Preoperative radiotherapy with concomitant fluoropyrimidine-based chemotherapy for resectable locally advanced rectal cancer

Abstract

To investigate the treatment results and tumor and patient characteristics in patients with resectable locally advanced rectum cancer (LARC) who were treated with preoperative chemoradiation. METHODS T3/T4 rectal adenocarcinoma patients (n=50) were evaluated retrospectively. Tumors were located within 5 cm of the anal verge in 60% of patients. Twenty-four (48%) of the patients had positive lymph nodes. Pelvic radiotherapy was administered with a median dose of 45Gy in linear accelerator. Concurrent fluoropyrimidine was given orally (n=18) or intravenously (n=32). RESULTS Median follow-up was 17 months. Two-year local control, disease- free survival and overall survival were 93.6%, 90.3% and 93.3%, respectively. Sphincter-preserving surgery rate was 43% for distal tumors. Downstaging was observed in 35% with seven ypT0N0 cT4 (p=0.01), lymphovascular-perineural invasion (p=0.01) and pN+ (p=0.02) were predictive for a worse prognosis. Grade 3 toxicity was observed in 8% of patients. CONCLUSION Preoperative chemoradiotherapy demonstrated similar benefit regarding sphincter preservation with that of standard postoperative multimodality therapies in LARC patients.

Keywords

• Rectal Neoplasms,Neoadjuvant Therapy,Chemotherapy, Adjuvant,Adenocarcinoma,Survival,Pyrimidines,Preoperative Period,Radiotherapy

Rezeke edilebilir lokal ileri evre rektum kanserinde floroprimidin bazlı kemoterapi ile eş zamanlı ameliyat öncesi radyoterapi

Öz

AMAÇ Rezeke edilebilir lokal ileri evre rektum kanserinde ameliyat öncesi kemoradyoterapi sonrası tedavi cevapları, sağkalım süreleri, tümör ve hastaların demografik özellikleri değerlendirildi. GEREÇ VE YÖNTEM T3/T4 rektum adenokarsinomu tanılı, 50 (dağılım, 36-77 yaş) hasta incelendi. Tedavi öncesi 30 (%60) hastada tümör başlangıcı anal girimden ilk 5 cm içindeydi. Yirmi dört (%48) hastada nod pozitifti. Radyoterapi doğrusal hızlandırıcıyla konformal teknikle pelvik alana ortanca 45 Gy uygulandı. Eş zamanlı floroprimidin oral (n=18) veya intravenöz olarak (n=32) olarak verildi. BULGULAR Ortanca takip 17 ay, iki yıllık lokal kontrol, hastalıksız sağkalım ve tüm sağkalım oranları sırasıyla %93,6, %90,3 ve %93,3 idi. Distal tümörlerde sfinkter koruyucu cerrahi oranı %43, tüm hastalarda evre küçülmesi oranı %35 idi. Yedi hastada tam cevap (ypT0N0) elde edildi. kT4 hastalık (p=0,01), lenfovasküler- perinöral invazyon (p=0,01) ve pN+ (p=0,02) kötü prognoz göstergesiydi. Derece 3 yan etki oranı %8 idi. SONUÇ Ameliyat sonr ası ted av iye benzer sonuçları ve sfinkt eri kor um a şansıyla amel iyat öncesi mult im odal ite yaklaşımı, lokal ileri evre rektum kanserinde ted avi kararında iyi bir seçenek olabilir.

Anahtar Kelimeler

• Kemoradyoterapi, neoadjuvan tedavi, rektum kanseri, Türk nüfusu.

Kaynakça

1. 1. Gastrointestinal Tumor Study Group. Prolongation of the disease-free interval in surgically treated rectal carcinoma. N Engl J Med 1985;312(23):1465-72.
2. 2. Swedish Rectal Cancer Trial. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med 1997;336(14):980-7.
3. 3. Tveit KM, Guldvog I, Hagen S, Trondsen E, Harbitz T, Nygaard K, et al. Randomized controlled trial of postoperative radiotherapy and short-term time-scheduled 5-fluorouracil against surgery alone in the treatment of Dukes B and C rectal cancer. Norwegian Adjuvant Rectal Cancer Project Group. Br J Surg 1997;84(8):1130-5.
4. 4. Colorectal Cancer Collaborative Group. Adjuvant radiotherapy for rectal cancer: a systematic overview of 8,507 patients from 22 randomised trials. Lancet 2001;358(9290):1291-304.
5. 5. Fisher B, Wolmark N, Rockette H, Redmond C, Deutsch M, Wickerham DL, et al. Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from NSABP protocol R-01. J Natl Cancer Inst 1988;80(1):21-9.
6. 6. Thomas PR, Lindblad AS. Adjuvant postoperative radiotherapy and chemotherapy in rectal carcinoma: a review of the Gastrointestinal Tumor Study Group experience. Radiother Oncol 1988;13(4):245-52.
7. 7. Cammà C, Giunta M, Fiorica F, Pagliaro L, Craxì A, Cottone M. Preoperative radiotherapy for resectable rectal cancer: A meta-analysis. JAMA 2000;284(8):1008-15.
8. 8. NIH consensus conference. Adjuvant therapy for patients with colon and rectal cancer. JAMA 1990;264(11):1444-50.

