Introduction: Recently Tattooless patient positioning using Surface Imaging Guided Radiotherapy (SGRT) has become popular for the setup of breast cancer radiotherapy. However, the use of permanent skin tattoos in alignment with in-room lasers is still the standard setup approach. In this study, we compared the setup accuracy between traditional tattoo based and tattooless approaches. Materials and Methods: This study involved 27 whole breast cancer patients undergoing 3D planned tangent beam radiotherapy via Varian TrueBeam. They were randomly divided into two groups: 13 were positioned using traditional tattoo markers aligned with in-room lasers and without SGRT, and 14 were positioned tattooless using AlignRT surface imaging technology (London, UK). Each patient consented to participate in the study and the study received approval from our institutional IRB. Prior to radiation delivery in each fraction, patient setup for both groups of patients wasverified with onboard daily CBCT. Setup error was defined as position displacement from planning CT to daily CBCT. Wilcoxon rank sum test was used for statistical analysis. Results and Analysis: A total of 171 daily patient setups were measured from 14 patients with Tattooless setup approach using SGRT while 226 were measured from 13 patients with Traditional Tattoo based setup approach. For tattooless setup, the median absolute shifts were 0.25cm in Anterior-Posterior (AP) direction (range 0∼0.88cm), 0.2cm in Superior-Inferior (SI) direction (0∼0.94cm) and 0.2cm in Lateral direction (0∼0.83cm). For the tattoo based setup approach, the corresponding median shifts were 0.37cm for AP (range 0∼2.14cm), 0.25cm for SI (range 0∼1.15cm), and 0.2cm for Lateral (0∼1.22cm). We found that the setup error was smaller in the AP direction for Tattooless by using the Wilcoxon rank sum test (p<0.05) while there was no significant difference in Lateral and SI directions between Tattooless and Tattooed approaches (P=0.93 and 0.37 respectively). For Tattooless setup, 10% of absolute shifts exceeded a magnitude of 8mm, while for traditional Tattoo based setup, a corresponding 16.8% exceeded 8mm. Discussions and Conclusions: Tattooless setup via AlignRT may have a better setup accuracy in the AP direction, and has an equivalent accuracy in SI and LR directions compared to a tattoo-based method. In addition, Tattooless method can reduce the frequency of large shifts from 16.8% to 10% as compared to traditional tattoo based setup approach. Citation Format: Mona Karim, Zhanrong Gao, Junsheng Cao. Evaluating Setup Accuracy via Daily CBCT of SGRT Based Tattooless vs Tattooed (Non-SGRT) Setup for Tangential Whole Breast Radiation [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P5-11-09.

TPS4670 Background: Local progression causes up to 30% of deaths from pancreatic cancer (PC) and is also a significant source of morbidity. Stereotactic body radiotherapy (SBRT) offers the potential for improved therapeutic index over standard fractionation, but current regimens of 5 fractions of 5-7 Gy/fraction are constrained by nearby organ tolerance and offer only palliation without improving survival. Safe dose escalation may be necessary to improve SBRT efficacy. Avasopasem, a superoxide dismutase mimetic, selectively converts superoxide (O2•-) to hydrogen peroxide (H2O2) and oxygen. O2•-initiates normal tissue damage due to RT. Avasopasem is in a Phase 3 trial (NCT03689712) to reduce RT-induced oral mucositis in head and neck cancer, based on positive results in a randomized Phase 2 trial for that indication (Anderson, JCO 2019). Avasopasem improved the survival of mice receiving 8.5 Gy x 5 to the upper abdomen. Cancer cells are less tolerant to elevated H2O2, and more tolerant to elevated O2•-, than normal cells, and avasopasem demonstrated mechanism-dependent synergy with high dose-fraction RT in a human tumor xenograft with inducible expression of catalase (Sishc, AACR 2018). Thus, adding avasopasem to SBRT may increase both the efficacy and the safety of the latter. Methods: 48 patients with locally advanced PC, who have completed medically-indicated induction chemotherapy, are randomized 1:1 to placebo or avasopasem, 90 mg IV, prior to each of 5 consecutive daily (M-F) SBRT fractions. A phase I/II Late Onset Efficacy/ Toxicity tradeoff (LO-ET) based adaptive design adaptive model drives assignment of SBRT dose escalation in each arm based on a dual endpoint (Gr 3-4 GI toxicity or death; local stable disease or better) by 90 days post SBRT. The planned dose levels are 10, 11 and 12Gy x 5 fractions (BED10 = 100,112.5 and 132Gy, respectively) as an integrated boost to the gross tumor volume (GTV). Primary endpoint: Maximum tolerated dose of SBRT with avasopasem or placebo. Secondary endpoints progression-free survival, response rate, and acute (90 day) and late (12 month) radiation toxicity with avasopasem vs placebo. Exploratory correlative studies include ctDNA, tumor exome/transcriptome sequencing, and immune profiling. Clinical trial information: NCT03340974 .

