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Published in: Radiation Oncology 1/2010

Open Access 01-12-2010 | Research

Chemo-radiation with or without mandatory split in anal carcinoma: experiences of two institutions and review of the literature

Authors: Christoph Oehler, Sawyna Provencher, David Donath, Jean-Paul Bahary, Urs M Lütolf, I Frank Ciernik

Published in: Radiation Oncology | Issue 1/2010

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Abstract

Background

The split-course schedule of chemo-radiation for anal cancer is controversial.

Methods

Eighty-four patients with invasive anal cancer treated with definitive external beam radiotherapy (RT) with a mandatory split of 12 days (52 patients, Montreal, Canada) or without an intended split (32 patients, Zurich, Switzerland) were reviewed. Total RT doses were 52 Gy (Montreal) or 59.4 Gy (Zurich) given concurrently with 5-FU/MMC.

Results

After a mean follow-up of 40 ± 27 months, overall survival and local tumor control at 5 years were 57% and 78% (Zurich) compared to 67% and 82% (Montreal), respectively. Split duration of patients with or without local relapse was 15 ± 7 d vs. 14 ± 7 d (Montreal, NS) and 11 ± 11 d vs. 5 ± 7 d (Zurich; P < 0.001). Patients from Zurich with prolonged treatment interruption (≥ 7 d) had impaired cancer-specific survival compared with patients with only minor interruption (<7 d) (P = 0.06). Bowel toxicity was associated with prolonged RT (P = 0.03) duration as well as increased relapse probability (P = 0.05). Skin toxicity correlated with institution and was found in 79% (Montreal) and 28% (Zurich) (P < 0.0001).

