Planning Tumor Volume Research Articles

Impact of Dosimetric Parameters on Local Control after SBRT for Pancreatic Cancer

<h3>Purpose/Objective(s)</h3> Stereotactic body radiotherapy (SBRT) for pancreatic cancer is an emerging modality to provide local control (LC) in patients deemed to have borderline resectable or locally advanced disease. Given the possibility for significant heterogeneity in dose distributions between SBRT plans, our objective was to determine if there were dosimetric variables associated with improved LC for pancreatic cancer patients. We hypothesized that higher gross tumor volume (GTV), internal target volume (ITV), and planning tumor volume (PTV) doses covering 90% of the volume (D90) as well as minimum (Dmin) and maximum (Dmax) doses would be associated with improved local control. <h3>Materials/Methods</h3> This was a retrospective cohort study including patients who received SBRT for pancreatic adenocarcinoma at a single institution, initially diagnosed as borderline resectable or locally advanced unresectable disease between 2015-2021. Baseline and treatment characteristics were collected including age, gender, performance status, tumor location, staging, CA 19-9 at diagnosis, and use of chemotherapy and/or surgery. Dosimetric parameters included target volume sizes as well as Dmin, Dmax, and D90 for the GTV, ITV, and PTV. These were then converted to BED using the linear/quadratic model based on an alpha/beta of 10Gy. The primary endpoint was LC. The secondary endpoint was overall survival (OS). The Cox proportional hazards model was used for univariate regression analyses (UVA) and the Kaplan-Meier method was utilized to estimate local control. <h3>Results</h3> A total of 55 patients were included in the study. Median follow-up was 9.5 months. All but two patients received 3300cGy in 5 fractions. 49 patients received chemotherapy non-concurrently. 8 patients underwent surgery following RT. On UVA, the Dmin was found to be significantly associated with LC for GTV (p=0.028), ITV (p=0.028), and PTV (p=0.037). D90 for ITV (p=0.010) and PTV (p=0.025) were also associated with LC. Dmax was not significantly associated for any target volume. Other variables significantly associated with LC were performance status (p=0.039), chemotherapy (p=0.008), GTV (p=0.019), and ITV (p=0.028). Patients receiving > 53Gy compared to those receiving ≤ 53Gy had a median time to local recurrence of 15.1 months vs 6.6 months, respectively (p=0.031). No variables on UVA were associated with OS. <h3>Conclusion</h3> This comprehensive dosimetric analysis demonstrates that local control after SBRT for pancreatic cancer is significantly associated with dosimetric factors despite our cohort's relative uniformity in prescription dose. Specifically, an ITV D90 with a BED_α/β10Gy> 53Gy was associated with better LC. This likely reflects the large impact that critical organs-at-risk may have on pancreatic SBRT plans and highlights the need for dosimetric parameter specifications in future studies. Further investigation is warranted for lesions amenable to dose escalation with SBRT to improve LC.

Planning Tumor Volume and Local Control Following Stereotactic Body Radiation Therapy of Early-Stage NSCLC

<h3>Purpose/Objective(s)</h3> Stereotactic body radiation therapy (SBRT) is often used to treat primary early-stage non-small cell lung carcinoma (NSCLC) as an alternative to surgical management. The planning methods used for delivering SBRT differs across institutions with various planning target volume (PTV) margins utilized. The purpose of this study is to evaluate the impact of PTV margin and other factors on local control following SBRT. <h3>Materials/Methods</h3> A total of 283 patients with single lesion early-stage NSCLC treated with SBRT at our institution between 2017-2019 were included in this retrospective analysis. The median age was 75 years, with 57% female gender. Of the treated tumors, 68.6% were peripheral while 31.4% were central. Adenocarcinoma was the most common histology at 35.3% followed by 27.2% squamous cell carcinoma with other/unknown histology in the remaining 37.5% of patients. Mean gross tumor volume (GTV) was 9.7 cc (0.3-92.1) and mean PTV was 33.5 cc (5.3-170). The most common fractionation scheme used was 54 Gy in 3 fractions followed by 48 Gy in 4 fractions with mean biologically effective dose at α/β=10 (BED10) of 149.5 Gy. Local recurrence was based on recurrence of the treated lesion on follow-up imaging, defined as either significant enlargement not consistent with post-treatment radiation fibrosis or significant residual FDG-avidity if a PET/CT scan was obtained. Univariate analysis was performed via Kaplan-Meier analysis to analyze the association of local control with GTV volume, ratio of PTV to GTV volume, BED10, histology, and tumor location. <h3>Results</h3> The median follow-up was 1.6 years. Overall, 30 of the 283 patients (10.6%) developed a local recurrence. Kaplan-Meier analysis of local control and patients with a PTV to GTV ratio greater than the median of 4.74 showed statistically significant better local control at 3-years of 90.9% versus 67.7% (p=0.004). Local control was also significantly associated with GTV volume with 3-year local control of 91.9% for tumors <5 cc versus 67.7% for those >5 cc (p=0.007). The BED10 was significantly associated with local control with a 3-year local control of 82.2% for >150 Gy BED10 versus 78.3% for 100-150 Gy BED10 (p=0.016). Local control was not associated with histology (p=0.146) or central versus peripheral location (p=0.25). <h3>Conclusion</h3> Larger PTV to GTV ratio, smaller tumor volume, and a BED10 of greater than 150 Gy were significantly associated with better local control in patients treated with SBRT for early-stage NSCLC. These factors should be considered when treatment planning for SBRT in these patients.

