Comparing the clinical outcomes of initial surgery and primary definitive radiotherapy with a dosage of 6600 cGy or higher in cT1-2N0M0 oral cavity squamous cell carcinoma: A nationwide cohort study.

BACKGROUND: To compare the clinical outcomes of two treatment modalities, initial surgery and primary definitive radiotherapy (RT), in Taiwanese patients diagnosed with cT1-2N0M0 oral cavity squamous cell carcinoma (OCSCC). METHODS: Between 2011 and 2019, we analyzed data for 13,542 cT1-2N0M0 patients who underwent initial surgery (n = 13,542) or definitive RT with a dosage of at least 6600 cGy (n = 145) for the treatment of OCSCC. To account for baseline differences, we employed propensity score (PS) matching, resulting in two well-balanced study groups (initial surgery, n = 580; definitive RT, n = 145). RESULTS: Before PS matching, the 5-year disease-specific survival (DSS) rates were 88% for the surgery group and 58% for the RT group. After PS matching, the 5-year DSS rates of the two groups were 86% and 58%, respectively. Similarly, the 5-year overall survival (OS) rates before PS matching were 80% for the surgery group and 36% for the RT group, whereas after PS matching, they were 73% and 36%, respectively. All these differences were statistically significant (p < 0.0001). A multivariable analysis identified treatment with RT, older age, stage II tumors, and a higher burden of comorbidities as independent risk factors for both DSS and OS. We also examined the 5-year outcomes for various subgroups (margin ≥5 mm, margin <5 mm, positive margins, RT combined with chemotherapy, and RT alone) as follows: DSS, 89%/88%/79%/63%/51%, respectively, p < 0.0001; OS, 82%/79%/68%/39%/32%, respectively, p < 0.0001. CONCLUSIONS: In Taiwanese patients with cT1-2N0M0 OCSCC, a remarkably low proportion (1.1%) completed definitive RT. A significant survival disparity of 30% was observed between patients who underwent initial surgery and those who received definitive RT. Interestingly, even patients from the surgical group with positive surgical margins exhibited a significantly superior survival compared to those in the definitive RT group.

Should sub-millimeter margins be deemed positive in oral cavity squamous cell carcinoma?

BACKGROUND: While several studies have indicated that a margin status of < 1 mm should be classified as a positive margin in oral cavity squamous cell carcinoma (OCSCC), there is a lack of extensive cohort studies comparing the clinical outcomes between patients with positive margins and margins < 1 mm. METHODS: Between 2011 and 2020, we identified 18,416 Taiwanese OCSCC patients who underwent tumor resection and neck dissection. Of these, 311 had margins < 1 mm and 1013 had positive margins. To compare patients with margins < 1 mm and those with positive margins, a propensity score (PS)-matched analysis (n = 253 in each group) was conducted. RESULTS: The group with margins < 1 mm displayed a notably higher prevalence of several variables: 1) tongue subsite, 2) younger age, 3) smaller depth of invasion), 4) early tumor stage, and 5) treatment with surgery alone. Patients with margins < 1 mm demonstrated significantly better disease-specific survival (DSS) and overall survival (OS) rates compared to those with positive margins (74 % versus 53 %, 65 % versus 43 %, both p < 0.0001). Multivariable analysis further confirmed that positive margins were an independent predictor of worse 5-year DSS (hazard ratio [HR] = 1.38, p = 0.0103) and OS (HR = 1.28, p = 0.0222). In the PS-matched cohort, the 5-year outcomes for patients with margins < 1 mm compared to positive margins were as follows: DSS, 71 % versus 59 %, respectively (p = 0.0127) and OS, 60 % versus 48 %, respectively (p = 0.0398). CONCLUSIONS: OCSCC patients with a margin status < 1 mm exhibited distinct clinicopathological characteristics and a more favorable prognosis compared to those with positive resection margins.

Is elective neck dissection justified in cT2N0M0 oral cavity cancer defined according to the AJCC eighth edition staging system?

