The impact of time between surgery and adjuvant chemoradiotherapy in advanced oral cavity squamous cell carcinoma.

Objective: In advanced oral squamous cell carcinoma (OSCC), adjuvant therapy (AT) is an important part of the treatment to ensure extended locoregional control after primary surgical resection. The impact of the time interval between surgery and AT on the oncological prognosis remains unclear, particularly in high-risk constellations. The aim of this study is to categorize treatment delays and to determine their impact on the oncological prognosis within the context of the histopathological risk parameters of patients with advanced OSCC. Methods: In this single-institutional retrospective cohort study, all patients treated for OSCC between 2016 and 2021 and who received postoperative chemoradiation (POCRT) were included. Patients were divided into two groups: Group I: ≤ 6 weeks between surgery and POCRT; and Group II: > 6 weeks between surgery and POCRT. Results: Overall, 202 patients were included (Group I: 156 (77.2%) vs. Group II: 46 (22.8%)). There were no statistically significant differences in epidemiological aspects and histopathological risk factors between the two groups. The maximum time to initiation of POCRT was 11 weeks. Delayed POCRT initiation had no statistically significant influence on the 5-year OS (61.6% vs. 57.3%, p = 0.89), locoregional control rate (38.6% vs. 43.3%, p = 0.57), and RFS (32.3% vs. 30.4%, p = 0.21). On multivariate analysis, extracapsular spread (HR: 2.21, 95% CI: 1.21 - 4.04, p = 0.01) and incomplete surgical resection (HR: 2.01, 95% CI: 1.10 - 3.69, p = 0.02) were significantly correlated with OS. For RFS, ECS (HR: 1.82, 95% CI: 1.15 - 2.86, p = 0.01), incomplete resection (HR: 1.67, 95% CI: 1.04 - 2.71, p = 0.04), and vascular infiltration of the tumor (V-stage; HR: 2.15, 95% CI: 1.08 - 4.27, p = 0.03) were significant risk predictors. Conclusion: Delays in POCRT initiation up to 11 weeks after surgical resection for advanced OSCC were not statistically significantly associated with impaired survival. In cases of prolonged surgical treatment due to management of complications, a small delay in AT beyond the recommended time limit may be justified and AT should still be pursued.

Resection status and margin control in intraoperative frozen sectioning analysis of oral squamous cell carcinoma.

PURPOSE: Intraoperative frozen section analysis (IFSA) is a well-established procedure for determining the intraoperative soft tissue resection status in patients with oral squamous cell carcinoma (OSCC). Margin status is a major predictor of the patient´s outcome, histologically free margins of ≥ 5 mm are demanded. This study evaluates the accuracy of IFSA, the impact of margin status and the impact of intraoperative margin revision on disease-free survival (DFS) and overall survival (OS). METHODS: This retrospective study included 213 patients with OSCC. IFSA results were compared with definitive histopathological reports, Kaplan-Meier analysis was performed. Cut-off values were calculated for resection margins considering known risk factors. RESULTS: IFSA showed positive margins in 8 cases (3.8%). Kaplan-Meier analysis revealed no significant differences for OS or DFS if R0-status was achieved by initial resection or immediate re-resection. Final histopathological evaluation revealed false-positive IFSA in 3/8 cases (37.5%) and false-negative IFSA in 1/205 cases (0.5%). Sensitivity was 83.3% and specificity was 98.6%. Analysis of optimal cut-off values showed no general need for larger resection margins in patients with risk factors. Cut-off values were slightly higher for patients with the risk factor alcohol consumption (7 mm for OS and DFS) or pN + ECS- disease (7 mm for DFS). Optimal cut-off values for tumour-margin-distance were around 6 mm. CONCLUSION: IFSA provides a valuable assessment method for intraoperative soft tissue resection margins. Risk factors seemingly do not significantly influence the extent of tumour resection.

A modified pull-through approach with a pedicled bone flap for oral and oropharyngeal cancer resection: a feasibility study.

