Simultaneous Integrated Boost Plans Research Articles

In Silico Study of Simultaneous Integrated Boost Carbon-Ion Radiotherapy for Locally Advanced Pancreatic Cancer.

Carbon-ion radiotherapy (CiRT) has been used for the treatment of locally advanced pancreatic cancer (LAPC) with uniform dose plan. The aim of the present study is to investigate the effectiveness of a simultaneous integrated boost (SIB) technique with scanned CiRT against LAPC. Data of 21 patients with LAPC were used to compare two treatment planning approaches: a conventional uniform dose approach and a SIB approach. A relative biological effectiveness (RBE)-weighted dose (DRBE) of 55.2 Gy (RBE) in 12 fractions was prescribed to the planning target volume (PTV) in the conventional approach. In the SIB approach, DRBE of 67.2 Gy (RBE) and 43.2 Gy (RBE) in 12 fractions were prescribed to a high-risk PTV (HR-PTV) and low-risk PTV (LR-PTV), respectively. The DRBE and dose-averaged linear energy transfer (LETd) of targets and gastrointestinal tracts as organs at risk (OARs) were evaluated. The HR-PTV D90% and LR-PTV D90% were 64.4±0.6 and 42.5±0.1 Gy (RBE) in SIB approach compared to the PTV D90% of 54.1±0.4 Gy (RBE) in the conventional approach. All SIB plans achieved the D2cc lower than 46 Gy (RBE) and V30 lower than 4 cm3 within OARs. The SIB approach increased the minimum LETd within the GTV to 44 keV/μm or higher for 20 out of 21 patients as compared to 16 out of 21 patients in the conventional approach. The SIB approach effectively increased the RBE-weighted dose and LETd within the HR-PTV and GTV by accumulating the high-LET stopping carbon-ions into the HR-PTV in addition to the decreased RBE-weighted dose to OARs.

Dose-Painting Proton Radiotherapy Guided by Functional MRI in Non-enhancing High-Grade Gliomas

AimsThis study aimed to demonstrate the feasibility and evaluate the dosimetric effect and clinical impact of dose-painting proton radiotherapy (PRT) guided by functional MRI in non-enhancing high-grade gliomas (NE-HGGs). Materials and methodsThe 3D-ASL and T2 FLAIR MR images of ten patients with NE-HGGs before radiotherapy were studied retrospectively. The hyperintensity on T2 FLAIR was used to generate the planning target volume (PTV), and the high-perfusion volume on 3D-ASL (PTV-ASL) was used to generate the simultaneous integrated boost (SIB) volume. Each patient received pencil beam scanning PRT and photon intensity-modulated radiotherapy (IMRT). There were five plans in each modality: (1) Uniform plans (IMRT60 vs. PRT60): 60Gy in 30 fractions to the PTV. (2)–(5) SIB plans (IMRT72, 84, 96, 108 vs. PRT72, 84, 96, 108): Uniform plan plus additional dose boost to PTV-ASL in 30 fractions to 72, 84, 96, 108 Gy. The dosimetric differences between various plans were compared. The clinical effects of target volume and organs at risk (OARs) were assessed using biological models for both tumor control probability (TCP) and normal tissue complication probability (NTCP). ResultsCompared with the IMRT plan, the D2 and D50 of the PRT plans with the same prescription dose increased by 1.27–4.12% and 0.64–2.01%, respectively; the R30 decreased by > 32%; the dose of brainstem and chiasma decreased by > 27% and >32%; and the dose of normal brain tissue (Br-PTV), optic nerves, eyeballs, lens, cochlea, spinal cord, and hippocampus decreased by > 50% (P < 0.05). The maximum necessary dose was 96GyE to achieve >98% TCP for PRT, and it was 84Gy to achieve >91% TCP for IMRT. The average NTCP of Br-PTV was 1.30% and 1.90% for PRT and IMRT at the maximum dose escalation, respectively. The NTCP values of the remaining OARs approached zero in all PRT plans. ConclusionThe functional MRI-guided dose escalation using PRT is feasible while sparing the OARs constraints and demonstrates a potential clinical benefit by improving TCP with no or minimal increase in NCTP for tissues outside the PTV. This retrospective study suggested that the use of PRT-based SIB guided by functional MRI may represent a strategy to provide benefits for patients with NE-HGGs.

Dosimetric evaluation of ultrafractionated dose escalation with simultaneous integrated boost to intraprostatic lesion using 1.5-Tesla MR-Linac in localized prostate cancer.

