A study on treatment of locally advanced squamous cell carcinoma of head and neck with radiation along with cisplatin or gefitinib

Background: Cisplatin based Concurrent chemo-radiation (CTRT) is the corner stone for treatment of locally advanced head and neck carcinoma. Epidermal growth factor receptor(EGFR) expression by squamous cell carcinoma which is associated with cancer development and progression,leads to emergence of anti-EGFR agents as a therapeutic option. In this study we compare cisplatin based CTRT against gefitinib based CTRT in terms of disease control and acute toxicity profile. Material and Methods: Stage III and IV squamous cell carcinoma of Head and neck region (excluding nasopharynx) were randomised into two groups. Control group received conventionally fractionated radiotherapy of 66Gy in 33fractions, over six and half weeks with concurrent weekly cisplatin. Study group received same dose of radiation with concurrent daily oral Gefitinib. All patients were followed up weekly during the treatment and then 6-8 weeks after completion of treatment and thereafter 3 monthly. Results: Overall response rate (complete response + partial response) was comparable for both arms (75% vs 76.2%, p value-0.881). Radiation with cisplatin was associated with significantly higher skin (28.6% vs 15%,p value-0.037) and mucosal (23.8% vs 5%,p-value-0.047) toxicities. Gefitinib containing arm showed significantly higher grade 3 diarrhoea (10% vs 0%, p-value-0.01) and skin rash (6% vs 0%, p -value-<0.001).With a median follow-up of 12.5 months Disease free survival (DFS) was not significantly different between the arms(12 vs 13 months). Conclusion: Gefitinib based CTRT is non-inferior to cisplatin based CTRT for the treatment of locally advanced head and neck carcinoma with acceptable toxicity profile.

Identification and clinical validation of gene signatures with grade and survival in head and neck carcinomas

This study aimed to explore gene expression profiles that drive malignancy from low- to high-grade head and neck carcinomas (HNC), as well as to analyze their correlations with survival. Gene expressions and clinical data of HNC were downloaded from the Gene Expression Omnibus (GEO) repository. The significantly differential genes (SDGs) between low- and high-grade HNC were screened. Cox regressions were performed to identify prognostic SDGs of progression-free survival (PFS) and disease-specific survival (DSS). The genes were experimentally validated by RT-PCR in clinical tissue specimens. Thirty-five SDGs were identified in 47 low-grade and 30 high-grade HNC samples. Cox regression analyses showed that CXCL14, SLC44A1, and UBD were significantly associated with DSS, and PPP2R2C and SLC44A1 were associated with PFS. Patients were grouped into high-risk or low-risk groups for prognosis based on gene signatures. High-risk patients had significantly shorter DSS and PFS than low-risk patients (P=0.033 and P=0.010, respectively). Multivariate Cox regression showed HPV (P=0.033), lymph node status (P=0.032), and residual status (P<0.044) were independent risk factors for PFS. ROC curves showed the risk score had better efficacy to predict survival both for DSS and PFS (AUC=0.858 and AUC=0.901, respectively). The results showed CXCL14 and SLC44A1 were significantly overexpressed in the low-grade HNC tissues and the UBD were overexpressed in the high-grade HNC tissues. Our results suggested that SDGs had different expression profiles between the low-grade and high-grade HNC, and these genes may serve as prognostic biomarkers to predict survival.

A comparative study of concomitant boost radiation versus concomitant boost with concurrent chemoradiation versus standard fractionation chemoradiation in locally advanced head-and-neck cancer

Context: As the number of head-and-neck cancer (HNC) patients are high in our subcontinent, the study was designed to reduce the treatment time and increase efficacy. Aims: Comparative evaluation of the efficacy, toxicity, local control, and survival of concomitant boost radiotherapy (CBRT), CBRT with concurrent chemoradiation (CBRT + CCT) and conventionally fractionated radiotherapy with concomitant chemotherapy (CFRT + CCT) in locally advanced HNC (LAHNC). Materials and Methods: Patients with LAHNC were randomly assigned to 3-groups of 30-patients each. Group I (CBRT) received, 45 Gy/25#/5-weeks and 18 Gy/10# concomitant boost in the last 2-week of treatment, receiving a total dose of 63 Gy. Group II (CBRT + CCT) received CBRT with concomitant cisplatin 75 mg/m 2 on day 1, 17, and 34. Group III (CFRT + CCT) received 64 Gy/32#/6.2 weeks, concurrent with injection cisplatin 75 mg/m 2 on day 1, 22, and 42. Statistical Analysis Used: Stata 9.0 SPSS and Chi-square test were used for analysis and disease-free survival (DFS) rates were calculated using the Kaplan–Meier method. Results: The median follow-up period was 8.2 months. At last follow-up, locoregional control was 36%, 57%, and 40% and DFS was seen in 33%, 53%, and 40% of patients in Group I, II, and III, respectively. Grade-3 cutaneous reactions were significantly higher in Group-II as compared to that of Group-III (P = 0.033) and Group-I (P = 0.715). Conclusion: All three groups have similar response rates and DFS with manageable toxicity

