Normal Tissue Constraints Research Articles

Impact of mediastinal tumor burden and lymphatic spread in locally advanced non-small-cell lung cancer: A secondary analysis of the multicenter randomized PET-Plan trial

PurposeThe aim of this secondary analysis of the prospective randomized phase 2 PET-Plan trial (ARO-2009-09; NCT00697333) was to evaluate the impact of mediastinal tumor burden and lymphatic spread in patients with locally advanced non-small-cell lung cancer (NSCLC). MethodsAll patients treated per protocol (n = 172) were included. Patients received isotoxically dose-escalated chemoradiotherapy up to a total dose of 60–74 Gy in 30–37 fractions, aiming as high as possible while adhering to normal tissue constraints. Radiation treatment (RT) planning was based on an 18F-FDG PET/CT targeting all lymph node (LN) stations containing CT positive LNs (i.e. short axis diameter > 10 mm), even if PET-negative (arm A) or targeting only LN stations containing PET-positive nodes (arm B). LN stations were classified into echelon 1 (ipsilateral hilum), 2 (ipsilateral station 4 and 7), and 3 (rest of the mediastinum, contralateral hilum). The endpoints were overall survival (OS), progression-free survival (PFS), and freedom from local progression (FFLP). ResultsThe median follow-up time (95 % confidence interval [CI]) was 41.1 (33.8 − 50.4) months. Patients with a high absolute number of PET-positive LN stations had worse OS (hazard ratio [HR] = 1.09; 95 % CI 0.99 − 1.18; p = 0.05) and PFS (HR = 1.12; 95 % CI 1.04 − 1.20; p = 0.003), irrespective of treatment arm allocation. The prescribed RT dose to the LNs did not correlate with any of the endpoints when considering all patients. However, in patients in arm B (i.e., PET-based selective nodal irradiation), prescribed RT dose to each LN station correlated significantly with FFLP (HR=0.45; 95 % CI 0.24–0.85; p = 0.01). Furthermore, patients with involvement of echelon 3 LN stations had worse PFS (HR = 2.22; 95 % CI 1.16–4.28; p = 0.02), also irrespective of allocation. ConclusionMediastinal tumor burden and lymphatic involvement patterns influence outcome in patients treated with definitive chemoradiotherapy for locally advanced NSCLC. Higher dose to LNs did not improve OS, but did improve FFLP in patients treated with PET-based dose-escalated RT.

Safety of combined ablative radiotherapy and immune checkpoint inhibitors in three phase I trials

BackgroundStereotactic body radiotherapy (SBRT) is safe and effective for treatment of extracranial metastatic disease, but its safety when combined with immune checkpoint inhibitors (ICI) has not yet been comprehensively reported. Here we report adverse events (AEs) associated with combined SBRT and ICI using prospectively-collected data on patients in three trials investigating multi-site SBRT combined with ICI. MethodsPatients were included from three prospective trials of ICI (pembrolizumab; nivolumab/urelumab or nivolumab/cabiralizumab; nivolumab/ipilimumab) with SBRT to 1–4 sites. AEs were recorded prospectively using the CTCAE v4.0. Survival was analyzed using Kaplan-Meier method with a 90-day landmark. Association of patient characteristics with cumulative incidence of AEs was assessed using Fine-Gray regression. Results213 patients were included, with a median follow-up of 10 months. Over the follow-up period, 50 % and 27 % of patients experienced at least one grade ≥ 2 or grade ≥ 3 AE, respectively. Cumulative incidences of grade ≥ 2 and grade ≥ 3 AEs at 6 months were 47 % and 23 %, respectively. Three grade 5 AEs rated “possibly” related to treatment occurred outside the 90-day dose-limiting toxicity window. Landmarked survival analysis of patients with or without grade ≥ 3 AEs showed no significant difference in progression-free or overall survival. Dual-agent ICI was significantly associated with grade ≥ 3 AE. ConclusionThis analysis features the largest prospectively evaluated cohort of patients treated with combination ablative SBRT and ICI to date and provides context for future trial design. We conclude that multi-site SBRT and ICI can be safely co-administered when SBRT is delivered with prioritization of normal tissue constraints.

Dosimetric comparison of proton therapy and CyberKnife in stereotactic body radiation therapy for liver cancers

Stereotactic body radiation therapy (SBRT) has been increasingly used for the ablation of liver tumours. CyberKnife and proton beam therapy (PBT) are two advanced treatment technologies suitable to deliver SBRT with high dose conformity and steep dose gradients. However, there is very limited data comparing the dosimetric characteristics of CyberKnife to PBT for liver SBRT. PBT and CyberKnife plans were retrospectively generated using 4DCT datasets of ten patients who were previously treated for hepatocellular carcinoma (HCC, N = 5) and liver metastasis (N = 5). Dose volume histogram data was assessed and compared against selected criteria; given a dose prescription of 54 Gy in 3 fractions for liver metastases and 45 Gy in 3 fractions for HCC, with previously published consensus-based normal tissue dose constraints. Comparison of evaluation parameters showed a statistically significant difference for target volume coverage and liver, lungs and spinal cord (p < 0.05) dose, while chest wall and skin did not indicate a significant difference between the two modalities. A number of optimal normal tissue constraints was violated by both the CyberKnife and proton plans for the same patients due to proximity of tumour to chest wall. PBT resulted in greater organ sparing, the extent of which was mainly dependent on tumour location. Tumours located on the liver periphery experienced the largest increase in organ sparing. Organ sparing for CyberKnife was comparable with PBT for small target volumes.

Abstract PO2-22-05: A prospective phase I-II study of hypofractionated accelerated breast and nodal intensity modulated radiation therapy delivered in the prone position

