Early relapse is an adverse prognostic factor for survival outcomes in patients with oral cavity squamous cell carcinoma: results from a nationwide registry study.

BACKGROUND: The prognostic significance of the relapse interval in patients with resected oral cavity squamous cell carcinoma (OCSCC) is a matter of ongoing debate. In this large-scale, registry-based, nationwide study, we examined whether the time interval between surgery and the first disease relapse may affect survival outcomes in Taiwanese patients with OCSCC. METHODS: Data made available by the Taiwan Health Promotion Administration as of 2004 were obtained. The study cohort consisted of patients who were included in the registry between 2011 and 2017. Disease staging was performed according to the American Joint Committee on Cancer (AJCC) Staging Manual, Eight Edition. We retrospectively reviewed the clinical records of 13,789 patients with OCSCC who received surgical treatment. A total of 2327 (16.9%) patients experienced a first disease relapse. The optimal cutoff value for the relapse interval was 330 days when both 5-year disease-specific survival (DSS) and overall survival (OS) (≤ 330/>330 days, n = 1630/697) were taken into account. In addition, we undertook a propensity score (PS)-matched analysis of patients (n = 654 each) with early (≤ 330 days) versus late (> 330 days) relapse. RESULTS: The median follow-up time in the entire study cohort was 702 days (433 and 2001 days in the early and late relapse groups, respectively). Compared with patients who experienced late relapse, those with early relapse showed a higher prevalence of the following adverse prognostic factors: pT4, pN3, pStage IV, poor differentiation, depth of invasion ≥ 10 mm, and extra-nodal extension. Multivariable analysis revealed that early relapse was an independent adverse prognostic factor for both 5-year DSS and OS (average hazard ratios [AHRs]: 3.24 and 3.91, respectively). In the PS-matched cohort, patients who experienced early relapse showed less favorable 5-year DSS: 58% versus 30%, p < 0.0001 (AHR: 3.10 [2.69 - 3.57]) and OS: 49% versus 22%, p < 0.0001 (AHR: 3.32 [2.89 - 3.81]). CONCLUSION: After adjustment for potential confounders and PS matching, early relapse was an adverse prognostic factor for survival outcomes in patients with OCSCC. Our findings may have significant implications for risk stratification.

A Comparison Study of Outcomes and Complications Between Marginal Mandibulectomy With or Without Additional Mandibulotomy in Tongue Cancers.

BACKGROUND: Marginal mandibulectomy with or without additional mandibulotomy could represent the alternatives to avoid segmental mandibulectomy in carefully selected tongue cancers. AIM AND OBJECTIVES: This study investigated a subgroup of tongue cancers with suspected involvement to the alveolar bone because of the shallow and deformed mouth floor. We aimed to compare the functional outcomes, postoperative complications, and disease control efficacy between the 2 different marginal mandibulectomy approaches, with or without additional mandibulotomy. MATERIALS AND METHODS: A retrospective study of 29 marginal mandibulectomies and 26 combined mandibulotomies for tongue cancer wide excisions and flap reconstruction at Chang Gung Memorial Hospital Linkou Branch during 2014 to 2019 was performed. RESULTS: The combined mandibulotomy group had more advanced T-status ( P < 0.001) and greater tumor diameters ( P < 0.001) but not increased preexisting trismus, bone invasions, or positive margins. The additional mandibulotomy increased flap necrosis ( P = 0.044), late infections ( P = 0.004), and tongue movement limitations ( P = 0.044) but not osteoradionecrosis. Osteoradionecrosis was unrelated to the resected mandibular length or the mandibulotomy sites. Feeding tube dependence was greater in the combined group at discharge ( P = 0.014), but no long-term differences were noted. Kaplan-Meier overall survival ( P = 0.052) and disease-free survival ( P = 0.670) were both comparable between the 2 groups. CONCLUSIONS: The combined procedure of mandibulotomy and marginal mandibulectomy in large tongue cancers without bone invasions is associated with increased soft tissue-related complications but not bone-related complications. However, comparable disease control, survival, and long-term tube feeding outcomes were noted.

Factors in oral-related quality of life of betel quid users receiving oral mucosal screening: a cross­sectional study in Taiwan.

