Skip to main content

Advertisement

SpringerLink
Log in

Stereobody radiotherapy for nodal recurrences in oligometastatic patients: a pooled analysis from two phase I clinical trials

  • Research Paper
  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Abstract

Stereotactic body radiotherapy (SBRT) has been shown to achieve high local control rates in limited metastatic burden of disease. Few papers reported on the efficacy of SBRT in nodal oligometastases. The primary aim of the present paper was to analyze the treatment outcome in this setting. Data from DESTROY-1 and SRS-DESTROY-2 phase I clinical trials were reviewed and analyzed. These trials were based on a 5 fractions and a single fraction regimens, respectively. End-points of this analysis were toxicity rates, overall response rate (ORR), and local control (LC). Patients treated between December 2003 and January 2018, with any metastatic site, and primary tumor type and histology were included. One hundred-eighty-one patients (M/F: 93/88; median age: 67, range 37–88) treated with SBRT on 253 nodal lesions were analyzed. Initially, the used technique was 3D-CRT (20.9%), while subsequently treatments were delivered by VMAT (79.1%). The total dose to the PTV ranged between 12 Gy/single fraction to 50 Gy/5 fractions. With a median follow-up of 21 months (2–124), no grade 3 acute or late toxicity was recorded. ORR based on functional imaging was 92.5% with a complete response rate of 76%. Two- and three-year actuarial LC were 81.6% and 76.0%, respectively. Our large pooled analysis confirms the efficacy and safety of SBRT/SRS in patients with nodal metastases and identifies clinical and treatment variables able to predict complete response and local control rate.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

SBRT:

Stereotactic body radiotherapy

RT:

Radiotherapy

LC:

Local control

MTD:

Maximum tolerated dose

SRS:

Stereotactic radio-surgery

3D-CRT:

3-Dimensional conformal radiotherapy

VMAT:

Volumetric modulated arc therapy

ECOG:

Eastern cooperative oncology group

SBF:

Stereotactic body frame

GTV:

Gross tumor volume

CT:

Computer tomography

PET:

Positron emission tomography

MRI:

Magnetic resonance imaging

CTV:

Clinical target volume

PTV:

Planning target volume

BED:

Biologic effective dose

ORR:

Overall response rate

CR:

Complete response

PR:

Partial response

CB:

Clinical benefit

SD:

Stable disease

MFS:

Metastases free-survival

PFS:

Progression free-survival

OS:

Overall survival

References

  1. Guckenberger M, Lievens Y, Bouma AB, Colette L, Dekker A, deSouza NM et al (2020) Characterisation and classification of oligometastatic disease: a European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer consensus recommendation. Lancet Oncol 21:e18–e28. https://doi.org/10.1016/S1470-2045(19)30718-1

    Article  PubMed  Google Scholar 

  2. Tree AC, Khoo VS, Eeles RA, Ahmed M, Dearnaley DP, Hawkins MA et al (2013) Stereotactic body radiotherapy for oligometastases. Lancet Oncol 14:e28–37. https://doi.org/10.1016/S1470-2045(12)70510-7

    Article  PubMed  Google Scholar 

  3. Milano MT, Katz AW, Zhang H, Okunieff P (2012) Oligometastases treated with stereotactic body radiotherapy: long-term follow-up of prospective study. Int J Radiat Oncol Biol Phys 83:878–886. https://doi.org/10.1016/j.ijrobp.2011.08.036

    Article  PubMed  Google Scholar 

  4. de Vin T, Engels B, Gevaert T et al (2014) Stereotactic radiotherapy for oligometastatic cancer: a prognostic model for survival. Ann Oncol 25:467–471. https://doi.org/10.1093/annonc/mdt537

    Article  PubMed  Google Scholar 

  5. Chang DT, Schellenberg D, Shen J, Kim J, Goodman KA, Fisher GA et al (2009) Stereotactic radiotherapy for unresectable adenocarcinoma of the pancreas. Cancer 115:665–672. https://doi.org/10.1002/cncr.24059

    Article  PubMed  Google Scholar 

  6. Wersall PJ, Blomgren H, Lax I, Kälkner KM, Linder C, Lundell G et al (2005) Extracranial stereotactic radiotherapy in primary and metastatic renal cell carcinoma. Radiother Oncol 77:88–95. https://doi.org/10.1016/j.radonc.2005.03.022