Abstract Background In patients with breast cancer, prone radiotherapy (RT) has been shown to reduce heart and lung dose. Routinely used for whole breast (WB) RT, its use to treat regional lymph nodes (LNs) is not widespread. Methods In this phase I-II study (NCT02308488) patients treated with lumpectomy or mastectomy with 1-5 pathologically involved LNs underwent WBRT or post-mastectomy RT plus regional nodal RT using IMRT to the supraclavicular and level III axillary LNs. The prescription was 40.5Gy in 15 daily 2.7Gy fractions with a daily concomitant 0.5Gy tumor bed boost. Patients who underwent sentinel LN biopsy (SLNB) alone (no axillary dissection) had the level I-II axilla included in the RT field. The primary endpoints were incidence of &amp;gt;grade 2 acute toxicity per CTCAE v 3.0 and dosimetric feasibility. The secondary endpoint was late toxicity. Clinical outcomes were local recurrence (LR), disease free survival (DFS), distant recurrence free survival (DRFS) and overall survival (OS). Coverage constraints included planning target volume [PTV] V48Gy ≥ 98%, PTV breast V40.5Gy ≥ 95% and PTV nodes V38.5Gy ≥ 95%. Normal tissue constraints included heart V5Gy &amp;lt; 5%, ipsilateral lung V10Gy &amp;lt; 20%, contralateral lung V5Gy &amp;lt; 15%, ipsilateral brachial plexus (BP) maximal dose (Dmax) &amp;lt; 42Gy, spinal cord Dmax ≤ 3 7.5Gy, thyroid contralateral lobe Dmax ≤ 15Gy, esophagus V30Gy &amp;lt; 50% and Dmax ≤ 40.5Gy. Results From 2011-2016, 97 patients with stage IB-IIA breast cancer were enrolled. 66 underwent lumpectomy and 31 underwent mastectomy. 16 had SLNB alone. There were no grade 3 acute toxicities meeting the primary toxicity endpoint. Common acute low-grade toxicities included fatigue (grade 1: 65 [66.3%]; grade 2: 7 [7.1%]), esophagitis (grade 1: 7 [7.1%]; grade 2: 10 [10.2%]), dermatitis (grade 1: 82 [83.7%]; grade 2: 7 [7.1%]). At median and maximum follow up of 8.02 (IQR: 3.31) and 13.3 years, respectively, there were 2 LRs (2.1%). 8-year DRFS, DFS and OS were 88.1% (95% CI 81.3%, 95.4%), 85.7% (95% CI 78.4%, 94.6%) and 90.5% (95% CI 84%, 97.6%), respectively. Clinician-rated cosmesis (n=64) was excellent/good in 67.2% of cases and fair/poor in 6.3%. Patient- rated cosmesis (n=47) was excellent/good in 91.5% and fair/poor in 8.5%, with patients rating themselves more favorably than their physicians (p=0.0014). The incidence of maximum grade 1, 2 and 3 late toxicities were 49 (62.8%), 15 (19.2%), and 3 (3.8%), respectively. This included 2 grade 3 asymmetries,1 grade 3 pigmentation change, and 1 grade 2 pneumonitis. There was no brachial plexopathy. Among the 28 patients who underwent reconstruction, 17 were implant-based and 11 were autologous. Of the implant-based, 9 underwent RT to the tissue expander and 8 to the permanent implant. 11/28 patients had long-term plastic surgery follow up. There were 3 hospitalizations with reoperation post-RT (1 unplanned revision, 1 implant removal for threatened exposure, and 1 excision of fat necrosis). There was 1 incident of wound infection/cellulitis. With regard to dosimetric constraints, 54.3% of plans (95% CI 43.6%, 64.8%) met all constraints. 92% (95% CI 83%, 97%), 98% (95% CI 93%, 100%) and 89% (95% CI 80%, 94%) met the PTV tumor V48Gy, PTV breast V40.5Gy, and PTV nodes V38.5Gy coverage constraints, respectively. Heart, contralateral lung, spinal cord, and esophagus constraints were met by all patients. 95% (95% CI 88.6%, 98.4%) met the ipsilateral lung V10Gy and 99% (95% CI 94%, 100%) met the thyroid contralateral lobe constraint. The BP constraint was met in 73% (95% CI 63.0%, 81.0%) of plans with a mean increase of 1.61 Gy (SD 1.96 Gy) over target. Conclusion Toxicity was low and outcomes were excellent in this prospective trial of hypofractionated regional nodal RT in the prone position. Dosimetric constraints were only met in 54% of plans with the nodal coverage and the BP constraint as the most frequently unmet. These constraints may need to be modified and/or techniques refined to optimize hypofractionated prone nodal RT. Citation Format: Juhi Purswani, Olivier Maisonet, Julie Xiao, Jose R Teruel, Christine Hitchen, Xiaochun Li, Judith D. Goldberg, Carmen A. Perez, Silvia C. Formenti, Naamit K. Gerber. A prospective phase I-II study of hypofractionated accelerated breast and nodal intensity modulated radiation therapy delivered in the prone position [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-22-05.

Simulation and pre-planning omitted radiotherapy (SPORT): a feasibility study for prostate cancer

This study explored the feasibility of on-couch intensity modulated radiotherapy (IMRT) planning for prostate cancer (PCa) on a cone-beam CT (CBCT)-based online adaptive RT platform without an individualized pre-treatment plan and contours. Ten patients with PCa previously treated with image-guided IMRT (60 Gy/20 fractions) were selected. In contrast to the routine online adaptive RT workflow, a novel approach was employed in which the same preplan that was optimized on one reference patient was adapted to generate individual on-couch/initial plans for the other nine test patients using Ethos emulator. Simulation CTs of the test patients were used as simulated online CBCT (sCBCT) for emulation. Quality assessments were conducted on synthetic CTs (sCT). Dosimetric comparisons were performed between on-couch plans, on-couch plans recomputed on the sCBCT and individually optimized plans for test patients. The median value of mean absolute difference between sCT and sCBCT was 74.7 HU (range 69.5–91.5 HU). The average CTV/PTV coverage by prescription dose was 100.0%/94.7%, and normal tissue constraints were met for the nine test patients in on-couch plans on sCT. Recalculating on-couch plans on the sCBCT showed about 0.7% reduction of PTV coverage and a 0.6% increasing of hotspot, and the dose difference of the OARs was negligible (<0.5 Gy). Hence, initial IMRT plans for new patients can be generated by adapting a reference patient’s preplan with online contours, which had similar qualities to the conventional approach of individually optimized plan on the simulation CT. Further study is needed to identify selection criteria for patient anatomy most amenable to this workflow.

Pencil Beam Scanning Carbon Ion Radiotherapy for Hepatocellular Carcinoma.

Carbon ion radiotherapy (CIRT) has emerged as a promising treatment modality for hepatocellular carcinoma (HCC). However, evidence of using the pencil beam scanning (PBS) technique to treat moving liver tumors remains lacking. The present study investigated the efficacy and toxicity of PBS CIRT in patients with HCC. Between January 2016 and October 2021, 90 consecutive HCC patients treated with definitive CIRT in our center were retrospectively analyzed. Fifty-eight patients received relative biological effectiveness-weighted doses of 50-70 Gy in 10 fractions, and 32 received 60-67.5 Gy in 15 fractions, which were determined by the tumor location and normal tissue constraints. Active motion-management techniques and necessary strategies were adopted to mitigate interplay effects efficiently. Oncologic outcomes and toxicities were evaluated. The median follow-up time was 28.6 months (range 5.7-74.6 months). The objective response rate was 75.0% for all 90 patients with 100 treated lesions. The overall survival rates at 1-, 2- and 3-years were 97.8%, 83.3% and 75.4%, respectively. The local control rates at 1-, 2- and 3-years were 96.4%, 96.4% and 93.1%, respectively. Radiation-induced liver disease was not documented, and 4 patients (4.4%) had their Child-Pugh score elevated by 1 point after CIRT. No grade 3 or higher acute non-hematological toxicities were observed. Six patients (6.7%) experienced grade 3 or higher late toxicities. The active scanning technique was clinically feasible to treat HCC by applying necessary mitigation measures for interplay effects. The desirable oncologic outcomes as well as favorable toxicity profiles presented in this study will be a valuable reference for other carbon-ion centers using the PBS technique and local effect model-based system, and add to a growing body of evidence about the role of CIRT in the management of HCC.

