Stereotactic Magnetic Resonance Research Articles

Stereotactic Magnetic Resonance–Guided Daily Adaptive Radiation Therapy for Localized Prostate Cancer: Acute and Late Patient-Reported Toxicity Outcomes

ObjectiveTo report acute and late bowel, urinary and sexual dysfunction patient reported outcome measures (PROMS), amongst localised prostate cancer patients who underwent Stereotactic MRI-guided daily adaptive radiotherapy (SMART). MethodsAll patients who completed a baseline 12 item Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), before undergoing 36.25 Gy in 5 fractions by SMART, were subsequently followed up with the same graded questionnaire at set time points. Latest PSA levels were recorded. The percentage of patients who reported no change from their baseline AE or reported a new ≥ ‘frequent’ or’ severe’ AE grade during follow up was calculated. The maximum PRO-CTCAE grade for each item was recorded for each patient. The percentage of toxicity levels for each separate AE item at set time points were calculated. ResultsThe total number of patients was 69 with a median follow-up of 27 months. Median age of cohort 73 (range 54-85). The median pre-treatment PSA, T stage and Gleason score was 7.5 mmol/l (4.5-32 mmol/l), T2b (T2-T3b) and Gleason Score of 7 (3+4, range: 6-9) respectively. No patient had biochemical failure during follow up. Regarding bowel symptoms, >80% of men reported no change from baseline toxicity during follow up. New ≥ frequent diarrhoea was reported in 9% of patients. ‘Almost constant’ diarrhoea peaked at 1 month but was absent at >33 months. Regarding urinary symptoms, increased urinary urgency was the most common complaint (39%). 20% of men reported new ≥ frequent urinary urgency incidence peaking at 1 month but absent at >33 months. New “severe” sexual dysfunction was seen in 26% of patients and was persistent at >33 months. ConclusionOur study is one the largest patient reported outcomes study post prostate SMART. It shows acceptable levels of toxicity even up to 2 years post treatment.

Stereotactic MR-guided on-table adaptive radiation therapy (SMART) for borderline resectable and locally advanced pancreatic cancer: A multi-center, open-label phase 2 study

Background and purposeRadiation dose escalation may improve local control (LC) and overall survival (OS) in select pancreatic ductal adenocarcinoma (PDAC) patients. We prospectively evaluated the safety and efficacy of ablative stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) for borderline resectable (BRPC) and locally advanced pancreas cancer (LAPC). The primary endpoint of acute grade ≥ 3 gastrointestinal (GI) toxicity definitely related to SMART was previously published with median follow-up (FU) 8.8 months from SMART. We now present more mature outcomes including OS and late toxicity. Materials and methodsThis prospective, multi-center, single-arm open-label phase 2 trial (NCT03621644) enrolled 136 patients (LAPC 56.6 %; BRPC 43.4 %) after ≥ 3 months of any chemotherapy without distant progression and CA19-9 ≤ 500 U/mL. SMART was delivered on a 0.35 T MR-guided system prescribed to 50 Gy in 5 fractions (biologically effective dose10 [BED10] = 100 Gy). Elective coverage was optional. Surgery and chemotherapy were permitted after SMART. ResultsMean age was 65.7 years (range, 36–85), induction FOLFIRINOX was common (81.7 %), most received elective coverage (57.4 %), and 34.6 % had surgery after SMART. Median FU was 22.9 months from diagnosis and 14.2 months from SMART, respectively. 2-year OS from diagnosis and SMART were 53.6 % and 40.5 %, respectively. Late grade ≥ 3 toxicity definitely, probably, or possibly attributed to SMART were observed in 0 %, 4.6 %, and 11.5 % patients, respectively. ConclusionsLong-term outcomes from the phase 2 SMART trial demonstrate encouraging OS and limited severe toxicity. Additional prospective evaluation of this novel strategy is warranted.

Patient Selection is Critical When Evaluating Candidates for 5-Fraction Stereotactic MRI-Guided Adaptive Radiotherapy (SMART) for Locally Advanced Pancreatic Cancer