BACKGROUND: The current NCCN guidelines recommend considering elective neck dissection (END) for early-stage oral cavity squamous cell carcinoma (OCSCC) with a depth of invasion (DOI) exceeding 3 mm. However, this DOI threshold, determined by evaluating the occult lymph node metastatic rate, lacks robust supporting evidence regarding its impact on patient outcomes. In this nationwide study, we sought to explore the specific indications for END in patients diagnosed with OCSCC at stage cT2N0M0, as defined by the AJCC Eighth Edition staging criteria. METHODS: We examined 4723 patients with cT2N0M0 OCSCC, of which 3744 underwent END and 979 were monitored through neck observation (NO). RESULTS: Patients who underwent END had better 5-year outcomes compared to those in the NO group. The END group had higher rates of neck control (95% vs. 84%, p < 0.0001), disease-specific survival (DSS; 87% vs. 84%, p = 0.0259), and overall survival (OS; 79% vs. 73%, p = 0.0002). Multivariable analysis identified NO, DOI ≥5.0 mm, and moderate-to-poor tumor differentiation as independent risk factors for 5-year neck control, DSS, and OS. Based on these prognostic variables, three distinct outcome subgroups were identified within the NO group. These included a low-risk subgroup (DOI <5 mm plus well-differentiated tumor), an intermediate-risk subgroup (DOI ≥5.0 mm or moderately differentiated tumor), and a high-risk subgroup (poorly differentiated tumor or DOI ≥5.0 mm plus moderately differentiated tumor). Notably, the 5-year survival outcomes (neck control/DSS/OS) for the low-risk subgroup within the NO group (97%/95%/85%, n = 251) were not inferior to those of the END group (95%/87%/79%). CONCLUSIONS: By implementing risk stratification within the NO group, we found that 26% (251/979) of low-risk patients achieved outcomes similar to those in the END group. Therefore, when making decisions regarding the implementation of END in patients with cT2N0M0 OCSCC, factors such as DOI and tumor differentiation should be taken into account.

A multicenter retrospective analysis of patients with salivary gland carcinoma treated with postoperative radiotherapy alone or chemoradiotherapy.

BACKGROUND: The aim of this study was to interrogate if the use of postoperative chemoradiotherapy (POCRT) correlated with superior oncological outcomes for certain subgroups of patients with high-risk salivary gland carcinoma (SGC), compared with postoperative radiotherapy (PORT) alone. METHODS: This multicenter retrospective study included 411 patients with surgically resected SGC who underwent PORT (n = 263) or POCRT (n = 148) between 2000 and 2015. Possible correlations of clinical parameters with outcomes were examined using the Kaplan-Meier analysis and Cox proportional-hazards regression model. RESULTS: The median follow-up of survivors is 10.9 years. For the entire cohort, adding concurrent chemotherapy to PORT was not associated with OS, PFS, or LRC improvement. However, patients with nodal metastasis who underwent POCRT had significantly higher 10-year OS (46.2% vs. 18.2%, P = 0.009) and PFS (38.7% vs. 10.0%, P = 0.009) rates than those treated with PORT alone. The presence of postoperative macroscopic residual tumor (R2 resection) was identified as an independent prognosticator for inferior OS (P = 0.032), PFS (P = 0.001), and LRC (P = 0.007). Importantly, POCRT significantly correlated with higher 10-year LRC rates in patients with R2 resection (74.2% vs. 40.7%, P = 0.034) or adenoid cystic carcinoma (AdCC, 97.6% vs. 83.6%, P = 0.039). On multivariate analyses, the use of POCRT significantly predicted superior OS (P = 0.037) and PFS (P = 0.013) for node-positive patients and LRC for patients with R2 resection (P = 0.041) or AdCC (P = 0.005). CONCLUSIONS: For surgically resected SGC, POCRT was associated with improved long-term OS and PFS for patients with nodal metastasis and superior LRC for patients with R2 resection or AdCC.

The added values of 18F-FDG PET/CT in differentiating cancer recurrence and osteoradionecrosis of mandible in patients with treated oral squamous cell carcinoma.

