Lymph Node Oligometastases Research Articles

Results of a Single-Arm Phase 2 Clinical Trial: Online Adaptive Stereotactic Body Radiation Therapy for Abdominal-Pelvic Oligometastases.

This study reports on the clinical outcomes of the single-arm phase-2 STEAL trial investigating online adaptive stereotactic body radiation therapy (SBRT) for abdominal-pelvic lymph node (A-P LN) oligometastases. Patients with oligometastatic A-P LN were enrolled and treated to a total dose of 45 Gy in 5 fractions on the CyberKnife. For each patient, a library of 3 plans was created using a pretreatment diagnostic computed tomography (CT) scan and the treatment planning CT scan. Following a decision tree, the radiation therapy technologist (RTT) selected the best plan of the day, ie, the plan with the highest target coverage without exceeding organs at risk constraints. The primary endpoint was local control (LC), and the secondary endpoints were toxicity and overall survival. In total, 52 patients were included, and 55 online adaptive treatments were performed. The primary tumor was prostate adenocarcinoma in 19 patients (37%), colorectal in 17 (33%), and had a different origin in 16 patients (31%). After a median follow-up of 38.5 months, LC at 1 year was 96% and 80% at 3 years; 20 patients had died, resulting in a median overall survival of 4.1 years. No grade ≥4 toxicity was observed. One patient (2%) developed a grade 3 ureteral stenosis. CT-guided online adaptive SBRT for A-P LN oligometastases using an RTT-only library of plans strategy is feasible, safe, and resulted in an excellent LC with a low toxicity rate.

Long-Term Results of a Phase 1 Dose Escalation Trial of Ablative Stereotactic Body Radiation Therapy

Stereotactic body radiation therapy (SBRT) is increasingly used for oligometastatic disease as well as palliation, but treatment protocols for non-spine bone and nodal metastases are lacking, with a wide variety of schedules applied. Therefore, a prospective dose-escalation trial was initiated, involving 90 patients, among whom 52 (58%) had primary prostate tumors, 13 had breast tumors (14%), and 25 (28%) had other primary tumor types. All visible lymph node and/or non-spine bone oligometastases were treated in three consecutive cohorts: 5×7.0 Gy, 3×10.0 Gy, or 1×20.0 Gy. Initial results revealed no dose-limiting toxicity after a median follow-up of 17.2 months. This update provides information on long-term toxicity, local failure (LF), and progression-free survival (PFS). After a median follow-up of 50 months, no new safety signals were observed. Grade 2 toxicity was 13%, 7% and 10% in the respective cohorts (p=0.9), without grade 3-5 toxicities. LF rates were 9%, 3%, and 6% (P=.5) for the respective treatment groups, with an overall cumulative risk of LF of 7% (95% CI 2-12) at 4 years. Median PFS was 16.5 months (95% CI 9.8-21.5), and 4-year PFS was 21% (95% CI 14-32). Median overall survival across groups was not reached (95% CI 52.8 – not reached), 4-year OS was 68% (95% CI 59-78). A subset of patients (23%) remained long-term disease-free, 37% had oligoprogressive disease at first recurrence and 40% developed polymetastatic relapse. In conclusion, the safe and effective use of dose-escalated single-fraction SBRT for bone and lymph node metastases is supported by this trial, especially considering patient-convenience and cost-effectiveness. Caution is needed when generalizing these outcomes beyond breast and prostate cancer, given their underrepresentation in our study.

Comprehensive analysis of Japanese nationwide cohort data of particle beam therapy for pulmonary, liver and lymph node oligometastases: particle beam therapy versus high-precision X-ray radiotherapy.

