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## Complete Summary

#### GUIDELINE TITLE

The role of porfimer sodium (Photofrin™) in the ablation of high-grade
dysplasia associated with Barrett´s esophagus.

#### BIBLIOGRAPHIC SOURCE(S)

Malthaner RA, Rumble RB, Program in Evidence-based Care. The role of
porfimer sodium (photofrin) in the ablation of high-grade dysplasia
associated with Barrett\'s esophagus. Toronto (ON): Cancer Care Ontario
(CCO); 2006 Jun 14. 14 p. (DQTC-SOS advice report; no. 2). \[12
references\]

#### GUIDELINE STATUS

This is the current release of the guideline.

Please visit the [Cancer Care Ontario Web
site](http://www.cancercare.on.ca/pdf/pebcdqtc2f.pdf) for details on any
new evidence that has emerged and implications to the guidelines.

### COMPLETE SUMMARY CONTENT

 SCOPE\
 METHODOLOGY - including Rating Scheme and Cost Analysis\
 RECOMMENDATIONS\
 EVIDENCE SUPPORTING THE RECOMMENDATIONS\
 BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS\
 QUALIFYING STATEMENTS\
 IMPLEMENTATION OF THE GUIDELINE\
 INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT
CATEGORIES\
 IDENTIFYING INFORMATION AND AVAILABILITY\
 DISCLAIMER

### SCOPE

#### DISEASE/CONDITION(S)

High-grade dysplasia associated with Barrett\'s esophagus that can\'t be
treated surgically

#### GUIDELINE CATEGORY

Assessment of Therapeutic Effectiveness\
Treatment

#### CLINICAL SPECIALTY

Oncology

#### INTENDED USERS

Physicians

#### GUIDELINE OBJECTIVE(S)

To evaluate the role of porfimer sodium in the ablation of high-grade
dysplasia associated with Barrett\'s esophagus

#### TARGET POPULATION

Adult patients with high-grade dysplasia associated with Barrett\'s
esophagus that have either refused surgical treatment or who have
contraindications to surgical treatment and for whom therapy with
porfimer sodium is being considered

#### INTERVENTIONS AND PRACTICES CONSIDERED

Photodynamic therapy with porfimer sodium followed by laser light

#### MAJOR OUTCOMES CONSIDERED

-   Amelioration of dysplasia with biopsy evidence of eradication

-   Prevention of esophageal cancer

-   Adverse effects

-   Strictures

-   Survival

### METHODOLOGY

#### METHODS USED TO COLLECT/SELECT EVIDENCE

Hand-searches of Published Literature (Primary Sources)\
Hand-searches of Published Literature (Secondary Sources)\
Searches of Electronic Databases

#### DESCRIPTION OF METHODS USED TO COLLECT/SELECT THE EVIDENCE

**Literature Search Strategy**

The MEDLINE database was searched from 1966 to May (week 4) 2006. The
following Medical subject headings (MeSH) \"dihematoporphyrin ether,\"
porfimer sodium,\" \"photofrin,\" \"Barrett\'s esophagus,\" and
\"esophageal neoplasms\" were combined, with results limited to English
only. The Cochrane library database of systematic reviews was also
searched through Issue 4, 2005 for completed reviews or posted protocols
of in-progress reviews. Relevant articles were selected and read by two
reviewers, and the reference lists from those sources were searched for
additional trials. Additionally, the National Cancer Institute\'s
database of ongoing clinical trials
(<http://www.cancer.gov/Search/SearchClinicalTrialsAdvanced.aspx>) was
searched for open trials investigating the use of porfimer sodium in the
ablation of high-grade dysplasia in patients with Barrett\'s esophagus
(see Appendix 3 in the original guideline document).

**Inclusion Criteria**

Articles were selected for inclusion in the systematic review of the
evidence if they were fully published English-language reports of:

1.  Randomized controlled trials (RCTs) comparing porfimer sodium with
    any other therapy in the ablation of high-grade dysphasia associated
    with Barrett\'s esophagus

2.  Phase II trials comparing porfimer sodium with any other therapy in
    the ablation of high-grade dysphasia associated with Barrett\'s
    esophagus.

3.  Any other study design that provided data on porfimer sodium with
    any other therapy in the ablation of high-grade dysphasia associated
    with Barrett\'s esophagus

**Exclusion Criteria**

1.  Letters and editorials

2.  Non-English publications

3.  Non-human studies

4.  Studies reporting on fewer than 10 patients

#### NUMBER OF SOURCE DOCUMENTS

A total of six studies were obtained.

#### METHODS USED TO ASSESS THE QUALITY AND STRENGTH OF THE EVIDENCE

Expert Consensus (Committee)

#### RATING SCHEME FOR THE STRENGTH OF THE EVIDENCE

Not applicable

#### METHODS USED TO ANALYZE THE EVIDENCE

Systematic Review with Evidence Tables

#### DESCRIPTION OF THE METHODS USED TO ANALYZE THE EVIDENCE

As only one of the trials obtained was a randomized controlled trial
(RCT), no pooling of outcome data was possible.