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.

Indications for elective neck dissection in cT1N0M0 oral cavity cancer according to the AJCC eight edition: A nationwide study.

OBJECTIVES: 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. METHODS: Of the 3886 patients diagnosed with cT1N0M0 included in the study, 2065 underwent END and 1821 neck observation. RESULTS: 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. CONCLUSION: 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.

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.

Optimizing margin status for improving prognosis in patients with oral cavity squamous cell carcinoma: A retrospective study from the two highest-volume Taiwanese hospitals.

Background: In the treatment of oral cavity squamous cell carcinoma (OCSCC), surgical quality measures which are expected to affect outcomes, including the achievement of a clear margin, are surgeon-dependent but might not be invariably associated with hospital volume. Our objective was to explore surgical margin variations and survival differences of OCSCC between two highest-volume hospitals in Taiwan. Materials and methods: A total of 2009 and 1019 patients with OCSCC who were treated at the two highest-volume Taiwanese hospitals (termed Hospital 1 and Hospital 2, respectively) were included. We examined how a pathological margin <5 mm impacted patient outcomes before and after propensity score (PS) matching. Results: The prevalence of margins <5 mm was markedly lower in Hospital 1 than in Hospital 2 (34.5%/65.2%, p<0.0001). Compared with Hospital 2, tumor severity was higher in Hospital 1. On univariable analysis, being treated in Hospital 2 (versus Hospital 1; hazard ratio [HR] for 5-year disease-specific survival [DSS] = 1.34, p=0.0002; HR for 5-year overall survival [OS] = 1.17, p=0.0271) and margins <5 mm (versus ≥5 mm; HR for 5-year DSS = 1.63, p<0.0001; HR for 5-year OS = 1.48, p<0.0001) were identified as adverse factors. The associations of treatment in Hospital 2 and margins <5 mm with less favorable outcomes remained significant after adjustment for potential confounders in multivariable analyses, as well as in the PS-matched cohort. The 5-year survival differences between patients operated in Hospital 1 and Hospital 2 were even more pronounced in the PS-matched cohort (before PS matching: DSS, 79%/74%, p=0.0002; OS, 71%/68%, p=0.0269; after PS matching: DSS, 84%/72%, p<0.0001; OS, 75%/66%, p<0.0001). In the entire cohort, the rate of adjuvant therapy was found to be lower in patients with margins ≥5 mm than in those with margins <5 mm (42.7%/57.0%, p<0.0001). Conclusions: Within the two highest-volume hospitals in Taiwan, patients with OCSCC with a clear margin status (≥5 mm) achieved more favorable outcomes. These results have clinical implications and show how initiatives aimed at improving the margin quality can translate in better outcomes. A clear margin status can reduce the need for adjuvant therapy, ultimately improving quality of life.

Prospective Investigation of 18FDG-PET/MRI with Intravoxel Incoherent Motion Diffusion-Weighted Imaging to Assess Survival in Patients with Oropharyngeal or Hypopharyngeal Carcinoma.

To prospectively investigate the prognostic value of 18F-FDG PET/MRI in patients with oropharyngeal or hypopharyngeal squamous cell carcinomas (OHSCC) treated by chemoradiotherapy. The study cohort consisted of patients with OHSCC who had undergone integrated PET/MRI prior to chemoradiotherapy or radiotherapy. Imaging parameters derived from intravoxel incoherent motion (IVIM), dynamic contrast-enhanced MRI (DCE-MRI), and 18F-FDG PET were analyzed in relation to overall survival (OS) and recurrence-free survival (RFS). In multivariable analysis, T classification (p < 0.001), metabolic tumor volume (p = 0.013), and pseudo-diffusion coefficient (p = 0.008) were identified as independent risk factors for OS. The volume transfer rate constant (p = 0.015), initial area under the curve (p = 0.043), T classification (p = 0.018), and N classification (p = 0.018) were significant predictors for RFS. The Harrell's c-indices of OS and RFS obtained from prognostic models incorporating clinical and PET/MRI predictors were significantly higher than those derived from the traditional TNM staging system (p = 0.001). The combination of clinical risk factors with functional parameters derived from IVIM and DCE-MRI plus metabolic PET parameters derived from 18F-FDG PET in integrated PET/MRI outperformed the information provided by traditional TNM staging in predicting the survival of patients with OHSCC.

