Patterns of recurrence in anal cancer: a detailed analysis
Tóm tắt
Anal cancer is a rare disease, which might be the reason for the “one size fits all” approach still used for radiotherapy target contouring. To refine and individualize future guidelines, detailed and contemporary pattern of recurrence studies are needed. Consecutive anal cancer patients, all treated with curative intent intensity-modulated radiotherapy (IMRT), were retrospectively studied (n = 170). Data was extracted from medical records and radiological images. Radiotherapy planning CT’s and treatment plans were reviewed, and recurrences were mapped and categorized according to radiation dose. The mean dose to the primary tumor was 59.0 Gy. With a median follow-up of 50 months (range 14–117 months), 5-year anal cancer specific survival was 86.1%. Only 1 of 20 local recurrences was located outside the high dose (CTVT) volume. More patients experienced a distant recurrence (n = 34; 20.0%) than a locoregional recurrence (n = 24; 14.1%). Seven patients (4.2%) had a common iliac and/or para-aortic (CI/PA) recurrence. External iliac lymph node involvement (P = 0.04), and metastases in ≥3 inguinal or pelvic lymph node regions (P = 0.02) were associated with a 15–18% risk of CI/PA recurrence. Following chemoradiotherapy, 6 patients with recurrent or primary metastatic CI/PA lymph nodes were free of recurrence at last follow-up. The overall rate of ano-inguinal lymphatic drainage (AILD) recurrence was 2 of 170 (1.2%), and among patients with inguinal metastases at initial diagnosis it was 2 of 65 (3.1%). We conclude that other measures than increased margins around the primary tumor are needed to improve local control. Furthermore, metastatic CI/PA lymph nodes, either at initial diagnosis or in the recurrent setting, should be considered potentially curable. Patients with certain patterns of metastatic pelvic lymph nodes might be at an increased risk of harboring tumor cells also in the CI/PA lymph nodes.
Tài liệu tham khảo
Gunderson LL, Winter KA, Ajani JA, Pedersen JE, Moughan J, Benson AB 3rd, Thomas CR Jr, Mayer RJ, Haddock MG, Rich TA, 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(35):4344–51.
James RD, Glynne-Jones R, Meadows HM, Cunningham D, Myint AS, Saunders MP, Maughan T, McDonald A, Essapen S, Leslie M, 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 x 2 factorial trial. Lancet Oncol. 2013;14(6):516–24.
Martin D, Balermpas P, Winkelmann R, Rodel F, Rodel C, Fokas E. Anal squamous cell carcinoma - state of the art management and future perspectives. Cancer Treat Rev. 2018;65:11–21.
Bentzen AG, Guren MG, Vonen B, Wanderas EH, Frykholm G, Wilsgaard T, Dahl O, Balteskard L. Faecal incontinence after chemoradiotherapy in anal cancer survivors: long-term results of a national cohort. Radiother Oncol. 2013;108(1):55–60.
Joseph K, Vos LJ, Warkentin H, Paulson K, Polkosnik LA, Usmani N, Tankel K, Severin D, Nijjar T, Schiller D, et al. Patient reported quality of life after helical IMRT based concurrent chemoradiation of locally advanced anal cancer. Radiother Oncol. 2016;120(2):228–33.
Sterner A, Derwinger K, Staff C, Nilsson H, Angenete E. Quality of life in patients treated for anal carcinoma-a systematic literature review. Int J Color Dis. 2019;34(9):1517–28.
UK guidelines for IMRT in anal cancer. http://analimrtguidance.co.uk/national-anal-imrt-guidance-v3.pdf. Accessed 6 May 2020.
Myerson RJ, Garofalo MC, El Naqa I, Abrams RA, Apte A, Bosch WR, Das P, Gunderson LL, Hong TS, Kim JJ, et al. Elective clinical target volumes for conformal therapy in anorectal cancer: a radiation therapy oncology group consensus panel contouring atlas. Int J Radiat Oncol Biol Phys. 2009;74(3):824–30.