Japanese national oncological experts convened to evaluate the efficacy and safety of particle beam therapy (PT) for pulmonary, liver and lymph node oligometastases (P-OM, L-OM and LN-OM, respectively) and to conduct a statistically comparative analysis of the local control (LC) rate and overall survival (OS) rate of PT versus those of X-ray stereotactic body radiotherapy (X-SBRT) and X-ray intensity-modulated radiotherapy (X-IMRT). They conducted [1] an analysis of the efficacy and safety of metastasis-directed therapy with PT for P-OM, L-OM and LN-OM using a Japanese nationwide multi-institutional cohort study data set; [2] a systematic review of X-ray high-precision radiotherapy (i.e. X-SBRT/X-IMRT) and PT for P-OM, L-OM and LN-OM; and [3] a statistical comparison between LC and OS of the cohort data set in PT and that of the extracted historical data set in X-SBRT/X-IMRT from the preceding systematic review. Safety was evaluated as the incidence of grade ≥ 3 adverse events, while statistical comparisons of LC and OS were conducted by estimating the incidence rate ratios (IRR) for local progression and mortality, respectively. This study demonstrated that PT provided durable LC (3-year LC rate: 72.8-83.2%) with acceptable OS (3-year OS rate: 38.5-68.1%) and risk of severe toxicity incidence of 0.8-3.5% in radical metastasis-directed therapy for P-OM, L-OM and LN-OM. Compared to LC with X-SBRT or X-IMRT, LC with PT was potentially superior for P-OM; superior for L-OM; and equivalent for LN-OM. In particular, this study demonstrated that PT may be a new treatment option for L-OM tumors measuring > 5cm.

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

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

Online adaptive MR-guided radiotherapy: Conformity of contour adaptation for prostate cancer, rectal cancer and lymph node oligometastases among radiation therapists and radiation oncologists.

Online adaptive MR-guided treatment planning workflows facilitate daily contour adaptation to the actual anatomy. Allocating contour adaptation to radiation therapists (RTTs) instead of radiation oncologists (ROs) might allow for increasing workflow efficiency. This study investigates conformity of adapted target contours provided by dedicated RTTs and ROs. In a simulated online procedure, 6 RTTs and 6 ROs recontoured targets and organs at risk (OAR) in prostate cancer (n=2), rectal cancer (n=2) and lymph node-oligometastases (n=2) cases. RTTs gained contouring competence beforehand by following a specific in-house training program. For all target contours and the reference delineations volumetric differences were determined and Dice similarity coefficient (DSC), conformity index (CI) and generalized CI were calculated. Delineation time and -confidence were registered for targets and OAR. Impact of contour adaptation on treatment plan quality was investigated. Delineation conformity was generally high with DSC, CI and generalized CI values in the range of 0.81-0.94, 0.87-0.95 and 0.63-0.85 for prostate cancer, rectal cancer and LN-oligometastasis, respectively. Target volumes were comparable for both, RTTs and ROs. Time needed and confidence in contour adaptation was comparable as well. Treatment plans derived with adapted contours did not violate dose volume constrains as used in clinical routine. After tumor site specific training, daily contour adaptations as needed in adaptive online radiotherapy workflows can be accurately performed by RTTs. Conformity of the derived contours is high and comparable to contours as provided by ROs.

Impact of magnetic resonance-guided versus conventional radiotherapy workflows on organ at risk doses in stereotactic body radiotherapy for lymph node oligometastases.

Magnetic resonance (MR)-linac delivery is expected to improve organ at risk (OAR) sparing. In this study, OAR doses were compared for online adaptive MR-linac treatments and conventional cone beam computed tomography (CBCT)-linac radiotherapy, taking into account differences in clinical workflows, especially longer session times for MR-linac delivery. For 25 patients with pelvic/abdominal lymph node oligometastases, OAR doses were calculated for clinical pre-treatment and daily optimized 1.5T MR-linac treatment plans (5×7Gy) and compared with simulated CBCT-linac plans for the pre-treatment and online anatomical situation. Bowelbag and duodenum were re-contoured on MR-imaging acquired before, during and after each treatment session. OAR hard constraint violations, D0.5cc and D10cc values were evaluated, focusing on bowelbag and duodenum. Overall, hard constraints for all OAR were violated less often in daily online MR-linac treatment plans compared with CBCT-linac: in 5% versus 22% of fractions, respectively. D0.5cc and D10cc values did not differ significantly. When taking treatment duration and intrafraction motion into account, estimated delivered doses to bowelbag and duodenum were lower with CBCT-linac if identical planning target volume (PTV) margins were used for both modalities. When reduced PTV margins were achievable with MR-linac treatment, bowelbag doses were lower compared with CBCT-linac. Compared with CBCT-linac treatments, the online adaptive MR-linac approach resulted in fewer hard planning constraint violations compared with single-plan CBCT-linac delivery. With respect to other bowelbag/duodenum dose-volume parameters, the longer duration of MR-linac treatment sessions negatively impacts the potential dosimetric benefit of daily adaptive treatment planning.

