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Background: Osteoradionecrosis (ORN) of the jaw requires a differential diagnosis to exclude cancer recurrence. Here, we sought to develop a scoring system comprising 18F-FDG PET/CT parameters for distinguishing between the two conditions in patients with oral squamous cell carcinoma (OSCC). Methods: The study consisted of 103 OSCC patients with suspected ORN of the jaw. All participants underwent 18F-FDG PET/CT imaging within 6 months of diagnostic histopathology. Following extraction of PET parameters, we identified clinical and imaging predictors of mandibular recurrence-free survival (MRFS) using receiver operating characteristic curve analysis and multivariate Cox regression models. Results: The results of histopathology revealed mandibular cancer recurrence in 24 patients (23.3%). Multivariate Cox regression analyses identified an age at diagnosis ≤ 52 years (P = 0.013), a location of the SUVmax voxel with soft tissue predominance (P = 0.019), and mandibular total lesion glycolysis (TLG) > 62.68 g (P < 0.001) as independent risk factors for MRFS. A scoring system was devised with scores from 0 (no risk factor) to 3 (presence of all three risk factors). High-risk patients with a score of 2–3 compared with score of 0–1 had a significantly higher likelihood of mandibular cancer recurrence (hazard ratio: 32.50, 95% confidence interval: 8.51–124.18, P < 0.001). The scoring system had a sensitivity of 87.50%, a specificity of 82.28%, and an accuracy of 83.50% for identifying mandibular cancer recurrence. Conclusions: The scoring system of our study is clinically useful for identifying mandibular cancer recurrence in patients with suspected ORN of the jaw. [ABSTRACT FROM AUTHOR]

Objectives: Perineural invasion (PNI) was quantitatively analyzed in oral squamous cell carcinoma (OSCC) specimens obtained by radical surgery to correlate with survival outcomes. Methods: This is a retrospective study that reviewed the Cancer registry data between 2009 and 2015. Inclusion criteria were oral cavity cancer, treatment by radical surgery, presence of PNI, and available pathologic samples for S100 staining. Patients with M1 disease and those with synchronous or metachronous cancer during staging work-up were excluded. All pathologic samples were reviewed to confirm PNI status and processed by immunohistochemical staining for S100 to quantify PNI. Pathologic information and staging results were also reviewed, and clinical outcomes were analyzed. Results: The retrospective study included 92 patients; 63 had intratumoral PNI (IPNI) and 29 had extratumoral PNI (EPNI). The average number of PNI foci (APNI) was higher in the EPNI group than in the IPNI group (6.7 vs 3.8, t -test 2-tail significance = 0.021). The 3-year overall survival (OS) and time-to-recurrence (TTR) rates of all patients were 82.5% and 81.2%, respectively. Univariate analysis showed that pathological T4 or N2-3 stage correlated with poor OS, whereas APNI ≥4 correlated with poor TTR. In multivariate analysis, only the pathological N2-3 stage was significantly correlated with poor OS, whereas only APNI ≥ 4 was an independent factor of poor TTR. The 3-year TTR rates were 92.4% and 65.6% for diseases with APNI < 4 and ≥ 4, respectively (P =.008). Conclusions: In patients with OSCC with PNI, a greater amount of PNI identified by S100 staining indicated a poorer TTR regardless of stage and other prognostic factors. Quantification of PNI by S100 immunohistochemistry is a potential method for prognosis prediction. [ABSTRACT FROM AUTHOR]

Purpose: After suddenly stopping smoking after an initial oral cancer (OC) diagnosis, patients may restart smoking and nicotine dependence. This study sought to identify factors associated with high nicotine dependence in OC patients who restarted smoking post‐treatment. Design: A cross‐sectional study. Methods: A group of 220 OC patients who restarted smoking post‐treatment were recruited from the outpatient radiation department of a single cancer center in northern Taiwan. Demographic and clinical characteristics were recorded, and patients were assessed for nicotine and smoking dependence, physical activity and function, socio‐emotional function, social support, and depression. Results: Among patients