ARTICLE
Auteur(s) : Nicolas
Magné1, Jean-François Daisne2, Luigi
Moretti1, Dorothée Berben2, Nicolas
Meert3, Ruth Alen4, Samuel Bral4,
Ann Van Cleef5, Karin Haustermans2, Paul Van
Houtte1, Pierre Scalliet3
1Department of Radio-Oncology, Institut-Jules-Bordet,
Bruxelles, Belgium
2Department of Radiotherapy, Universitair Ziekenhuis
Gasthuisberg, Leuven, Belgium
3Department of Radiotherapy, Cliniques Universitaires
Saint-Luc, Brussel, Belgium
4Department of Radiotherapy, Universitair Ziekenhuis
Gent, Gent, Belgium
5Department of Radiotherapy, Onze Lieve Vrouwziekenhuis,
Aalst, Belgium
Article reçu le 8 Août 2008, accepté le 20 Octobre 2008
Colorectal carcinoma is the third cause of death from cancer
worldwide [1]. Rectal cancer is nearly 2.5 times less frequent
than colon cancer, and has a different natural history [2]. Despite
radical surgery, locoregional failure frequently occurs in patients
with transmural or node-positive rectal cancers [3]. Adjuvant
chemoradiation for rectal cancer is an established treatment that
improves clinical outcomes compared with surgical resection alone
in patients with locally advanced or lymph node-positive invasion.
Neoadjuvant chemoradiation has been increasingly used to improve
outcomes such as local control rates or sphincter preservation, and
pathologic response to neoadjuvant therapy might have prognostic
significance [4-7].
In 1995, a Peer Review Commission was initiated by the Belgian
Ministry of Health as part of a larger pilot project promoting
quality in medicine. In 1999, the Peer Review Committee performed a
survey of rectal cancer management including diagnostic procedures
and therapeutic approaches. Results were partly published in 2004
[8]. Furthermore, data from International Collaborative Groups
reported that management practices for patients with rectal cancer
have evolved over the last two decades [9-12]. Additionally, in an
attempt to achieve harmonious patient care, consensus conferences
have established guidelines in the USA and Europe [13, 14]. These
guidelines provide clinicians with precise recommendations for
patient management.
The aim of the present study was to perform a case-based peer
review and a general survey in the field of rectal cancer
management in order to reassess six years later the Belgian
practice.
Materials and methods
A general questionnaire and a practical case (description and
CT-images on a CD-Rom) were sent to the specialists in GI
radiotherapy in 16 different Belgian centers (with a good balance
between French – and Dutch-speaking hospitals and academic and
non-academic centres). Global management of the survey, analysis of
the questionnaire and comparison of the various plans based on the
test case, were carried out by the Belgian residents in radiation
oncology, in their 4th year of training, as an integral part of
their curriculum. Each of the eight residents discussed and
collected data for two centres. NM and JFD assumed analysis,
manuscript preparation and data centralization.
Survey of the practice in rectal cancer management
Based on a clinical case (described below), a questionnaire was
addressed to the radiation oncologists in charge of rectal cancer
management in 16 different Belgian hospitals. These 16 centres were
selected among the 25 Belgian centres of radiotherapy, with a
balance between academic and non-academic, public and private, and
French or Flemish speaking institutions. All 16 centres have
answered to the questionnaire. It took into account the past
questionnaire of the previous Peer Review Commission of 1999 and
questions involving diagnostic and staging procedure, radiation
techniques, use and types of chemotherapy, indications for
preoperative and adjuvant treatments, and the timing of surgery in
the treatment. In addition, based on the clinical case report and a
computed tomography (CT) scan of the abdomen and pelvis transmitted
by CD Rom, a treatment planning has been requested according to the
local common practice.
