High Local Control Rates Research Articles

Organ preservation surgery for laryngeal cancer in a trombone player

Introduction. Modern treatments for early glottic carcinoma achieve high rates of local control and long-term survival, but potential side effects of some of these treatments have a substantial impact on a patient?s quality of life. There is a small quantity of available scientific research on the effects of organ-preservation surgery on musicians, highlighting the challenge of balancing functional outcomes with their occupational demands. Case report. We present a successful surgical treatment of a mid-membranous left vocal fold squamous cell carcinoma (T1a stage) in a professional trombonist with a history of many years of smoking. Due to suboptimal exposure during initial microlaryngoscopy, open cordectomy was performed for tumor removal instead of transoral laser microsurgery. After the operation and the proper rehabilitation, the patient continued to play the brass instrument unhindered and managed to fulfill all the obligations of a professional musician in a national orchestra. Conclusion. Selecting a method for the treatment of glottic cancers in professional musicians who play brass instruments remains challenging due to limited literature and the potential harm to the ability of performance and the musician?s career. Partial open laryngectomies for laryngeal cancer treatment are shown to be feasible without compromising the musician?s performance.

NEUTROPHIL-LYMPHOCYTE RATIO (NLR) AND LYMPHOPENIAAS PROGNOSTIC FACTORS OF OVERALL SURVIVAL IN LOCALADVANCED RECTAL CANCER

Purpose: Inammation is a marker associated with carcinogenesis in solid tumours. In locally advanced rectal cancer (LARC), neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) is the standard treatment with high rates of local control, although we lack prognostic factors that involve the patient's immune status. Specic immunity measured in a blood count can be helpful in determining the neutrophil-lymphocyte ratio (NLR) and lymphopenia. Method: Retrospective study in 137 patients diagnosed with LARC, who underwent nCRT and TME. Blood analysis was obtained prior to initiation of nCRT to obtain lymphocytes and NLR with a cut-off value of 3, the cut-off value of lymphopenia was determined for toxicity scale of Common Terminology Criteria for Adverse Events (CTCAE v5.0), and the sample were divided in two groups: 0-3 and 4-5 toxicity scale. Both prognostic factors were compared with tumour regression grade (TRG) and overall survival (OS). Results: Pre-operative NLR showed 75,2% of patients with a value under 3 a 24,8% with a value up 3, with a signicantly pathologic regression (p=0,004) and with OS (p=0,001) in favor to low NLR. Lymphopenia was signicantly higher in the second group (p=0,034) and associated with poor OS. The follow-up were 34,35 months. Conclusion: Elevated pre-operative NLR and lymphopenia are prognostic factors for poor outcome and OS in rectal cancer patients. Therefore, these factors may be considered as potential biomarkers that need to be further validated by prospective studies.

Tumor Control and Hearing Preservation After Gamma Knife Radiosurgery for Vestibular Schwannomas in Neurofibromatosis Type 2—A Retrospective Analysis of 133 Tumors

This study was conducted with the aim to estimate long-term tumor control and hearing preservation rates in patients with neurofibromatosis 2 (NF2)-related vestibular schwannoma (VS), document retreatment success rate, and assess the associated predictive factors. This was a retrospective analysis of patients with NF2-associated VS who underwent Gamma Knife radiosurgery (GKRS) between 2009 and 2020 and had a minimum follow-up of 1 year. Loss of tumor control was defined as greater than 10% increase in volume in more than one follow-up imaging or the need for retreatment in the form of repeat GKRS or surgery. The Kaplan-Meier method was used to evaluate actuarial tumor control and hearing preservation rates. In total, 85 patients with 133 VSs were included in the study. The mean age was 29.8 years. In total, 57 tumors showed tumor regression, 35 showed stable disease, and 23 progressed in size at last follow up. Actuarial tumor control rates after 1, 3, 5, and 9 years were 95%, 79%, 75%, and 55%, respectively, with overall tumor control rate being 85%. Hearing worsened in 39 patients, and facial nerve dysfunction occurred in 4 patients. Five tumors underwent retreatment with GKRS at a median duration of 27.6 months (19-36 months) following the first GKRS. This is the largest radiosurgical series of NF2-associated VS reported to date. GKRS provides a high rate of long-term local tumor control with a low risk of neurologic deprivation for patients with these tumors. The need for retreatment with GKRS, although low, is associated with good tumor control and lesser complications.

Specimen-Based Resection Margins and Local Control during Transoral Robotic Surgery for Oropharyngeal HPV-Mediated Squamous Cell Carcinoma

Objectives: The aim of the study was to investigate the association of surgical margin conditions, including positive specimen margins revised to negative relative to local recurrence, disease-free survival, and overall survival (OS) within a cohort of HPV-mediated oropharyngeal squamous cell carcinoma (OPSCC) who underwent en bloc resection via transoral robotic surgery (TORS). Materials and Methods: Retrospective cohort of patients with untreated HPV-mediated OPSCC cT1 or T2 undergoing TORS resection between October 2014 and March 2020. The methodologic description of our interdisciplinary institutional approach, number of cut-through margins (CTMs) during intraoperative consultation, percentage of final positive margin cases, and disease-free survival and OS stratified by margin status and margin tumor-free distance is identified. Results: 135 patients with primary cT1/T2 HPV-mediated OPSCC met inclusion criteria. Twenty-eight of 135 (20.7%) specimens revealed CTM and were revised during the same operative setting. Three of 135 (2.2%) surgical cases had positive final margin status. Local control rate was 97%. On univariate analysis, margin distance did not impact OS. CTM and final positive margins had lower OS than initially negative margins (p = 0.044). Pathologic N-stage significantly impacted OS (p < 0.001). Conclusions: High local control rate and low final positive margin status confound the study of specimen margin-based techniques in HPV-mediated OPSCC resected en bloc with TORS. Pathologic N-stage may impact OS more than margin status. Larger numbers are needed to confirm differences.