who restarted smoking after treatment for OC, 75.9% reported low‐to‐moderate dependence on smoking, while 24.1% reported high nicotine dependence. Factors associated with high nicotine dependence included higher incidence of smoking per day, greater dependence on smoking, less physical activity per week, and poorer social–emotional function. Those highly dependent on nicotine were younger, unmarried, had less education, and had begun smoking earlier than those with low‐to‐moderate nicotine dependence. Conclusions: The amount of smoking per day, greater smoking behavioral dependence, less physical activity per week, and worse social–emotional function affected high nicotine dependence. Clinical relevance: Smoking cessation training and counseling for OC patients may help them better control their use of tobacco after treatment. [ABSTRACT FROM AUTHOR]

Objective: To compare the levels of social support, physical function, and social-emotional function between oral cavity cancer survivors who did or did not resume work 6 months or longer after treatment completion.Methods: This cross-sectional study examined survivors of oral cavity cancer who were treated at the outpatient radiation department of a medical center in Northern Taiwan. Questionnaires were used to collect data regarding perceived social support, physical function, social-emotional function, and return to work status after treatment. Logistic regression was conducted to determine factors related to returning to work.Results: We examined 174 survivors of oral cavity cancer, 55.2% of whom returned to work after treatment. Relative to survivors who returned to work, those who did not return to work reported needing greater tangible social support, having fewer positive social interactions, having poorer physical function, and having poorer social-emotional function. Multivariable analysis indicated that younger age (OR = 0.864, P < .05), higher family income (OR = 10.835, P < .05), sufficient tangible social support (OR = 0.943, P < .05), positive social interaction (OR = 1.025, P < .05), and better physical function (OR = 1.062, P < .05) were significantly associated with the return to work.Conclusions: Survivors of oral cavity cancer who did not return to work had worse physical and social-emotional function and required more tangible social support and positive social interactions. Providing occupational rehabilitation and counseling for oral cavity cancer survivors may help them return to work. [ABSTRACT FROM AUTHOR]

Methods: We sought to compare the prognostic impact of tumor differentiation with respect to adverse risk factors (RFs) identified by the National Comprehensive Cancer Network (NCCN) guidelines––including extranodal extension (ENE), positive/close margins, perineural invasion, lymphatic invasion, and vascular invasion––in patients with locally advanced oral cavity squamous cell carcinoma (OCSCC). Results: Between 1996 and 2018, 1179 consecutive patients with first primary pT3–4 OCSCC were included. A three‐level grading system was adopted––in which the final classification was assigned according to the most prevalent tumor grade. We identified 382/669/128 patients with well/moderately/poorly differentiated tumors, respectively. Compared with well/moderately differentiated tumors, poorly differentiated OCSCC had a higher prevalence of the following variables: female sex (4%/6%/11%), ENE, (14%/36%/61%), positive margins (0.5%/2%/4%), close margins (10%/14%/22%), perineural invasion (22%/50%/63%), lymphatic invasion (2%/9%/17%), vascular invasion (1%/4%/10%), and adjuvant therapy (64%/80%/87%). The 5‐year rates of patients with well/moderately/poorly differentiated OCSCC were as follows: local control (LC, 85%/82%/84%, p = 0.439), neck control (NC, 91%/83%/70%, p < 0.001), distant metastases (DM, 6%/18%/40%, p < 0.001), disease‐free survival (DFS, 78%/63%/46%, p < 0.001), disease‐specific survival (DSS, 85%/71%/49%, p < 0.001), and overall survival (OS, 68%/55%/39%, p < 0.001). Multivariable analysis identified the following variables as independent prognosticators for 5‐year outcomes: ENE (LC/NC/DM/DFS/DSS/OS), poorly differentiated tumors (NC/DM/DFS/DSS/OS), positive margins (LC/DFS), lymphatic invasion (DFS/DSS/OS), perineural invasion (DM), and age ≥65 years (OS). Conclusions: In addition to ENE, poor tumor differentiation was identified as the second most relevant adverse RF for patients with pT3–4 OCSCC. We suggest that the NCCN guidelines should include poor tumor differentiation as an adverse RF to refine and tailor clinical management. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study of posttreatment oral cavity cancer (OCC) patients was to identify factors associated with self-reported overall body image, perceived attractiveness, and dissatisfaction with body appearance.Methods: This cross-sectional study recruited patients with OCC from the outpatient radiation department of a single cancer center in Northern Taiwan. Demographic and clinical characteristics were recorded, and patients were assessed using the Hospital Anxiety and Depression Scale (HADS), the Liebowitz Social Anxiety Scale (LSAS), the University of Washington Quality of Life Scale (UW-QOL), and the Body Image Scale (BIS).Results: A total of 168 patients were included in this current study, 76 females and 92 males. Negative overall body image was associated with greater degree of depression, greater fear of social interactions, poorer social-emotional function, receipt of surgery, female gender, and greater avoidance of social interaction; these factors explained 49.0% of the variance in this outcome measure. Poor perceived attractiveness was associated with greater depression, greater fear of social interaction, and receipt of surgery; these factors explained 25.4% of the variance in this outcome measure. Dissatisfaction with body appearance was associated with poor social-emotional function, greater fear of social interaction, receipt of reconstruction, advanced cancer stage, and female gender; these factors explained 52.2% of the variance in this outcome measure.Conclusions: This study of posttreatment OCC patients indicated that depression and fear of social interaction strongly influenced overall body image, perceived attractiveness, and dissatisfaction with body appearance. [ABSTRACT FROM AUTHOR]

Objectives: Simultaneous second primary tumors (SSPT) are not uncommon in patients with oral cavity squamous cell carcinoma (OSCC) living in areas where the habit of betel quid chewing is widespread. We sought to identify the main prognostic factors in OSCC patients with SSPT and incorporate them into a risk stratification scheme. Methods: A total of 1822 consecutive patients with primary OSCC treated between January 1996 and February 2014 were analyzed for the presence of SSPT. The 18-month and 5-year overall survival (OS) rates served as the main outcome measures. Results: Of the 1822 patients, 77 (4%) were found to have SSPT (i.e, two malignancies identified within one month of each other). The 18-month and 5-year OS rates in patients without SSPT and with SSPT were 82% and 69%, and 72% and 53%, respectively (p = 0.0063). Patients with SSPT were further divided into patients with either esophageal cancer or hepatocellular carcinoma (eso-HCC subgroup, n = 8) and other tumors (NO eso-HCC subgroup, n = 69). After multivariate analysis, neck nodal extracapsular spread (ECS, n = 18) and the presence of eso-HCC were identified as independent adverse prognostic factors. The 18-month OS rates of SSPT patients with both eso-HCC and ECS (n = 5) vs. the remaining patients (n = 72) were 0% and 78%, respectively (p < 0.0001). Conclusion: OSCC patients with neck nodal ECS and esophageal cancer or hepatocellular carcinoma as SSPT have a dismal short-term prognosis. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to identify factors associated with unmet supportive care needs in family caregivers of patients with oral cancer after surgery. Methods In a cross-sectional study, we recruited patient-family caregiver dyads from the otolaryngology head and neck surgery wards of a medical center in northern Taiwan. Patients were assessed using a set of structured questionnaires to measure symptom distress, sleep quality, and depression. Social support and supportive care needs of family caregivers were measured. Results Of the 102 dyads surveyed, needs for supportive care in information domain and healthcare professional/healthcare services domain were highest. Patients with more severe symptoms and family caregivers who received less social support from family were associated with greater overall unmet supportive care needs. Conclusions Family caregivers report the need for more information and healthcare services after a family member has had oral surgery. Caregiving training programs should be developed for caregivers on the basis of meeting reported needs. