European Archives of Oto-Rhino-Laryngology (2021) 278:4373–4381 https://doi.org/10.1007/s00405-021-06957-5 LARYNGOLOGY Salvage carbon dioxide transoral laser microsurgery for laryngeal cancer after (chemo)radiotherapy: a European Laryngological Society consensus statement Cesare Piazza1,2 · Alberto Paderno1,2 · Elisabeth V. Sjogren3 · Patrick J. Bradley4 · Hans E. Eckel5 · Antti Mäkitie6 · Nayla Matar7 · Vinidh Paleri8 · Giorgio Peretti9 · Roberto Puxeddu10 · Miquel Quer11 · Marc Remacle12 · Vincent Vander Poorten13,14 · Isabel Vilaseca15 · Ricard Simo16 Received: 16 April 2021 / Accepted: 23 June 2021 / Published online: 5 July 2021 © The Author(s) 2021 Abstract Purpose To provide expert opinion and consensus on salvage carbon dioxide transoral laser microsurgery ­(CO2 TOLMS) for recurrent laryngeal squamous cell carcinoma (LSCC) after (chemo)radiotherapy [(C)RT]. Methods Expert members of the European Laryngological Society (ELS) Cancer and Dysplasia Committee were selected to create a dedicated panel on salvage C ­ O2 TOLMS for LSCC. A series of statements regarding the critical aspects of decision- making were drafted, circulated, and modified or excluded in accordance with the Delphi process. Results The expert panel reached full consensus on 19 statements through a total of three sequential evaluation rounds. These statements were focused on different aspects of salvage ­CO2 TOLMS, with particular attention on preoperative diagnostic work-up, treatment indications, postoperative management, complications, functional outcomes, and follow-up. Conclusion Management of recurrent LSCC after (C)RT is challenging and is based on the need to find a balance between oncologic and functional outcomes. Salvage C ­ O2 TOLMS is a minimally invasive approach that can be applied to selected patients with strict and careful indications. Herein, a series of statements based on an ELS expert consensus aimed at guiding the main aspects of ­CO2 TOLMS for LSCC in the salvage setting is presented. Keywords Carbon dioxide laser · Transoral laser microsurgery · Laryngeal cancer · Radiotherapy · Chemoradiation · Salvage surgery Introduction hence the need to opt for other treatments. Open-neck con- servative options are hampered by RT-induced tissue modi- Radiotherapy (RT) and chemoradiation (CRT) are well- fications that frequently lead to complications and unpre- established treatments for laryngeal squamous cell carci- dictable recurrence patterns, possibly reducing the rates of noma (LSCC), with oncologic outcomes comparable with laryngeal preservation and disease control. This prevented those obtained by surgery when appropriate patient selec- their widespread acceptance and application, while different tion has been accomplished. However, local recurrence after groups confirmed their effectiveness in very selected cases primary RT is not a rare event even in early–intermediate even in the rescue setting [9–11]. As a consequence, in most LSCC, ranging from 5 to 20 and from 25 to 30% in cT1 and instances, total laryngectomy is still considered the standard cT2 lesions, respectively [1–5]. This poses a significant issue salvage treatment for patients previously treated with (C) in patient management given the limited salvage treatment RT experiencing LSCC recurrence. However, in such cases, options after (C)RT. Laryngeal re-irradiation is rarely possi- ensuing complications and unavoidable functional sequelae ble due to poor oncological and functional results [6–8], and (i.e., loss of physiologic phonation and swallowing impair- ment) almost invariably lead to a decreased quality of life. For these reasons, carbon dioxide transoral laser micro- * Alberto Paderno surgery ­(CO2 TOLMS) definitively represents, when fea- albpaderno@gmail.com sible, an extremely attractive option [12]. Several authors Extended author information available on the last page of the article have confirmed the feasibility and oncological soundness 13 Vol.:(0123456789) 4374 European Archives of Oto-Rhino-Laryngology (2021) 278:4373–4381 of salvage C­ O2 TOLMS (Table 1) [13–28]. However, the were considered achieving borderline consensus (thus need- suggested indications are highly variable and shared guide- ing modification and supplementary evaluation) when scores lines strongly needed. Therefore, the European Laryngologi- ranged between 6 and 7, or more than 7 with outlier respond- cal Society (ELS) selected an expert