Conclusions

The study design did not allow demonstrating a clear difference in efficacy between the treatment regimens with or without short mandatory split. Cause-specific outcome appears to be impaired by unplanned prolonged interruption.
Appendix
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Literature
1.
go back to reference 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: 1914-1921. 10.1001/jama.299.16.1914CrossRefPubMed 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: 1914-1921. 10.1001/jama.299.16.1914CrossRefPubMed
2.
go back to reference Flam M, John M, Pajak TF, 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: 2527-2539.PubMed Flam M, John M, Pajak TF, 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: 2527-2539.PubMed
3.
go back to reference Epidermoidanal cancer: results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. UKCCCR Anal Cancer Trial Working Party. UK Co-ordinating Committee on Cancer Research. Lancet 1996, 348: 1049-1054. 10.1016/S0140-6736(96)03409-5CrossRef Epidermoidanal cancer: results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. UKCCCR Anal Cancer Trial Working Party. UK Co-ordinating Committee on Cancer Research. Lancet 1996, 348: 1049-1054. 10.1016/S0140-6736(96)03409-5CrossRef
4.
go back to reference Bartelink H, Roelofsen F, Eschwege F, et al.: 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: 2040-2049.PubMed Bartelink H, Roelofsen F, Eschwege F, et al.: 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: 2040-2049.PubMed
5.
go back to reference 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. 10.1016/0360-3016(91)90265-6CrossRefPubMed 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. 10.1016/0360-3016(91)90265-6CrossRefPubMed
6.
go back to reference 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.PubMed 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.PubMed
7.
go back to reference Bosset JF, Roelofsen F, Morgan DA, 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 Gastrointestinal Cooperative Groups. Eur J Cancer 2003, 39: 45-51. 10.1016/S0959-8049(02)00377-5CrossRefPubMed Bosset JF, Roelofsen F, Morgan DA, 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 Gastrointestinal Cooperative Groups. Eur J Cancer 2003, 39: 45-51. 10.1016/S0959-8049(02)00377-5CrossRefPubMed
8.
go back to reference Konski A, Garcia M Jr, John M, 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. 10.1016/j.ijrobp.2007.12.027PubMedCentralCrossRefPubMed Konski A, Garcia M Jr, John M, 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. 10.1016/j.ijrobp.2007.12.027PubMedCentralCrossRefPubMed
9.
go back to reference 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. 10.1016/S0360-3016(03)00016-6CrossRefPubMed 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. 10.1016/S0360-3016(03)00016-6CrossRefPubMed
10.
go back to reference Vuong T, Kopek N, Ducruet T, et al.: 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 2007, 67: 1394-1400. 10.1016/j.ijrobp.2006.11.038CrossRefPubMed Vuong T, Kopek N, Ducruet T, et al.: 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 2007, 67: 1394-1400. 10.1016/j.ijrobp.2006.11.038CrossRefPubMed
11.
go back to reference Meyer A, Meier Zu Eissen J, Karstens JH, Bremer M: Chemoradiotherapy in patients with anal cancer: impact of length of unplanned treatment interruption on outcome. Acta Oncol 2006, 45: 728-735. 10.1080/02841860600726729CrossRefPubMed Meyer A, Meier Zu Eissen J, Karstens JH, Bremer M: Chemoradiotherapy in patients with anal cancer: impact of length of unplanned treatment interruption on outcome. Acta Oncol 2006, 45: 728-735. 10.1080/02841860600726729CrossRefPubMed
12.
go back to reference Oehler-Janne C, Seifert B, Lutolf UM, et al.: Clinical outcome after treatment with a brachytherapy boost versus external beam boost for anal carcinoma. Brachytherapy 2007, 6: 218-226. 10.1016/j.brachy.2007.02.152CrossRefPubMed Oehler-Janne C, Seifert B, Lutolf UM, et al.: Clinical outcome after treatment with a brachytherapy boost versus external beam boost for anal carcinoma. Brachytherapy 2007, 6: 218-226. 10.1016/j.brachy.2007.02.152CrossRefPubMed
13.
go back to reference Huang EY, Wang CJ, Chen HC, et al.: Multivariate analysis of pulmonary fibrosis after electron beam irradiation for postmastectomy chest wall and regional lymphatics: evidence for non-dosimetric factors. Radiother Oncol 2000, 57: 91-96. 10.1016/S0167-8140(00)00211-5CrossRefPubMed Huang EY, Wang CJ, Chen HC, et al.: Multivariate analysis of pulmonary fibrosis after electron beam irradiation for postmastectomy chest wall and regional lymphatics: evidence for non-dosimetric factors. Radiother Oncol 2000, 57: 91-96. 10.1016/S0167-8140(00)00211-5CrossRefPubMed
