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Background and purpose: Tumours in the liver often develop on a background of liver cirrhosis and impaired liver function. As a result, radiotherapy treatments are limited by radiation-induced liver disease, parameterised by the liver mean dose (LMD). Liver function is highly heterogeneous, especially in liver cancer, but the use of LMD does not take this into account. One possible way to improve liver treatments is to use quantitative imaging techniques to assess liver health and prioritise the sparing of healthy liver tissue. Materials and methods: Anatomical T2 and quantitative iron-corrected T1 (cT1) images were made available for 10 patients with liver metastases. Functional liver volumes were automatically segmented on the quantitative images using a threshold. Liver stereotactic ablative body radiotherapy (SABR) plans were made using a departmental protocol. Liver-sparing plans were then made by reducing the dose to the functional sub-volume. Results: The sparing plans achieved a statistically significant (p=0.002) reduction in the functional liver mean dose, with a mean reduction of 1.4 Gy. The LMD was also significantly different (p=0.002) but had a smaller magnitude with a mean reduction of 0.7 Gy. There were some differences in the planning target volume D99% (p=0.04) but the sparing plans remained within the optimal tolerance and the D95% was not significantly different (p=0.2). Conclusions: This study has, for the first time, demonstrated the use of cT1 maps in radiotherapy showing significant reductions in dose to the healthy liver. Further work is needed to validate this in liver cancer patients, who would likely benefit most.

Background and purpose: The impact of respiratory motion management strategies for abdominal radiotherapy, such as abdominal compression (AC) and breath hold (BH), on abdominal organ at risk (OAR) delineation on magnetic resonance imaging (MRI) is unknown. This feasibility study compared the inter- and intra- observer delineation variation on MRI acquired with AC, BH for three critical abdominal OAR. Materials and methods: T2-weighted (W) 3D MRI in free-breathing (FB) and with AC, and T1W 3D mDixon exhale BH were acquired. Four observers blinded to motion management strategy used, delineated stomach, liver, and duodenum on all MRI. One case per strategy was repeated over 6 weeks later to quantify intra-observer variation. Simultaneous truth and performance level estimation (STAPLE) contours for each OAR were generated, median and IQR mean distance to agreement (mDTA) and maximum Hausdorff distance (HD) between observer and STAPLE contours were calculated. Observers scored organ visibility on each MRI using a four-point Likert scale. Results: A total of 27 scans including repeats were delineated. Pooled mDTA for all OARs was 1.3 mm (0.5 mm) with AC, 1.4 mm (1.0 mm) with BH, and 1.3 mm (0.5 mm) in FB. Intra-observer mDTA was highest for all organs in FB with 10.8 mm for duodenum, 1.8 mm for liver, and 2.7 mm for stomach. The pooled mean perceptual quality score value was highest for AC across organs. Conclusions: No motion management strategy demonstrated superior similarity across OAR, emphasizing the need for personalised approaches based on individual clinical and patient factors.

Purpose/objective(s): The growing use of stereotactic body radiotherapy (SBRT) in metastatic cancer has led to its use in varying anatomic locations. The objective of this study was to review our institutional SBRT experience for axillary metastases (AM), focusing on outcomes and process. Materials/methods: Patients treated with SBRT to AM from 2014 to 2022 were reviewed. Cumulative incidence functions were used to estimate the incidence of local failure (LF), with death as competing risk. Kaplan-Meier method was used to estimate progression-free (PFS) and overall survival (OS). Univariate regression analysis examined predictors of LF. Results: We analyzed 37 patients with 39 AM who received SBRT. Patients were predominantly female (60 %) and elderly (median age: 72). Median follow-up was 14.6 months. Common primary cancers included breast (43 %), skin (19 %), and lung (14 %). Treatment indication included oligoprogression (46 %), oligometastases (35 %) and symptomatic progression (19 %). A minority had prior overlapping radiation (18 %) or surgery (11 %). Most had prior systemic therapy (70 %).Significant heterogeneity in planning technique was identified; a minority of patient received 4-D CT scans (46 %), MR-simulation (21 %), or contrast (10 %). Median dose was 40 Gy (interquartile range (IQR): 35–40) in 5 fractions, (BED10 = 72 Gy). Seventeen cases (44 %) utilized a low-dose elective volume to cover remaining axilla.At first assessment, 87 % had partial or complete response, with a single progression. Of symptomatic patients (n = 14), 57 % had complete resolution and 21 % had improvement. One and 2-year LF rate were 16 % and 20 %, respectively. Univariable analysis showed increasing BED reduced risk of LF. Median OS was 21.0 months (95 % [Confidence Interval (CI)] 17.3-not reached) and median PFS was 7.0 months (95 % [CI] 4.3–11.3). Two grade 3 events were identified, and no grade 4/5. Conclusion: Using SBRT for AM demonstrated low rates of toxicity and LF, and respectable symptom improvement. Variation in treatment delivery has prompted development of an institutional protocol to standardize technique and increase efficiency. Limited followup may limit detection of local failure and late toxicity.

To further personalise treatment in metastatic cancer, the indications for metastases-directed local therapy (MDT) and the biology of oligometastatic disease (OMD) should be kept conceptually apart. Both need to be vigorously investigated. Tumour growth dynamics – growth rate combined with metastatic seeding efficiency – is the single most important biological feature determining the likelihood of success of MDT in an individual patient, which might even be beneficial in slowly developing polymetastatic disease. This can be reasonably well assessed using appropriate clinical imaging. In the context of considering appropriate indications for MDT, detecting metastases at the edge of image resolution should therefore suggest postponing MDT. While three to five lesions are typically used to define OMD, it could be argued that countability throughout the course of metastatic disease, rather than a specific maximum number of lesions, could serve as a better parameter for guiding MDT. Here we argue that the unit of MDT as a treatment option in metastatic cancer might best be defined not as a single procedure at a single point in time, but as a series of treatments that can be delivered in a single or multiple sessions to different lesions over time. Newly emerging lesions that remain amenable to MDT without triggering the start of a new systemic treatment, a change in systemic therapy, or initiation of best supportive care, would thus not constitute a failure of MDT. This would have implications for defining endpoints in clinical trials and registries: Rather than with any disease progression, failure of MDT would only be declared when there is progression to polymetastatic disease, which then precludes further options for MDT.

Stereotactic ablative radiotherapy (SAbR) is an emerging non-invasive definitive treatment option for primary renal cell carcinoma (RCC), particularly when surgery is not ideal. Employing ablative doses, SAbR delivered in one to five fractions to the primary tumor has been shown to achieve high local control rates with favorable toxicity profile in multiple retrospective and prospective series, and has dispelled previous notions of RCC radio-resistance. Moreover, emerging evidence suggests possible immunomodulatory effects, leading to clinical investigations of SAbR in combination with systemic and surgical management in patients with metastatic disease. In this review, we summarize key evidence supporting SAbR delivered to the primary tumor including preclinical rationale, dose escalation studies, recent prospective trials, and outcomes from ongoing multi-institutional registries. We also discuss areas of active clinical investigation including the use of primary SAbR in combination with systemic therapies in patients with metastatic disease. The accumulated body of evidence supports SAbR as promising indication being increasingly incorporated into the multi-disciplinary management of primary RCC.

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

Summary: The treatment of oligometastatic disease using MR guidance is an evolving field. Since August 2018 patients are treated on a 1.5 Tesla MR-Linac (MRL). We present current workflows and practice standards from seven institutions for the initial patients treated for lymph node and liver metastases.

