10.14639/0392-100X-suppl.1-42-2022-09
COVID-19 severely impacted the healthcare system in most industrialised countries and contributed to the postponement of many elective healthcare services. As most national and international surgical associations promptly drew up guidelines to preserve time-dependent surgery, the Lombardy Region, the epicentre of the outbreak of COVID-19 in Italy, also created differentiated pathways for COVID-19 and non-COVID-19-related health services based on a hub/spoke design. At the Department of Otorhinolaryngology and Head and Neck Surgery of the European Institute of Oncology (IEO), we needed to rearrange our as- sistance pathways, as a designated oncological hub, to guarantee gold-standard treatments to cancer patients. Specific protocols were developed for the management of regional pa- tients and extra-regional patients confined to self-isolation due to the lockdown and stay-at- home policy. Specific assistance trajectories were created for cancer patients coming from other hospitals needing life-saving procedures. Herein, we report the outcomes of patients undergoing head and neck treatments at the IEO Department of Otorhinolaryngology and Head and Neck Surgery, with the aim to evaluate the efficacy of all the measures adopted as an oncological hub during the COVID-19 pandemic and compare our data with that in the international peer-reviewed published medical literature regarding the consequences of COVID-19 on the management of head and neck cancer patients.
text/xml
1827-675X
2113
en
Mohssen Ansarin
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ACTA Otorhinolaryngologica Italica
treatment
COVID-19 and head and neck cancer management. Experience of an oncological hub comprehensive cancer centre and literature review
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2022-04-26
2022-04-06
2022-04-28
2022-04-28
S79-S86
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Mohssen Ansarin
2022/04/26
10.14639/0392-100X-suppl.1-42-2022-09
S79
Department of Otorhinolaryngology and Head and Neck Surgery, European Institute of Oncology IRCCS, Milan, Italy
1827-675X
treatment
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COVID-19 and head and neck cancer management. Experience of an oncological hub comprehensive cancer centre and literature review
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ACTA OTORHINOLARYNGOLOGICA ITALICA 2022;42(SUPPL.1):S79-S86; doi: 10.14639/0392-100X-suppl.1-42-2022-09




COVID-19 and head and neck cancer management.
Experience of an oncological hub comprehensive
cancer centre and literature review
COVID-19 e gestione dei tumori testa e collo. Esperienza di un hub oncologico,
Centro di riferimento terziario, e review della letteratura
Francesco Chu1, Jacopo Zocchi1, Rita De Berardinis1, Francesco Bandi1, Giacomo Pietrobon1, Donatella Scaglione2,
Davide Radice3, Marta Tagliabue1,4, Mohssen Ansarin1
1
  Department of Otorhinolaryngology and Head and Neck Surgery, European Institute of Oncology IRCCS, Milan, Italy; 2 Trial
Management and Data Management, Clinical Trial Office, Scientific Direction, European Institute of Oncology IRCCS, Milan, Italy;
3
  Division of Epidemiology and Biostatistics, European Institute of Oncology IRCCS, Milan, Italy; 4 Department of Biomedical
Sciences, University of Sassari, Sassari, Italy


