Background:Patients with pancreatic cancer have a poor prognosis apart from the few suitable for surgery. Photodynamic therapy (PDT) produces localised tissue necrosis but previous studies using the photosensitiser meso-tetrahydroxyphenylchlorin (mTHPC) caused prolonged skin photosensitivity. This study assessed a shorter acting photosensitiser, verteporfin.Methods:Fifteen inoperable patients with locally advanced cancers were sensitised with 0.4 mg kg−1 verteporfin. After 60–90 min, laser light (690 nm) was delivered via single (13 patients) or multiple (2 patients) fibres positioned percutaneously under computed tomography (CT) guidance, the light dose escalating (initially 5 J, doubling after each three patients) until 12 mm of necrosis was achieved consistently.Results:In all, 12 mm lesions were seen consistently at 40 J, but with considerable variation in necrosis volume (mean volume 3.5 cm3 at 40 J). Minor, self-limiting extrapancreatic effects were seen in multifibre patients. No adverse interactions were seen in patients given chemotherapy or radiotherapy before or after PDT. After PDT, one patient underwent an R0 Whipple's pancreaticoduodenectomy.Conclusions:Verteporfin PDT-induced tumour necrosis in locally advanced pancreatic cancer is feasible and safe. It can be delivered with a much shorter drug light interval and with less photosensitivity than with older compounds.

The first study of photodynamic therapy in the human gastrointestinal tract using 5 aminolaevulinic acid (ALA) (Gut 1995; 36: 67-75)

Abstract. We report on the first stages of a clinical study designed to test elastic-scattering spectroscopy, mediated by fiberoptic probes, for three specific clinical applications in breast-tissue diagnosis: (1) a transdermal-needle (interstitial) measurement for instant diagnosis with minimal invasiveness similar to fine-needle aspiration but with sensitivity to a larger tissue volume, (2) a hand-held diagnostic probe for use in assessing tumor/resection margins during open surgery, and (3) use of the same probe for real-time assessment of the ''sentinel'' node during surgery to determine the presence or absence of tumor (metastatic). Preliminary results from in vivo measurements on 31 women are encouraging. Optical spectra were measured on 72 histology sites in breast tissue, and 54 histology sites in sentinel nodes. Two different artificial intelligence methods of spectral classification were studied. Artificial neural networks yielded sensitivities of 69% and 58%, and specificities of 85% and 93%, for breast tissue and sentinel nodes, respectively. Hierarchical cluster analysis yielded sensitivities of 67% and 91%, and specificities of 79% and 77%, for breast tissue and sentinel nodes, respectively. These values are expected to improve as the data sets continue to grow and more sophisticated data preprocessing is employed. The study will enroll up to 400 patients over the next two years. © 2000 Society of Photo-Optical Instrumentation Engineers. [S1083-3668(00)

Interstitial photodynamic therapy (IPDT) is a technique for applying photodynamic therapy (PDT) to internal tumours using light delivered via fibres inserted percutaneously. This phase I -II study assessed the safety and efficacy of IPDT for patients with persistent or recurrent head and neck cancer unsuitable for further treatment with surgery, radiotherapy or chemotherapy, recruited for 'last hope' salvage treatment. Patients were sensitised with 0.15 mg kg À1 mTHPC (meso-tetrahydroxyphenyl chlorin) 4 days prior to light delivery from fibres inserted directly into the target tumour (20 J per site at 652 nm) under image guidance. In all, 45 patients were treated. Nine achieved a complete response. Five are alive and free of disease 10 -60 months later. Symptomatic relief (mainly for bleeding, pain or tumour debulking) was achieved in a further 24. The median survival (Kaplan -Meier) was 16 months for the 33 responders, but only 2 months for the 12 nonresponders. The only serious complication was a carotid blow out 2 weeks after PDT. No loss of function was detected in nerves encased by treated tumours. Interstitial photodynamic therapy provides worthwhile palliation with few complications and occasional long-term survivors for otherwise untreatable advanced head and neck cancers. It is a treatment option worth adding to those available to integrated head and neck oncology teams.

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PDT using ALA for dysplasia of the mouth produces consistent epithelial necrosis with excellent healing and is a simple and effective way to manage these patients. Results in invasive cancers are less satisfactory, mainly because the PDT effect is too superficial with current treatment regimens using ALA as the photosensitizing agent.

Summary Selective sensitisation of malignant tumours to monochromatic light (photodynamic therapy, PDT) is a promising approach to cancer treatment, but current sensitisers are unsatisfactory and the parameters controlling effects produced in normal and neoplastic tissue are poorly understood. To quantify the effects in a relatively homogeneous organ, we carried out experiments in the livers of normal rats following systemic sensitisation with haematoporphyrin derivative (HpD) and a new sensitiser, a sulphonated aluminium phthalocyanine (AlSPc) using light from an Argon pumped tunable dye laser. Damage from PDT (dominant at lOOmW laser power) could be distinguished from that due to local hyperthermia (dominant at 400mW). For both sensitisers, the extent of PDT necrosis increased with the applied light energy and was abolished by occluding the hepatic blood flow during therapy. With HpD, the extent of PDT necrosis was maximum with only a few hours between sensitisation and therapy, and was not detectable when this interval was increased to a week. With AlSPc, the extent of necrosis in liver changed little with sensitisation times from 1 h to 1000 h (6 weeks), and declined slowly thereafter, matching the amount of AlSPc measurable by alkali extraction, although prolonged photosensitisation was not seen with AlSPc in muscle. Less cutaneous photosensitivity was seen with AlSPc than with HpD. AlSPc is easier to produce and handle than HpD, has a more appropriate strong absorption peak (at 675nm) and from these results, warrants further study as a photosensitiser for PDT.

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