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective This study aimed to examine changes in physical symptom severity, functional status, supportive care needs, and related factors in oral cavity cancer patients during 6 months after beginning radiation therapy (RT) or concurrent chemotherapy and radiation therapy (CCRT). Methods A prospective longitudinal study was conducted involving oral cavity cancer patients from an RT clinic at a medical center in northern Taiwan. Patients were assessed for supportive care needs and physical symptoms at five time points: before the beginning of RT or CCRT and at 1, 2, 3, and 6 months after beginning RT or CCRT. The generalized estimating equation was used to identify predictors of overall needs as well as six specific dimensions of needs. Results A total of 82 patients completed the 6 months of follow-up. Patients had moderate to high levels of supportive care needs over the 6 months. Although the highest information need was at the pretreatment phase, in general, the peak for overall and individual care needs was at 2 months since first receiving RT or CCRT. Patients without religious beliefs as well as those with higher educational level, functional level, overall physical symptom severity, and baseline anxiety reported more supportive care needs. Anxiety level before treatment was the most common factor across most supportive care needs. Individual physical symptoms, including fatigue, swallowing difficulty, and oral mucositis, were significantly related to higher physical and daily living needs. Conclusions A systematic clinical assessment to detect patients' care needs is necessary to improve the provision of timely cancer care and meet patients' healthcare needs. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Purpose: In the American Joint Committee on Cancer 2010 classification system, pT1–2N0 oral cavity squamous cell carcinoma (OSCC) is considered an early-stage cancer treatable with surgery alone (National Comprehensive Cancer Network 2010 guidelines). Our aim was to evaluate the feasibility of surgery alone for pT1–2N0 OSCC patients. Methods and Materials: Among 1279 previously untreated OSCC patients referred to our hospital between January 1996 and May 2008, we identified 457 consecutive patients with pT1–2N0 disease. All had radical tumor excision with neck dissection. A total of 387 patients showing pathologic margins greater than 4 mm and treated by surgery alone were included in the final analysis. All were followed up for at least 24 months after surgery or until death. The 5-year rates of control, distant metastasis, and survival were the main outcome measures. Results: The 5-year rates in the entire group of pT1–2N0 patients were as follows: local control, 91%; neck control, 92%; distant metastases, 1%; disease-free survival, 85%; disease-specific survival, 93%; and overall survival, 84%. Multivariate analysis identified poor differentiation and pathologic tumor depth of 4 mm or greater as independent risk factors for neck control, disease-free survival, and disease-specific survival. A scoring system using poor differentiation and tumor depth was formulated to define distinct prognostic groups. The presence of both poorly differentiated tumors and a tumor depth of 4 mm or greater resulted in significantly poorer 5-year neck control (p < 0.0001), disease-free (p < 0.0001), disease-specific (p < 0.0001), and overall survival (p = 0.0046) rates. Conclusion: The combination of poor differentiation and pathologic tumor depth of 4 mm or greater identified a subset of pT1–2N0 OSCC patients with poor outcome, who may have clinical benefit from postoperative adjuvant radiotherapy. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this retrospective study was twofold: (1) to investigate prognostic factors for clinical outcomes in patients with poorly differentiated oral cavity squamous cell carcinoma and (2) to identify specific prognostic subgroups that may help to guide treatment decisions. Methods and Materials: We examined 102 patients with poorly differentiated oral cavity squamous cell carcinoma. All patients were followed for at least 24 months after surgery or until death. The 5-year rates of local control, neck control, distant metastasis, disease-free, disease-specific, and overall survival served as main outcome measures. Results: The 5-year rates were as follows: local control (79%), neck control (64%), distant metastases (27%), disease-free survival (48%), disease-specific survival (52%), and overall survival (42%). Multivariable analysis showed that the number of pathologically positive nodes (≥4 vs. ≤3) was a significant predictor of neck control, distant metastasis, and disease-free, disease-specific, and overall survival rates. In addition, the presence of tumor depth of ≥11 mm (vs. <11 mm) was a significant predictor of distant metastasis, disease-specific survival, and overall survival rates. The combination of the two predictors (26.5%, 27/102) was independently associated with poorer neck control (p = 0.0319), distant metastasis (p < 0.0001), and disease-free (p < 0.0001), disease-specific (p < 0.0001), and overall survival (p < 0.0001) rates. Conclusions: In patients with poorly differentiated oral cavity squamous cell carcinoma, the presence of at least 4 pathologically positive lymph nodes and of a pathological tumor depth ≥11 mm identifies a subset of subjects with poor clinical outcomes. Patients carrying both risk factors are suitable candidates for the development of novel therapeutic approaches. [ABSTRACT FROM AUTHOR]

Objective: According to the AJCC 2017 Staging Manual, oral cavity squamous cell carcinoma (OCSCC) with pN2 disease (based on the AJCC 2010 criteria) and extra-nodal extension (ENE) should be classified as pN3b. We performed a detailed outcome analyses in this patient subgroup.Material and Methods: We retrospectively reviewed the clinical records of consecutive OCSCC patients who underwent radical surgery between 1996 and 2017. Patients with pN3b disease (n = 365) were divided into a pN+ ≥8/ENE ≥5 subgroup (defined by the presence of pN+ ≥8 nodes or ENE ≥5 nodes, n = 77) and a pN+ ≤7/ENE ≤4 subgroup (defined by the presence of pN+ ≤7 nodes and ENE ≤4 nodes, n = 288). Patients with pN0/pN1/pN2 (n = 1192/179/197) disease were included for comparison purposes.Results: Patients in the pN+ ≥8/ENE ≥5 subgroup had less favorable 5-year outcomes than those in the pN+ ≤7/ENE ≤4/pN2/pN1/pN0 groups (local control, 64%/79%/86%/83%/88%, p < 0.001; neck control, 55%/75%/80%/86%/93%, p < 0.001; distant metastases, 67%/28%/20%/12%/3%, p < 0.001; disease-free survival, 21%/51%/64%/72%/82%, p < 0.001; disease-specific survival, 25%/55%/71%/82%/92%, p < 0.001; overall survival, 19%/40%/54%/64%/82%, p < 0.001; respectively). Among patients with pN3b disease, multivariable analysis identified the pN+ ≥8/ENE ≥5 subgroup, lower neck (level IV/V) metastases, and depth of invasion ≥25 mm as independent adverse prognostic factors for 5-year distant metastases and survival rates.Conclusions: Patients in the pN+ ≥8/ENE ≥5 subgroup have an unfavorable prognosis and their classification as pN3b is advisable. In contrast, patients in the pN+ ≤7/ENE ≤4 subgroup should be classified as pN3a. [ABSTRACT FROM AUTHOR]

• NCCN maintains that END should be considered for cT1-2N0M0 OCSCC with a DOI > 3 mm. • DOI > 2.5 mm and poor differentiation predict adverse outcomes in cT1N0M0 OCSCC. • The decision to perform END should be guided by DOI and tumor differentiation. • This strategy allows avoiding END in 48.6% of patients, without compromising outcomes. According to the NCCN guidelines, there is weak evidence to support the use of elective neck dissection (END) in early-stage oral cavity squamous cell carcinoma (OCSCC). We sought to examine the indications for END in patients with cT1N0M0 OCSCC defined according to the AJCC Staging Manual, Eight Edition. Of the 3886 patients diagnosed with cT1N0M0 included in the study, 2065 underwent END and 1821 neck observation. The 5-year outcomes for patients who received END versus neck observation before and after propensity score matching (n = 1406 each) were as follows: neck control, 96 %/90 % (before matching), p < 0.0001; 