Case report
A 52-year-old male from Japanese origin presented with rectal
bleeding and pain. There was no family history of polyps or
carcinoma of the bowel, and no previous medical history. On digital
rectal examination (DRE), a suspicious mass was palpated at the
finger top. Tumor carcinoembryonic antigen marker (CEA) value was
slightly elevated to 5.2 ng/mL (laboratory normal limit is
2.5 ng/mL). Rectoscopy showed an exophytic, right-sided
semi-circular lesion in the middle third of the rectum. Pathology
showed an adenocarcinoma with an unspecified degree of
differentiation. The CT-scan of the abdomen and pelvis demonstrated
a middle third rectal tumour with a thickness of 14 mm
associated with centimetric perirectal lymph nodes. At endorectal
ultrasound examination, the rectal tumour extended through the
muscularis propria into the perirectal fat (3 cm diameter). No
distant metastases were detected. Clinical stage was cT3N1M0 (Stage
III according to the AJCC-UICC 6th edition classification).
Statistical analysis
Data regarding dose distribution homogeneities were entered into a
computerized database and analysed using SPSS 11 for Windows. After
transformation of the values to obtain gaussian samples, mean CTV
and PTV volumes were calculated and box-plots graphics were
analysed to detect any outlier. Mean minimal dose (Dmin)
to the CTV and the PTV were statistically compared to the 95% ICRU
level, and mean maximal dose (Dmax) to the CTV and the
PTV were statistically compared to the 107% ICRU level, both using
a single sample t-test. Alpha level of significance is at 0.05.
Results
General practice
In all 16 centres, there was a multidisciplinary treatment decision
with the systematic presence of gastro-enterologists, medical
oncologists, surgeons and radiation oncologists.
Staging procedure and work-up
Table 1 compares the results of the
staging procedures performed in 1999 to the current analysis. In
2005, all patients were assessed by endorectal ultrasound,
colonoscopy, CEA and an initial pathological diagnosis. Bone scan
was no longer prescribed in 2005, while pelvis MRI was prescribed
in half of the centres. FDG-PET was done in 2 out of 16.
The distance between the lower pole of the tumour and the anal
sphincter was systematically assessed in all centres with slight
differences between them. In 10 out of 16 centres by flexible
endoscopy under general anaesthesia plus DRE, 2/16 by MRI plus DRE
and 4/16 by DRE only. In all centres, the surgeon before
neoadjuvant treatment performed DRE.
Twelve out of 16 centres restaged the tumour after preoperative
treatment, before surgery: this was done by CT-pelvis in eight
centres, by endoscopy in nine centres and by both procedures in
four centres. Out of the four centres using only preoperative
radiotherapy (without concomitant chemotherapy), two did not
perform a reassessment.
After the end of therapy, surgery was planned within four to six
weeks (five centres), six to eight weeks (eight centres) and less
than one week (three centres). Two of these three centres have
initially performed a short duration course of preoperative
radiotherapy (25 Gy in one week).
Table 1 Recommended staging procedures at first peer
review in 1999 and up dated in 2005.
|
Peer review
|
Peer review
|
|
1999
|
2005
|
|
Number of centers investigated
|
24
|
16
|
|
Barium enema
|
5/24
|
6/16
|
|
Bone scan
|
6/24
|
0/16
|
|
CEA
|
24/24
|
16/16
|
|
Colonoscopy
|
20/24
|
16/16
|
|
CT-abdomen
|
ND
|
15/16
|
|
CT-brain
|
0/24
|
0/16
|
|
CT-pelvis
|
24/24
|
9/16
|
|
CT-thorax
|
5/24
|
4/16
|
|
Echo-endoscopy
|
15/24
|
16/16
|
|
FDG-PET
|
1/24
|
2/16
|
|
MRI (liver)
|
0/24
|
0/16
|
|
MRI (pelvis)
|
0/24
|
8/16
|
|
Rx-thorax
|
23/24
|
13/16
|
|
Ultrasound abdomen
|
ND
|
2/16
|
Theoretical treatment indication
For T1-2N0, the majority of centres did not prescribe a
preoperative treatment or rarely preoperative radiotherapy alone;
for T3N0, there was a trend favouring a preoperative
radiochemotherapy. Patients with T4N0 or any positive N were always
prescribed preoperative treatment. Almost, all centres offered a
combined chemoradiotherapy, regardless of the tumour location
(lower, mid, upper third) and the position of the involved nodes
(table 2).
