Shyam B. Paryani M.D., M.S., M.H.A & Nitesh N. Paryani, M.D. May 1 st, th Annual Cardiovascular & Medicine Symposium St. Augustine, Florida

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1 Shyam B. Paryani M.D., M.S., M.H.A & Nitesh N. Paryani, M.D. May 1 st, th Annual Cardiovascular & Medicine Symposium St. Augustine, Florida

2 Outline Terminology & Background A brief historical overview Cancer cure rates over time Biological basis for curability of oligometastatic disease Questions we must ask Review of evidence by site Questions & Discussion

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4 Terminology & Background Oligometastases Coined by Weishcelbaum and Hellman in 2005 An intermediate state between local and metastatic disease, as per the spectrum hypothesis Five or less sites of distant disease and primary can be controlled Oligorecurrence Less than or equal to five lesions Primary under controlled Possibility of rendering patient disease free once again

5 Terminology & Background Radiosurgery or Stereotactic Body Radiotherapy The concept of giving high doses of radiation over a few treatments Focusing the beam on the tumor and a small rim of healthy tissue Like surgery, but non-invasive Side effects usually minimal; treatment well tolerated Originally pioneered in Japan, now widely accepted and utilized

6 Historical Overview Must look back before we can look forward How did we come to current understanding of cancer behavior? Remember, the world was once flat

7 History 1907 Halsted, our favorite cocaine addicted surgeon Locoregional spread through surrounding tissue Cancer can be cured if diagnosed early and treated with aggressive surgery

8 History 70 years later, Fisher model Cancer is always a systemic disease Mets always present Can happen early in disease course Systemic therapy is the cornerstone Aggressive local therapy may not be as necessary

9 History The Spectrum hypothesis Disease ranges between local and disseminated at time of diagnosis Progression occurs as a result of acquired somatic mutations and chromosomal rearrangements during the course of the disease Seed and soil phenomenon Tumor dormancy is possible, likely due to immune response Some cancers may never metastasize

10 Radiation Oncology Evolution 1960s 1980s Late 1990s 2000s 2D 3D Conformal IMRT IGRT Stereotactic Treatments T R E N D I M P R O V I N G P R E C I S I O N

11 PARYANI PARADIGM SHIFT FROG has been around for over 50 years to see these changes in knowledge, and is constantly adapting!

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14 Biologic Rationale Multiple studies have evaluated genetic differences between patients with oligo- and polymetastatic disease. Multiple (>100) genetic differences between tumor cells from each cohort Polymetastatic tumors also have more cell-cycle regulatory genes active A preliminary 11-gene classifier exists to distinguish poly from oligometastatic More research is needed

15 Other Factors to Consider Number of mets Prognostic of survival in most studies Several studies have found 4 mets the critical number Disease free interval for oligorecurrence Lymph node status those without do better Nomograms there are many microrna profile under investigation

16 Questions to ask Do patients with limited metastatic disease exist? Do a subset of these patients behave differently; do they have a slower natural history? true oligomets. Does aggressive treatment improve outcomes? How can we make sure these patients get they treatment they need?

17 Do they exist? And if so, are there ones with a more indolent course? I think we can all agree yes on this...

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19 Favorable subset Singh et al., IJROBP 2005 showed that prostate cancer with patients with <= 5 mets have similar survival to those without mets (~75% 5 year, 45% 10 year), and better survival than those with > 5 mets (45% and 18%). Dorn et al., IJROBP 2011 showed similar differences for breast patients (60% vs 12% 5 year) Torok et al presented their data at ASTRO 2013 for lung: 13 month median survival vs 7 month for oligomet patients

20 You don t always spell things correctly either

21 Evidence by site Liver Lung Spine/bone CNS

22 Liver Frequent site of mets for GI/sarcoma/breast Surgery, SBRT, RFA all utilized for limited mets 10 year follow up exists for hepatic resection with limited mets for colorectal cancer Survival up to 28% (JCO 2007) 5 year data for breast cancer Ranges from 21-61% Neuroendocrine tumors can see 95% survival

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24 Liver All of these studies centered on resection From the pre-sbrt era, of course, but

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26 Evidence by site Liver Lung Spine/bone CNS

27 Lung Most extensively studied site of oligomets Pastorino et al looked at 5206 cases Multiple primaries, all with resected lung mets 5 year OS 36% R0 resection vs 13% R MFMER slide-27

28 Lung

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30 Evidence by site Liver Lung Spine/bone CNS

31 Bone Bone mets account for 20% of mets We know bone only breast cancer patients live longer Surgery is much more invasive and disabling for many bone lesions SBRT is increasingly being adopted in this site

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33 2012 MFMER slide-33

34 Evidence by site Liver Lung Spine/bone CNS

35 CNS Most commonly studied in NSCLC patients First large series of patients with synchronous resections of pulmonary lesions and CNS primary date back to year survival was 15% Pooling together retrospective series, survival has been as high as 30% at 5 years

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39 PARYANI PARADIGM SHIFT Chance to cure those who we thought were incurable Or at least, prolong their lives and improve the quality Changing the paradigm in the battle against cancer These patients need to be evaluated by experienced and innovative radiation oncologists Not just given chemo, and wait to die We stand ready to help your patients beat their cancer And remain humbled by the opportunity to provide cancer care to this community for over 50 years

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