SUMMARY
COVID-19 severely impacted the healthcare system in most industrialised countries and
contributed to the postponement of many elective healthcare services. As most national and
international surgical associations promptly drew up guidelines to preserve time-dependent
surgery, the Lombardy Region, the epicentre of the outbreak of COVID-19 in Italy, also
created differentiated pathways for COVID-19 and non-COVID-19-related health services
based on a hub/spoke design. At the Department of Otorhinolaryngology and Head and
Neck Surgery of the European Institute of Oncology (IEO), we needed to rearrange our as-
sistance pathways, as a designated oncological hub, to guarantee gold-standard treatments
to cancer patients. Specific protocols were developed for the management of regional pa-
tients and extra-regional patients confined to self-isolation due to the lockdown and stay-at-
home policy. Specific assistance trajectories were created for cancer patients coming from
other hospitals needing life-saving procedures. Herein, we report the outcomes of patients
undergoing head and neck treatments at the IEO Department of Otorhinolaryngology and
Head and Neck Surgery, with the aim to evaluate the efficacy of all the measures adopted            Received: January 17, 2022
                                                                                                    Accepted: January 27, 2022
as an oncological hub during the COVID-19 pandemic and compare our data with that in
the international peer-reviewed published medical literature regarding the consequences of
                                                                                                    Correspondence
COVID-19 on the management of head and neck cancer patients.
                                                                                                    Rita De Berardinis
KEY WORDS: head and neck cancer, COVID-19, delay, oncological hub, treatment                        Division of Otolaryngology and Head and Neck
                                                                                                    Surgery, European Institute of Oncology IRCCS,
                                                                                                    via Ripamonti 435, 20141 Milan, Italy.
RIASSUNTO                                                                                           E-mail: rita.deberardinis@ieo.it
Il COVID-19 ha avuto un grave impatto sul sistema sanitario di molti paesi industrializzati
e ha contribuito al ritardo di esecuzione di numerosi trattamenti e procedure chirurgiche
                                                                                                      How to cite this article: Chu F, Zocchi J, De
in elezione. La maggior parte delle associazioni chirurgiche nazionali e internazionali ha            Berardinis R, et al. COVID-19 and head and
prontamente redatto delle linee guida per cercare di preservare i tempi di attesa relativi a          neck cancer management. Experience of an
chirurgie inderogabili. La Regione Lombardia, epicentro dell’epidemia di COVID-19 in                  oncological hub comprehensive cancer centre
Italia, ha creato percorsi differenziati per pazienti COVID-19 e non COVID-19 basati su               and literature review. Acta Otorhinolaryngol
un sistema di centri hub/spoke. Presso il Dipartimento di Otorinolaringoiatria e Chirur-              Ital 2022;42(SUPPL.1):S79-S86. https://doi.
gia Cervico-Facciale dello IEO, divenuto hub oncologico, abbiamo dovuto riorganizzare i               org/10.14639/0392-100X-suppl.1-42-2022-09
nostri percorsi di assistenza, per garantire le cure standard ai malati di cancro. Sono stati
sviluppati protocolli specifici per la gestione dei pazienti regionali ed extraregionali, co-       © Società Italiana di Otorinolaringoiatria
                                                                                                    e Chirurgia Cervico-Facciale
stretti all’autoisolamento a causa della politica di lockdown e “stay-at-home”. Sono state
create specifiche traiettorie di assistenza per i malati di cancro provenienti da altri ospedali
                                                                                                                   OPEN ACCESS
e necessitanti di chirurgie salvavita. In questo lavoro, riportiamo i risultati relativi al trat-
tamento dei pazienti oncologici, testa collo, presso la Divisione di Otorinolaringoiatria e         This is an open access article distributed in accordance with
                                                                                                    the CC-BY-NC-ND (Creative Commons Attribution-Non-
Chirurgia Cervico-Facciale dell’Istituto Europeo di Oncologia, di Milano, con l’obiettivo           Commercial-NoDerivatives 4.0 International) license. The
di valutare l’efficacia di tutte le misure adottate come hub oncologico durante il COVID-19         article can be used by giving appropriate credit and mentio-
e confrontare i nostri dati con quelli della letteratura internazionale.                            ning the license, but only for non-commercial purposes and
                                                                                                    only in the original version. For further information: https://
PAROLE CHIAVE: tumori testa e collo, COVID-19, ritardo, hub oncologico, trattamento                 creativecommons.org/licenses/by-nc-nd/4.0/deed.en