    Article  PubMed  Google Scholar 

  7. Wulf J, Hadinger U, Oppitz U, Thiele W, Flentje M (2004) Stereotactic boost irradiation for targets in abdomen and pelvis. Radiother Oncol 70:31–36. https://doi.org/10.1016/j.radonc.2003.10.013

    Article  PubMed  Google Scholar 

  8. Jereczek-Fossa BA, Piperno G, Ronchi S, Catalano G, Fodor C, Cambria R et al (2014) Linac-based stereotactic body radiotherapy for oligometastatic patients with single abdominal lymph node recurrent cancer. Am J Clin Oncol 37:227–233. https://doi.org/10.1097/COC.0b013e3182610878

    Article  CAS  PubMed  Google Scholar 

  9. Zeng XL, Wang HH, Meng MB, Wu ZQ, Song YC, Zhuang HQ et al (2016) Stereotactic body radiation therapy for patients with recurrent pancreatic adenocarcinoma at the abdominal lymph nodes or postoperative stump including pancreatic stump and other stump. Onco Targets Ther 9:3985–3992. https://doi.org/10.2147/OTT.S102784

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Nagata Y, Matsuo Y, Takayama K, Norihisa Y, Mizowaki T, Mitsumori M et al (2007) Current status of stereotactic radiotherapy for lung cancer. Int J Clin Oncol 12:3–7. https://doi.org/10.1007/s10147-006-0646-6

    Article  PubMed  Google Scholar 

  11. Ricardi U, Badellino S, Filippi AR (2015) Stereotactic body radiotherapy for early stage lung cancer: history and updated role. Lung Cancer 90:388–396. https://doi.org/10.1016/j.lungcan.2015.10.016

    Article  PubMed  Google Scholar 

  12. Horne ZD, Richman AH, Dohopolski MJ, Clump DA, Burton SA, Heron DE (2018) Stereotactic body radiation therapy for isolated hilar and mediastinal non-small cell lung cancers. Lung Cancer 115:1–4. https://doi.org/10.1016/j.lungcan.2017.10.014

    Article  PubMed  Google Scholar 

  13. Macchia G, Lazzari R, Colombo N, Laliscia C, Capelli G, D'Agostino GR et al (2019) A large, multicenter, retrospective study on efficacy and safety of stereotactic body radiotherapy (SBRT) in oligometastatic ovarian cancer (MITO RT1 study): a collaboration of MITO, AIRO GYN, and MaNGO groups. Oncologist. https://doi.org/10.1634/theoncologist.2019-0309

    Article  PubMed  PubMed Central  Google Scholar 

  14. Bignardi M, Navarria P, Mancosu P, Cozzi L, Fogliata A, Tozzi A et al (2011) Clinical outcome of hypofractionated stereotactic radiotherapy for abdominal lymph node metastases. Int J Radiat Oncol Biol Phys 81:831–838. https://doi.org/10.1016/j.ijrobp.2010.05.032

    Article  PubMed  Google Scholar 

  15. Casamassima F, Masi L, Menichelli C, Bonucci I, Casamassima E, Lazzeri M et al (2011) Efficacy of eradicative radiotherapy for limited nodal metastases detected with choline PET scan in prostate cancer patients. Tumori 97:49–55

    Article  CAS  Google Scholar 

  16. Franzese C, Cozzi L, Franceschini D, D'Agostino G, Comito T, De Rose F et al (2016) Role of stereotactic body radiation therapy with volumetric-modulated arcs and high-intensity photon beams for the treatment of abdomino- pelvic lymph-node metastases. Cancer Invest 34:348–354. https://doi.org/10.1080/07357907.2016.1197235

    Article  CAS  PubMed  Google Scholar 

  17. Franzese C, Lopci E, Di Brina L, D'Agostino GR, Navarria P, Mancosu P et al (2017) 11C-choline-pet guided stereotactic body radiation therapy for lymph node metastases in oligometastatic prostate cancer. Cancer Invest 35:586–593. https://doi.org/10.1080/07357907.2017.1375116

    Article  CAS  PubMed  Google Scholar 

  18. Jereczek-Fossa BA, Fanetti G, Fodor C, Ciardo D, Santoro L, Francia CM et al (2017) Salvage stereotactic body radiotherapy for isolated lymph node recurrent prostate cancer: single institution series of 94 consecutive patients and 124 lymph nodes. Clin Genitourin Cancer 15:e623–e632. https://doi.org/10.1016/j.clgc.2017.01.004

