Factors influencing local control after MR-guided stereotactic body radiotherapy (MRgSBRT) for adrenal metastases.

Purpose: Stereotactic body radiotherapy (SBRT) is an effective treatment for adrenal gland metastases, but it is technically challenging and there are concerns about toxicity. We performed a multi-institutional pooled retrospective analysis to study clinical outcomes and toxicities after MR-guided SBRT (MRgSBRT) using for adrenal gland metastases. Methods and Materials: Clinical and dosimetric data of patients treated with MRgSBRT on a 0.35 T MR-Linac at 11 institutions between 2016 and 2022 were analyzed. Local control (LC), local progression-free survival (LPFS), distant progression-free survival (DPFS) and overall survival (OS) were estimated using Kaplan-Meier method and log-rank test. Results: A total of 255 patients (269 adrenal metastases) were included. Metastatic pattern was solitary in 25.9 % and oligometastatic in 58.0 % of patients. Median total dose was 45 Gy (range, 16-60 Gy) in a median of 5 fractions, and the median BED10 was 100 Gy (range, 37.5-132.0 Gy). Adaptation was done in 87.4 % of delivered fractions based on the individual clinicians' judgement. The 1- and 2- year LPFS rates were 94.0 % (95 % CI: 90.7-97.3 %) and 88.3 % (95 % CI: 82.4-94.2 %), respectively and only 2 patients (0.8 %) experienced grade 3 + toxicity. No local recurrences were observed after treatment to a total dose of BED10 > 100 Gy, with single fraction or fractional dose of > 10 Gy. Conclusions: This is a large retrospective multi-institutional study to evaluate the treatment outcomes and toxicities with MRgSBRT in over 250 patients, demonstrating the need for frequent adaptation in 87.4 % of delivered fractions to achieve a 1- year LPFS rate of 94 % and less than 1 % rate of grade 3 + toxicity. Outcomes analysis in 269 adrenal lesions revealed improved outcomes with delivery of a BED10 > 100 Gy, use of single fraction SBRT and with fraction doses > 10 Gy, providing benchmarks for future clinical trials.

Clinical outcomes of MR-guided adrenal stereotactic ablative radiotherapy with preferential sparing of organs at risk.

Background and purpose: The optimal stereotactic ablative radiotherapy (SABR) doses for adrenal tumors are unknown. Some trials have specified that organ at risk (OAR) dose constraints should take priority over target coverage. We performed a retrospective review of the outcomes of MR-guided adrenal SABR (MRgRT) delivered with OAR sparing. Materials and methods: Patients who underwent adrenal MRgRT between 2016 and 2023 were identified from our Ethics-approved institutional database. Dose ranged between 8 and 24 Gy per fraction, delivered in 1-5 fractions. A 3 mm margin was added to the breath-hold gross tumor volume (GTV) to derive a PTV. Plan were delivered to an 'optimized' PTV that was generated by excluding any overlap with OARs. Results: Adrenal SABR was performed in 107 patients (114 metastases). The commonest scheme used 5 fractions of 10 Gy (53.5 %); 82 % of plans delivered a BED10 ≧ 80 Gy. Systemic therapy was administered within 3 months preceding or following SABR in 53.5 % of patients. Grade 3 acute toxicity (CTCAE v5.0) occurred in 0.9 % of patients, and 4.4 % reported late toxicity, consisting of adrenal insufficiency and a vertebral collapse. Median follow-up was 13.8 months (range, 0.0-73.4 months). Local progression occurred in 7.4 % of evaluable patients. PTV underdosage was frequent, with a coverage compromise index (D99/prescription dose) of < 0.90 in 52 % of all plans. Recurrences were independent of the prescription doses. Conclusion: MRgRT for adrenal metastases is well tolerated with high local control rates despite prioritizing OAR sparing over PTV coverage. Studies using deformable dose accumulation may lead to a better understanding of dose-response relationship with adaptive SABR.