panel to discuss and ers. Statements were considered without consensus (and reach consensus on key statements regarding preoperative therefore deleted) when the score was less than 6, regardless management, treatment indications, and follow-up of LSCC of the presence or not of outliers. after (C)RT. These statements represent the ensuing opin- The process required a total of three rounds. In the first ion coming from such a consensus and, in our view, could round, responses were double-blinded (to both responders potentially guide the decision-making process in the salvage and analyzers). In this phase, the statements without con- ­CO2 TOLMS scenario. sensus were deleted, while those with borderline consensus were selected, modified to better specify the rationale of the items, and re-evaluated in a second round. The second round Methods was single-blinded (only to responders) to allow subsequent feedback from those in disagreement (scores lower than 5). Members of the panel were selected from the ELS Commit- The third round consisted in personal communication among tee on Laryngeal Cancer and Dysplasia (9 members, one panel members to negotiate a final consensus. of which declined participation) and other ELS members with proven experience in ­CO2 TOLMS until reaching the number of 15. This number was agreed to ensure enough Results variation and, at the same time, allow an odds ratio for which a consensus was reached. Response rates to the survey were 100% (15 of 15 panelists) The initial statements were drafted by two authors (C.P. for the first and second rounds, while only two members of and A.P.) based on their personal experience and relevant the panel were involved in the third round. literature. A modified Delphi survey was constructed for distribution throughout the group of authors (C.P., A.P., First round E.V.S., P.J.B, H.E.E., A.M., N.M., V.P., G.P., R.P., M.Q., M.R., V.V.P., I.V., and R.S.) to determine the consensus for A total of 20 statements were drafted and submitted to all each provisory recommendation [29]. members. Among those, 13 reached a full consensus in this phase (mean score, 8.2; range 7.6–8.7). Conversely, one Modified Delphi process statement did not reach consensus (score, 5.9) and was there- fore deleted, while 6 reached a borderline consensus due to The modified Delphi process was utilized to determine insufficient score in 3 (mean score, 6.4; range 6.1–6.7), or which statements achieved full consensus. Through this outlier responses in 3. Statements reaching borderline con- method, each expert on the panel expressed his/her opinion sensus were subsequently modified and re-submitted in the for each proposed statement using a dedicated online survey. second round. Responses for the modified Delphi survey were collected electronically. Results were analyzed using a Likert scale Second round ranging from 1 to 9, utilizing the following anchor points: 1 (strongly disagree), 3 (disagree), 5 (neutral), 7 (agree), A total of 6 statements, modified from the first round, were and 9 (strongly agree). Statements were defined as achiev- submitted to all members. Five reached full consensus ing full consensus if there was a mean score of 7 or greater, (mean score, 7.9; range, 7.6–8.4), while one reached border- and no outlier responses (scores lower than 5). Statements line consensus due to outlier responses by 2 panelists. The Table 1  Oncologic outcomes Authors Year No. of patients T-categories 5-year DSS 5-year OS of ­CO2 TOLMS in the salvage setting reported in the recent Quer et al. [14] 2000 24 rT1-rT2 100% 76% literature and including only Steiner et al. [17] 2004 34 rT1-rT4 86% 53% series with 5-year results Ansarin et al. [19] 2007 37 rTis-rT2 – 86% Roedel et al. [22] 2010 53 rT1-rT3 68.6% 53.3% Han et al. [23] 2012 18 rT1-rT2 90% 84.3% Del Bon et al. [24] 2012 35 rT1-rT2 94% 91% Meulemans et al. [28] 2018 33 rT1-rT3 95.5% 80.3% 13 European Archives of Oto-Rhino-Laryngology (2021) 278:4373–4381 4375 statement not reaching full consensus was further discussed Preoperative staging is a crucial step in planning salvage in the third round. ­ O2 TOLMS. Underestimation of rT-category is a frequent C issue due to diagnostic difficulties in the post-(C)RT setting Third round [22]. In particular, RT-related inflammation and mucosal alterations may be a significant confounding factor leading to Consensus on the last statement was reached by direct