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Short-course preoperative radiotherapy combined with chemotherapy in resectable locally advanced rectal cancer: local control and quality of life

Radioterapia ipofrazionata short-course neoadiuvante in associazione alla chemioterapia nelle neoplasie rettali operabili in stadio localmente avanzato: controllo locale e qualità di vita

  • Radiotherapy / Radioterapia
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Abstract

Purpose

The authors sought to evaluate the clinical outcome after preoperative short-course radiotherapy (SC-RT) for locally advanced resectable rectal cancer in terms of local control (LC) and quality of life (QoL).

Materials and methods

Patients with locally advanced rectal cancer enrolled between 1997 and 2008 in an observational study of preoperative SC-RT were analysed. The treatment algorithm was neo-adjuvant chemotherapy (CT) administered for four cycles, followed by preoperative SC-RT administered 1 week after chemotherapy completion, delivering 20 Gy in five fractions over 1 week. Immediately in the following week surgery was performed. The adjuvant 5-FU-based CT was planned for pathological stage UICC≥II. LC, overall survival (OS), disease-free survival (DFS), early and late complications (RTOG scale) were analysed. All patients completed the EORTC QoL (C-30 and C-38), Faecal Incontinence QoL, and International Index of Erectile Function questionnaires (IIEF).

Results

A total of 67 patients were analysed. Chemotherapy and radiotherapy were well tolerated. At the pathological analysis, stable disease was obtained in 24 patients (36%), reduction of disease stage in 34 patients (50.7%), and progression in nine cases (13.3%). Adjuvant chemotherapy was indicated in 21 patients. Two locoregional recurrences, both within the radiotherapy volume, were observed, resulting in a 5-year LC of 97%. The 5-year DFS was 84%, with mean time to systemic progression of 24 months. After a mean follow-up of 114 months, the 5-year OS rate was 67%. Late toxicity >grade II was observed in 9% of patients. High anterior resection (AR) patients had significantly better scores than low AR or abdomino-perineal resection (APR). A total of 89% of the patients treated with conservative surgery had regular anal sphincter function. In male patients undergoing AR or APR, erectile dysfunction was found in 47% and 75% of the cases, respectively.

Conclusions

Preoperative SC-RT combined with chemotherapy for locally advanced resectable rectal cancers was well tolerated. This treatment resulted in favourable LC, OS, low rates of toxicity and satisfying QoL.

Riassunto

Obiettivo

Il presente studio si propone di valutare i risultati clinici, in termini di controllo locale di malattia e di qualità di vita, in pazienti affetti da neoplasia rettale operabile in stadio localmente avanzato e sottoposti a un trattamento di radioterapia ipofrazionata short-course neoadiuvante in associazione alla chemioterapia.

Materiali e metodi

Dal 1997 al 2008 i pazienti affetti da neoplasia del retto localmente avanzato sono stati arruolati in uno studio osservazionale di radioterapia ipofrazionata pre-operatoria. L’approccio terapeutico prevedeva un trattamento sistemico neoadiuvante (4 cicli) seguito da radioterapia ipofrazionata short-course per una dose totale di 20 Gy in 5 sedute consecutive erogate in una settimana. Nella settimana successiva al termine del trattamento radiante, tutti i pazienti venivano sottoposti a intervento chirurgico. La chemioterapia adiuvante con 5-FU veniva indicata per gli stadi > II sec. UICC. Per tutti i pazienti in studio sono stati analizzati il controllo locale, la sopravvivenza globale, la sopravvivenza libera da malattia, le complicanze acute e tardive. Inoltre, ciascun paziente ha compilato appositi questionari relativi alla qualità di vita [EORTC QoL (C-30 and C-38), Faecal Incontinence QoL, and International Index of Erectile Function questionnaires (IIEF)].

Risultati

In questo studio sono stati arruolati 67 pazienti. Lo schema terapeutico è stato in generale ben tollerato. All’esame istologico definitivo, una stabilità di malattia è stata ottenuta in 24 pazienti (36%), una riduzione di malattia in 34 pazienti (50,7%) e una progressione in solo 9 casi (13,3%). La chemioterapia adiuvante è stata eseguita in 21 pazienti. Nel corso del follow-up sono state evidenziate due recidive loco-regionali (entrambe in campo di trattamento radioterapico) con un controllo locale a 5 anni del 97%. La sopravvivenza libera da malattia a 5 anni è risultata pari all’84%, con un tempo medio di progressione sistemica di 24 mesi. Dopo un follow-up medio di 114 mesi, il tasso di sopravvivenza globale è risultato pari al 67%. Il 9% dei pazienti ha manifestato una tossicità tardiva di grado superiore al II. In relazione alla qualità di vita, i pazienti sottoposti a chirurgia conservativa hanno collezionato punteggi maggiori ai questionari specifici, riportando nella maggior parte dei casi regolare funzionalità sfinterica anale (89%) e preservazione della funzionalità erettile (75%).

Conclusioni

Il trattamento radioterapico ipofrazionato neoadiuvante associato a chemioterapia nei tumori del retto localmente avanzati risulta essere ben tollerato, con ottimi risultati in termini di controllo locale, sopravvivenza globale e qualità di vita dei pazienti.