We analyzed a dose escalation of 36.25 Gy to the entire prostate and a dose increment up to 40 Gy with 1.25 Gy increments to intraprostatic lesion (IPL) using simultaneous integrated boost (SIB) in five fractions. Eighteen low- and intermediate-risk prostate cancer patients treated with 1.5T MR-Linac were retrospectively evaluated. The same planning computed tomography (CT) images generated four plans: no SIB, 37.5 Gy SIB, 38.75 Gy SIB, and 40 Gy SIB. In four plans, planning target volume (PTV) doses, organ at risk (OAR) doses, and PTV-SIB homogeneity index (HI), gradient index (GI) and conformity index (CI) were compared. All plans met the criteria for PTV and PTV-SIB coverage. PTV 40 Gy plan has higher maximum PTV and PTV-SIB doses than other plans. The PTV HI was significantly higher in the SIB 40 Gy plan (0.135 ± 0.007) compared to SIB 38.75 Gy plan (0.099 ± 0.007; p = 0.001), SIB 37.5 Gy (0.067 ± 0.008; p < 0.001), and no SIB plan (0.049 ± 0.010; p < 0.001), while there were no significant differences in HI, GI and CI for PTV-SIB between three plans. Four rectum and bladder plans had similar dosimetric parameters. The urethra D5 was significantly higher in SIB 40 Gy plan compared to no SIB plan (37.7 ± 1.1 Gy vs. 37.0 ± 0.7 Gy; p = 0.009) and SIB 37.5 Gy plan (36.9 ± 0.8 Gy; p = 0.008). There was no significant difference in monitor units between the four consecutive plans. Ultra-hypofractionated dose escalation to IPL up to 40 Gy in 5 fractions with a 1.5-T MR-linac is dosimetrically feasible, potentially paving the way for clinical trials.

A head and neck treatment planning strategy for a CBCT-guided ring-gantry online adaptive radiotherapy system.

A planning strategy was developed and the utility of online-adaptation with the Ethos CBCT-guided ring-gantry adaptive radiotherapy (ART) system was evaluated using retrospective data from Head-and-neck (H&N) patients that required clinical offline adaptation during treatment. Clinical data were used to re-plan 20 H&N patients (10 sequential boost (SEQ) with separate base and boost plans plus 10 simultaneous integrated boost (SIB)). An optimal approach, robust to online adaptation, for Ethos-initial plans using clinical goal prioritization was developed. Anatomically-derived isodose-shaping helper structures, air-density override, goals for controlling hotspot location(s), and plan normalization were investigated. Online adaptation was simulated using clinical offline adaptive simulation-CTs to represent an on-treatment CBCT. Dosimetric comparisons were based on institutional guidelines for Clinical-initial versus Ethos-initial plans and Ethos-scheduled versus Ethos-adapted plans. Timing for five components of the online adaptive workflow was analyzed. The Ethos H&N planning approach generated Ethos-initial SEQ plans with clinically comparable PTV coverage (average PTVHigh V100% =98.3%, Dmin,0.03cc =97.9% and D0.03cc =105.5%) and OAR sparing. However, Ethos-initial SIB plans were clinically inferior (average PTVHigh V100% =96.4%, Dmin,0.03cc =93.7%, D0.03cc =110.6%). Fixed-field IMRT was superior to VMAT for 93.3% of plans. Online adaptation succeeded in achieving conformal coverage to the new anatomy in both SEQ and SIB plans that was even superior to that achieved in the initial plans (which was due to the changes in anatomy that simplified the optimization). The average adaptive workflow duration for SIB, SEQ base and SEQ boost was 30:14, 22.56, and 14:03 (min: sec), respectively. With an optimal planning approach, Ethos efficiently auto-generated dosimetrically comparable and clinically acceptable initial SEQ plans for H&N patients. Initial SIB plans were inferior and clinically unacceptable, but adapted SIB plans became clinically acceptable. Online adapted plans optimized dose to new anatomy and maintained target coverage/homogeneity with improved OAR sparing in a time-efficient manner.

Magnetic resonance imaging‐only‐based radiation treatment planning for simultaneous integrated boost of multiparametric magnetic resonance imaging‐defined dominant intraprostatic lesions

Objective To assess the feasibility of using synthetic computed tomography for treatment planning of the dominant intraprostatic lesion (DIL), a high-risk region of interest that offers potential for increased local tumor control. Methods A dosimetric study was performed on 15 prostate cancer patients with biopsy-proven prostate cancer who had undergone magnetic resonance imaging. DILs were contoured based on the turbo spin echo T2-weighted and diffusion weighted images. Air, bone, fat, and soft tissue were segmented and assigned bulk-density HU values of –1000, 285, –50, and 40, respectively, to create a synthetic computed tomography. Simultaneous integrated boost (SIB) and standard treatment plans were created for each patient. The total dose was 79.2 Gy to the non-boosted planning target volume for both plans with a boost of 100 Gy for the DIL in the SIB plan. A radiobiological model was created to determine individualized dose–response curves based on the patient's apparent diffusion coefficient maps. Results Mean doses to the non-boost planning target volume were 81.2 ± 0.3 Gy with the SIB and 81.0 ± 0.4 Gy without. For the DIL, the boosted mean dose was 102.6 ± 0.6 Gy. Total motor unit was 860 ± 100 with the SIB and 730 ±100 without. Femoral heads, rectum, bladder, and penile bulb were within established dose guidelines for either treatment technique. The average tumor control probability was 94% with the SIB compared with 78% without boosting the DIL. Conclusion This study showed the feasibility of magnetic resonance imaging-only treatment planning for patients with prostate cancer with a SIB to the DIL. DIL dose can be escalated to 100 Gy on synthetic computed tomography, while maintaining the original 79.2 Gy prescription dose and the organ of interest clinical dose limits.

