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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.

Highlights • MR-guidance enables high precision single-fraction lung SABR delivery. • Breath-hold gating resulted in a mean tracked GTVt coverage of 99.6% during beam-on. • On-table plan adaptation improved PTV coverage, but had little impact on GTV doses. • Improved techniques are needed to allow for consistent MR-tracking of small tumors., 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.

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 «predicted» 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.

Objectives Treatment patterns in patients with stage III non-small cell lung cancer (NSCLC) vary considerably between countries, for reasons that are not well understood. We studied factors influencing treatment decision-making at thoracic multidisciplinary tumor boards (MDT’s) and outcome for patients treated between 2015–2017, at a regional network comprising 5 hospitals. Materials and methods Details of all patients, including comorbidities, with stage III NSCLC were collected in an ethics-approved database. Weekly MDT’s were conducted. The preferred radical intent treatments (RIT) for suitable patients were assumed to be concurrent chemoradiotherapy and/or surgery and other therapies were non-radical intent treatments (n-RIT). Results Of 197 patients identified, 95 % were discussed at an MDT. RIT were recommended in 61 % of patients, but only 48 % finally received RIT. The estimated median OS was significantly better for patients undergoing RIT (28.3 months, CI-95 % 17.3–39.3), versus those who did not (11.2 months, CI-95 % 8.0−14.3). Patient age ≥70 years and a WHO-PS ≥2 were the most important predictors of not recommending RIT. Deaths due to progressive lung cancer within 2 years were observed in 36, 26 and 29 % of patients who received RIT, sequential chemoradiotherapy or radical radiotherapy. Corresponding comorbidity related deaths within 2 years were 3, 12 and 38 %. Conclusion A large number of patients who underwent MDT review were considered too old or not fit for RIT. More effective and better tolerated systemic treatments are required for patients presenting with stage III NSCLC.

Contains fulltext : 232797.pdf (Publisher’s version ) (Open Access) PURPOSE: Although various studies have reported that stereotactic body radiation therapy (SBRT) for liver metastases has high local control rates and relatively low toxicity, most series included a small number of patients. We aimed to validate these outcomes in a large multi-institution patient cohort treated in accordance with a common protocol. METHODS AND MATERIALS: A shared web-based registry of patients with liver metastases treated with SBRT was developed by 13 centers (12 in the Netherlands and 1 in Belgium). All the centers had previously agreed on the items to be collected, the fractionation schemes, and the organs-at-risk constraints to be applied. Follow-up was performed at the discretion of the centers. Patient, tumor, and treatment characteristics were entered in the registry. Only liver metastases treated individually as independent targets and with at least 1 radiologic follow-up examination were considered for local control analysis. Toxicity of grade 3 or greater was scored according to the Common Terminology Criteria of Adverse Events (v4.03). RESULTS: Between January 1, 2013, and July 31, 2019, a total of 515 patients were entered in the web-based registry. The median age was 71 years. In total, 668 liver metastases were registered, and 447 were included for local control analysis. The most common primary tumor origin was colorectal cancer (80.3%), followed by lung cancer (8.9%) and breast cancer (4%). The most-used fractionation scheme was 3x18-20 Gy (36.0%), followed by 8x7.5 Gy (31.8%), 5x11-12 Gy (25.5%), and 12x5 Gy (6.7%). The median follow-up time was 1.1 years for local control and 2.3 years for survival. Actuarial 1-year local control was 87%; 1-year overall survival was 84%. Toxicity of grade 3 or greater was found in 3.9% of the patients. CONCLUSIONS: This multi-institutional study confirms the high rates of local control and limited toxicity in a large patient cohort. Stereotactic body radiation therapy should be considered a valuable part of the multidisciplinary approach to treating liver metastases.