Side effect of radioactive 125I seed implantation for recurrent malignant tumor of head and neck assisted by 3D-printing individual guide plate / 中华放射医学与防护杂志

Objective To investigate the acute side effect of 3D printing individual non-coplanar template for 125I seed implantation in head and neck recurrent/ metastatic carcinoma.Methods Between January 2016 and December 2016,42 patients of local recurrent malignant tumor of head and neck received 3D printing guide plate assist radioactive seeds implantations,and included in the study.The tumor volume ranged from 2.4 to 102.8 cm3 (median 28.6 cm3).The prescribed dose is 110-160 Gy,and the seeds activity were 0.34 to 0.70 mCi (1 Ci =3.7 × 1010 Bq).All patients carried out preoperative planning design,individual guide plate production,seed implantation,postoperative dose assessment,and followup.The side effects of skin,mucous membrane,blood and spinal cord were statistically analyzed.Results All patients were operated successfully.The follow-up time was 4-14 months (median 8.5 months).There were no adverse reactions at grade three or above.Three patients had grade one skin reaction.One patient experienced grade one mucosal reaction,two experienced grade two mucosal reactions.The skin response was correlated with the dose of the skin (x2 =7.067,P =0.032).No hematologic toxicity or radiation myelopathy was observed and no seed displacement was found.Conclusions 3D-printing guide plate can provide good accuracy for positioning and direction.For local recurrent malignant tumor of head and neck,there were no obvious adverse reactions and the operation was simple and the dosage was accurate.

Diagnostic value of ultrasound-guided fine needle aspiration in assessment of cervical lymph node in head and neck carcinoma / 中国癌症杂志

Treatment and the clinical outcome of patients with head and neck cancer are determined by accurate staging and assessment of the cervical lymph nodes for metastases is an important step of this process. Ultrasonography, ultrasonography-guided fine needle aspiration (FNA), CT, MRI and PET/CT are used in the assessment of cervical lymph nodes. Ultrasonography guided FNA is advantageous in ease of application, minimumal invasiveness to patients, and less contraindications. Combined with cell block and molecular biology, FNA can be an effective tool for the diagnosis. The present article reviewed the diagnostic value of ultrasonography guided FNA in cervical lymph node assessment in patients with head and neck cancer.

The advances of clinical application of PET/CT in head and neck carcinoma / 中国癌症杂志

Head and neck carcinoma (HNC) is one of the common malignancies in the world. Because of its deep location and complicated surroundings, patients usually receive definitive radiotherapy or concurrent chemoradio-therapy. Early prediction has significant importance to guide physicians in making treatment decisions. Traditional im-aging techniques have obvious limitations. However, positron emission tomography (PET), as a non-invasive functional imaging, allows quantitative assessment of many biologic processes before the anatomic changes, such as proliferation, apoptosis and hypoxia. PET/CT is more and more widely used in HNC nowadays. This article reviewed the advances of clinical application of PET/CT in HNC in this paper

Carcinomas de cabeza y cuello, experiencia de un centro oncológico del estado de Durango, México / Head and neck carcinomas, experience of a cancer center in the state of Durango, Mexico

Antecedentes: los carcinomas de cabeza y cuello son relativamente frecuentes, presentan diversos tipos histológicos y características clínicas, mismas que se asocian con una variedad de riesgos de mortalidad. Objetivo: El propósito de este trabajo fue examinar en un periodo de cinco años carcinomas de cabeza y cuello tratados en el Centro Estatal de Cancerología. Material y métodos: Este estudio se realizó de manera retrospectiva, se revisaron factores de riesgo y tratamientos, se hicieron análisis univariados y multivariados para evaluar factores pronóstico y supervivencia. Resultados: Se obtuvieron un total de 32 expedientes que cumplían con las características del estudio, el periodo de seguimiento fue de 2 a 32 meses. La variante histológica predominante fue carcinoma epidermoide, el tratamiento primario más común fue cirugía. Conclusiones: La supervivencia en los carcinomas de cabeza y cuello disminuye en pacientes en etapas clínicas avanzadas, edad e historia de tabaquismo y/o alcoholismo, la mayoría de ellos muere por progresión de enfermedad y metástasis.