PURPOSE: Compromised swallowing, speaking, and local complications are the major disadvantages of established approaches to the posterior tongue and oropharynx. The mandibular split involves an esthetically unpleasant bipartition of the lower lip and is prone to bony non-union or sequestration. The conventional pull-through technique on the other hand lacks the secure reattachment of the lingually released soft tissues. METHODS: The feasibility of a new modified pull-through approach was tested on three anatomical specimens. CAD/CAM cutting guides were used to design a retentive bone flap to properly refixate the genioglossus and geniohyoid muscles after the procedure. The radiographic assessment and treatment planning was performed on 12 cadavers. The entire procedure was tested surgically via dissection in three of those cases. This procedure was then applied in a clinical case. RESULTS: Precise repositioning and dynamic compression of bony segments was possible reproducibly and without injury to adjacent structures. In all dissected cases, a median lingual foramen was found and in two cases vessels entering it could be dissected Radiologic anatomical landmarks were sufficient in all 12 cases to perform the clinical planning procedure. Clinically, the osteotomized segment demonstrated good blood supply and plateless repositioning was verified postoperatively via cone beam scan. CONCLUSION: The method presented is safe and easy to perform. Individual cutting guides improve the safety and accuracy of the procedure, potentially eliminating the need for osteosynthesis. We provide the anatomical and radiologic basis for clinical evaluation of this pedicled bone flap procedure and present the clinical application of this modified pull-through approach.

Biomechanical evaluation of CAD/CAM magnesium miniplates as a fixation strategy for the treatment of segmental mandibular reconstruction with a fibula free flap.

Titanium patient-specific (CAD/CAM) plates are frequently used in mandibular reconstruction. However, titanium is a very stiff, non-degradable material which also induces artifacts in the imaging. Although magnesium has been proposed as a potential material alternative, the biomechanical conditions in the reconstructed mandible under magnesium CAD/CAM plate fixation are unknown. This study aimed to evaluate the primary fixation stability and potential of magnesium CAD/CAM miniplates. The biomechanical environment in a one segmental mandibular reconstruction with fibula free flap induced by a combination of a short posterior titanium CAD/CAM reconstruction plate and two anterior CAD/CAM miniplates of titanium and/or magnesium was evaluated, using computer modeling approaches. Output parameters were the strains in the healing regions and the stresses in the plates. Mechanical strains increased locally under magnesium fixation. Two plate-protective constellations for magnesium plates were identified: (1) pairing one magnesium miniplate with a parallel titanium miniplate and (2) pairing anterior magnesium miniplates with a posterior titanium reconstruction plate. Due to their degradability and reduced stiffness in comparison to titanium, magnesium plates could be beneficial for bone healing. Magnesium miniplates can be paired with titanium plates to ensure a non-occurrence of plate failure.

Oncologic Outcome in Advanced Oral Squamous Cell Carcinoma After Refusal of Recommended Adjuvant Therapy.

Importance: Clinicians may be confronted with patients refusing recommended adjuvant therapy (AT) after the primary resection of an advanced oral squamous cell carcinoma (OSCC). However, for this tumor entity, data are lacking regarding the oncological outcomes and associated factors after refusal of AT. Objective: To evaluate the difference in survival and disease recurrence for patients with and without recommended AT after resection of advanced OSCC. Design, Setting, and Participants: In this single-center retrospective matched cohort study, patients with advanced OSCC who refused recommended AT between January 2010 and December 2021 were matched 1:1 according to Union for International Cancer Control tumor staging with patients who completed AT. Exposures: Patients with advanced OSCC who refused or completed recommended AT between 2010 and 2021. Main Outcomes and Measures: The primary outcome of this study was the comparison of overall survival (OS) and recurrence-free survival (RFS) between the 2 study groups. Results: A total of 82 patients (mean [SD] age at time of surgery, 68.0 [11.3] years; 38 [46.3%] female, 44 [53.7%] male) with and without AT (41 per study group) were included in the analysis. Patients refusing AT developed more frequent disease recurrence than patients who completed AT (61.0% vs 26.8%; difference, 34.2%; odds ratio, 4.26; 95% CI, 1.68-10.84). In addition, patients who refused AT presented with lower 2-year OS (72.7% vs 88.6%; difference, 15.9%; 95% CI, 8.6%-40.6%) and much lower 2-year RFS (39.1% vs 74.2%; difference, 35.1%; 95% CI, 0.2%-70.5%). In the patient cohort who rejected AT, a worse OS was associated with female sex (48.6% vs 90.5%; difference, 41.9%; 95% CI, 0.6%-84.4%), pT1-2 category (57.1% vs 92.3%; difference, 35.2%; 95% CI, 3.3%-73.6%), and pN1 or higher category (61.2% vs 82.6%; difference, 21.4%; 95% CI, 14.1%-56.8%). Lower RFS was associated with female sex (37.9% vs 90.9%; difference, 53.0%; 95% CI, 8.0%-97.9%), advanced T category (pT3-4, 35.3% vs 80.0%; difference, 44.7%; 95% CI, 6.4%-95.3%), lymph node yield of 20 or greater (31.4% vs 80.6%; difference, 49.2%; 95% CI, 4.9%-93.4%), and lymph node ratio of less than 4.6% (36.6% vs 84.4%; difference, 47.8%; 95% CI, 1.8%-93.1%). Conclusions and Relevance: In this cohort study of patients with advanced OSCC, refusal of AT was associated with worse oncological outcomes. The prevalence of disease recurrence during follow-up was 34% higher in patients who refused AT than in patients who completed AT. The results from this study may assist clinicians in guiding patients who are considering refusal of or withdrawal from AT.

