Radiomics-enhanced early regression index for predicting treatment response in rectal cancer: a multi-institutional 0.35 T MRI-guided radiotherapy study.

PURPOSE: The accurate prediction of treatment response in locally advanced rectal cancer (LARC) patients undergoing MRI-guided radiotherapy (MRIgRT) is essential for optimising treatment strategies. This multi-institutional study aimed to investigate the potential of radiomics in enhancing the predictive power of a known radiobiological parameter (Early Regression Index, ERITCP) to evaluate treatment response in LARC patients treated with MRIgRT. METHODS: Patients from three international sites were included and divided into training and validation sets. 0.35 T T2*/T1-weighted MR images were acquired during simulation and at each treatment fraction. The biologically effective dose (BED) conversion was used to account for different radiotherapy schemes: gross tumour volume was delineated on the MR images corresponding to specific BED levels and radiomic features were then extracted. Multiple logistic regression models were calculated, combining ERITCP with other radiomic features. The predictive performance of the different models was evaluated on both training and validation sets by calculating the receiver operating characteristic (ROC) curves. RESULTS: A total of 91 patients was enrolled: 58 were used as training, 33 as validation. Overall, pCR was observed in 25 cases. The model showing the highest performance was obtained combining ERITCP at BED = 26 Gy with a radiomic feature (10th percentile of grey level histogram, 10GLH) calculated at BED = 40 Gy. The area under ROC curve (AUC) of this combined model was 0.98 for training set and 0.92 for validation set, significantly higher (p = 0.04) than the AUC value obtained using ERITCP alone (0.94 in training and 0.89 in validation set). CONCLUSION: The integration of the radiomic analysis with ERITCP improves the pCR prediction in LARC patients, offering more precise predictive models to further personalise 0.35 T MRIgRT treatments of LARC patients.

A Phase 2 Randomized Clinical Trial Evaluating 4-Dimensional Computed Tomography Ventilation-Based Functional Lung Avoidance Radiation Therapy for Non-Small Cell Lung Cancer.

PURPOSE: To determine whether 4-dimensional computed tomography (4DCT) ventilation-based functional lung avoidance radiation therapy preserves pulmonary function compared with standard radiation therapy for non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: This single center, randomized, phase 2 trial enrolled patients with NSCLC receiving curative intent radiation therapy with either stereotactic body radiation therapy or conventionally fractionated radiation therapy between 2016 and 2022. Patients were randomized 1:1 to standard of care radiation therapy or functional lung avoidance radiation therapy. The primary endpoint was the change in Jacobian-based ventilation as measured on 4DCT from baseline to 3 months postradiation. Secondary endpoints included changes in volume of high- and low-ventilating lung, pulmonary toxicity, and changes in pulmonary function tests (PFTs). RESULTS: A total of 122 patients were randomized and 116 were available for analysis. Median follow up was 29.9 months. Functional avoidance plans significantly (P < .05) reduced dose to high-functioning lung without compromising target coverage or organs at risk constraints. When analyzing all patients, there was no difference in the amount of lung showing a reduction in ventilation from baseline to 3 months between the 2 arms (1.91% vs 1.87%; P = .90). Overall grade ≥2 and grade ≥3 pulmonary toxicities for all patients were 24.1% and 8.6%, respectively. There was no significant difference in pulmonary toxicity or changes in PFTs between the 2 study arms. In the conventionally fractionated cohort, there was a lower rate of grade ≥2 pneumonitis (8.2% vs 32.3%; P = .049) and less of a decline in change in forced expiratory volume in 1 second (-3 vs -5; P = .042) and forced vital capacity (1.5 vs -6; P = .005) at 3 months, favoring the functional avoidance arm. CONCLUSIONS: There was no difference in posttreatment ventilation as measured by 4DCT between the arms. In the cohort of patients treated with conventionally fractionated radiation therapy with functional lung avoidance, there was reduced pulmonary toxicity, and less decline in PFTs suggesting a clinical benefit in patients with locally advanced NSCLC.

Combining Dual Checkpoint Immunotherapy with Ablative Radiation to All Sites of Oligometastatic Non-Small Cell Lung Cancer: Toxicity and Efficacy Results of a Phase 1b Trial.

