X. Sharon Qi

Evaluation of a commercial biologically based IMRT treatment planning system

A new inverse treatment planning system (TPS) for external beam radiation therapy with high energy photons is commercially available that utilizes both dose-volume-based cost functions and a selection of cost functions which are based on biological models. The purpose of this work is to evaluate quality of intensity-modulated radiation therapy (IMRT) plans resulting from the use of biological cost functions in comparison to plans designed using a traditional TPS employing dose-volume-based optimization. Treatment planning was performed independently at two institutions. For six cancer patients, including head and neck (one case from each institution), prostate, brain, liver, and rectal cases, segmental multileaf collimator IMRT plans were designed using biological cost functions and compared with clinically used dose-based plans for the same patients. Dose-volume histograms and dosimetric indices, such as minimum, maximum, and mean dose, were extracted and compared between the two types of treatment plans. Comparisons of the generalized equivalent uniform dose (EUD), a previously proposed plan quality index (fEUD), target conformity and heterogeneity indices, and the number of segments and monitor units were also performed. The most prominent feature of the biologically based plans was better sparing of organs at risk (OARs). When all plans from both institutions were combined, the biologically based plans resulted in smaller EUD values for 26 out of 33 OARs by an average of 5.6 Gy (range 0.24 to 15 Gy). Owing to more efficient beam segmentation and leaf sequencing tools implemented in the biologically based TPS compared to the dose-based TPS, an estimated treatment delivery time was shorter in most (five out of six) cases with some plans showing up to 50% reduction. The biologically based plans were generally characterized by a smaller conformity index, but greater heterogeneity index compared to the dose-based plans. Overall, compared to plans based on dose-volume optimization, plans with equivalent target coverage obtained using the biologically based TPS demonstrate improved dose distributions for the majority of normal structures.

Is α/β for breast cancer really low?

PURPOSE Low α/β ratio for breast cancer has drawn a growing interest for exploring hypofractionation for breast irradiation. This work is to confirm the low α/β ratio based on large randomized clinical trials of breast irradiation. METHODS AND MATERIALS A model based on the generalized linear-quadratic (LQ) model and Poisson statistical model was developed to calculate disease-free survival with consideration of clonogen proliferation during the course of radiation treatment and exponential behavior of survival rate with follow-up time. Outcome data from a series of randomized clinical trials of early-stage breast radiotherapy were fitted to estimate the model parameters. Other clinical outcomes, including treatments with surgery alone or radiotherapy alone were used to validate the model and the estimated parameters. Hypofractionation regimens were proposed based on the newly estimated LQ parameters. RESULTS Plausible population averaged radiobiologic parameters for breast cancer (95% confidence level) are α/β=2.88 (0.75-5.01) Gy; α=0.08±0.02Gy(-1); potential doubling time T(d)=14.4±7.8day. The analysis of the radiation-alone data suggested an α/β ratio of 3.89±6.25Gy, verifying the low α/β ratio based on the post-lumpectomy irradiation data. The hypofractionation regimens that are equivalent to the conventional regimen of 2.0Gy×25 in 5weeks include 2.26Gy×20, 3.34Gy×10, 4.93Gy×5 or 3.39Gy×10 (BID). CONCLUSIONS The analysis of the available clinical data from multiple institutions support that breast cancer has a low ratio of α/β, encouraging hypofractionated radiotherapy regimens for breast cancer.

Improved critical structure sparing with biologically based IMRT optimization

The impact of using biological models in treatment planning on plan quality is studied by comparing IMRT plans generated using selected commercially available treatment planning systems (TPSs) employing biological models/quantities in IMRT optimization (bIMRT) and the conventional physically (dose-volume) based optimization (pIMRT). A total of 25 IMRT plans, generated for five cases of different anatomic sites (brain, head and neck, lung, pancreas, and prostate) using five TPSs, two bIMRT (CMS Monaco and Phillips Pinnacle3 P3IMRT) and three pIMRT (CMS Xio, Phillips Pinnacle3, and Tomotherapy) systems, were compared. Dose-volume histograms, maximum, minimum, and mean doses, target heterogeneity and conformity indices, equivalent uniform dose (EUD), and an overall plan-ranking index (fEUD) were used in the comparison. It is clear from the comparison that the use of biological models in treatment planning optimization can generate IMRT plans with significantly improved normal tissue sparing with similar or slightly increased dose heterogeneity in the target, as compared to the conventional dose-volume based optimization for the same beam arrangement. For example, the bIMRT plans lead to smaller EUDs in 32 out of 37 normal structures in all five cases combined, as compared to the pIMRT plans. Caution should be exercised in choosing appropriate models and/or model parameters and in evaluating the plan obtained when using the biologically based treatment planning system.

