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The Oligometastatic State and the Evolving Paradigms
Mark Farrugia MD, PhDRadiation Medicine
PGY-3
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Ok, so maybe the title was a little ambitious
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Outline
• General approach to cancer treatment• Oligometastatic state• Novel treatment approaches in oligometastases
• Future directions
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Outline
• General approach to cancer treatment• Oligometastatic state• Novel treatment approaches in oligometastases
• Future directions
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General approach to solid tumors
• Local/Locoregionaldisease‐> surgery and/or radiation±chemotherapy
• Curative intent• Best chance of local control
• Short and possibly long term morbidity
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General approach to solid tumors
• Stage IV – metastatic (systemic) disease, uncurable
• Rely on systemic treatments (chemotherapy)
+ disease in bones
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Metastatic disease
• Gross disseminated disease accompanied by more subclinical
• Local treatments add morbidity
• Systemic treatments control, don’t cure
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Outline
• General approach to cancer treatment• Oligometastatic state• Novel treatment approaches in oligometastases
• Future directions
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Are all metastatic patients equal?
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Oligometastatic State
• First described by Hellman and Weichselbaumin 1995
• Definitions can vary• May represent a more favorable biology• Patients may benefit from aggressive local therapies
Metastatic·ish
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Biology
• Tumor type and natural history
• Clinical aggressiveness
1990 2001
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Disease Burden
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Response to treatment
• Response of known disease predicts response of unknown disease
• Longer duration of disease control• Progression is not favorable
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Patient Selection!
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Outline
• General approach to cancer treatment• Oligometastatic state• Novel treatment approaches in oligometastases
• Future directions
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Changing landscapes
• Systemic therapy is improving• Failure is common at known sites of disease• Benefit to local therapy in this setting?
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Local treatments in metastatic disease
• Local treatment to lower volume metastatic disease is not new
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Stereotactic body radiation therapy (SBRT)
• High doses of radiation therapy• Five or less fractions• Highly conformal• Very precise
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Stereotactic body radiation therapy (SBRT)
• Requires resources (SBRT bags, fiducials)• Time consuming• Expensive• Possibly higher rates of complications
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Recent trials
• Often NSCLC• At least stable disease after chemotherapy• 3‐5 sites of disease• RT to primary and sites of metastatic disease• Various dosing regimens used
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Doses
• Often hypofractionated regimens ( e.g. 15fx) for primary tumor or mediastinum
• SBRT doses included 20‐24Gy/1‐3fx, 30‐33Gy/ 3‐5fx
• Other trials did 30‐60Gy in 3‐8fx or 16‐24Gy in a single fraction (Brain or spine)
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Median PFS:3.5 mo vs 9.7mo
Median OS1yr vs NYR
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PFS:3.9 mo vs 11.9 mo
OS:17 mo vs 41 mo
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Median OS28 mo vs 41 mo
Grade 2 toxicity 61% w/ SBRT
3 out 66 had treatment related deaths
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Overall findings
• Consolidative local therapy significantly improves disease‐free survival
• Overall survival was improved in NSCLC patients and likely with many other cancers
• SBRT is associated with improved OS over standard palliative regimens
• SBRT is not necessarily benign
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Outline
• General approach to cancer treatment• Oligometastatic state• Novel treatment approaches in oligometastases
• Future directions
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Ongoing work
• Multiple Phase II in specific disease sites• SABR‐COMET 10• BR‐002• LONESTAR Trial (Phase III)
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ASTEROID Trial
• Assessing Single‐fraction SBRT versus STandard PalliativE RadiatiOn In patients with Metastatic Disease (ASTEROID)
• SBRT vs standard for quality of life and pain relief due to metastases
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Conclusions
• Oligometastatic state is a function of tumor biology, disease burden, and treatment efficacy
• Local treatments improve outcome in oligometastatic patients
• SBRT appears superior to conventional RT
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Questions?