Oral cancer represents over 30% of cancers reported in low middle-income countries (LMIC), like India and is the leading cause of cancer death among Indian men. Surgery, radiation and chemo therapies are the mainstay of management but are either too expensive, unavailable for people or have extensive side effects. An alternate effective therapy for oral cancer is photodynamic therapy (PDT), a light based spatially targeted cytotoxic therapy that has shown excellent healing of the oral mucosa post treatment. We here combined engineering, optics and biochemistry to produce a low-cost, mobile LED-based light source with 3D printed light applicators for smart phone-based, image-guided PDT. After validating the devices in preclinical models, we performed an ergonomics study on 10 healthy volunteers at the MGH, where the comfort level of the applicators (anterior buccal cheek, posterior buccal cheek and retromolar positions) and presence of fatigue or numbness in the mouth due to the applicators was evaluated. We found that the retromolar and posterior applicators were the most comfortable and well tolerated. After these initial steps, the device was tested in clinical studies of early oral cancer in India. We observe in subjects with T1N0M0 oral lesions that our applicator and light system combination delivered light to cover the entire lesion area and yielded effective PDT response. Of the 18 treatments so far, 14 subjects have responded, with no residual/recurrent disease in follow-up biopsy. The significance of this work is that it offers an alternative treatment modality for early disease without associated morbidities.
Standard of care in the management of cancer of the oral tongue is complete extirpation with clear margins. There is a direct correlation between the radial margin distance and local failure and death from disease.
Surgical resection of this site is balanced between resection of enough tissue to ensure clear margins and excessive resection that would result in unnecessary oral dysfunction. The optimal margin distance is 5 mm on permanent fixed histological assessment
Mucosal margins are obtained primarily using visual inspection with a reasonable degree of accuracy. More difficult is the deep margin which cannot be seen during the resection, where surgeons must rely on manual palpation to estimate the depth invasion and the needed deep margin tissue thickness.
Over the last three years we have utilized intraoperative ultrasound to improve the likelihood of a clear deep margin. Preliminary analysis has shown that using this technique we are able to reliably clear the deep margin with an improved rate of local control.
Drawing upon our preliminary findings using intraoperative ultrasound for surgical navigation, we have designed a study to employ dual functional antibody conjugates as a theranostic tool to allow molecular based optical imaging of tumor margins, improving precision of the resection and utilizing a benzoporphyrin derivative to provide for a tumor specific photodynamic therapy treatment at the time of resection.
Techniques and preliminary oncologic and margin outcomes of intraoperative ultrasound as well as the concepts of the use of dual functional antibody conjugates in surgical navigation will be discussed.