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Journal of Cranio-Maxillo-Facial Surgery 45 (2017) 2097e2104

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Journal of Cranio-Maxillo-Facial Surgery

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A worldwide comparison of the management of T1 and T2 anteriorfloor of the mouth and tongue squamous cell carcinoma e Extent ofsurgical resection and reconstructive measures

Katinka Kansy a, *, 1, Andreas Albert Mueller b, 1, Thomas Mücke c, 1, Friederike Koersgen a, 1,Klaus Dietrich Wolff d, 1, Hans-Florian Zeilhofer b, 1, Frank H€olzle e, 1, Winnie Pradel f, 1,Matthias Schneider g, 1, Andreas Kolk d, 1, Ralf Smeets h, 1, Julio Acero i, 2, Piet Haers j, 2,G.E. Ghali k, 2, Jürgen Hoffmann a, 1

a Department of Cranio- and Maxillofacial Surgery, Heidelberg University Hospital, Heidelberg, Germanyb Department of Oral and Maxillofacial Surgery, Universit€atsspital Basel, University of Basel, Basel, Switzerlandc Department of Oral and Maxillofacial Surgery, Malteser Kliniken Rhein-Ruhr, Uerdingen, Krefeld, Germanyd Department of Oral and Maxillofacial Surgery, Klinikum Rechts der Isar, Technische Universit€at München, München, Germanye Department of Oral and Maxillofacial Surgery, Aachen University Hospital, Aachen, Germanyf Department of Oral and Maxillofacial Surgery, Dresden University Hospital, Dresden, Germanyg Department of Oral and Maxillofacial Surgery, Dresden-Neustadt Hospital, Dresden, Germanyh Department of Oral and Maxillofacial Surgery, Hamburg University Hospital, Eppendorf, Hamburg, Germanyi Department of Oral and Maxillofacial Surgery, Ramon y Cajal University Hospital, Alcal�a University, Madrid, Spainj South Thames Cleft Service, Guy's and St Thomas' NHS Trust, London, UKk Department of Oral & Maxillofacial Surgery, Louisiana State University School of Medicine e Shreveport, USA

a r t i c l e i n f o

Article history:Paper received 8 April 2017Accepted 14 September 2017Available online 21 September 2017

Keywords:MicrosurgeryFree tissue flapsHead and neck oncologyOSCCFloor of mouth carcinomaTongue cancer

* Corresponding author. Department of Oral and MaHospital Heidelberg, Im Neuenheimer Feld 400, 6912

E-mail address: katinka.kansy@med.uni-heidelber1 D€OSAK collaborative group for microsurgical re

with the IAOMS.2 International Association of Oral and Maxillofacia

https://doi.org/10.1016/j.jcms.2017.09.0121010-5182/© 2017 European Association for Cranio-M

a b s t r a c t

Introduction: Microvascular surgery following tumor resection has become an important field of oralmaxillofacial surgery (OMFS). Following the results on general aspects of current reconstructive practicein German-speaking countries, Europe and worldwide, this paper presents specific concepts for themanagement of resection and reconstruction of T1/T2 squamous cell carcinoma (SCC) of the anteriorfloor of the mouth and tongue.Methods: The DOESAK questionnaire was distributed in three different phases to a growing number ofmaxillofacial units worldwide. Within this survey, clinical patient settings were presented to participantsand center-specific treatment strategies were evaluated.Results: A total of 188 OMFS units from 36 different countries documented their treatment strategies forT1/T2 anterior floor of the mouth squamous cell carcinoma and tongue carcinoma. For floor of mouthcarcinoma close to the mandible, a wide variety of concepts are presented: subperiosteal removal of thetumor versus continuity resection of the mandible and reconstruction ranging from locoregional closureto microvascular bony reconstruction. For T2 tongue carcinoma, concepts are more uniform.Conclusion: These results demonstrate the lack of evidence and the controversy of different guidelinesfor the extent of safety margins and underline the crucial need of global prospective randomized trials onthis topic to finally obtain evidence for a common guideline based on a strong community of OMFS units.