Patient-specific 3D-printed mini-versus reconstruction plates for free flap fixation at the mandible: Retrospective study of clinical outcomes and complication rates.

This study aimed to compare the clinical outcomes and complication rates of patient-specific 3D-printed mini- and reconstruction plates for free flap fixation in mandibular reconstruction. A retrospective monocentric study was carried out between April 2017 and December 2021 to analyze patients undergoing immediate mandibular reconstruction using fibula free flaps and osteosynthesis using patient-specific 3D-printed implants. Eighty-three patients with a mean age of 63.6 years were included. The mean follow-up period was 18.5 months. Patient-specific 3D-printed plates were designed as reconstruction plates (38 patients), miniplates (21 patients) or a combination of reconstruction- and miniplates (24 patients). With miniplates, plate removal was performed significantly more often via an intraoral approach (p < 0.001) and in an outpatient setting (p = 0.002). Univariate analysis showed a higher fistula rate with reconstruction plates (p = 0.037). Multivariate analysis showed no significant differences in complications. Case-control matching demonstrated significantly lower rates of fistula (p = 0.017) and non-union (p = 0.029) in the combined group. This retrospective study shows a tendency towards reduced complication rates with patient-specific 3D-printed miniplates in comparison to patient-specific 3D-printed reconstruction plates for immediate mandibular reconstruction with fibula free flaps.

Sentinel lymph node biopsy in recurrent or secondary oral squamous cell carcinoma after previous neck dissection.

OBJECTIVES: The aim of this retrospective study was to evaluate the potential of sentinel lymph node biopsy (SLNB) in patients with recurrent or a secondary oral squamous cell carcinoma (OSCC) without clinical signs of lymph node metastases (cN0), who were previously treated with a surgical approach. PATIENTS AND METHODS: Retrospective analysis of all patients with cN0 recurrent or secondary OSCC, who were treated using SLNB after previous neck dissection. Endpoints were sentinel lymph node (SLN) detection rate, negative predictive value (NPV) and sensitivity. RESULTS: A total of 17 patients with a mean age of 68.6 years were included. SLN were detected in 15 of 17 cases (detection rate: 88.2%). In seven patients (41.2%), a bilateral or contralateral lymph drainage of a unilateral carcinoma was found. Two patients (11.8%) demonstrated a positive SLN upon pathohistological analysis, which led to an upstaging. In one case, a non-SLN was positive, which is considered a false-negative result. The mean follow-up for all patients with histologically negative SLN including the patients without a detected SLN was 11.8 months (range: 0-31 months). Of these, one patient developed (isolated) neck recurrence after 12 months resulting in an overall NPV of 86.7% and a sensitivity of 50.0% for the SLNB as a neck staging procedure. CONCLUSION: SLNB can improve the staging of patients with recurrent or secondary OSCC, who present with a history of a previous neck dissection. Further studies are required to demonstrate the oncological benefit of SLNB in this patient cohort.

Adjuvant Radiotherapy in Patients with Squamous Cell Carcinoma of the Oral Cavity or Oropharynx and Solitary Ipsilateral Lymph Node Metastasis (pN1)-A Prospective Multicentric Cohort Study.