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References/Bibliografia

  1. Kamangar F, Dores GM, Andreson WF (2006) Pattern of incidence, mortality and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 24:2137–2150

    Article  PubMed  Google Scholar 

  2. GITGS (1985) Prolongation of the disease-free interval in surgically treated rectal carcinoma. N Engl J Med 312:1465–1472

    Article  Google Scholar 

  3. Krook JE, Moertel CG, Gunderson LL et al (1991) Effective surgical adjuvant therapy for high-risk rectal carcinoma. New Engl J Med 324:709–715

    Article  PubMed  CAS  Google Scholar 

  4. Tveit KM, Guldvog I, Hagen S et al (1997) Randomized controlled trial of postoperative radiotherapy and shortterm time-scheduled 5-fluorouracil against surgery alone in the treatment of Dukes B and C rectal cancer. Norwegian Adjuvant Cancer Project Group. Br J Surg 84:1130–1135

    Article  PubMed  CAS  Google Scholar 

  5. Frykholm GJ, Glimelius B, Pahlman L (1993) Pre-operative 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 36:564–572

    Article  PubMed  CAS  Google Scholar 

  6. Sauer R, Becker H, Hohenberger W et al (2004) Pre-operative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351:1731–1740

    Article  PubMed  CAS  Google Scholar 

  7. Stockholm Rectal Cancer Study Group (1990) Preoperative short-term radiation therapy in operable rectal carcinoma: a prospective randomized trial. Cancer 66:49–55

    Article  Google Scholar 

  8. Stockholm Rectal Cancer Study Group (1997) Randomized study on preoperative radiotherapy in resectable rectal cancer. Swedish Rectal Cancer Trial. N Engl J Med 1997 336:980–987

    Google Scholar 

  9. Kapiteijn E, Marijnen CAM, Nagtegaal ID et al (2001) Preoperative radiotherapy combined with total mesorectal excission for resectable rectal cancer. N Engl J Med 345:638–646

    Article  PubMed  CAS  Google Scholar 

  10. Bosset JF, Calais G, Mineur L et al (2005) Pre-operative radiation therapy (Preop RT) in rectal cancer: effect and timing of additional chemotherapy (CT) 5-year results of the EORTC 22921 trial. 2005 ASCO Annual Meeting Proc. J Clin Oncol 23:S247

    Article  Google Scholar 

  11. Gerard J, Romestaig P, Bonnetain F et al (2005) Preoperative concurrent chemoradiotherapy (CT-RT) improves local control in T3-T4 rectal cancers; results of the FFCD 9203 randomized trial. Int J Rad Oncol Biol Phys 63:S2–S3

    Article  Google Scholar 

  12. Birgisson H, Pahlman L, Gunnarsson U et al (2005) Adverse effects of preoperative radiation therapy for rectal cancer: long term follow-up of the Swedish Rectal Cancer Trial. J Clin Oncol 23:8697–8705

    Article  PubMed  Google Scholar 

  13. Scott NW, Fayers PM, Bottomley A et al (2006) Comparing translations of the EORTC QLQ-C30 using differential item functioning analyses. Qual Life Res 15:1103–1115; discussion 1117–1120

    Article  PubMed  CAS  Google Scholar 

  14. Sprangers MA, te Velde A, Aaronson NK et al (1999) The construction and testing of the EORTC colorectal cancer-specific quality of life questionnaire module (QLQ-CR38). European Organization for Research and Treatment of Cancer Study Group on Quality of Life. Eur J Cancer 35:238–247

    Article  PubMed  CAS  Google Scholar 

  15. Peeters KC, Marijnen CA, Nagtegaal ID et al; Dutch Colorectal Cancer Group (2007) The TME trial after a median follow-up of 67 years: increased local control but no survival benefit in irradiated patients, with resectable rectal cancer carcinoma. Ann Surg 246:693–701

    Article  PubMed  Google Scholar 

  16. Sebag-Montefiore D, Stephens RJ, Steele R, et al (2009) Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet 373:811–820

    Article  PubMed  PubMed Central  Google Scholar 

  17. Bosset JF, Collette L, Calais G et al; EORTC Radiotherapy Group Trial 22921 (2006) Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 355:1114–1123

    Article  PubMed  CAS  Google Scholar 

  18. Gerard JP, Conroy T, Bonnetain F et al (2006) Preoperative radiotherapy with or without concurrent fluorouracil and leucoverin in T3–4 rectal cancers: results of FFCD 9203. J Clin Oncol 24:4620–4625

    Article  PubMed  Google Scholar 

  19. Bujko K, Nowacki MP, Nasierowska-Guttmejer A et al (2006) Long term results of a randomized trail comparing preoperative shortcourse radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Br J Surg 93:1215–1223

    Article  PubMed  CAS  Google Scholar 

  20. Braendengen M, Tveit KM, Berglund A et al (2008) Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in nonresectable rectal cancer. J Clin Oncol 26:3687–3694