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Introduction                                                    mandatory upon entry, and body temperature was meas-
                                                                ured via infrared thermometers.
Since February 2020, the COVID-19 pandemic declaration
                                                                Before hospitalisation, head and neck cancer patients un-
led most national authorities and governments to impose
                                                                derwent a telephone triage, investigating their general
restrictive measures, primarily aimed at containing the
                                                                health status and possible contacts with COVID-19 pa-
spread of the virus, and thus preventing the national health-
                                                                tients. At the hospital, all patients underwent blood analysis
care systems from reaching a “breaking point”.
                                                                and chest X-ray as per protocol. From April 1st 2020, a na-
The “lockdown”, a term referring explicitly to actions
                                                                sopharyngeal swab was also collected during preoperative
related to mass quarantines or “stay-at-home” orders, se-
                                                                assessment. The date of the surgery was scheduled within
verely impacted the healthcare system in most industrial-
                                                                five days from the swab, during which time all patients
ised countries and contributed to many elective healthcare
                                                                were instructed to self-isolate.
services being postponed.
                                                                The treatment of low-risk tumours, such as thyroid tu-
During the first COVID-19 wave, it was estimated that at
                                                                mours, was temporarily ceased, and patients were offered
least 21 million elective operations were cancelled glob-
                                                                active surveillance.
ally, partly due to concerns over post-operative SARS-
                                                                We worked to optimise the oncological network and the
CoV-2 infection and partly due to capacity issues within
                                                                continuity of care for patients coming from other COV-
hospitals 1,2. Most national and international surgical asso-
                                                                ID-19 hospitals. Specific management pathways were de-
ciations promptly drew up guidelines to protect time-de-
                                                                veloped to evaluate head and neck cancer patients coming
pendent surgery from the same consequence 3.
                                                                from other centres, including rapid accesses to the IEO for
The Lombardy Region was the epicentre of the first out-
                                                                new visits and surgical procedures scheduled on the basis
break of COVID-19 in Italy. The Lombardy Regional Au-
                                                                of the patient’s condition and urgency of treatment.
thorities created differentiated pathways for COVID-19
                                                                We made every effort to reduce surgical times and avoid
and non-COVID-19-related health services to face the
                                                                postoperative stay in the Intensive Care Unit, by opting for
emergency, based on a hub/spoke design 4. More specifi-
                                                                minimally-invasive techniques rather than open approach-
cally, new healthcare pathways were defined by temporar-
ily abrogating private for-profit activities, thus extending    es. Where possible, we chose to reconstruct surgical defects
the service availability to cancer patients needing nondefer-   with local flaps rather than with free vascularised flaps.
rable life-saving treatments 4.                                 The anaesthetic protocol was set to minimise aerosol gen-
The European Institute of Oncology (IEO) has become a           eration and potential exposure to undetected COVID-19
regional reference “hub” for the treatment of cancer pa-        infection in patients with false-negative swab tests 5. All
tients, together with the National Cancer Institute of Milan.   the staff involved was obliged to wear complete personal
At the IEO Department of Otorhinolaryngology and Head           protection equipment (PPE), and only the anaesthetist and
and Neck Surgery, we needed to rearrange the assistance         the nurse had access to the operating room during the an-
pathways to guarantee gold-standard treatments to patients      aesthetic procedure. As the operators were in contact with
debilitated by cancer-related dysphagia or by the disease       areas with a high possibility of viral infection, they had to
itself. At the same time, it was mandatory to perform life-     wear full PPE throughout the surgical procedure. During
saving surgeries to avoid possible complications such as        the post-operative period, all patients were in single rooms
airway obstruction of the upper respiratory tract or haemor-    with surgical masks, and healthcare professionals who vis-
rhage, thus minimising the hospitalisation time.                ited them were equipped with full PPE. Meticulous atten-
In this paper, we report the outcomes of patients undergoing    tion was paid to patients with a tracheotomy. Healthcare
head and neck treatments at the IEO Department of Otorhi-       professionals were asked to wear FFP2 masks associated
nolaryngology and Head and Neck Surgery of Milan with           with a surgical mask, water-repellent disposable gown or
the aim to evaluate the efficacy of all the measures adopted    apron, gloves and protective goggles or visor. The surgeons
as an oncological hub during the COVID-19 lockdowns.            provided the patient’s family members with a daily update
We also provide a contemporary review of the most recent        on the outcome of the intervention and clinical progress by
international peer-reviewed biomedical publications.            telephone 5.
                                                                For the outpatient and follow-up visits, all patients were
                                                                evaluated with a telephone or telemedicine visit during the
Materials and methods                                           Italian lockdown in March and April 2020. Asymptomatic
Oncological hub reorganisation                                  patients were rescheduled with follow-up visits after at
From the beginning of pandemic outbreak, access to the          least 6 months. Patients from other Italian regions reporting
hospital was granted to patients only. Surgical masks were      suspicious symptoms were asked to refer to local hospitals



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and healthcare providers, while patients in the Lombardy         written in English and with fully available abstracts. One
region were scheduled with emergency IEO outpatient vis-         author, F.B., reviewed all the abstracts and selected only
its.                                                             the articles focusing on the impact of COVID-19 on the
The study was approved by the Institutional Ethical Com-         healthcare system. Only articles reporting the incidence
mittee and comply with the principles stated in the Declara-     of cancer, the time to visit (CPI), diagnosis, staging and
tion of Helsinki “Ethical Principles for Medical Research        treatment (TTI), compared to non-COVID controls, were
Involving Human Subjects”.                                       selected for data extraction.

