Consent Forms Project A working party consisting of members of the ORF and led by Dr David Sherriff, was set up to assist in the development of a comprehensive set of site-specific consent forms which would be available to download from the College s website. The listing of specific early and late side-effects was felt to be vital in view of the considerable variation across the country with regard to written documentation of side-effects, particularly second malignancy www.rcr.ac.uk/content.aspx?pageid=727. A consent form which explicitly lists the expected early/late side effects could be seen as a check-list to ensure that all relevant details are discussed. It would be expected that further information e.g. Cancerbackup booklets and/or departmental leaflets would also be offered. After reviewing the available literature we produced examples of consent forms for breast, gynae/pelvis, head & neck, oesophagus, rectum, anus and pituitary. These were reviewed at meetings of the ORF and Patients Liaison Group. There was concern that the proposed forms might over-estimate the magnitude of risk of side effects if the evidence base used relied upon trials using out-dated techniques or equipment. Ideally, as a result of local audit, centres would know the expected percentage risk of early/late effects in their population. Following further discussion it was decided that attempting to introduce standardised consent forms was impractical but that it would be useful to develop the project work into a training and information resource which is presented here. This includes examples of the consent forms and an assessment of the quality of evidence for some of the sites, complete with references.
Possible side-effects during and after radiotherapy to the breast (and lymph nodes) Early: Common: Tiredness Red, sore skin of breast Less common: Breast swelling Skin breakdown Dry cough and shortness of breath (<1%) Change in breast shape Change in skin appearance Breast/chest wall tenderness Rarely: Fracture of underlying ribs Scarring of lung (<1%) Effects on heart (Left breast only, usually 10 years later) Small risk of cancer due to radiation If lymph nodes treated: Shoulder stiffness Swelling of arm/hand (lymphoedema) (approximately 9% risk if RT alone or RT plus node sampling, up to 38% if RT plus node clearance) Small risk of damage to nerves in arm (<1%) Ref. Type of evidence Dose/Fractionation Number Modern technique? Comments 1 prospective 40Gy 15# 334 yes Leeds. 2 Literature review 79 references 3 prospective 45Gy 25# 1022 mainly Indian 4 RCT 40Gy 15# 50Gy 25# 2215 yes START B
References: 1: Ash DV, et al. Seven year follow-up on 334 patients treated by breast conserving surgery and short course postoperative radiotherapy: A report of the Yorkshire Breast Cancer Group. Clin Oncol 1995;7:93-96. 2: Senkus-Konefka E, et al. Complications of breast-cancer Radiotherapy. Clin Oncol 2006;18:229-235. 3: Budrukkar AN, et al. Cosmesis, late sequelae and local tumour control after breast-conserving therapy: Influence of tumour bed boost and adjuvant chemotherapy. Clin Oncol 2007;19:596-603. 4: The START Trialists Group. The UK standardisation of breast radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet 2008;371:1098-1107. 5: Kissin MW, et al. Risk of Lymphoedema following the treatment of breast cancer. Br J Surg 1986 Jul;73(7):580-584. 6: Yap J, et al. Sarcoma as a second malignancy after treatment for breast cancer. Int J Radiat Oncol Biol Phys 2002;52(5):1231-1237. 7: Taylor CW, et al. Cardiac risks of breast cancer radiotherapy: A contemporary view. Clin Oncol 2006;18:236-246. 8: Powell SN, et al. Risk of lymphoedema after regional nodal irradiation with breast conservation therapy. Int J Radiat Oncol Biol Phys 2003;55:1209-1215.
Possible side-effects during and after short-course preoperative radiotherapy for rectal cancer: Early: Diarrhoea (less than 2%) Delayed healing of skin if Abdomino-perineal resection performed (up to 30%) Temporary nerve pain/numbness in legs (less than 1%) (Many of these symptoms are experienced following surgery alone but may be more pronounced or more frequent with the addition of radiotherapy) Loose and/or frequent stools (common) Reduced bowel control/anal leakage mild (rarely) to severe (daily) (up to 60%) Passage of mucus or blood (up to 30%) Reduced bladder control/urine leakage mild (rarely) to severe (daily) (up to 30%) Reduced sexual function (common) Infertility and early menopause if appropriate (100%) Bowel damage/narrowing requiring operation (< 5%) Narrowing of blood vessels impairing circulation (rare) Small risk of secondary cancer due to radiation Ref. Type of evidence Dose/Fractionation Number Modern technique? Comments 1 RCT 25Gy 5# 695 yes Dutch TME Acute SE 2 Prospective/ Questionnaire 25Gy 5# 597 yes Dutch TME Late SE 3 Retrospective 25Gy 5# 156 yes Birmingham References:
1: Marijen C, et al. Acute side effects and complications after short-term preoperative radiotherapy combined with total mesorectal excision in primary rectal cancer: Report of a multicenter randomised trial. J Clin Oncol 2002;20:817-825. 2: Van de Velde C, et al. Late side effects of short-course preoperative radiotherapy with total mesorectal excision for rectal cancer: Increased bowel dysfunction in irradiated patients a Dutch Colorectal Cancer Study Group study. J Clin Oncol 2005;23:6199-6206. 3: King M, et al. Late toxicity after short-course preoperative radiotherapy and total mesorectal excision for rectal cancer. Clin Oncol 2003;15:233-236. 4: Marijen C, et al. Impact of short-term preoperative radiotherapy on health-related quality of life and sexual functioning in primary rectal cancer: Report of a multicenter randomised trial. J Clin Oncol 2005;23:1847-1858. 5: Pollack, J et al. Late adverse effects of short-course preoperative radiotherapy in rectal cancer. British Journal of Surgery 2006;93:1519-1525. 6: Information for doctors about pelvic radiotherapy side effects. Cancer Research UK 2007. www.cancerhelp.org.uk Possible side-effects during and after pelvic radiotherapy for gynaecological cancers (locally advanced uterine cervix):
Early: Common: Tiredness Red, sore skin Dysuria (burning sensation on passing urine) Diarrhoea Loss of pubic hair Less common: Nausea Rectal bleeding or mucus Change in bowel habit and rectal symptoms (<10%) Passing urine more often Vaginal dryness Vaginal narrowing/ulceration (10-15%) Early menopause Infertility Lymphoedema (swelling of legs) Rarely (<5%): Narrowing of bowel Abnormal passage between organs (fistula) Blood in urine Narrowing of urethra Weakness of pelvic bones, causing fracture or pain Small risk of secondary cancer due to radiation Ref. Type of evidence Dose/Fractionation Number Modern technique? Comments 1 Prospective audit 45Gy 25# 57 yes 2 Retrospective 1784 no POP 98% review 3 Prospective 45Gy 25# 59 mainly POP 35% audit 4 Prospective 45Gy 25# 195 mainly POP/4-field 5 Metaanalysis 1.8 2.5Gy/# 8 RCT s mainly 50% SE reported References:
1: King M, et al. Improved survival after concurrent weekly cisplatin with radiotherapy for cervical carcinoma with assessment of acute and late effects. Clin Oncol 2006;18:38-45. 2: Eifel P, et al. Time course and incidence of late complications in patients treated with radiation therapy for FIGO stage 1B carcinoma of the uterine cervix. Int J Radiat Oncol Biol Phys 1995;32(5):1289-1300. 3: Tan, et al. Acute toxicity of chemoradiotherapy for cervical cancer: The Addenbrookes Experience. Clin Oncol 2004;16:255-260. 4: Morris M, et al. Pelvic radiation with concurrent chemotherapy compared with pelvic plus para-aortic radiation for high risk cervical cancer. N Eng J Med 1999;340:1137-1143. 5: Lukka H, et al. Concurrent cisplatin-based chemotherapy plus radiotherapy for cervical cancer a meta-analysis. Clin Oncol 2002;14:103-212 6: Feltl D, et al. Symptomatic osteoradionecrosis of pelvic bones in patients with gynaecological malignancies-result of a long term follow up. Int J Gynecol Cancer 2006;16(2):478-483. 7: Perez CA, et al. Radiation therapy morbidity in carcinoma of the cervix: dosimetric and clinical correlation. Int J Radiat Oncol Biol Phys 1999;44(4):855-866. 8: Penderson D, et al. Early and late radiotherapeutic morbidity in 442 consecutive patients with locally advanced carcinoma of the uterine cervix. Int J Radiat Oncol Biol Phys 1994;29(5):941-952 9: Sundar S, et al. Tolerance of pelvic organs to radiation treatment for carcinoma of cervix. Clin Oncol 2003;15:240-247 Possible side-effects during and after radiotherapy (with chemotherapy) for cancer of the anus
Early: Tiredness (very common) Sore skin with breakdown in skin creases (up to 100%) Painful skin with ulceration and bleeding (up to 50%) Loose/frequent bowel motions (up to 100%) Anal discharge with /without blood staining (up to 100%) Increased frequency of passing urine/cystitis (up to 100%) Loss of pubic hair (up to 100%) Severe diarrhoea possibly with reduced bowel control (up to 10%) Common: Loose/frequent bowel motions (up to 50%) Occasional leakage from anus (approximately 20%) Impotence in men (30-50%) Early menopause and reduced sexual function in women Infertility Less common: Loss of bowel control (approximately 5%) Ulceration of anal area (less than 10%) Increased frequency of passing urine (less than 10%) Ulceration of skin/groins (less than 5%) Severe thickening of skin in groins/genital area (less than 5%) Swelling of legs lymphoedema (less than 10%) Bowel damage/narrowing requiring operation (less than 5%) Small risk of secondary cancer due to radiation Failure of treatment to control tumour possibly requiring surgical treatment (up to 35%) Chemotherapy causes additional side-effects and will be discussed separately. References:
1: James R, et al. The second UK phase III anal cancer trial of chemoradiation and maintenance therapy (ACT II): Preliminary results on toxicity and outcome. Proceedings of ASCO 2003 (abstract 1151). 2: Madhu J, et al. Ten-year results of chemoradiation for anal cancer: Focus on late morbidity. Int J Radiat Biol Phys 1996;34(1):65-69. 3: The UKCCCR Anal Cancer Trial Working Party. Epidermoid anal cancer: results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil and mitomycin. Lancet 1996;348:1049-1054. 4: Vordermark D, et al. Curative-intent radiation therapy in anal carcinoma: quality of life and sphincter function. Radiother Oncol 1999;52:239-243. 5: Bartelink H, et al. Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: Results of a phase III randomised trial of the EORTC radiotherapy and gastrointestinal cooperative groups. J Clin Oncol 1997;15:2040-2049. 6: Putta S, et el. Faecal incontinence: A late side-effect of pelvic radiotherapy. Clin Oncol 2005;17(6):469-477. 7: Dzik-Jurasz A, et el. What is the prevalence of symptomatic or asymptomatic femoral head osteonecrosis in patients previously treated with chemoradiation? A magnetic resonance study of anal cancer patients. Clin Oncol 2001; 13(2):130-134. Possible side-effects during and after radiotherapy for head and neck cancers
Early: Common: Tiredness Red, itchy skin Dry mouth Stringy saliva Taste change Loss of hair in treatment area Painful swallowing Less common: Skin breakdown (up to 10%) Soreness of mouth (severe in 20-40%) Change / loss of voice (15-20%) Cough Dry mouth (severe in up to 20%) Change in appearance of skin (severe in 1-2%) Swelling of face and neck (lymphoedema) (severe in 2-7%) Tightening of jaw muscles (up to 20%) Thinning/tightening of soft tissues of mouth (severe in 1-2%) Difficulty swallowing (5-7%) Voice problems (6-8% if larynx treated) Necrosis of larynx (1-2%) Breakdown of jaw bone (osteo-radionecrosis) (1-2%) Transient or permanent damage to spinal cord (< 1%) Hypothyroidism corrected by thyroxine tablets (up to 30%) Dental decay (up to 10%) Cataracts (only if lens treated) Hearing problems Small risk of secondary cancer due to radiation Chemotherapy causes additional side-effects and will be discussed separately. References: 1: Jereczek F. et al. Fatigue during head and neck radiotherapy: prospective study on 117 consecutive patients. Int J Radiat Biol Phys 2007;68(2):403-415.
2: Norris A, et al. Hypothyroidism when the thyroid is included only in the low neck field during head and neck radiotherapy. Am J Clin Onc 2006;29(5):442-445. 3: Tell R, et al. Long-term incidence of hypothyroidism after radiotherapy in patients with head and neck cancer. Int J Radiat Biol Phys 2004;60(2):395-400. 4: Bernier J, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Eng J Med 2004;350(19):1945-1952. 5: Cooper JS, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Eng J Med 2005;350(19):1937-1944. 6: Mavroidis P, et al. Determination and clinical verification of dose-response parameters for oesophageal stricture from head and neck radiotherapy. Acta oncologica 2003;42(8):865-881. 7: Forastiere AA, et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Eng J Med 2003;349(22):2091-2098. 8: Horiot JC, et al. Dental preservation in patients irradiated for head and neck tumours: A 10 year experience with topical fluoride and a randomised trial between two fluoridation methods. Radiother Oncol 1983;1(1):77-82. Possible side-effects during and after radiotherapy for pituitary tumours Early: Tiredness Nausea
Headache Red, sore skin on scalp Some hair loss Need for replacement hormones eg. Thyroxine (50% at 20 years) Visual problems due to radiation (1-2%) Increased risk of stroke (up to 4 times general population risk) Small risk of secondary cancer due to radiation References: 1: Brada M, et al. Clin Endocrinology 1993;38:571-578. 2: Brada M, et al. Int J Radiat Biol Phys 1999; 45(3):693-698. 3: Minniti G, et al. J Clin Endocrinol Metab 2005;90(2):800-804. Possible side-effects during and after radiotherapy for oesophageal cancer Early: Tiredness (common) Nausea (severe in 15-20%) Painful swallowing (severe in 10-25)
Chest discomfort Hair loss over treatment area Redness of skin Breathlessness / coughing (less than 5%) Risk of abnormal passage between oesophagus and the airways (less than 1%) Scarring of the lung (1-3%) Difficulty swallowing which may require dilatation/stenting (<5%) Damage to the heart (2-5%) Hypothyroidism requiring treatment (if neck treated) Small risk of secondary cancer due to radiation Chemotherapy (if given) causes additional side-effects and may be discussed separately References: 1: Ishikura S, et al. Long-term toxicity after definitive chemoradiotherapy for squamous cell carcinoma of the thoracic oesophagus. J Clin Oncol 2003;21(14):2697-2702. 2: Kumekawa Y, et al. Late toxicity in complete response cases after definitive chemo-radiotherapy for oesophageal squamous cell carcinoma. J Gastroenterol 2006;41:425-432. 3: Kaneko K, et al. Definitive chemo-radiotherapy for patients with malignant stricture due to T3 or T4 squamous cell carcinoma of the oesophagus. Br J Cancer 2003;88:18-24. Dr David Sherriff