Voxel-Level BED Corrected Dosimetric and Radiobiological Assessment of 2 Kinds of Hybrid Radiotherapy Planning Methods for Stage III NSCLC.

Background/purpose: To access the comparative dosimetric and radiobiological advantages of two methods of intensity-modulated radiation therapy (IMRT)-based hybrid radiotherapy planning for stage III nonsmall cell lung cancer (NSCLC). Methods: Two hybrid planning methods were respectively characterized by conventional fraction radiotherapy (CFRT) and stereotactic body radiotherapy (SBRT) and CFRT and simultaneous integrated boost (SIB) planning. All plans were retrospectively completed using the 2 methods for 20 patients with stage III NSCLC. CFRT and SBRT dose regimes 2 Gy × 30 f and 12.5 Gy × 4 f were, respectively, used for planning target volume of lymph node (PTVLN) and planning target volume of the primary tumor (PTVPT), while dose regimes 2 Gy × 26 f for PTVLN and sequential 2 Gy × 4 f for PTVLN combined with 12.5 Gy × 4 f for PTVPT were adopted for CFRT and SIB plans. SBRT and SIB EQD2 dose were calculated voxel by voxel, and then, respectively, superimposed with 30-fraction and 26-fraction CFRT plan dose to achieve biological equivalent dose (BED) dosimetric parameters of CFRT and SBRT and CFRT and SIB plans. Tumor control probability (TCP)/normal tissue complication probability (NTCP) was, respectively, calculated by equivalent uniform dose/Lyman–Kutcher–Burman models. BED plan parameters and TCP/NTCP were analyzed between 2 methods of hybrid planning. Primary tumor/lymph node (LN)/total TCP values were, respectively, evaluated as a function of the radiation dose needed to control 50% of tumor (TCD50) for 20 patients. Dosimetric errors were analyzed by nontransit electronic portal imaging device dosimetry measurement during hybrid plan delivery. Results: Statistically lower BED plan parameters of PTVLN D2 and homogeneity index resulted in slightly lower averaged LN/total TCP curves by CFRT and SIB planning. The gaps between Max and Min LN/total TCP curves were significantly closer for CFRT and SIB planning, which indicated better robustness of LN/total TCPs. A lower esophagus dose resulted in a lower esophagus NTCP by CFRT and SIB planning, which may be compromised by 1 week shorter overall treatment time by CFRT and SIB irradiation. Spinal cord Dmax was significantly reduced by CFRT and SIB plans. The dose verification results of the subplans involved in hybrid plans were acceptable, which showed that the 2 methods of hybrid planning could be delivered accurately in our center. Conclusion: CFRT and SIB plannings have more advantages on BED plan parameters and TCP/NTCP than CFRT and SBRT planning, and both methods of IMRT-based hybrid planning could be executed accurately for stage III NSCLC. The effectiveness of the results needs to be validated in the hybrid trial.

In Silico Feasibility Study of Carbon Ion Radiotherapy With Simultaneous Integrated Boost for Head and Neck Adenoid Cystic Carcinoma.

PurposeIn carbon ion radiotherapy (CIRT), a simultaneous integrated boost (SIB) approach has not been fully exploited so far. The feasibility of a CIRT-SIB strategy for head and neck adenoid cystic carcinoma (ACC) patients was investigated in order to improve treatment planning dose distributions.Methods and MaterialsCIRT plans of 10 ACC patients treated at the National Center for Oncological Hadrontherapy (CNAO, Pavia, Italy) with sequential boost (SEQ) irradiation and prescription doses of 41.0 Gy [relative biological effectiveness (RBE)]/10 fractions to low-risk (LR) clinical target volume (CTV) plus 24.6 Gy(RBE)/6 fractions to the high-risk (HR) CTV were re-planned with two SIB dose levels to the LR-CTV, namely, 48.0 Gy(RBE) and 54.4 Gy(RBE). While planning with SIB, the HR-CTV coverage had higher priority, with fixed organ-at-risk dose constraints among the SIB and SEQ plans. The homogeneity and conformity indexes were selected for CTV coverage comparison. The biologically effective dose (BED) was calculated to compare the different fractionation schemes.ResultsComparable HR-CTV coverage was achieved with the treatment approaches, while superior conformality and homogeneity were obtained with the SIB technique in both CTVs. With the SEQ, SIB48.0, and SIB54.4, the LR-CTV median doses were respectively 50.3%, 11.9%, and 6.0% higher than the prescriptions. Significant reductions of the median and near-maximum BEDs were achieved with both SIB dose levels in the LR-CTV.ConclusionsThe SIB approach resulted in highly conformal dose distributions with the reduction of the unintended dose to the LR-CTV. A prescription dose range for the LR-CTV will be clinically defined to offer tailored personalized treatments, according to the clinical and imaging characteristics of the patients.

