Préoperative hyperfractionated accelerated radiotherapy (HART) in locally advanced rectal cancer (LARC) immediately followed by surgery. A prospective trial.
[en] Abstract
Background and purpose: We aim to report on local control in a phase II trial on preoperative hyperfractionated and
accelerated radiotherapy schedule (HART) in locally advanced resectable rectal cancer (LARC). This fractionation
schedule was designed to keep the overall treatment time (OTT) as short as possible.
Patients and methods: This is a prospective trial on patients with UICC stages II and III rectal cancer. The patients were
submitted to a total dose of 41.6 Gy, delivered in 2.5 weeks at 1.6 Gy per fraction twice a day with a 6-h interfraction
interval. Surgery was performed within 1 week after the end of irradiation. Adjuvant chemotherapy was delivered in a
subset of patients.
Results: Two hundred and seventy nine patients were entered and 250 are fully assessable, with a median follow-up of
39 months. The 5-years actuarial local control (LC) rate is 91.7%. The overall survival (OS) is 59.6%. The freedom from
disease relapse (FDR) is 71.5%. Downstaging was observed in 38% of the tumors.
Conclusion: The actuarial LC at 5 years is 91.7%, although we are dealing with stages II–III LARC, mainly located in the
lower rectum (median distanceZ5 cm). The pattern of failure is dominated by distant metastases and treatment intensification will obviously require a systemic approach.
q 2006 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 79 (2006) 52–58.
Disciplines :
Oncology Hematology
Author, co-author :
Coucke, Philippe ; Centre Hospitalier Universitaire de Liège - CHU > Radiothérapie
Notter, M
Stamm, Bernard; Kantonspital Aarau, Aarau
Matter, M
Fasolini, F
Schlumpf, R
Matzinger, O
Bouzourene, H
Language :
English
Title :
Préoperative hyperfractionated accelerated radiotherapy (HART) in locally advanced rectal cancer (LARC) immediately followed by surgery. A prospective trial.
Bosset J.F., Calais G., Mineur L., et al. Preoperative radiation (Preop RT) in rectal cancer: effect of timing of additional chemotherapy (CT) 5-year results of the EORTC 22921 trial. J Clin Oncol 23 (2005) 3505
Bouzourene H., Bosman F.T., Seelentag W., et al. Importance of tumour regression assessment in predicting the outcome of patients with locally advanced rectal carcinoma who are treated with preoperative radiotherapy. Cancer 94 (2001) 1121-1130
Bouzourene H., Bosman F.T., Matter M., et al. Predictive factors in locally advanced rectal cancer treated with preoperative hyperfractionated and accelerated radiotherapy. Hum Pathol 34 (2003) 541-548
Bouzourene H., Chaubert P., Gebhard S., et al. Role of methallothionein in irradiated human rectal carcinoma. Cancer 95 (2002) 1003-1008
Bujko K., Nowacki M.P., Nasierowska-Guttmejer A., et al. Sphincter preservation following preoperative radiotherapy for rectal cancer: report of a randomized trial comparing short-term radiotherapy vs. conventionally fractionated radiochemotherapy. Radiother Oncol 72 (2003) 15-24
Camma C., Giunta M., Fiorica F., et al. Preoperative radiotherapy for resectable rectal cancer. J Am Med Assoc 284 (2000) 1008-1015
Coucke P.A., Cuttat J.-F., and Mirimanoff R.-O. Adjuvant postoperative accelerated hyperfractionated radiotherapy in rectal cancer: a feasibility study. Int J Radiat Oncol Biol Phys 27 (1993) 885-889
Coucke P.A., Sartorelli B., Cuttat J.-F., et al. The rationale to switch from postoperative hyperfractionated accelerated radiotherapy to preoperative hyperfractionated accelerated radiotherapy in rectal cancer. Int J Radiat Oncol Biol Phys 32 (1995) 181-188