Respiratory Organ Motion and Dosimetric Impact on Breast and Nodal Irradiation

PURPOSE To examine the respiratory motion for target and normal structures during whole breast and nodal irradiation and the resulting dosimetric impact. METHODS AND MATERIALS Four-dimensional CT data sets of 18 patients with early-stage breast cancer were analyzed retrospectively. A three-dimensional conformal dosimetric plan designed to irradiate the breast was generated on the basis of CT images at 20% respiratory phase (reference phase). The reference plans were copied to other respiratory phases at 0% (end of inspiration) and 50% (end of expiration) to simulate the effects of breathing motion on whole breast irradiation. Dose-volume histograms, equivalent uniform dose, and normal tissue complication probability were evaluated and compared. RESULTS Organ motion of up to 8.8mm was observed during free breathing. A large lung centroid movement was typically associated with a large shift of other organs. The variation of planning target volume coverage during a free breathing cycle is generally within 1%-5% (17 of 18 patients) compared with the reference plan. However, up to 28% of V(45) variation for the internal mammary nodes was observed. Interphase mean dose variations of 2.2%, 1.2%, and 1.4% were observed for planning target volume, ipsilateral lung, and heart, respectively. Dose variations for the axillary nodes and brachial plexus were minimal. CONCLUSIONS The doses delivered to the target and normal structures are different from the planned dose based on the reference phase. During normal breathing, the dosimetric impact of respiratory motion is clinically insignificant with the exception of internal mammary nodes. However, noticeable degradation in dosimetric plan quality may be expected for the patients with large respiratory motion.

Impact of Computed Tomography Image Quality on Image-Guided Radiation Therapy Based on Soft Tissue Registration

PURPOSE In image-guided radiation therapy (IGRT), different computed tomography (CT) modalities with varying image quality are being used to correct for interfractional variations in patient set-up and anatomy changes, thereby reducing clinical target volume to the planning target volume (CTV-to-PTV) margins. We explore how CT image quality affects patient repositioning and CTV-to-PTV margins in soft tissue registration-based IGRT for prostate cancer patients. METHODS AND MATERIALS Four CT-based IGRT modalities used for prostate RT were considered in this study: MV fan beam CT (MVFBCT) (Tomotherapy), MV cone beam CT (MVCBCT) (MVision; Siemens), kV fan beam CT (kVFBCT) (CTVision, Siemens), and kV cone beam CT (kVCBCT) (Synergy; Elekta). Daily shifts were determined by manual registration to achieve the best soft tissue agreement. Effect of image quality on patient repositioning was determined by statistical analysis of daily shifts for 136 patients (34 per modality). Inter- and intraobserver variability of soft tissue registration was evaluated based on the registration of a representative scan for each CT modality with its corresponding planning scan. RESULTS Superior image quality with the kVFBCT resulted in reduced uncertainty in soft tissue registration during IGRT compared with other image modalities for IGRT. The largest interobserver variations of soft tissue registration were 1.1 mm, 2.5 mm, 2.6 mm, and 3.2 mm for kVFBCT, kVCBCT, MVFBCT, and MVCBCT, respectively. CONCLUSIONS Image quality adversely affects the reproducibility of soft tissue-based registration for IGRT and necessitates a careful consideration of residual uncertainties in determining different CTV-to-PTV margins for IGRT using different image modalities.