If there was no preoperative treatment and the pathological
report of the surgical specimen shows a pT3 or pN+ tumour, all
centres prescribed a course of postoperative radiochemotherapy:
Dose prescribed was 45 Gy to the posterior pelvis in 25
fractions of 1.8 Gy (16 centres), with a boost of
5.4-9 Gy (eight centres), concurrently with a protracted
intravenous infusion of 5-fluorouracil 225 mg/m2
per day. After a preoperative treatment and the lack of
contra-indications for chemotherapy, postoperative adjuvant
chemotherapy was offered for pT4N0 and for pT any N+ (16 centres),
for high-grade T3N0 (12 centres) and for low-grade pT3N0 (three
centres).
Table 2 Peroperative strategy according to TNM status,
to node involvement in the mesorectum, to rectal tumor location (N
= 16 centers).
|
|
Preoperative attitude
|
|
Nothing
|
RT short course
|
RT long course
|
Radiochemotherapy
|
|
Rectal location
|
L/M/U
|
L/M/U
|
L/M/U
|
L/M/U
|
|
T1N0
|
13/14/15
|
2/2/1
|
0/0/0
|
1/0/0
|
|
T2N0
|
11/13/14
|
2/2/1
|
0/1/1
|
3/0/0
|
|
T3N0
|
0/0/2
|
3/5/4
|
1/2/2
|
12/9/8
|
|
T4N0
|
0/0/0
|
0/0/0
|
0/0/1
|
16/15/15
|
|
Nodes involvement in the mesorectum
|
|
T1N1-2
|
1/1/2
|
2/2/1
|
0/1/1
|
13/12/12
|
|
T2N1-2
|
0/0/2
|
2/2/0
|
0/1/1
|
14/13/13
|
|
T3N1-2
|
0/0/0
|
1/1/1
|
0/0/2
|
15/15/13
|
|
T4N1-2
|
0/0/0
|
0/0/0
|
0/0/1
|
16/16/15
|
|
Nodes outside of the mesorectum
|
|
T1N1-2
|
1/1/2
|
1/1/0
|
0/1/1
|
14/13/13
|
|
T2N1-2
|
0/0/1
|
1/1/0
|
0/1/1
|
15/14/14
|
|
T3N1-2
|
0/0/0
|
0/0/0
|
0/0/2
|
16/16/14
|
|
T4N1-2
|
0/0/0
|
0/0/0
|
0/0/1
|
16/16/15
|
Clinical case
Treatment indication
Preoperative radiochemotherapy was proposed in 13/16 centres and
preoperative radiotherapy alone in 3/16 centres. Radiation therapy
was delivered to the posterior pelvis at a dose of 45 Gy to
the tumor (GTV) and to the whole pelvis (PTV including CTV plus
security margin) in 14 centres, with 1.8 Gy daily fractions,
five times a week. Two centres used an exclusive preoperative
radiation to a total dose of 25 Gy (five fractions of
5 Gy). Radiotherapy was always delivered with a linear
accelerator. The chemotherapy regimen was either a protracted
intravenous infusion of 5-fluorouracil 225 mg/m2
per day, by portable ambulatory infusion pump during the entire
period of pelvic irradiation (for 11 centres) or an intravenous
bolus of 5-fluorouracil 400 mg/m2 within two hours
of radiation on days 1-4 during the 1st and 5th weeks of radiation
plus an intravenous bolus of leucovorin 20 mg/m2
per day, immediately before each fluorouracil dose on days 1-4
during the 1st and 5th weeks of radiation (two centres).
Radiotherapy techniques and dosimetry study
Most radiotherapy departments were treating their patients in prone
position (12/16), using contrast medium (11/16) during simulation
in order to better delineate the target volume and organs at risk.
More than half of the centres use belly-board (8/16) or any sort of
device (13/16) to reduce the irradiated bowel volume [21].