Comparison of Library of Plans with two daily adaptive strategies for whole bladder radiotherapy.

Background and purposeWhole bladder radiotherapy is challenging due to inter- and intrafraction size and shape changes. To account for these changes, currently a Library of Plans (LoP) technique is often applied, but daily adaptive radiotherapy is also increasingly becoming available. The aim of this study was to compare LoP with two magnetic resonance imaging guided radiotherapy (MRgRT) strategies by comparing target coverage and volume of healthy tissue inside the planning target volume (PTV) for whole bladder treatments.Methods and materialsData from 25 MRgRT lymph node oligometastases treatments (125 fractions) were used, with three MRI scans acquired at each fraction at 0, 15 and 30 min. Bladders were delineated and used to evaluate three strategies: 1) LoP with two plans for a 15 min fraction, 2) MRgRT15min for a 15 min fraction and 3) MRgRT30min for a 30 min fraction. The volumes of healthy tissue inside and bladder outside the PTV were analyzed on the simulated post-treatment images.ResultsMRgRT30min had 120% and 121% more healthy tissue inside the PTV than LoP and MRgRT15min. For LoP slightly more target outside the PTV was found than for MRgRT30min and MRgRT15min, with median 0% (range 0–23%) compared to 0% (0–20%) and 0% (0–10%), respectively.ConclusionsTaking into account both target coverage and volume of healthy tissue inside the PTV, MRgRT15min performed better than LoP and MRgRT30min for whole bladder treatments. A 15 min daily adaptive radiotherapy workflow is needed to potentially benefit from replanning compared to LoP.

Progression-free survival in patients with 68Ga-PSMA-PET-directed SBRT for lymph node oligometastases

Background Prostate cancer oligometastatic disease can be treated using stereotactic body radiotherapy (SBRT) in order to postpone start of systemic treatments such as androgen deprivation therapy (ADT). 68Ga-PSMA-PET/CT imaging allows for diagnosis of oligometastases at lower PSA values. We analysed a cohort of patients with prostate cancer lymph node oligometastases detected on PSMA-PET/CT. Materials and methods Ninety patients with metachronous oligometastatic prostate cancer received SBRT for 1–3 lymph node metastases diagnosed on 68Ga-PSMA-PET/CT. The primary end point was progression free survival (PFS), with disease progression defined as occurrence of either target lesion progression, new metastatic lesion or biochemical progression. Secondary outcomes were biochemical PFS (BPFS), ADT-free survival (ADT-FS), toxicity and quality of life (QoL). Baseline patient characteristics were tested for association with PFS and a preliminary risk score was created. Results Median follow-up was 21 months (interquartile range 10–31 months). Median PFS and BPFS were 16 and 21 months, respectively. Median ADT-FS was not reached (73% (95%-CI 62–86%) at 24 months). In multivariable analysis, younger age, higher PSA prior to SBRT and extrapelvic location were associated with shorter PFS. Grade 1 fatigue was the most predominant acute toxicity (34%). Highest grade toxicity was grade 2 for acute and late events. QoL analysis showed mild, transient increase in fatigue at 1–4 weeks after SBRT. Conclusion A median PFS of 16 months was attained after SBRT for patients with PSMA-PET positive oligometastatic lymph nodes from prostate cancer. Higher pre-SBRT PSA, younger age and extrapelvic location were found to be predictors of shorter PFS.