Data extraction                                                  Statistical analysis
We retrospectively reviewed the department databases and         Patient characteristics were summarised either by count
clinical records of all head and neck cancer patients exam-      and percent or mean and standard deviation (SD) for all
ined or treated at the IEO Department of Otorhinolaryngol-       categorical variables and age at the first visit, respectively.
ogy and Head and Neck Surgery, during our COVID-19               Categorical variables were compared by Fisher’s exact test;
hub activity.                                                    the Shapiro-Wilk test was used to check the normality as-
For outpatient visits, we retrospectively reviewed data from     sumption for the distribution of age; calendar years were
the 2020 oral cavity, pharyngeal and laryngeal databases.        then compared by the two-sample Wilcoxon test. TTI and
Two dedicated surgeons, F.C and R.D.B., reviewed all clin-       CPI were estimated by the Kaplan-Meier method; calen-
ical records to retrospectively assess any reported delay in     dar years were compared for the delay in surgery by the
the first visit/follow-up due to COVID-19 infection or fear      log-rank test. At the time of the analysis, there were no
of accessing hospitals.                                          censored times. After checking the proportional hazard as-
For all the head and neck cancer patients surgically treat-      sumption, univariate Cox regression analysis was run using
ed in our institute, we performed data extraction from the       surgery as the event of interest, and the results were tabu-
multidisciplinary board (MDB) discussion database be-            lated as hazard ratios (HR) alongside 95% confidence inter-
tween April and June 2020 (Group A). This period repre-          val (CI). The 2019 calendar year entered the Cox model as
sents the most critical time in terms of rearrangement of        a reference level. All tests were two-tailed and considered
the healthcare system and management of cancer patients,         significant at the 5% level. All analyses were done using
under special institutional guidelines during the COVID-19       SAS 9.4 (Cary, N.C., USA).
pandemic 6.
We collected data regarding age, tumour site, clinical stag-
                                                                 Results
ing defined as early (I-II), intermediate (III) and advanced
(IV) and type of surgery. Surgical treatments included mi-       Between March and April 2020, due to COVID-19, 60% of
ni-invasive procedures such as transoral laser microsurgery      all IEO scheduled outpatient visits (both first and follow-up
(TLM), open partial horizontal laryngectomy (OPHL),              visits) were postponed. From the outpatient visit database,
transoral glossectomy or oral cavity resections, robotic sur-    we noted a COVID-19 related reduction of about 11% in
gery (TORS), or major surgical (sub/total excision of the        March, and 20% in April. All follow-up visits were resched-
organ with the possible need for reconstruction).                uled as telephone contacts or remote visits. Nonetheless, in
We retrospectively assessed the “care pathway interval”          2020, about 31% of patients treated in our Department for
(CPI), defined as the time between the onset of symptoms         head and neck cancer had experienced a COVID-19-related
and the first visit, and the “time-to-treatment interval”        delay in accessing the hospital for the first visit due to the
(TTI), defined as the interval between MDB and treatment.        lockdown and fear of COVID-19 contagion.
For statistical analysis, the 2020 retrospective cohort of pa-   For the head and neck cancer patients treated in our insti-
tients (Group A) was compared with a homogenous control          tution, Group A (April-June 2020) comprised 81 patients.
group (Group B) from the 2019 MDB database (April to             Among these, radiotherapy or chemoradiotherapy was in-
June 2019).                                                      dicated in 42 cases (52%), and best supportive care was
                                                                 indicated for only one (1%) case. Two (2%) patients ex-
Contemporary literature review                                   perienced the impact of COVID-19 infection: one suffered
We conducted a literature review of the latest studies using     from pneumonia during preoperative assessment, without
the Pubmed (National Library of Medicine, USA) and Em-           any influence or delay on the patient’s treatment; the other
base (Elsevier) bibliographic databases. For the search, we      patient did not complete radiation therapy, and underwent
used the key-words (“COVID” AND “delay” AND “head                surgery.
and neck” AND “cancer”). We considered only articles             Therefore, surgery was indicated in 38 cases (47%). Four



