Adjuvant pulse-dose-rate brachytherapy for oral cavity and oropharynx carcinoma: Outcome and toxicity assessment of 66 patients.

Purpose: Brachytherapy (BT) is a validated radiation technique for treatment of early stage tumors of oral cavity and oropharynx. This study aimed to analyze the results of our institute's patients after replacing low-dose-rate (LDR) with pulse-dose-rate (PDR) brachytherapy. Material and methods: We retrospectively collected data from all patients treated between 2009 and 2020 for squamous cell carcinoma (floor of the mouth, tongue, and oropharynx) using adjuvant interstitial BT with or without external RT. Primary outcome was local control. Secondary outcomes were regional control rate and toxicity. Statistical analysis of local and regional recurrences were described using Kaplan-Meier method. Prognostic value of each factor for recurrence or toxicity was evaluated with bivariate Fine-Gray model. Results: Data from 66 patients were analyzed. Local and regional recurrences were reported in 11% and 20% of the patients, respectively. No significant factors were identified in the present study. Grade 2 and 3 acute mucositis were reported in 21% of patients, and were more frequent in the BT only group. Almost half (47%) of the patients described acute pain following BT, and 26% required stage 2 or 3 analgesics. Trophic disorders were observed in 16 patients. Five patients presented with soft tissue necrosis (STN) and required medical treatment, of whom one subsequently required hyperbaric oxygen therapy. No predictive factors were identified for STN risk. Two patients developed osteoradionecrosis. Conclusions: Oral and oropharyngeal PDR-BT as adjuvant treatment is safe and effective for well-defined indications.

CT predictors of sub-centimeter occult lymph node metastases in oral cavity squamous cell carcinoma: A case-control study.

BACKGROUND: For patients with oral cavity squamous cell carcinoma (OCSCC) without evidence of nodal metastasis (cN0) on pre-operative evaluation, there are no clear guidelines who should undergo elective neck dissection (END) versus clinical surveillance. OBJECTIVE: To identify CT imaging characteristics of sub-centimeter lymph nodes that would help predict the likelihood of nodal metastases on pathology. METHODS: Retrospective review of cN0 OCSCC patients at a tertiary academic medical center was performed. Inclusion criteria included elective neck dissection, pre-operative CT imaging and presence of metastatic disease within lymph nodes. Control group consisted of patients without nodal metastases on pathology. CT features that were evaluated included asymmetric size, disrupted fatty hilum, asymmetric number, presence of cortical nodule, cortical nodule size, and round/oval shape. We evaluated the associations between CT LN features and the presence of metastases using multi-level mixed-effects logistic regression models. Model evaluation was performed using 5-fold cross-validation. The positive predictive value (PPV) and negative predictive value (NPV) were calculated. RESULTS: 26 patients in each study and control groups were included. Three-level mixed-effects logistic regression models indicated round/oval shape (OR = 1.39, p = .01), asymmetric number (OR = 7.20, p = .005), and disrupted fatty hilum (OR = 3.31, p = .04) to be independently predictive in a 3-variable model with sensitivity = 38.0%, specificity = 92.0%, and PPV = 93.8%. CONCLUSIONS: In cN0 OCSCC patients undergoing END, round/oval shape, asymmetric number, and disrupted fatty hilum of lymph nodes on pre-operative CT imaging are novel and highly predictive of occult nodal disease.

Relationship between transcriptional expression of pyruvate dehydrogenase and local control of disease in patients with oral cavity carcinomas / Relación entre la expresión transcripcional de piruvato deshidrogenasa y el control local de la enfermedad en pacientes con cáncer en la cavidad oral

Background The altered cellular metabolism is one of the hallmarks of the cancer cells, favoring the process of aerobic glycolysis, known as the Warburg effect. The pyruvate dehydrogenase (PDH) complex is one of the elements involved in this metabolic process. The present study aims to evaluate the relationship between the transcriptional expression of PDHB and the risk of local recurrence in patients with oral cavity carcinomas. Methods We determined the transcriptional expression of PDHB in biopsies from 41 patients with oral cavity carcinomas treated with surgery. The PDHB expression was categorized according to the local control of the disease with a recursive partitioning analysis. Results During the follow-up period 13 patients (31.7%) had a local recurrence of the tumor. Considering local disease control as the dependent variable, the recursive partitioning analysis classified the patients in two categories according to high (n=16, 39.0%) or low (n=25, 61.0%) PDHB expression. Five-year local recurrence-free survival for patients with high PDHB expression was 84.8% (95% CI: 65.2-100%), and for patients with low expression it was 54.3% (95% CI: 34.3–74.2 %) (P=0.034). The results of multivariate analysis showed that patients with a low PDHB expression had a 4.90 times higher risk of local recurrence of the tumor (95% CI: 1.02–22.68, P=0.042). Conclusion There is a relationship between the metabolic characteristics of the tumor and its aggressiveness. According to our results, patients with oral cavity carcinomas with low transcriptional expression levels of PDHB have a significantly higher risk of local tumor recurrence. (AU)

