Correlation Between Vascular Endothelial Growth Factor Expression And Presence Of Lymph Node Metastasis In Advanced Squamous Cell Carcinoma Of The Larynx.

Squamous cell carcinoma is the most common neoplasm of the larynx, and its evolution depends on tumor staging. Vascular endothelial growth factor is a marker of angiogenesis, and its expression may be related to increased tumor aggressiveness, as evidenced by the presence of cervical lymphatic metastases. To evaluate the expression of the vascular endothelial growth factor marker in non-glottic advanced squamous cell carcinoma of the larynx (T3/T4) and correlate it with the presence of cervical lymph node metastases. Retrospective clinical study and immunohistochemical analysis of vascular endothelial growth factor through the German scale of immunoreactivity in products of non-glottic squamous cell carcinomas. This study analyzed 15 cases of advanced non-glottic laryngeal tumors (T3/T4), four of which exhibited cervical lymphatic metastases. There was no correlation between vascular endothelial growth factor expression and the presence of cervical metastases. Although vascular endothelial growth factor was expressed in a few cases, there was no correlation with the spread of cervical lymph metastases.

Squamous cell carcinoma of the larynx with subglottic extension: is larynx preservation possible?. Plattenepithelkarzinom des Larynx mit subglottischer Ausdehnung: ist ein Larynxerhalt möglich ?

PURPOSE: Squamous cell carcinoma of larynx with subglottic extension (sSCC) is a rare location described to carry a poor prognosis. The aim of this study was to analyze outcomes and feasibility of larynx preservation in sSCC patients. PATIENTS AND METHODS: Between 1996 and 2012, 197 patients with sSCC were treated at our institution and included in the analysis. Stage III-IV tumors accounted for 76 %. Patients received surgery (62 %), radiotherapy (RT) (18 %), or induction chemotherapy (CT) (20 %) as front-line therapy. RESULTS: The 5-year actuarial overall survival (OS), locoregional control (LRC), and distant control rate were 59 % (95 % CI 51-68), 83 % (95 % CI 77-89), and 88 % (95 % CI 83-93), respectively, with a median follow-up of 54.4 months. There was no difference in OS and LRC according to front-line treatments or between primary subglottic cancer and glottosupraglottic cancers with subglottic extension. In the multivariate analysis, age > 60 years and positive N stage were the only predictors for OS (HR 2, 95 % CI 1.2-3.6; HR1.9, 95 % CI 1-3.5, respectively). A lower LRC was observed for T3 patients receiving a larynx preservation protocol as compared with those receiving a front-line surgery (HR 14.1, 95 % CI 2.5-136.7; p = 0.02); however, no difference of ultimate LRC was observed according to the first therapy when including T3 patients who underwent salvage laryngectomy (p = 0.6). In patients receiving a larynx preservation protocol, the 5-year larynx-preservation rate was 55 % (95 % CI 43-68), with 36 % in T3 patients. The 5-year larynx preservation rate was 81 % (95 % CI 65-96) and 35 % (95 % CI 20-51) for patients who received RT or induction CT as a front-line treatment, respectively. CONCLUSION: Outcomes of sSCC are comparable with other laryngeal cancers when managed with modern therapeutic options. Larynx-preservation protocols could be a suitable option in T1-T2 (RT or chemo-RT) and selected T3 sSCC patients (induction CT).

HIGH EXPRESSION OF CANCER TESTIS ANTIGENS MAGE-A, MAGE-C1/CT7, MAGE-C2/CT10, NY-ESO-1, AND GAGE IN ADVANCED SQUAMOUS CELL CARCINOMA OF THE LARYNX

