Prognostic factor and disease-free survival analysis of patients with oral tongue cancer in Bihar, India: A hospital-based prospective study

Background: Racial and gender disparities in the incidence and outcome of head and neck cancers have been known Men are much more likely to develop HNSCC than women (40,220 cases v 14,850 cases in the US in 2014). Racial outcome disparities have been observed in head and neck cancer with black patients consistently reported to have diminished survival compared to whites. Nationally, from 2003-2009, 5 year relative survival for oral cavity and pharyngeal cancer was 67% for whites and 46% for blacks. For laryngeal cancer, the relative survival was 64% for whites and 52 % for blacks (www.cancer.org/research/cancerfactsstatistics/cancerfactsfigures2014/). The etiology of this racial survival disparity appears to be multifactorial in origin. To investigate this further, we performed a retrospective analysis of HNSCC patients treated at the University of Maryland Greenebaum Cancer Center (UMGCC) Methods: We retrospectively analyzed 1318 patients with first primary HNSCC treated at the UMGCC from 2000 to 2010. Demographic and clinical characteristics as well as overall survival (OS) were compared between black and white patients. Results: Of the 1318 patients analyzed, 65.9% were white, 30.7% were black and 3.3% were other races. Striking differences in the distribution of patients by disease site were noted. Black patients were far less likely to present with oral cavity cancer (15.6% of cases) and far more likely to present with laryngeal or hypopharyngeal (65.6% of cases) cancer. White patients were more likely to have early stage (I and II) disease, especially in the oral cavity. In the full cohort, overall survival for black patients was significantly worse than for white patients (median 2.5 years vs. 4.8 years, p<0.0001). Multivariable Cox regression analysis showed black patients had significantly worse survival accounting for age, gender, stage, primary site, tobacco and alcohol consumption. Black patients had worse median OS in both oral cavity (5.7 vs 3.2 years, p<0.0001) and oropharyngeal cancer (4.9 vs.2.1 years p<0.0001). However, multivariable analysis showed that race was only significantly associated with survival in oropharyngeal cancer. There was no difference in OS between races in laryngeal or hypopharyngeal cancer. The difference in survival in oral cavity cancers resulted from the larger proportion of white patients with Stage I or II disease. White patients with oral cavity and oropharyngeal cancer were more likely to have surgery as primary treatment than blacks reflecting the higher prevalence of early stage disease. No difference was noted in the rates of chemoradiotherapy between black and white patients with advanced disease in oropharynx, hypopharynx and larynx. Analysis of HPV associated oropharyngeal cancer over time shows that these cancers are much more common in blacks than in whites, but are increasing for both races. Our data are corroborated by SEER data and other investigators. Interestingly between 1975 and 2007 the incidence of oral cavity cancer as a whole fell by 51%. For black women, the incidence of oral tongue cancer fell by a similar 55% during that time period. The incidence of oral tongue cancer for white women increased by 21% during the same period, driven significantly by a 111% increase in young white women. (Patel 2011, JCO 29: 1488). The etiology of this increase in oral tongue cancer among white women does not appear to be associated with HPV or smoking and its causes are unclear. Conclusion: We observed striking differences in site of disease, stage at presentation and survival comparing black and white patients. The difference in survival between the two groups overall is driven by a large difference specifically in oropharyngeal cancer. This is consistent with previous reports of differences in the incidence of HPV in the two ethnic groups, but likely reflects other factors as well. An emerging gender and racial disparity in the incidence of oral tongue cancer remains unexplained. Citation Format: Kevin Cullen. Racial and gender-based survival disparities in head and neck cancer. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr IA02.