Dahlberg M., Glimelius B., and Pahlman L. Improved survival and reduction in local failure rates after preoperative radiotherapy: evidence for the generalizability of the results of Swedish Rectal Cancer Trial. Ann Surg 229 (1999) 493-497
Dahlberg M., Glimelius B., Graf W., et al. Preoperative irradiation affects functional results after surgery for rectal cancer. Dis Colon Rectum 41 (1998) 543-551
Dahlberg M., Sternberg A., Pahlman L., et al. Cost effectiveness of preoperative radiotherapy in rectal cancer: results from the Swedish Rectal Cancer Trial. Int J Radiat Oncol Biol Phys 54 (2002) 654-660
François Y., Nemoz C., Baulieux J., et al. Influence of the interval between preoperative radiation therapy and surgery in downstaging and on the rate of sphincter-sparing surgery for rectal cancer: the Lyon R90-01 randomized trial. J Clin Oncol 17 (1999) 2396-2402
Gerard J.P. Radiotherapy in the conservative treatment of rectal cancer. Evidence-based medicine and opinion. Radiother Oncol 74 (2004) 227-233
Gerard J.P., Bonnetain F., Conroy T., et al. Preoperative (preop) radiotherapy (RT) in T3-4 rectal cancers: results of the FFCD 9203 randomized trial. J Clin Oncol 23 (2005) 3504
Giralt J., de las Heras M., Cerezo L., et al. The expression of epidermal growth factor receptor results in a worse prognosis for patients with rectal cancer treated with preoperative radiotherapy: a multicenter, retrospective analysis. Radiother Oncol 74 (2005) 101-108
Glimelius B., Isacsson U., Jung B., et al. Radiotherapy in addition to radical surgery in rectal cancer: evidence for a dose response effect favouring preoperative treatment. Int J Radiat Oncol Biol Phys 37 (1997) 281-287
Glimelius B. Role of adjuvant chemoradiotherapy for abdominal malignancies. Dig Surg 20 (2003) 169-179
Graf W., Dahlberg M., Osman M.M., et al. Short-term preoperative radiotherapy results in down-staging of rectal cancer: a study of 1316 patients. Radiother Oncol 43 (1997) 133-137
Gunderson L.L., Russell H.A., Llewellynn H.J., et al. Treatment planning for colorectal cancer. Radiation and surgical techniques and value of small bowel films. Int J Radiat Oncol Biol Phys 11 (1985) 1379-1393
Heald R.J., and Ryall R.D.H. Recurrence and survival after total mesorectal excision for rectal cancer. Lancet 1 (1986) 1479-1482
Heald R.J., Moran B.J., Ryall R.D.H., et al. The Basingstoke experience of total mesorectal excision, 1978-1997. Arch Surg 133 (1998) 894-899
Hermanek P., and Hermanek P.J. Role of the surgeon as a variable in the treatment of rectal cancer. Semin Surg Oncol 19 (2000) 325-329
Hoskin P.J., de Canha S.M., Bownes P., et al. High dose rate afterloading intraluminal brachytherapy for advanced inoperable rectal carcinoma. Radiother Oncol 73 (2004) 195-198
Kapiteijn E., Marijnen C.A.M., Nagtegaal I.D., et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 345 (2001) 638-646
Kapiteijn E., Putter H., van de Velde C.J.H., and Cooperative investigators of the Dutch ColoRectal Cancer Group. Impact of the introduction and training of total mesorectal excision on recurrence and survival in rectal cancer in The Netherlands. Br J Surg 89 (2002) 1142-1149
King M., Tolan S., Giridharan S., et al. Late toxicity after short course preoperative radiotherapy and total mesorectal excision for resectable rectal cancer. Clin Oncol 15 (2003) 233-236
Lusinchi A., Wibault P., Lasser P., et al. Abdominoperineal resection combined with pre- and postooperative radiation therapy in the treatment of low-lying rectal carcinoma. Int J Radiat Oncol Biol Phys 37 (1997) 59-65
MacFarlane J.K., Ryall R.D., and Heald R.J. Mesorectal excsion for rectal cancer. Lancet 341 (1993) 457-460
