A Pilot Study of Response-Driven Adaptive Radiation Therapy for Patients With Locally Advanced Non-Small Cell Lung Cancer

Lung cancer is the leading cause of cancer death in the United States and worldwide. In 2012,
there were 226,160 new cases and 160,340 deaths related to lung cancer in the United States.
Approximately, 80-85% of lung cancers are NSCLC (Non-small Cell Lung Cancer), and 40% of
these are locally advanced (stage II/III) at diagnosis. The current standard of care for
these patients is "one size fits all" RT (Radiation Therapy) with concurrent chemotherapy in
uniform regimens. Even after concurrent chemoradiation, however, the five year overall
survival was still about 15%; almost one half of the patients failed locally. At the same
time, intensification of both radiotherapy and concurrent chemotherapy may result in
excessive toxicity or incomplete treatment. Therefore, it is critical to tailor the treatment
to each individual's sensitivity in combination with functional imaging guided
response-driven treatment and biomarker guided individualized dose prescription, thus taking
into consideration both the tumor and toxicity profile.

Evidence suggests that high-dose radiation has the potential to improve local-regional
control and overall survival in patients treated with fractionated therapy with concurrent
chemotherapy.

However, it is challenging to deliver high dose RT in the majority of patients with locally
advanced NSCLC without exceeding doses to organs at risk and causing significant side
effects.

Investigators hypothesized that they could develop safer and more effective therapy by
adapting treatment to the individual patient's response. With respect to the tumor,
investigators hypothesized, that they could improve outcome by redistributing dose to the
more aggressive regions of the tumor, assessed using mid-treatment FDG-PET (Positron Emission
Tomography) scanning. With respect to uninvolved organs, investigators need methods of
estimating tolerable radiation doses for the individual patient rather than the population
average. Such a strategy requires assessing both global and regional normal lung function and
the technology to deliver dose in a manner that minimizes damage to functional lung and
esophagus.

During-RT FDG-PET/CT potentially can provide important benefits to individual patients by
intensifying dose to more resistent tumor, allowing early changes to alternative, more
efficacious treatment or by avoiding the unnecessary toxicity related to ineffective therapy.

Patients will also undergo a during treatment V/Q SPECT (Single-photon Emission Computed
Tomography) scan, as an adaptive plan based on during-treatment SPECT may further optimize
PART (Personalized Adaptive Radiotherapy) to avoid high dose radiation to the
well-functioning regions, and would thus decrease RILT (Radiation Induced Lung Toxicity).

The combination of pre- and during V/Q SPECT can classify the lung into different functional
regions, and a strategy to give differential priority to the regions has been developed to
minimize lung damage.

Investigators plan to continue to collect data on serum biomarkers to further refine their
biophysical model with the ultimate goal of individualizing radiation dose prescription.

By identifying high risk patients and adjusting OAR (Organs at Risk) dose limits to the
threshold of tolerance, investigators anticipate a significant reduction in the incidence of
toxicity from UMCC 2007.123 without compromised tumor control by applying the model to
optimize radiation planning.

Inclusion Criteria:

- Patients must have FDG-avid and pathologically proven Stage IIA-IIIB non-small cell
lung cancer.

- Patients must be considered unresectable or inoperable.

- Patients must be 18 years of age or older.

- Patients must have a Karnofsky performance (A measure general well-being and
activities of daily life. Scores range between 0 and 100 where 100 represents normal
and 0 represents death.) of score > or = to 70.

- Patients must have adequate organ and marrow function.

- Patient must be willing to use effective contraception if female with reproductive
capability.

- Patients must be informed of the investigational nature of this study and given
written informed consent in accordance with institutional and federal guidelines.

Exclusion Criteria:

- Patients with any component of small cell lung carcinoma

- Patients with evidence of a malignant pleural or pericardial effusion

- Prior radiotherapy to the thorax such that composite radiation would significantly
overdose critical structures, either per estimation of the treating radiation
oncologist or defined by failure to meet normal tissue tolerance constraints

- Patients cannot tolerate concurrent chemotherapy

- Pregnant women are excluded from this study because radiation has the potential for
teratogenic or abortifacient effects.

- Prisoners are excluded for this study.