Adaptive Stereotactic Body Radiotherapy Research Articles

Interfractional Geometric Variations and Dosimetric Benefits of Online Adaptive Stereotactic Body Radiotherapy of Prostate Bed After Radical Prostatectomy

To evaluate volumetric and shape variations of target and organs-at-risk (OAR) of prostate patients receiving stereotactic body radiotherapy (SBRT) after radical prostatectomy and to investigate potential dosimetric benefits of MRI guided online adaptive planning (MRgART) to compensate for these variations.CTV and OAR were contoured by a single physician on the setup MRI images of 11 patients treated with an MR-Linac and enrolled on a phase II trial of post-prostatectomy SBRT. All patients followed institutional bladder and rectum filling protocols and received 5 fractions of 6-6.8 Gy to the prostate bed. Changes in interfractional volume were calculated and shape deformation was quantified by the Dice similar index (DSC). Dosimetric changes in CTV V95%, bladder maximum dose, V32.5 Gy, and rectal maximum dose, V32.5Gy and V27.5Gy were predicated by recalculating the initial treatment plan on the daily MRI. MRgART was retrospectively simulated if the predicted dose exceeds pre-set dosimetric criteria and the potential dosimetric improvement of MRgART was evaluated.Interfractional CTV volume and shape remained stable with median volumetric change of 3.0% (IQR -3.0% to 11.5%) and median DSC of 0.83 (IQR 0.79 to 0.88). Relatively large volumetric changes in bladder (median -24.5%, IQR -34.8% to 14.5%) and rectum (median 5.5%, IQR -9.7% to 20.7%) were observed while shape changes were moderate (median DSC of 0.79 and 0.67, respectively). Median CTV V95% was 98.4% (IQR 94.9% to 99.6%) for the predicted doses. However, MRgART would have been deemed necessary for 78% of the 55 fractions based on CTV undercoverage (16%), exceeding OAR constraints (50%), or both (11%). Simulated online ART improved the plan dosimetry and met dosimetric criteria in all adaptive fractions. Moderate correlations between CTV V95% and target DSC (R-squared = 0.73) and bladder mean dose versus bladder volumetric changes (R-squared = 0.61) were observed.Interfractional dosimetric variations resulting from target and OAR deformation are commonly encountered with post-prostatectomy RT and can be mitigated with MRgART.

Impact of hydrogel peri-rectal spacer insertion on seminal vesicles intrafraction motion during 1.5 T-MRI-guided adaptive stereotactic body radiotherapy for localized prostate cancer.

MR-guided daily-adaptive radiotherapy is improving the accuracy in the planning and delivery phases of the treatment. Rectal hydrogel-spacer may help in mitigating organ motion, but few data are currently available. We aimed to assess any potential impact of the device on seminal vesicles motion by measuring translational and rotational shifts between the pre- and post-treatment MRI scans of a total of 50 fractions in the first 10 patients who underwent MR-guided prostate SBRT (35 Gy/5 fx). Of them, five patients received the hydrogel-spacer. The comparative analysis was performed using the Mann-Whitney U-test. Median rotational shifts were: in anteroposterior 0° (range, 0.097°/0.112°; SD = 0.05°) vs 0° (-0.162/0.04°; SD = 0.07°) in the no-spacer subgroup (p = 0.36); lateral shifts were 0° (-0.1°/0.54°; SD = 0.28°) vs -0.85° in the no-spacer cohort (-1.56°/0.124°; SD = 0.054°; p = 0.22). Cranio-caudal shifts were 0° (-0.121°/0.029°; SD = 0.06°) in the spacer-cohort vs 0° (-0.066°/0.087°; SD = 0.69°; p = 0.53). Median translational shifts were: in anteroposterior 0.9 mm (-0.014 mm/0.031 mm; SD = 0.036 mm) in the spacer-group vs 0.030 mm (-0.14 mm/0.03 mm; SD = 0.032 mm; p = 0.8); latero-lateral shifts were -0.042 mm (-0.047 mm/0.07 mm; SD = 0.054 mm), vs -0.023 mm (-0.027 mm/-0.01 mm; SD = 0.023 mm) in the no-spacer group (p = 0.94). In cranio-caudal, statistically significant shifts were reported: 0.082 mm (0.06 mm/0.15 mm; SD = 0.04 mm) vs 0.06 mm (-0.06/0.08 mm; SD = 0.09 mm) in the no-spacer cohort (p = 0.031). A favorable impact of the hydrogel-spacer on seminal vesicles motion was observed only in cranio-caudal translational shifts, although being not clinically significant. Further studies are required to fully investigate the potential contribution of this device on vesicles motion. MR-guided daily adaptive radiotherapy may represent a game changer for prostate stereotactic body radiotherapy, given the possibility to better visualize soft-tissues anatomy and to daily recalculate the treatment plan based on real-time conditions. The use of devices like rectal ballon or rectal gel spacers has gained interest in the last years for the possibility to better spare the rectum during prostate radiotherapy. This is one of the first experiences exploring the role of rectal spacer on seminal vesicles intrafraction motion during MR-guided SBRT for prostate cancer.