    Article  PubMed  Google Scholar 

  19. Loi M, Frelinghuysen M, Klass ND, Oomen-De Hoop E, Granton PV, Aerts J et al (2018) Locoregional control and survival after lymph node SBRT in oligometastatic disease. Clin Exp Metastasis 35:625–633. https://doi.org/10.1007/s10585-018-9922-x

    Article  PubMed  PubMed Central  Google Scholar 

  20. Napieralska A, Miszczyk L, Stąpór-Fudzińska M (2016) CyberKnife stereotactic ablative radiotherapy as an option of treatment for patients with prostate cancer having oligometastatic lymph nodes: single-center study outcome evaluation. Technol Cancer Res Treat 15:661–673. https://doi.org/10.1177/1533034615595945

    Article  PubMed  Google Scholar 

  21. Trippa F, Casale M, Draghini L, Anselmo P, Arcidiacono F, Maranzano E (2016) Stereotactic body radiotherapy for lymph node relapse in ovarian cancer. Clin Oncol 1:1038

    Google Scholar 

  22. Wang Z, Wang J, Zhuang H, Wang P, Yuan Z (2016) Stereotactic body radiation therapy induces fast tumor control and symptom relief in patients with iliac lymph node metastasis. Sci Rep 6:37987. https://doi.org/10.1038/srep37987

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Bae SH, Kim MS, Cho CK, Kang JK, Kang HJ, Kim YH et al (2012) High dose stereotactic body radiotherapy using three fractions for colorectal oligometastases. J Surg Oncol 106:138–143. https://doi.org/10.1002/jso.23058

    Article  PubMed  Google Scholar 

  24. Franceschini D, De Rose F, Fogliata A, Navarria P, Ascolese AM, Franzese C et al (2016) Volumetric modulated arc therapy for thoracic node metastases: a safe and effective treatment for a neglected disease. Oncotarget 7:53321–53329

    Article  Google Scholar 

  25. Jereczek-Fossa BA, Ronchi S, Orecchia R (2015) Is stereotactic body radiotherapy (SBRT) in lymph node oligometastatic patients feasible and effective? Rep Pract Oncol Radiother 20:472–483. https://doi.org/10.1016/j.rpor.2014.10.004

    Article  PubMed  Google Scholar 

  26. Deodato F, Macchia G, Grimaldi L et al (2009) Stereotactic radiotherapy in recurrent gynecological cancer: a case series. Oncol Rep 22:415–419

    PubMed  Google Scholar 

  27. Macchia G, Morganti AG, Cilla S et al (2012) Quality of life and toxicity of stereotactic radiotherapy in pancreatic tumors: a case series. Cancer Invest 30:149–155. https://doi.org/10.3109/07357907.2011.640649

    Article  PubMed  Google Scholar 

  28. Deodato F, Cilla S, Macchia G et al (2013) Extracranial radiosurgery with volumetric modulated arc therapy: Feasibility evaluation of a phase I trial. Oncol Lett 5:1889–1896. https://doi.org/10.3892/ol.2013.1276

    Article  PubMed  PubMed Central  Google Scholar 

  29. Macchia G, Deodato F, Cilla S, Torre G, Corrado G, Legge F et al (2014) Volumetric intensity modulated arc therapy for stereotactic body radiosurgery in oligometastatic breast and gynecological cancers: feasibility and clinical results. Oncol Rep 32(5):2237–2243. https://doi.org/10.3892/or.2014.3412

    Article  PubMed  Google Scholar 

  30. Deodato F, Cilla S, Macchia G, Torre G, Caravatta L, Mariano G, Mignogna S, Ferro M, Mattiucci GC, Balducci M, Frascino V, Piermattei A, Ferrandina G, Valentini V, Morganti AG (2014) Stereotactic radiosurgery (SRS) with volumetric modulated arc therapy (VMAT): interim results of a multi-arm phase I trial (DESTROY-2). Clin Oncol (R Coll Radiol) 26(12):748–756. https://doi.org/10.1016/j.clon.2014.08.005

    Article  CAS  Google Scholar 

  31. Deodato F, Macchia G, Cilla S, Ianiro A, Sallustio G, Cammelli S, Buwenge M, Mattiucci GC, Valentini V, Morganti AG (2019) Dose escalation in extracranial stereotactic ablative radiotherapy (DESTROY-1): a multiarm phase I trial. Br J Radiol 92:1094. https://doi.org/10.1259/bjr.20180422

