Photodiagnosis and Photodynamic Therapy (2006) 3, 1—2
EDITORIAL COMMENT
Salvage photodynamic therapy for persistent oesophageal cancer after chemo/radiation therapy Although oesophagectomy has been regarded as the standard treatment for oesophageal cancer, over 50% of patients are inoperable at presentation and 60—70% of cases have locally advanced tumour at diagnosis. Of the patients who undergo successful complete resection the majority succumb to local recurrence or metastatic disease [1—3], therefore, pre-operative chemotherapy (neo-adjuvant therapy) and chemo/radiotherapy (CRT) have been promoted for oesophageal cancer patients destined to be treated by surgical resection [2—4]. General and local pathological tumour response, as well as the patients’ tolerance to chemotherapy, are subject to variations. These influence both the postchemotherapy operability rate and outcome [5—7]. The idea of the endoscopic use of photodynamic therapy (PDT) in patients with local recurrence for residual endoluminal oesophageal cancer following neo-adjuvant chemotherapy or CRT, who cannot or will not have surgical resection is basically sound and is oncologically attractive. It is based on the premise that chemotherapy will affect the micro-metastatic lesions and that PDT will dispose of the tumour recurrence, or its residue, locally. Wolfsen and Hemminger [8] in this issue of the journal report on seven patients who were scheduled to have surgical resection following CRT. However, for various reasons, they did not undergo the intended surgery and were found to have local residual cancer. These patients were submitted to endoscopic Photofrin® PDT with encouraging results. Despite the limitations imposed by the small number of patients in the study, and its retroDOIs of original articles:10.1016/S1572-1000(06)00002-0, 10.1016/S1572-1000(06)00004-4, 10.1016/S1572-1000(06)00005-6.
spectiveness, the article presents some interesting features, which could be usefully discussed. The series (seven patients) forms 5% of the total oesophageal cancers treated in the authors institution during the study period. Nevertheless, they were amongst many others who, following CRT, did not continue with surgical treatment. It could be speculated that in a prospective study much more than 5% of such patients could enter into a PDT course. All seven patients had residual tumour despite CRT and the five patients with adenocarcinoma within columnar epithelial lined oesophagus (Barrett’s oesophagus) had between 5—10 cm of metaplastic mucosa in their oesophagus at the start of PDT, confirming the assumption that CRT is not expected to change the metaplastic mucosa even if and/or when it can deal with dysplastic or neoplastic changes within the Barrett’s mucosa. This implies that more careful selection of patients with adenocarcinoma in Barrett’s oesophagus should be made to avoid administering CRT or neo-adjuvant chemotherapy to those who may not ultimately undergo resection. All the patients reported by Wolfsen and Hemminger developed oesophageal stricture following PDT: a 100% rate. This is considerably higher than that reported in the literature. Stricture formation following PDT has been reported by a number of authors with the varying rate between 5.5% and 50% [9—11]. Panjehpour et al. [11] have recently suggested that the rate of post-PDT stricture formation in Barrett’s oesophagus with dysplasia or early carcinoma relates to the light dose as well as previous therapy with PDT or external beam radiation (XRT). In that study, which also used Photofrin® PDT, 15.5%
1572-1000/$ — see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/S1572-1000(06)00003-2
2 of patients who received a light dose of above 100 J/cm (115 J/cm) developed stricture whereas 5.5% stricture was present in those receiving light dose of less than 100 J/cm. They, therefore, postulated that the rate of stricture formation correlates with the strength of light dose illumination. Wolfsen and Hemminger, in this study [8], have used a higher light dose of 200 J/cm. It could, therefore, be argued that their high rate of post-PDT stricture could be the consequence of too high a dose of light exposure. However, in our experience of over 100 patients with early and advanced endo-oesophageal cancer submitted to Photofrin® PDT the light dose was 200 J/cm of the tumour and the rate of stricture formation after therapy was 8% [10]. Some patients in this series had received external beam radiotherapy/brachytherapy prior to PDT. Also in a recent study by Foroulis and Thorpe [12] concerning 31 patients with Barrett’s oesophagus and high grade dysplasia or early adenocarcinoma undergoing endoscopic Photofrin® PDT the light dose was 200 J/cm and post-PDT stricture was noted in 2 patients (6%). No chemotherapy or radiotherapy was used in their patients. It, therefore, follows that light dose alone does not appear to be responsible for the high rate of post-PDT stricture formation. I believe Wolfsen and Hemminger have entered into an as-yet uncharted territory for the indications of PDT, that is; making PDT available to those who are ineligible for oesophagectomy following CRT or neo-adjuvant chemotherapy, but who still harbour endoluminal tumour. There are many such patients and therapeutic choices are limited. For the future it seems reasonable to suggest endoscopic PDT in selected patients following CRT or neoadjuvant therapy in a cohort of non-responders with local residual disease who cannot or will not go through surgical resection. An extension of the idea would be to plan a prospective randomised study of PDT and chemotherapy versus chemotherapy alone in a neoadjuvant therapy setting.