(1) Background: Evaluation of impact of adjuvant radiation therapy (RT) in patients with oral squamous cell carcinoma of the oral cavity/oropharynx (OSCC) of up to 4 cm (pT1/pT2) and solitary ipsilateral lymph node metastasis (pN1). A non-irradiated group with clinical follow-up was chosen for control, and survival and quality of life (QL) were compared; (2) Methods: This prospective multicentric comprehensive cohort study included patients with resected OSCC (pT1/pT2, pN1, and cM0) who were allocated into adjuvant radiation therapy (RT) or observation. The primary endpoint was overall survival. Secondary endpoints were progression-free survival and QL after surgery; (3) Results: Out of 27 centers, 209 patients were enrolled with a median follow-up of 3.4 years. An amount of 137 patients were in the observation arm, and 72 received adjuvant irradiation. Overall survival did not differ between groups (hazard ratio (HR) 0.98 [0.55-1.73], p = 0.94). There were fewer neck metastases (HR 0.34 [0.15-0.77]; p = 0.01), as well as fewer local recurrences (HR 0.41 [0.19-0.89]; p = 0.02) under adjuvant RT. For QL, irradiated patients showed higher values for the symptom scale pain after 0.5, two, and three years (all p < 0.05). After six months and three years, irradiated patients reported higher symptom burdens (impaired swallowing, speech, as well as teeth-related problems (all p < 0.05)). Patients in the RT group had significantly more problems with mouth opening after six months, one, and two years (p < 0.05); (4) Conclusions: Adjuvant RT in patients with early SCC of the oral cavity and oropharynx does not seem to influence overall survival, but it positively affects progression-free survival. However, irradiated patients report a significantly decreased QL up to three years after therapy compared to the observation group.

Patient-specific miniplates versus patient-specific reconstruction plate: A biomechanical comparison with 3D-printed plates in mandibular reconstruction.

BACKGROUND: Patient-specific 3D-printed miniplates for free flap fixation in mandibular reconstruction were recently associated with enhanced osseous union. Higher mechanical strains resulting from these plates are discussed as reasons, but biomechanical studies are missing. This study aims to examine, whether patient-specific 3D-printed miniplates provide an increased interosteotomy movement (IOM) and lower stiffness compared with reconstruction plates. METHODS: Polyurethane (PU) mandible and fibula models (Synbone AG, Malans, Schweiz) were used to simulate mandibular reconstruction with a one segment fibula flap equivalent. Osteosynthesis was performed using either four patient-specific 3D-printed miniplates (3D-Mini) or one patient-specific 3D-printed reconstruction plate (3D-Recon). Mastication was simulated using cyclic dynamic loading with increasing loads until material failure or a maximum load of 1000 N. Continuous IOM recording was carried out using a 3D optical tracking system (ARAMIS, Carl Zeiss GOM Metrology, Braunschweig, Germany). FINDINGS: The averaged stiffness at a load of 100-300 N load did not differ between the groups (p = 0.296). There was a faster 1.0 mm vertical displacement in the 3D-Mini group (26 376 ± 14 190 cycles versus 44 817 ± 30 430 cycles, p = 0.018). The IOM were higher with miniplate fixation in the distal gap (p = 0.040). In the mesial gap, there was no significant difference between the groups (p = 0.160). INTERPRETATION: Fixation with patient-specific 3D-printed miniplates results in higher mechanical strains. Lower rates of pseudarthrosis, as seen in clinical studies, might be caused by this phenomenon. Surgeons should evaluate the primary use of 3D-printed miniplates in mandibular reconstruction due to advantages of intraoral plate removal alongside safe osteosynthesis.

Management of the Contralateral Neck in Unilateral Node-Positive Oral Squamous Cell Carcinoma.

INTRODUCTION: In lateralized oral squamous cell carcinoma (OSCC) with ipsilateral cervical lymph node metastasis (CLNM), the surgical management of the unsuspicious contralateral neck remains a matter of debate. The aim of this study was to analyze this cohort and to compare the outcomes of patients with and without contralateral elective neck dissection (END). MATERIAL AND METHODS: A retrospective analysis of patients with lateralized OSCC, ipsilateral CLNM (pN+) and contralateral cN0-stage was performed. Patients were divided into two groups according to the surgical management of the contralateral neck: I: END; and II: no END performed. Adjuvant radiotherapy was applied bilaterally in both groups according to individual risk. RESULTS: A total of 65 patients (group I: 16 (24.6%); group II: 49 (75.4%)) with a median follow-up of 28 months were included. Initially, there was no case of contralateral CLNM after surgery. During follow-up, 6 (9.2%) patients presented with recurrent CLNM. In 5 of these cases (7.7%), the contralateral neck (group I: 3/16 (18.8%); group II: 2/49 (4.1%)) was affected. Increased ipsilateral lymph node ratio was associated with contralateral CLNM (p = 0.07). END of the contralateral side showed no significant benefit regarding OS (p = 0.59) and RFS (p = 0.19). CONCLUSIONS: Overall, the risk for occult contralateral CLNM in patients with lateralized OSCC ipsilateral CLNM is low. Our data suggest that END should not be performed routinely in this cohort. Risk-adapted radiotherapy of the contralateral neck alone seems to be sufficient from the oncological point of view.

