Squamous Cell Carcinoma Of The Oral Cavity Research Articles

CD56 Expression on Natural Killer Cells and its Correlation with Clinical Outcomes in Oral Squamous Cell Carcinoma Patients

Background: Squamous cell carcinoma (SCC) of the oral cavity can grow quickly and the response to therapy in each patient is different. The immune system plays a major role in the development of cancer cells, especially in SCC of the oral cavity. Natural killer cells (NK cells) play a major role in both innate immunity and adaptive immunity. Objective: To evaluation CD56 expression on NK cells and the correlation with clinical outcomes in oral squamous cell carcinoma. Methods: We collect the literature from Journal, Pubmed, Web of Science, Scopus, Crossref, and Google Scholar. CD56 expression was examined by immunohistochemical staining in cancer tissue. On each slide, the number of positive stained cells was read on 5 high power fields (HPF) 400x, then the number of cells stained on each HPF was added up and section 5. Cells with positive CD56 showed brown staining in the intracytoplasm regardless of the intensity of the staining. Results: High CD56 expression was associated with good overall survival (OS) (HR 0.27; 95%CI 0.12-0.60; p=0.001), good progression-free survival (PFS). (HR 0.35; 95%CI 0.17-0.74; p=0.005), and good distant metastasis-free survival (DMFS) (HR 0.27; 95%CI 0.13-0.55; p=0.0004) in head and neck SCC. Other study in oropharyngeal SCC, that high CD56 expression had good OS (HR 0.32; 95%CI 0.10-0.96; p=0.04). The meta-analysis study showed that the CD56 marker on NK cell was a good prognostic marker for OS in head and neck SCC (HR 0.19, 95%CI 0.11-0.35, p<0.00001). Conclusion: NK cells with CD56 expression will increase cytotoxic function. The presence of CD56 can increase infiltration into tumor tissue. Based on these data, CD56 on NK cells can be used as an indicator of cancer prognosis in patients with SCC of the oral cavity. Apart from that, it can be used as an immunotherapy target which functions to restore the immune response against cancer cells.

EPIDEMIOLOGY, RISK FACTORS AND SOCIAL DETERMINANTS OF PATIENTS WITH EPIDERMOID CARCINOMA OF THE ORAL CAVITY AND OROPHARYNX

Objective To analyze the risk factors, social determinants, and epidemiology of squamous cell carcinoma (SCC) in the oral cavity and oropharynx. Study Design Retrospective cross-sectional study conducted with data collection from physical and digital medical records. A total of 555 patients with oral cancer, from 2010 to 2020, and 625 patients with oropharyngeal cancer, from 2010 to 2018, were selected, with a total sample of 1,180 patients selected by convenience. Results The profile of patients diagnosed with SCC of the oral cavity and oropharynx consisted of white men, with an education level ranging from complete to incomplete elementary school, with a mean age of 59 years, whose primary site was the tongue. In this case, the estimated survival in years for patients with cancer of the oral cavity was approximately 5 years, compared to 3 years for cases of oropharynx. Conclusion Advanced stages "III and IV" influenced the prognosis and impacted the overall survival of the two strata; smoking and alcohol consumption were associated with the profile of affected individuals; and there is a growing number of young adults under 59 years of age upon diagnosis of oropharyngeal SCC associated with HPV. To analyze the risk factors, social determinants, and epidemiology of squamous cell carcinoma (SCC) in the oral cavity and oropharynx. Retrospective cross-sectional study conducted with data collection from physical and digital medical records. A total of 555 patients with oral cancer, from 2010 to 2020, and 625 patients with oropharyngeal cancer, from 2010 to 2018, were selected, with a total sample of 1,180 patients selected by convenience. The profile of patients diagnosed with SCC of the oral cavity and oropharynx consisted of white men, with an education level ranging from complete to incomplete elementary school, with a mean age of 59 years, whose primary site was the tongue. In this case, the estimated survival in years for patients with cancer of the oral cavity was approximately 5 years, compared to 3 years for cases of oropharynx. Advanced stages "III and IV" influenced the prognosis and impacted the overall survival of the two strata; smoking and alcohol consumption were associated with the profile of affected individuals; and there is a growing number of young adults under 59 years of age upon diagnosis of oropharyngeal SCC associated with HPV.