Palliative radiotherapy for hepatic tumors: a narrative review of indications and recommendations.

Primary and metastatic liver cancer presents heterogeneously. New radiotherapy techniques have reduced toxicity concerns, leading to increased use of liver radiotherapy. This review synthesizes available evidence and offers recommendations for palliative radiotherapy for liver cancer. PubMed, Ovid Medline, Embase, Cochrane Central, and Web of Science were searched from from inception to December 28th, 2022. Articles reporting local control (LC), survival, toxicity, symptom control, and response after stereotactic body radiotherapy (SBRT), partial-liver, or whole-liver radiotherapy (WLRT) techniques were reviewed. We also identified nomograms identifying patients who may benefit from radiotherapy. Nine randomized-controlled trials were found, in addition to many retrospective, feasibility, and phase I or II studies. Patients with favorable prognosis may receive SBRT using 30-50 Gray (Gy) in 3-5 fractions for primary cancer and up to 60 Gy for metastases, provided normal-tissue constraints are met. Select patients with multiple (>5) or large (>10 cm) lesions or macrovascular invasion (MVI) may be considered, but with potentially reduced LC and increased toxicity. Lower SBRT doses (i.e., 25 Gy in 5 fractions) can be considered on a cautionary basis for patients with poorer liver function or health. Patients with larger tumor burden, poor performance status (PS), or inability to tolerate SBRT positioning or motion-management can consider partial-liver three-dimensional conformal radiotherapy (3DCRT). For patients with extremely guarded prognosis and/or extremely poor performance, WLRT provides pain and symptom relief over several weeks. Combining radiotherapy and systemic therapy may allow radiotherapy de-escalation while maintaining good outcomes. Radiotherapy has a definite role for palliation of liver cancer with practical research providing guidance in the use of techniques and different regimens in various patient subgroups. Future investigation, including randomized trials, is needed to optimize patient selection, radiotherapy techniques, and integration with other therapies.

Clinical Impact of Contouring Variability for Prostate Cancer Tumor Boost.

In the FLAME randomized phase III trial, adding a focal radiotherapy (RT) boost to tumors visible on MRI improved prostate cancer disease-free survival, local control, and regional/distant metastasis-free survival without increasing toxicity. In a prospective study (ReIGNITE RT Boost), we found substantial variability in radiation oncologists' attempts to contour prostate cancer tumors on MRI. Participants' accuracy and reliability improved when they used a quantitative MRI biomarker for cancer called the restriction spectrum imaging restriction score (RSIrs). Here, we measure the impact of radiation oncologists' tumor contour attempts on RT plans and predicted probability of biochemical failure. A total of 44 radiation oncologists (participants) from multiple institutions contoured prostate tumors on 30 patient cases, some with only conventional MRI and some with conventional MRI plus RSIrs maps. We developed a knowledge-based planning automated algorithm to generate RT plans with focal tumor boost per the FLAME trial protocol: 77 Gy in 35 fractions to prostate and integrated boost up to 95 Gy to the focal target, provided no normal tissue constraints were violated. We applied this algorithm to each participant's tumor contour and compared dosimetric parameters to those achieved when using the expert-defined tumor (consensus of two radiologists and a radiation oncologist). The primary metric was dose covering 98% of the expert-defined tumor (D98%), which was associated with probability of biochemical failure in a model published with the FLAME trial. In this preliminary analysis, 42 target volumes were analyzed from 20 participants and two patient cases: case 1 was contoured with conventional MRI alone and case 2 with RSIrs. All plans had adequate coverage of the prostate and met all key normal tissue constraints. For case 1 (without RSIrs), the expert's D98% was 87.1 Gy. By comparison, median D98% for participants was 82.2 Gy (IQR 77.8 - 84.6 Gy). Per the FLAME trial model, the predicted probability of biochemical failure at 7 years is 6% for the expert, but participants' plans yielded a median failure probability of 11% (IQR 18 - 9%). For case 2 (with RSIrs), the expert's D98% was 82.8 Gy, while median D98% for participants was 80.6 Gy (IQR 80.0 - 81.0 Gy). Predicted probability of biochemical failure is 12% for the expert-defined target and median 13% (IQR 14 - 13%) for participants. Variability in radiation oncologists' prostate tumor contours can lead to clinically meaningful changes to focal RT boost plans. The probability of biochemical failure for one patient case increased from 6% to a median of 11% when using conventional MRI alone. Use of RSIrs may mitigate this problem by increasing the accuracy and reliability of radiation oncologists' tumor contours.

Short Course Radiotherapy (SCRT) with Simultaneous Integrated Boost (SIB) in the Treatment of Rectal Cancer: Feasibility and Early Toxicities

To report the feasibility and early toxicities of dose-escalated SCRT in rectal cancer patients receiving total neoadjuvant therapy (TNT). This retrospective cohort study included 13 patients treated via a TNT approach (guided by RAPIDO trial) for locally advanced rectal cancer. The planned radiation was a standard dose of 25 Gy in 5 fractions to the primary tumor and at-risk lymphatics (PTV_Low). The dose-escalation was achieved via SIB delivering 30 Gy to the primary tumor (PTV_Mid) and 40 Gy (PTV_High) to inoperable lateral pelvic lymph nodes (LN), when present, over 5 fractions. A 5 mm margin was added to the rectal tumor and lateral pelvic LN to create the SIB targets. All patients were planned for intensity modulated radiation therapy via Varian EclipseTM (Palo Alto, CA) treatment planning system. Prior to treatment patients underwent kV and cone beam CT (CBCT) imaging for image guidance. Shifts were not performed solely to accommodate the boost target volume if it was felt to compromise the coverage of at-risk lymphatics. Normal tissue constraints were prioritized over boost coverage. Early toxicities were assessed for 30 days following treatment and graded using the Common Terminology Criteria for Adverse Events version 5.0. Offline image review was performed to determine the frequency at which the gross tumor volume (GTV) was captured within the 5 mm planning target volume (PTV_Mid) margin on daily CBCT scans. If a misalignment (tumor crossing outside of PTV_High) was discovered, the direction of misalignment (lateral/anterior/posterior) and location (superior/inferior) in relation to the superior border of the pubic symphysis was documented. An additional 5 mm margin from the PTV_Mid was created to determine if this would have captured the target. Twelve of the 13 patients were ≥ 30 days from treatment completion and were included in the toxicity analysis. The most common grade 1-2 toxicities were proctitis and diarrhea, which occurred in 42% and 25% of patients, respectively. Other toxicities were new onset rectal bleeding (17%), rectal pain (17%) and radiation dermatitis (8%). No grade 3+ toxicities were observed. Given five fractions for each of the 13 patients, a total of 65 CBCTs were reviewed and compared to the planning CT obtained at simulation. A total of 14/65 (22%) misalignments were discovered across six patients. All occurred above the superior edge of the pubic symphysis. Four misalignments were multi-directional. Nine were anterior, 6 were lateral, and 1 was posterior. Twelve of the 14 (86%) would have been covered within the additional 5 mm expansion volume. In this cohort of patients who received dose-escalated SCRT, the composite rate of acute toxicity was expectedly low. Feasibility of treatment delivery was established but could be improved upon with an addition 5 mm expansion, specifically in locations cranial to the superior edge of the pubic symphysis.

