Photodynamic Therapy (PDT)

Short Introduction 
 

Photodynamic therapy (PDT) combines a drug (called a photosensitizer or photosensitizing agent) with a specific type of light to kill cancer cells.
 

Advantages 
 

 • Relatively selective and specific for tumorous cells
 • Effective in treating many kinds of tumors.
 • The cure rate is high as 90% for some early cancer (esophageal and lung cancer). For advanced cancer, more than 70% of patients experience improvement.
 • No toxicity, no immunosuppression, or bone marrow suppression
 • No negative effect when combined with other therapies (chemo/radiotherapies); instead, they have a complementary effect.
 • Short treatment time and efficacy occurs within 48-72 hours

 

 

Clinical use
 

Oral- pharyngeal tumor

Early oral, nosal and nasopharyngeal cancer: PDT had effective rates of 75%-100%.

Esophageal cancer

 • PDT had radical effect for early esophageal cancer
 • PDT can effectively ameliorate obstruction of advanced esophageal carcinoma
 • Very effective for cervical esophageal cancer
 • Able to treat undermucosal disseminated and latent cancer
 • For cancer which grows into intracavity and stent has been placed, PDT can eradicate neoplasm in cavity
 

Barrett esophagus 
 

PDT can effectively eradicate Barrett epithelium and early adenocarcinoma.
 

Lung cancer 
 

 • For lung cancer with bronchial obstruction, PDT induced improvement for air-way obstructions
 • For early bronchial cancer, PDT has a cure rate of 90%; for obstructive cancer, the improvement rate is 85%.
Gastric cancer
 • PDT can eradicate cancer for up to 80% of early gastric cancer
 • PDT can improve symptoms of advanced gastric cancer
 

Bladder cancer
 

Cancer in situ can be eradicated by PDT. Seventy-one percent of advanced cancer cases experience improvement after PDT.
Other cancers for which PDT is effective:
Colon-rectal carcinoma, cholangiocarcinoma (especially bile duct cancer in hepatic hilum, pancreatic carcinoma and cancer of Vater~s ampulla, tumor in abdominal cavity, pleural and peritoneal mesothelioma, liver cancer, brain tumor tumors of the genitourinary tract skin and subcutaneous tumor).

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Detailed Explanation
 

Photodynamic therapy (PDT), as a scientific, appropriate, noninvasive therapy, will usher in a new age in tumor therapy, just as penicillin helped to revolutionize pneumonia treatments in the 1930s.
 

PRINCIPLE
 

PDT is a non-thermal light chemical reaction and requires oxygen, photosensitive substance (photo-sensitizer) and laser simultaneously. The photo-sensitizer is absorbed by neoplasm tissue and accumulates in the cells for a long time. The photo-sensitizer is activated with the appropriate wavelength of light and reacts with oxygen to generate reactive single state oxygen and a hotochemical substance that are toxic to cells. This leads to apoptosis and necrosis of cancer; PDT can result in local vascular lesion of tumor. PDT can make tumor tissue ischemic necrosis and initiate immune reaction of antitumor.

 

 

 

 

PROCEDURE
 

 • Photosensitizer (Photofrin, porfimer sodium), 2mg/kg,is administrated intravenously 48 hours before scheduled light activation. 
 

 

• Laser light irritation: 48 hours after photosensitizer administration, 630-nm red laser light is delivered through optic cables (thin fibers that transmit light) to deliver light to areas inside the body. The light used for PDT can come from a laser or other sources of light. The total light dose administered ranges from 20 to 30 J/cm2. The light irritation is often repeated 72 hours after photo-sensitizer administration.

 

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• The delivery of laser fiber may be through endoscopes, such as gastrointestinal endoscope (for esophageal or gastric cancer) or bronchendoscope (for lung cancer), or it may be delivered intraoperatively.
 

 • PDT may also be repeated and may be used with other therapies, such as surgery, radiation, or chemotherapy.

INDICATION
 

Formally Approved

America
  • Esophageal cancer (via particles or completely obstructive)
  • Redical treatment of early stage esophageal cancer
  • Microinvasive non-small cell lung cancer, unable to be given surgery and radiotherapy
  • Obstructing, non-small cell lung cancer

Europe
  • Esophageal cancer and lung cancer
  • Radical treatment of early stage lung cancer
 

Japan
  • Early stage of lung cancer
  • Superficial esophageal cancer
  • Superficial gastric cancer
  • Early cervical cancer and metaplastic proliferation
 

Canada
  • Obstructing esophageal cancer, unable to be given Nd:YAG laser therapy
  • Early non-small cell lung cancer
 

Good effects shown by study

Barrett~s esophagus with high-degree displasia and esophageal adenocarcinoma
 

Effective report from clinics
Early stage of carcinoma of oral cavity, tumor of head-neck, brain tumor, pleural or peritoneal mesothelioma, sarcoma in abdominal cavity, eye tumor, asophary geal cancer, tumor of chest wall, breast cancer, gynecologic cancer, rectal cancer, Kaposi sarcoma, skin cancer

Good prospects of application
Bone marrow, rheumatoid arthrositis, arteriolosclerosis, prevention of restricture after vascular plasticity, macula degeneration, streptococcus infection in peridentium, helicobacter pylori, wound infection.
 

