SBRT (Stereotactic Body Radiation Therapy) vs. Surgery in High Risk Patients With Early Stage Lung Cancer

The development of SBRT for treatment of stage I NSCLC (non-small cell lung cancer) inspired
the collaboration between thoracic surgery and radiation oncology and has prompted the
investigators to work closely together to evaluate the relative role of SBRT and surgery.
Comparative studies of these modalities have been limited in number and are often difficult
to interpret due to variability in methodological issues. The productive collaboration has
resulted in publication of several studies comparing SBRT and surgery utilizing propensity
score based analyses to match patients from each group. However, matching on limited numbers
of variables between patients ultimately selected for therapy based largely on their real or
perceived comorbidity leads to significant reporting bias, and therefore methods to
comprehensively assess comorbidity are necessary.

As extension of above, a very real ongoing challenge that the investigators have evaluated
within clinical practice is that current guidelines defining the high risk patient are
subjective and prone to physician bias. A recent secondary analysis of clinical trial
inclusion criteria for SBRT underscored this bias by demonstrating that many patients that
were considered inoperable were perhaps reasonable surgical candidates. Based on standard
pulmonary function tests the inoperable SBRT patients had a diffusion capacity 33% higher
than the high risk surgical patients in ACOSOG Z4032. Conversely, stratification of high risk
surgical patients within ACOSOG Z4032 trial identified an extremely high risk subset (median
DLCO% 30%, FEV1% 39%) with a 90-day 3+ adverse event rate of 48% compared to the lowest risk
subset (DLCO% 69%, FEV1% 56%) with a 90-day 3+ adverse event rate of only 24%. In the absence
of a clinical trial or a prospective database, there is currently no objective algorithm to
guide the assignment of surgery versus SBRT.

Attempts to objectively stratify risk within the surgical population have been challenging.
Risk models based on the European Thoracic Database and the Society of Thoracic Surgeons
Database are not yet robust enough to guide decision-making regarding treatment assignment or
classification of the very high risk surgical patient where alternative therapies may be
preferable. Unfortunately, one of the current limitations to stratifying these high risk
patients is that these patients are followed by physicians in independent specialties. The
STS Thoracic Surgical Database does not include patients that undergo SBRT therefore it is
difficult to create an inclusive algorithm for operable and inoperable patients. A principle
objective of the study is to create a validated risk model for treatment selection. This will
greatly enhance the ability to counsel patients regarding their specific risks/benefit ratio
for surgery or SBRT. This will improve informed decision making on the part of the patient,
and remove much of the subjectivity of treatment selection. Inclusion of unique metrics such
as HRQOL data will further bolster the benefit to the patient by making it more
patient-centric, rather than focusing on cancer outcomes alone.

As the implementation of the Affordable HealthCare Act (AHCA) continues, physicians will
experience additional pressure to cut costs while maintaining or improving the quality of
care provided. The current fee-for-service system is often criticized for being
compartmentalized and fragmented without well-defined incentives for quality improvement.

Initiatives of the AHCA have included efforts to test care models to reduce hospital
associated conditions, bundled payment plans for care improvement, and shared savings
programs for accountable care organizations whereby participating providers who meet certain
quality standards share in any savings achieved for the Medicare program. These are just some
of the efforts designed to rein in the cost of medical care while improving the transparency
and quality of care. Pilot efforts involving bundling of payments for coronary artery bypass
grafting resulted in Medicare savings of $40 million with simultaneous reduced in-hospital
mortality. These types of initiatives are likely to become more commonplace in the United
States as efforts to create new models of care to constrain cost are introduced.

With the stimulus of these initiatives for novel systems of healthcare delivery the
investigators recognized that a model of bundled payment for treatment of stage I NSCLC may
not only reduce overall costs associated with treatment of stage I lung cancer but
potentially improve the quality of care provided. At Washington University the investigators
have taken a preemptive measure to create an accountable care organization (ACO) between the
Department of Radiation Oncology and the Department of Thoracic Surgery with a focused
approach on the treatment of stage I NSCLC. Important components of this collaborative effort
include a bundled payment system for episodes of care involving the treatment selection,
implementation, and follow up care of patients with stage I lung cancer as well as
prospective assessment of quality of care measures.

The impetus for the development of this unique collaboration between radiation oncology and
thoracic surgery stems from the ongoing interest in improving the quality of care for
patients with early stage NSCLC. The clinical research focus has been on determining the best
treatment strategies for the significant number of patients with stage I lung cancer
considered medically inoperable or high risk surgical candidates. In the aging population,
pulmonary insufficiency, cardiac disease, as well as other comorbidities may preclude surgery
or place patients at significant risk for complications after surgery. The evolution of
stereotactic body radiotherapy (SBRT) in the medically inoperable population has resulted in
relatively low local recurrence rates ranging from 3-20% with favorable overall and
disease-free survival in inoperable patients with Stage I NSCLC.

Inclusion Criteria:

- Newly diagnosed suspected or proven clinical stage I NSCLC (T1 or T2, N0, M0) with no
prior treatment for this disease.

- At least 18 years of age.

- Ability to understand and willingness to sign an IRB approved written informed consent
document (or that of legally authorized representative, if applicable).