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\begin{document}

\title{Comparison of Concurrent Chemoradiotherapy or Radiotherapy alone after
Induction Chemotherapy for Hypopharyngeal Cancer}



\author[1]{Meng Wan}%
\author[1]{Dan Zhao}%
\author[1]{Weixin Liu}%
\author[1]{Xiaolong Xu}%
\author[1]{Baomin Zheng}%
\author[1]{Shaowen Xiao}%
\author[1]{Yan Sun}%
\author[1]{Weihu Wang}%
\affil[1]{Peking University Cancer Hospital}%


\vspace{-1em}



  
  \date{May 23, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Objectives Our study aimed to compare the efficacy and toxicity of
induction chemotherapy (IC) followed by concurrent chemoradiotherapy
(CCRT) or radiotherapy (RT) alone in patients with locally advanced
hypopharyngeal squamous cell carcinoma (HPSCC). Design: Cohort
Retrospective study Settings: Data of HPSCC patients collected from 2008
to 2020 Participants: 83 HPSCC patients Main outcomes measures: 83
patients with HPSCC in our center, who received IC followed by either
CCRT or RT alone according to multidisciplinary team (MDT) discussion,
were eligible for analysis. Among these patients, 52 patients underwent
CCRT and 31 received RT alone after IC and we compared the two groups.
Then we further compared the IC + CCRT and IC+RT groups in IC responders
showing complete response (CR) and partial response (PR). Survival,
toxicities clinical efficacy and outcomes were analyzed. Results For IC
responders, IC+CCRT compared to IC+RT improved the locoregional
relapse-free survival (LRPFS) (median: 39.3 vs.15.13 months; P=0.033),
distant metastasis-free survival (DMFS) (median: 21.37 vs. 13.6 months;
P=0.044), PFS (median: 27.87 vs.11.37 months; P=0.048) and the overall
survival (OS) (median: 39.33 vs. 18.03 months, P=0.027). A multivariate
analysis confirmed IC+CCRT was a positive prognostic factor for LRPFS
and OS. However, for either all patients or IC non-responders, IC+CCRT
did not improve the survival compared to IC+RT. Regarding acute
toxicity, toxicities except [?]2 leucopenia were not statistically
different between the two groups. Conclusion In the IC responders, CCRT
may possess the survival benefit compared to RT alone in patients with
HPSCC. Moreover, the toxicities of two groups were comparable during the
therapy. Keywords hypopharyngeal carcinoma, induction chemotherapy,
chemoradiotherapy, radiotherapy, survival%
\end{abstract}%



\sloppy


\textbf{Comparison of Concurrent Chemoradiotherapy or Radiotherapy alone
after Induction Chemotherapy for Hypopharyngeal Cancer}

\textbf{Running title:} ``IC+CCRT'' or ``IC+RT'' for hypopharyngeal
Cancer

\textbf{Authors:} Meng Wan\textsuperscript{\textbf{1}} , BSc; Dan
Zhao\textsuperscript{\textbf{1}} , MD; Weixin Liu, MD; Xiaolong Xu, MSc;
Baomin Zheng, MD; Shaowen Xiao, MD, PhD; Yan Sun, MD; Weihu Wang, BSc

\textsuperscript{\textbf{1}} Meng Wan and Dan Zhao contribute equally to
this study

\textbf{Affiliations:} Key Laboratory of Carcinogenesis and
Translational Research (Ministry of Education/Beijing), Department of
Radiation Oncology, Peking University Cancer Hospital and Institute,
Beijing 100142, People's Republic of China. (M.W., D.Z., W.X.L., X.L.X.,
B.M.Z., S.W.X., Y.S., W.H.W.)

\textbf{Correspondence: Weihu Wang} , BSc, Department of Radiation
Oncology, Peking University Cancer Hospital, No.52 Fucheng Road, Haidian
District, Beijing 100142. Email: wangweihu88@163.com; and\textbf{Yan
Sun} , MD, Department of Radiation Oncology, Peking University Cancer
Hospital, No.52 Fucheng Road, Haidian District, Bejing 100142. Email:
lisaysun@139.com.