Respiration Induced Heart Motion and Indications of Gated Delivery for Left-Sided Breast Irradiation

PURPOSE To investigate respiration-induced heart motion for left-sided breast irradiation using a four-dimensional computed tomography (4DCT) technique and to determine novel indications to assess heart motion and identify breast patients who may benefit from a gated treatment. METHODS AND MATERIALS Images of 4DCT acquired during free breathing for 20 left-sided breast cancer patients, who underwent whole breast irradiation with or without regional nodal irradiation, were analyzed retrospectively. Dose distributions were reconstructed in the phases of 0%, 20%, and 50%. The intrafractional heart displacement was measured in three selected transverse CT slices using D(LAD) (the distance from left ascending aorta to a fixed line [connecting middle point of sternum and the body] drawn on each slice) and maximum heart depth (MHD, the distance of the forefront of the heart to the line). Linear regression analysis was used to correlate these indices with mean heart dose and heart dose volume at different breathing phases. RESULTS Respiration-induced heart displacement resulted in observable variations in dose delivered to the heart. During a normal free-breathing cycle, heart-induced motion D(LAD) and MHD changed up to 9 and 11 mm respectively, resulting in up to 38% and 39% increases of mean doses and V(25.2) for the heart. MHD and D(LAD) were positively correlated with mean heart dose and heart dose volume. Respiratory-adapted gated treatment may better spare heart and ipsilateral-lung compared with the conventional non-gated plan in a subset of patients with large D(LAD) or MHD variations. CONCLUSION Proposed indices offer novel assessment of heart displacement based on 4DCT images. MHD and D(LAD) can be used independently or jointly as selection criteria for respiratory gating procedure before treatment planning. Patients with great intrafractional MHD variations or tumor(s) close to the diaphragm may particularly benefit from the gated treatment.

Possible fractionated regimens for image-guided intensity-modulated radiation therapy of large arteriovenous malformations.

The aim of this study was to estimate a plausible alpha/beta ratio for arteriovenous malformations (AVMs) based on reported clinical data, and to design possible fractionation regimens suitable for image-guided intensity-modulated radiation therapy (IG-IMRT) for large AVMs based on the newly obtained alpha/beta ratio. The commonly used obliteration rate (OR) for AVMs with a three year angiographic follow-up from many institutes was fitted to linear-quadratic (LQ) formalism and the Poisson OR model. The determined parameters were then used to calculate possible fractionation regimens for IG-IMRT based on the concept of a biologically effective dose (BED) and an equivalent uniform dose (EUD). The radiobiological analysis yields a alpha/beta ratio of 2.2 +/- 1.6 Gy for AVMs. Three sets of possible fractionated schemes were designed to achieve equal or better biological effectiveness than the single-fraction treatments while maintaining the same probability of normal brain complications. A plausible alpha/beta ratio was derived for AVMs and possible fractionation regimens that may be suitable for IG-IMRT for large AVM treatment are proposed. The sensitivity of parameters on the calculation was also studied. The information may be useful to design new clinical trials that use IG-IMRT for the treatment of large AVMs.

Megavoltage CT imaging quality improvement on TomoTherapy via tensor framelet.

PURPOSE This work is to investigate the feasibility of improving megavoltage imaging quality for TomoTherapy using a novel reconstruction technique based on tensor framelet, with either full-view or partial-view data. METHODS The reconstruction problem is formulated as a least-square L1-type optimization problem, with the tensor framelet for the image regularization, which is a generalization of L1, total variation, and wavelet. The high-order derivatives of the image are simultaneously regularized in L1 norm at multilevel along the x, y, and z directions. This convex formulation is efficiently solved using the Split Bregman method. In addition, a GPU-based parallel algorithm was developed to accelerate image reconstruction. The new method was compared with the filtered backprojection and the total variation based method in both phantom and patient studies with full or partial projection views. RESULTS The tensor framelet based method improved the image quality from the filtered backprojection and the total variation based method. The new method was robust when only 25% of the projection views were used. It required ∼2 min for the GPU-based solver to reconstruct a 40-slice 1 mm-resolution 350×350 3D image with 200 projection views per slice and 528 detection pixels per view. CONCLUSIONS The authors have developed a GPU-based tensor framelet reconstruction method with improved image quality for the megavoltage CT imaging on TomoTherapy with full or undersampled projection views. In particular, the phantom and patient studies suggest that the imaging quality enhancement via tensor framelet method is prominent for the low-dose imaging on TomoTherapy with up to a 75% projection view reduction.