    Article  Google Scholar 

  32. Hurkmans CW, Cuijpers JP, Lagerwaard FJ et al (2009) Recommendations for implementing stereotactic radiotherapy in peripheral stage IA non-small cell lung cancer: report from the Quality Assurance Working Party of the randomised phase III ROSEL study. Radiat Oncol 4:1

    Article  Google Scholar 

  33. Cilla S, Ianiro A, Deodato F, Macchia G, Digesù C, Valentini V, Morganti AG (2018) Optimal beam margins in linac-based VMAT stereotactic ablative body radiotherapy: a Pareto front analysis for liver metastases. Med Dosim 43(3):291–301

    Article  Google Scholar 

  34. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L et al (2000) New guidelines to evaluate the response to treatment in solid tumors (RECIST guidelines). J Natl Cancer Inst 92:205–216. https://doi.org/10.1093/jnci/92.3.205

    Article  CAS  PubMed  Google Scholar 

  35. Young H, Baum R, Cremerius U, Herholz K, Hoekstra O, Lammertsma AA et al (1999) Measurement of clinical and subclinical response using [18 20 F]-fluorodeoxiglucose and positron emission tomography: review and 1999 EORTC recommendations. Eur J Cancer 35:1773–1782. https://doi.org/10.1016/s0959-8049(99)00229-4

    Article  CAS  PubMed  Google Scholar 

  36. Cox JD, Stetz J, Pajak TF (1995) Toxicity criteria of the radiation therapy oncology group (RTOG) and the Eropean organization for research and treatment of cancer (EORTC). Int J Radiat Oncol Biol Phys 31:1341–1346. https://doi.org/10.1016/0360-3016(95)00060-C

    Article  CAS  PubMed  Google Scholar 

  37. National Cancer Institute (2020) Common Terminology Criteria for Adverse Events v.4.03 (CTCAE v.4.03). https://ctep.cancer.gov/protocolDevelopment

  38. Scorsetti M, Bignardi M, Alongi F, Fogliata A, Mancosu P, Navarria P et al (2011) Stereotactic body radiation therapy for abdominal targets using volumetric intensity modulated arc therapy with RapidArc: feasibility and clinical preliminary results. Acta Oncol 50:528–538. https://doi.org/10.3109/0284186X.2011.558522

    Article  PubMed  Google Scholar 

  39. Tanadini-Lang S, Rieber J, Filippi AR, Fode MM, Streblow J, Adebahr S, Andratschke N, Blanck O, Boda-Heggemann J, Duma M, Eble MJ, Ernst I, Flentje M, Gerum S, Hass P, Henkenberens C, Hildebrandt G, Imhoff D, Kahl H, Klass ND, Krempien R, Lohaus F, Petersen C, Schrade E, Wendt TG, Wittig A, Høyer M, Ricardi U, Sterzing F, Guckenberger M (2017) Nomogram based overall survival prediction in stereotactic body radiotherapy for oligo-metastatic lung disease. Radiother Oncol 123(2):182–188. https://doi.org/10.1016/j.radonc.2017.01.003

    Article  CAS  PubMed  Google Scholar 

  40. Klement RJ, Abbasi-Senger N, Adebahr S, Alheid H, Allgaeuer M, Becker G, Blanck O, Boda-Heggemann J, Brunner T, Duma M, Eble MJ, Ernst I, Gerum S, Habermehl D, Hass P, Henkenberens C, Hildebrandt G, Imhoff D, Kahl H, Klass ND, Krempien R, Lewitzki V, Lohaus F, Ostheimer C, Papachristofilou A, Petersen C, Rieber J, Schneider T, Schrade E, Semrau R, Wachter S, Wittig A, Guckenberger M, Andratschke N (2019) The impact of local control on overall survival after stereotactic body radiotherapy for liver and lung metastases from colorectal cancer: a combined analysis of 388 patients with 500 metastases. BMC Cancer 19(1):173. https://doi.org/10.1186/s12885-019-5362-5

    Article  PubMed  PubMed Central  Google Scholar 

  41. Franceschini D, De Rose F, Franzese C, Comito T, Di Brina L, Radicioni G, Evangelista A, D'Agostino GR, Navarria P, Scorsetti M (2019) Predictive factors for response and survival in a cohort of oligometastatic patients treated with stereotactic body radiation therapy. Int J Radiat Oncol Biol Phys 104(1):111–121. https://doi.org/10.1016/j.ijrobp.2018.12.049

