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Strahlentherapie und Onkologie

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01.04.2019 | Review Article

Chemoradiotherapy for anal cancer: are we as good as we think?

verfasst von: D. Martin, M.D., C. Rödel, E. Fokas

Erschienen in: Strahlentherapie und Onkologie | Ausgabe 5/2019

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Abstract

Definitive chemoradiotherapy (CRT) is the standard treatment for anal squamous cell carcinoma (ASCC). Data regarding treatment outcome according to TNM classification is scarce. Here, we review data of randomized trials and retrospective cohorts suggesting a poor 3‑year disease-free survival (DFS; or progression-free survival, PFS) of approximately 60%, or even lower, in patients with locally advanced T3–4 and/or N+ disease, while patients with T1–2N0 ASCC have 3‑year DFS/PFS rates exceeding 80%. These results are in line with our data in a cohort of 210 patients with ASCC treated with definitive 5‑fluorouracil/mitomycin C‑based CRT to a total dose of 50.4 Gy plus a boost of 3.6–10.8 Gy. The implications of these findings and the current trials testing radiotherapy dose escalation/de-escalation strategies are reported. Finally, we will discuss the strong rationale for testing immune checkpoint blockade (ICB) with CRT in clinical trials to improve results, especially in patients with advanced ASCC.

Shiels MS, Kreimer AR, Coghill AE et al (2015) Anal cancer incidence in the United States, 1977–2011: distinct patterns by histology and behavior. Cancer Epidemiol Biomarkers Prev 24:1548–1556. https://doi.org/10.1158/1055-9965.EPI-15-0044 CrossRefPubMedPubMedCentral

Nigro ND, Seydel HG, Considine B et al (1983) Combined preoperative radiation and chemotherapy for squamous cell carcinoma of the anal canal. Cancer 51:1826–1829CrossRefPubMed

Martin D, Balermpas P, Winkelmann R et al (2018) Anal squamous cell carcinoma—State of the art management and future perspectives. Cancer Treat Rev 65:11–21. https://doi.org/10.1016/j.ctrv.2018.02.001 CrossRefPubMed

James RD, Glynne-Jones R, Meadows HM et al (2013) 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 14:516–524. https://doi.org/10.1016/S1470-2045(13)70086-X CrossRefPubMed

Peiffert D, Tournier-Rangeard L, Gérard J‑P 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 30:1941–1948. https://doi.org/10.1200/JCO.2011.35.4837 CrossRefPubMed

Gunderson LL, Winter KA, Ajani JA 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 30:4344–4351. https://doi.org/10.1200/JCO.2012.43.8085 CrossRefPubMedPubMedCentral

Oblak I, Petric P, Anderluh F et al (2012) Long term outcome after combined modality treatment for anal cancer. Radiol Oncol. https://doi.org/10.2478/v10019-012-0022-2 CrossRefPubMedPubMedCentral

Tomaszewski JM, Link E, Leong T et al (2012) Twenty-five-year experience with radical chemoradiation for anal cancer. Int J Radiat Oncol Biol Phys 83:552–558. https://doi.org/10.1016/j.ijrobp.2011.07.007 CrossRefPubMed

Leon O, Guren M, Hagberg O et al (2014) Anal carcinoma—Survival and recurrence in a large cohort of patients treated according to Nordic guidelines. Radiother Oncol 113:352–358. https://doi.org/10.1016/j.radonc.2014.10.002 CrossRefPubMed

10.

Nilsson PJ, Svensson C, Goldman S, Glimelius B (2002) Salvage abdominoperineal resection in anal epidermoid cancer. Br J Surg 89:1425–1429. https://doi.org/10.1046/j.1365-2168.2002.02231.x CrossRefPubMed

11.

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

12.

Northover J, Glynne-Jones R, Sebag-Montefiore D et al (2010) 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 102:1123–1128. https://doi.org/10.1038/sj.bjc.6605605 CrossRefPubMedPubMedCentral

13.

Glynne-Jones R, Sebag-Montefiore D, Adams R et al (2013) Prognostic factors for recurrence and survival in anal cancer: generating hypotheses from the mature outcomes of the first United Kingdom Coordinating Committee on Cancer Research Anal Cancer Trial (ACT I). Cancer 119:748–755. https://doi.org/10.1002/cncr.27825 CrossRefPubMed

14.

Ajani JA, Winter KA, Gunderson LL et al (2008) Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial. JAMA 299:1914–1921. https://doi.org/10.1001/jama.299.16.1914 CrossRefPubMed

15.

Ajani JA, Winter KA, Gunderson LL et al (2010) Prognostic factors derived from a prospective database dictate clinical biology of anal cancer: the intergroup trial (RTOG 98-11). Cancer 116:4007–4013. https://doi.org/10.1002/cncr.25188 CrossRefPubMed

16.