BACKGROUND: Betel quid (BQ) chewing is associated with poor oral hygiene, psychological impairment, and acute and long-term addictive effects, resulting in worse oral-related quality of life (OHRQoL). The purpose of this study was to characterize the factors associated with OHRQoL among BQ users receiving oral mucosal screening. METHODS: A cross-sectional study was conducted. Data were collected by random sampling of BQ users who visited outpatient departments receiving oral mucosal screening in a medical center Taiwan. The oral health assessment tool, the state anxiety inventory, the betel quid dependence scale, and the oral health impact profile were used to measure oral health status, anxiety, BQ dependence, and OHRQoL, respectively. Pearson's product-moment coefficient was used to examine the relationship between OHRQoL and the selected independent variables. Independent-samples t-test was used to compare OHRQoL by annual family income, the presence of chronic disease, and BQ dependence. Hierarchical multiple linear regression analysis was used to identify factors associated with OHRQoL. RESULTS: A total of 175 BQ users were surveyed. Factors associated with OHRQoL included oral health status, anxiety, and BQ dependence. BQ users reporting low oral health status, greater anxiety, and more BQ dependence were more likely to have worse OHRQoL. CONCLUSIONS: Poor oral health status, anxiety, and BQ dependence negatively impact on OHRQoL among patients with BQ use receiving oral mucosal screening.

Comparison of the effect of 360° versus two-dimensional virtual reality video on history taking and physical examination skills learning among undergraduate medical students: a randomized controlled trial.

Before caring for patients, video instruction is commonly used for undergraduate medical students, and 360° virtual reality (VR) videos have gained increasing interest in clinical medical education. Therefore, the effect of immersive 360° VR video learning compared with two-dimensional (2D) VR video learning in clinical skills acquisition should be evaluated. This randomized, intervention-controlled clinical trial was aimed to assess whether immersive 360° VR video improves undergraduate medical students' learning effectiveness and reduces the cognitive load in history taking and physical examination (H&P) training. From May 1 2018 to October 30 2018, 64 senior undergraduate medical students in a tertiary academic hospital were randomized to receive a 10-min immersive 360° (360° VR video group; n = 32) or 2D VR instructional video (2D VR video group; n = 32), including essential knowledge and competency of H&P. The demographic characteristics of the two groups were comparable for age, sex, and cognitive style. The total procedure skill score, physical examination score, learner's satisfaction score, and total cognitive load in the 360° VR video group were significantly higher than those in the 2D VR video group (effect sizes [95% confidence interval]: 0.72 [0.21-1.22], 0.63 [0.12-1.13], 0.56 [0.06-1.06], and 0.53 [0.03-1.03], respectively). This study suggested that a10-minute 360° VR video instruction helped undergraduate medical students perform fundamental H&P skills as effectively as 2D VR video. Furthermore, the 360° VR video might result in significantly better procedural metrics of physical examinations with higher learner satisfaction despite the higher cognitive load. Supplementary Information: The online version contains supplementary material available at 10.1007/s10055-022-00664-0.

Clinical Outcomes of Taiwanese Patients with Resected Oral Cavity Squamous Cell Carcinoma Who Underwent Reconstruction with Free Versus Local Flaps.

BACKGROUND: We sought to compare the clinical outcomes of Taiwanese patients with resected oral cavity squamous cell carcinoma (OCSCC) who underwent reconstruction with free versus local flaps. METHODS: From 2011 to 2017, we examined 8646 patients with first primary OCSCC who received surgery either with or without adjuvant therapy. Of these patients, 7297 and 1349 received free and local flap reconstruction, respectively. Two propensity score-matched groups of patients who underwent free versus local flap (n = 1268 each) reconstructions were examined. Margin status was not included as a propensity score-matched variable. RESULTS: Compared with local flaps, patients who received free flaps had a higher prevalence of the following variables: male sex, age < 65 years, pT3-4, pN1-3, p-Stage III-IV, depth ≥ 10 mm, margin > 4 mm, extranodal extension (ENE), and adjuvant therapy (all p < 0.0001). Multivariable analysis identified the reconstruction method (local vs. free flaps, only overall survival [OS]), age ≥ 65 years, pT3-4, pN1-3, p-Stage III-IV, depth ≥ 10 mm (only OS), margins ≤ 4 mm, and ENE as independent adverse prognosticators for disease-specific survival (DSS) and OS. The results of propensity score-matched analyses revealed that, compared with free flaps, patients who underwent local flap reconstruction showed less favorable 5-year DSS (hazard ratio [HR] 1.26, 82%/77%; p = 0.0100) and OS (HR 1.21, 73%/68%; p = 0.0079). CONCLUSIONS: After adjusting for covariates using multivariate models, and also by propensity score modeling, OCSCC patients who underwent free flap reconstruction showed a higher frequency of clear margins and a significant survival advantage compared with those who received local flaps.

