Artificial intelligence-assisted quantitative CT analysis of airway changes following SABR for central lung tumors.

INTRODUCTION: Use of stereotactic ablative radiotherapy (SABR) for central lung tumors can result in up to a 35% incidence of late pulmonary toxicity. We evaluated an automated scoring method to quantify post-SABR bronchial changes by using artificial intelligence (AI)-based airway segmentation. MATERIALS AND METHODS: Central lung SABR patients treated at Amsterdam UMC (AUMC, internal reference dataset) and Peter MacCallum Cancer Centre (PMCC, external validation dataset) were identified. Patients were eligible if they had pre- and post-SABR CT scans with ≤ 1 mm resolution. The first step of the automated scoring method involved AI-based airway auto-segmentation using MEDPSeg, an end-to-end deep learning-based model. The Vascular Modeling Toolkit in 3D Slicer was then used to extract a centerline curve through the auto-segmented airway lumen, and cross-sectional measurements were computed along each bronchus for all CT scans. For AUMC patients, airway stenosis/occlusion was evaluated by both visual assessment and automated scoring. Only the automated method was applied to the PMCC dataset. RESULTS: Study patients comprised 26 from AUMC, and 33 from PMCC. Visual scoring identified stenosis/occlusion in 8 AUMC patients (31 %), most frequently in the segmental bronchi. After airway auto-segmentation, minor manual edits were needed in 9 % of patients. Segmentation for a single scan averaged 83sec (range 73-136). Automated scoring nearly doubled detected airway stenosis/occlusion (n = 15, 58 %), and allowed for earlier detection in 5/8 patients who had also visually scored changes. Estimated rates were 48 % and 66 % at 1- and 2-years, respectively, for the internal dataset. The automated detection rate was 52 % in the external dataset, with 1- and 2-year risks of 56 % and 61 %, respectively. CONCLUSION: An AI-based automated scoring method allows for detection of more bronchial stenosis/occlusion after lung SABR, and at an earlier time-point. This tool can facilitate studies to determine early airway changes and establish more reliable airway tolerance doses.

Evaluation of chest CT-scans following lung stereotactic ablative radiotherapy: Challenges and new insights.

Stereotactic ablative radiotherapy (SABR) is increasingly used for the treatment of early-stage non-small cell lung cancer (ES-NSCLC) and for pulmonary metastases. In patients with ES-NSCLC, SABR is highly successful with reported 5-year local control rates of approximately 90%. However, the assessment of local control following lung SABR can be challenging as radiological changes arising from radiation-induced lung injury (RILI) can be observed in up to 90% of patients. These so-called 'benign' radiological changes evolve with time and are often asymptomatic. Several radiological and metabolic features have been explored to help distinguish RILI from local recurrences (LR). These include the Response Evaluation Criteria for Solid Tumors (RECIST), high-risk features (HRF's) and maximum standardized uptake value (SUVmax) on FDG-PET-CT. However, use of some of these approaches have poor predictive values and low specificity for recurrence. A proposed new workflow for the evaluation of post-lung SABR radiological changes will be reviewed which uses the presence of so-called 'actionable radiological features' to trigger changes to imaging schedules and identifies the need for a multidisciplinary board review. Furthermore, this critical review of post-lung SABR imaging will highlight current challenges, new insights, and unknowns in this field.

Neoadjuvant and Adjuvant Treatment for Early-Stage Resectable Non-small Cell Lung Cancer (NSCLC): Consensus Recommendations from the International Association for the Study of Lung Cancer (IASLC).