Efficacy of Clomiphene Citrate Versus Enclomiphene Citrate for Male Infertility Treatment: A Retrospective Study.

Introduction Infertility and hypogonadism in males can greatly affect their reproductive health and overall well-being. Since exogenous testosterone administration for hypogonadism management may disrupt the normal hormonal cascade necessary for spermatogenesis, clomiphene citrate (CC) and enclomiphene citrate (EC) are medications often used to manage hypogonadism and male infertility. This study aims to directly compare the effects of CC and EC on serum testosterone levels and semen parameters in men to determine which medication may have an advantage in managing these conditions. Materials and methods We retrospectively analyzed ≥18-year-old men presenting with primary infertility, abnormal semen parameters, or hypogonadism who received CC or EC monotherapy for at least three months between January 2021 and December 2022. We compared baseline and follow-up hormone levels, semen parameters, and demographics. Variables were compared using paired and unpaired t-tests. Significance was assessed at p<0.05. Results A total of 46 men received EC and 32 men received CC. The median age was 42 (IQR: 34-47.75) years in men who received EC and 41 (IQR: 36-44) years in men who received CC (p=0.450). The two treatment groups exhibited a significant increase in serum total testosterone, while only EC had a statistically significant increase in FSH and LH. Semen volume and concentration did not significantly change with either treatment. Sperm motility increased in both groups, but total motile sperm count (TMSC) only significantly increased in men who received EC.  Conclusions Our study found that EC and CC are effective treatments in increasing total testosterone without negatively affecting spermatogenesis. EC demonstrated to be more effective in raising gonadotropin levels and TMSC.

Local control and toxicity after magnetic resonance imaging (MR)-guided single fraction lung stereotactic ablative radiotherapy.

PURPOSE: Magnetic resonance imaging (MR)-guided radiotherapy permits continuous intrafraction visualization and use of automatic triggered beam delivery, with use of smaller planning target volumes (PTV). We report on long-term clinical outcomes following MR-guided single fraction (SF) lung SABR on a 0.35 T linac. MATERIALS AND METHODS: Details of patients treated with SF-SABR for lung tumors were accessed from an ethics approved institutional database. A breath-hold 3D MR simulation scan was performed using a true FISP sequence, followed by a breath-hold 3D CT scan. The gross tumor volume (GTV) was first contoured on the breath-hold CT scan, which was then compared with contours on the 3D MR scan, before the GTV was finalized. SABR plans used step-and-shoot IMRT beams to a PTV derived by adding a 5 mm margin to the breath-hold GTV, and a 3 mm gating window was used. SABR was delivered during repeated breath-holds, using automatic beam gating with continuous visualization of the GTV in a sagittal MR plane. RESULTS: Between 2018-2022, 50 consecutive patients were treated, and 69% had a primary non-small cell lung cancer. Median PTV was 11.2 cc (range 3.9-53.5); 80% of GTV's were located ≤2.5 cm from the chest wall. Prescribed doses were 34 Gy (in 58%), 30 Gy (32%), or between 20-28 Gy (10%). After a median follow-up of 18.1 months (95% CI 12.8-23.5), the 2-year survival was 82% (89% for primary NSCLC and 62% for metastases). After a median follow-up of 16.1 months (95% CI 11.2-21.1), local recurrences developed in 2 patients (4%). The 3-year local control rate was 97%, and just 1 patient developed grade ≥3 toxicity (chest wall pain). CONCLUSION: MR-guided SF-SABR delivery to lung tumors on a 0.35 T linac, using repeated breath-holds with automatic beam gating, achieves good tumor control and low toxicity.

Tumor volume changes during stereotactic ablative radiotherapy for adrenal gland metastases under MRI guidance.