© 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rightsreserved.

xillofacial Surgery, University0 Heidelberg, Germany.g.de (K. Kansy).construction in cooperation

l Surgeons (IAOMS).

axillo-Facial Surgery. Published by

1. Introduction

Over the past decades microsurgery has gained more and moreimportance in reconstruction after complex OMFS tumor surgeryand has recently been explicitly formulated as the first choice ofreconstruction in the United Kingdom National Multidisciplinary

Elsevier Ltd. All rights reserved.

K. Kansy et al. / Journal of Cranio-Maxillo-Facial Surgery 45 (2017) 2097e21042098

Guidelines (Ragbir et al., 2016). This change enables the surgicaltreatment of more advanced tumor stages (Ling et al., 2013) and abetter esthetic and supposedly functional outcome (Urken et al.,1991; Canis et al., 2016). Despite this enormous development anda wide variety of different flaps used, common guidelines in thesense of a worldwide standard have not been established yet. Thismay be due to a multitude of different treatment options, con-founding variables and concepts. One approach to standard con-cepts and recommendations was to present a standard case settingand ask for different concepts in maxillofacial units first in German-speaking countries, then in Europe and finally worldwide. Thispaper presents the results for the treatment concepts of T1/T2anterior floor of the mouth and tongue SCC without infiltration ofthe mandible (Figs. 1e3).

2. Material and methods

To obtain treatment concepts three surveys were performed inGerman-speaking countries in 2010 (Mücke et al., 2011), all overEurope in 2012 (Kansy et al., 2014) and worldwide in 2014 (Kansyet al., 2015). Data collection occurred with the help of a question-naire created by the DOESAK collaborative group for microsurgicalreconstruction (Mücke et al., 2011). The original German ques-tionnaire was translated into English and afterward transferred toan online survey with the help of SurveyGizmo (SurveyGizmo,Boulder, USA) and finally revised and refined by the board of the

Fig. 1. Case studies: ge

IAOMS in 2014. The questionnaire is divided into three parts,whereas the second part contains the presented cases, T1/T2 floorof the mouth carcinoma and tongue carcinoma without boneinfiltration, and three more advanced T3/T4 cases that will beaddressed separately. Cases and questions were kept identical forall three phases of the survey to allow for comparison of concepts.Only centers that perform tumor surgery and have access tomicrovascular surgerywere included in the evaluation of treatmentconcepts to guarantee for full range of reconstructive options whenmaking treatment choices. In case of redundant concepts fromhospitals participating in more than one phase of the trial only themost recent concept was evaluated. General aspects (Fig. 1) and thedetailed description and questions of the presented cases can befound in Fig. 2 (floor of mouth) and Fig. 3 (tongue).

2.1. Data analysis

Statistics were analyzed using IBM SPSS® Statistics 21.0 (IBM SPSSStatistics forWindows, Version 21.0, released 2012, IBM Corporation,Armonk, NY, USA) and Microsoft® Office Excel (Microsoft Excel forWindows, release 2013, Microsoft Corporation, Redmond,WA, USA).

3. Results

A total of 188 OMFS departments from 36 different countriesqualified for evaluation of their case specific treatment concepts.

neral information.

Fig. 2. Case study 1: anterior floor of the mouth carcinoma without bony infiltration.

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General frequencies of tumor, reconstructive and microvascularsurgery of the participating departments are shown in Fig. 4.