Evaluation of Late Toxicities in Postoperative Cases of Oral Cavity Cancer Treated by Intensity-Modulated Radiotherapy (IMRT): A Retrospective Cohort Study

Introduction: Surgical intervention serves as the primary treatment modality for operable oral cavity cancer. However, patients with locally advanced disease or unfavourable prognostic factors often require adjuvant Radiotherapy (RT) with or without concurrent Chemotherapy (CT). Advanced radiation techniques, such as Intensity-Modulated Radiotherapy (IMRT), have shown potential in minimising radiation-related toxicities while ensuring effective tumour control. Aim: To assess common late toxicities, namely xerostomia, dysphagia, and hoarseness, in patients with postoperative Squamous Cell Carcinoma (SCC) of the oral cavity, who received adjuvant RT or concurrent Chemo-Radiotherapy (CRT) utilising IMRT with a Simultaneous Integrated Boost (SIB) approach. Materials and Methods: A retrospective cohort study was conducted in the Department of Radiotherapy at IMS, BHU, Varanasi, Uttar Pradesh, India, from June 2018 to December 2021. Study was done using the medical records of 62 patients with SCC of the oral cavity and received adjuvant radiation by the IMRT technique with or without concurrent CT. Late toxicities were evaluated according to the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0). Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) software version 28.0, and a logistic regression model was used to establish the association between Organ-At-Risk (OAR) doses and the development of late toxicities. Results: The median age of the study participants was 45 years (range: 25-68), and 95.2% (n=59) of the patients were male. A total of 62 patients (59 male, 3 female) were included. The median follow-up duration was 21.5 months. At two years, the cumulative incidence of xerostomia, dysphagia, and hoarseness was 28.5% (n=8), 21.4% (n=6), and 28.5% (n=8), respectively. Logistic regression showed that both the D mean of >26 Gy to the contralateral parotid (HR=4.32; 95% CI, 1.03- 18.05; p=0.045) and the D mean of >26 Gy to the contralateral Submandibular Gland (SMG) (HR=6.41; 95% CI, 1.48-27.81; p=0.013) were significantly associated with the incidence of xerostomia. The D mean of >47 Gy to the pharyngeal constrictors (HR=17.89; 95% CI, 3.15-101.62; p=0.001) and the D mean of >50 Gy to the larynx (HR=5.77; 95% CI, 1.82-18.24; p=0.003) had a significantly high risk of dysphagia and hoarseness, respectively. Conclusion: Adjuvant IMRT resulted in acceptable rates of late toxicities in oral cancer. Doses to the contralateral parotid and SMGs, pharyngeal constrictors, and larynx had a significant impact on late xerostomia, dysphagia, and hoarseness, respectively.

Preliminary Study on Prevalence of P16-Positive Squamous Cell Carcinoma of the Oral Cavity, Oropharynx and Larynx in Rizal Medical Center and its Histomorphologic Correlation

Background. A considerably large portion of the cases of cancer, particularly squamous cell carcinoma (SCC) involving the head and the neck may be due to consumption of tobacco and alcohol. However, its increase in occurrence at specific sites of the head and neck may indicate the possibility of other etiological factors. One of which is infection by certain high-risk human papillomavirus (HPV). P16 immunochemistry serves as a very good surrogate marker of active HPV in these tumors. The detection of HPV-related head and neck cancers have relevance in clinical practice because of its prognostic implications. Objectives. The general objective of this study is to determine the prevalence of p16-positive squamous cell carcinoma in the oral cavity, oropharynx, and larynx in Rizal Medical Center from January 2019 to December 2019.  The specific objective is to compare the Hematoxylin and Eosin (H&E) stain histomorphology (keratinization and mitotic activity) of p16-positive versus p16-negative specimens. Methodology. This is a cross-sectional study which included all routine histopathology specimens coming from the oral cavity, oropharynx and larynx in Rizal Medical Center for the year 2019 with a diagnosis of squamous cell carcinoma. The tissue specimens considered were those that measured at least 1 cm in diameter, or aggregate diameter if tissue is fragmented. The slides of all eligible cases were reviewed and immunohistochemically stained for p16. The p16 IHC slides were read as either positive or negative, while the mitotic activity and keratinization were observed in the H&E-stained slides. The interpretation of the diplomate pathologists for each of the slides were documented and corresponding statistical analyses were performed. Results. P16 IHC showed twenty-one (88%) p16 negative cases and three (12%) p16 positive cases. In terms of mitosis, ten cases have mitosis falling within the 1-10 per high power field (HPF) range (42%), six within 11-20 per HPF (25%), and 8 cases have ≥21 mitosis per HPF (33%). In terms of keratinization, three cases are non-keratinizing (12%) and twenty-one cases are keratinizing (88%).  There is significant difference in the keratinization histology (p<0.05) of the p16-positive versus the P16-negative cases. On the other hand, no significant difference in the mitotic activity (p>0.05) was noted. Conclusion. There is a low prevalence of HPV-related SCC of the oral cavity, oropharynx, and larynx in Rizal Medical Center.  The histomorphologic findings confirm that keratinization, significantly predicts HPV status in oropharyngeal SCC. Mitotic activity may not be reliable in predicting the HPV status or p16 IHC reactivity of a case. Keratinization in oropharyngeal SCCs may provide valuable information in certain instances, particularly when HPV testing is not immediately available, although the combined tumor morphology and p16 IHC is more ideal.