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Advantages
 

  • Relative selectivity and tissue specificity for tumor cells;
  • Low toxicity, good safety, no immuno-suppression and marrow inhibition;
  • No harmful effects on other therapies, complementary to surgery, radiotherapy and chemotherapy;
  • Short treatment time;
  • Initiating therapeutic effect within 48-72 hours;

CLINICAL APPLICATION
 

Oral- pharygeal tumor
 

For early oral, nosal and nasopharygeal cancer: PDT had effective rates of 75%-100%.
 

Esophageal cancer
 

  • PDT had radical effect for early esophageal cancer;
  • PDT brings the five-year survival rate of 74%-84% in T1 and T2 stage of esophageal squamous and adenocarcinoma; PDT can effectively ameliorate obstruction of advanced esophageal carcinoma. Very effective for cervical esophageal cancer. Able to treat undermucosal disseminated and latent cancer. For cancer which grows intracavity and a stent has been placed, PDT can eradicate neoplasm in cavity.

 

 

 

 

 

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Barrett esophagus

Normal squamous epithelium lining the esophagus is replaced by glandular columanar epithelium, a process known as called Barrett esophagus, which increases the risk of esophageal adenocarcinoma. PDT not only can effectively eradicate Barrett epithelium, but it also has good results for early adenocarcinoma.

 

 

Lung cancer
 

  • For lung cancer with bronchial obtruction, PDT induce improvement of air- way obstruction
  • Treatment of lung cancer with PDT was approved by the USA~s FDA
  • For early bronchial cancer, PDT has the cure rate of 90%; for obstructive cancer, the improvement rate is 85 percent. 
 

Gastric cancer
  • PDT can eradicate cancer for 80% of early gastric cancer
  • PDT can improve symptoms of advanced gastric cancer

Colon-rectal carcinoma
 

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  • PDT is especially indicated to colon-rectal adenocarcinoma and small cancer
  • PDT can improve symptoms, such as tenesmus, pain and bleeding, of 55% of patients with unresectable colon-rectal carcinoma

Cholangiocarcinoma
 

PDT can effectively eliminate obstruction of bile duct in patients with cholangiocarcinoma in hepatic hilum. This condition is difficult to treat with traditional methods.
 

Pancreatic carcinoma and cancer of Vater~s ampulla
 

PDT, which is performed with inserting a light-guiding fiber through endoscopy or percutaneously, can control development of pancreatic carcinoma and Vater~s ampulla cancer.
 

Tumor in abdominal cavity

It was reported that PDT can effectively treat the postoperative recurrent cancer of rectum in pelvic cavity, recurrent colonic carcinoma with local metastasis and sarcoma in abdominal cavity..

Bronchial carcinoma (lung cancer)

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In patients with stage 1 of bronchial carcinoma, 5-year survival ratebrought by PDT was as high as 93 percent.
In advanced bronchial carcinoma, 55% of the tumor mass shrank, while 49% improved after PDT.

Bronchial bleeding
 

PDT can induce stopping of hemoptysis induced by various causes.

 

 

 

 Pleural and peritoneal mesothelioma
 

  • Intraoperative application of PDT can eliminate tumor especially for patients with tumors that cannot be totally resected.
  • The 2-year survival rate of 23% was seen in 37 patients with mesothelioma, and the median survival was 61 months in patients with 1 and 2 stage of disease.
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Brain tumor
PDT has a special effect to brain tumor, especially to glioma, because cells of brain tumor have high capacity to concentrate photosensitizer.

Tumors of genitourinary tract
Bladder cancer in situ can be eradicated by PDT. Seventy-one percent of advanced cases showed improvement after PDT.
 

Skin and subcutaneous tumor
PDT can effectively treat various cancer and metastatic cancer of skin and subcutaneous tissues.
 

Gynecologic tumor
PDT is effective for treatment of vaginocarcinoma, cervical cancer in situ, and metastatic vaginocarcinoma.

LIMITATION OF PDT
 

The light needed to activate most photosensitizers cannot pass through tissue that is more than a centimeter (a third of an inch) thick. For this reason, PDT is usually used to treat tumors on or just under the skin or on the lining of internal organs or cavities. PDT is also less effective in treating large tumors, because the light cannot penetrate deeply into the tumors. PDT is a local treatment and generally cannot be used to treat cancer that has metastasized.

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SIDE EFFECTS

Porfimer sodium makes the skin and eyes sensitive to light for approximately 4 weeks after treatment. Thus, patients are advised to avoid direct sunlight and bright indoor light for at least 4 weeks.
 

Photo-sensitizers tend to build up in tumors and the activating light is focused on the tumor. As a result, there is minimal damage to healthy tissue. However, PDT can cause burns, swelling, pain, and scarring in nearby healthy tissue. Other side effects of PDT are related to the area that is treated. They can include coughing, trouble swallowing, stomach pain, painful breathing, or shortness of breath; these side effects are usually temporary.