Brain photodiagnosis (PD), fluorescence guided resection (FGR) and photodynamic therapy (PDT): past, present and future.

Intracranial tumours are an excellent target for photodiagnosis (PD), fluorescence guided resection (FGR) and photodynamic therapy (PDT), because the tumour to brain ratio of photosensitizers' concentration is very high. However, several attempts of proving the value of PDT in the most malignant type of brain tumours, gliobastoma multeforme (GBM) failed to demonstrate any significant worthwhile survival advantage in the past because of the very nature of this cancer and several compounding factors that led to this apparent disappointing outcome; variations in the photosensitizer and light dosages, variations in the photosensitizer administration to treatment time-intervals, and variations in photosensitizers used are just few to mention in this article. However, after a very long gestation period of brain PD, FGR and PDT, three randomized controlled trials (RCT) in brain PD, FGR and PDT were concluded by 2007. The first trial demonstrated that time to tumour progression (TTP) was significantly longer in patients who had PD and FGR compared to standard surgical resection but this difference did not translate into survival advantage in GBM due to the variability in the management of recurrent tumours and significant residual tumour cells left after FGR in about a third of patients leading to GBM relapse. The second trial compared single shot PDT in GBM and standard therapy. Neither the treatment nor the control group received PD or FGR. Again this RCT did not provide any survival advantage in patients who had had PDT due to the fact that standard surgical resection had left significant residual tumour in a large number of patients canceling any potential benefit from PDT. The last trial compared combined PD, FGR and repetitive PDT and standard therapy and confirmed that TTP was significantly longer in the treatment group and demonstrated that the treatment group had significant survival advantage in GBM. In conclusion, PD, FGR and PDT need to be combined to be effective in brain tumours and in the future, we will see more and more scientific evidence accumulating in support of brain PD, FGR and PDT. The next decade will see further refinement and evolution of the techniques and technology employed and expansion of the indications of brain PD, FGR and PDT.