Martin D, Balermpas P, Fokas E et al (2017) Are there HIV-specific differences for anal cancer patients treated with standard chemoradiotherapy in the era of combined antiretroviral therapy? Clin Oncol 29:248–255. https://doi.org/10.1016/j.clon.2016.12.010 CrossRef

17.

Gryc T, Ott O, Putz F et al (2016) Interstitial brachytherapy as a boost to patients with anal carcinoma and poor response to chemoradiation: single-institution long-term results. Brachytherapy 15:865–872. https://doi.org/10.1016/j.brachy.2016.08.003 CrossRefPubMed

18.

Pan YB, Maeda Y, Wilson A et al (2018) Late gastrointestinal toxicity after radiotherapy for anal cancer: a systematic literature review. Acta Oncol. https://doi.org/10.1080/0284186X.2018.1503713 CrossRefPubMed

19.

Martin V, Zanellato E, Franzetti-Pellanda A et al (2014) EGFR, KRAS, BRAF, and PIK3CA characterization in squamous cell anal cancer. Histol Histopathol 29:513–521. https://doi.org/10.14670/HH-29.10.513 CrossRefPubMed

20.

Serup-Hansen E, Linnemann D, Høgdall E et al (2015) KRAS and BRAF mutations in anal carcinoma. APMIS 123:53–59. https://doi.org/10.1111/apm.12306 CrossRefPubMed

21.

Casadei Gardini A, Capelli L, Ulivi P et al (2014) KRAS, BRAF and PIK3CA status in squamous cell anal carcinoma (SCAC). PLoS ONE 9:e92071. https://doi.org/10.1371/journal.pone.0092071 CrossRefPubMedPubMedCentral

22.

Garg MK, Zhao F, Sparano JA 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 35:718–726. https://doi.org/10.1200/JCO.2016.69.1667 CrossRefPubMedPubMedCentral

23.

Sparano JA, Lee JY, Palefsky J et al (2016) Cetuximab plus chemoradiotherapy for HIV-associated anal carcinoma: a phase II AIDS malignancy consortium trial. J Clin Oncol 35:727–733. https://doi.org/10.1200/JCO.2016.69.1642 CrossRefPubMedPubMedCentral

24.

Ott OJ, Schmidt M, Semrau S et al (2018) 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

25.

Ouhoummane N, Steben M, Coutlée F et al (2013) Squamous anal cancer: patient characteristics and HPV type distribution. Cancer Epidemiol 37:807–812. https://doi.org/10.1016/j.canep.2013.09.015 CrossRefPubMed

26.

Balermpas P, Martin D, Wieland U et al (2017) Human papilloma virus load and PD-1/PD-L1, CD8+ and FOXP3 in anal cancer patients treated with chemoradiotherapy: rationale for immunotherapy. Oncoimmunology 6:e1288331. https://doi.org/10.1080/2162402X.2017.1288331 CrossRefPubMedPubMedCentral

27.

Govindarajan R, Gujja S, Siegel ER et al (2016) Programmed cell death-ligand 1 (PD-L1) expression in anal cancer. Am J Clin Oncol. https://doi.org/10.1097/COC.0000000000000343 CrossRef

28.

Zhao Y‑J, Sun W‑P, Peng J‑H et al (2018) Programmed death-ligand 1 expression correlates with diminished CD8+ T cell infiltration and predicts poor prognosis in anal squamous cell carcinoma patients. Cancer Manag Res 10:1–11. https://doi.org/10.2147/CMAR.S153965 CrossRefPubMed

29.

Ott PA, Piha-Paul SA, Munster P et al (2017) Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal. Ann Oncol 28:1036–1041. https://doi.org/10.1093/annonc/mdx029 CrossRefPubMedPubMedCentral

30.

Morris VK, Salem ME, Nimeiri H et al (2017) Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study. Lancet Oncol 18:446–453. https://doi.org/10.1016/S1470-2045(17)30104-3 CrossRefPubMedPubMedCentral

31.

Topalian SL, Drake CG, Pardoll DM (2015) Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell 27:450–461. https://doi.org/10.1016/j.ccell.2015.03.001 CrossRefPubMedPubMedCentral

32.

Antonia SJ, Villegas A, Daniel D et al (2017) Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med 377:1919–1929. https://doi.org/10.1056/NEJMoa1709937 CrossRefPubMed

33.

Antonia SJ, Villegas A, Daniel D et al (2018) Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med. https://doi.org/10.1056/NEJMoa1809697 CrossRefPubMed

Titel: Chemoradiotherapy for anal cancer: are we as good as we think?
verfasst von: D. Martin, M.D.
C. Rödel
E. Fokas
Publikationsdatum: 01.04.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Strahlentherapie und Onkologie / Ausgabe 5/2019
Print ISSN: 0179-7158
Elektronische ISSN: 1439-099X
DOI: https://doi.org/10.1007/s00066-019-01444-7

Springer Medizin

Chemoradiotherapy for anal cancer: are we as good as we think?

Abstract

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

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