Hypofractionated Image-Guided Radiation Therapy (IGRT) in Patients With Stage II-III Non-Small Cell Lung Cancer

The study is designed to determine whether an accelerated course of hypofractionated
radiation therapy with daily image guidance and motion assessment/control will allow more
effective treatment of poor performance status patients with stage II-III NSCLC, who would
benefit from local therapy compared to standard radiation therapy (60 Gy in 2 Gy per
fraction). Poor performance status patients can be a heterogeneous group, with tumor-related
factors, other co-morbidities, or advanced age placing patients in the category. These
patients have traditionally been underrepresented in clinical trials, and thus no prospective
study has evaluated the efficacy of other radiotherapy dose fractionations in these patients.
One phase III trial of "poor-risk" locally advanced NSCLC (RTOG 93-04) included just over 40%
Karnofsky performance status 60-70 patients and showed median survival times of 9.5 and 10.3
months with 60Gy of conventional radiation therapy alone or with recombinant β-interferon
[18]. 1 year overall survival was just 44% in these patients.

This study includes randomization to two arms. Arm A (experimental arm) will include IGRT, 60
Gy in 15 fractions (3 weeks). Arm B will include conventional radiation, 60-66 Gy in 30-33
fractions (6 weeks) with optional concurrent with carboplatin/taxol .

The experimental arm dose for this trial is based on a dose escalation trial at University of
Texas Southwestern evaluating the maximum tolerated dose of hypofractionated IGRT in this
patient population (Phase I study IRB #072010-050). Doses were escalated from 3 Gy per
fraction (total dose 45 Gy) to 4 Gy per fraction (total dose 60 Gy) and evaluation for
treatment related toxicity was being performed. Critical structure dose constraints will be
expressed as organ dose-volume limits, with limits formulated with the approval of the study
investigators using known tolerance data, radiobiological conversion models, and norms used
in current practice at academic centers [27].

Randomization Schema:

Patients will be allocated to the treatment using a randomized permuted block within strata
to balance for patient factors other than institution. The stratifying variables are Zubrod
performance status (2 vs. > 2) and stage (II vs. III).

Inclusion Criteria:

- All patients must be willing and capable to provide informed consent to participate in
the protocol.

- Patients must have appropriate staging studies identifying them as AJCC stage II or
III non small cell lung cancer, (according to AJCC Staging, 6th edition; see appendix
III), or recurrent non small cell lung cancer. Histologic confirmation of cancer will
be required by biopsy or cytology within 6 months of study entry.

- Patients must have the potential for benefit from local therapy (at the discretion of
the investigator).

- The patient's Zubrod performance status must be 2 or greater OR patients with Zubrod
performance status 0-1 and weight loss >10% are considered eligible. In addition,
patients determined to be medically unfit or refusing combined modality therapy are
eligible.

- Age ≥ 18.

- Patients must have measurable or evaluable disease.

- Women of childbearing potential and male participants must agree to use an effective
method of contraception.

- Patients must sign study specific informed consent prior to study entry.

- Patients must not have plans for concurrent chemoradiation therapy.

- Patients must complete all required pretreatment evaluations

Exclusion Criteria:

- Total (aggregate) gross tumor volume > 500 cm3 (500 cc's or 0.5 Liters)

- Prior radiotherapy to the region of the study cancer that would result in direct
overlap of radiation therapy fields.

- Chemotherapy given within one week of study registration.

- Pregnant or lactating women, as treatment involves unforeseeable risks to the embryo
or fetus.