Photodynamic therapy and photothermal therapy for the treatment of peritoneal metastasis: a systematic review

Our plain-English summary of Photodynamic therapy and photothermal therapy for the treatment of peritoneal metastasis: a systematic review, by A. Pinto, M. Pocard (Pleura and Peritoneum, 2018).

The study

• Authors: A. Pinto, M. Pocard
• Journal: Pleura and Peritoneum
• Published: 2018;3(4):20180124
• Type of article: Review
• Cited by: 38 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: The aim of this review was to analyze preclinical studies and clinical trials evaluating photodynamic therapy (PDT), and photothermal therapy (PTT) in peritoneal metastasis (PM) treatment.

Content: Systematic review according PRISMA guidelines. Electronic searches using PubMed and Clinical Trials.

Summary: A total of 19 preclinical studies analyzing PDT in PM treatment were included. Each new generations of photosensitizers (PS) permitted to improve tumoral targeting. Phase III preclinical studies showed an important tumoral biodistribution (ratio 9.6 vs normal tissue) and significant survival advantage (35.5 vs 52.5 days for cytoreductive surgery vs cytoreductive surgery+PDT, p<0.005). Height clinical trials showed important side effects (capillary leak syndrome and bowel perforation), mainly explained by low tumor-selectivity of the PS used (first generation mainly).Peritoneal mesothelioma apparition with carbon nanotubes first limited the development of PTT. But gold nanoparticles, with a good tolerance, permitted a limitation of tumoral growth (reduction of bioluminescence to 37 % 20 days after PTT), and survival benefit (35, 32, and 26 days for PTT with cisplatine, PTT alone and laser alone, respectively).

Outlook: Recent improvement in tumor-selectivity and light delivery systems is promising but further development would be necessary before PDT and PTT routinely applied for peritoneal carcinomatosis.

In plain English

This article was a systematic review, not a new experiment. The authors searched PubMed and the Clinical Trials registry for studies of photodynamic therapy (PDT) and photothermal therapy (PTT), two light-activated treatments, for cancer that had spread to the abdominal lining (peritoneal metastasis). For PDT they included 19 animal studies and 8 human trials. For PTT they included nine animal studies. The human PDT trials mostly used the first-generation drug Photofrin, and in the five phase II trials the most important side effect described was capillary leak syndrome. The largest trial, of 100 patients, found no significant objective complete responses or long-term tumor control. Some of the PTT studies tested multi-wall carbon nanotubes, with asbestos used for comparison. In one rat study, crocidolite produced mesothelioma in 34.6% of animals versus 3.8% of vehicle controls, while the nanotubes did not induce mesothelioma (4 or 6%). Two other studies reported high mortality and frequent mesothelioma after nanotube injection. The authors concluded that PDT and PTT are promising. They noted that few survival studies exist and that animal models do not always replicate human results, so survival benefits cannot yet be affirmed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: systematic review of preclinical (animal) studies and clinical trials
• Who was studied: Published studies, not people. For PDT: 27 articles (19 preclinical animal studies and 8 clinical trials, of which 3 were phase I and 5 phase II). For PTT: 9 preclinical studies. Search dates are not stated.
• Exposure: Photodynamic therapy with several generations of photosensitizer drugs, and photothermal therapy with nanoparticles. In the PTT toxicity studies, multi-wall carbon nanotubes and gold nanoparticles were tested; crocidolite and amosite asbestos were used as positive controls in some of these animal studies.
• Main results:
  • Seven of the eight human PDT trials used Photofrin. The eight trials were 3 phase I and 5 phase II.
  • In the five phase II human PDT trials, the most important adverse effect described in each trial was capillary leak syndrome.
  • In one reviewed phase I trial (Delaney), major morbidity occurred in 9 of 39 (23%) patients who had surgery and PDT.
  • In the largest reviewed phase II trial (Hahn, 100 patients), no significant objective complete responses or long-term tumor control were found.
  • In a reviewed rat study (Song), cytoreductive surgery plus PDT gave survival of 45 days versus 15 days with surgery alone (p less than 0.01).
  • In a reviewed rat ovarian cancer study (Yokoyama), PDT with methyl-ALA plus clofibric acid gave a mean survival of 52.5 days, versus 35.5 days for cytoreductive surgery alone.
  • In a reviewed 24-month rat study (Muller), multi-wall carbon nanotubes with or without structural defects did not induce mesothelioma (4 or 6%, respectively). Crocidolite produced mesothelioma in 34.6% of animals, versus 3.8% in vehicle controls.
  • Two other reviewed studies (Takagi; Rittinghausen) reported high mortality after multi-wall carbon nanotubes, with mesothelioma at necropsy in up to 98% of animals given the high dose.
  • In a reviewed mouse ovarian cancer study (Zhang), cisplatin-loaded gold nanoparticles plus laser gave 100% survival over the 35-day observation period. Mice in the other four groups all died: survival times were 26.33, 24, 25.33 and 31.67 days for saline plus laser, cisplatin, nanoparticles alone, and nanoparticles without cisplatin plus laser, respectively.
• The authors' conclusion: The authors concluded that PDT and PTT are promising therapies for peritoneal metastasis. They added that clinical trials with new-generation photosensitizers are needed, and that it is not yet possible to affirm survival benefits.
• Limitations the authors state:
  • Only preclinical studies and clinical trials were included.
  • A limited number of articles was included.
  • Few preclinical survival (phase III) studies exist (4 for PDT, 2 for PTT), so survival benefits cannot yet be affirmed.
  • Animal models, mainly mice, do not always replicate human results.

Topics

Medical terms in this study, explained in our Lexicon: Metastasis, Systematic Review, Clinical Trial, Cytoreductive Surgery, Peritoneal Mesothelioma.

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