    Article  PubMed  Google Scholar 

  42. Valentini V, van Stiphout RG, Lammering G, Gambacorta MA, Barba MC, Bebenek M, Bonnetain F, Bosset JF, Bujko K, Cionini L, Gerard JP, Rödel C, Sainato A, Sauer R, Minsky BD, Collette L, Lambin P (2011) Nomograms for predicting local recurrence, distant metastases, and overall survival for patients with locally advanced rectal cancer on the basis of European randomized clinical trials. J Clin Oncol 29(23):3163–3172. https://doi.org/10.1200/JCO.2010.33.1595

    Article  PubMed  Google Scholar 

  43. Alongi F, Fogliata A, Clerici E, Navarria P, Tozzi A, Comito T et al (2012) Volumetric modulated arc therapy with flattening filter free beams for isolated abdominal/pelvic lymph nodes: report of dosimetric and early clinical results in oligometastatic patients. Radiat Oncol 7:204. https://doi.org/10.1186/1748-717X-7-204

    Article  PubMed  PubMed Central  Google Scholar 

  44. King CR, Brooks JD, Gill H, Presti JC Jr (2012) Long-term outcomes from a prospective trial of stereotactic body radiotherapy for low-risk prostate cancer. Int J Radiat Oncol Biol Phys 82:877–882. https://doi.org/10.1016/j.ijrobp.2010.11.054

    Article  PubMed  Google Scholar 

  45. Rieber J, Streblow J, Uhlmann L, Flentje M, Duma M, Ernst I, Blanck O, Wittig A, Boda-Heggemann J, Krempien R, Lohaus F, Klass ND, Eble MJ, Imhoff D, Kahl H, Petersen C, Gerum S, Henkenberens C, Adebahr S, Hass P, Schrade E, Wendt TG, Hildebrandt G, Andratschke N, Sterzing F, Guckenberger M (2016) Stereotactic body radiotherapy (SBRT) for medically inoperable lung metastases-a pooled analysis of the German working group "stereotactic radiotherapy". Lung Cancer 97:51–58. https://doi.org/10.1016/j.lungcan.2016.04.012

    Article  PubMed  Google Scholar 

  46. Andratschke N, Alheid H, Allgäuer M, Becker G, Blanck O, Boda-Heggemann J, Brunner T, Duma M, Gerum S, Guckenberger M, Hildebrandt G, Klement RJ, Lewitzki V, Ostheimer C, Papachristofilou A, Petersen C, Schneider T, Semrau R, Wachter S, Habermehl D (2018) The SBRT database initiative of the German Society for Radiation Oncology (DEGRO): patterns of care and outcome analysis of stereotactic body radiotherapy (SBRT) for liver oligometastases in 474 patients with 623 metastases. BMC Cancer 18(1):283. https://doi.org/10.1186/s12885-018-4191-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Author notes

  1. Alessio G. Morganti and Gabriella Macchia have share the last authorship.

Authors and Affiliations

  1. Radiotherapy Unit, Gemelli Molise Hospital, Campobasso, Italy

    Francesco Deodato, Milena Ferro, Alessia Re & Gabriella Macchia

  2. Medical Physic Unit, Gemelli Molise Hospital, Campobasso, Italy

    Savino Cilla & Anna Ianiro

  3. Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine – DIMES, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy

    Milly Buwenge & Alessio G. Morganti

  4. Radiology Unit, Gemelli Molise Hospital, Campobasso, Italy

    Giuseppina Sallustio

  5. Department of Radiology, Radiation Oncology and Hematology, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy

    Vincenzo Valentini

  6. Università Cattolica del Sacro Cuore, Istituto di Radiologia, Rome, Italy

    Vincenzo Valentini

Authors
  1. Francesco Deodato
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Milena Ferro
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Savino Cilla
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anna Ianiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Milly Buwenge
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alessia Re
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Giuseppina Sallustio
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Vincenzo Valentini
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Alessio G. Morganti
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Gabriella Macchia
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gabriella Macchia.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Deodato, F., Ferro, M., Cilla, S. et al. Stereobody radiotherapy for nodal recurrences in oligometastatic patients: a pooled analysis from two phase I clinical trials. Clin Exp Metastasis 37, 519–529 (2020). https://doi.org/10.1007/s10585-020-10039-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10585-020-10039-x

Keywords

Search

Navigation