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patients could be operated in their primary hospitals, and the                     ing, age and CPI. However, univariate analysis showed that
other two patients refused surgery. Thus, they were excluded                       median TTI in Group A (2020) was significantly lower than
from the statistical analysis. As shown in Figure 1A, 10 cases                     for to group B (2019), 13.0 days and 22.5 days, respectively
(31%) were clinically staged as early (I-II), 4 (13%) interme-                     (p = 0.01), (Tab. II and Fig. 2) which corresponds to a sig-
diate (III) and 18 (56%) advanced stage (IV). All early-stage                      nificantly higher hazard ratio (HR = 1.8, 95% CI: 1.2,3.0,
patients (100%) were treated with mini-invasive surgery. By                        p = 0.02) (Tab. III).
contrast, among the 4 intermediate-stage patients, 2 were re-
ferred for mini-invasive surgery (TORS/TLM), and the other                         Literature review
2 for major surgery. Among the 18 advanced-stage patients,                         A total of 82 records were retrieved based on the search
mini-invasive surgery was performed in 6 cases (33%), in-                          strategy. After manual screening for relevant titles and ab-
cluding 2 TORS, 1 TLM, 1 OPHL and two neck dissections                             stracts, a total of 6 studies were included in the literature
for an unknown primary tumour. Twelve (67%) advanced-                              review (Fig. 3).
stage patients received major surgery.                                             The incidence of head and neck cancer was evaluated in
Group B (April to June 2019) comprised 87 patients. Radio-                         three studies showing that, during the first wave, there were
therapy or chemoradiotherapy and best supportive care were                         significantly fewer (25%) new cases compared to the num-
indicated in 37 cases (43%) and 7 cases (8%), respectively.                        ber of new cases in 2019 (p = 0.01) 7-9. Regarding the trend
Surgery was indicated in 43 cases (49%). Among these, we                           of the time to visit defined as CPI, we found that there was
excluded 5 patients who were not treated in our institute                          a relevant increase in the study conducted by Tevetoğlu et
(n = 4) or refused surgery (n = 1). Thus, we considered 38                         al. (p = 0.02) 10 in contrast with the study by Kiong et al.
surgical patients for the statistical analysis. As shown in Fig-                   (p = 0.391) 8.
ure 1B, 9 cases (24%) were early stage (I-II), all treated with                    However, an extension of the time to diagnosis was not
mini-invasive surgery (100%). Among 13 intermediate cases                          significant in two studies 8,9, while Yao et al. reported a
(stage III; 34%), 10 patients (77%) underwent mini-invasive                        longer time to diagnosis (p = 0.02) but not to staging 11.
surgery, while 3 (23%) benefited from major surgery (all                           Four studies showed a significant increase in tumour size
cases were oral cavity cancers). Among 16 advanced cases                           (p = 0.042) 8 and in T stage 9,10,12 at presentation in the
(IV) (42%), 14 (88%) underwent major surgery, while 2                              COVID group. A worsening of N stage was not found 8,12.
(12%) mini-invasive treatments (1 TORS, 1 neck dissection                          Finally, concerning TTI, no alterations in initial thera-
for nodal recurrence of nasopharynx cancer).                                       pies modalities were registered 7,9-11, while only one study
At statistical analysis (Tab. I), no significant differences                       reported a significant extension of TTI (45 vs 35 days,
were observed in patient characteristics between groups A                          p = 0.004) between the same period in 2019 and 2020 12.
and B in terms of tumour site, type of surgery, clinical stag-                     Table IV summarises this data.


 A                                                                             B




Figure 1A-B. Type of surgery distribution in relation of clinical staging between group A (2020) and B (2019).