When facing a 40-year-old female patient without risk factors,diagnosed with invasive SCC of the anterior floor of mouth, 1.5 cmin diameter, adjacent to the lingual cortex, but mobile (no clinicalbone infiltration), 100% of the departments would chose a primarysurgical approach, none of the participating centers would advise

primary radiation as a standard treatment in the described case(Fig. 5). When it comes to resection, 30 units would perform asubperiosteal resection, 57 units would perform a marginal man-dibulectomy, 48 a partial mandibulectomy and 53 units wouldperform a continuity resection (Fig. 5). 178 units would reconstructthe soft tissues primarily, 10 secondarily. If secondary reconstruc-tion is the treatment of choice, time of reconstruction varies

Fig. 3. Case study 4: lateral tongue carcinoma.

K. Kansy et al. / Journal of Cranio-Maxillo-Facial Surgery 45 (2017) 2097e21042100

between one and twelve months after tumor resection. Soft tissuereconstruction is most frequently performed via a regional flap (84units), but almost as frequently with a microvascular tissue transfer(77 units) (Fig. 6). 19 units would reconstruct via pedicle flaps, eightchose alternative concepts (Fig. 6). Pedicle flaps include facial arterymusculomucosal flap, platysma, sublingual gland flap, mylohyoid,pectoralis major and nasolabial flap. Alternative concepts are skingrafts. The most frequently used microvascular free flap forreconstruction of the anterior floor of mouth is the radial free

forearm flap (RFFF) (65 units), followed by the lateral upper armflap (LUAF) (8) and the anterolateral thigh flap (ALTF) (4) as the firstchoice of treatment (Fig. 6). Following continuity resection, all ofthe participating centers would reconstruct primarily: 21 via a localclosure, 22 via a microvascular tissue transfer and 10 via a pedicleflap. Hence, primary reconstruction does not necessarily includebone replacement. Of the microvascular reconstruction concepts,19 would use a RFFF, one an ALTF and only two units would performa bony reconstruction via fibula flap (FF). The most frequent

Fig. 4. Frequency of tumor (blue)/reconstructive (red) and microvascular (green) surgery in the participating departments (n ¼ 188).

Fig. 5. Primary treatment modality and amount of resection following anterior floor of mouth carcinoma (case 1) and tongue carcinoma (case 4) (n ¼ 188).

K. Kansy et al. / Journal of Cranio-Maxillo-Facial Surgery 45 (2017) 2097e2104 2101

alternative treatment options are the LUAF (4), ALTF (8), RFFF (3)and iliac crest flap (ICF) (1).

For a 62-year-old female smoker presenting with a 2 � 2 cmlateral tongue carcinoma of the medial third of tongue, thefollowing concepts are chosen as first line of treatment: 187 de-partments would perform a primary surgical resection of the tu-mor, only one department would plan for primary radiationtherapy (Fig. 5). 179 units would reconstruct primarily, eightsecondarily, two weeks to twelve months after primary tumorsurgery. First choice for reconstruction would be a local flap in 55cases, microvascular reconstruction in 112 cases, a pedicle flap ineight cases and alternative concepts including local closure andskin graft in 12 cases (Fig. 6). For microvascular reconstruction, theflap of first choice is the RFFF (86 units), followed by ALTF (22 units)and LUAF (3) (Fig. 6). The most important alternative microvascularflap is the ALTF (12 units), the RFFF (10 units) and the LUAF (2 units).88 units do not have a preferred second choice for microvascularreconstruction of the tongue.

3.1. Differences by country

When it comes to the extent of resection for anterior floor ofmouth carcinoma, there are tremendous variations in radicalness.While some units perform a periosteal resection without inclusionof bone, others perform continuity resections as their first choice oftreatment. When analyzing concepts per country, Belgium (67%)performs more marginal mandibulectomies; Brazil (67%) mostlypartial mandibulectomies; China (60%), India (60%) and Japan (80%)mostly continuity resections; France mostly partial mandibulec-tomies (40%), subperiosteal resections (27%) and marginal man-dibulectomies (27%); Germany mostly marginal mandibulectomies(42%) but also subperiosteal resections (19%), partial mandibulec-tomies (22%) and continuity resections (17%); Italy mostly sub-periosteal resections (35%) and partial mandibulectomies (35%);the Netherlands both marginal mandibulectomies (50%) and con-tinuity resections (42%) and the United States only partial man-dibulectomies (45%) and continuity resections (55%). A completely

Fig. 6. Reconstructive modalities and choices of microvascular transplant following anterior floor of mouth carcinoma (case 1) (n ¼ 188) and tongue carcinoma (case 4) (n ¼ 187).The radial forearm flap is by far the most popular microvascular transplant for reconstruction.

