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British Journal of Radiology (2005) 78, 934-938
© 2005 British Institute of Radiology
doi: 10.1259/bjr/86650067
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Full Paper

Pathological complete response following pre-operative chemoradiotherapy in rectal cancer: analysis of phase II/III trials

A Hartley, MRCP, FRCR1, K F Ho, MRCP1, C McConkey, MSc2 and J I Geh, MRCP, FRCR1

1 Cancer Centre, Queen Elizabeth Hospital, Birmingham B15 2TH and 2 Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK


   Abstract
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 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Pathological complete response (pCR) has been used as a marker for the efficacy of pre-operative chemoradiotherapy (CRT) schedules in rectal cancer. To date there have been no randomized trials comparing CRT regimens in rectal cancer. Prospective phase II and CRT arms of randomized trials reported up to January 2004 were included, providing they defined the following minimum variables: drugs employed during CRT, radiotherapy dose and pCR rate. Multivariate analysis was used to examine the relationship of these variables on the pCR rate. In addition, the use of neoadjuvant chemotherapy, the type of publication (peer reviewed vs meeting abstract) and whether the tumours were stated to be unresectable/clinically fixed or to have threatened circumferential margins were investigated. The method of analysis was weighted linear modelling of the pCR rate which was normalized by the arcsine transformation. Phase II and phase III trials were identified including a total of 3157 patients. On multivariate analysis only the use of continuous infusion 5FU (p=0.01), the use of a second drug (p=0.001) and radiation dose (p=0.02) were associated with higher rates of pCR. The use of a two drug regimen, the mode of delivery of 5FU and the radiation dose appear to be related to the incidence of pCR following CRT for rectal cancer. These results may generate hypotheses for future randomized trials. Important factors not considered in this analysis include the variability in pathological examination and in the time interval between CRT and surgery. In addition, the toxicity of the CRT regimens requires further investigation.


   Introduction
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 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
The use of pre-operative chemoradiotherapy (CRT) in locally advanced rectal cancer results in a lower risk of local recurrence when compared with post-operative CRT (7% vs 11%; p=0.02 in a German randomized trial of 823 patients) [1]. When used in resectable rectal cancer, pre-operative CRT results in a lower risk of circumferential resection margin involvement when compared with short course pre-operative radiotherapy (4% vs 13%; p=0.017 in a Polish randomized trial of 316 patients) [2]. The published results of an EORTC study comparing a 25 fraction course of radiotherapy with or without synchronous chemotherapy are awaited [3].

All three of these trials used single agent 5FU chemotherapy given synchronously with radiotherapy. However, there has been multiple CRT trials using differing methods of administering 5FU (e.g. bolus 5FU, intermittent or continuous infusion 5FU or oral 5FU pro-drugs) and in some cases using a second chemotherapy drug with the radiotherapy [4–44]. Most trials report early efficacy endpoints and few document post-operative complications or long-term results in terms of efficacy or late toxicity. There have been no large randomized trials comparing various CRT regimens.

The most commonly reported early endpoint is the rate of pathological complete response (pCR). This is defined as the complete absence of intact tumour cells in the resected specimen. It appears to be associated in some non randomized studies with improvement in disease-free survival [45, 46]. However, any attempt at comparing the relative efficacy of CRT regimens using the observed pCR rate is subject to multiple confounding factors. These include the interstudy variability in: the rigour of pathological examination; the radiotherapy volume encompassed; the indications for CRT (resectable tumours vs locally advanced tumours); the differing imaging modalities used for defining the study group; and the time interval between radiotherapy and surgery. The latter has been shown in one randomized trial of pre-operative radiotherapy to influence the degree of downstaging with 10% of patients operated on within 2 weeks of radiotherapy experiencing pathological downstaging compared with 26% of patients operated on 6–8 weeks after radiotherapy (p=0.005) [47].

Interpretation of the attempts to compare CRT regimens should therefore be performed with caution. In the absence of results from randomized trials, data from such a comparison may help to generate hypotheses for the design of future randomized trials. The aim of this study was to perform a comparison of the pCR rates observed in prospective studies of CRT for rectal cancer using appropriate statistical methods in an attempt to account for the confounding factors.


   Methods
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 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
A search of the MEDLINE database from 1965 to January 2004 was performed using the terms rectal carcinoma; rectal cancer; chemoradiotherapy; chemoradiation; chemotherapy and radiotherapy. In addition, the electronic American Society of Clinical Oncology (ASCO) abstract database was searched using identical terms.

