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24.01.2020 | Original Article

Improved treatment outcome and lower skin toxicity with intensity-modulated radiotherapy vs. 3D conventional radiotherapy in anal cancer

verfasst von: Dr. med. Matthias Sauter, Norbert Lombriser, Simon Bütikofer, Georg Keilholz, Helmut Kranzbühler, Henriette Heinrich, Gerhard Rogler, Stephan R. Vavricka, Benjamin Misselwitz

Erschienen in: Strahlentherapie und Onkologie | Ausgabe 4/2020

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Abstract

Purpose

Radiochemotherapy is the standard treatment for anal carcinoma (ACa). Intensity-modulated radiotherapy (IMRT) has been introduced, allowing focused irradiation of the tumor area. Whether physical benefits of IMRT translate to clinical benefits has not been sufficiently demonstrated.

Methods

We retrospectively reviewed data from 82 patients with newly diagnosed ACa. Patients treated with IMRT were compared with previous patients treated with conventional three-dimensional computational radiotherapy (3D-CRT). The influence of IMRT on complete remission and acute and chronic side effects was analyzed in univariate and multivariate analyses.

Results

39/40 patients treated with IMRT were in complete remission after 1 year compared to 31/39 patients treated with 3D-CRT (p = 0.014). Multivariate analysis confirmed tumor T stage as well as lack of IMRT treatment as risk factors for persistent tumor at 6 months. No significant benefits of IMRT were apparent at later timepoints (median follow up 52 months, IQR: 31.5–71.8 months). Patients treated with IMRT had a significantly lower degree of skin toxicity (median 2 vs. 3 in a scale ranging from 0 to 3, p = 0.00092). Rates of hematological toxicity/proctitis were not reduced and rates of acute diarrhea increased (p = 0.034). Median length of hospitalization tended to be shorter in patients treated with IMRT (n. s.).

Conclusion

We present a real-world experience of shifting radiation technique from conventional 3D-CRT to IMRT. IMRT patients had better tumor control at 1 year and lower degrees of skin toxicity. Our data indicate that IMRT can enable therapies with lower side effects with equal or better oncological results for patients with ACa.

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Johnson LG, Madeleine MM, Newcomer LM, Schwartz SM, Daling JR (2004) Anal cancer incidence and survival: the surveillance, epidemiology, and end results experience, 1973–2000. Cancer 101(2):281–288CrossRefPubMed

Glynne-Jones R, Nilsson PJ, Aschele C, Goh V, Peiffert D, Cervantes A, Arnold D (2014) Anal cancer: ESMO-ESSO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 25(Suppl 3):iii10–iii20CrossRefPubMed

Nigro ND, Vaitkevicius VK, Considine B Jr. (1974) Combined therapy for cancer of the anal canal: a preliminary report. Dis Colon Rectum 17(3):354–356CrossRefPubMed

Bartelink H, Roelofsen F, Eschwege F, Rougier P, Bosset JF, Gonzalez DG, Peiffert D, van Glabbeke M, Pierart M (1997) Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: results of a phase III randomized trial of the European Organization for Research and Treatment of Cancer Radiotherapy and Gastrointestinal Cooperative Groups. J Clin Oncol 15(5):2040–2049CrossRefPubMed

UKCCCR Anal Cancer Trial Working Party, UK Co-ordinating Committee on Cancer Research (1996) Epidermoid anal cancer: results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5‑fluorouracil, and mitomycin. Lancet 348(9034):1049–1054CrossRef

Leichman L, Nigro N, Vaitkevicius VK, Considine B, Buroker T, Bradley G, Seydel HG, Olchowski S, Cummings G, Leichman C (1985) Cancer of the anal canal. Model for preoperative adjuvant combined modality therapy. Am J Med 78(2):211–215CrossRefPubMed

Flam M, John M, Pajak TF, Petrelli N, Myerson R, Doggett S, Quivey J, Rotman M, Kerman H, Coia L et al (1996) Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. J Clin Oncol 14(9):2527–2539CrossRefPubMed

Gunderson LL, Winter KA, Ajani JA, Pedersen JE, Moughan J, Benson AB, Thomas CR, Mayer RJ, Haddock MG, Rich TA et al (2012) 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 30(35):4344–4351CrossRefPubMedPubMedCentral

Mayer RJ, Venook AP, Schilsky RL (2014) Progress against GI cancer during the American Society of Clinical Oncology’s first 50 years. J Clin Oncol 32(15):1521–1530CrossRefPubMed

10.

