Ensure Target Coverage Research Articles

A heuristic node placement strategy for extending network lifetime and ensuring target coverage in mobile wireless sensor networks

A heuristic node placement strategy for extending network lifetime and ensuring target coverage in mobile wireless sensor networks

ROAR-A: re-optimization based Online Adaptive Radiotherapy of anal cancer, a prospective phase II trial protocol

BackgroundChemo-radiotherapy with curative intent for anal cancer has high complete remission rates, but acute treatment-related gastrointestinal (GI) toxicity is significant. Toxicity occurs due to irradiation of surrounding normal tissue. Current radiotherapy requires the addition of large planning margins to the radiation field to ensure target coverage regardless of the considerable organ motion in the pelvic region. This increases the irradiated volume and radiation dose to the surrounding normal tissue and thereby toxicity. Online adaptive radiotherapy uses artificial intelligence to adjust the treatment to the anatomy of the day. This allows for the reduction of planning margins, minimizing the irradiated volume and thereby radiation to the surrounding normal tissue.This study examines if cone beam computed tomography (CBCT)-guided oART with daily automated treatment re-planning can reduce acute gastrointestinal toxicity in patients with anal cancer.Methods/designThe study is a prospective, single-arm, phase II trial conducted at Copenhagen University Hospital, Herlev and Gentofte, Denmark. 205 patients with local only or locally advanced anal cancer, referred for radiotherapy with or without chemotherapy with curative intent, are planned for inclusion. Toxicity and quality of life are reported with Common Terminology Criteria of Adverse Events and patient-reported outcome questionnaires, before, during, and after treatment. The primary endpoint is a reduction in the incidence of acute treatment-related grade ≥ 2 diarrhea from 36 to 25% after daily online adaptive radiotherapy compared to standard radiotherapy. Secondary endpoints include all acute and late toxicity, overall survival, and reduction in treatment interruptions.ResultsAccrual began in January 2022 and is expected to finish in January 2026. Primary endpoint results are expected to be available in April 2026.DiscussionThis is the first study utilizing online adaptive radiotherapy to treat anal cancer. We hope to determine whether there is a clinical benefit for the patients, with significant reductions in acute GI toxicity without compromising treatment efficacy.Trial registrationClinicalTrials.gov Identifier: NCT05438836. Danish Ethical Committee: H-21028093

Methodology for small animals targeted irradiations at conventional and ultra-high dose rates 65 MeV proton beam

As part of translational research projects, mice may be irradiated on radiobiology platforms such as the one at the ARRONAX cyclotron. Generally, these platforms do not feature an integrated imaging system. Moreover, in the context of ultra-high dose-rate radiotherapy (FLASH-RT), treatment planning should consider potential changes in the beam characteristics and internal movements in the animal.A patient-like set-up and methodology has been implemented to ensure target coverage during conformal irradiations of the brain, lungs and intestines. In addition, respiratory cycle amplitudes were quantified by fluoroscopic acquisitions on a mouse, to ensure organ coverage and to assess the impact of respiration during FLASH-RT using the 4D digital phantom MOBY. Furthermore, beam incidence direction was studied from mice µCBCT and Monte Carlo simulations. Finally,in vivodosimetry with dose-rate independent radiochromic films (OC-1) and their LET dependency were investigated.The immobilization system ensures that the animal is held in a safe and suitable position. The geometrical evaluation of organ coverage, after the addition of the margins around the organs, was satisfactory. Moreover, no measured differences were found between CONV and FLASH beams enabling a single model of the beamline for all planning studies. Finally, the LET-dependency of the OC-1 film was determined and experimentally verified with phantoms, as well as the feasibility of using these filmsin vivoto validate the targeting.The methodology developed ensures accurate and reproducible preclinical irradiations in CONV and FLASH-RT without in-room image guidance in terms of positioning, dose calculation andin vivodosimetry.

Principal Component Analysis to Design Planning Target Volume in Oropharyngeal Cancers