Background. Despite diagnostic and therapeutic advances in head and neck cancer, the 5-year survival of patients with laryngeal cancer has not improved in the last 30 years. Several recent studies indicate that specific targets for immunotherapeutic approaches can be useful in the control of cancer. There is considerable interest in the expression of cancer testis antigens in human cancers since they may serve as the basis for an immunologic approach to therapy. Methods. We evaluated by immunohistochemical analysis the expression of cancer testis antigens MAGE-A4 (57B), MAGE-C1 (CT7-33), MAGE-A1 (MA454), MAGE-A3 (M3H67), MAGE-C2 (CT10.5), NY-ESO-1 (E978), and GAGE (GAGE) in squamous cell carcinoma (SCC) of the larynx. Results. A total of 63 cases (57 men and 6 women) of laryngeal SCC were available for this study. The findings were correlated with the clinical course and laboratory data. Expression of at least 1 cancer testis antigen was detected in 42 of 63 of the laryngeal SCCs (67%). In 34 of 42 of the positive cases (81%) there was simultaneous expression of >= 2 cancer testis antigens. There was significant correlation between antigen expression and advanced tumor stage (stage III/IV) in cases with reactivity to only 1 antibody (p = .01) as well as in the cases with reactivity to >= 2 primary antibodies (>= 2 mAbs, p = .04). There was no association between survival and expression of any of the analyzed antigens. Conclusions. We find a high incidence of cancer testis antigen expression in SCCs of the larynx, which was correlated with advanced clinical stage. Our data indicate that cancer testis antigens could be valuable vaccine targets in laryngeal tumors, especially in those with a worse prognosis. (C) 2010 Wiley Periodicals, Inc. Head Neck 33: 702-707, 2011

Carcinomes épidermoïdes de l'hypopharynx et du larynx : prise en charge fondée sur les preuves Squamous cell carcinoma of the hypopharynx and larynx: evidence-based care.

Les carcinomes épidermoïdes de l'hypopharynx et du larynx peuvent être traités par chirurgie et/ou radiothérapie en fonction de la taille tumorale. Pour les petites tumeurs, les résultats sont équivalents. Pour les tumeurs localement avancées, l'approche chirurgicale est mutilante et nécessite une (pharyngo)laryngectomie totale. La chimioradiothérapie exclusive a montré tout son intérêt mais au prix de séquelles tardives. Dans le but de diminuer ces séquelles et les mutilations, la chimiothérapie d'induction par cisplatine, docétaxel et 5FU à visée de préservation d'organe devient le standard de traitement mais il manque des études solides de comparaison de cette approche avec la chimioradiothérapie exclusive. Il n'est pas possible de conclure quant à la supériorité d'un schéma en survie globale. Quand la chimiothérapie d'induction est choisie, les modalités de potentialisation éventuelle de la radiothérapie ne sont pas établies. Squamous cell carcinomas of larynx and hypopharynx can be treated by surgery and/or radiotherapy according to tumor size. For small tumors, the results are similar. For locally advanced tumors, the surgical approach is mutilating and requires a total (pharyngo)laryngectomy. Exclusive chemoradiotherapy has shown its interest at the cost of late sequelae. In order to reduce these effects and mutilation, induction chemotherapy with cisplatin, docetaxel and 5FU for organ preservation becomes the standard treatment but there are no solid studies comparing this approach with the exclusive chemoradiotherapy. And it is not possible to conclude as to the superiority of a scheme in terms of overall survival. When chemotherapy is chosen, the modalities of any potentiation of radiation have not been yet established.

Genetic polymorphisms in the Cytochrome P450 family and squamous cell carcinoma of the oral cavity, pharynx and larynx

Objective:To analyze the genetic polymorphisms of the cytochrome P450 family and their relationship with squamous cell carcinoma of the oral cavity, pharynx and larynx.Methods: We present a narrative literature review, conducted in Pubmed, Lilacs and Cochrane Databases of articles published in the last five years correlating genetic polymorphisms of the cytochrome P450 family and cancer risk in different populations worldwide.Results: We initially found 65 articles and, after selection criteria, 20 case-control studies with various populations worldwide were eligible. The most studied polymorphisms were those of CYP2E1 and CYP1A1 subfamilies. There is little about the other subfamilies. The association found between polymorphisms and cancer risk amounted to a countless number of variables, amongst them: population, selection methods, racial factors and different modes of exposure to carcinogens, genotyping methods, and nomenclature of the polymorphisms.Conclusion: so far, there is no proven link between genetic polymorphisms of cytochrome P450 family and squamous cell carcinoma of the oral cavity, pharynx and larynx relationship.

