Planning Target Volume Reduction Research Articles

Skin/mucosa avoidance radiotherapy (SMART) versus conventional volumetric arc-based radiotherapy (VMAT) for the treatment of head and neck cancer: Dosimetric feasibility study.

Intensity modulated radiotherapy (IMRT) for head and neck cancer has led to a reduction in radiotherapy doses to normal tissues, like the salivary glands, while maintaining high rates of local control. Oral mucosal and skin toxicity is still a major source of treatment-related morbidity, occurring in most patients. We conducted a dosimetric feasibility study with the goal of creating a methodology that could theoretically reduce the dose of radiation to skin and oral mucosa, while maintaining comparable avoidance of other organs at risk, and planning target volume (PTV) coverage. The clinical plans of patients treated previously were replanned using coplanar VMAT arcs on a TrueBeam STx using the photon optimizer (PO) version 15.6 and the Acuros XB dose calculation algorithm. Comparisons were made between three methodologies: "Conventional," "Skin Sparing" and a skin/mucosa avoiding ("SMART") technique, with dose metrics being compared using analysis of variance, with a Bonferroni correction to account for multiple pairwise comparisons. The maximum grade of mucositis and radiation dermatitis during treatment was correlated to different dose-volume metrics to predict what could be clinically meaningful. Sixteen patients met the study criteria and were replanned using the skin sparing and SMART techniques. Maximum doses to the skin sparing structure were reduced from 64.2Gy to 56.6 and 55.9Gy, in the skin sparing and SMART plans (p<0.0001), and mean doses reduced from 26.7Gy to 20.0 and 20.2Gy, respectively (p<0.0001). Maximum doses to the oral cavity structure were not reduced by either technique, however mean dose to the oral cavity structure was reduced from 39.03Gy to 33.5Gy by the SMART technique (p<0.0001). There was a slight reduction in PTV_High coverage by the V95% in the SMART plans (99.52%vs. 98.79%, p=0.0073), and a similar slight reduction in PTV_Low coverage by the V95% by both the skin sparing and SMART plans (99.74%vs. 97.89%vs. 97.42%, p<0.0001). Maximum doses to organs at risk were not statistically different between techniques. Dose to oral cavity and maximum grade experienced during radiotherapy correlated. The Spearman correlation coefficient for dose to 20%, 50%, and 80% of the volume of oral cavity was 0.5 (p=0.048), 0.64 (p=0.007), and 0.62 (p=0.010), respectively. Skin toxicity grade was only found to be correlated with the D20% of the skin sparing structure (Spearman correlation coefficient of 0.58, p=0.0177). The SMART technique appears to be able to reduce maximum and mean skin dose, as well as mean oral cavity doses, while only slightly reducing PTV coverage, with acceptable OAR doses. We feel the improvements warrant investigation in a clinical trial.

Endobronchially Implanted Real-Time Electromagnetic Transponder Beacon–Guided, Respiratory-Gated SABR for Moving Lung Tumors: A Prospective Phase 1/2 Cohort Study

Endobronchial electromagnetic transponder beacons (EMT) provide real-time, precise positional data of moving lung tumors. We report results of a phase 1/2, prospective, single-arm cohort study evaluating the treatment planning effects of EMT-guided SABR for moving lung tumors. Eligible patients were adults, Eastern Cooperative Oncology Group 0 to 2, with T1-T2N0 non-small cell lung cancer or pulmonary metastasis ≤4 cm with motion amplitude ≥5 mm. Three EMTs were endobronchially implanted using navigational bronchoscopy. Four-dimensional free-breathing computed tomography simulation scans were obtained, and end-exhalation phases were used to define the gating window internal target volume. A 3-mm expansion of gating window internal target volume defined the planning target volume (PTV). EMT-guided, respiratory-gated (RG) SABR was delivered (54 Gy/3 fractions or 48 Gy/4 fractions) using volumetric modulated arc therapy. For each RG-SABR plan, a 10-phase image-guided SABR plan was generated for dosimetric comparison. PTV/organ-at-risk (OAR) metrics were tabulated and analyzed using the Wilcoxon signed-rank pair test. Treatment outcomes were evaluated using RECIST (Response Evaluation Criteria in Solid Tumours; version 1.1). Of 41 patients screened, 17 were enrolled and 2 withdrew from the study. Median age was 73 years, with 7 women. Sixty percent had T1/T2 non-small cell lung cancer and 40% had M1 disease. Median tumor diameter was 1.9 cm with 73% of targets located peripherally. Mean respiratory tumor motion was 1.25 cm (range, 0.53-4.04 cm). Thirteen tumors were treated with EMT-guided SABR and 47% of patients received 48 Gy in 4 fractions while 53% received 54 Gy in 3 fractions. RG-SABR yielded an average PTV reduction of 46.9% (P < .005). Lung V5, V10, V20, and mean lung dose had mean relative reductions of 11.3%, 20.3%, 31.1%, and 20.3%, respectively (P < .005). Dose to OARs was significantly reduced (P < .05) except for spinal cord. At 6 months, mean radiographic tumor volume reduction was 53.5% (P < .005). EMT-guided RG-SABR significantly reduced PTVs of moving lung tumors compared with image-guided SABR. EMT-guided RG-SABR should be considered for tumors with large respiratory motion amplitudes or those located in close proximity to OARs.