Standard translational shifts of the Clinical Target volume (CTV) to generate the Planning Target Volume (PTV) do not account for rotations. Head and neck positional misalignments derive in large part from rotations due to cervical spine arching and twisting in Cone Beam Computed Tomography (CBCT). Translational expansions do not track rotations, yielding coverage envelopes that unnecessarily overlap with adjacent structures. This work examines whether principal component analysis of the motion along all 6 degrees of freedom may be used to produce a more favorable PTV. Seventy-five CBCTs of ten oropharyngeal cases were included. The records of couch shifts needed to align individual bony structures (C1-5, mandible and mastoid) between the planning image and CBCTs were recorded. A Principal Component Analysis of the shifts was used to generate an ellipsoid inflation of each CTV vertex along 6 degrees of freedom. The result was compared to a 3D ellipsoid based translational expansion, and to a described ellipsoid based vertex expansion along 6 degrees of freedom, with axes oriented in parallel to the treatment reference frame. Themean (x, y) shifts in mm needed to align individually bodies C1 - C5 were respectively (-0.4, 0.5), (+.5, -0.2), (+-0.2, -0.2), (-0.2, +0.4), and (-0.5, +0.7), the monophasic pattern showing acquired curvature along both axes during treatment and demanding a PTV for coverage. A PTV was constructed using a described 6D ellipsoidal based boundary point expansion aligned along the reference frame axis or using a new theory to align against the principal components of the motion. A cyclical one-out method was used to validate the PTV models. Selected confidence intervals yielded complete coverage in >80% weeks in 80% cases. Validation testing disclosed similar complete coverage in 83-86% weekly CBCTs in the test cases with either method. The PCA 6D PTV could yield less normal structure overlap. A one out method was used to test overlap avoidance from PTVs constructed from a population of weekly CBCTs drawn from seven cases with one excluded. PTVs were drawn around target and constrictors on an extraneous case and imaged on a CT slice. Both a rolling 'ball' expansion of the vertices that applies a 3D translational ellipsoid and a PTV constructed using a 6D ellipsoid aligned against the standard reference frame overlapped with all or nearly all the constrictors in all but one trial (1/7). The 6D ellipsoid aligned against the principal motion components spared >70% of a constrictor in all trials (7/7). PTVs remain needed to ensure target coverage in head and neck radiotherapy even with daily CT accuracy because of acquired spinal curvatures resulting in rotational displacements. A described 6D ellipsoid oriented to the reference frame can yield good coverage, but with unneeded constrictor coverage. A PCA analysis yields a PTV with equally good coverage but able to spare 70% of a constrictor.

ARTIA-Bladder: Daily Online Adaptive Short-Course Radiation Therapy (RT) and Concurrent Chemotherapy for Muscle-Invasive Bladder Cancer (MIBC): A Prospective Trial of an Individualized Approach for Reducing Bowel and Bladder Toxicity

Concurrent chemo-radiotherapy is commonly prescribed for muscle-invasive bladder cancer (MIBC). Post hoc analysis of two large, randomized trials found that hypofractionation improves loco-regional control (LRC) vs. standard fractionation in this population. A challenge in traditional image-guided radiotherapy of the bladder is that daily changes in bladder position and size requires large margins to ensure target coverage. This makes it difficult to spare uninvolved bladder from high-dose treatment, increases the risk of bowel toxicity, and results in historical rates of acute G3+ toxicity exceeding 20-30%. Daily online adaptive RT (ART) may enable reduced, personalized margins that maintain target coverage while reducing dose to OARs. This prospective clinical trial will test whether: 1) participants undergoing ART for MIBC have a lower rate of acute G3+ GI/GU toxicity compared with the 31% historical control rate (Stage III BC2001 trial), and 2) 2-year LRC with ART will be non-inferior to historical controls (75%). This multi-national trial will enroll 165 adult subjects with stage cT2-T4aN0M0 urothelial MIBC. Subjects will have undergone an attempt at maximal transurethral resection of bladder tumor. Patients with clinically involved nodes or G2+ GI or G3+ GU symptoms/conditions at baseline are ineligible. Concurrent with chemotherapy, participants will receive (at the discretion of the investigator) either 55 Gy in 20 fx to whole-bladder or 46 Gy in 20 fx to whole-bladder plus simultaneous in-field boost of 55 Gy in 20 fx to tumor bed. A personalized ITV will be derived for each subject based on bladder expansion, as assessed on two CT simulations separated by 30 min. Daily ART will be attempted for all subjects. The primary endpoint is acute G3+ GI/GU toxicity. Secondary endpoints are LRC; quality of life (EORTC QLQ-BLM30, EPIC 26 bowel and urinary); global function (EQ-5D-5L ); 2-year disease-free, bladder intact event-free, and overall survival; 2-year bladder cancer-specific mortality; NTCP model of acute GI toxicity for hypofractionated bladder RT; workflow feasibility of ART; improved target coverage ± reduced dose to critical OARs vs. non-ART dosimetry; acute G3+ GI/GU toxicity rate in subjects with ≥75% of their treatments as ART; and acute G3+ GI/GU toxicity in the cohort treated with partial bladder boost. Exploratory translational and correlative endpoints will also be examined. This trial opened to enrollment on Feb 2, 2023; the study duration is expected to be 4-5 years. This prospective clinical trial will provide robust clinical data to inform healthcare providers' decisions on the use of daily online ART and hypofractionation as a bladder preservation strategy for this population.

Dosimetry and plan parameters study of three-dimensional-printed template-based intra-cavitary/interstitial interpolation technology using computed tomography-guided high-dose-rate brachytherapy in locally advanced cervical cancer.