Freezing Nodal Disease: Local Control Following Percutaneous Image-Guided Cryoablation of Locoregional and Distant Lymph Node Oligometastases: A 10-Year, Single-Center Experience

PurposeTo retrospectively assess the technical feasibility, safety, and oncologic outcomes of percutaneous image-guided cryoablation (PCA) of locoregional and distant lymph node metastases (LNMs). MethodsAll consecutive patients undergoing PCA of LNMs between February 2009 and December 2019 were identified using a retrospective database search. Every patient was followed up at 1, 3, 6, and 12 months after treatment using contrast-enhanced magnetic resonance imaging and at approximately 3–6-month intervals using computed tomography or positron emission tomography–computed tomography. The Kaplan-Meier method was used to calculate local tumor progression-free survival, disease-free survival, and overall survival. Locoregional and distant groups were compared using the Fisher test. Technical success, technique efficacy, complications, and oncologic outcomes were analyzed. ResultsFifty-six metachronous oligometastatic LNMs (median size, 15 mm [interquartile range, 13–15 mm; range, 9–36 mm]) were treated in 37 sessions in 29 patients and defined as locoregional (26/37 sessions) or distant (11/37 sessions). Seventeen patients had undergone prior surgery or radiotherapy. Six patients underwent 8 retreatments for locoregional progression. An additional visceral oligometastasis was treated in 4 of the 11 distant LNM PCA sessions. The technical success and primary technique efficacy rates were 100%. The complication rate was 5.4% (2 transient nerve palsies). At a median follow-up of 23 months, there were 2 instances of local tumor progression (5.6%); the 1-, 2-, and 3-year local tumor progression-free survival was 100%, 94.3%, and 94.3%, respectively. Thirteen (45%) patients demonstrated no disease progression. The 1-, 2-, and 3-year overall survival was 96.2%, 90.5%, and 70%, respectively. The patients were free from systemic oncologic therapy following 20 (54%) sessions, with a mean treatment break of 19.1 months. ConclusionsThe PCA of lymph node oligometastases is feasible and safe, and offers promising local tumor control at midterm follow-up.

Automatic dosimetric verification of online adapted plans on the Unity MR-Linac using 3D EPID dosimetry

Background and purposeThe Unity MR-Linac is equipped with an EPID, the images from which contain information about the dose delivered to the patient. The purpose of this study was to introduce a framework for the automatic dosimetric verification of online adapted plans using 3D EPID dosimetry and to present the obtained dosimetric results. Materials and methodsThe framework was active during the delivery of 1207 online adapted plans corresponding to 127 clinical IMRT treatments (74 prostate, 19 rectum, 19 liver and 15 lymph node oligometastases). EPID reconstructed dose distributions in the patient geometry were calculated automatically and then compared to the dose distributions calculated online by the treatment planning system (TPS). The comparison was performed by γ-analysis (3% global/2mm/10% threshold) and by the difference in median dose to the high-dose volume (ΔHDVD50). 85% for γ-pass rate and 5% for ΔHDVD50 were used as tolerance limit values. Results93% of the online plans were verified automatically by the framework. Missing EPID data was the reason for automation failure. 91% of the verified plans were within tolerance. ConclusionAutomatic dosimetric verification of online adapted plans on the Unity MR-Linac is feasible using in vivo 3D EPID dosimetry. Almost all online adapted plans were approved automatically by the framework. This newly developed framework is a major step forward towards the clinical implementation of a permanent safety net for the entire online adaptive workflow.

Stereotactic Body Radiotherapy for Lymph Node Oligometastases: Real-World Evidence From 90 Consecutive Patients.