PURPOSE: Ablative local treatment of all radiographically detected metastatic sites in patients with oligometastatic non-small cell lung cancer (NSCLC) increases progression-free survival (PFS) and overall survival (OS). Prior studies demonstrated the safety of combining stereotactic body radiation therapy (SBRT) with single-agent immunotherapy. We investigated the safety of combining SBRT to all metastatic tumor sites with dual checkpoint, anticytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), and anti-programmed cell death ligand 1 (anti-PD-L1) immunotherapy for patients with oligometastatic NSCLC. METHODS AND MATERIALS: We conducted a phase 1b clinical trial in patients with oligometastatic NSCLC with up to 6 sites of extracranial metastatic disease. All sites of disease were treated with SBRT to a dose of 30 to 50 Gy in 5 fractions. Dual checkpoint immunotherapy was started 7 days after completion of radiation using anti-CTLA-4 (tremelimumab) and anti-PD-L1 (durvalumab) immunotherapy for a total of 4 cycles followed by durvalumab alone until progression or toxicity. RESULTS: Of the 17 patients enrolled in this study, 15 patients received at least 1 dose of combination immunotherapy per protocol. The study was closed early (17 of planned 21 patients) due to slow accrual during the COVID-19 pandemic. Grade 3+ treatment-related adverse events were observed in 6 patients (40%), of which only one was possibly related to the addition of SBRT to immunotherapy. Median PFS was 42 months and median OS has not yet been reached. CONCLUSIONS: Delivering ablative SBRT to all sites of metastatic disease in combination with dual checkpoint immunotherapy did not result in excessive rates of toxicity compared with historical studies of dual checkpoint immunotherapy alone. Although the study was not powered for treatment efficacy results, durable PFS and OS results suggest potential therapeutic benefit compared with immunotherapy or radiation alone in this patient population.

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 PURPOSE: Radiation 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 METHODS: This 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. RESULTS: Mean 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. CONCLUSIONS: Long-term outcomes from the phase 2 SMART trial demonstrate encouraging OS and limited severe toxicity. Additional prospective evaluation of this novel strategy is warranted.

A Multi-Institutional Phase 2 Trial of Ablative 5-Fraction Stereotactic Magnetic Resonance-Guided On-Table Adaptive Radiation Therapy for Borderline Resectable and Locally Advanced Pancreatic Cancer.

PURPOSE: Magnetic resonance (MR) image guidance may facilitate safe ultrahypofractionated radiation dose escalation for inoperable pancreatic ductal adenocarcinoma. We conducted a prospective study evaluating the safety of 5-fraction Stereotactic MR-guided on-table Adaptive Radiation Therapy (SMART) for locally advanced (LAPC) and borderline resectable pancreatic cancer (BRPC). METHODS AND MATERIALS: Patients with LAPC or BRPC were eligible for this multi-institutional, single-arm, phase 2 trial after ≥3 months of systemic therapy without evidence of distant progression. Fifty gray in 5 fractions was prescribed on a 0.35T MR-guided radiation delivery system. The primary endpoint was acute grade ≥3 gastrointestinal (GI) toxicity definitely attributed to SMART. RESULTS: One hundred thirty-six patients (LAPC 56.6%, BRPC 43.4%) were enrolled between January 2019 and January 2022. Mean age was 65.7 (36-85) years. Head of pancreas lesions were most common (66.9%). Induction chemotherapy mostly consisted of (modified)FOLFIRINOX (65.4%) or gemcitabine/nab-paclitaxel (16.9%). Mean CA19-9 after induction chemotherapy and before SMART was 71.7 U/mL (0-468). On-table adaptive replanning was performed for 93.1% of all delivered fractions. Median follow-up from diagnosis and SMART was 16.4 and 8.8 months, respectively. The incidence of acute grade ≥3 GI toxicity possibly or probably attributed to SMART was 8.8%, including 2 postoperative deaths that were possibly related to SMART in patients who had surgery. There was no acute grade ≥3 GI toxicity definitely related to SMART. One-year overall survival from SMART was 65.0%. CONCLUSIONS: The primary endpoint of this study was met with no acute grade ≥3 GI toxicity definitely attributed to ablative 5-fraction SMART. Although it is unclear whether SMART contributed to postoperative toxicity, we recommend caution when pursuing surgery, especially with vascular resection after SMART. Additional follow-up is ongoing to evaluate late toxicity, quality of life, and long-term efficacy.

Toxicity and Patient-Reported Quality-of-Life Outcomes After Prostate Stereotactic Body Radiation Therapy With Focal Boost to Magnetic Resonance Imaging-Identified Prostate Cancer Lesions: Results of a Phase 2 Trial.