Reducing CTV to PTV Margins by Assessing Intrafractional Movement of Patients with Cervical Cancer Undergoing Definitive Adaptive Radiation

<h3>Purpose/Objective(s)</h3> The standard treatment for locally advanced gynecologic cancers typically involves pelvic chemoradiation. During radiation treatment planning, the cervix and uterus are delineated which constitute the clinical tumor volume (CTV). The expansion from CTV to planning tumor volume (PTV) ranges from 1.5 – 2.0 cm to account for uterocervical intra- and interfractional motion. With adaptive radiation therapy (ART) interfractional movement is accounted for. Thus, there is potential for CTV to PTV margins to be decreased to account for intrafractional movement and reduce the volume treated, but the correct CTV to PTV margin is unknown. In this pilot study, we compared pre-treatment to post-treatment cone beam CTs (CBCT) for patients undergoing radiation to determine intrafractional movement of the uterocervix. <h3>Materials/Methods</h3> A retrospective cohort of 14 patients with cervical cancer (FIGO stage IB3 – IIIC2) treated with definitive chemoradiation between April 2021 – February 2022 was included. Patients had a median age of 46 years (range 30 – 76 years). 9 patients treated with traditional non-adaptive radiation with 74 fractions had the uterocervix contoured on pre-treatment CBCTs and post-treatment CBCTs by a resident physician or physicist that were approved by the supervising attending physician. Anterior-posterior, lateral, and superior-inferior shifts were calculated based on contours and the average shift in all directions was calculated. Using this information, a CTV to PTV expansion was determined and verified on a validation cohort of 5 patients with 66 fractions treated with online CBCT based ART. <h3>Results</h3> For all 9 patients, the average anterior-posterior, lateral, and superior-inferior shifts were 0.45 ± 1.04 cm, 0.13 ± 0.54 cm, and 1.51 ± 1.92 cm, respectively. With a uniform expansion of 5 mm around the pre-treatment CTV, 98.85 ± 1.23% of the post-treatment CTV was covered. A 5 mm expansion to the pre-treatment CTV was applied to our validation cohort treated with ART, and 98.58 ± 1.99% of the post-treatment CTV was covered. <h3>Conclusion</h3> Based on our analysis of intrafractional movement, a CTV to PTV margin of 5 mm is adequate to encompass 99% of the CTV. We will continue to use this reduced margin to treat GYN patients with ART and determine whether our proposed margin is appropriate or needs to be changed. A significantly reduced margin could potentially decrease the toxicities associated with radiation for GYN patients and lead to improved patient reported toxicity outcomes.

Long-Term Outcome Following Intensity-Modulated Radiotherapy Delivered Using Individualized Clinical Target Volume Delineation Based on Stepwise Spread Pattern of Nasopharyngeal Carcinoma

<h3>Purpose/Objective(s)</h3> The optimal method for clinical target volume delineation in nasopharyngeal carcinoma has not yet been determined. We have developed an individualized CTV delineation protocol based on the stepwise spread patterns of NPC. This study aimed to determine the long-term outcomes and toxicities in NPC patients receiving intensity-modulated radiotherapy with individualized CTV delineation. <h3>Materials/Methods</h3> We retrospectively reviewed the data of patients with newly diagnosed nondisseminated NPC who underwent IMRT using our individualized CTV delineation protocol. A total of 7,262 patients with NPC (79.3% patients in stage III-IVA) treated between April 2009 and December 2015 were included in this study. Dose–volume statistics, clinical outcomes, patterns of failures and toxicities were assessed. To analyze dose distribution of patients with or without local recurrence, propensity score matching (PSM) was performed to compare the dose between the two groups matched by age, sex, histological type, T category, N category, chemotherapy and gross tumor volume of primary tumor and enlarged retropharyngeal lymph nodes (GTVnx) in a 1:1 ratio. <h3>Results</h3> Median follow-up was 67.3 (range, 2.0-118.7) months. The 5-year local relapse–free survival, regional relapse–free survival, distant metastasis–free survival, progression–free survival, and overall survival rates were 93.6%, 94.4%, 86.8%, 77.8%, and 86.0%, respectively. In-field failure is the major locoregional failure pattern, accounting for 92.3% patients of local and 86% of regional recurrence. Age and T classification were independent prognostic for LRFS, DMFS, PFS, and OS in multivariate analysis. Late grade 3 toxicities were mild and included ear injury (1.8%), xerostomia (0.2%), dysphagia (0.2%), brain injury (0.2%), and trismus (0.1%). No grade 4 toxicity occurred during IMRT or follow-up. PSM analysis revealed no significant difference between minimum (P = 0.815), maximum (P = 0.595), and mean (P = 0.700) dose to the planning tumor volume of primary tumor and enlarged retropharyngeal lymph nodes (PTVnx) between patients with local recurrence and the matched patients without local recurrence. <h3>Conclusion</h3> Our stepwise CTV delineation protocol appears to be a promising strategy for improving outcomes in NPC.