Ng M, Leong T, Chander S, Chu J, Kneebone A, Carroll S, Wiltshire K, Ngan S, Kachnic L. Australasian gastrointestinal trials group (AGITG) contouring atlas and planning guidelines for intensity-modulated radiotherapy in anal cancer. Int J Radiat Oncol Biol Phys. 2012;83(5):1455–62.
Biau J, Lapeyre M, Troussier I, Budach W, Giralt J, Grau C, Kazmierska J, Langendijk JA, Ozsahin M, O'Sullivan B, et al. Selection of lymph node target volumes for definitive head and neck radiation therapy: a 2019 update. Radiother Oncol. 2019;134:1–9.
Berger T, Seppenwoolde Y, Potter R, Assenholt MS, Lindegaard JC, Nout RA, de Leeuw A, Jurgenliemk-Schulz I, Tan LT, Georg D, et al. Importance of technique, target selection, contouring, dose prescription, and dose-planning in external beam radiation therapy for cervical Cancer: evolution of practice from EMBRACE-I to II. Int J Radiat Oncol Biol Phys. 2019;104(4):885–94.
Bagshaw HP, Sause WT, Gawlick U, Kim HT, Whisenant J, Cannon GM. Vulvar recurrences after intensity-modulated radiation therapy for squamous cell carcinoma of the anus. Am J Clin Oncol. 2018;41(5):492–6.
Dapper H, Habl G, Hirche C, Munch S, Oechsner M, Mayinger M, Sauter C, Combs SE, Habermehl D. Dosimetric quantification of the incidental irradiation of the 'true' (deep) ano-inguinal lymphatic drainage of anal cancer patients not described in conventional contouring guidelines. Acta Oncol. 2018;57(6):825–30.
Dapper H, Oechsner M, Hirche C, Munch S, Sauter C, Borm K, Peeken JC, Combs SE, Habermehl D. Dosimetric comparison of different radiation techniques (IMRT vs. 3-dimensional) of the "true" (deep) ano-inguinal lymphatic drainage of anal cancer patients. Radiat Oncol. 2018;13(1):227.
Dell'Acqua V, Kobiela J, Kraja F, Leonardi MC, Surgo A, Zerella MA, Arculeo S, Fodor C, Ricotti R, Zampino MG, et al. Genital marginal failures after intensity-modulated radiation therapy (IMRT) in squamous cell anal cancer: no higher risk with IMRT when compared to 3DCRT. Med Oncol. 2018;35(5):59.
Koeck J, Lohr F, Buergy D, Busing K, Trunk MJ, Wenz F, Mai S. Genital invasion or perigenital spread may pose a risk of marginal misses for Intensity Modulated Radiotherapy (IMRT) in anal cancer. Radiat Oncol. 2016;11:53.
Dapper H, Schiller K, Munch S, Peeken JC, Borm K, Weber W, Combs SE. Have we achieved adequate recommendations for target volume definitions in anal cancer? A PET imaging based patterns of failure analysis in the context of established contouring guidelines. BMC Cancer. 2019;19(1):742.
Swedish national guidelines for anal cancer. https://kunskapsbanken.cancercentrum.se/globalassets/cancerdiagnoser/tjock%2D%2Doch-andtarm-anal/vardprogram/nationellt-vardprogram-analcancer.pdf. Accessed 6 May 2020.
Leon O, Guren M, Hagberg O, Glimelius B, Dahl O, Havsteen H, Naucler G, Svensson C, Tveit KM, Jakobsen A, et al. Anal carcinoma - survival and recurrence in a large cohort of patients treated according to Nordic guidelines. Radiother Oncol. 2014;113(3):352–8.
Martin D, Rodel C, Fokas E. Chemoradiotherapy for anal cancer: are we as good as we think? Strahlentherapie und. 2019;195(5):369–73.
