Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials

Chang, Joe Y.; Senan, Suresh; Paul, Marinus A.; Mehran, Reza J.; Louie, Alexander V.; Balter, Peter A; Groen, Harry J.M.; McRae, Stephen E.; Widder, Joachim; Feng, Lei; Borne, Ben E. E. M. van den; Munsell, Mark F.; Hurkmans, Coen; Berry, Donald A.; Werkhoven, Erik van; Kresl, John J.; Dingemans, Anne Marie C.; Dawood, Omar Thanoon; Haasbeek, Cornelis J.A.; Carpenter, L. Steven; Jaeger, Katrien De; Komaki, Ritsuko; Slotman, Ben J.; Smit, Egbert F.; Roth, Jack A.

doi:10.1016/s1470-2045(15)70168-3

Cited by 1,266 publications

(989 citation statements)

References 26 publications

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“…The evaluated proximal airways D 2 ranged from 0.3 to 5.0 Gy for the ITV+5 conventional delivery. The potential of OAR dose decrease makes MLC tracking an interesting option, especially considering that SBRT might become an alternative for surgery 37 in the near future. Decreasing toxicity of lung SBRT while maintaining the high control rate will make the therapy applicable to younger patients than currently exposed to the hypofractionated regiment.…”

Section: Discussionmentioning

confidence: 99%

Real‐time 4D dose reconstruction for tracked dynamic MLC deliveries for lung SBRT

et al. 2016

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PurposeThis study provides a proof of concept for real‐time 4D dose reconstruction for lung stereotactic body radiation therapy (SBRT) with multileaf collimator (MLC) tracking and assesses the impact of tumor tracking on the size of target margins.MethodsThe authors have implemented real‐time 4D dose reconstruction by connecting their tracking and delivery software to an Agility MLC at an Elekta Synergy linac and to their in‐house treatment planning software (TPS). Actual MLC apertures and (simulated) target positions are reported to the TPS every 40 ms. The dose is calculated in real‐time from 4DCT data directly after each reported aperture by utilization of precalculated dose‐influence data based on a Monte Carlo algorithm. The dose is accumulated onto the peak‐exhale (reference) phase using energy‐mass transfer mapping. To investigate the impact of a potentially reducible safety margin, the authors have created and delivered treatment plans designed for a conventional internal target volume (ITV) + 5 mm, a midventilation approach, and three tracking scenarios for four lung SBRT patients. For the tracking plans, a moving target volume (MTV) was established by delineating the gross target volume (GTV) on every 4DCT phase. These were rigidly aligned to the reference phase, resulting in a unified maximum GTV to which a 1, 3, or 5 mm isotropic margin was added. All scenarios were planned for 9‐beam step‐and‐shoot IMRT to meet the criteria of RTOG 1021 (3 × 18 Gy). The GTV 3D center‐of‐volume shift varied from 6 to 14 mm.ResultsReal‐time dose reconstruction at 25 Hz could be realized on a single workstation due to the highly efficient implementation of dose calculation and dose accumulation. Decreased PTV margins resulted in inadequate target coverage during untracked deliveries for patients with substantial tumor motion. MLC tracking could ensure the GTV target dose for these patients. Organ‐at‐risk (OAR) doses were consistently reduced by decreased PTV margins. The tracked MTV + 1 mm deliveries resulted in the following OAR dose reductions: lung V 20 up to 3.5%, spinal cord D 2 up to 0.9 Gy/Fx, and proximal airways D 2 up to 1.4 Gy/Fx.ConclusionsThe authors could show that for patient data at clinical resolution and realistic motion conditions, the delivered dose could be reconstructed in 4D for the whole lung volume in real‐time. The dose distributions show that reduced margins yield lower doses to healthy tissue, whilst target dose can be maintained using dynamic MLC tracking.

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Section: Discussionmentioning

confidence: 99%

Real‐time 4D dose reconstruction for tracked dynamic MLC deliveries for lung SBRT

et al. 2016

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“…18 Although SABR is currently funded only for patients deemed medically unfit for surgery, recently reported trials suggest that more patients may benefit from this approach in the future. 19 The UK SABR Consortium offers guidance on using SABR in a number of other tumour sites including liver metastases, prostate cancer and spinal metastases, 20 although treatment of these disease sites is not yet common practice.…”

Section: Stereotactic Radiation-a Novel Opportunity To Improve Radiotmentioning

confidence: 99%

Stereotactic ablative radiotherapy and immunotherapy combinations: turning the future into systemic therapy?