Vuong T, Kopek N, Ducruet T, Portelance L, Faria S, Bahoric B, Devic S (2007) Conformal therapy improves the therapeutic index of patients with anal canal cancer treated with combined chemotherapy and external beam radiotherapy. Int J Radiat Oncol Biol Phys 67(5):1394–1400CrossRefPubMed

11.

Morris DE, Emami B, Mauch PM, Konski AA, Tao ML, Ng AK, Klein EA, Mohideen N, Hurwitz MD, Fraas BA et al (2005) Evidence-based review of three-dimensional conformal radiotherapy for localized prostate cancer: an ASTRO outcomes initiative. Int J Radiat Oncol Biol Phys 62(1):3–19CrossRefPubMed

12.

Eisbruch A, Ship JA, Dawson LA, Kim HM, Bradford CR, Terrell JE, Chepeha DB, Teknos TN, Hogikyan ND, Anzai Y et al (2003) Salivary gland sparing and improved target irradiation by conformal and intensity modulated irradiation of head and neck cancer. World J Surg 27(7):832–837CrossRefPubMed

13.

Zelefsky MJ, Fuks Z, Leibel SA (2002) Intensity-modulated radiation therapy for prostate cancer. Semin Radiat Oncol 12(3):229–237CrossRefPubMed

14.

Mell LK, Roeske JC, Mundt AJ (2003) A survey of intensity-modulated radiation therapy use in the United States. Cancer 98(1):204–211CrossRefPubMed

15.

Milano MT, Jani AB, Farrey KJ, Rash C, Heimann R, Chmura SJ (2005) Intensity-modulated radiation therapy (IMRT) in the treatment of anal cancer: toxicity and clinical outcome. Int J Radiat Oncol Biol Phys 63(2):354–361CrossRefPubMed

16.

Kachnic LA, Tsai HK, Coen JJ, Blaszkowsky LS, Hartshorn K, Kwak EL, Willins JD, Ryan DP, Hong TS (2012) 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 82(1):153–158CrossRefPubMed

17.

Kachnic LA, Winter K, Myerson RJ, Goodyear MD, Willins J, Esthappan J, Haddock MG, Rotman M, Parikh PJ, Safran H et al (2013) RTOG 0529: a phase 2 evaluation of dose-painted intensity modulated radiation therapy in combination with 5‑fluorouracil and mitomycin‑C for the reduction of acute morbidity in carcinoma of the anal canal. Int J Radiat Oncol Biol Phys 86(1):27–33CrossRefPubMed

18.

Vinayan A, Glynne-Jones R (2016) Anal cancer—what is the optimum chemoradiotherapy? Best Pract Res Clin Gastroenterol 30(4):641–653CrossRefPubMed

19.

Sauter M, Vavricka SR, Keilholz G, Heinrich H, Winder T, Kranzbuhler H, Lombriser N, Misselwitz B (2017) Surveillance of anal carcinoma after radiochemotherapy : a retrospective analysis of 80 patients. Strahlenther Onkol 193(8):639–647CrossRefPubMed

20.

Sauter M, Keilholz G, Kranzbuhler H, Lombriser N, Prakash M, Vavricka SR, Misselwitz B (2016) Presenting symptoms predict local staging of anal cancer: a retrospective analysis of 86 patients. BMC Gastroenterol 16:46CrossRefPubMedPubMedCentral

21.

Edge SBBD, Compton CC (eds) (2010) AJCC cancer staging handbook, 7th edn. Springer, New York

22.

Common Terminology Criteria for Adverse Events v4.0 (CTCAE). https://www.eortc.be/services/doc/ctc/ctcae_4.03_2010-06-14_quickreference_5x7.pdf. Accessed: 29 January 2018

23.

