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Original Article
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Kullathorn ephamongkhol, M.D., M.Sc.*, Arb-aroon Lertkhachonsuk, M.D., MMEd.**, Chomporn Sitathanee,
M.D.***, Petch Alisanant, M.D.****, Napapat Amornwichet, M.D., Ph.D.****, Chonlakiet Khorprasert, M.D.****,
Jidapa Bridhikitti M.D.*****, Pornpim Korpraphong, M.D.******, Kobkun Muangsomboon, M.D.******,
Sith
Phongkitkarun, M.D.*******, Saowanee Srirattanapong, M.D.*******, Duangkamon Prapruttam, M.D.*******,
aworn Dendumrongsup, M.D.********, Kewalee Sasiwimonphan, M.D.*********,
Chamnan Tanprasertkul, M.D.,
Ph.D.**********,***********, Mantana Dhanachai, M.D., MS.c.***,
Jayanton Patumanond, M.D., Dr.Sc.************,
Jiraporn Setakornnukul, M.D.*
*Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, ailand, **Gynecological
Oncology Unit, Department of Obstetrics and Gynecology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, ailand,
***Division of Radiation and Oncology, Department of Diagnostic and erapeutic Radiology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University
10400, Bangkok, ailand, ****Division of erapeutic Radiology and Oncology, Department of Radiology, King Chulalongkorn Memorial Hospital, Faculty
of Medicine, Chulalongkorn University, Bangkok 10330, ailand, *****Division of Radiation Oncology, Department of Radiology, Faculty of Medicine,
Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Songkhla 90110, ailand. ******Division of Diagnostic Radiology, Department of Radiology,
Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, ailand, *******Diagnostic Radiology Unit, Department of Diagnostic and
erapeutic Radiology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University 10400, Bangkok, ailand, ********Abdominal Imaging Section,
Department of Radiology, Faculty of Medicine, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Songkhla 90110, ailand, *********Division
of Diagnostic Radiology, Department of Radiology, King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University, Bangkok
10330, ailand, **********Minimally Invasive Gynecologic Unit, Department of Obstetrics and Gynecology, ammasat University, Pathum ani 12120,
ailand, ***********Center of Excellence in Applied Epidemiology, ammasat University, Pathum ani 12120, ailand, ************Center for Clinical
Epidemiology and Clinical Statistics, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ailand.
Propensity Score Matched Study of Tri-Weekly vs.
Weekly Platinum-Based Chemotherapy Concurrent
with Radiotherapy in the Treatment of Locally
Advanced Cervical Cancer
Corresponding author: Jiraporn Setakornnukul
E-mail: jiraporn.set@mahidol.ac.th
Received 23 December 2021 Revised 13 February 2022 Accepted 21 February 2022
ORCID ID: https://orcid.org/0000-0002-7201-0377
http://dx.doi.org/10.33192/Smj.2022.31
ABSTRACT
Objective: To compare tumor control and toxicity between tri-weekly chemotherapy and weekly platinum-based
chemotherapy in locally advanced cervical cancer using the propensity score matching method.
Materials and Methods: DESIGN: Retrospective cohort with propensity score matched population. SETTING: Four
university hospitals. PARTICIPANTS: 781 advanced local cervical cancer patients. INTERVENTION: tri-weekly
platinum-based chemoradiotherapy versus weekly chemoradiotherapy OUTCOMES: Overall survival (OS), local
recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS),
and toxicity, including hematological and renal toxicity.
Results: Overall median follow-up time was 59.5 months. Aer the propensity score matching process was completed,
326 patients were analyzed (163 in each group). e ve-year OS was 66% and 64% (p 0.630); ve-year LRFS was
85% and 81% (p 0.209); ve-year RRFS was 89% and 94% (p 0.307); and ve-year DMFS was 75% and 79% (p 0.420)
in the tri-weekly and weekly groups, respectively. e patients in the tri-weekly and the weekly group had grade 2
-3 neutropenia (10.5% vs 2.5%). e other toxicities appeared to be similar in both groups in terms of white blood
count, platelet and creatinine.