Towards an Improved Pathological Node Classification for Prognostic Stratification of Patients With Oral Cavity Squamous Cell Carcinoma: Results From a Nationwide Registry Study.

Background: To assess the prognostic significance of different nodal parameters [i.e., number of pathologically positive nodes, log odds of positive lymph nodes, lymph node ratio (LNR), and extra-nodal extension (ENE)] in Taiwanese patients with oral cavity squamous cell carcinoma (OCSCC), and to devise an optimized pN classification system for predicting survival in OCSCC. Methods: A total of 4287 Taiwanese patients with first primary OCSCC and nodal metastases were enrolled. Cox proportional hazards regression analysis with the spline method was applied to identify the optimal cut-off values for LNR, log odds of positive lymph nodes, and number of pathologically positive nodes. Results: On multivariable analysis, we identified a LNR ≥0.078/0.079, the presence of at least three pathologically positive nodes, and ENE as independent prognosticators for 5-year disease-specific survival (DSS) and overall survival (OS) rates. We therefore devised a four-point prognostic scoring system according to the presence or absence of each variable. The 5-year DSS and OS rates of patients with scores of 0-3 were 70%/62%/50%/36% (p <0.0001) and 61%/52%/40%25%, respectively (p <0.0001). On analyzing the AJCC 2017 pN classification, patients with pN3a displayed better survival rates than those with pN2 disease. The 5-year DSS and OS rates of patients with pN1/pN2/pN3a/pN3b disease were 72%/60%/67%/43% (p <0.0001) and 63%/51%/67%/33%, respectively (p <0.0001). Conclusions: Three nodal parameters (i.e., a LNR ≥0.078/0.079, the presence of at least three pathologically positive nodes, and ENE) assessed in combination provided a better prognostic stratification than the traditional AJCC pN classification.

Utilization of the lymph node-to-primary tumor ratio of PET standardized uptake value and circulating Epstein-Barr virus DNA to predict distant metastasis in nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: To determine the clinical impact of integrating Epstein-Barr virus (EBV) DNA and lymph node-to-primary tumor ratio (NTR) of positron emission tomography (PET) standardized uptake value (SUV) in predicting distant metastasis, such as distant metastasis-free survival (DMFS), in patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: We retrospectively reviewed patients diagnosed with non-disseminated NPC between 2010 and 2017. The optimal cut-off values of EBV DNA and SUV NTR were determined using receiver operating characteristic analysis. The prognostic values of SUV NTR and EBV DNA on DMFS and overall survival were evaluated using the Kaplan-Meier method. Univariate and multivariable analyses were performed using the Wald Chi-squared test and Cox proportional hazards regression, respectively. RESULTS: A total of 488 patients were included in the analysis. The median follow-up period was 61.6 months. The optimal cut-off values of EBV DNA and SUV NTR were 3377.5 copies per mL and 0.64, respectively. The five-year DMFS for patients with high vs low EBV DNA and SUV NTR levels were 64.9% vs 86.6% (p < 0.001) and 78.7% vs 87.4% (p = 0.021), respectively. In subgroup analysis, the high-risk group with high levels of pretreatment EBV DNA and SUV NTR had worse DMFS in either American Joint Committee on Cancer (AJCC) stage I-III or IVA-B (p = 0.001 and <0.001, respectively). Univariate and multivariable analyses showed the statistical significance of EBV DNA, SUV NTR, and their composite in DMFS (p < 0.001 for EBV DNA; p = 0.022 for SUV NTR; p < 0.001 for their composite). CONCLUSION: This study showed that EBV DNA and SUV NTR have independent and additive values as prognosticators for distant metastasis in patients with NPC, suggesting that these two individual factors, except the AJCC staging system, should be included in future studies.

