Radioterapia neoadjuvante no carcinoma do recto: resposta à terapêutica e sua toxicidade
Abstract
Introdução: O carcinoma do recto localmente avançado (CRLA) é habitualmente tratado com Radioterapia (RT) seguida por Cirurgia. Existem dois esquemas possíveis para irradiação neoadjuvante: o longo (EL), associado a quimioterapia (QT), e o curto (EC). Objectivos: Comparar resposta e toxicidade à terapêutica com EL e EC em doentes com CRLA. Material e Métodos: Foram incluídos doentes com CRLA tratados de 2002 a 2012, que realizaram RT pré-operatória segundo EL ou EC. A resposta foi avaliada pela classificação pTNM e regressão de Dworak (GRD); a toxicidade foi avaliada pela escala CTCAE3. Resultados: Foram incluídos 215 doentes de EL e 55 de EC. Os de EC tinham idade superior e Karnofsky inferior aos de EL (p<0,001). 20% dos EC eram estádio IV e 92,6% dos EL estádio III (p<0,001). Efectuaram cirurgia curativa 208 doentes após EL e 47 após EC; foram realizadas mais cirurgias conservadoras. Obteve-se GRD 4 em 16,8% vs. 6,4%, downstaging N em 66,3% vs. 23,4% e resposta loco-regional em 79,8% vs. 57,4% (EL vs. EC; p<0,001). Não foi descrita toxicidade aguda no EC; no EL ocorreu em 77,7% (p<0,001) mas apenas 7,9% com grau 3/4 (p=0,028). Não houve diferenças nas complicações pós-operatórias (p=0,299). Mais doentes EL realizaram QT adjuvante (p<0,001). Pior resposta patológica pTN e GRD 0-1 no EL estão associados a mais ressecções R+ (p<0,01). Conclusões: O EL aparenta estar associado a melhor resposta do que o EC, o que facilita uma ressecção curativa, à custa de uma toxicidade tolerável.
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References
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Improved survival with preoperative radiotherapy in resectable rectal cancer. Swedish Rectal Cancer Trial. N. Engl. J. Med. 336, 980–7 (1997)
Folkesson, J. et al. Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival and local recurrence rate. J. Clin. Oncol. 23, 5644–50 (2005)
Kapiteijn, E. et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N. Engl. J. Med. 345, 638–46 (2001)
Bosset, J.-F. et al. Chemotherapy with preoperative radiotherapy in rectal cancer. N. Engl. J. Med. 355, 1114–23 (2006)
Gérard, J.-P. et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J. Clin. Oncol. 24, 4620–5 (2006)
Sauer, R. et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N. Engl. J. Med. 351, 1731–40 (2004)
Sauer, R. et al. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J. Clin. Oncol. 30, 1926–33 (2012)
Francois, Y. et al. Influence of the interval between preoperative radiation therapy and surgery on downstaging and on the rate of sphincter-sparing surgery for rectal cancer: the Lyon R90-01 randomized trial. J. Clin. Oncol. 17, 2396 (1999)
Rödel, C. et al. Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J. Clin. Oncol. 23, 8688–96 (2005)
Kalady, M. F. et al. Predictive factors of pathologic complete response after neoadjuvant chemoradiation for rectal cancer. Ann. Surg. 250, 582–9 (2009)
Ngan, S. Y. et al. Randomized trial of short-course radiotherapy versus long course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group trial 01.04. J. Clin. Oncol. 30, 3827–33 (2012)
Bujko, K. et al. Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Br. J. Surg. 93, 1215–23 (2006)
Sloothaak, D. a M. et al. Optimal time interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer. Br. J. Surg. 100, 933–9 (2013)
Pettersson, D. et al. Interim analysis of the Stockholm III trial of preoperative radiotherapy regimens for rectal cancer. Br. J. Surg. 97, 580–7 (2010)
Dworak, O., Keilholz, L. & Hoffmann, a. Pathological features of rectal cancer after preoperative radiochemotherapy. Int. J. Colorectal Dis. 12, 19–23 (1997)
Glimelius, B., Tiret, E., Cervantes, A. & Arnold, D. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 24 Suppl 6, vi81–8 (2013)