Phase II Study of Hemithoracic Intensity-Modulated Pleural Radiation Therapy (IMPRINT) for Patients with Pleural Metastases from Thymic Malignancies

Pleural metastases are common sites for recurrence and progression in patients with thymic malignancies. The management of pleural metastases typically involves surgical resection with or without neoadjuvant or adjuvant systemic therapy. After surgical resection of pleural metastases, the 5-year progression-free survival (PFS) rate is about 29-45%. While radiation therapy (RT) is standardly used in the management of locally-advanced thymic malignancies, the role of RT in patients with pleural metastases in unclear. Intensity-modulated pleural radiation therapy (IMPRINT) is a RT technique currently being used to treat malignant pleural mesothelioma (MPM) patients with 2 intact lungs at centers that specialize in MPM treatment. This IMPRINT technique can potentially be extrapolated to thymic patients with pleural metastases. Because the risk of toxicity is of greater concern for thymic patients given their overall relatively favorable prognosis, the rate of toxicity, particularly radiation pneumonitis, needs to be established in the thymic patient population. This is a single-arm, single institution Phase II study of hemithoracic IMPRINT for patients with pleural metastases from thymic malignancies. The primary endpoint of this study is grade 3 or higher radiation pneumonitis within 4 months of completing RT. Secondary endpoints include any toxicity, progression-free survival, patterns of failure and overall survival. Patients must have a pathologically confirmed diagnosis of a thymic malignancy with radiologic or pathologic evidence of pleural metastases. Thymoma or thymic carcinoma are allowed. Patients may have de novo stage IVA disease or recurrent disease in the pleura. There must be no evidence of extrathoracic metastatic disease or contralateral pleural/pericardial disease. Surgical resection of the pleural nodules (ex: pleurectomy/decortication, debulking/metastasectomy) are allowed. Extrapleural pneumonectomy is not allowed. Patients are excluded if they have undergone prior thoracic radiation therapy preventing hemithoracic pleural IMRT, whereas prior thymic bed radiation and/or prior pleural SBRT are allowed. RT will be administered to the ipsilateral pleura to 50.4 Gy in 28 fractions. An optional dose-painting boost to gross disease up to 60 Gy while respecting normal tissue constraints is allowed. Patients can be treated with photon or proton therapy. Simulation, contouring and RT planning guidelines have been developed. Patients will be followed per protocol at regular intervals for at least 12 months following RT. The expected accrual is 36 patients over 4 years. Further information can be found on clinicaltrials.gov (NCT05354570). To be determined. To be determined.

Oncologic Outcomes and Safety after Spinal Re-Irradiation with Stereotactic Body Radiation Therapy

Management of spinal metastases that fail radiation therapy is a challenge, presenting a fine balance between the risk of pain and neurologic deficits if the tumor is not controlled and the increased risks associated with exceeding the tolerance of the spinal cord and other adjacent critical structures. Data regarding SBRT in the re-irradiation setting is limited. The purpose of this study was to report oncologic outcomes and toxicities for patients that received re-irradiation using SBRT. Patients treated with spine SBRT for re-irradiation at a target which overlapped or abutted a previous conventional RT or SBRT field at a single institution between 2010 and 2021 were retrospectively reviewed. The cumulative constraint to the neural avoidance structures were a BED3 ≤75 Gy (above the conus) or ≤106 Gy (below the conus) accounting for 25% repair at 6 months and 50% repair at 1 year following the first course of RT. Radiographic local recurrence was defined as progressive disease on CT and/or MRI in the treatment volume or at the margin of the treatment field compared with imaging studies before SBRT. Cumulative incidence of local recurrence was reported with death as a competing event, and overall survival was estimated with Kaplan-Meier. Toxicity grades were determined according to NCI CTCAE version 4.0. Ninety patients (225 vertebrae) with a median age of 56.5 years (range: 27-84 years) were included in the analyses. The most common histologies were NSCLC (17.7%), kidney (15.6%), prostate (14.4%), and breast (7.8%). The majority (51.1%) of metastases were in the T-spine, while 31.1% were in the L-spine and 13.3% in the C-spine. The median prescription dose was 27 Gy (range: 14-40 Gy) in a median of 3 fractions (range: 1-5). The median prescription isodose line was 59% (range: 48%-97%). The median time to re-irradiation with SBRT was 14 months (range: 1-89 months), and the most common prior spinal radiation dose was 30 Gy (range: 8-50 Gy) in a median of 5 fractions (range: 1-15). The median maximal BED3 of the spinal cord from prior radiation and re-irradiation were 52.6 Gy and 31.8 Gy, respectively. The median follow-up was 8.7 months (range: 0.4-43.9 months). The 6-month, 1-year, and 2-year local control rates were 88.9%, 83.4%, and 78.9%, respectively. Only 6.7% of patients underwent salvage surgery, at a median of 9 months after SBRT. The median overall survival was 14.0 months, and overall survival was 54.4% at 1 year and 27.8% at 2 years post-SBRT. All toxicities were grade < 2 and no patients developed spinal cord myelopathy. These data suggest excellent local control and low toxicity following SBRT for re-irradiation of spinal metastases. Future prospective and multi-institutional studies are needed to explore the optimal dose fractionation regimen and cumulative normal tissue constraints to maximize local control and minimize toxicity.