To explore differences in dosimetry and planning parameters between intra-cavitary/interstitial interpolation (IC + ISBT) three-dimensional (3D)-printed template-based (3D-printed) and simple intra-cavity (ICBT) radiation techniques using a fixed Rotterdam three-tube applicator (TT) for computed tomography-guided high-dose-rate brachytherapy in locally advanced cervical cancer. This retrospective study included 100 patients (n = 50 each in 3D-printed and Rotterdam three-tube applicator treatment groups) with FIGO stages IIB-IVB cervical cancer from May 2019 to May 2022. Using high-risk clinical target volume, 377 of 400 plans categorized at intervals of 10 cm3 into 20-30, 30-40, 40-50, 50-60, 60-70, and 70-80 cm3; 23 plans with < 20 and > 80 cm3 volume were excluded. Dosimetry parameters (D90 and D98 of high-risk clinical target volume, and D2cc of organs at risk, including bladder, rectum, sigmoid, and bowel) and planning parameters (homogeneity index [HI], conformation number [CN], and organ at risk sparing factor) were compared between the two groups separately for six high-risk clinical target volume plan categories. For the 3D-printing group, target coverage, organs at risk protection, and plan conformity and uniformity were better than those for the Rotterdam three-tube group. Particularly, in high-risk clinical target volume plans between 50-60 cm3, the mean D90 and D98 of high-risk clinical target volume were approximately 0.35 and 0.3 Gy higher, while the average D2cc of the bladder, rectum, sigmoid, and bowel were approximately 1.3, 0.9, 0.9, and 0.8 Gy significantly lower than those of the Rotterdam three-tube group, respectively (p < 0.05). The above-mentioned planning parameters differed significantly between the groups (p < 0.05). For the 3D-printing group, IC/ISBT reduced the dose for organs at risk while ensuring target coverage and conformation. This was especially noticeable for plans with high-risk clinical target volume of 50-60 cm3.

Clinical Experience and Feasibility of Using 2D-kVimage Online Intervention in the Ultrafractionated Stereotactic Radiation Treatment of Prostate Cancer

This study reports clinical experience and feasibility of using a 2-dimensional (2D)-kV image system with online intervention in the ultrafractionated stereotactic body radiation treatment (UF-SBRT) of prostate cancer. Fifteen patients with prostate cancer who had a low- to intermediate-risk marker implanted received UF-SBRT with online 2D-kV image tracking and a manual beam interruption strategy with a 2-mm motion threshold. A total of 180 kV paired setup images and 1272 intrabeam 2D-kV images were analyzed to evaluate the setup deviation and intratreatment target deviation. Correlation of expected treatment interruptions with a set of parameters (eg, image and treatment time; direction of deviation) was performed (Spearman test). A subset of the data from 22 fractions was re-evaluated to check the differences in analysis results between using the planning position and using the pretreatment setup position as a reference. Margins based on the derived system and random errors were calculated to evaluate the feasibility of the workflow in ensuring prostate coverage during treatment. Mean target motion in 3D propagated from 1.0 mm (setup at 0 minutes) to 2.0 mm (beam on at 7 minutes) to 2.4 mm (end at 13.5 minutes). Out of 75 fractions, 50 were found to require beam interruption. Interruption had a strong correlation with prostate motion along the longitudinal direction and had moderate correlation with prostate motion along the vertical direction and the prostate's treatment starting position along vertical and longitudinal directions. Using the pretreatment position as a reference for intrabeam monitoring, the magnitude of motion deviation from the reference position was reduced by 0.3 mm at a vertical direction and 0.4 mm at lateral and longitudinal directions. The calculated 3D margin to ensure target coverage was 3.7 mm, 4.6 mm, and 5.0 mm in lateral, vertical, and longitudinal directions, respectively. Prostate motion propagated over time. It is feasible to use a 2D-kV online intrabeam monitoring system with a proper intervention scheme to perform UF-SBRT for prostate cancer.

BgRT Motion Management Maintains Target Dose Coverage for Respiratory and Non-Respiratory Motion