96 %/90 % (after matching), p < 0.0001; disease-specific survival (DSS), 93 %/92 % (before matching), p = 0.0227; 93 %/92 % (after matching), p = 0.1436. Multivariable analyses revealed that neck observation, depth of invasion (DOI) > 2.5 mm, and poor differentiation were independent risk factors for 5-year outcomes. Upon the application of a scoring system ranging from 0 (no risk factor) to 3 (presence of the three risk factors), the following 5-year rates were observed: neck control, 98 %/95 %/84 %/85 %; DSS, 96 %/93 %/88 %/85 %; and overall survival, 90 %/86 %/79 %/59 %, respectively (all p < 0.0001). The survival outcomes of patients with scores of 0 and 1 were similar. The occult metastasis rates in the entire study cohort, DOI > 2.5 mm, and poor differentiation were 6.8 %/9.2 %/17.1 %, respectively. Because all patients who received neck observation had a score of 1 or higher, END should be performed when a DOI > 2.5 mm or poorly differentiated tumors are present. Under these circumstances, 48.6 % (1888/3886) of cT1N0M0 patients may avoid END without compromising oncological outcomes. [ABSTRACT FROM AUTHOR]

Abstract: Background: Although human papillomavirus (HPV) infections have been causally linked to oral cavity squamous cell carcinoma (OSCC), the potential role of low-risk HPV (LR-HPV) types in the pathogenesis of this malignancy remains unclear. Objectives: We sought to investigate the distribution of HPV genotypes and their prognostic significance in OSCC patients treated by radical surgery, either with or without adjuvant therapy. Study design: We studied two non-overlapping OSCC cohorts for the periods 2005–2006 (2005 cohort, n =204) and 2010–2011 (2010 cohort, n =206). Paraffin-embedded tissue blocks were collected, and the HPV genotype was determined using PCR plus HPV blot tests. The primary study endpoint was the prevalence of HPV genotypes. The secondary endpoints were the 2-year therapeutic outcomes. Results: The overall prevalence of HPV infections did not differ significantly in the two study cohorts. However, the prevalence of LR-HPV was significantly higher in the 2010 cohort than in the 2005 cohort (p =0.002). The overall prevalence of HPV infections was not significantly associated with the 2-year outcomes. However, multivariate analysis demonstrated that LR-HPV infection was a predictor of poor 2-year disease-free survival (p =0.036, hazard ratio [HR]=3.1), disease-specific survival (p =0.014, HR=3.8), and overall survival (p =0.016, HR=3.2) in the subgroups of OSCC patients with poor differentiation, pN2 lymph node metastases, or extracapsular spread (n =150). Conclusions: LR-HPV infections may have an important role in determining the clinical outcomes of certain OSCC patients bearing specific risk factors. [Copyright &y& Elsevier]

Summary: Objectives: We have previously shown that the resection outcomes of cT4a and cT4b oral cavity squamous cell carcinoma (OSCC) are comparable, but whether similar conclusions can be applied for the pathological stage of this disease needs investigation. In this study, we sought to compare the outcomes and to identify the risk factors for both pT4a and pT4b tumors. Methods: We retrospectively examined 181 pT4 OSCC patients who had radical resections between 2003 and 2010. The 5-year control and survival rates were the main outcome measures. Results: Of the 181 resected pT4 OSCC patients, 133 (73%) had pT4a disease, and 48 (27%) had pT4b disease. All of the resected T4b tumors were below the mandibular notch (infra-notch pT4b). The 5-year outcomes of the patients with infra-notch pT4b and pT4a were comparable: local control, 80% vs. 78%, p =0.7275; neck control, 87% vs. 82%, p =0.4798; distant metastases, 22% vs. 23%, p =0.8871; disease-free survival, 63% vs. 55%, p =0.2813; disease-specific survival, 68% vs. 60%, p =0.3526; and overall survival, 62% vs. 44%, p =0.2643, respectively. Extracapsular spread was the only independent prognostic factor for 5-year survival rates in pT4a patients. Poor tumor differentiation and pN2 status were the independent 5-year survival prognostic factors for the infra-notch pT4b tumor patients. Conclusions: Infra-notch pT4b had outcomes comparable with those of pT4a tumors, although they displayed different risk factors. We therefore recommend that resectable infra-notch pT4b tumors should be classified as pT4a disease in the AJCC tumor staging. [ABSTRACT FROM AUTHOR]