dis- late identification of recurrent mucosal lesions. Endoscopy cussion with the two experts in disagreement. After accurate plays a pivotal role in diagnostic assessment of recurrence. evaluation and contextualization of the statement, consensus Post-RT tissue modifications should be taken into account was reached without the need to modify the statement itself. and distinguished from tumor relapse. In line with ELS rec- ommendations for the follow-up of patients treated for LSCC [32], high-definition videolaryngoscopy, possibly integrated Discussion and recommendations with video recording, storage of images, and use of bioen- doscopy, is the most accurate clinical evaluation tool. This Diagnostic work‑up is especially true after (C)RT, thanks to the high accuracy of bioendoscopy in differentiating between neoplastic disease Assessment of pre‑(C)RT staging and post-RT inflammatory/cicatricial changes, even though mainly limited to the superficial aspect of the mucosal lin- • The pre-(C)RT staging of the disease needs to be care- ing and needing a longer learning curve than that observed fully assessed to determine the best salvage treatment. for naïve LSCC [33, 34]. Evaluation of vocal fold mobility Recurrent lesions after RT originating from a primary is also essential to direct treatment indications. Impaired tumor initially categorized as cT1 or cT2 without impair- vocal fold mobility or arytenoid fixation can result from RT- ment of vocal fold mobility and/or anterior transcom- induced damage of the vocal muscle or crico-arytenoid joint. missural extension can be considered for salvage C ­ O2 However, it can also be a sign of deep tumor infiltration that TOLMS. needs to be discerned by specific radiologic evaluation [35]. • Tumors initially categorized as cT2 with impaired vocal Good laryngeal exposure is an essential consideration cord mobility, anterior transcommissural extension, cT3 in previously irradiated patients and can be compromised for vocal cord/arytenoid fixation, or thyroid cartilage ero- because of reduced neck flexibility and tissue elasticity. The sion, and failed after (C)RT should be considered subop- Laryngoscore and the mini-Laryngoscore are preoperative timal candidates for salvage ­CO2 TOLMS. tools aimed at predicting laryngeal exposure by analyzing patient characteristics [36–39]. The Laryngoscore includes These considerations are related to the fact that tumor previous (C)RT as a negative factor for intraoperative expo- response to (C)RT does not induce a homogeneous concen- sure, and its influence should be considered together with tric shrinkage of the lesion; instead, multiple resistant tumor other anatomical variables. foci may residue in otherwise healthy/cicatricial tissues [30]. The possibility of underestimation of the T category prior Radiologic evaluation to (C)RT should be also taken into account. Consequently, safe resection margins can only be obtained by planning the • Cross-sectional imaging is warranted in all patients with excision in consideration of the initial tumor extent before recurrent LSCC after (C)RT. Magnetic resonance (MR) (C)RT. This cannot be obtained if the primary tumor was not should be preferred in view of its capability to better safely resectable by C­ O2 TOLMS in the first instance, as is distinguish between inflammation, scar, and neoplastic especially the case for cT3 lesions with vocal cord/arytenoid tissue. fixation or thyroid cartilage erosion [31]. • Preoperative imaging by chest computed tomography (CT) scan, total body CT scan, or positron emission Clinical and office‑based assessment of rT tomography (PET)/CT scan should be employed to exclude distant metastasis and synchronous tumors. • Preoperative evaluation should be performed by high- definition videolaryngoscopy, possibly using biologic Submucosal tumor spread of recurrent LSCC is a frequent endoscopy techniques such as Narrow Band Imaging occurrence, thus hindering detection through endoscopic (NBI), Storz Professional Image Enhancement System techniques. For these reasons, state-of-the-art radiologic (SPIES), I-Scan, or others. imaging should be employed. MR offers higher contrast • Preoperative prediction of laryngeal exposure can be of resolution than CT, and is particularly helpful in distin- help in treatment planning to identify patients at a high guishing tumor infiltration from peritumoral inflammation risk of difficult laryngeal