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Table I. Characteristics of Groups A and B.
 Characteristic                                                                                               Overall                       Calendar year                       p-value
                                                                                                            N = 70 (%)              Group A                Group B
                                                                                                                                     (2020)                 (2019)
                                                                                                                                   N = 32 (%)             N = 38 (%)
    Tumour site                                        Oral cavity                                           27 (38.6)              11 (34.3)              16 (42.1)
                                                       Larynx                                                16 (22.9)               9 (28.1)               7 (18.4)
                                                       Oropharynx                                            13 (18.5)               6 (18.8)               7 (18.4)
                                                       Other (i.e., skin, thyroid, paranasal sinus)           14 (20)                6 (18.8)              8 (21.1)               0.74
    Surgery type                                       Min-invasive surgery                                  38 (54.3)              17 (53.1)              21 (55.3)
                                                       Major surgery                                         32 (45.7)              15 (46.9)              17 (44.7)              0.81
    Clinical stage                                     Initial (I-II)                                        19 (27.1)              10 (31.3)               9 (23.7)
                                                       Intermediate (III)                                    17 (24.3)               4 (12.4)              13 (34.2)              0.12
                                                       Advanced (IV)                                         34 (48.6)              18 (56.3)              16 (42.1)
    Age, years b                                                                                            64.1 (13.1)            64.9 (13.4)            63.4 (13.1)             0.55
    Days from symptoms to first visit (CPI)                                                                 72 (34,93)             79 (34,121)            67 (30,93)              0.96
a
    Fisher’s exact test for all categorical variables, log-rank test for days from symptoms to first visit, two-sample Wilcoxon test for age. b Min: 17; Max: 82; SD: standard deviation.



Table II. Time-to-treatment interval (TTI) between group A and B.
 Risk factor                                                                                                   Events/at risk                Median (95% CI)               p-value
    Calendar year                                                                 2019                              38/38                       22.5 (16,30)
                                                                                  2020                              32/32                       13.0 (12,16)                 0.01
    Overall                                                                                                         70/70                        19 (15,22)
95% CI: 95% confidence interval.



Discussion
The COVID-19 pandemic brought about a sudden and in-
tense change in routine healthcare activities, constraining
most countries to implement emergency reorganisation
and legislative measures in order to cope with and limit the
spread of the virus 13.
During the pandemic outbreak, the IEO was nominated
as one of the comprehensive cancer centres eligible for
the building of the regional hub-and-spoke network. The
specialised hubs for oncology have been connected with
spokes to design a parallel health network for the specific
referral of patients with cancer, to direct the delivery of
nondeferrable healthcare 4.
The urgency of treatment for an oncologic patient in the
COVID-19 era is even more pressing when considering
head and neck cancer patients suffering from dysphagia,                                           Figure 2. Time to treatment interval (TTI) between group A and B.
hoarseness, or risk of fatal haemorrhage.
In our experience, even if one-third of the 2020 head and
neck cancer patients had a COVID-19-related delay in ac-                                          Table III. The risk of delayed day of treatment (surgery).
cessing hospitals, due to the stay-at-home policy, “lock-                                          Calendar year                              HR (95% CI)                         p-value
down” restrictions and fear of COVID-19 contagion, we                                               2019                                                   Ref
did not record any change, between 2020 and 2019, in the                                            2020                                              1.8 (1.1,3.0)                 0.02
surgery type, tumour clinical staging, or CPI.                                                    HR: hazard ratio; 95% CI: 95% confidence interval; Ref: reference.




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F. Chu et al.




Figure 3. Literature review flow chart.