9. 9. Roh MS, Petrelli N, Wiand H. Phase III radnomised trial of preoperative versus postoperative mult›modality therapy in patients with carcinoma of the rectum (NSABP R-03). J Clin Oncol 2 0 0 1 ; 2 0 (Suppl 1):123a.
10. 10. Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R; German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004;351(17):1731-40.
11. 11. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J. Am Stat Assoc 1958;53:457-81.
12. 12. Available from: http://ctep.cancer.gov/forms/CTCv20 _4-30-992.pdf
13. 13. Valentini V, Beets-Tan R, Borras JM, Krivokapi_ Z, Leer JW, Påhlman L, et al. Evidence and research in rectal cancer. Radiother Oncol 2008;87(3):449-74.
14. 14. Glynne-Jones R, Harrison M. Locally advanced rectal cancer: what is the evidence for induction chemoradiation? Oncologist 2007;12(11):1309-18.
15. 15.Janjan NA, Khoo VS, Abbruzzese J, Pazdur R, Dubrow R, Cleary KR, et al. Tumor downstaging and sphincter preservation with preoperative chemoradiation in locally advanced rectal cancer: the M. D. Anderson Cancer Center experience. Int J Radiat Oncol Biol Phys 1999;44(5):1027-38.
16. 16. García-Aguilar J, Hernandez de Anda E, Sirivongs P, Lee SH, Madoff RD, Rothenberger DA. A pathologic complete response to preoperative chemoradiation is associated with lower local recurrence and improved survival in rectal cancer patients treated by mesorectal excision. Dis Colon Rectum 2003;46(3):298-304.
17. 17.Chan AK, Wong A, Jenken D, Heine J, Buie D, Johnson D. Posttreatment TNM staging is a prognostic indicator of survival and recurrence in tethered or fixed rectal carcinoma after preoperative chemotherapy and radiotherapy. Int J Radiat Oncol Biol Phys 2005;61(3):665-77.
18. 18.Collette L, Bosset JF, den Dulk M, Nguyen F, Mineur L, Maingon P, et al. Patients with curative resection of cT3-4 rectal cancer after preoperative radiotherapy or radiochemotherapy: does anybody benefit from adjuvant fluorouracil-based chemotherapy? A trial of the European Organisation for Research and Treatment of Cancer Radiation Oncology Group. J Clin Oncol 2007;25(28):4379-86.
19. 19.Crane CH, Skibber JM, Birnbaum EH, Feig BW, Singh AK, Delclos ME, et al. The addition of continuous infusion 5-FU to preoperative radiation therapy increases tumor response, leading to increased sphincter preservation in locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 2003;57(1):84-9.
20. 20.Rich TA, Skibber JM, Ajani JA, Buchholz DJ, Cleary KR, Dubrow RA, et al. Preoperative infusional chemoradiation therapy for stage T3 rectal cancer. Int J Radiat Oncol Biol Phys 1995;32(4):1025-9.
21. 21. de la Torre A, García-Berrocal MI, Arias F, Mariño A, Valcárcel F, Magallón R, et al. Preoperative chemoradiotherapy for rectal cancer: randomized trial comparing oral uracil and tegafur and oral leucovorin vs. intravenous 5-fluorouracil and leucovorin. Int J Radiat Oncol Biol Phys 2008;70(1):102-10.
22. 22. Frykholm GJ, Glimelius B, Påhlman L. Preoperative or postoperative irradiation in adenocarcinoma of the rectum: final treatment results of a randomized trial and an evaluation of late secondary effects. Dis Colon Rectum 1993;36(6):564-72.
23. 23. Fietkau R, Barten M, Klautke G, Klar E, Ludwig K, Thomas H, et al. Postoperative chemotherapy may not be necessary for patients with ypN0-category after neoadjuvant chemoradiotherapy of rectal cancer. Dis Colon Rectum 2006;49(9):1284-92.
24. 24. Gérard JP, Conroy T, Bonnetain F, Bouché O, Chapet O, Closon-Dejardin MT, et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol 2006;24(28):4620-5.
25. 25.Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, et al; EORTC Radiotherapy Group Trial 22921. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 2006;355(11):1114-23.