AimsTo evaluate the efficacy and toxicity of extracranial stereotactic body radiotherapy (SBRT) in the treatment of oligometastatic lymph node involvement in the mediastinum, retroperitoneum, or pelvis, in a consecutive group of patients from real clinical practice outside clinical trials.MethodsA retrospective analysis of 90 patients with a maximum of four oligometastases and various primary tumors (the most common being colorectal cancers). The endpoints were local control of treated metastases (LC), freedom from widespread dissemination (FFWD), progression-free survival (PFS), overall survival (OS), and freedom from systemic treatment (FFST). Acute and delayed toxicities were also evaluated.ResultsThe median follow-up after SBRT was 34.9 months. The LC rate at three and five years was 68.4 and 56.3%, respectively. The observed median FFWD was 14.6 months, with a five-year FFWD rate of 33.7%. The median PFS was 9.4 months; the three-year PFS rate was 19.8%. The median FFST was 14.0 months; the five-year FFST rate was 23.5%. The OS rate at three and five years was 61.8 and 39.3%, respectively. Median OS was 53.1 months. The initial dissemination significantly shortened the time to relapse, death, or activation of systemic treatment—LC (HR 4.8, p < 0.001), FFWD (HR 2.8, p = 0.001), PFS (HR 2.1, p = 0.011), FFST (HR 2.4, p = 0.005), OS (HR 2.2, p = 0.034). Patients classified as having radioresistant tumors noticed significantly higher risk in terms of LC (HR 13.8, p = 0.010), FFWD (HR 3.1, p = 0.006), PFS (HR 3.5, p < 0.001), FFST (HR 3.2, p = 0.003). The multivariable analysis detected statistically significantly worse survival outcomes for initially disseminated patients as well as separately in groups divided according to radiosensitivity. No grade III or IV toxicity was reported.ConclusionOur study shows that targeted SBRT is a very effective and low toxic treatment for oligometastatic lymph node involvement. It can delay the indication of cytotoxic chemotherapy and thus improve and maintain patient quality of life. The aim of further studies should focus on identifying patients who benefit most from SBRT, as well as the correct timing and dosage of SBRT in treatment strategy.

OC-0452: Mature results of a phase I dose-escalation trial of SBRT for bone and lymph node oligometastases

OC-0452: Mature results of a phase I dose-escalation trial of SBRT for bone and lymph node oligometastases

Efficacy of local therapy for oligoprogressive disease after programmed cell death 1 blockade in advanced non-small cell lung cancer.

Immune checkpoint inhibitors (ICIs) have dramatically changed the strategy used to treat patients with non‐small‐cell lung cancer (NSCLC); however, the vast majority of patients eventually develop progressive disease (PD) and acquire resistance to ICIs. Some patients experience oligoprogressive disease. Few retrospective studies have evaluated clinical efficacy in patients with oligometastatic progression who received local therapy after ICI treatment. We conducted a retrospective analysis of advanced NSCLC patients who received PD‐1 inhibitor monotherapy with nivolumab or pembrolizumab to evaluate the effects of ICIs on the patterns of progression and the efficacy of local therapy for oligoprogressive disease. Of the 307 patients treated with ICIs, 148 were evaluated in our study; 42 were treated with pembrolizumab, and 106 were treated with nivolumab. Thirty‐eight patients showed oligoprogression. Male sex, a lack of driver mutations, and smoking history were significantly correlated with the risk of oligoprogression. Primary lesions were most frequently detected at oligoprogression sites (15 patients), and 6 patients experienced abdominal lymph node (LN) oligoprogression. Four patients showed evidence of new abdominal LN oligometastases. There was no significant difference in overall survival (OS) between the local therapy group and the switch therapy group (reached vs. not reached, P = .456). We summarized clinical data on the response of oligoprogressive NSCLC to ICI therapy. The results may help to elucidate the causes of ICI resistance and indicate that the use of local therapy as the initial treatment in this setting is feasible treatment option.

The Patterns of Care, Tolerability and Safety in the First Year of a Novel High Field MR-Linac

