Clinical utility of liquid biopsy and integrative genomic profiling in early-stage and oligometastatic cancer patients treated with radiotherapy.

BACKGROUND: Liquid biopsy and Integrative Genomic Profiling (IGP) are yet to be implemented into routine Radiation Oncology. Here we assess the utility of germline, tumour and circulating cell-free DNA-based genomic analyses for the clinical management of early-stage and oligometastatic cancer patients treated by precision radiotherapy. METHODS: We performed germline, tissue- and liquid biopsy NGS panels on 50 early-stage/oligometastatic cancer patients undergoing radiotherapy. We also monitored ctDNA variants in serial liquid biopsies collected during radiotherapy and follow-up and evaluated the clinical utility of such comprehensive approach. RESULTS: The integration of different genomic studies revealed that only 1/3 of the liquid biopsy variants are of tumour origin. Altogether, 55 tumour variants (affecting 3/4 of the patients) were considered potentially actionable (for treatment and prognosis), whereas potential follow-up biomarkers were identified in all cases. Germline cancer-predisposing variants were present in three patients, which would have not been eligible for hereditary cancer testing according to clinical guidelines. The presence of detectable ctDNA variants before radiotherapy was associated with progression-free survival both in oligometastatic patients and in those with early-stage. CONCLUSIONS: IGP provides both valuable and actionable information for personalised decision-making in Radiation Oncology.

CANVAS: A New Genetic Entity in the Otorhinolaryngologist's Differential Diagnosis.

OBJECTIVE: The biallelic inheritance of an expanded intronic pentamer (AAGGG)exp in the gene encoding replication factor C subunit 1 (RFC1) has been found to be a cause of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS). This study describes clinical and genetic features of our patients with clinical suspicion of the syndrome. STUDY DESIGN: A retrospective descriptive study from an ataxia database comprising 500 patients. SETTING: The study was performed at the Otorhinolaryngology Department of a hospital in the north of Spain. METHODS: Specific genetic testing for CANVAS was performed in 13 patients with clinical suspicion of complete or incomplete syndrome. The clinical diagnosis was supported by quantitative vestibular hypofunction, cerebellar atrophy, and abnormal sensory nerve conduction testing. RESULTS: Nine of 13 (69%) patients met clinical diagnostic criteria for definite CANVAS disease. The first manifestation of the syndrome was lower limb dysesthesia in 8 of 13 patients and gait imbalance in 5 of 13. Eleven of 13 (85%) patients were carriers of the biallelic (AAGGG)exp in RFC1. CONCLUSION: A genetic cause of CANVAS has recently been discovered. We propose genetic screening for biallelic expansions of the AAGGG pentamer of RFC1 in all patients with clinical suspicion of CANVAS, since accurate early diagnosis could improve the quality of life of these patients.

Next-generation sequencing for identification of actionable gene mutations in intestinal-type sinonasal adenocarcinoma.

Intestinal-type sinonasal adenocarcinoma (ITAC) is a rare tumor carrying poor prognosis and needing new treatment options. The aim of this study was to identify actionable gene mutations that can guide new personalized target-specific therapies in ITAC patients. A series of 48 tumor and 27 corresponding germline DNA samples were analyzed by next generation sequencing using a panel of 120 genes. In total, 223 sequence variants were found in 70 genes. Matched tumor/germline comparison in 27 cases revealed that 57% were in fact germline variants. In 20 of these 27 cases, 58 somatic variants in 33 different genes were identified, the most frequent being PIK3CA (5 cases), APC and ATM (4 cases), and KRAS, NF1, LRP1B and BRCA1 (3 cases). Many of the somatic gene variants affected PI3K, MAPK/ERK, WNT and DNA repair signaling pathways, although not in a mutually exclusive manner. None of the alterations were related to histological ITAC subtype, tumor stage or survival. Our data showed that thorough interpretation of somatic mutations requires sequencing analysis of the corresponding germline DNA. Potentially actionable somatic mutations were found in 20 of 27 cases, 8 of which being biomarkers of FDA-approved targeted therapies. Our data implicate new possibilities for personalized treatment of ITAC patients.