Clinical outcomes of patients with pT4a and pT4b oral cavity squamous cell carcinoma who had undergone surgery: Results from a Taiwanese registry-based, nationwide cohort study.

OBJECTIVES: While the NCCN guidelines maintain that T4b oral cavity squamous cell carcinoma (OCSCC) should undergo either non-surgical treatments or clinical trials, promising outcomes of T4b OCSCC having surgical excision have been reported. We analyzed and compared the clinical outcomes of Taiwanese patients with pT4a and pT4b OCSCC who had undergone surgical treatment. METHODS: From 2011 to 2017, a total of 4031 and 355 patients with first primary pT4a and pT4b OCSCC were identified. A propensity score (PS)-matched analysis of patients (n = 351 each) for pT4a and pT4b tumors was also performed. RESULTS: The 5-year disease-specific and overall survival (DSS/OS) rates were more favorable in patients with pT4a than in those with pT4b OCSCC (64%/55%, p < 0.0001; 55%/43%, p < 0.0001, respectively). Compared with pT4a, those with pT4b tumors had a higher burden of the following risk factors: buccal/retromolar/hard palate subsite, male sex, depth ≥ 10 mm, and positive margins. Before PS matching, multivariable analyses revealed that pT4b tumors (versus pT4a) were an adverse prognosticator for both 5-year DSS and OS (hazard ratios: 1.32 and 1.39, respectively). However, in the PS-matched cohort, no significant differences in 5-year DSS and OS rates were observed between pT4a and pT4b OCSCC (57%/56%, p = 0.4024; 48%/44%, p = 0.1807, respectively) CONCLUSIONS: No significant outcome differences were evident between pT4b and pT4a OCSCC after PS matching. The most plausible hypothesis for the observed survival difference between T4a and T4b tumors is that it was driven by positive margins. We suggest that T4b OCSCC should undergo initial surgical excision if adequate resection is possible.

Improved prognostic stratification of patients with pN3b oral cavity cancer based on maximum standardized uptake value of metastatic nodes, lymph node ratio, and level of cervical nodal metastases.

OBJECTIVES: The prognosis of pN3b oral cavity squamous cell carcinoma (OCSCC) remains heterogeneous. We sought to improve the prognostic stratification of patients with pN3b OCSCC through a combined analysis of FDG-PET parameters and clinicopathological risk factors (RFs). METHODS: From 2001 to 2019, complete data on maximum standardized uptake values derived from FDG-PET of neck metastatic nodes (SUV-nodal-max) and clinicopathological RFs were available for 257 patients with pN3b disease. RESULTS: Using the 5-year disease-free survival (DFS) as the outcome of interest, the optimal cutoff points for SUV-nodal-max and lymph node ratio (LNR) were 15.9 and 0.17, respectively. The 5-year DFS rates/(number of cases) for patients with pN3b disease were as follows: SUV-nodal-max < 15.9 versus ≥ 15.9, 49%(226)/21%(31), p = 0.000003; LNR < 0.17 versus ≥ 0.17, 49%(230)/17%(27), p = 0.000117; absence versus presence of neck level IV/V metastases, 49%(230)/15%(27), p = 0.000004. Multivariable analyses revealed that SUV-nodal-max ≥ 15.9, LNR ≥ 0.17, and level IV/V metastases were independent prognosticators for 5-year distant metastases (DM), DFS, disease-specific survival (DSS), and overall survival (OS) rates. Based on these variables, we devised a scoring system that identified three distinct prognostic subgroups at low (score 0, n = 190), intermediate (score 1, n = 51), and high (scores 2-3, n = 16) risk. The 5-year rates of patients with pN3b disease deemed to be at low/intermediate/high risk were as follows: DM, 31%/52%/89%; DFS, 54%/26%/0%; DSS, 59%/36%/8%; OS, 42%/31%/6%, respectively; all p < 0.001. CONCLUSIONS: A scoring system based on SUV-nodal-max, LNR, and level IV/V metastases improves the prognostic stratification of OCSCC patients with pN3b disease.

cN+pN0 disease does not portend a less favorable prognosis compared with cN0pN0 in patients with resected oral cavity squamous cell carcinoma.

