Photodiagnosis and Photodynamic Therapy (2006) 3, 93—95
HOW-TO-DO-IT
Endoscopic photodynamic therapy (PDT) for oesophageal cancer Keyvan Moghissi MD, FRCS (ED & Eng) ∗ The Yorkshire Laser Centre, Goole & District Hospital, Woodland Avenue, Goole, East Yorkshire DN14 6RX, UK Available online 2 May 2006 KEYWORDS PDT method; Oesophageal cancer
Summary Endoscopic photodynamic therapy (PDT) is undertaken only when tumour is visible endoscopically with malignancy biopsy confirmed. Patients will be either Group A: inoperable cases with locally advanced cancer when the aim is palliation of dysphagia, or Group E: patients with early stage I—II disease who are unsuitable for surgery or decline operation, when the intent is curative. Following assessment for suitability for PDT and counselling, Photofrin 2 mg/(kg bw) is administered 24—72 h before endoscopic illumination using a Diode 630 nm laser. Illumination may be either interstitial or intraluminal at a dose of 100—200 J/cm. © 2006 Elsevier B.V. All rights reserved.
Many oesophageal photodynamic therapists are amongst gastro-enterology physicians or surgeons though some are thoracic surgeons and they will have been involved in investigation, diagnosis, staging and selection of patients for photodynamic therapy (PDT). As a thoracic surgeon with special interest in PDT my own referral pattern is mixed. The majority of patients have had full investigation, diagnosis and staging prior to referral for PDT. A small minority are referred to me for investigation of upper-gastro-intestinal symptoms and require full investigation leading to diagnosis and treatment. All cases are only selected for PDT after the patient has had comprehensive investigations with histology-proven diagnosis of cancer and when the tumour has been staged using the international TNM stage classification. ∗
Tel.: +44 1724 290456; fax: +44 1724 290456. E-mail address: [email protected].
Patient selection There are two mandatory inclusion criteria: 1. The tumour should be visible endoscopically and confirmed by biopsy to be a malignant tumour. 2. The patient should be ineligible for surgical resection or has declined surgical undertaking. Clinical/laboratory investigations, imaging and endoscopic examinations with biopsy procedure dictate the preliminary selection. Patients are then placed into one of two categories for inclusion to endoscopic PDT; each of these has a defined objective. These are: (a) Patients with locally advanced inoperable cancer (Group A). (b) Patients with early cancer (Group E).
1572-1000/$ — see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.pdpdt.2006.03.005
94
K. Moghissi • The location within the oesophagus of the upper and lower limits of the cancer. • The approximate length of the tumour. • The extent of tumour circumferentially. • The extent of the tumour projection in the lumen. 2. Patient information: This consists of written and verbal communication highlighting the possible risks and the intended benefit of PDT. It is particularly impressed upon the patient the potential for photosensitivity skin reaction and the remote possibility of perforation and other hazards such as early oesophagitis and delayed stricture. 3. Intravenous injection of the photosensitiser: In an overall majority of patients Photofrin® 2 mg/(kg bw) has been used. 4. Endoscopic illumination is carried out 24—72 h after intravenous injection of the photosensitiser.
Anaesthetic and instrumentation
Figure 1 Flow chart of PDT for oesophageal cancer: how I do it.
• The aim in Group A patients is palliation of dysphagia with survival benefit if possible. After my first 60—70 [1,2] cases of PDT in such patients, those with advanced stage IV disease and cases with WHO performance status (PS) ≥4 are now excluded from endoscopic PDT, since dysphagia, which is the main concern can be alleviated by other endoscopic methods such as NdYAG laser with quicker response and relief of luminal obstruction. • Treatment in Group E patients is undertaken with curative intent. These patients have an early stage I or II disease and are technically operable but for reasons other than oncological are unsuitable for resectional surgery. Patients with poor cardio-respiratory function and chronic conditions fall within this group. Some patients refuse surgery and are also selected for endoscopic PDT.