The Pan-Cancer Landscape of Coamplification of the Tyrosine Kinases KIT, KDR, and PDGFRA.

PURPOSE: Amplifications of receptor tyrosine kinases (RTKS) are therapeutic targets in multiple tumor types (e.g. HER2 in breast cancer), and amplification of the chromosome 4 segment harboring the three RTKs KIT, PDGFRA, and KDR (4q12amp) may be similarly targetable. The presence of 4q12amp has been sporadically reported in small tumor specific series but a large-scale analysis is lacking. We assess the pan-cancer landscape of 4q12amp and provide early clinical support for the feasibility of targeting this amplicon. EXPERIMENTAL DESIGN: Tumor specimens from 132,872 patients with advanced cancer were assayed with hybrid capture based comprehensive genomic profiling which assays 186-315 genes for all classes of genomic alterations, including amplifications. Baseline demographic data were abstracted, and presence of 4q12amp was defined as 6 or more copies of KIT/KDR/PDGFRA. Concurrent alterations and treatment outcomes with matched therapies were explored in a subset of cases. RESULTS: Overall 0.65% of cases harbored 4q12amp at a median copy number of 10 (range 6-344). Among cancers with >100 cases in this series, glioblastomas, angiosarcomas, and osteosarcomas were enriched for 4q12amp at 4.7%, 4.8%, and 6.4%, respectively (all p < 0.001), giving an overall sarcoma (n = 6,885) incidence of 1.9%. Among 99 pulmonary adenocarcinoma cases harboring 4q12amp, 50 (50%) lacked any other known driver of NSLCC. Four index cases plus a previously reported case on treatment with empirical TKIs monotherapy had stable disease on average exceeding 20 months. CONCLUSION: We define 4q12amp as a significant event across the pan-cancer landscape, comparable to known pan-cancer targets such as NTRK and microsatellite instability, with notable enrichment in several cancers such as osteosarcoma where standard treatment is limited. The responses to available TKIs observed in index cases strongly suggest 4q12amp is a druggable oncogenic target across cancers that warrants a focused drug development strategy. IMPLICATIONS FOR PRACTICE: Coamplification of the receptor tyrosine kinases (rtks) KIT/KDR/PDGFRA (4q12amp) is present broadly across cancers (0.65%), with enrichment in osteosarcoma and gliomas. Evidence for this amplicon having an oncogenic role is the mutual exclusivity of 4q12amp to other known drivers in 50% of pulmonary adenocarcinoma cases. Furthermore, preliminary clinical evidence for driver status comes from four index cases of patients empirically treated with commercially available tyrosine kinase inhibitors with activity against KIT/KDR/PDGFRA who had stable disease for 20 months on average. The sum of these lines of evidence suggests further clinical and preclinical investigation of 4q12amp is warranted as the possible basis for a pan-cancer drug development strategy.

Effect of eccentric overload through isoinertial technology in basketball players / Efeito da sobrecarga excêntrica através da tecnologia isoinercial em jogadores profissionais de basquetebol

Abstract The present study investigated the effect of eccentric overload on professional basketball players. Participants were 8 players aged 18-25 years who play in a Leb Oro League team. There was an 8 week training cycle with 1 weekly session of half squats. The control group performed training following a traditional methodology -using free weights- whereas the experimental group used inertial technology, that is, the ProSquat machine from Proinertial®. Both vertical jump and 30-meter sprint were assessed before and after intervention. The following conclusions were reached: a) strength training with vertical vector improves the 30-meter sprint test and also the vertical jump; b) training program that affects the eccentric overload of the movement results in more improvements than traditional training with the same duration; c) training in the vertical vector also has an impact on the way force is manifested in the horizontal vector, showing improvements in the 30-meter sprint.