Relevance. Leiomyosarcomas is highly aggressive tumors with poor prognosis. Surgical resection is a standard treatment approach. However, data of long-term results of surgical treatment are lacking due to rarity of retroperitoneal form of leiomyosarcoma. Prognostic significance of tumor size, grade and recurrence type remains unclear as well. Aim. To analyze results of surgical treatment of patients with retroperitoneal leiomyosarcoma and to define prognostic factors which are associated with disease-free and overall survival. Materials and methods. The study included patients with primary retroperitoneal leiomyosarcomas who have received surgical or combined treatment between January 2003 and April 2019 at Blokhin National Medical Research Centre of Oncology. Short- and long-term clinical outcomes of surgical and combined treatment as well as recurrence rate, pattern of recurrence and morphological features were analyzed in order to define prognostic factors of disease-free and overall survival. Results. The study included 64 patients with primary retroperitoneal leiomyosarcomas 12 men (18%) and 52 women (82%). Median tumor size was 10.55.0 cm. Most of the operations (93.3%) were done by open approach. Combined resections were performed in 62.5% of cases (n=40), vascular resections in 17.2% cases (n=11). Radical (R0) resections were performed in 54 cases (85.9%). Postoperative morbidity and mortality rate were 39% and 0% respectively. Adjuvant chemotherapy or radiotherapy received 21 (35%) patients and 1 (1.7%) patient respectively. 46 (71.9%) patients had a disease recurrence. Recurrence type (local recurrence/distant metastases) did not influence overall survival (р=0.655). Median disease-free survival was 27 months (95% CI 1043.9). 3-year and 5-year disease-free survival was 43% and 21% respectively. Median overall survival was 79 months (95% CI 49108.9). 3-year and 5-year overall survival was 73% and 59% respectively. Among patients grade 2 and grade 3 tumors median disease-free survival was 49 vs. 18 months (р=0.271), median overall survival 146 vs. 58 months (р=0.018). There were no statistically significant differences in rate of radical resections among patients with different tumor location (р=0.804) or its size (р=0,520). Patients, who have undergone radical (R0) resection, had better overall (р=0.028) and disease-free survival (р0.001). Adjuvant chemotherapy was not associated lower risk of disease recurrence (p=0.976), type of recurrence (р=0.981) and lower overall survival (р=0.284). Conclusion. Tumor grade and radical resection are the most important prognostic factors in patients with retroperitoneal leiomyosarcoma. In our study, tumor size was not correlated with long-term results and possibility of radical resection.

Clinical features and outcomes in young adults with oral tongue cancer

BackgroundCancer of the oral tongue is the second most common cancer among males in various parts of India. Despite advances in diagnosis and treatment the failure rates in cancer of the oral tongue are high and survival poor. Majority of these failures occur in untreated neck.MethodA retrospective review of the records of 75 patients undergoing surgery for the treatment of squamous cell carcinoma of the oral tongue was carried out to ascertain the pattern of metastasis in the neck and to evaluate the sensitivity of clinical examination in predicting nodal spread.ResultsAll the patients underwent primary surgery. Cervical lymph node metastasis was found in 35.6% of T1 and T2 tumours and 62.35% of T3 and T4 tumours. Sensitivity of clinical examination was found to be 54.5% and specificity of 61.9%. Level II was the most commonly involved (63.6%). Isolated level IV involvement was never found in clinically negative neck. Tumour stage and node status were found to have a significant impact on disease free survival in both univariate and multivariate analysis.ConclusionsAs the sensitivity and specificity of the clinical examination is low we suggest that methods like ultrasound or CT Scan of the neck should be regularly employed to improve the sensitivity and specificity of the examination. Furthermore as isolated level IV involvement is never found in our series, we suggest that a prophylactic supraomohyoid neck dissection should be carried out in all patients with a clinically node negative neck with cancer of oral tongue, to achieve a better disease free survival.

Rising incidence of oral tongue cancer among white men and women in the United States, 1973–2012