Patients are given the choice of general or topical (with sedation) anaesthesia. The overall majority (85%) of cases are patients with advanced disease who have extensive local disease requiring lengthy exposure to light in tumours extending to ≥10 cm. In such cases the procedure can be long and exhausting for the patient and, therefore, general anaesthetic is preferable. The instrument of choice is the video-fibroscope, which allows a general view of the lesion by more than one observer and the possibility of static photography and dynamic video recording of the procedure. In occasional cases the rigid instrument is used prior to the video-fibroscope; this is for lavage of an impacted oesophagus below which the obstructive lesion is situated; without lavage efficient illumination is not possible due to poor visibility. Sometimes it is also necessary to carry out dilatation of much obstructed oesophagus. In such cases pre-
My algorithm for endoscopic PDT for oesophageal cancer is shown in Fig. 1. 1. Pre-PDT endoscopic assessment: This is carried out in order to determine:
Figure 2 Two types of illumination for oesophageal cancer.
Endoscopic photodynamic therapy for oesophageal cancer
Figure 3 Interstitial (intratumour) illumination for advanced exophytic tumours.
Figure 4 Intraluminal illumination for tumours involving circumferentially the oesophageal wall.
illumination dilatation is preferable using the rigid oesophagoscope and Maloney type of ‘‘bougies’’.
Light source, delivery devices and applicators Currently this is a Diode laser delivering 630 nm light. The light is delivered through a 600 nm optical fibre with a variable length (0.5—5 cm) cylindrical diffuser or a microlens. The former projects the light circumferentially, whereas the latter has a forward projection of the light. Two types of illumination are carried out according to the bulk of the tumour mass and the extent of circumferential wall involvement (Fig. 2). (a) In patients with bulky exophytic tumours; typically in advanced cancers interstitial illumination is employed when the diffuser is inserted into the mass of the tumour, using a diffuser whose length corresponds to the length of the tumour mass (Fig. 3). In a tumour whose size is in excess of the length of the diffuser, two or more placements are made in order to expose to the light the whole of the tumour.
95
(b) In cases with advanced cancer involving the oesophageal wall circumferentially, intraluminal illumination is carried out. (c) In a case of a superficial cancer, such as the case for early cancer, either surface or intraluminal illumination is performed. If the tumour partially involves the circumference of the oesophageal wall, I use a microlens with a forward projection. However, if the tumour is involving the wall circumferentially, intraluminal application is employed placing a diffuser of appropriate length within the lumen (Fig. 4). Alternatively, the system developed at the Yorkshire Laser Centre [3] (Fig. 4) is used. For interstitial therapy the light dose is 200 J/cm with a slightly lower dose (100—150 J/cm of the tumour) for superficial cancer. • Post PDT management Following PDT, the patient is kept for 2—3 h in the hospital. They are checked clinically and observed drinking some liquid before being discharged home. They are seen after a month in the out-patient clinic and oesophagoscoped between 4 and 6 after the PDT. On these visits the grade of dysphagia and symptoms are recorded and pathological response (whether complete/or partial response or no response are recorded). • Complication/unwanted events I have carried out endoscopic PDT in over 100 patients with carcinoma of the oesophagus [4]. There has been 5% mild photosensitivity skin reaction, and 8% post PDT stricture needing on average 2 dilatations/patient.
References [1] Moghissi K, Dixon K, Thorpe JAC, Stringer MR, Moore PJ. The role of photodynamic therapy (PDT) in inoperable oesophageal cancer. Eur J Cardiothorac Surg 2000;17:95—101. [2] Moghissi K, Dixon K, Hudson E, Stringer M. Photodynamic therapy of oesophageal cancer. Lasers Med Sci 1995;10:67—71. [3] Hudson E, Stringer MR, Dixon K, Moghissi K. A new diffuser/applicator for PDT in oesophagus published in the abstract book. In: Proceedings of the 5th International Photodynamic Association meeting, SPIE vol. 2371. September 1994. p. 563—6. [4] Moghissi K, Dixon K. Photodynamic therapy in oesophageal cancer: a surgical view of its indications based on 14 years experience. Technol Cancer Res Treat 2003;2:319—26.