Background and purpose: Spinal stereotactic ablative body radiotherapy (SABR) requires high precision. We evaluate the intrafraction motion during cone-beam computed tomography (CBCT) guided SABR with different immobilization techniques. Material and methods: Fifty-seven consecutive patients were treated for 62 spinal lesions with SABR with positioning corrected in six degrees of freedom. A surface monitoring system was used for patient set up and to ensure patient immobilization in 65% of patients. Intrafractional motion was defined as the difference between the last CBCT before the start of treatment and the first CT afterwards. Results: For all 194 fractions, the mean intrafractional motion was 0.1 cm (0–1.1 cm) in vertical direction, 0.1 cm (0–1.1 cm) in longitudinal direction and 0.1 cm (0–0.5 cm) in lateral direction. A mean pitch of 0.6° (0–4.3°), a roll of 0.5° (0–3.4°) and a rotational motion of 0.4° (0–3.9°) was observed. 95.5% of the translational errors and 95.4% of the rotational errors were within safety range. There was a significantly higher rotational motion for patients with arms along the body (p = 0.01) and without the use of the body mask (p = 0.05). For cervical locations a higher rotational motion was seen, although not significant (p = 0.1). The acquisition of an extra CBCT was correlated with a higher rotational (pitch) motion (p = 0

Background: Patients who experience a pelvic cancer recurrence in or near a region that received initial radiotherapy, typically have few options for treatment. Organs at risk (OAR) have often reached their dose constraint limits leaving minimal dose remaining for standard re-irradiation (reRT). However, photon based stereotactic ablative radiotherapy (SABR) has been utilised for reRT with promising initial results although meeting OAR constraints can be challenging. Proton beam therapy (PBT) could offer an advantage. Materials and methods: SABR plans used for treatment for ten pelvic reRT patients were dosimetrically compared to PBT plans retrospectively planned using the same CT and contour data. PBT plans were created to match the CTV dose coverage of SABR treatment plans with V100% ≥95%. An ‘as low as reasonably achievable’ approach was taken to OAR tolerances with consideration of OAR dose from the initial radiation (using equivalent dose in 2 Gy fractions). Results: Dosimetric comparison of relevant OAR statistics showed a decrease in OAR dose using PBT over SABR in all patients, with equivalent target coverage. The largest statistically significant reduction was seen for the colon D0.5 cm3 with a median reduction from 13.1 Gy to 5.9 Gy. There were statistically significant dose reductions in the median dose to small bowel, sacral plexus and cauda equina. Conclusion: PBT has the potential for significant dose reductions for OARs in the pelvic reRT setting compared to SABR. However, it remains unclear if the magnitude of these OAR dose reductions will translate into clinical benefit.

Aim: Stereotactic ablative radiotherapy (SABR) showed increasing survival in oligometastatic patients. Few studies actually depicted oligometastatic disease (OMD) evolution and which patient will remain disease-free and which will rapidly develop a polymetastatic disease (PMD) after SABR. Therefore, apart from the number of active metastases, there are no clues on which proven factor should be considered for prescribing local treatment in OMD. The study aims to identify predictive factors of polymetastatic evolution in lung oligometastatic colorectal cancer patients. Methods: This international Ethical Committee approved trial (Prot. Negrar 2019-ZT) involved 23 Centers and 450 lung oligometastatic patients. Primary end-point was time to the polymetastatic conversion (tPMC). Additionally, oligometastases number and cumulative gross tumor volume (cumGTV) were used as combined predictive factors of tPMC. Oligometastases number was stratified as 1, 2–3, and 4–5; cumGTV was dichotomized to the value of 10 cc. Results: The median tPMC in the overall population was 26 months. Population was classified in the following tPMC risk classes: low-risk (1–3 oligometastases and cumGTV ≤ 10 cc) with median tPMC of 35.1 months; intermediate-risk (1–3 oligometastases and cumGTV > 10 cc), with median tPMC of 13.9 months, and high-risk (4–5 oligometastases, any cumGTV) with median tPMC of 9.4 months (p = 0.000). Conclusion: The present study identified predictive factors of polymetastatic evolution after SABR in lung oligometastatic colorectal cancer. The results demonstrated that the sole metastases number is not sufficient to define the OMD since patients defined oligometastatic from a numerical point of view might rapidly progress to PMD when the cumulative tumor volume is high. A tailored approach in SABR prescription should be pursued considering the expected disease evolution after SABR, with the aim to avoid unnecessary treatment and toxicity in those at high risk of polymetastatic spread, and maximize local treatment in those with a favorable disease evolution.

Purpose/Objective: To evaluate the potential of stereotactic magnetic resonance-guided online adaptive radiotherapy (SMART) to fulfill dose recommendations for stereotactic body radiotherapy (SBRT) of adrenal metastases and spare organs at risk (OAR). Materials and methods: In this subgroup analysis of a prospective registry trial, 22 patients with adrenal metastases were treated on a 0.35 T MR-Linac in 5–12 fractions with fraction doses of 4–10 Gy. Baseline plans were re-calculated to the anatomy of the day. These predicted plans were reoptimized to generate adapted plans. Baseline, predicted and adapted plans were compared with regard to PTV objectives, OAR constraints and published dose recommendations. Results: The cohort comprised patients with large GTV (median 36.0 cc) and PTV (median 66.6 cc) and predominantly left-sided metastases. 179 of 181 fractions (98.9 %) were adapted because of PTV and/or OAR violations. Predicted plans frequently violated PTV coverage (99.4 %) and adjacent OAR constraints (bowel: 32.9 %, stomach: 32.8 %, duodenum: 10.4 %, kidneys: 10.8 %). In the predicted plans, the volume exposed to the maximum dose was exceeded up to 16-fold in the duodenum and up to 96-fold in the spinal cord. Adapted plans significantly reduced OAR violations by 96.4 % for the bowel, 98.5 % for the stomach, 85.6 % for the duodenum and 83.3 % for the kidneys. Plan adaptation improved PTV coverage from 82.7 ± 8.1 % to 90.6 ± 4.9 % (p grade II occurred. Conclusion: SMART fulfills established GTV and PTV dose recommendations while simultaneously sparing organs at risk even in a challenging cohort.

Objectives: The objective of this study is to assess the frequency of the novel sodium bicarbonate (NaHCO 3 )-responsive phenotype, wherein clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates are rendered susceptible to standard-of-care β-lactams in the presence of NaHCO 3 , in a collection of 103 clinical U.S. MRSA skin and soft-tissue infection (SSTI) isolates and 22 clinical European SSTI isolates. This study determined the correlation between specific phenotypic and genotypic metrics and the NaHCO 3 -responsive phenotype among U.S. SSTI isolates., Methods: Antimicrobial susceptibility testing was performed to determine susceptibility phenotypes. Targeted and whole-genome sequencing with a genome-wide sequence analysis were conducted to identify specific and novel genotypes of interest that may be associated with the NaHCO 3 -responsive phenotype. Gene expression analysis and targeted gene deletion were performed to assess the role of a specific novel genetic locus in the NaHCO 3 -responsive phenotype., Results: The NaHCO 3 -responsive phenotype was identified in 78/103 U.S. isolates and 4/22 UK isolates to cefazolin (CFZ), and in 17/103 U.S. isolates and 1/22 UK isolates to oxacillin. In U.S. isolates, a significant association was identified between NaHCO 3 -responsiveness to CFZ and: (a) susceptibility to amoxicillin-clavulanate; (b) a specific mecA genotype; (c) clonal complex type 8; and (d) spa type t008. Genome-wide sequence analysis identified single nucleotide polymorphisms (SNPs) in an AraC family regulator (SAUSA300_RS00540) to be exclusively found in NaHCO 3 -non-responsive SSTI strains. In vitro HCO 3 exposures of NaHCO 3 -responsive strains, but not -non-responsive strains, caused >2-fold upregulated expression of this gene. Deletion of this gene rendered NaHCO 3 -responsive strain MRSA 11/11 no longer NaHCO 3 -responsive to CFZ; we have termed this gene the staphylococcal AraC bicarbonate-response regulator., Discussion: NaHCO 3 -responsiveness is highly associated with clonal complex type 8/spa type t008, a commonly circulating genetic background in North America. The AraC bicarbonate-response regulator, staphylococcal AraC bicarbonate-response regulator, appears to be associated with the mechanism of NaHCO 3 -responsiveness, but more work is needed to verify., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.

