Photodiagnosis and Photodynamic Therapy (2006) 3, 15—16

INVITED COMMENTARY

Salvage PDT for persistent esophageal cancer after chemoradiotherapy Despite recent epidemiologic trends in North America and Europe, esophageal cancer is still a relatively uncommon tumor. Consequently no single centre is likely to accrue sufficient numbers of patients with all stages of esophageal malignancy to make definitive recommendations for management. The report by Wolfsen and Hemminger therefore evaluates a highly selected patient population, seven patients only, who were judged to be medically unfit for potentially curative surgery after induction chemoradiotherapy, and who were found to have persistent or recurrent esophageal carcinoma. The encouraging results achieved following salvage photodynamic therapy (PDT), specifically in terms of control of local disease in the five patients with adenocarcinoma, warrant further careful evaluation and future study to define the role of this innovative approach to treat recurrent or recalcitrant esophageal malignancy. With only modest improvement in outcome reported with increasing use of multimodality therapy for esophageal malignancy, surgery remains the mainstay of current treatment strategies, offering not only potential for cure, but also an improved quality of life. In modern practice, particularly in high-volume centres, esophageal resection and reconstruction is performed safely, with operative mortality rates below 5% even in patients considered to be ‘‘high-risk’’. Other than patient refusal, it is therefore important to define why, after induction chemoradiotherapy, patients would be reconsidered to be ‘‘not medically fit’’ to undergo DOIs of related articles:10.1016/S1572-1000(06)00002-0, 10.1016/S1572-1000(06)00003-2, 10.1016/S1572-1000(06)00005-6.

esophageal resection, especially if such patients were judged fit for induction therapy and surgery initially. Often a sufficient time interval exists after the completion of induction therapy to optimize medical management (cardio-respiratory function, nutritional status, etc.) in preparation for surgery. During this time, restaging studies (endoscopy, endoscopic ultrasound, CT scanning, PET scanning, etc.) are completed to assess tumor response to induction therapy, and as described in this report, it is essential to obtain a definitive cytologic or histologic diagnosis of persistent or recurrent disease. Therefore, if potentially curative surgical intervention is excluded because of tumor progression, patient refusal or for defined medical reasons, what options are available and what are realistic outcomes? At this stage of treatment, patient numbers at individual centres will generally be small (and highly selected), and in the absence of definitive evidence-based recommendations, therapeutic strategies will necessarily be individualized. Depending on the induction chemoradiotherapy regimen, it may well be possible to administer further external beam radiation therapy or to consider endoluminal brachytherapy. Similarly, use of second-line chemotherapy may be considered to enhance radiosensitivity or to control systemic disease. With the goal of maintaining swallowing and quality of life, local therapeutic modalities include esophageal stenting, bouginnage or ablation (mechanical, argon beam, PDT, etc.). Although PDT therapy in this series resulted in the apparent eradication of residual mucosal adenocarcinoma, the development of esophageal stricture in all patients, requiring repeated dilation,

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16 would be expected to diminish quality of life. In this patient population, it could be argued that quality of life may be the most relevant outcome, and future studies should incorporate an assessment of swallowing and quality of life in addition to disease recurrence, stricture formation, and survival. Whether the rate of recurrent stricture formation may be reduced by altering the dose and/or administration of PDT also requires further study. Furthermore, with any esophageal instrumentation, and especially when the organ is diseased or has been irradiated, there is a small but definite risk of perforation, a complication which may be particularly challenging to treat. One of the most interesting observations arising from this study, although patient numbers are limited, relates to the efficacy of salvage PDT by esophageal tumor histology. Based on epidemiologic observations of risk factors, and more recent molecular genetic studies, it is clear that

Invited commentary esophageal squamous cell carcinomas and primary esophageal adenocarcinomas are biologically different diseases, and therefore it is not surprising that individual response to PDT varies. If these preliminary observations are confirmed by subsequent larger studies, it would appear that further investigation of molecular mechanisms underlying response to PDT may well provide additional insight into esophageal tumor biology, with potential to modulate therapeutic response. Alan G. Casson FRCSC ∗ Professor, Dalhousie University, Chief, Division of Thoracic & Esophageal Surgery, QEII Health Sciences Centre, Halifax, NS, Canada NS B3H 2Y9 ∗ Tel.:

+1 902 473 2281; fax: +1 902 473 4426. E-mail address: [email protected] Available online 20 February 2006

Salvage PDT for persistent esophageal cancer after chemoradiotherapy.

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