Stereotactic magnetic resonance image-guided adaptive radiotherapy (SMART) allows for the safe delivery of biologically effective doses (BED10 ∼ 100 Gy) to patients with pancreatic cancer who otherwise have limited therapeutic avenues. In this study, we analyze long-term outcomes in the largest cohort of patients with borderline-resectable (BR), locally advanced (LA), or medically inoperable (MI) pancreatic cancer treated with a 5-fraction SMART technique. A single institution analysis of patients with BR, LA, or MI pancreatic cancer treated with SMART between 2015 and 2021 was performed. Patients with locally recurrent disease, non-adenocarcinoma histology, de-novo metastatic disease, or who did not receive induction chemotherapy were excluded. Baseline and treatment characteristics were collected. Local control (LC), progression free survival (PFS), and overall survival (OS) were calculated using the Kaplan-Meier method, and factors associated with outcomes were evaluated using Cox regression analyses. Oncologic outcomes measured from time of initial diagnosis; local control defined as freedom from local progression. A total of 129 patients were reviewed. Median age at diagnosis was 67 years. The majority were male (60%) and White (84%). 23% of patients had an ECOG 2. Most patients had LA disease (66%), followed by BR (20%) and MI (14%). Median follow up was 17.0 months (6-61 months). Median LC was not reached, and LC was 81%, 54%, and 48% at 1, 2, and 3-years, respectively. Median PFS was 12.9 months [95% confidence interval 11.8-14.71] with 1, 2, and 3-year PFS of 60%, 20%, and 7%, respectively. Median OS was 17.7 months [15.7-19.7] with 1, 2, and 3-year OS of 78%, 28%, 11%, respectively. On univariate analysis, increased duration of induction chemotherapy had a statistically significant impact on PFS and OS. Those receiving equal to or greater than 4 months of induction chemotherapy had a median OS of 19.2 months [17.2-21.2] as compared to 13.6 [11.9-15.3] for those with less than 4 months. In this patient population which included a large portion of patients with ECOG of 2 or greater and those deemed MI, a 5-fraction SMART regimen yielded durable long-term LC. The impact of increasing duration of induction chemotherapy underlies the importance of patient selection and improved understanding of tumor-specific biology when selecting patient's with locally advanced pancreatic cancer for aggressive local therapy.

Cost Analysis of MR-Guided vs. CT-Guided Radiation Therapy for Locally Advanced Pancreatic Cancer

Stereotactic magnetic resonance guided on-table adaptive radiotherapy (SMART) is an increasingly utilized radiotherapy (RT) treatment for locally advanced pancreatic cancer (LAPC), providing improved local control and overall survival with reduced toxicity. Computed tomography (CT) guided RT options include stereotactic body radiotherapy (SBRT) and hypofractionated RT with volumetric modulated arc therapy (VMAT). Currently there are no financial comparisons for MR vs CT-guided RT for LAPC. We completed a cost analysis comparing the physician and hospital charges associated with RT options for LAPC. To compare RT costs, we identified Current Procedural Terminology (CPT) codes utilized for 5-fraction SMART with adaptation (50 Gy, biological effective dose (BED) 100 Gy), 5-fraction CT-guided SBRT (33 Gy, BED 55 Gy), and 15-fraction CT-guided hypofractionated VMAT (67.5 Gy, BED 98 Gy) in a hospital-based practice setting. Physician and hospital Medicare prices associated with these codes together summarize the overall cost. We determined physician fees using the Centers for Medicare and Medicaid Services (CMS) Physician Fee Schedule Search to search the Healthcare Common Procedure Coding System (HCPCS) for "professional" costs included within "facility" costs. We determined hospital fees using the Outpatient Prospective Payment System addendum. To standardize costs, we searched for national payment amounts for the 2022 calendar year. Total cost of SMART with adaptation was 136% higher than the cost of CT-SBRT and 149% higher than the cost of hypofractionated RT. Physician fees for SMART were 173% higher and 157% higher than the fees for CT-SBRT and hypofractionated RT, respectively. Hospital fees for SMART were 129% higher and 147% higher than the fees for CT-SBRT and hypofractionated RT, respectively. The total cost of CT-SBRT was only 5% higher than cost of hypofractionated RT. The physician fees for hypofractionated RT were 6% higher than those for CT-SBRT, while the outpatient fees for CT SBRT were 7% higher than those for hypofractionated RT. With recent data demonstrating favorable efficacy and toxicity rates for SMART, practices may increasingly consider investing in this treatment modality. This is the first cost analysis comparing SMART to CT-guided SBRT and hypofractionated RT in LAPC. We demonstrate higher costs of SMART compared to CT-guided RT, attributable primarily to higher number of dosimetry calculations for this modality and for adapted fractions. We also demonstrate comparable costs of lower BED CT-guided SBRT and higher BED hypofractionated RT. Further investigation is needed to assess whether the survival benefit of SMART translates to favorable cost per quality adjusted life year.

A prospective registry study of stereotactic magnetic resonance guided radiotherapy (MRgRT) for primary liver tumors