Conformal radiotherapy was performed in 14 out of the 16 centres.
Thirteen out of 16 used a minimum of three fields a day (L-R-PA).
Fourteen out of 16 had a three-dimensional CT (3D CT)
reconstruction for volumes delineation, planning and dose
calculation.
The following nodal areas were considered “at risk” and included
in the CTV or encompassed by the field borders (when no delineation
was performed): pararectal lymph nodes, iliaca interna lymph nodes
and presacral lymph nodes (16/16 centres), obturia interna lymph
nodes (6/16), iliaca communis lymph nodes (3/16) and iliaca externa
lymph nodes and para-aortic lymph nodes (0/16). In 12/16, bladder
and small intestine were considered as organs at risk and
delineated. Lymph nodes and organs at risk were delineated
according to anatomical definitions.
14 and 10 centres delineated the CTV and PTV, respectively,
while five centres draw also the GTV. The geometric mean value for
CTV volume was 438 cc (IP 95% [232; 830]) (figure 1). No outlier was
detected at box-plot analysis. The geometric mean value for PTV
volume was 870 cc (IP 95% [608; 1534]) (table 3). One outlier was detected at box-plot
analysis (1396 cc). Major differences between centres were
attributable to the different treatment volumes of the
lymphatics.
All the institutions considered the reference dose at the
isocentre (ICRU 50). Mean Dmin to CTV and mean
Dmax to CTV and PTV were not found to be statistically
different from respective ICRU levels of –5% to +7% (P > 0.05).
However, mean Dmin to PTV (92% – range [86.0-95.3%]
was found to be significantly smaller than 95% (P = 0.02). This
highlights a partial non-compliance to ICRU reports 50 and 62
recommendations about dose homogeneities. This would perhaps be
improved if all centres performed a delineation of the PTV.
Table 3 Dose-specifications for CTV and PTV expressed
as a percentage of the reference dose at ICRU point.
|
Mean
|
Median
|
S.D.
|
Range
|
|
CTV: maximal dose
|
104.2
|
104.0
|
2.7
|
100.0-108.5
|
|
CTV: minimal dose
|
95.2
|
95.0
|
1.5
|
93.0-100.0
|
|
PTV: maximal dose
|
106.5
|
106.5
|
2.1
|
102.9-108.5
|
|
PTV: minimal dose
|
92.0
|
95.0
|
5.2
|
86.0-95.3
|
Discussion
To improve the treatment quality, it is helpful to use guidelines
and treatment protocols written by a multidisciplinary tumour
board, with a consensus between the different specialties
concerned. Moreover, peer review is a powerful quality assurance
tool driven by the profession. It is well accepted as long as it is
based on education rather than repression. Peer review and feedback
data have also been shown to bring the physicians to a critical
reflection on their own practice and, if necessary, to urge them to
adjust these practices [8, 15].
The 1999 Belgian survey showed that, out of 24 centres, 19 had a
systematic multidisciplinary tumour board and they recommend a
staging procedure including proctosigmoidoscopy, CT pelvis, liver
imaging and CEA. In 2005, all 16 centres performed a staging
procedure based on the international consensus. For staging and
restaging, contrast-enhanced CT was usually used, which is
sub-optimal since endorectal ultrasound or MRI are documented as
being more accurate [16]. In specialised centres, the endorectal
ultrasound may be preferred. The role and the place of PET-Scan in
the strategy are still to be determined. A large majority of
centres (12/16) restaged after the initial preoperative treatment,
as recently proposed by Chan et al. and others: the
pathological stage after neoadjuvant treatment has been reported to
strongly predict survival [17, 18].
Most of the centres followed the long time interval strategy
between preoperative treatment and surgery (four to eight weeks).
Indeed, one trial reported the impact of the delay between the end
of preoperative radiotherapy and surgery, comparing a short (two
weeks) to a long (six to eight weeks) interval. They observed a
higher proportion of patients with a clinical tumour response and
pathological down staging after a long interval; they defend the
opinion that such down staging is beneficial to the conservative
treatment [19].