<h3>Purpose/Objective(s)</h3> Biology-guided radiotherapy (BgRT) uses outgoing emissions after administration of an injected radiotracer to dynamically guide the delivery of radiation treatment to PET-avid targets. In this study, we evaluated the tracking performance of FDG-guided BGRT for two potential types of motion management (respiratory and non-respiratory (gastrointestinal)) while exploring different target shapes: spherical and non-spherical. BgRT is designed to ensure target coverage while keeping organ-at-risk (OAR) doses low. <h3>Materials/Methods</h3> A large custom anthropomorphic phantom with 2 robotic articulating arms was used to place a target and organ-at-risk inside a 27-liter water filled cavity. The targets consisted of an integrated ion chamber inside a 3D printed 22 mm sphere or a small non-spherical ovoid shape filled with FDG. The hot FDG-filled OAR consisted of either a 3D printed large C-shape annulus (mimicking a heart), large ovoid (mimicking a kidney), or a 30 mm sphere, all with integrated ion chambers. Both the 3D printed target and the OAR were filled with an 8:1 concentration ratio versus the water background. Three different 10 Gy/fraction treatment plans with two different target shapes and realistic nearby OARs were created with a 5 mm margin added to the CTV to generate the PTV. 3D printed targets and OARs were loaded with EBT-XD radiographic film. A 3D elliptical motion trajectory with breathing induced hysteresis with a maximum amplitude of +/- 12 mm was used for the respiratory motion model. An asymmetric slow-moving drift waveform with long-step shifts of +13/-5mm mm was used for the non-respiratory (gastrointestinal) motion model. Dosimetric results were evaluated based on 2-dimensional comparisons between measured film and planned dose distributions for the target and OAR. BgRT must maintain a prescription dose margin greater than 2 mm on the CTV for the three different motion experiments. Also, ion-chamber point dose and maximum film dose on the OAR must be within bounds predicted by the treatment planning system. <h3>Results</h3> BgRT was able to meet minimum margin requirements (a margin loss < 3mm) and meet prescription dose coverage in both motion management scenarios while maintaining OAR dose limits within the plan predicted bounds (see Table 1). <h3>Conclusion</h3> BgRT is able to provide motion management in complex cases that is agnostic to the type of motion. BgRT is able to maintain the PTV coverage with less than 3 mm reduction from the original 5mm margin.

Online adaptive radiotherapy of urinary bladder cancer with full re-optimization to the anatomy of the day: Initial experience and dosimetric benefits

Background and purposeOnline adaptive radiotherapy (oART) potentially reduces the dose to organs at risk (OARs) as the planning target volume (PTV) margins are reduced compared to a non-adaptive approach (non-ART). This study evaluates the feasibility and dosimetric impact of cone-beam computed tomography (CBCT)-guided oART of urinary bladder cancer for the first patients treated, using patient-specific margins. Materials and methodsSixteen consecutive patients with muscle-invasive bladder cancer received two or more (median = 23) fractions as oART, and remaining fractions as non-ART. The non-ART fractions were delivered with standard population-based margins, while reduced patient-specific margins based on intra-fractional variations extracted from 2-4 fractions were applied to the primary PTV (PTV-T) during the oART fractions. Target volume and coverage, and dose to OARs were compared between non-ART and oART plans, and the oART procedure time was recorded. ResultsIn total, 297/512 fractions were delivered as oART with full re-optimization to the anatomy of the day. The median (interquartile range, IQR) oART procedure time, measured from the end of CBCT generation to completion of plan review, and quality assurance was 13.9 (11.9;16.6) min. The median (IQR) volume reduction in PTV-T volume was 33.9 (24.2;45.0)%, comparing oART and non-ART plans, resulting in median (IQR) reductions in bowel bag V45Gy of 18.8 (12.7;27.9)% and rectum V50Gy of 70.7 (35.9;94.8)%. By re-optimizing the plan to the daily anatomy, full target coverage was achieved at all oART fractions. ConclusionsoART resulted in large reductions in treatment volumes and doses to OARs, compared to non-ART, while ensuring target coverage. This indicates potential reductions in gastrointestinal toxicity.

Abstract P1-17-12: Preliminary data from a phase I/II, multicenter, dose escalation study of OP-1250, an oral CERAN/SERD, in subjects with advanced and/or metastatic estrogen receptor (ER)-positive, HER2-negative breast cancer

