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Simple Summary: Skin cancer, particularly non-melanoma skin cancer, is the most common malignancy in the world. There are both common and uncommon types that receive treatment every day. Despite their commonality, the management of each is not perfectly defined in the scientific literature. Many require surgical removal, but the management of regional metastasis (such as lymph nodes in the neck) may or may not require surgical removal, or even anything beyond observation. Further complicating matters, some may have microscopic regional metastases that cannot be detected with a physical exam or imaging. This article seeks to summarize the current literature on this topic and to offer specific insight on how to manage non-melanoma skin cancer that has migrated away from the primary site to the regional lymph nodes. Non-melanoma skin cancer (NMSC) represents the most common malignancy in the world, comprising exceedingly common lesions such as basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) and rare lesions such as Merkel cell carcinoma. Risk factors are widely recognized and include ultraviolet (UV) light exposure, radiation exposure, immunosuppression, and many others. As a whole, survival and functional outcomes are favorable, but each histopathological subtype of NMSC behaves differently. Treatment regimens for the primary site usually include wide surgical excision and neck dissection in cases of clinically involved metastatic lymph nodes. The elective management of draining nodal basins, however, is a contested topic. Nearly all subtypes, excluding BCC, have a significant risk of lymphatic metastases, and have been studied with regard to sentinel lymph node biopsy (SLNB) and elective neck dissection. To date, no studies have definitively established a true single standard of care, as exists for melanoma, for any of the NMSCs. As a result, the authors have sought to summarize the current literature and identify indications and management options for the management of the cervical lymphatics for each major subtype of NMSC. Further research remains critically necessary in order to develop complete treatment algorithms. [ABSTRACT FROM AUTHOR]

Objective: To characterize cell line CAE606 derived from a squamous cell carcinoma (SCC) of the external auditory canal (EAC) and to show its usefulness as a model for testing candidate therapeutic agents. Study Design: Preclinical translational research. Setting: Biomedical research institute. Methods: The cell line was initiated from a moderately differentiated T2N0M0 EAC SCC. We studied its histologic and genetic features as well as growth and invasion parameters. Sensitivity to cell CDK4/6 cell cycle inhibitor palbociclib was analyzed. Results: CAE606 cells expressed heavy molecular weight cytokeratin, p63, and vimentin. The population doubling time was 25.8 hours, and the cells showed fast collective cell migration in a wound‐healing assay. Short tandem repeat analysis confirmed it to be derived from the primary tumor of the patient. Next‐generation sequencing revealed alterations in cell cycle regulation genes, including inactivating mutations in CDKN2A and TP53 and high‐level amplification of CCND1 and EGFR. CAE606 showed a strong decrease of phospo‐Rb expression upon exposure to the CDK4/6 inhibitor palbociclib, causing significant growth inhibition with an IC50 of 0.46 µM. Conclusion: This is the first report of a stable EAC SCC cell line. Its genetic features make it a useful tool for preclinical testing of new therapeutic agents for EAC SCC, particularly those targeting cell cycle regulation in combination with radio‐ and chemotherapy or other specific signaling pathway inhibitors. [ABSTRACT FROM AUTHOR]

Background: Surgical resection or radiotherapy (RT) are standard approaches for early-staged hypopharyngeal squamous cell carcinoma (HPSCC). Transoral laser microsurgery (TOLMS) seems to provide good oncological and functional results with few local complications. The aim of our study was to analyze the outcomes of TOLMS, with or without neck dissection or RT, in the treatment of HPSCC in a tertiary referral center. Methods: A retrospective study was conducted in patients with early T-category (T1–T2) HPSCC treated by TOLMS. Results: A total of 34 patients were included in the study. The series includes 17 (50%) T1 and 17 (50%) T2 classified tumors. The 5-year overall survival and disease-specific survival rates were 51% and 66%, respectively, with a 5-year local control rate of 92%. All patients reassumed oral diet and none of them had a tracheostomy at the end of the follow-up. Conclusions: TOLMS offers an effective treatment option in terms of oncologic control and function preservation in locally circumscribed HPSCC. [ABSTRACT FROM AUTHOR]

