PIET OST
OLIGOMETASTASESPicking the finest cherries?
DEPARTMENT OF RADIATION ONCOLOGY
DISCLOSURE & DISCLAIMER
An honorarium is provided by Accuray for this presentation
The views expressed in this presentation are those of the presenters and do not necessarily reflect the views or policies of Accuray Incorporated or its subsidiaries. No official endorsement by Accuray Incorporated or any of its subsidiaries of any vendor, products or services contained in this presentation is intended or should be inferred.
Advisory Role: Ferring Pharmaceuticals (Inst), Bayer AG (Inst)Research Funding: Merck (Inst)Travel, Accommodations, Expenses: Ipsen, Ferring Pharmaceuticals
BIOLOGY AND DEFINITIONS
METASTATIC SOLID TUMORS = PALLIATIVE TREATMENT?
Metastases from solid tumors are regarded as representative of disseminated cancer and are not considered curable, with the rare
exception, such as germ cell tumors.
BIOLOGICAL DEFINITION
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Tumors early in the chain of progression may havemetastases limited in number and location because thefacility for metastatic growth has not been fullydeveloped and the site for such growth is restricted.
Implication: metastatic disease may be cured withmetastasis-directed therapy.
Hellman & Weichselbaum, 1995
BIOLOGICAL RATIONALE FOR METASTASIS-DIRECTED THERAPY
If metastases are able to metastasize and systemic therapy inducesmore resistant and lethal clones, the addition of local therapy
directed at metastases might delay lethal disease progression…
Reyes et al. Oncotarget 2015
REMARK
There is NO universal “Oligometastases” definition
SBRT FOROLIGOMETASTASES
EARLY RESULTS
SYSTEMATIC REVIEW: NON-LIVER, NON-LUNG
Tree et al. Lancet Oncol 2012
OLIGOMETASTASES: A HYPE?
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THE EVIDENCE
SURVEILLANCE OR MDT: PHASE II RCT
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Eligibility:• Up to 3 metastases at time of
recurrence, excluding localrelapse
Primary endpoint: • time to ADT
• Symptoms• Local progression• Polymetastatic progression
Metastasis-directed therapy:• SBRT (30Gy in 3 fr) or surgery
55% Nodal45% Bone
55% Nodal45% Bone
Ost et al. JCO in press
BIOCHEMICAL PROGRESSION
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Surveillance: 35% of pts have a PSA declineMDT: 75% of pts have a PSA decline
Ost et al. JCO in press
TIME TO PALLIATIVE ADT
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ITT: median ADT-free survival 13 months vs 21 months HR: 0.60 [95% CI: 0.31 – 1.13], log-rank p=0.11
Table 2: indications for starting androgen deprivation therapy
Surveillance (n=31)
Metastasis-directed therapy (N=31)
Not started yet 6 (19%) 12 (39%)Polymetastatic progression 16 (55%) 19 (61%)Local progression 6 (23%) 0 (0%)Symptomatic progression 3 (10%)* 0 (0%)* Two patients with symptomatic progression also showed local and polymetastatic progression
Ost et al. JCO in press
TOXICITY AND QOL
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• 17% grade I toxicity with • No grade 2 or higher toxicity• No clinically significant decline in
QOL scores over time, • No QOL difference between
arms
Ost et al. JCO in press
LOCAL CONSOLIDATIVE THERAPY VERSUS MAINTENANCE THERAPY OR OBSERVATIONFOR PATIENTS WITH OLIGOMETASTATIC NON-SMALL-CELL LUNG CANCER WITHOUT PROGRESSION AFTER FIRST-LINE SYSTEMIC THERAPY
Eligibility:• NSCLC with up to 3 mets not
including the primary after first line systemic therapy
Primary endpoint:• Progression-free survival
Local therapy:• hypofractionated RT or SBRT: 48%• Surg+RT: 24% • Chemo-radiotherapy 8%• Hypo-fractionated radiotherapy
+chemoradiotherapy: 12% • Surg to all sites: 4%
- Gomez et al. Lancet Oncol 2016
PROGRESSION-FREE SURVIVAL
Median PFS • 4 vs 12 mo • (HR 0·35 p =
0.0054)
- Gomez et al. Lancet Oncol 2016
NEW LESION-FREE SURVIVAL
- Gomez et al. Lancet Oncol 2016
Median time• 5.7 vs 12 mo • (HR 0·35, p =
0.0497)
CONSOLIDATIVE RADIOTHERAPY FOR LIMITED METASTATIC NON–SMALL-CELL LUNG CANCER: A PHASE 2 RANDOMIZED CLINICAL TRIAL
Iyengaret al. JAMA Oncol 2017
Eligibility:• NSCLC with up to up to 6 sites of
extracranial disease (includingprimary) with no more than 3 sites in the liver or lung after first line systemic therapy
Primary endpoint:• Progression-free survival
Radiotherapy:• 1 fraction: 21-27 Gy• 3 fractions: 26.5-33 Gy• 5 fractions: 30-37.(Gy
PROGRESSION-FREE SURVIVAL
Median PFS:• 3.5 mo (maintenance alone) vs 9.7
mo (SAbR-plus- maintenance)
• HR: 0.304; (95% CI, 0.1-0.8; P = .01)
TAKE HOME MESSAGE
The first evidence of local therapy for“Oligometastases” is positive!
CONCLUSION
CONCLUSION The oligometastatic state exists.
First clinical trial results are promising
How to combine metastasis-directed therapy with systemictherapy?
Trials are coming: SABR-COMET NCT 01446744, ORIOLE, CORE
NCT02759783 and SARON NCT02417662, PulMiCC,…
OLIGOCARE: OBSERVATIONAL BASKET STUDY
Prof. Dr. Piet OstRadiation oncologistSenior Clinical Investigator of the Research Foundation
Dept of Radiation Oncology
@piet_ost
“To truth only a brief celebration of victory is allowedbetween the two long periods during which it iscondemned as paradoxical, or disparaged as trivial.”
- Arthur Schopenhauer -
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