Histologic Correlation Of Expression Of Ki-67 In Squamous Cell Carcinoma Of The Glottis According To The Degree Of Cell Differentiation.

Squamous cell carcinoma is the most common neoplasm of the larynx and glottis, and its prognosis depends on the size of the lesion, level of local invasion, cervical lymphatic spread, and presence of distant metastases. Ki-67 (MKI67) is a protein present in the core, whose function is related to cell proliferation. To evaluate the expression of marker Ki-67 in squamous cell carcinoma of the larynx and glottis and its correlation to pathological findings. Experimental study with immunohistochemistry analysis of Ki-67, calculating the percentage of the cell proliferation index in glottic squamous cell carcinomas. Sixteen cases were analyzed, with six well-differentiated and 10 poorly/moderately differentiated tumors. There was a correlation between cell proliferation index and degree of cell differentiation, with higher proliferation in poorly/moderately differentiated tumors. The cell proliferation index, as measured by Ki-67, may be useful in the characterization of histological degree in glottic squamous cell tumors.

Multifocalité du carcinome épidermoïde sur les voies digestive supérieure et respiratoire distale : technicité du diagnostic endoscopique [Multiple squamous cell carcinoma of the upper digestive and lower respiratory tracts : methodology of endoscopic screening]

L'étude porte sur 951 porteurs d'un cancer primaire bucco-pharyngo-laryngé, et révèle un taux de multifocalité du carcinome épidermoïde sur les voies digestive supérieure (bouche-pharynx-oesophage) et aérienne distale (larynx-trachée-bronches) s'élevant à 14,5 %. Les secondes localisations peuvent être simultanées (6,4 %) ou successives (8,1 %) à la découverte du premier cancer: dès la deuxième année du follow-up leur incidence dépasse celle des récidives. Elles se localisent tant au niveau ORL (8,5 %) qu'oesophagien (3 %) ou bronchique (3 %). Le cancer du voile présente un taux de multifocalité particulièrement élevé (51 %). Les auteurs décrivent un type d'endoscopie de dépistage (bucco-pharyngo-oesophago-laryngo-trachéobronchoscopie) dont la fiabilité repose sur une technicité spécifique d'une part, et sur la connaissance des caractéristiques propres aux secondes localisations d'autre part. Ce dépistage systématique permet de détecter les tumeurs secondaires à un stade le plus souvent précoce et encore asymptomatique.

Radiothérapie externe accélérée postopératoire des carcinomes épidermoïdes localement évolués de la sphère ORL: étude prospective de phase II [Prospective study of accelerated postoperative radiation therapy in patients with squamous-cell carcinoma of the head and neck]

PURPOSE: To assess the feasibility and efficacy of accelerated postoperative radiation therapy (RT) in patients with squamous-cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Between December 1997 and July 2001, 68 patients (male to female ratio: 52/16; median age: 60-years (range: 43-81) with pT1-pT4 and/or pN0-pN3 SCCHN (24 oropharynx, 19 oral cavity, 13 hypopharynx, 5 larynx, 3 unknown primary, 2 maxillary sinus, and 2 salivary gland) were included in this prospective study. Postoperative RT was indicated because extracapsular infiltration (ECI) was observed in 20 (29%), positive surgical margins (PSM) in 20 (29%) or both in 23 patients (34%). Treatment consisted of external beam RT 66 Gy in 5 weeks and 3 days. Median follow-up was 15 months. RESULTS: According to CTC 2.0, acute morbidity was acceptable: grade 3 mucositis was observed in 15 (22%) patients, grade 3 dysphagia in 19 (28%) patients, grade 3 skin erythema in 21 (31%) patients with a median weight loss of 3.1 kg (range: 0-16). No grade 4 toxicity was observed. Median time to relapse was 13 months; we observed only three (4%) local and four (6%) regional relapses, whereas eight (12%) patients developed distant metastases without any evidence of locoregional recurrence. The 2 years overall-, disease-free survival, and actuarial locoregional control rates were 85, 73 and 83% respectively. CONCLUSION: The reduction of the overall treatment time using postoperative accelerated RT with weekly concomitant boost (six fractions per week) is feasible with local control rates comparable to that of published data. Acute RT-related morbidity is acceptable.

