10.14639/0392-100X-N0895
Objective. The aim of this study is to focus attention on obstructive sleep apnoea hypopnoea syndrome (OSHAS) as a sequela of non-surgical treatments of selected head and neck cancer (HNca), sharing our experience in drug-induced sleep endoscopy (DISE). To the best of our knowledge, this is the first study that documents dynamic anatomical and functional alterations during sleep in irradiated OSAHS patients by DISE.
Methods. A retrospective study of patients affected by OSAHS referring to our department from January 2018 to December 2019 was carried out. Inclusion criteria were: patients who underwent radiation or chemo-radiation for HNca affecting upper airways that presented sleep-related breathing disorders after treatment. Results. 6 patients with moderate to severe OSAHS and a clinical story of previous nonsurgical treatment for an HNca were enrolled. DISE showed in all patients typical anatomical alterations observed in irradiated individuals. Four patients were treated with continuous positive airway pressure, while 2 subjects were treated with tailored minimal invasive surgery without post-operative complications.
Conclusions. Our results suggest that minimal invasive surgical treatments can be a good therapeutic option in very selected patients with post-irradiation iatrogenic OSAHS
application/xml
1827-675X
895
5
en
Pietro Salvatori
ACTA Otorhinolaryngologica Italica
obstructive sleep apnoea
Obstructive sleep apnoea after radiotherapy for head and neck cancer
Text.Serial.Journal
https://www.actaitalica.it/
40
Head and neck
2020-12-03
2020-05-31
2020-12-04
2020-12-04
338-342
1
Pietro Salvatori
2020/12/03
10.14639/0392-100X-N0895
338
Unit of Otorhinolaryngology, Head and Neck Surgery, Humanitas San Pio X, Milan, Italy
1827-675X
5
obstructive sleep apnoea
342
Obstructive sleep apnoea after radiotherapy for head and neck cancer
https://www.actaitalica.it/article/download/895/461
40
ACTA OTORHINOLARYNGOLOGICA ITALICA 2020;40:338-342; doi: 10.14639/0392-100X-N0895




Head and neck


Obstructive sleep apnoea after radiotherapy for head
and neck cancer
Apnee ostruttive del sonno dopo radioterapia per tumori del testa-collo
Federico Leone1, Giulia Anna Marciante1, Chiara Re1, Alessandro Bianchi1, Fabrizio Costantini1, Fabrizio Salamanca1,
Pietro Salvatori1
1
    Unit of Otorhinolaryngology, Head and Neck Surgery, Humanitas San Pio X, Milan, Italy