ObjectiveThe prognostic role of age among patients affected by Oral Tongue Squamous Cell Carcinoma (OTSCC) is a topic of debate. Recent cohort studies have found that patients diagnosed at 40 years of age or younger have a better prognosis. The aim of this cohort study was to clarify whether age is an independent prognostic factor and discuss heterogeneity of outcomes by stage and treatments in different age groups.MethodsWe performed a study on 577 consecutive patients affected by primary tongue cancer and treated with surgery and adjuvant therapy according to stage, at European Institute of Oncology, IRCCS. Patients with age at diagnosis below 40 years totaled 109 (19%). Overall survival (OS), disease-free survival (DFS), tongue specific free survival (TSFS) and cause-specific survival (CSS) were compared by age groups. Multivariate Cox proportional hazards models were used to assess the independent role of age.ResultsThe median follow-up time was 5.01 years (range 0–18.68) years with follow-up recorded up to February 2020. After adjustment for all the significant confounding and prognostic factors, age remained independently associated with OS and DSF (respectively, p = 0.002 and p = 0.02). In CSS and TSFS curves, the role of age seems less evident (respectively, p = 0.14 and p = 0.0.37). In the advanced stage sub-group (stages III–IV), age was significantly associated with OS and CSS with almost double increased risk of dying (OS) and dying from tongue cancer (CSS) in elderly compared to younger groups (OS: HR = 2.16 95%, CI: 1.33–3.51, p= 0.001; CSS: HR = 1.76 95%, CI: 1.03–3.01, p = 0.02, respectively). In our study, young patients were more likely to be treated with intensified therapies (glossectomies types III–V and adjuvant radio-chemotherapy). Age was found as a prognostic factor, independently of other significant factors and treatment. Also the T–N tract involved by disease and neutrophil-to-lymphocyte ratio ≥3 were independent prognostic factors.ConclusionsYoung age at diagnosis is associated with a better overall survival. Fewer younger people than older people died from tongue cancer in advanced stages.

BackgroundOverexpression of GOLPH3 (Golgi phosphoprotein 3, 34 kDa) is associated with the progression of many solid tumor types leading to an unfavorable clinical outcome. We aimed to investigate the clinical significance of GOLPH3 expression in the development and progression of clinically N0 (cN0) oral tongue cancer.MethodsReal-time PCR and Western blotting analyses were employed to examine GOLPH3 expression in four oral tongue cancer cell lines, primary cultured normal tongue epithelial cells (TEC), eight matched pairs of oral tongue cancer samples and adjacent noncancerous tissue samples from the same patient. Immunohistochemistry (IHC) was performed to examine GOLPH3 protein expression in paraffin-embedded tissues from 179 cN0 oral tongue cancer patients. Statistical analyses were applied to evaluate the diagnostic value and the associations of GOLPH3 expression with clinical parameters.ResultsGOLPH3 mRNA and protein was up-regulated in oral tongue cancer cell lines and cancerous tissues compared with that in primary cultured normal tongue epithelial cells (TEC) and adjacent noncancerous tissue samples. GOLPH3 protein level was positively correlated with clinical stage (P = 0.001), T classification (P = 0.001), N classification (P = 0.043) and recurrence (P = 0.009). Patients with higher GOLPH3 expression had shorter overall survival time, whereas those with lower GOLPH3 expression had longer survival time.ConclusionOur results suggest GOLPH3 overexpression is associated with poor prognosis for cN0 oral tongue cancer patients and may represent a novel and useful prognostic indicator for cN0 oral tongue cancer.

OP021: Tumor thickness as predictor of prognosis in carcinoma of tongue

Distinct Epidemiologic Characteristics of Oral Tongue Cancer Patients

ObjectivesOral tongue cancer is the most prevalent type of oral cavity cancer and presents the worst prognosis. With the use of TNM staging system, only the size of primary tumor and lymph node are considered. However, several studies have considered the primary tumor volume as a possible significant prognostic factor. Our study, therefore, aimed to explore the role of nodal volume from imaging as a prognostic implication. MethodsMedical records and imaging (either from Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scan) of 70 patients diagnosed with oral tongue cancer with cervical lymph node metastasis between January 2011 and December 2016 were retrospectively reviewed. The pathological lymph node was identified, and nodal volume was measured using the Eclipse radiotherapy planning system and was further analysed for its prognostic implications, particularly on overall survival, disease-free survival, and distant metastasis-free survival. ResultsFrom A Receiver Operating Characteristic (ROC) curve analysis, the optimal cut-off value of the nodal volume was 3.95 cm3, to predict the disease prognosis, in terms of overall survival and metastatic-free survival (p ≤ 0.001 and p = 0.005, respectively), but not the disease-free survival (p = 0.241). For the multivariable analysis, the nodal volume, but not TNM staging, was a significant prognostic factor for distant metastasis. ConclusionsIn patients with oral tongue cancer and cervical lymph node metastasis, the presence of an imaging nodal volume of ≥3.95 cm3 was a poor prognostic factor for distant metastasis. Therefore, the lymph node volume may have a potential role to adjunct with the current staging system to predict the disease prognosis. Level of Evidence2b.