Clinical outcomes and factors involved in the local control of proton beam therapy for oligometastatic liver tumors in patients with colorectal cancer.

There are no existing reports on proton beam therapy (PBT) for local control (LC) of liver metastasis of colorectal cancer (LMCRC). We calculated the LC rate of PBT for LMCRC and explored the influence of each factor on the LC rate. Cases in which PBT was performed at our center between 2009 and 2018 were retrospectively selected from the database. Patients with LMCRC without extrahepatic lesions and no more than three liver metastases were included. Effectiveness was assessed based on LC, overall survival (OS), and progression-free survival (PFS) rates. Adverse events (AEs) are described. Factors that may be related to LC were also investigated. This study included 23men and 18women, with amedian age of66 (range 24-87) years. Atotal of 63lesions were included in the study. The most frequent dose was 72.6 Gy (relative biological effectiveness)/22fractions. The median follow-up period was 27.6months. The 3‑year LC, OS, and PFS rates were 54.9%, 61.6%, and 16.7%, respectively. Our multivariate analysis identified the distance between the tumor and the gastrointestinal (GI) tract as afactor associated with LC (P = 0.02). No grade ≥ 3AEs were observed. None of the patients experienced liver failure during the acute or late phase. Care must be taken with tumors that have reduced planning target volume coverage owing to organs at risk restrictions, especially in tumors near the GI tract.

Importance of four-dimensional computed tomography simulation in locally advanced lung cancer radiotherapy: Impact on reducing planning target volume

Background/Aim. Four-dimensional (4D) computed tomography (CT) simulation is a useful tool for motion assessment in lung cancer radiotherapy. Conventional three-dimensional (3D) free-breathing (FB) simulation is static, with limited motion information on respiratory movements that can produce inaccuracies in the delineation process and radiotherapy planning. The aim of this study was to compare clinically significant differences between the target volumes defined on 3D CT vs. 4D CT simulation and the potential impact on the planning target volume (PTV), bearing in mind that a reduced PTV with precise coverage of the primary tumor is extremely important. In addition, quantification of movements of the primary tumor (gross tumor volume ? GTV) was performed during 4D CT simulation on three axes: Z-superoinferior (SI), X-mediolateral (ML), and Y-anteroposterior (AP). Methods. This retrospective study evaluated 20 lung cancer patients who underwent CT simulation for radical radiotherapy treatment. FB 3D CT and 4D CT simulations were acquired for each patient in accordance with our institutional protocol. A volumetric comparison of radiation volumes defined on 3D CT vs. 4D CT simulation was done on the following: GTV 3D vs. internal GTV (IGTV) 4D and PTV 3D vs. internal PTV (IPTV) 4D. The comparison of GTV movement in the FB phase GTV (GTV FB), phase 0 (GTV 0), phase 50 (GTV 50), and phase maximum intensity projection (GTV MIP) was made with GTV FB as the basic value. The evaluation was made on all three axes. Results. The comparison of volumetric values between GTV 3D vs. IGTV 4D was 63.15 cm3 vs. 85.51 cm3 (p &lt; 0.001), respectively. IGTV 4D was significantly larger than GTV 3D (p &lt; 0.001). The mean value of equivalent spherical diameter (ESD) for PTV 3D vs. IPTV 4D was 8.44 cm vs. 7.82 cm (p &lt; 0.001), respectively, and the mean value volume PTV 3D vs. IPTV 4D was 352.70 cm3 vs. 272.78 cm3 (p &lt; 0.001), respectively. PTV 3D was significantly larger than IPTV 4D (p &lt; 0.001). A statistically significant difference (p &lt; 0.05) was identified in the deviation related to the Z-axis between the upper and lower lobe. Conclusion. 4D CT simulation-based delineation can reduce PTV compared to 3D simulation-based radiation therapy; therefore, it is a prerequisite for high-quality and precise radiation therapy treatment.

Dosimetric benefits of dynamic conformal arc therapy-combined with active breath-hold in lung stereotactic body radiotherapy.

To test the hypothesis that dynamic conformal arc therapy (DCAT) in Monaco, compared with volumetric modulated arc therapy (VMAT), maintains plan quality with higher delivery efficiency for lung stereotactic body radiotherapy (SBRT) and to investigate dosimetric benefits of DCAT with active breath-hold (DCAT+ABH), compared with free-breathing (DCAT+FB) for varying tumor sizes and motions. Fifty DCAT plans were used for lung SBRT. Randomly selected 17 DCAT plans were evaluated with respect to the retrospectively generated volumetric modulated arc therapy (VMAT) plans. The maximum dose at 2 cm from planning target volume (PTV) in any direction (D2cm/Rx), the ratio of 50% prescription isodose volume to the PTV (R50%), conformity index (CI), the lung volume receiving ≥20 Gy (V20), and monitor unit (MU) were evaluated. A t-test was used to evaluate the difference of plan quality between DCAT and VMAT. Internal target volume (ITV)/integrated-gross target volume (GTV) attributed by intra-fraction motion and lung V20 were stratified for DCAT+ABH and DCAT+FB across varying GTVs. DCAT maintained plan quality (p = 0.154 for D2cm/Rx, p = 0.089 for R50%, p = 0.064 for CI, and p = 0.780 for lung V20) while reducing MUs up to 30% (p <0.001) from 2748 MU (VMAT) to 1868 MU (DCAT). DCAT+ABH, compared to DCAT+FB, reduced tumor motion, resulting in 19% volume reduction of PTV and 60% reduction in lung V20, on average. The difference in lung V20 between DCAT+ABH and DCAT+FB increased as the target size increased. The DCAT is a favorable approach compared with VMAT. These results support the utility of DCAT as a routine planning platform for lung SBRT, especially when utilized with respiratory motion management using the ABH.