Lam, V. W. T. et al. A systematic review of a liver-first approach in patients with colorectal cancer and synchronous colorectal liver metastases. 101–108 (2014). doi:10.1111/hpb.12083
NCCN. Practice Guidelines in Oncology – Rectal Cancer – NCCN 3.2014. (2014). at
van de Velde, C. J. H. et al. EURECCA colorectal: multidisciplinary mission statement on better care for patients with colon and rectal cancer in Europe. Eur. J. Cancer 49, 2784–90 (2013)
Gunnlaugsson, A. et al. Dose-volume relationships between enteritis and irradiated bowel volumes during 5-fluorouracil and oxaliplatin based chemoradiotherapy in locally advanced rectal cancer. Acta Oncol. 46, 937 44 (2007)
Baglan, K., Frazier, R. & Yan, D. The dose-volume realationship of acute small bowel toxicity from concurrent 5-FU-based chemotherapy and radiation therapy for rectal cancer. … J. Radiat. … 52, 176–183 (2002)
Tho, L. M. et al. Acute small bowel toxicity and preoperative chemoradiotherapy for rectal cancer: Investigating dose–volume relationships and role for inverse planning. Int. J. Radiat. Oncol. 66, 505–513 (2006)
Gallagher, M. & Brereton, H. A prospective study of treatment techniques to minimize the volume of pelvic small bowel with reduction of acute and late effects associated with pelvic irradiation. … J. Radiat. … 12, (1986)
Bujko, K. et al. Postoperative complications in patients irradiated pre operatively for rectal cancer: report of a randomised trial comparing short-term radiotherapy vs chemoradiation. Colorectal Dis. 7, 410–6 (2005)
Conde, S. et al. Impact of neoadjuvant chemoradiation on pathologic response and survival of patients with locally advanced rectal cancer. Reports Pract. Oncol. Radiother. 15, 51–59 (2010)
Collette, L. 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 Rad. J. Clin. Oncol. 25, 4379–86 (2007)
Fernández-Martos, C. et al. Preoperative uracil, tegafur, and concomitant radiotherapy in operable rectal cancer: a phase II multicenter study with 3 years’ follow-Up. J. Clin. Oncol. 22, 3016–22 (2004)
Kim, N. K. et al. Oncologic outcomes after neoadjuvant chemoradiation followed by curative resection with tumor-specific mesorectal excision for fixed locally advanced rectal cancer: Impact of postirradiated pathologic downstaging on local recurrence and survival. Ann. Surg. 244, 1024–30 (2006)
Park, I. J. et al. Neoadjuvant treatment response as an early response indicator for patients with rectal cancer. J. Clin. Oncol. 30, 1770–6 (2012)
Valentini, Vi. et al. Does downstaging predict improved outcome after preoperative chemoradiation for extraperitoneal locally advanced rectal cancer? A long-term analysis of 165 patients. Int. J. … 53, 664–674 (2002)
Janjan, N. a. et al. Improved Overall Survival Among Responders to Preoperative Chemoradiation for Locally Advanced Rectal Cancer. Am. J. Clin. Oncol. Cancer Clin. Trials 24, 107–112 (2001)
Crane, C. H. 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. 57, 84–89 (2003)
Lambregts, D. M. J. & Beets-Tan, R. G. H. Optimal imaging staging of rectal cancer. EJC Suppl. 11, 38–44 (2013)
Hermanek, P., Merkel, S. & Hohenberger, W. Prognosis of Rectal Carcinoma after Multimodal Treatment : ypTNM Classification and Tumor Regression Grading Are Essential. 566, 559–566 (2013)
Arredondo, J. et al. Prognosis Factors for Recurrence in Patients With Locally Advanced Rectal Cancer Preoperatively Treated With Chemoradiotherapy and Adjuvant Chemotherapy. Dis. Colon Rectum 56, 416–421 (2013)
Published
2015-12-01
How to Cite
CASALTA-LOPES, João et al.
Radioterapia neoadjuvante no carcinoma do recto: resposta à terapêutica e sua toxicidade.
Revista Portuguesa de Cirurgia, [S.l.], n. 35, p. 23-32, dec. 2015.
ISSN 2183-1165.
Available at: <https://revista.spcir.com/index.php/spcir/article/view/550>. Date accessed: 20 apr. 2024.
Section
Review Article