Advances in the multidisciplinary care of early-stage resectable non-small cell lung cancer (rNSCLC) are emerging at an unprecedented pace. Numerous phase 3 trials produced results that have transformed patient outcomes for the better, yet these findings also require important modifications to the patient treatment journey trajectory and re-organization of care pathways. Perhaps most notably, the need for multispecialty collaboration for this patient population has never been greater. These rapid advances have inevitably left us with important gaps in knowledge for which definitive answers will only become available in several years. To this end, the IASLC commissioned a diverse multidisciplinary international expert panel to evaluate the current landscape and provide diagnostic, staging, and therapeutic recommendations for patients with rNSCLC, with particular emphasis on patients with AJCC/UICC TNM 8th edition stage II and III disease. Using a team-based approach, we generated 19 recommendations, of which all but one achieved greater than 85% consensus amongst panel members. A public voting process was initiated, which successfully validated and provided qualitative nuance to our recommendations. Highlights include: 1) the critical importance of a multidisciplinary approach to the evaluation of patients with rNSCLC driven by shared clinical decision making of a multispecialty team of expert providers; 2) biomarker testing for rNSCLC; 3) a preference for neoadjuvant chemoimmunotherapy for stage III rNSCLC; 4) equipoise regarding the optimal management of patients with stage II between up-front surgery followed by adjuvant therapy and neoadjuvant/perioperative strategies; and 5) the robust preference for adjuvant targeted therapy for patients with rNSCLC and sensitizing EGFR and ALK tumor alterations. Our primary goals were to provide practical recommendations sensitive to the global differences in biology and resources for patients with rNSCLC, and to provide expert consensus guidance tailored to the individualized patient needs, goals, and preferences in their cancer care journey as these are areas where physicians must make daily clinical decisions in the absence of definitive data. These recommendations will continue to evolve as the treatment landscape for rNSCLC expands and more knowledge is acquired on the best therapeutic approach in specific patient and disease subgroups.

Optimal management of radiation pneumonitis: Findings of an international Delphi consensus study.

PURPOSE: Radiation pneumonitis (RP) is a dose-limiting toxicity for patients undergoing radiotherapy (RT) for lung cancer, however, the optimal practice for diagnosis, management, and follow-up for RP remains unclear. We thus sought to establish expert consensus recommendations through a Delphi Consensus study. METHODS: In Round 1, open questions were distributed to 31 expert clinicians treating thoracic malignancies. In Round 2, participants rated agreement/disagreement with statements derived from Round 1 answers using a 5-point Likert scale. Consensus was defined as ≥ 75 % agreement. Statements that did not achieve consensus were modified and re-tested in Round 3. RESULTS: Response rate was 74 % in Round 1 (n = 23/31; 17 oncologists, 6 pulmonologists); 82 % in Round 2 (n = 19/23; 15 oncologists, 4 pulmonologists); and 100 % in Round 3 (n = 19/19). Thirty-nine of 65 Round 2 statements achieved consensus; a further 10 of 26 statements achieved consensus in Round 3. In Round 2, there was agreement that risk stratification/mitigation includes patient factors; optimal treatment planning; the basis for diagnosis of RP; and that oncologists and pulmonologists should be involved in treatment. For uncomplicated radiation pneumonitis, an equivalent to 60 mg oral prednisone per day, with consideration of gastroprotection, is a typical initial regimen. However, in this study, no consensus was achieved for dosing recommendation. Initial steroid dose should be administered for a duration of 2 weeks, followed by a gradual, weekly taper (equivalent to 10 mg prednisone decrease per week). For severe pneumonitis, IV methylprednisolone is recommended for 3 days prior to initiating oral corticosteroids. Final consensus statements included that the treatment of RP should be multidisciplinary, the uncertainty of whether pneumonitis is drug versus radiation-induced, and the importance risk stratification, especially in the scenario of interstitial lung disease. CONCLUSIONS: This Delphi study achieved consensus recommendations and provides practical guidance on diagnosis and management of RP.

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

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

Challenges and controversies in resectable non-small cell lung cancer: a clinician's perspective.

The treatment landscape of resectable early-stage non-small cell lung cancer (NSCLC) is transforming due to the approval of novel adjuvant and neoadjuvant systemic treatments. The European Medicines Agency (EMA) recently approved adjuvant osimertinib, adjuvant atezolizumab, adjuvant pembrolizumab, and neoadjuvant nivolumab combined with chemotherapy, and the approval of other agents or new indications may follow soon. Despite encouraging results, many unaddressed questions remain. Moreover, the transformed treatment paradigm in resectable NSCLC can pose major challenges to healthcare systems and magnify existing disparities in care as differences in reimbursement may vary across different European countries. This Viewpoint discusses the challenges and controversies in resectable early-stage NSCLC and how existing inequalities in access to these treatments could be addressed.

