Adaptive Radiation Therapy Strategy Research Articles

Dosimetric benefits of adaptive radiation therapy for patients with stage III non-small cell lung cancer

BackgroundDaily adaptive radiation therapy (ART) of patients with non-small cell lung cancer (NSCLC) lowers organs at risk exposure while maintaining the planning target volume (PTV) coverage. Thus, ART allows an isotoxic approach with increased doses to the PTV that could improve local tumor control. Herein we evaluate daily online ART strategies regarding their impact on relevant dose-volume metrics.MethodsDaily cone-beam CTs (1 × n = 28, 1 × n = 29, 11 × n = 30) of 13 stage III NSCLC patients were converted into synthetic CTs (sCTs). Treatment plans (TPs) were created retrospectively on the first-fraction sCTs (sCT1) and subsequently transferred unaltered to the sCTs of the remaining fractions of each patient (sCT2−n) (IGRT scenario). Two additional TPs were generated on sCT2−n: one minimizing the lung-dose while preserving the D95%(PTV) (isoeffective scenario), the other escalating the D95%(PTV) with a constant V20Gy(lungipsilateral) (isotoxic scenario).ResultsCompared to the original TPs predicted dose, the median D95%(PTV) in the IGRT scenario decreased by 1.6 Gy ± 4.2 Gy while the V20Gy(lungipsilateral) increased in median by 1.1% ± 4.4%. The isoeffective scenario preserved the PTV coverage and reduced the median V20Gy(lungipsilateral) by 3.1% ± 3.6%. Furthermore, the median V5%(heart) decreased by 2.9% ± 6.4%. With an isotoxic prescription, a median dose-escalation to the gross target volume of 10.0 Gy ± 8.1 Gy without increasing the V20Gy(lungipsilateral) and V5%(heart) was feasible.ConclusionsWe demonstrated that even without reducing safety margins, ART can reduce lung-doses, while still reaching adequate target coverage or escalate target doses without increasing ipsilateral lung exposure. Clinical benefits by means of toxicity and local control of both strategies should be evaluated in prospective clinical trials.

Adaptive radiation therapy strategies in the treatment of prostate cancer patients using hypofractionated VMAT.

PurposeTo perform a comprehensive evaluation of eight adaptive radiation therapy strategies in the treatment of prostate cancer patients who underwent hypofractionated volumetric modulated arc therapy (VMAT) treatment.Material and methodsThe retrospective study included 20 prostate cancer patients treated with 40 Gy total dose over five fractions (8 Gy/fraction) using VMAT. Daily cone beam computed tomography images were acquired before the delivery of every fraction and then, with the application of deformable image registration used for the estimation of daily dose, contouring and plan re‐optimization. Dosimetric benefits of the various ART strategies were quantified by the comparison of dose and dose‐volume metrics derived from treatment planning objectives for original treatment plan and adapted plans with the consideration of target volumes (PTV and CTV) as well as critical structures (bladder, rectum, left, and right femoral heads).ResultsPercentage difference (ΔD) between planning objectives and delivered dose in the D99% > 4000cGy (CTV) metric was −3.9% for the non‐ART plan and 2.1% to 4.1% for ART plans. For D99% > 3800cGy and Dmax < 4280cGy (PTV), ΔD was −11.2% and −6.5% for the non‐ART plan as well as −3.9% to −1.6% and −0.2% to 1.8% for ART plans, respectively. For D15% < 3200 cGy and D20% < 2800 cGy (bladder), ΔD was −62.4% and −68.8% for the non‐ART plan as well as −60.0% to −57.4% and −67.0% to −64.0% for ART plans. For D15% < 3200 cGy and D20% < 2800 cGy (rectum), ΔD was −11.4% and −8.15% for non‐ART plan as well as −14.9% to −9.0% and −11.8% to −5.1% for ART plans.ConclusionsDaily on‐line adaptation approaches were the most advantageous, although strategies adapting every other fraction were also impactful while reducing relative workload as well. Offline treatment adaptations were shown to be less beneficial due to increased dose delivered to bladder and rectum compared toother ART strategies.