Phase I trials, hyperthermia trials and trials using variable chemotherapy agents were excluded. Prospective phase II trials and the CRT arms of randomized trials were included if the number of patients with pCR was documented and it was possible to categorise the CRT regimens as detailed below. Incomplete studies in abstract form were excluded. The studies were analysed by intention to treat, i.e. all patients entered into a study were included even if they did not undergo surgery.

CRT regimens were categorised as follows: radiotherapy dose <45 Gy, 45–50 Gy, 50.1–54.9 Gy, >54.9 Gy; chemotherapy regimen 1 or 2 drugs (excluding folinic acid); first chemotherapy agent bolus 5-flurouracil (5FU), 1 h infusion 5FU ("Bosset" type schedule) [5], intermittent infusion 5FU (5FU infused>1 h/24 h but not continuously throughout radiation), continuous infusion 5FU, capecitabine, other oral 5FU drug, raltitrexed; second drug: cisplatin, irinotecan, mitomycin, oxaliplatin, methotrexate.

In addition, studies were categorised by: publication type: peer reviewed paper, abstract; use of neoadjuvant chemotherapy: yes, no; study group (as stated in publication): unresectable or fixed or circumferential margin threatened vs resectable or not stated.

Statistical methods
A multivariate analysis was performed to examine the effect of the above variables on the pCR rate. Weighted linear modelling was applied to the study-specific pCR rates, which were variance stabilized by applying the square-root arcsine transformation. The weighting applied was the number of patients in each study group.


   Results
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 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
A total of 3157 patients were identified from the CRT arms of 7 randomized trials and 45 phase II trials (Table 1Go). There were 428 patients with documented pCR giving a 13.5% overall pCR rate for the population.


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  		Table 1. PhaseII/III studies included in analysis

 
On analysis, statistically significant factors associated with pCR were: the use of two drugs (p=0.001), the method of 5FU administration (p=0.01) and radiotherapy dose (p=0.02) (Table 2Go). The administration of a two drug regimen or the use of continuous infusion 5FU or capecitabine appeared to be associated with higher rates of pCR whereas lower rates of pCR appear to be associated with doses of radiotherapy <45 Gy.


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  		Table 2. Statistically significant factors effecting rate of pCR

 
There was no significant effect on the rate of pCR of publication type (abstract vs peer reviewed paper), the pre-operative assessment of the tumour (fixed/unresecteble/circumferential margin threatened) or the type of second drug used.


   Discussion
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 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
Despite the limitations of this analysis described in the introduction to this paper, higher rates of pCR appear to occur in studies using a two drug CRT regimen and/or when 5FU is administered as a continuous infusion or capecitabine. Radiation dose only appears to be a significant factor when doses less than 45 Gy were used when lower rates of pCR may be encountered.

The validity of pCR as a marker for improvement in long-term outcome is yet to be confirmed from a randomized trial. In addition, standard pathological guidelines for the assessment of tumour response are yet to be universally adopted. Journal editors and members of scientific committees for oncology meetings should ensure that future phase II trials wishing to quote pCR rates should include adequate information of how pCR was assessed, in addition to details of patient staging and CRT regimen employed. Some clinicians would prefer to use R0 resection rates in the group of patients with MRI defined threatened circumferential margin as an early efficacy endpoint. The expertise for both the pre-operative radiological and post-operative pathological assessment necessary for such a study is becoming more widespread. The absence in this study of a relationship between the stated resectability of the study group and the rate of pCR may be accounted for by the variation in staging and limitations of investigations employed prior to the advent of MRI.

This current analysis does not support radiotherapy dose escalation above 45 Gy. Conversely, the efficacy of experimental schedules using radiotherapy doses less than 45 Gy should be carefully monitored.

Whilst the use of two drug CRT regimens in combination with continuous 5FU infusion may in the light of this analysis seem attractive, it is important that the post-operative complications and late-toxicity of such combination treatments are adequately assessed and published. In addition, if the final results of the EORTC trial shows an advantage for pre-operative CRT over radiotherapy alone in terms of locoregional control or overall survival, the next logical question to be asked in a randomized trial is whether a two drug CRT schedule will have significant therapeutic benefits over infusional 5FU as a single agent. This study does not give any clues as to which second agent should be employed.

Received for publication November 4, 2004. Revision received February 3, 2005. Accepted for publication April 14, 2005.