\textbf{Funding sources} \textbf{and Conflict of interest:} 1) Beijing
Municipal Science \& Technology Commission No. Z181100001718192; 2)
National Natural Science Foundation No. 82073333; 3) Science Foundation
of Peking University Cancer Hospital No.18-03. There is no conflict of
interest to declare in our study.

\textbf{Disclosure Statement}

The authors declare no conflicts of interest

\textbf{Author contributions}

All the authorship contributed to the work and approved the final
version of

the manuscript.

Conception and study design, development of methodology: WWH and SY;

Data collection, formal analysis, writing -- original draft, review \&
editing: WM and ZD;

Data collection, writing -- review \& editing, supervision: WM and ZD;

Data analysis and assistance to manuscript writing: LWX, XXL and ZBM

Data check, modification: ZBM, XSW

Manuscript revision: WM, ZD, SY and WWH.

\textbf{Acknowledgements}

Not applicable

\textbf{Data sharing and date availability statement}

Data available upon reasonable request from the corresponding authors

\section*{Abstract}

{\label{abstract}}

\textbf{Objectives}

Our study aimed to compare the efficacy and toxicity of induction
chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) or
radiotherapy (RT) alone in patients with locally advanced hypopharyngeal
squamous cell carcinoma (HPSCC).

\textbf{Design:} Cohort Retrospective study

\textbf{Settings:} Data of HPSCC patients collected from 2008 to 2020

\textbf{Participants:} 83 HPSCC patients

\textbf{Main outcomes measures:}

83 patients with HPSCC in our center, who received IC followed by either
CCRT or RT alone according to multidisciplinary team (MDT) discussion,
were eligible for analysis. Among these patients, 52 patients underwent
CCRT and 31 received RT alone after IC and we compared the two groups.
Then we further compared the IC + CCRT and IC+RT groups in IC responders
showing complete response (CR) and partial response (PR). Survival,
toxicities clinical efficacy and outcomes were analyzed.

\textbf{Results}

For IC responders, IC+CCRT compared to IC+RT improved the locoregional
relapse-free survival (LRPFS) (median: 39.3 vs.15.13 months;\emph{P=}
0.033), distant metastasis-free survival (DMFS) (median: 21.37 vs. 13.6
months; \emph{P=} 0.044), PFS (median: 27.87 vs.11.37 months;\emph{P}
=0.048) and the overall survival (OS) (median: 39.33 vs. 18.03 months,
\emph{P} =0.027). A multivariate analysis confirmed IC+CCRT was a
positive prognostic factor for LRPFS and OS. However, for either all
patients or IC non-responders, IC+CCRT did not improve the survival
compared to IC+RT. Regarding acute toxicity, toxicities except [?]2
leucopenia were not statistically different between the two groups.

\textbf{Conclusion}

In the IC responders, CCRT may possess the survival benefit compared to
RT alone in patients with HPSCC. Moreover, the toxicities of two groups
were comparable during the therapy.

\textbf{Keywords}

hypopharyngeal carcinoma, induction chemotherapy, chemoradiotherapy,

radiotherapy, survival

\textbf{Key points}

\textbf{1:} Surgery for hypopharyngeal cancers remained unsatisfactory
especially for the patients with advanced stages.

\textbf{2:} Non-surgical approaches such as IC, CCRT and radiotherapy
were considered more and more for advanced HPSCC patients, however, we
have not reached an agreement for the non-surgical treatments due to the
limited clinical studies.

\textbf{3:} IC followed by CCRT was beneficial for survival of HPSCC
patients when compared to IC followed by RT alone in IC responders but
not in all the patients and IC non-responders.

\textbf{4:} IC followed by CCRT was the independent protective factor
for LRPFS and OS.