Use of Lattice Therapy for Dose-Escalation in Palliative Treatment of Bulky Head and Neck Tumors

Palliative radiation is used to relieve pain and bleeding in patients with locally advanced head and neck cancers. Lower doses are utilized to meet normal tissue tolerances, limiting the duration of palliation. Lattice therapy can achieve intratumoral dose escalation while sparing surrounding tissues, but a standard approach does not exist. In this study, we explore the impact of variation in the values and distributions of peak and valley doses in palliative lattice treatment plans. Five-fraction volumetric-arc based (VMAT) lattice plans were generated using a customized Python v3.6 script. For each combination of peak/valley doses and sphere size and spacing, a bounding box was generated around the gross tumor volume (GTV) and divided into equal segments in the x, y, and z planes. Individual spheres were constructed for a given parameter set and those fully encompassed within the target contracted by 2 cm were used to create peak dose targets with values of 30, 40, and 50 Gy. A valley dose of 20 Gy was chosen to match standard dosing for 5-fraction palliative plans and the associated target volumes were generated by subtracting an 8 mm expansion of the peak dose spheres from the overall target volume. Multi-criteria optimization (MCO) was used to generate a final plan. The planning target volume (PTV) was a uniform 3-mm expansion from the GTV. Target volume and OAR dosimetric parameters were analyzed using Mann-Whitney U and Kruskal-Wallis testing. A total of 72 unique plans were evaluated for 4 patients with large GTV sizes ranging from 159 to 413 cm3. The median time to generate an individual plan using the automated script was 20 minutes (IQR, 18 - 23). Median values of mean GTV and PTV doses were 27.9 Gy (IQR, 24.7 - 30.3) and 26.7 Gy (IQR, 23.9 - 29.1), respectively. Further analysis was then limited to plans containing ablative 50 Gy dose spheres. For these 24 plans, mean GTV and PTV doses increased to a median of 31.7 Gy (IQR, 29.6 - 33.3) and 29.6 Gy (IQR, 27.8 - 31.0), respectively. Mean doses to 1, 2, and 4 cm expansions around the GTV for this cohort had median values of 19.5 Gy, 15.1 Gy, and 9.7 Gy, respectively. Median doses to 0.03 cc of mandible, spinal cord, and esophagus were 28.2 Gy (range, 7.0 - 35.7), 14.7 Gy (range, 9.8 - 18.8), and 8.7 Gy (range, 0.8 - 16.2), respectively. Mean GTV dose was dependent on sphere spacing (median 29.9 Gy for 4 cm spacing vs. 33.5 Gy for 3 cm, p<0.001), but not on sphere size (median 31.3 Gy for 2 cm vs. 31.8 Gy for 1.5 cm vs. 31.5 Gy for 1 cm, p = 0.968). VMAT-based lattice planning allows dose escalation to bulky head and neck tumors, including significant coverage with ablative doses while meeting normal tissue constraints. Thus, lattice plans could enhance palliation while reducing toxicity. Mean target coverage is dependent on sphere spacing. Use of automated plan generation could also facilitate clinical application.

Examining the Efficacy and Safety Profile of Palliative Radiotherapy Using 30 Gy in 5 Fractions

Higher biological equivalent doses of radiotherapy (RT) can improve symptom palliation and local control in select tumor sites. However, not all patients meet criteria for treatment with stereotactic ablative radiotherapy (SABR). Furthermore, SABR is a resource intensive technique which may limit its use in many centers. The 30 Gray in 5 fractions regimen (30/5) stems from a modification of 5-fraction SABR regimens. It is a conformal, homogenous hypo-fractionated regimen that delivers higher dose than conventional palliative RT while still respecting the normal tissue constraints for 5-fraction SABR. It uses streamlined contouring and planning with less stringent requirements for immobilization and image guidance, compared to what is required for SABR. This study evaluates the clinical outcomes of patients receiving 30/5. A single institution retrospective review of clinical and treatment data was performed for patients who received 30/5 from October 2020 to August 2022. Local control (LC) was calculated for all treatment courses. Distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) were calculated for all patients. Survival analyses were analyzed by the Kaplan-Meier method and curves compared by log-rank test. Univariate and multivariate analyses were performed using cox-regression analysis. A total of 77 patients and 92 courses of 30/5 were available for analysis. The most common primary tumor was lung (44%), followed by gastrointestinal (GI; 20%), breast (10%), and genitourinary (10%). The median age of patients was 64 years (range: 37-93). The median tumor size treated was 11.4 cm^3 (range: 0.3 - 210.9 cm^3). Treatment sites included lung (31%), lymph nodes (22%), non-spine bone (20%), and spine (15%). At median follow-up of 10.1 months (mo), 25 deaths occurred. Median LC after receiving 30/5 was 18.5 mo (95% CI: 15.7-21.3 mo), median DMFS was 6.6 months (95% CI: 4.6-8.6 mo), median PFS was 6.4 mo (95% CI: 4.9-8.0 mo), and median OS was 18.1 mo (95% CI: 13.1-23.1 mo). Median time to initiating, restarting, or changing systemic therapy was 12.8 mo (95% CI: 7.6-18.0 mo). Radiosensitive (lung, prostate, breast, gynecological, and head/neck) tumors had better LC than radioresistant (GI, renal cell, sarcoma, melanoma) tumors (median 20.9 vs 12.1 mo, p < 0.02). Six grade 2 toxicities occurred (6.5% of all treatments). No grade 3 or higher toxicities occurred. The 30/5 regimen is a safe, well-tolerated, and resource efficient regimen with effective local control. This may serve as a practical alternative for patients who require palliative RT but not optimal candidates for SABR. As expected, radiosensitive tumors had better local control than radioresistant tumors. Future research can further explore the safety, efficacy, and indications of 30/5 as a palliative RT option.

Phase II study of hemithoracic intensity-modulated pleural radiation therapy (IMPRINT) for patients with pleural metastases from thymic malignancies.