Effectiveness of Standard Margin Stereotactic Radiosurgery Dose to Brain Metastases

This study aims to assess efficacy of a 15-Gy margin dose in terms with the hypothesis that efficacy will be comparable with historical controls with fewer radiation-related side effects. Patients who received single-fraction stereotactic radiosurgery (SRS) for metastatic brain tumors (prescribed 1500 cGy with 2-mm planning tumor volume) at the University of Missouri Hospital between 2004 and 2018 with at least 3 months of follow-up were retrospectively reviewed. Demographics, lesion dimensions, concurrent therapy, and treatment history before SRS were assessed. Outcomes included local control, distant control, radiation-related changes, survival, repeat SRS or whole-brain radiation therapy, and side effects. Data from the literature were pooled for a meta-analysis. A total of 142 patients had at least 3 months of follow-up data available. The 12-month actual local control rate among these patients was 92% per tumor. The overall intracranial control rate was 66.9% per patient. Radiation-related side effects occurred in 32.4% of patients (n= 46), with some patients having more than 1 side effect. Radiation-related radiographic changes occurred in 48 lesions (10.6%) in 37 patients (26%). Pathologically confirmed radiation necrosis occurred in 19 lesions (4%) and in 18 patients (12.6%). Local and distant control rates for this population was comparable with historical controls. Side effects in the literature are inconsistently reported, so rigorous comparative analysis is not possible. A single-fraction radiosurgery margin dose of 15 Gy to the planning tumor volume can effectively provide local control and distant control and is comparable with historical controls, which use 18-25 Gy, with a good toxicity profile.

Single-isocenter multiple-target stereotactic radiosurgery for multiple brain metastases: dosimetric evaluation of two automated treatment planning systems

PurposeAutomated treatment planning systems are available for linear accelerator (linac)-based single-isocenter multi-target (SIMT) stereotactic radiosurgery (SRS) of brain metastases. In this study, we compared plan quality between Brainlab Elements Multiple Brain Metastases (Elements MBM) software which utilizes dynamic conformal arc therapy (DCAT) and Varian HyperArc (HA) software using a volumetric modulated arc therapy (VMAT) technique.Patients and methodsBetween July 2018 and April 2021, 36 consecutive patients ≥ 18 years old with 367 metastases who received SIMT SRS at UPMC Hillman Cancer San Pietro Hospital, Rome, were retrospectively evaluated. SRS plans were created using the commercial software Elements MBM SRS (Version 1.5 and 2.0). Median cumulative gross tumor volume (GTV) and planning tumor volume (PTV) were 1.33 cm3 and 3.42 cm3, respectively. All patients were replanned using HA automated software. Extracted dosimetric parameters included mean dose (Dmean) to the healthy brain, volumes of the healthy brain receiving more than 5, 8,10, and 12 Gy (V5Gy, V8Gy, V10Gy and V12Gy), and doses to hippocampi.ResultsBoth techniques resulted in high-quality treatment plans, although Element MBM DCAT plans performed significantly better than HA VMAT plans, especially in cases of more than 10 lesions). Median V12Gy was 13.6 (range, 1.87–45.9) cm3 for DCAT plans and 18.5 (2.2–62,3) cm3 for VMAT plans (p < 0.0001), respectively. Similarly, V10Gy, V8Gy, V5Gy (p < 0.0001) and median dose to the normal brain (p = 0.0001) were favorable for DCAT plans.ConclusionsBoth Elements MBM and HA systems were able to generate high-quality plans in patients with up to 25 brain metastases. DCAT plans performed better in terms of normal brain sparing, especially in patients with more than ten lesions and limited total tumor volume.

The dose accumulation and the impact of deformable image registration on dose reporting parameters in a moving patient undergoing proton radiotherapy.

IntroductionPotential changes in patient anatomy during proton radiotherapy may lead to a deviation of the delivered dose. A dose estimate can be computed through a deformable image registration (DIR) driven dose accumulation. The present study evaluates the accumulated dose uncertainties in a patient subject to an inadvertent breathing associated motion.Materials and methodsA virtual lung tumour was inserted into a pair of single participant landmark annotated computed tomography images depicting opposite breathing phases, with the deep inspiration breath-hold the planning reference and the exhale the off-reference geometry. A novel Monte Carlo N-Particle, Version 6 (MCNP6) dose engine was developed, validated and used in treatment plan optimization. Three DIR methods were compared and used to transfer the exhale simulated dose to the reference geometry. Dose conformity and homogeneity measures from International Committee on Radioactivity Units and Measurements (ICRU) reports 78 and 83 were evaluated on simulated dose distributions registered with different DIR algorithms.ResultsThe MCNP6 dose engine handled patient-like geometries in reasonable dose calculation times. All registration methods were able to align image associated landmarks to distances, comparable to voxel sizes. A moderate deterioration of ICRU measures was encountered in comparing doses in on and off-reference anatomy. There were statistically significant DIR driven differences in ICRU measures, particularly a 10% difference in the relative D98% for planning tumour volume and in the 3 mm/3% gamma passing rate.ConclusionsT he dose accumulation over two anatomies resulted in a DIR driven uncertainty, important in reporting the associated ICRU measures for quality assurance.