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mixed picture can be seen in Spain and the UK. For reconstruction,local closure is popular in Brazil (67%), France (67%), India (60%),Japan (43%), the Netherlands (75%) and Spain (67%), while inBelgium (67%), China (60%), Germany (69%), Great Britain (67%) andthe United States (45%) microvascular reconstruction is the mostpopular choice of reconstruction following anterior floor of themouth carcinoma. For tongue carcinoma, microvascular recon-struction in general is more frequent and is the first choice oftreatment in Belgium (83%), China (60%), Germany (69%), Italy(71%), Japan (50%), Spain (58%), Great Britain (86%) and the UnitedStates (73%). Local closure is a frequent first choice of reconstruc-tion in France (47%), India (60%) and the Netherlands (50%).

3.2. Differences by number of tumor patients treated per year

The number of patients treated per year does not have anyimpact on the radicalness of resection in the presented survey. Oneof the two centers with less than ten tumor patients per yearchooses a partial mandibulectomy as the standard resectionconcept for the presented case of floor of mouth carcinoma, theother one a continuity resection. All variations of resection arefound for centers with 11e20 tumor patients per year and also forcenters treating more than 20 tumor patients per year. When itcomes to reconstruction however, the number of patients treatedper year does influence the therapeutic concept: a primary localclosure as their first choice of reconstruction is performed by bothof the centers with less than 10 tumor patients per year and 60% ofthe centers with 11e20 tumor patients, but only 46% of the centerswith 21e50 tumor patients per year, 35% of the centers with51e100 tumor patients per year and 43% of the centers with morethan 100 tumor patients per year. On the other hand, microvascularreconstruction is the treatment of choice for 25% of the centers with11e20 tumor patients per year, but for 33% of the centers with21e50 tumor patients, 53% of the centers with 51e100 tumor pa-tients and 45% of the centers with more than 100 tumor patientsper year.

For tongue carcinoma, this is different: while still none of thecenters with less than ten tumor patients per year choose micro-vascular reconstruction as their first line of treatment, 50% of thecenters with 11e20 tumor patients, 60% of the centers with 21e50tumor patients, 70% of the centers with 51e100 tumor patients and55% of the centers with more than 100 tumor patients per year do.Local closure is the first choice of treatment for T2 tongue

carcinoma in 20% of the centers with 11e20 tumor patients, in 35%of the centers with 21e50 tumor patients, in 20% of the centerswith 51e100 tumor patients and in 34% of centers with more than100 tumor patients per year.

4. Discussion

For both presented cases, a T1 floor of mouth carcinoma and a T2lateral tongue carcinoma, surgical resection is the first choice oftreatment. These findings may be due to the fact that the surveywas performed among surgeons. Within the literature, there are noprospective randomized trials comparing primary surgery andprimary radiation therapy for T1 floor of mouth carcinoma and a T2lateral tongue carcinoma, but a multitude of trials have identifiedclear tumor margins as one of the most important independentfactors of survival (Pfister et al., 2000, 2016; Brown et al., 2002;O'Brien et al., 2003; Kovacs, 2004; Patel et al., 2008; Wolff et al.,2012; Ling et al., 2013; Maxwell et al., 2015).

However, within the survey, there are no global uniform con-cepts concerning amount of resection and measures of recon-struction and there is no general agreement on how to obtain thesetumor-free margins.

