Stereotactic body radiotherapy (SBRT) for early stage non-small cell lung cancer (NSCLC)

Study PI:

Prof. Dr. Matthias Guckenberger
University Hospital Zurich
Matthias.Guckenberger@usz.ch

Study design:

● multi-center, international retrospective study

Study objective:

● To perform a patterns-of-care and patterns-of-outcome analysis of SBRT for early stage NSCLC in Germany, Austria and Switzerland
● To evaluate patient and treatment factor influencing outcome in SBRT for early stage NSCLC

Project status:

  • Data collection completed
  • 6 full manuscripts published
  • Project closed

Major findings and results:

John C, Dal Bello R, Andratschke N, et al (2021) In-field stereotactic body radiotherapy (SBRT) reirradiation for pulmonary malignancies as a multicentre analysis of the German Society of Radiation Oncology (DEGRO). Sci Rep. 2021;11(1):4590. https://pubmed.ncbi.nlm.nih.gov/33633130/

  • Aim of this study was to investigate feasibility and safety of a thoracic in-field reirradiation with two courses of SBRT
  • All plans and clinical data were centrally collected. 27 patients from 8 centers have been amenable for evaluation
  • A median dose of 38.5 Gy to the 65%-isodose over a median of 5 fractions was prescribed in the first course and 40 Gy in 5 fractions for the second SBRT-course
  • Median PTV of the second SBRT was 29.5 cm3, median PTV overlap 22 cm3
  • With a median interval of 20.2 months between the two SBRT-courses, 1-year OS, and -LCR were 78.3% and 70.3% respectively.
  • 3 patients developed grade 1 and one grade 2 pneumonitis. No grade > 2 toxicity was observed.
  • Peripheral location and dose were the only factors correlating with tumor control
  • A second SBRT-course with PTV overlap appears safe and achieves reasonable local control

Klement RJ, Sonke J-J, Allgäuer M, et al (2020) Correlating Dose Variables with Local Tumor Control in Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer: A Modeling Study on 1500 Individual Treatments. Int J Radiat Oncol Biol Phys 107:579–586.
www.pubmed.ncbi.nlm.nih.gov/32188579/

  • 1500 individual SBRT treatments of early-stage NSCLC were analysed retrospectively in order to correlate dose distribution patterns with local control
  • Minimum, maximum, and average biologically equivalent doses were assessed within the planning target volume
  • Median follow-up 20.7 months
  • Of 1500 treatments in 1434 patients, 117 tumors recurred locally resulting in a local control rate of 96.8% and 89.0% at 12 and 36 months, respectively
  • The average biologically equivalent dose correlated best with local tumor control
  • The average biologically equivalent dose correlated strongly with the mean gross tumor volume dose. Hence, adequate dose coverage of the gross tumor volume may be emphasised compared to dose coverage of the planning target volume

Roesch J, Panje C, Sterzing F et al. SBRT for centrally localized NSCLC - What is too central? Radiat Oncol 2016; 11: 157.
www.ncbi.nlm.nih.gov/pubmed/27912764

  • A survey performed at the annual meeting of the DEGRO working group Stereotactic radiotherapy evaluated patterns-of-practice of SSBRT for centrally located NSCLC. The surgery consisted of a questionnaire and nine case examples.
  • The majority of centers had experience in SBRT for central lung tumors (88%) and half of the centers reported more than ten cases treated during a median period of five years.
  • Most fractionation schedules used PTV encompassing doses of 48-60 Gy in eight fractions with maximum doses of 125-150%.
  • SBRT for centrally located NSCLC would have been practice by the large majority of the centers if the tumors were small (<4 cm) and if the minimal distance to the main bronchi was at least 2 cm.

Schanne DH, Nestle U, Allgauer M et al. Stereotactic body radiotherapy for centrally located stage I NSCLC: a multicenter analysis. Strahlenther Onkol 2015; 191: 125-132. www.ncbi.nlm.nih.gov/pubmed/25159135

  • A total of 90 patients treated with SBRT for centrally located NSCLC were identified among 613 cases in a database of 13 German and Austrian academic radiotherapy centers.
  • SBRT doses (PTV minimum doses converted to BED) varied significantly between central and peripheral lesions with a median BED10 of 72 Gy and 84 Gy, respectively (p < 0.001). Fractionation differed as well with medians of 5 (central) and 3 (peripheral) fractions (p < 0.001).
  • In the Kaplan-Meier analysis, 3-year actuarial overall survival was 29 % (central) and 51 % (peripheral; p = 0.004) and freedom from local progression was 52 % (central) and 84 % (peripheral; p < 0.001). Toxicity after treatment of central tumors was low with no grade III/IV and one grade V event.

Klement RJ, Allgauer M, Appold S et al. Support vector machine-based prediction of local tumor control after stereotactic body radiation therapy for early-stage non-small cell lung cancer. Int J Radiat Oncol Biol Phys 2014; 88: 732-738.
www.ncbi.nlm.nih.gov/pubmed/24411630

  • Local tumor control probability (TCP) modeling confirmed that machine learning techniques like support vector machines can be successfully applied to predict treatment outcome after SBRT for early stage NSCLC.
  • Improvements over traditional TCP modeling are expected through a nonlinear combination of multiple features, eventually helping in the task of personalized treatment planning.

Guckenberger M, Allgauer M, Appold S et al. Safety and Efficacy of Stereotactic Body Radiotherapy for Stage I Non-Small-Cell Lung Cancer in Routine Clinical Practice: A Patterns-of-Care and Outcome Analysis. J Thorac Oncol 2013; 8: 1050-1058.
www.ncbi.nlm.nih.gov/pubmed/23817193

  • Data of 582 patients treated at 13 institutions between 1998 and 2011 were collected.
  • After an average follow-up of 21 months, 3-year freedom from local progression and overall survival were 79.6% and 47.1%, respectively.
  • After treatment with > 106 Gy biological effective dose (BED) as planning target volume encompassing dose (N = 164), 3-year freedom from local progression and overall survival were 92.5% and 62.2%, respectively.

Guckenberger M, Klement RJ, Allgauer M et al. Applicability of the linear-quadratic formalism for modeling local tumor control probability in high dose per fraction stereotactic body radiotherapy for early stage non-small cell lung cancer. Radiother Oncol 2013; 109: 13-20.
www.ncbi.nlm.nih.gov/pubmed/24183066

  • Local tumor control probability (TCP) modeling showed strong evidence for a dose-response relationship in the total patient cohort, which was lacking in single-fraction SBRT.
  • PTV isocentric doses resulted in much better dose-response relationships than PTV encompassing doses.
  • The use of the linear-quadratic (LQ) model for calculation of biological effective doses (BED) was not inferior to the linear-quadratic linear (LQ-L) model.

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