PURPOSE: Gross tumor volume (GTV) changes during stereotactic ablative radiotherapy (SABR) for adrenal tumors are not well characterized. We studied treatment-induced GTV changes during, and after, 5-fraction MR-guided SABR on a 0.35 T unit. METHODS AND MATERIALS: Details of patients treated for adrenal metastases using 5-fraction adaptive MR-SABR were accessed. GTV changes between simulation and first fraction (ΔSF1) and all fractions were recorded. Wilcoxon paired tests were used for intrapatient comparisons. Logistic and linear regression models were used for features associated with dichotomous and continuous variables, respectively. RESULTS: Once-daily fractions of 8 Gy or 10 Gy were delivered to 70 adrenal metastases. Median simulation-F1 interval was 13 days; F1-F5 interval was 13 days. Median baseline GTVs at simulation and F1 were 26.6 and 27.2 cc, respectively (p < 0.001). Mean ΔSF1 was + 9.1% (2.9 cc) relative to simulation; 47% of GTVs decreased in volume at F5 versus F1. GTV variations of ≥ 20% occurred in 59% treatments at some point between simulation to end SABR, and these did not correlate with baseline tumor characteristics. At a median follow-up of 20.3 months, a radiological complete response (CR) was seen in 23% of 64 evaluable patients. CR was associated with baseline GTV (p = 0.03) and ΔF1F5 (p = 0.03). Local relapses were seen in 6%. CONCLUSION: Frequent changes in adrenal GTVs during 5-fraction SABR delivery support the use of on-couch adaptive replanning. The likelihood of a radiological CR correlates with the baseline GTV and intra-treatment GTV decline.

Prediction of pathologic complete response after single-dose MR-guided partial breast irradiation in low-risk breast cancer patients: the ABLATIVE-2 trial-a study protocol.

BACKGROUND: Partial breast irradiation (PBI) is standard of care in low-risk breast cancer patients after breast-conserving surgery (BCS). Pre-operative PBI can result in tumor downstaging and more precise target definition possibly resulting in less treatment-related toxicity. This study aims to assess the pathologic complete response (pCR) rate one year after MR-guided single-dose pre-operative PBI in low-risk breast cancer patients. METHODS: The ABLATIVE-2 trial is a multicenter prospective single-arm trial using single-dose ablative PBI in low-risk breast cancer patients. Patients ≥ 50 years with non-lobular invasive breast cancer ≤ 2 cm, grade 1 or 2, estrogen receptor-positive, HER2-negative, and tumor-negative sentinel node procedure are eligible. A total of 100 patients will be enrolled. PBI treatment planning will be performed using a radiotherapy planning CT and -MRI in treatment position. The treatment delivery will take place on a conventional or MR-guided linear accelerator. The prescribed radiotherapy dose is a single dose of 20 Gy to the tumor, and 15 Gy to the 2 cm of breast tissue surrounding the tumor. Follow-up MRIs, scheduled at baseline, 2 weeks, 3, 6, 9, and 12 months after PBI, are combined with liquid biopsies to identify biomarkers for pCR prediction. BCS will be performed 12 months after radiotherapy or after 6 months, if MRI does not show a radiologic complete response. The primary endpoint is the pCR rate after PBI. Secondary endpoints are radiologic response, toxicity, quality of life, cosmetic outcome, patient distress, oncological outcomes, and the evaluation of biomarkers in liquid biopsies and tumor tissue. Patients will be followed up to 10 years after radiation therapy. DISCUSSION: This trial will investigate the pathological tumor response after pre-operative single-dose PBI after 12 months in patients with low-risk breast cancer. In comparison with previous trial outcomes, a longer interval between PBI and BCS of 12 months is expected to increase the pCR rate of 42% after 6-8 months. In addition, response monitoring using MRI and biomarkers will help to predict pCR. Accurate pCR prediction will allow omission of surgery in future patients. TRIAL REGISTRATION: The trial was registered prospectively on April 28th 2022 at clinicaltrials.gov (NCT05350722).

Accuracy of deformable image registration-based intra-fraction motion management in Magnetic Resonance-guided radiotherapy.