A Prospective Study of a Resorbable Intravesical Fiducial Marker for Bladder Cancer Radiation Therapy

PurposeWe conducted a prospective pilot study to evaluate safety and feasibility of TraceIT, a resorbable radiopaque hydrogel, to improve image guidance for bladder cancer radiation therapy (RT). Methods and MaterialsPatients with muscle invasive bladder cancer receiving definitive RT were eligible. TraceIT was injected intravesically around the tumor bed during maximal transurethral resection of bladder tumor. The primary endpoint was the difference between radiation treatment planning margin on daily cone beam computed tomography based on alignment to TraceIT versus standard-of-care pelvic bone anatomy. The Van Herk margin formula was used to determine the optimal planning target volume margin. TraceIT visibility, recurrence rates, and survival were estimated by Kaplan-Meier method. Toxicity was measured by Common Terminology Criteria for Adverse Events version 4.03. ResultsThe trial was fully accrued and 15 patients were analyzed. TraceIT was injected in 4 sites/patient (range, 4-6). Overall, 94% (95% confidence interval [CI], 90%-98%) of injection sites were radiographically visible at RT initiation versus 71% (95% CI, 62%-81%) at RT completion. The median duration of radiographic visibility for injection sites was 106 days (95% CI, 104-113). Most patients were treated with a standard split-course approach with initial pelvic radiation fields, then midcourse repeat transurethral resection of bladder tumor followed by bladder tumor bed boost fields, and 14/15 received concurrent chemotherapy. Alignment to fiducials could allow for reduced planning target volume margins (0.67 vs 1.56 cm) for the initial phase of RT, but not for the boost (1.01 vs 0.96 cm). This allowed for improved target coverage (D95% 80%-83% to 91%-94%) for 2 patients retrospectively planned with both volumetric-modulated arc therapy and 3-dimensional conformal RT. At median follow-up of 22 months, no acute or late complications attributable to TraceIT placement occurred. No patients required salvage cystectomy. ConclusionsTraceIT intravesical fiducial placement is safe and feasible and may facilitate tumor bed delineation and targeting in patients undergoing RT for localized muscle invasive bladder cancer. Improved image guided treatment may facilitate strategies to improve local control and minimize toxicity.

MRI-Guided APBI Using Brachytherapy PTV Margins is Well Tolerated With Low Ipsilateral Breast Tumor Recurrence Risk

External beam accelerated partial breast irradiation (APBI) utilizes Planning Target Volume (PTV) expansions of 2 to 2.5 cm beyond the surgical cavity to assure treatment of target breast tissue. Decreasing the volume of irradiated breast with external beam accelerated partial breast irradiation (APBI) is a potential way to minimize dose to organs at risk and adverse cosmetic outcomes. Magnetic resonance guided radiation therapy (MRgRT) allows detailed pre-fraction imaging and continuous intrafraction monitoring which allows for external beam APBI treatments using a brachytherapy-style 1 cm surgical bed to PTV margin. We have previously shown that MRgRT APBI results in an average 52% reduction in PTV. In this study we report the outcomes of patients treated with reduced-margin APBI via MRgRT.Patients included women with early stage, node negative breast cancers treated with breast conserving surgery and adjuvant MRgRT APBI from March 2014 to July 2019. PTV was defined as the surgical cavity plus a uniform 1-cm margin of breast tissue (excluding chest wall, pectoral muscles, and 5mm from skin). The PTV received 38.5 Gy in ten fractions over five treatment days. Volumetric MR imaging was acquired prior to each fraction to localize the surgical cavity and a sagittal cine MR imaging during each treatment to monitor intrafraction motion; gating to the surgical bed was used as needed.242 patients were treated with MRgRT APBI with reduced margins. Eighty-one (33.5%) patients had pure DCIS and 161 (66.5%) patients had pT1N0 disease. Seventy-three (90.1%) patients with pure DCIS had hormone sensitive disease and 141 (87.6%) patients with invasive disease had hormone sensitive, her2/neu negative disease. Stratifying by ASTRO APBI Consensus guidelines, 36% of patients were categorized as Cautionary and one patient was Unsuitable solely due to age < 40. At a median follow up of 36 months (range, 14 - 82), two patients (0.8%) had biopsy-proven in-breast tumor recurrence (IBTR), both of whom were successfully salvaged. Per the Aaronson-modified Harris scale, providers reported 100% of patients had good/excellent cosmesis prior to APBI and at last follow-up. Nearly two thirds of patients experienced no acute skin toxicity with the remaining having small regions of grade 1 erythema. There were no observed CTCAEv4.0 grade 3+ toxicities following APBI.APBI with reduced margins using MR-IGRT is safe and has excellent cosmetic outcomes with acceptably low initial rates of IBTR.