Efficacy and safety of no-touch radiofrequency ablation for small hepatocellular carcinoma-a systematic review and single-arm meta-analysis

ObjectiveThe purpose of this study was to report the efficacy and safety of no-touch radiofrequency ablation (NT-RFA) in the treatment of small hepatocellular carcinoma (HCC). MethodsWe systematically searched for eligible studies in PubMed, Embase and Cochrane library until June 1, 2022. Random effect model was applied to synthesize the pooled proportions of local tumor progression-free survival (LTP), recurrence-free survival (RFS) and overall survival (OS) respectively, as well as adverse events, for small HCC treated by NT-RFA. ResultsOf the 10 included studies, 3 of them reported local tumor recurrence. One reported local tumor recurrence at 19 months (range, 12–24), and 2 studies had no tumor recurrence with 24-months of follow-up. The 1- and 2-year LTP pooled proportions were 99.3% (95%CI, 97.5–100) and 97.8% (95%CI, 94.6–99.6) respectively, and two studies reported a 3-year LTP rate of 96.4% (204/212, 36/37). The 1-yearRFS rates was 91.3% (95%CI, 84.1–98.4), 2-year was 86.4% (95%CI, 75.3–97.5). The 1-, 2- and 3- year OS rates were 92.4% (95%CI, 82.8–92.7), 84.1% (95%CI, 74.7–93.6) and 81.8% (116/181, 33/36) respectively, and only one study reported a 5-year OS rate of 47.0% (85/181). The ablative success rate of the HCC nodules was 96.6% (95%CI, 91.3–99.5) and the proportions of mild and severe adverse events following ablation were 18.3% (95%CI, 8.1–41.6) and 5.0%, respectively. ConclusionNT-RFA provides safely very high rate of sustained local control for the treatment of HCC up to 5 cm.

SURG-10. PERMANENT CARRIER-EMBEDDED CESIUM-131 BRACHYTHERAPY FOR THE SALVAGE TREATMENT OF PREVIOUSLY IRRADIATED, RECURRENT BRAIN METASTASES

Abstract BACKGROUND Salvage of recurrent, previously-irradiated brain metastases (rBrM) is a significant clinical challenge. High local failure is seen following salvage resection without adjuvant re-irradiation, while re-irradiation is associated with high radionecrosis rates. Salvage surgery plus intraoperative Cs131 brachytherapy may offer dosimetric and biologic advantages including improved local control versus observation, with reduced integral brain dose versus re-irradiation. METHODS A prospective registry of consecutively treated patients with post-stereotactic radiosurgery (SRS) rBrM was analyzed. Following resection, cavities were implanted with commercially-available, collagen-matrix embedded Cs131 seeds (GammaTile, GT Medical Technologies) prescribed to 60Gy at 5mm from the cavity. RESULTS Twenty patients underwent 24 operations with Cs131 implantation in 25 cavities. Previous SRS occurred a median of 358d preoperatively (range=56-1334). Median maximum preoperative diameter was 3.0cm (range=1.1-6.3) and enhancing volume was 9.5cm3 (range=0.6-69.7). Gross- or near-total resection was achieved in 60%. A median of 16 Cs131 seeds (range=6-30), with a median activity of 3.5U/seed were implanted. Maximal preoperative diameter and enhancing volume were weakly associated with the number of implanted seeds (correlation coefficients=0.50, 0.41, respectively). There was one postoperative wound dehiscence in a multiply resected and irradiated patient with hydrocephalus. With median follow-up of 1.6 years for survivors, 2 tumors recurred (one in-field, one marginal) resulting in 9.8% 1-year progression incidence (95%CI=0.0-23.2). Radiographic seed migration was identified in 7/25 cavities (28%) on scans ranging from 1.9-11.7 months post-implantation, without clinical sequelae. CONCLUSIONS With &amp;gt;1 year of follow-up, intraoperative brachytherapy with Cs131 implants was associated with a high rate of local control and a favorable toxicity profile. Modest correlation between preoperative tumor geometry and implanted tiles with high associated cost suggests a need to optimize planning criteria. A randomized trial of salvage resection with or without Cs131 is ongoing (NCT04690348) to assess the incremental benefit of brachytherapy.

NIMG-05. DYNAMIC SUSCEPTIBILITY CONTRAST MRI IN THE EVALUATION OF BRAIN METASTASES: CURRENT PRACTICE REVIEW AND RATIONALE FOR STUDY OF BASELINE PERFUSION IMAGING PRIOR TO STEREOTACTIC RADIOSURGERY (STARBEAM-X)

Abstract Stereotactic radiosurgery (SRS) is an established focal treatment for brain metastases with high local control rates. An important side-effect of SRS is the development of radionecrosis. On conventional MR imaging, radionecrosis and tumour progression often have similar appearances, but have contrasting management approaches. Perfusion MR imaging is often used in the post-treatment setting in order to help distinguish between the two, but image interpretation can be fraught with challenges.Perfusion MR plays an established role in the baseline and post-treatment evaluation of primary brain tumours and a number of studies have concentrated on the value of perfusion imaging in brain metastases. Of the parameters generated, relative cerebral blood volume is the most widely used variable in terms of its clinical value in differentiating between radionecrosis and tumour progression.Although it has been suggested that the rCBV tends to be elevated in active metastatic disease following treatment with radiosurgery, but not with treatment-related changes, the literature available on interpretation of the ratios provided in the context of defining tumour progression is not consistent.We provide an overview of the role perfusion MRI plays in the assessment of brain metastases and introduces the rationale for the STARBEAM-X study (Study of assessment of radionecrosis in brain metastases using MR perfusion extra imaging), which will prospectively evaluate baseline perfusion imaging in brain metastases. We present here the results of the first three patients recruited to the feasibility phase of this study. We hope this study will allow insight into the vascular appearance of metastases from different primary sites, and aid in the interpretation of post-treatment perfusion imaging.