In 1990, the National Institute of Health Consensus Conference
established adjuvant radiotherapy with chemotherapy as the standard
of care to achieve regional control of stage II and III rectal
cancer [20, 21]. In a recent meta-analysis, preoperative
radiotherapy with doses in excess of 30 Gy [22] reduced the
risk of local recurrences for resecable rectal cancer [13]. Short
preoperative radiation schedules seem to be at least as effective
as longer schedules [7, 12, 23]. The Swedish Rectal Cancer Trial
even demonstrated an advantage in overall survival with the
short-course of preoperative radiation regimen (5 × 5 Gy), but
it also lead to more sexual dysfunction, slower recovery of bowel
function and impaired daily activity [24, 25]. Today, preoperative
radiochemotherapy is considered a very efficient approach for down
staging the tumour and avoiding local failure as seen in recent
European and American phase III trials [26-30]. In the 1999 survey,
all radiotherapists proposed to perform a preoperative radiotherapy
with or without chemotherapy for T3 or N1 tumours. Seventeen
centres proposed a preoperative radiochemotherapy for T4 tumours.
In case of a combined treatment, the radiotherapy schedule was
always a long course delivering a total dose of 45 to 50 Gy,
in 25 fractions. In the 2005 Questionnaire, the majority of the
centres proposed for T3-4 N0 or any positive N a preoperative
radiochemotherapy approach. Currently, there is a trend in Belgium
to enlarge the indication of radiochemotherapy. The difference
between the two surveys reflects the evolution of the practice and
the impact of some recent publications.
The indications for adjuvant therapy for rectal cancer are based
on the pattern of failure after surgery. In 1999, there was a
consensus among radiotherapists for all pT3 and/or pN1 staged
patients. Furthermore, an adjuvant radiochemotherapy approach was
required in all cases where no preoperative treatment was given. In
2005, there was still a consensus for indications and for a long
conventional course of radiotherapy but the best chemotherapy
regimen is still not defined.
The dose inhomogeneity in the PTV was not in line with the ICRU
Reports 50 and 62 allowing –5/+7% of dose variation. Also there was
a wide variation in CTV and PTV volumes among the 16 centres. There
is thus room for improvement in the technical aspect of
radiotherapy for rectum cancer in Belgium. Importantly to note,
wide variations in CTV delineations represent one of major
challenges for radiotherapist community in order to harmonize
treatment protocol. A major question is how a PTV can be
defined and used by all radiation oncologists [31]. A work is
currently ongoing within the Belgian Society of Radiation Oncology
(ABRO-BVRO) to achieve consensus at the federal level regarding the
definition and delineation of the CTV. It is part of a broader
project including all aspects of rectum cancer treatment including
the staging procedure, the quality of the surgery, the process of
the specimen by the pathologist, and the use of chemotherapy (the
PROCARE project).
Acknowledgements
The authors thank the following Drs P. Barbier from the AZ
Sint-Maarten, Duffel; T. Boterberg from the UZ Gent, Gent; B.
Coster from Hôpital Saint-Joseph, Gilly; S. Cvilic from the
Clinique Saint-Jean, Bruxelles; N. De Becker from the Clinique
Sainte-Elisabeth, Bruxelles; L. Gilbeau from Centre Hospitalier
Jolimont, La Louvière; K. Haustermans from UZ Gasthuisberg,
Leuven; A.-R. Henry from the CHU Vésale, Charleroi; N. Lombard from
CHU de Liège, Liège; A. Maes from Virga Jesseziekenhuis, Hasselt;
C. Mahin from the Institut Jules-Bordet, Bruxelles, P. Scalliet
from the Cliniques Universitaires Saint-Luc, Bruxelles; K.
Vandeputte from the Clinique Sainte-Elisabeth, Namur; L. Verbeecke
from OL Vrouwziekenhuis, Aalst; V. Vinh-Hung from the AZ-VUB,
Bruxelles, R. Weytjens from AZ Sint-Augustinus, Antwerpen for their
kind and important participation.
