Late gastrointestinal toxicity after radiotherapy for anal cancer: a systematic literature review

References

• Wilkinson J, Morris E, Downing A, et al. The rising incidence of anal cancer in England 1990-2010: a population-based study. Colorectal Dis. 2014;16:O234–O239.
   PubMed Web of Science ®Google Scholar
• Siegel R, Miller K, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68:7–30.
   PubMed Web of Science ®Google Scholar
• Northover J, Glynne-Jones R, Sebag-Montefiore D, et al. Chemoradiation for the treatment of epidermoid anal cancer: 13-year follow-up of the first randomised UKCCCR Anal Cancer Trial (ACT I). Br J Cancer. 2010;102:1123–1128.
   PubMed Web of Science ®Google Scholar
• Ajani JA, Winter KA, Gunderson LL, et al. Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial. JAMA 2008;299:1914.
   PubMed Web of Science ®Google Scholar
• John M, Pajak T, Flam M, et al. Dose escalation in chemoradiation for anal cancer: preliminary results of RTOG 92-08. Cancer J Sci Am. 1996;2:205–211.
   PubMedGoogle Scholar
• James RD, Glynne-Jones R, Meadows HM, et al. Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2 × 2 factorial trial. Lancet Oncol. 2013;14:516–524.
   PubMed Web of Science ®Google Scholar
• Shridhar R, Shibata D, Chan E, et al. Anal cancer: current standards in care and recent changes in practice. CA Cancer J Clin. 2015;65:139–162.
   PubMed Web of Science ®Google Scholar
• Bentzen AG, Balteskard L, Wanderås EH, et al. Impaired health-related quality of life after chemoradiotherapy for anal cancer: late effects in a national cohort of 128 survivors. Acta Oncol. 2013;52:736–744.
   PubMed Web of Science ®Google Scholar
• Moher D, Liberati A, Tetzlaff J, et al. Reprint-preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Phys Ther. 2009;89:873–880.
   PubMed Web of Science ®Google Scholar
• National Cancer Institute [Internet]. Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Available from: https://www.eortc.be/services/doc/ctc/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf (last accessed 22 December 2013).
   Google Scholar
• Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European organization for research and treatment of cancer (EORTC). Int J Radiat Oncol. 1995;31:1341–1346.
   PubMed Web of Science ®Google Scholar
• Cummings BJ, Keane TJ, O’Sullivan B, et al. Epidermoid anal cancer: treatment by radiation alone or by radiation and 5-fluorouracil with and without mitomycin C. Int J Radiat Oncol Biol Phys. 1991;21:1115–1125.
   PubMed Web of Science ®Google Scholar
• John M, Flam M, Palma N. Ten-year results of chemoradiation for anal cancer: focus on late morbidity. Int J Radiat Oncol Biol Phys. 1996;34:65–69.
   PubMed Web of Science ®Google Scholar
• Janssen S, Glanzmann C, Bauerfeind P, et al. Clinical experience of SIB-IMRT in anal cancer and selective literature review. Radiat Oncol. 2014;9:199.
   PubMed Web of Science ®Google Scholar
• Lestrade L, De Bari B, Montbarbon X, et al. Radiochemotherapy and brachytherapy could be the standard treatment for anal canal cancer in elderly patients? A retrospective single-centre analysis. Med Oncol. 2013;30:402.
   PubMed Web of Science ®Google Scholar
• Ferrigno R, Nakamura R, Dos Santos Novaes P, et al. Radiochemotherapy in the conservative treatment of anal canal carcinoma: retrospective analysis of results and radiation dose effectiveness. Int J Radiat Oncol Biol Phys. 2005;61:1136–1142.
   PubMed Web of Science ®Google Scholar
• Doggett S, Green J, Cantril S. Efficacy of radiation therapy alone for limited squamous cell carcinoma of the anal canal. Int J Radiat Oncol Biol Phys. 1988;15:1069–1072.
   PubMed Web of Science ®Google Scholar
• Mai SK, Welzel G, Hermann B, et al. Long-term outcome after combined radiochemotherapy for anal cancer – retrospective analysis of efficacy, prognostic factors, and toxicity. Onkologie. 2008;31:251–257.
   PubMedGoogle Scholar
• De Bari B, Etitia Lestrade L, Pommier P, et al. Could concomitant radio-chemotherapy improve the outcomes of early-stage node negative anal canal cancer patients? A retrospective analysis of 122 patients. Cancer Invest. 2015;33:114–120.
   PubMed Web of Science ®Google Scholar
• Janssen S, Meier zu Eissen J, Kolbert G, et al. Anal cancer treated with radio-chemotherapy: correlation between length of treatment interruption and outcome. Int J Colorectal Dis. 2009;24:1421–1428.