1.5 T MR-Guided Daily Adapted SBRT on Lymph Node Oligometastases from Prostate Cancer.

Introduction: The aim of our study was to evaluate the efficacy and toxicity of a daily adaptive MR-guided SBRT on 1.5 T MR-linac in patients affected by lymph node oligometastases from PCa. Materials and Methods: The present study is a prospective observational study conducted in a single institution (protocol n°: MRI/LINAC n. 23748). Patients with oligometastatic lymph nodes from PCa treated with daily adaptive MR-guided SBRT on 1.5 T MR-linac were included in the study. There was a minimum required follow-up of 3 months after SBRT. The primary end-point was local progression-free survival (LPFS). The secondary end-points were: nodal progression-free survival (NPFS), progression-free survival (PFS), and toxicity. Results: A total of 118 lymph node oligometastases from PCa were treated with daily adaptive 1.5 T MR-guided SBRT in 63 oligometastatic patients. Of the patients, 63.5% were oligorecurrent and 36.5% were oligoprogressive. The two-year LPFS was 90.7%. The median NPFS was 22.3 months and the 2-year NPFS was 46.5%. Receiving hormone therapy before SBRT was correlated with a lower NPFS at the multivariate analysis (1 y NPFS 87.1% versus 42.8%; p = 0.002-HR 0.199, 95% CI 0.073-0.549). Furthermore, the oligorecurrent state during ADT was correlated with a lower NPFS than was the oligoprogressive state. The median PFS was 10.3 months and the 2-year PFS was 32.4%. Patients treated with hormone therapy before SBRT had a significantly lower 1-year PFS the others (28% versus 70.4%; p = 0.01-HR 0.259, 95% CI 0.117-0.574). No acute and late toxicities occurred during treatment. Conclusions: The present study is the largest prospective study of 1.5 T lymph node SBRT on MR-linac in patients with PCa. Lymph node SBRT by 1.5 T MR-linac provides high local control rates with an excellent toxicity profile.

Long-Term Results of a Multi-Institutional Phase II Study of Hypofractionated Proton Beam Irradiation of Unresectable Primary Liver Tumors

<h3>Purpose/Objective(s)</h3> To report the long-term outcomes of a prospective, multi-institutional phase II trial of hypofractionated proton beam therapy for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). <h3>Materials/Methods</h3> This single-arm, phase II, multi-institutional study enrolled 92 patients with localized, unresectable, biopsy-confirmed HCC or ICC with a Child-Turcotte-Pugh score (CTP) of A or B, and ECOG performance status of 0 to 2, to receive proton radiotherapy to a maximum dose of 67.5 GyRBE in 15 fractions. Overall survival (OS) and progression-free survival (PFS) rates were estimated using the Kaplan-Meier method. <h3>Results</h3> The patient characteristics, treatment techniques, and two-year outcomes have been previously reported on the 83 evaluable patients in this trial, including 44 with HCC and 39 with ICC who at that time had a median follow-up of 19.5 months. This updated analysis includes a median follow-up of 60.8 months (range 10.3–121.5) and 45.9 months (range 31.1–49.5) among the survivors with HCC and ICC, respectively. For those with HCC, the 5-year OS rate was 25.9% (95% CI 0.13-0.40), with a median OS of 29.2 months. For those with ICC, the 5-year OS rate was 12.3% (95% CI 0.03–0.27), with a median OS of 20.8 months. The 5-year PFS rate was 23.4% (95% CI 0.092-0.41) in HCC and 11.0% (95% CI 0.030-0.25) in ICC. As previously reported, two patients (6.8%) with HCC recurred locally, both within 2 years of treatment, and there were no further local failures. Among the patients with ICC, only one additional local failure occurred, for a total of 7/39 patients (17.9%), with a median time to recurrence of 26.1 months (range 5.5–42.3 months). All patients with local failure had CTP A scores, with a median tumor size of 5.8 cm (range 3.5–7.6 cm). The median radiation dose received by those who had a local recurrence was 58.0 GyRBE (range 45.0–67.5). Local failures occurred in 12.3% (7/57) of patients who received a BED less than 80.5 Gy and in 7.7% (2/26) of those who received a BED greater than 80.5 Gy. Distant failures, including intrahepatic non-local failures, occurred in 56.8% (25/44) of patients with HCC with a median time to progression of 10.2 months (range 2.7–63.6). In those with ICC, distant failures occurred in 61.5% of patients (24/39), with a median time to progression of 5.8 months (range 0.4–68.4). There were no grade 3 or greater late toxicities, including no late biliary toxicity. <h3>Conclusion</h3> Hypofractionated proton beam therapy is associated with durable, high rates of local control for both HCC and ICC, however, distant failures are common and remain a challenge. There were no significant late adverse effects, including no late biliary obstruction. Future strategies to incorporate radiation and systemic therapies, including immunotherapy, should be explored to further improve the long-term outcomes of HCC and ICC.

MSS06 Presentation Time: 4:10 PM: Single Institution Review of Hepatobiliary Brachytherapy for Bridging to Liver Transplant in Cholangiocarcinoma

<h3>Purpose</h3> Hepatobiliary cancers are rare neoplasms that often present in an inoperable state. In 2020 there were an estimated, newly diagnosed 42,810 "liver and intrahepatic bile duct" cancers and 11,980 "gallbladder and other biliary" cancers. Patients often present with malignant biliary tract obstruction in the setting of locally advanced or metastatic disease and radiation is reserved for palliative reasons. In some patients who are dispositioned to liver transplant (LTX), radiation can be used as a bridging therapy. The purpose of this study was to look at our institutions experience in treating patients with a combination of external beam radiation (EBRT) and hepatobiliary brachytherapy (BT) as they await LTX. <h3>Materials and Methods</h3> Medical records were retrospectively reviewed at our institution and patients diagnosed with cholangiocarcinoma who were also treated with hepatobiliary brachytherapy were included. These patients were considered for LTX. <h3>Results</h3> Between 2019 and 2021 a total of 6 patients were treated with EBRT and BT. Median age was 69.5 (range 60-86) and median follow up was 15 months (range 3-33). 3 patients (50%) presented with nodal disease at initial workup while 0 patients were metastatic. The 3 patients with nodal disease all received chemotherapy prior to radiation with median time to RT being 10 months in these patients. In the node negative patients, median time to EBRT was 1 month after diagnosis. 5 patients underwent conventionally fractionated EBRT, 45 Gy in 25 fractions, while 1 patient underwent stereotactic body radiotherapy (SBRT), 30 Gy in 5 fractions. All patients received concurrent chemotherapy. After completion of EBRT or SBRT, all patients underwent BT, 15 Gy in 5 fractions. Afterwards, 5 patients received adjuvant maintenance chemotherapy. While on maintenance chemotherapy, 4 patients progressed to have metastatic disease. 2 patients were able to undergo LTX, 7 months and 13 months after BT. In these patients, final pathology showed that there was no viable tumor in the areas where they were treated with BT. At most recent follow up, 1 of the patients who underwent LTX was alive while the other was deceased from unknown causes. Otherwise, 2 other patients were alive but with metastatic disease, 1 was deceased, and 1 was lost to follow up but with metastatic disease. Median survival in this cohort was 19 months and overall survival was 50%. <h3>Conclusions</h3> In well selected patients whose goal is to undergo LTX, EBRT and BT can be used as a bridging therapy. Though this is a small cohort, BT did demonstrate high rates of local control in patients able to undergo LTX.

