Low energy contact X-ray brachytherapy (the Papillon technique) for early stage rectal cancer

# Recommendations
In patients for whom surgery is not considered suitable, current evidence on the efficacy and safety of lowenergy contact Xray brachytherapy (CXB; the Papillon technique) for earlystage rectal cancer is adequate to support the use of this procedure, provided that normal arrangements are in place for clinical governance, consent and audit.
In patients for whom surgery is considered suitable, but who choose not to have an operation, the evidence on safety is adequate but the evidence on efficacy is inadequate. Therefore this procedure should only be used for these patients with special arrangements for clinical governance, consent and audit or research.
Clinicians wishing to do lowenergy CXB in patients for whom surgery is considered suitable, but who choose not to have an operation, should take the following actions:
Inform the clinical governance leads in their NHS trusts.
Ensure that patients and their carers understand the alternative options for treatment and the uncertainty about this procedure's efficacy and provide them with clear written information. In addition, the use of NICE's information for the public is recommended.
Patient selection should be done by a colorectal cancer multidisciplinary team, including a clinical oncologist and a colorectal surgeon with expertise in local excision techniques.
Clinicians should enter details about all patients having lowenergy CXB for earlystage rectal cancer onto the contact X-ray brachytherapy database. Clinical outcomes should also be reviewed locally.
NICE encourages further research into lowenergy CXB for earlystage rectal cancer. Research should clearly describe details of patient selection and treatment intent. It should document adjunctive treatments and subsequent procedures. Outcomes should include local recurrence, survival, diseasefree survival and quality of life. NICE may update the guidance on publication of further evidence.# Indications and current treatments
Rectal cancer is a common form of bowel cancer. The likelihood of developing it rises sharply with age. Symptoms include rectal bleeding and change in bowel habit, although the early stages may be asymptomatic.
Surgery is the main treatment for patients with rectal cancer who are treated with curative intent. It involves resection of the affected part of the rectum and the mesorectum. The anal sphincter is preserved whenever possible; a colostomy is formed when this is not possible.
In some patients, radiotherapy or chemotherapy or both are used before, during or after surgery to decrease the chances of local recurrence and metastatic disease. Radiotherapy may take the form of externalbeam radiotherapy (EBRT) or radioisotope brachytherapy. EBRT uses radiation from outside the body, which is focused on the cancer and surrounding lymph nodes. Radioisotope brachytherapy involves inserting radioactive pellets or seeds directly into the tumour (interstitial brachytherapy), or placing an endorectal treatment applicator near the tumour to deliver radiation from within the rectum (endorectal high dose rate brachytherapy).# The procedure
Lowenergy contact Xray brachytherapy (CXB; the Papillon technique) aims to improve local control or cure rectal cancer. The procedure involves inserting an Xray tube through the anus and placing it in close contact with the tumour, to kill cancer cells and reduce the size of the tumour.
Lowenergy CXB for rectal cancer is usually delivered in a daycare setting. The patient is given an enema before treatment, to clear the bowel. With the patient in a kneetochest, prone jackknife or supine position, local anaesthesia and glyceryl trinitrate are applied to the anal sphincter to numb the area and relax the sphincter muscles. A sigmoidoscope is inserted to check the size and position of the tumour. A rigid endorectal treatment applicator is then inserted and placed in contact with the tumour. A contact Xray tube is introduced into the applicator and treatment begins. The tube emits lowenergy Xrays that only penetrate a few millimetres. This minimises damage to deeper tissues that are not involved in the cancer. If the tumour does not respond to lowenergy CXB, or recurs after treatment, surgery may be performed.# Efficacy
This section describes efficacy 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 interventional procedure overview.
In a randomised controlled trial of 88 patients treated by both lowenergy contact Xray brachytherapy (CXB) and externalbeam radiotherapy (EBRT; n=45) or EBRT alone (n=43), overall actuarial survival rates (KaplanMeier estimates) were 55% and 56% respectively, at 10year followup (p=0.85). In the same study, diseasefree survival rates were 53% and 54% respectively, at 10year followup (p=0.99). In a case series of 101 patients treated by lowenergy CXB with or without interstitial brachytherapy boost, overall actuarial survival rates (KaplanMeier estimates) were 83% and 63% at 5 and 8 years respectively. In the same study, diseasespecific survival rates were 94% and 89% at 5 and 8 years respectively. Actuarial survival rates for patients with stage T1 and T2 tumours were 68% and 55% respectively, at 8year followup (p=0.73). Diseasespecific survival rates for patients with stage T1 and T2 tumours were 91% and 86% respectively, at 8year followup (p=0.82).
In a case series of 97 patients treated by lowenergy CXB with or without interstitial brachytherapy boost, a complete response (no definition provided) was reported in 85% (82/97) of patients at a median followup of 39 days. In a case series of 63 patients treated by lowenergy CXB followed by EBRT and interstitial brachytherapy boost, a complete clinical response (no definition provided) was reported in 92% (58/63) of patients at 2month followup.