Introduction: carcinomas of the head and neck are relatively common.They include diff erent histological types and present a rangeof clinical characteristics, and are associated with diverse risks of mortality. Objective: To perform a casuistic review of cases of head andneck carcinomas over a period of fi ve years at a State Cancer Center.Material and method: A retrospective study was conducted, in whichrisk factors and treatments were analyzed. Univariate and multivariatestatistical analyses were performed for the purpose of evaluatingprognostic and survival factors. Results: A total of 32 fi les were foundto meet the criteria required by the study. Patient follow-up ranged from2 to 32 months. The predominant histological variant identifi ed wasthe squamous cell carcinoma, while the most common primary treatment was surgery. Conclusions: This study shows that survival fromhead and neck carcinomas decreases in patients who are in advancedclinical stages, particularly those of a certain age with a history ofsmoking and/or alcohol use, most of whom die from the progression and metastasis of the disease.

Comparison of two different radiation fractionation schedules with concurrent chemotherapy in head and neck malignancy.

INTRODUCTION: The worldwide incidence of head and neck malignancy exceeds half a million cases annually. In radiotherapy (RT), conventional fractionation comprises giving five fractions per week from Monday to Friday. Accelerated RT includes administration of six fractions per week is being advocated. It gives better locoregional control and the median overall treatment time is 39 days as compared to 46 days in conventional group. Our study involved comparison of conventional versus accelerated RT with concurrent chemotherapy, in evaluation of local control and toxicity in the two arms. MATERIALS AND METHODS: Sixty patients of locally advanced squamous cell carcinoma head and neck region were studied. All the patients received cisplatin (30 mg/m2) weekly during the therapy. The patients received RT dose of 70 Gray (Gy) in 35 fractions (#). The patients were randomly assorted into two groups: Group 1 ‑ Study group (n = 30) ‑ Six fractions RT per week (Monday–Saturday). Group 2 ‑ Control group (n = 30) ‑ Five fractions RT per week (Monday–Friday). During and after the treatment, locoregional control, acute and late radiation toxicity were assessed. RESULTS AND OBSERVATION: There was no significant difference between the two schedules regarding locoregional control rate. The Grade 3 or higher acute toxicities were significantly higher in the accelerated arm although there was no significant difference in late toxicities between the two arms. CONCLUSION: Accelerated fractionation regimen was not more efficacious than conventional fractionation in the treatment of previously untreated head and neck carcinoma.

Significance of the Failure Patterns in Cervical Lymph Nodes Achieving a Complete Response to Radical Radiotherapy / 대한방사선종양학회지

PURPOSE: This study was performed to examine the neck failure patterns after a complete response (CR) to definitive radiotherapy for advanced head and neck cancer patients, as well as evaluate the clinical significance of the results of this study. MATERIALS AND METHODS: Between 1987 and 2008, the clinical data of patients who had been treated with radical radiotherapy for primary squamous cell carcinomas and enlarged cervical lymph nodes was analyzed retrospectively. Ultimately, the cases that showed CR of the cervical lymph node lesions to full-dose radiotherapy were included in this study. The recurrent rate and sites in the cervical lymphatic area were evaluated periodically by radiologic imaging studies, along with some factors which might have affected the rate of recurrence. RESULTS: A total of 73 patients who achieved CR in neck area after radiotherapy were included in this study. The rate of subsequent neck failure among those patients was 19.2%. There was only a 5.5% failure rate in the 55 patients who underwent radiotherapy in their primary site. Eighty percent of the recurrent cases were found within 3 years (median follow-up, 68 months). The majority of neck recurrent cases (47%) were accompanied with the failure of the primary lesions. The initial response of the primary site and the method of radiotherapy simulation were significant prognostic factors associated with the nodal recurrence rate. CONCLUSION: The recurrence rate of cervical nodes in patients with CR to radiotherapy in the primary site and neck area was about 5%. These patients could be followed up with close observation without a planned neck dissection.