Antecedentes La alteración del metabolismo celular es una de las características distintivas de las células cancerígenas, y favorece el proceso de la glucólisis aeróbica, conocido como efecto de Warburg. El complejo de piruvato deshidrogenasa (PDH) es uno de los elementos implicados en este proceso metabólico. El objetivo del presente estudio es evaluar la relación entre la expresión transcripcional de PDHB y el riesgo de recidiva local en los pacientes con cáncer en la cavidad oral. Métodos Determinamos la expresión transcripcional de PDHB en biopsias de 41 pacientes con cáncer en la cavidad oral tratados con cirugía. Se categorizó la expresión de PDHB de acuerdo con el control local de la enfermedad, con un análisis de partición recursiva. Resultados Durante el periodo de seguimiento, trece pacientes (31,7%) tuvieron una recidiva local del tumor. Considerando el control de la enfermedad local como variable dependiente, el análisis de partición recursiva clasificó a los pacientes en dos categorías, de acuerdo con la expresión de PDHB alta (n=16, 39%) o baja (n=25, 61%). La tasa de supervivencia libre de enfermedad a cinco años con expresión alta de PDHB fue del 84,8% (95% IC: 65,2–100%), siendo del 54,3% (95% IC: 34,3–74,2%) (P=0,034) para los pacientes con expresión baja. Los resultados del análisis multivariante reflejaron que los pacientes con expresión baja de PDHB tuvieron un riesgo 4,90 veces mayor de recidiva local del tumor (95% IC: 1,02–22,68, P=0,042). Conclusión Existe una relación entre las características metabólicas del tumor y su agresividad. Conforme a nuestros resultados, los pacientes con cáncer en la cavidad oral y bajos niveles transcripcionales de PDHB tienen un riesgo significativamente mayor de recidiva local del tumor. (AU)

Role of Selective Neck Dissection in Clinically Single Node Positive Disease in Oral Cavity Cancers.

Management of the neck in oral cavity squamous carcinoma is debatable. There is controversy regarding role of SND in single node positive neck in oral SCC. The aim of this study was to determine the efficacy of selective neck dissection (SND) for cN1 neck in patients with oral cancer. A retrospective chart review of 266 oral cancer patients who were clinically single node positive from August 2013 to December 2019 was done. Patients having clinical or radiological cN1 disease undergoing SND were included. Two hundred sixty-six patients were analysed with 86% male predominance. Median age was 48 years. The commonest primary site was Bucco-alveolar complex (64%). Total of 319 SNDs were done in 266 patients. At median follow-up of 29 months, 29 patients (9%) had neck recurrence among which 4 patients had recurrence at level V, along with recurrence at other nodal levels. Three-year regional control was 86%, while DFS and OS were 66% and 68% respectively. For oral cancer with single clinically node positive neck (cN1), SND is an effective and oncological safe treatment. Outcomes are similar with modified neck dissection reported in the literature.

Relationship between transcriptional expression of pyruvate dehydrogenase and local control of disease in patients with oral cavity carcinomas.