SUMMARY
Objective. The aim of this study is to focus attention on obstructive sleep apnoea hypo-
pnoea syndrome (OSHAS) as a sequela of non-surgical treatments of selected head and
neck cancer (HNca), sharing our experience in drug-induced sleep endoscopy (DISE). To
the best of our knowledge, this is the first study that documents dynamic anatomical and
functional alterations during sleep in irradiated OSAHS patients by DISE.
Methods. A retrospective study of patients affected by OSAHS referring to our department
from January 2018 to December 2019 was carried out. Inclusion criteria were: patients who
underwent radiation or chemo-radiation for HNca affecting upper airways that presented
sleep-related breathing disorders after treatment.
Results. 6 patients with moderate to severe OSAHS and a clinical story of previous non-
surgical treatment for an HNca were enrolled. DISE showed in all patients typical anatomi-
cal alterations observed in irradiated individuals. Four patients were treated with continu-
ous positive airway pressure, while 2 subjects were treated with tailored minimal invasive
surgery without post-operative complications.
                                                                                                 Received: May 31 , 2020
Conclusions. Our results suggest that minimal invasive surgical treatments can be a good         Accepted: August 9, 2020
therapeutic option in very selected patients with post-irradiation iatrogenic OSAHS.
KEY WORDS: radiotherapy, iatrogenic OSAHS, head and neck cancers, obstructive sleep              Correspondence
apnoea                                                                                           Federico Leone
                                                                                                 Unit of Otorhinolaryngology, Head and Neck Sur-
                                                                                                 gery, Humanitas, San Pio X Clinic, via Francesco
RIASSUNTO                                                                                        Nava 31, 20159 Milan, Italy
Obiettivo. Lo scopo di questo studio retrospettivo è focalizzare l’attenzione sull’OSAS          E-mail: federico.leone@email.com
come sequela di trattamenti non chirurgici per tumori del distretto testa-collo (HNca), con-
dividendo la nostra esperienza con la “drug induced sleep endoscopy” (DISE) e la nostra          Funding
casistica. Per quanto ne sappiamo, questo è il primo studio che documenta alterazioni ana-       None.
tomiche e funzionali dinamiche mediante DISE in pazienti irradiati che hanno sviluppato
OSAS.                                                                                            Conflict of interest
Metodi. È stato condotto uno studio retrospettivo su pazienti affetti da OSAS afferenti alla     The Authors declare no conflict of interest.
nostra struttura da gennaio 2018 a dicembre 2019. Sono stati inclusi nello studio pazienti
con anamnesi positiva per trattamento non chirurgico di HNca che hanno sviluppato OSAS             How to cite this article: Leone F, Marciante
dopo il trattamento.                                                                               GA, Re C, et al. Obstructive sleep apnoea after
Risultati. Sono stati arruolati 6 pazienti con OSAS da moderata a grave con una storia             radiotherapy for head and neck cancer. Acta
clinica di precedente trattamento non chirurgico per un HNca. La DISE ha mostrato in tutti         Otorhinolaryngol Ital 2020;40:338-342. https://
i nostri pazienti tipiche alterazioni anatomiche osservate pazienti irradiati. 4 pazienti sono     doi.org/10.14639/0392-100X-N0895
stati trattati con CPAP mentre 2 soggetti sono stati sottoposti a chirurgia mininvasiva senza
complicazioni post-operatorie.                                                                   © Società Italiana di Otorinolaringoiatria
Conclusioni. I nostri risultati suggeriscono che i trattamenti chirurgici mini invasivi posso-   e Chirurgia Cervico-Facciale
no essere una buona opzione terapeutica in pazienti con OSAS iatrogena post-radioterapia
ben selezionati.                                                                                                OPEN ACCESS

PAROLE CHIAVE: apnee ostruttive del sonno, roncopatia e radioterapia, roncopatia e               This is an open access article distributed in accordance with
                                                                                                 the CC-BY-NC-ND (Creative Commons Attribution-Non-
cancro, OSAS iatrogena, tumori testa-collo                                                       Commercial-NoDerivatives 4.0 International) license. The
                                                                                                 article can be used by giving appropriate credit and mentio-
                                                                                                 ning the license, but only for non-commercial purposes and
                                                                                                 only in the original version. For further information: https://
                                                                                                 creativecommons.org/licenses/by-nc-nd/4.0/deed.en




338
                                                                                  OSAHS after radiotherapy for head and neck cancer