Summary: Pathological lymph node metastases (pN+) are an established prognostic factor in oral cavity squamous cell carcinoma (OSCC). We retrospectively examined the prognostic significance of lymph node (LN) density in pN+ OSCC patients who underwent neck dissection (ND) and postoperative adjuvant therapy. We examined 309 pN+ patients who underwent levels I–III ND and 148 pN+ patients treated with levels I–V ND. The 5-year control and survival rates served as the main outcome measures. The 5-year rates for patients treated with levels I–III and I–V NDs were as follows: local control, 79%, 74% (p =0.0630); neck control, 81%, 68% (p =0.0014); distant metastasis, 21%, 36% (p =0.0003); disease-free survival (DFS), 59%, 43% (p =0.0001); disease-specific survival (DSS), 66%, 46% (p <0.0001); and overall survival (OS), 49%, 37% (p =0.0048), respectively. Multivariate analysis demonstrated that an LN density ⩾0.16 was an independent prognostic factor for 5-year neck control (all data presented as p, hazard ratio [95% confidence interval]) (0.003, 2.691 [1.412–5.128]), distant metastases (0.001, 2.831 [1.520–5.270]), DFS (<0.001, 2.464 [1.571–3.866]), and DSS (0.036, 1.781 [1.040–3.052]) in levels I–III ND patients. An LN density ⩾0.048 was an independent predictor of 5-year local control (0.004, 4.871 [1.654–14.344]), neck control (0.002, 24.738 [3.367–181.771]), DFS (<0.001, 4.151 [2.264–7.610]), DSS (<0.001, 3.791 [2.017–7.125]), and OS (<0.001, 2.806 [1.706–4.613]) in levels I–V ND patients. Our findings demonstrate the prognostic value of LN density for guiding treatment strategies in OSCC patients who are to receive adjuvant therapy. [Copyright &y& Elsevier]

Summary: Our aim was to retrospectively assess the diagnostic performance from combined positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) for the detection of bone marrow invasion of the mandible or maxilla in patients with oral cavity squamous cell carcinoma (OCSCC). A total of 114 patients with OCSCC, arising from or abutting the upper or lower alveolar ridge, underwent staging PET/CT and MRI studies before surgery. The possibility of bone marrow invasion on PET/CT and MRI was graded retrospectively on a 5-point score. Histopathology was taken as the reference standard. Sensitivity, specificity, predictive values and likelihood ratios were calculated. Clinical factors affecting the performance, like tumor origin and dentate status were also explored. PET/CT was found to be more specific than MRI (83% vs. 61%, respectively, p =0.0015) but less sensitive (78% vs. 97%, respectively, p =0.0391). Dentate status and tumor origin affected the diagnostic performance of PET/CT. In patients with positive MRI, sensitivity and specificity of PET/CT were 78% and 100% in dentate patients with alveolar ridge tumors, 75% and 80% in dentate patient with buccal tumors, 90% and 33% in edentulous patients with alveolar ridge tumors and 0% and 63% for edentulous patients with buccal tumors, respectively. PET/CT is more specific than MRI and can be used to complement the role of MRI. A negative MRI result can confidently exclude the presence of bone marrow invasion, while in patients with positive MRI findings, a negative PET/CT may be useful to rule out bone marrow invasion in dentate patients. [Copyright &y& Elsevier]

Purpose: A better understanding of the prognostic factors in oral cavity squamous cell carcinoma (OSCC) may optimize the therapeutic approach. In this study, we sought to investigate whether the combination of clinical information, pathologic results, and preoperative maximal standardized uptake value (SUVmax) at the primary tumor and regional lymph nodes might improve the prognostic stratification in this patient group. Methods and Materials: A total of 347 consecutive OSCC patients were investigated. All participants underwent fluorodeoxyglucose–positron emission tomography within 2 weeks before surgery and neck dissection. The duration of follow-up was at least 24 months in all surviving patients. The optimal cutoff values for SUVmax at the primary tumor (SUVtumor-max) and regional lymph nodes (SUVnodal-max) were selected according to the 5-year