Background and Purpose: Intra-fraction motion management is key in Stereotactic Ablative Radiotherapy (SABR) gated delivery. This study assessed the accuracy of automatic tumor segmentation in the delivery of MR-guided radiotherapy (MRgRT) by comparing it to manual delineations performed by experienced observers. Materials and Methods: Twenty patients previously treated with MR-guided SABR for thoracic and abdominal tumors were included. Five observers with at least two years of experience in MRgRT manually delineated the gross tumor volume (GTV) for 20 patients on 240 frames of a cine MRI on a sagittal plane. Deformable Image Registration (DIR) based GTV contours were propagated using four different algorithms from a reference frame to subsequent frames.Geometrical analysis based on the Dice Similarity Coefficient (DSC), centroid distance and Hausdorff Distance (HDD) were performed to assess the inter-observer variability and the accuracy of automatic segmentation. A Confidence Value (CV) metric for the reliability of the tumor auto-contouring was also calculated. Results: Inter-observer delineation variability resulted in mean DSC of 0.89, HDD of 5.8 mm and centroid distance of 1.7 mm. Tumor auto-contouring by the four DIR algorithms resulted in an excellent agreement with the manual delineations by the experienced observers. Mean DSC for each algorithm across all patients was greater than 0.90, whereas the HDD and centroid distances were below 4.0 mm and 1.5 mm, respectively. The CV showed a strong correlation with the DSC. Conclusions: DIR-based auto-contouring in MRgRT exhibited a high level of agreement with the manual contouring performed by experts, allowing accurate gated delivery.

Comparison of MR-guided radiotherapy accumulated doses for central lung tumors with non-adaptive and online adaptive proton therapy.

BACKGROUND: Stereotactic body radiation therapy (SBRT) of central lung tumors with photon or proton therapy has a risk of increased toxicity. Treatment planning studies comparing accumulated doses for state-of-the-art treatment techniques, such as MR-guided radiotherapy (MRgRT) and intensity modulated proton therapy (IMPT), are currently lacking. PURPOSE: We conducted a comparison of accumulated doses for MRgRT, robustly optimized non-adaptive IMPT, and online adaptive IMPT for central lung tumors. A special focus was set on analyzing the accumulated doses to the bronchial tree, a parameter linked to high-grade toxicities. METHODS: Data of 18 early-stage central lung tumor patients, treated at a 0.35 T MR-linac in eight or five fractions, were analyzed. Three gated treatment scenarios were compared: (S1) online adaptive MRgRT, (S2) non-adaptive IMPT, and (S3) online adaptive IMPT. The treatment plans were recalculated or reoptimized on the daily imaging data acquired during MRgRT, and accumulated over all treatment fractions. Accumulated dose-volume histogram (DVH) parameters of the gross tumor volume (GTV), lung, heart, and organs-at-risk (OARs) within 2 cm of the planning target volume (PTV) were extracted for each scenario and compared in Wilcoxon signed-rank tests between S1 & S2, and S1 & S3. RESULTS: The accumulated GTV D98% was above the prescribed dose for all patients and scenarios. Significant reductions (p < 0.05) of the mean ipsilateral lung dose (S2: -8%; S3: -23%) and mean heart dose (S2: -79%; S3: -83%) were observed for both proton scenarios compared to S1. The bronchial tree D0.1cc was significantly lower for S3 (S1: 48.1 Gy; S3: 39.2 Gy; p = 0.005), but not significantly different for S2 (S2: 45.0 Gy; p = 0.094), compared to S1. The D0.1cc for S2 and S3 compared to S1 was significantly (p < 0.05) smaller for OARs within 1-2 cm of the PTV (S1: 30.2 Gy; S2: 24.6 Gy; S3: 23.1 Gy), but not significantly different for OARs within 1 cm of the PTV. CONCLUSIONS: A significant dose sparing potential of non-adaptive and online adaptive proton therapy compared to MRgRT for OARs in close, but not direct proximity of central lung tumors was identified. The near-maximum dose to the bronchial tree was not significantly different for MRgRT and non-adaptive IMPT. Online adaptive IMPT achieved significantly lower doses to the bronchial tree compared to MRgRT.