Dosimetric Uncertainties in Dominant Intraprostatic Lesion Simultaneous Boost Using Intensity Modulated Proton Therapy

PurposeWhile intensity modulated proton therapy can deliver simultaneous integrated boost (SIB) to the dominant intraprostatic lesion (DIL) with high precision, it is sensitive to anatomic changes. We investigated the dosimetric effects from these changes based on pretreatment cone-beam computed tomographic (CBCT) images and identified the most important factors using a multilayer perceptron neural network (MLPNN). Methods and MaterialsDILs were contoured based on coregistered multiparametric magnetic resonance images for 25 previously treated prostate cancer patients. SIB plans were created with (1) prostate clinical target volume − V70 Gy = 98%; (2) DIL − V98 Gy > 95%; and (3) all organs at risk within clinical constraints. SIB plans were applied to daily CBCT-based deformed planning computed tomography (CT). DIL − V98 Gy, bladder/rectum maximum dose (Dmax) and volume changes, femur shifts, and the distance from DIL to organs at risk in both planning computed tomograms and CBCT were calculated. Wilcoxon signed-ranks tests were used to compare the changes. MLPNNs were used to model the change in ΔDIL − V98 Gy > 10% and bladder/rectum Dmax > 80 Gy, and the relative importance factors for the model were provided. The performances of the models were evaluated with receiver operating characteristic curves. ResultsComparing initial plan to the average from evaluation plans, respectively, DIL − V98 Gy was 89.3% ± 19.9% versus 86.2% ± 21.3% (P = .151); bladder Dmax 71.9 ± 0.6 Gy versus 74.5 ± 2.9 Gy (P < .001); and rectum Dmax 70.1 ± 2.4 Gy versus 74.9 ± 9.1Gy (P = .007). Bladder and rectal volumes were 99.6% ± 39.5% and 112.8% ± 27.2%, respectively, of their initial volume. The femur shift was 3.16 ± 2.52 mm. In the modeling of ΔDIL V98 Gy > 10%, DIL to rectum distance changes, DIL to bladder distance changes, and rectum volume changes ratio are the 3 most important factors. The areas under the receiver operating characteristic curves were 0.89, 1.00, and 0.99 for the modeling of ΔDIL − V98 Gy > 10%, and bladder and rectum Dmax > 80 Gy, respectively. ConclusionsDosimetric changes in DIL SIB with intensity modulated proton therapy can be modeled and classified based on anatomic changes on pretreatment images by an MLPNN.

Neoadjuvant Chemotherapy and Whole Ventricular Irradiation for Pure Intracranial Germinoma: A Comparison of Three Brain-Sparing Techniques.

ObjectiveTo quantitate and compare the dosimetric properties of three brain-sparing radiation therapy techniques for pure intracranial germinomas with dose-volume analysis of target and normal brain structures.MethodsWe identified 18 patients with central nervous system (CNS) germinoma who had achieved local control and had excellent neurocognitive outcomes. Four patients who were treated with a simultaneous integrated boost (SIB) plan of 22.5Gy to whole ventricle (WV) and 30Gy to primary were re-planned with 24Gy to WV-only and the Children’s Oncology Group (COG) protocol of 18Gy to WV with a sequential boost to 30Gy. Organ-at-risk (OAR) doses for hippocampi, temporal lobes, whole brain, whole brain minus whole ventricles planning target volume (WB-WVPTV), WVPTV, and boost volume were comparatively studied.ResultsFor patients treated with the SIB plan, an excellent neurocognitive function has previously been shown to be well preserved. Three-year event-free survival (EFS) and overall survival (OS) for this group have also previously been demonstrated (89.5% and 100%, respectively). Mean and integral OAR doses were comparable between SIB and WV-only plans but were lower for COG plans. Whole brain, whole brain minus WVPTV, and temporal lobe V20, V18, and V12, as well as hippocampi V20, V25, and V30, were comparable between SIB and WV-only plans but were lower for the COG plans.ConclusionCompared to the WV-only method, the SIB plan permits more dose to the primary site by 6 Gy without compromising neurocognitive control. While maintaining the 30Gy boost, the COG protocol reduces the WVPTV dose to 18Gy. It remains to be seen whether WV dose reduction risks reducing local control.

Ultra hypofractionated extended nodal irradiation using volumetric modulated arc therapy for oligorecurrent pelvic nodal prostate cancer.

