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\begin{document}

\title{Timeline for Carotid Blow-out in Head and Neck Cancer Patients, When to
Expect Major Bleeding?}



\author[1]{Murat Yener}%
\author[2]{Sinem Kara}%
\author[2]{Chinara Aliyeva}%
\author[2]{Firat Tevetoglu}%
\affil[1]{Istanbul Universitesi-Cerrahpasa}%
\affil[2]{Istanbul University-Cerrahpasa}%


\vspace{-1em}



  
  \date{May 23, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Abstract: Objectives: Carotid blow-out syndrome (CBS) is one of the
uncommon yet detrimental complications in head and neck cancer patients,
by presenting itself as a catastrophic bleeding. Various factors are
related with CBS. There is no timeline for the development of CBS in
patients with uncontrollable tumors. In this report we intended to
review our cases of CBS with special emphasis on risk factors, the
timeline for carotid rupture as well as the outcomes following ligation.
Design, Setting and Participants: A retrospective analysis was performed
on previously treated head and neck cancer patients who experienced
carotid blow-out syndrome (CBS) following tumor recurrence between 2015
and 2020. Results: All of the patients in this study were classified as
type III CBS and managed by carotid artery ligation. Three patients had
previous chemoradiotherapy while five had surgery and adjuvant treatment
as the primary treatment. Time to recurrence following primary treatment
was ranging between 6-19 months with a mean of 8.25\selectlanguage{ngerman}±5.11 months. Apart
from tumor infiltration seen in all of the patients, 3 had fistula, 5
had wound infection and 6 had necrosis. Conclusion: CBS is an uncommon
yet detrimental complication encountered in head and neck cancer
patients, which is mostly treated by endovascular approach. However,
surgical ligation is still a treatment option especially in patients
with type III rupture. Since, there is a limited time for those patients
preventive measures should be undertaken within 4 months following soft
tissue exposure, necrosis and fistula.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{Timeline for Carotid Blow-out in Head and Neck Cancer Patients,
When to Expect Major Bleeding?}

\textbf{Running Title:} Carotid Blow-out in Head and Neck Cancer

\textbf{Abstract:}

\textbf{Objectives:} Carotid blow-out syndrome (CBS) is one of the
uncommon yet detrimental complications in head and neck cancer patients,
by presenting itself as a catastrophic bleeding. Various factors are
related with CBS. There is no timeline for the development of CBS in
patients with uncontrollable tumors. In this report we intended to
review our cases of CBS with special emphasis on risk factors, the
timeline for carotid rupture as well as the outcomes following ligation.

\textbf{Design, Setting and Participants:} A retrospective analysis was
performed on previously treated head and neck cancer patients who
experienced carotid blow-out syndrome (CBS) following tumor recurrence
between 2015 and 2020.

\textbf{Results:} All of the patients in this study were classified as
type III CBS and managed by carotid artery ligation. Three patients had
previous chemoradiotherapy while five had surgery and adjuvant treatment
as the primary treatment. Time to recurrence following primary treatment
was ranging between 6-19 months with a mean of 8.25\selectlanguage{ngerman}±5.11 months. Apart
from tumor infiltration seen in all of the patients, 3 had fistula, 5
had wound infection and 6 had necrosis.

\textbf{Conclusion:} CBS is an uncommon yet detrimental complication
encountered in head and neck cancer patients, which is mostly treated by
endovascular approach. However, surgical ligation is still a treatment
option especially in patients with type III rupture. Since, there is a
limited time for those patients preventive measures should be undertaken
within 4 months following soft tissue exposure, necrosis and fistula.