Automatic Segmentation Using Deep Learning to Enable Online Dose Optimization During Adaptive Radiation Therapy of Cervical Cancer

This study investigated deep learning models for automatic segmentation to support the development of daily online dose optimization strategies, eliminating the need for internal target volume expansions and thereby reducing toxicity events of intensity modulated radiation therapy for cervical cancer. The cervix-uterus, vagina, parametrium, bladder, rectum, sigmoid, femoral heads, kidneys, spinal cord, and bowel bag were delineated on 408 computed tomography (CT) scans from patients treated at MD Anderson Cancer Center (n = 214), Polyclinique Bordeaux Nord Aquitaine (n = 30), and enrolled in a Medical Image Computing & Computer Assisted Intervention challenge (n= 3). The data were divided into 255 training, 61 validation, 62 internal test, and 30 external test CT scans. Two models were investigated: the 2-dimensional (2D) DeepLabV3+ (Google) and 3-dimensional (3D) Unet in RayStation (RaySearch Laboratories). Three intensity modulated radiation therapy plans were generated on each CT of the internal and external test sets using either the manual, 2D model, or 3D model segmentations. The dose constraints followed the External beam radiochemotherapy and MRI based adaptive BRAchytherapy in locally advanced CErvical cancer (EMBRACE) II protocol, with reduced margins of 5 and 3 mm for the target and nodal planning target volume. Geometric discrepancies between the manual and predicted contours were assessed using the Dice similarity coefficient (DSC), distance-to-agreement, and Hausdorff distance. Dosimetric discrepancies between the manual and model doses were assessed using clinical indices on the manual contours and the gamma index. Interobserver variability was assessed for the cervix-uterus, parametrium, and vagina for the definition of the primary clinical target volume (CTVT) on the external test set. Average DSCs across all organs were 0.67 to 0.96, 0.71 to 0.97, and 0.42 to 0.92 for the 2D model and 0.66 to 0.96, 0.70 to 0.97, and 0.37 to 0.93 for the 3D model on the validation, internal, and external test sets. Average DSCs of the CTVT were 0.88 and 0.81 for the 2D model and 0.87 and 0.82 for the 3D model on the internal and external test sets. Interobserver variability of the CTVT corresponded to a mean (range) DSC of 0.85 (0.77-0.90) on the external test set. On the internal test set, the doses from the 2D and 3D model contours provided a CTVT V42.75 Gy >98% for 98% and 91% of the CT scans, respectively. On the external test set, these percentages were increased to 100% and 93% for the 2D and 3D models, respectively. The investigated models provided auto-segmentation of the cervix anatomy with similar performances on 2 institutional data sets and reasonable dosimetric accuracies using small planning target volume margins, paving the way to automatic online dose optimization for advanced adaptive radiation therapy strategies.

Dosimetric Evaluation of Incorporating Patient Geometric Variations Into Adaptive Plan Optimization Through Probabilistic Treatment Planning in Head and Neck Cancers

Four-dimensional (4D) adaptive radiation therapy (ART) treatment planning is an alternative to the conventional margin-based treatment planning approach. In 4D ART, interfraction patient geometric variations, gathered from computed tomography (CT) or cone beam CT (CBCT) images acquired during the patient treatment course, are directly incorporated into the adaptive plan optimization using a probabilistic treatment planning method. The goal of the present planning study was to evaluate the dosimetric differences between 4D ART and conventional margin-based adaptive planning strategies for head and neck cancers. In addition, we examined whether the dose differences achieved with 4D ART would translate into clinically relevant toxicity reductions using the existing normal tissue complication probability (NTCP) models. For 18 head and neck cancer patients, the treatment plans were retrospectively generated for 4 different treatment strategies, including a solely image guided radiation therapy (IGRT) strategy (IGRT-only), 2 conventional adaptive treatment planning strategies using 3- and 0-mm planning target volume (PTV) margins, and the 4D ART strategy. In the IGRT-only strategy, a conventional 3-mm PTV margin treatment plan was applied for the entire treatment course. In the 2 conventional adaptive strategies, 2 new treatment plans were generated during the treatment course using diagnostic planning CT scans acquired after the 10th and 22nd fractions. The 4D ART followed the same adaptive schedule, except that the 4D adaptive plan was generated using 5 CBCT images acquired during the 5 most recent treatment fractions. For each strategy, the actual delivered dose for the entire treatment course was constructed by calculating the daily doses on 35 CBCT scans, deforming back to the pretreatment planning CT scan, and accumulating over all 35 fractions. The target coverage was evaluated using the percentage of target volume receiving ≥100% of the prescription dose (V100%) and the minimum dose to 99% of the target volume (D99). It was considered adequate if the V100% was ≥95% and the dose deficit in D99 was ≤2Gy (with respect to the prescription dose). For each strategy, the dose received by the organs at risk (OARs) was also evaluated, and the corresponding NTCP values were subsequently calculated using 3 NTCP models. Adequate target coverage was achieved for the primary clinical target volume (CTV1) and elective nodal CTV (CTV2) with a 3-mm PTV margin, regardless of adaptation. The 3-mm ART plan reduced the OAR mean dose by 1 to 2Gy compared with the IGRT-only plan. The 0-mm ART plan further reduced the OAR dose by another 2 to 3Gy at the expense of target coverage: 3 and 1 patient had V100% <95%, and 6 and 5 patients had a >2 Gy dose deficit in D99 for the CTV1 and CTV2, respectively. Use of 4D ART improved target coverage and attained OAR sparing similar to that with 0-mm ART. The number of patients with V100% <95% and >2 Gy D99 deficit decreased to 0 and 0 for CTV1 and 0 and 2 for CTV2, respectively. The NTCP calculations suggested that 4D ART could benefit a substantial portion of patients compared with IGRT-only because 17 and 12 patients had ≥5% and ≥10% NTCP reductions for parotid toxicity and 18 and 3 patients had ≥5% and ≥10% NTCP reductions for swallowing toxicity, respectively. Compared with margin-based adaptive planning strategies, 4D ART provides a better balance between target coverage and OAR sparing. NTCP estimation predicted for theoretical clinical benefits that warrant further clinical validation.