Prostate cancer (PCa) may recur after primary treatment but no standard of care exists for patients with pelvic nodal relapse. Based on obervational data, Extended Nodal Irradiation (ENI) might be associated with fewer treatment failures than Stereotactic Ablative Radiotherapy (SABR) to the involved node(s) alone. Ultra hypofractionated ENI is yet to be evaluated in this setting, but it could provide a therapeutic advantage if PCa has a low α/β ratio in addition to patient convenience/resource benefits. This volumetric modulated arc therapy (VMAT) planning study developed a class solution for 5-fraction Extended Nodal Irradiation (ENI) plus a simultaneous integrated boost (SIB) to involved node(s). Ten patients with oligorecurrent nodal disease after radical prostatectomy/post-operative prostate bed radiotherapy were selected. Three plans were produced for each dataset to deliver 25 Gy in 5 fractions ENI plus SIBs of 40, 35 and 30 Gy. The biologically effective dose (BED) formula was used to determine the remaining dose in 5 fractions that could be delivered to re-irradiated segments of organs at risk (OARs). Tumour control probability (TCP) and normal tissue complication probability (NTCP) were calculated using the LQ-Poisson Marsden and Lyman-Kutcher-Burman models respectively. Six patients had an OAR positioned within planning target volume node (PTVn), which resulted in reduced target coverage to PTV node in six, five and four instances for 40, 35 and 30 Gy SIB plans respectively. In these instances, only 30 Gy SIB plans had a median PTV coverage >90% (inter-quartile range 90-95). No OAR constraint was exceeded for 30 Gy SIB plans, including where segments of OARs were re-irradiated. Gross tumour volume node (GTVn) median TCP was 95.7% (94.4-96), 90.7% (87.1-91.2) and 78.6% (75.8-81.1) for 40, 35 and 30 Gy SIB plans respectively, where an α/β ratio of 1.5 was assumed. SacralPlex median NTCP was 43.2% (0.7-61.2), 12.1% (0.6-29.7) and 2.5% (0.5-5.1) for 40, 35 and 30 Gy SIB plans respectively. NTCP for Bowel_Small was <0.3% and zero for other OARs for all three plan types. Ultra hypofractionated ENI planning for pelvic nodal relapsed PCa appears feasible with encouraging estimates of nodal TCP and low estimates of NTCP, especially where a low α/β ratio is assumed and a 30 Gy SIB is delivered. This solution should be further evaluated within a clinical trial and compared against SABR to involved node(s) alone.

Small Animal IMRT Using 3D-Printed Compensators

Preclinical radiation replicating clinical intensity modulated radiation therapy (IMRT) techniques can provide data translatable to clinical practice. For this work, treatment plans were created for oxygen-guided dose-painting in small animals using inverse-planned IMRT. Spatially varying beam intensities were achieved using 3-dimensional (3D)-printed compensators. Optimized beam fluence from arbitrary gantry angles was determined using a verified model of the XRAD225Cx treatment beam. Compensators were 3D-printed with varied thickness to provide desired attenuation using copper/polylactic-acid. Spatial resolution capabilities were investigated using printed test-patterns. Following American Association of Physicists in Medicine TG119, a 5-beam IMRT plan was created for a miniaturized (∼1/8th scale) C-shape target. Electron paramagnetic resonance imaging of murine tumor oxygenation guided simultaneous integrated boost (SIB) plans conformally treating tumor to a base dose (Rx1) with boost (Rx2) based on tumor oxygenation. The 3D-printed compensator intensity modulation accuracy and precision was evaluated by individually delivering each field to a phantom containing radiochromic film and subsequent per-field gamma analysis. The methodology was validated end-to-end with composite delivery (incorporating 3D-printed tungsten/polylactic-acid beam trimmers to reduce out-of-field leakage) of the oxygen-guided SIB plan to a phantom containing film and subsequent gamma analysis. Resolution test-patterns demonstrate practical printer resolution of ∼0.7 mm, corresponding to 1.0 mm bixels at the isocenter. The miniaturized C-shape plan provides planning target volume coverage (V95% = 95%) with organ sparing (organs at risk Dmax < 50%). The SIB plan to hypoxic tumor demonstrates the utility of this approach (hypoxic tumor V95%,Rx2 = 91.6%, normoxic tumor V95%,Rx1 = 95.7%, normal tissue V100%,Rx1 = 7.1%). The more challenging SIB plan to boost the normoxic tumor rim achieved normoxic tumor V95%,Rx2 = 90.9%, hypoxic tumor V95%,Rx1 = 62.7%, and normal tissue V100%,Rx2 = 5.3%. Average per-field gamma passing rates using 3%/1.0 mm, 3%/0.7 mm, and 3%/0.5 mm criteria were 98.8% ± 2.8%, 96.6% ± 4.1%, and 90.6% ± 5.9%, respectively. Composite delivery of the hypoxia boost plan and gamma analysis (3%/1 mm) gave passing results of 95.3% and 98.1% for the 2 measured orthogonal dose planes. This simple and cost-effective approach using 3D-printed compensators for small-animal IMRT provides a methodology enabling preclinical studies that can be readily translated into the clinic. The presented oxygen-guided dose-painting demonstrates that this methodology will facilitate studies driving much needed biologic personalization of radiation therapy for improvements in patient outcomes.

A knowledge-based quantitative approach to characterize treatment plan quality: Application to prostate VMAT planning.

To characterize treatment plan (TP) quality, a quantitative quality control (QC) tool is proposed. The tool is validated using volumetric modulated arc therapy (VMAT) plans for treatment of prostate cancer by estimating the achievable organ at risk (OAR) sparing, based on the knowledge learned from prior plans. Prostate TP quality was investigated by evaluating the achieved OAR sparing in the rectum and bladder, based on their proximity to target surface. The knowledge base used in this work comprises 450 plans, consisting of 181 homogenous prostate plans and 269 simultaneous integrated boost (SIB) prostate plans. A knowledge-based algorithm was used to relate the absorbed doses of the OARs (rectum and bladder) and their proximity to the planning target volume (PTV). A metric (Mq,r value) was calculated to characterize the OAR sparing based on the weighted differences of the mean doses at binned distances to the PTV surface. The 90% probability ellipse of the normally distributed OARs Mq,r values was considered to define a threshold above which the treatment plan was re-optimized. Following re-optimization, 8/11 of the homogenous plans and 6/13 of the SIB plans outside the 90% probability ellipse could be re-optimized to gain better OAR sparing while achieving the same or better target coverage. However, 3/4 of the homogenous TPs and 1/9 of the SIB TPs between 80% and 90% were improved. Mq,r values of bladder and rectum after re-optimizing the plans in both groups of homogenous and SIB showed lower values compared to the corresponding values before re-optimization, which implies that better OARs sparing was achieved. This work demonstrates an effective anatomy-specific QC tool for identifying suboptimal plans and determining the achievable OAR sparing for each individual patient anatomy.