PURPOSE: In this prospective phase 2 trial, we investigated the toxicity and patient-reported quality-of-life outcomes in patients treated with stereotactic body radiation therapy (SBRT) to the prostate gland and a simultaneous focal boost to magnetic resonance imaging (MRI)-identified intraprostatic lesions while also de-escalating dose to the adjacent organs at risk. METHODS AND MATERIALS: Eligible patients included low- or intermediate-risk prostate cancer (Gleason score ≤7, prostate specific antigen ≤20, T stage ≤2b). SBRT was prescribed to 40 Gy in 5 fractions delivered every other day to the prostate, with any areas of high disease burden (MRI-identified prostate imaging reporting and data system 4 or 5 lesions) simultaneously escalated to 42.5 to 45 Gy and areas overlapping organs at risk (within 2 mm of urethra, rectum, and bladder) constrained to 36.25 Gy (n = 100). Patients without a pretreatment MRI or without MRI-identified lesions were treated to dose of 37.5 Gy with no focal boost (n = 14). RESULTS: From 2015 to 2022, a total of 114 patients were enrolled with a median follow-up of 42 months. No acute or late grade 3+ gastrointestinal (GI) toxicity was observed. One patient developed late grade 3 genitourinary (GU) toxicity at 16 months. In patients treated with focal boost (n = 100), acute grade 2 GU and GI toxicity was seen in 38% and 4% of patients, respectively. Cumulative late grade 2+ GU and GI toxicities at 24 months were 13% and 5% respectively. Patient-reported outcomes showed no significant long-term change from baseline in urinary, bowel, hormonal, or sexual quality-of-life scores after treatment. CONCLUSIONS: SBRT to a dose of 40 Gy to the prostate gland with a simultaneous focal boost up to 45 Gy is well tolerated with similar rates of acute and late grade 2+ GI and GU toxicity as seen in other SBRT regimens without intraprostatic boost. Moreover, no significant long-term changes were seen in patient-reported urinary, bowel, or sexual outcomes from pretreatment baseline.

The Role of Stereotactic Body Radiation Therapy in the Management of Liver Metastases.

The liver is a common site for metastatic spread for various primary tumor histologies. Stereotactic body radiation therapy (SBRT) is a non-invasive treatment technique with broad patient candidacy for the ablation of tumors in the liver and other organs. SBRT involves focused, high-dose radiation therapy delivered in one to several treatments, resulting in high rates of local control. Use of SBRT for ablation of oligometastatic disease has increased in recent years and emerging prospective data have demonstrated improvements in progression free and overall survival in some settings. When delivering SBRT to liver metastases, clinicians must balance the priorities of delivering ablative tumor dosing while respecting dose constraints to surrounding organs at risk (OARs). Motion management techniques are crucial for meeting dose constraints, ensuring low rates of toxicity, maintaining quality of life, and can allow for dose escalation. Advanced radiotherapy delivery approaches including proton therapy, robotic radiotherapy, and real-time MR-guided radiotherapy may further improve the accuracy of liver SBRT. In this article, we review the rationale for oligometastases ablation, the clinical outcomes with liver SBRT, tumor dose and OAR considerations, and evolving strategies to improve liver SBRT delivery.

Patterns of utilization and clinical adoption of 0.35 Tesla MR-guided radiation therapy in the United States - Understanding the transition to adaptive, ultra-hypofractionated treatments.

Purpose/Objective: Magnetic resonance-guided radiation therapy (MRgRT) utilization is rapidly expanding worldwide, driven by advanced capabilities including continuous intrafraction visualization, automatic triggered beam delivery, and on-table adaptive replanning (oART). Our objective was to describe patterns of 0.35Tesla(T)-MRgRT (MRIdian) utilization in the United States (US) among early adopters of this novel technology. Materials/Methods: Anonymized administrative data from all US MRIdian treatment systems were extracted for patients completing treatment from 2014 to 2020. Detailed treatment information was available for all MRIdian linear accelerator (linac) systems and some cobalt systems. Results: Seventeen systems at 16 centers delivered 5736 courses and 36,389 fractions (fraction details unavailable for 1223 cobalt courses), of which 21.1% were adapted. Ultra-hypofractionation (UHfx) (1-5 fractions) was used in 70.3% of all courses. At least one adaptive fraction was used for 38.5% of courses (average 1.7 adapted fractions/course), with higher oART use in UHfx dose schedules (47.7% of courses, average 1.9 adapted fractions per course). The most commonly treated organ sites were pancreas (20.7%), liver (16.5%), prostate (12.5%), breast (11.5%), and lung (9.4%). Temporal trends show a compounded annual growth rate (CAGR) of 59.6% in treatment courses delivered, with a dramatic increase in use of UHfx to 84.9% of courses in 2020 and similar increase in use of oART to 51.0% of courses. Conclusions: This is the first comprehensive study reporting patterns of utilization among early adopters of MRIdian in the US. Intrafraction MR image-guidance, advanced motion management, and increasing adoption of adaptive radiation therapy has led to a substantial transition to ultra-hypofractionated regimens. 0.35 T-MRgRT has been predominantly used to treat abdominal and pelvic tumors with increasing use of on-table adaptive replanning, which represents a paradigm shift in radiation therapy.