New systemic treatment paradigms in resectable non-small cell lung cancer and variations in patient access across Europe.

The treatment landscape of resectable early-stage non-small cell lung cancer (NSCLC) is set to change significantly due to encouraging results from randomized trials evaluating neoadjuvant and adjuvant immunotherapy, as well as adjuvant targeted therapy. As of January 2024, marketing authorization has been granted for four new indications in Europe, and regulatory approvals for other study regimens are expected. Because cost-effectiveness and reimbursement criteria for novel treatments often differ between European countries, access to emerging developments may lead to inequalities due to variations in recommended and available lung cancer care throughout Europe. This Series paper (i) highlights the clinical studies reshaping the treatment landscape in resectable early-stage NSCLC, (ii) compares and contrasts approaches taken by the European Medicines Agency (EMA) for drug approval to that taken by the United States Food and Drug Administration (FDA), and (iii) evaluates the differences in access to emerging treatments from an availability perspective across European countries.

First exploration of the on-treatment changes in tumor and organ uptake of a radiolabeled anti PD-L1 antibody during chemoradiotherapy in patients with non-small cell lung cancer using whole body PET.

BACKGROUND: In patients with locally advanced unresectable non-small cell lung cancer (NSCLC), durvalumab, an anti-programmed cell death ligand-1 (PD-L1) antibody, has shown improved overall survival when used as consolidation therapy following concurrent chemoradiotherapy (CRT). However, it is unclear whether CRT itself upregulates PD-L1 expression. Therefore, this study aimed to explore the changes in the uptake of the anti PD-L1 antibody [89Zr]Zr-durvalumab in tumors and healthy organs during CRT in patients with NSCLC. METHODS: Patients with NSCLC scheduled to undergo CRT were scanned 7±1 days after administration of 37±1 MBq [89Zr]Zr-durvalumab at baseline, 1-week on-treatment and 1 week after finishing 6 weeks of CRT. First, [89Zr]Zr-durvalumab uptake was visually assessed in a low dose cohort with a mass dose of 2 mg durvalumab (0.13% of therapeutic dose) and subsequently, quantification was done in a high dose cohort with a mass dose of 22.5 mg durvalumab (1.5% of therapeutic dose). Tracer pharmacokinetics between injections were compared using venous blood samples drawn in the 22.5 mg cohort. Visual assessment included suspected lesion detectability. Positron emission tomography (PET) uptake in tumoral and healthy tissues was quantified using tumor to plasma ratio (TPR) and organ to plasma ratio, respectively. RESULTS: In the 2 mg dose cohort, 88% of the 17 identified tumor lesions were positive at baseline, compared with 69% (9/13) for the 22.5 mg cohort. Although the absolute plasma concentrations between patients varied, the intrapatient variability was low. The ten quantitatively assessed lesions in the 22.5 mg cohort had a median TPR at baseline of 1.3 (IQR 0.7-1.5), on-treatment of 1.0 (IQR 0.7-1.4) and at the end of treatment of 0.7 (IQR 0.6-0.7). On-treatment, an increased uptake in bone marrow was seen in three out of five patients together with a decreased uptake in the spleen in four out of five patients. CONCLUSIONS: This study successfully imaged patients with NSCLC with [89Zr]Zr-durvalumab PET before and during CRT. Our data did not show any increase in [89Zr]Zr-durvalumab uptake in the tumor 1-week on-treatment and at the end of treatment. The changes observed in bone marrow and spleen may be due to an CRT-induced effect on immune cells. TRIAL REGISTRATION NUMBER: EudraCT number: 2019-004284-51.

Distinguishing recurrence from radiation-induced lung injury at the time of RECIST progressive disease on post-SABR CT scans using radiomics.