TPS8616 Background: Pleural metastases are common sites for recurrence and progression in patients with thymic malignancies. The management of pleural metastases typically involves surgical resection with or without neoadjuvant or adjuvant systemic therapy. After surgical resection of pleural metastases, the 5-year progression-free survival (PFS) rate is about 29-45%. While radiation therapy (RT) is standardly used in the management of locally-advanced thymic malignancies, the role of RT in patients with pleural metastases in unclear. Intensity-modulated pleural radiation therapy (IMPRINT) is a RT technique currently being used to treat malignant pleural mesothelioma (MPM) patients with 2 intact lungs at centers that specialize in MPM treatment. This IMPRINT technique can potentially be extrapolated to thymic patients with pleural metastases. Because the risk of toxicity is of greater concern for thymic patients given their overall relatively favorable prognosis, the rate of toxicity, particularly radiation pneumonitis, needs to be established in the thymic patient population. Methods: This is a single-arm, single institution Phase II study of hemithoracic IMPRINT for patients with pleural metastases from thymic malignancies. The primary endpoint of this study is grade 3 or higher radiation pneumonitis within 4 months of completing RT. Secondary endpoints include any toxicity, progression-free survival, patterns of failure and overall survival. Patients must have a pathologically confirmed diagnosis of a thymic malignancy with radiologic or pathologic evidence of pleural metastases. Thymoma or thymic carcinoma are allowed. Patients may have de novo stage IVA disease or recurrent disease in the pleura. There must be no evidence of extrathoracic metastatic disease or contralateral pleural/pericardial disease. Surgical resection of the pleural nodules (ex: pleurectomy/decortication, debulking/metastasectomy) are allowed. Extrapleural pneumonectomy is not allowed. Patients are excluded if they have undergone prior thoracic radiation therapy preventing hemithoracic pleural IMRT, whereas prior thymic bed radiation and/or prior pleural SBRT are allowed. RT will be administered to the ipsilateral pleura to 50.4 Gy in 28 fractions. An optional dose-painting boost to gross disease up to 60 Gy while respecting normal tissue constraints is allowed. Patients can be treated with photon or proton therapy. Simulation, contouring and RT planning guidelines have been developed. Patients will be followed per protocol at regular intervals for at least 12 months following RT. The expected accrual is 36 patients over 4 years. Further information can be found on clinicaltrials.gov (NCT05354570). Clinical trial information: NCT05354570 .

Abstract PD3-03: Preoperative robotic radiosurgery for early breast cancer: results of the phase II ROCK trial (NCT03520894)

Abstract Introduction. Breast-conserving surgery (BCS) followed by postoperative radiotherapy (RT) still represents the standard of care for early breast cancer (BC) patients. Hypofractionated schedules in maximum 15 fractions are currently accepted as the gold standard for external beam whole and partial breast irradiation (PBI). PBI for selected early BC patients allowed a shorter overall treatment duration and an improved patient compliance as compared to old-fashioned RT schedules. Preoperative PBI, due to the advantage of treating a well-defined volume, has been gaining attention in this multidisciplinary scenario. It avoids local treatment delay and might allow tumour downstaging with increased rates of BCS and improved cosmetic outcomes. Since local recurrence might be driven by biological mechanisms of radioresistance rather than geographical miss, higher dose per fraction may overcome repair mechanisms allowing tumoral cells to escape from conventional RT damage. We report the results of the phase II ROCK trial (NCT03520894), enrolling early BC patients treated with preoperative robotic radiosurgery (prRS), in terms of acute and early late toxicity, disease control, and cosmesis. Material and methods. The study recruited between August 2018 and September 2021 at the Radiation Oncology Unit of the University of Florence (Florence, Italy). Eligible patients were women aged 50+ years, with histologically proven invasive early BC, HR+/HER2- disease, without lymph vascular invasion, tumour size up to 25 mm suitable for BCS. Exclusion criteria were clinical node positive disease, multiple foci tumours, and patients with breast lesion limiting within 5 mm from the skin surface. The study aimed to prospectively assess the safety and feasibility of a single Cyberknife® (Accuray Incorporated, Sunnyvale, CA, USA) 21Gy-fraction prRS in preoperative setting, and to identify predictive factors for outcomes based on biologic and clinical features. The primary endpoint was the acute skin toxicity (from the end of prRS to surgery) according to the RTOG and the EORTC scales. Secondary endpoints were the rate of early late skin and non-skin toxicity as measured 90 days from the end of prRS, the rate of pathological complete response (pCR) according to Chevalier score. Cosmetic outcomes were prospectively scored every 6-month using the BCCT.core software. Results. From August 2018 to September 2021, a total of 70 patients were recruited and enrolled. Of those, 41 were excluded due to tumour biology exclusion criteria and 7 due to multiple foci breast disease evidenced at basal MRI. Therefore, 22 patients were successfully treated with pRS. Median age at diagnosis was 68 years (range 50-86), median tumour size was 14 mm (range 7.5-25). Required target dosimetric parameters were met in all patients, as well as normal tissue constraints. Patients received surgery after a median time of 29 days from biopsy, without any delay or postoperative complication. Overall, three G1 adverse events (13.6%) were recorded within 7 days from prRS (1 erythema, 2 breast pain). Three events (13.6%) were recorded between 7 and 30 days from prRS, one G2 breast oedema and two G1 breast pain. No acute toxicity greater than G2 was recorded. Five patients experienced early late G1 toxicity (1 breast pain, 4 breast induration). One patient reported G2 breast induration. No early late toxicity greater than G2 was observed. At a median follow up of 18 months (range 6-29.8), cosmetic results were scored excellent/good and fair in 14 and 5 patients, respectively, while 3 patients experienced a poor cosmetic outcome. Overall, pCR after surgery was reported in 2 patients (9%). Two patients received postoperative whole breast irradiation, according to histopathological results. Conclusions. ROCK trial showed that a single 21 Gy dose prRS represents a feasible technique for selected patients affected by early BC, showing a good safety profile and a promising effectiveness. Citation Format: Icro Meattini, Giulio Francolini, Vanessa Di Cataldo, Luca Visani, Carlotta Becherini, Erika Scoccimarro, Monica Mangoni, Viola Salvestrini, Laura Masi, Chiara Bellini, Raffaela Doro, Federica Di Naro, Marco Bernini, Jacopo Nori, Lorenzo Orzalesi, Simonetta Bianchi, Lorenzo Livi. Preoperative robotic radiosurgery for early breast cancer: results of the phase II ROCK trial (NCT03520894) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD3-03.

Dosimetric comparative study of conformal radiation techniques in patients with glioblastoma multiforme

Purpose: The purpose of the current study is to determine whether patients diagnosed with glioblastoma multiforme (GBM) who underwent radiotherapy (RT) using intensity-modulated RT (IMRT) technique were benefitting from this highly conformal treatment in terms of doses received by planning target volume (PTV) and organs at risk (OARs) in comparison to three-dimensional conventional RT (3DCRT). Materials and Methods: Twelve patients treated with IMRT for GBM were selected for dosimetric comparison with 3DCRT. The prescribed dose was 60 Gy in 30 fractions and seven non-coplanner beams were used in IMRT to cover 95% of target volume. The irradiated patients of GBM were retrieved and replanned with 3DCRT techniques. Dosimetric comparison was done by performing two plans for the same patient; prescription dose and normal tissue constraints were identical for both plans. The dose–volume histograms of target volumes and OAR, dose conformity, and dose homogeneity with 3DCRT and IMRT planning were compared. Statistical analysis was performed to determine the differences. Results: The mean conformity index was 0.99 ± 0.001 for IMRT and 0.97 ± 0.002 for 3DCRT, P = 0.001. The mean homogeneity index was 1.03 ± 0.02 for IMRT and 1.06 ± 0.009 for 3DCRT, P = 0.003, which is statistically significant. The IMRT technique enables dose reduction of normal tissues including brainstem (Dmean by 33.78 ± 5.34 and Dmax 51.84 ± 4.43), optic chiasm (Dmean by 36.92 ± 1.99 and Dmax 44.61 ± 3.72), left optic nerve (Dmean by 28.97 ± 6.51 and Dmax 46.08 ± 10.58), right optic nerve (Dmean by 31.93 ± 11.68 and Dmax 44.63 ± 13.54), left eye (Dmean by 18.66 ± 8.92 and Dmax 37.43 ± 13.47), right eye (Dmean by 14.40 ± 4.87 and Dmax 40.37 ± 11.37), left lens (by Dmax 5.45 ± 1.85), and right lens (Dmax 5.07 ± 0.63). Conclusion: The IMRT provides a real dosimetric advantage, especially for normal brain tissue, and in terms of target coverage. It allows treatment of tumors while respecting OARs' dose constraints. The IMRT technique shows significant advantage in PTV coverage, dose homogeneity, and conformity. In IMRT, the coverage is better where PTV was overlapping with critical OARs.