Tumor Suppressor miRNA-503 Inhibits Cell Invasion in Head and Neck Cancer through the Wnt Signaling Pathway via the WNT3A/MMP Molecular Axis.

Head and neck cancer (HNC) is the fifth most common cancer worldwide, and its incidence and death rates have been consistently high throughout the past decades. MicroRNAs (miRNAs) have recently gained significant attention because of their role in the regulation of a variety of biological processes via post-transcriptional silencing mechanisms. Previously, we determined a specific profile of miRNAs associated with HNC using a miRNA microarray analysis. Of the 23 miRNAs with highly altered expression in HNC cells, miR-503 was the most significantly downregulated miRNA. In this study, we confirmed that miR-503 acts as a tumor suppressor, as our results showed decreased levels of miR-503 in cancer cells and patients with HNC. We further characterized the role of miR-503 in the malignant functions of HNC. Although there was a minimal effect on cell growth, miR-503 was found to inhibit cellular invasion significantly. Algorithm-based studies identified multiple potential target genes and pathways associated with oncogenic mechanisms. The candidate target gene, WNT3A, was confirmed to be downregulated by miR-503 at both the mRNA and protein levels and validated by a reporter assay. Furthermore, miR-503 modulated multiple invasion-associated genes, including matrix metalloproteinases (MMPs), through the Wnt downstream signaling pathway. Overall, this study demonstrates that miR-503 suppresses HNC malignancy by inhibiting cell invasion through the Wnt signaling pathway via the WNT3A/MMP molecular axis. The modulation of miR-503 may be a novel therapeutic approach to intervene in cancer invasion.

Mild simulator sickness can alter heart rate variability, mental workload, and learning outcomes in a 360° virtual reality application for medical education: a post hoc analysis of a randomized controlled trial.

Virtual reality (VR) applications could be beneficial for education, training, and treatment. However, VR may induce symptoms of simulator sickness (SS) such as difficulty focusing, difficulty concentrating, or dizziness that could impair autonomic nervous system function, affect mental workload, and worsen interventional outcomes. In the original randomized controlled trial, which explored the effectiveness of using a 360° VR video versus a two-dimensional VR video to learn history taking and physical examination skills, only the former group participants had SS. Therefore, 28 undergraduate medical students who participated in a 360° VR learning module were included in this post hoc study using a repeated measures design. Data of the Simulator Sickness Questionnaire (SSQ), heart rate variability (HRV) analysis, Task Load Index, and Mini-Clinical Evaluation Exercise were retrospectively reviewed and statistically analyzed. Ten (36%) participants had mild SS (total score > 0 and ≤ 20), and 18 (64%) had no SS symptom. Total SSQ score was positively related to the very low frequency (VLF) band power, physical demand subscale, and frustration subscale, and inversely related to physical examination score. Using multilevel modeling, the VLF power mediated the relationship between total SSQ score and physical examination score. Furthermore, frustration subscale moderated the mediating effects of the VLF power. Our results highlight the importance of documenting SS to evaluate a 360° VR training program. Furthermore, the combination of HRV analysis with mental workload measurement and outcome assessments provided the important clinical value in evaluating the effects of SS in VR applications in medical education.

Association between multidisciplinary team care and the completion of treatment for oral squamous cell carcinoma: A cohort population-based study.

OBJECTIVES: This study investigates the relationship between multidisciplinary team care (MDTC) and patient completion of their treatment regimen for oral squamous cell carcinoma (OSCC). METHODS: We conducted a retrospective cohort study in patients diagnosed with OSCC in Taiwan from 1 January 2016 to 30 June 2018 using a linked cancer registry database. RESULTS: Of the 969 OSCC MDTC patients in the study cohort, 6.3% reported incomplete treatment, with 1.3% interrupting ongoing treatment and 5.0% terminating definitive treatment. Patients who had advanced-stage disease, experienced primary cancer recurrence or a secondary cancer, or were treated with surgery combined with chemotherapy, radiotherapy or chemoradiotherapy were more likely to terminate treatment before completion. The major reasons for interruption of ongoing treatment included 'patient or their family considered the patient to be in poor physical condition' and 'difficulty enduring physical discomfort caused by treatment'. The major reason for termination of definitive treatment was 'patient or their families or friends experienced negative treatment effects and worried about the side-effects of treatment'. CONCLUSION: Advanced-stage cancer, recurrence or secondary cancer, and surgery combined with chemotherapy, radiotherapy or chemoradiotherapy negatively affected treatment completion. MDTC allows for shared decision-making to determine the optimal treatment.

