐587: Optimal Volumetric Modulated Arc Radiotherapy Treatment Planning Technique for Multiple Brain Metastases with Increasing Number of Arcs

Purpose:To show improvements in dose conformity and normal brain tissue sparing using an optimal planning technique (OPT) against clinically acceptable planning technique (CAP) in the treatment of multiple brain metastases.Methods:A standardized international benchmark case with12 intracranial tumors was planned using two different VMAT optimization methods. Plans were split into four groups with 3, 6, 9, and 12 targets each planned with 3, 5, and 7 arcs using Eclipse TPS. The beam geometries were 1 full coplanar and half non‐coplanar arcs. A prescription dose of 20Gy was used for all targets. The following optimization criteria was used (OPT vs. CAP): (No upper limit vs.108% upper limit for target volume), (priority 140–150 vs. 75–85 for normal‐brain‐tissue), and (selection of automatic sparing Normal‐Tissue‐Objective (NTO) vs. Manual NTO). Both had priority 50 to critical structures such as brainstem and optic‐chiasm, and both had an NTO priority 150. Normal‐brain‐tissue doses along with Paddick Conformity Index (PCI) were evaluated.Results:In all cases PCI was higher for OPT plans. The average PCI (OPT,CAP) for all targets was (0.81,0.64), (0.81,0.63), (0.79,0.57), and (0.72,0.55) for 3, 6, 9, and 12 target plans respectively. The percent decrease in normal brain tissue volume (OPT/CAP*100) achieved by OPT plans was (reported as follows: V4, V8, V12, V16, V20) (184, 343, 350, 294, 371%), (192, 417, 380, 299, 360%), and (235, 390, 299, 281, 502%) for the 3, 5, 7 arc 12 target plans, respectively. The maximum brainstem dose decreased for the OPT plan by 4.93, 4.89, and 5.30 Gy for 3, 5, 7 arc 12 target plans, respectively.Conclusion:Substantial increases in PCI, critical structure sparing, and decreases in normal brain tissue dose were achieved by eliminating upper limits from optimization, using automatic sparing of normal tissue function with high priority, and a high priority to normal brain tissue.

Hard and soft tissue surgical complications in dental implantology.

This article discusses surgical complications associated with the placement of dental implants, specifically focusing on how they occur (etiology), as well as their management and prevention. Dental implant surgical complications can be classified into those of hard and soft tissues. In general, complications can be avoided with thorough preoperative treatment planning and proper surgical technique.

Impact of treatment planning and delivery factors on gastrointestinal toxicity: an analysis of data from the RADAR prostate radiotherapy trial.

BackgroundTo assess the impact of incremental modifications of treatment planning and delivery technique, as well as patient anatomical factors, on late gastrointestinal toxicity using data from the TROG 03.04 RADAR prostate radiotherapy trial.MethodsThe RADAR trial accrued 813 external beam radiotherapy participants during 2003–2008 from 23 centres. Following review and archive to a query-able database, digital treatment plans and data describing treatment technique for 754 patients were available for analysis. Treatment demographics, together with anatomical features, were assessed using uni- and multivariate regression models against late gastrointestinal toxicity at 18-, 36- and 54-month follow-up. Regression analyses were reviewed in the context of dose-volume data for the rectum and anal canal.ResultsA multivariate analysis at 36-month follow-up shows that patients planned using a more rigorous dose calculation algorithm (DCA) was associated with a lower risk of stool frequency (OR: 0.435, CI: 0.242–0.783, corrected p = 0.04). Patients using laxative as a method of bowel preparation had higher risk of having increased stool frequency compared to patients with no dietary intervention (OR: 3.639, CI: 1.502–8.818, corrected p = 0.04). Despite higher risks of toxicities, the anorectum, anal canal and rectum dose-volume histograms (DVH) indicate patients using laxative had unremarkably different planned dose distributions. Patients planned with a more rigorous DCA had lower median DVH values between EQD23 = 15 Gy and EQD23 = 35 Gy. Planning target volume (PTV), conformity index, rectal width and prescription dose were not significant when adjusted for false discovery rate. Number of beams, beam energy, treatment beam definition, positioning orientation, rectum-PTV separation, rectal length and mean cross sectional area did not affect the risk of toxicities.ConclusionsThe RADAR study dataset has allowed an assessment of technical modifications on gastrointestinal toxicity. A number of interesting associations were subsequently found and some factors, previously hypothesised to influence toxicity, did not demonstrate any significant impact. We recommend trial registries be encouraged to record technical modifications introduced during the trial in order for more powerful evidence to be gathered regarding the impact of the interventions.Electronic supplementary materialThe online version of this article (doi:10.1186/s13014-014-0282-7) contains supplementary material, which is available to authorized users.