Due to the nature of this study, it was not possible to collectreliable data on disease-free survival of the patients to correlatewith the suggested treatment concepts.

The controversy how to sufficiently obtain tumor-free marginsis also seen in current treatment guidelines: in everyday clinicalpractice this translates into the rule of thumb of a clinical safetymargin of around 10 mm from the tumor corresponding to an R0situation with a tumor-free margin of at least 3e5 mm at histo-pathologic analysis in the current German guidelines for diagnosisand treatment of oral cavity cancer and its update in 2015 (Wolffet al., 2012) and a clinical safety margin of 1.5e2 cm with atumor-free margin of at least 5 mm at histopathologic analysis inthe American NCCN guidelines (Pfister et al., 2016). The dilemma isalso reflected by the difficulty of finding an accurate uniform re-sidual tumor classification and the complex solution suggested byWittekind et al. (2009).

While the extent of resection for a T2 tongue carcinoma isrelatively simple as the anatomical unit of the tongue can still berespected following both guidelines, this is not true for anteriorfloor of mouth carcinoma with its proximity to the mandible. Thedifferences in the guidelines directly reflect the differences of

K. Kansy et al. / Journal of Cranio-Maxillo-Facial Surgery 45 (2017) 2097e2104 2103

treatment concept for anterior floor of mouth carcinoma in Ger-many and the United States in our survey: while in United States,the resection of choice is either a partial mandibulectomy (45%) or acontinuity resection (55%); in Germany mostly marginal man-dibulectomies (42%) but also subperiosteal resections (19%), partialmandibulectomies (22%) and continuity resections (17%) areperformed.

The results in the literature are controversial: while in theretrospective analysis of 50 patients of Guerra et al. comparingmarginal mandibulectomy and continuity resection showed higherrecurrence rates for marginal mandibulectomies, at the same time11 patients of the marginal mandibulectomy group but only twopatients of the continuity resection group showed bony invasionquestioning the impact of confounding variables and analyzing acohort not comparable to the presented case (Guerra et al., 2003).In another article, the same author then analyzed a larger cohortand found that mandibular preservation surgery was oncologicallysafe for patients with squamous carcinoma in early stages and thatthe marginal technique was not associated with worse prognosis(Munoz Guerra et al., 2003). O'Brien et al. compared marginal andsegmental resections even at the presence of histological provenbone invasion and found that conservative (marginal) resection ofthe mandible was safe as long as marginal mandibulectomy did notlead to a compromise of soft tissue margins (O'Brien et al., 2003).Brown et al. also found favorable results for a conservative resectionof the mandible as long as soft tissue margins were accurate andstretched the importance of the exact position of the tumor inrelation to the mandible with angling of the horizontal rim resec-tion when necessary (Brown et al., 2002). However, he found ahigher number of inaccurate soft tissue margins with rim re-sections. Patel compared marginal and segmental mandibulec-tomies retrospectively and found no differences in outcome for thetwo concepts regardless of the extent of bony invasion as long asmargins were clear (Patel et al., 2008). Studies on themechanism ofbone infiltration and metastatic spread showed no correlation be-tween the frequency of lymph node metastases and infiltration ofthe periosteum and bone in previously not irradiated patients(Marchetta et al., 1971; McGregor and MacDonald, 1988).

When an anatomical region like the oral cavity with a multitudeof complex functions and very high density of important anatomicalstructures is the primary site of tumor resection, this controversy isnot an academic but a true problem in everyday clinic with enor-mous consequences for every single patient involved. If margins arechosen too closely, the risk of incomplete resection and subsequentrecurrence increases, if chosen too widely, esthetic impairment andfunctional restrictions of speech, chewing and swallowing may betremendous, permanently limiting patients' quality of life (QOL).Also, as the results of the survey demonstrate, when a continuityresection is performed, microvascular reconstruction with a bonytransplant is only the first choice of treatment in 4% (2/53) of therespective departments. 40% (21/53) would perform a local closurefollowing continuity resection of the mandible as their first choice oftreatment, 19% (10/53) a pedicle flap. Hence, almost all of the pa-tients will not get a bony reconstruction of the resected mandible.Most likely, the majority of the correspondent departments willperform a diminution of the mandible and approximate theremaining segments of the mandible. However, this will lead to bothfunctional and esthetic impairments.