Definitive High-Dose Radiotherapy for Primary Vulvar Cancer: The DRIVE Multicenter Cohort Study

<h3>Purpose/Objective(s)</h3> There is limited published data on definitive chemoradiation therapy for vulvar cancer. A retrospective multi-institutional cohort study was conducted to determine the efficacy, patterns of failure and long-term toxicity of high-dose radiation therapy (RT) for the primary treatment of vulvar carcinoma. <h3>Materials/Methods</h3> DRIVE (definitive radiation therapy for primary vulvar cancer) is a multicenter cohort study evaluating outcome for definitive high-dose conformal RT (dRT) for first line treatment of vulvar cancer. Treatment compliance, toxicity and patterns of failure were investigated. Actuarial locoregional control (LRC) and survival (OS) were estimated using Kaplan-Meier method and compared using log rank test. Herein, we present our preliminary results. <h3>Results</h3> In total, 48 patients [median (interquartile range) age, 57 (46-67) years] who received dRT between 2010 and 2020 were analyzed. Median follow-up was 28 (2–113) months. Cohort included 15 (31%) with stage I-II, and 33 (69%) patients with stage III-IV disease. Inguinal nodes alone were involved in 13 patients (27%); 19 (40%) had inguinal and/or pelvic node metastases. Elective surgical staging of groins was performed in 16 (33%) patients, of whom 7 had involved nodes. Intensity-modulated RT (IMRT) was used in 45 (94%) patients, and 3 (6%) received 3D-conformal RT. Median tumor dose was 64Gy (52-74.8Gy). Concurrent platinum-based chemotherapy was administered in 40 (83%) patients (1-8 cycles). Clinical complete response (CR) was achieved in 81.3% (39/48) patients at the primary site, and 84% (27/32) at involved nodes. Eight (16.7%) patients had persistent/recurrent disease following treatment, all within treatment volume; 5 (10%) patients developed distant metastasis. Actuarial 2 and 5-year LRC was 77.7% and 73%, respectively. Two and 5-year overall survival were 71% and 55%, respectively. On univariate analysis, determinants of inferior LRC were stage III/IV (p=0.04), non-IMRT technique (p=0.05) and <2 cycles of chemo (p=0.03). Treatment compliance included 90% (43 patients) completing planned treatment, 11/48 (23%) hospitalization, 6/48 (12.5%) blood transfusion, 12/48 (25%) with >5 days interruptions and median weight loss of 2.6Kg during RT. Of 40 evaluable patients, 25 (63%) developed significant vaginal stenosis. Vulvar necrosis was observed in 5 (10%) patients, all received ≥64Gy [2 treated with hyperbaric oxygen, 1 had musculocutaneous flap-reconstruction]. No acute/chronic grade 3 GI or GU toxicity, or any grade 5 toxicities were seen. <h3>Conclusion</h3> Definitive high-dose RT for vulvar cancer achieves high rates of local control, good compliance with acceptable dose dependent long-term toxicity. Use of IMRT does not result in increased geographic miss and was associated with improved locoregional control over existing prospective data from GOG 205 study.

GPP04 Presentation Time: 8:30 AM: What is Appropriate Target Delineation for MRI-Based Brachytherapy for Medically Inoperable Endometrial Cancer?

<h3>Purpose</h3> While the incidence of medically inoperable endometrial cancer (MIEC) is anticipated to rise within the growing elderly population, practice patterns demonstrate persistent underutilization of brachytherapy (BT). Contemporary Image-guided BT (IGBT) offers superior target dose escalation while sparing adjacent organs at risk. However, the volumetric target of IGBT techniques is not well established. We propose a high-risk CTV (HRCTV) concept and report associated rates of local control and toxicity. <h3>Materials and Methods</h3> A retrospective review identified all patients with MIEC receiving definitive external beam radiotherapy (EBRT) followed by MRI-based IGBT at a single institution. BT dose was prescribed to a HRCTV defined as gross tumor volume plus endometrial cavity with a planning goal of a summed equivalent dose at 2Gy/fraction (EQD2) D90 of 85Gy or greater. An additional intermediate-risk volume (IRCTV) was developed by global 5mm expansion upon this HRCTV, removing any volume entering into organs at risk (OAR). The myometrium and uninvolved uterine body was not defined as target volume. OARs including rectum, bladder, sigmoid and bowel were limited to EQD2 constraints directly adapted from cervical cancer. Late gastrointestinal (GI), genitourinary (GU), and vaginal toxicity events were graded using CTCAE, version 5.0. Clinical endpoints including local progression-free survival (LPFS), progression-free survival (PFS), and overall survival (OS) were estimated via the Kaplan Meier method. <h3>Results</h3> 32 patients received MRI-based HDR-BT for MIEC between 12/2015 and 8/2020, with a median follow up of 19.8 months (IQR 8.9 - 27.6 months). Patients were a median 71.5 years at diagnosis (range, 43 - 91 years), with a median ECOG 1 performance status (IQR 1 - 2). FIGO stages included 1A (56%), IB (16%), II (3%), III (22%), and IV (3%). Common histologies included endometrioid (56%), serous adenocarcinoma (22%), and carcinosarcoma (13%). All patients completed EBRT (45 Gy/25 fractions, 69%; 50.4 Gy/28 fractions, 16%; other, 16%) followed by MRI-guided HDR-BT (27.5 Gy/5 fractions, 66%; 28 Gy/4 fractions, 28%; other, 6%). Composite dosimetry included the following median EQD2 values: D90 HRCTV 91.3 Gy (IQR 88.2 - 96.4 Gy), D98 HRCTV 78.2 Gy (73.7 - 82.6 Gy), D90 IRCTV 73.4 Gy (69.9 - 76.0 Gy), D2cc Bladder 72.9 Gy (66.7 - 76.4 Gy), D2cc Rectum 57.0 Gy (52.1 - 66.0 Gy), D2cc Sigmoid 65.0 Gy (63.3 - 70.3 Gy), D2cc Bowel 60.2 Gy (53.2 - 66.0 Gy), and D2cc Vagina 82.9 Gy (79.9 - 90.6 Gy). 16% of patients received hormonal therapy, and 3% of patients received chemotherapy. Figure 1 provides LPFS, PFS, and OS. There were 14 (44%) total deaths, 3 local recurrences (9%), 3 nodal recurrences (9%), and 5 distant recurrences (16%). 2-year LPFS was 88.8%, and 2-year OS was 65.8%, with no locoregional or distant progression observed beyond 24 months post-BT. For the 3 patients with local progression, median D90 HRCTV was 99.2 Gy (range 77.9 - 103.5 Gy), D98 HRCTV 80.2 Gy (68.6 - 89.4 Gy), and D90 IRCTV 73.3 Gy (66.0 - 83.5 Gy). For patients with stage I/II disease (n=24), LPFS was 100% at 12 months and 94% (95% CI 81.9 - 100%) at 24 months. 23 (72%) patients experienced no RT-related toxicity. Two grade 3+ toxicities (6%) were observed: one grade 3 vomiting event prompting hospitalization and one grade 5 GI bleed presumed secondary to RT-induced proctitis in the setting of longstanding clopidogrel use. <h3>Conclusions</h3> Patients with MIEC receiving definitive EBRT followed by MRI-based IGBT demonstrated high rates of long-term local control with a favorable toxicity profile, when dose was prescribed to the MRI-defined GTV and endometrial cavity. These data compare favorably to historical controls despite a significant proportion of patients with locally advanced disease and/or aggressive histology.