\textbf{5:} IC followed by CCRT did not bring about the severer acute
toxicities for HPSCC patients when compared to IC followed by RT alone.

\section*{Introduction}

{\label{introduction}}

Hypopharyngeal squamous cell carcinoma (HPSCC) is a rare malignancy,
merely accounting for about 3\%-5\% of head and neck
cancers.\textsuperscript{1, 2} Due to the distinct local anatomical
characteristics and enriched lymphatic and vascular networks, HPSCCs are
commonly diagnosed at an advanced stage.\textsuperscript{3, 4} According
to previous reports, the 5-year overall survival (OS) was only
30\%-35\%. \textsuperscript{3, 5}

Although advances in oncology treatment for head and neck cancers have
been proposed, treatment outcomes in patients with HPSCC are still
unsatisfactory, and only minimal improvement in survival has been
achieved over the years. In a retrospective study of 6647 HPSCC
patients, the average 5-year OS increased marginally from 37.5\%
(1973-1989) to 41.3\% (1990-2003).\textsuperscript{6}

Therefore, an ideal therapeutic strategy for HPSCC remains a challenge
that requires multidisciplinary teams (MDT) to collaborate for the best
outcomes. Before the 1990s, whereas total laryngectomy was the main
treatment for locally advanced HPSCCs, its negative impact on the
patients was unignorable which vastly affect the patient's quality of
life.\textsuperscript{7} Considering the disadvantages of surgical
method, non-surgical strategies were prioritized from two of the
representative random clinical trials in laryngeal
cancer\textsuperscript{8} and hypopharyngeal
cancer,\textsuperscript{9}which demonstrated that induction chemotherapy
(IC) plus radiotherapy (RT) outperformed laryngectomy in terms of both
laryngeal preservation and non-jeopardization of survival.

A variety of studies were recently conducted for the optimization of
non-surgical therapy; however, the trials were conducted in patients
with head and neck cancers,\textsuperscript{10-12} leading to an
insufficient evidence regarding non-surgical therapy for HPSCCs. And
there were still lacking the unified standard non-surgical therapies.
Further, according to the National Comprehensive Cancer Network (NCCN)
guideline,\textsuperscript{13} locally advanced HPSCCs are often managed
by IC followed by (chemo)radiotherapy as a non-surgical strategy.
However, the overall benefits of IC followed by concurrent chemotherapy
(CCRT) (IC+CCRT) and IC followed by RT alone (IC+RT) were not clear;
thus, our study was performed to assess the efficacy and toxicity
associated with the two approaches.

\section*{Materials and methods}

{\label{materials-and-methods}}

Patients and patient workup

This study was derived from 269 patients who were diagnosed with HPSCC
at our center between August 2008 and October 2020. 83 patients who
received IC followed by CCRT (n=52) or IC followed by RT alone (n=31)
were included after exclusions (Supplementary Figure 1). All patients
underwent disease staging using the eighth edition of the American Joint
Committee on Cancer (AJCC) staging system.\textsuperscript{13}

The study protocol was approved by the ethics committee of the Beijing
Cancer Hospital and Institute, Peking University School of Oncology
(approval number: 2019YJZ76). All patients were provided written
informed consent for the treatment.

Treatment

MDT collaboration was operated in our hospital, which aimed to provide
the patients with the most suitable approach. Based upon the advanced
stage of 83 patients, who appeared high risk of distant metastasis for
the patients with HPSCC, our center tended to treat the locally advanced
patients with IC first, and then decided which approach would be
conducted.

IC according to MDT included taxnanes plus platinum with fluorouracil
(TPF, n=54), taxanes with platinum (TP, n=15) and fluorouracil with
platinum (PF, n=14), all the modalities were administered every 3 weeks.