   PubMed Web of Science ®Google Scholar
• Sebag-Montefiore D, Meadows HM, Cunningham D, et al. Three cytotoxic drugs combined with pelvic radiation and as maintenance chemotherapy for patients with squamous cell carcinoma of the anus (SCCA): long-term follow-up of a phase II pilot study using 5-fluorouracil, mitomycin C and cisplatin. Radiother Oncol. 2012;104:155–160.
   PubMed Web of Science ®Google Scholar
• Call JA, Prendergast BM, Jensen LG, et al. Intensity-modulated radiation therapy for anal cancer: results from a Multi-Institutional Retrospective Cohort Study. Am J Clin Oncol. 2016;39:8–12.
   PubMed Web of Science ®Google Scholar
• Kapoor R, Khosla D, Shukla AK, et al. Dosimetric and clinical outcome in image-based high-dose-rate interstitial brachytherapy for anal cancer. Brachytherapy. 2014;13:388–393.
   PubMed Web of Science ®Google Scholar
• Mai SK, Grieger J, Lachmann R, et al. Radiochemotherapy for anal carcinoma - effectivity and late toxicity. Onkologie. 2002;25:55–59.
   PubMedGoogle Scholar
• Konski A Jr, John M, Krieg R, et al. Evaluation of planned treatment breaks during radiation therapy for anal cancer: update of RTOG 92-08. Int J Radiat Oncol Biol Phys. 2008;72:114–118.
   PubMed Web of Science ®Google Scholar
• Fraunholz IB, Haberl A, Klauke S, et al. Long-term effects of chemoradiotherapy for anal cancer in patients with HIV infection: oncological outcomes, immunological status, and the clinical course of the HIV disease. Dis Colon Rectum. 2014;57:423–431.
   PubMed Web of Science ®Google Scholar
• Bieri S, Allal A, Kurtz J. Sphincter-conserving treatment of carcinomas of the anal margin. Acta Oncol. 2001;40:29–33.
   PubMed Web of Science ®Google Scholar
• White EC, Khodayari B, Erickson KT, et al. Comparison of toxicity and treatment outcomes in HIV-positive versus HIV-negative patients with squamous cell carcinoma of the anal canal. Am J Clin Oncol. 2014;40:386–392.
   Web of Science ®Google Scholar
• Gunderson LL, Winter KA, Ajani JA, et al. Long-term update of US GI intergroup RTOG 98-11 phase III trial for anal carcinoma: survival, relapse, and colostomy failure with concurrent chemoradiation involving fluorouracil/mitomycin versus fluorouracil/cisplatin. J Clin Oncol. 2012;30:4344–4351.
   PubMed Web of Science ®Google Scholar
• Dewas CV, Maingon P, Dalban C, et al. Does gap-free intensity modulated chemoradiation therapy provide a greater clinical benefit than 3D conformal chemoradiation in patients with anal cancer? Radiat Oncol. 2012;7:201–210.
   PubMed Web of Science ®Google Scholar
• Vordermark D, Sailer M, Flentje M, et al. Curative-intent radiation therapy in anal carcinoma: quality of life and sphincter function. Radiother Oncol. 1999;52:239–243.
   PubMed Web of Science ®Google Scholar
• Tveit KM, Karlsen KO, Fosså SD, et al. Primary treatment of carcinoma of the anus by combined radiotherapy and chemotherapy primary treatment of carcinoma of the anus by combined radiotherapy and chemotherapy. Scand J Gastroenterol. 1989;24:1243–1247.
   PubMed Web of Science ®Google Scholar
• John M, Flam M, Lovalvo L, et al. Feasibility of non-surgical definitive management of anal canal carcinoma. Int J Radiat Oncol Biol Phys. 1987;13:299–303.
   PubMed Web of Science ®Google Scholar
• Tanum G, Tveit K, Karlsen K. Chemoradiotherapy of anal carcinoma: tumour response and acute toxicity. Oncology. 1993;50:14–17.
   PubMed Web of Science ®Google Scholar
• Gabriele A, Rovea P, Sola B, et al. Radiation therapy and chemotherapy in the conservative treatment of carcinoma of the anal canal: survival and late morbidity in a series of 25 patients. Anticancer Res. 1997;17:653–656.
   PubMed Web of Science ®Google Scholar
• Ortholan C, Ramaioli A, Peiffert D, et al. Anal canal carcinoma: early-stage tumors ≤10 mm (T1 or Tis): therapeutic options and original pattern of local failure after radiotherapy. Int J Radiat Oncol Biol Phys. 2005;62:479–485.