In the literature, complication rates following plate and softtissue reconstruction are higher than following bony reconstruc-tion, especially for central defects as in the presented case and forirradiated patients (Boyd et al., 1995). Concerning soft tissuecoverage, Cordeiro and Hidalgo showed a superiority of free flapscompared to the pectoralis major flap to cover plates (Cordeiro andHidalgo, 1994).

The impact of primary or secondary reconstruction of themandible on survival is difficult to determine with no prospectivedata in the literature available. A retrospective monocentric anal-ysis of Hanken et al. found no increased risk for local recurrence ordifferences in survival for T4 tumors after primary reconstruction(Hanken et al., 2015). As stated by other authors, in secondaryreconstruction, surgery becomes more demanding due to scarringand the reduced quality and number of recipient vessels (Reinertand Lentrodt, 1994).

QOL followingmicrovascular bony reconstructionof themandibleis superior to QOL for patients without reconstruction (Urken et al.,1991). For tumors <4 cm without adjuvant therapy, patients had aworse QOL following segmental resection in comparison with rimresections in the studyof Rogers et al. (2004), in linewith thefindingsof Becker et al. who demonstrated an inverse correlation betweenQOL and amount of resected bone (Becker et al., 2012).

For tongue reconstruction, evidence is sparse. While Canis et al.show a superiority of microvascular reconstruction in T3 tonguecarcinoma (Canis et al., 2016), most trials do not differentiate tumorsite nor tumor size nor compare microvascularly reconstructed andnon-reconstructed patients. Boyapati et al. found a satisfactory QOLfor local closure following early stage tongue and floor of mouthcarcinoma (Boyapati et al., 2013). A recentmeta-analysis comparingtongue reconstruction with RFFF versus ALTF found comparableoutcomes concerning appearance, swallowing and speech withfewer donor sitemorbidities for the ALTF (Chen et al., 2016). A studyretrospectively comparing QOL following tongue reconstructionwith RFFF versus pectoralis major pedicle flap showed bettershoulder function with RFFF but worse appearance (Li et al., 2016).However, both papers do not specify their modality of forearmclosure. Yang reports the successful application of LUAF for tonguereconstruction with good QOL in line with the results of our survey(Yang et al., 2016).

The by far most frequently used microvascular flap for the twocases is the RFFF also following continuity resection of themandible. Bony reconstruction following continuity resection ofthe anterior mandible is rare in this part of the survey. This is incontrast to the overall results (Mücke et al., 2011; Kansy et al., 2014,2015) and the literature (Soutar et al., 1983; Chen et al., 1994). Thismay be due to an alternative concept with approximation of butts.

5. Conclusion

Aside from general agreement on surgery as the first choice oftreatment, there are no uniform concepts for T1 floor of mouthcarcinoma among OMF surgeons worldwide. Despite the impor-tance of clear tumor margins, the amount of resection variesgreatly. Particularly surprising is the small number of microvascularbony reconstruction following continuity resection of the anteriormandible in this survey. For T2 tongue carcinoma, there are twomajor concepts of reconstruction following complete resection:either primary closure or microvascular reconstruction via radialforearm flap. The findings of the presented survey and currentevidence levels in the literature underline the crucial need for well-designed prospective multi-center trials to finally establish com-mon treatment concepts on an international guideline standard inthe treatment of early tongue and floor of mouth cancer.

FundingThis research did not receive any specific grant from funding

agencies in the public, commercial, or not-for-profit sectors.