Simultaneous Integrated Boost of Lung Tumors in the Stereotactic Ablative Setting using BgRT Tracked Delivery

Biology-guided radiotherapy is a new radiation modality that utilizes real-time partial FDG images of tumors to deliver a dynamically tracked dose distribution. A key application is to ablate moving lung tumors without prescribing the therapeutic dose to the entire motion envelope of the tumor as is done with internal tumor volume (ITV) techniques. Better normal tissue sparing with a BgRT tracked dose distribution may furthermore enable delivery of a simultaneous integrated boost (SIB) to the tracked GTV to improve tumor response. This study assesses the utility of the BgRT SIB approach for mobile lung tumors and compares resultant dosimetric parameters with SBRT-ITV technique. Two representative cases of lung tumors with meaningful motion profiles that previously underwent lung SBRT were selected for this BgRT planning study. The planning objective was to deliver 50 Gy to the planning target volume (PTV) and 60 Gy simultaneous integrated boost to the gross tumor volume (GTV) in 5 fractions. In BgRT, a single respiratory phase was used to contour the tracked GTV and a 5 mm expansion was used to delineate the tracked PTV. For SBRT, prescription volumes were contoured by summing target volumes across all respiratory phases to create an internal planning tumor volume (IPTV) and an internal gross tumor volume (IGTV). All SBRT and BgRT plans were generated on a prototype BgRT treatment planning system. Both tumors had maximum excursions of 1.2 cm. The BgRT SIB plans met all dosimetric objectives and normal tissue constraints. Maximum achieved GTV doses were 80 Gy and 74.4 Gy in the two patients, while corresponding lung V20s were 4.2% and 2.8%, respectively. The BgRT-PTV was 55.9% and 40.7% smaller in the two patients when compared to the corresponding SBRT-IPTV. Likewise, the BgRT-GTV prescription volume was reduced by 68% and 43.3%, respectively, when compared to the corresponding SBRT-IGTVs. Compared to SBRT-ITV plans, BgRT plans resulted in average relative percentage reductions in all lung dosimetric parameters; the lung V20, V10, V5, D1500cc, and MLD were reduced by 20.7%, 15.1%, 15.3%, 30% and 19.0%, respectively. BgRT plans resulted in reduced target volumes and better organ sparing compared to SBRT in the context of SIB to a moving lung target. This investigation provides proof-of-concept that dose distributions delivered by dynamic tracking based on partial FDG images can enable dose escalation to the GTV in the stereotactic ablative setting. This approach may be particularly beneficial for radioresistant lung metastases, such as those arising from colorectal or sarcoma primary tumors.

Dose-escalated volumetric modulated arc therapy for total marrow irradiation: A feasibility dosimetric study with 4DCT planning and simultaneous integrated boost.

To evaluate the planning feasibility of dose-escalated total marrow irradiation (TMI) with simultaneous integrated boost (SIB) to the active bone marrow (ABM) using volumetric modulated arc therapy (VMAT), and to assess the impact of using planning organs at risk (OAR) volumes (PRV) accounting for breathing motion in the optimization. Five patients underwent whole-body CT and thoraco-abdominal 4DCT. A planning target volume (PTV) including all bones and ABM was contoured on each whole-body CT. PRV of selected OAR (liver, heart, kidneys, lungs, spleen, stomach) were determined with 4DCT. Planning consisted of 9-10 full 6 MV photon VMAT arcs. Four plans were created for each patient with 12Gy prescribed to the PTV, with or without an additional 4Gy SIB to the ABM. Planning dose constraints were set on the OAR or on the PRV. Planning objective was a PTV Dmean<110% of the prescribed dose, a PTV V110%<50%, and OAR Dmean≤50-60%. PTV Dmean<110% was accomplished for most plans (n=18/20), while all achieved V110%<50%. SIB plans succeeded to optimally cover the boost volume (median ABM Dmean=16.3Gy) and resulted in similar OAR sparing compared to plans without SIB (median OAR Dmean=40-54% of the ABM prescribed dose). No statistically significant differences between plans optimized with constraints on OAR or PRV were found. Adding a 4Gy SIB to the ABM for TMI is feasible with VMAT technique, and results in OAR sparing similar to plans without SIB. Setting dose constraints on PRV does not impair PTV dosimetric parameters.

A planning study of focal dose escalations to multiparametric MRI-defined dominant intraprostatic lesions in prostate proton radiation therapy.