It is traditionally accepted that subglottic carcinoma has a worse prognosis than tumors arising in other subsites of the larynx, owing to its tendency to present in advanced stages, with a high incidence of cartilage invasion and extralaryngeal spread. The incidence of subglottic carcinoma varies among series, mainly because there is no uniform definition of the upper boundary of the subglottis. The extent of the tumor may be difficult to define because subglottic carcinoma may spread through the submucosa without visible mucosal changes. There is also a rich lymphatic network in the subglottis draining to the prelaryngeal and paratracheal lymph nodes, which are usually not involved by cancers arising in other laryngeal subsites. Current literature data indicates that early‐stage subglottic carcinoma can be treated using radiotherapy or chemoradiotherapy with high locoregional control and survival rates. In advanced stage subglottic carcinoma, combination of surgery followed by radiotherapy or chemoradiotherapy resulted in comparable outcomes, as in advanced carcinomas from the rest of the larynx. Stage for stage, it is likely that the prognosis for subglottic carcinoma and of glottic and supraglottic cancers is similar. [ABSTRACT FROM AUTHOR]

Given the presence of active viral replication and severe immunosuppression of the patient, it was decided to administer intralesional cidofovir as neoadjuvant therapy in order to prevent early recurrences after surgery. Treatment complications included pain and necrosis of the nail bed after drug infiltration, which did not change the planned surgical procedure (Figure 3). Mohs micrographic surgery was performed 1 week after the last dose and confirmed the presence of an extensive in situ component in the nail bed. [Extracted from the article]

Introduction: Transoral laser microsurgery (TLM) has become the standard approach for treatment of early-stage laryngeal carcinoma in most institutions due to their good oncological and functional results with few local complications. The purpose of this study was to analyze the oncological and functional results of TLM in the treatment of laryngeal tumors at our Hospital.Materials and methods: Patients with laryngeal squamous cell carcinoma (LSCC) treated from 1998 to 2013 with TLM with curative intention, and with a minimum follow-up of 24 months, were reviewed.Results: 203 patients with LSCC were included. 195 patients were men (96%) and 8 women (4%), with a mean age of 63 years. The series includes 134 (66%) T1, 40 (20%) T2, and 29 (14%) T3-classified tumors. 116 tumors (57%) were in the glottis, 79 (39%) in the supraglottis and 8 (4%) in the anterior commissure. 16 patients (8%) received adjuvant radiotherapy. Initial local control was obtained in 75.5% of patients. The 5-year overall survival rate was 84% and the 5-year disease-specific survival was 90%. The presence of nodal metastasis (p < 0.001) and the involvement of the surgical margins (p = 0.004) were associated with a lower disease-specific survival in the multivariate analysis. All but three patients with local control of the disease reassumed oral diet, and none were tracheostomy-dependent. The 5-year laryngeal preservation rate was 85%.Conclusions: TLM is a minimally invasive treatment for early and moderately-advanced laryngeal carcinomas, with good oncologic and functional outcomes, and few complications as well. [ABSTRACT FROM AUTHOR]

Abstract: Background: Lymph node ratio (LNR) is increasingly reported as a potential prognostic tool. The purpose of this review was to analyze the available literature on the prognostic significance of LNR in head and neck squamous cell carcinoma (HNSCC). Methods: A PubMed internet search was performed and articles meeting selection criteria were reviewed. Results: Twenty‐eight studies were identified in the literature dealing with the prognostic value of LNR. The published results are variable with a range of cutoff values of LNR associated with prognosis (overall survival [OS] and/or disease‐specific survival [DSS]) between 0.02 and 0.20, with an average of 0.09. Conclusion: The LNR is reported to be of value in assessing prognosis in the patients with HNSCC. Although it is easy to calculate and could be considered in the staging of these patients, the currently available evidence in the literature does not yet provide a solid base for implementation. [ABSTRACT FROM AUTHOR]

Adequate treatment of lymph node metastases is essential for patients with head and neck squamous cell carcinoma (HNSCC). However, there is still no consensus on the optimal surgical treatment of the neck for patients with a clinically positive (cN+) neck. In this review, we analyzed current literature about the feasibility of selective neck dissection (SND) in surgically treated HNSCC patients with cN + neck using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. From the reviewed literature, it seems that SND is a valid option in patients with cN1 and selected cN2 neck disease (non-fixed nodes, absence of palpable metastases at level IV or V, or large volume ->3 cm-multiple lymph nodes at multiple levels). Adjuvant (chemo) radiotherapy is fundamental to achieve good control rates in pN2 cases. The use of SND instead a comprehensive neck dissection (CND) could result in reduced morbidity and better functional results. We conclude that SND could replace a CND without compromising oncologic efficacy in cN1 and cN2 cases with the above-mentioned characteristics. [ABSTRACT FROM AUTHOR]