Retrospective evaluation of planning margins for patients undergoing radical radiation therapy treatment for bladder cancer using volumetric modulated arc therapy and cone beam computed tomography.

IntroductionCurrent contouring guidelines for curative radiation therapy for muscle‐invasive bladder cancer (MIBC) recommend margins of 1.5–2.0 cm, applied to the clinical target volume (CTV). This study assessed whether the use of volumetric modulated arc therapy (VMAT), cone beam computed tomography (CBCT) and strict bladder preparation allowed for a reduced planning target volume (PTV) expansion, resulting in lower doses to surrounding organs at risk (OARs).MethodsDaily CBCT images for 12 patients (382 scans total) were retrospectively reviewed against four potential PTV margins created on and exported with the reference CT scan. To form the PTVs, three isotropic expansions of 0.5, 1.0 and 1.5 cm were applied to the CTV, as well as an anisotropic expansion of 1.5 cm superiorly and 1.0 cm in all other dimensions. Following treatment completion, the CBCTs were visually assessed to determine the margins encapsulating the bladder. For retrospective planning purposes, the 1.0‐cm and anisotropic margins were compared with the previously recommended margins to determine differences in OAR doses.ResultsThe 0.5‐, 1.0‐ and 1.5‐cm isotropic margins (IM) and the anisotropic margin (ANIM) covered the CTV in 46.1, 96.8, 100 and 100% of CBCTs retrospectively. Doses to OARs were significantly lower for the reduced margin plans for the small bowel, rectum and sigmoid.ConclusionBladder planning target volumes may be safely reduced. We endorse a PTV margin of 1.0cm anteriorly, posteriorly and inferiorly with 1.0–1.5 cm superiorly for radical whole bladder cases using strict bladder preparation, VMAT and pretreatment CBCTs.

Impact of four-dimensional cone-beam computed tomography on target localization for gastric mucosa-associated lymphoid tissue lymphoma radiotherapy: reducing planning target volume

BackgroundRadiotherapy of gastric mucosa-associated lymphoid tissue (MALT) lymphoma should be delivered to the entire stomach with planning target volume (PTV) that accounts for variations in stomach volume, respiratory movement, and patient set-up error. In this study, we evaluated whether the use of four-dimensional cone-beam computed tomography (4D-CBCT) reduces the PTV.MethodsEight patients underwent radiotherapy with 15 fractions of gastric MALT lymphoma using 4D-CBCT. PTV structures of 5–30 mm margins (5 mm intervals) from the clinical target volume (CTV) delineated based on the 4D-CT images (CTV-4D) were generated. For the target localization, we performed matching based on skin marking (skin matching), bone anatomy (bone matching), and stomach anatomy (4D soft-tissue matching) based on registration between planning CT and 4D-CBCT images from 10 phases. For each patient, we calculated the covering ratio (CR) of the stomach with variable PTV structures, based on the 4D-CBCT images, with a total of 150 phases [CR (%) = (number of covering phases/150 phases) × 100], for three target localization methods. We compared the CR values of the different target localization methods and defined the PTV with an average CR of ≥ 95% for all patients.ResultsThe average CR for all patients increased from 17.9 to 100%, 19.6 to 99.8%, and 33.8 to 100%, in the skin, bone, and 4D soft-tissue matchings, respectively, as the PTV structures increased from 5 to 30 mm. The CR obtained by 4D soft-tissue matching was superior to that obtained by skin (P = 0.013) and bone matching (P = 0.008) for a PTV structure of 15 mm margin. The PTV required an additional margin of 20 mm (average CR: 95.2%), 25 mm (average CR: 99.1%), and 15 mm (average CR: 98.0%) to CTV-4D for the skin, bone, and 4D soft-tissue matchings, respectively.ConclusionsThis study demonstrates that the use of 4D-CBCT reduces the PTV when applying 4D soft-tissue matching, compared to skin and bone matchings. Additionally, bone matching does not reduce the PTV as compared with traditional skin matching.

Clinical implementation of artificial intelligence-driven cone-beam computed tomography-guided online adaptive radiotherapy in the pelvic region.