Stereotactic body radiotherapy of prostate cancer: influence of intrafraction motion of prostate on final dose distribution

Purpose: To determine impact of various planning tumour volume (PTV) margins on final dose distribution in patients with maximal intrafraction prostate displacement. Materials: We analyzed data of 15 prostate cancer patients with maximal (значения) prostate intrafraction displacement registered during stereotactic body radiotherapy (SBRT) — 5 fractions of 7.25 Gy. Prostate displacement was determined by cone beam CT that was performed before and after each fraction. Modeling of dose distribution considering prostate displacement was performed for every fraction by isocenter shift. Final dose distribution was calculated as the sum of all fractions and was evaluated for PTV with various margins: 5-5-5-3, 3-3-3-1, 5-5-5 and cropped rectum. Results: The dosimetric impact of maximal intrafraction prostate motion was minimal for target coverage even for PTV with minimal margins (3 in all directions and 1 mm — posterior): CTV V100% varied from 97.5 to 100%. Prostate displacement reduced the dose to the rectum in all but minimal doses were detected for PTV 3-3-3-1: average D2cc — 31.87 Gy (28.41–34.05). For PTV 3-3-3-1 average bladder V100% volume slightly increased from 3.67 (SBRT plan) to 4.87 cc (simulation of intrafraction prostate displacement). Conclusions: The dosimetric impact of maximal intrafraction prostate motion was minimal for target coverage and doses in rectum and bladder even for PTV with minimal (3-3-3-1) margins.

Bronchial Stenosis in Central Pulmonary Tumors Treated With Stereotactic Body Radiation Therapy

PurposeStereotactic body radiation therapy (SBRT) in lung tumors has an excellent local control due to the high delivered dose. Proximity of the proximal bronchial tree (PBT) to the high dose area may result in pulmonary toxicity. Bronchial stenosis is an adverse event that can occur after high dose to the PBT. Literature on the risk of developing bronchial stenosis is limited. We therefore evaluated the risk of bronchial stenosis for tumors central to the PBT and correlated the dose to the bronchi. Methods and MaterialsPatients with a planning tumor volume (PTV) ≤2 cm from PBT receiving SBRT (8 × 7.5 Gy) between 2015 to 2019 were retrospectively reviewed. Main bronchi and lobar bronchi were manually delineated. Follow-up computed tomography scans were analyzed for bronchial stenosis and atelectasis. Bronchial stenosis was assessed using Common Terminology Criteria for Adverse Events Version 4.0 (CTCAEv4). Patient, tumor, dosimetric factors and survival were evaluated between patients with and without stenosis using uni- and multivariate and Kaplan-Meier analysis. ResultsFifty-one patients were analyzed with a median age of 70 years and World Health Organization (WHO) performance status ≤1 in 92.2%. Median follow-up was 36 months (interquartile range [IQR], 19.6-45.4) and median overall survival 48 months (IQR 21.5-59.3). In 15 patients (29.4%) bronchial stenosis was observed on follow-up computed tomography scan. Grade 1 stenosis was seen in 21.6% (n = 11), grade 2 in 7.8% (n = 4). No grade ≥3 stenosis was observed. Median time to stenosis was 9.6 months (IQR 4.4-19.2). Patients who developed stenosis had significantly larger gross tumor volume with a median of 19 cm3(IQR 7.7-63.2) versus 5.2 cm3 (IQR 1.7-11.3, P <.01). Prognostic factors in multivariate analysis for stenosis were age (P = .03; odds ratio [OR] 1.1), baseline dyspnea (P = .02 OR 7.7), and the mean lobar bronchus dose (P = .01; OR 1.1). ConclusionsLow-grade (≤2) lobar bronchial stenosis is a complication in approximately one-third of patients after SBRT for lung tumors with a PTV ≤2 cm from PBT. Prognostic risk factors were age, baseline dyspnea and mean dose on a lobar bronchus.

The application of chair homogeneity index: The advantages of DMLC over VMAT in the radiotherapy for esophageal cancer

Dynamic multileaf-collimator (DMLC) and volumetric modulation arc therapy (VMAT) were compared carefully in radiotherapy for esophagus cancer (EC) with the help of a new plan quality index: chair homogeneity index (CHI). Thirty-five patients with EC who underwent RT were enrolled. The prescription for the planning tumor volume (PTV) was 54Gy/25f and for the boost volume was 60Gy/25f. Two plans were designed for each patient: DMLC and VMAT. The dose-volume constraints were the same for two kinds of plans of each patient. CHI was an index developed by us and described the dose heterogeneity in the PTV but excluding the Boost (P–B). Heterogeneity index (HI), conformity index (CI) and other plan qualities indexes were also collected. The mean CHIs of PTV and P–B were 1.70 and 1.79 in DMLC, significantly higher than 0.82 and 0.86 in VMAT, respectively. The mean HIs of PTV and PTV-Boost were 17.79% and 15.55% in DMLC, slightly higher than 19.33% and 16.83% in VMAT, respectively. From the data aforementioned, DMLC is superior to VMAT in the treatment for EC. The high values of CHI in plans with DMLC proposed that DMLC achieve a more ideal dose distribution inside a compound target than VMAT.

Dosimetric Comparison of the Heart and Left Anterior Descending Artery in Patients With Left Breast Cancer Treated With Three-Dimensional Conformal and Intensity-Modulated Radiotherapy.