Abstract: Background: Sinonasal cancer carries a poor prognosis, especially in recurrent stages, and it is a disease with very limited treatment options. Methods: The expression of programmed death ligand‐1 (PD‐L1) as a marker for immunotherapy was evaluated in 53 sinonasal squamous cell carcinoma (SCC) and 126 intestinal‐type adenocarcinoma (ITAC) samples. Results were correlated to clinicopathological characteristics and follow‐up data. Results: Membranous PD‐L1 staining of tumor cells was observed in 34% (18/53) of the sinonasal SCC samples and in 17% (22/126) of the ITAC samples. The PD‐L1 positivity on infiltrating immune cells occurred in 45% (24/53) of the sinonasal SCC samples and in 33% (41/126) of the ITAC samples. Expression of PD‐L1 showed no correlation to clinicopathological parameters and was not an independent risk factor for survival. Conclusion: The PD‐L1 positivity does not seem to have prognostic value. However, a proportion of patients with sinonasal SCC and ITAC may benefit from therapy with immune checkpoint inhibitors that recently have been approved for clinical application in head and neck cancer. [ABSTRACT FROM AUTHOR]

Although the majority of laryngeal malignancies are the conventional squamous cell carcinomas (SCC), a wide variety of malignant epithelial tumors can affect the larynx. Current treatment guidelines are designed to guide clinicians in management of conventional laryngeal SCC. Less is known about the biological behavior and responsiveness to therapy and overall outcomes of other malignant epithelial lesions. Because a spectrum of disease biology is represented by these rare phenotypes, an understanding of the basic biology can help direct management to optimize clinical outcome in this group of patients. This review provides a critical analysis of literature relating to the diagnosis, management, and outcome of patients with non-conventional squamous malignant epithelial neoplasms of the larynx. Particular attention is paid to features which are at variance with the conventional SCC and how these impact on management of these rare tumors. [ABSTRACT FROM AUTHOR]

Objective: To identify epigenetic events in intestinal-type sinonasal adenocarcinoma (ITAC) and sinonasal squamous cell carcinoma (SNSCC) and to evaluate their relation to clinicopathologic features and follow-up data.Study Design: Retrospective study.Setting: Academic research hospital.Subjects and Methods: The methylation status of 23 genes in 50 ITACs and 32 SNSCCs was analyzed by methylation-specific multiplex ligation-dependent probe amplification and its relation to clinicopathologic features and follow-up data.Results: Gene methylation was observed in 50% of all tumors. Recurrent methylated genes in SNSCC were RASSF1 and CDH13 (for both, 6 of 32 cases), CHFR (4 of 32 cases), and TIMP3 (2 of 32 cases). None of these genes showed significant correlation to clinicopathologic features or overall survival. In ITAC, recurrent methylated genes were CDH13 (18 of 50 cases), ESR1 (13 of 50 cases), APC (7 of 50 cases), TIMP3 (5 of 50 cases), CASP8 (3 of 50 cases), and HIC1 and RASSF1 (for both, 2 of 50 cases). Papillary and colonic ITAC subtypes carried a mean of 1.26 gene methylations per tumor versus 0.63 in solid and mucinous subtypes. Methylation of TIMP3 was associated with a significantly worse survival in ITAC patients.Conclusion: ITAC carries a higher number and a different profile of gene methylations as compared with SNSCC. Gene methylation plays a greater role in papillary and colonic ITAC subtypes, which may indicate a different tumorigenic pathway for these ITAC subtypes. These findings could be used as prognosticators and may have implications for future individualized therapies based on epigenetic changes. [ABSTRACT FROM AUTHOR]

