Treatment of oligometastases: Lung

Transcription

1 Treatment of oligometastases: Lung Themadag Catharina ZH 30 March 2017 Max Dahele Radiation Oncologist Vumc, Amsterdam

2 Do you all treat lung oligometastases? What is your definition of lung oligometastases? >5

3 How many lung lesions do you treat at once? Do you have a limit for lesion size? Do you have a limit for the lung dose? Who has seen serious toxicity?

4 Lung oligometastases: the beginning Pastorino et al. J Thorac Cardiovasc Surg Jan;113(1):37-49 Long-term results of lung metastasectomy: prognostic analyses based on 5206 cases.

5 Pastorino et al. J Thorac Cardiovasc Surg Jan;113(1):37-49

6 Surgical practice Embun et al. Pulmonary metastasectomy in colorectal cancer: a prospective study of demography and clinical characteristics of 543 patients in the Spanish colorectal metastasectomy registry (GECMP- CCR). BMJ Open May 28;3(5)

7 Surgical practice

8 What are people doing in radiotherapy? Named recipients in centres with at least 1 year's experience in /45 centres (Germany=10; Netherlands=6; England=8; Belgium=2; Denmark=3; Austria=1) 30 responded, 27/30 treating lung metastases 14/27 would treat 3 lung metastases 5 <3 lesions 8 up to 5 lesions (at least 2 centers in 2 phases) 24/30 felt there was enough evidence to Rx lung metastases Dahele et al. Acta Oncol. 2015;54(8):

9 What are people doing with radiotherapy? 20 centers, 700pts, NSCLC 210, CRC 153 Rieber et al. Stereotactic body radiotherapy (SBRT) for medically inoperable lung metastases-a pooled analysis of the German working group "stereotactic radiotherapy". Lung Cancer Jul;97:51-8

10 Definitions in radiation oncology studies VUmc April 2003-Feb 2013: 989 pts with T1-2N0M0 NSCLC (± pathology) or lung metastases 89/989 had metastatic disease 93.2% of the 989 pts had 1 lesion, 6.3% 2 lesions, 0.5% >2 treated simultaneously Peguret N et al. J Thorac Oncol Jan;9(1):114-7 SABR-COMET study Maximum 3 metastases in any single organ system, in total 5 lesions Palma DA et al. BMC Cancer Jul 23;12:305 OAR doses based on Timmerman. Semin Radiat Oncol Oct;18(4): fraction SBRT, Lung R+L, 1000cc <5x2.7Gy, 1500cc <5x2.5Gy SAFRON II study Maximum of 3 lung metastases from any non-hematological malignancy, non central and each lesion <5cm diameter, V5<1000cc Siva et al. BMC Cancer Mar 4;16:183

11 Overview of studies: single fraction Siva et al. J Thorac Oncol Jul;5(7):1091-9

12 Overview of studies: single fraction Siva et al. J Thorac Oncol Jul;5(7):1091-9

13 Overview of studies: multiple fractions Siva et al. J Thorac Oncol Jul;5(7):1091-9

14 Overview of studies: multiple fractions Siva et al. J Thorac Oncol Jul;5(7):1091-9

15 Overview of studies: multiple fractions Siva et al. J Thorac Oncol Jul;5(7):1091-9

16 CRC may do less well Binkley et al. Int J Radiat Oncol Biol Phys Aug 1;92(5):

17 Concerns raised about the existing evidence No control in the index surgical reference No RCT Selective citations Repeated authoritative publication Macbeth F, Treasure T. Pulmonary metastasectomy: where is the evidence? J Thorac Oncol Mar;10(3):e13-4 Macbeth F, Treasure T. Stereotactic Ablative Radiotherapy for 'Oligometastases': a Treatment in Search of Evidence. Clin Oncol (R Coll Radiol) Aug;28(8):501-2 Treasure T, Macbeth F. Stereotactic Body Radiotherapy (SBRT) Is as Yet of Unproven Benefit for Patients With Lung Metastases. Am J Clin Oncol Aug;39(4):423-4 Opened in 2010

18 Rating the evidence Examples of level 1=RCT; level 2=cohort study; level 3=case-control; level 4=case series; level 5=expert opinion without critical appraisal

19 Trials SABR-COMET, randomized phase II, SOC vs SBRT ±chemotherapy, primary outcome=os Recruitment closed, n=99 NCT SAFRON II, randomized phase II, single vs multi-fraction SBRT, primary outcome safety Recruiting, n=84 NCT SABR-SCAN, randomized, immediate vs delayed SBRT, primary outcome=pfs Recruiting, n=40, 1-3 lesions 0.8-3cm, CRC NCT CORE, randomized, SOC vs SBRT for extra-cranial oligometastases, primary outcome=pfs Recruiting, n=206, 3 lesions, 2 organ systems, no lung lesion >5cm, breast/prostate/nsclc NCT

20 A pragmatic and practical clinical approach Staging Discussion in site-specific MDO Awareness of risks Sharing of risks Oligo-metastasis radiotherapy team Open discussion with the patient Follow up Frequent review of literature and own results Griffioen et al. Radiotherapie bij oligometastasen. Ned Tijdscr Oncol 2014;11:51-8

21 Emerging risks

22 Systemic therapy SABR-COMET Prior chemotherapy allowed but no systemic therapy 4 weeks prior to first fraction of radiotherapy, during radiotherapy, or for two weeks after last fraction SAFRON II No cytotoxic chemotherapy within 3 weeks of commencement of treatment, or concurrently. Hormonal manipulation agents are not excluded No targeted agents within 7 days of commencement of treatment, or concurrently CORE Systemic Rx naive; commence SOC therapy within 4 weeks of SBRT

23 Surgery vs SBRT Widder et al. Pulmonary oligometastases: metastasectomy or stereotactic ablative radiotherapy? Radiother Oncol Jun;107(3): Although SABR was second choice after PME, survival after PME was not better than after SABR. Prospective comparative studies are clearly required to define the role of both, SABR and PME in OMD.

24 Many delivery systems

25 Equipment

26 Karolinksa group Greitz T et al. Stereotactic radiation therapy of intracranial lesions. Methodologic aspects. Acta Radiol Oncol. 1986;25(2):81-9. Lax I et al. Stereotactic radiotherapy of malignancies in the abdomen. Methodological aspects. Acta Oncol. 1994;33(6): : Liver, lung, retroperitoneal 2005: Kidney 2012: Sarcoma metastases

27 Clinical cases

28 Questions