BACKGROUND: The altered cellular metabolism is one of the hallmarks of the cancer cells, favoring the process of aerobic glycolysis, known as the Warburg effect. The pyruvate dehydrogenase (PDH) complex is one of the elements involved in this metabolic process. The present study aims to evaluate the relationship between the transcriptional expression of PDHB and the risk of local recurrence in patients with oral cavity carcinomas. METHODS: We determined the transcriptional expression of PDHB in biopsies from 41 patients with oral cavity carcinomas treated with surgery. The PDHB expression was categorized according to the local control of the disease with a recursive partitioning analysis. RESULTS: During the follow-up period 13 patients (31.7%) had a local recurrence of the tumor. Considering local disease control as the dependent variable, the recursive partitioning analysis classified the patients in two categories according to high (n=16, 39.0%) or low (n=25, 61.0%) PDHB expression. Five-year local recurrence-free survival for patients with high PDHB expression was 84.8% (95% CI: 65.2-100%), and for patients with low expression it was 54.3% (95% CI: 34.3-74.2 %) (P=0.034). The results of multivariate analysis showed that patients with a low PDHB expression had a 4.90 times higher risk of local recurrence of the tumor (95% CI: 1.02-22.68, P=0.042). CONCLUSION: There is a relationship between the metabolic characteristics of the tumor and its aggressiveness. According to our results, patients with oral cavity carcinomas with low transcriptional expression levels of PDHB have a significantly higher risk of local tumor recurrence.

Esophageal squamous cell carcinoma metastasizing to the oral cavity: a case report and literature review.

Introduction and Importance: Metastatic esophageal carcinoma to the oral cavity has been rarely reported, and most cases were adenocarcinoma metastasizing to the mandible. This first report of a case of metastatic esophageal squamous cell carcinoma to the floor of the mouth is crucial due to its rarity and difficulties in diagnosing and managing this condition. Case Presentation: A 53-year-old male had a painful submucosal mass on the left side of the floor of the mouth for 2 months. A biopsy indicated a moderately differentiated squamous cell carcinoma. Six months before the intraoral mass appeared, the patient had a moderately differentiated squamous cell carcinoma of the thoracic esophagus and was treated with concurrent chemoradiotherapy. With the previous history and pathological review, the diagnosis of metastatic esophageal squamous cell carcinoma to the floor of the mouth was made. Panendoscopy and an 18F-fluorodeoxyglucose positron emission tomography-computed tomography scan revealed no other abnormality or other distant metastasis. The patient underwent surgical resection with postoperative chemoradiotherapy. He was able to take a regular diet and had good speech function. Ten months after treatment completion, he has had recurrent disease at the floor of the mouth with lung metastasis. Conclusions: Oral metastasis from esophageal squamous cell carcinoma is very rare and should be differentiated from primary oral cancer using clinical and pathological features. 18F-fluorodeoxyglucose positron emission tomography-computed tomography scanning is the preferred imaging method to exclude primary tumor persistence and other metastases. Treatment is usually palliative; however, function-preserving surgery may be an option for a patient with limited disease in the oral cavity.

Oral cavity carcinoma in patients with and without a history of lichen planus: A comparative analysis.

BACKGROUND: Oral potentially malignant disorders (OPMD) are associated with the risk of malignant transformation (MT) into oral cavity carcinoma (OCC). Oral lichen planus (OLP) is one of the most common OPMDs in western countries. Although there is a substantial amount of research on progression to cancer, a specific analysis of the clinical characteristics and prognosis of cancer developed in patients with a history of OLP versus patients without a history of OLP has not been investigated so far. METHODS: Retrospective evaluation of 82 patients treated for OCC with a known history of OLP compared to a representative sample of 82 patients treated for OCC without a known history of LP. Comparative analyses were performed on age at presentation, sex, TNM staging, clinical characteristics, pathology characteristics, 2- and 5-year overall survival (OS), and disease-free survival (DFS). RESULTS: It was shown that patients with a history of LP were significantly younger at first presentation than patients without a history of LP (mean age difference 6.7 years, 95% CI 3.1-10.3, p < 0.05). Also, patients with a history of OLP were in higher proportion females. The main pathological stage at presentation was significantly lower in the OLP group (p < 0.05). The 2-year survival analysis showed that DFS and OS were significantly lower in patients without a known history of OLP, with a hazard ratio (HR) of 3.1 (95% CI 1.4-6.8) and HR of 2.6 (95% CI 1.3-5.3), respectively. The 5-year survival analysis showed that DFS and OS were significantly lower in patients without a known history of OLP, with a hazard ratio of 3.1 (95% CI 1.6-6.2) and of 2.9 (95% CI 1.5-5.6), respectively. CONCLUSIONS: Cancer arising from OLP has peculiar characteristics compared to cancer in naïve patients. It most commonly affects younger patients, women, and nonsmokers. It is usually diagnosed at earlier stages and appears to have less aggressive behavior at presentation. Moreover, when 2- and 5-year survival is analyzed, it appears that patients in OLP group have an overall and a disease-free survival advantage. These results suggest that cancer from OLP is less aggressive and thus has a potential biological difference with cancer arising in non-OLP patients. Further clinical and basic investigations are needed to confirm the results of this study.