A combined analysis of maximum standardized uptake value on FDG-PET, genetic markers, and clinicopathological risk factors in the prognostic stratification of patients with resected oral cavity squamous cell carcinoma.

OBJECTIVE: Clinical outcomes of patients with resected oral cavity squamous cell carcinoma (OCSCC) chiefly depend on the presence of specific clinicopathological risk factors (RFs). Here, we performed a combined analysis of FDG-PET, genetic markers, and clinicopathological RFs in an effort to improve prognostic stratification. METHODS: We retrospectively reviewed the clinical records of 2036 consecutive patients with first primary OCSCC who underwent surgery between 1996 and 2016. Of them, 345 underwent ultra-deep targeted sequencing (UDTS, between 1996 and 2011) and 168 whole exome sequencing (WES, between 2007 and 2016). Preoperative FDG-PET imaging was performed in 1135 patients from 2001 to 2016. Complete data on FDG-PET, genetic markers, and clinicopathological RFs were available for 327 patients. RESULTS: Using log-ranked tests based on 5-year disease-free survival (DFS), the optimal cutoff points for maximum standardized uptake values (SUV-max) of the primary tumor and neck metastatic nodes were 22.8 and 9.7, respectively. The 5-year DFS rates were as follows: SUVtumor-max ≥ 22.8 or SUVnodal-max ≥ 9.7 (n = 77) versus SUVtumor-max < 22.8 and SUVnodal-max < 9.7 (n = 250), 32%/62%, P < 0.001; positive UDTS or WES gene panel (n = 64) versus negative (n = 263), 25%/62%, P < 0.001; pN3b (n = 165) versus pN1-2 (n = 162), 42%/68%, P < 0.001. On multivariate analyses, SUVtumor-max ≥ 22.8 or SUVnodal-max ≥ 9.7, a positive UDTS/WES gene panel, and pN3b disease were identified as independent prognosticators for 5-year outcomes. Based on these variables, we devised a scoring system that identified four distinct prognostic groups. The 5-year rates for patients with a score from 0 to 3 were as follows: loco-regional control, 80%/67%/47%/24% (P < 0.001); distant metastases, 13%/23%/55%/92% (P < 0.001); DFS, 74%/58%/28%/7% (P < 0.001); and disease-specific survival, 80%/64%/35%/7% (P < 0.001) respectively. CONCLUSIONS: The combined assessment of tumor and nodal SUV-max, genetic markers, and pathological node status may refine the prognostic stratification of OCSCC patients.

Patients with oral cancer do not undergo surgery as primary treatment: A population-based study in Taiwan.

BACKGROUND: There are still oral cancer patients without surgery. To improve the survival, it is necessary to know the causes of the oral cancer patients without surgery. METHODS: 23,217 patients with a newly-diagnosed oral cancer in Taiwan Cancer Registry (TCR) database between 2011 and 2015 were enrolled. Data from TCR database named "Reason for No Surgery of Primary Site" were extracted for analysis of the causes of those without surgery. Overall survival plots were presented using the Kaplan-Meier method with log-rank test. RESULTS: 3263 (14%) patients did not received surgery. Among them, there were 720 patients (group 3) without surgery although surgery was advised, 154 patients (group 2) because of poor condition or death before surgery, and 2389 patients (group 1) because of other causes. Twenty-four percent of the patients with surgery were treated one month and more after diagnosis. The 5-year overall survival rates were 68.7%, 25.2%, 9.1% and 17.3% for surgery group, group 3, 2 and 1, respectively (p < 0.001). The mean age of the patients with and without surgery were 54.8 and 59.3, respectively (p < 0.01). Female patients were commoner in group 3 (p < 0.01). The patients without surgery was commoner in the middle (15.7%) and southern (14.8%) than in Northern Taiwan (12.1%). All groups without surgery had more advanced stage and lower BMI (p < 0.01). CONCLUSION: One-sevenths of patients were not treated surgically because of refusal, poor condition, older age, low BMI, and advanced stage. It is necessary to encourage the patients to undergo surgery with shortening the diagnosis-to-treatment interval.