LKB-1 Expression and High-Risk Histopathology are Independent Prognostic Factors for Patients with Oral Cavity Carcinoma.

The expression of liver kinase B1 (LKB-1) has been associated with prognosis in squamous cell carcinoma of the oral cavity (SCCOC). This study aimed to define the prognostic role of LKB-1 expression for patients with SCCOC and the suitability of its integration into a multivariate prognostic model. A retrospective cohort study of patients with SCCOC was conducted in a cancer center. Expression of LKB-1 was evaluated by immunohistochemistry, and multivariate analysis defined prognostic factors associated with recurrence, recurrence-free survival (RFS), and overall survival (OS). The logistic regression model was used to construct a predictive computer software program. Of the 201 patients in this study, 104 (51.7%) experienced recurrence of their disease. Lower expression of LKB-1, high-risk histopathology, and advanced tumor-node-metastasis (TNM) stages were independent factors via multivariate analysis associated with the increased recurrence risk, poor RFS, and poor OS. If lack of LKB-1 expression is considered the reference category, the factors independently associated with recurrence were low (odds ratio [OR], 0.157; 95% confidence interval [CI], 0.044-0.557), intermediate (OR, 0.073; 95% CI, 0.017-0.319), and intense (OR, 0.047; 95% CI, 0.007-0.304) expression of LKB-1. This model permitted construction of a computer software program capable of prediction with receiver operating characteristic analysis (area under the curve, 0.925) and led to the definition of five prognostic groups with a biologic gradient. These results suggest that LKB-1 expression in patients with SCCOC is of robust prognostic value and complements the TNM staging system. The proposed model requires external validation in prospective observational studies.

TERT Promoter Mutations Are Enriched in Oral Cavity Cancers and Associated With Locoregional Recurrence.

We retrospectively identified patients who were diagnosed with HNSCC between July 1, 2004, and October 12, 2017, at Memorial Sloan Kettering Cancer Center and whose tumors underwent next-generation sequencing using the MSK-IMPACT panel. Patients with HPV-positive oropharyngeal squamous cell carcinoma (SCC) were excluded. Cumulative incidence of LRF, patterns of failure, and overall survival were measured. We identified 117 patients with SCC of the oral cavity (OSCC), larynx, hypopharynx, or HPV-negative oropharynx whose tumors underwent next-generation sequencing. Sequencing was performed on 95 tumors that were obtained after recurrence and 22 that were obtained before recurrence. TERT promoter mutations were enriched in OSCC compared with laryngopharyngeal cancers (81.1% v 7.0%; P < .001), which was the largest genetic difference between these anatomic disease subsites. TERT promoter mutations were associated with LRF in OSCCs (Gray's test, P < .001) and in the overall cohort (Gray's test, P < .001). On multivariate analysis, TERT promoter mutations were associated with an increased risk for LRF (subdistribution hazard ratio, 2.82; 95% CI, 1.47 to 5.42; P = .0019), independent of oral cavity primary site and TP53 mutation status. TERT promoter status is associated with the cumulative incidence of LRF and patterns of failure. TERT promoter mutations may define a subset of OSCCs with unique pathogenesis that is associated with an increased risk of LRF. Validation in prospective cohorts is warranted.