BACKGROUND: We compared the clinical outcomes of patients with oral cavity squamous cell carcinoma (OCSCC) with cN+pN0 versus cN0pN0 disease. METHODS: A total of 1309 OCSCC patients with pN0 disease were included. Of them, 1019 and 290 cases had cN0pN0 and cN+pN0 disease, respectively. For comparison purposes, we also examined 799 patients with pN+disease (cN0pN+/cN+pN+, n = 239/560). Subgroup analysis was performed in a propensity score-matched cohort with cN0pN0 and cN+pN0 disease (n = 284 each). RESULTS: Compared with cN0pN0, patients with cN+pN0 had a higher prevalence of the following variables: betel chewing, pT3-4, depth ≥10 mm, perineural invasion, and treatment with surgery and adjuvant therapy. The prognosis of patients with cN+pN0 (mean: 52 nodes) and cN0pN0 (mean: 39 nodes) disease was similar both in the original cohort and after propensity score matching. However, the 5-year outcomes were more favorable for cN+pN0/cN0pN0 compared with cN0pN+/cN+pN+ (local control, 88%/88%/83%/81%; neck control, 94%/93%/82%/76%; distant metastases, 4%/3%/13%/31%; disease-free survival, 84%/83%/68%/52%; disease-specific survival, 92%/92%/77%/57%; overall survival, 81%/82%/59%/42%; all p values <0.001; cN+pN0 versus cN0pN0, all p values >0.05). cN+pN0 disease (vs. cN0pN0) was not significantly associated with local control, neck control, distant metastases, and survivals either in univariable or multivariable analyses. CONCLUSIONS: Despite a higher risk factor burden, the prognosis of patients with cN+pN0 disease did not differ from that of cases with cN0pN0. The higher nodal yield and the more frequent use of adjuvant therapy in cN+pN0 disease may explain the lack of significant differences in terms of neck control compared with cN0pN0 disease.

Poor tumor differentiation is an independent adverse prognostic variable in patients with locally advanced oral cavity cancer--Comparison with pathological risk factors according to the NCCN guidelines.

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.

Prognostic stratification of patients with AJCC 2018 pStage IVB oral cavity cancer: Should pT4b and pN3 disease be reclassified?

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.

Deep Learning for Fully Automated Prediction of Overall Survival in Patients with Oropharyngeal Cancer Using FDG-PET Imaging.

PURPOSE: Accurate prognostic stratification of patients with oropharyngeal squamous cell carcinoma (OPSCC) is crucial. We developed an objective and robust deep learning-based fully-automated tool called the DeepPET-OPSCC biomarker for predicting overall survival (OS) in OPSCC using [18F]fluorodeoxyglucose (FDG)-PET imaging. EXPERIMENTAL DESIGN: The DeepPET-OPSCC prediction model was built and tested internally on a discovery cohort (n = 268) by integrating five convolutional neural network models for volumetric segmentation and ten models for OS prognostication. Two external test cohorts were enrolled-the first based on the Cancer Imaging Archive (TCIA) database (n = 353) and the second being a clinical deployment cohort (n = 31)-to assess the DeepPET-OPSCC performance and goodness of fit. RESULTS: After adjustment for potential confounders, DeepPET-OPSCC was found to be an independent predictor of OS in both discovery and TCIA test cohorts [HR = 2.07; 95% confidence interval (CI), 1.31-3.28 and HR = 2.39; 95% CI, 1.38-4.16; both P = 0.002]. The tool also revealed good predictive performance, with a c-index of 0.707 (95% CI, 0.658-0.757) in the discovery cohort, 0.689 (95% CI, 0.621-0.757) in the TCIA test cohort, and 0.787 (95% CI, 0.675-0.899) in the clinical deployment test cohort; the average time taken was 2 minutes for calculation per exam. The integrated nomogram of DeepPET-OPSCC and clinical risk factors significantly outperformed the clinical model [AUC at 5 years: 0.801 (95% CI, 0.727-0.874) vs. 0.749 (95% CI, 0.649-0.842); P = 0.031] in the TCIA test cohort. CONCLUSIONS: DeepPET-OPSCC achieved an accurate OS prediction in patients with OPSCC and enabled an objective, unbiased, and rapid assessment for OPSCC prognostication.