A planning and delivery study of a rotational IMRT technique with burst delivery.

PURPOSE A novel rotational IMRT (rIMRT) technique using burst delivery (continuous gantry rotation with beam off during MLC repositioning) is investigated. The authors evaluate the plan quality and delivery efficiency and accuracy of this dynamic technique with a conventional flat 6 MV photon beam. METHODS Burst-delivery rIMRT was implemented in a planning system and delivered with a 160-MLC linac. Ten rIMRT plans were generated for five anonymized patient cases encompassing head and neck, brain, prostate, and prone breast. All plans were analyzed retrospectively and not used for treatment. Among the varied plan parameters were the number of optimization points, number of arcs, gantry speed, and gantry angle range (alpha) over which the beam is turned on at each optimization point. Combined rotational/step-and-shoot rIMRT plans were also created by superimposing multiple-segment static fields at several optimization points. The rIMRT trial plans were compared with each other and with plans generated using helical tomotherapy and VMAT. Burst-mode rotational IMRT plans were delivered and verified using a diode array, ionization chambers, thermoluminescent dosimeters, and film. RESULTS Burst-mode rIMRT can achieve plan quality comparable to helical tomotherapy, while the former may lead to slightly better OAR sparing for certain cases and the latter generally achieves slightly lower hot spots. Few instances were found in which increasing the number of optimization points above 36, or superimposing step-and-shoot IMRT segments, led to statistically significant improvements in OAR sparing. Using an additional rIMRT partial arc yielded substantial OAR dose improvements for the brain case. Measured doses from the rIMRT plan delivery were within 4% of the plan calculation in low dose gradient regions. Delivery time range was 228-375 s for single-arc rIMRT 200-cGy prescription with a 300 MU/min dose rate, comparable to tomotherapy and VMAT. CONCLUSIONS Rotational IMRT with burst delivery, whether combined with static fields or not, yields clinically acceptable and deliverable treatment plans.

Potential for Improved Intelligence Quotient Using Volumetric Modulated Arc Therapy Compared With Conventional 3-Dimensional Conformal Radiation for Whole-Ventricular Radiation in Children

PURPOSE To compare volumetric modulated arc therapy (VMAT) with 3-dimensional conformal radiation therapy (3D-CRT) in the treatment of localized intracranial germinoma. We modeled the effect of the dosimetric differences on intelligence quotient (IQ). METHOD AND MATERIALS Ten children with intracranial germinomas were used for planning. The prescription doses were 23.4 Gy to the ventricles followed by 21.6 Gy to the tumor located in the pineal region. For each child, a 3D-CRT and full arc VMAT was generated. Coverage of the target was assessed by computing a conformity index and heterogeneity index. We also generated VMAT plans with explicit temporal lobe sparing and with smaller ventricular margin expansions. Mean dose to the temporal lobe was used to estimate IQ 5 years after completion of radiation, using a patient age of 10 years. RESULTS Compared with the 3D-CRT plan, VMAT improved conformality (conformity index 1.10 vs 1.85), with slightly higher heterogeneity (heterogeneity index 1.09 vs 1.06). The averaged mean doses for left and right temporal lobes were 31.3 and 31.7 Gy, respectively, for VMAT plans and 37.7 and 37.6 Gy for 3D-CRT plans. This difference in mean temporal lobe dose resulted in an estimated IQ difference of 3.1 points at 5 years after radiation therapy. When the temporal lobes were explicitly included in the VMAT optimization, the mean temporal lobe dose was reduced 5.6-5.7 Gy, resulting in an estimated IQ difference of an additional 3 points. Reducing the ventricular margin from 1.5 cm to 0.5 cm decreased mean temporal lobe dose 11.4-13.1 Gy, corresponding to an estimated increase in IQ of 7 points. CONCLUSION For treatment of children with intracranial pure germinomas, VMAT compared with 3D-CRT provides increased conformality and reduces doses to normal tissue. This may result in improvements in IQ in these children.