exposure. and depicting cartilage invasion [40]. This is especially true 13 4376 European Archives of Oto-Rhino-Laryngology (2021) 278:4373–4381 using surface coils directly applied to the neck, designed Treatment indications to provide improved signal-to-noise ratios by limiting the spatial extent of the excitation and reception [35]. Glottic recurrence Finally, in the setting of persistent or recurrent LSCC after (C)RT, systemic imaging should be employed to rule • Glottic LSCCs recurring after (C)RT and categorized as out distant metastasis. PET/CT scan, carried out at least rcTis-T2 with normal vocal fold mobility can be consid- 12 weeks after treatment, demonstrated an adequate diag- ered for salvage ­CO2 TOLMS. However, pre-treatment nostic potential in LSCC and head and neck cancer in gen- staging and laryngeal exposure (see "Diagnostic work- eral [41–43]. However, its effectiveness in detecting occult up") should be carefully taken into account. nodal metastases in recurrent LSCC remains debated [44]. • Glottic rT1b with anterior commissure involvement and Alternative imaging protocols (i.e., total body CT or chest rT2 with anterior transcommissural extension should be CT scan) may be considered, especially in low-risk patients considered for ­CO2 TOLMS only in the presence of opti- [45], in view of their minor cost and broader availability. mal laryngeal exposure. Evaluation under general anesthesia Various authors described the oncologic outcomes of salvage ­CO2 TOLMS and proposed different indications • Tumor evaluation with high-definition rigid endoscopy in relation to complications and survival results [13–28]. (under white light and NBI/SPIES/I-Scan) and biopsy Most series included rTis-T2 tumors; however, in some under general anesthesia should be considered in all cases, indications were extended up to rT4a lesions [17, 22]. ­ O2 TOLMS and patients with an indication to salvage C Treatment of T3-T4a glottic LSCC has been described in indeterminate findings at the office-based evaluation. both primary and salvage ­CO2 TOLMS, but requires careful • Evaluation of the real exposure and transoral full visibil- selection and significant surgical and technical expertise, ity of the entire tumor through the laryngoscope should being associated with unpredictable functional outcomes, ideally precede C­ O2 TOLMS of any rT to improve treat- notwithstanding the frequent need for complementary (C) ment planning and patient counseling. RT, which is clearly not repeatable in a salvage setting. Moreover, rT3-T4a lesions, as well as rT2 with impaired Considering the potential difficulties and confounding vocal fold mobility or anterior transcommissural extension, factors related to office-based endoscopy after (C)RT, panen- may have unexpected patterns of spread due to their deep doscopy under general anesthesia should be performed with infiltration, thus increasing the risk of local recurrence. In a very low threshold in all cases with indeterminate or suspi- this setting, the results are strongly operator-dependent, cious findings at endoscopic and/or radiologic evaluation. and this factor prevents large-scale treatment adoption with Random biopsies should be avoided because of their limited homogeneous oncologic results. Furthermore, extensive diagnostic potential and risk of complications (e.g., soft- removal of the perichondrium and resection of the cartilage tissue edema, and chondritis with possible chondronecrosis). can lead to impaired wound healing, chondronecrosis, and Conversely, biopsies should be precisely targeted (eventu- necrosis of soft tissues. These complications often result in ally following laser incision to reach submucosal tissues) to severe functional impairment, impacting airway patency and suspicious areas found using biologic endoscopy techniques. swallowing, and may ultimately require total laryngectomy. Salvage ­CO2 TOLMS requires optimal laryngeal expo- The same holds true when considering recurrent LSCCs sure given the need for a more extensive resection and dif- originating from advanced primary lesions (i.e., cT3-T4). ficult discrimination of tumor boundaries. In patients with Adequate treatment of these lesions including the pre-(C) a high risk of difficult laryngeal exposure at preoperative RT tumor margins would require a resection extending to evaluation, assessment of exposure under general anesthe- the perichondrium or cartilage, thus