Surgical Margins Status and Prognosis after Resection of Oral Cavity Squamous Cell Carcinoma: Results from a Taiwanese Nationwide Registry-Based Study.

(1) Background: The optimal cutoff value that maximizes the prognostic value of surgical margins in patients with resected oral cavity squamous cell carcinoma has not yet been identified. (2) Methods: Data for this study were retrieved from the Taiwan Cancer Registry Database. A total of 13,768 Taiwanese patients with oral cavity squamous cell carcinoma were identified and stratified according to different margin statuses (0, 0.1-4 and > 4 mm). The five-year local control, disease-specific survival and overall survival rates were the main outcome measures. (3) Results: The 5-year local control, disease-specific survival and overall survival rates of patients with close margins (0 and 0.1-4 mm) were significantly lower than those observed in patients with clear margins (> 4 mm; all p values < 0.001). In multivariate analysis, margin status, depth of invasion and extra-nodal extension were identified as independent adverse prognostic factors for 5-year local control. (4) Conclusions: A thorough assessment of surgical margins can provide a reliable prognostic prediction in patients with OCSCC. This has potential implications for treatment approaches tailored to the individual level. The achievement of clear margins (>4 mm) should be considered a key surgical goal to improve outcomes in this patient group.

Development and validation of a prognostic model incorporating [18F]FDG PET/CT radiomics for patients with minor salivary gland carcinoma.

OBJECTIVES: The aim of this study was to develop and validate a prognostic model incorporating [18F]FDG PET/CT radiomics for patients of minor salivary gland carcinoma (MSGC). METHODS: We retrospectively reviewed the pretreatment [18F]FDG PET/CT images of 75 MSGC patients treated with curative intent. Using a 1.5:1 ratio, the patients were randomly divided into a training and validation group. The main outcome measurements were overall survival (OS) and relapse-free survival (RFS). All of the patients were followed up for at least 30 months or until death. Following segmentation of tumors and lymph nodes on PET images, radiomic features were extracted. The prognostic significance of PET radiomics and clinical parameters in the training group was examined using receiver operating characteristic curve analysis. Variables showing a significant impact on OS and RFS were entered into multivariable Cox regression models. Recursive partitioning analysis was subsequently implemented to devise a prognostic index, whose performance was examined in the validation group. Finally, the performance of the index was compared with clinical variables in the entire cohort and nomograms for surgically treated cases. RESULTS: The training and validation groups consisted of 45 and 30 patients, respectively. The median follow-up time in the entire cohort was 59.5 months. Eighteen relapse, 19 dead, and thirteen relapse, eight dead events were found in the training and validation cohorts, respectively. In the training group, two factors were identified as independently associated with poor OS, i.e., (1) tumors with both high maximum standardized uptake value (SUVmax) and discretized intensity entropy and (2) poor performance status or N2c-N3 stage. A prognostic model based on the above factors was devised and showed significant higher concordance index (C-index) for OS than those of AJCC stage and high-risk histology (C-index: 0.83 vs. 0.65, P = 0.005; 0.83 vs. 0.54, P < 0.001, respectively). This index also demonstrated superior performance than nomogram for OS (C-index: 0.88 vs. 0.70, P = 0.017) and that for RFS (C-index: 0.87 vs. 0.72, P = 0.004). CONCLUSIONS: We devised a novel prognostic model that incorporates [18F]FDG PET/CT radiomics and may help refine outcome prediction in patients with MSGC.