In the randomised controlled trial of 88 patients treated by lowenergy CXB and EBRT (n=45) or EBRT alone (n=43), actuarial local recurrence rates (KaplanMeier estimates) were 10% and 15% respectively, at 10year followup (p=0.69). Distant recurrence was reported in 27% (12/45) of patients in the lowenergy CXB and EBRT group and 26% (11/43) of patients in the EBRTalone group at 10year followup (no p value reported).
In the randomised controlled trial of 88 patients treated by lowenergy CXB and EBRT (n=45) or EBRT alone (n=43) all patients had surgery (either sphinctersaving procedures or abdominoperineal resections) after initial treatment. Sphinctersaving procedures were possible in 76% (34/45) of patients in the lowenergy CXB and EBRT group and 44% (19/43) of patients in the EBRTalone group (no p values reported). Abdominoperineal resections were needed in 24% (11/45) of patients in the lowenergy CXB and EBRT group and 56% (24/43) of patients in the EBRTalone group (no p values reported). In the same study, the actuarial colostomy rates (KaplanMeier estimates) were 29% in the lowenergy CXB and EBRT group and 63% in the EBRTalone group at 10year followup (p<0.001).
In a case series of 312 patients treated by lowenergy CXB and interstitial brachytherapy boost, a permanent colostomy was needed in 3% (8/312) of patients.
Specialist advisers listed the following key efficacy outcomes: overall survival, diseasefree survival, clinical response, local control rates, locoregional and distant recurrence rates, avoiding a permanent stoma, quality of life, as well as bowel, urinary and sexual function.# Safety
This section describes 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 interventional procedure overview.
Rectal bleeding was reported in 38.1% (24/63) of patients, 6 months after treatment, in a case series of 63 patients treated by lowenergy contact Xray brachytherapy (CXB) followed by externalbeam radiotherapy (EBRT) and interstitial brachytherapy boost. Bleeding lasted for up to 3 years. Patients were treated by medication or argon plasma coagulation. Only 1 patient needed occasional blood transfusions.
Authors reported that 'grade 2 rectal necrosis' occurred in 19% (12/63) of patients, at a median of 7 months after treatment, in the case series of 63 patients treated by lowenergy CXB followed by EBRT and interstitial brachytherapy boost. Details about the type of grading system for rectal necrosis were not provided. Authors stated that some patients had rectal necrosis which was accompanied by urgency and minor soiling. They highlighted that necrosis healed within 3 to 6 months in all patients.
Ulceration of the rectal mucosa was reported in 27% (27/101) of patients, at a median followup of 4 months, in a case series of 101 patients treated by lowenergy CXB with or without interstitial brachytherapy boost. Ulceration healed in all these patients with no late sequelae.
Slight proctitis was reported in 10% (32/312) of patients in a case series of 312 patients treated by lowenergy CXB and interstitial brachytherapy boost. The timing of occurrence was not reported.
Moderate tenesmus, urgency of bowel movement or diarrhoea was reported in 15% (15/101) of patients, during the course of treatment, in the case series of 101 patients treated by lowenergy CXB with or without interstitial brachytherapy boost.
In addition to safety outcomes reported in the literature, specialist advisers are asked about anecdotal adverse events (events which they have heard about) and about theoretical adverse events (events which they think might possibly occur, even if they have never done so). For this procedure, specialist advisers listed the following anecdotal adverse events: bowel perforation, rectal stenosis, rectovaginal fistula formation, incontinence. They considered that the following were theoretical adverse events: stricture formation, fistula formation, rectal perforation.# Further information
For related NICE guidance, see the NICE website.

# Information for patients
NICE has produced information on this procedure for patients and carers (information for the public). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance
NICE interventional procedures guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS.
This guidance was developed using the NICE interventional procedures guidance process.
We have produced information for the public explaining this guidance. Information about the evidence the guidance is based on is also available.
NICE produces guidance, standards and information on commissioning and providing highquality healthcare, social care, and public health services. We have agreements to provide certain NICE services to Wales, Scotland and Northern Ireland. Decisions on how NICE guidance and other products apply in those countries are made by ministers in the Welsh government, Scottish government, and Northern Ireland Executive. NICE guidance or other products may include references to organisations or people responsible for commissioning or providing care that may be relevant only to England.
Your responsibility
    This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.
Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to have due regard to the need to eliminate unlawful discrimination, advance equality of opportunity and foster good relations. Nothing in this guidance should be interpreted in a way that would be inconsistent with compliance with those duties.
Copyright
     National Institute for Health and Care Excellence 2015. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and notforprofit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.
ISBN: 978-1-4731-1399-2