Diagnostic and prognostic value of magnetic resonance imaging in the detection of tumor depth of invasion and bone invasion in patients with oral cavity cancer.

PURPOSE: To evaluate the accuracy of preoperative contrast-enhanced magnetic resonance imaging (MRI) in the assessment of radiological depth of invasion (rDOI) and bone invasion in patients with oral cavity cancer, and the prognostic value of preoperative rDOI. MATERIALS AND METHODS: This retrospective study included patients with surgically resected oral cavity cancer and preoperative MRI acquired within four weeks before surgery. Two readers evaluated the MRI to assess the superficial and deep bone invasion, preoperative T stage, and measured the rDOI. The rDOI was compared to the histopathological DOI (pDOI), used as reference standard. Prognostic value of preoperative features for the disease-specific survival was evaluated using the Kaplan-Meier curve and multivariable Cox proportional hazards analysis. RESULTS: The final population included 80 patients (50 males, mean age 67.7 ± 13.6 years). There was a strong statistically significant correlation between the rDOI (median 10 mm) and the pDOI (median 9 mm) (ρ: 0.978, p < 0.001). The agreement between MRI and histopathological T stage was excellent (k = 0.93, 95% CI 0.86, 0.99). The sensitivity and specificity of preoperative MRI were 93.3% and 98.8% for deep bone invasion, while they were 75.0% and 95.8% for superficial bone invasion, respectively. The rDOI > 10 mm was associated with poorer disease-specific survival (log-rank p = 0.016). The rDOI remained the only independent preoperative predictor associated with poorer disease-specific survival at multivariable analysis (hazard ratio 5.5; 95% CI 1.14, 26.58; p = 0.033). CONCLUSION: Preoperative MRI is accurate for the assessment of DOI and bone invasion. The rDOI is an independent preoperative predictor of disease-specific survival in patients with oral cavity cancer.

Oral Tongue Spontaneous Tumor Regression after Biopsy: A Case Report and Genomic Profile.

Spontaneous regression of a neoplasm is a rare oncologic phenomenon. Certain neoplasms, such as melanomas and neuroblastomas, display this phenomenon. To date, spontaneous regression of oral cavity squamous cell carcinomas has been documented in only a handful of case reports. We present a novel case of spontaneous regression of an oral tongue squamous cell carcinoma following biopsy. We discuss the tumor's unique genetic profile, immune response to cancer, and review the literature on possible mechanisms of spontaneous regression. Small-volume persistent cancer in our patient reinforces that tissue confirmation remains crucial to avoid missing remaining tumor. Further investigation is required to understand mechanisms of spontaneous regression and how these may be exploited to improve head and neck squamous cell carcinoma treatment.

Frequency of PIK3CA mutations in different subsites of head and neck squamous cell carcinoma in southern Thailand.

BACKGROUND: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations have been reported in many cancers, including head and neck squamous cell carcinoma (HNSCC). The frequency of these mutations varies among tumor locations and might be relevant to treatment outcomes among HNSCC. In this study, we examined the frequency of PIK3CA mutations in the different subsites of HNSCC. METHODS: Ninety-six fresh biopsy specimens were investigated for mutations in PIK3CA exons 4, 9, and 20 using allele-specific real-time polymerase chain reaction. Patient characteristics and survival were analyzed and compared between specimens with or without PIK3CA mutations. RESULTS: The study included primary tumors originating from the oral cavity (n=63), hypopharynx (n=23), and oropharynx (n=10). We identified mutations in 10.4% of patients (10 of 96 specimens). The overall mutational frequency was 17.4% (4/23) and 9.5% (6/63) in the hypopharynx and oral cavity, respectively. No patients with oropharyngeal carcinoma had mutations. Among the 10 mutant specimens, five were missense mutations (exon 9 [E545K] in two samples and exon 20 [H1047R] in three samples) and five were silent mutations in exon 20 (T1025T). Mutations were not found in exon 4. Among 84 patients with available clinical data, we found no significant differences in clinical characteristics and survival based on the presence or absence of PIK3CA mutations. CONCLUSIONS: The results indicate that PIK3CA mutations are involved in HNSCC carcinogenesis, and the hypopharynx should be considered a primary site of interest for future studies, particularly in Southeast Asian populations.