Background and PurposeStereotactic body radiation therapy (SBRT) has demonstrated safe and effective results for primary liver tumors. Magnetic Resonance guided Radiotherapy (MRgRT) is an innovative radiotherapy modality for abdominal tumors. The aim of this study is to report on acute and late toxicities and initial oncological results for primary liver tumors treated with MRgRT. Materials and MethodsWe prospectively included in our cohort all patients treated by MRgRT for a primary liver tumor at the Montpellier Cancer Institute. The primary endpoint was acute and late toxicities assessed according to CTCAE v 5.0. The mean prescribed dose was 50 Gy in 5 fractions. ResultsBetween October 2019 and April 2022, MRgRT treated 56 patients for 72 primary liver lesions. No acute or late toxicities of CTCAE grade greater than 2 attributable to radiotherapy were noted during follow-up. No cases of radiation-induced liver disease (RILD), either classical or non-classical, occurred. After a median follow-up of 13.2 months (95% CI [8.8; 15.7]), overall survival was 85.1% (95% CI: [70.8; 92.7]) at 1 year and 74.2% at 18 months (95% CI [52.6; 87.0]). Local control was 98.1% (95% CI: [87.4; 99.7]) and 94.7% (95% CI: [79.5; 98.7]) at 12 and 18 months, respectively. Among the HCC subgroup, no local recurrences were observed. ConclusionMRgRT for primary liver tumors is safe without severe adverse events and reach excellent local control. Numerous studies are underway to better assess the value of MRI guidance and adaptive process in these indications.

Stereotactic Magnetic Resonance–guided Adaptive Radiation Therapy for Localized Kidney Cancer: Early Outcomes from a Prospective Phase 1 Trial and Supplemental Cohort

Stereotactic magnetic resonance (MR)-guided adaptive radiotherapy (SMART) for renal cell carcinoma may result in more precise treatment delivery through the capabilities for improved image quality, daily adaptive planning, and accounting for respiratory motion during treatment with real-time MR tracking. In this study, we aimed to characterize the safety and feasibility of SMART for localized kidney cancer. Twenty patients with localized kidney cancer (ten treated in a prospective phase 1 trial and ten in the supplemental cohort) were treated to 40 Gy in five fractions on a 0.35 T MR-guided linear accelerator with daily adaptive planning and a cine MR-guided inspiratory breath hold technique. The median follow-up time was 17 mo (interquartile range: 13–20 months). A single patient developed local failure at 30 mo. No grade ≥3 adverse events were reported. The mean decrease in estimated glomerular filtration rate was –1.8 ml/min/1.73 m2 (95% confidence interval or CI [–6.6 to 3.1 ml/min/1.73 m2]), and the mean decrease in tumor diameter was –0.20 cm (95% CI [–0.6 to 0.2 cm]) at the last follow-up. Anterior location and overlap of the 25 or 28 Gy isodose line with gastrointestinal organs at risk were predictive of the benefit from online adaptive planning. Kidney SMART is feasible and, at the early time point evaluated in this study, was well tolerated with minimal decline in renal function. More studies are warranted to further evaluate the safety and efficacy of this technique. Patient summaryFor patients with localized renal cell carcinoma who are not surgical candidates, stereotactic magnetic resonance-–guided adaptive radiotherapy is a feasible and safe noninvasive treatment option that results in minimal impact on kidney function.

To fly or not to fly: Stereotactic MR-guided adaptive radiotherapy effectively treats ultracentral lung tumors with favorable long-term outcomes

BackgroundStereotactic radiotherapy of ultracentral lung tumors (ULT) is challenging as it may cause overdoses to sensitive mediastinal organs with severe complications. We aimed to describe long-term outcomes after stereotactic magnetic resonance (MR)-guided online adaptive radiotherapy (SMART) as an innovative treatment of ULT. Patients & methodsWe analyzed 36 patients that received SMART to 40 tumors between 02/2020 – 08/2021 inside prospective databases. ULT were defined by planning target volume (PTV) overlap with the proximal bronchial tree or esophagus. We calculated Kaplan Meier estimates for overall survival (OS) and progression-free survival (PFS), and competing risk estimates for the incidence of tumor progression and treatment-related toxicities. ULT patients (N = 16) were compared to non-ULT patients (N = 20). ResultsBaseline characteristics were similar between ULT and non-ULT, but ULT were larger (median PTV: ULT 54.7 cm3, non-ULT 19.2 cm3). Median follow-up was 23.6 months. ULT and non-ULT showed a similar OS (2-years: ULT 67%, non-ULT 60%, p = 0.7) and PFS (2-years: ULT 37%, non-ULT 34%, p = 0.73). Progressions occurred mainly at distant sites (2-year incidence of distant progression: ULT 63%, non-ULT 61%, p = 0.77), while local tumor control was favorable (2-year incidence of local progression: ULT 7%, non-ULT 0%, p = 0.22). Treatment of ULT led to significantly more toxicities ≥ grade (G) 2 (ULT: 9 (56%), non-ULT: 1 (5%), p = 0.002). Most toxicities were moderate (G2). Two ULT patients developed high-grade toxicities: 1) esophagitis G3 and bronchial bleeding G4 after VEGF treatment, 2) bronchial bleeding G3. Estimated incidence of high-grade toxicities was 19% (3–48%) in ULT, and no treatment-related death occurred. ConclusionOur small series supports SMART as potentially effective treatment of ULT. SMART with careful fractionation could reduce severe complications, but treatment of ULT remains a high-risk procedure and needs careful benefit-risk-assessment.