Dosimetric effect of the intestinal gas of online adaptive stereotactic body radiotherapy on target and critical organs without online electron density correction for pancreatic cancer.

This study aimed to assess the dosimetric effect of intestinal gas of stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) on target and critical organs for pancreatic cancer without online electron density correction (EDC). Thirty pancreatic cancer patients who underwent online SMART were selected for this study. The treatment time of each stage and the total treatment time were recorded and analyzed. The concerned dose-volume parameters of target and organs-at-risk (OAR) were compared with and without an intestinal gas EDC using the Wilcoxon-signed rank test. Analysis items with p value < 0.05 were considered statistically significant. The relationships between dosimetric differences and intestinal gas volume variations were investigated using the Spearman test. The average treatment time was 82 min, and the average EDC time was 8 min, which accounted for 10% of the overall treatment time. There were no significant differences in CTV (GTV), PTV, bowel, stomach, duodenum, and skin (p > 0.05) with respect to dose volume parameters. For the Dmax of gastrointestinal organs (p = 0.03), the mean dose of the liver (p = 0.002) and kidneys (p = 0.03 and p = 0.04 for the left and right kidneys, respectively), there may be a risk of slight overestimation compared with EDC, and for the Dmax of the spinal cord (p = 0.02), there may be a risk of slight underestimation compared with EDC. A weak correlation for D95 in the PTV and D0.5 cc in the duodenum was observed. For patients with similar inter-fractional intestinal gas distribution, EDC had little dosimetric effects on the D0.5 cc of all GI organs and dose volume parameters of target in most plans. By omitting the EDC of intestinal gas, the online SMART treatment time can be shortened.

Rectal spacer hydrogel in 1.5T MR-guided and daily adapted SBRT for prostate cancer: dosimetric analysis and preliminary patient-reported outcomes.

The main aim of the current analysis was to explore the hypothetical advantages using rectal spacer during 1.5T MR-guided and daily adapted prostate cancer stereotactic body radiotherapy (SBRT) compared to a no-rectal spacer hydrogel cohort of patients. The SBRT-protocol consisted of a 35 Gy schedule delivered in 5 fractions. Herein, we present a dosimetric analysis between spacer and no-spacer patients. Furthermore, treatment tolerability and feasibility were preliminarily assessed according to clinicians-reported outcomes at the end of treatment and patient-reported outcomes measures (PROMs) in both arms. Toxicity and quality of life were assessed at baseline and after treatment using the Common Terminology Criteria for Adverse Events v. 5.0, International Prostatic Symptoms Score, ICIQ-SF, IIEF-5, and EORTC-QLQ-C30 and PR-25 questionnaires. 120 plans (pre- and daily adaptive SBRT planning) were analyzed in 20 patients (10 patients in spacer group and 10 patients in no-spacer group) treated using 1.5T MR-guided adaptive SBRT. Statistically significant dosimetric advantages were observed in favor of the spacer insertion, improving the planning target volume coverage in terms of V33.2Gy >95% and planning target volume 37.5 Gy <2% mainly during daily-adapted SBRT. Also, rectum V32, V28 and V18Gy and bladder V35Gy <1 cc were significantly reduced in the spacer cohort. Concerning the PROMS, all questionnaires showed no difference between the pre- and post-SBRT evaluation in both arms, excepting the physical functioning item of EORTC QLQ-C30 questionnaire that was declined in the no-spacer group. These preliminary results strongly suggest the adoption of perirectal spacer due to dosimetric advantages not only for rectal sparing but also for target coverage. Longer follow-up is required to validate the clinical impact in terms of clinicians-reported toxicity and PROMs. This the first experience reporting preliminary data concerning the potential dosimetric impact of rectal hydrogel spacer on MR-guided SBRT for prostate cancer.