An ESTRO-ACROP guideline on quality assurance and medical physics commissioning of online MRI guided radiotherapy systems based on a consensus expert opinion.

OBJECTIVE: The goal of this consensus expert opinion was to define quality assurance (QA) tests for online magnetic resonance image (MRI) guided radiotherapy (oMRgRT) systems and to define the important medical physics aspects for installation and commissioning of an oMRgRT system. MATERIALS AND METHODS: Ten medical physicists and two radiation oncologists experienced in oMRgRT participated in the survey. In the first round of the consensus expert opinion, ideas on QA and commissioning were collected. Only tests and aspects different from commissioning of a CT guided radiotherapy (RT) system were considered. In the following two rounds all twelve participants voted on the importance of the QA tests, their recommended frequency and their suitability for the two oMRgRT systems approved for clinical use as well as on the importance of the aspects to consider during medical physics commissioning. RESULTS: Twenty-four QA tests were identified which are potentially important during commissioning and routine QA on oMRgRT systems compared to online CT guided RT systems. An additional eleven tasks and aspects related to construction, workflow development and training were collected. Consensus was found for most tests on their importance, their recommended frequency and their suitability for the two approved systems. In addition, eight aspects mostly related to the definition of workflows were also found to be important during commissioning. CONCLUSIONS: A program for QA and commissioning of oMRgRT systems was developed to support medical physicists to prepare for safe handling of such systems.

Same-day consultation, simulation and lung Stereotactic Ablative Radiotherapy delivery on a Magnetic Resonance-linac.

Background and Purpose: Magnetic resonance-guided radiotherapy (MRgRT) with real-time intra-fraction tumor motion monitoring allows for high precision Stereotactic Ablative Radiotherapy (SABR). This study aimed to investigate the clinical feasibility, patient satisfaction and delivery accuracy of single-fraction MR-guided SABR in a single day (one-stop-shop, OSS). Methods and Materials: Ten patients with small lung tumors eligible for single fraction treatments were included. The OSS procedure consisted of consultation, treatment simulation, treatment planning and delivery. Following SABR delivery, patients completed a reported experience measure (PREM) questionnaire. Prescribed doses ranged 28-34 Gy. Median GTV was 2.2 cm3 (range 1.3-22.9 cm3). A gating boundary of 3 mm, and PTV margin of 5 mm around the GTV, were used with auto-beam delivery control. Accuracy of SABR delivery was studied by analyzing delivered MR-cines reconstructed from machine log files. Results: All 10 patients completed the OSS procedure in a single day, and all reported satisfaction with the process. Median time for the treatment planning step and the whole procedure were 2.8 h and 6.6 h, respectively. With optimization of the procedure, treatment could be completed in half a day. During beam-on, the 3 mm tracking boundary encompassed between 78.0 and 100 % of the GTV across all patients, with corresponding PTV values being 94.4-100 % (5th-95th percentiles). On average, system-latency for triggering a beam-off event comprised 5.3 % of the delivery time. Latency reduced GTV coverage by an average of -0.3 %. Duty-cycles during treatment delivery ranged from 26.1 to 64.7 %. Conclusions: An OSS procedure with MR-guided SABR for lung cancer led to good patient satisfaction. Gated treatment delivery was highly accurate with little impact of system-latency.

Magnetic resonance imaging-guided radiotherapy for intermediate- and high-risk prostate cancer: Trade-off between planning target volume margin and online plan adaption.

Magnetic resonance-guided radiotherapy with daily plan adaptation for intermediate- and high-risk prostate cancer is time and labor intensive. Fifty adapted plans with 3 mm planning target volume (PTV)-margin were compared with non-adapted plans using 3 or 5 mm margins. Adequate (V95% ≥ 95%) prostate coverage was achieved in 49 fractions with 5 mm PTV without plan adaptation, however, coverage of the seminal vesicles (SV) was insufficient in 15 of 50 fractions. There was no insufficient coverage for prostate and SV using plan adaptation with 3 mm. Hence, daily adaptation is recommended to obtain adequate SV-coverage when using 3 mm PTV.