Brain Metastasis Growth Kinetics: A Novel Prognosticator for Stereotactic Radiotherapy

AimsThe rate of size change in brain metastasis may have clinical implications on tumour biology and prognosis for patients who receive stereotactic radiotherapy (SRT). We analysed the prognostic value of brain metastasis size kinetics and propose a model for patients with brain metastases treated with linac-based SRT in predicting overall survival. Materials and methodsWe analysed the patients receiving linac-based SRT between 2010 and 2020. Patient and oncological factors, including the changes in sizes of brain metastasis between the diagnostic and stereotactic magnetic resonance imaging, were collected. The associations between prognostic factors and overall survival were assessed using Cox regression with least absolute selection and shrinkage operator (LASSO) checked by 500 bootstrap replications. Our prognostic score was calculated by evaluating the most statistically significant factors. Patients were grouped and compared according to our proposed score, Score Index for Radiosurgery in Brain Metastases (SIR) and Basic Score for Brain Metastases (BS-BM). ResultsIn total, 85 patients were included. We developed the prognostic model based on the most important predictors of overall survival: growth kinetics, i.e. percentage change in brain metastasis size per day between the diagnostic and stereotactic magnetic resonance imaging (hazard ratio per 1% increase, 1.32; 95% confidence interval 1.06–1.65), extracranial oligometastatic diseases (≤5 involvements) (hazard ratio 0.28; 95% confidence interval 0.16–0.52) and the presence of neurological symptoms (hazard ratio 2.99; 95% confidence interval 1.54–5.81). Patients with scores 0, 1, 2 and 3 had a median overall survival of 44.4 (95% confidence interval 9.6–not reached), 20.4 (95% confidence interval 15.6–40.8), 12.0 (95% confidence interval 7.2–22.8) and 2.4 (95% confidence interval 1.2–not reached) years, respectively. The optimism-corrected c-indices for our proposed model, SIR and BS-BM were 0.65, 0.58 and 0.54, respectively. ConclusionsBrain metastasis growth kinetics is a valuable metric for survival outcomes of SRT. Our model is useful in identifying patients with brain metastasis treated with SRT with different overall survival.

Multi-Institutional Outcomes of Patients Aged 75 years and Older With Pancreatic Ductal Adenocarcinoma Treated With 5-Fraction Ablative Stereotactic Magnetic Resonance Image-Guided Adaptive Radiation Therapy (A-SMART).

Treatment options for pancreatic ductal adenocarcinoma (PDAC) are commonly limited for patients with advanced age due to medical comorbidities and/or poor performance status. These patients may not be candidates for more aggressive chemotherapy regimens and/or surgical resection leaving few, if any, other effective treatments. Ablative stereotactic MRI-guided adaptive radiation therapy (A-SMART) is both efficacious and safe for PDAC and can achieve excellent long-term local control, however, the appropriateness of A-SMART for elderly patients with inoperable PDAC is not well understood. A retrospective analysis was performed of inoperable non-metastatic PDAC patients aged 75years or older treated on the MRIdian Linac at 2 institutions. Clinical outcomes of interest included overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional (LRC). Toxicity was graded according to Common Terminology Criteria for Adverse Events (CTCAE, v5). A total of 49 patients were evaluated with a median age of 81years (range, 75-91) and a median follow-up of 14 months from diagnosis. PDAC was classified as locally advanced (46.9%), borderline resectable (36.7%), or medically inoperable (16.3%). Neoadjuvant chemotherapy was delivered to 84% of patients and all received A-SMART to a median 50Gy (range, 40-50Gy) in 5 fractions. 1Year LRC, PFS, and OS were 88.9%, 53.8%, and 78.9%, respectively. Nine patients (18%) had resection after A-SMART and benefited from PFS improvement (26 vs 6months, P = .01). ECOG PS <2 was the only predictor of improved OS on multivariate analysis. Acute and late grade 3 + toxicity rates were 8.2% and 4.1%, respectively. A-SMART is associated with encouraging LRC and OS in elderly patients with initially inoperable PDAC. This novel non-invasive treatment strategy appears to be well-tolerated in patients with advanced age and should be considered in this population that has limited treatment options.

Ablative 5-Fraction Stereotactic MRI-Guided Adaptive Radiotherapy for Oligometastatic Pancreatic Adenocarcinoma.