Transcatheter Arterial Chemoembolization Imaging Features in MR-Linac Radiation Therapy Planning for the Liver.

For MR-guided radiation therapy treatment planning, an MRI and CT of the intended treatment site are typically acquired. Patients' prior treatments or procedures can cause image artifacts in one or both scans, which may impact treatment planning or the radiation dose calculation. In this case report, a patient with several previous transcatheter arterial chemoembolization (TACE) procedures was planned for radiation therapy on a low-field MR-linac, and the impact of residual iodinated oil on the radiation dose calculation and MR-guided adaptive workflow was evaluated.

A Predictive Model of 2yDFS During MR-Guided RT Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer Patients.

Purpose: Distant metastasis is the main cause of treatment failure in locally advanced rectal cancer (LARC) patients, despite the recent improvement in treatment strategies. This study aims to evaluate the "delta radiomics" approach in patients undergoing neoadjuvant chemoradiotherapy (nCRT) treated with 0.35-T magnetic resonance-guided radiotherapy (MRgRT), developing a logistic regression model able to predict 2-year disease-free-survival (2yDFS). Methods: Patients affected by LARC were enrolled in this multi-institutional study. A predictive model of 2yDFS was developed taking into account both clinical and radiomics variables. Gross tumour volume (GTV) was delineated on the magnetic resonance (MR) images acquired during MRgRT, and 1,067 radiomic features (RF) were extracted using the MODDICOM platform. The performance of RF in predicting 2yDFS was investigated in terms of the Wilcoxon-Mann-Whitney test and area under receiver operating characteristic (ROC) curve (AUC). Results: 48 patients have been retrospectively enrolled, with 8 patients (16.7%) developing distant metastases at the 2-year follow-up. A total of 1,099 variables (1,067 RF and 32 clinical variables) were evaluated in two different models: radiomics and radiomics/clinical. The best-performing 2yDFS predictive model was a delta radiomics one, based on the variation in terms of area/surface ratio between biologically effective doses (BED) at 54 Gy and simulation (AUC of 0.92). Conclusions: The results of this study suggest a promising role of delta radiomics analysis on 0.35-T MR images in predicting 2yDFS for LARC patients. Further analyses including larger cohorts of patients and an external validation are needed to confirm these preliminary results.

In Silico Single-Fraction Stereotactic Ablative Radiation Therapy for the Treatment of Thoracic and Abdominal Oligometastatic Disease With Online Adaptive Magnetic Resonance Guidance.