Resumo O presente estudo investigou o efeito da sobrecarga excêntrica em jogadores profissionais de basquetebol. Os participantes foram 8 jogadores de uma equipe da Leb Gold League entre 18 e 25 anos. Um ciclo de treinamento de 8 semanas foi realizado com 1 sessão semanal no exercício de meio agachamento. O grupo controle realizou o treinamento com metodologia tradicional, com pesos livres, e o grupo experimental, por meio de tecnologia inercial, com a máquina ProSquat, Proinertial®. O salto vertical e o sprint de 30 metros foram avaliados antes e após a intervenção. As seguintes conclusões foram obtidas: a) o treinamento de força com um componente no vetor vertical mostra melhorias no teste de 30 metros e no salto vertical; b) um programa que afeta a sobrecarga de movimento excêntrico apresenta resultados com melhores desempenhos do que o treinamento tradicional; c) o treinamento no vetor vertical também afeta uma expressão da força no vetor horizontal, mostrando melhorias no sprint de 30 metros.

A novel molecular diagnostics platform for somatic and germline precision oncology.

BACKGROUND: Next-generation sequencing (NGS) opens new options in clinical oncology, from therapy selection to genetic counseling. However, realization of this potential not only requires succeeding in the bioinformatics and interpretation of the results, but also in their integration into the clinical practice. We have developed a novel NGS diagnostic platform aimed at detecting (1) somatic genomic alterations associated with the response to approved targeted cancer therapies and (2) germline mutations predisposing to hereditary malignancies. METHODS: Next-generation sequencing libraries enriched in the exons of 215 cancer genes (97 for therapy selection and 148 for predisposition, with 30 informative for both applications), as well as selected introns from 17 genes involved in drug-related rearrangements, were prepared from 39 tumors (paraffin-embedded tissues/cytologies), 36 germline samples (blood) and 10 cell lines using hybrid capture. Analysis of NGS results was performed with specifically developed bioinformatics pipelines. RESULTS: The platform detects single-nucleotide variants (SNVs) and insertions/deletions (indels) with sensitivity and specificity >99.5% (allelic frequency ≥0.1), as well as copy-number variants (CNVs) and rearrangements. Somatic testing identified tailored approved targeted drugs in 35/39 tumors (89.74%), showing a diagnostic yield comparable to that of leading commercial platforms. A somatic EGFR p.E746_S752delinsA mutation in a mediastinal metastasis from a breast cancer prompted its anatomopathologic reassessment, its definite reclassification as a lung cancer and its treatment with gefitinib (partial response sustained for 15 months). Testing of 36 germline samples identified two pathogenic mutations (in CDKN2A and BRCA2). We propose a strategy for interpretation and reporting of results adaptable to the aim of the request, the availability of tumor and/or normal samples and the scope of the informed consent. CONCLUSION: With an adequate methodology, it is possible to translate to the clinical practice the latest advances in precision oncology, integrating under the same platform the identification of somatic and germline genomic alterations.

Intensity-modulated radiotherapy for head and neck surgeons.

The development of intensity-modulated radiotherapy (IMRT) has played a major role in improving outcomes and decreasing morbidity in patients with head and neck cancer. This review addresses this vital modality with a focus on the important role of the head and neck surgeon. The technique as well as its benefits and points of caution are outlined, the definitions of tumor and treatment volumes are discussed, and the dose and fractionation are detailed. Following this are several sections dedicated to the role of the head and neck surgeon in the planning of both definitive and postoperative radiotherapy to the primary site and neck. There is a focus throughout on anatomic and surgical considerations; commonly encountered situations are illustrated. With a deeper understanding of this technique and their own pivotal contribution to target delineation, head and neck surgeons will be poised to expand their role and improve cancer care for their patients. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2368-E2373, 2016.