After IC, CCRT (n=52) or RT alone (n=31) was performed according to the
tolerance of patients and MDT discussion. Concurrent chemotherapy was
administered every 3 weeks combined with cisplatin or nedaplatin (100
mg/m\textsuperscript{2} or 80 mg/m\textsuperscript{2}, dependent on the
patients' health condition).

All patients underwent computed tomography (CT)-based RT planning with
intensity-modulated radiotherapy (IMRT). Gross tumor volume (GTV) was
divided into primary (GTVp) and nodal (GTVnd). Clinical target volume
(CTV) included GTVp and additional margins according to the location of
the lesion and the presence of adjacent invasions. The CTV of the nodal
regions was determined based on the levels of the metastatic lymph
nodes. The prescription doses of 95\% planning GTV (PGTV) and 95\%
planning CTV (PTV) were 70 Gy and 60 Gy, respectively, in 33 fractions
(once daily, 5 days per week).

Treatment-related toxicities were analyzed according to the National
Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE,
version 4.03).

Definition of clinical efficacy

The sites of treatment failure were assessed based on the patients'
medical records. The Response Evaluation Criteria in Solid Tumors
(RECIST version 1.1) was used to define response assessment after IC
treatment. In our study, both laryngoscopy and CT or MRI scans of the
neck were used to evaluate the efficacy of the primary tumor. The
patients were grouped based on the overall assessment of IC efficacy: IC
responders were defined as the patients with CR or PR, and IC
non-responders were defined as the patients with stable disease (SD) or
progressive disease (PD). OS, progression-free survival (PFS), distant
metastasis-free survival (DMFS) and locoregional progression-free
survival (LRPFS) were conducted to depict the survival of the patients,
all of which were calculated from the start of therapy and adopted the
varied endpoints.

Follow-up

Follow-up visits included evaluation of symptoms, physical examination,
blood tests, cancer biomarkers, thyroid function tests, endoscopy, CT or
magnetic resonance imaging (MRI) scans of the neck and thorax, and
ultrasonography of the cervical and abdominal regions. These were
accomplished 1 month after the completion of RT, every 3 months in the
first 2 years, every 6 months between years 3 and 5, and once a year
thereafter.

Statistical analyses

Categorical variables were compared using \selectlanguage{greek}χ\selectlanguage{english}2 tests or Fisher's exact
tests. OS, PFS, DMFS and LRPFS were compared using the Kaplan--Meier
method with log-rank test. Cox regression analysis was used to estimate
hazard ratios (HR) and 95\% confidence interval (CI). Variables with
a\emph{P} \textless{}0.10 in univariate analyses were included in a
multivariate analysis. Variables analyzed in our univariate analysis
study included gender (male vs female), age (\textless{}56y vs [?]56),
treatment modality (IC+CCRT vs IC+RT), smoking (no vs yes), alcohol
consumption (no vs yes), T stage (T1-2 vs T3-4), N stage (N0-2 vs N3),
overall stage (III/IVA vs IVB), modality of IC (PF/TP vs TPF), cycle of
IC treatment ([?]2 vs \textgreater{}2), and toxicities during treatment
(\textless{}3 grade vs [?]3 grade).

The SPSS Statistics for Windows, version 24.0 (IBM, Chicago, IL), was
used for statistical analysis. All statistical tests were based on a
two-sided significance level, and \emph{P} -values of \textless{}0.05,
were considered indicative of a statistically significant finding.

\section*{Results}

{\label{results}}

Patients' characteristics

The patients' characteristics are shown in Table 1. For the entire
cohort, 78 were male and 5 were female and the median age was 56
(39-72). The primary sites were in the pyriform sinus in 70 patients,
pharyngeal wall in 8, and post-cricoid pharynx in five. Two patients
were in stage III, 40 patients were in stage IVA, and 41 patients were
in stage IVB. Both median of cycles of IC and CCRT were 2 (1-4). The
detailed tumor-node-metastasis (TNM) stages before IC were shown in
Table S1. Besides, the baseline characteristics of the two subgroups of
IC responders and non-responders were shown in Table S2.