Metastatic pancreatic ductal adenocarcinoma (PDAC) carries a poor prognosis and significant morbidity from local tumor progression. We investigated outcomes among oligometastatic PDAC patients treated with stereotactic magnetic resonance image-guided ablative radiotherapy (SMART) to primary disease. We performed a retrospective multi-institutional analysis of oligometastatic PDAC at diagnosis or with metachronous oligoprogression during induction chemotherapy treated with primary tumor SMART. Outcomes of interest included overall survival (OS), progression-free survival (PFS), freedom from locoregional failure (FFLRF), and freedom from distant failure (FFDF). Acute and late toxicity were reported and in exploratory analyses patients were stratified by the number of metastases, SMART indication, and addition of metastasis-directed therapy. From 2019 to 2021, 22 patients with oligometastatic PDAC (range: 1-6 metastases) received SMART to the primary tumor with a median follow-up of 11.2months from SMART. Nineteen patients had de novo synchronous metastatic disease and three had metachronous oligoprogression. Metastasis location most commonly was liver only (40.9%), multiple organs (27.3%), lungs only (13.6%), or abdominal/pelvic nodes (13.6%). All patients received either FOLFIRINOX (64%) or gemcitabine/nab-paclitaxel (36%) followed by SMART (median 50Gy, 5 fractions) for local control (77%), pain control (14%), or local progression (9%). Additionally, 41% of patients received other metastasis-directed treatments. The median OS from diagnosis and SMART was 23.9months and 11.6months, respectively. Calculated from SMART, the median PFS was 2.4months with 91% of patients having distant progression, and 1-year local control was 68. Two patients (9%) experienced grade 3 toxicities, gastric outlet obstruction, and gastrointestinal bleed without grade 4 or 5 toxicity. There was minimal morbidity of local disease progression after SMART in this cohort of oligometastatic PDAC. As systemic therapy options improve, additional strategies to identify patients who may derive benefits from local consolidation or metastasis-directed therapy are needed.

Dosimetric evaluation of magnetic resonance imaging-guided adaptive radiation therapy in pancreatic cancer by extent of re-contouring of organs-at-risk.

The safety of online contouring and planning for adaptive radiotherapy is unknown. This study aimed to evaluate the dosimetric difference of the organ-at-risk (OAR) according to the extent of contouring in stereotactic magnetic resonance image-guided adaptive RT (SMART) for pancreatic cancer. We reviewed the treatment plan data used for SMART in patients with pancreatic cancer. For the online contouring and planning, OARs within 2 cm from the planning target volume (PTV) in the craniocaudal direction were re-controlled daily at the attending physician's discretion. The entire OARs were re-contoured retrospectively for data analysis. We termed the two contouring methods the Rough OAR and the Full OAR, respectively. The proportion of dose constraint violation and other dosimetric parameters was analyzed. Nineteen patients with 94 fractions of SMART were included in the analysis. The dose constraint was violated in 10.6% and 43.6% of the fractions in Rough OAR and Full OAR methods, respectively (p = 0.075). Patients with a large tumor, a short distance from gross tumor volume (GTV) to OAR, and a tumor in the body or tail were associated with more occult dose constraint violations-large tumor (p = 0.027), short distance from GTV to OAR (p = 0.061), tumor in body or tail (p = 0.054). No dose constraint violation occurred outside 2 cm from the PTV. More occult dose constraint violations can be found by the Full OAR method in patients with pancreatic cancer with some clinical factors in the online re-planning for SMART. Re-contouring all the OARs would be helpful to detect occult dose constraint violations in SMART planning. Since the dosimetric profile of SMART cannot be represented by a single fraction, patient selection for the Full OAR method should be weighted between the clinical usefulness and the time and workforce required.

Dosimetric Benefit of Adaptive Magnetic Resonance-Guided Stereotactic Body Radiotherapy of Liver Metastases.

(1) Background: To assess dosimetry benefits of stereotactic magnetic resonance (MR)-guided online adaptive radiotherapy (SMART) of liver metastases. (2) Methods: This is a subgroup analysis of an ongoing prospective registry including patients with liver metastases. Patients were treated at the MRIdian Linac between February 2020 and April 2022. The baseline plan was recalculated based on the updated anatomy of the day to generate the predicted plan. This predicted plan could then be re-optimized to create an adapted plan. (3) Results: Twenty-three patients received 30 SMART treatment series of in total 36 liver metastases. Most common primary tumors were colorectal- and pancreatic carcinoma (26.1% respectively). Most frequent fractionation scheme (46.6%) was 50 Gy in five fractions. The adapted plan was significantly superior compared to the predicted plan in regard to planning-target-volume (PTV) coverage, PTV overdosing, and organs-at-risk (OAR) dose constraints violations (91.5 vs. 38.0%, 6 vs. 19% and 0.6 vs. 10.0%; each p &lt; 0.001). Plan adaptation significantly increased median BEDD95 by 3.2 Gy (p &lt; 0.001). Mean total duration of SMART was 72.4 min. (4) Conclusions: SMART offers individualized ablative irradiation of liver metastases tailored to the daily anatomy with significant superior tumor coverage and improved sparing of OAR.

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.

