Kate Dixon

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.

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.

A controlled trial of Nd-YAG laser vs photodynamic therapy for advanced malignant bronchial obstruction

A prospective randomized study was set up to evaluate the efficacy of photodynamic therapy (PDT) compared with Neodymium Yttrium Aluminium Garnet (Nd-YAG) laser used endoscopically in patients with stage III inoperable lung cancer and substantial (>50%) endobronchial luminal obstruction: of the 26 patients in the study 11 were allocated to Nd-YAG laser treatment (Group I) and 15 to PDT (Group II). Patients were assessed clinically, radiologically, functinally and endoscopically before and at 1 monthly intervals after treatment for 3 months, then 3 monthly when applicable.Age, sex, pulmonary function and mean percentage of bronchial luminal opening before treatment were comparable in the two groups, and not statistically different.At 1 month after treatment all patients had subjective amelioration of their symptoms and objectively responded to treatment by a substantial increase in bronchial luminal opening. There was however a significantly greater improvement in the PDT (Group II) than the Nd-YAG laser treatment Group I (p<0.0006). The bronchial disobliteration was attended by improvement in pulmonary function which again was significantly greater in Group II (PDT) than in Group I (Nd-YAG).It was concluded that endoscopic PDT in patients with extensive lung cancer and major airway obstruction is more effective than Nd-YAG laser treatment.

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.

Photodynamic therapy (PDT) for bronchial carcinoma with the use of rigid bronchoscope

Endoscopic PDT was undertaken in nine patients with inoperable bronchial cancer. Eight patients had advanced metastatic disease and one was unsuitablefor surgery on account of age, respiratory function and location of tumour. Patients were injected with Photofrin II (no. 7) or Polyhaematoporphyrin derivative (no. 2) at 2 mg kg−1 of bodyweight before being irradiated 48 h later by 630 nm red light generated by a copper vapour laser (Oxford Lasers) for 200 J cm−1 tumour tissue. Treatment was undertaken under general anaesthetic using a rigid bronchoscope for ventilating and suction purposes with the fibre optic instrument introduced through the rigid bronchoscope for localization of tumour and placement of the diffusing fibre. One patient died 2 months after treatment from carcinomatosis. One patient had total response with negative histology for 10 months. All other patients with substantial endobronchial obstructive lesions had partial response with significant reduction in percentage obstruction and improved pulmonary function. There have been no post-operative complications.

Photodynamic therapy in the management of malignant pleural mesothelioma: A review.

BACKGROUND In the past decade there have been sporadic publications on malignant pleural mesothelioma (MPM). In the present trend of multi-modal treatment for MPM we aim to evaluate the current status of photodynamic therapy (PDT) in the management of MPM through a review study. METHODS Original publications in English were the main source of the review and their material analysed in respect of patient and disease characteristics, PDT methods, mortality and morbidity and survival. Ten articles concerned with 230 patients were analysed and 35 other publications relevant to the study were used for reference. In every case PDT was used as an adjuvant to surgery whose role appeared to be a cyto-reductive procedure of debulking, pleurectomy and decortication (DPD) with/without pulmonary resection. PDT methods used two photosensitisers; Photofrin™ [630nm laser light] (6 series=170 patients) or Foscan™ [652nm laser light] (4 series=60 patients). RESULTS Overall mortality and morbidity was 7.1% (4.9% for Photofrin™ and 13.3% for Foscan™ PDT) and 48% (38% for Photofrin™ and 70% for Foscan™ PDT) respectively. Better survival was achieved for DPD and early stage disease. CONCLUSIONS Intra-operative (IOP) PDT in MPM is a safe procedure that requires more development and work regarding photosensitisers and light distribution systems for use in intra-pleural situations. The role of surgery in IOP-PDT appears to be cyto-reduction to ≤5mm residual tumour thickness in order for PDT to be used effectively. Curative intent may depend on the stage of MPM and completeness of cyto-reduction with/without pulmonary resection.

A method for video-assisted thoracoscopic photodynamic therapy (VAT-PDT)

A technique is described for application of photodynamic therapy (PDT) to peripheral pulmonary and other intrathoracic malignant tumours. For video-assisted thoracoscopic-PDT we advocate the use of the flexible fibreoptic bronchoscope through an appropriately placed port. This, together with the standard thoracoscope and attached monitor can provide three-dimensional visualisation of the intrathoracic lesion and more importantly allow the accurate delivery of laser light to the tumour. At the present time we have successfully used this method without complication in three patients with advanced inoperable disease.

A Surgical View of Photodynamic Therapy in Oncology: A Review

Clinical photodynamic therapy (PDT) has existed for over 30 years, and its scientific basis has been known and investigated for well over 100 years. The scientific foundation of PDT is solid and its application to cancer treatment for many common neoplastic lesions has been the subject of a huge number of clinical trials and observational studies. Yet its acceptance by many clinicians has suffered from its absence from the undergraduate and/or postgraduate education curricula of surgeons, physicians, and oncologists. Surgeons in a variety of specialties many with years of experience who are familiar with PDT bear witness in many thousands of publications to its safety and efficacy as well as to the unique role that it can play in the treatment of cancer with its targeting precision, its lack of collateral damage to healthy structures surrounding the treated lesions, and its usage within minimal access therapy. PDT is closely related to the fluorescence phenomenon used in photodiagnosis. This review aspires both to inform and to present the clinical aspect of PDT as seen by a surgeon.