14.
go back to reference Allal AS, Mermillod B, Roth AD, et al.: The impact of treatment factors on local control in T2-T3 anal carcinomas treated by radiotherapy with or without chemotherapy. Cancer 1997, 79: 2329-2335. 10.1002/(SICI)1097-0142(19970615)79:12<2329::AID-CNCR6>3.0.CO;2-GCrossRefPubMed Allal AS, Mermillod B, Roth AD, et al.: The impact of treatment factors on local control in T2-T3 anal carcinomas treated by radiotherapy with or without chemotherapy. Cancer 1997, 79: 2329-2335. 10.1002/(SICI)1097-0142(19970615)79:12<2329::AID-CNCR6>3.0.CO;2-GCrossRefPubMed
15.
go back to reference Weber DC, Kurtz JM, Allal AS: The impact of gap duration on local control in anal canal carcinoma treated by split-course radiotherapy and concomitant chemotherapy. Int J Radiat Oncol Biol Phys 2001, 50: 675-680. 10.1016/S0360-3016(01)01510-3CrossRefPubMed Weber DC, Kurtz JM, Allal AS: The impact of gap duration on local control in anal canal carcinoma treated by split-course radiotherapy and concomitant chemotherapy. Int J Radiat Oncol Biol Phys 2001, 50: 675-680. 10.1016/S0360-3016(01)01510-3CrossRefPubMed
16.
go back to reference Graf R, Wust P, Hildebrandt B, et al.: Impact of overall treatment time on local control of anal cancer treated with radiochemotherapy. Oncology 2003, 65: 14-22. 10.1159/000071200CrossRefPubMed Graf R, Wust P, Hildebrandt B, et al.: Impact of overall treatment time on local control of anal cancer treated with radiochemotherapy. Oncology 2003, 65: 14-22. 10.1159/000071200CrossRefPubMed
17.
go back to reference Constantinou EC, Daly W, Fung CY, et al.: Time-dose considerations in the treatment of anal cancer. Int J Radiat Oncol Biol Phys 1997, 39: 651-657. 10.1016/S0360-3016(97)00329-5CrossRefPubMed Constantinou EC, Daly W, Fung CY, et al.: Time-dose considerations in the treatment of anal cancer. Int J Radiat Oncol Biol Phys 1997, 39: 651-657. 10.1016/S0360-3016(97)00329-5CrossRefPubMed
18.
go back to reference 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. 10.1016/j.radonc.2008.05.001CrossRefPubMed 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. 10.1016/j.radonc.2008.05.001CrossRefPubMed
19.
go back to reference Ferrigno R, Nakamura RA, Dos Santos Novaes PE, 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. 10.1016/j.ijrobp.2004.07.687CrossRefPubMed Ferrigno R, Nakamura RA, Dos Santos Novaes PE, 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. 10.1016/j.ijrobp.2004.07.687CrossRefPubMed
20.
go back to reference 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. 10.1007/BF00341219CrossRefPubMed 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. 10.1007/BF00341219CrossRefPubMed
21.
go back to reference Conroy T, Ducreux M, Lemanski C, et al.: Treatment intensification by induction chemotherapy (ICT) and radiation dose escalation in locally advanced squamous cell anal canal carcinoma (LAAC): Definitive analysis of the intergroup ACCORD 03 trial. J Clin Oncol 2009, 27. abstr 4033 Conroy T, Ducreux M, Lemanski C, et al.: Treatment intensification by induction chemotherapy (ICT) and radiation dose escalation in locally advanced squamous cell anal canal carcinoma (LAAC): Definitive analysis of the intergroup ACCORD 03 trial. J Clin Oncol 2009, 27. abstr 4033
22.
go back to reference Vuong T, Faria S, Ducruet T, et al.: Changes in treatment toxicity pattern using the combined treatment of patients with anal canal cancer and early local recurrence results associated with the introduction of new radiation technologies: 3D conformal therapy and intensity modulated radiation therapy. ASCO Meeting, Edition; 2008. Vuong T, Faria S, Ducruet T, et al.: Changes in treatment toxicity pattern using the combined treatment of patients with anal canal cancer and early local recurrence results associated with the introduction of new radiation technologies: 3D conformal therapy and intensity modulated radiation therapy. ASCO Meeting, Edition; 2008.
23.
go back to reference 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. 10.1097/00000658-199202000-00010PubMedCentralCrossRefPubMed 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. 10.1097/00000658-199202000-00010PubMedCentralCrossRefPubMed
24.
go back to reference 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. 10.1159/000121362CrossRefPubMed 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. 10.1159/000121362CrossRefPubMed
25.