Causes of Death Among Patients With Initially Inoperable Pancreas Cancer After Induction Chemotherapy and Ablative 5-fraction Stereotactic Magnetic Resonance Image Guided Adaptive Radiation Therapy

PurposeNearly all patients with pancreatic ductal adenocarcinoma (PDAC) eventually die of progressive cancer after exhausting treatment options. Although distant metastases (DMs) are a common cause of death, autopsy studies have shown that locoregional progression may be directly responsible for up to one-third of PDAC-related deaths. Ablative stereotactic magnetic resonance-guided adaptive radiation therapy (A-SMART) is a novel treatment strategy that appears to improve locoregional control compared with nonablative radiation therapy, potentially leading to improved overall survival. Methods and MaterialsA single-institution retrospective analysis was performed of patients with nonmetastatic inoperable PDAC treated between 2018 to 2020 using the MRIdian Linac with induction chemotherapy, followed by 5-fraction A-SMART. We identified causes of death that occurred after A-SMART. ResultsA total of 62 patients were evaluated, of whom 42 (67.7%) had died. The median follow-up time was 18.6 months from diagnosis and 11.0 months from A-SMART. Patients had locally advanced (72.6%), borderline resectable (22.6%), or resectable but medically inoperable PDAC (4.8%). All patients received induction chemotherapy, typically leucovorin calcium (folinic acid), fluorouracil, irinotecan hydrochloride, and oxaliplatin (69.4%) or gemcitabine/nab-paclitaxel (24.2%). The median prescribed dose was 50 Gy (range, 40-50), corresponding to a median biologically effective dose of 100 Gy10. Post-SMART therapy included surgery (22.6%), irreversible electroporation (9.7%), and/or chemotherapy (51.6%). Death was attributed to locoregional progression, DMs, cancer-related cachexia/malnutrition, surgery/irreversible electroporation complications, other reasons not due to cancer progression, or unknown causes in 7.1%, 45.2%, 11.9%, 9.5%, 11.9%, and 14.3% of patients, respectively. Intra-abdominal metastases of the liver and peritoneum were responsible for 84.2% of deaths from DMs. ConclusionsTo our knowledge, this is the first contemporary evaluation of causes of death in patients with PDAC receiving dose-escalated radiation therapy. We demonstrated that the predominant cause of PDAC-related death was from liver and peritoneal metastases; therefore novel treatment strategies are indicated to address occult micrometastatic disease at these sites.

Surgical and Pathologic Outcomes of Pancreatic Adenocarcinoma (PA) After Preoperative Ablative Stereotactic Magnetic Resonance Image Guided Adaptive Radiation Therapy (A-SMART)

PurposePreoperative radiation therapy (RT) for pancreatic adenocarcinoma reduces positive surgical margin rates, and when delivered to an ablative dose range it may improve local control and overall survival for patients with unresectable disease. Use of stereotactic body RT to achieve a higher biologically effective dose has been limited by toxicity to adjacent radiosensitive structures, but this can be mitigated by stereotactic magnetic resonance image guided adaptive radiation therapy (SMART). Methods and MaterialsWe describe our single-institution experience of high biologically effective dose SMART before resection of localized pancreatic adenocarcinoma. Toxicity was evaluated according to Common Terminology Criteria for Adverse Events (V 5.0). Tumor response was evaluated according to the College of American Pathologists tumor regression grading criteria. ResultsWe analyzed 26 patients with borderline resectable (80.8%), locally advanced (11.5%), and resectable (7.7%) tumors who received ablative dose SMART (A-SMART) followed by surgical resection. Median age at diagnosis was 68 years (range, 34-86). Most patients received chemotherapy (80.8%) before RT. All patients received A-SMART to a median dose of 50 (range, 40-50) Gy in 5 fractions. Toxicity data were collected prospectively and there were no acute grade 2+ toxicities associated with RT. The median time to resection was 50 days (range, 37-115), and the procedure types included Whipple (69%), distal (23%), or total pancreatectomy (8%). The R0 resection rate was 96% and no perioperative deaths occurred within 90 days. Pathologic response was observed in 88% of cases. The time from RT to surgery was associated with tumor regression grade (P = .0003). The median follow-up after RT was 16.5 months (range, 3.9-26.2). The derived median progression-free survival from RT was 13.2 months. ConclusionsThe initial surgical and pathologic outcomes after A-SMART are encouraging. Preoperative A-SMART was associated with low toxicity rates and no surgical or RT-associated mortality. The surgical morbidity was comparable to historic rates after upfront resection. These data also suggest that the time from stereotactic body RT to surgical resection is associated with pathologic response.

Induction Chemotherapy and Ablative Stereotactic Magnetic Resonance Image-Guided Adaptive Radiation Therapy for Inoperable Pancreas Cancer.