Magnetic resonance image-guided adaptive stereotactic body radiotherapy for prostate cancer: preliminary results of outcome and toxicity.

Using moderate or ultra-hypofractionation, which is also known as stereotactic body radiotherapy (SBRT) for treatment of localized prostate cancer patients has been increased. We present our preliminary results on the clinical utilization of MRI-guided adaptive radiotherapy (MRgRT) for prostate cancer patients with the workflow, dosimetric parameters, toxicities and prostate-specific antigen (PSA) response. 50 prostate cancer patients treated with ultra-hypofractionation were included in the study. Treatment was performed with intensity-modulated radiation therapy (step and shoot) technique and daily plan adaptation using MRgRT. The SBRT consisted of 36.25 Gy in 5 fractions with a 7.25 Gy fraction size. The time for workflow steps was documented. Patients were followed for the acute and late toxicities and PSA response. The median follow-up for our cohort was 10 months (range between 3 and 29 months). The median age was 73.5 years (range between 50 and 84 years). MRgRT was well tolerated by all patients. Acute genitourinary (GU) toxicity rate of Grade 1 and Grade 2 was 28 and 36%, respectively. Only 6% of patients had acute Grade 1 gastrointestinal (GI) toxicity and there was no Grade ≥ 2 GI toxicity. To date, late Grade 1 GU toxicity was experienced by 24% of patients, 2% of patients experienced Grade 2 GU toxicity and 6% of patients reported Grade 2 GI toxicity. Due to the short follow-up, PSA nadir has not been reached yet in our cohort. In conclusion, MRgRT represents a new method for delivering SBRT with markerless soft tissue visualization, online adaptive planning and real-time tracking. Our study suggests that ultra-hypofractionation has an acceptable acute and very low late toxicity profile. MRgRT represents a new markerless method for delivering SBRT for localized prostate cancer providing online adaptive planning and real-time tracking and acute and late toxicity profile is acceptable.

Adaptive SBRT by 1.5T MR-linac for prostate cancer: On the accuracy of dose delivery in view of the prolonged session time.

Adaptive Stereotactic Body Radiotherapy (SBRT) of prostate cancer (PC) by online 1.5T MRi-guidance prolongs session-time, due to contouring and planning tasks, thus increasing the risk of prostate motion. Hence, the interest to verify the adequacy of the delivered dose. For twenty PC patients treated by 35Gy (Dp) in five fractions, daily pre- and post- delivery MRi scans were respectively used for adapt-to-shape (ATS) optimization, and re-computation of the delivered irradiation (Drec). Two expansion recipes, from Clinical (CTV) to Planning target volume (PTV), which slightly differed in the posterior margin were used for groups I and II, of ten patients each. Plans had to assure D95%≥95%Dp to PTV, and D1cc≤Dp to rectum, bladder, penile bulb, and urethral planning-risk-volume (urethral-PRV). The adequacy of the delivered dose was estimated by inter-fraction average (ifa) of dose-volume metrics computed from Drec. A cumulative dose (Dsum) was calculated from the five daily Drec deformed onto the simulation MRi. For each patient, CTV coverage resulted in D95%>95%Dp when estimated as ifa by Drec. No significant difference for D95% and D99% metrics to CTV resulted between groups I and II. D1cc was<Dp for rectum, urethral-PRV, and penile bulb, whereas<103.5%Dp for the bladder. Significant correlations resulted between metrics computed by Dsum and as ifa by Drec, by both linear-correlation analysis, and Receiver-Operating-Characteristic curve analysis. Our results for PC-SBRT confirm the adequacy of the delivered dose by ATS with 1.5T MR-linac, and the consistency between dose-volume metrics computed by Drec and Dsum.