Background: In patients with oligometastatic recurrent prostate cancer, standard treatment is androgen deprivation therapy (ADT). However, ADT has many potential side effects that may result in impaired quality of life. Early identification to select patients suitable for stereotactic ablative radiotherapy (SABR) is of utmost importance to prevent or delay start of ADT and its side effects. Because Prostate-Specific Membrane Antigen-11-Positron Emission Tomography (PSMA-11-PET) has a higher sensitivity than choline-PET, we hypothesise that PSMA-11-PET based SABR results in longer response duration and subsequent longer delay in starting ADT than choline-PET. Methods: Patients with oligometastatic (≤4 metastases) recurrent prostate cancer (with no local recurrence) based on PSMA-11-PET or choline-PET treated with SABR from January 2012 until December 2017 were included. Primary endpoint was ADT-free survival. Secondary endpoints were Prostate Specific Antigen (PSA) response after SABR and time to PSA rise after SABR. Results: Fifty patients (n = 40 PSMA-11-PET and n = 10 choline-PET) with in total 72 lesions were included. Median follow-up was 24.3 months. PSMA-11-PET enabled eligibility of patients with lower PSA levels than choline-PET (median 1.8 versus 4.2 ng/mL, p = 0.03). The PSMA-11-PET group had a significant longer PSA response duration (median 34.0 months (95% confidence interval (CI), 16.0–52.0) versus 14.7 months (95% CI 4.7–24.7), p = 0.004) with a subsequent longer ADT-free survival (median 32.7 months (95% CI, 20.8–44.5) versus 14.9 months (95% CI, 5.7–24.1), p = 0.01). Conclusions: With PSMA-11-PET we are able to select patients with oligometastatic recurrent prostate cancer suitable for SABR in an earlier disease stage at lower PSA levels. PSMA-11-PET guided SABR resulted in a significant longer response duration and ADT-free survival compared with choline-PET and can therefore prevent or delay ADT related side effects.

A decision tool for radiographer-led image-guided radiotherapy (IGRT) using cone-beam CT (CBCT) for abdominal stereotactic radiotherapy was developed and successfully implemented in a single department. The confidence of 7 therapeutic radiographers when undertaking online CBCT review increased, and the pooled median online match time was reduced by 1 m 8 s. While this may be advantageous for abdominal SABR, further evaluation of this work in a larger cohort is required to validate these results.

Background and purpose: Stereotactic radiotherapy combines image guidance and high precision delivery with small fields to deliver high doses per fraction in short treatment courses. In preparation for extension of these treatment techniques to paediatric patients we characterised and compared doses out-of-field in a paediatric anthropomorphic phantom for small flattened and flattening filter free (FFF) photon beams. Method and materials: Dose measurements were taken in several organs and structures outside the primary field in an anthropomorphic phantom of a 5 year old child (CIRS) using thermoluminescence dosimetry (LiF:Mg,Cu,P). Out-of-field doses from a medical linear accelerator were assessed for 6 MV flattened and FFF beams of field sizes between 2 × 2 and 10 × 10 cm2. Results: FFF beams resulted in reduced out-of-field doses for all field sizes when compared to flattened beams. Doses for FFF and flattened beams converged for all field sizes at larger distances (>40 cm) from the central axis as leakage becomes the primary source of out-of-field dose. Rotating the collimator to place the MLC bank in the longitudinal axis of the patient was shown to reduce the peripheral doses measured by up to 50% in Varian linear accelerators. Conclusion: Minimising out-of-field doses by using FFF beams and aligning the couch and collimator to provide tertiary shielding demonstrated advantages of small field, FFF treatments in a paediatric setting.

Stereotactic ablative radiotherapy (SABR) is a highly effective treatment for medically inoperable patients with early stage NSCLC. Because of its noninvasive nature and favorable toxicity profile, the use of SABR continues to expand for eligible patients. We present here two uncommon cases of peripheral neuropathy secondary to SABR-induced injury to recurrent laryngeal and phrenic nerves, resulting in unilateral vocal cord and diaphragmatic paralysis, respectively.

Stereotactic ablative radiotherapy (SABR) has emerged as an effective, noninvasive alternative to surgery in patients with oligometastatic disease. Historically, select patients with adrenal oligometastases have been treated with adrenalectomies which can offer durable local control and reasonable survival rates. SABR is a promising noninvasive treatment alternative to surgery capable of delivering ablative doses of radiation to the tumor with the goal of achieving durable local control of adrenal metastases. We report on a case of a patient who underwent initial surgical resection for a locally advanced lung adenocarcinoma and subsequently developed an early, biopsy-proven, oligometastatic recurrence in the adrenal gland. He underwent chemotherapy and SABR using CyberKnife to the adrenal metastasis and is in remission 7 years after treatment with no late toxicity. Fractionated SABR is an attractive noninvasive alternative to surgery for adrenal metastases. This case demonstrates that select patients with adrenal oligometastases, can achieve long-term remission and even cure following SABR.

Background and purpose: Post-operative spine stereotactic body radiation therapy (SBRT) represents a significant challenge as there are many restrictions on beam geometry to avoid metal hardware as it surrounds the target volume. In this study, an international multi-institutional end-to-end test using an in-house spine phantom was developed and executed. The aim was to evaluate the impact of titanium spine hardware on planned and delivered dose for post-operative spine SBRT. Materials and methods: Five centers performed simulation, planning and irradiation of the spine phantom, with/without titanium metal hardware (MB/B), following our pre-specified protocol. The doses were calculated using the centers’ treatment planning system (TPS) and measured with radiophotoluminescent glass dosimeters (RPLDs) embedded within each phantom. Results: The dose differences between the RPLD measured and calculated doses in the target region were within ± 5% for both phantoms studied. Differences greater than 5% were observed for the spinal cord and the out-of-the target regions due to steeper dose gradient regions that are created in these plans. Dose measurements within ± 3% were observed between RPLDs that were embedded in MB and B inserts. For the spinal cord and the out-of-target regions surrounded by metal hardware, the dose measured using RPLDs was within 3% different near the titanium screws compared to the dose measured near only the metal rods. Conclusion: We have successfully performed the first multi-institutional end-to-end dose analysis using an in-house phantom built specifically for post-operative spine SBRT. The differences observed between the measured and planned doses in the presence of metal hardware were clinically insignificant.

Background and purpose: Peer-review of Target Volume (TV) and Organ at Risk (OAR) contours in radiotherapy planning are typically conducted visually; this can be time consuming and subject to interobserver variation. This study investigated automatic evaluation of contouring using conformity indices and supervised machine learning. Methods: A total of 393 contours from 253 Stereotactic Ablative Body Radiotherapy (SABR) benchmark cases (adrenal gland, liver, pelvic lymph node and spine), delineated by 132 clinicians from 25 centres, were visually evaluated for conformity against gold standard contours. Contours were scored as “pass” or “fail” on visual peer review and six Conformity Indices (CIs) were applied. CI values were mapped to pass/fail scores for each contour and used to train supervised machine learning models. A 5-fold cross validation method was employed to determine the predictive accuracies of each model. Results: The stomach structure produced models with the highest predictive accuracy overall (96% using Support Vector Machine and Ensemble models), whilst the liver GTV produced models with the lowest predictive accuracy (76% using Logistic Regression). Predictive accuracies across all models ranged from 68–96% (68–87% for TV and 71–96% for OARs). Conclusions: Although a final visual review by an experienced clinician is still required, the automatic contour evaluation method could reduce the time for benchmark case reviews by identifying gross contouring errors. This method could be successfully implemented to support departmental training and the continuous assessment of outlining for clinical staff in the peer-review process, to reduce interobserver variability in contouring and improve interpretation of radiological anatomy.