Background. Despite therapeutic improvements, patients with sinonasal squamous cell carcinoma (SCC) still face an unfavorable prognosis and there is great need for alternative treatments. Methods. SCCNC4 cells, originally derived from a T2N1M0 primary and untreated sinonasal SCC, were inoculated in the maxillary sinus of immunodeficient mice. Histology, invasive behavior, and genetic features were evaluated and compared with the original primary tumor. Results. The mice developed tumors that invaded bone, surrounding tissues, and brain, showing the same poor differentiation as the original primary tumor. Genetic analysis revealed an almost identical pattern of copy number alterations, except for the deletion and loss of expression of the genes CDKN2A and PTEN. Conclusion. This article shows the feasibility of an orthotopic mouse model of SCC of the maxillary sinus. Completed by genome-wide genetic profiling data, this model will be useful for preclinical testing of specific gene-targeted anticancer drugs. [ABSTRACT FROM AUTHOR]

Sinonasal squamous cell carcinomas (SCC) are rare tumors, etiologically related to occupational exposure to wood and leather dust. In spite of surgical and radiotherapeutic advances, the 5 year survival is still 30-50%. Therefore, alternative treatment options are needed. We report the establishment and characterization of six unique human sinonasal SCC cell lines, named SCCNC1, 2, 4, 5, 6 and 7. In vitro growth and invasion characteristics were evaluated and genetic profiles were compared to those of the original primary tumors. The population doubling times ranged from 21 to 34 hours. Cell lines SCCNC2 and 7 were highly invasive in matrigel. Five cell lines carried a high number of copy number alterations, including amplifications and homozygous deletions, while one showed only three abnormalities. Sequence analysis revealed three cell lines with TP53mutation and none with KRASor BRAF. Overexpression of p53 was observed in five, and of EGFR in four cell lines. None of the cell lines showed strong immunopositivity of p16 or presence of human papilloma virus. In conclusion, we have created six new cell lines that are clinically and genetically representative of sinonasal SCC and that will be a useful tool for the preclinical testing of new therapeutic agents. [ABSTRACT FROM AUTHOR]

Summary: Objectives: Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay is a method that has rarely been exploited in DNA methylation profiling of laryngeal squamous cell carcinoma (LSCC). Material and methods: Methylation of the gene was investigated by MS-MLPA in a well-characterized series of 53 LSCC and 30 samples of healthy mucosa. Aberrant promoter hypermethylation was confirmed using bisulfite pyrosequencing, and methylation-specific. Results: Promoter hypermethylation was observed in 36 of the 53 patients (68%). CDKN2B (28%), APC (17%), RARβ (15%), DAPK1 (11%) and CHFR (11%) were most frequently hypermethylated. Aberrant methylation of CHFR was mainly a late-stage event. Methylation-specific polymerase chain reaction and bisulfite pyrosequencing confirmed aberrant methylation for CDKN2B, APC and DAPK1. Conclusion: Promoter methylation profiling of LSCC using MS-MLPA identified CDKN2B, DAPK1, RARβ, APC, and CHFR as frequent epigenetic events. The clinical implications of these genes as biomarkers are highly relevant as attractive targets for cancer therapy, given the reversible nature of epigenetic gene silencing. [Copyright &y& Elsevier]

Summary: Objetives: Despite improvements in the field of surgery and radiotherapy, the overall prognosis of sinonasal carcinomas is poor, mainly due to the difficulty to resect the tumour completely in this anatomically complex region. Therefore, there is great need for alternative treatments. Knowledge of the KRAS and BRAF mutational status would become clinically important with regard to the possible use of anti-EGFR therapies. Material and methods: DNA was extracted from paraffin embedded tumour samples from 57 cases of sinonasal squamous cell carcinoma (SNSCC) and from fresh frozen tumour samples from 58 cases of intestinal-type sinonasal adenocarcinoma (ITAC). Point mutations were analysed for KRAS exon 2 (codons 12 and 13) and BRAF (exon 15, V600E) by direct sequencing. Results: Neither KRAS nor BRAF showed any mutations in the SNSCC, whereas 7/58 (12%) ITAC harboured KRAS mutations and no BRAF mutations. All seven cases with KRAS mutation concerned well-differentiated and less aggressive (papillary and colonic type) ITAC, all patients being woodworkers and 4/7 tobacco smokers. Conclusion: Neither of SNSCCs carried mutations in KRAS and BRAF and a low frequency of KRAS mutation was found in ITAC. This suggests that KRAS and BRAF mutations play a limited role in the development of sinonasal cancer and that mutation analysis is not useful as a screening test for sensitivity to anti-EGFR therapy in sinonasal cancer. [ABSTRACT FROM AUTHOR]