Introduction                                                   were excluded. Patients with known OSAHS before treat-
                                                               ment were also excluded.
Obstructive sleep apnoea-hypopnoea syndrome (OSAHS)
                                                               The diagnostic work-up included complete physical exami-
is characterised by recurring events of partial or complete
                                                               nation, fiberoptic endoscopic evaluation, polysomnograph-
upper airway collapse during sleep. Most apnoeas and hy-
                                                               ic study (PSG) and DISE. Treatment was planned taking
popnoeas lead to oxygen saturation drops and therefore to
                                                               into account clinical features and preferences of each pa-
intermittent hypoxia (IH). IH in OSAHS is an important
                                                               tient.
risk factor for development of hypertension, coronary ar-
                                                               Postoperative pain and dysphagia were evaluated by means
tery disease, arrhythmias and other cardiovascular dis-
                                                               of self-esteemed assessment questionnaires with vNRS-11
eases 1. Recent studies suggest that IH in OSAHS patients
                                                               and I-EAT 10 8.
might be involved in (or a cofactor for) the development of
                                                               All patients were followed for a minimum of 6 months
cancer 2. The relationship between OSAHS and cancer is
                                                               with ENT, pneumological and PSG evaluation. Follow-up
set to become an exciting area of research in the near fu-
                                                               data were available for all patients and no patients were
ture, although at the moment the clinical basis has not been
                                                               lost to follow-up. Epidemiological and clinical data, surgi-
completely demonstrated. Nevertheless, both pathophysi-
ological and animal studies appear to bestow credibility on    cal reports, images, complications, data on therapies and
this correlation 3.                                            follow-up information were reviewed. Finally, our results
To date, data on association between OSAHS and cancer          were critically analysed and discussed in light of the recent
are focused on pathophysiological points of view without       pertinent literature focusing on this topic.
considering correlations with specific kind of tumours.
Other associations can be observed focusing on head and        Results
neck cancers (HNca). OSAHS can develop as the first clini-
                                                               From January 2018 to December 2019, 6 patients with
cal presentation of a tumour (e.g. base of tongue, tonsils,
                                                               moderate to severe OSAHS with a clinical history of pre-
larynx), but even more frequently can be a consequence of
                                                               vious non-surgical treatment for an HNca were enrolled.
treatment for head and neck cancer. In fact, a higher preva-
                                                               Demographic data are reported in Table I.
lence of OSAHS has been observed in patients treated for
                                                               A slight predominance of male was found since only 2 pa-
HNca, both with surgery and radiation (RT) 4-7. The un-
                                                               tients were women (33.3%), while 4 were men (66.6%);
derlying mechanism consists in anatomical and functional
                                                               mean age was 58 ± 8.1 years (range 47-70). Mean BMI
alterations leading to narrowed upper airway and reduced
                                                               was 25.2 ± 1.3 kg/m2 (range 23.4-27). All patients had
compliance. A proper knowledge of this relationship be-
                                                               underwent chemo-radiation therapy for HNca: 3 patients
comes important for all specialists dealing with the prob-
                                                               (50%) were treated for a laryngeal squamous cell carci-
lem.
                                                               noma (SCC), 2 (33.3%) for an oropharyngeal SCC and 1
The aim of this study is to focus attention on OSHAS as
                                                               (16,6%) for an hypopharyngeal SCC. All subjects were di-
a sequela of non-surgical treatments of selected HNca,
                                                               agnosed with OSAHS and the mean time between end of
sharing our experience in drug-induced sleep endoscopy
(DISE) and a small case series of patients. To the best of     the treatment and diagnosis of OSAHS was 23 ± 8 months
our knowledge, this is the first study that documents dy-      (range 6-28). Four (66.6%) patients were affected by severe
namic anatomical and functional alterations during sleep in    OSAHS, while in only 2 cases (33.3%) moderate OSAHS
irradiated OSAHS patients by DISE.                             was found. In all patients, DISE showed typical anatomical
                                                               alterations (diffused oedema, floppy exuberant mucosa at
                                                               the level of arytenoid and ventricular folds, floppy epiglot-
Materials and methods                                          tis and cartilage malacia, etc.) observed in irradiated peo-
This study was performed in accordance with policies ap-       ple. These features were also found to be responsible for
proved by the local ethics Committee.                          UA obstruction in these patients. In relation to treatment of
A retrospective clinical study of patients affected by OS-     OSAHS, 4 patients (66.6%) were treated with CPAP ven-
AHS referring to the Department of Otorhinolaryngology,        tilation, while 2 subjects (33.3%) were surgically treated.
Humanitas San Pio X from January 2018 to December              In particular, 1 patient underwent an epiglottis stiffening
2019 was carried out. Inclusion criteria were as follows:      operation (ESO) sa described by Salamanca et al. 9 and 1
patients who underwent radiation or chemo-radiation for a      underwent trans-oral laser microsurgery (TLM) for floppy
head and neck cancer affecting the upper airways (pharynx,     exuberant tissue (ventricular fold and arytenoid). No post-
larynx) and who presented sleep-related breathing disor-       operative complications were reported and both patients
ders after treatment. Patients with a neoplastic recurrence    were discharged on the 1st postoperative day substantially