Background: To investigate progression free survival (PFS), local control (LC) and overall survival (OS) outcomes for patients treated with spine hypofractionated stereotactic ablative radiotherapy (SABR) and to evaluate possible predictors of rapid progression in view of a correct patient selection for this potentially curative SABR. Materials and methods: A cohort of 59 patients with spinal metastases were treated with SABR. Patient selection criteria were the following: histologically proven diagnosis of a solid tumor, a World Health Organization (WHO) score ≤ 2, life expectancy > 6 months, Spinal Instability Neoplastic Score (SINS) ≤ 12 points and presenting with radically treated oligometastatic disease (≤5 lesions) or stable polymetastatic disease with an oligoprogressive lesion. Results: From March 2015 to June 2019, 59 patients were treated with Linac-based SABR to 64 spinal metastases with a median follow-up of 55 months. SABR was standard delivered every other day in 3 to 10 fractions with median prescription dose of 27 Gy (range 21–49 Gy).The 1-,2- and 5-year PFS was 98%, 85% and 75% for all patients. OS at 5 years for all patients was 92%. Metachronous lesions (p

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: The management of oligometastatic clear cell renal cell carcinoma (ccRCC) varies widely, ranging from observation to resection or systemic therapies. Prolonged survival has been observed following resection or stereotactic ablative body radiotherapy (SABR). Immunotherapy combinations have shown survival benefits, however, toxicity is higher than that for monotherapy and complete response rates remain less than 10%. The combination of effective local therapies in conjunction with immunotherapy may provide more durable control and pre-clinical models have suggested a synergistic immune-priming effect of SABR. Objectives: and Methods: RAPPORT is a prospective, single arm, phase I/II study assessing the safety, efficacy and biological effects of single fraction SABR followed by pembrolizumab for oligometastatic ccRCC. The study will include 30 patients with histological confirmed ccRCC and 1–5 oligometastases, one or more of which must be suitable for SABR. Patients can have received prior systemic therapy but not prior immunotherapy. A single 20Gy of SABR is followed 5 days later by 8 cycles of 200 mg pembrolizumab, every 3 weeks. Adverse events are recorded using CTCAE V4.03 and tumour response evaluated by Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1). Tumour tissue and peripheral blood samples will be collected pre-, during and post‐treatment to assess longitudinal changes in immune subsets. Outcomes and significance: The RAPPORT study will provide important safety and early efficacy data on the combination of SABR and pembrolizumab in oligometastatic ccRCC and will provide an insight into the underlying biological effects of combination therapy. Trial registration: clinicaltrials.gov ID NCT02855203.

Purpose: In this single institution retrospective study of patients with stage I medically inoperable non-small cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy (SABR) we attempt to model overall survival (OS) using initial prognostic variables with specific attention on the Charlson co-morbidity index (CCI). Methods: Between 2008 and 2013, 335 patients with medically inoperable stage I NSCLC were treated with SABR or hypofractionated radiotherapy (50–60 Gy in at least 5 Gy or 4 Gy fractions respectively) at our institution. Medical comorbidities and Charlson scores were determined by individual chart review. Patients were stratified into 3 groups based on the CCI score (0–1, 2–3, 4–9) and again based on the age-adjusted Charlson Comorbidity score (aCCI). Cumulative survival for each stratum was determined using the Kaplan-Meier method. Non-significant and confounding variables were identified and discounted from survival modeling. 3 sex stratified Cox regression models were tested: (1) aCCI with age and comorbidity combined; (2) age and CCI; (3) age alone, comorbidity removed. Results: The median survival was 4.4 years and the median follow up 4.7 years. The median CCI and aCCI scores were 2 and 5 respectively. Patients with aCCI 7–12 had an increased hazard of death on univariate analysis HR 2.45 (1.15–5.22 95%CI, p = 0.02) and -excluding age as a competing variable- on multivariate analysis HR 2.25 (1.04–4.84 95%CI, p = 0.04). Patients with CCI 4-9 had an increased hazard of death on univariate analysis HR 1.57(1.30–2.90) but not on multivariate analysis. On formalized testing – with either continuous or categorical variables- all three survival models yielded similar coefficients of effect. Conclusion: We identify male gender, weight loss greater than 10% and age as independent prognostic factors for patients treated with medically inoperable NSCLC treated with SABR or hypofractionated radiotherapy. Based on our survival models, age alone can be used interchangeably with aCCI or CCI plus age with the same prognostic value. Age is more reliably recorded, less prone to error and therefore a more useful metric than Charlson score in this group of patients.

Aims: SCLC is the most aggressive lung cancer histology with a 5-year OS <10%. At the diagnosis, almost two-thirds of the SCLC an Extended Disease presentation. Two randomized studies (CASPIAN and ImPower133) demonstrated an OS improvement, when immunotherapy was prescribed as maintenance therapy after standard chemotherapy. To date, SABR has had a limited indication in managing metastatic SCLC, although recent reports proposed it as a valid treatment option in selected patients. We propose a retrospective multicentric analysis of patients treated with SABR for oligometastatic SCLC., Method: Data of patients affected by oligometastatic-SCLC treated with SABR between 2017 and 2022 in 11 Italian centers were collected. Clinical and therapeutic variables together with OS and time to next treatment were analyzed. Univariate analysis with Kaplan-Meier curve were calculated, and log-rank test were applied. Cox proportional hazard model was used for multivariate analysis., Results: Data from 93 patients and 132 metastatic lesions were analyzed. The median age was 64 years (36-86) and all but 1 had Performance Status 0 or 1. Fifty-two patients presented ED at diagnosis. The first line treatment was radiochemotherapy in 42%, CHT alone in 24% and CHT-IO in 28%, others treatment accounts for 4% and only 2% of patients underwent best supportive care. Of the 132 lesions treated with SBRT 55 were in brain, 27 in lung, 11 in liver, 10 in lymph nodes, 8 in bones and 20 in adrenal gland. Median OS was 14 months, 1 year-OS and 2 years OS were 53% and 27%, respectively. The median TtNT was 14 months for the entire population. Of all the analyzed variables only, the anatomical site of the metastases and their number showed statistical significance in the univariate analysist, confirmed in the subsequent multivariate., Conclusion: SABR seems to play a role in delaying further systemic lines in oligometastatic disease and to extend the use of ongoing treatment in oligoprogressive state. Prospective studies are needed to confirm these findings., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Stereotactic Ablative Radiation Therapy (SABR) is a therapeutic option for patients with inoperable oligometastatic colorectal carcinoma (CRC). Given the scarcity of prospective data on outcomes of SABR for metastatic CRC, this study aims to review SABR outcomes and determine predictive factors of local control (LC) and survival in patients with liver metastases from CRC., Materials and Methods: A retrospective review of SABR for CRC liver metastases between 2011 and 2019 was undertaken. Endpoints included LC, overall survival (OS), progression-free survival (PFS) and time to restarting systemic therapy. Univariate (UVA) and multivariable analyses (MVA) were performed to identify predictive factors., Results: Forty-eight patients were identified. The total number of tumors treated was 58. Median follow-up was 26.6 months. LC at 1, 2 and 3 years was 92.7%, 80.0%, and 61.2% respectively. Median time to local failure was 40.0 months (95% CI 31.8-76.1 months). Median OS was 31.9 months (95% CI 20.6-40.0 months). OS at 1, 2, and 3 years was 79.2%, 61.7%, and 44.9% respectively. Thirty-three patients (69%) restarted systemic therapy after completion of SABR. Median time to restarting chemotherapy was 11.0 months (95% CI 7.1-17.6 months). Systemic therapy free survival at 1, 2, and 3 years was 45.7%, 29.6%, and 22.6% respectively. On MVA, inferior LC was influenced by GTV volume ≥40 cm 3 (HR: 3.805, 95% CI 1.376-10.521, P = .01) and PTV D100% BED <100 Gy 10 (HR 2.971, 95% CI 1.110-7.953; P = .03). Inferior OS was associated with PTV volume ≥200 cm 3 (HR 5.679, 95% CI 2.339-13.755; P < .001)., Conclusion: SABR is an effective therapeutic option for selected patients with CRC liver metastases providing acceptable LC within the first 2 years. In many cases, it provides meaningful chemotherapy-free intervals. Higher biological effective doses are required to enhance LC., Competing Interests: Disclosure None, (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: The ideal non-operative treatment for patients with large, node-negative non-small cell lung cancer (NSCLC) is poorly defined. To inform optimal treatment paradigms for this cohort, we examined patterns of failure and the impact of radiation therapy (RT) and chemotherapy receipt., Materials and Methods: Node-negative NSCLC patients with 5+ cm primary tumors receiving definitive RT at our institution were identified. Sites of initial progression were analyzed. Local progression, regional/distant progression, progression-free survival, and overall survival were analyzed via cumulative incidence function and Kaplan-Meier. Associations between local vs. regional/distant progression with treatment and clinicopathologic variables were assessed via univariable and multivariable competing risks regression., Results and Conclusion: We identified 88 patients for analysis. Among patients with recurrent disease (N = 36), initial patterns of failure analysis showed that isolated distant (27.8%) and isolated regional progression (22.2%) were most common. Distant or regional failure as a component of initial failure was seen in 88.9% of patients who progressed, while isolated local failure was uncommon (11.1%). Univariable and multivariable competing risks regression showed that receipt of SBRT was associated with reduced risk of local progression (HR 0.23, P = .012), and receipt of chemotherapy was associated with reduced risk of regional/distant progression (HR 0.12, P = .040). In conclusion, patients with large, node-negative NSCLC treated with definitive RT are at high risk of regional and distant progression. SBRT correlates with a reduced risk of local failure while chemotherapy is associated with reduced regional/distant progression in this patient population. Ideal treatment may include SBRT when feasible with appropriate systemic therapy., (Copyright © 2022. Published by Elsevier Inc.)