Abstract Background: ER+, HER2- metastatic breast cancer (MBC) patients will receive sequential, endocrine based therapy, either as monotherapy or in combination with a targeted agent until endocrine resistance develops. OP-1250 is a small molecule Complete Estrogen Receptor Antagonist (CERAN) that completely inactivates ER by blocking the 2 activation functions of ER transcription (AF-1 &amp; AF-2). While complete antagonism is believed to be the most critical mechanism of action, OP-1250 is also a strong degrader of the ER. OP-1250 demonstrates anti-cancer activity in preclinical models, including activity against brain metastases and in tumors with activating mutations in ESR1. OP-1250 is orally bioavailable with favorable pharmacokinetics (PK) yielding high and steady drug levels in multiple species. The characteristics of OP-1250 including PK, ability to cross the blood brain barrier, and complete antagonism of the ER suggest that OP-1250 may have superior efficacy over standard of care and experimental agents, both as a monotherapy and in combination with other targeted therapies. Methods: OP-1250-001 is a phase I/II first-in-human study to determine the Dose Limiting Toxicity (DLT), Maximum Tolerated Dose (MTD) and/or Recommended Phase II Dose (RP2D) and to characterize the safety, PK profile and preliminary efficacy in subjects with ER+, HER2- MBC. Eligible patients received prior endocrine therapy. OP-1250 was given orally, once a day continuously in 28-day cycles. Using a rolling 6 design, cohorts of 3 - 6 subjects were sequentially enrolled and monitored for DLTs. The study allows for expansion of 1 or 2 doses for further evaluation of safety and PK to best inform selection of the RP2D. The phase II portion will evaluate the preliminary activity of OP-1250 in 3 cohorts: 1) measurable disease; and 2 exploratory cohorts: 2) evaluable &amp; non-measurable; and 3) central nervous system metastasis. Plasma is being collected for ctDNA sequencing to evaluate ESR1 and other relevant mutations. Results: Between August 5, 2020 and June 4, 2021, 28 subjects with a median age of 63 (range 37-82) have been enrolled. Of the 27 subjects for whom detailed data on prior therapy was reported, all subjects received &amp;gt; 1 prior endocrine therapy for MBC (74% received &amp;gt; 2 and 37% received &amp;gt; 3; range 1-6). All of the 27 subjects received a CDK4/6 inhibitor and 23 of 27 (85%) had received fulvestrant. 20 subjects of 28 (71%) subjects had visceral disease affecting the liver, lung, peritoneum, and/or pleura. OP-1250 was escalated through 5 dose cohorts (range 30 - 300 mg qd). 26 patients were evaluable for a DLT. As of the data cut-off date, no DLTs occurred. Most of the TEAE were grade 1 or 2. OP-1250 is orally bioavailable and extensively distributed with an effective half-life of approximately 2-3 days. Cmax and AUC show dose proportional increase. By cycle 2, exposure levels are at steady state with limited fluctuations and at all doses significantly higher than those seen with fulvestrant. Importantly, OP-1250 has now demonstrated clinical activity at doses that were well tolerated and within the predicted exposure windows where maximum efficacy was observed in preclinical models. Detailed response and safety data will be presented. Conclusion: OP-1250 is continuing evaluation in a phase I/II study. The population enrolled reflects the evolving standard of care in that all pts received prior CDK4/6 inhibitors and the majority also received fulvestrant. OP-1250 is well tolerated with a favorable PK across dose levels ensuring target coverage throughout the dosing interval. No MTD has been identified and selection of the RP2D will be based on consideration of long-term tolerability, efficacy, and the ability to combine with targeted agents. (NCT04505826) Citation Format: Manish Patel, Carlos Alemany, Zahi Mitri, Della Makower, Virginia Borges, Joseph Sparano, Trinh Le, Pamela Klein, Julia Lawrence, Peter Kushner, Demiana Faltaos, Cyrus Harmon, David Myles, JoAnne Zujewski, Erika Hamilton. Preliminary data from a phase I/II, multicenter, dose escalation study of OP-1250, an oral CERAN/SERD, in subjects with advanced and/or metastatic estrogen receptor (ER)-positive, HER2-negative breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-17-12.

Assessment of intra-fraction motion during automated linac-based SRS treatment delivery with an open face mask system.

To evaluate intra-fraction target shift during automated mono-isocentric linac-based stereotactic radiosurgery with open-face mask system and optical real-time tracking. Ninety-five patients were treated using automated linac-based stereotactic radiosurgery in 1-5 fractions with single isocenter for a total of 195 fractions. During treatment, patient positioning was tracked real-time with optical surface guidance and immobilized with a rigid open-face mask. Patients were re-positioned if optical surface guidance error exceeded 1mm magnitude or 1°. Translational and rotational intra-fractional changes were determined by post-treatment CBCT matched to the planning CT. Target specific error was calculated by translation and rotation matrices applied to isocenter and target spatial coordinates. For 132 fractions with isocenter within a single target, the median shift magnitude was 0.40mm with a maximum shift of 1.17mm. A total of 398 targets treated for plans having multiple or single targets that lied outside isocenter, resulted in a median shift magnitude of 0.46mm, with median translational shifts of 0.20mm and 0.20° rotational shifts. A 1mm PTV margin was insufficient in 18% of targets at a distance greater than 6cm away from isocenter, but sufficient for 96% of targets within 6cm. The findings of this study support 1mm PTV expansion due to intra-fraction motion to ensure target coverage for plans with isocenter placement less than 6cm away from the targets.

