Active search screening for oral potentially malignant disorders and oral cancer in the city of Piracicaba

Abstract Oral cancer is a public health problem worldwide with approximately 300,000 new cases diagnosed every year and more than 170,000 deaths annually. Squamous cell carcinoma (SCC) accounts for approximately 90% of all oral malignancies and it is frequently preceded by lesions known as oral potentially malignant disorders (OPMDs). Screening programs for early detection of oral lesions have been conducted. Therefore, the objective of this research was to carry out an active search in a screening program in the city of Piracicaba, Brazil. High-risk patients were identified at the city's health center through their medical records and referred for dental consultation. Other patients who opportunistically sought dental care were also seen and if they did not present risk factors for SCC, they were considered low-risk. A total of 756 patients were examined, and 445 met the criteria for the high-risk group and 311 for the low-risk group. It was possible to diagnose 27 OPMDs and six SCCs - 21 OPMDs and six SCCs occurred in high-risk patients and six OPMDs in low-risk patients. A chi-square test was applied and a statistically significant value (p = 0.006) was obtained for the detection of OPMD and SCC in patients of the high-risk group. Screening of high-risk patients through active search proved to be an effective program for diagnosing OPMD and SCC. Therefore, we encourage its implementation on a large scale to reduce the current scenario of this disease.

Técnica de mandibulotomía para la resección de carcinoma de cavidad oral: caso clínico / Mandibulotomy technique for the resection of an oral cavity carcinoma: a clinical case

El objetivo del presente trabajo es describir la técnica de mandibulotomía para resección de una lesión oncológica. Se describe el caso de una paciente de sexo femenino de 79 años con una formación vegetante que se extiende desde el polo inferior amigdalino izquierdo hasta surco glosoepiglótico homolateral y pared lateral de hipofaringe, con diagnóstico de carcinoma epidermoide poco diferenciado invasor. Se realizó la resección del tumor bajo anestesia general en el Hospital Sirio Libanés en mayo de 2019. La técnica de mandibulotomía utilizada en este caso clínico permitió acceder a la cavidad oral y orofaringe para la resección de un tumor no accesible a través de la boca abierta (AU)

Investigating the Feasibility of Targeted Next-Generation Sequencing to Guide the Treatment of Head and Neck Squamous Cell Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is a deadly disease in which precision medicine needs to be incorporated. We aimed to implement next-generation sequencing (NGS) in determining actionable targets to guide appropriate molecular targeted therapy in HNSCC patients. MATERIALS AND METHODS: Ninety-three tumors and matched blood samples underwent targeted sequencing of 244 genes using the Illumina HiSeq 2500 platform with an average depth of coverage of greater than 1,000×. Clinicopathological data from patients were obtained from 17 centers in Korea, and were analyzed in correlation with NGS data. RESULTS: Ninety-two of the 93 tumors were amenable to data analysis. TP53 was the most common mutation, occurring in 47 (51%) patients, followed by CDKN2A (n=23, 25%), CCND1 (n=22, 24%), and PIK3CA (n=19, 21%). The total mutational burden was similar between human papillomavirus (HPV)–negative vs. positive tumors, although TP53, CDKN2A and CCND1 gene alterations occurred more frequently in HPV-negative tumors. HPV-positive tumors were significantly associated with immune signature-related genes compared to HPV-negative tumors. Mutations of NOTCH1 (p=0.027), CDKN2A (p < 0.001), and TP53 (p=0.038) were significantly associated with poorer overall survival. FAT1 mutations were highly enriched in cisplatin responders, and potentially targetable alterations such as PIK3CA E545K and CDKN2A R58X were noted in 14 patients (15%). CONCLUSION: We found several targetable genetic alterations, and our findings suggest that implementation of precision medicine in HNSCC is feasible. The predictive value of each targetable alteration should be assessed in a future umbrella trial using matched molecular targeted agents.

Palliative weekly chemotherapy along with cetuximab in recurrent and metastatic head and neck cancers: A retrospective analysis.