Towards mechanobiologically optimized mandible reconstruction: CAD/CAM miniplates vs. reconstruction plates for fibula free flap fixation: A finite element study.

Due to their advantages in applicability, patient-specific (CAD/CAM) reconstruction plates are increasingly used in fibula free flap mandible reconstruction. In addition, recently, CAD/CAM miniplates, with further advantages in postoperative management, have been introduced. However, biomechanical conditions induced by CAD/CAM systems remain partially unknown. This study aimed to evaluate the primary fixation stability of CAD/CAM fixators. For a patient-specific scenario, the biomechanical conditions induced in a one segmental fibula free flap stabilized using either a CAD/CAM reconstruction plate or CAD/CAM miniplates were determined using finite element analysis. The main output parameters were the strains between intersegmental bone surfaces and stresses in the fixation systems due to different biting scenarios. CAD/CAM miniplates resulted in higher mechanical strains in the mesial interosseous gap, whereas CAD/CAM reconstruction plate fixation resulted in higher strains in the distal interosseous gap. For all investigated fixation systems, stresses in the fixation systems were below the material yield stress and thus material failure would not be expected. While the use of CAD/CAM miniplates resulted in strain values considered adequate to promote bone healing in the mesial interosseous gap, in the distal interosseous gap CAD/CAM reconstruction plate fixation might result in more beneficial tissue straining. A mechanical failure of the fixation systems would not be expected.

Prognostic value of lymph node involvement in oral squamous cell carcinoma.

OBJECTIVES: Different parameters have been identified in patients with oral squamous cell carcinomas (OSCC) that have a serious impact on survival, including residual tumour and extracapsular spread. Moreover, other factors, including the lymph node ratio (LNR) and lymph node yield (LNY), have been suggested as prognostic markers. MATERIAL AND METHODS: This retrospective study included patients diagnosed with OSCC and cervical lymph node metastases during the years 2010-2020. Patients' records were evaluated regarding lymph node status, final therapy regime, tumour recurrence, time to death, tumour association with death, disease-free survival (DSF), and overall survival (OS). RESULTS: In 242 patients with a mean age of 63.57 ± 11.24 years, treated either by selective neck dissection (SND; n = 70) or by modified radical neck dissection (MRND; n = 172), 5772 lymph nodes were detected. The LNR and LNY were identified as independent risk factors in OS and DFS. The optimal cut-off point for the LNY was ≥ 17 lymph nodes in the SND and ≥ 27 lymph nodes in the MRND group. The metastatic lymph node clearance (MLNC) was established as a score to relate the LNR and LNY to the extent of lymph node removal. Survival analysis showed statistically significant differences among score levels. CONCLUSIONS: As information about the extent of nodal dissection is excluded from LNR and LNY, we propose the use of a new scoring system comprising individual cut-off values for LNY and LNR with regard to the extent of neck dissection. CLINICAL RELEVANCE: MLNC might help to identify high-risk OSCC patients with metastatic lymph nodes.

Modified McLaughlin's Dynamic Muscle Support in the 21st Century? A Retrospective Study With a Prospective Follow-Up Analysis for Patients With Long Standing Facial Paralysis.