Occurrence of Epidermal Growth Factor Receptor Expression in Squamous Cell Carcinoma of Oral Cavity and Adjacent Sites: A Retrospective Observational Study

AbstractIntroduction Oral cavity squamous cell carcinomas (OCSCCs) are one of the most common malignancies encountered. They have diverse clinicopathologic profiles. Epidermal growth factor receptor (EGFR) is an important marker of OCSCC for diagnosis, prognosis, and therapy.Objective The study aimed to evaluate the distribution of clinicopathological parameters in cases of squamous cell carcinoma (SCC) of the oral cavity and adjacent sites and their EGFR expression. An attempt was made to correlate EGFR scores with different parameters.Materials and Methods An observational retrospective study was undertaken for 1 year. Patients with histologically proven SCC of the oral cavity and adjacent sites were included. Clinicopathologic and immunohistochemical features of each case were analyzed.Results A total of 59 cases of SCC were included of which 41 (69%) were males. The mean age of the patients was 56.4 ± 10.3 years. The most common location of the tumors was oral cavity (31, 53%) followed by larynx (10, 16%). Most cases were moderately differentiated tumors (31, 53%). Immunohistochemical analysis showed low EGFR score in 7 (11.9%) cases, intermediate in 6 (10.1%), and high in 46 (78%) cases. Association between gender of patients and EGFR score was statistically significant (p = 0.000159). Most lesions of the oral cavity (31 cases, 53%) had a high EGFR score (23 cases, 74.2%). A statistically significant correlation was found between tumor grade and EGFR score (p = 0.03338).Conclusion This study from eastern region of India reveals unique characteristics of EGFR expression in SCC of the oral cavity and adjacent sites.

Multifocal intracranial and spinal metastasis from oral squamous cell carcinoma: A rare case report

Oral cancer is the second most common cancer in India, with squamous cell carcinoma (SCC) noted in 90% of cases. Distant metastasis (brain metastasis) from oral SCCs is rare. The incidence of intracranial metastasis is about 0.4% and 2%–8% and approximately 5% to 10% of all cancer patients develop spinal metastasis. However, vertebral metastasis is rare form of distant metastasis from SCC of the oral cavity. Multifocal metastases to the brain and spine of primary oral squamous cell carcinomas have not been reported till date which prompted us to report this case. A 35-year-old male with a history of radical resection done for SCC of the buccal mucosa followed by postoperative chemoradiotherapy presented with complaints of headache and convulsions accompanied by severe low backache and left lower limb radiculopathy with no motor or sensory deficit. Positron-emission tomography scan showed increased uptake in the left frontal lobe and in the dorsal and lumbar spine suggestive of metastasis. Magnetic resonance imaging of the brain and spine with contrast was done which showed a well-defined lesion in the left frontal lobe and contrast-enhancing lesions L5, L2, and T5 vertebra levels. Craniectomy with gross total excision of the left frontal lobe lesion was done. Histopathological examination was suggestive of metastatic SCC. The patient was advised for follow-up for spinal decompression followed by radiotherapy. We need to have a high index of suspicion for metastasis in brain and spine lesions in patients who have been diagnosed previously with oral malignancies for prompt management and better life expectancy.

Accuracy of 18-F Fluorodeoxyglucose Positron Emission Tomographic/Computed Tomographic Imaging in Primary Staging of Squamous Cell Carcinoma of the Oral Cavity

Squamous cell carcinoma (SCC) of the oral cavity is one of the most common tumor entities worldwide. Precise initial staging is necessary to determine a diagnosis, treatment, and prognosis. To examine the diagnostic accuracy of preoperative 18-F fluorodeoxyglucose (FDG) positron emission tomographic/computed tomographic (PET/CT) imaging in detecting cervical lymph node metastases. This prospective diagnostic study was performed at a single tertiary reference center between June 1, 2013, and January 31, 2016. Data were analyzed from April 7, 2018, through May 31, 2019. Observers of the FDG PET/CT imaging were blinded to patients' tumor stage. A total of 150 treatment-naive patients with clinical suspicion of SCC of the oral cavity were enrolled. All patients underwent FDG PET/CT imaging before local tumor resection with selective or complete neck dissection. The accuracy of FDG PET/CT in localizing primary tumor, lymph node, and distant metastases was tested. Histopathologic characteristics of the tissue samples served as the standard of reference. Of the 150 patients enrolled, 135 patients (74 [54.8%] men) with a median age of 63 years (range, 23-88 years) met the inclusion criteria (histopathologically confirmed primary SCC of the oral cavity/level-based histopathologic assessment of the resected lymph nodes). Thirty-six patients (26.7%) in the study cohort had neck metastases. Use of FDG PET/CT detected cervical lymph node metastasis with 83.3% sensitivity (95% CI, 71.2%-95.5%) and 84.8% specificity (95% CI, 77.8%-91.9%) and had a negative predictive value of 93.3% (95% CI, 88.2%-98.5%). The specificity was higher than for contrast-enhanced cervical CT imaging (67.0%; 95% CI, 57.4%-76.7%; P < .01) and cervical magnetic resonance imaging (62.6%; 95% CI, 52.7%-72.6%; P < .001). Ipsilateral lymph node metastasis in left- or right-sided primary tumor sites was detected with 78.6% sensitivity (95% CI, 63.4%-93.8%) and 83.1% specificity (95% CI, 75.1%-91.2%), and contralateral metastatic involvement was detected with 66.7% sensitivity (95% CI, 28.9%-100.0%) and 98.6% specificity (95% CI, 95.9%-100.0%). No distant metastases were observed. In this study, FDG PET/CT imaging had a high negative predictive value in detecting cervical lymph node metastasis in patients with newly diagnosed, treatment-naive SCC of the oral cavity. Routine clinical use of FDG PET/CT might lead to a substantial reduction of treatment-related morbidity in most patients.

