Phase I Study of IMRT and Molecular-Image Guided Adaptive Radiation Therapy for Advanced HNSCC

PRIMARY OBJECTIVES:

I. To determine the feasibility of integrating molecular imaging (PET with FLT tracer) into
current state-of-the-art image-guided adaptive radiation therapy (IGART) of head and neck
cancer.

II. To determine within a predefined range the maximum tolerated radiation dose for
concurrent cisplatin and molecular and anatomic image-based IGART of head and neck cancer.

SECONDARY OBJECTIVES I. To compare gross tumor volumes defined by FDG-PET, FLT-PET, CBCT,
and regular FBCT before, during, and following completion of chemo-radiation therapy.

II. To evaluate the impact of escalated doses to tumor sub-volumes with high FLT and FDG
uptake prior to and during radiation therapy using post-treatment FDG images as an early
surrogate for sub-volume-specific local control.

III. To develop a database consisting of all molecular and anatomic images, including daily
CBCT data sets, obtained during chemo-radiation therapy to support further research.
Potential applications include determination of optimal adaptive re-planning frequency and
the benefits of basing IGART on 4D anatomic data sets derived from deformably registering
daily CBCT and FBCT data sets.

IV. Determine patient long-term toxicities and survival. V. To evaluate the impact of daily
image-guided setup; off-line every other week adaptive re-planning; and molecular-image
based targeting on sparing of tissues and organs responsible for late and early treatment
sequelae.

OUTLINE: This a dose-escalation study of intensity-modulated radiotherapy.

Patients undergo intensity-modulated image-guided adaptive radiotherapy once daily 5 days a
week for 6 weeks. Patients also receive cisplatin IV on days 1 and 22. Treatment continues
in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 2 and 4 weeks, 2, 3, 4, 5,
6, 9, and 12 months, every 6 months for 2 years, and then annually for 2 years.

Inclusion Criteria:

- Histologic or cytologic confirmation of head and neck malignancy without clinical or
radiographic evidence of metastatic disease

- Locally advanced HN SCC, stages III, IV, and bulky (> 27 cm^3 volume) stage II,
excluding larynx and nasopharynx, of no more than 150 cm^3 volume base on CT scan

- All patients must be informed of the investigational nature of this study and must
give written informed consent in accordance with institutional and federal guidelines

- Candidate for chemotherapy

- Zubrod performance score of 0 or 1

- Absolute granulocyte count (AGC) >= 2000 cells/mm^3

- Platelet count >= 100,000 cells/mm^3

- Hemoglobin > 8.0 g/dl based upon CBC/differential obtained within 2 weeks prior to
registration on study

- Serum creatinine =< 1.5 mg/dl or measured or calculated creatinine clearance >= 50
ml/min

- Negative pregnancy test within 2 weeks prior to registration for women of
childbearing potential

Exclusion Criteria:

- Prior invasive malignancy except non-melanomatous skin cancers unless patient has
been disease free for at least 3 years

- Prior cancer treatment for this cancer, including gross total tumor excision

- Prior radiation treatment to the HN region

- Patients with known syndromes that alter radiosensitivity

- Any medical contraindications for chemotherapy

- Pregnant or lactating women

- Women (of childbearing potential) and men who are sexually active and are not
willing/able to use a medically acceptable form of contraception throughout the
treatment and 60 days thereafter