The guidelines for metastatic colorectal cancer crudely state that the best local treatment should be selected from a &lsquo, toolbox&rsquo, of techniques according to patient- and treatment-related factors. We created an interdisciplinary, consensus-based algorithm with specific resectability and ablatability criteria for the treatment of colorectal liver metastases (CRLM). To pursue consensus, members of the multidisciplinary COLLISION and COLDFIRE trial expert panel employed the RAND appropriateness method (RAM). Statements regarding patient, disease, tumor and treatment characteristics were categorized as appropriate, equipoise or inappropriate. Patients with ECOG&le, 2, ASA&le, 3 and Charlson comorbidity index &le, 8 should be considered fit for curative-intent local therapy. When easily resectable and/or ablatable (stage IVa), (neo)adjuvant systemic therapy is not indicated. When requiring major hepatectomy (stage IVb), neo-adjuvant systemic therapy is appropriate for early metachronous disease and to reduce procedural risk. To downstage patients (stage IVc), downsizing induction systemic therapy and/or future remnant augmentation is advised. Disease can only be deemed permanently unsuitable for local therapy if downstaging failed (stage IVd). Liver resection remains the gold standard. Thermal ablation is reserved for unresectable CRLM, deep-seated resectable CRLM and can be considered when patients are in poor health. Irreversible electroporation and stereotactic body radiotherapy can be considered for unresectable perihilar and perivascular CRLM 0-5cm. This consensus document provides per-patient and per-tumor resectability and ablatability criteria for the treatment of CRLM. These criteria are intended to aid tumor board discussions, improve consistency when designing prospective trials and advance intersociety communications. Areas where consensus is lacking warrant future comparative studies.

Purpose: Use of stereotactic body radiation therapy (SBRT) is increasing in patients with localized prostate cancer, but concerns about early and late gastrointestinal (GI) and genitourinary (GU) toxicity exist after moderately or extremely hypofractionated radiation therapy schemes. Magnetic resonance guided radiation therapy (MRgRT) was clinically introduced in 2014. MrgRT allows for SBRT delivery with smaller uncertainty margins and permits daily adaptive planning. A phase 2 study in patients with localized prostate cancer was performed to study early GI and GU toxicity after SBRT using MRgRT. Methods and Materials: One hundred one patients with clinical stage T1-3bN0M0 prostate cancer were enrolled in this prospective phase 2 study. All but 4 patients had intermediate- or high-risk prostate cancer, and 82.2% received adjuvant hormonal treatment. MRgRT was delivered in 5 fractions of 7.25 Gy to the target volume using daily plan adaptation with simultaneous relative sparing of the urethra to a dose of 6.5 Gy per fraction. Early toxicity was studied using both clinician- (Common Terminology Criteria for Adverse Events and Radiation Therapy Oncology Group) and patient-reported outcome measurements (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30, Quality of Life Questionnaire PR25, and International Prostate Symptom Scoring). Results: The maximum cumulative grade ≥2 early GU and GI toxicity measured by any symptom at any study time point was 23.8% and 5.0%, respectively. No early grade 3 GI toxicity was observed. Early grade 3 GU toxicity was 0% and 5.9% according to the Common Terminology Criteria for Adverse Events and Radiation Therapy Oncology Group and scoring systems, respectively, as a result of different grading of radiation cystitis. The low incidence of early GI toxicity was confirmed by patient-reported outcome data. GU grade ≥2 toxicity peaked to 19.8% at the end of MRgRT, followed by a return to the baseline average score at 3-month follow-up. Conclusions: This prospective study of MRgRT in patients with localized prostate cancer observed a low incidence of early GI and GU toxicity, both in clinician- and patient-reported outcome measurements.

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.