    Article  PubMed  CAS  Google Scholar 

  21. Colorectal Cancer Collaborative Group(2001) Adjuvant radiotherapy for rectal cancer: a systematic overview of 8,507 patients from 22 randomised trials. Lancet 2001 358:1921–1304

    Google Scholar 

  22. Bujko K, Nowacki MP, Nasierowska-Guttmejer A et al (2004) Sphincter preservation following preoperative radiotherapy for rectal cancer: report of a randomised trial comparing shortterm radiotherapy vs conventionally fractionated radiochemotherapy. Radiother Oncol 72:15–24

    Article  PubMed  CAS  Google Scholar 

  23. Mohiuddin M, Marks J, Marks G (2008) Management of rectal cancer: short vs. long-course preoperative radiation. Int J Radiat Oncol Biol Phys 72:636–643

    Article  PubMed  Google Scholar 

  24. Latkauskas T, Paskauskas S, Dambrauskas Z et al (2010) Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer: a metaanalysis. Colorectal Dis 12:1075–1083

    Article  PubMed  CAS  Google Scholar 

  25. Francois Y, Nemoz CJ, Bauliex J et al (1999) Influence of the interval between preoperative radiontherapy and surgery on downstaging and on the rate of sphincter-sparing surgery for rectal cancer. Lyon R90-01 randomized trial. J Clin Oncol 17:2396

    PubMed  CAS  Google Scholar 

  26. Radu C, Berglund A, Pahlman L, Glimelius B (2008) Short course preoperative radiotherapy with delayed sugery in rectal cancer- a retrospective study. Radiotherapy and Oncology 87:343–349

    Article  PubMed  Google Scholar 

  27. Pahlmann L (2008) Preoperative short-course radiotherapy in locally advanced rectal cancer: the attitude on how to use radiotherapy in rectal cancer is changing. Onkologie 31:165

    Article  PubMed  Google Scholar 

  28. Garajova I, Di Girolamo S, de Rosa F et al (2011) Neoadjuvant treatment in rectal cancer: actual status. Chemother Res Pract 839742

  29. Ishi Y, Hasegawa H, Endo T et al (2010) Medium term results of neoadjuvant systemic chemotherapy using irinotecan, 5-fluorouracil, and leucovorin in patients with locally advanced rectal cancer. Eur J Surg Onco 36:1061–1065

    Article  Google Scholar 

  30. Schrag D, Weiser MR, Goodman KA et al (2010) Neodjuvant FOLFOX-bev without radiation for locally advanced rectal cancer. J Clin Oncol 28:263S

    Article  Google Scholar 

  31. Glynne-Jones R, Anyamene N, Moran B, Harrison M (2012) Neoadjuvant chemotherapy in MRI-staged highrisk rectal cancer in addition to or as an alternative to preoperative chemoradiation. Ann Oncol 23:2517–2526

    Article  PubMed  CAS  Google Scholar 

  32. Jacques AE, Rockall AG, Alijani M et al (2007) MRI demonstration of the effect of neoadjuvant radiotherapy on rectal carcinoma. Acta Oncol 46:989–995

    Article  PubMed  Google Scholar 

  33. Bujko K, Nowacki MP, Kepka L et al (2005) Polish Colorectal Study Group. Postoperative complications in patients irradiated pre-operatively for rectal cancer: report of a randomised trial comparing short-term radiotherapy vs chemoradiation. Colorectal Dis 7:410–416

    CAS  Google Scholar 

  34. Pieterse AH, Stiggelbout AM, Baas-Thijssen MC et al (2007) Benefit from preoperative radiotherapy in rectal cancer treatment: disease-free patients’ and oncologists’ preferences. Br J Cancer 97:717–724

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  35. Birgisson H, Påhlamn L, Gunnarsson U, Glimelius B (2007) Late adverse affects of radiation therapy for rectal cancer-a systematic overview. Acta Oncol 46:504–516

    Article  PubMed  Google Scholar 

  36. Marijnen CA, van de Velde CJ, Putter H et al (2005) Impact of short term preoperative radiotherapy on health related quality of life and sexual functioning in primary rectal cancer:report of a multicenter randomized trial. J Clin Oncol 23:1847–1858

    Article  PubMed  Google Scholar 

  37. Pollack J, Holm T, Cedermark B et al (2006) Late adverse effects of short-course pre-operative radiotherapy in rectal cancer. Br J Surg 93:1519–1525

    Article  PubMed  CAS  Google Scholar 

  38. Prabhudesai AG, Cornes P, Glees JP, Kumar D (2005) Long-term morbidity following short-course, pre-operative radiotherapy and total mesorectal excision for rectal cancer. Surgeon 3:347–351

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Patrizia Ciammella.

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Ciammella, P., Ruggieri, M.P., Galeandro, M. et al. Short-course preoperative radiotherapy combined with chemotherapy in resectable locally advanced rectal cancer: local control and quality of life. Radiol med 118, 1397–1411 (2013). https://doi.org/10.1007/s11547-013-0939-6

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  • DOI: https://doi.org/10.1007/s11547-013-0939-6

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