The GEC ESTRO guideline has been widely adopted in cervical cancer treatment that combines external beam radiation therapy (EBRT) and CT-guided HDR brachytherapy (BT). In this guideline the minimum dose to 90% (D90) High Risk Clinical Target Volume (HRCTV), to 2cc of bladder (BD(2cc)) or rectum (RD(2cc)) are used for plan evaluation. The total dose in EQD2 is obtained by direct summation of EQD2 dose from EBRT and BT. However, in fractionated BT the high dose region varies due to variation of tumor volume, insertion configuration, and bladder/rectum shape. Direct dose summation thus introduces dosimetric uncertainties. With recent advances in image fusion software, we can also estimate these parameters from deformable composite dose. In this study, we use MiM Software (v6.04) to obtain deformable composite dose of all BT plans. D90, BD(2cc)/RD(2cc) are extracted from the final composite dose, and then compared with those estimated per GEC ESTRO. Total of 30 HDR BT plans for 6 patients with stage IB2-IIB cervical cancer were retrospectively reviewed. All 30 insertions were planned in Oncentra (v4.3). The prescribed dose was 5∼6 Gy/fraction x 5. The HRCTV, bladder/rectum were contoured, and D90, BD(2cc)/RD(2cc) were evaluated per GEC ESTRO in clinic. Each plan was then imported into MiM. RT dose was converted into EQD2 in MiM. Using the CT dataset for the 5th fraction as the primary image set, deformable image fusion and composite dose were performed sequentially with the other 4 fractions. The total dose was obtained for each patient. During image fusion, the tandem and smit sleeve were used as markers. The alignment of HRCTV was the primary fusion objective. D90, BD(2cc)/RD(2cc) were then extracted from the composited DVH. Our result shows that BD(2cc)/RD(2cc) per GEC ESTRO are generally higher than those extracted in MiM. On average, RD(2cc) is 5.3Gy higher (ranging 2.2∼12 Gy), and BD(2cc) is 1.1Gy higher (ranging -0.7∼3.3Gy). The difference for D90 between that reported per GEC ESTRO and that in MiM ranges -11∼13.1Gy. The D90 in 5 patents' treatments meet GEC ESTRO criteria (within 80∼90 Gy), and one is 78.9 Gy. However, the reported D90 in MiM is > 90Gy when HRCTV decreases linearly after each treatment. Otherwise it is < 80 Gy. The HRCTV in 2 out of 6 patients reduces continuously from the 1st to 5th treatment. Our retrospective study suggests that the GEC ESTRO criteria for BD(2cc)/RD(2cc) are relatively conservative. The actual maximum dose to rectum/bladder may be overestimated with GEC ESTRO. Current D90 reported per GEC ESTRO may present moderate uncertainty in overall dose delivered to target. A cross check using deformable composite dose may be beneficial. However the difference of D90 between that per GEC ESTRO and that from deformable composite dose needs further investigation.

Purpose: Bladder/rectum sparing is always the challenge in HDR 3D CT‐guided brachytherapy treatment planning for cervical cancer due to the tight separation between them and High Risk Clinical Target Volume (HRCTV). In this study, we analyzed the minimum CTV‐to‐Bladder distance (MCBD), the minimum CTV‐to‐Rectum distance (MCRD), dose to 2cc of bladder (BD(2cc)) and rectum (RD(2cc)) respectively. The potential application of MCBD and MCRD as plan optimization indicators was investigated. Methods: Total 49 consecutive HDR plans for 11 patients with stage I–IIB cervical cancer were retrospectively reviewed. The prescribed dose (PD) was either 6 Gy/fraction × 5 or 7 Gy/fraction × 4 fractions. For each plan, MCBD and MCRD were measured on relevant transverse CT slices. BD(2cc), RD(2cc), the minimum dose cover 90% HRCTV (D90) were recorded. All plans were optimized with dose constrains BD(2cc)<80%PD, RD(2cc)<70%PD, D90>90%PD. Results: For 49 insertions, MCRD was 14±7mm. MCBD was 2±1mm. D90 was 100±15%PD. RD(2cc) and BD(2cc) were 57±12%, 74±10% of PD respectively. The correlation coefficient of MCBD and BD(2cc) was 0.31(p=0.03), indicating that bladder dose was significantly impacted by MCBD.Among 49 insertions, 19 cases had MCBD<=1mm with BD(2cc)>75% PD and D90 96±13%PD. 13 cases had 1mm75% PD. 17 out of 49 insertions had MCBD>2mm with D90 105±15%PD. Only 2/17 cases had BD(2cc)>75% PD. For 46/49 insertions, MCRD was >=5mm, which caused RD(2cc) extremely low. Conclusion: Our study shows that bladder sparing is correlated with MCBD. 65% of 49 insertions had MCBD<=2mm. Among them, 72% cases had BD(2cc)>75%PD. We believe that MCBD and MCRD can be used as plan optimization indicators. When any of them is <2mm, the target coverage would be comprised in order to spare bladder or rectum. This allows physicians have a reasonable expectation before plan is completed and guide further insertions.