References
1 Fietkau R, Zettl H, Klocking S, Kundt G.
Incidence, therapy and prognosis of colorectal cancer in different
age groups. A population-based cohort study of the Rostock
Cancer Registry. Strahlenther Onkol 2004 ; 180 : 478-87.
2 Bosset JF, Pelissier E, Arbez-Gindre F,
Mantion G, Camelot G, Gillet M, et al. Cancers
of the rectum: predictive factors for locoregional recurrence.
Multifactorial study. Gastroenterol Clin Biol 1986 ; 10 :
525-6.
3 Bosset JF, Magnin V, Maingon P, Mantion G,
Pelissier EP, 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.
4 Bosset JF, Pelissier EP, Mantion G,
Horiot JC, Pavy JJ. Concomitant preoperative
radiochemotherapy for rectal cancers. Ann Chir 1996 ;
50 : 302-10.
5 Fritzmann J, Hunerbein M, Slisow W,
Gellerman J, Wust P, Rau B. Influence of
preoperative (hyperthermic) radiochemotherapy on manometric anal
sphincter function in locally advanced rectal cancer. Strahlenther
Onkol 2004 ; 180 : 281-8.
6 Gerard JP, Buyse M, Nordlinger B,
Loygue J, Pene F, Kempf P, et al. Preoperative
radiotherapy as adjuvant treatment in rectal cancer. Final results
of a randomized study of the European Organization for Research and
Treatment of Cancer (EORTC). Ann Surg 1988 ; 208 :
606-14.
7 Kapiteijn E, Marijnen CAM, Nagtegaal ID,
Putter H, Steup WH, Wiggers T, et al.
Preoperative radiotherapy radiotherapy combined with total
mesorectal excision for respectable rectal cancer. N Engl J Med
2001 ; 345 : 638-46.
8 Beauduin M, Deneufbourg JM, De Neve W,
Hermans J, Hoornaert MT, Scalliet P, et al. The
management of rectal cancer in Belgium: a survey of our practice.
Acta Gastroenterol Belg 2004 ; 67 : 9-13.
9 Arnaud JP, Nordlinger B, Bosset JF,
Boes GH, Sahmoud T, Schlag PM, et al. Radical
surgery and postoperative radiotherapy as combined treatment in
rectal cancer. Final results of a phase III study of the European
Organization for Research and Treatment of Cancer. Br J Surg
1997 ; 84 : 352-7.
10 Rodel C, Sauer R. Radiotherapy and concurrent
radiochemotherapy for rectal cancer. Surg Oncol 2004 ;
13 : 93-101.
11 Sauer R, Becker H, Hohenberger W,
Rodel C, Wittekind C, Fietkau R, et al.
Preoperative versus postoperative chemoradiotherapy for rectal
cancer. N Engl J Med 2004 ; 351 : 1731-40.
12 Sauer R, Fietkau R, Wittekind C, Rodel C,
Martus P, Hohenberger W, et al. Adjuvant vs.
neoadjuvant radiochemotherapy for locally advanced rectal cancer:
the German trial CAO/ARO/AIO-94. Colorectal Dis 2003 ;
5 : 406-15.
13 Figueredo A, Zuraw L, Wong RK, Agboola O,
Rumble RB, Tandan V, et al. The use of preoperative
radiotherapy in the management of patients with clinically
resectable rectal cancer: a practice guideline. BMC Med 2003 ;
1 : 1.
14 Gerard JP. Radiotherapy in the conservative treatment of
rectal cancer. Evidence-based medicine and opinion. Radiother Oncol
2005 ; 74 : 227-33.
15 Kouloulias VE, Bosset JF, van Tienhoven G,
Davis BJ, Pierart M, Poortmans P, et al.
European Organization for Research and Treatment of Cancer. Quality
assurance in the EORTC 22921 trial on preoperative radiotherapy
with or without chemotherapy for resectable rectal cancer:
evaluation of the individual case review procedure. Eur J Cancer
2002 ; 38 : 1849-56.