Impact of a vacuum cushion on intrafraction motion during online adaptive MR-guided SBRT for pelvic and para-aortic lymph node oligometastases

Background and purposeVacuum cushion immobilization is commonly used during stereotactic body radiotherapy (SBRT) to reduce intrafraction motion. We investigated target and bony anatomy intrafraction motion (translations and rotations) during online adaptive SBRT on an MR-linac for pelvic/para-aortic lymph node metastases with and without vacuum cushion. Materials and methodsThirty-nine patients underwent 5x7 Gy SBRT on a 1.5T MR-linac, 19 patients were treated with vacuum cushion, 19 without and 1 patient sequentially with and without. Intrafraction motion was calculated for target lymph nodes (GTVs) and nearby bony anatomy, for three time intervals (pre-position verification (PV), pre-post, PV-post, relating to the online MRI scans) per treatment fraction. ResultsVacuum cushion immobilization significantly reduced anterior-posterior translations for the pre-PV and pre-post intervals, for bony anatomy and pre-post interval for GTV (p < 0.05). Mean GTV intrafraction motion reduction in posterior direction was 0.7 mm (95% confidence interval 0.3–1.1 mm) for pre-post interval (mean time = 32 min). Shifts in other directions were not significantly reduced. More motion occurred in pre-PV interval than in PV-post interval (mean time = 16 min for both); vacuum cushion immobilization did not reduce intrafraction motion during the beam-on period. ConclusionA vacuum cushion reduces GTV and bony anatomy intrafraction motion in posterior direction during pelvic/para-aortic lymph node SBRT. This motion reduction was found for the first 16 min per session. For single targets this motion can be corrected for directly with an MR-linac. Intrafraction motion was not reduced during the second half of the session, the period of radiotherapy delivery on an MR-linac. Vacuum cushion immobilization may not be necessary for patients with single lymph node oligometastases undergoing SBRT on an MR-linac.

Assessment of online adaptive MR-guided stereotactic body radiotherapy of liver cancers.

Online Adaptive Radiotherapy (ART) with daily MR-imaging has the potential to improve dosimetric accuracy by accounting for inter-fractional anatomical changes. This study provides an assessment for the feasibility and potential benefits of online adaptive MRI-Guided Stereotactic Body Radiotherapy (SBRT) for treatment of liver cancer. Ten patients with liver cancer treated with MR-Guided SBRT were included. Prescription doses ranged between 27 and 50Gy in 3-5 fx. All SBRT fractions employed daily MR-guided setup while utilizing cine-MR gating. Organs-at-risk (OARs) included duodenum, bowel, stomach, kidneys and spinal cord. Daily MRIs and contours were utilized to create each adapted plan. Adapted plans used the beam-parameters and optimization-objectives from the initial plan. Planning target volume (PTV) coverage and OAR constraints were used to compare non-adaptive and adaptive plans. PTV coverage for non-adapted treatment plans was below the prescribed coverage for 32/47 fractions (68%), with 11 fractions failing by more than 10%. All 47 adapted fractions met prescribed coverage. OAR constraint violations were also compared for several organs. The duodenum exceeded tolerance for 5/23 non-adapted and 0/23 for adapted fractions. The bowel exceeded tolerance for 5/34 non-adaptive and 1/34 adaptive fractions. The stomach exceeded tolerance for 4/19 non-adapted and 1/19 for adaptive fractions. Accumulated dose volume histograms were also generated for each patient. Online adaptive MR-Guided SBRT of liver cancer using daily re-optimization resulted in better target conformality, coverage and OAR sparing compared with non-adaptive SBRT. Daily adaptive planning may allow for PTV dose escalation without compromising OAR sparing.

1.5\u2009T MR-guided and daily adapted SBRT for prostate cancer: feasibility, preliminary clinical tolerability, quality of life and patient-reported outcomes during treatment

