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JOURNAL READING

Pembimbing
Pembimbing :: dr.
dr. Bambang
Bambang sugeng,
sugeng, sp. b

QORRY AMANDA 01.209.5986


KOAS BEDAH FK UNISSULA SEMARANG
JOURNAL IDENTITY
Title
Title :Preoperative radiotherapy versus selective
selective postoperative
postoperative
chemoradiotherapy
chemoradiotherapy in patients with
with rectal
rectal cancer
cancer (MRC
(MRC CR07 and
and
NCIC-CTG
NCIC-CTG C016): a multicentre, randomised trial

Writers
Writers : David Sebag-Montefi ore, Richard J Stephens, Robert Steele,
John
John Monson,
Monson, Robert
Robert Grieve,
Grieve, Subhash Khanna,
Khanna, Phil
Phil Quirke,
Quirke, Jean
Jean
Couture,
Couture, Catherine
Catherine de Metz, Arthur Sun Myint, Eric Bessell, Gareth
Griffi
Griffi ths,
ths, Lindsay
Lindsay CC Thompson,
Thompson, Mahesh
Mahesh Parmar,
Parmar, on
on behalf
behalf of
of all
all the
the
trial
trial collaborators*
collaborators*

Published
Published date : March
March 2009
2009

Published
Published by : The Lancet of Oncology
BACKGROUND
Randomised controlled trials published before
1998 showed a high rate of local recurrence after surgery
Alone Loco-regional recurrence after resection of rectal cancer is
difficult to treat and is associated with severe debilitating
symptoms. The prognosis after a local recurrence is
poor, with a median survival of 1218 months

a reduction in local recurrence with


radiotherapy used either preoperatively
or postoperatively.
the Swedish rectal cancer trialwas the largest (1168 patients) and
showed that the addition of a 1-week (short) course of pelvic
radiation (25 Gy in five fractions) before surgery resulted in a
statistically significant reduction in local recurrence rate and
improvement in overall survival compared with surgery alone (at 5
years: local recurrence 11% vs27%, overall survival 58% vs48%).

Chemotherapy can also be added to radiotherapy; the


use of postoperative concurrent chemoradiotherapy
reduced local recurrence rates and improved survival
The consensus statement by the US National Institutes for Health in 1990
recommended postoperative chemoradiotherapy as standard treatment in
the USA for all patients with completely resected stage II or III rectal cancer.
Nevertheless, pelvic radiotherapy is associated with an increased risk of late
complications, including a substantial increase in bowel frequency and
incontinence and delayed healing of the perineal wound when an
abdominoperineal excision is done

Therefore, targeting radiotherapy to patients considered at high


risk of local recurrence is an attractive option, especially if the
number of such patients can be kept to a minimum
MAIN PURPOSE: PRIMARY OUTCOME:
to compare the use of The primary outcome
routine short-course measure was local
preoperative recurrence,
radiotherapy with irrespective of any
initial surgery and occurrence of distant
selective metastases.
postoperative SECONDARY
chemoradiotherapy OUTCOME:
reserved for patients Secondary outcome
who had involvement measures were overall
of the circumferential survival, disease-free
resection margin. survival, local-
recurrence-free
survival,
postoperative
morbidity
METHOD & MATERIAL
Eligible consenting patients were randomly
assigned to treatment groups by the MRC Clinical
Trials Unit by a minimisation procedure, with
stratification for surgeon, distance of distal tumour
extent from the anal verge, and WHO performance
status
Patients were assigned to either
a preoperative radiotherapy regimen of 25 Gy in five
consecutive daily fractions followed by surgery
(recommended to take place within 7 days of the last
fraction of radiotherapy), or to
a selected postoperative chemoradiotherapy regimen
of initialsurgery with selective postoperative
concurrent chemoradiotherapy of 45 Gy in 25
fractions with concurrent 5-fluorouracil (either
continuous infusion 200 mg/m per day or weekly bolus
5-fl uorouracil 300 mg/m and leucovorin 20 mg/m) for
patients with involvement of the circumferential
resection margin (1 mm).
Surgeons were encouraged to use total mesorectal excision, although it
was not mandated in the trial protocol.

This approach was already in clinical use in the UK at the time that the
trial was launched.

No formal training or accreditation programme was used for surgeons


participating in the trial.

a validated audit method to assess whether total mesorectal excision was


done, or to assess the quality of the surgical specimen, did not exist.

After randomisation, follow-up forms were required at 3, 6, 9, and 12


months, and then every 6 months to 3 years and yearly thereafter.

Patient-reported quality of life was collected with the validated


questionnaires SF36,and EORTC (European Organisation for Research and
Treatment of Cancer) quality-of-life questionnaire CR-38
DISCUSSION
Results show that both local control and disease
free survival are improved by
preoperativeradiotherapy compared with
selectivepostoperative chemoradiotherapy.
Three trials compared short-course preoperative
radiotherapy followed by surgery with surgery alone,
although 316 of the 557 patients in the Stockholm II
trial were also included in the Swedish Rectal Trial.

The pooled data of the remaining two trials show a


highly consistent and significant reduction in the
rate of local recurrence with the use of preoperative
radiotherapy (HR 046, 95% CI 038056; figure 3)
Both trials assessed short-course preoperativeradiotherapy
with a highly selective postoperative radiotherapy regimen.

The CR07 trial used postoperative concurrent chemo


radiotherapy, whereas the Dutch trial used radiotherapy
alone in the selective postoperative group. The combined
data from the CR07 trial and the Dutch trial (the two largest
adjuvant radiotherapy trials, totalling 3211 patients) show a
highly significant reduction in the rate of local recurrence
with the use of preoperative radiotherapy (HR 038, 95% CI
029049) when combined with total mesorectal excision
The preoperative radiotherapy regimen is also a very
cost-effective way to deliver treatment, since it
uses only five fractions of radiation.