HOW-TO-DO-IT
Endoscopic photodynamic therapy (PDT) for oesophageal cancer Keyvan Moghissi MD, FRCS (ED & Eng) ∗ The Yorkshire Laser Centre, Goole & District Hospital, Woodland Avenue, Goole, East Yorkshire DN14 6RX, UK Available online 2 May 2006 KEYWORDS PDT method; Oesophageal cancer
Summary Endoscopic photodynamic therapy (PDT) is undertaken only when tumour is visible endoscopically with malignancy biopsy confirmed. Patients will be either Group A: inoperable cases with locally advanced cancer when the aim is palliation of dysphagia, or Group E: patients with early stage I—II disease who are unsuitable for surgery or decline operation, when the intent is curative. Following assessment for suitability for PDT and counselling, Photofrin 2 mg/(kg bw) is administered 24—72 h before endoscopic illumination using a Diode 630 nm laser. Illumination may be either interstitial or intraluminal at a dose of 100—200 J/cm. © 2006 Elsevier B.V. All rights reserved.
Many oesophageal photodynamic therapists are amongst gastro-enterology physicians or surgeons though some are thoracic surgeons and they will have been involved in investigation, diagnosis, staging and selection of patients for photodynamic therapy (PDT). As a thoracic surgeon with special interest in PDT my own referral pattern is mixed. The majority of patients have had full investigation, diagnosis and staging prior to referral for PDT. A small minority are referred to me for investigation of upper-gastro-intestinal symptoms and require full investigation leading to diagnosis and treatment. All cases are only selected for PDT after the patient has had comprehensive investigations with histology-proven diagnosis of cancer and when the tumour has been staged using the international TNM stage classification. ∗
Tel.: +44 1724 290456; fax: +44 1724 290456. E-mail address: [email protected].
Patient selection There are two mandatory inclusion criteria: 1. The tumour should be visible endoscopically and confirmed by biopsy to be a malignant tumour. 2. The patient should be ineligible for surgical resection or has declined surgical undertaking. Clinical/laboratory investigations, imaging and endoscopic examinations with biopsy procedure dictate the preliminary selection. Patients are then placed into one of two categories for inclusion to endoscopic PDT; each of these has a defined objective. These are: (a) Patients with locally advanced inoperable cancer (Group A). (b) Patients with early cancer (Group E).
1572-1000/$ — see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.pdpdt.2006.03.005
94
K. Moghissi • The location within the oesophagus of the upper and lower limits of the cancer. • The approximate length of the tumour. • The extent of tumour circumferentially. • The extent of the tumour projection in the lumen. 2. Patient information: This consists of written and verbal communication highlighting the possible risks and the intended benefit of PDT. It is particularly impressed upon the patient the potential for photosensitivity skin reaction and the remote possibility of perforation and other hazards such as early oesophagitis and delayed stricture. 3. Intravenous injection of the photosensitiser: In an overall majority of patients Photofrin® 2 mg/(kg bw) has been used. 4. Endoscopic illumination is carried out 24—72 h after intravenous injection of the photosensitiser.
Anaesthetic and instrumentation
Figure 1 Flow chart of PDT for oesophageal cancer: how I do it.
• The aim in Group A patients is palliation of dysphagia with survival benefit if possible. After my first 60—70 [1,2] cases of PDT in such patients, those with advanced stage IV disease and cases with WHO performance status (PS) ≥4 are now excluded from endoscopic PDT, since dysphagia, which is the main concern can be alleviated by other endoscopic methods such as NdYAG laser with quicker response and relief of luminal obstruction. • Treatment in Group E patients is undertaken with curative intent. These patients have an early stage I or II disease and are technically operable but for reasons other than oncological are unsuitable for resectional surgery. Patients with poor cardio-respiratory function and chronic conditions fall within this group. Some patients refuse surgery and are also selected for endoscopic PDT.