Bazan JG, Hara W, Hsu A, Kunz PA, Ford J, Fisher GA, Welton ML, Shelton A, Kapp DS, Koong AC et al (2011) Intensity-modulated radiation therapy versus conventional radiation therapy for squamous cell carcinoma of the anal canal. Cancer 117(15):3342–3351CrossRefPubMed

24.

Chuong MD, Freilich JM, Hoffe SE, Fulp W, Weber JM, Almhanna K, Dinwoodie W, Rao N, Meredith KL, Shridhar R (2013) Intensity-modulated radiation therapy vs. 3D conformal radiation therapy for squamous cell carcinoma of the anal canal. Gastrointest Cancer Res 6(2):39–45PubMedPubMedCentral

25.

Dasgupta T, Rothenstein D, Chou JF, Zhang Z, Wright JL, Saltz LB, Temple LK, Paty PB, Weiser MR, Guillem JG et al (2013) Intensity-modulated radiotherapy vs. conventional radiotherapy in the treatment of anal squamous cell carcinoma: a propensity score analysis. Radiother Oncol 107(2):189–194CrossRefPubMed

26.

Dewas CV, Maingon P, Dalban C, Petitfils A, Peignaux K, Truc G, Martin E, Khoury C, Dewas S, Crehange G (2012) Does gap-free intensity modulated chemoradiation therapy provide a greater clinical benefit than 3D conformal chemoradiation in patients with anal cancer? Radiat Oncol 7:201CrossRefPubMedPubMedCentral

27.

Fredman ET, Abdel-Wahab M, Kumar AMS (2017) Influence of radiation treatment technique on outcome and toxicity in anal cancer. J Radiat Oncol 6(4):413–421CrossRefPubMedPubMedCentral

28.

Koerber SA, Slynko A, Haefner MF, Krug D, Schoneweg C, Kessel K, Kopp-Schneider A, Herfarth K, Debus J, Sterzing F (2014) Efficacy and toxicity of chemoradiation in patients with anal cancer—a retrospective analysis. Radiat Oncol 9:113CrossRefPubMedPubMedCentral

29.

Muirhead R, Drinkwater K, O’Cathail SM, Adams R, Glynne-Jones R, Harrison M, Hawkins MA, Sebag-Montefiore D, Gilbert DC (2017) Initial results from the Royal College of Radiologists’ UK national audit of anal cancer radiotherapy 2015. Clin Oncol (R Coll Radiol) 29(3):188–197CrossRef

30.

Pollom EL, Wang G, Harris JP, Koong AC, Bendavid E, Bhattacharya J, Chang DT (2017) The impact of intensity modulated radiation therapy on hospitalization outcomes in the SEER-medicare population with anal squamous cell carcinoma. Int J Radiat Oncol Biol Phys 98(1):177–185CrossRefPubMedPubMedCentral

31.

Kemmerer EMA, Ranganna S, Price R, Komarnicky L, Poli J (2016) (P044) Comparison of toxicity-related breaks in treatment utilizing intensity-modulated radiation therapy (IMRT) vs three-dimensional (3D) Conformal techniques in the treatment of anal cancer. Oncology 30(Suppl 1). https://www.cancernetwork.com/ars-2016/p044-comparison-toxicity-related-breaks-treatment-utilizing-intensity-modulated-radiation-therapy

32.

Cendales R, Vasquez J, Arbelaez J, Bobadilla I, Torres F, Gaitan A (2014) IMRT, RapidArc(R) and conformal radiotherapy in the treatment of tumours of the anal canal. Ecancermedicalscience 8:469PubMedPubMedCentral

33.

Chang Y, Yang ZY, Li GL, Li Q, Yang Q, Fan JQ, Zhao YC, Song YQ, Wu G (2016) Correlations between radiation dose in Bone marrow and hematological toxicity in patients with cervical cancer: a comparison of 3DCRT, IMRT, and rapidARC. Int J Gynecol Cancer 26(4):770–776CrossRefPubMed

34.

Kumar T, Schernberg A, Busato F, Laurans M, Fumagalli I, Dumas I, Deutsch E, Haie-Meder C, Chargari C (2019) Correlation between pelvic bone marrow radiation dose and acute hematological toxicity in cervical cancer patients treated with concurrent chemoradiation. Cancer Manag Res 11:6285–6297CrossRefPubMedPubMedCentral

35.

