Keyvan Moghissi

Photodynamic Therapy (PDT): PDT Mechanisms

Photodynamic therapy (PDT) is a light based therapy used to ablate tumors. As practiced in oncology a photosensitizing agent is applied and then activated by a specific wavelength and energy of light. This light energy in the presence of oxygen will lead to the creation of the photodynamic reaction which is cyto and vasculo toxic. This paper will review the mechanisms of action of PDT and how they may be manipulated to improve clinical outcome in cancer patients.

The place of bronchoscopic photodynamic therapy in advanced unresectable lung cancer: experience of 100 cases

OBJECTIVES The objectives of the study were: (1) to evaluate effectiveness of photodynamic therapy (PDT) for symptom palliation in patients with inoperable lung cancer; (2) to determine survival benefit in a subset of patients. METHODS One hundred patients, 68 male, 32 female, aged 44-81 years (mean 62.5) with advanced inoperable bronchogenic cancer and endobronchial luminal obstruction were prospectively studied. Eighty-two percent had previous chemo/radiotherapy. The pre-treatment protocol consisted of: clinical, radiological and bronchoscopic examination, pulmonary function testing, assessment of WHO performance status and clinical staging. Treatment protocol was: intravenous injection of 2 mg/kg body weight of photofrin/polyhaematoporphyrin and interstitial illumination using 630 nm laser light 24-72 h later. Follow-up was at 6-8 weeks for 1 year. Then every 3-6 months if applicable. Repeat PDT as necessary. RESULTS All patients were stage IIIa-IV. The histology of the tumour was: non small cell in 90 and small cell in 10. There was no treatment related mortality. Mean endoluminal obstruction fell from 85.8% to 17.5%, mean forced vital capacity (FVC) and forced expiratory volume in 1s (FEVI) improvement was 430 ml and 280 ml, respectively. Ninety patients died from 6 weeks to 37 months, mean and median survival: 9 months and 5 months, respectively. Ten patients are alive from 13 to 72 months, mean 36 months, median 29 months. Overall 2-year survival was 19%. Multivariant analysis indicated that age, sex, histology and stage of disease did not influence survival significantly but performance status did. Patients with WHO < 2 had mean and median survival of 17.8 and 14 months versus WHO > 2, 6.9 mean and 4 months median survival (log-rank P < 0.0001). CONCLUSIONS (1) PDT is effective in palliation of inoperable advanced lung cancer. (2) Subset of patients with a better performance status have added survival benefit.

Photodynamic therapy (PDT) in early central lung cancer: a treatment option for patients ineligible for surgical resection

Objectives: To review the Yorkshire Laser Centre experience with bronchoscopic photodynamic therapy (PDT) in early central lung cancer in subjects not eligible for surgery and to discuss diagnostic problems and the indications for PDT in such cases. Methods: Of 200 patients undergoing bronchoscopic PDT, 21 had early central lung cancer and were entered into a prospective study. Patients underwent standard investigations including white light bronchoscopy in all and autofluorescence bronchoscopy in 12 of the most recent cases. Indications for bronchoscopic PDT were recurrence/metachronous endobronchial lesions following previous treatment with curative intent in 10 patients (11 lesions), ineligibility for surgery because of poor cardiorespiratory function in 8 patients (9 lesions) and declined consent to operation in 3 patients. PDT consisted of intravenous administration of Photofrin 2 mg/kg followed by bronchoscopic illumination 24–48 h later. Results: 29 treatments were performed in 21 patients (23 lesions). There was no procedure-related or 30 day mortality. One patient developed mild skin photosensitivity. All patients expressed satisfaction with the treatment and had a complete response of variable duration. Six patients died at 3–103 months (mean 39.3), three of which were not as a result of cancer. Fifteen patients were alive at 12–82 months. Conclusion: Bronchoscopic PDT in early central lung cancer can achieve long disease-free survival and should be considered as a treatment option in those ineligible for resection. Autofluorescence bronchoscopy is a valuable complementary investigation for identification of synchronous lesions and accurate illumination in bronchoscopic PDT.

Oncologic photodynamic therapy: clinical strategies that modulate mechanisms of action.

Photodynamic therapy (PDT) is an elegant minimally invasive oncologic therapy. The clinical simplicity of photosensitizer (PS) drug application followed by appropriate illumination of target leading to the oxygen dependent tumor ablative Photodynamic Reaction (PDR) has gained this treatment worldwide acceptance. Yet the true potential of clinical PDT has not yet been achieved. This paper will review current mechanisms of action and treatment paradigms with critical commentary on means to potentially improve outcome using readily available clinical tools.