Spot Scanning Proton Therapy for Malignancies of the Base of Skull: Treatment Planning, Acute Toxicities, and Preliminary Clinical Outcomes

To describe treatment planning techniques and early clinical outcomes in patients treated with spot scanning proton therapy for chordoma or chondrosarcoma of the skull base. From June 2010 through August 2011, 15 patients were treated with spot scanning proton therapy for chordoma (n=10) or chondrosarcoma (n=5) at a single institution. Toxicity was prospectively evaluated and scored weekly and at all follow-up visits according to Common Terminology Criteria for Adverse Events, version 3.0. Treatment planning techniques and dosimetric data were recorded and compared with those of passive scattering plans created with clinically applicable dose constraints. Ten patients were treated with single-field-optimized scanning beam plans and 5 with multifield-optimized intensity modulated proton therapy. All but 2 patients received a simultaneous integrated boost as well. The mean prescribed radiation doses were 69.8 Gy (relative biological effectiveness [RBE]; range, 68-70 Gy [RBE]) for chordoma and 68.4 Gy (RBE) (range, 66-70) for chondrosarcoma. In comparison with passive scattering plans, spot scanning plans demonstrated improved high-dose conformality and sparing of temporal lobes and brainstem. Clinically, the most common acute toxicities included fatigue (grade 2 for 2 patients, grade 1 for 8 patients) and nausea (grade 2 for 2 patients, grade 1 for 6 patients). No toxicities of grades 3 to 5 were recorded. At a median follow-up time of 27 months (range, 13-42 months), 1 patient had experienced local recurrence and a second developed distant metastatic disease. Two patients had magnetic resonance imaging-documented temporal lobe changes, and a third patient developed facial numbness. No other subacute or late effects were recorded. In comparison to passive scattering, treatment plans for spot scanning proton therapy displayed improved high-dose conformality. Clinically, the treatment was well tolerated, and with short-term follow-up, disease control rates and toxicity profiles were favorable.

TU‐A‐BRE‐01: The Relative Biological Effectiveness of Proton Beams Relative to Photon Beams

Proton therapy patients receive a 10% lower physical dose than the dose administered using photons, i.e. the proton relative biological effectiveness (RBE) is 1.1 in comparison to high‐energy photons. The use of a generic, spatially invariant RBE within tumor targets and normal tissue structures disregards a large body of evidence indicating that proton RBE tends to increase with increasing linear energy transfer (LET). Because the doseaveraged proton LET in the distal edge of a spread out Bragg peak (SOBP) is larger than the LET in the plateau region or proximal edge of a SOBP, the use of a spatially invariant RBE is not well justified from a mechanistic point of view. On the other hand, the available clinical data on local tumor control rates and early or late side effects do not provide strong evidence against the continued use of a constant and spatially invariant clinical RBE. The only potential downside to the ongoing use of a constant RBE of 1.1 seems to be that we are missing a potential opportunity to enhance the therapeutic ratio, i.e., design proton therapy treatments in ways that exploit, rather than mitigate, spatial variations in proton RBE. Speakers in this symposium will:1‐review the laboratory and clinical evidence for and against the continued use of a spatially invariant RBE of 1.1,2‐examine some of the putative mechanisms connecting spatial variations in particle LET to estimates of the proton RBE at the molecular, cellular and tissue levels3‐assess the possible clinical significance of incorporating models for spatial variations in proton RBE into treatment planning systems.4‐discuss treatment planning and delivery techniques that will exploit the spatial variations of RBE within proton beams.Learning Objectives: To review laboratory and clinical evidence for and against the continued use of a constant RBE of 1.1 To understand major mechanisms connecting proton LET to RBE at the molecular, cellular and tissue levels. To quantify the potential opportunities and potential pitfalls of neglecting spatial variations in proton RBE in treatment plans To understand the minimum requirements required to design proton treatment plans that benefit from a spatially changing RBE and discuss some of the technological challenges they may require.