Stereotactic Magnetic Resonance Guided Adaptive Radiation Therapy (SMART) for Abdominopelvic Oligometastases: A Combined Analysis of Prospective and Retrospective Cohorts

<h3>Purpose/Objective(s)</h3> Stereotactic body radiation therapy can be an effective treatment for oligometastases. However, safe delivery of ablative radiation therapy is commonly limited by the proximity of mobile organs at risk (OARs), as interfraction and intrafraction motion can result in severe complications. The goal of this study is to determine the feasibility, safety, and disease control outcomes of stereotactic magnetic resonance guided adaptive radiation therapy (SMART) in patients with abdominopelvic oligometastases. <h3>Materials/Methods</h3> We identified 101 patients with abdominopelvic oligometastases, including 20 patients enrolled on phase 1 protocols, who were consecutively treated with SMART on a 0.35 T MR Linac at a single institution from October 2019 to September 2021, excluding patients with metastases of the liver, kidneys, or adrenal glands. Local control and overall survival were analyzed using the Kaplan-Meier method. Adverse effects were assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. <h3>Results</h3> Overall, 114 sites of disease were treated. The most common histology was prostate adenocarcinoma (53.5%, n=60), and 57.0% (n=65) of sites were centered in the pelvis. 79.8% of sites (n=91) were treated to 8 Gy × 5, and 43.0% (n=49) were treated with breath hold. Online adaptation was used in 86.6% of delivered fractions to either improve the sparing of OARs (57.2%) or target coverage (29.4%). In addition, there were two cases where the on-board MRI allowed for the detection of bowel which had displaced the target to such a degree as to interfere with safe treatment delivery. These two fractions were postponed to either later the same day or a subsequent day. The median time required for adaptation was 24 minutes, and the median time in the treatment room was 58 minutes. With median follow-up of 11.4 months, the 12-month local control was 93% and higher for prostate adenocarcinoma vs other histologies (100% vs 84%, log-rank <i>P</i>=0.009). The 12-month overall survival was 96% and higher for prostate adenocarcinoma vs other histologies (100% vs 91%, log-rank <i>P</i>=0.046). Three patients developed grade 3 toxicities (colonic hemorrhage at 3.4 months and urinary tract obstructions secondary to ureteral stenoses at 10.1 and 18.4 months). <h3>Conclusion</h3> SMART is a feasible and safe method for delivering ablative radiation therapy to abdominopelvic oligometastases. Early data indicate a high rate of local control and low risk of significant toxicity. Adaptive planning was necessary in the large majority of cases. The advantages of SMART warrant its further investigation as a standard option for the treatment of abdominopelvic oligometastases.

Mature Outcomes of Stereotactic Body Radiotherapy for Spinal Metastases with 30 Gy in 4 Fractions

<h3>Purpose/Objective(s)</h3> At our institution, 30 Gy in 4 spine stereotactic body radiotherapy (SBRT) fractions is typically delivered for larger volume when multiple segments are included in the treatment volume and/or for the retreatment of spinal metastases. We report MRI-based local failure (LF) and vertebral compression fracture (VCF) rates for patients (pts) treated with 30 Gy/4Fx of spine SBRT. <h3>Materials/Methods</h3> A retrospective analysis of all pts with spine metastases treated with 30 Gy/4Fx from 2010 to 2021 from an institutional registry was performed. Demographic, clinical, dosimetric, and radiological data were summarized, and the primary endpoint was the MRI-based LF rate. Secondary endpoints included the incidence of VCF and overall survival (OS). Kaplan Meier was used to calculate LF and VCF per segment and OS per patient. <h3>Results</h3> Were included 116 pts with 245 treated segments in this analysis. The median number of consecutive segments in the treatment volume was 3 (1-7), and the median clinical target volume (CTV) was 126 cc (range, 10-863). Kidney (25%), lung (20%), breast (19%), prostate (19%), and colon (10%) cancer were the most common primary histologic types. 38% of pts had oligometastatic disease and 24% spine metastases only. 15% (17/116) of the patients were treated with postoperative SBRT. 31% of segments were re-irradiated for conventional palliative radiation, and 26% prior SBRT, failures. 25% of segments had a baseline VCF, 46% epidural disease, and 53% paraspinal tumor extension. The median follow-up per patient was 18.5 (range, 0.1-61) and per segment 10.7 mos (range, 0.1-59). The LF rates at 12 and 24 mos were 10.7% (95% CI 7.1-15.2) and 16% (95% CI 11.5-21.2), and for VCF were 7.3% (95% CI 4.4-11.2) and 11.2% (95% CI 7.5-15.8), respectively. 60% of failures had an epidural, and 23% a paraspinal, component. Age <68y (HR=0.43, 95% CI 0.19-0.95, p=0.038), volume of CTV <72cc (HR=0.09, 95% CI 0.01-0.70, p=0.021), and prior surgical stabilization (HR=0.25, 95% CI 0.07-0.81, p=0.021) were protective predictors for VCF on multivariable analyses (MVA). In particular, the VCF rate at 24 mos was 1.8% for pts with CTV volume <72 vs 14.6% for ≥72cc. Median OS was 20.3 mos (95% CI 14.8-27.1). Low grade or no epidural disease (HR=0.42, 95% CI 0.21-0.84, p=0.014), paraspinal disease (HR=3.07, 95% CI 1.68-5.62, p<0.001) and kidney primary cancer (HR=2.43, 95% CI 1.08-5.44, p=0.031) were predictors for OS on MVA, with a trend for oligometastatic disease (HR=0.56, 95% CI 0.31-1.02, p=0.059). No radiation-induced myelopathy was observed. <h3>Conclusion</h3> This first report for 30 Gy/4Fx as a novel fractionation for spine SBRT suggests high rates of local control and a low rate of VCF, particularly for those target volumes with a CTV<72 cc. However, our rate of VCF in very large treatment volumes (≥72cc) is comparable to the SBRT-induced VCF literature, where optimal management remains an active area of investigation.