BackgroundAdjuvant radiotherapy plays an important role in the management of breast cancer, along with surgery and chemotherapy. However, postoperative radiotherapy poses an increased risk of radiation-induced heart diseases in patients with left-sided breast cancer due to damage of the coronary arteries, which can cause myocardial fibrosis and coronary artery disease; however, there is a lack of sufficient evidence for it. Hence, the present study aimed to assess the dosimetric parameters of the heart and left anterior descending (LAD) coronary artery in patients with left breast cancer treated with three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT).MethodologyThis study included 20 patients with left-sided breast cancer treated between January and July 2019. Patients were equally divided into two groups as follows: group I included those treated with 3DCRT and group II included those treated with IMRT. Radiotherapy was administered to the chest wall and regional lymph nodes. The dose administered for the planning target volume was 50 Gy in 25 daily fractions over five weeks with 6 MV photons. Dosimetric parameters of planning tumor volume (PTV; V95%, V90%, Dmax, Dmin, Dmean, V53.5 Gy, conformity index, and homogeneity index) along with the heart (V5%, V30%, and Dmean) and LAD artery (mean and V25%) were evaluated. Dose-volume histograms were generated and compared. The LAD artery was contoured virtually retrospectively during the study to determine the dosimetric parameters; the dose to the LAD artery was not considered during planning.ResultsDosimetric parameters of the PTV were similar for 3DCRT and IMRT; D95 (38.53 vs. 41.61 Gy), D90 (43.67 vs. 44.77 Gy), Dmean (48.3 vs. 48.72 Gy), conformity index (1.10 vs. 1.06), and homogeneity index (0.50 and 0.28) did not show a significant difference. The Dmean for the LAD artery was significantly higher than that for the heart on 3DCRT (23.66 Gy vs. 8.46 Gy; p < 0.0000) and IMRT (31.53 vs. 17.7 Gy; p < 0.0000). The V25 for the LAD artery was significantly higher than that for the heart on 3DCRT (40.27 vs. 14.13 Gy; p < 0.0024) and IMRT (66.21 vs. 27.74 Gy; p < 0.0002).ConclusionsRadiation doses to the LAD artery and heart must be evaluated prior to radiotherapy in patients with left breast cancer. Long-term follow-up is needed to evaluate cardiac complications and their association with dosimetric parameters.

Is it necessary for clinical tumor volume including neck muscles in target volume delineation of nasopharyngeal carcinoma?

ObjectivesTo calculate the shrinkage of the neck muscles and dosimetric changes and to clarify the necessity of covering part of the muscle in neck node region delineation for patients with nasopharyngeal carcinoma (NPC) treated with intensity‐modulated radiotherapy.MethodsIn total, 44 patients with NPC were enrolled. Distances between the lateral border of the neck muscles and longitudinal midline were measured on every selected slice. This process was repeated three times, and the mean values of the three distances of planning computed tomography (CT) images and repeated CT images were adopted (labeled d1 and d2). The mean value of the differences between d1 and d2 was regarded as the medial shrinkage of the neck muscles. The initial clinical target volume of cervical lymph nodes (CTV‐n) was shifted medially with the value of shrinkage, yielding a new CTV‐n. Doses that covered 95% of the planning tumor volume (PTV) (D95), 99% of the PTV (D99), mean dose (Dmean), and maximum dose (Dmax) were used to calculate the dosimetric variation between the initial and new CTV‐n. Comparisons were performed using the paired samples t test.ResultsThe median d1 was 3.81 cm (range: 1.19‐8.20 cm), and the median d2 was 3.68 cm (range: 0.94‐9.59 cm), with a statistically significant difference (P < .001). The mean difference between d1 and d2 was 1.5 ± 3.1 mm (SD). The D95 and D99 of PTV of initial CTV‐n decreased by 0.38% and 0.62% (P < .001 and P < .001, respectively).ConclusionPatients with NPC experienced medial shrinkage of the neck muscles by 1.5 mm, and the consequent dose variation was negligible. It is unnecessary to cover part of the muscles in the delineation of the CTV‐n.

Proposed Model of Dose Escalation in Localized Pancreatic Cancer Patients Eligible for Surgical Exploration: Neoadjuvant Intensity Modulated Radiation Therapy (IMRT) vs. Stereotactic Body Radiation Therapy (SBRT) and Intra-Operative Radiotherapy (IORT)