BackgroundUnity Elekta is a unique magnetic resonance (MR)-linac that conjugates a 1.5 Tesla MR unit with a 7 MV flattening filter free accelerator.A prospective observational study for the clinical use of Elekta Unity is currently ongoing in our department. Herein, we present our preliminary report on the feasibility, quality of life, and patient-reported outcomes measures (PROMs) for localized prostate cancer (PC) treated with stereotactic body radiotherapy (SBRT).MethodsThe SBRT protocol consisted of a 35 Gy schedule delivered in 5 fractions within 2 weeks. Toxicity and quality of life (QoL) were assessed at baseline and after treatment using the Common Terminology Criteria for Adverse Events v5.0, International Prostatic Symptoms Score (IPSS), ICIQ-SF, IIEF-5, and EORTC-QLQ-C30 and PR-25 questionnaires.ResultsBetween October 2019 and January 2020, 25 patients with localized PC were recruited. The median age was 68 years (range, 54–82); 4 were low risk, 11 favorable intermediate risk (IR) and 10 unfavorable IR. Median iPSA was 6.8 ng/ml (range, 1–19), and 9 of these patients (36%) received concurrent androgen deprivation therapy. Median prostate volume was 36 cc (range, 20–61); median baseline IPSS was 5 (range, 0–10). Median time for fraction was 53 min (range, 34–86); adaptive strategy with daily critical structure and target re-contouring and daily replanning (adapt to shape) was performed in all cases. No grade ≥ 3 adverse event was observed, three patients (12%) reported grade 2 acute genitourinary toxicity (urinary frequency, urinary tract pain and urinary retention), while only one patient reported mild rectal pain. No relevant deteriorations were reported in PROMs.ConclusionTo the best of our knowledge, this is the first experience reporting feasibility, clinician-reported outcome measurements, and PROMs for 1.5 T MR-guided adaptive SBRT for localized prostate cancer. The preliminary data collected here report optimal safety and excellent tolerability, as also confirmed by PROMs questionnaires. Moreover, the data on technical feasibility and timing of online daily adapted planning and delivery are promising. More mature data are warranted.Trial registrationDate of approval April 2019 and numbered MRI/LINAC n°23,748.

Radiothérapie stéréotaxique extra crânienne. Comment mieux protéger les tissus sains ?

The use of stereotactic body radiotherapy (SBRT) has increased rapidly over the past decade. Optimal preservation of normal tissues is a major issue because of their high sensitivity to high doses per session. Extreme hypofractionation can convert random errors into systematic errors. Optimal preservation of organs at risk requires first of all a rigorous implementation of this technique according to published guidelines. The robustness of the imaging modalities used for planning, and training medical and paramedical staff are an integral part of these guidelines too. The choice of SBRT indications, dose fractionation, dose heterogeneity, ballistics, are also means of optimizing the protection of normal tissues. Non-coplanarity and tracking of moving targets allow dosimetric improvement in some clinical settings. Automatic planning could also improve normal tissue protection. Adaptive SBRT, with new image guided radiotherapy modalities such as MRI, could further reduce the risk of toxicity.

Assessment of Online Adaptive MR-Guided SBRT of Liver Cancers

Online Adaptive Radiotherapy (ART) with daily MR imaging has the potential to improve target coverage by taking into account for anatomical changes during radiotherapy. The purpose of this study is to provide an assessment of potential benefits of online adaptive MRI-Guided Stereotactic Body Radiotherapy (SBRT) for treatment of liver cancer. Five patients with liver cancer who were treated with MR-Guided SBRT were included. Prescription doses ranged between 27-50 Gy in 3-5fx, with the 90%-95% of the PTV covered by 100% of the prescription dose. All patients underwent a planning MRI and setup MRIs prior to each fraction, all acquisitions utilized breath-hold conditions. All SBRT fractions were delivered under MR guidance with cine-MR gating of the gross tumor volume (GTV) based on a modified breath-hold technique. Patients received visual feedback throughout treatment delivery. The planning target volume (PTV) was created by expanding the GTV by 3mm uniform margin. The initial treatment plan was generated using step-and-shoot IMRT and utilized 9-12 beam groups, each beam group consisted of 3 equally spaced Co-60 beams. The electron density (ED) map and contours from planning MR were propagated to daily setup MRI using deformable image registration and were reviewed/edited by the physician. Each adapted plan was obtained by re-optimizing based on the contours on daily setup MRI using the same beam parameters and optimization objectives from the initial MR plan. Non-adaptive plans for each patient were created by recalculating the dose from the initial plan on the daily setup MRI, daily ED map and edited contours. The non-adaptive and adaptive plans were compared using PTV coverage and dose-volume constraints for OARs: duodenum, bowel, stomach, kidneys, and spinal cord. Daily plan adaptation provided increased PTV coverage for 11 of 23 fractions. While 7 fractions required adaptations due to violation of maximum dose constraint for duodenum and 3 fractions required adaptation due to violation of V30Gy <5cc constraint for bowel. Up to 27% decrease in mean dose to liver-GTV was achieved when using daily adaption even though this constraint was satisfied for all fractions. Similarly, up to 28% reduction in maximum cord dose and up to 18% reduction in mean kidney dose was achieved with daily adaptation. Online ART MR-Guided SBRT of liver cancer using daily re-optimization resulted in better target conformity and OAR sparing compared with non-adaptive SBRT. In our experience, adaptation provides the largest benefit when two or more OARs are proximal to the target additionally the larger the intra-fractional motion of the target and OARs the greater the benefit. Significant OAR sparing was still achieved for fractions that did not exceed OAR tolerances. Daily adaptation may allow for PTV dose escalation without compromising OAR sparing as compared to non-adaptive treatments. Further studies are needed to determine the limits to any dose escalation strategy.