Conclusion: ere was a potential small benet of local control (4%) and overall survival (2%) with the tri-weekly
regimen but we could not demonstrate statistical signicance. However, this came at the price of an increase of
7% to 8% in grade 2-3 neutropenia.
Keywords: Cervical cancer; chemotherapy; radiotherapy; weekly regimen; tri-weekly regimen (Siriraj Med J 2022;
74: 245-255)
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INTRODUCTION
A 1999 US National Cancer Institute announcement
dened concurrent platinum-based chemotherapy with
radiotherapy as the standard of care for women with
locally advanced cervical cancer due to approximately
10% added survival benet aer ve years without a
signicant increase in late toxicities.
1
is was based on
the results of ve randomized controlled trials.
2-4,5,6
Despite this, the frequency of the platinum-based
regimen remains heterogeneous and routine chemotherapy
is dierent among hospitals. For example, some hospitals
administer weekly chemotherapy sessions whereas
others give tri-weekly chemotherapy. To compare these
treatment methods, many randomized controlled have
been carried out.
7-14
Interestingly, most of the evidence
remains conicting in terms of both tumor control and
toxicity. For example, a randomized controlled trial from
the University of Ulsan, Korea in 2008
13
showed that
the weekly regimen not only improved compliance but
was comparable with the tri-weekly regimen in response
and survival rate. On the other hand, a collaborative
randomized controlled trial by the Korea Institute of
Radiological and Medical Sciences, Dongnam Institute of
Radiological and Medical Sciences and National Cancer
Institute, Korea
12
showed that the tri-weekly regimen
was 20% more eective in terms of overall survival and
had less grade 3-4 neutropenia than the weekly regimen.
Moreover, evidence from meta-analyses looking at
the same question is also conicting. Zhu J et al,
15
carried
out a meta-analysis based on six randomized controlled
trials and two retrospective studies. It showed that the
tri-weekly regimen was superior to the weekly regimen
only in local recurrence but not overall survival. e
same results were reported in a recent meta-analysis
16
based on eight randomized controlled trials. Meanwhile,
a meta-analysis was also carried out by Petrelli et
al,
17
based on four randomized controlled trials and
four retrospective studies. Its results showed that the
platinum-based combined therapy should be the preferred
treatment over weekly regimen due to benets in overall
survival.
As a result, there are dierent policies for the weekly
and tri-weekly regimen. e routine regimen at the Radiation
Oncology Division at Siriraj Hospital is weekly cisplatin
(40 mg/m
2
) or carboplatin (AUC2), but some hospitals
have a routine tri-weekly regimen of cisplatin (75-100
mg/m
2
) (or carboplatin AUC5) with or without 5FU. We
are still waiting for high-quality evidence, notably results
of the Tri-weekly Cisplatin Based Chemoradiation in
Locally Advanced Cervical Cancer (TACO) trial (Clinical
Trials. gov Identier: NCT01561586). In the meantime,
we still require evidence for solving this issue. Hence,
we collected data from a multicenter in ailand where
locally advanced cervical cancer patients underwent
concurrent chemoradiotherapy. is could help provide
a suitable answer to a controversial issue with the help
of advanced statistical analysis, such as propensity score
matching that can simulate pseudo randomization by
matching pre-treatment variable factors.
MATERIALS AND METHODS
We used retrospective cohort data from a multicenter
in ailand (Siriraj Hospital (SI), Ramathibodi Hospital
(RA), King Chulalongkorn Memorial Hospital (CU) and
Songklanagarind Hospital (PSU). We recruited patients
with squamous cell carcinoma, adenocarcinoma, or
adenosquamous carcinoma of locally advanced cervical
cancer who were denitively treated with concurrent
chemoradiotherapy between Jan 2007 to Dec 2015. For
staging purposes, all patients underwent a CT scan with
contrast media of the whole abdomen, chest X-ray and
cystoscopy. Diagnostic radiologists in each hospital
newly reviewed the lymphadenopathy status according
to the pelvic lymphatic pathway.