Feasibility of Robotic Surgical System in the Field of Head and Neck Surgery / 대한이비인후과학회지

The current trend in managing head and neck cancer is to perform organ preservation therapy which improves quality of life and decreases treatment related morbidity. Transoral robotic surgery (TORS) can overcome the limit of "line of sight" often met in classic transoral procedure. We utilized robotic surgical system for the treatment of oropharyngeal, hypopharyngeal and laryngeal cancer. TORS was performed using the da Vinci surgical robot (Intuitive Surgical, Inc., Sunnyvale, CA). It is consisted of a surgeon's console and a manipulator cart equipped with 3 robotic arms. The surgeon is provided with 3-dimensional magnified images from the endoscopic arm and can control 2 instrument arms for delicate operations from the console. TORS can provide magnified three dimensional views and overcome the limitation resulting from the "line of sight" which hinders classic transoral procedure. Safe resection of the head and neck cancer lesion was possible with the 3-dimensional magnified images and two robotic arms which have 360 degree joint motion. The application of TORS for lateral oropharyngectomy, partial hypopharyngectomy and partial laryngectomy is technically feasible and safe

Advances in the study of carotid injury after radiotherapy in head and neck tumors / 中国癌症杂志

Radiotherapy is the main treatment method for treating head and neck tumors. however, carotid injury after irradiation is a major concern which contributes to the quality of life in head and neck patients, especially in long term survivors. At present, duplex Doppler ultrasound is commonly used in detecting the change of carotid artery after irradiation in the clinic. Internal diameter and mean intima-media thickness(IMT) of carotid artery are predominant objects of observation. Precaution and management of carotid artery damage after irradiation have signifi cant clinical value to long term survivors. In this view, we summarized the advances in the study of carotid artery damage of head and neck tumors after irradiation.

A Clinical Study of Distant Metastases in Head and Neck Cancer / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: There are many failed cases with distant metastases (DMs) of head and neck cancer. In such cases, patients usually have poor prognosis, with a median duration of survival between 4 and 6 months. To find out the correlation between the general clinical aspects and distant metastases in patients with head and neck cancer, we analyzed our previous experiences. MATERIALS AND METHOD: We reviewed records retrospectively in 41 of 460 patients with head and neck cancers from 1986 to 1995. DMs were confirmed with X-ray, CT, MRI, liver scan, FNAC, PCNA, and biopsy. We used the staging system of American Joint Committee on Cancer. RESULTS: 1) Clinically manifested DMs were found in 8.9% (41/460) of patients. 2) DMs were frequently observed in the oropharynx (13.8%), oral cavity (11.4%), and larynx (10.3%) cancer. 3) The lung is the most common site of DMs for head and neck cancer. Liver and bone are the only other sites of DMs that are commonly clinically diagnosed. 4) DMs usually occur within 2 years of the initial diagnosis. 5) The incidence of DMs was significantly higher in the advanced T, N stages and clinical stage than in the early T, N stages and clinical stage (p<0.05). CONCLUSION: The results of this study suggest that the advanced T, N stages and clinical stage may be some of the most critical factors influencing the eventual development of DMs.

Amplification of Cyclin D1 in Head and Neck Squamous Cell Carcinomas / 대한이비인후과학회지

BACKGROUND: Amplification of the chromosome 11q13 region has been observed in a variety of human cancers, including head and neck squamous cell carcinoma and carcinomas of breast, esophagus, lung, bladder, and liver. The chromosome 11q13 region has various putative oncogenes, of which cyclin D1 is most consistently amplfied and overexpressed. OBJECTIVES: To estabilsh the frequency and clinicopathologic correlations of cyclin D1 amplification in head and neck squamous cell carcinomas. MATERIALS AND METHODS: Fresh tissue samples were obtained from 26 patients with head and neck cancers undergoing surgery or biopsy. Amplification of cyclin D1 was evaluated in 26 head and neck squamous cell carcinomas by Southern blotting. The presence or absence of amplification was correlated with anatomic site, tumor stage, and differentiation pattern. RESULTS: Five tumors of 26(19%) showed a twofold to 4-fold amplification of cyclin D1 compared with beta-actin control prove. Amplified and nonamplified groups revealed no differences in anatomic primary site, stage, N stage, and pathologic differentiation. CONCLUSION: We showed a significant incidence of cyclin D1 amplification in head and neck squamous cell carcinomas, but cannot demonstrate an association with clinical presentation and pathologic findings.