Photodynamic therapy (PDT) for lung cancer

Clinical PDT began in the early 1980s and lung cancer was one of the first indications for which the procedure was tried. Initially patients with advanced inoperable cancer and major bronchial obstruction were targeted with the objective of relief of airway obstruction and symptom palliation. In the past 30 years, assisted by progress in imaging methods and advances of technological developments, PDT indications have expanded to incorporate a multitude of lung cancer presentations which this review aims to display. Locally advanced and early stage endobronchial cancer continues to be the major indications albeit with a more precise diagnostic and guided illumination devices. Peripheral parenchymal disease has been a technical challenge but there is still ongoing development. Multifocal synchronous, recurrence and metachronous endobronchial disease following lung resection are now an up and coming indication with rewarding outcome. More importantly PDTs role within a multi-disciplinary assault on lung cancer is receiving acceptance.

The role of photodynamic therapy (PDT) in inoperable oesophageal cancer.

OBJECTIVE To evaluate the role of PDT in palliation of patients with inoperable oesophageal cancer and to identify subgroups in which this role is of particular significance. METHODS Sixty-five patients (37 male, 28 female) aged 42-89 (mean 65.6) with advanced and inoperable oesophageal cancer were the subjects of this study. Inoperability was due to advanced stage of the disease in 61 and because of general condition in 4. Fifty-eight (89%) had previous treatments, other than PDT. All patients had dysphagia of whom 20 could not swallow fluid. Pre-PDT clinical, radiological and endoscopic examinations were carried out. Performance status (PS) and clinical staging was assessed. PDT protocol consisted of: intravenous injection of 2 mg/kg; photofrin (or equivalent polyhaematoporphyrin) followed 24-72 h later by endoscopic illumination using 630 nm laser light. MAIN OUTCOME MEASUREMENTS (1) Relief of dysphagia generally and specifically in those with cervical and post-cricoid carcinoma who were previously treated by external beam radiotherapy (EBR) (n=6) and those with previous intubation or stent (n=9); (2) Survival. RESULTS There was no PDT related mortality. Three patients (4.6%) developed a mild skin photosensitivity reaction. Dysphagia was relieved in all patients. The mean and median survival of the 58 patients who have died was 7. 7 and 6 months respectively. Seven patients are alive from 2-30 months (mean 16). Survival was not significantly influenced by tumour histology, location in the oesophagus, severity of dysphagia on admission, or by previous therapy. Survival was significantly influenced by Performance Status prior to treatment (P=0.03 log rank, for PS < or =2 vs. PS=3), an most significantly by the stage of the disease (P=0.0001 log rank, for Stage III vs. Stage IV). CONCLUSIONS (1) PDT is safe and effective for palliation of dysphagia in inoperable oesophageal cancer. This is particularly important in post-cricoid and cervical oesophageal cancer previously treated by other methods and for patients with recurrent malignant obstruction who previously had intubation or stent placement. (2) Survival is influenced by better PS (< or =2) and in those with disease Stage III rather than patients in Stage IV. This study has not been able to determine the influence of complete tumour staging on survival because, apart from four patients, all others were Stages III and IV cancer.

Photodynamic Therapy (PDT) in Esophageal Cancer: A Surgical View of its Indications Based on 14 Years Experience:

The aim of this paper is to present the updated experience of the Yorkshire Laser Centre in PDT for esophageal cancer and to identify its role in specific subsets of patients. Also, in the light of this experience, to compare and contrast the results of PDT with appropriate subsets of patients treated in my esophageal surgery practice. 102 consecutive patients; 84 with advanced (Group A) and 18 with early (Group E) stage esophageal cancer undergoing endoscopic PDT were entered into a prospective study. Every patient had standard work up including clinical staging. PDT protocol was intravenous administration of Photofrin 2mg/kg body weight followed 24–72 hours later by endoscopic illumination using 630 nm laser light. Assessment of results was made on the basis of mortality, morbidity, patient satisfaction to treatment, symptom relief and survival. For comparison of PDT role with non PDT treated patients, reference is made to 3 previous publications comprising over 1100 patients [Moghissi, K., Br. J. Surg. 79, 935–937 (1992) (ref. 1); Sawant, D., Moghissi, K. Eur. J. Cardio-Thorac. Surg. 8, 113–117 (1994) (ref. 2); Sharpe, D. A. C., Moghissi, K. Eur. J. Cardiothorac. Surg. 10, 359–364 (1996) (ref. 3)]. There was no mortality associated with PDT. All patients expressed satisfaction to treatment. Post PDT complications consisted of photosensitivity skin reaction (sunburn) in 5 patients (5%) and esophageal stricture in 8 (8%) patients. Group A: There was significant symptom and dysphegia grade improvement. Mean survival was 9.5 months. Group E: There were no significant symptoms pre or post PDT and mean survival was 60.5 months. Comparison of PDT results in Group A with results of other palliative treatment methods, indicates that palliation can be achieved in all intraluminal cancer using PDT which is at least as good as other treatments. There is, in addition, advantage over other methods in patients with cervical esophageal cancer and in cases with re-growth of tumor obstructing previously placed stents. In early cases PDT appears capable of replicating surgical results in selected cases. PDT is an effective and safe treatment method in esophageal cancer. In advance disease it improves swallowing. In early stage disease it offers long survival and the prospect of cure in some patients. At present the role of PDT in early stage cancer should be limited to patients who are unsuitable for surgical resection. Therefore, PDT should be considered as a valid oncological option to be applied in selected cases.