INTRODUCTION: Facial nerve paralysis can dramatically affect the life of a patient as it leads to significant alterations of the facial symmetry and functional limitations. Various methods exist including free neuromuscular flaps to reanimate patients suffering from uni- or even bilateral facial nerve paralysis. The more than 60-year-old technique described by McLaughlin continues to offer an alternative with distinct advantages for the individual patient. The present study aimed to evaluate clinical outcome and satisfaction of patients treated with a modified McLaughlin's Dynamic Muscle Support. MATERIALS AND METHODS: A total of 13 patients (mean age of 58.4 years) who received a modified McLaughlin's Dynamic Muscle Support due to uni- or bilateral long-standing facial paralysis were included. Medical records were reviewed retrospectively, and patients were contacted for additional follow-up. Patients who agreed to participate in the follow-up study were asked to answer a self-developed questionnaire. RESULTS: In all patients, a rehabilitation of facial symmetry with an improvement of the mimic expression could be achieved. Mean length of inpatient stay was 6.5 days and average duration of surgery was 121 minutes. No surgical site infection occurred. Mean follow-up was 23 months. Most of the patients were fully satisfied with the result and could experience functional and esthetic improvement.Patients who participated in the prospective follow-up study were very satisfied with the esthetic result and functional outcome. CONCLUSIONS: Even in times of advanced microsurgical techniques, McLaughlin's Dynamic Muscle Support appears to be a good alternative for the successful treatment of long-standing facial paralysis.

Increased rate of pseudarthrosis in the anterior intersegmental gap after mandibular reconstruction with fibula free flaps: a volumetric analysis.

OBJECTIVES: Pseudarthrosis after mandibular reconstruction leads to chronic overload of the osteosynthesis and impedes dental rehabilitation. This study evaluates the impact of gap site on osseous union in mandible reconstruction using a new volumetric analysis method with repeated cone-beam computed tomography (CBCT). METHODS: The degree of bone regeneration was evaluated in 16 patients after mandible reconstruction with a fibula free flap and patient-specific reconstruction plates. Percentual bone volume and width changes in intersegmental gaps were retrospectively analyzed using a baseline CBCT in comparison to a follow-up CBCT. Patients' characteristics, plate-related complications, and gap sites (anterior/posterior) were analyzed. Detailed assessments of both gap sites (buccal/lingual/superior/inferior) were additionally performed. RESULTS: Intersegmental gap width (p = 0.002) and site (p < 0.001) significantly influence bone volume change over two consecutive CBCTs. An initial larger gap width resulted in a lower bone volume change. In addition, anterior gaps showed significantly less bone volume changes. Initial gap width was larger at posterior segmental gaps (2.97 vs 1.65 mm, p = 0.017). CONCLUSIONS: A methodology framework has been developed that allows to quantify pseuarthrosis in reconstructed mandibles using CBCT imaging. The study identifies the anterior segmental gap as a further risk factor for pseudarthrosis in reconstructions with CAD/CAM reconstruction plates. Future research should evaluate whether this outcome is related to the biomechanics induced at this site.

Pattern of cervical lymph node metastases in squamous cell carcinoma of the upper oral cavity - How to manage the neck.

OBJECTIVES: Oral squamous cell carcinoma (OSCC) arising from the upper oral cavity is rare compared to other localizations. While cervical lymph node metastasis (CLNM) can be predicted to some extent, the probability of occult CLNM remains high. The aim of this study is to determine risk factors affecting clinical decision making. MATERIALS AND METHODS: A retrospective analysis of patients surgically treated between 2012 and 2017 for OSCC of the upper oral cavity was performed. RESULTS: A total of 66 patients were included. Of these, 25 patients (37.9%) presented with CLNM after histopathological examination (pN+/cN0: 10/44 (22.7%); pN+/cN+: 15/22 (68.2%)). Lymph vessel infiltration (p = 0.03) and grade of differentiation (p = 0.03) were associated with an increased probability for CLNM. Patients with positive nodal disease at the time of primary surgery showed higher tumor depth of invasion (DOI) than patients without CLNM (mean 10.3 mm ± 6.9 versus mean 6.1 mm ± 4.9; p = 0.02). The optimal DOI cutoff value for the prediction of CLNM was 4.5 mm. The OS was significantly higher in patients with a tumor DOI ≤ 4.5 mm (p = 0.01). CONCLUSION: Elective neck dissection should be preferably performed for OSCC of the upper oral cavity. For early-stage and clinically node-negative patients, sentinel-lymph node biopsy can be an alternative, especially in patients with a DOI ≤ 4.5 mm. Since this group had no occult CLNM below this DOI cutoff value, watch and wait might be an alternative for selected patients.

Patient-Specific 3D-Printed Miniplates for Free Flap Fixation at the Mandible: A Feasibility Study.