Background and purposeStudies have demonstrated the potential of online adaptive radiotherapy (oART). However, routine use has been limited due to resource demanding solutions. This study reports on experiences with oART in the pelvic region using a novel cone-beam computed tomography (CBCT)-based, artificial intelligence (AI)-driven solution.Material and methodsAutomated pre-treatment planning for thirty-nine pelvic cases (bladder, rectum, anal, and prostate), and one hundred oART simulations were conducted in a pre-clinical release of Ethos (Varian Medical Systems, Palo Alto, CA). Plan quality, AI-segmentation accuracy, oART feasibility and an integrated calculation-based quality assurance solution were evaluated. Experiences from the first five clinical oART patients (three bladder, one rectum and one sarcoma) are reported.ResultsAuto-generated pre-treatment plans demonstrated similar planning target volume (PTV) coverage and organs at risk doses, compared to institution reference. More than 75% of AI-segmentations during simulated oART required none or minor editing and the adapted plan was superior in 88% of cases. Limitations in AI-segmentation correlated to cases where AI model training was lacking. The five first treated patients complied well with the median adaptive procedure duration of 17.6 min (from CBCT acceptance to treatment delivery start). The treated bladder patients demonstrated a 42% median primary PTV reduction, indicating a 24%-30% reduction in V45Gy to the bowel cavity, compared to non-ART.ConclusionsA novel commercial oART solution was demonstrated feasible for various pelvic sites. Clinically acceptable AI-segmentation and auto-planning enabled adaptation within reasonable timeslots. Possibilities for reduced PTVs observed for bladder cancer indicated potential for toxicity reductions.

Low Rates of Chest Wall Toxicity When Individualizing the Planning Target Volume Margin in Patients With Early Stage Lung Cancer Treated With Stereotactic Body Radiation Therapy

PurposeChest wall (CW) toxicity is a potentially debilitating complication of stereotactic body radiation therapy for non-small cell lung cancer, occurring in 10% to 40% of patients. Smaller tumor-to-CW distance has been identified as a risk factor for CW toxicity. We report our experience with individualizing the planning target volume (PTV) along the CW in an effort to reduce the volume of this organ at risk receiving 30 Gy to 50 Gy. Methods and materialsWe performed an institutional review board–approved retrospective analysis of patients with stage I (T1-2aN0M0) non-small cell lung cancer who received stereotactic body radiation therapy between June 2009 and July 2016. Four-dimensional computed tomography was used for treatment planning. A uniform 5-mm expansion of the internal target volume was generated for the PTV. Areas of overlap with the CW were removed from the PTV. Treatment was delivered with cone beam computed tomography guidance. CW toxicity was assessed per the Common Terminology Criteria for Adverse Events, version 5. Descriptive statistics were used to analyze outcomes. ResultsThe median follow-up time was 36.8 months. A total of 260 tumors were treated in 225 patients. 225 tumors in 203 patients were peripheral. The internal target volumes for 143 tumors (63.6%) were located within 5 mm of the CW. The median total dose was 48 Gy (range, 42-60 Gy) in 4 fractions (range, 3-5 fractions). The overall rate of grade 1 to 2 CW toxicity was 2.2%, and 2.8% for tumors located within 5 mm of the CW. There were no grade 3/4 cases and no increase in local recurrences with the use of a truncated PTV with a 3-year local control of 92.1% (95% confidence interval, 87.4%-96.8%). ConclusionsTruncation of the PTV margin along the CW resulted in a marked reduction of CW toxicity for tumors in close proximity to the CW, with only a 2.8% rate of grade 1 to 2 CW toxicity. Despite PTV reduction, there was no appreciable increase in local failures. A multi-institutional validation of this technique is needed before general incorporation into clinical practice.

68Ga-DOTATATE PET/MRI as an Adjunct Imaging Modality For Radiation Treatment Planning Of Meningiomas

Meningiomas express somatostatin receptor 2 (SSTR2). PET imaging with [68Ga]-DOTATATE, which targets SSTR2, has demonstrated clinical utility in delineating meningioma versus reactive dural thickening, particularly in the postoperative setting. Our study provides comparative volumetric and dosimetric analyses validating DOTATATE PET/MRI-assisted target delineation for radiotherapeutic planning of meningiomas. As a secondary aim, adverse events and 6-month progression-free survival rates are reported. We identified 9 residual / recurrent meningiomas in 8 patients who underwent 68Ga-DOTATATE PET/MRI prior to fractionated stereotactic radiosurgery (SRS) from 1/1-12/31/19. Demographic and clinical data were collected. CT simulation scans were fused with DOTATATE PET/MRI. Gross target volumes (GTV) were derived from the MRI and DOTATATE PET (acquired simultaneously). All GTV were given a 3.0 mm isometric expansion to generate the planning target volume (PTV). Patients received SRS to a nominal dose of 35 Gy in 5 fractions. Ascribing an α/β = 6 for atypical meningiomas produced a biologically equivalent dose (BED) of 75.83 Gy. Each patient was retrospectively recontoured per the RTOG 0539 intermediate-risk group cohort and received 54 Gy in 30 fractions (BED = 70.2 Gy). Planning volumes from DOTATATE PET/MRI-assisted and SOC plans were compared. All treatment related data were converted to EQD2 for dosimetric analysis. Mean and maximum equivalent doses were generated for target volumes, and OARs within 1 cm of the PTV, and compared using Wilcoxon matched pairs signed rank test. The cohort comprised 8 recurrent / residual WHO grade II meningiomas and 1 recurrent WHO grade I meningioma. BED max and mean were higher among DOTATATE-PET/MRI-guided plans (table). While PET/MRI-guided planning did not significantly reduce mean GTV, it significantly reduced mean PTV, and mean and max dose to the whole brain, optic nerves and scalp. While underpowered to reach significance, DOTATATE-guided plans reduced mean and max doses to the lens, eyes, chiasm, cochlea, brainstem, and hippocampi by at least 50%. Acute side effects were limited to focal alopecia in 1 patient. No recurrences were detected among 3 patients who underwent 6-month post-treatment imaging. [68Ga]-DOTATATE-PET/MRI improves post-operative target delineation for radiotherapy in patients with intracranial meningiomas, often resulting in PTV reduction and decreased OAR dose, compared with plans generated from SOC (MRI-based) planning. Our findings warrant larger studies evaluating DOTATATE-PET/MRI in the radiotherapeutic planning of meningiomas.Abstract 3552; TableParameterDOTATATE- unassisted planDOTATATE - planpGTV mean (cc)16.44.1>0.05PTV mean (cc)71.411.1<0.05BED mean (Gy)55.262.9<0.05BED max (Gy)62.674.9<0.05Whole brain mean dose (Gy)6.581.61<0.05Whole brain max dose (Gy)60.971.4<0.05Scalp max dose (Gy)54.318.8<0.05Optic nerve max (Gy)41.317.3<0.05 Open table in a new tab