Cell-cell adhesion genes CTNNA2 and CTNNA3 are tumour suppressors frequently mutated in laryngeal carcinomas.

Laryngeal squamous cell carcinoma is a frequent and significant cause of morbidity and mortality. Here we explore the biological basis of this aggressive tumour, and identify two cell-cell adhesion genes as recurrently mutated in this malignancy. We first perform exome sequencing of four laryngeal carcinomas and their matched normal tissues. Among the 569 genes found to present somatic mutations, and based on their recurrence or functional relevance in cancer, we select 40 for further validation in 86 additional laryngeal carcinomas. We detect frequent mutations (14 of 90, 15%) in CTNNA2 and CTNNA3-encoding α-catenins. Functional studies reveal an increase in the migration and invasive ability of head and neck squamous cell carcinoma cells producing mutated forms of CTNNA2 and CTNNA3 or in cells where both α-catenins are silenced. Analysis of the clinical relevance of these mutations demonstrates that they are associated with poor prognosis. We conclude that CTNNA2 and CTNNA3 are tumour suppressor genes frequently mutated in laryngeal carcinomas.

Prelamin A causes progeria through cell-extrinsic mechanisms and prevents cancer invasion.

Defining the relationship between ageing and cancer is a crucial but challenging task. Mice deficient in Zmpste24, a metalloproteinase mutated in human progeria and involved in nuclear prelamin A maturation, recapitulate multiple features of ageing. However, their short lifespan and serious cell-intrinsic and cell-extrinsic alterations restrict the application and interpretation of carcinogenesis protocols. Here we present Zmpste24 mosaic mice that lack these limitations. Zmpste24 mosaic mice develop normally and keep similar proportions of Zmpste24-deficient (prelamin A-accumulating) and Zmpste24-proficient (mature lamin A-containing) cells throughout life, revealing that cell-extrinsic mechanisms are preeminent for progeria development. Moreover, prelamin A accumulation does not impair tumour initiation and growth, but it decreases the incidence of infiltrating oral carcinomas. Accordingly, silencing of ZMPSTE24 reduces human cancer cell invasiveness. Our results support the potential of cell-based and systemic therapies for progeria and highlight ZMPSTE24 as a new anticancer target.

Refining the role of PMS2 in Lynch syndrome: germline mutational analysis improved by comprehensive assessment of variants.

BACKGROUND AND AIM: The majority of mismatch repair (MMR) gene mutations causing Lynch syndrome (LS) occur either in MLH1 or MSH2. However, the relative contribution of PMS2 is less well defined. The aim of this study was to evaluate the role of PMS2 in LS by assessing the pathogenicity of variants of unknown significance (VUS) detected in the mutational analysis of PMS2 in a series of Spanish patients. METHODS: From a cohort of 202 LS suspected patients, 13 patients showing loss of PMS2 expression in tumours were screened for germline mutations in PMS2, using a long range PCR based strategy and multiplex ligation dependent probe amplification (MLPA). Pathogenicity assessment of PMS2 VUS was performed evaluating clinicopathological data, frequency in control population and in silico and in vitro analyses at the RNA and protein level. RESULTS: Overall 25 different PMS2 DNA variants were detected. Fourteen were classified as polymorphisms. Nine variants were classified as pathogenic: seven alterations based on their molecular nature and two after demonstrating a functional defect (c.538-3C>G affected mRNA processing and c.137G>T impaired MMR activity). The c.1569C>G variant was classified as likely neutral while the c.384G>A remained as a VUS. We have also shown that the polymorphic variant c.59G>A is MMR proficient. CONCLUSIONS: Pathogenic PMS2 mutations were detected in 69% of patients harbouring LS associated tumours with loss of PMS2 expression. In all, PMS2 mutations account for 6% of the LS cases identified. The comprehensive functional analysis shown here has been useful in the classification of PMS2 VUS and contributes to refining the role of PMS2 in LS.