   References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

  1. Sauer R. Adjuvant versus neoadjuvant combined modality treatment for locally advanced rectal cancer: first results of the German Rectal Cancer Study (CAO/ARO/AIO-94). Int J Radiat Oncol Biol Phys 2003;57:S124.[Medline]
  2. Bujko K, Nowacki M, Naiserowska-Guttmejer A, Bebenek M, Pudeko M, Kryj M, et al. Sphincter preservation following preoperative radiotherapy for rectal cancer: report of a randomised trial comparing short-term radiotherapy vs. conventionally fractionated radiochemotherapy. Radiother Oncol 2004;72:15–24.[CrossRef][Medline]
  3. Bosset J, Calais G, Daban A, Collette L, Mineur L, Radosevic-Jelic L, et al. Preoperative chemoradiotherapy (preop XRT-CT) versus preoperative radiotherapy (preop XRT) in rectal cancer: effect of adding CT on the pathological parameters. Report of the 22921 randomised trial conducted by the EORTC radiotherapy group. Pro ASCO Gastrointestinal Symposium 2004;A202.
  4. Bhagarva P, Smyczynzki M, Swanson W, Wassef W, Counihan T, Paterson J, et al. Preoperative chemoradiotherapy with weekly paclitaxel for localised rectal cancer. Pro ASCO 2003;A1485.
  5. Bosset J, Magnin V, Maingon M, Mantion G, Pelissier E, Mercier M, et al. Preoperative radiochemotherapy in rectal cancer: long term results of a phase II trial. Int J Radiat Oncol Biol Phys 2000;46:323–7.[CrossRef][Medline]
  6. Boulis-Wassif S, Gerard A, Loygue J, Camelot D, Buyse M, Duez N. Final results of a randomised trial on the treatment of rectal cancer with preoperative radiotherapy alone or in combination with 5-flurouracil followed by radical surgery. Cancer 1984;53:1811–8.[CrossRef][Medline]
  7. Carau B, Orru P, Orru S, Dessi M, Nagliati M, Lay G, et al. Neoadjuvant radiochemotherapy treatment in locally advanced rectal adenocarcinoma. Tumori 2003;89 (4 Suppl.):7–8.
  8. Carraro S, Roca E, Milano C, Pennella E, Sardi M, Rafailovici L, et al. Rectal cancer: preoperative radiochemotherapy with 5-FU, leucovorin and cisplatin. A three year follow up analysis. Pro ASCO 1999:A1073.
  9. Carraro S, Roca E, Cartelli C, Rafailovici L, Castillo Odena S, Wasserman E. Radiochemotherapy with short daily infusion of low dose oxaliplatin, leucovorin and 5FU in T3-T4 unresectable rectal cancer: a phase II IATTGI study. Int J Radiat Oncol Biol Phys 2002;54:397–402.[CrossRef][Medline]
  10. Chan A, Wong A, Langevin J, Jenken D, Heine J, Buie D, et al. Preoperative chemotherapy and pelvic radiation for tethered or fixed rectal cancer: a phase II dose escalation study. Int J Radiat Oncol Biol Phys 2000;48:843–56.[Medline]
  11. Chang H, Jian J, Cheng S, Liu M, Leu S, Wang F, et al. Preoperative concurrent chemotherapy and radiotherapy in rectal cancer patients. J Formos Med Assoc 1998;97:32–7.[Medline]
  12. Chari R, Tyler D, Anscher M, Russell L, Clary B, Hathorn J, et al. Preoperative radiation and chemotherapy in the treatment of adenocarcinoma of the rectum. Ann Surg 1995;221:778–87.[Medline]
  13. Chau I, Allen M, Cunningham D, Tait D, Brown G, Hill M, et al. Neoadjuvant systemic flurouracil and mitomycin C prior to synchronous chemoradiation is an effective strategy in locally advanced rectal cancer. Br J Cancer 2003;88:1017–24.[CrossRef][Medline]
  14. Chen E, Mohiuddin M, Brodowsky H, Fishbein G, Marks G. Downstaging of advanced rectal cancer following combined preoperative chemotherapy and high dose radiation. Int J Radiat Oncol Biol Phys 1994;30:169–75.[Medline]
  15. Ciabatoni A, Cavallaro A, Potenza A, Colli R, Maurizi F, Micciche F, et al. Preoperative concomitant radiochemotherapy with a 5-flurouracil plus folinic acid bolus in the combined treatment of locally advanced extraperitoneal rectal cancer: a long-term analysis on 27 patients. Tumori 2003;89:157–63.[Medline]