Autofluorescence Image-Guided Endoscopy in the Management of Upper Aerodigestive Tract Tumors.

At this juncture, autofluorescence and narrow-band imaging have resurfaced in the medicine arena in parallel with current technology advancement. The emergence of newly developed optical instrumentation in addition to the discovery of new fluorescence biomolecules have contributed to a refined management of diseases and tumors, especially in the management of upper aerodigestive tract tumors. The advancement in multispectral imaging and micro-endoscopy has also escalated the trends further in the setting of the management of this tumor, in order to gain not only the best treatment outcomes but also facilitate early tumor diagnosis. This includes the usage of autofluorescence endoscopy for screening, diagnosis and treatment of this tumor. This is crucial, as microtumoral deposit at the periphery of the gross tumor can be only assessed via an enhanced endoscopy and even more precisely with autofluorescence endoscopic techniques. Overall, with this new technique, optimum management can be achieved for these patients. Hence, the treatment outcomes can be improved and patients are able to attain better prognosis and survival.

Characterization of the immune response in patients with cancer of the oral cavity after neoadjuvant immunotherapy with the IRX-2 regimen.

OBJECTIVE: IRX-2 is a homologous cell-derived multi-cytokine biologic with multifaceted immune modulatory effects that has been shown to induce increased lymphocyte infiltration into primary tumors in oral cavity carcinoma. Our objective was to characterize tumor immune gene expression and epigenomic changes after neoadjuvant IRX-2 immunotherapy in patients with squamous cell carcinoma of the oral cavity. METHODS: A randomized phase II trial was conducted of the IRX regimen 3 weeks prior to surgery for previously untreated patients with Stage II-IV oral cavity carcinoma. The treatment regimen consisted of low dose (300 mg/m2) cyclophosphamide (day 1) followed by 10 days of regional perilymphatic IRX-2 cytokine injections and daily oral indomethacin, zinc and omeprazole (Regimen 1) compared to the identical regimen without the IRX-2 cytokines (Regimen 2). The NanoString immune panel (730 genes) and Infinium MethylationEPIC BeadChip were performed to assess the gene expression and DNA methylation signatures, respectively, in pre- and post-immunotherapy tumor samples. RESULTS: A total of 51 and 79 immune-related genes were found upregulated and downregulated, respectively, in the samples from Regimen 1 patients after treatment, while 51 and 56 were found upregulated and downregulated in the samples for Regimen 2. When comparing the changes between the two regimens, we identified 9 genes significantly different, including DMBT1, a potential tumor suppressor, functioning in tumor invasion of head and neck cancer. The exploration of DNA methylation showed slight overall hypermethylation after treatment in both regimens, especially for Regimen 1 immune responders, and methylation-based cell type deconvolution demonstrated high concordance with tumor infiltrating T lymphocyte cell counts. CONCLUSION: While a consistent patient response after treatment was observed, most changes were similar between regimens, indicating a subtle, targeted, or patient-specific effect of IRX-2 cytokines. Change in DMBT1 expression was a unique finding that will require further study to better understand its significance.

A preliminary assessment of guideline adherence and clinical variation in oral cancer treatment: a MarketScan database study.

BACKGROUND: To assess variations in adherence to guideline-recommended processes of care for oral cavity cancer patients. METHODS: Retrospective study using a U.S. healthcare research database (MarketScan). Index diagnoses were considered from 2010 to 2012 with follow-up from 2013 to 2014. Diagnostic and procedure codes were utilized to identify oral cavity patients with a defined treatment modality. Compliance with guideline-recommended processes of care, which included pre-treatment imaging, thyroid-function testing (TFTs), multidisciplinary consultation and gastrostomy-tube insertion rates, were assessed. RESULTS: A total of 2752 patients were identified. Surgery alone was the most common treatment (60.8%), followed by surgery with adjuvant chemoradiotherapy (20.4%) and surgery with adjuvant radiotherapy (18.8%). Head/neck and chest imaging were obtained in 60% and 62.5% of patients respectively. Significant geographical differences in head and neck imaging were observed between North-central (64%), South (58.4%) and West (56.1%) regions (p = 0.026). Differences in chest imaging were also present between North-east (65%) and West (56.8%; p = 0.007). TFTs were obtained in 54.4% of the patients after radiation treatment, and 18.6% of patients had multidisciplinary consultation during the 6 months before and 3 months after initiation of treatment. During the year after treatment initiation, 21.2% of patients underwent G-tube placement, with significantly higher rates in patients receiving triple modality treatment (58%) when compared to surgery plus radiation (27%) and surgery alone (15%; p < 0.01). CONCLUSION: Adherence to evidence-based practices was low based on the database coding. These data suggest a potential to improve adherence and increase the routine use of practices delineated in national clinical practice guidelines. CLINICAL RELEVANCE: This study reflects a suboptimal adherence to guidelines based on the database employed. This study should be considered by healthcare providers and efforts should be maximized to follow the processes of care which have proven to impact on patient's outcomes.