Evaluation of a collapsed-cone convolution algorithm for esophagus and surface mold 192Ir brachytherapy treatment planning

PurposeTG43 does not account for a lack of scatter and tissue and applicator heterogeneities. The advanced collapsed-cone engine (ACE) algorithm available for use in the Oncentra Brachy treatment planning system (Elekta AB, Stockholm, Sweden) can model these conditions more accurately and is evaluated for esophageal and surface mold brachytherapy treatments. Methods and MaterialsACE was commissioned for use then compared against TG43 for five esophageal and five surface mold treatment plans. Dosimetric differences between each algorithm were assessed using superimposed comparisons and dose-volume histogram statistics. ResultsEsophagus (6 Gy per fraction): Compared with TG43, ACE demonstrated up to a 0.63% and 0.05 Gy reduction in planning target volume (PTV) V100% and PTV D98, respectively. Lung D2cc and bone D2cc deviated by up to 0.09 Gy and 0.03 Gy, respectively. Lung D0.1 cc and bone D0.1 cc both deviated by up to 0.12 Gy.Surface mold (4.5 Gy per fraction): Compared with TG43, ACE demonstrated up to a 12.5% and 0.18 Gy reduction in PTV V80% and PTV D98, respectively. Bone D2cc and D0.1 cc both reduced by up to 0.2 Gy when modeled with ACE. Increasing mold size laterally increased the dosimetric differences between TG43 and ACE. ConclusionsTG43 generally overestimated dose delivered to the target volume and organs at risk for the sites investigated. Dosimetric differences observed for esophageal treatments were minimal; however, surface mold treatments would benefit from the increased dosimetric accuracy offered by ACE.Implementation should be considered for surface mold 192Ir treatment planning, but increased calculation time, additional contouring, and mass density assignment requirements should be scrutinized with regard to their potentially negative impact on current clinical practice.

Effectiveness of rectal displacement devices in managing prostate motion: asystematic review.

To determine whether rectal displacement devices (RDDs) have aprostate-stabilizing effect during prostate external beam radiotherapy (EBRT). Asystematic literature search using the PubMed database from January1, 2000 to December30th, 2019 was conducted. The effect of RDDs on inter- and intra-fractional prostate displacements was extracted. From 356 articles identified via the PubMed database and hand search, 21articles were included in the systematic review. There was no randomized study. Twelve studies evaluated the role of the endorectal balloon (ERB) in managing prostate motion. Four studies reported the effect of hydrogel spacer on prostate motion. Four studies examined the effect of the rectal retractor (RR) on intra-fractional prostate motion, and only one study assessed the impact of ProSpare (Nottinghamshire, UK) in reducing prostate motion. Using an ERB significantly reduces intra-fractional prostate motion. This prostate-stabilizing effect of the ERB can translate into reduced planning target volume (PTV) margins and additional rectal dose sparing. Even with an ERB in place, inter-fractional prostate displacements are seen. As aconsequence, ERB application does not obviate daily verification; however, this is not acrucial topic because pretreatment imaging is always done nowadays. As compared with ERB, the hydrogel spacer significantly reduces rectal dose and toxicity without influencing prostate immobilization. The RR can increase prostate and rectal inter- and intra-fractional stability without aclear influence on the reduction of rectal toxicity. Finally, it is unclear whether ProSpare is asuitable device reducing prostate motion. Further study will be required to clarify whether the prostate-stabilizing effects of the ERB and RR can result in asafe reduction of PTV margins and further sparing of organs at risks, especially the rectum.