Combined proton–photon treatment for breast cancer

Objective. Proton therapy remains a limited resource due to gantry size and its cost. Recently, a new design without a gantry has been suggested. It may enable combined proton–photon therapy (CPPT) in conventional bunkers and allow the widespread use of protons. In this work, we explore this concept for breast cancer. Methods. The treatment room consists of a LINAC for intensity modulated radiation therapy (IMRT), a fixed proton beamline (FBL) with beam scanning and a motorized couch for treatments in lying positions with accurate patient setup. Thereby, proton and photon beams are delivered in the same fraction. Treatment planning is performed by simultaneously optimizing IMRT and IMPT plans based on the cumulative dose. The concept is investigated for three breast cancers where the goal is to minimize mean dose to the heart and lung while delivering 40.05 Gy in 15 fractions to the PTV with a SIB of 48 Gy to the tumor bed. The probabilistic approach is applied to mitigate the sensitivity to range uncertainties. Results. CPPT is particularly advantageous for irradiating concave target volumes that wrap around a curved chest wall. There, protons may deliver dose to the peripheral and medial parts of the target volume including lymph nodes. Thereby, the mean dose in normal tissues is reduced compared to single-modality IMRT. However, tangential photon beams may treat parts of the target volume near the interface to the lung. To ensure target coverage for range undershoot in an IMPT plan, proton beams have to deliberately overshoot into the lung tissue—a problem that can be mitigated via the photon component which ensures plan conformity and robustness. Conclusion. CPPT using an FBL may represent a realistic approach to make protons available to more patients. In addition, CPPT may generally improve treatment quality compared to both single-modality proton and photon treatments.

Assessment of a diaphragm override strategy for robustly optimized proton therapy planning for esophageal cancer patients.

PurposeTo ensure target coverage in the treatment of esophageal cancer, a density override to the region of diaphragm motion can be applied in the optimization process. Here, we evaluate the benefit of this approach during robust optimization for intensity modulated proton therapy (IMPT) planning.Materials and methodsFor 10 esophageal cancer patients, two robustly optimized IMPT plans were created either using (WDO) or not using (NDO) a diaphragm density override of 1.05 g/cm3 during plan optimization. The override was applied to the excursion of the diaphragm between exhale and inhale. Initial robustness evaluation was performed for plan acceptance (setup errors of 8 mm, range errors of ±3%), and subsequently, on all weekly repeated 4DCTs (setup errors of 2 mm, range errors of ±3%). Target coverage and hotspots were analyzed on the resulting voxel‐wise minimum (Vwmin) and voxel‐wise maximum (Vwmax) dose distributions.ResultsThe nominal dose distributions were similar for both WDO and NDO plans. However, visual inspection of the Vwmax of the WDO plans showed hotspots behind the right diaphragm override region. For one patient, target coverage and hotspots improved by applying the diaphragm override. We found no differences in target coverage in the weekly evaluations between the two approaches.ConclusionThe diaphragm override approach did not result in a clinical benefit in terms of planning and interfractional robustness. Therefore, we do not see added value in employing this approach as a default option during robust optimization for IMPT planning in esophageal cancer.

RARE-06. OPTIMIZATION OF PROTON RADIATION THERAPY FOR GIANT CRANIOPHARYNGIOMAS

Craniopharyngiomas are benign intracranial tumors located in the sellar and suprasellar region. Their size and extent of invasion into surrounding structures vary considerably. While the majority of craniopharyngiomas on presentation are between 1–3 cm without hypothalamic invasion, a significant proportion of patients present with ‘giant’ craniopharyngiomas of >4cm in dimension with large cystic extension through the 3rd ventricle. These tumors pose a challenge both for surgical resection as well as for radiation therapy. Proton beam therapy (PBT) has become the preferred standard of care after subtotal resection of pediatric craniopharyngiomas. In the setting of giant craniopharyngioma, the use of proton therapy allows a reduction of dose to surrounding normal brain, but changes in cyst volume can result in either under-coverage of tumor or excess dose to surrounding brain, an effect further magnified by the sharp gradients associated with proton dose distributions. In this case report we describe the proton treatment planning and intra-treatment monitoring of two patients with giant craniopharyngiomas with largest pre-operative of dimension 6cm, and 9cm, respectively, and 6cm and 5.5cm, respectively, pre-radiation. Both patients had drains inserted to Ommaya reservoirs. We performed surveillance imaging during RT utilizing spiral computer tomography (CT) on a weekly basis and reconstructed the treatment dose on the surveillance CTs to ensure target coverage and normal tissue sparing. We compared the dosimetry in these cases for PBT versus intensity-modulated radiation therapy, characterized the cyst evolution during treatment in 3 dimensions, and define an optimized protocol for treatment planning and intra-treatment monitoring.

Creating planning margins and imaging intervals for intracranial stereotactic radiosurgery treatment using patient log files

To account for intra-fractional patient movement during stereotactic radiosurgery, Cyberknife utilises two orthogonal ceiling mounted kV sources that can be used to track patient movement with a variable imaging interval of between 15 and 150 s according to the user’s discretion. Imaging intervals can be optimised to keep imaging dose to a minimum while retaining delivery accuracy. Log files recorded during the treatment delivery can be used to establish both optimum imaging interval and also a suitable treatment margin to account for the patient movement that cannot be accounted for by imaging. Log files for 56 intracranial patients (100 fractions, 5000 image pairs) were retrospectively assessed for patient movement. Movement between consecutive images was investigated, along with the movement of the patient over the duration of the treatment. It was found that from image to image, patient movement did not vary with respect to interval times. The standard deviation (SD) for the movement between images was found to be 0.32, 0.36 and 0.33 mm for superior/inferior (SI), left/right (LR) and anterior/posterior (AP) movement respectively. The rate of drift between the images was used to calculate that an interval of 28 s was required to restrict the translational movement of the patient to 0.1 mm for 95% of the population. As no relationship could be found between the interval times and movement, it cannot be assumed that the patient movement between images is linear. This movement cannot be accounted for by additional imaging but could be accounted for using additional planning margins. This work shows that log files that have been verified can be used to create treatment margins and imaging intervals. To ensure target coverage, a 0.8 mm margin (0.7 for stochastic and 0.1 for systematic) is recommended, and an imaging interval of 30 s.