18,19
Depending on the
policy of each hospital, a weekly or tri-weekly regimen of
cisplatin or carboplatin concurrently with radiotherapy
was given to the patient. Generally, 46-50 Gy of external
beam radiotherapy and 4 fractions of each 6.5 to 7.0 Gy
high dose rate brachytherapy were routinely prescribed.
For chemotherapy, usually, the clinical policy of SI, CU
and PSU is to give cisplatin weekly whereas RA gives
cisplatin tri-weekly. Additionally, Siriraj Hospital may
also adhere to the weekly carboplatin regimen as it is the
preference of some radiation oncologists regardless of
the patient’s performance status. e main outcome of
this study was overall survival. e secondary outcomes
were local-recurrence free survival, regional-recurrence
free survival and distant metastasis-free survival, which
were dened as rst day of radiotherapy to the date of
rst failure at cervical area, regional pelvic or paraaortic
lymph node and visceral distant metastases or lymph
node metastases above the diaphragm respectively.
Hematological toxicity (hemoglobin, white blood cell
count, neutrophil count and platelet) and renal toxicity in
the maximum grade of each patient were also reported.
Sample size
A randomized controlled trial from Korea
12
showed
that the tri-weekly regimen was more eective in overall
survival. is study reported a hazard ratio of 0.375.
When using this hazard ratio, 0.05 type I error and
80% statistical power, the sample size contained only 38
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patients in each arm. However, we planned to include
more patients as per our data availability.
Statistical analysis
In order to eliminate the selection bias of weekly
or tri-weekly chemotherapy regimen, we performed a
propensity score-matching analysis. is method is based
on balancing baseline characteristics of patients to simulate
randomization. eoretically, the best propensity score
came from factors that clinicians unfairly selected in the
weekly or tri-weekly regimen, such as patient or tumor
characteristics before treatment, especially pelvic or
para-aortic lymph nodes. In this study, we used the new
2018 FIGO stage, which included pelvic and para-aortic
lymphadenopathy status, histology, tumor grade, tumor
size, age, initial hemoglobin and hydronephrosis status.
For this purpose, we used MatchIt package version 3.02
in R soware version 4.05. Logistic regression with the
factors above was used to predict the linearized propensity
score. We then used this score in the MatchIt function
with the nearest method with varying caliper distances.
We further proved whether this procedure worked by
comparing baseline characteristics before and aer the
propensity score-matched procedure.
Aer we got the matched population, we also explored
whether the factors aer the start of the treatment were
well-balanced, especially the chemotherapy regimen
(cisplatin or carboplatin). We aimed to control this
additional confounder in non-parametric analysis. For
time-to-event analysis, we used the Kaplan Meier method
and log-rank test to determine the hypothesis. Non-
parametric analysis was performed to show a dierence
with 95% condence interval. For toxicity comparison,
we used the Fisher exact test to test the hypothesis.
Institutional Review Board Statement: e study was
conducted according to the guidelines of the Declaration
of Helsinki, and approved by the Institutional Review
Board of Faculty of Medicine Siriraj Hospital, Mahidol
University (Si 312/2016).
RESULTS
e patient characteristics before and aer the
propensity score matching process is shown in Table 1.
Missing data were in only histopathological grade,
which was available 80%. Before the matching process,
a total of 781 patients (618 in the weekly group and 163
patients in the tri-weekly group) were compared. e
patients in the tri-weekly group seemed to have a better
prognosis in terms of 2018 FIGO stage. For example, less
pelvic lymph node metastases (stage IIIc1, 20.2%) were
observed in the tri-weekly group, compared with the
weekly group (stage IIIc1, 34.3%). Aer the propensity
score matching process was completed (163 patients
in the weekly group and 163 patients in the tri-weekly
group), there was a similar prognosis, especially in terms
of FIGO staging. e pelvic lymph node metastases were
only 20.2% in both the weekly and tri-weekly groups.
Also, the proportion of histology was very similar in
terms of adenocarcinoma (22.1% in the weekly group
and 22.7% in the tri-weekly group). Furthermore, age,
tumor type, tumor size, tumor grade, initial hemoglobin
and also any side eects of hydronephrosis were better
balanced in both groups (Table 1). Despite the balance
in these prognostic factors, the chemotherapy regimens
(cisplatin or carboplatin) were dierent in both groups.