Tumor responses to induction chemotherapy

As shown in Table 2, the responders with overall CR and PR were 57.8\%
(n=48) and non-responders with SD or PD were 42.2\% (n=35). The reasons
why non-responders received RT or CCRT rather than surgery were
individual inclination to non-surgical strategies (n=15, 42.9\%),
inoperable tumors (n=2, 5.7\%), and low surgical curability (n=18,
51.4\%). Conclusively, based upon the inaccessibility to surgery and
overall evaluation from the MDT, the IC non-responders underwent the
CCRT or RT instead of surgery.

Clinical efficacy and Patterns of failure

At the end of treatment, the clinical efficacy of all the patients and
IC responders was shown in Table S3. Besides, differed patterns of
failure as the endpoints for LRPFS, DMFS and PFS of all the patients and
IC responders were shown in Table S4.

Survival

The median follow-up time for all patients was 30.2 months. For all
patients, IC+CCRT group showed no prolonged LRPFS (median: 21 vs.15.3
months, \emph{P} =0.825; Figure 1A), DMFS (median: 21.37 vs. 13.6
months,\emph{P} =0.839; Figure 1B), PFS (median: 20.17 vs.11.38
months,\emph{P} =0.906; Figure 1C) and OS (median: 27.1 vs.18.03
months,\emph{P} =0.846; Figure 1D) compared to IC+RT alone group.
However, for IC responders, IC+CCRT comparing to IC+RT alone
significantly prolonged the LRPFS (median: 39.3 vs. 15.13 months,
\emph{P} =0.033; Figure 2A), DMFS (median: 27.87 vs.13.6 months,
\emph{P} =0.044; Figure 2B), PFS (median:27.87 vs.11.37 months, \emph{P}
=0.048; Figure 2C) and OS (median:39.33 vs.18.03 months, \emph{P}
=0.027; Figure 2D). Notably, IC+CCRT failed to benefit for survival
compared to IC+RT alone in IC non-responders (Supplementary Figure
2A-D).

Further, multivariate analysis for the IC responders showed that IC+CCRT
was benefit factor for LRPFS (HR: 0.391, 95\% CI: 0.16-0.957,\emph{P}
=0.04), and OS (HR:0.361, 95\% CI:0.141-0.922, \emph{P} =0.033) (see
Table 3).

Acute Toxicities

The most common [?]3 grade toxicities were neutropenia (n=21, 25.3\%) and
leukopenia (n=14, 16.9\%) during IC and mucositis (n=26, 31.3\%),
radiation dermatitis (n=5, 6.0\%), leukopenia (n=5, 6.0\%), and
neutropenia (n=5, 6.0\%) during (chemo)radiotherapy. The toxicities
during therapies between the IC+CCRT and IC+RT groups were shown in
Table 4. Except that the [?]2 grade leukopenia during IC was lower in the
IC+CCRT group than in the IC+RT group (23.1\% vs. 67.7\%, \emph{P}
\textless{}0.001), other toxicities had no differences between IC+CCRT
and IC+RT.

Laryngeal outcomes at the last follow-up

In the last follow-up, 38 patients remained alive, of whom 13
experienced grade 1 voice alteration and one experienced grade 2 voice
alteration; moreover, 12 patients had grade 1 dysphagia and 2 had grade
2 dysphagia. Only one patient each underwent percutaneous gastrectomy
and tracheotomy due to severe pharyngeal dysfunction after 4 months of
RT.

\section*{Discussion}

{\label{discussion}}

IC is an organ-preserving therapeutic approach for treating locally
advanced hypopharyngeal cancers. Our study represents a retrospective
single-center analysis of assessment of CCRT or RT after IC and
demonstrated that IC+CCRT could improve LRPFS and OS in the group of IC
responders. To the best of our knowledge, this study is the first to
compare the efficacy and toxicity of CCRT and RT following IC in
patients with HPSCC.