\textbf{Key words:} carotid blow-out syndrome; carotid rupture; carotid
artery ligation; head neck cancer; radiotherapy

\textbf{Key Points}

\begin{enumerate}
\tightlist
\item
  Carotid blow-out syndrome (CBS) is one of the uncommon yet detrimental
  complications in head and neck cancer patients, by presenting itself
  as a catastrophic bleeding.
\item
  There are various risk factors for CBS such as prior radiotherapy,
  prior radical neck dissection, mucocutaneous fistula, flap necrosis,
  wound infection, poor nutrition and tumor recurrence.
\item
  Prevention may be the most effective treatment by using various
  reconstructive procedures such as myocutaneous flaps to hinder the
  exposure of carotid artery and to avoid pharyngocutaneous fistula.
\item
  Regardless of the treatment choice; angiography is accepted as gold
  standard for diagnosis, by also having the advantage of evaluating the
  patency of contralateral carotid system with balloon occlusion test,
  thus leading the treatment option.
\item
  Since, it has a high mortality and neurologic morbidity, preventing
  CBS would be the most effective treatment method, because the
  countdown is approximately set to 4 months.
\end{enumerate}

\textbf{INTRODUCTION}

Carotid blow-out syndrome (CBS) is one of the uncommon complications in
head and neck cancer(1)(2). It may occur due to tumor invasion or
fibrosis of adventitia of the artery as a complication of cancer
treatment resulting in rupture of carotid artery(3). Common presenting
symptoms are catastrophic bleeding from oral cavity, oropharynx or an
exposed wound on the neck. Incidence of CBS in patients with major head
and neck surgery ranges between 3-4.5\%(4)(5), with 7.6 fold increase
with previous history of irradiation(6). There are various risk factors
such as prior radiotherapy, prior radical neck dissection, mucocutaneous
fistula, flap necrosis, wound infection, poor nutrition and tumor
recurrence(7); with previous curative radiotherapy being the main risk
factor after salvage surgery, especially a total radiation dose over 70
Gy(5)(8). Incidence of CBS following re-irradiation may increase up to
17\%(5). Another factor is tumor encasement of carotid artery,
infiltration of carotid wall by tumor causing inflammation and weakening
of carotid artery(5)(9). Although modern surgical reconstruction methods
decreased the rate of CBS, morbidity and mortality still remains with
rates up to 76\% for mortality(10) and 16-60\% for neurologic
morbidity(11).

Prevention may be the most effective treatment by using various
reconstructive procedures such as myocutaneous flaps to hinder the
exposure of carotid artery and to avoid pharyngocutaneous fistula(7).
Ligation of common carotid artery (CCA) or internal carotid artery (ICA)
is the traditional management of CBS with higher rates of neurologic
sequela(4). Yet another and more frequent option is embolization or
stenting of carotid artery by endovascular approach with less
complication rates. However, not every patient is suitable for
endovascular approach; patients with open wound and active bleeding are
still being managed by ligation.

There is no timeline for development of CBS in patients with
uncontrollable tumors. In few reports regarding salvage surgery, carotid
rupture was seen within 10-40 days following surgery(5), yet there is no
knowledge in literature about the time to carotid rupture due to
unresectable tumors or patients with open wounds. In this report we
intended to review our cases with CBS with special emphasis on risk
factors, timeline for carotid rupture as well as the outcomes following
ligation.

\textbf{MATERIALS AND METHODS}

\emph{\textbf{Design, Setting and Participants}}

A retrospective analysis was performed on previously treated head and
neck cancer patients who experienced CBS following tumor recurrence
between 2015 and 2020. From medical records of 348 patients, 8 patients
with CBS who had open approach surgical ligation of carotid artery were
detected. Patients treated with endovascular intervention, untreated
cancer patients and patients lost to follow-up were excluded. All of the
patients had head and neck cancer with primary surgery and adjuvant
treatment or salvage surgery and referred to our center with active
bleeding due to CBS who were treated by open surgery with carotid
ligation. CBS was classified as type I (threatened) CBS occurring when
carotid artery was exposed through soft tissue breakdown, type II
(impending) with limited, sentinel bleeding and type III (rupture) with
active bleeding as suggested by Chaloupka et al(1) and Powitzky et
al(12). Demographic data (age, sex), primary site of tumor, neck stage
during primary treatment, type of surgery, radiotherapy history,
predisposing factors (fistula, wound infection, necrosis), site of
rupture, time to recurrence of tumor and time to CBS from exposure of
neck soft tissues were obtained by a review of medical history.
Variables were expressed as percentage, mean ± standard deviation. The
reporting guideline of choice was STROBE (Strengthening the Reporting of
Observational studies in Epidemiology) for this article. (13)