Comparison of contrast-enhanced ultrasound and contrast-enhanced computed tomography for the diagnosis of cervical lymph node metastasis in squamous cell carcinoma of the oral cavity

Early detection of cervical lymph node metastasis (CLNM) from squamous cell carcinoma (SCC) of the oral cavity remains challenging. This prospective study was performed to evaluate the ability of contrast-enhanced ultrasound (CEUS) to detect CLNM from oral cavity SCC. Additionally, its diagnostic value was compared with that of contrast-enhanced computed tomography (CECT). Forty-eight consecutive patients with SCC of the oral cavity were enrolled. All subjects were examined preoperatively with both CEUS and CECT. Subsequently, neck dissections were performed for these patients, and cervical lymph nodes separated from the surgical specimens were assessed histologically. The diagnostic performance of these two examinations was compared based on the results of histopathology. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and Youden index for CEUS and CECT were 69.39% vs. 44.90%, 94.71% vs. 97.12%, 89.88%% vs. 87.16%, 75.56% vs. 78.57%, 92.92% vs. 88.21%, and 64.10% vs. 42.02%, respectively. A significant difference was observed in terms of sensitivity (P=0.024) and Youden index (rate difference 22.08%, 95% confidence interval 2.72–41.44%). Therefore, CEUS appears to be a promising diagnostic tool that is superior to CECT for detecting CLNM from SCC of the oral cavity, with a higher sensitivity.

Platysma myocutaneous flap revised in the free flaps era: clinical experience in 61 patients.

SUMMARYReconstruction of oral cavity and oropharyngeal defects following radical surgery for squamous cell carcinoma (SCC) can be achieved by a variety of options. In selected cases myocutaneous platysma flap (MPF) may be a valid choice. However, several anatomical and oncological controversies on the use of this flap are debated. A retrospective study on 61 patients treated between January 2005 and December 2017 in two referral centres in which MPF was used for the reconstruction of defects following surgical resection of SCC of the oral cavity and oropharynx was conducted. The technique of flap harvesting with anatomic details is described. In all cases the submental artery was sacrificed preserving the facial artery. All clinical data were collected. Tumours involved the oral cavity in 95.1% of cases, and the oropharynx in 4.9%. Pathological staging (TNM 7th edition) of tumours was: pT1 (42.6%), pT2 (39.3%), pT3 (4.9%) and pT4a (13.1%). Success rate of the flap was 93.4%. Four (6.5%) patients developed a partial necrosis of the skin paddle without platysma muscle involvement; none required surgical revision. The mean follow-up was 69 months (5-153 months). Thirteen patients (21.3%) developed a local recurrence, and in 1 patient was associated with contralateral neck metastasis. The MPF can be a suitable option in head and neck reconstruction of small or medium-sized defects in selected cases. The vascular pedicle can be provided by branches of the facial artery achieving both oncological radicality and optimal flap vascular supply.

The Effect of High Dose Rate Interstitial Implant on Early and Locally Advanced Oral Cavity Cancers: Update and Long-Term Follow-Up Study.