Image-Guided Radiation Therapy (IGRT) increases the precision and accuracy of external beam radiation therapy and provides a safer delivery of higher, more curative levels of radiation dose. However, when significant changes to internal anatomy occur, IGRT alone will not be able to compensate for the dose degradation that may occur from using the original IMRT plan. A real-time planning (RTP) or adaptive planning technique would enable the continued use of tight margins with the assurance of full target coverage and efficient normal tissue sparing. In its current stage, the adaptive planning technique requires a physician to manually redraw the involved structures before each treatment. These day-to-day contouring variations could potentially be significant and thus overestimate the superiority of the newly created adaptive IMRT plan. A total of 60 CT scans were used during the course of IMRT treatment of 6 prostate cancer patients. An in-room diagnostic CT-on-Rails was used for the purposes of performing daily IGRT in conjunction with an adaptive IMRT planning technique. While the data was analyzed for the standard purposes of IGRT, a brand new optimized IMRT plan was created based on a new set of structures drawn by the on-call physician. This resulting plan was then compared to the initial IMRT plan or "recalculated plan" which was copied onto the new data set and recalculated with the daily IGRT implemented shifts. The RTP plan consistently showed at least equal effectiveness in target coverage and normal-tissue sparing as the initial IMRT recalculated plan. In 25% of the cases, greater rectal sparing was seen in the RTP plan with the largest single case reducing V50 by 40% and V60 by 50%. The most frequent anomalies seen in this study, however, were target coverage of the prostate and PTV. While the RTP plan maintained minimum prescription dose coverage of 97% to the prostate, the recalculated IMRT plan's minimum dose routinely fell below 95%, and in 20% of the cases, it dropped below 90%. In terms of PTV minimum coverage, the recalculated IMRT plan showed consistent dose degradation with 90% of the cases falling below 90% of the prescribed dose. Daily changes of the internal anatomy warrant the need for RTP. To our knowledge, we are one of the first to implement this technique in our daily clinical practice on a consistent basis. RTP possesses the ability to treat other cancer sites besides the prostate and its full potential maybe realized once better and faster auto-segmentation programs are available to minimize manual contouring variability.

PURPOSE:The daily shifts of prostate gland have been intensively reported in literatures. However, few papers reported daily shifts of prostate bed due to several practical difficulties (e.g. limited soft tissue contrast in MVCT and CBCT and significant deformation of prostate cavity). We have routinely performed IGRT for both prostate gland and bed with ct-on-rails, and the superior image quality allows us not only to differentiate both bony anatomy and soft tissue contrast of prostate gland and bed. In this study, we investigated if the shift of prostate bed is signifiant difference from that of prostate gland. METHODS:we reviewed shift data of 50 prostate gland patients who underwent 43 fractions and 22 patients of prostatectomy underwent 37 fractions. In total 2150 CT scans were reviewed for prostate gland and 814 scans for prostate bed. RESULTS:Of the reviewed 814 CT images from 22 prostate bed patients, the standard deviation of shift was found to be 5.9 mm in AP direction (ranges from -22.4mm to 22mm), 3.2mm in SI direction (ranges from -14mm to 14mm), and 4.1mm in lateral direction (ranges from -15mm to 22mm). Of the 2150 CT images of prostate gland from 50 patients, the standard deviation of the shift was found to be 5.4 mm in AP direction (-20mm to 18 mm), 5.0mm in SI direction (-26mm to 20mm), and 4.3mm in lateral direction (range from-15 to 30mm). F tests of systematic /random shift distribution in three orthogonal directions between prostate gland and prostate bed were subsequently performed, it was found that the systematic shift in SI direction for prostate bed is smaller than for prostate gland (p=0.003). CONCLUSIONS:Our result suggests no significant difference existing in shift between prostate bed and gland. Therefore strategies for daily prostate gland motion can be directly applied to prostate bed.