Background: Patients undergoing surgery for early stage non-small cell lung cancer (NSCLC) may be at high risk for postoperative mortality. Access to stereotactic body radiation therapy (SBRT) may facilitate more appropriate patient selection for surgery., Research Question: Is postoperative mortality associated with early stage NSCLC lower at facilities with higher use of SBRT?, Study Design and Methods: Patients with early stage NSCLC reported to the National Cancer Database between 2004 and 2015 were included. Use of SBRT was defined by each facility's SBRT experience (in years) and SBRT to surgery volume ratios. Multivariate logistic regression was used to test for the associations between SBRT use and postoperative mortality., Results: The study cohort consisted of 202,542 patients who underwent surgical resection of cT1-T2N0M0 NSCLC tumors. The 90-day postoperative mortality rate declined during the study period from 4.6% to 2.6% (P < .001), the proportion of facilities that used SBRT increased from 4.6% to 77.5% (P < .001), and the proportion of patients treated with SBRT increased from 0.7% to 15.4% (P < .001). On multivariate analysis, lower 90-day postoperative mortality rates were observed at facilities with > 6 years of SBRT experience (OR, 0.84; 95% CI, 0.76-0.94; P = .003) and SBRT to surgery volume ratios of more than 17% (OR, 0.85; 95% CI, 0.79-0.92; P < .001). Ninety-day mortality also was associated with surgical volume, region, year, age, sex, and race, among other covariates. Interaction testing between these covariates showed negative results., Interpretation: Patients who underwent resection for early stage NSCLC at facilities with higher SBRT use showed lower rates of postoperative mortality. These findings suggest that the availability and use of SBRT may improve the selection of patients for surgery who are predicted to be at high risk of postoperative mortality., (Published by Elsevier Inc.)

Introduction: Stereotactic body radiotherapy (SBRT) has been shown to result in excellent disease control rates for early-stage non-small-cell lung cancer (NSCLC). It remains unknown which patients would most benefit from SBRT in treating NSCLC., Patients and Methods: We conducted a retrospective analysis of 346 patients treated with SBRT for early-stage NSCLC at 2 institutions (86 patients from City of Hope National Medical Center and 260 patients from The Newport Beach Radiosurgery Center/Hoag Hospital) from February 2010 to July 2019. The primary endpoint was overall survival (OS). The omnibus test of model coefficients was performed to study the associations between clinical factors and OS. Survival analyses were performed by the log-rank test and Cox proportional hazards regression., Results: Under the univariate analysis, variables associated with a decreased likelihood of death included age < 65 years (P = .040) and being a surgical candidate (P = .010). Multivariate analysis found that surgical candidates still had a significantly decreased likelihood of death compared to nonsurgical candidates (Hazard ratio 0.360, 95% confidence interval 0.153-0.848, P = .019). Median OS was significantly increased for surgical candidates versus nonsurgical candidates (83 vs 53 months, P = .017). The local failure rate was 9.1%, the locoregional failure rate was 12.7%, and the distant failure rate was 10.7%., Conclusion: Patients who are deemed to be candidates for surgery have improved OS compared to those who are not when treated with SBRT. This raises the question of selection bias in trials comparing surgery with SBRT in NSCLC, as patients who are deemed to be surgical candidates and then go on to undergo surgery may have an inherent OS benefit., (Copyright © 2021. Published by Elsevier Inc.)

Introduction: The impact of lung parenchymal-only failure on patient survival after stereotactic ablative body radiotherapy (SABR) for early-stage non-small-cell lung cancer (NSCLC) remains unclear., Patients and Methods: The study population included 481 patients with early-stage NSCLC who were treated with 3- to 5-fraction SABR between 2000 and 2016. The primary study objective was to assess the impact of out-of-field lung parenchymal-only failure (OLPF) on overall survival (OS)., Results: At a median follow-up of 5.9 years, the median OS was 2.7 years for all patients. Patients with OLPF did not have a significantly different OS compared to patients without failure (P = .0952, median OS 4.1 years with failure vs. 2.6 years never failure). Analysis in a 1:1 propensity score-matched cohort for Karnofsky performance status, comorbidity score, and smoking status showed no differences in OS between patients without failure and those with OLPF (P = .8). In subgroup analyses exploring the impact of time of failure on OS, patients with OLPF 6 months or more after diagnosis did not have significantly different OS compared to those without failure, when accounting for immortal time bias (P = .3, median OS 4.3 years vs. 3.5 years never failure). Only 7 patients in our data set experienced failure within 6 months of treatment, of which only 4 were confirmed to be true failures; therefore, limited data are available in our cohort on the impact of OLPF for ≤ 6 months on OS., Conclusion: OLPF after SABR for early-stage NSCLC does not appear to adversely affect OS, especially if occurring at least 6 months after SABR. More studies are needed to understand if OLPF within 6 months of SABR is associated with adverse OS. These data are useful when discussing prognosis of lung parenchymal failures after initial SABR., (Copyright © 2020 Elsevier Inc. All rights reserved.)