GSOR19 Presentation Time: 12:00 PM: High-Dose Rate Brachytherapy for Female Urethral Cancer: A Multi-Center Review Over Two Decades

<h3>Purpose</h3> Primary urethral cancer is an uncommon and aggressive malignancy that accounts for less than 1% of all genitourinary malignancies. Treatment paradigm often includes high-dose rate (HDR) brachytherapy, however data on treatment techniques, clinical outcomes, and toxicity remain limited. This study reviews our institutional experience treating female urethral cancer with brachytherapy over the past 2 decades. <h3>Materials and Methods</h3> The medical records of all adult female patients who had received treatment for urethral cancer between January 2000 and December 2021 within a multi-center academic hospital system were queried. Baseline clinicopathologic features, radiation treatment details, and outcomes were recorded. HDR brachytherapy dose homogeneity index (DHI) was defined as (V100 - V150)/V100. Survival analysis was performed using multivariable Cox proportional hazards regression. <h3>Results</h3> There were 37 females with urethral cancer identified in this study, of whom 10 (median age at diagnosis 65 years, median follow-up 35 months, see Table 1) underwent HDR brachytherapy. All 10 patients received a combination of external beam radiotherapy (EBRT) and HDR brachytherapy. Eight patients received treatment for primary disease, and 2 patients for recurrent disease. HDR brachytherapy was delivered in the neoadjuvant (10%), adjuvant (30%), and definitive treatment settings (60%). One patient received adjuvant intraoperative radiotherapy (IORT) 15 Gy in 1 fraction after pelvic exenteration for a positive margin, followed by adjuvant EBRT. Non-IORT brachytherapy regimens in the remaining 9 patients ranged from 18.5 Gy to 33.0 Gy in 3-5 fractions. Median size of HR-CTV was 22 cc (range 11-76 cc). Perineal Syed template with a urethral catheter was used in 7 patients; 6 of these patients were also treated with interstitial catheters (median 5 catheters, range 4-8). During conventionally fractionated EBRT, T4 disease (40%) was treated to 54.0-64.8 Gy and gross nodal disease (20%) to 55.8-59.4 Gy. Total EQD2 to the HR-CTV D90 exceeded 85 Gy in all cases except one, where an emerging fistula invoked under-coverage (71 Gy). The constraints of bladder D_2cc < 90 Gy and rectum D_2cc < 75 Gy were each unmet by one patient (20%); both of these patients had T4 disease. Acute toxicities from radiation included grade 2 urinary frequency (40%) and diarrhea (30%), while chronic toxicities included grade 2 pelvic pain (40%), grade 3 urethral stricture requiring dilation (20%), and grade 2 vesicovaginal (10%) and urethrocutaneous (10%) fistula. Brachytherapy DHI less than 0.2 was 75% sensitive and 100% specific for predicting the development of a fistula or urethral stricture. Among all 37 women in this cohort, the 10 who received brachytherapy had a trend toward longer recurrence-free survival (median 43 vs. 22 months, HR 0.35, 95% CI 0.11-1.13, <i>P</i>=0.079) after adjustment for stage and age at diagnosis. <h3>Conclusions</h3> Primary urethral cancer is an uncommon malignancy with sparse evidence to guide treatment. Brachytherapy may offer improved freedom from recurrence, but there is risk of severe toxicity especially when treatment volumes are large or dose homogeneity is poor. Additional studies are needed to further refine target dose and normal tissue constraints.

Conformal Pencil Beam Scanning Proton Therapy for Delivery of Flank Radiation in Children with Renal Tumors

<h3>Purpose/Objective(s)</h3> Post-operative flank radiotherapy (RT) is standard for many children with renal tumors for treatment of microscopic disease in the retroperitoneal (RP) renal bed/ para-aortic lymph nodes (PALN). Standard APPA X-ray (XRT) fields include normal tissues (NT) within abdomen not at risk for malignant contamination, and do not conform to RP region. We report results of planned interim analysis from a study evaluating use of conformal pencil beam scanned proton therapy (PBS) for RT of RP. <h3>Materials/Methods</h3> Patients (pts) were enrolled on Phase II trial with IRB approval; eligibility included Wilms tumor or clear cell sarcoma of kidney (CCSK) requiring flank-only RT according to Children's Oncology Group guidelines. Primary endpoint: toxicity (CTCv4.0). Secondary endpoints: patient reported outcomes (PRO), NT dosimetry, local recurrence (LR), and overall survival (OS). After 4D simulation, pre-operative images were fused. Superior/ inferior/ lateral GTV were determined by pre-op disease extent, with 1cm tool used to contour RP space; GTV was expanded 1cm to create CTV; PALN included when involved. Standard RT (10.8 Gy/6 fx) was condensed to 10 Gy/5 fx. Normal tissue constraints (NTC) included kidney (CK) (V80<10Gy), cord (max 12Gy), heart (max 11Gy, V50<10Gy), liver (V70<20Gy). <h3>Results</h3> From 1/2018-12/2021, 11 pts enrolled with planned interim analysis after 10th: 8 boys/3 girls, 6 black/ 5 white, median age 3y (range 1-9 y), 2 with clinical Beckwith-Wiedemann syndrome, 7 requiring daily anesthesia. Nine had unilateral (UL) tumors (5 left-sided, 8 Wilms tumor (7 favorable histology, 2 diffuse anaplasia (DA)), 1 CCSK); 2 had bilateral Wilms with UL DA. Overall stage was I (1), II (2), III (4), IV (2), V (2) and local I (2), II (2), III (7). All had chemotherapy, 8 pre-operatively. Total dose was 10 Gy/ 5 fx for 9 pts given in one week; 2 required additional 9 Gy for unresected PALN (1) and positive margin (1). PBS was delivered to CTV using two energy-degraded beams from 230 MeV cyclotron (posterior and posterior oblique) with daily IGRT. Of 10 pts analyzed, none experienced LR (median follow-up 26 m (range 12-48 m). One fx to 1 pt was given with x-rays due to proton downtime; no other missed fx. No pt experienced G2+ toxicity; 2 had hypertension at diagnosis which has resolved. Most common PRO were constipation (n=3), nausea (n=2), vomiting (n=1). NTC and >=98% CTV receiving >=98% of planned dose were met for all pts. Median dose to 50% of liver was 0.7 Gy (R 0.09-10), CK 1.35 Gy (R 0.3-2.8 Gy), bowel 5.1 Gy (R 1.2-11.4 Gy), compared to expected 10 Gy, 2 Gy, and 10 Gy with XRT to flank. <h3>Conclusion</h3> Based on planned interim analysis, the use of conformal PBS proton fields to treat the RP space for children requiring RT for Wilms tumor appears feasible and safe, allowing reduction in exposure of NT compared to XRT flank fields. Change in regimen from 6 to 5 fx has been well-tolerated. These findings support continuation of the planned trial.