The purpose of this study is to investigate the dosimetric effect and clinical impact of delivering a focal radiotherapy boost dose to multiparametric MRI (mp-MRI)-defined dominant intraprostatic lesions (DILs) in prostate cancer using proton therapy. We retrospectively investigated 36 patients with pre-treatment mp-MRI and CT images who were treated using pencil beam scanning (PBS) proton radiation therapy to the whole prostate. DILs were contoured on co-registered mp-MRIs. Simultaneous integrated boost (SIB) plans using intensity-modulated proton therapy (IMPT) were created based on conventional whole-prostate-irradiation for each patient and optimized with additional DIL coverage goals and urethral constraints. DIL dose coverage and organ-at-risk (OAR) sparing were compared between conventional and SIB plans. Tumor control probability (TCP) and normal tissue complication probability (NTCP) were estimated to evaluate the clinical impact of the SIB plans. Optimized SIB plans significantly escalated the dose to DILs while meeting OAR constraints. SIB plans were able to achieve 125, 150 and 175% of prescription dose coverage in 74, 54 and 17% of 36 patients, respectively. This was modeled to result in an increase in DIL TCP by 7.3-13.3% depending on and DIL risk level. The proposed mp-MRI-guided DIL boost using proton radiation therapy is feasible without violating OAR constraints and demonstrates a potential clinical benefit by improving DIL TCP. This retrospective study suggested the use of IMPT-based DIL SIB may represent a strategy to improve tumor control. This study investigated the planning of mp-MRI-guided DIL boost in prostate proton radiation therapy and estimated its clinical impact with respect to TCP and NTCP.

Patterns of Failure Observed in the 2-Step Institution Credentialing Process for NRG Oncology/Radiation Therapy Oncology Group 1005 (NCT01349322) and Lessons Learned

PurposeTo investigate patterns of failure in institutional credentialing submissions to NRG/RTOG 1005 with the aim of improving the quality and consistency for future breast cancer protocols. Methods and MaterialsNRG/RTOG 1005 allowed the submission of 3-dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), and simultaneous integrated boost (SIB) breast plans. Credentialing required institutions to pass a 2-step quality assurance (QA) process: (1) benchmark, requiring institutions to create a plan with no unacceptable deviations and ≤1 acceptable variation among the dose volume (DV) criteria, and (2) rapid review, requiring each institution’s first protocol submission to have no unacceptable deviations among the DV criteria or contours. Overall rates, number of resubmissions, and reasons for resubmission were analyzed for each QA step. ResultsIn total, 352 institutions participated in benchmark QA and 280 patients enrolled had rapid review QA. Benchmark initial failure rates were similar for 3DCRT (18%), IMRT (17%), and SIB (18%) plans. For 3DCRT and IMRT benchmark plans, ipsilateral lung most frequently failed the DV criteria, and SIB DV failures were seen most frequently for the heart. Rapid review contour initial failures (35%) were due to target rather than organs at risk. For 29% of the rapid review initial failures, the planning target volume boost eval volume was deemed an unacceptable deviation. ConclusionsThe review of the benchmark and rapid review QA submissions indicates that acceptable variations or unacceptable deviations for the ipsilateral lung and heart dose constraints were the most commonly observed cause of benchmark QA failure, and unacceptable deviations in target contouring, rather than normal structure contouring, were the most common cause of rapid review QA failure. These findings suggest that a rigorous QA process is necessary for high quality and homogeneity in radiation therapy in multi-institutional trials of breast cancer to ensure that the benefits of radiation therapy far outweigh the risks.

Feasibility study of conformal forward planned simultaneous integrated boost technique comparable to IMRT and VMAT in pelvic irradiation for locally advanced cervical cancer

Abstract Aim: To check the feasibility of simultaneous integrated boost (SIB) using a forward planned field in field (FIF) conformal technique for the treatment of carcinoma of the cervix IIIB and compare it dosimetrically with other advanced inverse planning techniques. Methods: In our study 33 patients of carcinoma of the cervix IIIB were planned for SIB using conformal FIF technique and they were compared with retrospectively planned IMRT and VMAT techniques. SIB using conformal FIF was planned by two different methods. Results: The results of our study indicate that forward planned Conformal SIB techniques are comparable with inverse planned techniques dosimetrically, in terms of conformity Index, Homogeneity Index, Maximum dose, etc. The ability of FIF SIB plans to produce dose contrast in differential dose accumulation was compared and analyzed and the results were encouraging. To treat an advanced/bulky disease like Carcinoma of the Cervix IIIB in centers with large patient load, utilizing advanced techniques such as IMRT and VMAT is both technically and practically difficult. Despite VMAT’s shorter delivery time, the procedures involved are time-consuming. Conclusion: Hence forward planned SIB techniques may be used to achieve similar dosimetric effects of IMRT and VMAT techniques without much compromise in plan quality and patient throughput for treating bulky carcinoma of the cervix IIIB cases. However, the clinical results need to be carefully compared and evaluated and reported.

Dosimetric Comparison of Sequential Versus Simultaneous-integrated Boost in Early-stage Breast Cancer Patients Treated With Breast-conserving Surgery.