High field MR-Linacs are promising because they may enable unique anatomic and response adaptive treatment paradigms. The first commercial device received regulatory approval in late 2018. Because high field MR-guided therapy is new, little is known about how clinicians are using it, how patients tolerate daily high field MRIs and the toxicity patterns of such treatments. Herein we report the first years’ experience within an international registry study (MOMENTUM). The MOMENTUM Study (NCT04075305), a project of the MR-Linac Consortium, is an international registry that collects clinical and technical patient data with informed consent. All patients treated on an MR-Linac at participating centers are eligible. We reviewed the experience of patients treated from Dec. 5th 2018 to Jan. 15th 2020 and used descriptive statistics to describe the patterns of care, tolerability (defined as the percent of patients discontinuing the MR-Linac course early) and safety (defined by grade 3-5 CTCAE v.5 acute toxicity within 3 months of the end of treatment). The study cohort includes 393 patients treated at seven institutions in four countries (Netherlands, U.K., U.S. and Canada) and represents over 50% of all patients treated globally with high field MR-guided therapy in the first year after regulatory approval. Median age was 68 years (range 29-93 years) and 78% were male. There were 23 different tumor sites treated the most common being prostate (32%), lymph node oligometastases (20%), rectum (11%), brain (7%), and oropharynx (6%). Radiation of the primary tumor (71%) was the most common clinical indication followed by regional lymph node (19%), distant metastases (8%) and cancer recurrence at the primary tumor site (2%). In the total cohort, 51% (150/395) had contours adjusted with every fraction (adapt-to-shape). In the subset for whom complete course of therapy data was available (n = 228), the median number of fractions per course was 5 (range: 1-35) and 97% (222/228) had radiotherapy on the MR-Linac only. Two (1%) MR-Linac courses were discontinued early. One discontinuation was due to technical problems and in one case the treating physician decided to discontinue treatment after disease progression on imaging and clinical decline of the patient. In the subset for whom complete acute toxicity data was available (n = 97), acute grade 3 toxicity occurred in 4% and grade 4-5 toxicities were not observed. In the first year after initial regulatory approval of high field MR-guided therapy, we observed a wide variety of treatment sites and indications. Daily high field MR was well tolerated and our initial acute toxicity assessment was reassuring.

Stereotactic Body Radiation Therapy (SBRT) in Pelvic Lymph Node Oligometastases

The role of stereotactic body radiation therapy (SBRT) in achieving durable local control and palliation of pain in pelvic lymph node oligometastatic disease is not well-studied. We performed a retrospective analysis of 30 patients with 43 pelvic lymph node oligometastases from various primary cancers all but one with non-prostate primaries treated at our institution with SBRT. The median follow-up time was 21 months. The median SBRT dose was 24 Gy in four fractions. The one-, two-, and five-year local control was 74%, 71%, and 70% and one-, two-, and five-year overall survival was 70%, 47%, and 31%. Toxicities were mild with no grade 3 or higher.

Impact of a vacuum cushion on intrafraction motion during online adaptive MR-guided SBRT for pelvic and para-aortic lymph node oligometastases

Background and purposeVacuum cushion immobilization is commonly used during stereotactic body radiotherapy (SBRT) to reduce intrafraction motion. We investigated target and bony anatomy intrafraction motion (translations and rotations) during online adaptive SBRT on an MR-linac for pelvic/para-aortic lymph node metastases with and without vacuum cushion. Materials and methodsThirty-nine patients underwent 5x7 Gy SBRT on a 1.5T MR-linac, 19 patients were treated with vacuum cushion, 19 without and 1 patient sequentially with and without. Intrafraction motion was calculated for target lymph nodes (GTVs) and nearby bony anatomy, for three time intervals (pre-position verification (PV), pre-post, PV-post, relating to the online MRI scans) per treatment fraction. ResultsVacuum cushion immobilization significantly reduced anterior-posterior translations for the pre-PV and pre-post intervals, for bony anatomy and pre-post interval for GTV (p < 0.05). Mean GTV intrafraction motion reduction in posterior direction was 0.7 mm (95% confidence interval 0.3–1.1 mm) for pre-post interval (mean time = 32 min). Shifts in other directions were not significantly reduced. More motion occurred in pre-PV interval than in PV-post interval (mean time = 16 min for both); vacuum cushion immobilization did not reduce intrafraction motion during the beam-on period. ConclusionA vacuum cushion reduces GTV and bony anatomy intrafraction motion in posterior direction during pelvic/para-aortic lymph node SBRT. This motion reduction was found for the first 16 min per session. For single targets this motion can be corrected for directly with an MR-linac. Intrafraction motion was not reduced during the second half of the session, the period of radiotherapy delivery on an MR-linac. Vacuum cushion immobilization may not be necessary for patients with single lymph node oligometastases undergoing SBRT on an MR-linac.