Ethical Consideration

Ethics committee approved the study design and informed consents were
obtained from patients or their caregivers.

\textbf{RESULTS}

Demographics, previous N stage, type of surgery, time to recurrence and
time to carotid rupture of 8 patients were presented in Table 1. All of
the patients in this study were type III CBS and managed by carotid
artery ligation. Age of the patients was between 54 and 69 with a mean
of 62.75±5.6 years.

All of the patients had untreatable locoregional recurrence. Primary
site was oral cavity in 3(37.5\%), oropharynx-hypopharynx in 3(37.5\%)
and larynx in 2(25\%) patients with primary N stages as N1 in 1(12.5\%),
N2 in 3(37.5\%) and N3 in 4(50\%) patients. Three patients(37.5\%) had
previous radiotherapy or chemoradiotherapy for curative intent. Five
patients (62.5\%) had surgery and postoperative adjuvant treatment,
radical neck dissection was performed in 3 (60\%) and functional neck
dissection was performed in 2(40\%)(Table 1). Time to recurrence
following primary treatment was between 6-19 months with a mean of
8.25±5.11 months. Apart from tumor infiltration seen in all of the
patients, three had fistula, 5 had wound infection and 6 had necrosis at
bleeding site(Table 1). Bleeding was from CCA near bifurcation in
5(62.5\%), ICA in 2(25\%) and from main trunk of external carotid artery
just above bifurcation in one(12.5\%) patient(Table 1). Time from
detection of recurrence-soft tissue exposure to CBS was ranging from 2
to 12 months with a mean of 5.37±3.11 months and in patients having
fistula and necrosis blow-out was earlier(6 patients; 2-4 with a mean of
4±1.2 months). Postoperatively 2 patients had major neurologic morbidity
(hemiplegia; 25\%). In postoperative follow-up period 7 patients were
detected to be deceased(87.5\%) and mean time to death was 7.71±6.15
months(1-17 months).

\textbf{DISCUSSION}

First described in 1962 by Borsany(14), CBS still is an important
complication in head and neck cancer, with a mortality of 40\% and
neurologic morbidity of 60\%(1)(15). Prior radiotherapy, prior radical
neck dissection, mucocutaneous fistula, flap necrosis, wound infection,
poor nutrition and tumor recurrence can be counted as risk factors for
CBS(5)(7)(8). Tumor encasement and infiltration of carotid artery
causing inflammation and weakening of carotid artery wall, also plays an
important role(5)(9). Overall incidence of CBS in head and neck cancer
ranges from 2.5\% to 4.5\%(2)(5)(10). After examination of medical
records of 348 patients treated for head and neck cancer in our clinic,
8 patients with CBS treated by open approach carotid artery ligation,
were determined, having a slightly lower rate compared to the
literature(2.3\%).

CBS was classified as type I(threatened) CBS occurring when carotid
artery was exposed through soft tissue breakdown, type II(impending)
with limited, sentinel bleeding and type III(rupture) with active
bleeding(1)(12). Type III is the most common type of CBS(over 60\%)
followed by type II and I, respectively(12)(16). Chaloupka et al.,
reported their findings on endovascular treatment of CBS. Among 4
patients with type I, 10 patients with type II and 5 patients with type
III CBS; most common pathologic finding was pseudoaneurysms, followed by
tumor encasement(1). However, in another study, extravasation was the
most common pathologic finding(in 8 out of 10 patients), while
pseudoaneurysm was seen in only 2 patients, which could be explained as
all these 8 patients were type III CBS(17). All of our patients
presented with acute rupture(type III CBS), thus most common finding was
extravasation, followed by pseudoaneurysm.