Novel germline CDKN2A mutation associated with head and neck squamous cell carcinomas and melanomas.

BACKGROUND: The ability to identify individuals at increased risk of cancer is of immediate clinical relevance. Germline mutations in the CDKN2A locus, encoding the key tumor suppressor proteins p16/INK4A and p14/ARF, are frequently present in kindreds with hereditary cutaneous melanoma but have seldom been reported in families with genetic susceptibility to head and neck squamous cell carcinomas (HNSCC). METHODS: We report the pedigree of a patient with an unusually high incidence of HNSCC and melanomas. CDKN2A mutation analysis was performed with standard capillary sequencing and multiplex ligation-dependent probe amplification. RESULTS: A previously unreported germline CDKN2A mutation affecting only the p16/INK4A open reading frame, c.106delG (p.Ala36ArgfsX17), was detected in the proband. This mutation causes a premature termination codon. CONCLUSIONS: Our report emphasizes the need to consider germinal CDKN2A mutations in the differential diagnosis of familial HNSCC and the importance of awareness of these tumors in carriers of CDKN2A mutations.

Néstor-Guillermo progeria syndrome: a novel premature aging condition with early onset and chronic development caused by BANF1 mutations.

Progeria syndromes are rare disorders that involve premature aging. Mutations in BANF1 have been recently reported to cause a new hereditary progeroid syndrome that we now propose to call the Néstor-Guillermo progeria syndrome (NGPS). We describe herein the clinical features of the first two NGPS patients, who phenocopy features of classic progerias (i.e., Hutchinson-Gilford progeria syndrome or mandibuloacral dysplasia), such as aged appearance, growth retardation, decreased subcutaneous fat, thin limbs, and stiff joints. However, these NGPS patients have a distinctive phenotype. In their early adulthood (32 and 24 years of age), they have no signs of cardiovascular impairment, diabetes mellitus, or hypertriglyceridemia. In contrast, they suffer profound skeletal abnormalities that affect their quality of life. The observed differences are of utmost importance to patients and their families and palliation of osseous manifestations is a priority, given their relatively long lifespan. We define NGPS as a chronic progeria because of its slow clinical course and relatively long survival, despite its early onset. Understanding the differences between progeria syndromes might contribute to the development of treatment strategies for common skeletal conditions, as well as aging itself.

Novel germline SDHD deletion associated with an unusual sympathetic head and neck paraganglioma.

BACKGROUND: Paragangliomas (PGLs) are rare tumors arising either from sympathetic or parasympathetic-associated chromaffin tissue. PGLs can occur either sporadically or as part of a hereditary syndrome. Sympathetic head and neck PGLs are extremely rare tumors and only a few cases have been reported to date. METHODS: We report the pedigree of a patient with a head and neck PGL arising from the right sympathetic trunk. SDHD mutation analysis was performed using standard sequencing, multiplex ligation-dependent probe amplification, chromosome 11-specific comparative genome hybridization, and long-range/short-range polymerase chain reaction (PCR) approaches. RESULTS: A previously unreported chromosome 11q deletion encompassing 5 annotated genes (SDHD, DLAT, PIH1D2, C11Orf57, and TIMM8B) was detected in the proband. CONCLUSION: PGL families considered "mutation-negative" may be attributable to large gene deletions not detectable by standard sequencing methods. Therefore, deletion analysis should be offered to families or individuals at risk for hereditary PGLs.

[Prognostic significance of angiogenesis in surgically treated supraglottic squamous cell carcinomas of the larynx]. / Significado pronóstico de la angiogénesis en los carcinomas epidermoides de laringe supraglótica tratados con cirugía.