IntroductionBrachytherapy, with or without external beam radiation therapy (EBRT), can be an alternative to surgery for organ preservation in early and locally advanced oral cavity cancers. This study aims to evaluate the effect of high dose rate (HDR) interstitial brachytherapy on early and locally advanced squamous cell carcinoma (SCC) of the oral cavity when used alone or as a boost to EBRT.MethodsA total of 125 patients with histologically proven stage T1-3/N0-1 SCC of the oral cavity were included in the study. A total of 15 patients with stage I disease received an interstitial implant dose of 3,850 cGy at 350 cGy per fraction, two fractions a day. Another 53 patients had stage II, and 57 patients had stage III disease; these patients received EBRT of 50 Gy in 25 fractions along with an HDR brachytherapy boost of 21 Gy in seven fractions of 3 Gy per fraction twice daily. The stage III patients also received concurrent chemotherapy with injections of cisplatin (70 mg/m2) given every three weeks for three days in divided doses. All node-positive patients received a boost to the node of up to 64 Gy by external beam radiation. Disease response rates, five-year disease-free survival rates, and toxicities were analyzed.ResultsThe median follow-up was 60 months. Among the patients, 103 (82.4%) had a complete response, while 22 (17.6%) had residual disease and were referred for surgical salvage. The five-year disease-free survival was 100% in stage I, 83% in stage II, and 77.2% in stage III; 4% of patients developed grade 3 acute skin toxicity and 23.2% developed acute grade 3 mucositis. Eleven patients died during the follow-up period. Two patients died due to myocardial infarction but had achieved a complete tumor response. One patient had pulmonary tuberculosis and died due to fulminant infection after three years of disease-free survival period. One patient developed a second primary in the brain stem that presented with quadriplegia and expired. Seven patients died due to the progression of the initial disease.ConclusionsProper brachytherapy technique and meticulous planning can minimize the toxicity while providing better tumor control and achieve high local control rates. Brachytherapy, with or without EBRT, can be a surrogate to surgery in early oral cavity cancers as it can achieve organ preservation while providing good functional outcomes.

Cutaneous Metastasis of Bladder Cancer

Skin meta stases (SM) are infrequent secondary locations of deepneoplasia that can sometimes be indicative of primary cancer. They represent 0.2 to 10% of metastases from solid tumors [1]. The most frequent primary tumors in men were carcinoma of the lung (24%), carcinoma of the large intestine (19%), melanoma (13%), and squamous cellcarcinoma of the oral cavity (12%). The most common primary tumors in women were carcinoma of the breast (69%), carcinoma of the large intestine (9%), melanoma (5%), and carcinoma of the ovary (4%) [2]. The incidence of cutaneous involvement by all urolo gicalm alignanciesis 1.1% to 2.5% [3]. The kidneyis the most common organ to serve as a source of meta stasis to the skin [4]. Bladder cancers are lesslikely to metastasize to the skin We report a new case of skin metastases presenting as a large tumor in the thoraciclevel in a patient followed for a urothelial carcinoma of the bladder.

Risk factors for failure in the contralateral neck after adjuvant radiotherapy for squamous cell carcinoma of the oral cavity (SCCOC)

Risk factors for failure in the contralateral neck after adjuvant radiotherapy for squamous cell carcinoma of the oral cavity (SCCOC)

Welding and the risk of head and neck cancer: the ICARE study

ObjectiveTo investigate the association between occupational exposure to welding and the risk of head and neck cancer in a large French population-based case-control study, the Investigation of occupational and environmental...

Abstract CT124: Sitravatinib and nivolumab in oral cavity cancer window of opportunity study (SNOW)