PURPOSE: To investigate, in the setting of stereotactic ablative radiation therapy (SABR) for early-stage non-small cell lung cancer, the incidence and patterns of change in high-risk radiologic features (HRFs) in patients known to have no local recurrence.METHODS AND MATERIALS: Computed tomography (CT) scans of patients treated using volumetric modulated arc therapy SABR between 2008 and 2013 were eligible if follow-up scans were available for 2 years and no local recurrences were diagnosed. All scans were reviewed at a workstation using an add-on tool for ClearCanvas (Synaptive Medical). Five clinicians who were blinded to clinical outcomes scored the presence of HRFs: enlarging opacity (EO), sequential enlarging opacity, enlarging opacity after 12 months (EO12), bulging margin, loss of linear margins, cranio-caudal growth, and loss of air bronchogram. After each review, clinicians recommended follow-up procedures based on published recommendations.RESULTS: A total of 88 patients (747 CT scans) were evaluated. The HRFs most frequently recorded by ≥3 observers on at least 1 follow-up scan were EO (64.8%), EO12 (50.0%), and sequential enlarging opacity (13.6%). Fifty-six patients developed EO within the first year after SABR, and of these, 46 also developed subsequent EO (EO12). In 76 patients who developed EO after 1 year of follow-up, 30 had not manifested EO previously. Three or more HRFs have been associated with recurrences, and this was observed on CT scan in 22.7% of patients. In their routine care, 6 patients had undergone a positron emission tomography scan because of a suspected local recurrence, and 4 underwent an attempt at biopsy.CONCLUSIONS: More than 50% of patients without a local recurrence after SABR develop HRFs. Because ≥3 HRFs were present in nearly 25% of patients, further refinement of follow-up recommendations are necessary.

Introduction Treatment patterns in stage III NSCLC can vary considerably between countries. The PACIFIC trial reported improvements in progression-free and overall survival with adjuvant durvalumab after concurrent chemoradiotherapy (CCRT). We studied treatment decision-making by three Dutch regional thoracic multidisciplinary tumor boards between 2015 and 2019, to identify changes in practice when adjuvant durvalumab became available. Methods Details of patients presenting with stage III NSCLC were retrospectively collected. Both CCRT and multimodality schemes incorporating planned surgery were defined as being radical-intent treatment (RIT). Results Of 855 eligible patients, most (95%) were discussed at a thoracic multidisciplinary tumor board, which recommended a RIT in 63% (n = 510). Only 52% (n = 424) of the patients finally received a RIT. Predictors for not recommending RIT were age greater than or equal to 70 years, WHO performance score greater than or equal to 2, Charlson comorbidity index greater than or equal to 2 (excluding age), forced expiratory volume in 1 second less than 80% of predicted value, N3 disease, and period of diagnosis. Between 2015 to 2017 and 2018 to 2019, the proportion of patients undergoing CCRT increased from 34% to 42% (p = 0.02) and use of sequential chemoradiotherapy declined (21%–16%, p = 0.05). Rates of early toxicity and 1-year mortality were comparable for both periods. After 2018, 57% of the patients who underwent CCRT (90 of 159) received adjuvant durvalumab. Conclusions After publication of the PACIFIC trial, a significant increase was observed in the use of CCRT for patients with stage III NSCLC with rates of early toxicity and mortality being unchanged. Since 2018, 57% of the patients undergoing CCRT went on to receive adjuvant durvalumab. Nevertheless, approximately half of the patients were still considered unfit for a RIT.

Stereotactic ablative radiotherapy (SABR) is a treatment for early-stage lung cancer with local control rates comparable to surgery. After SABR, benign radiation induced lung injury (RILI) results in tumour-mimicking changes on computed tomography (CT) imaging. Distinguishing recurrence from RILI is a critical clinical decision determining the need for potentially life-saving salvage therapies whose high risks in this population dictate their use only for true recurrences. Current approaches do not reliably detect recurrence within a year post-SABR. We measured the detection accuracy of texture features within automatically determined regions of interest, with the only operator input being the single line segment measuring tumour diameter, normally taken during the clinical workflow. Our leave-one-out cross validation on images taken 2–5 months post-SABR showed robustness of the entropy measure, with classification error of 26% and area under the receiver operating characteristic curve (AUC) of 0.77 using automatic segmentation; the results using manual segmentation were 24% and 0.75, respectively. AUCs for this feature increased to 0.82 and 0.93 at 8–14 months and 14–20 months post SABR, respectively, suggesting even better performance nearer to the date of clinical diagnosis of recurrence; thus this system could also be used to support and reinforce the physician’s decision at that time. Based on our ongoing validation of this automatic approach on a larger sample, we aim to develop a computer-aided diagnosis system which will support the physician’s decision to apply timely salvage therapies and prevent patients with RILI from undergoing invasive and risky procedures.