Cisplatin was given to half of the patients (56%) in the
weekly group, but almost all the (96%) patients in the tri-
weekly group. is dierence was then further adjusted
in a statistical analysis.
e overall median follow-up time was 59.5 months.
e follow-up rate for disease recurrence status and
for death status was 87% and 100% respectively. For
tumor control outcome, the tri-weekly group showed
an unadjusted non-statistically small benet in overall
survival (Fig 1A). is small benet was only 2%-3% as
per the follow-up time (Supplementary Fig S1). Aer
chemotherapy regimen (cisplatin or carboplatin) adjustment,
this small dierence disappeared and the survival curve
seemed to cross each other (Fig 1B). Interestingly, the
tri-weekly group showed better local recurrence-free
survival (Fig 2A). is dierence was about 6%-7% in
the rst two years of follow-up and about 3%-4% in the
third to h year (Supplementary Fig S2). Unfortunately,
with our limited sample size, a statistical dierence could
not be detected. Again, aer chemotherapy regimen
adjustment, this dierence disappeared (Fig 2B). For
regional recurrence-free survival (Fig 3A) and distant
metastasis-free survival (Fig 4A), the dierence between
the weekly group and tri-weekly group was small and
not consistent with the follow-up time (Fig 3B and Fig
4B). Also, the adjustment of chemotherapy regimen
(Supplementary Fig S3 and Fig S4) showed no signicant
change from unadjusted analysis.
Toxicity outcome was available for 96% of study
population. For grade 2 or greater toxicity (Table 2),
the patients in the tri-weekly group had more absolute
neutrophil count toxicity (10.5%), when compared
to patients in the weekly group (2.5%). On the other
hand, patients in the tri-weekly group seemed to have
less hemoglobin toxicity (29.4%) when compared to
patients in the weekly group (33.8%). ese results are
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TABLE 1. Patient characteristics before and aer propensity score matching.
Before Propensity score Matching After Propensity score Matching
Patient Characteristics Weekly Tri-weekly
p-value
Weekly Tri-weekly
p-value
n=618 n=163 n=163 n=163
Age 53.8(11.7) 54.1(10.6) 0.80 54.7(11.7) 54.1(10.6) 0.59
Stage:I-II 132(21.4%) 51(31.3%) 0.004 51(31.3%) 51(31.3%) 0.92
IIIa-b 180(29.1%) 55(33.7%)  53(32.5%) 55(33.7%)
IIIc1 212(34.3%) 33(20.2%)  33(20.2%) 33(20.2%)
IIIc2 82(13.3%) 20(12.3%)  24(14.7%) 20(12.3%)
IVa 12(1.9%) 4(2.5%)  2(1.2%) 4(2.5%)
Type:Exophytictype 428(69.3%) 129(79.1%) 0.015 120(73.6%) 129(79.1%) 0.30
Ulcerativetype 190(30.7%) 34(20.9%)  43(26.4%) 34(20.9%)
Tumorsize 4.43(1.54) 4.15(1.37) 0.036 4.21(1.41) 4.15(1.37) 0.72
Histology:SCC 475(76.9%) 121(74.2%) 0.50 122(74.8%) 121(74.2%) 1.00
Adenocarcinoma 117(18.9%) 37(22.7%)  36(22.1%) 37(22.7%)
Adenosquamouscarcinoma (4.2%) 5(3.1%)  5(3.1%) 5(3.1%)
Differentiation:Well 119(19.3%) 37(22.7%) <0.001 38(23.3%) 37(22.7%) 0.96
Moderate 227(36.7%) 30(18.4%)  30(18.4%) 30(18.4%)
Poorly 153(24.8%) 61(37.4%)  64(39.3%) 61(37.4%)
Unknown 119(19.3%) 35(21.5%)  31(19.0%) 35(21.5%)
InitialHb 11.5(1.8) 11.6(1.6) 0.38 11.5(1.9) 11.6(1.6) 0.76
Hydronephrosis:No 550(89.0%) 143(87.7%) 0.68 143(87.7%) 143(87.7%) 1.00
Yes 68(11.0%) 20(12.3%)  20(12.3%) 20(12.3%)
approximately the same when we categorized to cisplatin
and carboplatin (Supplementary Table S1). e other
toxicities appeared to be very similar in both groups in
terms of white blood count, platelet and creatinine. e
compliance towards chemotherapy in both groups was
very good (79.14% in ve cycles or more in the weekly
group and 89.6% in two cycles or more in the tri-weekly
group).