Background: This study was conducted to evaluate the feasibility, clinical outcomes, and accuracy of patient-specific 3D-printed miniplates for mandible reconstruction with fibula free flaps. Methods: A feasibility study was conducted with 8 patients. Following virtual planning, patient-specific 1.0 mm titanium non-locking miniplates were produced via laser selective melting. 3D-printed cutting and drilling guides were used for segmental mandible resection and flap harvesting. Flap fixation was performed with two 4-hole miniplates and 2.0 mm non-locking screws (screw length 7 mm) for each intersegmental gap. Clinical follow-up was at least 6 months. Preoperative and postoperative CT/cone beam CT data were used for 3D accuracy analysis and evaluation of bone healing. Plate-related complications were monitored clinically. Results: Patient-specific miniplate fixation of all flaps was successfully conducted (4 mono-segmental, 4 dual-segmental) with high accuracy (3.64 ± 1.18 mm) between the virtual plan and postoperative result. No technical complications were encountered intraoperatively. Osseous union occurred in all intersegmental gaps (1 partial, 18 complete) after 10 ± 2 months. No material fracture, dislocation, or plate exposure was observed. Conclusions: Based on this pilot observational study including a limited number of patients, free flap fixation for mandibular reconstruction with patient-specific 3D-printed miniplates is feasible and associated with high accuracy, bone healing, and remote soft tissue complications.

Prognostic Significance of Estrogen Receptor Alpha in Oral Squamous Cell Carcinoma.

INTRODUCTION: Several studies suggest an estrogen receptor alpha (ERα)-mediated influence on the pathogenesis of oral squamous cell carcinoma (OSCC), as described for other malignancies that are not considered to be primarily hormone-dependent. Recently, an association between ERα expression and improved survival in oropharyngeal squamous cell carcinoma (OPSCC) has been found. However, the prognostic relevance of ERα in OSCC has not been proven to date. Therefore, the aim of this study was to evaluate ERα expression in OSCC in a large patient cohort and analyze its influence on survival and recurrence. MATERIAL AND METHODS: A total of 316 patients with primary OSCC who received initial surgical therapy were included in this analysis. The expression of ERα was evaluated on tissue microarrays by immunohistochemistry in the primary tumor and/or primary lymph node metastases. The expression level was quantified by light microscopy using the immunoreactive score (IRS) for estrogen receptor detection. An IRS equal to or greater than 2 was considered positive. The 5-year overall survival (OS) and relapse-free survival (RFS) were examined by the Kaplan-Meier method and log-rank test. RESULTS: A total of 316 patients (111 females; 205 males) with a mean age of 61.3 years (range 27-96 years) were included in this study. In 16 patients (5.1%; 6 females and 10 males), positive ERα expression was found in the primary tumor (n = 11; 11/302) or lymph node metastases (n = 5; 5/52). Patients with positive ERα expression in primary tumors/primary lymph node metastases had a significantly lower OS and RFS (p = 0.012; p = 0.0053) compared to ERα-negative patients. Sub-group analysis in relation to gender revealed a highly significant influence of ERα expression on OS and RFS in males but not in females, both for the ERα-positive primary tumor cohort (males: p = 0.0013; p < 0.0001; females: p = 0.56; p = 0.89) and the ERα-positive primary tumor/primary lymph node metastasis cohort (males: p < 0.0001; p < 0.0001; females: p = 0.95; p = 0.96). In multivariate cox regression analysis, the ERα IRS of primary tumors (dichotomized; ERα+ vs. ERα-) was an independent risk factor for OS (HR = 4.230; 95%CI 1.616-11.076; p = 0.003) and RFS (HR = 12.390; 95%CI 4.073-37.693; p < 0.001) in the male cohort. There was a significant difference (p = 0.006) of ERα positivity with regard to the localization of the primary tumor. ERα positivity in the primary tumor was significantly associated (p = 0.026) with UICC stage, with most of the cases being diagnosed in stage IV. Furthermore, there was a significantly (p = 0.049) higher rate of bone infiltration in ERα-positive patients. CONCLUSION: Expression of ERα is rare in OSCC; however, it is associated with a dramatic decrease in OS in male patients. Further studies are necessary to confirm our results and to evaluate the exact mechanism underlying this observation. Hence, ERα-positive OSCC patients might benefit from an ER-based therapeutic (adjuvant) approach in the future.