Evaluation of various head flexion angles in hippocampal-avoidance whole-brain radiotherapy using volumetric modulated arc therapy

Whole-brain radiotherapy (WBRT) with hippocampal avoidance improves neurocognitive function deterioration. To improve both planning and treatment efficiency, we investigated the feasibility of using the coplanar volumetric-modulated arc therapy (VMAT) technique with various head flexion angles for hippocampal avoidance during WBRT. Six patients with brain metastases were selected for the study. We rotated patient CT images by 90° and changed the couch angle to simulate different head flexion angles. The plan with a head angle of 0° had the lowest planning target volume (PTV) coverage and the highest normal organ dose (i.e., hippocampus and bilateral lenses). When the angle was equal to or greater than 15°, the maximum dose of the hippocampus and the PTV V30 met all dose constraints. The results obtained with head angles equal to or greater than 25° were better than those obtained at angles below 25° with the obviously decreased dose of the bilateral lenses. The VMAT treatment plans of each patient were computed under various head flexion angles using the Eclipse Treatment Planning System. The study demonstrated that 15° is the minimum head flexion angle that should be adopted in clinical practice. For better dose coverage and uniformity for whole-brain PTV and dose reduction of critical organs, the study results suggested utilizing a head angle equal to or greater than 25°, while ensuring that patient comfort is maintained with larger head flexion angles. Compared with non-coplanar linac-based techniques, a tilted head angle with the coplanar VMAT technique not only reduces plan complexity but also improves treatment efficiency.

Impact of Intra-Fractional Motion on Dose Distributions in Lung IMRT.

To investigate the impact of intra-fractional motion on dose distribution in patients treated with intensity-modulated radiation therapy (IMRT) for lung cancer. Twenty patients who had undergone IMRT for non-small cell lung cancer were selected for this retrospective study. For each patient, a four-dimensional computed tomography (CT) image set was acquired and clinical treatment plans were developed using the average CT. Dose distributions were then re-calculated for each of the 10 phases of respiratory cycle and combined using deformable image registration to produce cumulative dose distributions that were compared with the clinical treatment plans. Intra-fractional motion reduced planning target volume (PTV) coverage in all patients. The median reduction of PTV volume covered by the prescription isodose was 3.4%; D98 was reduced by 3.1 Gy. Changes in the mean lung dose were within ±0.7 Gy. V20 for the lung increased in most patients; the median increase was 1.6%. The dose to the spinal cord was unaffected by intra-fractional motion. The dose to the heart was slightly reduced in most patients. The median reduction in the mean heart dose was 0.22 Gy, and V30 was reduced by 2.5%.The maximum dose to the esophagus was also reduced in most patients, by 0.74 Gy, whereas V50 did not change significantly. The median number of points in which dose differences exceeded 3%/3 mm was 6.2%. Intra-fractional anatomical changes reduce PTV coverage compared to the coverage predicted by clinical treatment planning systems that use the average CT for dose calculation. Doses to organs at risk were mostly over-predicted.

42 EXPLORING POST-ZYGOTIC GENETIC VARIATION IN TOURETTE SYNDROME

Novel cancer drugs are subject to strict scientific evaluation of safety and efficacy and usually undergo a cost effectiveness analysis before approval for use in clinical practice. For new techniques in radiotherapy (RT) such as image-guided radiotherapy (IGRT), this is often not the case. We performed a randomized controlled trial to compare daily cone beam computer tomography (CBCT) IGRT with reduced planning target volume (PTV) margins vs weekly orthogonal portal imaging with conventional PTV margins. The primary aim of the study was to investigate the effect of two different image guidance techniques on patient reported outcome (PRO) using early side effects as proxy outcome of late rectal side effects in patients receiving curative RT for prostate cancer.This open label, phase 3 trial conducted at two RT centers in Norway enrolled men aged 18 years or older with previously untreated histologically proven intermediate or high-risk adenocarcinoma of the prostate. Patients eligible for radical RT received it after 3 months of total androgen blockage and were randomly assigned to 78 Gy in 39 fractions guided either by weekly offline orthogonal portal imaging (15 mm margins to PTV) or by daily online CBCT IGRT (7 mm margins to PTV). Based on previous results indicating that acute rectal side effects are a valid proxy outcome for late rectal side effects, the primary outcome was acute rectal toxicity at end of RT as evaluated by rectal bother scale (five of the items from PRO’s QUFW94). The RIC-trial is registered with ClinicalTrials.gov, number NCT01550237.Between October 2012 and June 2015, 257 patients were randomly assigned to weekly offline portal imaging (n = 129) or daily online CBCT IGRT (n = 128). Out of 250 evaluable patients, 96% completed PROs at baseline and 97% at end of RT. Baseline analyses demonstrated balance between groups for baseline characteristics as well as for PROs. In general, patients reported a small degree of side effects at end of RT, and there was no difference between groups for primary outcome (rectal bother scale of QUFW94 1.871 vs 1.884, p = 0.804). In addition, there were no significant differences between groups for any other gastrointestinal or urinary symptom as reported by QUFW94. Health related quality of life analyses (EORTC QLQ 30) demonstrated no differences between groups.In radical RT for prostate cancer, daily CBCT IGRT with reduced PTV margins demonstrated no advantage with respect to patient reported side effects at end of RT as compared to weekly orthogonal offline portal imaging with standard PTV margins.