Stereotactic ablative radiotherapy (SABR) is a highly effective treatment for patients with early-stage lung cancer who are inoperable. However, SABR causes benign radiation-induced lung injury (RILI) which appears as lesion growth on follow-up CT scans. This triggers the standard definition of progressive disease, yet cancer recurrence is not usually present, and distinguishing RILI from recurrence when a lesion appears to grow in size is critical but challenging. In this study, we developed a tool to do this using scans with apparent lesion growth after SABR from 68 patients. We performed bootstrapped experiments using radiomics and explored the use of multiple regions of interest (ROIs). The best model had an area under the receiver operating characteristic curve of 0.66 and used a sphere with a diameter equal to the lesion's longest axial measurement as the ROI. We also investigated the effect of using inter-feature and volume correlation filters and found that the former was detrimental to performance and that the latter had no effect. We also found that the radiomics features ranked as highly important by the model were significantly correlated with outcomes. These findings represent a key step in developing a tool that can help determine who would benefit from follow-up invasive interventions when a SABR-treated lesion increases in size, which could help provide better treatment for patients.

Sub-lobar resections for peripheral non-small cell lung cancer measuring ≤ 2 cm: Insights from recent clinical trials.

The findings of two well conducted trials that randomised 1803 patients with a peripheral non-small cell lung cancer measuring ≤ 2 cm to a lobar to sub-lobar resection have established the latter as a new standard of care. It is important for non-surgical oncologists to appreciate the details of study design and outcomes of both studies, given the possible impact they have for considerations of stereotactic ablative radiotherapy (SABR) for operable patients with early-stage NSCLC. Differences in overall survival between the study populations highlight the impact of confounding factors like smoking history and comorbidities on reported outcomes. For example, despite low post-operative mortality rates in both trials, the 5-year disease-free survival rate in the CALGB 140503 trial was only approximately 60 % with either surgical procedure. Both phase III trials required guideline recommended nodal staging, which does not reflect real world surgical practice, and which may limit the generalisability of the reported findings to local institutional outcomes. Furthermore, the emergence of other malignancies was recorded in 15-18 % of study patients during follow-up, and patients who underwent sub-lobar resections had a better long-term survival associated with a higher likelihood of undergoing additional curative treatments. These findings from the JCOG0802 and the CALGB 140503 will encourage more interest in enrolling patients into ongoing trials comparing surgical resection with SABR.

Superior Sulcus Tumors Invading the Spine: Multimodal Treatment Outcomes From the Preimmunotherapy Era.

Introduction: Curative-intent treatment of superior sulcus tumors (SSTs) of the lung invading the spine presents considerable challenges. We retrospectively studied outcomes in a single center, uniformly staged patient cohort treated with induction concurrent chemoradiotherapy followed by surgical resection (trimodality therapy). Methods: An institutional surgical database from the period between 2002 and 2021 was accessed to identify SSTs in which the resection included removal of at least part of the vertebral body. All patients were staged using fluorodeoxyglucose positron emission tomography (/computed tomography), computed tomography scan of the chest/upper abdomen, and brain imaging. Surgical morbidity was assessed using the Clavien-Dindo classification. Overall and disease-free survival were calculated using the Kaplan-Meier method. Results: A total of 18 patients were included: 8 complete and 10 partial vertebrectomies were performed, with six of the eight complete vertebrectomies involving two vertebral levels, resulting in Complete surgical resection (R0) in 94%. Nine patients had a 1-day procedure, and nine were staged over 2 days. The median follow-up was 30 months (interquartile range 11-57). The 90-day postoperative morbidity was 44% (grade III/IV), with no 90-day surgery-related mortality. There were 83% who had a major pathologic response, associated with improved survival (p = 0.044). The 5-year overall and disease-free survival were 55% and 40%, respectively. Disease progression occurred in 10 patients, comprising locoregional recurrences in two and distant metastases in eight patients. Conclusions: Multimodality treatment in selected patients with a superior sulcus tumor invading the spine is safe and results in good survival. Such patients should be referred to expert centers. Future research should focus on improving distant control (e.g. [neo]adjuvant immunotherapy).