go back to reference Das P, Bhatia S, Eng C, et al.: Predictors and patterns of recurrence after definitive chemoradiation for anal cancer. Int J Radiat Oncol Biol Phys 2007, 68: 794-800. 10.1016/j.ijrobp.2006.12.052CrossRefPubMed Das P, Bhatia S, Eng C, et al.: Predictors and patterns of recurrence after definitive chemoradiation for anal cancer. Int J Radiat Oncol Biol Phys 2007, 68: 794-800. 10.1016/j.ijrobp.2006.12.052CrossRefPubMed
26.
go back to reference Tanum G, Tveit K, Karlsen KO, Hauer-Jensen M: Chemotherapy and radiation therapy for anal carcinoma. Survival and late morbidity. Cancer 1991, 67: 2462-2466. 10.1002/1097-0142(19910515)67:10<2462::AID-CNCR2820671012>3.0.CO;2-1CrossRefPubMed Tanum G, Tveit K, Karlsen KO, Hauer-Jensen M: Chemotherapy and radiation therapy for anal carcinoma. Survival and late morbidity. Cancer 1991, 67: 2462-2466. 10.1002/1097-0142(19910515)67:10<2462::AID-CNCR2820671012>3.0.CO;2-1CrossRefPubMed
27.
go back to reference Gerard JP, Chapet O, Samiei F, et al.: Management of inguinal lymph node metastases in patients with carcinoma of the anal canal: experience in a series of 270 patients treated in Lyon and review of the literature. Cancer 2001, 92: 77-84. 10.1002/1097-0142(20010701)92:1<77::AID-CNCR1294>3.0.CO;2-PCrossRefPubMed Gerard JP, Chapet O, Samiei F, et al.: Management of inguinal lymph node metastases in patients with carcinoma of the anal canal: experience in a series of 270 patients treated in Lyon and review of the literature. Cancer 2001, 92: 77-84. 10.1002/1097-0142(20010701)92:1<77::AID-CNCR1294>3.0.CO;2-PCrossRefPubMed
28.
go back to reference Nguyen BT, Joon DL, Khoo V, et al.: Assessing the impact of FDG-PET in the management of anal cancer. Radiother Oncol 2008, 87: 376-382. 10.1016/j.radonc.2008.04.003CrossRefPubMed Nguyen BT, Joon DL, Khoo V, et al.: Assessing the impact of FDG-PET in the management of anal cancer. Radiother Oncol 2008, 87: 376-382. 10.1016/j.radonc.2008.04.003CrossRefPubMed
29.
go back to reference Gretschel S, Warnick P, Bembenek A, et al.: Lymphatic mapping and sentinel lymph node biopsy in epidermoid carcinoma of the anal canal. Eur J Surg Oncol 2008, 34: 890-894.CrossRefPubMed Gretschel S, Warnick P, Bembenek A, et al.: Lymphatic mapping and sentinel lymph node biopsy in epidermoid carcinoma of the anal canal. Eur J Surg Oncol 2008, 34: 890-894.CrossRefPubMed
30.
go back to reference Sischy B, Doggett RL, Krall JM, et al.: Definitive irradiation and chemotherapy for radiosensitization in management of anal carcinoma: interim report on Radiation Therapy Oncology Group study no. 8314. J Natl Cancer Inst 1989, 81: 850-856. 10.1093/jnci/81.11.850CrossRefPubMed Sischy B, Doggett RL, Krall JM, et al.: Definitive irradiation and chemotherapy for radiosensitization in management of anal carcinoma: interim report on Radiation Therapy Oncology Group study no. 8314. J Natl Cancer Inst 1989, 81: 850-856. 10.1093/jnci/81.11.850CrossRefPubMed
31.
go back to reference Ceresoli GL, Ferreri AJ, Cordio S, Villa E: Role of dose intensity in conservative treatment of anal canal carcinoma. Report of 35 cases. Oncology 1998, 55: 525-532. 10.1159/000011907CrossRefPubMed Ceresoli GL, Ferreri AJ, Cordio S, Villa E: Role of dose intensity in conservative treatment of anal canal carcinoma. Report of 35 cases. Oncology 1998, 55: 525-532. 10.1159/000011907CrossRefPubMed
32.
go back to reference Grabenbauer GG, Kessler H, Matzel KE, et al.: Tumor site predicts outcome after radiochemotherapy in squamous-cell carcinoma of the anal region: long-term results of 101 patients. Dis Colon Rectum 2005, 48: 1742-1751. 10.1007/s10350-005-0098-5CrossRefPubMed Grabenbauer GG, Kessler H, Matzel KE, et al.: Tumor site predicts outcome after radiochemotherapy in squamous-cell carcinoma of the anal region: long-term results of 101 patients. Dis Colon Rectum 2005, 48: 1742-1751. 10.1007/s10350-005-0098-5CrossRefPubMed
33.
go back to reference 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. 10.1200/JCO.2007.12.0170CrossRefPubMed 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. 10.1200/JCO.2007.12.0170CrossRefPubMed
34.
go back to reference 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. 10.1016/j.ijrobp.2005.02.030CrossRefPubMed 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. 10.1016/j.ijrobp.2005.02.030CrossRefPubMed
Metadata
Title
Chemo-radiation with or without mandatory split in anal carcinoma: experiences of two institutions and review of the literature
Authors
Christoph Oehler
Sawyna Provencher
David Donath
Jean-Paul Bahary
Urs M Lütolf
I Frank Ciernik
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2010
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/1748-717X-5-36

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