Abstract Background: Squamous cell carcinoma of the oral cavity (SCCOC) often presents at early stages but its prognosis remains guarded, with a 5-year survival rate of 60% despite curative-intent therapies. Preoperative window-of-opportunity (WOO) studies in resectable SCCOC enable pharmacodynamic evaluation of molecular endpoints without compromising curative-intent treatment. Preoperative nivolumab in SCCOC was safe and showed promising tumor responses in CheckMate-358 WOO study (Ferris et al. ESMO 2017, LBA46). Sitravatinib, a receptor tyrosine kinase inhibitor which potently inhibits Tyro, AXL, Mer, and VEGF family of receptors, has shown encouraging results when combined with nivolumab in non-small cell lung cancer patients who have progressed on anti-PD-1 agents (Leal et al. ESMO 2018, 1129O). We hypothesize that sitravatinib and nivolumab have synergistic antitumor and immunogenic effects by increasing tumor immune infiltration and by blocking oncogenic pathways implicated in disease progression and immune-checkpoint resistance. Methods: Trial design: SNOW is a single-center, non-randomized WOO study of preoperative sitravatinib and nivolumab in patients with resectable SCCOC. Sitravatinib 120 mg is given orally once daily from day 1 until 48h before surgery or for a maximum period of 28 days. Nivolumab 240mg is given intravenously on day 15 for one dose only. Surgery is planned between days 23-30 following study treatment initiation. Fresh tumor biopsies and serial blood samples for extensive immunophenotyping and evaluation of other pharmacodynamic biomarkers, as well as clinical photographs of the tumor, are collected at baseline, on day 15 prior to nivolumab and at the time of surgery. 18FAZA-PET scans are performed at baseline and before surgery. Key eligibility criteria: previously untreated and resectable SCCOC; T2-4a, N0-2 or T1 (greater than 1 cm)-N2; no history of tumor bleeding or invasion of major vessels; adequate organ function; no autoimmune disorders; no immunosuppressive therapy. Study objectives: primary objective is to evaluate the immune and pharmacodynamic effects of sitravatinib plus nivolumab. Secondary objectives are: safety and tolerability including toxicity, rate of surgery completion within the planned window and rate of postoperative complications; antitumor activity including rate of complete pathological response; pharmacokinetics of sitravatinib alone and in combination with nivolumab. Correlative studies: tumor and blood immunophenotyping, tumor genome and transcriptome analysis, changes in intratumoral hypoxia based on 18FAZA-PET testing. Sample size: SNOW is a proof-of-concept study with no specific statistical assumptions at trial onset. We plan to enroll 12-15 patients evaluable for correlative studies. Study activation: Aug 30th, 2018. Two patients enrolled as of Jan 10th2019. Clinical trial identification: NCT03575598. Citation Format: Marc Oliva Bernal, Douglas Chepeha, Amy Prawira, Douglass Vines, Anna Spreafico, Scott Bratman, John De Almeida, Aaron Hansen, David Goldstein, Ralph Gilbert, Patrick Gullane, Dale H. Brown, Ilan Weinreb, Bayardo Perez-Ordoñez, Pamela S. Ohashi, Tracy McGaha, Ben X. Wang, Jonathan Irish, Isan Chen, Lillian L. Siu. Sitravatinib and nivolumab in oral cavity cancer window of opportunity study (SNOW) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT124.

Occupational exposure to petroleum-based and oxygenated solvents and oral and oropharyngeal cancer risk in men: A population-based case-control study in France

ObjectiveTo examine the association between occupational exposure to petroleum-based and oxygenated solvents and the risk of oral and oropharyngeal cancer. MethodsThe ICARE study is a large population-based case-control study conducted in France between 2001 and 2007. This present analysis was restricted to men and included 350 and 543 cases of squamous cell-carcinoma of the oral cavity and oropharynx, respectively, and 2780 controls. Lifetime tobacco, alcohol consumption and complete occupational history were assessed through detailed questionnaires. Job-exposure matrices allowed us to assess occupational exposure to five petroleum-based solvents (white spirits; diesel/fuel oils/kerosene; gasoline; benzene; special petroleum products) and five oxygenated solvents (diethyl ether; tetrahydrofuran; ketones and esters; alcohols; ethylene glycol). Odds-ratios (ORs), adjusted for age, smoking, alcohol consumption and socioeconomic status, and 95% confidence intervals (CI) were estimated using unconditional logistic models. ResultsAssociations between oral cancer risk and exposure to white spirits and diesel/fuel oils/kerosene were suggested, but there was no exposure-response trend. Concerning exposure to oxygenated solvents, participants with the highest levels of cumulative exposure to diethyl ether had a significant excess risk of oropharyngeal cancer (OR = 7.78, 95%CI 1.42 to 42.59; p for trend = 0.04). Ever exposure to tetrahydrofuran was associated with a borderline significant increased risk of oral cancer (OR = 1.87, 95%CI 0.97 to 3.61), but no exposure-response trend was observed. Additional adjustments for exposure to other solvents did not substantially change the results. ConclusionOur results do not provide evidence for a major role of petroleum-based and oxygenated solvents in the occurrence of oral and oropharyngeal cancers in men.

Management of incidental discovery of microscopic squamous cell carcinoma in zones of osteoradionecrosis of the mandible

ObjectivesOsteoradionecrosis (ORN) of the mandible is a common complication of head and neck radiotherapy and often requires surgical treatment. Squamous cell carcinoma (SCC) can be exceptionally discovered within zones of ORN on histological examination of the operative specimen. The authors discuss the management of these lesions based on a short patient series. Materials and methodsThis single-centre retrospective study was based on patients managed between 2012 and 2014 for ORN with incidental discovery of microscopic SCC. ResultsFive patients with incidental discovery of microscopic SCC in a zone of ORN of the mandible were included in this study. The mean time to onset of ORN after the end of radiotherapy for locally advanced SCC of the oral cavity or oropharynx was 42 months. Surgical treatment consisted of marginal or segmental mandibulectomy with free flap reconstruction. No recurrence was observed with a mean follow-up of 35 months [24–46]. ConclusionThe incidental discovery of microscopic SCC in a zone of ORN of the mandible is a rare event and has not been reported in the literature. Optimal management cannot be reliably defined due to the lack of data in the literature, but the present study supports careful histological examination of ORN specimens. Treatment must be as conservative as possible to avoid excessively invasive surgery.