To compare simultaneous-integrated boost (SIB) versus sequential-boost (SB) delivered in the context of whole-breast irradiation (WBI) via volumetric-modulated arc therapy (VMAT) and helical-tomotherapy (HT). Planning target-volume (PTV) dosimetric parameters and organs at risk (OAR) were analyzed for SB plan (50 Gy plus 16 Gy boost) and SIB plan (50.4 Gy WBI and 64.4 Gy tumor bed boost) in VMAT and HT techniques. Conformity and homogeneity for target-volume doses were better in HT plans compared to VMAT plans. There were no significant differences in ipsilateral lung doses between VMAT and HT plans for SB/SIB techniques, except for a significantly higher lung V5 value with VMAT-SB, and lung V13 value with HT-SIB technique. HT provided a statistically significant decrease in contralateral lung mean V5. The SIB technique showed better target-volume dose distribution in both HT and VMAT plans, and better sparing heart in HT compared to the SB technique.

Breast-conserving radiotherapy with simultaneous integrated boost; field-in-field three-dimensional conformal radiotherapy versus inverse intensity-modulated radiotherapy - A dosimetric comparison: Do we need intensity-modulated radiotherapy?

Background and Purpose:To examine the feasibility of improving breast-conserving radiotherapy with simultaneous integrated boost (SIB) and analyzing the efficiency of forward versus inverse intensity-modulated radiotherapy (IMRT) techniques in providing the same.Materials and Methods:Three-dimensional conformal radiotherapy (3DCRT) field-in-field (FIF) plans with simultaneous and sequential boost and IMRT SIB plans were generated for the datasets of 20 patients who had undergone breast-conserving surgery. The 3 plans were compared dosimetrically for efficiency in terms of planning target volume (PTV) coverage (PTV 95%), homogeneity and conformity, dose delivered to ipsilateral/contralateral lungs (I/L: V10, V20, C/L: Vmean, V5), heart and contralateral breast (Vmean, V30 for heart and Vmean, V1, V5 for C/L breast).Results:The FIF 3DCRT plan with SIB (PLAN B) was more homogeneous than the classical technique with sequential boost (PLAN A). There were less hot spots in terms of Dmax (63.7 ± 1.3) versus Dmax (68.9 ± 1), P < 0.001 and boost V107%, B (0.3 ± 0.7) versus A (3.5 ± 5.99), P = 0.001. The IMRT SIB (PLAN C) did not provide any significant dosimetric advantage over the 3DCRT SIB technique. IMRT SIB plan C was associated with increased dose to contralateral lung in-terms of V5 (10.35 +/- 18.23) vs. (1.13 +/- 4.24), P = 0.04 and Vmean (2.12 ± 2.18) versus Vmean (0.595 ± 0.89), P = 0.008. There was 3-fold greater exposure in terms of Monitor Unit (MU) (1024.9 ± 298.32 versus 281.05 ± 20.23, P < 0.001) and treatment delivery time.Conclusions:FIF 3DCRT SIB provides a dosimetrically acceptable and technically feasible alternative to the classical 3DCRT plan with sequential boost for breast-conserving radiotherapy. It reduces treatment time by 2 weeks. IMRT SIB does not appear to have any dosimetric advantage; it is associated with significantly higher doses to contralateral lung and heart and radiation exposure in terms of MU.

Potential of Proton Therapy to Reduce Acute Hematologic Toxicity in Concurrent Chemoradiation Therapy for Esophageal Cancer

PurposeRadiation therapy dose escalation using a simultaneous integrated boost (SIB) is predicted to improve local tumor control in esophageal cancer; however, any increase in acute hematologic toxicity (HT) could limit the predicted improvement in patient outcomes. Proton therapy has been shown to significantly reduce HT in lung cancer patients receiving concurrent chemotherapy. Therefore, we investigated the potential of bone marrow sparing with protons for esophageal tumors.Methods and MaterialsTwenty-one patients with mid-esophageal cancer who had undergone conformal radiation therapy (3D50) were selected. Two surrogates for bone marrow were created by outlining the thoracic bones (bone) and only the body of the thoracic vertebrae (TV) in Eclipse. The percentage of overlap of the TV with the planning treatment volume was recorded for each patient. Additional plans were created retrospectively, including a volumetric modulated arc therapy (VMAT) plan with the same dose as for 3D50; a VMAT SIB plan with a dose prescription of 62.5 Gy to the high-risk subregion within the planning treatment volume; a reoptimized TV-sparing VMAT plan; and a proton therapy plan with the same SIB dose prescription. The bone and TV dose metrics were recorded and compared across all plans and variations with respect to PTV and percentage of overlap for each patient.ResultsThe 3D50 plans showed the highest bone mean dose and TV percentage of volume receiving ≥30 Gy (V30Gy) for each patient. The VMAT plans irradiated a larger bone V10Gy than did the 3D50 plans. The reoptimized VMAT62.5 VT plans showed improved sparing of the TV volume, but only the proton plans showed significant sparing for bone V10Gy and bone mean dose, especially for patients with a larger PTV.ConclusionsThe results of the present study have shown that proton therapy can reduced bone marrow toxicity.