PURPOSE:On-line adaptive IMRT requires a highly efficient radiotherapy team and an intensive amount of work, as well as significant amount of Quality Assurance (QA). With regard to patient specific QA, it is clinically unrealistic to perform fluence measurements via a QA phantom while patient is setup awaiting treatment. We therefore developed an alternative way to check point dose and the IMRT fluence right before beam delivery.METHODS:In this study, 28 IMRT plans were generated with Prowess Panther 5.1 for three prostate cancer patients on 28 CT datasets with CTV and critical organs contoured by treating physicians. The corresponding QA plans were generated by Prowess, and then transfered to Pinnacle 9.2 for fluence recalculation on a flat surface phantom, In addition 28 QA plans were delivered on a Siemens Artiste accelerator and fluence were measured with Matrixx IMRT Device. We analyzed both point dose and fluence for these 28 samples.RESULTS:Of all 28 IMRT plans, the point dose difference between Prowess and Pinnacle are well within 1%. The point dose difference between measurements and Prowess calculation are all within 3%. The passing rates using gamma criteria (3%3mm) for the fluence comparison between Prowess and Pinnacle calculation are at least 98.5% while the passing rates of the gamma analysis between fluence measurement and Prowess calculation are all better than 98.5%. The passing rate of gamma difference between Prowess vs Pinnacle and Prowess vs QA measurement is less than 1.5% for all 28 samples. Therefore, second TPS (e.g. Pinnacle) can be used to verify planned fluencies and can serve as a valuable patient specific QA when conventional IMRT QA measurement is not feasible.CONCLUSIONS:A new IMRT plan is desired if significant anatomy change from the date of original CT scan is observed before the radiation delivery. It is not clinically feasible to check the fluence on the machine before radiation delivery while the patient is in the treatment suite awaiting radiation delivery. Our method showed here is an alternative way to verify the planned fluence with a second TPS and can serve as a valuable IMRT patient specific QA in online adaptive radiotherapy.

191 Background: Image guided radiation therapy (IGRT) corrects for the interfractional movements of the target/CTV. However, the anatomic changes of CTV, and movements of the adjacent organs, are not accounted for. By modifying an online adaptive radiation technique proposed by Li, we have clinically deployed a daily “real-time treatment planning” (RTP) technique for treatment of primary prostate cancers. The technique, rationale and experience of our first 60 RTP treatments are presented. To our knowledge, this is the first clinical implementation of daily treatment planning. Methods: The RTP process is as follows: a) daily CT images are acquired via an in-room diagnostic CT-on-Rails; b) while IGRT evaluation is performed, new target and tissue contours (prostate, rectum and bladder) are drawn, c) new IMRT plan is computed (RTP plan); d) IGRT plan is compared to the RTP plan; e) if RTP plan is dosimetric superior, it will be delivered after f) necessary QA process. This entire process takes less than 20 minutes (excluding IMRT delivery). 60 RTP’s were delivered (10 daily RTP/patient) in 6 consecutive patients. Results: Auto-contouring via auto-segmentation was inadequate when compared to manual anatomic re-contouring. The RTP plan is always superior to or equal to the original IGRT plan. In 20% of the cases, the CTV-DVH by RTP improved by >10%. Slight changes in manual contouring variation can lead to significant change in volume variation. For example, with initial prostate volumes of 15, 20, 30, 40 and 50 cc, a 1 mm increase in contour variation results in an increase volume of 26%, 24%, 21%,19% and 17% respectively, and absolute volume increase of 3.9cc, 4.8cc, 6.2cc, 7.4cc and 8.6cc respectively. Rectal dose improved significantly with RTP when compared to IGRT. In one extreme case, the rectal dose improvement is shown (Table). Conclusions: Daily RTP is feasible for prostate cancer treatments and is superior to IGRT. RTP is especially necessary with extreme anatomic changes. [Table: see text]