Fractionated Radiosurgery Associated with High Rates of Local Control for Large Volume Intact Brain Metastases

<h3>Purpose/Objective(s)</h3> Radiosurgery is a well-established treatment modality for patients with intact brain metastases, and there is a known impact of tumor size and volume on tumor control. Based on desires to improve local control rates and reduce radiation necrosis rates, along with improvements in available technology, fractionated radiosurgery (FSR) is increasingly employed using both linear accelerators (LINAC) and GammaKnife (GK) units. Utilizing our single-institution database, we investigated outcomes for patients with intact brain metastases treated with FSR using LINAC or GK modalities. <h3>Materials/Methods</h3> Institutional records of patients with intact brain metastases treated with FSR were retrospectively reviewed. Patients treated with either GK or LINAC-based FSR were included. Descriptive analyses were performed of primary histology, lesion location, dose/fractionation, modality, tumor volume, and maximum tumor dimension. T-test and chi-square statistics were performed to compare characteristics and outcomes between patients treated with GK versus LINAC FSRT. Kaplan-Meier was used for survival estimates. Univariate analyses and Cox regression models were generated. <h3>Results</h3> 56 patients with 137 brain metastases were reviewed. 67.2% of lesions were treated via GK and 32.8% were treated via LINAC. Median prescription dose was 25 Gy (16-30 Gy) delivered in 2-5 fractions, with a medial lesion volume of 1.27 cc (0.01-77.0 cc). The most common treatment regimens were 24 Gy in 3 fractions and 30 Gy in 5 fractions. The most common primary tumors were lung (38.7%) and breast (28.5%). Median and mean maximum tumor dimension for the entire cohort were 1.73 cm and 2.16 cm (0.27-8.59 cm), respectively. Mean tumor volume was 6.10 cc (0.01-76.97 cc). There was a significant correlation between tumor volume and prescription dose, with larger tumors being more likely to receive a greater number of treatment fractions. The 1-y OS for all patients was 54.1% with a median OS of 15 mos. With a median follow-up of 6 months, the 1-year local control rate was 94.5%. For lesions ≤2 cc, 1-y LC was 97.4% compared to 91% for lesions > 2 cc, though this difference was not statistically significant. On Cox regression, neither maximum tumor dimension nor volume were predictive of local control. Univariate analysis demonstrated increased local recurrence in patients with prior history of neurosurgical intervention. No differences in LC or OS were observed between GK and LINAC. <h3>Conclusion</h3> FSR using 3 to 5 fractions for large volume intact metastases was associated with a high rate of LC compared to rates historically achieved with single fraction radiosurgery for tumors of similar volume. No statistically significant differences in LC or OS were detected according to maximum tumor dimension, volume, fractionation schedule, or treatment modality. FSR should be considered for larger brain metastases to improve LC.

Stereotactic Body Radiotherapy for Sarcoma Pulmonary Metastases

<h3>Purpose/Objective(s)</h3> Stereotactic body radiotherapy (SBRT) is standard for patients with inoperable early-stage NSCLC and is frequently utilized for pulmonary metastases with limited data. We hypothesized that SBRT for sarcoma pulmonary metastases would achieve high rates of local control with acceptable toxicity and that patients with oligometastatic disease may achieve prolonged survival following SBRT. <h3>Materials/Methods</h3> This IRB-approved retrospective review included patients at our institution treated with SBRT for sarcoma pulmonary metastases. SBRT was delivered in 1 - 8 fractions at the discretion of the treating clinician. Patients were classified as oligometastatic if they had ≤ 3 sites of disease or progression at ≤ 3 sites of metastatic disease. Cumulative incidence of local failure (LF) was calculated using competing risks analysis and compared across groups using Grey's test. LF was defined as progression in the SBRT field on 2 consecutive follow-up scans with LF date backdated to the earliest scan showing progression. We also evaluated toxicity and overall survival from the time of SBRT. Overall survival (OS) was estimated using the Kaplan-Meier method and compared across groups using the Log rank test and Cox proportional hazards regression. <h3>Results</h3> Between 2011 and 2021, 69 patients with 101 sarcoma pulmonary metastases were treated with SBRT to a median dose of 48 Gy (range: 25 – 60 Gy) in 4 fractions (range: 1 – 8 fractions). The most common histologies were leiomyosarcoma (<i>n</i> = 20 patients), liposarcoma (<i>n</i> = 8 patients), and osteosarcoma (<i>n</i> = 7 patients). The median follow-up time from SBRT was 26.1 months (95% CI 20.9-34.4) and 19.8 months for patients alive at last follow-up. A total of 35 patients (51%) were oligometastatic. The cumulative incidence of LF at 12 and 24 months was 6% (95% CI 3% to 12%) and 11% (95% CI 6% to 19%), respectively. The cumulative incidence of LF was significantly lower for peripheral compared to central lesions (12-month LF 11.4% vs 0% and 24-month LF 20.7% vs 0%, <i>p</i> = 0.002). OS at 12 and 24 months was 76% (95% CI 66% to 87%) and 52% (95% CI 40% to 67%), respectively. On univariable analysis, OS was significantly higher for patients with oligometastatic disease (12-month OS 85% vs 66%, <i>p</i> < 0.001, HR [95% CI] 0.29 [0.14, 0.59]) and Karnofsky Performance Status ≥ 90 (12-month OS 83 vs 63%, <i>p</i> = .03, HR [95% CI] 0.48 [0.24, 0.93]) but not age, sex, or time between initial pathologic diagnosis and SBRT. Among patients with oligometastatic disease, the median time to next systemic therapy or last follow-up was 10.0 months (range: 1 to 44.4 months). Three patients (4.3%) had grade 2 pneumonitis, and one patient (1.4%) had grade 2 esophagitis. No patients had ≥ grade 3+ toxicity. <h3>Conclusion</h3> To the best of our knowledge, this is the largest series of patients treated with SBRT for pulmonary sarcoma metastases. SBRT offers a safe alternative to surgical resection with excellent local control. Minimal toxicity was observed. Patients with oligometastatic disease had prolonged survival after SBRT.