incurring in the above- sia is essential to direct the subsequent treatment approach. mentioned issues. In all cases, optimal laryngeal exposure with a large-bore As in the primary setting, management of tumors with laryngoscope should be obtained, allowing adequate visu- anterior commissure involvement remains a debated issue. In alization up to the anterior commissure. Excellent laryngeal this regard, oncologic results in the salvage setting are vari- exposure is an absolute prerequisite for salvage C ­ O2 TOLMS able and their evaluation is severely impaired by the small (even more than in the primary setting), since safe resection sample size of the cohorts reported [15, 17, 19, 22]. In fact, margins can usually be obtained only by more enlarged pro- some authors confirm anterior commissure involvement as cedures (Type III–VI cordectomy) and accurate microscopic a risk factor for recurrence, while others understate its risk assessment. Patients presenting suboptimal exposure should potential. However, in view of the complex anatomical and be evaluated for alternative approaches regardless of their technical management of this subsite [46], optimal laryn- rT-category. geal exposure should always be ensured before embarking 13 European Archives of Oto-Rhino-Laryngology (2021) 278:4373–4381 4377 into a salvage C­ O2 TOLMS addressing the region. This by concomitant ­CO2 TOLMS and neck dissection have a recommendation has also been confirmed by Steiner and significant risk of complications (such as fistula formation coworkers, highlighting a lower laryngeal preservation rate or subcutaneous emphysema) and postoperative laryngeal in patients with anterior commissure involvement and sub- edema. In this view, the “cost–benefit ratio” of salvage C ­ O2 optimal laryngeal exposure [17]. TOLMS tends to increase dramatically in case of advanced lateral neck recurrence (rN > 1), both in terms of oncologic Supraglottic recurrence results and complication rate. • Supraglottic LSCCs categorized as rcTis-T2 can be effec- Postoperative management and complications tively treated by salvage CO2 TOLMS. • Prophylactic antibiotic therapy should be used to prevent As for glottic LSCC, various authors have described postoperative infection/chondritis/chondronecrosis. the technical feasibility of transoral supraglottic resection • Resumption of oral feeding is usually straightforward up to rT3 lesions [13, 14, 21, 25, 26]. However, the fibro- after glottic procedures; however, in supraglottic resec- cartilaginous laryngeal framework does not effectively stem tions, there is often a need for nasogastric feeding tube bulky T3 and T4a tumors that invariably require resection for some days. of the hyoid bone, thyrohyoid membrane, thyroid cartilage, • Patients should be carefully monitored to detect early and soft tissues of the neck. Surgery in this setting becomes signs of perichondritis, chondritis, or chondronecrosis so particularly challenging, hampering its widespread adoption that appropriate therapeutic measures can be instigated. with satisfying oncologic outcomes. The ensuing functional results are often suboptimal and worsened by frequent post- Salvage ­CO2 TOLMS can lead to reduced sensitivity operative and long-term complications (e.g., chronic aspira- and mobility of the larynx, resulting in an increased risk tion, pneumonia, chondronecrosis, and soft-tissue necrosis). of aspiration during the early postoperative period. Patients rcTis-T2 tumors may be more easily approached and undergoing supraglottic resections (particularly if reaching treated by salvage C ­ O2 TOLMS. However, patient selec- the aryepiglottic fold and/or the arytenoid) or extensive glot- tion plays a crucial role in treatment planning. Functional tic procedures are at higher risk of aspiration and therefore outcomes are invariably worse than in the primary setting, prolonged use of a nasogastric feeding tube [47]. and patients should be able to tolerate chronic subclinical Perichondral damage following ­CO2 TOLMS may allow aspiration and a lengthy swallowing rehabilitation program. bacteria to gain access to the cartilage with possible infec- In particular, extensive resection of the aryepiglottic fold tion. This may lead to perichondritis, an inflammatory with arytenoidectomy should be avoided given the extremely process of the perichondrium that precedes chondritis and high risk of postoperative acute and chronic