Holliday EB, Lester SC, Harmsen WS, Eng C, Haddock MG, Krishnan S, Das P, Hallemeier CL. Extended-field Chemoradiation therapy for definitive treatment of Anal Canal squamous cell carcinoma involving the Para-aortic lymph nodes. Int J Radiat Oncol Biol Phys. 2018;102(1):102–8.
Bartelink H, Roelofsen F, Eschwege F, Rougier P, Bosset JF, Gonzalez DG, Peiffert D, van Glabbeke M, Pierart M. 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. 1997;15(5):2040–9.
Bentzen AG, Guren MG, Wanderas EH, Frykholm G, Tveit KM, Wilsgaard T, Dahl O, Balteskard L. Chemoradiotherapy of anal carcinoma: survival and recurrence in an unselected national cohort. Int J Radiat Oncol Biol Phys. 2012;83(2):e173–80.
Das P, Bhatia S, Eng C, Ajani JA, Skibber JM, Rodriguez-Bigas MA, Chang GJ, Bhosale P, Delclos ME, Krishnan S, et al. Predictors and patterns of recurrence after definitive chemoradiation for anal cancer. Int J Radiat Oncol Biol Phys. 2007;68(3):794–800.
Flam M, John M, Pajak TF, Petrelli N, Myerson R, Doggett S, Quivey J, Rotman M, Kerman H, Coia L, et al. 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. 1996;14(9):2527–39.
Northover J, Glynne-Jones R, Sebag-Montefiore D, James R, Meadows H, Wan S, Jitlal M, Ledermann J. 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(7):1123–8.
Peiffert D, Tournier-Rangeard L, Gerard JP, Lemanski C, Francois E, Giovannini M, Cvitkovic F, Mirabel X, Bouche O, Luporsi E, 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(16):1941–8.
Rouard N, Peiffert D, Rio E, Mahe MA, Delpon G, Marchesi V, Falk AT, Salleron J, Serre AA. Intensity-modulated radiation therapy of anal squamous cell carcinoma: relationship between delineation quality and regional recurrence. Radiother Oncol. 2019;131:93–100.
Tomaszewski JM, Link E, Leong T, Heriot A, Vazquez M, Chander S, Chu J, Foo M, Lee MT, Lynch CA, et al. Twenty-five-year experience with radical chemoradiation for anal cancer. Int J Radiat Oncol Biol Phys. 2012;83(2):552–8.
Wright JL, Patil SM, Temple LK, Minsky BD, Saltz LB, Goodman KA. Squamous cell carcinoma of the anal canal: patterns and predictors of failure and implications for intensity-modulated radiation treatment planning. Int J Radiat Oncol Biol Phys. 2010;78(4):1064–72.
Shakir R, Adams R, Cooper R, Downing A, Geh I, Gilbert D, Jacobs C, Jones C, Lorimer C, Namelo WC, et al. Patterns and predictors of relapse following radical Chemoradiation therapy delivered using intensity modulated radiation therapy with a simultaneous integrated boost in anal squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 2020;106(2):329–39.
Jhaveri J, Rayfield L, Liu Y, Chowdhary M, Tian S, Cassidy RJ, Gillespie T, Patel PR, Landry JC, Patel KR. Impact of intensity modulated radiation therapy on survival in anal cancer. J Gastrointest Oncol. 2018;9(4):618–30.
Otter S, Whitaker S, Chatterjee J, Stewart A. The Human Papillomavirus as a Common Pathogen in Oropharyngeal, Anal and Cervical Cancers. Clin Oncol. 2019;31(2):81–90.
Serup-Hansen E, Linnemann D, Skovrider-Ruminski W, Hogdall E, Geertsen PF, Havsteen H. Human papillomavirus genotyping and p16 expression as prognostic factors for patients with American joint committee on Cancer stages I to III carcinoma of the anal canal. J Clin Oncol. 2014;32(17):1812–7.