PURPOSE: Although SABR can improve oncologic outcomes for patients with oligometastatic disease, treatment of metastases near critical organs remains challenging. The purpose of this study is to determine the dosimetric feasibility of delivering magnetic resonance imaging (MRI)-guided adaptive SABR in a single fraction for abdominal and thoracic metastases. METHODS AND MATERIALS: Previously delivered MRI-guided radiation therapy plans for 20 patients with oligometastatic disease in the thorax or abdomen, with 70% (14/20) of the lesions within 8 mm from dose-limiting organs at risk (OARs), were used to simulate the delivery of 24 Gy in a single fraction. Planning objectives included planning target volume (PTV) V95% >90%, optimized PTV (PTVopt) V95% >90%, and PTVopt D99% >20 Gy with no OAR dose violations, where PTVopt removed overlap with nearby planning organ at risk volume (PRV). Single-fraction plans were simulated on the first 5 daily setup breath-hold MRI scans, and the plans were reoptimized to consider variations in setup position and anatomy. RESULTS: The mean PTV V95% for single-fraction SABR plans was lower compared with multifraction plans (mean 85.4% vs 92.6%, P = .02), but mean PTVopt V95% was not different (95.3% vs 98.2%, P = .62). After reoptimization of the single-fraction plan to the treatment day MRI, there was an increase in mean PTV V95% (85.0% vs 88.1%, P = .05), increase in mean PTVopt V95% (92.7% vs 96.3%, P = .02), increase in mean PTVopt D99% (19.7 Gy vs 23.8 Gy, P < .01), increase in mean frequency of meeting PTV D99% >20 Gy (52% vs 87%, P < .01), and increase in mean gross tumor volume minimum dose (17.5 Gy vs 19.3 Gy, P < .01). Reoptimization decreased mean frequency of OAR dose constraint violation (48% vs 0%, P < .01). CONCLUSIONS: Single-fraction MRI-guided SABR is a dosimetrically feasible treatment for oligometastases that allows for on-table adaptation to avoid OAR dose constraint violations, but this method requires clinical validation.

Combining Stereotactic Body Radiotherapy and Microwave Ablation Appears Safe and Feasible for Renal Cell Carcinoma in an Early Series.

Microwave (MW) ablation and stereotactic body radiation therapy (SBRT) are both used in treating inoperable renal cell carcinoma (RCC). MW ablation and SBRT have potentially complementary advantages and limitations. Combining SBRT and MW ablation may optimize tumor control and toxicity for patients with larger (> 5 cm) RCCs or those with vascular involvement. Seven patients with RCC were treated at our institution with combination of SBRT and MW ablation, median tumor size of 6.4 cm. Local control was 100% with a median follow-up of 15 months. Four patients experienced grade 2 nausea during SBRT. Three patients experienced toxicities after MW ablation, 2 with grade 1 hematuria and 1 with grade 3 retroperitoneal bleed/collecting system injury. Median eGFR (estimated glomerular filtration rate) preceding and following SBRT and MW ablation was 69 mL/min/1.73 m2 and 68 mL/min/1.73 m2 (P = .19), respectively. In patients who are not surgical candidates, larger RCCs or those with vascular invasion are challenging to treat. Combination treatment with SBRT and MW ablation may balance the risks and benefits of both therapies and demonstrates high local control in our series. MW ablation and SBRT have potentially complementary advantages and limitations.

Evaluating dose constraints for radiation induced liver damage following magnetic resonance image guided Stereotactic Body radiotherapy.

This study reports dose corresponding to visible radiation induced liver damage following Stereotactic Body Radiation Therapy (SBRT) for liver metastasis, and the optimal time for follow up scans using post radiation imaging. Diagnostic magnetic resonance scans of nine patients treated with liver SBRT using a 0.35 T MRI-guided radiotherapy system were analyzed. The dice coefficients between the region of visible liver damage and the delivered dose were calculated. A median dose of 35 Gy correlated most closely with the visible radiation induced liver damage. We compared scans over two to nine months and observed maximal dice coefficients at two to five months post radiation. We have presented a new method for developing treatment planning guidelines for liver SBRT.

Delta radiomics for rectal cancer response prediction using low field magnetic resonance guided radiotherapy: an external validation.

INTRODUCTION: A recent study performed on 16 locally advanced rectal cancer (LARC) patients treated using magnetic resonance guided radiotherapy (MRgRT) has identified two delta radiomics features as predictors of clinical complete response (cCR) after neoadjuvant radio-chemotherapy (nCRT). This study aims to validate these features (ΔLleast and Δglnu) on an external larger dataset, expanding the analysis also for pathological complete response (pCR) prediction. METHODS: A total of 43 LARC patients were enrolled: Gross Tumour Volume (GTV) was delineated on T2/T1* MR images acquired during MRgRT and the two delta features were calculated. Receiver Operating Characteristic (ROC) curve analysis was performed on the 16 cases of the original study and the best cut-off value was identified. The performance of ΔLleast and Δglnu was evaluated at the best cut-off value. RESULTS: On the original dataset of 16 patients, ΔLleast reported an AUC of 0.81 for cCR and 0.93 for pCR, while Δglnu 0.72 and 0.54 respectively. The best cut-off values of ΔLleast was 0.73 for both outcomes, while Δglnu reported 0.54 for cCR and 0.93 for pCR. At the external validation, ΔLleast showed an accuracy of 81% for cCR and 79% for pCR, while Δglnu reported 63% for cCR and 40% for pCR. CONCLUSION: The accuracy of ΔLleast in predicting cCR and pCR is significantly higher than those obtained considering Δglnu, but inferior if compared with other image-based biomarker, such as the early-regression index. Studies with larger cohorts of patients are recommended to further investigate the role of delta radiomic features in MRgRT.

