Stereotactic body radiotherapy (SBRT) pulmonary metastases

Study PI:

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

Dr. Juliane Hörner-Rieber
University Hospital Heidelberg
Juliane.Hoerner-Rieber@med.uni-heidelberg.de

Study design:

● Multicenter, international retrospective study

Study objective:

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

Project status:

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

Major findings and results:

Hörner-Rieber J, Bernhardt D, Blanck O, et al (2019) Long-term Follow-up and Patterns of Recurrence of Patients With Oligometastatic NSCLC Treated With Pulmonary SBRT. Clin Lung Cancer 20:e667–e677.
www.pubmed.ncbi.nlm.nih.gov/31327644/

  • The purpose of this multicenter study was to analyze outcome as well as early versus late patterns of recurrence following pulmonary SBRT for patients with oligometastatic NSCLC.
  • A total of 301 patients with oligometastatic NSCLC treated with SBRT for 336 lung metastases at 24 German and Swiss departments between 1997 and 2017 were included in the analysis.
  • Outside of prospective trials, SBRT for pulmonary oligometastatic NSCLC resulted in favorable LC and promising OS.
  • The dominant failure pattern was distant with a continuously high risk of disease progression for many years.
  • Although local recurrence rarely occurred after 2 years, with 3-year and 4-year local failure rates of only 4.0%, and 7.6%, the risk of distant progression remained high, with 3-and 4-year distant failure rates of 13.3% and 24.1% with no plateau observed.
  • Future studies therefore need to focus on the combination of local ablative therapy with more effective systemic treatments (eg, immunotherapy).

Klement RJ, Hoerner-Rieber J, Adebahr S, Andratschke N, Blanck O, Boda-Heggemann J, Duma M, Eble MJ, Eich HC, Flentje M, Gerum S, Hass P, Henkenberens C, Hildebrandt G, Imhoff D, Kahl KH, Klass ND, Krempien R, Lohaus F, Petersen C, Schrade E, Wendt TG, Wittig A, Guckenberger M.: Stereotactic body radiotherapy (SBRT) for multiple pulmonary oligometastases: Analysis of number and timing of repeat SBRT as impact factors on treatment safety and efficacy. Radiother Oncol. 2018 May;127(2)
www.ncbi.nlm.nih.gov/pubmed/29510865

  • Out of 637 patients, 145 patients were treated for multiple pulmonary metastases.
  • 88 patients received all SBRT treatments within one month whereas 57 patients were treated with repeat SBRT separated by at least one month.
  • Median OS for the total patient population was 23.5 months and OS was not significantly influenced by the overall number of SBRT treatments or the number and timing of repeat SBRT courses.
  • The risk of early death within 3 and 6 months was not increased in patients treated with multiple SBRT treatments, and no grade 4 or grade 5 toxicity was observed in these patients.

Tanadini-Lang S, Rieber J, Filippi AR et al. Overall survival prediction in stereotactic body radiotherapy for oligo-metastatic lung disease.
Radiother Oncol 2017, 123:182-188
www.ncbi.nlm.nih.gov/pubmed/28169042

  • A nomogram for prediction of overall survival after stereotactic body radiotherapy (SBRT) for pulmonary metastases was developed and externally validated.
  • A multi-institutional database of 670 patients treated with SBRT for pulmonary metastases was used as training cohort. Karnofsky performance index, type of the primary tumor, control of the primary tumor, maximum diameter of the largest treated metastasis and number of metastases (1 versus >1) were significant prognostic factors in the Cox model (all p < 0.05).
  • The calculated concordance-index for the nomogram was 0.73 (concordance indexes of all prognostic factors between 0.54 and 0.6). Based on the nomogram the training cohort was divided into 4 groups and 2-year OS ranged between 24.2% and 76.1% (predicted OS between 30.2% and 78.4%). The nomogram discriminated between risk groups in the two validation cohorts (concordance index 0.68 and 0.67) of 145 and 92 patients treated with SBRT for pulmonary metastases.
  • This tool might be helpful for interdisciplinary discussion and evaluation of local and systemic treatment options in the oligo-metastatic setting.

Hoerner-Rieber J, Duma M, Blanck O et al. Stereotactic Body Radiotherapy (SBRT) for pulmonary metastases from renal cell carcinoma- a multicenter analysis of the German working group ”Stereotactic Radiotherapy“. J Thorac Dis 2017

  • Renal cell carcinoma (RCC) is traditionally considered to be radioresitant.
  • Radioresistance was overcome by applying SBRT for pulmonary RCC oligo-metastases.
  • SBRT especially with BEDiso ≥ 130 Gy for pulmonary RCC metastases resulted in excellent local control with only minimal acute and late toxicity.
  • OS following pulmonary SBRT in RCC patients was comparable to surgical series.
  • SBRT is a valid treatment option for RCC patients with inoperable lung metastases.
  • Future studies are needed to evaluate the potential of SBRT in combination with target molecular agents and/or immunotherapy in the treatment of oligo-metastatic RCC patients.

