Radioterapia del grupo ganglionar retrofaríngeo y retroestiloídeo: ¿Cuándo y a quién? Una revisión de la literatura / Radiotherapy for retropharyngeal and retrostyloid lymph node groups: When and who? A review of the literature

La radioterapia de cabeza y cuello posee un rol central en el tratamiento de las neoplasias otorrinolaringológicas, ya sea como tratamiento adyuvante a la cirugía o como terapia definitiva. Dentro de este campo de estudio, un tópico aún poco explorado y motivo de debate, es la indicación de irradiación de los ganglios linfáticos retrofaríngeos, correspondientes a los niveles VIIa y VIIb de cuello. Hemos llevado a cabo una revisión sistemática con el objetivo de dilucidar criterios de irradiación electiva de estos grupos nodales y de emitir recomendaciones en cuanto a su inclusión en la práctica de la radio-oncología.

Radiation therapy has a central role in the management of head and neck malignancies, either as adjuvant treatment after surgery or as definitive therapy. Within this field of study, a still poorly explored and matter-of-debate topic is the indication for irradiation of retropahyngeal lymph nodes, corresponding to neck levels VIIa and VIIb. We have conducted a systematic review with the objective of elucidating elective irradiation criteria for these nodal groups and to issue recommendations about its inclusion in the practice of radiation oncology.

Pharmacological PI3K inhibition in head and neck squamous cell carcinoma: A systematic review.

BACKGROUND: This systematic review aimed to investigate the in vitro and in vivo effects of phosphatidylinositol-3-kinase (PI3K) inhibitors on head and neck squamous cell carcinoma (HNSCC). Considering the role of PI3K and its downstream effectors in cell proliferation, invasion, and survival, it is reasonable to expect that treatment with PI3K inhibitors could control HNSCC onset and progression. Thus, the research question for our review was whether pharmacological inhibition of PI3K affects HNSCC progression. METHODS: In vitro and in vivo studies were selected from six databases. We collected data regarding cell viability, apoptosis, and the regulation of protein expression levels from in vitro studies. For the in vivo studies, we analyzed the reduction in tumor size or gene and protein expression. RESULTS: The included studies showed reduced cell proliferation and apoptosis after treatment with PI3K inhibitors. PI3K inhibitors in combination with other drugs had an enhanced anticancer effects compared to those of single-drug treatments. CONCLUSIONS: The results support the potential of PI3K inhibitors as candidates for clinical trials in HNSCC.

Accuracy of MRI, CT, and Ultrasound imaging on thickness and depth of oral primary carcinomas invasion: a systematic review.

OBJECTIVES: The aim of this study was to perform a systematic review to assess the sensitivity, specificity, and accuracy of magnetic resonance imaging (MRI), computed tomography (CT), and intraoral ultrasound (US) to determine the depth of invasion (DOI) and/or tumor thickness (TT) in oral cavity cancers, with histopathological evaluation as the gold standard. METHODS: Articles whose primary objective was to evaluate the accuracy (sensitivity and specificity) of MRI, CT, and US imaging to assess DOI and/or TT were searched in six major electronic databases, in addition to three grey literature databases. The methodological quality of the selected studies was evaluated by using the Quality Assessment Tool for Diagnostic Accuracy Studies-2. RESULTS: Twelve studies met the inclusion criteria and underwent qualitative analysis: six studies on MRI, three on US, and one on CT. The accuracy values for MRI ranged from 67 to 83%, with sensitivity values above 80% and specificity above 75%. For US, mean values of sensitivity ranged from 91 to 93%. For CT, accuracy was 75%. CONCLUSIONS: For the application of US, CT, MRI, good accuracy was reported in DOI and/or TT, as evaluated in the preoperative period. US offered advantages for detection of small lesions.

Predictive value of transcriptional expression of Krüppel-like factor-6 (KLF6) in head and neck carcinoma patients treated with radiotherapy.

PURPOSE: To analyse the relationship between the transcriptional expression of Krüppel-like factor-6 (KLF6) and local response to treatment with radiotherapy in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: We determined the transcriptional expression of KLF6 in tumour biopsies obtained before treatment with radiotherapy in 83 HNSCC patients. The KLF6 expression was categorized according to the local control of the disease with a recursive partitioning analysis. RESULTS: During the follow-up period, 27 patients (32.5%) had a local recurrence of the tumour. Patients with local recurrence had significantly higher levels of KLF6 expression than patients in which radiotherapy achieved local control of the disease (P = 0.029). Five-year local recurrence-free survival for patients with a high transcriptional expression of KLF6 (n = 46) was 51.1% (95% CI 36.4-66.2%), and for patients with low expression it was 85.6% (95% CI 73.9-97.3%) (P = 0.0001). The results of a multivariate analysis showed that patients with a high KLF6 expression had a 3.8 times higher risk of local recurrence after treatment with radiotherapy (95% CI 1.4-10.5, P = 0.008). CONCLUSION: Transcriptional expression of KLF6 was significantly related to local control in HNSCC patients treated with radiotherapy. Patients with high levels of KLF6 expression had a significantly higher risk of local recurrence after treatment.