Detectability of Head and Neck Cancer via New Computed Tomography Reconstruction Tools including Iterative Reconstruction and Metal Artifact Reduction.

State-of-the-art technology in Computed Tomography (CT) includes iterative reconstruction algorithms (IR) and metal artefact reduction (MAR) techniques. The objective of the study is to show the benefits of this technology for the detection of primary and recurrent head and neck cancer. A total of 131 patients underwent contrast-enhanced CT for diagnosis of primary and recurrent Head and Neck cancer; 110 patients were included. All scans were reconstructed using iterative reconstruction, and metal artifact reduction was applied when indicated. Tumor detectability was evaluated dichotomously. Histopathological findings were used as a standard of reference. Data were analyzed retrospectively, statistics was performed through diagnostic test characteristics. State-of-the-art Head and Neck CT showed a sensitivity of 0.83 (95% CI; 0.61-0.95) with 0.93 specificity (95% CI; 0.84-0.98) for primary tumor detection. Recurrent tumors were identified with a 0.94 sensitivity (95% CI; 0.71-0.99) and 0.93 specificity (95% CI; 0.84-0.98) in this study. Conclusion: State-of-the-art reconstruction tools improve the diagnostic quality of Head and Neck CT, especially for recurrent tumor detection, compared with data published for standard CT. IR and MAR are easily implemented in routine clinical settings and improve image evaluation by reducing artifacts and image noise while lowering radiation exposure.

Sentinel Lymph Node Biopsy in Early Stages of Oral Squamous Cell Carcinoma Using the Receptor-Targeted Radiotracer 99mTc-Tilmanocept.

Neck management in patients with early-stage, clinically node-negative oral squamous cell carcinoma (OSCC) remains a matter of discussion. Sentinel lymph node biopsy (SLNB) represents a treatment alternative to avoid elective neck dissection (END) in this cohort and different protocols and tracers exist. Here we present the clinical outcome of SLNB using 99mTc-tilmanocept in a two-day protocol in patients suffering from early-stage OSCC. A total of 13 patients (males: 6; females: 7; mean age: 65.7 years, ranging from 47 to 89 years) were included in this study. Most of the patients suffered from an OSCC of the floor of mouth (n = 6), followed by tongue (n = 5) and upper alveolar crest/hard palate (n = 2). Sentinel lymph nodes (SLNs) were successfully identified in all cases (range: 1-7). The average length of hospital stay was 4.7 days (range: 3-8 days) and mean duration of surgical intervention was 121 min (range: 74-233 min). One patient who suffered from an OSCC of the tongue was sentinel lymph node positive (SLN+). The mean follow-up for all sentinel lymph node negative (SLN-) patients (n = 12) was 20.3 months (range: 10-28 months). No local or nodal recurrences were observed within the observation period. In our patient cohort, SLNB using 99mTc-tilmanocept in a two-day protocol proved to be a reliable and safe staging method for patients suffering from early-stage, clinically node-negative OSCC. These results and their possible superiority to colloid tracers have to be confirmed in a prospective randomized controlled study.

Value of Panendoscopy in the Identification of Synchronous Malignancies in Patients Suffering from Oral Squamous Cell Carcinoma Without Clinical Signs of a Second Primary Tumor.

BACKGROUND/AIM: The aim of the present study was to assess the value of panendoscopy of the upper aero-digestive tract in the identification of synchronous tumors in OSCC patients without clinical signs of a second primary tumor. PATIENTS AND METHODS: In this retrospective study, patients diagnosed with a primary OSCC who received surgical therapy between January 1st, 2012 and December 31st, 2017 were included. Participants must have undergone panendoscopy during the staging process. None of these patients showed clinical signs of a second primary tumor. RESULTS: A total of 265 patients (99 females and 166 males; mean age=63.3 years, range=26-96 years) were included. The mean (SD) follow-up was 25.88 (±20.479 SD) months. Five synchronous secondary tumors (1.9%) could be identified within this cohort. Of these, only two (0.8%) were located within the area of panendoscopy and were diagnosed in patients with regular alcohol and/or tobacco abuse. Eighteen metachronous second primary tumors were diagnosed, 10 being located within the upper aero-digestive tract. CONCLUSION: The relevance of routinely performed panendoscopy in patients suffering from an oral squamous cell carcinoma without clinical signs of a secondary tumor should be critically re-evaluated, especially in patients without typical risk factors.