Dosimetric Impact of Perirectal Hydrogel Spacer for Focal Intraprostatic Lesion Ablative Microboost: Which Patients Benefit?

<h3>Purpose/Objective(s)</h3> Recent trials have demonstrated a benefit in biochemical free survival with focal ablative microboost (FAM) to the dominant intraprostatic lesion (DIL) in localized prostate cancer (LPC). Full DIL coverage was not always achieved due to prioritization of organs at risk. A dosimetric study was conducted to characterize the advantage of iodinated hydrogel (HG) spacer placement based on lesion location in both the IMRT and SBRT setting. <h3>Materials/Methods</h3> Ten prostate patients with pre- and post- HG placement imaging were evaluated. A GU-radiologist delineated all DILs on post-HG placement MRIs. IMRT (77-95 Gy/35 fx) and SBRT (36.25-40-50 Gy/5 fx) plans were generated on both pre- and post-HG imaging, with and without urethral constraints. Normal tissue constraints were utilized from prior randomized trials. Full coverage of the DIL was defined as D95 and V95 ≥95% of volume. Additional plans with theoretical DILs in varying positions throughout the prostate were created to develop a generalized model of HG benefit for FAM radiotherapy. The model was then applied to 125 patients with biopsy-confirmed DILs from the Prostate-MRI-US-Biopsy (PMUB) dataset to better approximate the real-world benefit of HG placement. <h3>Results</h3> The mean prostate-rectal separation with HG placement at mid prostate was 12.8 mm (<i>SD</i> 2.85). The mean lesion size was 9 mm (range 4.3-14.8). There were no post-operative complications from HG placement. In the majority of patients both pre- and post-HG plans were able to achieve pre-specified dose-constraints for both SBRT and IMRT plans. In two patients (20%), full coverage of the DIL was not able to be achieved until after HG placement due to proximity of the rectum for both SBRT and IMRT. Post-HG plans had lower maximum rectal point dose, D0.1cc, and achieved significant reduction of D1cc to the rectum for SBRT (<i>p</i>=0.045) and IMRT (<i>p</i>=0.015). In the model, DIL coverage was compromised when the DIL was located within 1.5 mm of the urethra, 2.0 mm of the rectum or 1.5 mm of the bladder. In the PMUB dataset, an estimated 32 (25.6%) patients could potentially benefit from HG placement to improve DIL coverage if planned for FAM with either SBRT or IMRT. <h3>Conclusion</h3> We developed a model to assess the benefit of HG spacer for FAM in LPC. Our data suggest HG spacer placement may provide benefit in improving DIL coverage for select patients, typically for LPC with DILs that are within 2.0 mm of the posterior prostate-rectum interface. The majority of prostate patients do not require HG placement to achieve both full DIL coverage and standard dose constraints.

Five-Fraction Radiotherapy for Breast Cancer: Which are the Most Suitable Patients?

<h3>Purpose/Objective(s)</h3> FAST-Forward trial reported that five-fraction radiotherapy (5fx-RT) schedule with 26 Gy in adjuvant setting after breast-conserving surgery for early-breast cancer (BC) was non-inferior to the standard hypo-fx (SHfx) schedule with 40 Gy in 15fx in terms of local tumor control. Since the COVID-19 pandemic started RT expert groups encouraged professionals to implement hypo-fx schedules in order to decrease visits of patients to hospitals. The aim of this study is to help radiation oncologists choose the most suitable patients for 5fx-RT schedule according to anatomical features. <h3>Materials/Methods</h3> Between March 2020 and December 2021, 239 patients suitable for 5fx-RT schedule were referred to our department. Prescribed RT dose was 26 Gy in 5fx to the whole breast plus a simultaneously integrated boost (SIB) up to 29 Gy to tumor bed if indicated. Patients were divided into 3 groups: Group A: Patients treated with 5fx-RT schedule that met all the FAST-Forward constraints for normal tissues; Group B: Patients treated with 5fx-RT schedule that slightly did not meet all constraints, Group C: Patients switched to SHfx schedule as they did not meet constraints in an acceptable way. For each patient, we draw an imaginary straight line connecting the medial and lateral borders of PTV in the axial slice of simulation CT where the longest anteroposterior diameter was found. From midpoint of this line, we measured the tangent distance to PTV margin and collected the data as medial-to-lateral tangent (MELT). Data was analyzed using statistical software. <h3>Results</h3> 150 patients were included in group A, 75 in group B and 14 in group C. The median MELT distance was: 1.91cm, 2.48cm and 3cm respectively. We found that the increase in MELT distance was significantly associated with a poorer compliance of normal tissue constraints (p<0.0001). Patient´s distribution among 3 groups for MELT distance intervals are shown in table 1. Median V8 for ipsilateral lung was: 13.1, 15.46 and 20.49% for groups A, B and C respectively. For the heart, median mean dose was: 1.06, 1.8 and 2.25 Gy for left breast cancer patients and 0.28, 0.33 and 0.48 Gy for right breast cancer patients for groups A, B and C respectively. We found a moderate positive correlation between MELT distance and dosimetric parameters assessed above (r=0.545, 0.475 and 0.418 respectively). According to laterality, for a higher MELT distance the % of left BC patients increased significantly (p=0.039). <h3>Conclusion</h3> MELT distance is an easy tool that helps radiation oncologists predict which BC patients are the most suitable for 5fx-RT before RT planning begins. This could avoid delays in starting RT for patients with a high MELT distance directly planning them with the SHfx schedule.