Overcoming Bile Duct Cancer with Light

MNM | March 31, 2014 | Cholangiocarcinoma, Discoveries | No Comments

The prognosis of bile duct cancers, especially perihilar cholangiocarcinoma (CCC), is generally quite poor. Though not likely to metastasize, CCC tumors can impinge on vital structures of the liver and tend to grow into the sheath that surrounds certain nerve fibers in the lower torso (perineum), often with deadly consequences. Most patients are diagnosed at an advanced stage, and over half of all cases are inoperable at the time of diagnosis. The five-year survival rate is somewhere between 20 and 40 percent. Chemotherapy has generally had very limited effectiveness against this rare yet deadly form of cancer.

In a recent three-year clinical trial, researchers at the Asan Medical Centre in Seoul (Korea) randomly assigned 21 patients with inoperable cholangiocarcinoma to receive either photodynamic therapy (PDT) alone or PDT plus systemic chemotherapy. The patients treated with PDT plus chemo showed higher one-year survival rate compared with the patients treated with PDT alone (76% versus 32%) and prolonged overall survival (17 months versus 8 months). In addition, the PDT plus chemo group had better progression-free survival compared with PDT alone (10 months versus 2 months).

The Korean research team observed no differences in the number of PDT sessions, the frequency of cholangitis, and overall adverse events or the quality of life in either group. The lead investigators of this study concluded that PDT plus chemotherapy was well tolerated and was associated with a significant improvement of overall survival and progression-free survival compared with PDT alone in patients with inoperable cholangiocarcinoma. These findings were published in the 30 January 2014 European Journal of Cancer.

In another recent study, researchers at the University of Virginia School of Medicine in Charlottesville (Virginia, USA) reported on their clinical experience with PDT in 55 patients with inoperable cholangiocarcinoma who received treatment with PDT over a six-year period. Because cholangiocarcinoma is a rare cancer, this is considered to be one of the largest studies to date.

The median survival for patients who received both PDT and chemotherapy/radiation therapy was nearly nine months, and this compared favorably to the three- to six-month median survival that is typically seen with chemotherapy/radiotherapy alone. Statistically speaking, there was no difference between the groups receiving PDT alone and those who receiving PDT along with the conventional treatments. However, those who received PDT were able to receive lower doses of radiation than those used in the standard radiotherapy regimens.

Other recent research has shown that PDT is a reasonably well tolerated and safe procedure that may help improve tumor control in patients with cholangiocarcinoma who are awaiting liver transplantation. Many transplant centers use internal radiation therapy in the form of endoscopically directed brachytherapy to provide better disease control in patients with otherwise incurable cholangiocarcinoma as they await liver transplantation.

In summary, there is now compelling evidence that laser PDT can remove bile duct tumors. When combined with the standard practice known as biliary stenting (draining the bile ducts), PDT can substantially lower complications and improve median survival and quality of life, as reported in a 2013 issue of Clinical Endoscopy. Two randomized clinical trials have clearly demonstrated that PDT is superior to biliary stenting alone in the treatment of inoperable cholangiocarcinoma. In these trials, there was a doubling to tripling in survival for patients receiving laser PDT. Thus, PDT offers a strong primary treatment option for patients facing this difficult diagnosis, and future clinical trials are likely to further confirm the efficacy of this approach.

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Sources

Park DH1, Lee SS2, Park SE2, Lee JL3, Choi JH2, Choi HJ2, Jang JW2, Kim HJ4, Eum JB2, Seo DW2, Lee SK2, Kim MH2, Lee JB5. Randomised phase II trial of photodynamic therapy plus oral fluoropyrimidine, S-1, versus photodynamic therapy alone for unresectable hilar cholangiocarcinoma. Eur J Cancer. 2014 Jan 30. [Epub ahead of print]

Cosgrove ND1, Al-Osaimi AM, Sanoff HK, Morris MM, Read PW, Cox DG, Mann JA, Argo CK, Berg CL, Pelletier SJ, Maluf DG, Wang AY. Photodynamic therapy provides local control of cholangiocarcinoma in patients awaiting liver transplantation. Am J Transplant. 2014 Feb;14(2):466-71

Yao D, Kunam VK, Li X. A review of the clinical diagnosis and therapy of cholangiocarcinoma. J Int Med Res. 2014 Feb;42(1):3-16

Talreja JP, Degaetani M, Ellen K, Schmitt T, Gaidhane M, Kahaleh M. Photodynamic therapy in unresectable cholangiocarcinoma: not for the uncommitted. Clin Endosc. 2013 Jul;46(4):390-4

Lee TY, Cheon YK, Shim CS. Current status of photodynamic therapy for bile duct cancer. Clin Endosc. 2013;46(1):38-44.