Background: This study was undertaken to report the results of weekly combination chemotherapy with cetuximab in recurrent/metastatic head and neck squamous cell carcinoma (R/M SCCHN). Materials and Methods: Retrospective analysis of 35 R/M SCCHN patients who received cetuximab with weekly paclitaxel and platin (cisplatin/carboplatin) from SCCHN August 2006 to October 2008 at our Institute was performed. Results: Thirty-five patients (33 [94.3%] males and 2 [5.7%] females) received the planned weekly chemotherapy protocol. Median age of these patients was 52 years. Of the SCCHN 32 evaluable patients, 25 patients showed symptomatic improvement and 7 showed no improvement. Radiological responses using RECIST criteria reported CR in 1 patient (3.1%), PR in 17 patients (53.1%), and SD in 6 patients (18.8%). The remaining six patients demonstrated disease progression while two could not be assessed. Median overall survival (OS) was 8.016 months (95% CI; 6.572--9.461) and median PFS was 5.782 months (95% CI; 4.521--7.044). The major chemotherapy-related grades 2 and 3 toxicity recorded was cetuximab-induced rash reported in 24 patients. No treatment-related death within 30 days was observed. Conclusion: Cetuximab with weekly combination chemotherapy (Paclitaxel + Platinum compound) has shown promise, demonstrating comparable response and outcomes with acceptable toxicity in R/M SCCHN patients.

Cetuximab plus radiotherapy in patients with unresectable locally advanced squamous cell carcinoma of head and neck region - A open labelled single arm phase II study.

Purpose : To evaluate feasibility, safety and outcome of cetuximab concurrent with radiotherapy in locally advanced head−neck cancer. Materials and Methods: Between March 2007 and January 2008 eligible cases of locally advanced unresectable (Stage IV) squamous cell carcinoma of head and neck were enrolled in this single arm, open labeled phase II Study. They were treated with cetuximab for a duration of 8 weeks and concomitant RT for 7 weeks (starting one week after initiating Cetuximab) Results: A total of 19 eligible patients were enrolled. The median age of patients was 53 years, all patients happening to be male. The performance status of the patients was 0/1. The location of the primary tumor was oropharynx in 12 cases, oral cavity in 4, larynx in 2, and hypopharynx in one case. The overall response rate (ORR) was 68.42% and the overall survival at 2 year was 84 %. All 13 patients who completed two years follow-up after completion of study treatment continued to be alive with no evidence of disease progression. One patient also remained alive with progressive disease. Conclusions: Cetuximab concurrent with radiotherapy is a safe and effective option in advanced head−neck cancer patients.

Cetuximab with radiotherapy in patients with loco-regionally advanced squamous cell carcinoma of head and neck unsuitable or ineligible for concurrent platinum-based chemo-radiotherapy: Ready for routine clinical practice.

Purpose : To report outcomes of cetuximab concurrent with radiotherapy in advanced head-neck cancer unsuitable for platinum-based chemo-radiotherapy. Materials and Methods : Retrospective chart review of 37 patients treated with cetuximab and radiotherapy at a comprehensive cancer centre. Results : Median age of study cohort was 59 years. Thirty four (92%) patients had advanced stage disease (stage III-IV). Reasons for ineligibility for platinum included impaired creatinine-clearance, old age, and/or co-morbidities. Thirty-two (86%) patients completed planned radiotherapy without interruption; 29 (80%) patients received ≥6 cycles of cetuximab. Fifteen patients (40.5%) developed ≥grade 3 dermatitis; 9 patients (25%) experienced ≥grade 3 mucositis. At a median follow-up of 16 months, the 2-year loco-regional control, disease-free survival, and overall survival was 35.5%, 29.5%, and 44.4% respectively. Stage grouping and severe dermatitis were significant predictors of outcome. Conclusions : Cetuximab concurrent with radiotherapy is a reasonable alternative in advanced head-neck cancer patients with acceptable compliance and outcomes, but higher skin toxicity.