Multi-agent chemotherapy and radiation therapy (RT) has increased the proportion of locally advanced pancreatic cancer (LAPC) patients (pts) able to undergo resection and improve overall survival compared to those who are not resected. However, prior data from our institution (2016-2019) indicate that despite an R0 rate of 88%, LF developed in > 30% of LAPC pts resected after neoadjuvant therapy (NAT). This high LF rate is a rationale to explore dose escalation (DE) in the NAT setting, as data highlighting the value of DE have been limited to unresectable disease. Importantly, the optimal method for DE remains unclear. While conformal external beam RT can ablate part of the target, under-coverage in close proximity to the stomach and bowel remains problematic. For pancreatic head tumors, Whipple resection presents an opportunity for subsequent DE with IORT, as the duodenum is resected and direct access to microscopic peri-vascular residual disease is allowed. It also allows for precise DE based on the surgeons' recommendations. Herein, we model DE approaches, comparing pre-operative DE-IMRT with an approach in which a high-dose rate (HDR)-IORT boost is given after SBRT, with a goal biological effective dose (BED10) of 100 Gy.Ten consecutive LAPC pts were modeled with both DE-IMRT to 75 Gy in 25 fractions and SBRT to 40 Gy in 5 fractions followed by HDR-IORT to 15 Gy, using an 192Ir source. Notably, to minimize LF after surgery, our clinical tumor volume (CTV) has been the "Heidelberg Triangle" of tissue between the celiac, superior mesenteric, and common hepatic arteries and portal vein, which contains perineural and lymphatic tissue at risk of harboring subclinical disease. A 5mm planning tumor volume (PTV) expansion was used. A 3mm expansion on stomach and bowel was constrained to 60 Gy and 40 Gy for DE-IMRT and SBRT, respectively. For IORT modeling, the Freiburg Flap was superimposed on the planning CT, and dose was prescribed to the target volume surface. Given rapid dose fall-off with HDR-IORT, SBRT was optimized to compensate for IORT under-coverage, with higher dose allowed posteriorly but with an overall hotspot less than 50 Gy. Descriptive statistics were generated for coverage to target structures.With DE-IMRT, mean V75Gy for the CTV and PTV was only 79% +/- 14.4% and 52% +/- 13%, respectively. In comparison, posteriorly optimizing the SBRT plan in anticipation of anterior IORT supplementation improved coverage with ablative BED. For the anterior half of the target volume, HDR-IORT created a dose gradient of 10-15 Gy, whereas for the posterior half of the target volume, HDR-IORT created a dose gradient of 5-10 Gy. Optimizing the SBRT plan to complement this with 40 Gy to the anterior half of the volume and 45 Gy to the posterior half of the volume was feasible with > 90% coverage with BED10 of 100Gy in composite.Dose escalation with SBRT/IORT may allow for better target coverage with ablative RT dose as compared to DE-IMRT and should be explored clinically.

PO-1165 Dosimetric parameters in hypofractionated radiotherapy in NSCLC cohort during SARS-COV-2 pandemia

Purpose or Objective: Moderate hypofractionation has been more popular in the last years, however no standard dosimetric parameters has been stablished. The majority of the dose-volume-constraints (DVCs) published refer to conventional 2 Gy/ fraction. In this study, we analyse different dosimetric parameters in patients (pts) with non-small cell lung cancer (NSCLC) treated with concomitant radiochemotherapy (RCT) or radiotherapy (RT) alone with radical intention and hypofractionated scheme in pandemic era. Due to the lack of consensus on this aspect, we analyse the relationship between tolerance to treatment and dosimetric parameters to aid its use in the clinic. Materials and Methods: Retrospective and multicentric study of 49 pts with locally advanced NSCLC treated from November 2019 to December 2020. During SARS-CoV-2 pandemic, hypofractionated schedules have allowed to decrease the duration of thoracic radiotherapy. The hypofractionated scheme used was 20 fractions of 2.75 Gy/daily (total dose 55 Gy, BED10=70 Gy). 3-dimensional conformal radiation therapy (3DCRT), intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) were allowed. We report gross tumour volume (GTV), planning tumour volume (PTV) and D98% and D95% PTV. Organ-at-risk (OARs) examined included lungs- GTV (V20<35% and mean-dose<20Gy), heart (V25<10%) and oesophagus (V50<40% and mean-dose<34 Gy). To evaluate toxicity during the treatment, we use CTCAE v.5 scale. Results: Mean GTV was 85.6 cc (3.3cc-581.3cc) and mean PTV was 268.8 cc (13cc-1047.4cc). Mean D98% PTV was 53 Gy and mean D95% PTV was 53.8 Gy. Most pts had G1-G2 cardiac toxicity like pericarditis, oesophagitis and pneumonitis. Only two pts (4%) had G3 oesophagitis and G3 pneumonitis (2%). No grade 4-5 toxicity was reported. In the analysis of DVCs, lungs-GTV V20<35% and lungs-GTV mean-dose < 20 Gy were associated with more pneumonitis regardless of grade (p 0.018 and p 0.027). In terms of oesophagitis, V50<40%, was associated with more oesophagitis regardless of grade (p 0.037). Mean dose < 34 Gy in oesophagus and heart DVCs were no associated with more toxicity in our study. There were not differences between T stage (<T3 vs ≥ T3) and N stage (<N2 vs ≥ N2) and mean PTV (p 0.55 and p 0.178). There were not differences in terms of cancer-specific survival and PTV (p 0.195). Conclusion: In moderately hypofractionation, it is important to consider that dosimetric parameters cannot be the same as in standard fractionation (2 Gy/fraction). Due to changing radiotherapy technique, DVCs may need to be adjusted based on different dose distribution. According to our results, hypofractionated radiotherapy in NSCLC is well-tolerated with low rates of grade 3-4- 5 toxicity but lungs-GTV V20<35%, lungs-GTV mean-dose < 20 Gy and oesophagus V50<40% were associated with more toxicity regardless of grade. Because of that, we consider it worth investigating the relationship between dosimetric parameters and toxicity in order to reach a consensus in daily clinical practice.

Dosimetric Factors and Radiomics Features Within Different Regions of Interest in Planning CT Images for Improving the Prediction of Radiation Pneumonitis.