Conflict of interest statement/disclosureAll authors disclose any financial and personal relationships

with other people or organizations that could inappropriately

K. Kansy et al. / Journal of Cranio-Maxillo-Facial Surgery 45 (2017) 2097e21042104

influence their work. Conflicts of interest: none. All authors haveapproved the final article.

References

Becker ST, Menzebach M, Kuchler T, Hertrampf K, Wenz HJ, Wiltfang J: Quality oflife in oral cancer patients e effects of mandible resection and socio-culturalaspects. J Craniomaxillofac Surg 40: 24e27, 2012

Boyapati RP, Shah KC, Flood V, Stassen LF: Quality of life outcome measures usingUW-QOL questionnaire v4 in early oral cancer/squamous cell cancer resectionsof the tongue and floor of mouth with reconstruction solely using localmethods. Br J Oral Maxillofac Surg 51: 502e507, 2013

Boyd JB, Mulholland RS, Davidson J, Gullane PJ, Rotstein LE, Brown DH, et al: Thefree flap and plate in oromandibular reconstruction: long-term review andindications. Plast Reconstr Surg 95: 1018e1028, 1995

Brown JS, Kalavrezos N, D'Souza J, Lowe D, Magennis P, Woolgar JA: Factors thatinfluence the method of mandibular resection in the management of oralsquamous cell carcinoma. Br J Oral Maxillofac Surg 40: 275e284, 2002

Canis M, Weiss BG, Ihler F, Hummers-Pradier E, Matthias C, Wolff HA: Quality of lifein patients after resection of pT3 lateral tongue carcinoma: microvascularreconstruction versus primary closure. Head Neck 38: 89e94, 2016

Chen H, Zhou N, Huang X, Song S: Comparison of morbidity after reconstruction oftongue defects with an anterolateral thigh cutaneous flap compared with aradial forearm free-flap: a meta-analysis. Br J Oral Maxillofac Surg 54:1095e1101, 2016

Chen YB, Chen HC, Hahn LH: Major mandibular reconstruction with vascularizedbone grafts: indications and selection of donor tissue. Microsurgery 15:227e237, 1994

Cordeiro PG, Hidalgo DA: Soft tissue coverage of mandibular reconstruction plates.Head Neck 16: 112e115, 1994

Guerra MF, Campo FJ, Gias LN, Perez JS: Rim versus sagittal mandibulectomy for thetreatment of squamous cell carcinoma: two types of mandibular preservation.Head Neck 25: 982e989, 2003

Hanken H, Wilkens R, Riecke B, Al-Dam A, Tribius S, Kluwe L, et al: Is immediatebony microsurgical reconstruction after head and neck tumor ablation associ-ated with a higher rate of local recurrence? J Craniomaxillofac Surg 43:373e375, 2015

Kansy K, Müller AA, Mücke T, Koersgen F, Wolff KD, Zeilhofer HF, et al: Microsur-gical reconstruction of the head and neck region: current concepts of maxil-lofacial surgery units worldwide. J Craniomaxillofac Surg 43: 1364e1368, 2015

Kansy K, Müller AA, Mücke T, Kopp JB, Koersgen F, Wolff KD, et al: Microsurgicalreconstruction of the head and neck e current concepts of maxillofacial surgeryin Europe. J Craniomaxillofac Surg 42: 1610e1613, 2014

Kovacs AF: Relevance of positive margins in case of adjuvant therapy of oral cancer.Int J Oral Maxillofac Surg 33: 447e453, 2004

Li W, Zhang P, Li R, Liu Y, Kan Q: Radial free forearm flap versus pectoralis majorpedicled flap for reconstruction in patients with tongue cancer: assessment ofquality of life. Med Oral Patol Oral Cir Bucal 21: e737ee742, 2016

Ling W, Mijiti A, Moming A: Survival pattern and prognostic factors of patients withsquamous cell carcinoma of the tongue: a retrospective analysis of 210 cases.J Oral Maxillofac Surg 71: 775e785, 2013