Usefulness of EZFluence software for radiotherapy planning of breast cancer treatment

This study compared the EZFluence planning technique for irradiation of the breast with commonly used Field-in-Field (FiF) technique by analyzing the dose uniformity, the dose to the lung, heart, and other organs at risk, the total Monitor Unit (MU), and the time spent for planning. Two different 3-dimensional conformal dose plans were created for 20 breast cancer patients. Six patients were treated to a dose of 5000 cGy in 25 fractions and 14 were treated to a dose of 4256 cGy in 16 fractions. Average breast volume was 800 cc (range 128 to 1892 cc). For the FiF technique, the planner manually created between 2 to 4 subfields per gantry angle and sequentially blocked the 115% and 110% isodose line until a homogenous dose distribution was achieved. For the EZFluence technique, the planner implemented the EZFluence script that created an optimal fluence pattern, which was then imported into Eclipse where dose was calculated. Both techniques were optimized to make sure 95% of the breast planning target volume (PTV) received at least 95% of the prescribed dose. Compared to FiF technique, the plans produced by using EZFluence technique, showed the MU increased by 36.9% (p = 0.0002), whereas the planning time decreased significantly by 84.6% (p = 0.00001). The mean heart dose and the relative volume of the heart receiving ≥ 30 Gy (V30) were similar for both techniques. The mean lung dose and the relative volume of lung receiving ≥ 20 Gy (V20) were also comparable between 2 techniques. The contralateral breast mean dose and its relative volume receiving ≥ 3 Gy (V3) and ≥10 Gy (V10) were equally spared and avoided. EZFluence planning technique yielded a 4.6% (p = 0.04) reduction in PTV receiving 105% of the prescribed dose (V105) for the large breast with separation > 22 cm and PTV volume > 650 cc. The EZFluence planning technique yielded the overall comparable or improved dosimetry while significantly reducing planning time.

Monitoring anatomical changes of individual patients using statistical process control during head-and-neck radiotherapy.

Reduced toxicity while maintaining loco-regional control rates have been reported after reducing planning target volume (PTV) margins for head-and-neck radiotherapy (HNRT). In this context, quantifying anatomical changes to monitor patient treatment is preferred. This retrospective feasibility study investigated the application of deformable image registration (DIR) and Exponentially Weighted Moving Average (EWMA) Statistical Process Control (SPC) charts for this purpose. DIR between the computed tomography for treatment planning (pCT) images of twelve patients and their daily on-treatment cone beam computed tomography (CBCT) images quantified anatomical changes during treatment. EWMA charts investigated corresponding trends. Uncertainty analysis provided 90% confidence limits which were used to confirm whether a trend previously breached a threshold. Trends in patient positioning reproducibility occurred before the end of treatment week four in 54% of cases. Using SPC process limits, only 24% of these were confirmed at a 90% confidence level before the end of treatment. Using an a priori clinical limit of 2 mm, absolute changes in patient pose were detected in 39% of cases, of which 82% were confirmed. Soft tissue trends outside SPC process limits occurring before the end of treatment week four were confirmed in 90% of cases. Structure specific action thresholds enabled detection of systematic anatomical changes during the first four weeks of treatment. Investigation of the dosimetric impact of the observed deviations is needed to show the efficacy of SPC to timely indicate required treatment adaptation and provide a safety net for PTV margin reduction.

Evaluating the potential benefit of reduced planning target volume margins for low and intermediate risk patients with prostate cancer using real-time electromagnetic tracking

PurposeThe aim of this study is to quantify and describe the feasibility, clinical outcomes, and patient-reported outcomes of reduced planning target volume (PTV) margins for prostate cancer treatment using real-time, continuous, intrafraction monitoring with implanted radiation frequency transponder beacons. Methods and materialsFor this prospective, nonrandomized trial, the Calypso localization system was used for intrafraction target localization in 31 patients with a PTV margin reduced to 2 mm in all directions. A total of 1333 fractions were analyzed with respect to movement of the prostate, pauses and interruptions, and dosimetric data. Pre- and posttreatment quality-of-life scores were tracked at baseline, during treatment, and up to 24 months after treatment. ResultsThe mean time of daily treatment was 10 minutes, with 96.1% of all treatments falling within a 20-minute treatment window standard. On average, beacon motion exceeded 3 mm during active treatment only 1.76% of the time. The average length of treatment interruption was 34.2 seconds, with an average of 1 interruption every 3.39 fractions. The displacement or excursion of the prostate was the greatest in the superior or inferior dimension (0.11 mm and 0.09 mm, respectively) and anterior or posterior dimension (0.07 mm and 0.13 mm, respectively), followed by the left or right dimension (0.05 mm and 0.06 mm, respectively). At 6 months, patients demonstrated a smaller change in Expanded Prostate Cancer Index Composite scores than the ProtecT comparator group (decreased short-term morbidity). However, in the Bowel and Urinary domains at 12 and 24 months, there was no significant difference. ConclusionsOur data confirm and support that the use of Calypso tracking with intensity modulated radiation therapy reliably provides minimal disruption to daily treatments and overall time of treatment, with the PTV only moving outside of a 3-mm margin < 2% of the time. The use of a 3-mm PTV margin provides adequate dosimetric coverage while minimizing genitourinary and gastrointestinal toxicity.