This study aimed to establish machine learning models using dosimetric factors and radiomics features within 5 regions of interest (ROIs) in treatment planning computed tomography images to improve the prediction of symptomatic radiation pneumonitis (RP) (grade ≥2). This study retrospectively collected data on 79 patients with lung cancer (25 RP ≥2) who underwent chemoradiotherapy between 2015 and 2018. We defined 5 ROIs in planning computed tomography images: gross tumor volume (GTV), planning tumor volume (PTV), PTV-GTV, total lung (TL)-GTV, and TL-PTV. We calculated the mean dose, V5, V10, V20, and V30 within TL-GTV and TL-PTV and the mean dose within the other ROIs. A total of 1924 radiomics features were extracted from all 5 ROIs. We selected the best predictors for classifying 2 groups of patients using a sequential backward elimination support vector machine model. A permutation test was used to assess its statistical significance (P < .05). The best predictors for symptomatic RP were the combination of 11 radiomics features, 5 dosimetric factors, age, and T stage, achieving an area under the curve (AUC) of 0.94 (95% confidence interval [CI], 0.85-1) (accuracy, 90%; sensitivity, 80% [95% CI, 44%-96%]; specificity, 95% [95% CI, 73%-100%]; P = 8 × 10-4). The clinical characteristics, dosimetric factors, and their combination showed limited predictive power (accuracy, 63.3%, 70%, and 70%; AUC [95% CI]: 0.73 [0.54-0.92], 0.53 [0.31-0.75], and 0.72 [0.51-0.92], respectively). The radiomics features of PTV-GTV and TL-PTV outperformed those of the other ROIs (accuracy, 76.7% and 76.7%; AUC [95% CI]: 0.82 [0.65-0.99] and 0.80 [0.59-1], respectively). Combining dosimetric factors and radiomics features within different ROIs can improve the prediction of symptomatic RP. Our results can help physicians adjust the radiation dose distribution of the dose-sensitive lungs and target volumes based on personalized RP estimates.

Acute Toxicity in Hypofractionated/Stereotactic Prostate Radiotherapy of Elderly Patients: Use of the Image-guided Radio Therapy (IGRT) Clarity System.

The use of intra-fractional monitoring and correction of prostate position with the Image Guided Radio Therapy (IGRT) system can increase the spatial accuracy of dose delivery. Clarity is a system used for intrafraction prostate-motion management, it provides a real-time visualization of prostate with a transperineal ultrasound. The aim of this study was to evaluate the use of Clarity-IGRT on proper intrafraction alignment and monitoring, its impact on Planning Tumor Volume margin and on urinary and rectal toxicity in elderly patients not eligible for surgery. Twenty-five elderly prostate cancer patients, median age=75 years (range=75-90 years) were treated with Volumetric Radiotherapy and Clarity-IGRT using 3 different schemes: A) 64.5/72 Gray (Gy) in 30 fractions on prostate and seminal vesicles (6 patients); B) 35 Gy in 5 fractions on prostate and seminal vesicles (12 patients); C): 35 Gy in 5 fractions on prostate (7 patients). Ultrasound identification of the overlapped structures to the detected ones during simulation has been used in each session. A specific software calculates direction and entity of necessary shift to obtain the perfect match. The average misalignment in the three-dimensional space has been determined and shown in a box-plot. All patients completed treatment with mild-moderate toxicity. During treatment, genitourinary toxicity was 32% Grade 1; 4% Grade 2, rectal was 4% Grade 1. At follow-up of 3 months, genitourinary toxicity was 20% Grade 1; 4% Grade 2, rectal toxicity was 4% Grade 2. At follow-up of 6 months, genitourinary toxicity was 4% Grade 1; 4% Grade 2. Rectal toxicity was 4% Grade 2. Radiotherapy with the Clarity System allows a reduction of PTV margins, the amount of fractions can be reduced increasing the total dose, not exacerbating urinary and rectal toxicity with greater patient's compliance.

Dosimetric comparison of three-field and four-field 3D conformal radiation therapy ballistics for rectal cancer treatment

The tremendous improvement made over the last ten years in radiotherapy has been achieved mainly by developing particle acceleration techniques. Three-dimensional conformal radiation therapy [3D-CRT] is crucially applied for decreasing the shape of advanced rectal tumors yet has several side consequences. Our investigation examined the dose distribution in planning target volumes (PTV), the protection of healthy organs at risk (OAR), and the quality of therapy for the two strategies based on the three fields and four fields ballistic used in treating rectal cancers. Using the Varian Linear Accelerator system (Varian Medical Systems, Inc., Palo Alto, CA, USA) integrated with an Eclipse MLC 2100 planning system including Pencil Beam Convolution PBC dose calculation algorithm. Two different treatments of rectal cancer based on the two approaches are performed. A dosimetric comparison of the parameters is made to evaluate the feasibility of each ballistic. These parameters, including the target volume coverage indicators, included average dose, conformity index (CI), and homogeneity index (HI) of planning tumor volume; OAR included the bladder and bilateral proximal femurs. The results achieved in this dosimetric comparative study advocate for the clinical application of three fields ballistic in all specialties already compared, except for the planning target volume PTV dose distribution. The study has shown that the three-field technique (an anterior and two opposing lateral fields with the portals orientation 0°, 90°, 270°) and applied energy photons of 18 MV and 6 MV provides the best bladder protection. According to the dose distribution in the target (PTV), all evaluated plans have not indicated any significant differences. The risk of morbidity in the femoral heads for all the applied methods, in a dose up to 56.396 Gy, was not a therapeutic problem. However, the three-field approach with beams orientation 0°, 120°, 240°gave the best sparing effect for femoral heads.