  16. Conzo G, Caraco C, Vacca R, Di Marzo M, Amore A, Muto P, et al. Neoadjuvant chemoradiotherapy in the treatment of rectal cancer: preliminary results. G Chir 2000;21:319–22.[Medline]
  17. De la Torre A, Ramos S, Valcarcel F, Candal A, Regueiro C, Romero J, et al. Phase II study of radiochemotherapy with UFT and low-dose oral leucovorin in patients with unresectable rectal cancer. Int J Radiat Oncol Biol Phys 1999;45:629–34.[CrossRef][Medline]
  18. Feliu J, Calvilio J, Escribano A, de Castro J, Sanchez M, Mata A, et al. Neoadjuvant therapy of rectal carcinoma with UFT-leucovorin plus radiotherapy. Ann Oncol 2002;13:730–6.[Abstract/Free Full Text]
  19. Fernandez-Martos C, Aparacio J, Bosch C, Torregrossa D, Campos J, Vicent J, et al. Pre-operative therapy with oraluracil and tegafur (UFT) and concomitant irradiation in operable rectal cancer. Preliminary results of a multicenter phase II study. Pro ASCO 2001;A590.
  20. Frykholm G, Pahlman L, Glimelius B. Combined chemo- and radiotherapy vs. radiotherapy alone in the treatment of primary, nonresectable adenocarcinoma of the rectum. Int J Radiat Oncol Biol Phys 2001;50:427–34.[CrossRef][Medline]
  21. Galizia E, Antognoli S, Bracci R, Grillo-Ruggieri F, Mantello G, Marmorale C, et al. Preoperative chemotherapy plus concomitant radiotherapy in rectal cancer patients: a phase II study. Pro ASCO 2002;A2374.
  22. Gerard J, Chapet O, Nemoz C, Romestaing P, Mornex F, Coquard R, et al. Preoperative concurrent chemoradiotherapy in locally advanced rectal cancer with high-dose radiation and oxaliplatin-containing regimen: the Lyon R0-04 phase II trial. J Clin Oncol 2003;21:1119–24.[Abstract/Free Full Text]
  23. Grann A, Feng C, Wong D, Saltz L, Paty P, Guillem J, et al. Preoperative combined modality therapy for clinically resectable uT3 rectal adenocarcinoma. Int J Radiat Oncol Biol Phys 2001;49:987–95.[CrossRef][Medline]
  24. Kim J, Kim J, Cho M, Song K, Yoon W. Preoperative chemoradiation using oral capecitabine in locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 2002;54:402–8.
  25. Kim N, Min J, Park J, Yun S, Sung J, Jung H, et al. Intravenous 5-flurouracil versus oral doxifluridine as preoperative concurrent chemoradiation for locally advanced rectal cancer: prospective randomised trials. Jpn J Clin Oncol 2001;31:25–9.[Abstract/Free Full Text]
  26. Klautke G, Kirchner R, Hopt U, Rainer F. Continuous infusion of 5FU and weekly irinotecan with concurrent radiotherapy as neoadjuvant treatment for locally advanced or recurrent rectal cancer. Pro ASCO 2001;A555.
  27. Kocakova I, Spelda S, Svoboda M, Vyzula R, Kocak I, Brancikova D, et al. Combined therapy of locally advanced rectal adenocarcinoma with capecitabine and concurrent radiotherapy. Pro ASCO 2003;A1295.
  28. Mermershtain W, Walfisch S, Koretz M, Geffen D, Cohen Y. Preoperative radiochemotherapy treatment in advanced rectal carcinoma. Pro ASCO 1998;A1144.
  29. Mehta V, Poen J, Ford J, Edelstain P, Vierra M, Bastidas, et al. Radiotherapy, concomitant protracted-venous-infusion 5-flurouracil and surgery for ultrasound-staged T3 or T4 rectal cancer. Dis Colon Rectum 2001;44:52–8.[CrossRef][Medline]
  30. Mehta V, Cho C, Ford J, Jambalos C, Poen J, Koong A, et al. Phase II trial of preoperative 3D conformal radiotherapy, protracted venous infusion 5-flurouracil, and weekly CPT-11 followed by surgery for ultrasound-staged T3 rectal cancer. Int J Radiat Oncol Biol Phys 2003;55:132–7.[CrossRef][Medline]
  31. Mohiuddin M, Regine W, John W, Hagihara P, McGrath P, Kennedy D, et al. Preoperative chemoradiation in fixed distal rectal cancer: dose time factors for pathological complete response. Int J Radiat Oncol Biol Phys 2000;46:883–8.[CrossRef][Medline]