For prostate cancer radiation therapy, daily sessions spanning approximately 2 months has been considered the standard of care for patients managed with curative intent. In recent years, data has emerged which supports the use of higher dose per fraction schemes leading to a reduced duration of treatment. This form of radiation-generally termed moderate hypofractionation or stereotactic body radiation therapy-increasingly appears to be a safe and effective alternative to the conventional course. This review summarizes salient data from the literature on outcomes, toxicities, and future directions for this innovative strategy of care., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: As there is increasing evidence for comparable survival after either stereotactic body radiotherapy (SBRT) or surgery for patients with stage I non-small-cell lung cancer (NSCLC), treatment impact on the quality of life (QoL) is essential for well-informed decision-making. Our previous work evaluated health utility between surgery and SBRT in stage I NSCLC. The aim of this secondary analysis is to directly compare QoL in the first year after SBRT and surgery., Materials and Methods: QoL was assessed at baseline and 3, 6, and 12 months after treatment. Two prospectively collected databases of patients with clinically proven stage I NSCLC, from 2 large hospitals in the Netherlands, were pooled (n = 306; 265 patients were treated with SBRT and 41 patients with surgery). To correct for confounding, propensity scores were calculated, to be selected for surgical treatment. A mixed model analysis was used to study differences in QoL between the 2 treatments., Results: The 41 surgical patients were matched to 41 SBRT patients on propensity score with a 1:1 ratio. At baseline, patients in the surgery group report a lower QoL compared with patients in the SBRT group. However, during the first year after treatment, no clinical meaningful differences were observed, except for role functioning, between patients treated using either modality., Conclusion: This study comparing a matched cohort revealed no clinically significant differences in QoL following either SBRT or surgery for early stage NSCLC. These results support the hypothesis that surgery and SBRT are comparable treatments., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Radiotherapy produces immune-promoting effects, which may be blunted by the delivery of corticosteroids (CS). We thus aimed to evaluate the impact of CS use on recurrence and survival outcomes of patients with early stage non-small-cell lung cancer treated with stereotactic ablative radiotherapy (SABR)., Materials and Methods: A prospectively registered database of patients with stage I to II (T1-3N0M0) stage non-small-cell lung cancer treated with SABR from 2004 to 2015 was queried. Concurrent CS administration was defined as receipt of CS within 2 days of the SABR course. Statistics included Kaplan-Meier survival analysis, Cox proportional hazards modeling, and cumulative incidence analysis utilizing death as a competing risk., Results: Of 912 patients, 87 (9.5%) received CS with their SABR course. The most common agent was prednisone (64.4%). Indications for CS use were chronic obstructive pulmonary disease in 53 cases (60.9%), chemotherapy in 7 (8.0%), arthritis in 7 (8.0%), chronic pain in 4 (4.6%), transplant-related in 3 (3.4%), and "others" in 13 (14.9%; pneumonia, asthma, anemia, etc.). The median follow-up time was 59.3 months. Compared with patients who did not receive CS, receipt of CS was associated with poorer overall survival (P = .004). However, CS administration was not associated with worse time to progression (P = .766) or any recurrence when using death as a competing risk (local P = .119, regional P = .449, distant P = .847, and any recurrence P = .708). Toxicity rates were not statistically different between cohorts., Conclusions: These data do not suggest increased recurrence rates when patients undergoing SABR are administered corticosteroids. However, owing to limitations of retrospective analyses, individualized judgment is still recommended., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction/background: Many patients with early stage non-small-cell lung cancer (ES-NSCLC) undergoing stereotactic body radiation therapy (SBRT) develop metastases, which is associated with poor outcomes. We sought to identify factors predictive of metastases after lung SBRT and created a risk stratification tool., Materials and Methods: We included 363 patients with ES-NSCLC who received SBRT; the median follow-up was 5.8 years. The following patient and tumor factors were retrospectively analyzed for their association with metastases (defined as nodal and/or distant failure): gender; age; lobe involved; centrality; previous NSCLC; smoking status; gross tumor volume (GTV); T-stage; histology; dose; minimum, maximum, and mean GTV dose; and parenchymal lung failure. A metastasis risk-score linear-model using beta coefficients from a multivariate Cox model was built., Results: A total of 111 (27.3%) of 406 lesions metastasized. GTV and dose were significantly associated with metastases on univariate and multivariate Cox proportional hazards modeling (P < .001 and hazard ratio [HR], 1.02 per mL; P < .05 and HR, 0.99 per Gy, respectively). Histology, T-stage, centrality, lung parenchymal failures, and previous NSCLC were not associated with development of metastasis. A metastasis risk-score model using GTV and prescription dose was built: risk score = (0.01611 × GTV) - (0.00525 × dose [BED 10 ]). Two risk-score cutoffs separating the cohort into low-, medium-, and high-risk subgroups were examined. The risk score identified significant differences in time to metastases between low-, medium-, and high-risk patients (P < .001), with 3-year estimates of 81.1%, 63.8%, and 38%, respectively., Conclusion: GTV and radiation dose are associated with time to metastasis and may be used to identify patients at higher risk of metastasis after lung SBRT., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Stereotactic body radiation therapy (SBRT) is standard for medically inoperable stage I non-small-cell lung cancer (NSCLC) and is emerging as a surgical alternative in operable patients. However, limited long-term outcomes data exist, particularly according to operability. We hypothesized long-term local control (LC) and cancer-specific survival (CSS) would not differ by fractionation schedule, tumor size or location, or operability status, but overall survival (OS) would be higher for operable patients., Patients and Methods: All consecutive patients with stage I (cT1-2aN0M0) NSCLC treated with SBRT from June 2009 to July 2013 were assessed. Thoracic surgeon evaluation determined operability. Local failure was defined as growth following initial tumor shrinkage or progression on consecutive scans. LC, CSS, and OS were calculated using Cox proportional hazards regression., Results: A total of 186 patients (204 lesions) were analyzed. Most patients were inoperable (82%) with Eastern Cooperative Oncology Group performance status of 1 (59%) or 2 (26%). All lesions received biological effective doses ≥ 100 Gy most commonly (94%) in 3 to 5 fractions. The median follow-up was 4.0 years. LC at 2 and 5 years were 95.6% (95% confidence interval, 92%-99%) and 93.7% (95% confidence interval, 90%-98%), respectively. Compared with operable patients, inoperable patients did not have significant differences in 5-year LC (93.1% vs. 96.7%; P = .49), nodal failure (31.4% vs. 11.0%; P = .12), distant failure (12.2% vs. 10.4%; P = .98), or CSS (80.6% vs. 91.0%; P = .45) but trended towards worse OS (34.2% vs. 45.3%; P = .068). Tumor size, location, and fractionation did not significantly influence outcomes., Conclusions: SBRT has excellent, durable LC and CSS rates for early-stage NSCLC, although inoperable patients had somewhat lower OS than operable patients, likely owing to greater comorbidities., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Up to 15% of patients undergoing positron emission tomography (PET)/computed tomography (CT) before stereotactic body radiotherapy (SBRT) harbor occult nodal disease. In the absence of invasive mediastinal staging, the clinical significance of enlarged nonhypermetabolic lymph nodes (LNs) remains unclear. We performed what is to our knowledge the first study to address whether enlarged nonhypermetabolic LNs were associated with higher post-SBRT failure rates., Patients and Methods: Two academic centers assessed 157 consecutive patients treated with SBRT for cT1-2aN0M0 non-small-cell lung cancer who underwent PET/CT without pathologic nodal staging. The cutoff of an enlarged node was ≥ 1.0 cm, although a 7 mm threshold was also evaluated. Local recurrence-free survival (RFS), regional RFS, distant metastasis-free survival, RFS, and overall survival (OS) were calculated by Kaplan-Meier methodology. Multivariate Cox modeling addressed factors associated