The overall goal of this project is to improve the survival and quality of life of patients with pancreatic and biliary tract carcinoma using photodynamic therapy (PDT). This clinical project involves a number of phase I and III studies using two different photosensitizers (PS), and derives from experimental and early clinical studies of PDT in pancreatic and biliary tract malignancies by our group. In addition, new means for non- invasively measuring PS concentrations and light transmission within tissue will be usedto provide monitoring information that could ultimately be used to manipulate PDT in real time and produce a more effective and uniform therapeutic outcome. The overall theme of the hypotheses tested here is that a reduction in tumor burden can be achieved safely with PDT, and will lead to improvements in survival and quality of life of patients with pancreatic and biliary tract cancer.
In Aim 1, following on from our recently completed phase II study of porfimer sodium PDT in biliary tract carcinoma (ETC), a phase III study of palliative PDT plus stenting vs. stenting alone will be performed in patients with locally advanced or metastatic BTC.
Aim 2 will test the feasibility and safety of neoadjuvant PDT using porfimer sodium in patients undergoing attempted curative surgical resection of proximal biliary tract carcinoma, with the goal of improving RO resection rates and overall survival. Accurate techniques for dosimetry with photosensitizer and structural treatment planning will also be developed, with the aims of improving PDT dose accuracy and prediction of effect in biliary tract cancer.
In Aim 3, in a standard phase I/II dose ranging study using a single fiber followed by a non-randomized phase II multiple fiber study, verteporfin PDT will be administered to patients with locally advanced pancreatic carcinoma to identify the treatment parameters with which to achieve safe and effective tumor necrosis. The results of this study will then be used to inform Aim 4, a randomized phase ll/lll study of verteporfin PDT + standard chemotherapy vs. chemotherapy alone for locally advanced pancreatic cancer. This latter trial will involve full light dose treatment planning with implantation of multiple diffusing fibers into the prescribed volume. The completion of these aims will test the clinical hypotheses that PDT can be successfully incorporated into pancreatobiliary cancer management as a combination approach, either adjuvant or neoadjuvant. Potential benefits to public health: this study with 4 clinical trials could provide new treatments for two cancers, PanCa and BTCwhich currently have few treatment options and are usually fatal putting a heavy burden on society in terms of cost and suffering.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-GRB-P)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts General Hospital
United States
Zip Code
O'Brien, Darragh P; Sandanayake, Neomal S; Jenkinson, Claire et al. (2015) Serum CA19-9 is significantly upregulated up to 2 years before diagnosis with pancreatic cancer: implications for early disease detection. Clin Cancer Res 21:622-31
Samkoe, Kimberley S; Tichauer, Kenneth M; Gunn, Jason R et al. (2014) Quantitative in vivo immunohistochemistry of epidermal growth factor receptor using a receptor concentration imaging approach. Cancer Res 74:7465-74
Skipworth, J R A; Keane, M G; Pereira, S P (2014) Update on the management of cholangiocarcinoma. Dig Dis 32:570-8
Huggett, Matthew T; Passant, Helen; Hurt, Chris et al. (2014) Outcome and patterns of care in advanced biliary tract carcinoma (ABC): experience from two tertiary institutions in the United Kingdom. Tumori 100:219-24
Jermyn, Michael; Davis, Scott C; Dehghani, Hamid et al. (2014) CT contrast predicts pancreatic cancer treatment response to verteporfin-based photodynamic therapy. Phys Med Biol 59:1911-21
Spring, Bryan Q; Abu-Yousif, Adnan O; Palanisami, Akilan et al. (2014) Selective treatment and monitoring of disseminated cancer micrometastases in vivo using dual-function, activatable immunoconjugates. Proc Natl Acad Sci U S A 111:E933-42
Spring, Bryan Q; Palanisami, Akilan; Hasan, Tayyaba (2014) Microscale receiver operating characteristic analysis of micrometastasis recognition using activatable fluorescent probes indicates leukocyte imaging as a critical factor to enhance accuracy. J Biomed Opt 19:066006
Kanick, Stephen Chad; Davis, Scott C; Zhao, Yan et al. (2014) Dual-channel red/blue fluorescence dosimetry with broadband reflectance spectroscopic correction measures protoporphyrin IX production during photodynamic therapy of actinic keratosis. J Biomed Opt 19:75002
Anand, Sanjay; Rollakanti, Kishore R; Horst, Ronald L et al. (2014) Combination of oral vitamin D3 with photodynamic therapy enhances tumor cell death in a murine model of cutaneous squamous cell carcinoma. Photochem Photobiol 90:1126-35
Keane, Margaret G; Bramis, Konstantinos; Pereira, Stephen P et al. (2014) Systematic review of novel ablative methods in locally advanced pancreatic cancer. World J Gastroenterol 20:2267-78

Showing the most recent 10 out of 101 publications