#### METHODS USED TO FORMULATE THE RECOMMENDATIONS

Expert Consensus

#### DESCRIPTION OF METHODS USED TO FORMULATE THE RECOMMENDATIONS

This advice report was commissioned by the Program in Evidence-Based
Care (PEBC). A member of the Gastrointestinal Cancer Disease Site Group
(DSG) agreed to serve as the clinical lead on this topic as it was not
formally part of the Gastrointestinal Cancer DSG\'s guideline portfolio.
This advice report is a convenient and up-to-date source of the best
available evidence on the role porfimer sodium in the ablation of
high-grade dysplasia associated with Barrett\'s esophagus, developed
through a systematic review of the available evidence.

The early treatment of Barrett\'s esophagus with photodynamic therapy
(PDT) in an attempt to prevent the possible later development of
adenocarcinoma is clinically compelling. Presently, the best evidence in
favour of PDT with porfimer sodium for these patients is the randomized
controlled trial (RCT), which showed superiority for PDT treatment over
treatment with omeprazole alone for both complete ablation of high-grade
dysplasia (HGD) associated with Barrett\'s esophagus and the later
development of adenocarcinoma. However, a randomized controlled trial
comparison between surgery alone and PDT with porfimer sodium for these
patients has yet to be published. The remaining data are currently
limited to two case-series studies, and both report high-grade dysplasia
ablation rates lower than 60% with a single course of treatment. In one
of the trials PDT alone only ablated the dysplasia in eight of 73
patients (11%), while the remaining 35 patients required the additional
treatment of neodymium-doped Yttrium Aluminum Garnet (Nd:YAG) laser to
ablate the high-grade dysplasia. Also, the adverse effects observed with
PDT using porfimer sodium are significant (e.g. stricture formation,
light sensitivity) and are potentially fatal (e.g. esophageal
perforation). The development of dysphagia secondary to stricture
formation following PDT cannot be ignored. It is also possible that
following PDT ablation, normal squamous tissue may grow over any
remaining Barrett\'s tissue, which could possibly develop into an
adenocarcinoma, while remaining hidden to endoscopic inspection for
malignant conversion. Considering this, the role of PDT with porfimer
sodium in the ablation of high-grade dysplasia associated with
Barrett\'s esophagus remains unclear, especially as it\'s efficacy in
comparison to the standard treatment of surgery is unknown.

Despite this, PDT provides some benefits over surgery alone. In the
studies reviewed, PDT with porfimer sodium has a post-treatment
mortality rate approaching zero, while surgical interventions report
post-treatment mortality rates ranging from 6% to 14%, however, newer
studies report that post-operative mortality with surgery alone also
approaches zero. One benefit with PDT using porfimer sodium is that
treatment may be given in multiple courses with minimal time between
cycles (see Appendix 1 in the original guideline document).

It is recommended that for patients who are not candidates for surgery,
either due to contraindications or patient preference, in the primary
treatment of high-grade dysplasia associated with Barrett\'s esophagus,
PDT with porfimer sodium could be considered.

#### RATING SCHEME FOR THE STRENGTH OF THE RECOMMENDATIONS

Not applicable

#### COST ANALYSIS

A formal cost analysis was not performed and published cost analyses
were not reviewed.

#### METHOD OF GUIDELINE VALIDATION

Internal Peer Review

#### DESCRIPTION OF METHOD OF GUIDELINE VALIDATION

Feedback from the Gastrointestinal Cancer Disease Site Group\'s Chair
was obtained on an early draft report that did not include the results
from the single randomized controlled trial obtained.

### RECOMMENDATIONS

#### MAJOR RECOMMENDATIONS

-   For patients with high-grade dysplasia associated with Barrett\'s
    esophagus and who are willing and able to tolerate surgery, surgery
    alone should be the first treatment of choice.

-   For patients with high-grade dysplasia associated with Barrett\'s
    esophagus with contraindications to surgery, or who choose not to
    receive surgery, there are randomized controlled trial data
    confirming that photodynamic therapy (PDT) with porfimer sodium
    followed by laser light shows superiority over omeprazole alone in
    the ablation of high-grade dysplasia. Therefore, photodynamic
    therapy with porfimer sodium could be considered a treatment option
    for these patients.

See Appendix 1 in the original guideline document for recommended
regimens and dosages, and Appendix 2 in the original guideline for the
regimens and dosages used in the included trials.

#### CLINICAL ALGORITHM(S)

None provided

### EVIDENCE SUPPORTING THE RECOMMENDATIONS

#### TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

The recommendations are supported by one randomized controlled trial
(RCT), three prospective case-series, one retrospective, and one
post-treatment patient satisfaction survey.

### BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS

#### POTENTIAL BENEFITS

-   One randomized controlled trial involving 208 patients comparing
    photodynamic therapy with porfimer sodium plus omeprazole versus
    omeprazole alone showed benefits for photodynamic therapy with
    porfimer sodium in both the complete ablation of high-grade
    dysplasia (p\<0.0001) and the later development of adenocarcinoma
    (p\<0.006).

-   Two case-series of 100 patients (including 73 patients with
    high-grade dysplasia associated with Barrett\'s esophagus) and 102
    patients (including 69 patients with high-grade dysplasia associated
    with Barrett\'s esophagus) using photodynamic therapy with porfimer
    sodium were able to remove 59% and 52% of high-grade dysplasia
    associated with Barrett\'s esophagus.

#### POTENTIAL HARMS

Adverse effects associated with photodynamic therapy using porfimer
sodium include esophageal strictures, perforation, photosensitivity, and
mucosal overgrowth over remaining Barrett\'s epithelium.

### QUALIFYING STATEMENTS

#### QUALIFYING STATEMENTS

Care has been taken in the preparation of the information contained in
this document. Nonetheless, any person seeking to apply or consult the
evidence-based series is expected to use independent medical judgment in
the context of individual clinical circumstances or seek out the
supervision of a qualified clinician. Cancer Care Ontario makes no
representation or guarantees of any kind whatsoever regarding their
content or use or application and disclaims any for their application or
use in any way.

### IMPLEMENTATION OF THE GUIDELINE

#### DESCRIPTION OF IMPLEMENTATION STRATEGY

An implementation strategy was not provided.

### INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT CATEGORIES

#### IOM CARE NEED

Living with Illness

#### IOM DOMAIN

Effectiveness

### IDENTIFYING INFORMATION AND AVAILABILITY

#### BIBLIOGRAPHIC SOURCE(S)

Malthaner RA, Rumble RB, Program in Evidence-based Care. The role of
porfimer sodium (photofrin) in the ablation of high-grade dysplasia
associated with Barrett\'s esophagus. Toronto (ON): Cancer Care Ontario
(CCO); 2006 Jun 14. 14 p. (DQTC-SOS advice report; no. 2). \[12
references\]

#### ADAPTATION

Not applicable: The guideline was not adapted from another source.

#### DATE RELEASED

2006 Jun 14

#### GUIDELINE DEVELOPER(S)

Program in Evidence-based Care - State/Local Government Agency
\[Non-U.S.\]

#### GUIDELINE DEVELOPER COMMENT

The Program in Evidence-based Care (PEBC) is a Province of Ontario
initiative sponsored by Cancer Care Ontario and the Ontario Ministry of
Health and Long-Term Care.

#### SOURCE(S) OF FUNDING

Cancer Care Ontario\
Ontario Ministry of Health and Long-Term Care

#### GUIDELINE COMMITTEE

Cancer Care Ontario\'s Program in Evidence-Based Care

#### COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

*Primary Authors*: R.A. Malthaner; R.B. Rumble

#### FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

Neither of the authors declared any conflicts of interest.

#### GUIDELINE STATUS

This is the current release of the guideline.

Please visit the [Cancer Care Ontario Web
site](http://www.cancercare.on.ca/pdf/pebcdqtc2f.pdf) for details on any
new evidence that has emerged and implications to the guidelines.

#### GUIDELINE AVAILABILITY

Electronic copies: Available in Portable Document Format (PDF) from the
[Cancer Care Ontario Web
site](http://www.cancercare.on.ca/pdf/pebcdqtc2f.pdf).

#### AVAILABILITY OF COMPANION DOCUMENTS

The following are available:

-   The role of porfimer sodium (Photofrin™) in the ablation of
    high-grade dysplasia associated with Barrett\'s esophagus. Summary.
    Toronto (ON): Cancer Care Ontario (CCO), 2006 Jun 14. Various p.
    Electronic copies: Available in Portable Document Format (PDF) from
    the [Cancer Care Ontario Web
    site](http://www.cancercare.on.ca/pdf/pebcdqtc2s.pdf).

-   Browman GP, Levine MN, Mohide EA, Hayward RSA, Pritchard KI, Gafni
    A, et al. The practice guidelines development cycle: a conceptual
    tool for practice guidelines development and implementation. J Clin
    Oncol 1995;13(2):502-12.

#### PATIENT RESOURCES

None available

#### NGC STATUS

This NGC summary was completed by ECRI on October 26, 2006. The
information was verified by the guideline developer on November 24,
2006.

#### COPYRIGHT STATEMENT

This NGC summary is based on the original guideline, which is subject to
the guideline developer\'s copyright restrictions. Please refer to the
[Copyright and Disclaimer
Statements](http://www.cancercare.on.ca/ontariocancernews/copyright.html)
posted at the Program in Evidence-Based Care section of the Cancer Care
Ontario Web site.

### DISCLAIMER

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© 1998-2008 National Guideline Clearinghouse

Date Modified: 11/3/2008