Concurrent Chemotherapy Plus HFR Radiation Therapy in Inoperable NSCLC

Lung cancer is the leading cause of cancer related deaths for both men and women in the
United States. In 2014 the estimated number of new lung cancer cases in the United States is
224,210. Approximately 159,260 people are estimated to die from lung cancer in 2014.
Non-small cell lung cancer (NSCLC) constitutes 80% of all lung cancer cases. The standard
treatment for patients with NSCLC and clinically negative lymph nodes remains surgery per
NCCN guidelines. Five year survival for patients with stage I non-small cell lung cancer is
generally greater than 50% after surgical resection with lobectomy. A significant number of
these patients have cardio-pulmonary or other co-morbidities which preclude them from
undergoing curative surgery. Studies have shown that majority of these patients die from
their cancer and not from their co-morbidities. This forms the rationale for treating
medically inoperable early stage lung cancer patients with definitive therapy.

Treatment with radiotherapy (RT) has been the standard option for patients unable to undergo
surgery. Radiation alone leads to slightly better outcomes but still not equivalent to
surgery with 60-70% local failure with conventional fractionated radiotherapy over several
weeks. The development of three-dimensional conformal radiotherapy (3DCRT) has allowed for
more focused treatment while avoiding nearby normal tissue resulting in improved disease
specific survival but overall survival is still poor.

There is currently no data supporting the use of chemotherapy in the medically inoperable
group either in an adjuvant setting or concurrently with RT in those with early stage lung
cancer. In patients with unresectable Stage IIIA and IIIB NSCLC, combined chemo-RT has been
proven to be superior to RT alone. Two randomized studies that compared concurrent versus
sequential chemo-radiotherapy found that the concurrent approach provides superior outcomes.
However this approach has not been studied in early stage lung cancer in the medically
inoperable group. The medically inoperable patient cohort often does not undergo surgical
staging, which increases the odds that they harbor occult regional disease. Chemotherapy
given concurrently with radiation will act as a radiosensitizer and improve local disease
control and could decrease rate of distant metastases. It is possible that the medically
inoperable population also experience more side effects due to their co-morbidities and poor
performance status. Hence there is a need to determine if concurrent chemoradiation is
feasible and tolerable in the medically inoperable patients. The main side effect associated
with concurrent chemoradiation in stage III NSCLC is esophagitis. This arises due to effect
of radiation therapy to the regional lymph node (LN). The investigators' study population
with early stage lung cancer has no nodal involvement. Hence, the investigators do not
anticipate esophagitis being a major side effect in the researchers' study.

There is recent data for adjuvant chemotherapy in the medically operable group. Data from the
Lung Adjuvant Cisplatin Evaluation (LACE) showed with a median follow-up time of 5.2 years,
the overall HR of death was 0.89 (95% CI, 0.82 to 0.96; P = .005), corresponding to a 5-year
absolute benefit of 5.4% from chemotherapy. A similar trial evaluating the role of sequential
chemotherapy after stereotactic body radiation therapy (SBRT) in the medically inoperable
population was attempted at the investigators' institution but was closed due to poor
accrual. Hence, the investigators are looking at the role of concurrent chemo-RT in this
population.

Inclusion Criteria:

- Pathologically or cytologically proven diagnosis of non-small cell lung carcinoma.

- Solitary [T1bN0M0, T2aN0M0, T2bN0M0] lesion measuring 2-7cm in size. Staging is per
AJCC 7th edition of TNM classification.

- Patient must meet criteria for receipt of hypofractionated radiation therapy

- Medically inoperable pulmonary status, cardiac status, or other serious co-morbidity,
or patient refusal of primary surgery for lung cancer.

- ECOG Performance status of 0-2.

- Patients may have prior treatment for lung cancer based on the following criteria:

1. Surgical resection is allowed if surgery was > 12 months ago.

2. Patients treated with prior radiation are eligible if radiation was > 12 months
ago and there is no evidence of progression and if the lesion is in a different
lobe.

3. Prior chemotherapy if > 18 months ago

Exclusion Criteria:

- Node positive or metastatic disease.

- Other active malignancy (specifically, risk of recurrence in 3 years estimated to be
greater than 50%) except for non-melanoma skin cancer, in-situ cervical carcinoma
(CIN), or low-risk prostate carcinoma on active surveillance are to be excluded.

- Inability to receive systemic therapy or radiation therapy per protocol.

- Inability to fulfill requirements of the protocol.

- Any co-morbidity or condition which, in the opinion of the investigator, may interfere
with the assessments and procedures of this protocol.