BACKGROUND: Sinonasal squamous cell carcinomas (SNSCCs) are rare tumors with no etiologic link to tobacco or alcohol, as opposed to other squamous cell carcinomas of the head and neck. Despite improvements in the field of surgery and radiotherapy, patients with these tumors still face a very unfavorable prognosis, partly because of their localization in a complex anatomic area, which has special relevance for surgery and postoperative treatment. Therefore, there is a need for new therapeutic possibilities for patients with these tumors. METHODS: Gene copy numbers of epidermal growth factor receptor ( EGFR) and v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 ( ERBB2) were analyzed by fluorescence in situ hybridization and multiplex ligand-dependent probe amplification, and protein expression was evaluated by immunohistochemistry in 54 SNSCC specimens. The results were correlated with clinicopathologic and follow-up data. RESULTS: EGFR gene copy number increases were observed in 20 of 45 tumors (44%), and 21 of 54 tumors (39%) had EGFR protein overexpression. Eight of 38 tumors (21%) had ERBB2 copy number increases, and 4 of 54 tumors (7%) exhibited elevated protein expression levels. Both copy number increases and protein overexpression of EGFR and ERBB2 were mutually exclusive. v-Ki- ras2 Kirsten rat sarcoma viral oncogene homolog ( KRAS) mutations were absent in 37 tumors that were analyzed. CONCLUSIONS: A substantial proportion of SNSCCs carried alterations in EGFR or ERBB2. Together with the absence of KRAS mutations, these findings indicate that therapies targeting these molecules may be promising additions to the therapeutic options for patients with SNSCC. Cancer 2012;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background. Sinonasal squamous cell carcinomas (SCCs) are rare tumors with no etiologic link to tobacco and alcohol, as opposed to other SCCs of the head and neck (HNSCC). Little is known about the genetic changes in sinonasal SCC. Methods. DNA copy number changes of sinonasal SCC were analyzed by multiplex ligation-dependent probe amplification (MLPA) and microarray comparative genomic hybridization (maCGH), and results were related to clinicopathologic features. Results. Copy number losses most frequently included genes at 9p21, 13q14, 17p13, 17q21, and 18q11. Frequent gains were observed on 8q24, 11q13, 17q12, 19p13, and 20q11-q13. Conclusion. The genomic profile of sinonasal SCC showed a number of chromosomal regions with copy number changes similar to those known in HNSCC, in spite of the differences in etiology. [ABSTRACT FROM AUTHOR]

Sinonasal squamous cell carcinoma (SNSCC) is an aggressive tumor predominantly arising in the maxillary sinus and nasal cavities. Advances in imaging, surgical and radiotherapeutic techniques have reduced complications and morbidity; however, the prognosis generally remains poor, with an overall 5-year survival rate of 30–50%. As immunotherapy may be a new therapeutic option, we analyzed CD8+ tumor-infiltrating lymphocytes (TILs) and the tumor microenvironment immune type (TMIT, combining CD8+ TILs and PD-L1) in a series of 57 SNSCCs. Using immunohistochemistry, tissue samples of 57 SNSCCs were analyzed for expression of CD8 on TILs and of PD-L1 on tumor cells. The results were correlated to the clinical and survival data. In total, 88% (50/57) of the tumors had intratumoral CD8+ TILs; 19% (11/57)—CD8high (>10%); and 39/57 (68%)—CD8low (1–10%). PD-L1 positivity (>5%) was observed in 46% (26/57) of the SNSCCs and significantly co-occurred with CD8+ TILs (p = 0.000). Using univariate analysis, high intratumoral CD8+ TILs and TMIT I (CD8high/PD-L1pos) correlated with a worse survival rate. These results indicate that SNSCCs are immunogenic tumors, similar to head and neck squamous cell carcinomas. Nineteen percent of the cases were both CD8high and PD-L1pos and this subgroup may benefit from therapy with immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Simple Summary: The role of the immune response to cancer is of increasing importance, with a determining role in the response to the treatments and prognosis of patients. In this work, we studied whether the immune response (local and systemic) can influence the treatment response and prognosis of patients with laryngeal and hypopharyngeal carcinoma receiving induction chemotherapy (ICT). We observed that the relationship between neutrophils and lymphocytes (NLR) in peripheral blood and PD-L1 expression in the tumor is related to ICT response and patient prognosis. The identification of new biomarkers related to the immune response may allow a better selection of treatments and the identification of potential therapeutic targets. Our goal was to assess the correlation of immune parameters with the response to induction chemotherapy (ICT) in head and neck squamous cell carcinoma (HNSCC) patients. Pretreatment biopsies from 64 patients with HNSCC that received ICT were assessed for PD-L1 protein expression and density of CD8+ and FOXP3+ tumor infiltrating lymphocytes (TIL). In addition, the neutrophil-to-lymphocyte ratio (NLR) was calculated from pretreatment whole blood counts. In total, 55% of cases exhibited PD-L1 combined proportion score (CPS) positivity (≥1% stained cells). PD-L1 CPS positivity correlated with a high density of both CD8+ (p = 0.01) and FOXP3+ (p < 0.001) TILs. There was no correlation between PD-L1 expression or TIL density and NLR values. In univariate analyses, the absence of PD-L1 CPS expression (p = 0.042) and a high NLR (p = 0.034) were significantly correlated with response to ICT. Neither CD8+ TIL (p = 0.99) nor FOXP3+ TIL densities (p = 0.71) were associated with response to ICT. In multivariate analysis, only a high NLR was associated with response to ICT (HR = 4.06, 95% CI = 1.06–15.5, p = 0.04). In addition, a high NLR was also independently associated with lower disease-specific (p = 0.03) and overall survival rates (p = 0.04), particularly in the subset of patients who received definitive surgical treatment. These results suggest that NLR could emerge as a predictive biomarker of response to ICT. [ABSTRACT FROM AUTHOR]

