Preoperative chemoradiation for rectal cancer: kudos and a caution.

作者: Hartley S. Stern , Wayne S. Kendal

DOI:

关键词: SurgeryColorectal cancerTotal mesorectal excisionBiopsyPreoperative careMedicineCancerProctoscopyChemotherapyRadiation therapy

摘要: With the first results of German rectal cancer trial (CAO/ ARO/AIO-94)1 now made public, we have a prospective randomized study that has confirmed what those treating long suspected: preoperative chemoradiation provides significant advantage over postoperative therapy in terms pelvic control and sphincter preservation. Full-course radiation with 5-fluorouracil-based chemotherapy, similar to employed trial,1 clinical complete response (clinical CR) rates 19%– 38% pathologic CR 8%– 30% (Table 1).1,2,3,4,5,6,7,8,9,10,11,12,13,14 Such therapy, as distinct from short-course radiotherapy came into wide use after Swedish trial,15 can provide for downstaging bulky nonresectable cancers.2,4,9 full-course 60%–90% clinically tumours be resectable.2,4 Table 1 The apparent success led some ask whether surgery is necessary CR. For example, Rossi colleagues6 reported on 16 patients low infiltrative cancers who were treated chemoradiation. The 6 achieved followed without by monthly proctoscopy. After 34 months follow-up only 1 patient remained free disease; other 5 developed local recurrence periods 1–10 months. authors concluded was view temporary nature most CRs. Nakagawa associates13 provided data series 104 mid- or low- adenocarcinomas 10 sustained (confirmed proctoscopic biopsy) examinations every 3 Of these patients, 8 (80%) recurrent within median period months, whom 4 salvaged surgical intervention. Only 2 CRs disease-free at 37.5 58 These likewise should not go prompt surgery. Interestingly, Habr-Gama coworkers7 very different conclusion. They 38 an initial physical exam, biopsy, transrectal ultrasound CT) immediate surgery. (21%) required resection disease 3–14 Nonetheless, 30 36 it acceptable delay management CRs. further suggested salvage could done time detriment patients.7 Habr-Gama colleagues' study7 raises number issues, such accuracy staging. This particular question been examined extensively. when Kahn coauthors16 evaluated postradiation staging 25 they observed limitations Computed tomography accurately stage 23% cases, endorectal 17%. Digital examination had negative predictive value 24%. current methods reliably distinguish between residual postirradiation fibrosis. Furthermore, unable predict which did require definitive surgery.16 Another issue raised potential rate nonsurgical follow-up. best available are necessarily drawn studies curative Garcia-Aguilar coworkers17 one 87 patients. At recurrence, fewer than one-half their suitable surgery; resected intent, 5-year survival 35%. Clearly, up community, serious problem. It would reasonable expect concern alone. Beyond two issues there remains fundamental difference treatment surgery, certain any tissue removed will never contribute recurrence; limitation stems cancerous removed. effectiveness well illustrated technique total mesorectal excision (TME). In Dutch CKVO 95-04 study,18,19 failure TME alone about 12%20 — excellent achievement. The effects clear-cut Typically administered 25–33 daily treatments several weeks, each affects fixed fraction tumour cells field. On semilogarithmic plot dose – curve approximates form shown Fig. 1: straight line. A typical might initially consist 1010–1011 cells; orders magnitude reduction attain CR, leaving aggregated cell volume mm3, say. To achieve possibly order necessary. approach TME, 5–6 needed. Essentially, then, twice much equivalent CR. FIG. 1. Dose–response neoadjuvant Chemoradiation typically multiple fractions 4–6 weeks. proportion inactivated, so ... Each modality its advantages disadvantages. When extensive microscopic disease, usefulness limited. limited tolerances normal intrinsic resistance cells, but sterilize regions either cannot ought spared. through combination modalities optimized. trial1 reduced 11% 7% figures keeping rectal-cancer accompanying sufficient permit preservation. Preoperative established important component cancer. form, considered refuse operative unfit

参考文章(19)
Improved survival with preoperative radiotherapy in resectable rectal cancer. The New England Journal of Medicine. ,vol. 336, pp. 980- 987 ,(1997) , 10.1056/NEJM199704033361402
Wilson T. Nakagawa, Benedito M. Rossi, Fábio de O. Ferreira, Robson Ferrigno, Waldec J. David Filho, Inês N. Nishimoto, Rene A. C. Vieira, Ademar Lopes, Chemoradiation instead of surgery to treat mid and low rectal tumors: Is it safe? Annals of Surgical Oncology. ,vol. 9, pp. 568- 573 ,(2002) , 10.1007/BF02573893
Julio García-Aguilar, Enrique Hernandez de Anda, Prayuth Sirivongs, Suk-Hwan Lee, Robert D. Madoff, David A. Rothenberger, A pathologic complete response to preoperative chemoradiation is associated with lower local recurrence and improved survival in rectal cancer patients treated by mesorectal excision. Diseases of The Colon & Rectum. ,vol. 46, pp. 298- 304 ,(2003) , 10.1007/S10350-004-6545-X
Mohammed Mohiuddin, William F Regine, William J John, Patrick F Hagihara, Patrick C McGrath, Daniel E Kenady, Gerald Marks, Preoperative chemoradiation in fixed distal rectal cancer: dose time factors for pathological complete response. International Journal of Radiation Oncology Biology Physics. ,vol. 46, pp. 883- 888 ,(2000) , 10.1016/S0360-3016(99)00486-1
Salvatore Pucciarelli, Maria Luisa Friso, Paola Toppan, Adriano Fornasiero, Sandro Carnio, Elisabetta Marchiori, Mario Lise, PREOPERATIVE COMBINED RADIOTHERAPY AND CHEMOTHERAPY FOR MIDDLE AND LOWER RECTAL CANCER: PRELIMINARY RESULTS Annals of Surgical Oncology. ,vol. 7, pp. 38- 44 ,(2000) , 10.1007/S10434-000-0038-5
Benedito M. Rossi, Wilson T. Nakagawa, Paulo E. Novaes, Waldec D. J. Filho, Ademar Lopes, Radiation and chemotherapy instead of surgery for low infiltrative rectal adenocarcinoma: a prospective trial. Annals of Surgical Oncology. ,vol. 5, pp. 113- 118 ,(1998) , 10.1007/BF02303843
Gregory M.M Videtic, Barbara J Fisher, Francisco E Perera, Glenn S Bauman, Walter I Kocha, Marianne Taylor, Mark D Vincent, E.A Plewes, C.Jay Engel, Larry W Stitt, Preoperative radiation with concurrent 5-fluorouracil continuous infusion for locally advanced unresectable rectal cancer International Journal of Radiation Oncology Biology Physics. ,vol. 42, pp. 319- 324 ,(1998) , 10.1016/S0360-3016(98)00214-4
C Berger, S Kirscher, C Félix-Faure, B Chauvet, P Vincent, Y Brewer, F Reboul, Radiochimiothérapie concomitante préopératoire pour cancer du rectum Cancer Radiotherapie. ,vol. 2, pp. 260- 265 ,(1998) , 10.1016/S1278-3218(98)80003-6
Julio Garcia-Aguilar, John W. Cromwell, Claudio Marra, Suk-Hwan Lee, Robert D. Madoff, David A. Rothenberger, Treatment of locally recurrent rectal cancer. Diseases of The Colon & Rectum. ,vol. 44, pp. 1743- 1748 ,(2001) , 10.1007/BF02234449