Treatment patterns for adrenal metastases using surgery and SABR during a 10-year period.

We studied treatment patterns for adrenal metastases using surgery or SABR at a single institution during a 10-year period. The number of patients undergoing SABR doubled since 2016, without a change in numbers undergoing surgery. Both treatments resulted in low rates of acute toxicity and similar survivals.

Renal atrophy following gated delivery of stereotactic ablative radiotherapy to adrenal metastases.

Stereotactic ablative radiotherapy (SABR) planning for adrenal metastases aims to minimize doses to the adjacent kidney. Renal dose constraints for SABR delivery are not well defined. In 20 patients who underwent MR-guided breath-hold SABR in five daily fractions of 8-10 Gy, ipsilateral renal volumes receiving ≥20 Gy best correlated with loss of renal volumes, with median renal volume reduction being 6% (range: 3%-11%, 10th-90th percentiles). Organ function did not deteriorate in 18 patients, who had post treatment renal function tests available. This suggests that the ipsilateral renal volume receiving 20 Gy can be used as partial organ dose constraint for SABR to targets in the upper abdomen.

Potential contributors to low dose methotrexate toxicity in a patient with rheumatoid arthritis and pernicious anemia: case report.

BACKGROUND: Low dose methotrexate toxicity rarely occurs, but may present with severe complications, such as pancytopenia, hepatotoxicity, mucositis, and pneumonitis. Known risk factors for methotrexate toxicity include dosing errors, metabolic syndrome, hypoalbuminemia, renal dysfunction, lack of folate supplementation, and the concomitant use of drugs that interfere with methotrexate metabolism. Vitamin B12 deficiency leads to megaloblastic anemia and may cause pancytopenia, but its role in methotrexate toxicity has not been described. CASE PRESENTATION: We present a case of a patient with rheumatoid arthritis who was admitted with febrile neutropenia, pancytopenia, and severe mucositis, likely secondary to low dose methotrexate toxicity. She had multiple factors that potentially contributed to the development of toxicity, including concurrent sulfasalazine use for rheumatoid arthritis. An evaluation of the patient's macrocytic anemia revealed pernicious anemia. The patient's illness resolved with cessation of methotrexate and sulfasalazine, leucovorin treatment and vitamin B12 repletion. CONCLUSIONS: This case illustrates the multiple factors that may potentially contribute to low dose methotrexate toxicity and highlights the importance of testing for vitamin B12 deficiency in rheumatoid arthritis patients with macrocytic anemia. Addressing all the modifiable factors that potentially contribute to low dose methotrexate toxicity may improve outcomes.

Dose accumulation for personalized stereotactic MR-guided adaptive radiation therapy in prostate cancer.

BACKGROUND AND PURPOSE: Adaptive MR-guided radiotherapy (MRgRT) is an innovative approach for delivering stereotactic body radiotherapy (SBRT) in prostate cancer (PC). Despite the increased clinical use of SBRT for PC, there is limited data on the relation between the actual delivered dose and toxicity. We aimed to identify dose parameters based on the total accumulated delivered bladder dose (DOSEACCTX). Furthermore, for future personalization, we studied whether prospective accumulation of the first 3 of 5 fractions (DOSEACC3FR) could be used as a representative of DOSEACCTX. MATERIALS AND METHODS: We deployed a recently validated deformable image registration-based dose accumulation strategy to reconstruct DOSEACCTX and DOSEACC3FR in 101 PC patients treated with stereotactic MRgRT. IPSS scores at baseline, end of MRgRT, at 6 and 12 weeks after treatment were analyzed to identify a clinically relevant increase of acute urinary symptoms. A receiver operator characteristic curve analysis was used to investigate the correlation of an increase in IPSS and bladder DOSEACCTX (range V5-V36.25 Gy, D1cc, D5cc) and DOSEACC3FR (range V6-V21.8 Gy, D1cc, D5cc) parameters. RESULTS: A clinically relevant increase in IPSS in the three months following MRgRT was observed in 25 patients. The V20Gy-32Gy from DOSEACCTX and V15Gy-18Gy from DOSEACC3FR showed good correlation with IPSS increase with area under the curve (AUC) values ranging from 0.71 to 0.75. In contrast, baseline dosimetry showed a poor correlation with AUC values between 0.53 and 0.62. CONCLUSION: DOSEACCTX was superior to baseline dosimetry in predicting acute urinary symptoms. Because DOSEACC3FR also showed good correlation, this can potentially be used to optimize MRgRT for the remaining fractions.