The presence of tumor-infiltrating lymphocytes (TIL) in the tumor microenvironment has been demonstrated to be of prognostic value in various cancers. In this systematic review and meta-analysis, we investigated the prognostic value of TIL in laryngeal squamous cell carcinoma (LSCC). We performed a systematic search in PubMed for publications that investigated the prognostic value of TIL in LSCC. A meta-analysis was performed including all studies assessing the association between TIL counts in hematoxylin-eosin (HE)-stained sections, for CD8+ and/or CD3+/CD4+ TIL and overall survival (OS) or disease-free survival (DFS). The pooled meta-analysis showed a favorable prognostic role for stromal TIL in HE sections for OS (HR 0.57, 95% CI 0.36–0.91, p = 0.02), and for DFS (HR 0.56, 95% CI 0.34–0.94, p = 0.03). High CD8+ TIL were associated with a prolonged OS (HR 0.62, 95% CI 0.4–0.97, p = 0.04) and DFS (HR 0.73, 95% CI 0.34–0.94, p = 0.002). High CD3+/CD4+ TIL demonstrated improved OS (HR 0.32, 95% CI 0.16–0.9, p = 0.03) and DFS (HR 0.23, 95% CI 0.10–0.53, p = 0.0005). This meta-analysis confirmed the favorable prognostic significance of TIL in LSCC. High stromal TIL evaluated in HE sections and intra-tumoral and stromal CD3+, CD4+ and/or CD8+ TIL might predict a better clinical outcome. [ABSTRACT FROM AUTHOR]

Simple Summary: There are no randomized studies comparing organ-preservation protocols with chemo-selection to the classical total laryngectomy plus (chemo)radiotherapy. Thus, we performed a matched-pair analysis to compare these two treatments with respect to locoregional control, disease-specific survival (DSS), and overall survival (OS) in patients with locally advanced squamous cell carcinoma of the larynx and hypopharynx. The results did not show differences between the two treatments for patients with T3/T4a larynx and T2–T4a hypopharynx cancer with respect to OS and DSS, locoregional control, and metastasis-free survival. Background: We performed a comparative analysis between an organ-preservation protocol and surgery followed by radiotherapy in patients with locally advanced squamous cell carcinoma of the larynx and hypopharynx; Methods: 60 previously untreated patients who were treated with induction chemotherapy followed by chemoradiotherapy in responders were compared with a control group of 60 patients treated with up-front surgery. Both groups were statistically comparable, according to the subsite, TNM (tumor-node-metastasis) stage, age, and sex; Results: Mean age was 58 years and 92% were male. No significant statistical difference was observed for overall survival (OS) (HR 0.75; 95% CI 0.48–1.18; P = 0.22) and disease-specific survival (DSS) (HR 0.98; 95% CI 0.52–1.83, P = 0.96). Also, there was no significant difference for recurrence-free survival (HR 0.931; 95% CI 0.57–1.71; P = 0.81), metastases-free survival (HR 2.23; 95% CI 0.67–7.41; P = 0.19), and the appearance of second primary tumors (HR 1.22; 95% CI 0.51–2.88; P = 0.64); Conclusions: The results of the organ-preservation approach did not appear inferior to those of surgery plus (chemo)radiotherapy for patients with T3/T4a larynx and T2–T4a hypopharynx cancer with respect to OS and DSS, locoregional control and metastases-free survival. [ABSTRACT FROM AUTHOR]