Classifying Neck Lymph Nodes of Head and Neck Squamous Cell Carcinoma in MRI Images with Radiomic Features.

The aim of this study is to develop a computer-aided diagnosis method to help classify medical images of neck lymph nodes in head and neck cancer patients. According to the current practice guidelines, the classification of lymph node status is critical for patient stratification before treatment. Take extra-nodal extension (ENE) of metastatic neck lymph nodes, the status of ENE has been considered a single factor affecting the decision of whether systemic treatment with toxicity should be given to patients with otherwise non-advanced cancer status. Medical imaging prior to surgery serves as tools for clinical staging and determining the extent of neck lymph node dissection during the tumor resection surgery. The information contained in these images may also help determine the status of ENE and thus stratify patients for more precise treatment. In the current practice, there has been not a reliable computer-aided tool for this task. In this study, we used open-source software to investigate radiomic features that help distinguish malignant from benign and ENE from non-ENE lymph nodes. We have identified 89 features that can differentiate malignant from benign and 4 features that can differentiate ENE from non-ENE lymph nodes. Furthermore, we fed the significant features to a multilayer perceptron neural network to predict malignancy and ENE of lymph nodes and achieved 84% and 77% of accuracy in each task, respectively.

Tumor Depth of Invasion (Tumor > 4 cm/Depth > 10 mm and Depth > 20 mm) and Through Cortex/Skin Invasion are Both Valid Criteria for Classifying Tumors as pT4a in AJCC 2018 Oral Cavity Cancer Staging System.

BACKGROUND: According to the AJCC third to seventh edition staging manuals (1988-2010), the presence of through cortex and/or skin invasion in oral cavity squamous cell carcinoma (OCSCC) identifies T4a tumors. The AJCC eighth edition (2018) introduced a depth of invasion (DOI) > 20 mm as a criterion for pT4a. Subsequently, a revision maintained that tumors > 4 cm with a DOI > 10 mm should be classified as pT4a. We sought to analyze the prognostic impact of the three distinct criteria identifying pT4a disease. METHODS: We examined 667 consecutive patients with pT3-4 buccal/gum/hard palate/retromolar SCC who underwent surgery between 1996 and 2016. pT1/pT2 (n = 108/359) disease were included for comparison purposes. RESULTS: The 5-year outcomes of patients with pT1/pT2/without (n = 406)/with tumor > 4 cm/DOI > 10 mm (n = 261), pT1/pT2/DOI ≤ 20 mm (n = 510)/> 20 mm (n = 157), and pT1/pT2/without (n = 305)/with through cortex/skin invasion (n = 362) were as follows: disease-specific survival (DSS), 98%/89%/79%/65%, p < 0.001, 98%/89%/78%/59%, p < 0.001, and 98%/89%79%/69%, p < 0.001; overall survival (OS), 90%/79%/63%/51%, p < 0.001, 90%/79%/63%/42%, p < 0.001, and 90%/79%/65%/52%, p < 0.001. In pT3-4 disease, a tumor > 4 cm/DOI > 10 mm was an independent adverse prognosticator for 5-year DSS rate, DOI > 20 mm was an independent adverse prognosticator for 5-year DSS and OS rates, whereas through cortex/skin invasion independently predicted 5-year OS rates. CONCLUSIONS: All of the three criteria (tumor > 4 cm/DOI > 10 mm, DOI > 20 mm, and through cortex/skin invasion) identify high-risk patients, which should be reflected in further revisions of pT4a classification in OCSCC.

Cognitive Style and Mobile E-Learning in Emergent Otorhinolaryngology-Head and Neck Surgery Disorders for Millennial Undergraduate Medical Students: Randomized Controlled Trial.