Oligometastases in head and neck carcinoma and their impact on management.

Historically, patients with head and neck squamous cell carcinoma (HNSCC) with distant metastases were regarded as palliative. Oligometastasis (OM) refers to patients with a limited number of distant metastatic deposits. Treatment of patients with OMs has been reported in patients with lung, colon, breast, prostate and brain malignancies. Selected patients with oligometastatic HNSCC have a higher probability of durable disease control and cure and these patients should be treated aggressively. Treatment options for patients with HNSCC OMs include single or combinations of the three arms of cancer treatment, that is surgery, radiotherapy and chemotherapy/immunotherapy. To date, there are limited studies reporting the management of OM with head and neck malignancy. This review will give insights into the management of OMs in HNSCC.

Tumor infiltrating lymphocytes after neoadjuvant IRX-2 immunotherapy in oral squamous cell carcinoma: Interim findings from the INSPIRE trial.

OBJECTIVES: IRX-2 is a primary-cell-derived immune-restorative consisting of multiple human cytokines that act to overcome tumor-mediated immunosuppression and provide an in vivo tumor vaccination to increase tumor infiltrating lymphocytes (TILs). A randomized phase II trial was conducted of the IRX regimen 3 weeks prior to surgery consisting of an initial dose of cyclophosphamide followed by 10 days of regional perilymphatic IRX-2 cytokine injections and daily oral indomethacin, zinc and omeprazole (Regimen 1) compared to the identical regimen without IRX-2 cytokines (Regimen 2). METHODS: A total of 96 patients with previously untreated, stage II-IV oral cavity SCC were randomized 2:1 to experimental (1) or control (2) regimens (64:32). Paired biopsy and resection specimens from 62 patients were available for creation of tissue microarray (n = 39), and multiplex immunohistology (n = 54). Increases in CD8+ TIL infiltrate scores of at least 10 cells/mm2 were used to characterize immune responders (IR). RESULTS: Regimen 1 was associated with significant increases in CD8+ infiltrates (p = 0.01) compared to Regimen 2. In p16 negative cancers (n = 26), significant increases in CD8+ and overall TILs were evident in Regimen 1 (p = 0.004, and 0.04 respectively). IRs were more frequent in Regimen 1 (74% vs 31%, p = 0.01). Multiplex immunohistology for PD-L1 expression confirmed an increase in PD-L1 H score for Regimen 1 compared to Regimen 2 (p = 0.11). CONCLUSIONS: The findings demonstrate significant increases in TILs after perilymphatic IRX-2 injections. Three quarters of patients showed significant immune responses to IRX-2. (NCT02609386).

Neutrophil-to-lymphocyte ratio as a prognostic indicator for overall and cancer-specific survival in squamous cell carcinoma of the head and neck.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) is a biomarker that is correlated with systemic inflammation and poor prognosis in solid tumors. We investigated the value of NLR in predicting survival in a large population of head and neck cancer patients in the United States. METHODS: We performed a retrospective cohort study of Veterans Affairs patients with head and neck squamous cell carcinoma (HNSCC) diagnosed between January 2000 and December 2017. We compared 5-year overall survival and cancer-specific survival for different NLR tertiles using cox proportional hazards modeling with adjustment for covariates. RESULTS: The primary cohort consisted of 14 644 subjects of which 99% were male. Relative to patients with NLRs in the lower tertile, patients with NLRs in the top tertile had an 71% increased hazard of all-cause mortality (P < .001) and 44% increased hazard of cancer-specific mortality (P < .001) at 5 years. CONCLUSIONS: Elevated NLR in HNSCC confers a poor prognosis.