The Role of Daily Adaptive Stereotactic MR-Guided Radiotherapy for Renal Cell Cancer.

Novel magnetic-resonance-guided radiotherapy (MRgRT) permits real-time soft-tissue visualization, respiratory-gated delivery with minimal safety margins, and time-consuming daily plan re-optimisation. We report on early clinical outcomes of MRgRT and routine plan re-optimization for large primary renal cell cancer (RCC). Thirty-six patients were treated with MRgRT in 40 Gy/5 fractions. Prior to each fraction, re-contouring of tumor and normal organs on a pretreatment MR-scan allowed daily plan re-optimization. Treatment-induced toxicity and radiological responses were scored, which was followed by an offline analysis to evaluate the need for such daily re-optimization in 180 fractions. Mean age and tumor diameter were 78.1 years and 5.6 cm, respectively. All patients completed MRgRT with an average fraction duration of 45 min. Local control (LC) and overall survival rates at one year were 95.2% and 91.2%. No grade ≥3 toxicity was reported. Plans without re-optimization met institutional radiotherapy constraints in 83.9% of 180 fractions. Thus, daily plan re-optimization was required for only a minority of patients, who can be identified upfront by a higher volume of normal organs receiving 25 Gy in baseline plans. In conclusion, stereotactic MRgRT for large primary RCC showed low toxicity and high LC, while daily plan re-optimization was required only in a minority of patients.

Changes in gastric anatomy after delivery of breath-hold MR-guided SABR for adrenal metastases.

Delivery of breath-hold MR-guided SABR is time-consuming, and the use of real-time tumor-tracking in a sagittal plane may fail to detect out-of-plane displacements of organs-at-risk. Analysis of daily MR-scans performed pre- and post-SABR revealed frequent decreases in stomach volumes, and in the planned stomach doses.

Clinical Outcomes of Stereotactic MR-Guided Adaptive Radiation Therapy for High-Risk Lung Tumors.

PURPOSE: Magnetic resonance (MR)-guided SABR was performed for patients with lung tumors in whom treatment delivery was challenging owing to tumor location, motion, or pulmonary comorbidity. Because stereotactic MR-guided adaptive radiation therapy (SMART) is a novel approach, we studied clinical outcomes in these high-risk lung tumors. METHODS AND MATERIALS: Fifty consecutive patients (54 lung tumors) underwent SMART between 2016 and 2018 for either a primary lung cancer (29 patients) or for lung metastases (21 patients). Eligible patients had risk factors that could predispose them to toxicity, including a central tumor location (n = 30), previous thoracic radiation therapy (n = 17), and interstitial lung disease (n = 7). A daily 17-second breath-hold MR scan was acquired in treatment position, and on-table plan adaptation was performed using the anatomy of the day. Gated SABR was delivered during repeated breath-holds under continuous MR guidance. RESULTS: All but 1 patient completed the planned SMART schedule. With daily plan adaptation, a biologically effective dose ≥100 Gy to 95% of the planning target volume was delivered in 50 tumors (93%). Median follow-up was 21.7 months (95% confidence interval, 19.9-28.1). Local control and overall and disease-free survival rates at 12 months were 95.6%, 88.0%, and 63.6%, respectively. Local failures developed in 4 patients: in 2 after reirradiation for a recurrent lung cancer and in 2 patients with a colorectal metastasis. Overall rates of any grade ≥2 and ≥3 toxicity were 30% and 8%, respectively. Commonest toxicities were grade ≥2 radiation pneumonitis (12%) and chest wall pain (8%). No grade 4 or 5 toxicities were observed. CONCLUSIONS: Use of MR-guided SABR resulted in low rates of high-grade toxicity and encouraging early local control in a cohort of high-risk lung tumors. Additional studies are needed to identify patients who are most likely to benefit from the SMART approach.