Individualized Adaptive Stereotactic Body Radiotherapy for Liver Tumors in Patients at High Risk for Liver Damage

Patients with preexisting liver dysfunction could benefit the most from personalized therapy for liver tumors to balance maximal tumor control and minimal risk of liver failure. We designed an individualized adaptive trial testing the hypothesis that adapting treatment based on change in liver function could optimize the therapeutic index for each patient. To characterize the safety and efficacy of individualized adaptive stereotactic body radiotherapy (SRBT) for liver tumors in patients who have preexisting liver dysfunction. From 2010 to 2014, 90 patients with intrahepatic cancer treated with prior liver-directed therapy were enrolled in this large phase 2, single-arm, clinical trial at an academic medical center. All patients had at least 1 year of potential follow-up. Using indocyanine green retention at 15 minutes (ICGR15) as a direct biomarker of liver function and a Bayesian adaptive model, planned SBRT was individually modified midway through the course of therapy to maintain liver function after the complete course. The primary outcome was local control; the secondary outcome was safety and overall survival. Patients were 34 to 85 years of age, and 70% (63) were male. Ninety patients (69 [77%] with hepatocellular carcinoma, 4 [4%] with intrahepatic cholangiocarcinoma, and 17 [19%] with metastatic) received treatment to 116 tumors. Sixty-two patients (69%) had cirrhosis, 21 (23%) were Child-Pugh (CP) grade B. The median tumor size was 3 cm; 16 patients (18%) had portal vein involvement. Sixty-two (69%) received all 5 fractions (47 full dose, 15 dose-reduced owing to rising ICGR15). Treatment was well tolerated, with a lower than expected complication rate without adaptation: 6 (7%) experienced a 2-point decline in CP 6 months post-SBRT. The 1- and 2-year local control rates were 99% (95% CI, 97%-100%) and 95% (95% CI, 91%-99%), respectively. We demonstrated that the treatment strategy of individualized adaptive therapy based on a direct biomarker of liver function can be used to achieve both high rates of local control and a high degree of safety without sacrificing either. Individualized adaptive radiotherapy may represent a new treatment paradigm in which dose is based on individual, rather than population-based, tolerance to treatment. clinicaltrials.gov Identifier: NCT01522937.

Phase II study of individualized adaptive stereotactic body radiotherapy (SBRT) for patients at high risk for liver damage.