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

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

Ten years outcomes after SABR in central and ultracentral primary lung tumors.

PURPOSE: SABR performed for central and ultracentral lung tumors is associated with increased toxicity but limited data is available on late toxicities. We studied toxicity in patients followed-up ≥ 2 years post-SABR at a single-institution. METHODS: All patients were treated using VMAT for a primary or recurrent central lung cancer between 2008-2015. 60 Gy was delivered in 8 or 12 fractions. Grade ≥ 3 clinical and radiological bronchial toxicity was scored. Multivariable Cox regression models were used to estimate hazard ratios. RESULTS: Of 127 eligible patients, 63% were treated with 8 fractions. Median tumor diameter was 4.4 cm (range 1.3-12.0). Median overall survival was 25.0 months (95% CI 16.5-33.5); 4% developed isolated local recurrences. The actuarial 5-year rate for severe clinical toxicity was 34.1% (95% CI 21.2-44.9). Both clinical toxicity and fatal lung haemorrhage were most observed when tumors were located ≤ 1 cm from the trachea or main bronchi (46% of all cases). The 5-year actuarial rate of radiological bronchial toxicity was 37.5% (95% CI 21.5-50.2). Multivariable analysis revealed that a performance score of 2 or 3 (HR 3.6; 95% CI 1.7-7.8), and tumor location ≤ 1 cm from the trachea or main bronchi (HR 4.3; 95% CI 1.2-14.9) were significant predictors for severe clinical toxicity. CONCLUSION: The actuarial rates for both severe clinical and radiological bronchial toxicity after central SABR was approximately 35% in patients surviving 5 years. Patients with tumors located ≤ 1 cm from the trachea or main bronchus were at the highest risk for severe clinical toxicity.

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

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

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

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

Treatment of Oligometastatic Non-Small Cell Lung Cancer: An ASTRO/ESTRO Clinical Practice Guideline.

PURPOSE: This joint guideline by American Society for Radiation Oncology (ASTRO) and the European Society for Radiotherapy and Oncology (ESTRO) was initiated to review evidence and provide recommendations regarding the use of local therapy in the management of extracranial oligometastatic non-small cell lung cancer (NSCLC). Local therapy is defined as the comprehensive treatment of all known cancer-primary tumor, regional nodal metastases, and metastases-with definitive intent. METHODS: ASTRO and ESTRO convened a task force to address 5 key questions focused on the use of local (radiation, surgery, other ablative methods) and systemic therapy in the management of oligometastatic NSCLC. The questions address clinical scenarios for using local therapy, sequencing and timing when integrating local with systemic therapies, radiation techniques critical for oligometastatic disease targeting and treatment delivery, and the role of local therapy for oligoprogression or recurrent disease. Recommendations were based on a systematic literature review and created using ASTRO guidelines methodology. RESULTS: Based on the lack of significant randomized phase 3 trials, a patient-centered, multidisciplinary approach was strongly recommended for all decision-making regarding potential treatment. Integration of definitive local therapy was only relevant if technically feasible and clinically safe to all disease sites, defined as 5 or fewer distinct sites. Conditional recommendations were given for definitive local therapies in synchronous, metachronous, oligopersistent, and oligoprogressive conditions for extracranial disease. Radiation and surgery were the only primary definitive local therapy modalities recommended for use in the management of patients with oligometastatic disease, with indications provided for choosing one over the other. Sequencing recommendations were provided for systemic and local therapy integration. Finally, multiple recommendations were provided for the optimal technical use of hypofractionated radiation or stereotactic body radiation therapy as definitive local therapy, including dose and fractionation. CONCLUSIONS: Presently, data regarding clinical benefits of local therapy on overall and other survival outcomes is still sparse for oligometastatic NSCLC. However, with rapidly evolving data being generated supporting local therapy in oligometastatic NSCLC, this guideline attempted to frame recommendations as a function of the quality of data available to make decisions in a multidisciplinary approach incorporating patient goals and tolerances.

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

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

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

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