16 Wallengren NO, Holtas S, Andrén-Sandberg A,
Jonsson E, Kristofferson DT, McGill S. Rectal
carcinoma: double-contrast MR imaging for preoperative staging.
Radiology 2000 ; 215 : 108-14.
17 Chan AKP, Wong A, Jenken D, Heine J,
Buie D, Johnson D. Post-treatment 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 :
665-77.
18 Reerink O, Verschueren RC, Szabo BG,
Hospers GA, Mulder NH. A favourable pathological stage
after neoadjuvant radiochemotherapy in patients with initially
irresectable rectal cancer correlates with a favourable prognosis.
Eur J Cancer 2003 ; 39 : 192-5.
19 Francois Y, Nemoz CJ, Baulieux J,
Vignal J, Grandjean JP, Partensky C, et al.
Influence of the interval between preoperative radiation therapy
and surgery on down staging and on the rate of sphincter-sparing
surgery for rectal cancer: the Lyon R90-01 randomized trial. J Clin
Oncol 1999 ; 17 : 2396-402.
20 Colorectal Cancer Collaborative Group. Adjuvant radiotherapy
for rectal cancer: a systematic overview of 8507 patients from 22
randomized trials. Lancet 2001 ; 358 : 1291-304.
21 NIH consensus conference. Adjuvant therapy for patients with
colon and rectal cancer. JAMA 1990 ; 264 : 1444-50.
22 Gerard JP, Chapet O, Nemoz C, Hartweig J,
Romestaing P, Coquard R, et al. Improved sphincter
preservation in low rectal cancer with high-dose preoperative
radiotherapy: the lyon R96-02 randomized trial. J Clin Oncol
2004 ; 22 : 2404-9.
23 Bujko K, Nowacki MP, Nasierowska-Guttmejer A,
Michalski W, Bebenek M, Pudelko 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.
24 King M, Tolan S, Giridharan S,
McConkey C, Hartley A, Geh JI. Late toxicity after
short-course preoperative radiotherapy and total mesorectal
excision for resectable rectal cancer. Clin Oncol (R Coll Radiol)
2003 ; 15 : 233-6.
25 Marijnen CAM, van de Velde CJH, Putter H, van
den Brink M, Maas CP, Martijn H, et al. 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 2005 ; 23 :
1847-58.
26 Bosset JF, Calais G, Daban A, Berger C,
Radosevic-Jelic L, Maingon P, et al. Preoperative
chemoradiotherapy versus preoperative radiotherapy in rectal cancer
patients: assessment of acute toxicity and treatment compliance.
Report of the 22921 randomised trial conducted by the EORTC
Radiotherapy Group. Eur J Cancer 2004 ; 40 : 219-24.
27 Bosset JF, Calais G, Mineur L, Maingon P,
Radosevic-Jelic L, Daban A, et al. Does the addition
of chemotherapy (ct) to preoperative radiotherapy (preoprt)
increase the pathological response in patients with rectal cancer:
report of the 22921 EORTC phase III trial. Proc Am Soc Clin Oncol
2004 ; (abstract 3504).
28 Gerard JP, 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.
29 Gerard JP, Romestaing P, Chapet O,
Baulieux J. Overview of the role of preoperative radiotherapy
to increase sphincter preservation for rectal cancer. Front Radiat
Ther Oncol 2004 ; 38 : 24-7.
30 Roh MS, Petrelli N, Wieand S,
Colangelo L, Smith R, Mamounas E, et al. Phase
III randomized trial of preoperative versus postoperative
multimodality therapy in patients with carcinoma of the rectum
(NSABP R-03). Proc Am Soc Clin Oncol 2001 : 20 ;
(Abstract 123).
31 Letschert JG, Lebesque JV, Aleman BM,
Bosset JF, Horiot JC, Bartelink H, et al. The
volume effect in radiation-related late small bowel complications:
results of a clinical study of the EORTC Radiotherapy Cooperative
Group in patients treated for rectal carcinoma. Radiother Oncol
1994 ; 32 : 116-23.
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