Dosimetric feasibility of hypofractionation for SBRT treatment of lymph node oligometastases on the 1.5T MR-linac

PurposeAt our department, MR-guided stereotactic body radiation therapy (SBRT) using the 1.5T MR-linac system (Unity, Elekta AB, Stockholm, Sweden) has been initiated for patients with lymph node oligometastases. Superior soft tissue contrast and the possibility for online plan adaptation on the Unity may allow for hypofractionated treatment. The purpose of this study was to investigate the dosimetric feasibility and compare the plan quality of different hypofractionated schemes. Methods and materialsData was used from 12 patients with single lymph node oligometastases (10 pelvic, 2 para-aortic), which were all treated on the Unity with a prescribed dose of 5x7 Gy to 95% of the PTV. Hypofractionation was investigated for 3x10 Gy and 1x20 Gy schemes (all 60 Gy BED α/β = 10). The pre-treatment plans were evaluated based on dose criteria and plan quality. If all criteria were met, the number of online adapted plans which also met all dose criteria was investigated. For pre-treatment plans meeting the criteria for all three fractionation schemes, the plan quality after online adaptation was compared using the four parameters described in the NRG-BR001 phase 1 trial. ResultsPre-treatment plans met all clinical criteria for the three different fractionation schemes in 10, 9 and 6 cases. 50/50, 45/45 17/30 of the corresponding online adapted plans met all criteria, respectively. Violations were primarily caused by surrounding organs at risk overlapping or adjacent to the PTV. The 1x20 Gy treatment plans were, in general, of lesser quality than the 5x7 Gy and 3x10 Gy plans. ConclusionHypofractionated radiotherapy for lymph node oligometastases on the 1.5T MR-linac is feasible based on dose criteria and plan quality metrics. The location of the target relative to critical structures should be considered in choosing the most suitable fractionation scheme. Especially for single fraction treatment, meeting all dose criteria in the pre-treatment situation does not guarantee that this also applies during online treatment.

Assessing the role of Stereotactic Body Radiation Therapy in a large cohort of patients with lymph node oligometastases: Does it affect systemic treatment’s intensification?

Background and purposeLymph nodes (LN) are common site of oligometastases and stereotactic body radiation therapy (SBRT) represents an effective ablative treatment. Aim of this study was to analyze a large cohort of nodal oligometastases treated with SBRT to identify impact on systemic therapy intensification, pattern of recurrence, and predictive factors. Materials and methodsWe included patients with a maximum of 5 oligometastases. Concomitant treatments were allowed. Patients were treated with Volumetric Modulated Arc Therapy (VMAT) and end points were local control of treated metastases (LC), locoregional nodal control (LRNC), distant nodal control (DNC), distant metastases free survival (DMFS), overall survival (OS) and freedom from treatment intensification (FFTI). Results418 LN were treated in 278 patients with 327 SBRT treatments. Patients were more commonly affected by colorectal (20.9%) and prostate cancer (17.99%). Most represented schedule was 45 Gy in 6 fractions, with a median BED10 of 78.75 Gy. After median follow-up of 15.1 months, LC at 1 and 2 years were 87.2% and 76.8%, respectively. Prostate primary tumor, small volume, oligorecurrence, and BED10 ≥75 Gy were associated with higher LC. One and 2 years FFTI were 82.8% and 74.5%; in patients reporting intensification of systemic therapy, median time was 8.43 months, while for patients who repeated SBRT, median FFTI was 14.6 months. Rates of LRNC at 1 and 2 years were 70.9% and 57.6%, and DNC were 82.0% and 77.9%. ConclusionWith the present analysis, we confirmed on a large cohort the benefit from SBRT on lymph node oligometastases in multidisciplinary management. Combination of SBRT with new systemic therapies, including immunotherapy and targeted therapy, should be investigated to reduce the risk of progression out of the field of irradiation.