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.

Feasibility of concomitant cisplatin with hypofractionated radiotherapy for locally advanced head and neck squamous cell carcinoma.

BACKGROUND: The evolution of radiotherapy over recent decades has reintroduced the hypofractionation for many tumor sites with similar outcomes to those of conventional fractionated radiotherapy. The use of hypofractionation in locally advanced head and neck cancer (LAHNC) has been already used, however, its use has been restricted to only a few countries. The aim of this trial was to evaluate the safety and feasibility of moderate hypofractionated radiotherapy (HYP-RT) with concomitant cisplatin (CDDP). METHODS: This single-arm trial was designed to evaluate the safety and feasibility of HYP-RT with concomitant CDDP in LAHNC. Stage III and IV patients withnonmetastatic disease were enrolled. Patients were submitted to intensity modulatedradiation therapy, which comprised 55 Gy/20 fractions to the gross tumor and44-48 Gy/20 fractions to the areas of subclinical disease. Concomitant CDDPconsisted of 4 weekly cycles of 35 mg/m2. The primary endpoints were the treatment completion rate and acute toxicity. RESULTS: Twenty patients were enrolled from January 2015 to September 2016, and 12 (60%) were classified as unresectable. All patients completed the total dose of radiotherapy, and 19 patients (95%) received at least 3 of 4 cycles of chemotherapy. The median overall treatment time was 29 days (27-34). Grade 4 toxicity was reported twice (1 fatigue and 1 lymphopenia). The rates of grade 3 dermatitis and mucositis were 30% and 40%, respectively, with spontaneous resolution. Nasogastric tubes were offered to 15 patients (75%) during treatment; 4 patients (20%) needed feeding tubes after 2 months, and only 1 patient needed a feeding tube after 12 months. CONCLUSION: HYP-RT with concomitant CDDP was considered feasible for LAHNC, and the rate of acute toxicity was comparable to that of standard concomitant chemoradiation. A feeding tube was necessary for most patients during treatment. Further investigation of this strategy is warranted. TRIAL REGISTRATION: ClinicalTrials, NCT03194061 . Registered 21 Jun 2017 - Retrospectively registered.

Differentially expressed proteins in positive versus negative HNSCC lymph nodes.

BACKGROUND: Lymph node metastasis is one of the most important prognostic factors in head and neck squamous cell carcinomas (HNSCCs) and critical for delineating their treatment. However, clinical and histological criteria for the diagnosis of nodal status remain limited. In the present study, we aimed to characterize the proteomic profile of lymph node metastasis from HNSCC patients. METHODS: In the present study, we used one- and two-dimensional electrophoresis and mass spectrometry analysis to characterize the proteomic profile of lymph node metastasis from HNSCC. RESULTS: Comparison of metastatic and non-metastatic lymph nodes showed 52 differentially expressed proteins associated with neoplastic development and progression. The results reinforced the idea that tumors from different anatomical subsites have dissimilar behaviors, which may be influenced by micro-environmental factor including the lymphatic network. The expression pattern of heat shock proteins and glycolytic enzymes also suggested an effect of the lymph node environment in controlling tumor growth or in metabolic reprogramming of the metastatic cell. Our study, for the first time, provided direct evidence of annexin A1 overexpression in lymph node metastasis of head and neck cancer, adding information that may be useful for diagnosing aggressive disease. CONCLUSIONS: In brief, this study contributed to our understanding of the metastatic phenotype of HNSCC and provided potential targets for diagnostic in this group of carcinomas.

Carcinoma epidermoide de orofaringe. Experiencia institucional / Squamous cell carcinoma of the oropharynx. Institutional experience

Los carcinomas epidermoides de cabeza y cuello (CECC), son un grupo poco frecuente de neoplasias, en los Estados Unidos representan el 3.2% de todos los cánceres1,2. Si bien su frecuencia global se encuentra en disminución, los tumores localizados en la orofaringe han aumentado de forma considerable2. El virus del papiloma humano (HPV) es responsable de este aumento. Se ha descripto que los tumores de orofaringe, asociados al HPV, ocurren en pacientes más jóvenes, con enfermedad de bajo volumen a nivel del tumor primario, pero elevada incidencia de metástasis ganglionares, con adenopatías quísticas2,3. La detección del virus del HPV, por inmunohistoquímica (IHQ) o por reacción en cadena de la polimerasa (PCR) son factores pronósticos importantes que siempre deben ser tenidos en cuenta para el tratamiento de estos tumores (AU)

Epidermoid carcinomas of the head and neck are a rare group of tumors, in the United States they account for 3.2% of all cancers. Although their overall frequency is decreasing, tumors located in the oropharynx have increased considerably. Human papillomavirus (HPV) is responsible for this increase. It has been described that oropharyngeal tumors, associated with HPV, occur in younger patients, with low volume disease at the primary tumor level but a high incidence of lymph node metastases, with cystic lymphadenopathy. Detection of HPV virus by immunohistochemistry (IHC) or polymerase chain reaction (PCR) are important prognostic factors that should always be taken into account for the treatment of these tumors (AU)

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.