with RFS and OS., Results: There were 120 patients (76%) with LNs < 1 cm and 37 (24%) with nodes ≥ 1 cm. Most patients had peripheral and/or T1 tumors. Median follow-up was 25.5 months. There were no differences between cohorts in actuarial local RFS, regional RFS, distant metastasis-free survival, RFS, or OS (P > .05 for all). Thirteen percent of patients experienced any nodal relapse, 15% of which occurred in the same station as that of the largest pre-SBRT LN. Stratification by largest LN location in an N1 versus N2 station showed no differences in RFS or OS (P > .05 for both). A 7 mm cutoff also showed no differences in outcomes (P > .05 for all). LN size was not correlated with RFS/OS on multivariable analysis (P > .05 for both)., Conclusion: The presence of enlarged nonhypermetabolic LNs on PET/CT is not associated with increased post-SBRT failure rates., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To evaluate differences in outcomes of early-stage peripheral non-small-cell lung cancer (NSCLC) treated with either 3- or 5-fraction stereotactic body radiotherapy (SBRT) at 2 institutions., Patients and Methods: Patients diagnosed with peripherally located early-stage NSCLC who received either a median dose of 60 Gy (interquartile range [IQR], 60-60, biologically effective dose, 151-151) in 3 fractions or a median dose of 50 Gy (IQR, 50-50, biologically effective dose, 94-94) in 5 fractions were included in this study. All data were retrospectively collected and reviewed in an institutional review board-approved database., Results: A total of 192 lesions in 192 patients were identified: 94 received 3-fraction SBRT and 98 received 5-fraction SBRT. Patients in the 5-fraction cohort had significantly smaller tumors (P = .0021). Larger tumor size was associated with worse overall survival (hazard ratio, 1.40, P = .0013) for all patients. A single grade 3 toxicity was reported in each cohort. A propensity score-matched cohort of 94 patients was constructed with a median follow-up of 29.3 months (IQR, 17.3-44.6) for the 3-fraction cohort and 31.0 months (IQR, 17.0-48.5) for the 5-fraction cohort (P = .84). There were no statistically significant differences between these 2 cohorts in overall survival (P = .33), progression-free survival (P = .40), local failure (P = .86), and nodal or distant failure (P = .57) at 2 years., Conclusion: The 3- and 5-fraction SBRT regimens for early-stage peripheral NSCLC had comparable clinical outcomes. Both regimens were well tolerated. A large tumor size was an adverse prognostic factor for worse survival., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: To compare the clinical outcomes of patients with early-stage non-small-cell lung cancer (NSCLC) who had undergone either single-fraction (SF) or three-fraction (TF) stereotactic body radiation therapy (SBRT) at a single institution during over 8-year period., Patients and Methods: Patients with peripherally located early-stage NSCLC who had undergone SBRT from February 2007 to November 2015 were included in the present study. SBRT was delivered without heterogeneity correction. Data were retrospectively reviewed and collected in an institutional review board-approved database. R software (version 3.3.2) was used for statistical analysis., Results: Of 159 total lung tumors, 65 lesions received 30 Gy (median, 30 Gy) in 1 fraction, and 94 lesions received 48 to 60 Gy (median, 60 Gy) in 3 fractions. Patients with a Karnofsky performance status < 80 were more common in the SF-SBRT cohort (P = .050). After a median follow-up of 22.2 and 26.2 months for the SF-SBRT and TF-SBRT cohorts, respectively (P = .29), no statistically significant difference was found in overall survival (P = .86), progression-free survival (P = .95), local failure (P = .95), nodal failure (P = .91), and distant failure (P = .49) at 24 months. At 1 and 2 years, the overall survival rates were 86.1% and 63.2% for the SF-SBRT cohort and 80.8% and 61.6% for the TF-SBRT cohort, respectively. At 1 and 2 years, the local control rates were 95.1% and 87.8% for the SF-SBRT cohort and 92.7% and 86.2% for the TF-SBRT cohort, respectively. Both regimens were well tolerated., Conclusion: Despite more patients with poor performance status in the SF-SBRT cohort, the SF- and TF-SBRT regimens showed no differences in clinical outcomes. SF-SBRT is now our standard approach., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: Stereotactic body radiation therapy (SBRT) is now the standard of care in medically inoperable stage I NSCLC, yielding high rates of local control. It is unknown whether SBRT can be safely utilized in the locally advanced NSCLC setting. This multi-institution phase I study evaluated the safety of 44 Gy of conventionally fractionated thoracic radiation with concurrent chemotherapy plus dose-escalated SBRT boost to both the primary tumor and involved mediastinal lymph nodes. The primary end point of this study was to establish the maximum tolerated dose (MTD) of the SBRT boost., Methods: Inclusion criteria included unresectable stage IIIA or IIIB disease, primary tumor 8 cm or smaller, and N1 or N2 lymph nodes 5 cm or smaller. Tumors were staged with positron emission tomography/computed tomography (CT), and four-dimensional CT simulation was used for radiation planning. The treatment schema was 44 Gy of thoracic radiation (2 Gy/d) with weekly carboplatin and paclitaxel chemotherapy. A second CT simulation was obtained after 40 Gy had been delivered, and a SBRT boost was planned to the remaining gross disease at the primary site and involved mediastinal lymph nodes. Consolidation chemotherapy was given at the discretion of the treating medical oncologist. Four SBRT boost dose cohorts were tested: cohort 1 (9 Gy × 2), cohort 2 (10 Gy × 5), cohort 3 (6 Gy × 5), and cohort 4 (7 Gy × 5). Patients were treated in cohorts of three patients, and the Bayesian escalation with overdose control method was used to determine the MTD of the SBRT boost. Dose-limiting toxicities (DLTs) were defined as any grade 3 or higher toxicities within 30 days of treatment attributed to treatment, not including hematologic toxicity, or any grade 5 toxicity attributed to treatment., Results: The study enrolled 19 patients from November 2012 to December 2016. There were four screen failures, and 15 patients were treated on study. There were no DLTs in dose cohort 1 (n = 3) and 2 (n = 6). DLT developed in one patient in dose cohort 3 (n = 3) and in 2 patients in dose cohort 4 (n = 3). The calculated MTD was 6 Gy × 5. The DLT observed at this dose level was a tracheoesophageal fistula; given this substantial toxicity, there was investigator reluctance to enroll further patients at this dose level. Thus, the calculated MTD was 6 Gy × 5; however, 10 Gy × 2 is thought to be a reasonable dose as well, given that no grade 5 toxicities occurred with that dose., Conclusions: The MTD of a SBRT boost combined with 44 Gy of thoracic chemoradiation was 6 Gy × 5. A SBRT boost dose of 10 Gy × 2 could be considered safer, with no grade 3 or higher toxicities observed at this dose level during the follow-up period in this study., (Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: Although T1-T2N0 non-small cell lung cancer can be managed with stereotactic body radiotherapy (SBRT) alone, this management has often been extrapolated to T1-T2N0 small cell lung cancer (SCLC). This secondary analysis of a multi-institutional cohort study investigated whether the addition of chemotherapy and prophylactic cranial irradiation (PCI) improved the outcomes for these patients., Materials and Methods: All cases of histologically confirmed T1-T2N0M0 SCLC were obtained from 24 institutions' prospectively collected SBRT databases. The clinical and treatment characteristics, toxicities, outcomes, and patterns of failure were assessed. We used Kaplan-Meier analysis to evaluate the survival outcomes. Univariate and multivariate analyses identified the predictors of outcomes., Results: From 24 institutions, 76 lesions were treated in 74 patients (median follow-up, 18 months). Chemotherapy and PCI were delivered in 56% and 23% of cases, respectively. The median SBRT dose per fraction was 50 Gy/5 fractions. Patients receiving chemotherapy experienced increased median disease-free survival (61.3 vs. 9.0 months; P = .02) and overall survival (31.4 vs. 14.3 months; P = .02). Chemotherapy independently predicted for better outcomes for disease-free survival and overall survival on multivariate analysis (P = .01). Toxicities were uncommon; 5.2% experienced grade ≥ 2 pneumonitis. Post-treatment failures were most commonly distant (45.8% of recurrences), followed by nodal (25.0%), and elsewhere in the lung (20.8%). The median time to each was 5 to 7 months., Conclusion: Patients undergoing primary SBRT for T1-T2N0 SCLC should also undergo additional chemotherapy. No established role was found for PCI in this population., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Stereotactic