Rieber J, Streblow J, Uhlmann L et al. Stereotactic body radiotherapy (SBRT) for medically inoperable lung metastases-A pooled analysis of the German working group "stereotactic radiotherapy". Lung Cancer 2016; 97: 51-58.
www.ncbi.nlm.nih.gov/pubmed/27237028

  • A total number of 700 patients with medically inoperable lung metastases treated with SBRT in 20 centers between 1997 and 2014 were included in the DEGRO AG database and used for analysis in this study.
  • After a median follow-up time of 14.3 months, 2-year local control and overall survival were 81.2% and 54.4%, respectively.
  • In multivariate analysis, overall survival was most significantly influenced by pretreatment performance status, maximum metastasis diameter, primary tumor histology, time interval between primary tumor diagnosis and SBRT treatment and number of metastases.
  • For local tumor control modelling, independent prognostic factors were pretreatment performance status, biological effective dose (BED) at PTV isocenter and single fraction (PTV-encompassing) dose in multivariate analysis.

Guckenberger M, Klement RJ, Allgauer M et al. Local tumor control probability modeling of primary and secondary lung tumors in stereotactic body radiotherapy. Radiother Oncol 2016; 118: 485-491.
www.ncbi.nlm.nih.gov/pubmed/26385265

  • A retrospective multi-institutional (n=22) database of 399 patients with stage I NSCLC and 397 patients with 525 lung metastases was analyzed.
  • After median follow-up of 19 months and 16 months (n.s.), local tumor control was observed in 87.7% and 86.7% of the primary and secondary lung tumors (n.s.), respectively.
  • A strong dose-response relationship was observed in the primary NSCLC and metastatic cohort but dose-response relationships were not significantly different: the TCD90 (dose to achieve 90% TCP; BED of maximum planning target volume dose) estimates were 176 Gy (151-223) and 160 Gy (123-237) (n.s.), respectively.
  • The dose-response relationship was not influenced by the primary cancer site within the metastatic cohort.

Klement RJ, Allgauer M, Andratschke N et al. Bayesian Cure Rate Modeling of Local Tumor Control: Evaluation in Stereotactic Body Radiation Therapy for Pulmonary Metastases. Int J Radiat Oncol Biol Phys 2016; 94: 841-849.
www.ncbi.nlm.nih.gov/pubmed/26972657

  • Most radiobiological models for prediction of tumor control probability (TCP) do not account for the fact that many events could remain unobserved because of censoring. We therefore evaluated a set of TCP models that take into account this censoring.
  • We applied 2 fundamental Bayesian cure rate models to a sample of 770 pulmonary metastasis treated with stereotactic body radiation therapy at German, Austrian, and Swiss institutions: (1) the model developed by Chen, Ibrahim and Sinha (the CIS99 model); and (2) a mixture model similar to the classic model of Berkson and Gage (the BG model).
  • In the CIS99 model the number of clonogens surviving the radiation treatment follows a Poisson distribution, whereas in the BG model only 1 dominant recurrence-competent tissue mass may remain.
  • Delivered dose, female sex, peripheral tumor location and having received no chemotherapy before RT were associated with higher TCP in all models.
  • In practice, application of such models to the clinical setting could allow for adaption of treatment doses depending on whether local control should be achieved in the short or longer term.

Rieber J, Abbassi-Senger N, Adebahr S et al. Influence of Institutional Experience and Technological Advances on Outcome of Stereotactic Body Radiation Therapy for Oligometastatic Lung Disease. Int J Radiat Oncol Biol Phys 2016.
www.ncbi.nlm.nih.gov/pubmed/27843031

  • A database of 700 patients treated with SBRT for lung metastases in 20 centers between 1997 and 2014 was used for analysis.
  • Median follow-up time was 14.3 months (maximum 132 months), with 2-year LC and OS of 81.2% and 54.4%, respectively.
  • In multivariate analysis, all treatment technologies except FDG-PET staging did not significantly influence outcome. Patients who received pre-SBRT FDG-PET staging showed superior 1- and 2-year OS of 82.7% and 64.8%, compared with patients without FDG-PET staging resulting in 1- and 2-year OS rates of 72.8% and 52.6%, respectively (P=.012).
  • Experience with SBRT was identified as the main prognostic factor for LC: institutions with higher SBRT experience (patients treated with SBRT within the last 2 years of the inclusion period) showed superior LC compared with less-experienced centers (P≤.001). Experience with SBRT within the last 2 years was independent from known prognostic factors for LC.

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