BACKGROUND: Electronic learning (e-learning) through mobile technology represents a novel way to teach emergent otorhinolaryngology-head and neck surgery (ORL-HNS) disorders to undergraduate medical students. Whether a cognitive style of education combined with learning modules can impact learning outcomes and satisfaction in millennial medical students is unknown. OBJECTIVE: The aim of this study was to assess the impact of cognitive styles and learning modules using mobile e-learning on knowledge gain, competence gain, and satisfaction for emergent ORL-HNS disorders. METHODS: This randomized controlled trial included 60 undergraduate medical students who were novices in ORL-HNS at an academic teaching hospital. The cognitive style of the participants was assessed using the group embedded figures test. The students were randomly assigned (1:1) to a novel interactive multimedia (IM) group and conventional Microsoft PowerPoint show (PPS) group matched by age, sex, and cognitive style. The content for the gamified IM module was derived from and corresponded to the textbook-based learning material of the PPS module (video lectures). The participants were unblinded and used fully automated courseware containing the IM or PPS module on a 7-inch tablet for 100 min. Knowledge and competence were assessed using multiple-choice questions and multimedia situation tests, respectively. Each participant also rated their global satisfaction. RESULTS: All of the participants (median age 23 years, range 22-26 years; 36 males and 24 females) received the intended intervention after randomization. Overall, the participants had significant gains in knowledge (median 50%, interquartile range [IQR]=17%-80%, P<.001) and competence (median 13%, IQR=0%-33%, P=.006). There were no significant differences in knowledge gain (40%, IQR=13%-76% vs 60%, IQR=20%-100%, P=.42) and competence gain (0%, IQR= -21% to 38% vs 25%, IQR=0%-33%, P=.16) between the IM and PPS groups. However, the IM group had a higher satisfaction score (8, IQR=6-9 vs 6, IQR=4-7, P=.01) compared with the PPS group. Using Friedman's two-way nonparametric analysis of variance, cognitive styles (field-independent, field-intermediate, or field-dependent classification) and learning modules (IM or PPS) had significant effects on both knowledge gain (both adjusted P<.001) and satisfaction (both adjusted P<.001). CONCLUSIONS: Mobile e-learning is an effective modality to improve knowledge of emergent ORL-HNS in millennial undergraduate medical students. Our findings suggest the necessity of developing various modules for undergraduate medical students with different cognitive styles. TRIAL REGISTRATION: Clinicaltrials.gov NCT02971735; https://clinicaltrials.gov/ct2/show/NCT02971735 (Archived by WebCite at http://www.webcitation.org/6waoOpCEV).

Clinical Outcomes in pT4 Tongue Carcinoma are Worse than in pT3 Disease: How Extrinsic Muscle Invasion Should be Considered?

BACKGROUND: The identification of extrinsic tongue muscle invasion in oral cavity cancer remains challenging. Notably, the most recent American Joint Committee on Cancer (AJCC 2017, 8th edition) staging manual indicates that extrinsic muscle invasion does not lead to the diagnosis of a T4 tumor. Because this approach carries the risk of tumor downstaging, we compared the clinical outcomes of patients with oral tongue squamous cell carcinoma (SCC) staged as pT3 vs. pT4 according to the AJCC 2010, 7th edition criteria. METHODS: We retrospectively examined the records of consecutive patients with pT3 (n = 135) and pT4 (n = 68) tongue SCC who underwent radical surgery. Of the 68 pT4 tongue SCC, 63 (93%) had extrinsic muscle involvement alone. The 5-year locoregional control (LRC), distant metastasis (DM), and disease-free survival (DFS) rates served as outcome measures. RESULTS: Compared with pT3 tongue SCC, pT4 patients presented significantly more frequently with pN2 disease, extranodal extension, poor tumor differentiation, tumor depth >15 and >20 mm, margin status ≤4 mm, perineural invasion, vascular invasion, and were more frequently treated with surgery plus concurrent chemoradiotherapy. Less favorable 5-year outcomes were observed in patients with pT4 than pT3 tumors (LRC 50 vs. 75%, p < 0.001; DM 27 vs. 14%, p = 0.013; DFS 43 vs. 69%, respectively, p < 0.001). We identified pT4 disease (vs. pT3) as an independent adverse prognostic factor for LRC and DFS. CONCLUSIONS: We suggest classifying patients with tongue SCC and extrinsic muscle invasion as having pT4 disease.

Clinical Outcomes of Taiwanese Patients with cT4 Oral Cavity Squamous Cell Carcinoma: Toward the Identification of the Optimal Initial Treatment Approach for cT4b Patients.