ESTRO ACROP guideline for target volume delineation of skull base tumors

Background and purposeFor skull base tumors, target definition is the key to safe high-dose treatments because surrounding normal tissues are very sensitive to radiation. In the present work we established a joint ESTRO ACROP guideline for the target volume definition of skull base tumors. Material and methodsA comprehensive literature search was conducted in PubMed using various combinations of the following medical subjects headings (MeSH) and free-text words: “radiation therapy” or “stereotactic radiosurgery” or “proton therapy” or “particle beam therapy” and “skull base neoplasms” “pituitary neoplasms”, “meningioma”, “craniopharyngioma”, “chordoma”, “chondrosarcoma”, “acoustic neuroma/vestibular schwannoma”, “organs at risk”, “gross tumor volume”, “clinical tumor volume”, “planning tumor volume”, “target volume”, “target delineation”, “dose constraints”. The ACROP committee identified sixteen European experts in close interaction with the ESTRO clinical committee who analyzed and discussed the body of evidence concerning target delineation. ResultsAll experts agree that magnetic resonance (MR) images with high three-dimensional spatial accuracy and tissue-contrast definition, both T2-weighted and volumetric T1-weighted sequences, are required to improve target delineation. In detail, several key issues were identified and discussed: i) radiation techniques and immobilization, ii) imaging techniques and target delineation, and iii) technical aspects of radiation treatments including planning techniques and dose-fractionation schedules. Specific target delineation issues with regard to different skull base tumors, including pituitary adenomas, meningiomas, craniopharyngiomas, acoustic neuromas, chordomas and chondrosarcomas are presented. ConclusionsThis ESTRO ACROP guideline achieved detailed recommendations on target volume definition for skull base tumors, as well as comprehensive advice about imaging modalities and radiation techniques.

Re-irradiation of recurrent glioblastoma using helical TomoTherapy with simultaneous integrated boost: preliminary considerations of treatment efficacy

Although there is still no standard treatment for recurrent glioblastoma multiforme (rGBM), re-irradiation could be a therapeutic option. We retrospectively evaluated the efficacy and safety of re-irradiation using helical TomoTherapy (HT) with a simultaneous integrated boost (SIB) technique in patients with rGBM. 24 patients with rGBM underwent HT-SIB. A total dose of 20 Gy was prescribed to the Flair (fluid-attenuated inversion recovery) planning tumor volume (PTV) and 25 Gy to the PTV-boost (T1 MRI contrast enhanced area) in 5 daily fractions to the isodose of 67% (maximum dose within the PTV-boost was 37.5 Gy). Toxicity was evaluated by converting the 3D-dose distribution to the equivalent dose in 2 Gy fractions on a voxel-by-voxel basis. Median follow-up after re-irradiation was 27.8 months (range 1.6–88.5 months). Median progression-free survival (PFS) was 4 months (95% CI 2.0–7.9 months), while 6-month PFS was 41.7% (95% CI 22.2–60.1 months). Median overall survival following re-irradiation was 10.7 months (95% CI 7.4–16.1 months). There were no cases of re-operation due to early or late toxicity. Our preliminary results suggest that helical TomoTherapy with the proposed SIB technique is a safe and feasible treatment option for patients with rGBM, including those large disease volumes, reducing toxicity.

Application of Patient-Customized Cast Type M3 Wax Bolus using a 3D printing for Photon Beam Radiation Therapy in Patients with Scalp Malignant Tumor

Introduction: We investigated the usefulness of patient-customized cast type M3 wax bolus (MWB) in radiation therapy in scalp malignant tumor patients by 3D conformal radiation therapy (3D CRT) and intensity-modulated radiation therapy (IMRT). Material and Methods: A helmet-type polylactic acid (PLA) hollow model was fabricated using a 3D Printing, and the molten MWB was poured into the mold and allowed to harden. Subsequently, a solid MWB head cast was obtained by removing the PLA. The radiation volume was verified using a metal oxide semiconductor field-effect transistor (MOSFET) dosimeter and EBT3 film. Results: Radiation dose verification was performed at the anterior, right, and left angles of planning tumor volume. The error rate demonstrated a maximum value of 5.5% and an average of 3.3% using the MOSFET dosimeter, and a maximum value of 7.0% and an average of 5.4% applying the EBT3 film. The homogeneity indices of the treatment plans were obtained as 0.09 and 0.12 using 3D CRT and IMRT, respectively. Moreover, the conformity number of the treatment plans was reported as 0.79 using 3D CRT and 0.81 applying IMRT. Conclusion: The density of the MWB head cast was 1.05 g/cm3 which is closer to that of the equivalent tissue than the existing helmet type bolus material. In addition, it reduces the processing time and associated pain during custom manufacturing and has little air gaps. Therefore, it can be considered an effective method for the treatment of patients with scalp malignant tumors.