Delivery of magnetic resonance-guided single-fraction stereotactic lung radiotherapy.

BACKGROUND AND PURPOSE: Single-fraction stereotactic ablative radiotherapy (SABR) is an effective treatment for early-stage lung cancer, but concerns remain about the accurate delivery of SABR in a single session. We evaluated the delivery of single-fraction lung SABR using magnetic resonance (MR)-guidance. MATERIALS AND METHODS: An MR-simulation was performed in 17 patients, seven of whom were found to be unsuitable, largely due to unreliable tracking of small tumors. Ten patients underwent single-fraction SABR to 34 Gy on a 0.35 T MR-linac system, with online plan adaptation. Gated breath-hold SABR was delivered using a planning target volume (PTV) margin of 5 mm, and a 3 mm gating window. Continuous MR-tracking of the gross tumor volume (GTVt) was performed in sagittal plane, with visual patient feedback provided using an in-room monitor. The real-time MR images were analyzed to determine precision and efficiency of gated delivery. RESULTS: All but one patient completed treatment in a single session. The median total in-room procedure was 120 min, with a median SABR delivery session of 39 min. Review of 7.4 h of cine-MR imaging revealed a mean GTVt coverage by the PTV during beam-on of 99.6%. Breath-hold patterns were variable, resulting in a mean duty cycle efficiency of 51%, but GTVt coverage was not influenced due to real-time MR-guidance. On-table adaptation improved PTV coverage, but had limited impact on GTV doses. CONCLUSIONS: Single-fraction gated SABR of lung tumors can be performed with high precision using MR-guidance. However, improvements are needed to ensure MR-tracking of small tumors, and to reduce treatment times.

Stereotactic MR-guided adaptive radiation therapy for peripheral lung tumors.

BACKGROUND AND PURPOSE: We studied the benefits of using stereotactic MR-guided adaptive radiation therapy (SMART) for delivery of SABR in peripherally located lung tumors. METHODS AND MATERIALS: Twenty-three patients (25 peripheral lung tumors) underwent SMART in 3-8 fractions on an MR Linac or Cobalt-60 system. Before each fraction, a breath-hold MR scan was acquired, followed by on-table plan adaptation based on the anatomy-of-the-day. Breath-hold gated delivery was performed under continuous MR-guidance using an in-room monitor. Benefits of on-table adaptation were studied by comparing 112 «predicted¼ plans, which are the baseline plans recalculated on the anatomy-of-the-day, with the on-table reoptimized plans. RESULTS: The full SMART procedure took a median of 48 and 62 minutes on the MR Linac and Cobalt-60 system, respectively. Median SMART-PTVs were 9.5 cm3 (range, 3.1-55.6). In 14 patients who had undergone a free-breathing 4DCT, SMART-PTVs measured 53.7% (range, 31.9-75.0) of PTVs that would have been generated using a motion-encompassing internal target volume approach. On-table adaptation improved prescription dose coverage of the PTV from a median of 92.1% in predicted plans, to 95.0% in reoptimized ones, thereby increasing the proportion of fractions delivering ≥100 Gy (BED10Gy) to 95% of PTV, from 90.2% to 100.0%. CONCLUSION: Delivery of gated breath-hold SABR using MR-guidance resulted in significantly smaller target volumes than would have been the case with an ITV-based approach. Although on-table adaptation ensured delivery of ablative doses in all fractions, the dosimetric benefits were modest, suggesting that daily online plan adaptation may not benefit most patients with peripheral lung tumors.