In our study, the CR rate for primary sites and survival were lower than
their counterparts reported in the European Organization for Research
and Treatment of Cancer (EORTC) 24891.\textsuperscript{9} Several
factors could cause this difference. Firstly, it may be due to the
majority of patients in our study belonging to T3-4 (79.5\%) and stage
IV (97.6\%), according to the EORTC 24891, patients with T2 stage HPSCC
(18/22, 82\%) were found to be more accessible to CR (\emph{P} =0.002)
than patients with T3 (34/71, 48\%) and T4 stages (0/4). Secondly, this
is likely due to the different measurements involved in the efficiency
assessment in our study. Both laryngoscopy and neck CT scan were
involved in our study; however, a neck CT scan was not mandatory in
EORTC 24891. Lastly, our study included patients with PR and
non-responders besides CR patients.

Except for EORTC 24891, the OS in our study resembled that of a previous
study.\textsuperscript{14} Some other RCTs showed higher CR rate and OS
in patients with a higher proportion of T2-3 and N0-1 compared to our
study.\textsuperscript{10, 15} Moreover, laryngeal cancer was included
in the research cohorts in some of those RCTs.

In our study, higher LRPFS and OS occurred in the IC responders who
received CCRT than in those who received RT alone. Based on our
findings, an effort to improve responsiveness to IC becomes the key
point. Admittedly, compared to CCRT alone, IC+CCRT has not yet been
validated to be advantageous for the survival of patients with locally
advanced head and neck cancers in phase III clinical
trials.\textsuperscript{16, 17} But it has been demonstrated that IC
could reduce the risk of distant metastasis \textsuperscript{18}.
Besides, IC was considered advantageous for survival when performing in
the patients with heavily affected primary sites or advanced nodal
involvement (cN2c-N3) \textsuperscript{19}. Based on the high proportion
of N2c (n=27, 32.5\%) and N3b (n=37,44.6\%) in our study, which had the
high risk of distant metastasis, IC was chosen as the prior treatment.

A recent phase II/III trial indicated that patients who underwent IC
followed by CCRT had better survival outcomes than those who underwent
CCRT alone for head and neck cancer (median survival: 54.7 vs.
31.7\%,\emph{P} =0.03).\textsuperscript{20} Furthermore, a retrospective
study aiming at laryngeal and hypopharyngeal cancers demonstrated a
similar conclusion that IC+CCRT resulted in a longer median OS (64.7 vs.
21\%,\emph{P} =0.003) than CCRT alone for hypopharyngeal cancers, but no
survival benefit was found in laryngeal cancers.\textsuperscript{21} IC
plays a crucial role in laryngeal preservation(LP)-oriented combination
therapy for HPSCCs. This is also supported by the NCCN guideline in
which IC was recommended as a strategy for LP.\textsuperscript{13}

As concluded in our study, the effect of CCRT after IC correlated with
IC responses. The French Groupe d'Oncologie Radioth\selectlanguage{ngerman}érapie Tête et Cou
(GORTEC) 2000-01 trial, which included 213 patients with laryngeal or
hypopharyngeal cancer, demonstrated the superiority of the TPF regimen
over PF in terms of ORR (80.0\% vs. 59.2\%, \emph{P} =0.002) and LP rate
(70.3\% vs. 57.5\%, \emph{P} =0.03).\textsuperscript{15} With the
exception of ORR and LP rates, another two RCT trials showed that TPF
markedly improved PFS and OS in locally advanced head and neck
cancers.\textsuperscript{22, 23} Conceivably, aiming at the
effectiveness of CCRT combined with IC, TPF should be prioritized for IC
treatment rather than PF.