Disease Control and Hepatotoxicity Following Stereotactic Body Radiotherapy for Hepatocellular Carcinoma

<h3>Purpose/Objective(s)</h3> Stereotactic body radiotherapy (SBRT) is increasingly utilized in the definitive management of patients with hepatocellular carcinoma (HCC), but long-term data regarding treatment efficacy and hepatotoxicity are lacking. We present our experience with SBRT and analyze patient and tumor characteristics associated with local control (LC), overall survival (OS), worsening of Child-Pugh (CP) score, and albumin-bilirubin grade (ALBI). <h3>Materials/Methods</h3> Patients with HCC treated with SBRT at a large referral center were included in this IRB-approved retrospective institutional database. Baseline patient characteristics, SBRT dose and fractionation, and laboratory data were collected by chart review. LC and OS were calculated using the Kaplan-Meier method starting from the date of the cross-sectional imaging study diagnosing the HCC lesion treated with SBRT. LC (at lesion level) was computed with a cumulative incidence function censoring for death. Local progression was defined by the interpreting radiologist, interdisciplinary review, or any decision to intervene with salvage therapy. A mixed-effects multivariable analysis (MVA) using a Cox proportional hazards model was performed using patient age, performance status, gender, HCC diameter (maximum length per-lesion), biological effective dose (alpha/beta = 10), number of prior treatments to the target lesion, and pre-treatment CP score as regression variables. CP score and ALBI were used to quantify hepatotoxicity following SBRT. <h3>Results</h3> A total of 130 HCC lesions in 104 patients (69% male) were included and median follow up was 1.6 years (range 0.3 – 6.8). Hepatitis C was the most common etiology for underlying liver disease (n = 44, 42%). The medians for MVA variables were age = 65 years, ECOG performance status = 1, maximum lesion diameter = 2.4 cm, BED10 = 112.5 Gy, CP = A6, and ALBI = grade 1. LC and OS for the entire cohort were 92% and 80% at 1-year, and 89% and 46% at 3-years, respectively. On MVA, no variables were significantly associated with either LC or OS (all p-values > 0.05). At 3-months post-SBRT, the number of patients with a worsening in CP score of 2 and 3+ points were 7 (7%) and 4 (4%), respectively, while the number of patients with a decline in ALBI score of 1 and 2 grades was 27 (26%) and 2 (2%), respectively. Of 12 lesions with local progression following radiation, salvage therapy was delivered in 11 with the most common technique being thermal ablation (n = 7, 64%). There was one documented local failure after salvage treatment. <h3>Conclusion</h3> SBRT with an ablative dose is associated with excellent LC with little hepatotoxicity in well-selected patients. High rates of LC after SBRT appear maintained with longer follow up, but overall survival remains limited.

Frameless Cobalt60-Based Hypofractionated Stereotactic Radiosurgery (HSRS) for Brain Metastases: Impact of Dose and Volume

<h3>Purpose/Objective(s)</h3> Frameless, gated, image-guided, Cobalt⁶⁰-based hypofractionated stereotactic radiosurgery (Co⁶⁰-HSRS) is a novel technical paradigm in the treatment of brain metastases that allows for both the dosimetric benefits of the Co⁶⁰ based stereotactic radiosurgery (SRS) platform as well as the biologic benefits of fractionation. We report mature local control (LC) and adverse radiation effects (ARE) outcomes following 5 fraction Co⁶⁰-HSRS for intact brain metastases. <h3>Materials/Methods</h3> All patients with intact brain metastases treated with 5-fraction Co⁶⁰-HSRS between 2017-2020 were retrospectively reviewed. Patients were typically selected for HSRS as opposed to single fraction SRS if the metastases were larger (>2cm diameter), were in eloquent areas, or were in proximity to another lesion receiving HSRS. Survival estimates were determined per patient using Kaplan Meier methods, and LC as well as symptomatic ARE rates were determined per lesion using competing risk methods. Univariable competing risk regression using Fine and Gray's methods were performed, and subsequent multivariable (MVA) regression using a backwards step-wise selection technique generated the final adjusted models. <h3>Results</h3> In total 299 metastases in 146 patients were identified. The median clinical and radiologic follow-up was 10.6 (range 0.5-49.9) and 10.7 months (range 0.5-47.6), respectively. The median maximum tumor diameter and volume were 1.7 cm (range, 0.2-3.9 cm) and 2.38 cc (range, 0.004-24.92 cc), respectively. The median total dose and prescription isodose was 27.5 Gy (range, 20-27.5 Gy) in 5 daily fractions and 52% (range, 45%-93%), respectively. The median overall survival (OS) was 12.7 months and the 1-year LC rate was 85%. MVA identified a total dose of 27.5 Gy vs. ≤25 Gy (hazard ratio [HR] 0.59, p = 0.042), and prior chemotherapy exposure (HR 1.99, p = 0.015), as significant predictors of LC. The 1-year ARE rate was 10.8% and the symptomatic ARE rate was 1.8%. MVA identified a gross tumor volume of ≥4.5cc (HR 7.29, p < 0.001) and a mean intra-tumoral dose of ≥39 Gy (HR 3.17, p = 0.034) as significant predictors of symptomatic ARE. <h3>Conclusion</h3> Moderate total doses in 5 daily fractions of Co⁶⁰-HSRS were associated with high rates of LC and a low incidence of symptomatic ARE. A prescription dose of 27.5 Gy was superior with respect to local control versus ≤25 Gy in 5 daily fractions. Target volumes of 4.5cc or larger as well as mean dose >39 Gy, were associated with higher rates of symptomatic necrosis. Further study will help refine the optimal dosimetric constraints for Co⁶⁰-HSRS.