INTRODUCTION AND OBJECTIVES: It is now generally accepted that angiogenesis is crucial in tumour growth. However, controversy still exists regarding the prognostic significance of angiogenesis in head and neck carcinomas. The aim of this paper is to determine the prognostic significance of angiogenesis in a homogeneously treated group of supraglottic squamous cell carcinomas. MATERIAL AND METHODS: 108 patients surgically treated for squamous cell carcinoma of the supraglottic larynx were studied. Angiogenesis was estimated in the primary tumour and in the nodal metastases by determining microvessel density using the "hot spot" method. Anti-CD34 antibody was used to stain blood vessels. RESULTS: The mean microvessel density in primary tumours was 72+/-34 vessels/mm(2) and 58.5+/-31.5 vessels/mm(2) in nodal metastases. No correlation was found between microvessel density in the primary tumours and the corresponding nodal metastasis (P=0.195). No significant differences in microvessel density were observed in relation to clinico-pathological parameters or survival (P=0.19). CONCLUSIONS: Our results suggest that microvessel density is not a useful prognostic marker in surgically treated supraglottic squamous cell carcinomas.

The Stem Cell Network model: clinical implications in cancer.

This review will discuss the aspects of stem cell biology that can contribute to explain tumor development and why standard oncology treatments sometimes fail. We also propose an integrated model of tumor progression based on the putative occurrence of Stem Cell Networks (SCNs). In a SCN, the somatic stem cells are derived from a common embryonic stem cell, share a specific molecular profile and maintain a high degree of cell-cycle synchronization. In the study of cancer, the SCN model introduces an additional conceptual frame to the interpretation of both the cancer stem cell (CSC) hypothesis and the field cancerization concept. The CSC model may explain how the cancer fields develop, justifies their sizes and shapes, contribute to explain the local recurrences in patients with free margins, the second primary tumors, the success of organ preserving surgical approaches or the trend of different tumors to metastasize to certain locations. We propose that the SCN model of cancer provides some clues for further understanding tumor progression and raises promising experimental and clinical implications.

[Is it necessary to perform neck dissections as a staged procedure in laser supraglottic laryngectomy?]. / Es necesario diferir los vaciamientos cervicales en las laringectomías supraglóticas con láser?

INTRODUCTION AND OBJECTIVES: Endoscopic CO2 laser supraglottic laryngectomy has similar oncological results to the classical open approach. Treatment of the neck is of paramount importance in these tumours and it is usually performed as a staged procedure. The aim of this work is to ascertain if it is safe to perform the neck dissections at the same time as the laser supraglottic laryngectomy. METHODS: Twenty-four patients with supraglottic epidermoid carcinoma, who underwent laser CO2 supraglottic laryngectomy and bilateral neck dissection, were studied. In 12 patients the neck dissections were performed as a staged procedure (a mean of 15 days after the laryngectomy), and in the remaining 12 they were performed simultaneously. Both groups were comparable in terms of age and the staging of their tumours. RESULTS: No significant differences were found between the groups in terms of surgical complications (P=.18), tracheostomy rates (1 post-operative tracheostomy in each group; P=.99), aspiration pneumonia (P=.48), and the mean for nasogastric tube feeding (P=.36). The mean hospital stay was five days longer in the group with staged neck dissections. CONCLUSIONS: It is a safe procedure to perform neck dissections at the same time as the supraglottic laryngectomy. We did not find any increase in the complications rate and the hospital stay was shorter.

Membrane-bound serine protease matriptase-2 (Tmprss6) is an essential regulator of iron homeostasis.

Proteolytic events at the cell surface are essential in the regulation of signal transduction pathways. During the past years, the family of type II transmembrane serine proteases (TTSPs) has acquired an increasing relevance because of their privileged localization at the cell surface, although our current understanding of the biologic function of most TTSPs is limited. Here we show that matriptase-2 (Tmprss6), a recently described member of the TTSP family, is an essential regulator of iron homeostasis. Thus, Tmprss6(-/-) mice display an overt phenotype of alopecia and a severe iron deficiency anemia. These hematologic alterations found in Tmprss6(-/-) mice are accompanied by a marked up-regulation of hepcidin, a negative regulator of iron export into plasma. Likewise, Tmprss6(-/-) mice have reduced ferroportin expression in the basolateral membrane of enterocytes and accumulate iron in these cells. Iron-dextran therapy rescues both alopecia and hematologic alterations of Tmprss6(-/-) mice, providing causal evidence that the anemic phenotype of these mutant mice results from the blockade of intestinal iron export into plasma after dietary absorption. On the basis of these findings, we conclude that matriptase-2 activity represents a novel and relevant step in hepcidin regulation and iron homeostasis.