Marijnen C.A.M., Nagtegaal I.D., and Klein Kranenbarg E. No downstaging after short term-preoperative radiotherapy in rectal cancer. J Clin Oncol 19 (2001) 1976-1984
Marijnen C.A.M., Kapiteijn E., van de Velde C.J.H., et al. Acute side effects and complications after short-term preoperative radiotherapy combined with total mesorectal excision in primary rectal cancer: report of a multicenter randomized trial. J Clin Oncol 20 (2002) 817-825
Marijnen C.A.M., Nagtegaal I.D., Kapiteijn E., et al. Radiotherapy does not compensate for positive resection margins in rectal cancer patients: report of a multicenter randomized trial. Int J Radiat Oncol Biol Phys 55 (2003) 1311-1320
Martling A.L., Holm T., Rutqvist L.-E., et al. Effect of a surgical training programme on outcome of rectal cancer in the County of Stockholm. Lancet 356 (2000) 93-96
Nagtegaal I.D., Marijnen C.A.M., Klein Kranenbarg E., et al. Circumferential margin involvement is still an important predictor of local recurrence in rectal carcinoma. Not one millimeter but two millimeters is the limit. Am J Surg Pathol 26 (2002) 350-357
NIH Consensus Conference. Adjuvant therapy for patients with colon and rectal cancer. J Am Med Assoc 264 (1990) 1444-1450
Oken M.M., Creech R.H., Tormey D.C., et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 5 (1982) 649-655
Onaitis M.W., Noone R.B., Fields R., et al. Complete response to neoadjuvant chemoradiation for rectal cancer does not influence survival. Ann Surg Oncol 8 (2001) 801-806
Pahlman L., and Glimelius B. Pre- or postoperative radiotherapy in rectal and rectosigmoid carcinoma. Report from a randomized multicenter trial. Ann Surg 211 (1990) 187-195
Quirke P. The pathologist, the surgeon and colorectal cancer-get it right because it matters. Prog Pathol 4 (1998) 201-213
Quirke P., and Dixon M.F. How I do it. Prediction of local recurrence in rectal adenocarcinoma by hostopathological examination. Int J Colorectal Dis 3 (1988) 127-131
Quirke P., Durdey P., Dixon M.F., et al. Local recurrence of rectal adenocarcinoma due to inadequate surgical resection: histopathological study of lateral tumor spread and surgical excision. Lancet 2 (1986) 996-999
Read T.E., Myerson R.J., Fleshman J.W., et al. Surgeon specialty is associated with outcome in rectal cancer treatment. Dis Colon Rectum 45 (2002) 904-914
Sauer R., Becker H., Hohenberger W., et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 17 (2004) 1731-1740
Sigmon W.R., Randall M.E., Olds W.O., et al. Increased chronic bowel complications with split-course pelvic irradiation. Int J Radiat Oncol Biol Phys 28 (1994) 349-353
In: Sobin L.H., and Wittekind C. (Eds). TNM classification of malignant tumors. 5th ed (1997), Wiley, New York
Stein D.E., Mahmoud N.N., Rani Anné P., et al. Longer time interval between completion of neoadjuvant chemoradiation and surgical resection does not improve downstaging of rectal carcinoma. Dis Colon Rectum 46 (2003) 448-453
Suwinsky R., Taylor J.M.G., and Withers H.R. Rapid growth of microscopic rectal cancer as a determinant of response to preoperative radiation therapy. Int J Radiat Oncol Biol Phys 42 (1998) 943-951
Swedish Rectal Cancer Trial. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med 336 (1997) 980-987
Valentini V., Glimelius B., Minsky B., et al. The multidisciplinary rectal cancer treatment: main convergences, controversial aspects and investigational areas with support the need for an European concencus. Radiother Oncol 76 (2005) 241-250
Voelter V., Stupp R., Matter M., et al. Preoperative hyperfractionated accelerated radiotherapy (HART) and concommittant CPT-11 in locally advanced rectal carcinoma. A phase I study. Int J Radiat Oncol Biol Phys 56 (2003) 1288-1294