Editorial comment
References [1] Sharpe DAC, Moghissi K. Resectional surgery in carcinoma of the oesophagus and cardia: what influences long term survival. Eur J Cardiothorac Surg 1996;10:359— 64. [2] Lerut T. Oesophageal surgery at the end of millennium. J Thorac Cardiovasc Surg 1998;116:1—20. [3] Lerut T, Decker G. In: Moghissi K, Thorpe AJC, Ciulli F, editors. Cancer of the oesophagus in Moghissi’s essentials of thoracic and cardiac surgery. 2nd ed. Amsterdam, Boston, London: Elsevier; 2003. p. 349—97. [4] Urschel JD, Vassan H, Blewtt CJ. A meta analysis of randomised controlled trials that compared neo adjuvant chemotherapy and surgery to surgery alone for resectable oesophageal cancer. Ann J Surg 2004;183: 274—9. [5] Zacherl J, Sendler A, Stein HJ, et al. Current status of neoadjuvant therapy for adeno carcinoma of distal oesophagus. World J Surg 2003;27:1067—74. [6] Kelsen DP, Ginsberg R, Rajak TF, et al. Chemotherapy followed by surgery compared with surgery alone for localised oesophageal cancer. N Eng J Med 1998;339:1979—84. [7] Medical Research Council Oesophageal Cancer Working Party. Surgical resection with or without neoadjuvant chemotherapy in oesophageal cancer: a randomised controlled trial. Lancet 2002;359:1727—33. [8] Wolfson HC, Hemminger LL. Salvage photodynamic therapy for persistent oesophageal cancer after chemo/radiation therapy. Photodiagn Photodyn Ther 2006;3:11—4. [9] Overholt BF, Panjehpour M, Hayde K. Photodynamic therapy for Barrett’s oesophagus follow up of 100 patients. J Clin Laser Med Surg 1999;49:1—7. [10] Moghissi K, Dixon K. Photodynamic therapy (PDT) in oesophageal cancer: a surgical review and its indications based on 14 years experience. Technol Cancer Res Treat 2003;2:319—26. [11] Panjehpour M, Overholt BF, Phan MN, Haydek JM. Optimization of light dosimetry for photodynamic therapy of Barrett’s oesophagus: efficacy vs incidence of stricture after treatment. Gastro-intes Endosc 2005;61:13—8. [12] Foroulis CN, Thorpe JAC. Photodynamic therapy (PDT) in Barrett’s oesophagus with dysplasia or early cancer. Eur J Cardiothorac Surg 2006;29:30—4.
K. Moghissi MD, FRCS Yorkshire Laser Centre E-mail address: [email protected]
EDITORIAL COMMENT
Salvage photodynamic therapy for persistent oesophageal cancer after chemo/radiation therapy Although oesophagectomy has been regarded as the standard treatment for oesophageal cancer, over 50% of patients are inoperable at presentation and 60—70% of cases have locally advanced tumour at diagnosis. Of the patients who undergo successful complete resection the majority succumb to local recurrence or metastatic disease [1—3], therefore, pre-operative chemotherapy (neo-adjuvant therapy) and chemo/radiotherapy (CRT) have been promoted for oesophageal cancer patients destined to be treated by surgical resection [2—4]. General and local pathological tumour response, as well as the patients’ tolerance to chemotherapy, are subject to variations. These influence both the postchemotherapy operability rate and outcome [5—7]. The idea of the endoscopic use of photodynamic therapy (PDT) in patients with local recurrence for residual endoluminal oesophageal cancer following neo-adjuvant chemotherapy or CRT, who cannot or will not have surgical resection is basically sound and is oncologically attractive. It is based on the premise that chemotherapy will affect the micro-metastatic lesions and that PDT will dispose of the tumour recurrence, or its residue, locally. Wolfsen and Hemminger [8] in this issue of the journal report on seven patients who were scheduled to have surgical resection following CRT. However, for various reasons, they did not undergo the intended surgery and were found to have local residual cancer. These patients were submitted to endoscopic Photofrin® PDT with encouraging results. Despite the limitations imposed by the small number of patients in the study, and its retroDOIs of original articles:10.1016/S1572-1000(06)00002-0, 10.1016/S1572-1000(06)00004-4, 10.1016/S1572-1000(06)00005-6.