Diagnostic Performance of MRI for Esophageal Carcinoma: A Systematic Review and Meta-Analysis.

Background Although CT, endoscopic US, and PET are critical in determining the appropriate management of esophageal carcinoma (squamous cell carcinoma and adenocarcinoma), previous reports show that staging accuracy remains low, particularly for nodal involvement sensitivity. Purpose To perform a systematic review and meta-analysis to determine the diagnostic performance of MRI for multiple staging thresholds in patients with biopsy-proven esophageal carcinoma (differentiation of stage T0 disease from stage T1 or higher disease, differentiation of stage T2 or lower disease from stage T3 or higher disease, and differentiation of stage N0 disease from stage N1 or higher disease [where T refers to tumor stage and N refers to nodal stage]). Materials and Methods Studies of the diagnostic performance of MRI in determining the stage of esophageal carcinoma in patients before esophagectomy and pathologic staging between 2000 and 2019 were searched in PubMed, Scopus, Web of Science, and Cochrane Library by a librarian and radiation oncologist. Pooled diagnostic performance of MRI was calculated with a bivariate random effects model. Bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (version 2) tool. Results Twenty studies with a total of 984 patients were included in the analysis. Pooled accuracy for stage T0 versus stage T1 or higher had a sensitivity of 92% (95% CI: 82, 96) and a specificity of 67% (95% CI: 51, 81). Pooled accuracy for stage T2 or lower versus stage T3 or higher had a sensitivity of 86% (95% CI: 76, 92) and a specificity of 86% (95% CI: 75, 93). Pooled accuracy for stage N0 versus stage N1 or higher had a sensitivity of 71% (95% CI: 60, 80) and a specificity of 72% (95% CI: 64, 79). The concern for applicability was low for the patient selection, index test, and reference test domains, except for 10% of studies (two of 20) that had unclear concern for patient selection applicability. Conclusion MRI has high sensitivity but low specificity for the detection of esophageal carcinoma, which shows promise for determining neoadjuvant therapy response and for detecting locally advanced disease for potential trimodality therapy. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Leeflang in this issue.

Reduction of cardiac dose using respiratory-gated MR-linac plans for gastro-esophageal junction cancer.

Treatment of locally advanced adenocarcinoma of the gastroesophageal junction (GEJ) with chemoradiation may be associated with high rates of symptomatic cardiac toxicity. Large margins are typically required to ensure coverage of GEJ tumors with free-breathing volumetric modulated arc therapy (VMAT) radiotherapy. The purpose of this study is to determine whether treatment with tighter margins enabled by maximum-inhalation breath hold (MIBH)-gated intensity modulated radiation therapy (IMRT) on an integrated MRI-linear accelerator system (MR-linac) can decrease radiation doses to the heart and cardiac substructures. Ten patients with locally advanced GEJ adenocarcinoma underwent both free breathing 4-dimensional computed tomography (4DCT) and MIBH MRI simulation scans. MR-linac IMRT plans were created with a 3 mm clinical target volume (CTV) to planning target volume (PTV) isotropic margin and 4DCT VMAT plans were created with a 11, 13, and 9 mm CTV to PTV anisotropic margins in the left-right, cranial-caudal, and anterior-posterior directions according to GEJ-specific PTV expansion recommendations by Voncken et al. Prescription dose to PTV was 50.4 Gy in 28 fractions. Dosimetry to the heart and cardiac substructures was compared with paired t test; p < 0.05 was considered significant. Mean PTV on the MR-linac IMRT plans was significantly smaller compared to the 4DCT VMAT plans (689 cm3vs 1275 cm3, p < 0.01). Mean dose to the heart and all cardiac substructures was significantly lower in the MR-linac IMRT plans compared to the 4DCT VMAT plans: heart 20.9 Gy vs 27.8 Gy, left atrium 29.6 Gy vs 39.4 Gy, right atrium 20.5 Gy vs 25.6 Gy, left ventricle 21.6 Gy vs 29.6 Gy, and right ventricle 18.7 Gy vs 25.2 Gy (all p values <0.05). MIBH-gated MR-linac IMRT treatment of locally advanced GEJ adenocarcinoma can significantly decrease doses to the heart and cardiac substructures and this may translate to reduced rates of cardiac toxicity.