DISCUSSION
e standard treatment for locally advanced cervical
cancer is concurrent platinum-based chemotherapy
and radiotherapy.
1
e frequency of the chemotherapy
regimen is either weekly or tri-weekly administration
according to clinical practice guideline of some institution
in ailand.
20
e weekly regimen is easy to manage in
terms of no requirements for patient admission and
possibly fewer side eects, however, there is still the
concern that the weekly regimen might not be enough
in terms of tumor control. erefore, any additional
evidence may potentially provide a benet in routine
management of chemotherapy in this setting.
Our results show that the tri-weekly group
experienced 8% more neutrophil count grade 2 or greater
toxicity than the weekly group. is eect led to no
signicant reduction in compliance. Interestingly, our
results also showed a potential 6%-7% benet in local
control and possibly a small benet (2%-3%) in overall
Thephamongkhol et al.
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Fig 1. Kaplan-Meier survival estimate comparison between weekly and tri-weekly chemotherapy, unadjusted curve (le) and adjusted by
chemotherapy regimen (carboplatin or cisplatin) (right).
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250
Supplementary Fig S1. Absolute dierence of overall survival with 95% condence interval.
Absolute difference
3-yrOS 0.03%(-0.7%to1.2%)
5-yrOS 0.03%(-0.8%to1.3%)
Absolute difference
3-yrOS 0.04%(-0.04%to0.12%)
5-yrOS 0.04%(-0.04%to0.13%)
Absolute difference
3-yrOS -0.01%(-0.06%to0.05%)
5-yrOS -0.04%(-0.11%to0.03%)
Supplementary Fig S2. Absolute dierence of local recurrence-free survival with 95% condence interval.
Supplementary Fig S3. Absolute dierence of regional recurrence-free survival with 95% condence interval.
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Supplementary Fig S4. Absolute dierence of distant metastasis-free survival with 95% condence interval.
Absolute difference
3-yrOS -0.01%(-0.11%to0.08%)
5-yrOS -0.03%(-0.13%to0.08%)
TABLE 2. Toxicity and compliance between weekly and triweekly chemotherapy.
Weekly Tri-weekly p-value
n=163 n=163
Compliance
Noofcycle 1 2(1%) 14(9%) Notapplicable
2 8(5%) 132(81%)
3 2(1%) 14(9%)
4 20 (12%) -
5 91 (56%) -
6 38(23%) -
7 1(1%) -
Missingdata 1(1%) 3(1%)
Toxicity
Hemoglobin 0 44(27.0%) 25(15.3%) 0.011
1 60(36.8%) 81(49.7%)
2 51(31.3%) 40(24.5%)
3 4(2.5%) 8(4.9%)
Missingdata 4(2.5%) 9(5.5%)
Whitebloodcell 0 51(31.3%) 45(27.6%) 0.43
1 77(47.2%) 73(44.8%)
2 28(17.2%) 29(17.8%)
3 3(1.8%) 7(4.3%)
Missingdata 4(2.5%) 9(5.5%)
ANC 0 123(75.5%) 102(62.6%) 0.009
1 32(19.6%) 35(21.5%)
2 4(2.5%) 12(7.4%)
3 0 5(3.1%)
Missingdata 4(2.5%) 9(5.5%)
Platelet 0 109(66.9%) 145(89.0%) <0.001
1 50(30.7%) 14(8.6%)
2 1 (0.6%) 1 (0.6%)
3 0 0
Missingdata 3(1.8%) 3(1.8%)
Creatinine 0 139(85.3%) 141(86.5%) 0.80
1 19(11.7%) 14(8.6%)
2 1 (0.6%) 2 (1.2%)
3 0(0.0%) 1(0.6%)
Missingdata 4(2.5%) 5(3.1%)
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SUPPLEMENTARY TABLE S1. Toxicity and compliance between weekly and triweekly cisplatin and carboplatin.
