Transcript Curing the incurable

Shyam B. Paryani M.D., M.S., M.H.A &
Nitesh N. Paryani, M.D.
May 1st, 2015
16th Annual Cardiovascular & Medicine Symposium
St. Augustine, Florida
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
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
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
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…
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
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
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
Radiation Oncology Evolution
1960s
1980s
2D
3D Conformal
T R E N D
Late 1990s
–
IMRT
I M P R O V I N G
2000s
IGRT
Stereotactic
Treatments
P R E C I S I O N
PARYANI PARADIGM SHIFT
 FROG has
been around
for over 50
years to see
these
changes in
knowledge,
and is
constantly
adapting!
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
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
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?
Do they exist?
 And if so, are there ones with a more indolent course?
 I think we can all agree yes on this....
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
You don’t
always
spell things
correctly
either
Evidence by site
 Liver
 Lung
 Spine/bone
 CNS
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
Liver
 All of these studies centered on resection
 From the pre-SBRT era, of course, but…
Evidence by site
 Liver
 Lung
 Spine/bone
 CNS
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+
©2012
MFMER |
slide-27
Lung
Evidence by site
 Liver
 Lung
 Spine/bone
 CNS
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
©2012
MFMER |
slide-33
Evidence by site
 Liver
 Lung
 Spine/bone
 CNS
CNS
 Most commonly studied in NSCLC patients
 First large series of patients with synchronous
resections of pulmonary lesions and CNS primary date
back to 1976
 10 year survival was 15%
 Pooling together retrospective series, survival has been
as high as 30% at 5 years
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