CCA emerged as the most common site of origin of rupture in our study,
which was consistent with the literature reporting a rate of over 60\%
(5)(12)(17)(18). Bleeding was found to be from CCA near bifurcation in
5(62.5\%), ICA in 2(25\%) and from main trunk of external carotid artery
just above bifurcation in one(12.5\%) patient. However, in a study
consisting of 6 patients with CBS, ICA was found to be the most common
site(in 4 out of 6 patients), followed by CCA(2). In addition, in a
larger scale study, again ICA was reported to be the most common site
with a rate of greater than 50\%, while CCA was being the least
common(1).

Previous radiotherapy is considered to be the most important risk
factor, by increasing the risk up to seven fold(6)(19), even to 14-fold
in case of a radiation dose of \textgreater{}70 Gy(8). After exclusion
of patients who were previously irradiated, CBS rate was found to be
only 0\%--2.4\%; however, when patients received radiotherapy analyzed
separately, CBS rate increases to 4.5\%--21.1\% (5). Free radical
production triggered by radiotherapy is considered to be causative agent
by inducing thrombosis of vaso vasorum, fibrosis of adventitia, and
premature atherosclerosis; eventually resulting in weakening of arterial
wall(19). In Estomba et al.'s study, except for one out of six patients
with CBS had a previous history of radiotherapy and cause of CBS was
proved to be radiation induced necrosis in 3 patients, pharyngocutaneous
fistula in 2 patients, and tumor recurrence in 1 patient(2). Durmaz et
al., stated that history of radiotherapy was the common future in all of
their 10 patients with CBS, 7 with recurred cancer and 5 with
pharyngocutaneous fistula(17). In a large review by Powitzky, among 140
patients and 161 CBS cases, previous history of radiotherapy was found
to be the most common shared feature(89\%), followed by nodal
metastasis(69\%), neck dissection(63\%), necrosis(55\%), mucocutaneous
fistula (40\%)(12). Being another risk factor, neck dissection -
especially radical neck dissection, with stripping of the carotid -- was
reported to increase the risk of CBS to eight fold(8). Among 8 patients
included in this study, all had a previous history of radiotherapy, with
3 as primary curative treatment and 5 as adjuvant treatment. 3 of the
latter also had a history of radical neck dissection. Pharyngocutaneos
fistula in 3, wound infection in 5 and necrosis at bleeding site in 6 of
the patients were seen, apart from tumor infiltration which was present
in all.

Most common tumor primary sites were larynx(23\%), hypopharynx(22\%) and
nasopharynx (21\%)(12). In a study consisting of 10 patients with CBS,
in a six-year period, 3 had had primary tumor in larynx, 2 each in oral
cavity, hypopharynx, nasopharynx, and 1 in salivary gland(17). In our
study, primary site was oral cavity in 3(37.5\%), oropharynx-hypopharynx
in 3(37.5\%) and larynx in 2(25\%) of the patients.

Surgical ligation has been traditionally the treatment of choice for
CBS(18)(20). However, after the introduction of the detachable balloons
specifically for treatment of impending CBS in 1984 by Osguthorpe and
Hungerford(21), there has been an increasing tendency towards
endovascular approach. Over 90\% of patients reported in the past
fifteen years were treated by endovascular approach, either by stenting
or embolization; while surgical ligation was the preferred method in
less than 10\%(12). Drawbacks of surgical ligation; such as hemodynamic
instability complicating perioperative management, hypotension deepened
with general anesthesia resulting in cerebral ischemia, consumption
coagulopathy due to blood loss resulting in uncontrollable
re-hemorrhage, challenging surgical dissection caused by previous
operations and radiotherapy; played role in this change of treatment
preferences(1). In a paper reporting 6 cases with CBS, among 3 patients
managed by endovascular approach, 1 had neurologic sequel; while 1
patient managed by surgical ligation also suffered neurologic
complication(2).

