MF HOYan Chai Hospital

20/4/2013

BackgroundFrequently observed after treatment of pelvic

tumour, e.g. CA prostate, CA cervixDue to microvascular injury and disruption of

mucosal blood flowNeovascularization plays a roleSeverity related to total dose, dose

frequency, area of exposure, source geometryAcute vs Chronic radiation change

Complications associated with of pelvic irradiation

ProctitisUlcerationStrictureIncontinenceFistula formation

PresentationFeverRectal painTenesmusConstipation / diarrhoeaMucus passagePR bleedingFistula formation

Clinical assessmentSubject symptoms

Bleeding, diarrhoea, tenesmus, pain, incontinence

Physical examinationRectal telangiectasia, ulceration, stricture

Endoscopic assessmentEndoscopy, endorectal ultrasound

Functional assessment: Anal manometry, defaecatory proctogram

Grading of severityLENT – SOMA ( Late Effect Normal Tissue –

Subjective Objective Management Analysis) Scale

National Cancer Institute Common Toxicity Criteria for Adverse Event Version 4

Various grading system employed across different studies

Frequency of symptoms and requirement of intervention

IncidenceVaries due to different classification systemVaries due to different scheme of RT use1

External beam irradiation : 8-39%Brachytherapy: 8-13%Combine 8-21%

May increase if patient has concomitant inflammatory bowel disease2

1. Nhue L. Do et al. Radiation proctitis: Current Strategies in management. Gastroenterology Research and Practice. Volume 2011.

2. C.G. Wilet et al. Acute and late toxicity of patients with inflammatory bowel disease undergoing irradiation for abdominal and pelvic neoplasms. Int J Rad Onc Bio Phy. Vol 46, No. 4 pp 995-998, 2000

Management strategyTopical treatment

Oral medications

Endoscopic treatment

Hyperbaric oxygen

Surgical intervention

Topic treatmentSulcrafateMesalazinePrednisolone / HydrocortisoneMisoprostolShort chain fatty acid enemaFormalin dab / instillation

Topic treatmentAdvantages

Easy to apply, patient directedMinimal complications

DisadvantagesLimited efficacyStudies using combination of oral and topical

agentsRelieve mainly bleeding symptoms

FormalinAdvantages

Higher efficacy1

Ablative effect by protein hydrolysis

DisadvantagesOffice procedureFurther injury to rectal mucosaHigher complication rate: anal pain, tenesmus,

fever, diarrhoeaKnown Human carcinogen - WHO International

Agency for Research on Cancer (IARC)

1. V.P. Nelamangala Ramakrishnaiah et al. Colorectal Disease 2012, Vol 14, 876-882.

Ref: V.P. Nelamangala Ramakrishnaiah et al. Colorectal Disease 2012, Vol 14, 876-882.

Oral medicationsAminosalicylic acidTransaminVitamin A / CAntibioticsLaxatives

Part of standard careUsually combined with other modalities of

treatmentNot useful in acute situations

Endoscopic treatmentArgon plasma coagulationCryotherapyRadiofrequency ablationLaser therapyHeater probeFormalin dab / irrigation

Argon plasma coagulation

Superficial ablative therapy – limited penetration

Useful in acute setting – haemostasisAllow assessment and treatment in same

sessionLess local side effect compared with Formalin

Not for “ultra-low” lesionColonic perforation has been reported

Argon plasma coagulationKaramanolis et al. Endoscopy 2009.

56 patients with radiation proctitis treated with APC

Average treatment session of 26/56 patients failed to response (extent of

telangiectasia and anaemia)38 patients followed > 1 yr24/38 (63% has no further bleeding symptoms)

Non comparative studyHigh drop out rate

Argon plasma coagulationAlfadhli et al. Cancer J Gastroenterology 2008.

22 patients treated with APC and /or formalin11 APC, 8 formalin, 3 APC + formalinAnaemia responded in :

11/14 patients with APC 7/11 patient with formalin

Side effects more prominent in formalin group (9 in formalin vs 2 in APC)

Only comparative study availableOverlapping treatment without intention to treat

analysisSmall group of patientsHighlighted lower in side effect in APC group

Hyperbaric oxygen (HBO)Treatment of choice in refractory radiation

proctitis before consideration of surgeryNNT = 31

Satisfactory response in documented series

Limited accessRisks of barotrauma / oxygen toxicity

1. R.E. Clake et al. Hyperbaric oxygen treatment of chronic refectory radiation proctitis: A randomized and controlled double blind crossover trial with long term follow up. Int J Rad Onc Bio Phy. Vol 72, No.1. pp 134-143, 2008.

Surgical interventionRefractory bleedingComplete obstructionFistula / abscess formation

Proctectomy +/- proximal diversion colostomyProximal diversion colostomyPerineal procedures

Comparing 50 patients with radiation proctitis using formalin dab vs tap water irrigation and antibiotics treatment from 2010 to 2012

Patients with other complications from radiation e.g. fistula, rectal ulcers, strictures were excluded

Patient was assessed 8 weeks after treatmentSymptoms, satisfaction, sigmoidoscopy findings

Results

Randomized studyComparing new treatment with current

standard of treatmentAdditional advantage of treating post

irritation constipation

Symptoms severity before treatment was not compared? Difference in baseline symptoms severity

Results are not presented well? Why comparing difference of difference

between 2 treatment groupsIrrigation was given with antibiotics

Cannot distinguish treatment effect from irrigation / antibiotics

Short duration of follow upRT change delay up to 2 years after RT

ConclusionRadiation proctitis is commonly encountered as

radiotherapy to pelvis is increasingly used

Topical and oral medication are more of maintenance therapy

Acute bleeding can be dealt with ablative therapyHyperbaric oxygen can be employed in refractory

case

Surgery is the last resort, risks needed to be considered

Reference Management of Radiation Proctitis. William M . Mendenhall et al. American Journal of Clinical

Oncology, 2012.

A randomized controlled trial comparing colonic irrigation and oral antibiotics administration versus 4% formalin application for treatment of haemorrhagic radiation proctitis. Chucheep Sahakitrungruang et al. Dis Colon rectum 2012; 55: 1053-1058.

Endoscopic and medical therapy for chronic radiation proctopathy: a systematic review. Brian Hanson et at. Dis Colon Rectum 2012; 55: 1081-1095

Nhue L. Do et al. Radiation proctitis: Current Strategies in management. Gastroenterology Research and Practice. Volume 2011.

C. G. Wilet et al. Acute and late toxicity of patients with inflammatory bowel disease undergoing irradiation for abdominal and pelvic neoplasms. Int J Rad Onc Bio Phy. Vol 46, No. 4 pp 995-998, 2000

V.P. Nelamangala Ramakrishnaiah et al. Colorectal Disease 2012, Vol 14, 876-882.

Alfadhli et al. Efficacy of argon plasma coagulation compared to topical formalin application for chronic radiation proctopathy. Cancer J Gastroenterology 2008.

Karamanolis et al. Argon plasma coagulation has a long-lasting therapeutic effect in patients with chronic radiation proctitis. Endoscopy 2009.

R.E. Clake et al. Hyperbaric oxygen treatment of chronic refectory radiation proctitis: A randomized and controlled double blind crossover trial with long term follow up. Int J Rad Onc Bio Phy. Vol 72, No.1. pp 134-143, 2008