424 Background: Patients (Pts) with pre-existing liver dysfunction are at high risk for further damage after SBRT. We completed a phase 2 study of individualized SBRT, utilizing pre- and during-treatment indocyanine green (ICG) clearance to adapt treatment and maximize both safety and efficacy. Methods: From 5/10-10/14, pts with hepatocellular carcinoma (HCC) or metastases (mets) were enrolled and underwent SBRT planning up to a target dose of 50-60 Gy or as limited by a 15% normal tissue complication probability for radiation-induced liver disease (RILD). ICG retention at 15 minutes (ICGR15) was measured prior to and 1 month after 3 of 5 planned treatments. Using a Bayesian adaptive model, RT dose was scaled down as necessary for the final 2 treatments to keep ICGR15 &lt; 44% after the full treatment and thus minimize toxicity. Follow up was every 3 months for 2 years. Results: 90 pts received SBRT to 116 tumors and had at least 1 year of potential follow up. Median age was 62 years, range 34-85. 69 had HCC, 4 intrahepatic cholangiocarcinoma, and 17 mets. 62 had cirrhosis, most commonly HCV and alcoholic. Median Child-Pugh (CP) score was 6, range 5-9. 20 pts were CP B/C. Median pre-RT ICGR15 was 22, range 4-75, normal 4-10. Pts had a median of 1.5 (range 0-6) prior liver-directed therapies, most commonly transarterial chemoembolization (70), prior RT (36), and radiofrequency ablation (13). Median tumor size was 3 cm, and 12 had portal vein involvement. 63 received all 5 fractions (48 full dose, 15 with dose reduction due to elevated ICGR15); 27 received only 3 treatments. Median prescription dose was 47 Gy. Treatment was well tolerated with no classical RILD and a lower complication rate than expected without adaptation. 4 pts had grade 3 ascites. 2 pts had GI bleed after SBRT. 14% and 10% of pts experienced at least a 1 or 2 point increase in CP 6 months post SBRT. Local control (95%CI) at 1 and 2 yrs was 99 (96,100)% and 90 (81,100)%. 4 recurrent tumors were 3 HCC and 1 met, measuring 26, 12, 30, 38mm; treated to 30, 50, 33, 30 Gy. Conclusions: Individualized adaptive SBRT, based on ICG clearance is a promising method of allowing pts to receive the maximally aggressive dose based on each pt’s individual tolerance to RT. Funded by P01 CA59827

Tumor Volume Change With Stereotactic Body Radiotherapy (SBRT) for Early-stage Lung Cancer

To quantify gross tumor volume (GTV) change during stereotactic body radiotherapy (SBRT) and on first follow-up, as well as to evaluate for any predictive prognostic risk factors related to GTV decrease. An attempt was also made to identify the potential timing for adaptive SBRT. Twenty-five tumors in 24 consecutive patients were treated with SBRT to total dose of 50 Gy in 5 fractions. Median age was 72.5 years. Tumor stage was T1, 68%; T2, 20%; and other, 12%. The GTVs of on the 5 cone-beam computed tomographies (CBCT1-5) obtained before each fraction and the first follow-up CT (CTPOST) were analyzed. Median time from diagnosis to initiation of radiotherapy was 64 days. GTV on CBCT1 was the baseline for comparison. GTV decreased by a mean of 7% on CBCT2 (P=0.148), 11% on CBCT3 (P=0.364), 19% on CBCT4 (P=0.0021), and 32% on CBCT5 (P=0.0004). Univariate analyses of GTV shrinkage was significantly associated with "time from CBCT5 to CTPOST" (P=0.027) and "T-stage" (P=0.002). In multivariate analyses, "T-stage" remained significant with T1 tumors showing greater GTV shrinkage than T2 tumors. Significant decrease in GTV volume based on daily CBCT was demonstrated during SBRT treatment. Adaptive SBRT has the potential to minimize integral dose to the surrounding normal tissues without compromising GTV coverage.

Accumulated Dose in Liver Stereotactic Body Radiotherapy: Positioning, Breathing, and Deformation Effects

To investigate the accumulated dose deviations to tumors and normal tissues in liver stereotactic body radiotherapy (SBRT) and investigate their geometric causes. Thirty previously treated liver cancer patients were retrospectively evaluated. Stereotactic body radiotherapy was planned on the static exhale CT for 27-60 Gy in 6 fractions, and patients were treated in free-breathing with daily cone-beam CT guidance. Biomechanical model-based deformable image registration accumulated dose over both the planning four-dimensional (4D) CT (predicted breathing dose) and also over each fraction's respiratory-correlated cone-beam CT (accumulated treatment dose). The contribution of different geometric errors to changes between the accumulated and predicted breathing dose were quantified. Twenty-one patients (70%) had accumulated dose deviations relative to the planned static prescription dose >5%, ranging from -15% to 5% in tumors and -42% to 8% in normal tissues. Sixteen patients (53%) still had deviations relative to the 4D CT-predicted dose, which were similar in magnitude. Thirty-two tissues in these 16 patients had deviations >5% relative to the 4D CT-predicted dose, and residual setup errors (n = 17) were most often the largest cause of the deviations, followed by deformations (n = 8) and breathing variations (n = 7). The majority of patients had accumulated dose deviations >5% relative to the static plan. Significant deviations relative to the predicted breathing dose still occurred in more than half the patients, commonly owing to residual setup errors. Accumulated SBRT dose may be warranted to pursue further dose escalation, adaptive SBRT, and aid in correlation with clinical outcomes.