Nuclear Survivin as a Prognostic Factor in Squamous-Cell Carcinoma of the Oral Cavity.

Oral squamous-cell carcinoma (OSCC) and most human tumors are characterized by an imbalance of regulatory mechanisms controlling cell processes such as apoptosis. Survivin, a member of the inhibitor of apoptosis family, is overexpressed in most solid and hematological malignancies and correlates with a reduced overall survival rate. Thus, the aim of this study was to find a correlation between nuclear Survivin expression and clinicopathologic data and the prognosis in OSCC patients. A total of 152 OSCC samples were investigated by immunohistochemistry for nuclear Survivin expression. Then, Survivin was scored semiquantitatively using an immunoreactivity score (IRS), calculated by multiplying the percentage of positive cells with the staining intensity. Using a digital image analysis software, OSCC patients were stratified into 4 groups. Results showed that patients with a lower IRS score displayed better survival rates than patients with a higher IRS score, reaching statistical significance. As the expression of Survivin at the nuclear level seems to suggest a poor prognosis in OSCC patients, the evaluation of nuclear Survivin IRS may be a useful tool to identify patients with more aggressive and disseminated disease, influencing follow-up and therapeutic protocols.

Association of Oral Cavity and Oropharyngeal Cancer Biomarkers in Surgical Drain Fluid With Patient Outcomes

Survival rates for head and neck cancer have been relatively stable for several decades. Individualized prognostic indicators are needed to identify patients at risk for poorer outcomes. To determine whether biomarker levels in surgical drain fluid of patients with head and neck cancer are associated with poor cancer outcomes. This prospective cohort study enrolled patients with squamous cell carcinoma (SCC) of the oral cavity and oropharynx who required surgical treatment from April 1, 2011, to February 1, 2016, at a tertiary or academic care center. Twenty patients, including 14 with stage IV disease, had complete specimen collection. Differences in cytokine and MMP levels by disease outcomes were evaluated. Patients underwent surgical treatment with drain placement as dictated by the standard of care. Drain fluid samples were collected every 8 hours postoperatively until drains were removed because of clinical criteria. Levels of cytokines and matrix metalloproteinases (MMPs) were measured using electrochemiluminescent, patterned array, multiplex technology. The primary clinical outcome measures were survival outcome and recurrence. The biomarkers measured included the cytokines basic fibroblastic growth factor, vascular endothelial growth factor isoform A, soluble fms-like tyrosine kinase-1 (sFlt-1), and placental growth factor (PIGF) and MMP-1, MMP-3, and MMP-9. Other clinical and pathologic cancer characteristics were recorded. In this cohort of 20 patients with SCC (15 men and 5 women; mean [SD] age, 63.5 [9.9] years), a significant association with recurrence was found for levels of MMP-1 (relative difference between groups, 2.78; 95% CI, 1.23-6.29), MMP-3 (relative difference between groups, 5.29; 95% CI, 2.14-13.05), and sFlt-1 (relative difference between groups, 3.75; 95% CI, 1.84-7.65). No biomarkers were associated with disease outcome. Vascular endothelial growth factor isoform A was associated with nodal metastasis (relative difference between groups, 1.98; 95% CI, 1.12-3.51), and basic fibroblastic growth factor was associated with lymphovascular invasion (relative difference between groups, 1.74; 95% CI, 1.02-2.97). In this pilot sample of patients with SCC of the oral cavity and oropharynx, MMP-1, MMP-3, and sFlt-1 levels in wound fluid were associated with poor clinical cancer outcomes in the form of recurrence. This finding is consistent with the literature of tumor microenvironment in saliva, serum, and tumor tissue biomarkers. To our knowledge, this report is the first of such findings in surgical drain fluid, an easily accessible means of cytokine measurement. Measurement of these biomarkers in surgical fluid potentially represents a novel means of assessing cancer prognosis in this population.