Table IV. Summary results of the literature review.
 Year          Author                Country         COVID group -           Outcomes                  Results - differences in COVID group
                                                    pre-COVID group
                                                        n (time)
 Feb 21          Kiong KL et al. 8        USA       183 (May-Jun 20)          Incidence            Reduction in new H&NC (25%). No longer time to
                                                           –              Time to visit (CPI)       visit (p = 0.391), no longer time from histologic
                                                    252 (May-Jun 19)      Time to diagnosis       diagnosis to visit (p = 0.133). Significant increase
                                                                           Time to staging        in tumor size (p = 0.042) and T stage (p = 0.025)
                                                                                                      but no increase in N stage or AJCC 8th stage
 Oct 21          Gazzini L et al. 9       Italy    45 (Mar 20-Jan 21)         Incidence           Fewer cases per month (p = 0.01) and fewer new
                                                           –              Time to diagnosis        diagnoses (p = 0.01). Non-significant increase in
                                                   79 (May 19-Mar 20)      Time to staging         time to diagnosis (73.5 vs 64 days, p = 0.18) or
                                                                        Time to treatment (TTI)    time to treatment (30.4 vs 28.9, p = 0.77). Less
                                                                                                   early cT stage (p = 0.03) and more advanced cT
                                                                                                                           stage
 Feb 21         Tevetoğlu F et al. 10   Turkey     61 (Mar-Sep 20)        Time to visit (CPI)     Significant increase of T3-4 tumors (p = 0.049),
                                                           –                Time to staging           increased N stage in oral cavity cancer (p =
                                                    64 (Mar-Sep 19)     Time to treatment (TTI)      0.024), increased time to visit (p = 0,02). No
                                                                                                   significant increase in time to surgery (p = 0.06)
 Oct 21            Yao P et al. 11        USA        26 (Mar-Jul 20)      Time to diagnosis        Longer time to diagnosis (P = 0.02; hazard ratio
                                                            –              Time to staging          [HR], 0.54; 95% CI, 0.32-0.92). No statistically
                                                   68 (Sep 19-Jan 20)   Time to treatment (TTI)   significant differences in time to staging or time to
                                                                                                                        treatment
 Aug 21         Metzger K et al. 12      Germany    59 (Jan-Dec 20)        Time to staging           Longer time to treatment (45 vs 35 days, p =
                                                           –            Time to treatment (TTI)      0.004), higher pathological T (p = 0.046), no
                                                      566 (10-19)                                  difference in pN (p = 0.843), higher UICC stages
                                                                                                                       (p = 0.116)



This aspect is clearly in contrast with other investigators               Similarly, Yao et al. found that patients in the COVID-19
who report a longer time to diagnosis and tumour staging                  group had a significantly longer time to diagnosis than the
at the time of diagnosis. In 2021, Teveteglu et al. reported              pre-COVID-19 group after adjustment for age and cancer
a significantly higher (p = 0.02) mean time from the be-                  diagnosis (p = 0.02; HR, 0.54; 95% CI, 0.32-0.92) 11.
ginning of the first symptom to hospital admission in pa-                 Such discrepancies might be explained by the fact that,
tients treated in 2020 compared to those treated in 2019 10.              despite difficulties in accessing our institute, the intensive



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                                                                                              COVID-related delay and head and neck cancer




telephone triage and remote follow-up visits helped to           Conflict of interest statement
identify and distinguish patients who needed critical atten-     The authors declare no conflict of interest.
tion and a short-term hospital visit from those who could
be postponed.                                                    Funding
Furthermore, in contrast to findings reported by other inves-    This work was partially supported by the Italian Ministry
tigators 8,9,12 regarding a higher incidence of advanced-stage   of Health with Ricerca Corrente and 5 x 1000 funds.
diseases during COVID-19, we did not observe any sig-
nificant difference between Group A (2020) and Group B           Authors’ contributions
(2019). In addition to the protective effect of the telephone    MA: conceptualization; DS, FB and GP: data curation; DR:
triage and telemedicine visits for patients from outside the     formal analysis; FC and JZ: writing – original draft. MT,
region, the oncological network with the other regional          RDB and FC: writing – review and editing.
hospitals enabled us to facilitate patient management by
establishing dedicated outpatient visits and operating room      Ethical consideration
sessions. Patients coming from other hospitals were sched-       This study was approved by the Institutional Ethics Com-
uled for surgery after a quick preoperative assessment           mittee (Istituto Europeo di Oncologia, IRCCS) (code IEO
where the primary non-IEO referring surgeon was asked to         2432).
                                                                 The research was conducted ethically, with all study pro-
complete a detailed form with the patient’s characteristics
                                                                 cedures being performed in accordance with the require-
and tumour staging. This synergised effort led to Group A
                                                                 ments of the World Medical Association’s Declaration of
(2020) having a lower risk of experiencing a treatment de-
                                                                 Helsinki.
lay than Group B (2019) (p = 0.02). Indeed, we did not ob-
                                                                 Written informed consent was obtained from each partici-
serve any difference in clinical staging between 2020 and
                                                                 pant/patient for study participation and data publication.
2019, due to tumour progression before treatment.
Long-term follow-up data of patients operated in 2020 are
not yet available. Future studies will permit evaluation of      References
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