Regardless of the treatment choice; angiography is accepted as gold
standard for diagnosis(22), by also having the advantage of evaluating
the patency of contralateral carotid system with balloon occlusion test,
thus leading the treatment option(23)(24). Hence, every treatment should
be preceded by angiographic evaluation; yet it may not be possible in
every case due to need of emergent intervention.

Average time to CBS from initial time of diagnosis was 2.7 years, mostly
originating from proximal part of the carotid bifurcation(12). Among
patients who had a second regime of radiotherapy, median time for CBS to
occur, from beginning of re-irradiation, was 7.5 months, ranging up to
four to five years, in certain cases(10). In our patient population,
time to recurrence following primary treatment was between 6-19 months
with a mean of 8.25±5.11 months. Time from detection of recurrence or
soft tissue exposure to CBS, was from 2 to 12 months with a mean of
5.37±3.11 months, with being earlier in patients having fistula and
necrosis (6 patients; 2-4 months with a mean of 4±1.2 months). In this
regard, following massive neck or local recurrence with soft tissue
exposure, necrosis and fistula, carotid blow-out is to be expected
within 4 months and preventive measures must be undertaken during this
period.

\textbf{CONCLUSIONS}

CBS is an uncommon yet detrimental complication encountered in head and
neck cancer patients, especially with a history of radiotherapy and
radical neck dissection. It is an emergency which necessitates the use
of angiography for diagnosis, and in most cases for treatment. However,
surgical ligation could still be a treatment option. Since, it has a
high mortality and neurologic morbidity, preventing CBS would be the
most effective treatment method, especially in patients with soft tissue
exposure, necrosis and fistula because the countdown is approximately
set to 4 months.

\textbf{References}

1. Chaloupka JC, Putman CM, Citardi MJ, Ross DA, Sasaki CT. Endovascular
therapy for the carotid blowout syndrome in head and neck surgical
patients: diagnostic and managerial considerations. Am J Neuroradiol.
1996;17(5).

2. Miguel C, Estomba C, Alberto F, Reinoso B, Velasquez AO, Macia OC, et
al. Carotid blowout syndrome in patients treated by larynx cancer \selectlanguage{english}jh.
Braz J Otorhinolaryngol {[}Internet{]}. 2017;83(6):653--8. Available
from: http://dx.doi.org/10.1016/j.bjorl.2016.08.013

3. Sooby P, Tarmal A, Townsley R. Management of catastrophic haemorrhage
in palliative head and neck cancer : creation of a new protocol using
simulation. 2020;1--5.

4. Lu HJ, Chen KW, Chen MH, Chu PY, Tai SK, Wang LW, et al. Predisposing
factors, management, and prognostic evaluation of acute carotid blowout
syndrome. J Vasc Surg. 2013 Nov;58(5):1226--35.

5. Su\selectlanguage{ngerman}árez C, Fernández-Alvarez V, Hamoir M, Mendenhall WM, Strojan P,
Quer M, et al. Carotid blowout syndrome: Modern trends in management.
Vol. 10, Cancer Management and Research. Dove Medical Press Ltd; 2018.
p. 5617--28.

6. Macdonald S, Gan J, McKay AJ, Edwards RD. Endovascular treatment of
acute carotid blow-out syndrome. J Vasc Interv Radiol. 2000
Oct;11(9):1184--8.

7. Gleysteen J, Clayburgh D, Cohen J. Management of Carotid Blowout from
Radiation Necrosis. Vol. 49, Otolaryngologic Clinics of North America.
W.B. Saunders; 2016. p. 829--39.

8. Chen YJ, Wang CP, Wang CC, Jiang RS, Lin JC, Liu SA. Carotid blowout
in patients with head and neck cancer: Associated factors and treatment
outcomes. Head Neck. 2015 Feb;37(2):265--72.