                                                                                                                              339
F. Leone et al.




Table I. Preoperative data and outcomes.
 #    Sex Age Histology Site Subsite                         Stage       Treatment        Time          BMI         AHI            DISE             Treatment         AHI     FU
                                                             (8ed.)                     between       (kg/m2)       pre                                               post    (m)
                                                                                         RT and
                                                                                        OSA (m)
 1       M        57       SCC          O        BOT        cT3cN2c       CHT+RT            19           24        72.1     Floppy epiglottis,    CPAP 13.7             4       6
                                                                                                                                 epiglottis         cmH2O
                                                                                                                                  malacia,
                                                                                                                                 edema of
                                                                                                                               supraglottis
 2       M        70       SCC          S         AF        cT2cN2b       CHT+RT            27          25.6       62.3         Esuberant       TLM:debulking          1.3     11
                                                                                                                            flapping mucosa vNRS-11: 0
                                                                                                                            of ventricular fold   I-EAT10: 1
 3       M        47       SCC          S         AF        cT3cN2b       CHT+RT            21          23.4       27.3         Esuberant          CPAP 15             3.2     28
                                                                                                                            flapping mucosa         cmH2O
                                                                                                                            of ventricular fold
                                                                                                                              and aritenoid,
                                                                                                                                floppy and
                                                                                                                                edematous
                                                                                                                                 epiglottis
 4        F       63       SCC          H         PS        cT2cN0        CHT+RT            15           26        32.8         Esuberant          CPAP 13             3.6     25
                                                                                                                            flapping mucosa         cmH2O
                                                                                                                               of arytenoid,
                                                                                                                            epiglottis malacia
 5       M        58       SCC          S          E        cT2cN2b       CHT+RT            37          25.3       47.7     Floppy epiglottis,       ESO               4.7      8
                                                                                                                            epiglottis malacia vNRS-11: 1
                                                                                                                                                  I-EAT10: 1
 6        F       52       SCC          O        BOT        cT3cN2c       CHT+RT            17           27        24.8     Floppy epiglottis,      CPAP 8             3.8     12
                                                                                                                                 epiglottis         cmH2O
                                                                                                                                  malacia,
                                                                                                                                 edema of
                                                                                                                               supraglottis
M: male; F: female; BMI: body mass index; m: months; SCC: squamous cell carcinoma; O: oropharynx; S: supraglottis; H: hypopharynx; BOT: base of tongue; AF: aryepiglottic
fold; PS: pyriform sinus; E: epiglottis; CHT+RT: chemo-radiotherapy; AHI: apnoea hypopnoea index; ESO: epiglottis stiffening operation; TLM: trans-oral laser microsurgery; CPAP:
continuous positive airway pressure; vNRS-11: verbal Numerical Rating Scale 11; I-EAT-10: Eating Assessment Tool 10 (Italian version); DISE: drug-induced sleep endoscopy; FU:
follow up.



without pain (vNRS-11: 0 and 1) and without dysphagia or                                     point of view, several studies have shown an association
aspiration (I-EAT 10: 1 and 1). Follow-up ranged between                                     between OSAHS (particularly when evaluated by hypoxae-
6 and 28 months (mean follow-up period 15 ± 9 months)                                        mia) and cancer incidence and mortality, although their ret-
and no patients were lost. Postoperative fiberoptic evalu-                                   rospective nature means that more in-depth and prospective
ation was performed on the 7th and 30th postoperative day                                    studies will be required before a more definitive conclusion
and showed good surgical results. Moreover, all patients                                     can be reached 1,3,10-12.
underwent a PSG that confirmed resolution of OSAHS in                                        To date, data on relationship between OSAHS and cancer
all 6 patients.                                                                              are focused on pathophysiological points of view without
                                                                                             considering correlations with specific kinds of tumours.
Discussion                                                                                   Focusing on Head and Neck cancers (HNca), we can ap-
OSAHS is characterised by recurrent partial or complete                                      preciate other kind of correlations: OSAHS can be the first
upper airway narrowing during sleep. As a consequence of                                     clinical presentation of a HNca due to a mass effect on the
apnoea and hypopnoea, oxygen saturation may be altered                                       upper airways (UA). The reduction of pharyngo-laryngeal
causing IH. IH in OSAHS is an important risk factor for                                      space can sometimes develop as a consequence of surgical
development of hypertension, coronary artery disease, ar-                                    treatment, for example after bulky flap reconstructions as
rhythmias and other cardiovascular diseases 1. Recent stud-                                  reported by Rombaux et al. 6. Furthermore, HNca patients
ies suggest that IH in OSA patients might be involved in (or                                 may experience upper airway obstruction from the anatom-
a cofactor for) the development of cancer 2. From a clinical                                 ic and functional alterations related to RT.