A Phase 1 Dose Escalation Study of Neoadjuvant SBRT Plus Elective Nodal Radiation with Concurrent Capecitabine for Resectable Pancreatic Cancer.

PURPOSE: The role of neoadjuvant radiation for resectable pancreatic adenocarcinoma is controversial. We performed a prospective dose-escalation study of neoadjuvant stereotactic body radiation therapy (SBRT) with concurrent capecitabine and elective nodal irradiation (ENI) followed by surgical resection to explore the toxicity and feasibility of this approach. METHODS AND MATERIALS: Patients with biopsy proven, resectable cancers of the pancreatic head were enrolled. A 4 + 4 dose-escalation design was employed delivering 5 fractions of 5 to 7 Gy to primary tumor with concurrent capecitabine. The maximum tolerated dose level was expanded for an additional 4 patients. Patients at all dose levels were treated with ENI delivering 25 Gy in 5 fractions. Dose-limiting toxicity was defined as any grade ≥3 nonhematologic toxicity (National Cancer Institute Common Terminology Criteria for Adverse Events v4.0) attributable to chemoradiation occurring within 90 days of SBRT. RESULTS: A total of 17 patients were enrolled with 16 patients evaluable and 13 patients ultimately proceeding to surgery. The most common toxicity was nausea (56%). There were no dose-limiting toxicities, and SBRT was maximally dose escalated to 35 Gy in 5 fractions for 8 patients. All patients completing surgery had R0 resections. Seven patients (54%) had moderate treatment effect identified in pathologic specimens. Three patients (23%) developed locoregional recurrences, with 2 (15%) partially included within the treated volume. CONCLUSIONS: SBRT was safely dose escalated to 35 Gy in 5 fractions along with concurrent capecitabine and ENI. This regimen will be used in a future expansion cohort.

External Validation of Early Regression Index (ERITCP) as Predictor of Pathologic Complete Response in Rectal Cancer Using Magnetic Resonance-Guided Radiation Therapy.

PURPOSE: Tumor control probability (TCP)-based early regression index (ERITCP) is a radiobiological parameter that showed promising results in predicting pathologic complete response (pCR) on T2-weighted 1.5 T magnetic resonance (MR) images of patients with locally advanced rectal cancer. This study aims to validate the ERITCP in the context of low-tesla MR-guided radiation therapy, using images acquired with different magnetic field strength (0.35 T) and image contrast (T2/T1). Furthermore, the optimal timing for pCR prediction was estimated, calculating the ERI index at different biologically effective dose (BED) levels. METHODS AND MATERIALS: Fifty-two patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation therapy were enrolled in this multi-institutional retrospective study. For each patient, a 0.35 T T2/T1-weighted MR image was acquired during simulation and on each treatment day. Gross tumor volume was contoured according to International Commission on Radiation Units Report 83 guidelines. According to the original definition, ERITCP was calculated considering the residual tumor volume at BED = 25 Gy. ERI was also calculated in correspondence with several BED levels: 13, 21, 32, 40, 46, 54, 59, and 67. The predictive performance of the different ERI indices were evaluated in terms of receiver operating characteristic curve. The robustness of ERITCP with respect to the interobserver variability was also evaluated considering 2 operators and calculating the intraclass correlation index. RESULTS: Fourteen patients showed pCR. ERITCP correctly 47 of 52 cases (accuracy = 90%), showing good results in terms of sensitivity (86%), specificity (92%), negative predictive value (95%), and positive predictive value (80%). The analysis at different BED levels shows that the best predictive performance is obtained when this parameter is calculated at BED = 25 Gy (area under the curve = 0.93). ERITCP results are robust with respect to interobserver variability (intraclass correlation index = 0.99). CONCLUSIONS: This study confirmed the validity and the robustness of ERITCP as a pCR predictor in the context of low-tesla MR-guided radiation therapy and indicate 25 Gy as the best BED level to perform predictions.

Investigating split-filter dual-energy CT for improving liver tumor visibility for radiation therapy.