CBCT-guided evolutive library for cervical adaptive IMRT.

In the context of adaptive radiation therapy (ART) for locally advanced cervical carcinoma (LACC), this study proposed an original cone-beam computed tomography (CBCT)-guided "Evolutive library" and evaluated it against four other known radiotherapy (RT) strategies. For 20 patients who underwent intensity-modulated radiation therapy (IMRT) for LACC, three planning CTs [with empty (EB), intermediate (IB), and full (FB) bladder volumes], a CT scan at 20 Gy and bi-weekly CBCTs for 5 weeks were performed. Five RT strategies were simulated for each patient: "Standard RT" was based on one IB planning CT; "internal target volume (ITV)-based RT" was an ITV built from the three planning CTs; "RT with one mid-treatment replanning (MidTtReplan)" corresponded to the standard RT with a replanning at 20 Gy; "Pretreatment library ART" using a planning library based on the three planning CTs; and the "Evolutive library ART", which was the "Pretreatment library ART" strategy enriched by including some CBCT anatomies into the library when the daily clinical target volume (CTV) shape differed from the ones in the library. Two planning target volume (PTV) margins of 7 and 10 mm were evaluated. All the strategies were geometrically compared in terms of the percentage of coverage by the PTV, for the CTV and the organs at risk (OAR) delineated on the CBCT. Inadequate coverage of the CTV and OARs by the PTV was also assessed using deformable image registration. The cumulated dose distributions of each strategy were likewise estimated and compared for one patient. The "Evolutive library ART" strategy involved a number of added CBCTs: 0 for 55%; 1 for 30%; 2 for 5%; and 3 for 10% of patients. Compared with the other four, this strategy provided the highest CTV geometric coverage by the PTV, with a mean (min-max) coverage of 98.5% (96.4-100) for 10 mm margins and 96.2% (93.0-99.7) for 7 mm margins (P < 0.05). Moreover, this strategy significantly decreased the geometric coverage of the bowel. CTV undercoverage by PTV occurred in the anterior and superior uterine regions for all strategies. The dosimetric analysis at 7 mm similarly demonstrated that the "Evolutive library ART" increased the V42.75Gy of the CTV by 27%, 20%, 13%, and 28% compared with "Standard RT", "ITV-based RT", "MidTtReplan", and "Pretreatment library ART", respectively. The dose to the bowel was also decreased by the "Evolutive library ART" compared with that by the other strategies. The "Evolutive library ART" is a personalized ART strategy that comprises a pretreatment planning library of three CT scans, enriched for half of the patients by one to three per-treatment CBCTs. This original strategy increased both the CTV coverage and bowel sparing compared with all the other tested strategies and enables us to consider a PTV margin reduction.