340
                                                                                          OSAHS after radiotherapy for head and neck cancer




This significant anatomic and functional heterogeneity in         ment. DISE allowed us to identify the problem, but put us
HNca patients partially explains the wide range in previously     in front of a difficult choice. A surgical option in irradiated
reported prevalence of OSAHS in this population (8-92%) 4,5,7.    patient, in fact, may be risky leading to complications that
Our aim was to investigate the effects of radiation therapy       negatively affect the quality of life such as dysphagia.
on the larynx and oropharynx during sleep in irradiated           After adequate counselling, 2 patients categorically refused
patients developing OSAHS after treatment. In addition to         CPAP despite being aware of the surgical risks. However,
some case reports 13,14, we found a study that looked specifi-    if a good selection of the patients is performed, the results
cally at the nonsurgical HNca patient in these two subsites.      suggest that minimal invasive surgical treatments can be a
In their prospective study, Huyett et al. 4 found that half of    good therapeutic option in very selected cases, especially in
patients with a history of RT for oropharyngeal or laryn-         young patients and without other morbidity, as confirmed
geal cancers demonstrated objective evidence of OSAHS,            by our experience.
considerably higher than in the general population. To the
best of our knowledge, this is the first study documenting        Conclusions
dynamic anatomical and functional alterations during sleep
in irradiated OSAHS patients by DISE.                             OSAHS is a public health problem and a very common
The identification of specific site upper respiratory tract       disorder, with the same prevalence as diabetes and large
obstruction site(s) in OSAHS patients is important in order       economic impact on public healthcare. In particular, the re-
to select the best therapeutic strategy. Nowadays, among          lationship between OSAHS and cancer is set to become an
different diagnostic tools, DISE, although not ideal, plays       exciting area of research.
a key role in the decision making process 15. The introduc-       As a consequence of both RT and surgical therapy, a de-
tion of routinely use of DISE in OSAHS patients has been          crease in the pharyngo-laryngeal space can lead to the onset
reported to help the customisation of treatment demonstrat-       of iatrogenic OSAHS, as suggested by a higher prevalence
ing that UA obstruction results from the collapse of one or       of this disorder in patients treated for HNca. Proper knowl-
more pharyngeal and/or laryngeal structures 16,17.                edge of this relationship becomes important for specialists
Laryngeal involvement is less frequent than pharyngeal,           dealing with these problems because the management of
consisting in epiglottis collapse in the large majority of na-    OSAHS in irradiated patients may be more challenging.
ïve patients. The collapse can be described as primary (the       Our results suggest that surgery can be considered in these
so called “floppy epiglottis”) or secondary (when related to      types of patients. Minimally-invasive surgical treatments
a bulky tongue base). In our sample of irradiated patients,       can be a good alternative therapeutic option in very select-
the larynx was the most affected site due to typical mucosal      ed patients, especially if young and without comorbidity.
alterations induced by RT: massive oedema of supra-glot-          In our opinion, DISE is confirmed to be a valid tool for
tis structures with exuberant floppy mucosa of ventricular        patient selection and should always be performed before
fold, arytenoid, aryepiglottic fold, epiglottis malacia and       considering surgery as the last approach. A larger case se-
instability were found at the evaluation. According to our        ries, hopefully a prospective multicentre study with longer
findings, all these alterations (isolated or in variable combi-   follow-up, is needed in order to confirm these results.
nation) were responsible for obstruction in sleep.
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