Interventional procedures consultation document - photodynamic therapy for brain tumours

NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE

 

Interventional Procedure Consultation Document

Photodynamic therapy for brain tumours

Brain tumours may arise from brain tissue or spread from cancers in other parts of the body. Treatment usually consists of an operation to establish the nature of the tumour and, when possible, remove as much of it as seems safe. Photodynamic therapy (often abbreviated to PDT) has been developed as additional therapy (to enhance the effect of surgery) or as a treatment for tumours that are inoperable. Itinvolves giving the patient a drug that makes the tissue sensitive to light. A laser light source is used during the operation and in some cases for a few days afterwards to activate the light‑sensitive substance with the aim of destroying the tumour cells.

 

The National Institute for Health and Clinical Excellence (NICE) is examining photodynamic therapy for brain tumours and will publish guidance on its safety and efficacy to the NHS in England, Wales, Scotland and Northern Ireland. NICE's Interventional Procedures Advisory Committee has considered the available evidence and the views of Specialist Advisers, who are consultants with knowledge of the procedure. The Advisory Committee has made provisional recommendations about photodynamic therapy for brain tumours.

This document summarises the procedure and sets out the provisional recommendations made by the Advisory Committee. It has been prepared for public consultation. The Advisory Committee particularly welcomes:

  • comments on the provisional recommendations
  • the identification of factual inaccuracies
  • additional relevant evidence.

Note that this document is not NICE's formal guidance on this procedure. The recommendations are provisional and may change after consultation.

The process that NICE will follow after the consultation period ends is as follows.

  • The Advisory Committee will meet again to consider the original evidence and its provisional recommendations in the light of the comments received during consultation.
  • The Advisory Committee will then prepare draft guidance which will be the basis for NICE's guidance on the use of the procedure in the NHS in England, Wales, Scotland and Northern Ireland.

For further details, see the Interventional Procedures Programme manual, which is available from our website (www.nice.org.uk/ipprogrammemanual).

NICE is committed to promoting through its guidance race and disability equality and equality between men and women, and to eliminating all forms of discrimination. One of the ways we do this is by trying to involve as wide a range of people and interest groups as possible in the development of our guidance on interventional procedures. In particular, we aim to encourage people and organisations from groups in the population who might not normally comment on our guidance to do so. We also ask consultees to highlight any ways in which draft guidance fails to promote equality or tackle discrimination and give suggestions for how it might be improved.

Closing date for comments: 16 December 2008

Target date for publication of guidance: March 2009

 

Note that this document is not the Institute's guidance on this procedure. The recommendations are provisional and may change after consultation.
1 Provisional recommendations
1.1 Current evidence on the safety and efficacy of photodynamic therapy for brain tumours is limited in both quality and quantity. Therefore, this procedure should only be used in the context of randomised controlled trials with well defined inclusion criteria and treatment protocols, and with collection of both survival and quality of life outcomes.
2 The procedure
2.1 Indications and current treatments
2.1.1 Brain tumours may be primary tumours from glial, neuronal or meningeal cells, or metastases from tumours elsewhere in the body. Primary brain tumours (such as astrocytoma, oligodendroglioma, glioblastoma and meningioma) are graded using a World Health Organization (WHO) classification from I (low grade and least aggressive) to IV (high grade and most aggressive). Patients with high-grade tumours often have a poor prognosis, usually surviving only a few months after diagnosis.
2.1.2 The symptoms of a brain tumour are determined by its location and size. Depending on its location in the brain, a tumour can cause limb weakness or speech disturbance. Any brain swelling caused by a tumour can result in raised intracranial pressure, which can lead to headache, vomiting and reduced consciousness.
2.1.3 Some patients can be treated by surgical resection, with the aim of removing tumour material and reducing intracranial pressure without worsening neurological function. In most patients curative resection is not possible because of growth of the tumour into normal brain parenchyma. Non-surgical treatment options include chemotherapy and radiotherapy. A combination of these treatments may be used, or surgery may be followed by chemotherapy and radiotherapy.
2.2 Outline of the procedure
2.2.1 Photodynamic therapy (PDT) is usually undertaken with the patient under general anaesthesia, at the same operation as surgical resection, when as much of the tumour has been removed as possible. A photosensitising agent is injected, usually intravenously, although direct injection into the tumour is also possible. The photosensitising agent is activated by illuminating the selected area, usually with a low-power laser. The photosensitising agent absorbs the light and forms high-energy oxygen molecules that interact with the brain tissue to cause tumour necrosis through a photochemical effect. Occasionally, repeated PDT sessions are performed after surgery via access maintained through the skull. To minimise the risks associated with skin photosensitivity, patients are advised to avoid exposure to bright light and direct sunlight for several weeks after the procedure.
2.2.2 Various devices and photosensitising agents can be used for this procedure.
Sections 2.3 and 2.4 describe efficacy and safety outcomes from the published literature that the Committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the overview, available at www.nice.org.uk/IP538overview.
2.3 Efficacy
2.3.1 A randomised controlled trial (RCT) of 27 patients with newly diagnosed glioblastoma and a Karnofsky score³ 60 (on a scale where 100 is ‘perfect health' and 0 is ‘death') reported an increase in mean survival in 13 patients who received PDT after surgery compared with 14 patients treated by surgical resection alone (52.8 weeks and 24.1 weeks respectively; p = 0.001). A case series of 112 patients treated by PDT following surgical resection reported median survival of 30 weeks in patients with gliomas and 24 weeks in patients with metastatic carcinoma (follow-up not stated). A case series of 126 patients treated by PDT following surgical resection reported that median survival from initial diagnosis was 76.5 months for patients with primary anaplastic astrocytoma and 14.3 months for patients with glioblastoma multiforme (p = 0.001), with a minimum follow-up of 3 years. Duration of survival was not associated with the location of the tumours in the brain (p = 0.54). A case series of 26 patients with recurrent glioblastoma (WHO grade IV) treated by PDT following surgical resection reported median survival of 8.5 months.
2.3.2 The case series of 26 patients reported that median time to disease progression was 6 months.
2.3.3 The RCT reported an improvement in mean Karnofsky score from 60 to 80 points in the PDT after surgery group but no change from 70 points in the surgical resection group (follow-up not stated; p < 0.05).
2.3.4 The Specialist Advisers considered key efficacy outcomes to include overall and progression-free survival, completeness of resection and quality of life.
2.4 Safety
2.4.1 In the case series of 112 patients, 3% (3/112) died following the operation, 1 of pulmonary embolism and 2 of tumour cavity haemorrhage. Deep vein thrombosis occurred in 4% (4/112), infection (not otherwise specified) in 4% (4/112), and cerebrospinal fluid leak in 1% (1/112) of patients (no further details stated).
2.4.2 The case series of 26 patients reported transient oedema of the treated area in 4% (1/26) of patients.
2.4.3 Across three case series, sunburn due to light exposure occurred at a rate of between 2% (1/112, 2/136) and 8% (2/26).
2.4.4 The Specialist Advisers considered adverse events associated with PDT for brain tumours to include cerebral oedema, raised intracranial pressure, hypersensitivity reactions and skin photosensitisation. They stated that additional theoretical adverse events may include damage to the normal brain and cerebral blood vessels, stroke, and compromise of further treatments by increasing the sensitivity of the brain to their toxic side effects

Bruce Campbell

Chairman, Interventional Procedures Advisory Committee

September 2008

This page was last updated: 30 March 2010