Patients are given the choice of general or topical (with sedation) anaesthesia. The overall majority (85%) of cases are patients with advanced disease who have extensive local disease requiring lengthy exposure to light in tumours extending to ≥10 cm. In such cases the procedure can be long and exhausting for the patient and, therefore, general anaesthetic is preferable. The instrument of choice is the video-fibroscope, which allows a general view of the lesion by more than one observer and the possibility of static photography and dynamic video recording of the procedure. In occasional cases the rigid instrument is used prior to the video-fibroscope; this is for lavage of an impacted oesophagus below which the obstructive lesion is situated; without lavage efficient illumination is not possible due to poor visibility. Sometimes it is also necessary to carry out dilatation of much obstructed oesophagus. In such cases pre-
My algorithm for endoscopic PDT for oesophageal cancer is shown in Fig. 1. 1. Pre-PDT endoscopic assessment: This is carried out in order to determine:
Figure 2 Two types of illumination for oesophageal cancer.
Endoscopic photodynamic therapy for oesophageal cancer
Figure 3 Interstitial (intratumour) illumination for advanced exophytic tumours.
Figure 4 Intraluminal illumination for tumours involving circumferentially the oesophageal wall.
illumination dilatation is preferable using the rigid oesophagoscope and Maloney type of ‘‘bougies’’.
Light source, delivery devices and applicators Currently this is a Diode laser delivering 630 nm light. The light is delivered through a 600 nm optical fibre with a variable length (0.5—5 cm) cylindrical diffuser or a microlens. The former projects the light circumferentially, whereas the latter has a forward projection of the light. Two types of illumination are carried out according to the bulk of the tumour mass and the extent of circumferential wall involvement (Fig. 2). (a) In patients with bulky exophytic tumours; typically in advanced cancers interstitial illumination is employed when the diffuser is inserted into the mass of the tumour, using a diffuser whose length corresponds to the length of the tumour mass (Fig. 3). In a tumour whose size is in excess of the length of the diffuser, two or more placements are made in order to expose to the light the whole of the tumour.
95
(b) In cases with advanced cancer involving the oesophageal wall circumferentially, intraluminal illumination is carried out. (c) In a case of a superficial cancer, such as the case for early cancer, either surface or intraluminal illumination is performed. If the tumour partially involves the circumference of the oesophageal wall, I use a microlens with a forward projection. However, if the tumour is involving the wall circumferentially, intraluminal application is employed placing a diffuser of appropriate length within the lumen (Fig. 4). Alternatively, the system developed at the Yorkshire Laser Centre [3] (Fig. 4) is used. For interstitial therapy the light dose is 200 J/cm with a slightly lower dose (100—150 J/cm of the tumour) for superficial cancer. • Post PDT management Following PDT, the patient is kept for 2—3 h in the hospital. They are checked clinically and observed drinking some liquid before being discharged home. They are seen after a month in the out-patient clinic and oesophagoscoped between 4 and 6 after the PDT. On these visits the grade of dysphagia and symptoms are recorded and pathological response (whether complete/or partial response or no response are recorded). • Complication/unwanted events I have carried out endoscopic PDT in over 100 patients with carcinoma of the oesophagus [4]. There has been 5% mild photosensitivity skin reaction, and 8% post PDT stricture needing on average 2 dilatations/patient.
References [1] Moghissi K, Dixon K, Thorpe JAC, Stringer MR, Moore PJ. The role of photodynamic therapy (PDT) in inoperable oesophageal cancer. Eur J Cardiothorac Surg 2000;17:95—101. [2] Moghissi K, Dixon K, Hudson E, Stringer M. Photodynamic therapy of oesophageal cancer. Lasers Med Sci 1995;10:67—71. [3] Hudson E, Stringer MR, Dixon K, Moghissi K. A new diffuser/applicator for PDT in oesophagus published in the abstract book. In: Proceedings of the 5th International Photodynamic Association meeting, SPIE vol. 2371. September 1994. p. 563—6. [4] Moghissi K, Dixon K. Photodynamic therapy in oesophageal cancer: a surgical view of its indications based on 14 years experience. Technol Cancer Res Treat 2003;2:319—26.