Regarding IC non-responders, more careful therapeutic considerations are
required. Nowadays, with the advancement of individualized cancer care
with increasing precision and more implications, and with the
incorporation of multicenter novel therapies, such as immunotherapy, the
access to an ideal trade-off status between the expected clinical
outcomes and a less-affected quality of life potentially comes into real
practice.\textsuperscript{24}

Regarding the exclusiveness of this series, owing to the prevailing
characteristics of many studies involving multiple sites of head and
neck cancer, HPSCC comprises only a minority of the ensemble population
due to its low prevalence. In some researchers about head and neck
subsites, hypopharyngeal cancer generally merged with laryngeal cancer.
Therefore, critical featured information for HPSCC treatment would be
incomprehensive, leading to a shortage of definite conclusions.
Exploration of optimal treatment for HPSCCs to some degree counts on the
personal experiences of clinicians and the results, including the
confounding factors that may render them less convincing. Herein, our
study focused only on patients with HPSCC and offered exclusive
information regarding their treatment, which will be helpful in clinical
practice. The overall efficacy assessment for IC was used to group the
patients in our study rather than only aiming for the primary sites,
which brought about more reasonable evaluations for the comparison of
CCRT and RT alone.

Regarding limitations of our study, due to the small sample size and
retrospective nature of our study, the comparison of CCRT and RT alone
according to IC responses requires further investigation with larger
cohorts or prospective trials. Moreover, as no patients achieved CR
after IC treatment, more studies are required to investigate the
necessity of CCRT.

\textbf{Conclusion}

In our study, a comparison of IC+CCRT and IC+RT responses showed that
IC+CCRT improved the survival of IC responders and brought about
manageable toxicities in all patients. Based on limited numbers of
reports about HPSCC, our study has conveyed the detailed clinical data
about HPSCC and indicate that IC+CCRT would be a promising non-surgical
strategy in patients with locally advanced HPSCC.

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\textbf{Figure legends}

Figure 1 Kaplan-Meier estimation of LRPFS (A), DMFS (B), PFS (C), OS (D)
cures for 83 patients stratified as IC+CCRT and IC+RT groups.

Abbreviations: LRPFS=locoregional progression-free survival;
DMFS=distant metastasis-free survival; PFS=progress-free survival;
OS=overall survival; IC=induction chemotherapy; CCRT=concurrent
chemoradiotherapy; RT=radiotherapy.

Figure 2 Kaplan-Meier estimation of LRPFS (A), DMFS (B), PFS (C), OS (D)
cures for 48 patients with responders to IC stratified as IC+CCRT and
IC+RT groups.

Abbreviations: LRPFS=locoregional progression-free survival; DMFS=
distant metastasis-free survival; PFS=progress-free survival; OS=overall
survival; IC=induction chemotherapy; CCRT=concurrent chemoradiotherapy;
RT=radiotherapy.

Supplementary Figure 1 Flow diagram of our study.

Abbreviations: IC=induction chemotherapy; RT=radiotherapy;

CCRT=concurrent chemoradiotherapy.

Supplementary Figure 2 Kaplan-Meier estimation of LRPFS (A), DMFS (B),
PFS (C), OS (D) cures for 35 patients with non-responders to IC
stratified as IC+CCRT and IC+RT groups.

Abbreviations: LRPFS=locoregional progression-free survival;
DMFS=distant metastasis-free survival; PFS=progress-free survival;
OS=overall survival; IC=induction chemotherapy; CCRT=concurrent
chemoradiotherapy; RT=radiotherapy.\selectlanguage{english}
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\textbf{Hosted file}

\verb`Table 1.xlsx`  available at \url{https://authorea.com/users/729972/articles/709989-comparison-of-concurrent-chemoradiotherapy-or-radiotherapy-alone-after-induction-chemotherapy-for-hypopharyngeal-cancer}

\textbf{Hosted file}

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\textbf{Hosted file}

\verb`Table 4.xlsx`  available at \url{https://authorea.com/users/729972/articles/709989-comparison-of-concurrent-chemoradiotherapy-or-radiotherapy-alone-after-induction-chemotherapy-for-hypopharyngeal-cancer}

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