BACKGROUND: The National Comprehensive Cancer Network guidelines recommend that patients with oral cavity squamous cell carcinoma (OSCC) and cT4b disease should be either included in clinical trials or treated with a nonsurgical approach. However, surgery may be feasible in selected patients with adequate safety margins. Using the nationwide Taiwanese Cancer Registry Database, we examined the prognosis of cT4b OSCC patients in relation to their treatment approach. METHODS: Of the 18,910 patients with previously untreated first primary OSCC identified between 2004 and 2010, 492 (2.6 %) had cT4b tumors. Of them, 327 (66 %) received initial treatment with surgery, whereas 165 (34 %) were initially treated with a nonsurgical approach. Of the latter group, 78 patients subsequently underwent surgery. A 5-year disease-specific survival (DSS) ≥45 % was considered as a favorable outcome. RESULTS: Better 5-year DSS and overall survival (OS) rates were observed in cT4b patients initially treated with surgery (vs. nonsurgery; DSS, 51 vs. 38 %; OS, 43 vs. 27 %, respectively, p < 0.001). Of the participants initially treated with surgery, patients with cN0-2 disease had better 5-year survival rates (DSS: cN0, 59 %; cN1, 53 %; cN2, 46 %; OS: cN0, 49 %; cN1, 50 %; cN2, 37 %) than those with cN3 disease (DSS: 0 %; OS: 0 %). Among cT4b patients who initially received a nonsurgical treatment, subjects who subsequently underwent surgery showed better outcomes. CONCLUSIONS: Primary surgery is performed in approximately two-thirds of cT4b OSCC patients, with cN0-2 cases showing a good prognosis. Patients who initially received a nonsurgical approach can subsequently be treated with surgery and achieve favorable outcomes.

Clinical impact of PET/CT imaging after adjuvant therapy in patients with oral cavity squamous cell carcinoma.

PURPOSE: This single-center retrospective study of prospectively collected data was aimed at comparing the clinical outcomes of positron emission tomography/computed tomography (PET/CT) for patients with oral cavity squamous cell carcinoma (OSCC) with symptomatic recurrences identified by PET/CT imaging following adjuvant therapy (Group A) versus those of cases with asymptomatic recurrences diagnosed through periodic post-adjuvant therapy PET/CT surveillance (Group B). We also sought to establish the priority of salvage therapy in the two study groups. METHODS: We identified 111 patients with advanced resected OSCC who developed recurrences following adjuvant therapy (51 in Group A and 60 in Group B). Histopathology served as the gold standard for recurrent lesions. The impact of post-adjuvant therapy PET/CT surveillance was examined with Kaplan-Meier curves and Cox proportional hazards regression models. RESULTS: The 2-year DSS and OS rates were marginally or significantly higher in Group B than in Group A (P = 0.073 and P = 0.025, respectively). Time-dependent ROC curve analysis demonstrated that the optimal cutoff values for time to positive PET/CT findings in relation to OS were 12 months for Group A and 9 months for Group B, respectively. Independent risk factors identified in multivariate analyses were used to devise two prognostic scoring systems for 2-year DSS and OS in each study group (all P < 0.001). CONCLUSIONS: Scheduled periodic PET/CT surveillance is a valuable tool for early detection of recurrent lesion(s) in asymptomatic OSCC patients who bear risk factors for disease recurrence. The presence of clinical symptoms and a short time to positive PET/CT findings were adverse prognostic factors for clinical outcome in patients with advanced OSCC. The priority of salvage therapy is discussed in each patient subgroup according to the devised prognostic scoring systems.

Body image in head and neck cancer patients treated with radiotherapy: the impact of surgical procedures.

BACKGROUND: In this study, we aimed to investigate the impact of surgical procedures on the body image of head and neck cancer patients treated with radiotherapy and with or without radical surgery. METHODS: A cross-sectional survey of 150 patients with head and neck cancer was conducted. Sixty patients had nasopharyngeal cancer treated with definitive radiotherapy without surgery, and 90 patients had oral cavity cancer treated with radical surgery plus adjuvant radiotherapy. All participants completed a 10-item Body Image Scale (BIS) questionnaire to assess body image dissatisfaction. Among all patients, the socio-demographic and clinical variables were age, gender, partnership, education, employment, and radical surgery. In surgically-treated patients, the clinical variables were facial skin sacrificed, mouth angle sacrificed, glossectomy, maxillectomy, and mandibulectomy. ANOVAs, t-tests, and multiple regressions were used to evaluate the relationships between these variables and BIS results. RESULTS: In all patients, radical surgery was the strongest independent predictor of BIS scores. Surgically-treated patients had significantly worse BIS scores than the patients without surgery. In surgically-treated patients, facial skin sacrificed, mouth angle sacrificed, maxillectomy, and mandibulectomy were significantly associated with body image. According to multivariable analyses, inferior maxillectomy and segmental mandibulectomy were independent prognosticators of a poor BIS score in surgically-treated patients. CONCLUSION: Radical surgery for head and neck cancer patients has a significant impact on their body image, especially for those undergoing facial bone destructive surgery.