BackgroundRadiation therapy (RT) dose for inoperable pancreatic ductal adenocarcinoma (PDAC) has historically been non-ablative to avoid injuring gastrointestinal (GI) organs at risk (OARs). Accruing data suggest that dose escalation, in select patients, may significantly improve clinical outcomes. Early results of ablative stereotactic magnetic resonance image-guided adaptive radiation therapy (A-SMART) have been encouraging, although long-term outcomes are not well understood.MethodsA single institution retrospective analysis was performed of inoperable non-metastatic PDAC patients who received induction chemotherapy then 5-fraction A-SMART on a 0.35T-MR Linac from 2018-2021.ResultsSixty-two patients were evaluated with a median age of 66 years (range 35-91) and nearly all achieved Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (96.8%). Locally advanced disease was common (72.6%), otherwise borderline resectable (22.6%), or medically inoperable (4.8%). All received induction chemotherapy for a median 4.2 months (range, 0.2-13.3) most commonly FOLFIRINOX (n=43; 69.4%). Median prescribed dose was 50 Gy (range 40-50); median biologically effective dose (BED10) was 100 Gy10. The median local control (LC), progression-free survival (PFS), and overall survival (OS) from diagnosis were not reached, 20 months, and 23 months, respectively. Also, 2-year LC, PFS, and OS were 68.8%, 40.0%, and 45.5%, respectively. Acute and late grade 3+ toxicity rates were 4.8% and 4.8%, respectively.ConclusionsTo our knowledge, this is the largest series of induction chemotherapy followed by ablative 5-fraction SMART delivered on an MR Linac for inoperable PDAC. The potential for this novel treatment strategy is to achieve long-term LC and OS, compared to chemotherapy alone, and warrants prospective evaluation.

Multi-Institutional Outcomes of Stereotactic Magnetic Resonance Image Guided Adaptive Radiation Therapy With a Median Biologically Effective Dose of 100 Gy10 for Non-bone Oligometastases

PurposeRandomized data show a survival benefit of stereotactic ablative body radiation therapy in selected patients with oligometastases (OM). Stereotactic magnetic resonance guided adaptive radiation therapy (SMART) may facilitate the delivery of ablative dose for OM lesions, especially those adjacent to historically dose-limiting organs at risk, where conventional approaches preclude ablative dosing. Methods and MaterialsThe RSSearch Registry was queried for OM patients (1-5 metastatic lesions) treated with SMART. Freedom from local progression (FFLP), freedom from distant progression (FFDP), progression-free survival (PFS), and overall survival (LS) were estimated using the Kaplan-Meier method. FFLP was evaluated using RECIST 1.1 criteria. Toxicity was evaluated using Common Terminology Criteria for Adverse Events version 4 criteria. ResultsNinety-six patients with 108 OM lesions were treated on a 0.35 T MR Linac at 2 institutions between 2018 and 2020. SMART was delivered to mostly abdominal or pelvic lymph nodes (48.1%), lung (18.5%), liver and intrahepatic bile ducts (16.7%), and adrenal gland (11.1%). The median prescribed radiation therapy dose was 48.5 Gy (range, 30-60 Gy) in 5 fractions (range, 3-15). The median biologically effective dose corrected using an alpha/beta value of 10 was 100 Gy10 (range, 48-180). No acute or late grade 3+ toxicities were observed with median 10 months (range, 3-25) follow-up. Estimated 1-year FFLP, FFDP, PFS, and OS were 92.3%, 41.1%, 39.3%, and 89.6%, respectively. Median FFDP and PFS were 8.9 months (95% confidence interval, 5.2-12.6 months) and 7.6 months (95% confidence interval, 4.5-10.6 months), respectively. ConclusionsTo our knowledge, this represents the largest analysis of SMART using ablative dosing for non-bone OM. A median prescribed biologically effective dose of 100 Gy10 resulted in excellent early FFLP and no significant toxicity, likely facilitated by continuous intrafraction MR visualization, breath hold delivery, and online adaptive replanning. Additional prospective evaluation of dose-escalated SMART for OM is warranted.

SMART ablation of lymphatic oligometastases in the pelvis and abdomen: Clinical and dosimetry outcomes

PurposeTo demonstrate dosimetry benefits and report clinical outcomes of stereotactic magnetic resonance (MR)-guided online adaptive radiotherapy (SMART) of abdominopelvic lymphatic oligometastases. Patients & MethodsProspective registry data of 26 patients with 31 oligoprogressive lymphatic metastases (1–2 lesions) who received SMART between April 2020 and April 2021 was analyzed. Prostate cancer was the most common histology (69%). Most patients (63%) had received previous abdominopelvic radiotherapy (RT). SMART was delivered in 3–7 fractions based on planning target volume (PTV) location and previous dose exposures. For SMART, the baseline plan was recalculated on daily 3D MR-imaging (predicted plan), and plan adaptation was mandatory in case of planning objective violations. ResultsPlan adaptation was mostly performed due to violation of planning objectives in the predicted plan (134/140 fractions, 96%) and significantly improved plan dosimetry: (1) PTV coverage was increased (predicted: median 89%, adapted: median 95%, p < 0.001), (2) organs-at-risk (OAR) overdoses were reduced (predicted: 27/140 (19%), adapted: 1/140 (1%), p < 0.001) and (3) PTV overdoses were reduced (predicted: 21/140 (15%), adapted: 1/140 (1%), p < 0.001). After a median follow-up of 9.8 months, one patient had in-field tumor progression and twelve patients had out-field tumor progression (at 6 months: progression-free survival: 63% [46–88%], local control rate: 97% [90–100%]). Treatment was tolerated well and no grade ≥3 toxicity was reported. ConclusionSMART improves target volume coverage and yields superior OAR protection compared to non-adaptive radiotherapy, thus representing an innovative approach to challenging cases, such as repeated radiotherapy.