BackgroundThe purpose of the study was to evaluate survival outcomes in post-operative oral tongue cancer patients undergoing adjuvant radiotherapy (RT) at a tertiary cancer care center and to critically review the impact of various clinical-pathological factors on recurrence and survival. Demographic factors, stage of all the histology proven oral tongue cancer, and treatment details were documented. Overall survival (OS) and recurrence-free survival (RFS) were analyzed along with the potential prognostic factors affecting outcome.ResultsOne hundred forty-four post-operative oral tongue cancer patients referred to our department for adjuvant treatment were evaluated. Median age at presentation was 45 years. Forty-seven patients had pathological early stage disease (stages I and II) and 95 had locally advanced (stages III and IV) disease while post-op details were not present in 2 patients. At a median follow-up of 87 months (60–124) of alive patients, the median RFS for entire cohort was 62 months while median OS was 74 months respectively. Age, perineural invasion (PNI), and grade of the tumor emerged as independent prognostic factors for OS and RFS. Among patients with early stage disease, depth of invasion (DOI), age, and PNI were found as independent prognostic factors for RFS and OS. In locally advanced disease, higher grade, age, and PNI independently impacted the respective survival end points.ConclusionsAge (> 45 years), higher grade, and presence of PNI showed inferior survival outcomes across the sub-groups (early versus locally advanced disease). This may warrant adjuvant treatment intensification. DOI > 10 mm was particularly found to worsen survival in early node negative SCC oral tongue patients.

CCR4 Expression Is Associated With Poor Prognosis in Patients With Early Stage (pN0) Oral Tongue Cancer

This study aims to identify miRNA-mediated regulation of the cell cycle in oral tongue cancer. Comprehensive computational analysis was performed on the GEO dataset "GSE168227". DIANA Tool-mir path v.3, STRING, Cytoscape 3.6.0, Enrichr, and TargetScan Human 7.2 were utilized to identify and analyze miRNAs and their targets in oral tongue cancer. The identified miRNA and its target genes were further analyzed in oral tongue cancer patients using qPCR and immunohistochemistry (IHC). Computational analysis revealed miR-17 as a differentially expressed miRNA in oral tongue cancer. Database analysis indicated potential binding sites of miR-17 for CDKN1A and CCND1 mRNA at 3'-UTR. In oral tongue cancer samples, miR-17, CDKN1A, and CCND1expression were upregulated compared to controls. IHC demonstrated overexpression of p21 and Cyclin D1 across various tumor grades, with predominant cytoplasmic expression of p21 observed in oral tongue cancer samples. The findings suggest that miR-17 may regulate the G1-S transition of the cell cycle in oral tongue cancer. Further validation and functional studies are warranted to confirm their role as biomarkers.

Does a mandibular access osteotomy improve survival in pT2 oral tongue cancers? Retrospective study at a single institution

While evidence suggests an increasing incidence of tongue cancer in young adults, published findings regarding the prognostic role of age at diagnosis are inconsistent. We performed a meta‐analysis of the literature to highlight key points that might help in understanding the association between age of oral tongue cancer patients at diagnosis and their prognosis. According to age at diagnosis, a systematic literature review of all published cohort studies assessing the recurrence risks and mortality associated with tongue cancer was conducted. We compared the risk estimates between patients aged >45 years and those aged <45 years at diagnosis. Random‐effects models were used to calculate summary relative risk estimates (SRRs) according to different clinical outcomes and sources of between‐study heterogeneity (I2) and bias. We included 31 independent cohort studies published between 1989 and 2019; these studies included a total of 28,288 patients. When risk estimations were not adjusted for confounders, no significant association was found between age at diagnosis and overall survival (OS). Conversely, after adjustment for confounders, older age at diagnosis was associated with a significantly increased risk of mortality. The difference between SRRs for adjusted and unadjusted estimates was significant (p < 0.01). Younger patients had a significantly higher risk of local recurrence. Younger patients with oral tongue cancer have better OS but a greater risk of recurrence than older patients. These findings should be validated in a large prospective cohort study which considers all confounders and prognostic factors.