Local Rhomboid Flap Reconstruction for Skin Defects After Excising Large Parotid Gland Tumors.

Most parotid tumors grow slowly, and sometimes these patients do not request surgical treatment until the tumors become large and affect their appearance. The surgical treatment of these large tumors is usually accompanied by large skin defects after excision, and it is challenging for surgeons to close the defect primarily. This report describes the case of a 68-year-old man with a left parotid gland tumor (largest dimension, 110 mm) and the case of a 79-year-old man with a left parotid gland tumor measuring approximately 77 mm that had existed for decades. These patients underwent facial nerve dissection and parotidectomy with skin sacrifice. The large skin defects after the parotidectomy were successfully reconstructed with local rhomboid flaps. No facial palsy, wound disruption, flap edge loss, or major complications occurred after the surgeries. Except for the scars, the color of the cheek flap was not apparent from the periphery. In conclusion, local rhomboid flap reconstruction is a rapid and practical technique for reconstructing medium to large skin defects in the cheek and upper neck regions after tumor excisions. The flap was reliable in blood supply and cosmetic outcome.

Roles of preoperative C-reactive protein are more relevant in buccal cancer than other subsites.

BACKGROUND: C-reactive protein (CRP) is an early marker for inflammation, and a relationship between serum CRP levels and survival in oral cancer has been demonstrated previously. In this study, we investigated the roles of CRP in different oral cancer subsites. METHODS: Three hundred and forty-three oral squamous cell carcinoma patients between June 1999 and March 2015 were retrospectively reviewed. Serum CRP levels were measured preoperatively. RESULTS: The elevation of CRP levels (≥5.0 mg/L) was significantly correlated with pathologic tumor status, pathologic nodal status, nodal extracapsular spread, tumor stage, skin invasion, tumor depth (≥10 mm), and bone invasion. The correlation between elevation of CRP and clinicopathologic factors was more evident in the buccal cancer compared to other tumor subsites. The disease-free survival and overall survival correlation was significant in buccal cancer (p = 0.003 and p < 0.001) but not in tongue cancer (p = 0.119 and p = 0.341) or other oral cancer subsites (p = 0.246 and p = 0.696). CONCLUSIONS: Preoperative serum CRP level was a prognosticator in oral squamous cell carcinoma, and its effect was more prominent in buccal cancer that occurs more frequently in areca-quid (AQ) endemic regions.

Induction chemotherapy with dose-modified docetaxel, cisplatin, and 5-fluorouracil in Asian patients with borderline resectable or unresectable head and neck cancer.

BACKGROUND/PURPOSE: Significant ethnic differences in susceptibility to the effects of chemotherapy exist. Here, we retrospectively analyzed the safety and efficacy of induction chemotherapy (ICT) with dose-modified docetaxel, cisplatin, and 5-fluorouracil (TPF) in Asian patients with borderline resectable or unresectable head and neck squamous cell carcinoma (HNSCC). METHODS: Based on the incidence of adverse events that occurred during daily practice, TPF90 (90% of the original TPF dosage; docetaxel 67.5 mg/m2 on Day 1, cisplatin 67.5 mg/m2 on Day 1, and 5-fluorouracil 675 mg/m2 on Days 1-5) was used for HNSCC patients who were scheduled to receive ICT TPF. RESULTS: Between March 2011 and May 2014, 52 consecutive patients with borderline resectable or unresectable HNSCC were treated with ICT TPF90 followed by concurrent chemoradiotherapy. Forty-four patients (84.6%) received at least three cycles of ICT TPF90. The most commonly observed Grade 3-4 adverse events included neutropenia (35%), anemia (25%), stomatitis (35%), diarrhea (16%), and infections (13.5%). In an intention-to-treat analysis, the complete and partial response rates after ICT TPF90 were 13.5% and 59.6%, respectively. The complete and partial response rates following radiotherapy and salvage surgery were 42.3% and 25.0%, respectively. The estimated 3-year overall survival and progression-free survival rates were 41% [95% confidence interval (CI): 25-56%] and 23% (95% CI: 10-39%), respectively. The observed median overall survival and progression-free survival were 21.0 months (95% CI: 13.3-28.7 months) and 16.0 months (95% CI: 10.7-21.3 months), respectively. CONCLUSION: TPF90 is a suitable option for Asian patients with borderline resectable or unresectable HNSCC who are scheduled for ICT.