   PubMed Web of Science ®Google Scholar
• Balamucki C, Zlotecki R, Rout W, et al. Squamous cell carcinoma of the anal margin: the university of Florida experience. Am J Clin Oncol. 2011;34:406–410.
   PubMed Web of Science ®Google Scholar
• De Bari B, Jumeau R, Bouchaab H, et al. Efficacy and safety of helical tomotherapy with daily image guidance in anal canal cancer patients. Acta Oncol. 2016;55:767–773.
   PubMed Web of Science ®Google Scholar
• Oblak I, Petric P, Anderluh F, et al. Anal cancer chemoirradiation with curative intent - a single institution experience. Neoplasma. 2009;56:150–155.
   PubMed Web of Science ®Google Scholar
• Peiffert D, Bey P, Pernot M, et al. Conservative treatment by irradiation of epidermoid cancers of the anal canal: prognostic factors of tumoral control and complications . Int J Radiat Oncol Biol Phys. 1997;37:313–324.
   PubMed Web of Science ®Google Scholar
• Nguyen NP, Vock J, Sroka T, et al. Feasibility of image-guided radiotherapy based on tomotherapy for the treatment of locally advanced anal carcinoma. Anticancer Res. 2011;31:4393–4396.
   PubMed Web of Science ®Google Scholar
• Di Santo S, Trignani M, Neri M, et al. Radiochemotherapy in anal cancer: cCR, clinical outcomes and quality of life using two different treatment schedules. Reports Pract Oncol Radiother. 2015;20:128–134.
   PubMedGoogle Scholar
• Oblak I, Petric P, Anderluh F, et al. Long term outcome after combined modality treatment for anal cancer. Radiol Oncol. 2012;46:145–152.
   PubMed Web of Science ®Google Scholar
• Jones RD, Symonds RP, Robertson AG, et al. Changes in the radiation treatment of cancer of the anus in Glasgow. Br J Radiol. 1993;66:797–800.
   PubMed Web of Science ®Google Scholar
• Schlienger M, Krzisch C, Pene F, et al. Epidermoid carcinoma of the anal canal treatment results and prognostic variables in a series of 242 cases. Int J Radiat Oncol Biol Phys. 1989;17:1141–1151.
   PubMed Web of Science ®Google Scholar
• Beck D, Karulf R. Combination therapy for epidermoid carcinoma of the anal canal. Dis Colon Rectum. 1994;37:1118–1125.
   PubMed Web of Science ®Google Scholar
• Allal A, Kurtz J, Pipard G, et al. Chemoradiotherapy versus radiotherapy alone for anal cancer: a retrospective comparison. Int J Radiat Oncol Biol Phys. 1993;27:59–66.
   PubMed Web of Science ®Google Scholar
• Cordoba A, Escande A, Leroy T, et al. Low-dose-rate interstitial brachytherapy boost for the treatment of anal canal cancers. Brachytherapy. 2017;16:230.
   PubMed Web of Science ®Google Scholar
• Sandhu APS, Symonds RP, Robertson AG, et al. Interstitial iridium-192 implantation combined with external radiotherapy in anal cancer: ten years experience. Int J Radiat Oncol Biol Phys. 1998;40:575–581.
   PubMed Web of Science ®Google Scholar
• Widder J, Kastenberger R, Fercher E, et al. Radiation dose associated with local control in advanced anal cancer: retrospective analysis of 129 patients. Radiother Oncol. 2008;87:367–375.
   PubMed Web of Science ®Google Scholar
• Eng C, Chang GJ, You YN, et al. Long-term results of weekly/daily cisplatin-based chemoradiation for locally advanced squamous cell carcinoma of the anal canal. Cancer. 2013;119:3769–3775.
   PubMed Web of Science ®Google Scholar
• Vaizey CJ, Carapeti E, Cahill JA, et al. Prospective comparison of faecal incontinence grading systems. Gut. 1999;44:77–80.
   PubMed Web of Science ®Google Scholar
• Broens P, Van Limbergen E, Penninckx F, et al. Clinical and manometric effects of combined external beam irradiation and brachytherapy for anal cancer. Int J Colorectal Dis. 1998;13:68–72.
   PubMed Web of Science ®Google Scholar
• Vordermark D, Flentje M, Sailer M, et al. Intracavitary afterloading boost in anal canal carcinoma. Results, function and quality of life. Strahlenther Onkol. 2001;177:252–258.
   PubMed Web of Science ®Google Scholar
• Bentzen AG, Guren MG, Vonen B, et al. Faecal incontinence after chemoradiotherapy in anal cancer survivors: long-term results of a national cohort. Radiother Oncol. 2013;108:55–60.