disease-free survival (DFS) rate. Independent prognosticators were identified by Cox regression analysis. Results: In multivariate analysis, a cutoff SUVtumor-max of 8.6, a cutoff SUVnodal-max of 5.7, and the presence of pathologic lymph node metastases were found to be significant prognosticators for the 5-year DFS. A scoring system using these three prognostic factors was formulated to define distinct prognostic groups. The 5-year rates for patients with a score between 0 and 3 were as follows: neck control, 94%, 86%, 77%, 59% (p < 0.0001); distant metastases, 1%, 7%, 22%, 47% (p < 0.0001); disease-specific survival, 93%, 85%, 61%, 36%, respectively (p < 0.0001). Conclusion: Based on the study findings, the combined evaluation of pathologic node status and SUVmax at the primary tumor and regional lymph nodes may improve prognostic stratification in OSCC patients. [Copyright &y& Elsevier]

Abstract: The aim of this study was to clarify relevant alterations of gene expression associated with the invasive phenotype of oral cancer. To reduce heterogeneity and to obtain data on genes specifically involved in invasive mechanism, we established a highly invasive ORC subline through in vitro Matrigel invasion method. Affymetrix microarrays were used for transcriptome profiling between parental and the highly invasive subline. Seventy-nine genes were differentially expressed at least 2-fold, including 38 up-regulated and 41 down-regulated. After analyzing the microarray data by MetaCore™ algorithm, a total of 12 regulatory pathways were found to be associated with invasive phenotype (p <0.001). Two functional pathways were most significant: the cell adhesion through extracellular matrix remodeling (p =4.964e−06), and MHC-class-I mediated antigen presentation (p =9.843e−05). To shed more light on the biological functions of invasiveness, two genes highly over-expressed in the invasive subline, Cyr61 and CD44 were further validated. RNAi knockdown of these two genes led to significant suppression of cell growth (32% and 31%, respectively at day 3), cell migration (45% and 96%, respectively at 24h), and cell invasion (83% and 87%, respectively at day 3). These results suggested important roles of these genes in regulating invasive phenotype, and demonstrated the confidence of this study design in the search of invasive associated genes. The identified pathways associated with invasion mechanism may be novel targets for manipulation of the cancer behavior with consequences on treatment outcome. [Copyright &y& Elsevier]

Objectives: pStage IVB oral cavity squamous cell carcinoma (OCSCC) is defined as either pT4b or pN3 disease. We sought to devise an improved prognostic stratification of this patient group.Methods: Between December 2003 and January 2018, we retrospectively reviewed the clinical records of 1331 consecutive patients with OCSCC who received tumor excision and neck dissection. The number of patients with pT4a/pT4b, pT1N3b/pT2N3b/pT3N3b/pT4N3b, and pStage IVA/IVB was 370/83, 3/49/42/142, and 332/295, respectively.Results: The 5-year rates of disease-free survival (DFS) and disease-specific survival (DSS) for patients with pT4a/pT4b disease were 64%/63% (p = 0.973) and 72%/69% (p = 0.672), respectively. The 5-year DFS and DSS rates for patients with pT1N3b/pT2N3b/pT3N3b/pT4N3b disease were 67%/65%/40%/42% (p < 0.001; pT1-2N3b versus pT3-4N3b, p = 0.002) and 100%/68%/45%/49% (p < 0.001; pT1-2N3b versus pT3-4N3b, p = 0.002), respectively. We devised a new definition for pStage IV by considering patients with pT4bN0-2 and pT1-2N3b diseases as pStage-IVA. The number of patients with pStage IVA/IVB (pT3-4N3b) was 443/184. The 5-year rates of AJCC pStage IVA/IVB and the newly proposed pStage IVA/IVB (pT3-4N3b) were as follows: DFS, 74%/52% and 72%/42%; DSS, 83%/58% and 81%/47%; respectively, all p value < 0.001.Conclusions: The clinical outcomes of pT4b and pT4a OCSCC are similar. However, patients with pT3-4N3b disease have a less favorable 5-year prognosis compared with cases with pT1-2N3b. In light of the unfavorable outcomes, pT3-4N3b disease should continue to be classified as pStage IVB. Conversely, pT4bN0-2 and pT1-2N3b diseases portend a less adverse prognosis and should therefore be downstaged to pStage IVA. [ABSTRACT FROM AUTHOR]