9. Yazici G, Sanli TY, Cengiz M, Yuce D, Gultekin M, Hurmuz P, et al. A
simple strategy to decrease fatal carotid blowout syndrome after
stereotactic body reirradiaton for recurrent head and neck cancers.
Radiat Oncol. 2013 Oct;8(1).

10. McDonald MW, Moore MG, Johnstone PAS. Risk of carotid blowout after
reirradiation of the head and neck: A systematic review. Int J Radiat
Oncol Biol Phys. 2012 Mar;82(3):1083--9.

11. Upile T, Triaridis S, Kirkland P, Archer D, Searle A, Irving C, et
al. The management of carotid artery rupture. Eur Arch
Oto-Rhino-Laryngology. 2005 Aug;262(7):555--60.

12. Powitzky R, Vasan N, Krempl G, Medina J. Carotid Blowout in Patients
With Head and Neck Cancer. 2010;119(7):476--84.

13. Vandenbroucke JP, von Elm E, Altman DG, Gøtzsche PC, Mulrow CD,
Pocock SJ, et al. Strengthening the Reporting of Observational Studies
in Epidemiology (STROBE): Explanation and Elaboration. PLoS Med
{[}Internet{]}. 2007 Oct 16 {[}cited 2021 Apr 29{]};4(10):e297.
Available from: https://dx.plos.org/10.1371/journal.pmed.0040297

14. Borsany SJ. Rupture of the carotids following radical neck surgery
in irradiated patients. Ear Nose Throat J. 1962;41:531--3.

15. Citardi MJ, Chaloupka JC, Son YH, Ariyan S, Sasaki CT. Management of
carotid artery rupture by monitored endovascular therapeutic occlusion
(1988-1994). Laryngoscope {[}Internet{]}. 1995 {[}cited 2021 Jan
12{]};105(10):1086--92. Available from:
https://pubmed.ncbi.nlm.nih.gov/7564841/

16. Liang NL, Guedes BD, Duvvuri U, Singh MJ, Chaer RA, Makaroun MS, et
al. Outcomes of interventions for carotid blowout syndrome in patients
with head and neck cancer. In: Journal of Vascular Surgery
{[}Internet{]}. Mosby Inc.; 2016 {[}cited 2021 Jan 13{]}. p. 1525--30.
Available from: https://pubmed.ncbi.nlm.nih.gov/26926937/

17. Durmaz H, Ergun O, Birgi E, Bayir Ö, Saylam G. Endovascular
management of the carotid blowout syndrome\selectlanguage{english} : a single \selectlanguage{english}- center
experience. Eur Arch Oto-Rhino-Laryngology {[}Internet{]}. 2019;1--6.
Available from: https://doi.org/10.1007/s00405-019-05548-9

18. Razack MS, Sako K. Carotid artery hemorrhage and ligation in head
and neck cancer. J Surg Oncol {[}Internet{]}. 1982 {[}cited 2021 Jan
12{]};19(4):189--92. Available from:
https://pubmed.ncbi.nlm.nih.gov/7078171/

19. Cohen J, Rad I. Contemporary management of carotid blowout
{[}Internet{]}. Vol. 12, Current Opinion in Otolaryngology and Head and
Neck Surgery. Curr Opin Otolaryngol Head Neck Surg; 2004 {[}cited 2021
Jan 13{]}. p. 110--5. Available from:
https://pubmed.ncbi.nlm.nih.gov/15167047/

20. Coleman JJ. Treatment of the Ruptured or Exposed Carotid Artery; a
Rational Approach. South Med J {[}Internet{]}. 1985 {[}cited 2021 Jan
12{]};78(3):262--7. Available from:
https://pubmed.ncbi.nlm.nih.gov/3975736/