Multiple articles have established the importance of image guided radiation therapy (IGRT). Conventional IGRT corrects the 3 dimensional shifts of the target volume (TV), but do not account for the TVs change in shape and size, or the change in shape/ positions of the adjacent normal structures. In this study, we investigate a new treatment strategy that we called "Instant Re-planning Radiation Therapy" (IRRT). This re-planning strategy prior to each daily radiation (to mitigate the change in shape/volume of TV) is possible with diagnostic images obtained by a CT-on-rails in the linac suite and with current commercial software that re-plans within 5 minutes. We retrospectively selected 3 patients with rising PSA after radical prostatectomy to illustrate the limitation of conventional IGRT. These patients all have surgical staples in the prostatic fossa (PF), and all had significant interfractional AP-PA shifts as delineated by the anterior border of the rectum. The PF, rectum, and bladder were then contoured on the daily CT images (5 CT datasets per patient) and the initial CT simulation images. Treatment plans with various margins (3, 5, 8, 10mm) in different dimensions were generated. These plans were then transposed to the subsequent daily CT images to determine the adequacy of IGRT vs IRRT (detailed methodology to be presented). The daily diagnostic CT images obtained showed significant changes in size and shape of the rectum, bladder and the prostatic fossa (PF). The various directional movements of the surgical staples further confirmed the changes in shape of the PF. The interfractional PF volume ranged from.38.6cc -44.3c, 46.5cc-54.6cc and 27.5cc-34.3cc among the 3 patients respectively. Significant changes in rectal and bladder volumes were also observed. A minimal 5 mm PTV margin is needed for IGRT to adequately cover the change in shape or size of the PF. With a 3 mm PTV margin, IGRT is inadequate with a D99 coverage degradation of 2-8% for each fraction due to PF volumetric changes. With IRRT, a 3mm PTV margin can give adequate coverage. With a 5mm PTV margins when only IGRT is used, the mean rectal and bladder dose is increased by up to 13% when compared to a 3mm margin required by IRRT. A 14 mm PTV margin is required when neither IGRT nor IRRT is used. Thus, IRRT lead to an 11 mm margin reduction with significant rectal dose reduction. This study illustrates the principle and importance of IRRT when there are daily TV shape or size changes in the treatment of PF, and the limitation of current IGRT. Over 10 mm PTV margin reduction can be achieved with IRRT. IRRT maybe especially important with the use of hypofraction technique.

Intensive publications in the past decade have established the importance of image guided radiation therapy (IGRT) to correct for the interfractional shifts of the prostate glands. However, few reports on the use of IGRT of the prostatic fossa in patients with recurrent prostate cancers after radical prostectomy The prostate fossa is delineated posteriorly by the rectum, laterally by the pelvic diaphragms and superiorly influenced by the bladder. Thus, it is subjected to the variations of these structures. Without a prostate gland, fiducial implantation for IGRT is difficult. We now report our IGRT result and technique of IGRT for these cancers. From 2005 to 2010, 43 of patients with rising PSA and diagnosed with recurrent prostate cancer were treated with external beam radiation therapy (RT). Various fractions of IGRT were used throughout the RT course. 22 patients received the entire 37 fractions with IGRT, while 21 patients had 5-15 fractions of IGRT. A total of 1009 CT images were reviewed. IGRT technique was performed as previously described. The methodology of prostatic fossa delineation and localization will be presented. The PTV to CTV margin was 1 cm except the posterior margin (5mm). A separate presentation will address the change in shape and size of the prostatic fossa. The prostatic fossa can be imaged clearly for IGRT localization. Of the 1009 CT images reviewed, 35.4% required no setup adjustments in the anterior-poster (AP) direction (no adjustment if shift < 3 mm), 23.8% had shifts of 3-5 mm, 32% had shifts of 6-10mm, and 6.6% had shifts >10mm. In the superior-inferior (SI) direction, the corresponding shifts were 60.1%, 23.7%, 15% and 0.5% respectively. . In the left-right (LR) direction, the corresponding shifts were 60.7%, 22.6%, 11.9% and 4.3% respectively The margins as used adequately covered the prostatic fossa with IGRT (result to be presented). If no IGRT is performed, the posterior margin would have to be enlarged by at least 6mm since 38% have interfractional APPA shifts greater than 6 mm. Such increase in posterior margin has significant impact on rectal dose. Using in room CT, it is possible to perform daily image localization of the prostate bed. The superior image quality of the in room CT allows the prostate tumor bed to be clearly delineated and thus, allow daily localization of the prostate bed. Without IGRT, a larger margin would be required with resultant higher dosage to the rectum. Our result has significant implications for hypofractionation treatments of this disease.