Widening the Therapeutic Window for Central and Ultra-Central Thoracic Oligometastatic Disease with Stereotactic MR-Guided Adaptive Radiation Therapy (SMART)

<h3>Purpose/Objective(s)</h3> Central ©/ultra-central (UC) thoracic tumors are challenging to treat with stereotactic radiotherapy due to the narrow therapeutic window. Stereotactic MR guided adaptive radiation therapy (SMART) may improve the therapeutic window through motion control with breath hold gating and real-time MR imaging as well as the option for daily online adaptive replanning (ARP) to account for changes in target and/or organ-at-risk (OAR) location. Iso-toxic (OAR constraints-driven plan adaptation) SMART may provide an optimal balance of safety and local control (LC) for C/UC thoracic oligo-metastases (OM) or oligo-progression (OP). Here we report our institutional experience. <h3>Materials/Methods</h3> In this IRB-approved retrospective study, we reviewed the records of patients with C/UC thoracic OM/OP tumors treated with 5-fraction isotoxic SMART in 10/2019-8/2021. Tumor was considered UC if the planning target volume (PTV) abutted/overlapped the proximal tracheobronchial tree (PBT), great vessels, or esophagus. Data collection included dose to targets/OARS, frequency/clinical necessity for ARP, toxicity (CTCAE v5.0), and outcomes. Typical OAR constraints observed were PBT V40, great vessel V52.5, and esophagus V35 <0.03 cc. Local failures were defined as recurrences overlapping the PTV. <h3>Results</h3> 5 C/17 UC thoracic tumors were treated with SMART in 20 patients. Median age was 66 yrs (range 35-77). 73% had OP on systemic therapy and 27% were OM. Histology included non-small cell lung cancer (32%), and 9% each of mesothelioma, colorectal, prostate/bladder, and cervical/uterine. 55% of tumors were located in lung/pleura and 45% in hilum/mediastinum. All PTVs were <2 cm from any mediastinal organ and 59% <2 cm from the PBT. PTV abutted/overlapped the PBT in 32%, great vessel in 36%, heart in 36%, and esophagus in 41%. Median target volume was 10 cc for GTV and 18 cc for PTV (margin 3-5 mm). Median dose prescribed was 50 Gy in 5 fractions (range 35-60 Gy). 104/109 (95%) fractions required ARP, necessary to meet OAR constraints in 79% and target coverage in 21%. Median PTV V95 was 94% (range 53-100). Median follow up was 9 months. 1-yr LC rate was 94% (1/22 local failure for NUT-midline paraesophageal metastasis receiving 40 Gy/5 fx). 1-yr distant failure rate was 83% (n=16). 1-yr OS rate was 64%. 14% had acute G2 toxicities (esophagitis, dysphagia, or anorexia). There were no G3+ acute or late toxicities, and no G2+ pneumonitis. 8 (40%) patients had patient reported outcome measures available pre- and post-SMART with EORTC QLQ-C30 (symptom: median Δ -5 [-15, 15]; functional: median Δ 2 [-36, 13]; global health: median Δ -4 [-42, 17]) and QLQ-LC13 (median Δ 0 [-8, 3]) showing most had minimal negative change. <h3>Conclusion</h3> Iso-toxic 5-fraction SMART, with ARP 95% of the time to ensure OAR sparing and target coverage, resulted in high rates of LC and minimal toxicity. This approach may widen the therapeutic window for high-risk OM/OP thoracic tumors; further study in larger cohorts is needed.

Phantom Study of the Optimum Irradiation Angle for Proton Beam Therapy in Hepatocellular Carcinoma

<h3>Purpose/Objective(s)</h3> Passive proton beam therapy (PPBT) for hepatocellular carcinoma (HCC) has a higher local control rate than surgery or photon beam therapy. Moreover, it is attracting attention as one of the new treatment options. In the PPBT planning, the selection of the beam angle is determined according to the subjective judgment of the planner. Therefore, there are differences in the dose distribution depending on the planner. It has not yet been clarified which the irradiation angle can be selected to reduce unnecessary dose on the organ-at-risks and maintain the target coverage. The purpose of this study was to determining the optimal beam angle for liver S8 lesions. <h3>Materials/Methods</h3> The subjects were fifty-four treatment plans for HCC located in S8 irradiated using PPBT during the period of 2012.6-2021.3 at the National Cancer Center Hospital East. Tumor sizes were aggregated from the subjects. Clinical Target Volume (CTV) of the subject's liver ranged from 4 cm3 to 1370 cm3. Tumor sizes ranged from 132 cm to 655 cm3. From these results, the average CTV were represented on a virtual phantom, the dose distribution using PPBT was optimized using two irradiation angles. For the calculation of the optimum irradiation angle, the combination of the two beams rotated every 10 degrees and the best dose distribution was considered to be the optimum angle. The Conformity Index (CI) and Homogeneity Index (HI) of the CTV and the V30 (%) of the liver were calculated using the Dose volume histogram (DVH). <h3>Results</h3> The combination of beam angles showing 1 in the Conformity Index was 360 ° and 250 °, 350 ° and 230 °, 260 ° and 190 ° for small tumor volumes. Homogeneity Index and V30 averaged 1.06 and 28.0%, respectively. At the time of large tumor volume, it was 350 ° and 270 °, 350 ° and 250 °, 250 ° and 170 °. Homogeneity Index and V30 averaged 1.07 and 47.6%, respectively. The treatment schemes beam-arranged with a 70 ° difference in angle between the two beams were the most homogeneous with respect to the target. A significant difference was found in Conformity Index when compared to the most heterogeneous 190 ° difference (p <0.05). <h3>Conclusion</h3> Based on our findings, we recommend using a 2-beam configuration with a beam tilted by approximately 70 ° between the two beams for passive irradiation of hepatocellular carcinoma located in S8. This has the potential to achieve a uniform dose distribution within the target and at the same time reduce the hepatic dose. However, it should be noted that there is a difference in dose increase / decrease depending on the positional relationship of organs and tumors. Further treatment planning studies on aspects of respiration and organ movement need to be conducted.