Objective: To determine the effectiveness and outcomes of SND in the treatment of patients with squamous cell carcinoma of the head and neck (SCCHN) with clinically positive neck (cN+) at diagnosis.Material and Methods: We retrospectively reviewed 159 patients with SCCHN with cN+ at diagnosis, who underwent a SND with curative intent at a tertiary care academic teaching hospital in Spain. We registered patient and tumor characteristics, date and site of recurrences, together with the outcomes. Survival rates were calculated by the Kaplan-Meier method. The minimum follow-up was 18 months or till death.Results: A total of 28 neck recurrences were found in the whole series but only 10 neck recurrences occurred in absence of local recurrence. The regional control in the neck in absence of local recurrence was observed in 94% of patients. The neck recurrence rates did not correlated with the pN classification (P = 0.49), the administration of postoperative radiotherapy (P = 0.49) or extranodal extension (P = 0.43). The 5-year regional recurrence-free survival rate was 80% and 92% if only isolated neck recurrences are considered.Conclusions: SND offers an effective and oncologically safe surgical procedure in selected patients with clinically positive metastatic nodes in the neck. Our findings suggest that in cN1 and cN2 tumors, SND could replace the modified radical neck dissection without compromising oncologic efficacy. [ABSTRACT FROM AUTHOR]

BACKGROUND Intralesional methotrexate (il-MTX) has been used as neoadjuvant therapy for cutaneous squamous cell carcinoma (cSCC) but studies on its effects on tumor thickness are lacking. OBJECTIVE The objective of this study was to evaluate il-MTX response with ultrasound examination. METHODS The authors conducted a prospective study in 40 patients with histologically confirmed cSCC. Neodjuvant il-MTX therapy was administered before surgery. Ultrasound evaluation was performed before the first infiltration and before surgical treatment. RESULTS Response to neoadjuvant treatment was observed in 92.5% of patients, both clinically and sonographically. There was a good correlation between both types of measurements, with r = 0.892 for the minor diameter and r = 0.944 for the major diameter (p < .001). The authors found an ultrasound overestimation compared to the clinical measurements in 92.5% of patients (mean overestimation: 1.08 mm). There was a good correlation between ultrasound and histological measurements in tumor thickness with r = 0.932 (p < .01), with an ultrasound overestimation in 97.5% of cases (mean overestimation: 0.90 mm). CONCLUSION Neoadjuvant il-MTX can reduce not only surface tumor dimensions but also tumor thickness. Ultrasound improves treatment response control with greater accuracy than clinical assessment alone. [ABSTRACT FROM AUTHOR]

Abstract The pattern of clinical behaviour and response to treatment of recurrent and/or metastatic head and neck squamous cell carcinoma is heterogeneous. Treatment strategies that can be employed vary from potentially curative salvage surgery and re-irradiation to palliative systemic therapies and best supportive care. The advent of new therapeutic options, in terms of more sophisticated surgical approaches and techniques, highly conformal and precise radiation techniques and immunotherapy may offer improved control of disease and longer survival. Moreover, the epidemiological changes during the last decades, including the increase of human papilloma virus-related oropharyngeal primary tumors, are also reflected in the recurrent and metastatic setting. In this complex context the identification of predictive and prognostic factors is urgently needed to tailor treatment, to increase its efficacy, and to avoid unnecessary toxicities. A better knowledge of prognosis may also help the patients and caregivers in decision making on the optimal choice of care. The purpose of our review is to highlight the current evidence and shortcomings in this field. [ABSTRACT FROM AUTHOR]