Furthermore, evidence from the 13-year follow-up


from the Swedish rectal cancer trial, and data from
three meta-analyses, lend support to the view that
preoperative radiotherapy prevents a proportion of
patients from developing local recurrence rather
than merely delaying the event
Two
Two recent
recent phase
phase III
III trialshave
trialshave shown
shown aa significant
significant
reduction
reduction in
in local
local recurrence
recurrence with
with the
the use
use of
of preoperativeconcurrent
preoperativeconcurrent
chemoradiotherapy
chemoradiotherapy with
with 5-fluorouracil
5-fluorouracil and
and leucovorin
leucovorin compared
compared with
with long-
long-
course
course radiotherapy
radiotherapy alone.
alone.

AA further
further trial
trial has
has shown
shown aa significant
significant reduction
reduction in
in both
both local
local recurrence
recurrence
and
and late
late toxic
toxic eff
eff ects
ects in
in favour
favour of
of preoperativechemoradiotherapy
preoperativechemoradiotherapy
compared
compared with
with postoperativechemoradiotherapy.
postoperativechemoradiotherapy.

This
This finding
finding has
has affected
affected the
the US
US policy
policy of
of postoperative
postoperative chemoradiotherapy,
chemoradiotherapy,
with
with aa shift
shift to
to the
the use
use of
of preoperative
preoperative chemoradiotherapy
chemoradiotherapy in in selected
selected
patients.
patients. These
These results
results suggest
suggest that
that aa direct
direct comparison
comparison of
of short-course
short-course
preoperative
preoperative radiotherapy
radiotherapy and
and preoperative
preoperative chemoradiotherapy
chemoradiotherapy is is needed.
needed.
CRITICAL APPRAISAL
Abstrak

Consisted of 4 paraghraphs
Components : background, methods,findings, and interpretations
More than 250 words 328 words
No keywords mentioned
PRIMARY OUTCOME
Local Recurence 27 preoperative
radiotherapy vs 72
selectivepostoperative
Chemoradiotherapy
a reduction of 61% in the
relative risk of local
recurrence for patients
receiving preoperative
radiotherapy (hazard
ratio [HR] 039, 95% CI
027058, p<00001)
SECONDARY OUTCOME
Overall Survival Overall survival did not diff er between the
groups (HR 091, 95% CI 073113, p=040)
Disease Free Survival a relative improvement in disease-free survival
of 24% for patients receiving preoperative
radiotherapy (HR 076, 95% CI 062094,
p=0013)
Local Reccurence-Free Survival Comparison of the Kaplan-Meier curves (fi gure
2A) gives an HR of 039 (95% CI 027058;
p<00001), indicating a 61% relative reduction
in the risk of recurrence with preoperative
radiotherapy.
Post Operative Morbidity 147 disease-related events were recorded in
the preoperative radiotherapy group and 189 in
the selective postoperative chemoradiotherapy
group.

Comparison of the Kaplan-Meier curves (fi gure


2B) gives an HR of 076 (95% CI 062094;
p=0013), indicating a 24% relative reduction in
the risk of a disease-related event with
preoperative radiotherapy.
Bukti valid
Pertanyaan

Apakah alokasi pasien pada penelitian ini dilakukan Ya


secara acak?
Apakah pengamatan pasien dilakukan secara cukup Ya, dari 16
panjang dan lengkap? Maret 1998 5
Agustus 2005

Apakah semua pasien dalam kelompok yang diacak, Ya


dianalisis?
Apakah pasien dan dokter tetap blind dalam Tidak
melakukan terapi, selain dari terapi yang diuji?

Apakah kelompok terapi dan kontrol sama? Tidak; 674 allocated


to preoperative
radiotherapy, 676
allocated to
selective
postoperative CRT
aplikasi

APPLICABLE

Apakah pada pasien kita terdapat TIDAK


perbedaan bila dibandingkan dengan yang
terdapat pada penelitian sblmnya sehingga
hasil tersebut tidak dapat diterapkan pada
pasien kita?
Apakah pemberian terapi tersebut Ya
mungkin dapat diterapkan pada pasien
kita?
Apakah pasien memiliki potensi yang Ya
menguntungkan pemberian terapi tersebut
diterapkan?
RELATIVE RISK LOCAL RECURENCE Total
+ -
Preoperative 27 (4%) 647 (96%) 674 (100%)
radiotherapy
Postoperative 72 (10.65%) 604 (89.35%) 676 (100%)
chemoradiotherapy

Benefit Relative Risk Absolute Risk Number


Reduction Reduction Needed to
(RRR) (ARR) Treat (NNT)
Control Experimenta (EER-CER)/CER EER-CER 1/ARR
Event Rate l Event Rate
(CER) (EER)

72/676 27/674 0.64 0.07 14.28


= 0.11 = 0.04
RR : a / a+b : c / c+d = 27/674 : 72 /
676 = 0.36
Artinya : jika RR < 1 maka treatment
pemberian radiotherapy preoperative
mengurangi resiko kejadian rekurensi
karsinoma rekti.
ARR : 0.07
Artinya : keuntungan absolut dari
pemberian radiotherapy preoperative
karsinoma rekti adalah 7 % dalam
mengurangi terjadinya rekurensi
karsinoma rekti.
RRR : 0,64
Artinya : penurunan jumlah rekurensi
karsinoma rekti sebesar 64 % dalam
kelompok preoperatif radiotherapy
NNT : 14.28
Artinya : 14 pasien harus diberi
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