Joint Hospital Surgical Grand Round Radiation Proctitis MF

Joint Hospital Surgical Grand Round Radiation Proctitis MF HO Yan Chai Hospital 20/4/2013

Background �Frequently observed after treatment of pelvic tumour, e. g. CA prostate, CA cervix �Due to microvascular injury and disruption of mucosal blood flow �Neovascularization plays a role �Severity related to total dose, dose frequency, area of exposure, source geometry �Acute vs Chronic radiation change

Complications associated with of pelvic irradiation �Proctitis �Ulceration �Stricture �Incontinence �Fistula formation

Presentation �Fever �Rectal pain �Tenesmus �Constipation / diarrhoea �Mucus passage �PR bleeding �Fistula formation

Clinical assessment �Subject symptoms �Bleeding, diarrhoea, tenesmus, pain, incontinence �Physical examination �Rectal telangiectasia, ulceration, stricture �Endoscopic assessment �Endoscopy, endorectal ultrasound �Functional assessment: �Anal manometry, defaecatory proctogram

Grading of severity �LENT – 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

Incidence �Varies due to different classification system �Varies due to different scheme of RT use 1 �External beam irradiation : 8 -39% �Brachytherapy: 8 -13% �Combine 8 -21% �May increase if patient has concomitant inflammatory bowel disease 2 1. 2. 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

Management strategy �Topical treatment �Oral medications �Endoscopic treatment �Hyperbaric oxygen �Surgical intervention

Topic treatment �Sulcrafate �Mesalazine �Prednisolone / Hydrocortisone �Misoprostol �Short chain fatty acid enema �Formalin dab / instillation

Topic treatment �Advantages �Easy to apply, patient directed �Minimal complications �Disadvantages �Limited efficacy �Studies using combination of oral and topical agents �Relieve mainly bleeding symptoms

Formalin �Advantages �Higher efficacy 1 �Ablative effect by protein hydrolysis �Disadvantages �Office procedure �Further injury to rectal mucosa �Higher complication rate: anal pain, tenesmus, fever, diarrhoea �Known 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 medications �Aminosalicylic acid �Transamin �Vitamin A / C �Antibiotics �Laxatives �Part of standard care �Usually combined with other modalities of treatment �Not useful in acute situations

Endoscopic treatment �Argon plasma coagulation �Cryotherapy �Radiofrequency ablation �Laser therapy �Heater probe �Formalin dab / irrigation

Argon plasma coagulation �Superficial ablative therapy – limited penetration �Useful in acute setting – haemostasis �Allow assessment and treatment in same session �Less local side effect compared with Formalin �Not for “ultra-low” lesion �Colonic perforation has been reported

Argon plasma coagulation �Karamanolis et al. Endoscopy 2009. � 56 patients with radiation proctitis treated with APC �Average treatment session of 2 � 6/56 patients failed to response (extent of telangiectasia and anaemia) � 38 patients followed > 1 yr � 24/38 (63% has no further bleeding symptoms) �Non comparative study �High drop out rate

Argon plasma coagulation �Alfadhli et al. Cancer J Gastroenterology 2008. � 22 patients treated with APC and /or formalin � 11 APC, 8 formalin, 3 APC + formalin � Anaemia 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 available � Overlapping treatment without intention to treat analysis � Small group of patients � Highlighted lower in side effect in APC group

Hyperbaric oxygen (HBO) �Treatment of choice in refractory radiation proctitis before consideration of surgery �NNT = 31 �Satisfactory response in documented series �Limited access �Risks 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 intervention �Refractory bleeding �Complete obstruction �Fistula / abscess formation �Proctectomy +/- proximal diversion colostomy �Perineal 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 treatment �Symptoms, satisfaction, sigmoidoscopy findings

Results

�Randomized study �Comparing new treatment with current standard of treatment �Additional 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 groups �Irrigation was given with antibiotics �Cannot distinguish treatment effect from irrigation / antibiotics �Short duration of follow up �RT change delay up to 2 years after RT

Conclusion �Radiation 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 therapy �Hyperbaric 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