Photofrin PDT for early stage oesophageal cancer: Long term results in 40 patients and literature review

BACKGROUND Yorkshire Laser Centre experience of PDT in early oesophageal cancer (EOCa) to determine long survival at 3 and 5 years (absolute) and factors which might influence outcome. MATERIAL/METHOD The records of patients who had PDT (1997-2009) for oesophageal cancer were reviewed and those with EOCa were studied and analysed. All patients had standard work up and staging. PDT was carried out using Photofrin 2 mg/kw bw, iv followed 24-72 h later by endoscopic illumination with 630 nm laser light. Results were assessed based on pathological response to treatment and survival at 3 and 5 years post-PDT. RESULTS There were 40 patients with EOCa amongst 144 who had PDT for oesophageal cancer. 30 male and 10 female (mean age 77, range 48-84). 35 had adenocarcinoma and 5 squamous cell carcinoma. 20 of the former had Barretts mucosa. There was no operative or 30-day mortality and no serious complications. Adverse effects were noted in 10 patients including 2 with skin photosensitivity and 3 with mild stricture requiring one dilatation. The median follow up was 76.1 (range 36-150 months). In this period 24 patients have died between 2 and 150 months (median 41 months). 16 patients are alive in between 36 and 110 months. 3 and >or=5 years or more survival (absolute) were 72.5% and 53.8%, respectively. CONCLUSION Endoscopic PDT should be considered as the treatment of choice in patients with EOCa who are ineligible for surgical resection. We suggest that a carefully designed study of a cohort of patients with EOCa comparing surgical resection with endoscopic PDT is warranted.

Photodiagnosis and fluorescence imaging in clinical practice.

For cancer diagnosis clinicians rely upon histo pathological preparations in their broadest sense and the characteristic microscopic features which represent malignant changes. Standard method of in-vivo sampling (biopsy) uses white light indicating abnormal tissue. The manner in which light interacts with a specific tissue type is dictated by the wavelength dependent scattering and absorbtion properties. In the UV and visible part of the spectrum the tissue optical properties are dominated by the endogenous chromophores which is different for normal/abnormal tissue. It follows that abnormal tissue, absorbs light and fluoresces differently to normal tissue at specific light wavelengths. Autofluorescence takes advantage of this principle. Enhanced fluorescence employs exogenous markers to produce better definition. Fluorescence imaging has become an important diagnostic tool to highlight cancer at an early stage of development and/or to guide biopsy from representative samples.

Photodynamic therapy (PDT) for lung cancer: the Yorkshire Laser Centre experience

BACKGROUND The Yorkshire Laser Centre team have been engaged in photodynamic therapy (PDT) since 1990. In this article we review our experience in bronchoscopic PDT for lung cancer and outline our current indications and results. METHODS 160 patients in 2 groups entered into a prospective study: Group A (N=144) were symptomatic with advanced inoperable disease and with presence of >50% bronchial obstruction. Group E (N=16) with early stage cancer and presence of superficial lesion confined to bronchial tree. All patients had standard investigation and work-up bronchoscopy and biopsy confirmation of cancer by cyto-histology. PDT method was intravenous administration of 2mg/kg BW of Photofrin (Porfimer Sodium) followed by bronchoscopic illumination of 630nm laser light. RESULTS There was no treatment-related mortality. Nine patients (5.6%) presented with skin photosensitivity reaction and another eight with respiratory complication. Group A: Symptom relief was achieved in all. This was matched by significant improvement in bronchial opening (58.1%). Survival was 9.6 months (mean) and 5 months (median), respectively. This was greater in patients with better performance status and lower stage of disease. Group E: Every patient had a complete response to treatment, some after two treatments. Survival in this group was 75.4 months (mean) and 69 months (median). CONCLUSIONS Bronchoscopic PDT is indicated in both advanced and early stage lung cancer. In the former it provides symptomatic relief in all and survival benefit in some; in the latter it achieves long survival and potential cure.