Radiotherapy Is Associated with an Accelerated Risk of Ischemic Stroke in Oral Cavity Cancer Survivors after Primary Surgery.

The number of oral cavity carcinoma (OCC) survivors continues to increase due to advances in definitive surgery and radiation therapy (RT), however the risk of ischemic stroke is unclear in long-term survivors. In this study, survivors are defined as those who survived for >5 years after a diagnosis of OCC. They were matched at a 1:5 ratio with normal controls. Those who received surgery alone versus surgery+RT were also matched at a 1:1 ratio. From 2000 to 2005, 5172 OCC survivors who received surgery alone (n = 3205) or surgery+RT (n = 1967), and 25,860 matched normal controls were analyzed using stratified Cox regression models. Adjusted HRs (aHR) revealed that the surgery+RT group (aHR = 1.68, p < 0.001) had an elevated risk of stroke, but this was not seen in the surgery alone group (aHR = 0.99, p = 0.953). Furthermore, the age at stroke onset was at least 10 years earlier in the surgery+RT group than in the controls. In conclusion, radiotherapy increased the risk of ischemic stroke by 68% and also accelerated the onset of stroke in long-term OCC survivors after primary surgery compared with matched normal controls. Secondary prevention should include stroke as a late complication in OCC survivorship programs.

Evaluation of Locoregional Recurrence Patterns Following Adjuvant (Chemo)Radiotherapy for Oral Cavity Carcinoma.

AIMS: To evaluate patterns of locoregional recurrence following adjuvant (chemo)radiotherapy for oral cavity squamous cell carcinomas. MATERIALS AND METHODS: One hundred and one patients who received adjuvant radiotherapy ± chemotherapy for oral cavity squamous cell carcinoma between 2013 and 2016 were analysed. For documented locoregional recurrence, recurrence imaging was deformably co-registered to the planning computed tomography scan. The volume of recurrence was delineated (Vrec). Vrec coverage by 95% of the corresponding planning target volume prescription dose was determined and the location compared with planning target volumes. Sites of recurrence were classified using a combined volume and centroid-based method: (A) central high dose, (B) peripheral high dose, (C) central low dose, (D) central peripheral dose, (E) extraneous. RESULTS: The median follow-up was 36 months. Forty-three per cent and 53% of patients received radiotherapy to the ipsilateral neck only and bilateral neck, respectively. Three-year overall survival, disease-free survival, local control, regional control and distant metastases-free survival were 63.0, 65.6, 88.0, 85.1 and 85.3%, respectively. Of 10 episodes of primary site recurrences, five were type A, four type B and one was type E. Of 14 episodes of regional recurrence, five were type A, two type C, two type D and five type E. Five of 21 (24%) patients with oral tongue carcinoma with an undissected/unirradiated contralateral neck had a type E contralateral neck recurrence, including 2/11 with pN0, 1/4 with pN1 and 2/6 with pN2 disease. CONCLUSIONS: Marginal and out-of-field recurrences remain a significant pattern of failure. We advocate generous target delineation postoperatively and, for oral tongue carcinomas, a comprehensive approach with bilateral neck irradiation.

Contemporary Approach to Locally Advanced Oral Cavity Squamous Cell Carcinoma.

PURPOSE OF REVIEW: Surgical management of locally advanced oral cavity squamous cell carcinomas (OCSCC) has long been recognized as a primary treatment modality. Technological advances have led to significant improvements in our surgical approach, from improvement in the visualization of tumors to more efficient and precise reconstruction. Here, we review the latest technological advances in surgical extirpation and reconstruction of locally advanced OCSCCs. RECENT FINDINGS: The focus of technological innovation in surgical extirpation has been on improving visualization, with the use of intraoperative ultrasound for margin delineation, intraoperative navigation, narrow-band imaging, and the use of fluorescence. Though early, these are promising steps to ensuring complete resection of the cancer. Advances in reconstruction have been centered on the incorporation of computer assisted design, manufacturing, and virtual surgical planning, allowing for more complex three-dimensional defects to be expeditiously reconstructed. As these technologies are still under development, their impact on oncologic outcomes are not yet robustly defined; however, as technology continues to advance and become more widely available, new technologies will undoubtedly become integrated into enhancing surgical precision and planning.