   PubMed Web of Science ®Google Scholar
• De Francesco I, Thomas K, Wedlake L, et al. Intensity-modulated radiotherapy and anal cancer: clinical outcome and late toxicity assessment. Clin Oncol. 2016;28:604–610.
   PubMed Web of Science ®Google Scholar
• Vieillot S, Fenoglietto P, Lemanski C, et al. IMRT for locally advanced anal cancer: clinical experience of the Montpellier Cancer Center. Radiat Oncol. 2012;7:45.
   PubMed Web of Science ®Google Scholar
• Mitchell MP, Abboud M, Eng C, et al. Intensity-modulated radiation therapy with concurrent chemotherapy for anal cancer: outcomes and toxicity. Am J Clin Oncol. 2014;37:461–466.
   PubMed Web of Science ®Google Scholar
• Fakhrian K, Sauer T, Klemm S, et al. Radiotherapy with or without chemotherapy in the treatment of anal cancer: 20-year experience from a single institute. Strahlenther Onkol. 2013;189:18–25.
   PubMed Web of Science ®Google Scholar
• Lestrade L, De Bari B, Pommier P, et al. Role of brachytherapy in the treatment of cancers of the anal canal: long-term follow-up and multivariate analysis of a large monocentric retrospective series. Strahlenther Onkol. 2014;190:546–554.
   PubMed Web of Science ®Google Scholar
• Koerber SA, Slynko A, Haefner MF, et al. Efficacy and toxicity of chemoradiation in patients with anal cancer–a retrospective analysis. Radiat Oncol. 2014;9:113.
   PubMed Web of Science ®Google Scholar
• Badvie S, Andreyev HJN. Topical phenylephrine in the treatment of radiation-induced faecal incontinence. Clin Oncol (R Coll Radiol). 2005;17:122–126.
   PubMed Web of Science ®Google Scholar
• Maeda Y, Høyer M, Lundby L, et al. Temporary sacral nerve stimulation for faecal incontinence following pelvic radiotherapy. Radiother Oncol. 2010;97:108–112.
   PubMed Web of Science ®Google Scholar
• Oehler-Jänne C, Seifert B, Lütolf UM, et al. Clinical outcome after treatment with a brachytherapy boost versus external beam boost for anal carcinoma. Brachytherapy. 2007;6:218–226.
   PubMed Web of Science ®Google Scholar
• Kapp KS, Geyer E, Gebhart FH, et al. Experience with split-course external beam irradiation +/- chemotherapy and integrated Ir-192 high-dose-rate brachytherapy in the treatment of primary carcinomas of the anal canal. Int J Radiat Oncol Biol Phys. 2001;49:997–1005.
   PubMed Web of Science ®Google Scholar
• Peiffert D, Bey P, Pernot M, et al. Conservative treatment by irradiation of epidermoid carcinomas of the anal margin. Int J Radiat Oncol Biol Phys. 1997;39:57–66.
   PubMed Web of Science ®Google Scholar
• Myerson RJ, Outlaw ED, Chang A, et al. Radiotherapy for epidermoid carcinoma of the anus: thirty years’ experience. Int J Radiat Oncol Biol Phys. 2009;75:428–435.
   PubMed Web of Science ®Google Scholar
• Vuong T, Devic S, Belliveau P, et al. Contribution of conformal therapy in the treatment of anal canal carcinoma with combined chemotherapy and radiotherapy: results of a phase II study. Int J Radiat Oncol Biol Phys. 2003;56:823–831.
   PubMed Web of Science ®Google Scholar
• Edelman S, Johnstone PAS. Combined modality therapy for HIV-infected patients with squamous cell carcinoma of the anus: Outcomes and toxicities. Int J Radiat Oncol Biol Phys. 2006;66:206–211.
   PubMed Web of Science ®Google Scholar
• Bosset JF, Roelofsen F, Morgan DAL, et al. Shortened irradiation scheme, continuous infusion of 5-fluorouracil and fractionation of mitomycin C in locally advanced anal carcinomas. Results of a phase II study of the European Organization for Research and Treatment of Cancer. Radiotherapy and Gastr. Eur J Cancer.2003;39:45–51.
   PubMed Web of Science ®Google Scholar
• Flam M, John M, Mowry P, et al. Definitive combined modality therapy of carcinoma of the anus. A report of 30 cases including results of salvage therapy in patients with residual. Dis Colon Rectum. 1987;30:495–502.
   PubMed Web of Science ®Google Scholar
• Flam M, John M, Lovalvo L, et al. Definitive nonsurgical therapy of epithelial malignancies of the anal canal. A report of 12 cases. Cancer. 1983;51:1378–1387.