Marchetta FC, Sako K, Murphy JB: The periosteum of the mandible and intraoralcarcinoma. Am J Surg 122: 711e713, 1971

Maxwell JH, Thompson LD, Brandwein-Gensler MS, Weiss BG, Canis M, Purgina B,et al: Early oral tongue squamous cell carcinoma: sampling of margins fromtumor bed and worse local control. JAMA Otolaryngol Head Neck Surg 141:1104e1110, 2015

McGregor AD, MacDonald DG: Routes of entry of squamous cell carcinoma to themandible. Head Neck Surg 10: 294e301, 1988

Mücke T, Müller AA, Kansy K, Hallermann W, Kerkmann H, Schuck N, et al:Microsurgical reconstruction of the head and neck e current practice ofmaxillofacial units in Germany, Austria, and Switzerland. J CraniomaxillofacSurg 39: 449e452, 2011

Munoz Guerra MF, Naval Gias L, Campo FR, Perez JS: Marginal and segmentalmandibulectomy in patients with oral cancer: a statistical analysis of 106 cases.J Oral Maxillofac Surg 61: 1289e1296, 2003

O'Brien CJ, Adams JR, McNeil EB, Taylor P, Laniewski P, Clifford A, et al: Influence ofbone invasion and extent of mandibular resection on local control of cancers ofthe oral cavity and oropharynx. Int J Oral Maxillofac Surg 32: 492e497, 2003

Patel RS, Dirven R, Clark JR, Swinson BD, Gao K, O'Brien CJ: The prognostic impact ofextent of bone invasion and extent of bone resection in oral carcinoma.Laryngoscope 118: 780e785, 2008

Pfister DG, Ang K, Brockstein B, Colevas AD, Ellenhorn J, Goepfert H, et al: NCCNpractice guidelines for head and neck cancers. Oncology (Williston Park) 14:163e194, 2000

Pfister DG, Spencer S, Adelstein D, Adkins D, Brizel DM, Burtness B, et al: NCCNguidelines version 1.2016 panel members. Head and neck cancers. J Natl ComprCanc Netw, 2016

Ragbir M, Brown JS, Mehanna H: Reconstructive considerations in head and necksurgical oncology: United Kingdom National Multidisciplinary Guidelines.J Laryngol Otol 130: S191eS197, 2016

Reinert S, Lentrodt J: Results and special aspects of secondary microsurgical bonetransfer in the area of the facial skull. Fortschr Kiefer Gesichtschir 39: 126e128,1994

Rogers SN, Devine J, Lowe D, Shokar P, Brown JS, Vaugman ED: Longitudinal health-related quality of life after mandibular resection for oral cancer: a comparisonbetween rim and segment. Head Neck 26: 54e62, 2004

Soutar DS, Scheker LR, Tanner NS, McGregor IA: The radial forearm flap: a versatilemethod for intra-oral reconstruction. Br J Plast Surg 36: 1e8, 1983

Urken ML, Buchbinder D, Weinberg H, Vickery C, Sheiner A, Parker R, et al: Func-tional evaluation following microvascular oromandibular reconstruction of theoral cancer patient: a comparative study of reconstructed and nonreconstructedpatients. Laryngoscope 101: 935e950, 1991

Wittekind C, Compton C, Quirke P, Nagtegaal I, Merkel S, Hermanek P, et al:A uniform residual tumor (R) classification: integration of the R classificationand the circumferential margin status. Cancer 115: 3483e3488, 2009

Wolff KD, Follmann M, Nast A: The diagnosis and treatment of oral cavity cancer.Dtsch Arztebl Int 109: 829e835, 2012

Yang XD, Zhao SF, Zhang Q, Wang YX, Li W, Hong XW, et al: Use of modified lateralupper arm free flap for reconstruction of soft tissue defect after resection of oralcancer. Head Face Med 12: 9, 2016