Organ Preservation for the Management of Locally Advanced Head and Neck Cancer / 한양의대학술지

The multidisciplinary approach to treat squamous cell carcinoma of the head and neck cancer is evolving and complex. Induction chemotherapy has been used in resectable disease for organ preservation, and has shown similar survival when compared with concurrent chemoradiotherapy. Thus, concurrent cisplatin-based chemoradiotherapy is considered as standard treatment for organ preservation for larynx, hypopharynx, and oropharynx cancers. Given that recent evidence of survival benefits with taxane-containing combination chemotherapy for induction chemotherapy, the concept of induction chemotherapy followed by concurrent chemotherapy is being revised. Also, with advances in molecular biology of cancer, a new molecular targeted agent, epidermal growth factor inhibitor (EGFR) antagonist such as EGFR monoclonal antibody showed promising results in the treatment of patients with both locoregionally advanced and metastatic squamous cell carcinoma of the head and neck cancer. Trials with incorporation of this agent are ongoing. In this article, some recent advances in the treatment of squamous cell carcinoma of the head and neck cancer, in particular the expanding role of chemotherapy in organ preservation will be reviewed.

Correlations among Tumor Microvessel Density, p53 Protein Expression, and Cervical Lymph Node Metastasis in Squamous Cell Carcinoma of the Head and Neck / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Angiogenesis is a crucial step in tumor growth and progression, and regulated by the net balance between positive and negative angiogenic factors. Recent studies suggested that angiogenesis is controlled by p53 regulation. immunohistochemical study was carried out using monoclonal antibodies against p53 protein and CD34. In this study, immunohistochemical study was carried out using monoclonal antibodies against p53 protein and CD34 in order to determine the relationship between p53 protein expression and angiogenesis in squamous cell carcinoma in the head and neck. MATERIALS AND METHODS: Tumor tissues from 35 cases of paraffin block specimens of head and neck cancers were used from the archives of Department of Pathology in Chonnam University hospital to study the relationship between p53 protein expression and angiogenesis. RESULTS: p53 protein expression was present in 20 (57.1%) of 35 cases and the median micro-vessel count (MVD) was 49.0 (9-126) in x200 microscopic field. MVD was 45.5 (20-126) in cases with p53 protein expression and 50.0 (9-108) in cases without p53 protein expression. There was no statistical significance between MVD and p53 protein expression. An inverse relationship was seen between MVD and primary tumor size. P53 protein expression was not associated with nodal metastasis and primary tumor size. CONCLUSION: There were no significant relations between MVD and p53 protein expression, nor among MVD, p53 and nodal metastasis in head and neck squamous cell carcinoma.

Effects of IFN - gamma on Spheroid and Raft Culture of Squamous Cell Carcinoma of the Head and Neck / 대한암학회지

PURPOSE: To establish new in vitro model systems that better reflect in vivo condition, multicellular tumor spheroids(MTS) and raft culture were developed using cell lines of squamous cell carcinoma(SCCHN) of the head and neck. In these 3-dimensional systems, the expression of cell surface molecules which are important for modulation of physiology of tumor cells were studied with or without the treatment of interferon(IFN)-gamma. MATERIALS AND METHODS: Four SCCHN cell lines were used for MTS and raft culture. The effects of interferon-gamma on SCCHN cells were examined by immunohistochemistry. RESULTS: All cell lines formed MTS, but only Tu-138 showed a good stratification at the air-liquid interface in the raft culture system. Immunohistochemical studies of MTS using monoclonal antibodies revealed a strong staining for MHC class I, no staining for MHC-DR, a weak patch expression of ICAM-1 and a central strong staining for integrin a 6. Staining patterns were similar for the raft cultures except integrin a 6(intense full-thickness positivity). In both systems, IFN-gamma enhanced the expression of MHC-DR and ICAM-1. No significant change was found in the expression of MHC class I and integrin a 6. CONCLUSIONS: MTS and raft culture system were established successfully from the SCCHN cell lines. IFN-gamma can modulate the surface molecules of tumor cells in the 3-dimensional culture systems.