   PubMed Web of Science ®Google Scholar
• Doyen J, Benezery K, Follana P, et al. Predictive factors for early and late local toxicities in anal cancer treated by radiotherapy in combination with or without chemotherapy. Dis Colon Rectum. 2013;56:1125–1133.
   PubMed Web of Science ®Google Scholar
• Oehler-Jänne C, Seifert B, Lutolf UM, et al. Local tumor control and toxicity in HIV-associated anal carcinoma treated with radiotherapy in the era of antiretroviral therapy. Radiat Oncol. 2006;1:29.
   PubMed Web of Science ®Google Scholar
• Fraunholz I, Weiss C, Eberlein K, et al. Concurrent chemoradiotherapy with 5-fluorouracil and mitomycin C for invasive anal carcinoma in human immunodeficiency virus-positive patients receiving highly active antiretroviral therapy. Int J Radiat Oncol Biol Phys. 2010;76:1425–1432.
   PubMed Web of Science ®Google Scholar
• Touboul E, Schlienger M, Buffat L, et al. Epidermoid carcinoma of the anal canal. Results of curative-intent radiation therapy in a series of 270 patients. Cancer. 1994;73:1569–1579.
   PubMed Web of Science ®Google Scholar
• Tanum G, Tveit K, Karlsen KO, et al. Chemotherapy and radiation therapy for anal carcinoma. Survival and late morbidity. Cancer. 1991;67:2462–2466.
   PubMed Web of Science ®Google Scholar
• Schneider IH, Grabenbauer GG, Reck T, et al. Combined radiation and chemotherapy for epidermoid carcinoma of the anal canal. Int J Colorectal Dis. 1992;7:192–196.
   PubMed Web of Science ®Google Scholar
• Serkies K, Bednaruk-Mlynski E, Dziadziuszko R, et al. Conservative treatment for carcinoma of the anus-a report of 35 patients. Neoplasma. 2003;50:152–158.
   PubMed Web of Science ®Google Scholar
• Hwang JM, Rao AR, Cosmatos HA, et al. Treatment of T3 and T4 anal carcinoma with combined chemoradiation and interstitial 192Ir implantation: a 10-year experience. Brachytherapy. 2004;3:95–100.
   PubMedGoogle Scholar
• Raffetto N, Monaco A, Banelli E. Radiotherapy and chemotherapy in the conservative treatment of anal canal carcinoma. Anticancer Res. 2008;28:1335–1339.
   PubMed Web of Science ®Google Scholar
• Allal AS, Obradovic M, Laurencet F, et al. Treatment of anal carcinoma in the elderly: feasibility and outcome of radical radiotherapy with or without concomitant chemotherapy. Cancer. 1999;85:26–31.
   PubMed Web of Science ®Google Scholar
• Tomaszewski JM, Link E, Leong T, et al. Twenty-five-year experience with radical chemoradiation for anal cancer. Int J Radiat Oncol Biol Phys. 2012;83:552–558.
   PubMed Web of Science ®Google Scholar
• Peiffert D, Tournier-Rangeard L, Gérard JP, et al. Induction chemotherapy and dose intensification of the radiation boost in locally advanced anal canal carcinoma: final analysis of the randomized UNICANCER ACCORD 03 trial. J Clin Oncol. 2012;30:1941–1948.
   PubMed Web of Science ®Google Scholar
• Oehler-Jänne C, Huguet F, Provencher S, et al. HIV-specific differences in outcome of squamous cell carcinoma of the anal canal: a multicentric cohort study of HIV-positive patients receiving highly active antiretroviral therapy. J Clin Oncol. 2008;26:2550–2557.
   PubMed Web of Science ®Google Scholar
• Holland JM, Swift PS. Tolerance of patients with human immunodeficiency virus and anal carcinoma to treatment with combined chemotherapy and radiation therapy. Radiology. 1994;193:251–254.
   PubMed Web of Science ®Google Scholar
• Hammad N, Heilbrun L, Gupta S, et al. Squamous cell cancer of the anal canal in HIV-infected patients receiving highly active antiretroviral therapy: a single institution experience. Am J Clin Oncol. 2011;34:135–139.
   PubMed Web of Science ®Google Scholar
• Jephcott CR, Paltiel C, Hay J. Quality of life after non-surgical treatment of anal carcinoma: a case control study of long-term survivors. Clin Oncol (R Coll Radiol). 2004;16:530–535.
   PubMed Web of Science ®Google Scholar
• Han K, Cummings BJ, Lindsay P, et al. Prospective evaluation of acute toxicity and quality of life after IMRT and concurrent chemotherapy for anal canal and perianal cancer. Int J Radiat Oncol Biol Phys. 2014;90:587–594.