Role of high-dose salvage radiotherapy for oligometastases of the localised abdominal/pelvic lymph nodes: a retrospective study

BackgroundAbdominal/pelvic lymph node (LN) oligometastasis, a pattern of treatment failure, is observed occasionally, and radiotherapy may work as salvage therapy. The optimal prescription dose, however, is yet to be determined. This study assessed the efficacy of high-dose radiotherapy.MethodsThe medical records of 113 patients at 4 institutes were retrospectively analysed who had 1 to 5 abdominal/pelvic LN oligometastases and were treated with definitive radiotherapy between 2008 and 2018. The exclusion criteria included non-epithelial tumours, uncontrolled primary lesions, palliative intent, and re-irradiation. The prescription dose was evaluated by using the equivalent dose in 2 Gy fractions (EQD2). Patients receiving EQD2 ≥ 60 Gy were placed into the high-dose group, and the remaining others the low-dose group. Kaplan-Meier analyses were performed to evaluate overall survival (OS), local control (LC), and progression-free survival (PFS). Univariate log-rank and multivariate Cox proportional hazards model analyses were performed to explore predictive factors. Adverse events were compared between the high-dose and low-dose groups.ResultsThe primary tumour sites included the colorectum (n = 28), uterine cervix (n = 27), endometrium (n = 15), and ovaries (n = 10). The rate of 2-year OS was 63.1%, that of LC 59.7%, and that of PFS 19.4%. On multivariate analyses, OS were significantly associated with solitary oligometastasis (hazard ratio [HR]: 0.48, p = 0.02), LC with high-dose radiotherapy (HR: 0.93, p < 0.001), and PFS with long disease-free interval (HR: 0.59, p = 0.01). Whereas high-dose radiotherapy did not significantly improve 2-year OS in the entire cohort (74.8% in the high-dose vs. 52.7% in the low-dose; p = 0.08), it did in the subgroup of solitary oligometastasis (88.8% in the high-dose vs. 56.3% in the low-dose; p = 0.009). As for Late grade ≥ 3 adverse event, ileus was observed in 7 patients (6%) and gastrointestinal bleeding in 4 (4%). No significant association between the irradiation dose and adverse event incidence was found.ConclusionsAs salvage therapy, high-dose radiotherapy was recommendable for oligometastasis in the abdominal/pelvic LNs. For solitary oligometastasis, LC and OS were significantly better in the high-dose group.

Target coverage and dose criteria based evaluation of the first clinical 1.5T MR-linac SBRT treatments of lymph node oligometastases compared with conventional CBCT-linac treatment

Background and purposePatients were treated at our institute for single and multiple lymph node oligometastases on the 1.5T MR-linac since August 2018. The superior soft-tissue contrast and additional software features of the MR-linac compared to CBCT-linacs allow for online adaptive treatment planning. The purpose of this study was to perform a target coverage and dose criteria based evaluation of the clinically delivered online adaptive radiotherapy treatment compared with conventional CBCT-linac treatment. Materials and methodsPatient data was used from 14 patients with single lymph node oligometastases and 6 patients with multiple (2–3) metastases. All patients were treated on the 1.5T MR-linac with a prescribed dose of 5 × 7 Gy to 95% of the PTV and a CBCT-linac plan was created for each patient. The difference in target coverage between these plans was compared and plans were evaluated based on dose criteria for each fraction after calculating the CBCT-plan on the daily anatomy. The GTV coverage was evaluated based on the online planning and the post-delivery MRI. ResultsFor both single and multiple lymph node oligometastases the GTV V35Gy had a median value of 100% for both the MR-linac plans and CBCT-plans pre- and post-delivery and did not significantly differ. The percentage of plans that met all dose constraints was improved from 19% to 84% and 20% to 67% for single and multiple lymph node cases, respectively. ConclusionTarget coverage and dose criteria based evaluation of the first clinical 1.5T MR-linac SBRT treatments of lymph node oligometastases compared with conventional CBCT-linac treatment shows a smaller amount of unplanned violations of high dose criteria. The GTV coverage was comparable. Benefit is primarily gained in patients treated for multiple lymph node oligometastases: geometrical deformations are accounted for, dose can be delivered in one plan and margins can be reduced.