SU-E-T-630: Adaptive Liver SBRT: Daily Re-Planning to Compensate for Non-Rigid Anatomy Changes Improves Dose Distributions

Purpose: In stereotactic body radiotherapy(SBRT) of livertumors, daily image guidance based on contrast enhanced CT‐scans enables precise delivery of high tumordoses with small margins. However non‐rigid patient anatomy changes could still cause OAR dose constraint violations. In this study we evaluated the impact of daily re‐planning based on contrast‐ enhanced CT‐scans to compensate for non‐rigid anatomy changes. Methods: For eight patients with twelve tumors in different liver regions, three planning strategies were simulated. In all strategies, the patient was shifted each fraction to correct for the tumor displacement derived from registration of the daily CT‐scan. In the first strategy, the patient is irradiated with the non‐coplanar treatment plan that was based on the planning CT‐scan. In the second strategy the fluence profiles of the treatment beams were re‐ optimized based on the daily CT scan (beam angles remained the same as for the planning scan). In the last strategy, for each fraction a completely new plan (beam angles and profiles) was generated based on the daily CT‐ scan. Non‐rigid registration and LQ‐corrections were used to obtain cumulative dose distributions. Results: In 50% of the patients, constraint violations occurred for the repeated plan when we look at the dose distributions of the single fractions. For 33% of those patients, severe constraint violations in a single fraction even resulted in constraint violations in the integral dose distribution. In those cases, the beamweight plan and adaptive plan were easily capable of taking those OAR deformations into account and both methods designed good treatment plans without constraint violations. The adaptive plan performed slightly better than the beamweight plan, but the latter requires only some minutes computation time while full re‐optimization would take a few hours. Conclusions: Adaptive re‐optimization of fluence profiles based on daily CT scans can significantly improve dose distributions in liverSBRT.

Cone-Beam CT-Based Delineation of Stereotactic Lung Targets: The Influence of Image Modality and Target Size on Interobserver Variability

It is generally agreed that the safe implementation of stereotactic body radiotherapy requires image guidance. The aim of this work was to assess interobserver variability in the delineation of lung lesions on cone-beam CT (CBCT) images compared with CT-based contouring for adaptive stereotactic body radiotherapy. The influence of target size was also evaluated. Eight radiation oncologists delineated gross tumor volumes in 12 patient cases (non-small cell lung cancer I-II or solitary metastasis) on planning CTs and on CBCTs. Cases were divided into two groups with tumor diameters of less than (Group A) or more than 2 cm (Group B). Comparison of mean volumes delineated by all observers and range and coefficient of variation were reported for each case and image modality. Interobserver variability was assessed by means of standard error of measurement, conformity index (CI), and its generalized observer-independent approach. The variance between single observers on CT and CBCT images was measured via interobserver reliability coefficient. Interobserver variability on CT images was 17% with 0.79 reliability, compared with 21% variability on CBCT and 0.76 reliability. On both image modalities, values of the intraobserver reliability coefficient (0.99 for CT and 0.97 for CBCT) indicated high reproducibility of results. In general, lower interobserver agreement was observed for small lesions (CI(genA)= 0.62 ± 0.06 vs. CI(genB)= 0.70 ± 0.03, p < 0.05). The analysis of single patient cases revealed that presence of spicules, diffuse infiltrations, proximity of the tumors to the vessels and thoracic wall, and respiration motion artifacts presented the main sources of the variability. Interobserver variability for Stage I-II non-small cell lung cancer and lung metastasis was slightly higher on CBCT compared with CT. Absence of significant differences in interobserver variability suggests that CBCT imaging provides an effective tool for tumor localization, and image data could be also used for target volume delineation purposes.