Outcome of superficial squamous cell carcinoma of the esophagus: a clinicopathological study

PURPOSE: To analyze the clinicopathological features and outcome of patients with pathologically proven superficial squamous cell carcinoma of the esophagus. METHODS: A total of 234 consecutive cases of esophageal carcinoma in a 15-year period were reviewed. RESULTS: Superficial esophageal cancer was found in five patients (2.1%). They were four men and one woman and the mean age was 52.5 years. Smoking and alcohol were the main risk factors. Achalasia due to Chagas disease occurred in one patient and a second primary tumor developed in the larynx in another patient. Four patients underwent esophagectomy and one patient received chemoradiotherapy. The histopathologic diagnosis was of squamous cell carcinoma in all cases. Intramucosal tumor (Tis) was identified in three cases and superficially invasive carcinoma in two cases. Four patients are free of disease with survival times of two, four, six and nine years. The patient who developed laryngeal cancer died six years after esophagectomy. CONCLUSION: Long-term survival in patients with esophageal cancer is related to early diagnosis. Therefore, a less aggressive surgical approach, such as endoscopic resection, may be a good option for these patients, if depth of tumor invasion can be accurately predicted by the new imaging tools.

Stromal Myofibroblasts In Squamous Cell Carcinoma Of The Tongue In Young Patients - A Multicenter Collaborative Study.

The purpose of this study was to evaluate the presence of myofibroblasts, frequently associated with a more aggressive neoplastic behavior, in oral tongue squamous cell carcinoma (TSCC) of young patients and to compare with the distribution observed in older patients. Tumor samples from 29 patients younger than 40 years old affected by TSCC were retrieved and investigated for the presence of stromal myofibroblasts by immunohistochemical reactions against α smooth muscle actin, and the results obtained were compared to TSCC cases affecting older patients. No positive reaction could be found in the stromal areas devoid of neoplastic tissue, whereas myofibroblasts were present in 58.6% of the lesions in young patients and in 75.9% of the older ones. No significant difference was found when comparing the invasive front and the overall stroma of both groups, and no correlation could be obtained with stromal α smooth muscle actin expression, higher tumor grades or clinical stage (P > .05). There was no significant difference between the presence of stromal myofibroblasts of TSCC affecting young and old individuals.

Phase I trial of DNA-hsp65 immunotherapy for advanced squamous cell carcinoma of the head and neck

Considering that mycobacterial heat-shock protein 65 (hsp65) gene transfer can elicit a profound antitumoral effect, this study aimed to establish the safety, maximum-tolerated dose (MTD) and preliminary efficacy of DNA-hsp65 immunotherapy in patients with advanced head and neck squamous cell carcinoma (HNSCC). For this purpose, 21 patients with unresectable and recurrent HNSCC were studied. Each patient received three ultrasound-guided injections at 21-day intervals of: 150, 600 or 400 mu g of DNA-hsp65. Toxicity was graded according to CTCAE directions. Tumor volume was measured before and after treatment using computed tomography scan. The evaluation included tumor mass variation, delayed-type hypersensitivity response and spontaneous peripheral blood mononuclear cell proliferation before and after treatment. The MTD was 400 mg per dose. DNA-hsp65 immunotherapy was well tolerated with moderate pain, edema and infections as the most frequent adverse effects. None of the patients showed clinical or laboratory alterations compatible with autoimmune reactions. Partial response was observed in 4 out of 14 patients who completed treatment, 2 of which are still alive more than 3 years after the completion of the trial. Therefore, DNA-hsp65 immunotherapy is a feasible and safe approach at the dose of 400 mg per injection in patients with HNSCC refractory to standard treatment. Further studies in a larger number of patients are needed to confirm the efficacy of this novel strategy.

