There has been significant effort over the past two decades in the treatment of malignancies of epithelial origin,
including some of the most devastating of cancers, such as colorectal cancer (CRC), squamous call carcinoma of the
head and neck (HNSCC), and carcinomas of the pancreas, lungs, (both Small Cell and Non-Small Cell), renal cell,
prostate, bladder and breast. Recurring, refractory HNSCC is a particularly difficult cancer to treat once the tumors
recur due to mutations that are resistant to repeat chemotherapy and radiation. In addition, repeat surgery is often
difficult due to the requirement of significant surgical margins that may not be possible due to the attending potential
functional deficits (e.g., salivary glands, nerves and major blood vessels in confined areas). In this study FaDu HNSCC
xenograft tumors in SCID mice were imaged, and “optical”, as opposed to “surgical” margins defined for the tumor
being treated. The subsequent two-photon treatment irradiation was computer-controlled to carry out the tumor
treatment by rastering the laser beam throughout the tumor volume plus the defined optical margins simultaneously. In
our initial studies, up to 85% regression in tumor volume was observed in 5 days post PDT, with complete tumor
regression in 18 days. No re-growth was observed up to 41 days post-PDT, with little or no scarring and complete hair
re-growth. However, competition between imaging and PDT moieties was also observed in some mouse models,
possibly favoring tumor re-growth. Strategies to selectively optimize the PDT effect will be discussed.
|