  32. Ngan S, Burmeister B, Fisher R, Rischin D, Schache D, Kneebone A, et al. Early toxicity from preoperative radiotherapy with continuous infusion 5-flurouracil for resectable adenocarcinoma of the rectum: a phase II trial for the Trans-Tasman Radiation Oncology Group. Int J Radiat Oncol Biol Phys 2001;50:883–7.[CrossRef][Medline]
  33. Porter H, Anwar S, Grieve R, Carrington B, Shatwell W, Khoo V, et al. Concurrent raltitrexed and radiotherapy for locally advanced rectal carcinoma. Pro ASCO 2003;A1390.
  34. Roh M, Petrelli N, Wieand S, Colangelo L, Smith R, Mamounas E, et al. Phase III randomised trial of preoperative versus postoperative multimodality therapy in patients with carcinoma of the rectum (NSABP R-03). Pro ASCO 2001;A490.
  35. Ronzoni M, Cozzarini C, Villa E, San Raffaele H. Tumour downstaging and sphincter preservation with preoperative hyperfractionated radiation therapy and concurrent chemotherapy in locally advanced rectal cancer. Pro ASCO 2002;A2299.
  36. Seong J, Cho J, Kim N, Min J, Suh C. Preoperative chemoradiotherapy with oral doxifluridine plus low-dose oral leucovorin in unresectable primary rectal cancer. Int J Radiat Oncol Biol Phys 2001;50:435–9.[Medline]
  37. Tamberi S, Luppi G, Perrone A, Frezza G, Santantonio M, Emiliani E, et al. Preoperative 5-flurouracil (5-FU) in continuous infusion concurrent to radiotherapy and sphincter preservation in distal rectal adenocarcinoma: results of a multicentre study. Pro ASCO 2001;A2239.
  38. Tjandra J, Reading D, McLachlan S, Gunn I, Green M, McLaughlin S, et al. Phase II clinical trial of preoperative combined chemoradiation for T3 and T4 resectable rectal cancer. Dis Colon Rectum 2001;44:1113–22.[CrossRef][Medline]
  39. Uzcudun A, Batlle J, Velasco J, Santos M, Carpeno J, Grande A, et al. Efficacy of preoperative radiation therapy for resectable rectal adenocarcinoma when combined with oral tegafur-uracil modulated with leucovorin. Dis Colon Rectum 2002;45:1349–58.[CrossRef][Medline]
  40. Valentini V, Coco C, Cellini N, Picciocchi A, Fares M, Rosetto M, et al. Ten years of preoperative chemoradiation for extraperitoneal T3 rectal cancer: acute toxicity, tumor response, and sphincter preservation in three consecutive studies. Int J Radiat Oncol Biol Phys 2001;51:371–83.[Medline]
  41. Vicario G, Santori C, Manente P, Gava A, Pastorelli D, Bortolin M, et al. A phase II study of neoadjuvant chemoradiotherapy in patients with adenocarcinoma of the rectum. Pro ASCO 2002;A2363.
  42. Wiltshire K, Brierley J, Swallow C, Oza A, Cummings B, Ringash J, et al. Preoperative radiation with concurrent chemotherapy for resectable rectal cancer: effect of dose escalation on pathological complete response and wound complication rates. Pro ASCO Gastrointestinal symposium 2004;A291.
  43. Wong S, Sadasiwan C, Erickson B, Ota D, Mulkerin D, Thomas J, et al. A phase II trial of preoperative capecitabine and concurrent radiation for locally advanced rectal cancer. Pro ASCO Gastrointestinal symposium 2004;A281.
  44. Yoon W, Choi J, Kin J, Kim T, Lim K, Hwang B, et al. Enhanced tumoricidal effect of preoperative chemoradiation using capecitabine for locally advanced rectal cancer. Pro ASCO 2001;A2165.
  45. Janjan N, Crane C, Feig B, Cleary K, Dubrow R, Curley S, et al. Improved overall survival among responders to preoperative chemoradiation for locally advanced rectal cancer. Am J Clin Oncol 2001;24:107–12.[CrossRef][Medline]
  46. Valentini V, Coco C, Picciocchi A, Morganti A, Trodella L, Ciabattoni A, 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 Radiat Oncol Biol Phys 2002;53:664–74.[CrossRef][Medline]
  47. Francois Y, Nemoz C, Baulieux J, Vignal J, Grandjean J, Partensky C, 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 1999;17:2396–402.[Abstract/Free Full Text]



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