aspiration [47]. chondronecrosis. In hypovascularized and irradiated tissues, infection initiates a vicious cycle leading to tissue damage Regional recurrence and hypoxia, compromised vascularity, and further progres- sion of the infective/inflammatory process [48, 49]. Con- • Concomitant local (rT > 1) and regional (rN > 1) recur- sequently, chondronecrosis is significantly more likely in rence after (C)RT should be considered a suboptimal patients who received high-dose RT combined with expo- indication to salvage ­CO2 TOLMS. sure or disruption of the perichondrium. For this reason, prophylactic antibiotic therapy may be helpful in patients Salvage ­CO2 TOLMS should not be considered as a receiving resections exposing the perichondrium, while no first-line treatment for patients with extensive loco-regional data are yet available on the utility of this aid. recurrence of LSCC because of different factors. First of all, Once developed, laryngeal chondronecrosis is often irre- the presence of regional recurrence should be regarded as versible. Total laryngectomy is frequently required because a sign of potential underestimation of the true primary and/ of life-threatening bleeding, laryngeal framework collapse, or recurrent tumor extension. Lateral neck metastasis may and ensuing airway obstruction. Chondronecrosis should be be related to undetected deep tumor extension and lympho- monitored and evaluated according to the grading system vascular invasion. proposed by Chandler et al. [50]. Grades I and II are com- Moreover, it is not possible to adequately address the mon post-RT changes and typically respond favorably to lymphatic vessels connecting the tumor with pathologic conservative treatments (i.e., humidification, voice restraint, lymph nodes (the so-called “T-N tract”) through a purely discontinuation of smoking, and antibiotics), while Grade transoral approach. In-transit metastatic cells may be left III and IV reactions are more severe and have less favorable in the soft tissues between the endoscopic surgical field outcomes. Perichondritis, chondritis, and chondronecrosis and the neck dissection specimen. Finally, patients treated may respond well to hyperbaric oxygen therapy, even though 13 4378 European Archives of Oto-Rhino-Laryngology (2021) 278:4373–4381 persistent tumor should be absolutely ruled out before con- roughness, breathiness, asthenia, and strain score) showed sidering this treatment to avoid hyperbaric oxygen-induced mild, moderate, and severe dysphonia in 12.5%, 25%, and tumor acceleration [51, 52]. However, Grades III and IV 37.5% of patients, respectively. Furthermore, videolaryn- are significantly less likely to be successfully treated by a gostroboscopy showed incomplete glottic closure in 56% conservative approach. of patients [18]. Complications of salvage ­CO2 TOLMS reported in the recent literature are summarized in Table 2. Follow‑up Functional outcomes • Follow-up policy should strictly observe guidelines pro- vided by the ELS, with particular attention to the indica- • Tracheotomy and gastrostomy tube placement are infre- tions after (C)RT. quently, and usually only temporarily, needed in the sal- vage ­CO2 TOLMS setting. Follow-up has a critical role in the overall management • Vocal outcomes after salvage C ­ O2 TOLMS are usually of patients treated by salvage ­CO2 TOLMS. In fact, recur- inferior to those obtained in the primary setting. Moder- rences are more frequent and less easily detected than in the ate or severe dysphonia should be expected. primary setting. All measures described in the “Diagnostic • A slower and more gradual resumption of swallowing work-up” section should be undertaken when evaluating a should be expected in supraglottic resections compared newly developed lesion or functional alteration. In adjunc- with purely glottic procedures. tion, the development of treatment-related complications should also be monitored in the medium and long terms. The length of feeding tube dependency and chronic aspi- The ELS has proposed a series of recommendations ­ O2 TOLMS ration rate are significantly higher in salvage C for the follow-up of patients treated for LSCC to provide [53]. Nevertheless, according to a recent systematic review, an up-to-date, evidence-based protocol that is meaningful postoperative tracheotomy and gastrostomy in patients and applicable to all European health care systems [32]. treated by ­CO2 TOLMS were