Dose painting to combat tumor hypoxia while sparing urethra in prostate IMRT: a biologically based adaptive approach accounting for setup uncertainties and organ motion

Enhanced resistance to radiation could be caused by both chronic hypoxia and acute hypoxic which has been reported in prostate cancer in various studies. Therefore currently used dose prescriptions (70Gy in 35 fractions) for external beam radiation therapy (EBRT) of prostate cancer has been suggested insufficient to provide optimum clinical outcome. In this study, we propose a Biologically Guided Radiation Therapy approach to boost dose in hypoxic prostate tumor regions while sparing the urethra. A previously proposed hypoxia model was modified for prostate cancer and incorporated into treatment plan optimization. The concept of equivalent uniform dose (EUD) was used in the optimization and evaluation of results. CT data from 25 prostate cancer patients who recently received EBRT at the British Columbia Cancer Agency (BCCA) and hypothetical hypoxic regions manually drawn on these CT scans were selected for this study. The results show that our methods could boost dose in target volume to substantially higher levels. EUD of planning target volume increased to more than 80Gy, despite accounting for effects of hypoxia. This increase was achieved with only minor changes in dose in normal tissues, typically less than 5Gy. Notably, urethra sparing was excellent with a EUD around 64Gy. Robustness of the proposed approach is verified against various hypoxic settings. EUD comparison between RT plans in biological guided and conventional approaches using the same RT technique (Volumetric Modulated Arc Therapy) also suggests that biologically guided radiation therapy (BGRT) approach is more suitable for dose painting purposes with the advantage of delivering sufficient dose to hypoxia region in different scenarios and sparing normal tissue better. Furthermore, we also investigated the impact of inter-fraction patient set-up error and intra-fraction organ motion on the high dose gradients achieved with this proposed dose painting method and explored the feasibility of adapting geometrical uncertainties (represented as systematic error and random error) into treatment planning. Image error obtained from EPID images are used to derive systematic uncertainty and random uncertainty. During the geometrical uncertainty adapted optimization, dose matrix in PTV is shifted based on systematic error and convolved with a Gaussian kernel which is pre-calculated using random error. CT sets and organ contours from five patients who enrolled in the previous dose painting i study are selected. For each of them, seven plans are generated using cumulated uncertainty data which was collected after every five fractions. We also present the outcome in terms of equivalent uniform dose (EUD). For four of the patients, EUD history of all seven plans suggests using the proposed optimization method with uncertainty data from the first five fractions, it is possible to achieve the same target coverage of static treatment plans (difference in EUD less than 1Gy). Meanwhile, the elimination of PTV margin also leads to a significant dose reduction (more than 15Gy) in rectum.Science, Faculty ofPhysics and Astronomy, Department ofGraduat

Perfusion SPECT guided dose escalation in radiation therapy for lung cancer patients

Radiation therapy (RT) is a standard of care for patients with locally advanced inoperable non-small cell lung cancer (NSCLC). Prognosis for these patients is poor with 2-years survival below 20%. A substantial proportion of the lung cancer patients receiving RT develop symptomatic radiation pneumonitis (RP) as radiationinduced side effects. Thus, sparing of normal lung is one of the important goals for lung cancer patients receiving RT. Currently in clinical practice, the sparing of lung is assessed based on the dosevolume histogram (DVH) assuming homogeneous lung function which is clearly not valid. Lung perfusion scan using Single Photon Emission Computed Tomography (SPECT) with ⁹⁹mTc macroaggregated albumin (⁹⁹mTc-MAA) provides unique functional information (lung perfusion i.e. blood flow) about the lung and holds the potential to improve normal tissue sparing in RT. Incorporating functional information from perfusion SPECT scan into RT treatment planning allows for identifying and sparing the well perfused parts of lung, thus reducing the risk of clinically significant radiation-induced lung complications. From February 2008 to May 2011, 22 lung cancer patients in BC Cancer Agency were recruited into this ethics board approved SPECT study. The goal of this study is to establish a framework for SPECT-guided RT treatment planning and dose escalation trials. In this study, the incorporation of SPECT into RT treatment planning is carried out in a sequential manner including: 1. Reconstruction of SPECT images and investigating the metric of functional sparing for treatment planning 2. Evaluation of SPECT image registration algorithms 3. Developing the methodology of SPECT-guided intensity modulated radiation therapy (IMRT) treatment planning with a Monte Carlo based beamlets dose calculation 4. Evaluation of the effectiveness of SPECT-guided RT through a planning study comparing DVH and SPECT-driven IMRT plans. In conclusion, comparing to conventional DVH driven IMRT plans, we found that SPECT-driven IMRT plans provide better sparing of both lung function and volume. Mean lung dose and SPECT-weighted mean dose can be reduced by 10.8% and 13.1%, respectively. We suggest that the use of SPECT guided IMRT treatment planning improves the sparing of lung functionality and makes possible dose escalations in patients with non-small cell lung cancers.Science, Faculty ofPhysics and Astronomy, Department ofGraduat

Stereotactic body proton therapy for liver tumors: Dosimetric advantages and their radiobiological and clinical implications