21. Osguthorpe JD, Hungerford GD. Transarterial Carotid Occlusion: Case
Report and Review of the Literature. Arch Otolaryngol {[}Internet{]}.
1984 {[}cited 2021 Jan 12{]};110(10):694--6. Available from:
https://pubmed.ncbi.nlm.nih.gov/6477267/

22. Morrissey DD, Andersen PE, Nesbit GM, Barnwell SL, Everts EC, Cohen
JI. Endovascular management of hemorrhage in patients with head and neck
cancer. Arch Otolaryngol - Head Neck Surg {[}Internet{]}. 1997 {[}cited
2021 Jan 13{]};123(1):15--9. Available from:
https://pubmed.ncbi.nlm.nih.gov/9006498/

23. Gleysteen J, Clayburgh D. M a n a g e m e n t o f C a ro t i d B l o
w o u t f ro m R a d i a t i o n N ec ros is Carotid blowout
Endovascular Radiation complication. Otolaryngol Clin NA {[}Internet{]}.
2016;49(3):829--39. Available from:
http://dx.doi.org/10.1016/j.otc.2016.02.001

24. Mbbs DJYW, Bmbs CD, Mbbs LTL, Andrew F, Mbbs C, Mbbs CG, et al.
Safety and effectiveness of endovascular embolization or stent-graft
reconstruction for treatment of acute carotid blowout syndrome in
patients with head and neck cancer\selectlanguage{english} : Case series and systematic review
of observational studies. 2017;(August):1--9.\selectlanguage{english}
\begin{longtable}[]{@{}lll@{}}
\toprule
\begin{minipage}[b]{0.30\columnwidth}\raggedright\strut
Patients\strut
\end{minipage} & \begin{minipage}[b]{0.30\columnwidth}\raggedright\strut
Patients\strut
\end{minipage} & \begin{minipage}[b]{0.30\columnwidth}\raggedright\strut
8\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Age (min-max; mean\selectlanguage{ngerman}±std dev)\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Age (min-max; mean\selectlanguage{ngerman}±std dev)\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
54-69; 62.75\selectlanguage{ngerman}±5.6\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Gender (Male/Female)\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Gender (Male/Female)\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
7/1\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Primary Tumor Site\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Oral Cavity\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
3\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Oropharynx/Hypopharynx\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
3\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Larynx\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
2\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
N Stage\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
N1\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
1\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
N2\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
3\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
N3\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
4\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Previous Radiotherapy\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Previous Radiotherapy\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
3/8\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Neck Dissection\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Functional\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
2\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Radical\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
3\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Adjuvant Treatment\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
RT\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
4\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
CRT\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
4\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Time to Recurrence Following Primary Treatment; months (min-max;
mean\selectlanguage{ngerman}±std dev)\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Time to Recurrence Following Primary Treatment; months (min-max;
mean\selectlanguage{ngerman}±std dev)\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
6-18; 11.37\selectlanguage{ngerman}±3.8\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Predisposing Factors\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Tumor infiltration\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
8/8\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Fistula\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
3/8\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Wound Infection\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
5/8\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Necrosis\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
6/8\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Site of Rupture\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Common Carotid\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
5\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Internal Carotid\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
2\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
External Carotid\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
1\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Type of Carotid Blow-out\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Type III\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
8/8\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
Time to Carotid Blow-out; months (min-max; mean\selectlanguage{ngerman}±std dev)\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
Time to Carotid Blow-out; months (min-max; mean\selectlanguage{ngerman}±std dev)\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
2-8; 4.5\selectlanguage{ngerman}±1.8\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}\selectlanguage{ngerman}

\textbf{Table 1:} Patient demographics and data

\textbf{Hosted file}

\verb`Carotid Blow-out - Table.docx`  available at \url{https://authorea.com/users/314762/articles/709905-timeline-for-carotid-blow-out-in-head-and-neck-cancer-patients-when-to-expect-major-bleeding}

\selectlanguage{english}
\FloatBarrier
\end{document}