Multi-institutional outcomes of patients aged 75 years and older with pancreatic ductal adenocarcinoma treated with ablative 5-fraction stereotactic magnetic resonance image-guided adaptive radiation therapy (SMART).

569 Background: Dose escalated radiation therapy (RT) may improve long-term clinical outcomes compared to standard radiation dose for patients with initially inoperable pancreatic ductal adenocarcinoma (PDAC). Favorable outcomes have recently been reported of ablative stereotactic magnetic resonance image-guided adaptive radiation therapy (SMART) delivered in 5 fractions. The appropriateness of ablative SMART inoperable PDAC patients with advanced age (&gt;75 years) is not well understood. Methods: A retrospective analysis was performed of inoperable non-metastatic PDAC patients aged 75 year or older treated on a 0.35T-MR Linac at two institutions. Patients were excluded who did not have at least 3 months follow up after SMART. Fiducial markers were not used. Treatment delivery was typically in breath hold. Most (65.3%) were treated to gross disease only without elective coverage. On-table adaptive replanning was performed for each fraction if needed, primarily to account for interfraction anatomic changes and ensure all organ-at-risk (OAR) constraints were met. Treatment response was defined using RECIST 1.1 criteria and CTCAE v5 criteria was used to assess toxicity. Results: 49 patients were evaluated with median age of 81 years (range 75-91). ECOG performance status (PS) was 0-1 in 89.8%. PDAC was locally advanced (46.9%), borderline resectable (36.7%), or medically inoperable (16.3%). Median CA19-9 at diagnosis was 235.8 U/mL. Most received induction chemotherapy (83.7%), usually gemcitabine/nab-paclitaxel (63.3%) and rarely FOLFIRINOX (12.2%), for a median 3.2 months. Median prescribed dose was 50 Gy (range, 40-50 Gy). Surgery was performed in 18.4% after a median 10 weeks from SMART, all having negative margins. Median follow-up was 14 months from diagnosis. Median and 1-year local control (LC) was 29 months and 88.9%, respectively. Median and 1-year progression free survival (PFS) was 13 months and 53.8%, respectively. Median and 1-year estimated overall survival (OS) was 23 months and 78.9%, respectively. ECOG PS &lt; 2 was the only significant predictor of improved OS on multivariate analysis with a trend towards significance for induction chemotherapy &gt;3 months. Acute and late grade 3+ toxicity rates were 8.2% and 4.1%, respectively. Conclusions: Ablative 5-fraction SMART is associated with encouraging long-term LC and OS among elderly patients with PDAC. This novel treatment strategy is noninvasive, does not require anesthesia, is remarkably well tolerated among patients with advanced age despite the high prescription dose, and therefore should be strongly considered especially among older patients who have limited treatment options.

Comparison of Electrophysiological and Radiological Subthalamic Nucleus Length and Volume.

To investigate the surgical value of MER recordings and improve surgical technique by demonstrating the consistency between preoperative radiological STN volume and intraoperative neurophysiological STN length. Sixty-one patients with PD were enrolled. The volumes of the STN were measured using magnetic resonance images 3-dimensional volume reconstructions of stereotactic magnetic resonance images. MER were performed in all patient and the maximal electrophysiologic length of the STN was recorded each patient. In the postoperative period, the permanent electrode was modeled and reconstructed in 3D, and the longest distance traveled in the STN was calculated. A total of 61 patients who underwent surgery between 2012-2022 were included in the study. Thirty-six (59%) of the patients were male, and 25 (41%) were female. A total of 122 STNs were performed with 166 electrodes. The most common end alignment used was center with 86. STN length averaged 4.9 mm (0-10.5 mm). The mean STN volume was 0.11 cm3. The STN Volume of men were significantly higher than women. The STN Length, Volume, and the target MER length showed a positive correlation significantly. With radiological advances, it is possible to better visualize the target points and define the boundaries better, and direct methods can be used more in making targeting plans. MER records obtained during surgery and STN dimensions in presurgical planning show compatibility, and it is seen that there may be differences between the right and left sides because of brain shifting. Although radiology is increasingly providing better support, electrophysiological recordings provides real-time information on the electrodes? locations and give the opportunity to surgical team choosing alternative target.