[Molecular alterations in nodal metastases and its primary tumors in squamous cell carcinomas of the larynx]. / Alteraciones moleculares en las metástasis ganglionares y sus tumores primarios en los carcinomas epidermoides de laringe.

INTRODUCTION AND OBJECTIVES: The successive acquisition of molecular alterations determines tumour progression. During this progression, the development of nodal metastases is one of the most important prognostic factors in laryngeal squamous cell carcinomas. The aim of this study is to analyze if, in these carcinomas, the molecular alterations in the nodal metastases are different from those present in the primary tumour. MATERIAL AND METHOD: Paired samples of primary tumour and nodal metastases from 51 patients with squamous cell carcinoma of the supraglottic larynx were studied. Using immunohistochemistry, we analyzed the expression of p53, E-cadherin, FAK, annexin A2 and HIF-1a proteins. In addition, the apoptotic index (measuring activated caspase-3) and the degree of vascularization (identified by CD34 antigen expression) were also studied. RESULTS: A close correlation in the expression of the proteins studied was observed in the nodal metastases and the corresponding primary tumour, with the exception of HIF-1a expression and the degree of vascularization. CONCLUSIONS: Most of the molecular alterations in the nodal metastases are already present in the primary tumour, suggesting that these alterations are early events in carcinogenesis.

Oncologic outcomes of transoral laser surgery of supraglottic carcinoma compared with a transcervical approach.

BACKGROUND: To evaluate the oncologic effectiveness of transoral laser surgery of supraglottic cancer, we compared a group of patients treated with laser surgery, with a stage-matched group treated with a transcervical approach. METHODS: Twenty-six patients who underwent laser surgery were retrospectively compared with 26 patients who underwent a transcervical approach. In both groups, the patients were classified as follows: 8% stage I, 23% stage II, 46% stage III, and 23% stage IV. RESULTS: The 5-year disease-specific survival rates were 80% for the laser group and 72% for the transcervical group (p = .5). The ultimate 5-year laryngeal preservation rate was 86% in the laser group and 80% in the transcervical group (p = .6). In both arms, all patients classified as T1 and T2 who survived 5 years after the surgical treatment of tumors retained the larynx. CONCLUSIONS: The oncologic results of transoral laser surgery of supraglottic cancer are equivalent to those of the classic transcervical approach.

Supraglottic laryngectomy: analysis of 267 cases.

Horizontal supraglottic laryngectomy (HSL) allows the preservation of a functioning larynx and avoids permanent tracheotomy. In this retrospective study we report our experience with HSL and describe the functional and oncological results of the procedure. A total of 267 previously untreated patients with squamous cell carcinoma of the supraglottis underwent a supraglottic laryngectomy at our Department from January 1978 to May 2002. The main outcome measures were: local and regional control, disease-specific survival and laryngeal preservation rate. The overall recurrence rate was 29% (78/267). The local recurrence rate was 8% (22 patients) and the regional recurrence rate was 17% (45 patients). The 5-year disease-specific survival rate was 73%. The 5-year laryngeal preservation rate was 82%. Multivariate analysis showed two parameters that were independent predictors of a reduced disease specific survival: cervical lymph node metastases of class N3 (P = 0.0003) and primary tumour classified as T4 (P = 0.004). HSL provided, in our experience, an optimal locoregional oncological control for laryngeal preservation.