   PubMed Web of Science ®Google Scholar
• Tournier-rangeard L, Mercier M, Peiffert D, et al. Radiochemotherapy of locally advanced anal canal carcinoma: prospective assessment of early impact on the quality of life (randomized trial ACCORD 03) Radiother Oncol. 2008;87:391–397.
   PubMed Web of Science ®Google Scholar
• Zachariah B, Gwede CK, James J, et al. Octreotide acetate in prevention of chemoradiation-induced diarrhea in anorectal cancer: randomized RTOG trial 0315. J Natl Cancer Inst. 2010;102:547–556.
   PubMedGoogle Scholar
• Oehler C, Provencher S, Donath D, et al. Chemo-radiation with or without mandatory split in anal carcinoma: experiences of two institutions and review of the literature. Radiat Oncol. 2010;5:36.
   PubMed Web of Science ®Google Scholar
• Grabenbauer GG, Schneider IH, Gall FP, et al. Epidermoid carcinoma of the anal canal: treatment by combined radiation and chemotherapy. Radiother Oncol. 1993;27:59–62.
   PubMed Web of Science ®Google Scholar
• Deo S, Shukla N, Raina V, et al. Organ-preserving multimodality management of squamous cell carcinoma of anal canal. Indian J Gastroenterol. 2005;24:210–214.
   Google Scholar
• Zampino MG, Magni E, Leonardi MC, et al. Concurrent cisplatin, continuous infusion fluorouracil and radiotherapy followed by tailored consolidation treatment in non metastatic anal squamous cell carcinoma. BMC Cancer. 2011;11:55.
   PubMed Web of Science ®Google Scholar
• Rabbani AN, Zlotecki RA, Kirwan J, et al. Definitive radiotherapy for squamous cell carcinoma of the anal canal. Am J Clin Oncol. 2010;33:47–51.
   PubMed Web of Science ®Google Scholar
• Mitra D, Hong TS, Horick N, et al. Long-term outcomes and toxicities of a large cohort of anal cancer patients treated with dose-painted IMRT per RTOG 0529. Adv Radiat Oncol. 2017;2:110–117.
   PubMedGoogle Scholar
• Saarilahti K, Arponen P, Vaalavirta L, et al. The effect of intensity-modulated radiotherapy and high dose rate brachytherapy on acute and late radiotherapy-related adverse events following chemoradiotherapy of anal cancer. Radiother Oncol. 2008;87:383–390.
   PubMed Web of Science ®Google Scholar
• Pironi D, Panarese A, Vendettuoli M, et al. Chronic radiation-induced proctitis: the 4% formalin application as non-surgical treatment. Int J Colorectal Dis. 2013;28:261–266.
   PubMed Web of Science ®Google Scholar
• De Parades V, Etienney I, Bauer P, et al. Formalin application in the treatment of chronic radiation-induced hemorrhagic proctitis - an effective but not risk-free procedure: a prospective study of 33 patients. Dis Colon Rectum. 2005;48:1535–1541.
   PubMed Web of Science ®Google Scholar
• Rich TA, Ajani JA, Morrison WH, et al. Chemoradiation therapy for anal cancer: radiation plus continuous infusion of 5-fluorouracil with or without cisplatin. Radiother Oncol. 1993;27:209–215.
   PubMed Web of Science ®Google Scholar
• Glover M, Smerdon GR, Andreyev HJ, et al. Hyperbaric oxygen for patients with chronic bowel dysfunction after pelvic radiotherapy (HOT2): a randomised, double-blind, sham-controlled phase 3 trial. Lancet Oncol. 2016;17:224–233.
   PubMed Web of Science ®Google Scholar
• Khanfir K, Ozsahin M, Bieri S, et al. Patterns of failure and outcome in patients with carcinoma of the anal margin. Ann Surg Oncol. 2008;15:1092–1098.
   PubMed Web of Science ®Google Scholar
• Cantril S, Green J, Schall G, et al. Primary radiation therapy in the treatment of anal carcinoma. Int J Radiat Oncol Biol Phys. 1983;9:1271–1278.
   PubMed Web of Science ®Google Scholar
• Myerson R, Shapiro S, Lacey D, et al. Carcinoma of the anal canal. Am J Clin Oncol. 1995;18:32–39.
   PubMed Web of Science ®Google Scholar
• Newman G, Calverley DC, Acker BD, et al. The management of carcinoma of the anal canal by external beam radiotherapy, experience in Vancouver 1971-1988. Radiother Oncol. 1992;25:196–202.