Dosimetry and Survival From an Adaptive Radiation Therapy Clinical Trial for Limited-Stage Small Cell Lung Cancer

When added to chemotherapy, radiation therapy (RT) improves local control and overall survival for limited-stage small cell lung cancer (LS-SCLC) patients. Evidence suggests RT dose intensification improves outcomes, but normal tissue toxicity usually limits RT dose escalation goals. Rapidly-responding tumors such as SCLC may be amenable to an adaptive radiation therapy strategy to achieve safe RT dose escalation. The purpose of this trial was to assess feasibility, quantify the dosimetric advantages, and assess failure patterns and survival associated with an adaptive RT planning strategy in LS-SCLC patients.

Developing an adaptive radiation therapy strategy for nasopharyngeal carcinoma

Adaptive radiotherapy (ART) has recently been introduced to restore the planned dose distribution by accounting for the anatomic changes during treatment. By quantifying the anatomic changes in nasopharyngeal carcinoma (NPC) patients, this study aimed to establish an ART strategy for NPC cases. A total of 30 NPC patients treated with helical tomotherapy were recruited. In the pretreatment megavoltage CT images, the anatomic changes of the posterolateral wall of nasopharynx (P-NP), neck region and parotid glands were measured and assessed. One-way repeated measure ANOVA was employed to define threshold(s) at any time-point. The presence of a threshold(s) would indicate significant anatomical change(s) such that replanning should be suggested. A pragmatic schedule for ART was established by evaluating the threshold for each parameter. Results showed the P-NP, parotid gland and neck volumes demonstrated significant regressions over time. Respectively, the mean loss rates were 0.99, 1.35, and 0.39 %/day, and the mean volume losses were 35.70, 47.54 and 11.91% (all P < 0.001). The parotid gland shifted medially and superiorly over time by a mean of 0.34 and 0.24 cm, respectively (all P < 0.001). The neck region showed non-rigid posterior displacement, which increased from upper to lower neck. According to the threshold occurrences, three replans at 9th, 19th and 29th fractions were proposed. This ART strategy was able to accommodate the dosimetric consequences due to anatomic deviation over the treatment course. It is clinically feasible and would be recommended for centers where an adaptive planning system was not yet available.

Implementation of adaptive radiation therapy for urinary bladder carcinoma: Imaging, planning and image guidance

Background. Adaptive radiation therapy (ART) for urinary bladder cancer has emerged as a promising alternative to conventional RT with potential to minimize radiation-induced toxicity to healthy tissues. In this work we have studied bladder volume variations and their effect on healthy bladder dose sparing and intrafractional margins, in order to refine our ART strategy. Material and methods. An online ART treatment strategy was followed for five patients with urinary bladder cancer with the tumors demarcated using Lipiodol®. A library of 3–4 predefined treatment plans for each patient was created based on four successive computed tomography (CT) scans. Cone beam CT (CBCT) images were acquired before each treatment fraction and after the treatment at least weekly. In partial bladder treatment the sparing of the healthy part of the bladder was investigated. The bladder wall displacements due to bladder filling were determined in three orthogonal directions (CC, AP, DEX-SIN) using the treatment planning CT scans. An ellipsoidal model was applied in order to find the theoretical maximum values for the bladder wall displacements. Moreover, the actual bladder filling rate during treatment was evaluated using the CBCT images. Results. In partial bladder treatment the volume of the bladder receiving high absorbed doses was generally smaller with a full than empty bladder. The estimation of the bladder volume and the upper limit for the intrafractional movement of the bladder wall could be represented with an ellipsoidal model with a reasonable accuracy. Observed maximum growth of bladder dimensions was less than 10 mm in all three orthogonal directions during 15 minute interval. Conclusion. The use of Lipiodol contrast agent enables partial bladder treatment with reduced irradiation of the healthy bladder volume. The ellipsoidal bladder model can be used for the estimation of the bladder volume changes and the upper limit of the bladder wall movement during the treatment fraction.