needed only in 2.3% and 6.6% These recommendations represent an optimal framework of patients, respectively [54]. Furthermore, several studies from which to structure patient follow-up after salvage ­CO2 have reported higher gastrostomy tube dependency rates in TOLMS. supraglottic recurrences compared to glottic ones [25, 26]. However, the number of patients involved was not sufficient for precise and reliable comparisons. Conclusions Objective data assessing vocal outcomes in salvage ­CO2 TOLMS are scarce and heterogeneous. In general, the Management of recurrent LSCC after (C)RT is particularly results seem to be inferior to those in the primary setting, challenging and requires careful evaluation to select the opti- while a small study providing a direct comparison did not mal therapeutic option according to the characteristics of find significant differences [24]. In a study by Puxeddu and the patient and tumor. In this setting, ­CO2 TOLMS has the coworkers, postoperative perceptual voice evaluation (grade, crucial role to allow a conservative and minimally invasive Table 2  Complications reported in the recent literature Authors Year No. of patients Reported complications Quer et al. [14] 2000 24 Laryngeal stenosis (N = 2) De Gier et al. [15] 2001 44 Chondritis (N = 2) Steiner et al. [17] 2004 34 Synechiae (N = 3), aspiration pneumonia (N = 1), chondronecrosis (N = 1), laryngeal stenosis (N = 1) Puxeddu et al. [18] 2004 16 None Ansarin et al. [19] 2007 37 Laryngeal stenosis (N = 4) Roedel et al. [22] 2010 53 Laryngeal edema (N = 5), synechiae (N = 4), laryngeal stenosis (N = 3), postoperative bleeding (N = 2), chondronecrosis (N = 1) Han et al. [23] 2012 18 Excessive granulation tissue (N = 3), temporary lingual numbness (N = 2), temporary hypoglossal palsy (N = 1) Del Bon et al. [24] 2012 35 Chondronecrosis (N = 2), chondritis (N = 1), postoperative bleeding (N = 1) Abouyared et al. [26] 2014 52 Prolonged postoperative pain (N = 13), chondronecrosis (N = 12) Fink et al. [27] 2016 42 Laryngeal edema (N = 1) 13 European Archives of Oto-Rhino-Laryngology (2021) 278:4373–4381 4379 approach even after failure of primary non-surgical therapy. 7. 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Eckel5 · Antti Mäkitie6 · Nayla Matar7 · Vinidh Paleri8 · Giorgio Peretti9 · Roberto Puxeddu10 · Miquel Quer11 · Marc Remacle12 · Vincent Vander Poorten13,14 · Isabel Vilaseca15 · Ricard Simo16 13 European Archives of Oto-Rhino-Laryngology (2021) 278:4373–4381 4381 1 9 Department of Otorhinolaryngology—Head and Neck Department of Otorhinolaryngology—Head and Neck Surgery, ASST—Spedali Civili di Brescia, University Surgery, IRCCS Ospedale Policlinico San Martino, of Brescia, Piazza Spedali Civili 1, 25123 Brescia, Italy University of Genoa, Genoa, Italy 2 10 Department of Medical, Surgical and Radiological Sciences Unit of Otorhinolaryngology—Head and Neck Surgery, and Public Health, University of Brescia, Brescia, Italy Azenda Ospedaliero Universitaria, Presidio Ospedaliero 3 Duilio Casula, Cagliari, Italy Department of Otolaryngology—Head and Neck Surgery, 11 Leiden University Medical Centre, Leiden, The Netherlands Department of Otolaryngology—Head and Neck Surgery, 4 University Hospital de la Santa Creu i Sant Pau, Universitat Department of ORL‑HNS, Queens Medical Centre Campus, Autonòma de Barcelona, Barcelona, Spain Nottingham University Hospitals, Derby Road, Nottingham, 12 UK Department of Otolaryngology, Centre Hospitalier du 5 Luxembourg, Luxembourg, Luxembourg Department of Oto‑Rhino‑Laryngology—Head and Neck 13 Surgery, Klagenfurt General Hospital, Klagenfurt, Austria Department of Otorhinolaryngology—Head and Neck 6 Surgery, Leuven Cancer Institute, University Hospitals Department of Otorhinolaryngology—Head and Neck Leuven, Leuven, Belgium Surgery, University of Helsinki and HUS Helsinki University 14 Hospital, Helsinki, Finland Department of Oncology, Section Head and Neck Oncology, 7 KU Leuven, Leuven, Belgium Department of Otolaryngology—Head and Neck Surgery, 15 Saint Joseph University, Hotel Dieu de France Hospital, Otorhinolaryngology Service, Hospital Clinic de Barcelona, Beirut, Lebanon Universitat de Barcelona, Barcelona, Spain 8 16 Head and Neck Unit, The Royal Marsden NHS Foundation Department of Otorhinolaryngology—Head and Neck Trust, London, UK Surgery, Head, Neck and Thyroid Cancer Unit, Guy’s and St Thomas Hospital NHS Foundation Trust, London, UK 13