spectiveness, the article presents some interesting features, which could be usefully discussed. The series (seven patients) forms 5% of the total oesophageal cancers treated in the authors institution during the study period. Nevertheless, they were amongst many others who, following CRT, did not continue with surgical treatment. It could be speculated that in a prospective study much more than 5% of such patients could enter into a PDT course. All seven patients had residual tumour despite CRT and the five patients with adenocarcinoma within columnar epithelial lined oesophagus (Barrett’s oesophagus) had between 5—10 cm of metaplastic mucosa in their oesophagus at the start of PDT, confirming the assumption that CRT is not expected to change the metaplastic mucosa even if and/or when it can deal with dysplastic or neoplastic changes within the Barrett’s mucosa. This implies that more careful selection of patients with adenocarcinoma in Barrett’s oesophagus should be made to avoid administering CRT or neo-adjuvant chemotherapy to those who may not ultimately undergo resection. All the patients reported by Wolfsen and Hemminger developed oesophageal stricture following PDT: a 100% rate. This is considerably higher than that reported in the literature. Stricture formation following PDT has been reported by a number of authors with the varying rate between 5.5% and 50% [9—11]. Panjehpour et al. [11] have recently suggested that the rate of post-PDT stricture formation in Barrett’s oesophagus with dysplasia or early carcinoma relates to the light dose as well as previous therapy with PDT or external beam radiation (XRT). In that study, which also used Photofrin® PDT, 15.5%
1572-1000/$ — see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/S1572-1000(06)00003-2
2 of patients who received a light dose of above 100 J/cm (115 J/cm) developed stricture whereas 5.5% stricture was present in those receiving light dose of less than 100 J/cm. They, therefore, postulated that the rate of stricture formation correlates with the strength of light dose illumination. Wolfsen and Hemminger, in this study [8], have used a higher light dose of 200 J/cm. It could, therefore, be argued that their high rate of post-PDT stricture could be the consequence of too high a dose of light exposure. However, in our experience of over 100 patients with early and advanced endo-oesophageal cancer submitted to Photofrin® PDT the light dose was 200 J/cm of the tumour and the rate of stricture formation after therapy was 8% [10]. Some patients in this series had received external beam radiotherapy/brachytherapy prior to PDT. Also in a recent study by Foroulis and Thorpe [12] concerning 31 patients with Barrett’s oesophagus and high grade dysplasia or early adenocarcinoma undergoing endoscopic Photofrin® PDT the light dose was 200 J/cm and post-PDT stricture was noted in 2 patients (6%). No chemotherapy or radiotherapy was used in their patients. It, therefore, follows that light dose alone does not appear to be responsible for the high rate of post-PDT stricture formation. I believe Wolfsen and Hemminger have entered into an as-yet uncharted territory for the indications of PDT, that is; making PDT available to those who are ineligible for oesophagectomy following CRT or neo-adjuvant chemotherapy, but who still harbour endoluminal tumour. There are many such patients and therapeutic choices are limited. For the future it seems reasonable to suggest endoscopic PDT in selected patients following CRT or neoadjuvant therapy in a cohort of non-responders with local residual disease who cannot or will not go through surgical resection. An extension of the idea would be to plan a prospective randomised study of PDT and chemotherapy versus chemotherapy alone in a neoadjuvant therapy setting.
Editorial comment
References [1] Sharpe DAC, Moghissi K. Resectional surgery in carcinoma of the oesophagus and cardia: what influences long term survival. Eur J Cardiothorac Surg 1996;10:359— 64. [2] Lerut T. Oesophageal surgery at the end of millennium. J Thorac Cardiovasc Surg 1998;116:1—20. [3] Lerut T, Decker G. In: Moghissi K, Thorpe AJC, Ciulli F, editors. Cancer of the oesophagus in Moghissi’s essentials of thoracic and cardiac surgery. 2nd ed. Amsterdam, Boston, London: Elsevier; 2003. p. 349—97. [4] Urschel JD, Vassan H, Blewtt CJ. A meta analysis of randomised controlled trials that compared neo adjuvant chemotherapy and surgery to surgery alone for resectable oesophageal cancer. Ann J Surg 2004;183: 274—9. [5] Zacherl J, Sendler A, Stein HJ, et al. Current status of neoadjuvant therapy for adeno carcinoma of distal oesophagus. World J Surg 2003;27:1067—74. [6] Kelsen DP, Ginsberg R, Rajak TF, et al. Chemotherapy followed by surgery compared with surgery alone for localised oesophageal cancer. N Eng J Med 1998;339:1979—84. [7] Medical Research Council Oesophageal Cancer Working Party. Surgical resection with or without neoadjuvant chemotherapy in oesophageal cancer: a randomised controlled trial. Lancet 2002;359:1727—33. [8] Wolfson HC, Hemminger LL. Salvage photodynamic therapy for persistent oesophageal cancer after chemo/radiation therapy. Photodiagn Photodyn Ther 2006;3:11—4. [9] Overholt BF, Panjehpour M, Hayde K. Photodynamic therapy for Barrett’s oesophagus follow up of 100 patients. J Clin Laser Med Surg 1999;49:1—7. [10] Moghissi K, Dixon K. Photodynamic therapy (PDT) in oesophageal cancer: a surgical review and its indications based on 14 years experience. Technol Cancer Res Treat 2003;2:319—26. [11] Panjehpour M, Overholt BF, Phan MN, Haydek JM. Optimization of light dosimetry for photodynamic therapy of Barrett’s oesophagus: efficacy vs incidence of stricture after treatment. Gastro-intes Endosc 2005;61:13—8. [12] Foroulis CN, Thorpe JAC. Photodynamic therapy (PDT) in Barrett’s oesophagus with dysplasia or early cancer. Eur J Cardiothorac Surg 2006;29:30—4.
K. Moghissi MD, FRCS Yorkshire Laser Centre E-mail address: [email protected]