   PubMed Web of Science ®Google Scholar
• Stojanović S, Radošević-Jelic L, Dabić-Stankovic K, et al. External beam radiotherapy plus brachytherapy boost in treatment of anal canal carcinoma. Acta Chir Iugosl. 2007;54:33–38.
   PubMedGoogle Scholar
• Wexler A, Berson AM, Goldstone SE, et al. Invasive anal squamous-cell carcinoma in the HIV-positive patient: Outcome in the era of highly active antiretroviral therapy. Dis Colon Rectum. 2008;51:73–81.
   PubMed Web of Science ®Google Scholar
• Fallai C, Cerrotta A, Valvo F, et al. Anal carcinoma of the elderly treated with radiotherapy alone or with concomitant radio-chemotherapy. Crit Rev Oncol Hematol. 2007;61:261–268.
   PubMed Web of Science ®Google Scholar
• Chadha M, Rosenblatt E. a, Malamud S, et al. Squamous-cell carcinoma of the anus in HIV-positive patients. Dis Colon Rectum. 1994;37:861–865.
   PubMed Web of Science ®Google Scholar
• Wolff H, Raus I, Jung K, et al. High-grade acute organ toxicity as a positive prognostic factor in primary radiochemotherapy for anal carcinoma. Int J Radiat Oncol Biol Phys. 2011;79:1467–1478.
   PubMed Web of Science ®Google Scholar
• Doci R, Zucali R, La MG, et al. Primary chemoradiation therapy with fluorouracil and cisplatin for cancer of the anus: results in 35 consecutive patients. J Clin Oncol. 1996;14:3121–3125.
   PubMed Web of Science ®Google Scholar
• Young SC, Solomon MJ, Hruby G, et al. Review of 120 anal cancer patients. Colorectal Dis. 2009;11:909–914.
   PubMed Web of Science ®Google Scholar
• Falk A, Claren A, Benezery K, et al. Interstitial high-dose rate brachytherapy as boost for anal canal cancer. Radiat Oncol. 2014;9:240.
   PubMed Web of Science ®Google Scholar
• Doci R, Zucali R, Bombelli L, et al. Combined chemoradiation therapy for anal cancer. A report of 56 cases. Ann Surg. 1992;215:150–156.
   PubMed Web of Science ®Google Scholar
• Wagner J, Mahe MA, Romestaing P, et al. Radiation therapy in the conservative treatment of carcinoma of the anal canal. Int J Radiat Oncol Biol Phys. 1994;29:17–23.
   PubMed Web of Science ®Google Scholar
• Barriger BR, Calley C, Cárdenes HR. Treatment of anal carcinoma in immune-compromised patients. Clin Transl Oncol. 2009;11:609–614.
   PubMed Web of Science ®Google Scholar
• Gerard JP, Ayzac L, Hun D, et al. Treatment of anal canal carcinoma with high dose radiation therapy and concomitant fluorouracil-cisplatinum. Long-term results in 95 patients. Radiother Oncol. 1998;46:249–256.
   PubMed Web of Science ®Google Scholar
• Aaronson NK, Ahmedzai S, Bergman B, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85:365–376.
   PubMed Web of Science ®Google Scholar
• Joseph K, Vos LJ, Warkentin H, et al. Patient reported quality of life after helical IMRT based concurrent chemoradiation of locally advanced anal cancer. Radiother Oncol.2016;120:228–233.
   PubMed Web of Science ®Google Scholar
• Allal AS, Sprangers M, Laurencet F, et al. Assessment of long-term quality of life in patients with anal carcinomas treated by radiotherapy with or without chemotherapy. Br J Cancer. 1999;80:1588–1594.
   PubMed Web of Science ®Google Scholar
• Sparano JA, Lee JY, Palefsky J, et al. Cetuximab plus chemoradiotherapy for HIV-associated anal carcinoma: a phase II AIDS malignancy consortium trial. J Clin Oncol. 2017;35:727–733.
   PubMed Web of Science ®Google Scholar
• Gujral S, Conroy T, Fleissner C, et al. Assessing quality of life in patients with colorectal cancer: an update of the EORTC quality of life questionnaire. Eur J Cancer. 2007;43:1564–1573.
   PubMed Web of Science ®Google Scholar
• Eypasch E, Williams J, Wood-Dauphinee S, et al. Gastrointestinal Quality of Life Index: development, validation and application of a new instrument. Br J Surg. 1995;82:216–222.
   PubMed Web of Science ®Google Scholar
• Provencher S, Oehler C, Lavertu S, et al. Quality of life and tumor control after short split-course chemoradiation for anal canal carcinoma. Radiat Oncol. 2010;5:41–49.