PURPOSE: Accurate liver tumor delineation is crucial for radiation therapy, but liver tumor volumes are difficult to visualize with conventional single-energy CT. This work investigates the use of split-filter dual-energy CT (DECT) for liver tumor visibility by quantifying contrast and contrast-to-noise ratio (CNR). METHODS: Split-filter DECT contrast-enhanced scans of 20 liver tumors including cholangiocarcinomas, hepatocellular carcinomas, and liver metastases were acquired. Analysis was performed on the arterial and venous phases of mixed 120 kVp-equivalent images and VMIs at 57 keV and 40 keV gross target volume (GTV) contrast and CNR were calculated. RESULTS: For the arterial phase, liver GTV contrast was 12.1 ± 10.0 HU and 43.1 ± 32.3 HU (P < 0.001) for the mixed images and 40 keV VMIs. Image noise increased on average by 116% for the 40 keV VMIs compared to the mixed images. The average CNR did not change significantly (1.6 ± 1.5, 1.7 ± 1.4, 2.4 ± 1.7 for the mixed, 57 keV and 40 keV VMIs (P > 0.141)). For individual cases, however, CNR increases of up to 607% were measured for the 40 keV VMIs compared to the mixed image. Venous phase 40 keV VMIs demonstrated an average increase of 35.4 HU in GTV contrast and 121% increase in image noise. Average CNR values were also not statistically different, but for individual cases CNR increases of up to 554% were measured for the 40 keV VMIs compared to the mixed image. CONCLUSIONS: Liver tumor contrast was significantly improved using split-filter DECT 40 keV VMIs compared to mixed images. On average, there was no statistical difference in CNR between the mixed images and VMIs, but for individual cases, CNR was greatly increased for the 57 keV and 40 keV VMIs. Therefore, although not universally successful for our patient cohort, split-filter DECT VMIs may provide substantial gains in tumor visibility of certain liver cases for radiation therapy treatment planning.

Validation of an MR-guided online adaptive radiotherapy (MRgoART) program: Deformation accuracy in a heterogeneous, deformable, anthropomorphic phantom.

BACKGROUND AND PURPOSE: To investigate deformable image registration (DIR) and multi-fractional dose accumulation accuracy of a clinical MR-guided online adaptive radiotherapy (MRgoART) program, utilizing clinically-based magnitudes of abdominal deformation vector fields (DVFs). MATERIALS AND METHODS: A heterogeneous anthropomorphic multi-modality abdominal deformable phantom was comprised of MR and CT anatomically-relevant materials. Thermoluminescent dosimeters (TLDs) were affixed within regions of interest (ROIs). CT and MR simulation scans were acquired. CT was deformed to MR for dose calculations. MRgoART was executed on a MR-linac (MRIdian) for 5 Gy/5 fractions. Before each fraction, a deformation was applied. Ground truth was known for ROI volume, TLD position, and TLD dose measured by an accredited dosimetry calibration laboratory. To validate the range of applied deformations, phantom DVFs were compared to DVFs of clinical abdominal MRgoART fractions. MR-MR deformation accuracy was quantified through dice similarity coefficient (DSC), Hausdorff distance (HD), mean distance-to-agreement (MDA), and as mean-absolute-error (MAE) for CT-MR-MR deformation. Arithmetic-summation of calculated dose at respective TLD positions and deform-accumulated dose (MIM) was compared to TLD measured dose, respectively. MR-MR deformation statistics were quantified for MRIdian and MIM. RESULTS: Mean phantom DVFs were 5.0 ± 2.9 mm compared to mean DVF of clinical abdominal patients at 5.2 ± 3.0 mm. Respective mean DSC, HD, MDA was 0.93 ± 0.03, 0.74 ± 0.80 cm, 0.08 ± 0.03 cm for MRIdian and 0.93 ± 0.03, 0.54 ± 0.27 cm, 0.08 ± 0.03 cm for MIM (N = 80 ROIs). Mean MAE was 20.5 HU. Respective mean and median dose differences were 0.3%, -0.3% for arithmetic-summation and 4.1%, 0.6% for deformed-accumulation. Maximum differences were 0.21 Gy (arithmetic-summation), 0.31 Gy (deformed-accumulation). CONCLUSIONS: MRgoART deformation and dosimetric accuracy has been benchmarked for mean fractional DVFs of 5 mm in a multiple-rigid-body deformable phantom. Deformation accuracy was within TG132 criteria and clinically acceptable end-to-end MRgoART dosimetric agreement was observed for this phantom. Further efforts are needed in validation of deform-accumulated dose.