Boronophenylalanine (BPA)-Based Boron Neutron Capture Therapy (BNCT) in the Treatment Head and Neck Tumors

This is a single BNCT-facility, non-randomized, non-comparative, open-label, phase I to II trial to determine the value of BNCT in the treatment of inoperable, irradiated, locally advanced cancers of the head and neck region. An attempt to perform 18F-labeled boronophenylalanine (18F-BPA) SPECT or PET imaging will be made before BNCT. Patients whose tumor uptake is >2.5 times that of the corresponding normal head and neck tissue will be enrolled, and treated with a single fraction BPA-based BNCT twice, 3 to 5 weeks apart. Another 18F-BPA SPECT or PET study may be performed 1 to 3 months after BNCT to determine the SPECT/PET response.

The neutron irradiation site is the FiR 1 reactor site, located at Otaniemi, Espoo, Finland, about 6 kilometers from the Helsinki University Central Hospital, Helsinki, where patient evaluation and post-irradiation care will take place.

Prior to BNCT, BPA is infused as a fructose complex (l-BPA-F) into a peripheral vein over 2 hours. Blood samples will be taken for monitoring whole blood boron concentration before starting the BPA infusion, and thereafter at 20 to 40 minute intervals during the infusion, following infusion, and after delivering neutron irradiation. The blood samples will be analyzed for blood boron concentration to estimate the average blood boron concentration during neutron irradiation.

All patients will be evaluated for response using CT or magnetic resonance imaging (MRI).

Inclusion criteria

• Histologically confirmed, malignant head and neck cancer.
• Inoperable tumor, prior surgery may or may not have been done.
• Prior radiotherapy or chemoradiotherapy has been given.
• If prior SPECT or PET with 18F-BFA has been done, BPA needs to accumulate at least 2.5 times more in the tumor than in the corresponding contralateral normal tissue.
• WHO performance status <3.
• WBC >2,500/mm3, platelets >75,000/mm3, serum creatinine <180 umol/L.
• A written informed consent.

Exclusion criteria

• Lymphoma or other tumor type that is expected to respond to cancer chemotherapy or to a dose of conventional radiation therapy that can be safely given.
• A non-experimental, effective treatment option is available.
• Expected survival less than 3 months.
• Concomitant systemic chemotherapy (prior cancer chemotherapy is allowed).
• Other concurrent experimental therapy, or such therapy is being planned to be given.
• Less than 3 months since prior radiation therapy.
• Untreated or severe, treated congestive heart failure or renal failure.
• A cardiac pace-maker or an unremovable metal implant present in the head and neck region that will interfere with MRI-based dose-planning.
• Restlessness or inability to lie in a cast for 30 to 60 minutes.
• Clinical follow-up after therapy cannot be arranged or the patient is not willing to participate in follow-up.
• Pregnancy.
• Age less than 18.
• The patient is not able to understand the treatment options.