Background and Purpose: Photon Stereotactic Body Radiotherapy (SBRT) for primary and metastatic tumors of the liver is challenging for larger lesions. An in silico comparison of paired SBRT and Stereotactic Body Proton Therapy (SBPT) plans was performed to understand the potential advantages of SBPT as a function of tumor size and location. Methods and materials: Theoretical tumor volumes with maximum diameter of 1–10 cm were contoured in the dome, right inferior, left medial, and central locations. SBRT and SBPT plans were generated to deliver 50 Gy in 5 fractions, max dose <135%. When organs-at-risk (OAR) constraints were exceeded, hypothetical plans (not clinically acceptable) were generated for comparison. Liver normal tissue complication probability (NTCP) models were applied to evaluate differences between treatment modalities. Results: SBRT and SBPT were able to meet target goals and OAR constraints for lesions up to 7 cm and 9 cm diameter, respectively. SBPT plans resulted in a higher integral gross target dose for all lesions up to 7 cm (mean dose 57.8 ± 2.3 Gy to 64.1 ± 2.2 Gy, p < 0.01). Simultaneously, SBPT spared dose to the uninvolved liver in all locations (from 11.5 ± 5.3 Gy to 8.6 ± 4.4 Gy, p < 0.01), resulting in lower NTCP particularly for larger targets in the dome and central locations. SBPT also spared duodenal dose across all sizes and positions (from 7.3 ± 1.1 Gy to 1.1 ± 0.3 Gy, p < 0.05). Conclusion: The main advantages of SBPT over SBRT is meeting plan goals and constrains for larger targets, particularly dome and central locations, and sparing dose to uninvolved liver. For such patients, SBPT may allow improvements in tumor control and treatment safety. Keywords: Proton SBRT, Liver SBRT, NTC

Prospective MRI-based imaging study to assess feasibility of proton therapy for post-prostatectomy radiation

<p><b>Purpose/Objectives</b>: To optimize delivery of post-prostatectomy radiation (PPRT) with protons by examining dosimetric effects of variations in physician contouring, organ motion, and patient alignment during a course of PPRT. <b>Material and methods</b>: We enrolled 10 patients receiving PPRT in a prospective imaging study. All patients underwent combined computed tomography (CT)/magnetic resonance imaging (MRI) simulation with endorectal balloon (ERB) and received intensity modulated radiation therapy (IMRT) per institutional standards. Study patients underwent weekly MRI verification scans in the treatment position. Three radiation oncologists contoured clinical target volumes (CTV) on initial and verification scans using two consensus guidelines (RTOG and EORTC). We generated IMRT, double scattering (DS), and pencil beam scanning (PBS) proton plans and examined the dosimetric impact of contour variations, inter-fraction motion, and patient alignment techniques. <b>Results</b>: Inter-observer variations in contouring reduced median CTV coverage (D100) by 0.9% for IMRT plans, 2.8% for DS proton plans, 3.4–4.9% for PBS Proton Plans. Inter-fraction changes in target volumes due to internal organ motion resulted in a median loss of target dose coverage (D98) of 0% with IMRT, 3.5% with DS, and 8.1–8.3% with PBS. Median bladder V65Gy increased during the treatment course with all techniques (6.0–7.5%). Changes in the median rectal V60Gy remained small regardless of the treatment technique (0.5–3.1% increase). Alignment to the ERB after cranio-caudal bony alignment reduced CTV displacement compared to bony alignment alone, and as a result CTV coverage (D98) changed <2% with IMRT, DS, and PBS. <b>Conclusion</b>: Proton-based treatments are more sensitive to changes in inter-fraction organ motion during PPRT compared to IMRT, and therefore motion management and patient alignment methods are critical. Patient alignment using bony anatomy as well as the ERB minimizes displacement of the CTV, and reduces variation in target dose coverage particularly for PBS proton therapy.</p

Automated knowledge-based intensity-modulated proton planning: An international multicenter benchmarking study

Background: Radiotherapy treatment planning as an increasingly automated and knowledge-based planning has been shown to match and sometimes improve upon manual clinical plans, with increased consistency and efficiency. In this study, we benchmarked a novel prototype knowledge-based intensity-modulated proton therapy (IMPT) planning solution, against three international proton centers. Methods: A model library was constructed, comprising 50 head and neck cancer (HNC) manual IMPT plans from a single center. Three external-centers each provided seven manual benchmark IMPT plans. A knowledge-based plan (KBP) using a standard beam arrangement for each patient was compared with the benchmark plan on the basis of planning target volume (PTV) coverage and homogeneity and mean organ-at-risk (OAR) dose. Results: PTV coverage and homogeneity of KBPs and benchmark plans were comparable. KBP mean OAR dose was lower in 32/54, 45/48 and 38/53 OARs from center-A,-B and-C, with 23/32, 38/45 and 23/38 being >2 Gy improvements, respectively. In isolated cases the standard beam arrangement or an OAR not being included in the model or being contoured differently, led to higher individual KBP OAR doses. Generating a KBP typically required <10 min. Conclusions: A knowledge-based IMPT planning solution using a single-center model could efficiently generate plans of comparable quality to manual HNC IMPT plans from centers with differing planning aims. Occasional higher KBP OAR doses highlight need for beam angle optimization and manual review of KBPs. The solution furthermore demonstrated the potential for robust optimization