Practical lookup tables for ensuring target coverage in a clinical setup for skin cancer electron therapy

AbstractAimTo create practical lookup tables containing percent depth dose (PDD) and profile parameters of electron beams and to demonstrate clinical application of the lookup tables to skin cancer treatment to ensure target coverage in a clinical setup.Materials and methodsFor 6 and 9 MeV electron energies, PDDs and profiles at clinically relevant depths [i.e., R95 (distal depth of 95% maximum dose), R90, R85 and R80] were measured in water at 100 cm source-to-surface distance for an 10×10 cm2 open field and circular cutouts with diameters of 4, 5, 6, 7 and 8 cm. Then PDD parameters along with profile parameters such as width of isodose lines and penumbra at the clinically relevant depths were determined. Output factors for the cutouts were measured at dmax in water and solid water.ResultsWith PDD and profile parameters, dosimetry lookup tables were generated. Based upon the lookup tables, target coverage at prescribed depths was retrospectively reviewed for three skin cancer cases. The lookup tables suggested larger cutouts for adequate target coverage.FindingsDosimetry lookup tables for electron beam therapy should include profile parameters at clinically relevant depths and be provided to clinicians to ensure target coverage in a clinical setup.

A Pilot Study Evaluating the Effectiveness of Dual-Registration Image-Guided Radiotherapy in Patients with Oropharyngeal Cancer

PurposeThe purpose of the article was to determine the impact of Dual Registration (DR) image-guided radiotherapy (IGRT) on clinical judgement and treatment delivery for patients with oropharyngeal cancer before implementation. MethodsNinety cone beam computed tomography images from 10 retrospective patients were matched using standard clipbox registration (SCR) and DR. Three IGRT specialist radiographers performed all registrations and evaluated by intraclass correlation to determine inter-rater agreement, Bland-Altman with 95% limits of agreement to determine differences between SCR and DR procedures, changes in clinical judgment, time taken to perform registrations, and radiographer satisfaction. ResultsInter-rater agreement between radiographers using both SCR and DR was high (0.867 and 0.917, P ≤ .0001). The 95% limits of agreement between SCR and DR procedures in the mediolateral, cranial–caudal, and ventrodorsal translational directions were −6.40 to +4.91, −7.49 to +6.05, and −7.00 to +5.44 mm, respectively. The mediolateral direction demonstrated significant proportional bias (P ≤ .001) suggesting non-agreement between SCR and DR. Eighty percent of DR matches resulted in a change in clinical judgement to ensure maximum target coverage. Mean registration times for SCR and DR were 94 and 115 seconds, respectively, and radiographers found DR feasible and satisfactory. ConclusionThe standard method using SCR in patients with oropharyngeal cancer underestimates the deviation in the lower neck. In these patients, DR is an effective IGRT tool to ensure target coverage of the inferior neck nodes and has demonstrated acceptability to radiotherapy clinical practice.

The Use of Established Methods to Quantify Proton Range Uncertainty Reduction When Using Proton Tomography