Walshaw¹,

Honeychurch²,

Illidge³

2016

BJR

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Radiotherapy (RT) is effective at cytoreducing tumours and until relatively recently the focus in radiobiology has been on the direct effects of RT on the tumour. Increasingly, however, the effect of RT on the tumour vasculature, tumour stroma and immune system are recognized as important to the overall outcome. RT is known to lead to the induction of immunogenic cell death (ICD), which can generate tumour-specific immunity. However, systemic immunity leading to "abscopal effects" resulting in tumour shrinkage outside of the RT treatment field is rare, which is thought to be caused by the immunosuppressive nature of the tumour microenvironment. Recent advances in understanding the nature of this immunosuppression and therapeutics targeting immune checkpoints such as programmed death 1 has led to durable clinical responses in a range of cancer types including malignant melanoma and non-small-cell lung cancer. The effects of RT dose and fraction on the generation of ICD and systemic immunity are largely unknown and are currently under investigation. Stereotactic ablative radiotherapy (SABR) provides an opportunity to deliver single or hypofractionated large doses of RT and potentially increase the amount of ICD and the generation of systemic immunity. Here, we review the interplay of RT and the tumour microenvironment and the rationale for combining SABR with immunomodulatory agents to generate systemic immunity and improve outcomes. THE INTERPLAY OF RADIOTHERAPY WITH THE TUMOUR MICROENVIRONMENTIt is estimated that radiotherapy (RT) is required in the treatment of over 50% of all patients with cancer. 1,2 The focus of radiobiology over previous decades has been on the direct cytoreductive effect that RT exerts on cancer cells by inducing DNA damage and only relatively recently have the effects of RT on tumour vasculature, stroma and the immune system received more attention. RT is known to have a number of effects on the generation of tumour-specific immunity, which include enhanced antigen release, expression of Natural killer receptor G2D (NKG2D) ligands, production of Type I Interferon (IFN) and complement, increased major histocompatibility complex and neoantigen expression and the induction of immunogenic cell death (ICD). [3][4][5][6][7][8][9]

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“…SBRT has been shown to provide effective local control with acceptable toxicity 3. It is the preferred treatment modality for medically inoperable stage I non‐small‐cell lung cancer (NSCLC) patients, and there is emerging evidence and investigation regarding its role for selected operable NSCLC patients,4, 5, 6 as well as for stage I small‐cell lung cancer patients 7, 8…”

Section: Introductionmentioning

confidence: 99%

Exploratory analysis using machine learning to predict for chest wall pain in patients with stage I non‐small‐cell lung cancer treated with stereotactic body radiation therapy

Chao

Valdés

Luna

et al. 2018

J Applied Clin Med Phys

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Background and purposeChest wall toxicity is observed after stereotactic body radiation therapy (SBRT) for peripherally located lung tumors. We utilize machine learning algorithms to identify toxicity predictors to develop dose–volume constraints.Materials and methodsTwenty‐five patient, tumor, and dosimetric features were recorded for 197 consecutive patients with Stage I NSCLC treated with SBRT, 11 of whom (5.6%) developed CTCAEv4 grade ≥2 chest wall pain. Decision tree modeling was used to determine chest wall syndrome (CWS) thresholds for individual features. Significant features were determined using independent multivariate methods. These methods incorporate out‐of‐bag estimation using Random forests (RF) and bootstrapping (100 iterations) using decision trees.ResultsUnivariate analysis identified rib dose to 1 cc < 4000 cGy (P = 0.01), chest wall dose to 30 cc < 1900 cGy (P = 0.035), rib Dmax < 5100 cGy (P = 0.05) and lung dose to 1000 cc < 70 cGy (P = 0.039) to be statistically significant thresholds for avoiding CWS. Subsequent multivariate analysis confirmed the importance of rib dose to 1 cc, chest wall dose to 30 cc, and rib Dmax. Using learning‐curve experiments, the dataset proved to be self‐consistent and provides a realistic model for CWS analysis.ConclusionsUsing machine learning algorithms in this first of its kind study, we identify robust features and cutoffs predictive for the rare clinical event of CWS. Additional data in planned subsequent multicenter studies will help increase the accuracy of multivariate analysis.

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Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials

Cited by 1,266 publications

References 26 publications

Real‐time 4D dose reconstruction for tracked dynamic MLC deliveries for lung SBRT

Real‐time 4D dose reconstruction for tracked dynamic MLC deliveries for lung SBRT

Stereotactic ablative radiotherapy and immunotherapy combinations: turning the future into systemic therapy?

Exploratory analysis using machine learning to predict for chest wall pain in patients with stage I non‐small‐cell lung cancer treated with stereotactic body radiation therapy

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