Dose Escalation for Locally Advanced Lung Cancer Using Adaptive Radiation Therapy With Simultaneous Integrated Volume-Adapted Boost

To test the feasibility of a planned phase 1 study of image-guided adaptive radiation therapy in locally advanced lung cancer. Weekly 4-dimensional fan beam computed tomographs (4D FBCT) of 10 lung cancer patients undergoing concurrent chemoradiation therapy were used to simulate adaptive radiation therapy: After an initial intensity modulated radiation therapy plan (0-30 Gy/2 Gy), adaptive replanning was performed on week 2 (30-50 Gy/2 Gy) and week 4 scans (50-66 Gy/2 Gy) to adjust for volume and shape changes of primary tumors and lymph nodes. Week 2 and 4 clinical target volumes (CTV) were deformably warped from the initial planning scan to adjust for anatomical changes. On the week 4 scan, a simultaneous integrated volume-adapted boost was created to the shrunken primary tumor with dose increases in 5 0.4-Gy steps from 66 Gy to 82 Gy in 2 scenarios: plan A, lung isotoxicity; plan B, normal tissue tolerance. Cumulative dose was assessed by deformably mapping and accumulating biologically equivalent dose normalized to 2 Gy-fractions (EQD2). The 82-Gy level was achieved in 1 in 10 patients in scenario A, resulting in a 13.4-Gy EQD2 increase and a 22.1% increase in tumor control probability (TCP) compared to the 66-Gy plan. In scenario B, 2 patients reached the 82-Gy level with a 13.9 Gy EQD2 and 23.4% TCP increase. The tested image-guided adaptive radiation therapy strategy enabled relevant increases in EQD2 and TCP. Normal tissue was often dose limiting, indicating a need to modify the present study design before clinical implementation.

Combined Online and Offline Adaptive Radiation Therapy

Adaptive Radiation therapy (ART) can be classified as offline and online ART. Offline ART is typically used to correct for systematic variations, while online ART is capable of accounting for both systematic and random variations but requires extensive online effort while the patient is lying on the treatment Table. The purpose of this work is to introduce a combined “online and offline” ART strategy, that is dosimetrically equivalent to existing online ART but with substantially reduced online effort.

A Volumetric Trend Analysis of the Prostate and Seminal Vesicles During a Course of Intensity-Modulated Radiation Therapy

The purpose of this study was to evaluate the volumetric changes of the prostate and seminal vesicles (SV) during a definitive course of intensity-modulated radiation therapy using a combined computed tomography (CT)-linear accelerator system. Fifteen patients were enrolled in this IRB-approved prospective study. The treatment plan was designed to deliver a total dose of 75.6 Gy over 42 fractions to 98% of the planning target volume. In-room CT scans were acquired using a CT-on-rails system 3 times weekly just before daily treatment throughout the course of radiation therapy. Rates of volume change over time for the prostate and SV were calculated using linear regression analysis. Fifteen patients had a total of 369 CT scans during the study. For 53% of patients (N = 8), there was a statistically significant decrease in prostate volume over time (range, 0.05-0.47 mL/d or 0.7%-3.5% per week). The median volume reduction was -11.5% (4.9 mL) at the end of the treatment. There was no significant change in the volume of the SV during the course of treatment. The decrease in prostate volume was significantly correlated with the initial volume of the prostate, with larger glands shrinking more during treatment (P = 0.001). Patients with enlarged prostates may experience volumetric reduction in their gland size during a protracted course of radiation therapy. However, the magnitude of the volume reduction is relatively small. In the current era of dose escalation, future studies with adaptive radiation therapy strategy may be appropriate to minimize radiation exposure to normal tissues.

KV-Cone Beam CT as an IGRT Tool in the Treatment of Early Stage Prostate Cancer: A Literature Review

Image-guided radiation therapy (IGRT) is an important quality assurance measure that can be used in tandem with conformal radiation therapy treatment. Cone beam computed tomography (CBCT) is a sophisticated IGRT technology that has recently been introduced to the clinical setting. Cone beam equipment includes kilovoltage (kV) CBCT that produces online, high-quality, three-dimensional images of the prostate gland. Interfractional displacements of the prostate can be quantified and adjustments made using kV-CBCT so that daily RT can be accurately delivered. In addition, the volumetric nature of CBCT allows deformations of the prostate gland and surrounding anatomy to be accounted for using adaptive radiation therapy strategies. This article provides an introduction to the main IGRT tools that can be used in parallel with conformal radiation therapy of prostate cancer. A literature review is performed to describe the major IGRT approaches; however, the focus will remain primarily on the technical and clinical applications of kV-CBCT. Important considerations including patient dose, resource implications, and possible changes to the radiation therapist's scope of practice are also discussed.