Cisplatin Carboplatin
Weekly Tri-weekly Weekly Tri-weekly
n=92 n=157 P value n=71 n=6 p-value
Compliance
Noofcycle 1 0(0%) 13(8%) NA 2(3%) 1(17%) NA
2 3(3%) 128(82%) 5(7%) 4(67%)
3 2(2%) 13(8%) 0(0%) 1(17%)
4 11(12%) - 9(13%) -
5 49(53%) - 42(59%) -
6 26(28%) - 12(17%) -
7 0(0%) - 1(1%) -
Missingdata 1(1%) 3(2%) 0(0%) 0(0%)
Toxicity
Hemoglobin 0 28(30%) 24(15%) 0.003 16(23%) 1(17%) 0.553
1 30(33%) 78(50%) 30(42%) 3(50%)
2 31(34%) 39(25%) 20(28%) 1(17%)
3 1(1%) 8(5%) 3(4%) 0(0%)
Missingdata 2(2%) 8(5%) 2(3%) 1(17%)
WBC 0 22(24%) 44(28%) 0.417 29(41%) 1(17%) 0.085
1 43(47%) 71(45%) 34(48%) 2(33%)
2 23(25%) 27(17%) 5(7%) 2(33%)
3 2(2%) 7(4%) 1(1%) 0(0%)
Missingdata 2(2%) 8(5%) 2(3%) 1(17%)
ANC 0 66(72%) 99(63%) 0.285 57(80%) 3(50%) 0.025
1 20(22%) 34(22%) 12(17%) 1(17%)
2 4(4%) 11(7%) 0(0%) 1(17%)
3 0(0%) 5(3%) 0(0%) 0(0%)
Missingdata 2(2%) 8(5%) 2(3%) 1(17%)
Platelet 0 61(66%) 141(90%) <0.001 48(68%) 4(67%) 1.000
1 29(32%) 12(8%) 21(30%) 2(33%)
2 1(1%) 1(1%) 0(0%) 0(0%)
3 0(0%) 0(0%) 0(0%) 0(0%)
Missingdata 1(1%) 3(2%) 2(3%) 0(0%)
Creatinine 0 81(88%) 137(87%) 0.842 58(82%) 4(67%) 0.413
1 9(10%) 12(8%) 10(14%) 2(33%)
2 1(1%) 2(1%) 0(0%) 0(0%)
3 0(0%) 1(1%) 0(0%) 0(0%)
Missingdata 1(1%) 5(3%) 3(4%) 0(0%)
Thephamongkhol et al.
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Original Article
SMJ
survival. ese results could lead to potential benets in
individual clinical judgment, especially in the context
of a university hospital in ailand while we wait for
stronger evidence.
Nowadays, strong evidence to clearly support
weekly or tri-weekly platinum-based chemotherapy
with radiotherapy in locally advanced cervical cancer
is limited. Two famous randomized controlled trials
from Korea provide conicting results and dierent
points (Table 3). e rst study from Korea
13
showed a
comparable tumor control eect and more compliance
with weekly chemotherapy. e reasons behind this
could be that the tri-weekly combined chemotherapy
regimen with cisplatin and 5FU has poor compliance
due to 15% grade 4 hematological toxicity, compared
with only 2% in the weekly group. erefore, the weekly
group in this study might display a similar eect because
of inadequate chemotherapy in the tri-weekly group due
to toxicity. On the other hand, the second randomized
controlled trial from Korea
12
showed that the tri-weekly
regimen was 20% more eective in terms of overall
survival and had less grade 3-4 neutropenia than the
weekly regimen. Less toxicity can be explained by the fact
that the regimen in this study was only cisplatin without
5FU. Interestingly, even with planned randomization,
the baseline characteristics in this second study were not
well-balanced. e patients in the weekly chemotherapy
group had much poorer prognosis. For example, the
patients in the weekly group had an advanced stage of
disease (stage III and stage IVA 45.1%), compared with
TABLE 3. Comparison of two Korean randomized controlled trials and this study.