PHASE I/II STUDY OF ERLOTINIB COMBINED WITH CISPLATIN AND RADIOTHERAPY IN PATIENTS WITH LOCALLY ADVANCED SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK

Purpose: Erlotinib, an oral tyrosine kinase inhibitor, is active against head-and-neck squamous cell carcinoma (HNSCC) and possibly has a synergistic interaction with chemotherapy and radiotherapy. We investigated the safety and efficacy of erlotinib added to cisplatin and radiotherapy in locally advanced HNSCC. Methods and Materials: In this Phase I/II trial 100 mg/m(2) of cisplatin was administered on Days 8, 29, and 50, and radiotherapy at 70 Gy was started on Day 8. During Phase I, the erlotinib dose was escalated (50 mg, 100 mg, and 150 mg) in consecutive cohorts of 3 patients, starting on Day 1 and continuing during radiotherapy. Dose-limiting toxicity was defined as any Grade 4 event requiring radiotherapy interruptions. Phase 11 was initiated 8 weeks after the last Phase I enrollment. Results: The study accrued 9 patients in Phase I and 28 in Phase II; all were evaluable for efficacy and safety. No dose-limiting toxicity occurred in Phase I, and the recommended Phase 11 dose was 150 mg. The most frequent nonhematologic toxicities were nausea/vomiting, dysphagia, stomatitis, xerostomia and in-field dermatitis, acneiform rash, and diarrhea. Of the 31 patients receiving a 150-mg daily dose of erlotinib, 23 (74%; 95% confidence interval, 56.8%-86.3%) had a complete response, 3 were disease free after salvage surgery, 4 had inoperable residual disease, and 1 died of sepsis during treatment. With a median 37 months` follow-up, the 3-year progression-free and overall survival rates were 61% and 72%, respectively. Conclusions: This combination appears safe, has encouraging activity, and deserves further studies in locally advanced HNSCC. (C) 2010 Elsevier Inc.

Predictors of higher number of stages in Mohs micrographic surgery for the treatment of squamous cell carcinoma of the head

BACKGROUND - Squamous cell carcinomas of the skin of the bead are better treated with Mobs micrographic surgery which has the lowest recurrence rates and allows spare normal tissue. There are some characteristics of squamous cell carcinoma that can be related to a higher number of surgical stages. OBJECTIVE - To study characteristic of head squamous cell carcinoma that predicts a higher number of Mohs surgical stages. METHODS - A retrospective analysis of 51 squamous cell carcinomas of the bead treated with Mobs surgery was performed to determine risk factors for a higher number of surgical stages. The characteristics analyzed were clinical limits, morphology, recurrence, histological differentiation and size and compared to the number of surgical stages. The analysis was performed by Fisher`s exact test and multivariate logistic regression. RESULTS - The recurrent squamous cell carcinomas showed a tendency for a higher number of stages (p=0,081). The Odds Ratio for a higher number of Mobs stages was three for inaccurate limits; although not statistically significant, it corroborates clinical and previous publication. CONCLUSION - Clinical characteristics of squamous cell carcinoma as recurrence and inaccurate limits would not predict, but could indicate tendency of a higher number of Mobs micrographic surgery stages.

Extent of Pelvic Lymphadenectomy in Women With Squamous Cell Carcinoma of the Uterine Cervix: Is There Any Prognostic Value?

Background and Objectives: Some authors states that the removal of lymph node would only contribute towards assessing the lymph node status and regional disease control, without any benefit for the patients` survival. The aim of this paper was to assess the influence of the number of surgically dissected pelvic lymph nodes (PLN) on disease-free Survival. Methods: Retrospective cohort study on 42 women presenting squamous cell carcinoma (SCC) of the uterine cervix, with metastases in PLN treated by radical surgery. The Cox model was used to identify risk factors for recurrence. The model variables were adjusted for treatment-related factors (year of treatment, surgical margins and postoperative radiotherapy). The cutoff value for classifying the lymphadenectomy as comprehensive (15 PLN or more) or non-comprehensive (<15 PLN) was determined from analysis of the ROC curve. Results: Fourteen recurrences (32.6%) were recorded: three pelvic, eight distant, two both pelvic and distant, and one at an unknown location. The following risk factors for recurrence were identified: invasion of the deep third of the cervix and number of dissected lymph nodes <15. Conclusions: Deep invasion and non-comprehensive pelvic lymphadenectomy are possible risk factors for recurrence of SCC of the uterine cervix with metastases in PLN. J. Surg. Oncol. 2009;100:252-257. (C) 2009 Wiley-Liss, Inc.