The dosimetric advantage of treatment with proton beam therapy shows tremendous clinical promise. In proton treatment planning, kV CT images are converted using the stoichiometric method to obtain a model of the relative stopping powers (RSP) of the patient’s tissues. This process has inherent errors in accurately predicting the RSP values within the patient. To ensure target coverage in the presence of these uncertainties, additional margins are added to a proton field resulting in unwanted dose to healthy tissues. Several studies have systematically evaluated the magnitude of range calculation uncertainties when using kV CT imaging, with each yielding similar recommendations. In this study, we used the identical evaluation methods to calculate the potential range uncertainty if the patient model was obtained via direct proton transmission tomography (pCT) rather than kV X-ray imaging. pCT images of a phantom designed with materials of known RSP were obtained and reconstructed using a most likely path length method. The accuracy of the reconstructed images in predicting the RSP varied from 0.1% up to 0.8% for different materials. Using these uncertainties in the pCT images, evaluations for uncertainty margins were made using the identical method as in prior studies. An attempt was made to quantify potential reductions in range uncertainty in a case where pCT is used for the patient model. Table 1 summarizes the potential reduction in range uncertainty margins if pCT images were used to obtain the RSP distributions and compared to RSP distributions obtained using the stoichiometric method from prior studies. Results show that if the error evaluation methods used in the prior studies are re-evaluated using the reported errors of the pCT phantom images, considerable reductions in range uncertainty margins could be obtained.Abstract 3752Tissue TypeRange Error with kV CTRange Error with Proton CTConfidence LevelCommentsMoyers (2010)Soft Tissue3.5%1.4%2.0 SigmaCurrent TechnologySoft Tissue2.2%0.9%2.0 SigmaWith Dual Energy CT and MCYang (2012)Lung5.0%1.0%1.0 SigmaSoft Tissue1.6%0.5%1.0 SigmaBone2.4%0.6%1.0 SigmaPagganetti (2012)4.6%4.0%1.5 SigmaLocal Inhomogeneities2.4%1.4%1.5 SigmaLocal Inhomogeneities w/ MC Open table in a new tab The use of pCT images for modeling the RSP of proton therapy patients will considerably reduce the magnitude of the margins needed to account for proton range uncertainty. With the clinical implementation of more advanced proton delivery, especially multi field optimization methods, the reduction of range uncertainty has become even more critical. Further development in the clinical implementation of pCT in proton therapy departments would greatly benefit proton patients.

Image-guided tandem and cylinder brachytherapy as monotherapy for definitive treatment of inoperable endometrial carcinoma.

Management of endometrial cancer consists of surgical staging with adjuvant therapy guided by risk factors, though some women cannot undergo surgery due to comorbidities. We present a series of women treated with definitive high-dose rate image-guided tandem and cylinder brachytherapy (HDR-IGBT) alone. Patients with grade 1-2, clinical stage I endometrial adenocarcinoma, <50% myometrial invasion, and tumor≤2cm were reviewed. Definitive treatment consisted of 5-6 fractions HDR-IGBT alone with CT- or MRI-based planning. Local-regional control (LRC) was defined as complete imaging response and/or cessation of vaginal bleeding. From 2007 to 2016, 45 patients were treated to a median dose of 37.5Gy. The median gross tumor volume (GTV) and clinical target volume (CTV) were 5.9cm3 (range, 0.7-18.7) and 80.9cm3 (17.2-159.0), respectively. The median cumulative dose to 90% (D90) of the GTV was 132.8Gy (76.5-295.6) equivalent 2Gy dose, and the median CTV D90 was 49.7Gy (34.5-57.2). Median follow-up among living patients was 18.6months (3.0-64.3). Cessation of vaginal bleeding occurred in 98%. Among those with post-treatment MRI (64%), complete radiographic response was demonstrated in 90%. The 2-year LRC, cancer-specific survival, and overall survival rates were 90%, 86%, and 97%, respectively. No grade 3+ acute or late toxicity was observed. HDR-IGBT alone for treatment of early-stage, medically inoperable endometrial cancer is feasible with excellent response rates and clinical results. This approach also allows sparing of critical organs and ensures target coverage, which contributed to the low toxicity rate and high LRC in comparison with 2D point-based series.

Towards fast online intrafraction replanning for free-breathing stereotactic body radiation therapy with the MR-linac

The hybrid MRI-radiotherapy machines, like the MR-linac (Elekta AB, Stockholm, Sweden) installed at the UMC Utrecht (Utrecht, The Netherlands), will be able to provide real-time patient imaging during treatment. In order to take advantage of the system’s capabilities and enable online adaptive treatments, a new generation of software should be developed, ranging from motion estimation to treatment plan adaptation. In this work we present a proof of principle adaptive pipeline designed for high precision stereotactic body radiation therapy (SBRT) suitable for sites affected by respiratory motion, like renal cell carcinoma (RCC). We utilized our research MRL treatment planning system (MRLTP) to simulate a single fraction 25 Gy free-breathing SBRT treatment for RCC by performing inter-beam replanning for two patients and one volunteer. The simulated pipeline included a combination of (pre-beam) 4D-MRI and (online) 2D cine-MR acquisitions. The 4DMRI was used to generate the mid-position reference volume, while the cine-MRI, via an in-house motion model, provided three-dimensional (3D) deformable vector fields (DVFs) describing the anatomical changes during treatment. During the treatment fraction, at an inter-beam interval, the mid-position volume of the patient was updated and the delivered dose was accurately reconstructed on the underlying motion calculated by the model. Fast online replanning, targeting the latest anatomy and incorporating the previously delivered dose was then simulated with MRLTP. The adaptive treatment was compared to a conventional mid-position SBRT plan with a 3 mm planning target volume margin reconstructed on the same motion trace. We demonstrate that our system produced tighter dose distributions and thus spared the healthy tissue, while delivering more dose to the target. The pipeline was able to account for baseline variations/drifts that occurred during treatment ensuring target coverage at the end of the treatment fraction.