ablative radiotherapy (SABR) is currently not the guideline-recommended treatment for lung tumors measuring more than 5 cm. However, improvements in radiotherapy techniques have led to increasing use of SABR for larger tumors., Methods: We analyzed the clinical outcomes in patients with a primary or recurrent NSCLC measuring more than 5 cm and treated with five or eight fractions of SABR at our center. Patients who had prior thoracic radiotherapy were excluded., Results: A total of 63 consecutive patients with a median tumor diameter of 5.8 cm (range 5.1-10.4) were identified; 81% had T2N0 disease and 18% had T3N0 disease. The median Charlson comorbidity index was 2 (range 0-6). After a median follow-up of 54.7 months, median survival was 28.3 months. Disease-free survival at 2 years was 82.1%, and the local, regional, and distant control rates at 2 years were 95.8%, 93.7%, and 83.6%, respectively. An out-of-field distant recurrence at one or more sites was the most common pattern of failure (10%). Grade 3 or higher toxicity was recorded in 30% of patients, with radiation pneumonitis being the most common toxicity (19%). A likely (n = 4) or possible (n = 8) treatment-related death was scored in 19% of patients. There was preexisting interstitial lung disease in eight patients (13%), with fatal toxicity developing in five of them (63%)., Conclusions: Lung SABR in tumors larger than 5 cm resulted in high local control rates and acceptable survival outcomes in a patient population with appreciable comorbidity. Patients with interstitial lung disease should be considered a very high-risk population for SABR., (Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Stereotactic body radiotherapy (SBRT) is an alternative to surgery for patients with early stage non-small cell lung cancer (NSCLC) who are inoperable due to comorbid disease or who refuse surgery. SBRT results in an excellent local control rate of more than 90%, which is comparable to surgery, while short and long-term overall toxicity is low. Surgically treated patients are often more extensively staged pre-operatively, e.g. with endobronchial ultrasound and/or mediastinoscopy, and typically undergo intra-operative lymph node dissection or sampling. Occult nodal metastases (ONM), detected by lymph node dissection, have been shown to increase the incidence of regional recurrence (RR) after surgery, which is associated with poor outcome. In patients undergoing SBRT, however, definite pathological nodal staging is lacking and so other ways to identify patients at high risk for ONM and RR are desirable. The aim of this systematic review is to summarize the incidence of, and risk factors for, RR after SBRT and compare these to those after surgery. The available evidence shows the incidence of RR after SBRT or surgery to be comparable, despite more elaborate pre- and intra-operative lymph node evaluation in surgical patients. However, the fact that this finding is based on mostly retrospective studies in which the majority of patients treated with SBRT were inoperable, needs to be taken into consideration. For now, there is no evidence that inoperable clinical stage I patients with no indication of pathological lymph nodes on PET/CT will benefit from more invasive lymph node staging prior to SBRT., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: The objective of this study was to determine the predictors and patterns of regional recurrence (RR) following stereotactic body radiotherapy (SBRT) for primary lung cancers., Material and Methods: Details of patient factors, treatment, and outcome factors were extracted from a multi-institutional (5) database. All events were calculated from the end of radiotherapy. Estimates of local recurrence, RR, and distant metastases (DM) were calculated using the competing risk method. Cause-specific and overall survival were calculated using the Kaplan-Meier method. Details of locations and number of simultaneous RRs were categorized by lymph node anatomic station., Results: A total of 734 patients were analyzed. The median follow-up was 3.0 years in surviving patients. Four hundred seventy-six (65%) patients had pathologic proof of disease. There were 64 patients with RR. The 2-year local recurrence, RR, and distant metastases rates were 5.6%, 9.0%, and 14.6% respectively. The 2-year cause-specific and overall survival were 89.9% and 63.7%, respectively. There were 136 simultaneous sites of RR. There were 21 recurrences in stations 4R (15.4%), 9 (6.6%) in 4L, 30 (22%) in 7, 19 (13.9%) in 10R, and 14 (10.3%) in 10L. The most common stations for isolated recurrence (n = 19) were station 7 (n = 5; 26.3%) and station 10R (n = 6; 31.6%). The most common RR levels were stations 4 and 7 for right and left upper lobe, stations 5, 7, and 10 for left lower lobe tumors, and stations 7 and 10 for right lower lobe tumors., Conclusion: Stations 4, 7, and 10 were the most common stations for RR. These patterns of recurrence may guide nodal staging procedures prior to SBRT., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: The objective of this study was to investigate fludeoxyglucose F 18 positron emission tomography/computed tomography ( 18 FDG-PET/CT) parameters as predictive of response after stereotactic ablative radiotherapy (SABR) for lung oligometastases., Methods: The inclusion criteria of the current retrospective study were as follows: (1) lung oligometastases treated by SABR, (2) presence of 18 FDG-PET/CT before and after SABR for at least two subsequent evaluations, (3) Karnofsky performance status higher than 80, and (4) life expectancy longer than 6 months. All patients were treated with a biologically equivalent dose of at least 100 Gy with an alpha/beta ratio of 10. The following metabolic parameters were semiquantitatively defined: maximum standardized uptake value (SUV max ), mean standardized uptake value (SUV mean ), metabolic tumor volume, and total lesion glycolysis., Results: A total of 50 patients met the inclusion criteria, for a total of 70 lung metastases. The pre-SABR median SUV max was 6.5 (range 4-17), the median SUV mean was 3.7 (range 2.5-6.5), and the median metabolic tumor volume was 2.3 cm 3 (0.2-31 cm 3 ). The following metabolic parameters were significantly related to complete response at 6 months: SUV max less than 5 (p < 0.001) and SUV mean less than 3.5 (p = 0.03). ΔSUV max at 3 to 6 months was +126% for lesions with in-field progression versus -26% for the remaining lesions (p = 0.002). ΔSUV mean at 3 to 6 months was +15% for lesions with in-field progression versus -26% for the remaining metastases (p = 0.008)., Conclusions: In the current analysis, complete response from lung metastasis at 6 months after stereotactic body radiation therapy was significantly associated with both the maximum and mean values of pre-SABR 18 FDG-PET/CT SUV. Longer-term trials are strongly advocated to improve the personalization of the monitoring of tumor response in patients with lung oligometastases and, consequently, monitoring of the cost-effectiveness of the health care., (Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Purpose: Stereotactic body radiation therapy (SBRT) is the standard of care for medically inoperable patients with early-stage NSCLC. However, NSCLC is composed of several histological subtypes and the impact of this heterogeneity on SBRT treatments has yet to be established., Methods: We analyzed 740 patients with early-stage NSCLC treated definitively with SBRT from 2003 through 2015. We calculated cumulative incidence curves using the competing risk method and identified predictors of local failure using Fine and Gray regression., Results: Overall, 72 patients had a local failure, with a cumulative incidence of local failure at 3 years of 11.8%. On univariate analysis, squamous histological subtype, younger age, fewer medical comorbidities, higher body mass index, higher positron emission tomography standardized uptake value, central tumors, and lower radiation dose were associated with an increased risk for local failure. On multivariable analysis, squamous histological subtype (hazard ratio = 2.4 p = 0.008) was the strongest predictor of local failure. Patients with squamous cancers fail SBRT at a significantly higher rate than do those with adenocarcinomas or NSCLC not otherwise specified, with 3-year cumulative rates of local failure of 18.9% (95% confidence interval [CI]: 12.7-25.1), 8.7% (95% CI: 4.6-12.8), and 4.1% (95% CI: 0-9.6), respectively., Conclusion: Our results demonstrate an increased rate of local failure in patients with squamous cell carcinoma. Standard approaches for radiotherapy that demonstrate efficacy for a population may not achieve optimal results for individual patients. Establishing the differential dose effect of SBRT across histological groups is likely to improve efficacy and inform ongoing and future studies that aim to expand indications for SBRT., (Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)