Elson JK, Kachnic LA, Kharofa JR (2018) Intensity-modulated radiotherapy improves survival and reduces treatment time in squamous cell carcinoma of the anus: a national cancer data base study. Cancer 124(22):4383–4392CrossRefPubMed

36.

Peiffert D, Tournier-Rangeard L, Gerard JP, Lemanski C, Francois E, Giovannini M, Cvitkovic F, Mirabel X, Bouche O, Luporsi E et al (2012) 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 30(16):1941–1948CrossRefPubMed

37.

Ferris RL, Blumenschein G Jr., Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C et al (2016) Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 375(19):1856–1867CrossRefPubMedPubMedCentral

38.

Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, Wolchok JD, Hersey P, Joseph RW, Weber JS et al (2013) Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med 369(2):134–144CrossRefPubMedPubMedCentral

39.

Morris VK, Salem ME, Nimeiri H, Iqbal S, Singh P, Ciombor K, Polite B, Deming D, Chan E, Wade JL et al (2017) Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study. Lancet Oncol 18(4):446–453CrossRefPubMedPubMedCentral

40.

Martin D, Rodel C, Fokas E (2018) Nivolumab for pretreated metastatic anal cancer : immune checkpoint blockade is also advised in combination with radiochemotherapy. Strahlenther Onkol 194(4):356–357CrossRefPubMed

41.

Martin D, Rodel C, Fokas E (2019) Chemoradiotherapy for anal cancer: are we as good as we think? Strahlenther Onkol 195(5):369–373CrossRefPubMed

42.

Leon O, Guren MG, Radu C, Gunnlaugsson A, Johnsson A (2015) Phase I study of cetuximab in combination with 5‑fluorouracil, mitomycin C and radiotherapy in patients with locally advanced anal cancer. Eur J Cancer 51(18):2740–2746CrossRefPubMed

43.

Garg MK, Zhao F, Sparano JA, Palefsky J, Whittington R, Mitchell EP, Mulcahy MF, Armstrong KI, Nabbout NH, Kalnicki S et al (2017) Cetuximab plus Chemoradiotherapy in immunocompetent patients with anal carcinoma: a Phase II Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group Trial (E3205). J Clin Oncol 35(7):718–726CrossRefPubMedPubMedCentral

44.

Kouloulias V, Plataniotis G, Kouvaris J, Dardoufas C, Gennatas C, Uzunoglu N, Papavasiliou C, Vlahos L (2005) Chemoradiotherapy combined with intracavitary hyperthermia for anal cancer: feasibility and long-term results from a phase II randomized trial. Am J Clin Oncol 28(1):91–99CrossRefPubMed

45.

Ott OJ, Schmidt M, Semrau S, Strnad V, Matzel KE, Schneider I, Raptis D, Uter W, Grutzmann R, Fietkau R (2019) Chemoradiotherapy with and without deep regional hyperthermia for squamous cell carcinoma of the anus. Strahlenther Onkol. https://doi.org/10.1007/s00066-018-1396-x CrossRefPubMed

46.

Ajani JA, Winter KA, Gunderson LL, Pedersen J, Benson AB 3rd, Thomas CR Jr., Mayer RJ, Haddock MG, Rich TA, Willett C (2008) Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial. JAMA 299(16):1914–1921CrossRefPubMed

Titel: Improved treatment outcome and lower skin toxicity with intensity-modulated radiotherapy vs. 3D conventional radiotherapy in anal cancer
verfasst von: Dr. med. Matthias Sauter
Norbert Lombriser
Simon Bütikofer
Georg Keilholz
Helmut Kranzbühler
Henriette Heinrich
Gerhard Rogler
Stephan R. Vavricka
Benjamin Misselwitz
Publikationsdatum: 24.01.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Strahlentherapie und Onkologie / Ausgabe 4/2020
Print ISSN: 0179-7158
Elektronische ISSN: 1439-099X
DOI: https://doi.org/10.1007/s00066-019-01534-6

Springer Medizin

Improved treatment outcome and lower skin toxicity with intensity-modulated radiotherapy vs. 3D conventional radiotherapy in anal cancer