Study Kim et al
13
(RCT) Ryu et al
12
(RCT) Our study (PS matched)
Weekly Tri-weekly Weekly Tri-weekly Weekly Tri-weekly
(Cis) (Cis+5FU) (Cis) (Cis) (Cis, carbo) (Cis, carbo)
(n=77) (n=78) (n=51) (n=53) (n=163) (n=163)
Patient StageII StageII StageII StageII StageI-II StageI-II
characteristics =58(75%) =52(67%) =28(55%) =34(64%) =51(31.3%) =51(31.3%)
StageIII-Iva StageIII-Iva StageIII-Iva StageIII-Iva StageIII-Iva StageIII-Iva
=19(25%) =26(33%) =23(45%) =19(36%) =112(68.7%) =112(68.7%)
PelvicLN+ PelvicLN+ PelvicLN+ PelvicLN+ PelvicLN+ PelvicLN+
=31(40%) =32(41%) =29(57%) =27(51%) =33(20%) =33(20%)
PAN+ PAN+ PAN+ PAN+
=7(14%) =5(9%) =24(15%) =20(12%)
Chemotherapy >80% >80% >=5cycles >=2cycles >=5cycles >=2cycles
compliance planned planned =98% =94% =80% =90%
dose dose
=64(83%) =47(60%)  
Hematological Grade3-4 Grade3-4 Neutropenia Neutropenia Neutropenia Neutropenia
toxicity =19(25%) =32(41%)
Grade4 Grade4 Grade3-4 Grade3-4 Grade3-4 Grade3-4
=2(3%) =15(19%) =20(39%) =12(23%) =0(0%) =5(3%)
Thrombocytopenia Thrombocytopenia Thrombocytopenia Thrombocytopenia
Grade3-4 Grade3-4 Grade3-4 Grade3-4
=4(8%) =3(6%) =0(0%) =0(0%)
Overall survival 4year:67% 4year:70% 5year:67% 5year:89% 5year:64% 5year:66%
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the tri-weekly group (stage III and stage IVA 35.9%).
Moreover, positive pelvic and paraaortic lymph nodes
were more frequent in the weekly group (70.6%) than
in patients in the tri-weekly group (61.3%). is also
could be a reason why the weekly group had poorer
tumor control.
Our study had some strengths. First, it included real-
world data from a multi-centered study from university
hospitals in ailand, meaning it was more generalized
than a single-institute study. Second, we used advanced
statistical analysis to match patients who showed well-
balanced baseline characteristics. ird, this study had
adequately long-term follow-up time. However, there
were several limitations of this study as well. First, our
data came from the two-dimensional brachytherapy
era. Nowadays, many hospitals use three-dimensional
brachytherapy, which likely leads to more local control
of the primary site. erefore, the benet of tri-weekly
chemotherapy might be less than that seen in this study.
Also, our sample size was not large enough to detect any
actual dierence.
CONCLUSION
In summary, the tri-weekly chemotherapy regimen
showed a non-statistically potential benet over the
weekly regimen in terms of local control and overall
survival but with more neutrophil toxicity. Further
evidence with adequate sample size could validate this
result. In the meantime, individual judgment using this
data can be discussed with patients.
ACKNOWLEDGMENTS
Lalita Chunkoh as the main patient-data collector
at SI, RA and CU Hospitals; Ladathip Suwan as the
patient-data collector and supervisor of data collection
at RA Hospital; Buntipa Netsawang as the supervisor of
patient-data collection at CU Hospital; Siriporn Wong as
an additional patient-data collector at CU Hospital; Dr.
Poompis Pattaranutaporn as the supervisor of laboratory
data collection at RA Hospital.
Conict of interest: None to declare
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