   PubMed Web of Science ®Google Scholar
• Welzel G, Hägele V, Wenz F, et al. Quality of life outcomes in patients with anal cancer after combined radiochemotherapy. Strahlenther Onkol. 2011;187:175–182.
   PubMed Web of Science ®Google Scholar
• Milano MT, Jani AB, Farrey KJ, et al. Intensity-modulated radiation therapy (IMRT) in the treatment of anal cancer: toxicity and clinical outcome. Int J Radiat Oncol Biol Phys. 2005;63:354–361.
   PubMed Web of Science ®Google Scholar
• Salama JK, Mell LK, Schomas DA, et al. Concurrent chemotherapy and intensity-modulated radiation therapy for anal canal cancer patients: a multicenter experience. J Clin Oncol. 2007;25:4581–4586.
   PubMed Web of Science ®Google Scholar
• Franco P, Mistrangelo M, Arcadipane F, et al. Intensity-modulated radiation therapy with simultaneous integrated boost combined with concurrent chemotherapy for the treatment of anal cancer patients : 4-year results of a consecutive case series. Cancer Invest. 2015;33:259–266.
   PubMed Web of Science ®Google Scholar
• Tozzi A, Cozzi L, Iftode C, et al. Radiation therapy of anal canal cancer: from conformal therapy to volumetric modulated arc therapy. BMC Cancer. 2014;14:833–842.
   PubMed Web of Science ®Google Scholar
• Tagliaferri L, Manfrida S, Barbaro B, et al. MITHRA - Multiparametric MR/CT image adapted brachytherapy (MR/CT-IABT) in anal canal cancer: a feasibility study. J Contemp Brachytheraphy. 2015;5:336–345.
   Web of Science ®Google Scholar
• Kachnic LA, Tsai HK, Coen JJ, et al. Dose-painted intensity-modulated radiation therapy for anal cancer: a multi-institutional report of acute toxicity and response to therapy. Int J Radiat Oncol Biol Phys. 2012;82:153–158.
   PubMed Web of Science ®Google Scholar
• Devisetty K, Mell LK, Salama JK, et al. A multi-institutional acute gastrointestinal toxicity analysis of anal cancer patients treated with concurrent intensity-modulated radiation therapy (IMRT) and chemotherapy. Radiother Oncol. 2009;93:298–301.
   PubMed Web of Science ®Google Scholar
• Julie DAR, Oh JH, Apte AP, et al. Predictors of acute toxicities during definitive chemoradiation using intensity-modulated radiotherapy for anal squamous cell carcinoma. Acta Oncol (Madr). 2016;55:208–216.
   PubMed Web of Science ®Google Scholar
• Engineer R, Mallik S, Mahantshetty U, et al. Impact of radiation dose on locoregional control and survival on squamous cell carcinoma of anal canal. Radiother Oncol. 2010;95:283–287.
   PubMed Web of Science ®Google Scholar
• Stone HB, Coleman CN, Anscher MS, et al. Effects of radiation on normal tissue: consequences and mechanisms. Lancet Oncol. 2003;4:529–536.
   PubMed Web of Science ®Google Scholar
• Alsadius D, Hedelin M, Lundstedt D, et al. Mean absorbed dose to the anal-sphincter region and fecal leakage among irradiated prostate cancer survivors. Int J Radiat Oncol Biol Phys. 2012;84:e181.
   PubMed Web of Science ®Google Scholar
• Peeters STH, Hoogeman MS, Heemsbergen WD, et al. Rectal bleeding, fecal incontinence, and high stool frequency after conformal radiotherapy for prostate cancer: normal tissue complication probability modeling. Int J Radiat Oncol Biol Phys. 2006;66:11–19.
   PubMed Web of Science ®Google Scholar
• Heemsbergen WD, Hoogeman MS, Hart GA, et al. Gastrointestinal toxicity and its relation to dose distributions in the anorectal region of prostate cancer patients treated with radiotherapy. Int J Radiat Oncol Biol Phys. 2005;61:1011–1018.
   PubMed Web of Science ®Google Scholar
• Buettner F, Gulliford SL, Webb S, et al. The dose-response of the anal sphincter region-an analysis of data from the MRC RT01 trial. Radiother Oncol. 2012;103:347–352.
   PubMed Web of Science ®Google Scholar
• Rubin EB, Buehler AE, Halpern SD. States worse than death among hospitalized patients with serious illnesses. JAMA Intern Med. 2016;176:1557–1559.
   PubMed Web of Science ®Google Scholar
• Sodergren SC, Johnson CD, Gilbert A, et al. Phase I-III development of the EORTC QLQ-ANL27, a health-related quality of life questionnaire for anal cancer. Radiother Oncol. 2018;126:222–228.
   PubMed Web of Science ®Google Scholar