Immunotherapy for recurrent/metastatic head and neck cancer

Purpose of review In the last decade, after cetuximab (anti-epidermal growth factor receptor), none of the novel investigated compounds has demonstrated benefit in head and neck squamous cell cancers (HNSCC), both in advanced and curative settings. Therefore, prognosis of recurrent/metastatic (R/M) HNSCC patients remains dismal, especially in platinum-refractory cohort. In the last few years, a new important class of drugs has affirmed its role. HNSCC, even if less 'immunogenic' than other malignancies (e.g. melanoma), was field of application of several new immune agents. To date, the most important data regard drugs acting on PD-1 (programmed death-1)/PD-L1 (programmed death-ligand 1) axis that is a crucial checkpoint used by tumor for immune escape. Our purpose is to summarize the results of these PD-1/PD-L1 inhibitors, outlining some critical points and few practical suggestions. Recent findings Nivolumab was recently approved by main regulatory agencies as second-line treatment for platinum-refractory R/M HNSCC. In the same setting, pembrolizumab was approved by FDA. Atezolizumab and durvalumab have already showed similar benefit in phase Ia and II studies, respectively. Summary Anti-PD1/PD-L1 agents are new effective therapies in R/M HNSCC. Their combination with conventional/novel compounds, as well as a better selection of responding patients, could lead to improve current results. Correspondence to Salvatore Alfieri, MD, Department of Head and Neck Cancer Medical Oncology 3, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Giacomo Venezian 1, zip code 20133, Milan, Italy. Tel: +39 02 2390 2765; e-mail: salvatore.alfieri@istitutotumori.mi.it Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Reducing morbidity and complications after major head and neck cancer surgery: the (future) role of enhanced recovery after surgery protocols

Purpose of review To review the development and the benefits of enhanced recovery after surgery (ERAS) protocols in non-head and neck disciplines and to describe early implementation efforts in major head and neck surgeries. Recent findings Several groups have adopted ERAS protocols for major head and neck surgery and demonstrated its feasibility and effectiveness. Summary There is growing evidence that clinical and financial outcomes for patients undergoing major head and neck surgery rehabilitation can be significantly improved by standardizing preoperative, intraoperative, and postoperative treatment protocols. Current experience is limited to single centers. A future goal is to broaden the adoption of ERAS in head and neck surgical oncology to include national and international collaboration, data sharing, and learning. Correspondence to Gerhard F. Huber, MD, MSc, Lead Head & Neck surgical oncology, ENT clinic, University Hospital of Zurich, Frauenklinikstrasse 24, 8091 Zurich, Switzerland. Tel: +41 71 494 6433; fax: +41 71 494 2888; e-mail: gerry.huber@usz.ch; Surgical oncology, ENT clinic, Kantonsspital St. Gallen, Rorschacher Strasse 95, 9007 St. Gallen, Switzerland. E-mail: gerhard.huber@kssg.ch Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Association of the nod-like receptor 3 (NLRP3) gene variability with recurrent aphthous stomatitis in the Czech population

Abstract

Background

Recurrent aphthous stomatitis (RAS) is a multifactorial disease with unclear etiopathogenesis in which disturbance of immunological processes maybe involved. The aim of our study was to investigate three single nucleotide polymorphisms (SNPs) rs3806265, rs4612666, rs10754558 in NOD-like receptor 3 (NLRP3), the gene encoding the component of inflammasome, in patients with RAS and healthy controls in the Czech population.

Methods

A total of 207 subjects were included in this case-control study. Sixty-four patients with RAS and 143 healthy controls were genotyped by a method based on polymerase chain reaction using 5′ nuclease TaqMan^® assays. Detailed anamnestic, clinical and laboratory data were obtained from all subjects.

Results

The allele and genotype frequencies of NLRP3 polymorphisms (rs10754558 and rs3806265) between both groups were similar. However, statistically significant differences in NLRP3 rs4612666 genotypes between the patients with RAS and controls were found; carriers of the TT genotype had a higher risk of developing RAS than subjects with the CT+CC genotypes (OR=14.69, 95%CI=1.73-124.72, P=0.004, P_corr<0.05). No associations between NLRP3 haplotypes and RAS were observed.

Conclusions

Our study indicates that the NLRP3 rs4612666 polymorphism may be involved in the development of RAS in the Czech population.

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Immunotherapy for recurrent/metastatic head and neck cancer

Purpose of review In the last decade, after cetuximab (anti-epidermal growth factor receptor), none of the novel investigated compounds has demonstrated benefit in head and neck squamous cell cancers (HNSCC), both in advanced and curative settings. Therefore, prognosis of recurrent/metastatic (R/M) HNSCC patients remains dismal, especially in platinum-refractory cohort. In the last few years, a new important class of drugs has affirmed its role. HNSCC, even if less 'immunogenic' than other malignancies (e.g. melanoma), was field of application of several new immune agents. To date, the most important data regard drugs acting on PD-1 (programmed death-1)/PD-L1 (programmed death-ligand 1) axis that is a crucial checkpoint used by tumor for immune escape. Our purpose is to summarize the results of these PD-1/PD-L1 inhibitors, outlining some critical points and few practical suggestions. Recent findings Nivolumab was recently approved by main regulatory agencies as second-line treatment for platinum-refractory R/M HNSCC. In the same setting, pembrolizumab was approved by FDA. Atezolizumab and durvalumab have already showed similar benefit in phase Ia and II studies, respectively. Summary Anti-PD1/PD-L1 agents are new effective therapies in R/M HNSCC. Their combination with conventional/novel compounds, as well as a better selection of responding patients, could lead to improve current results. Correspondence to Salvatore Alfieri, MD, Department of Head and Neck Cancer Medical Oncology 3, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Giacomo Venezian 1, zip code 20133, Milan, Italy. Tel: +39 02 2390 2765; e-mail: salvatore.alfieri@istitutotumori.mi.it Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2BU3m2Y

Reducing morbidity and complications after major head and neck cancer surgery: the (future) role of enhanced recovery after surgery protocols

Purpose of review To review the development and the benefits of enhanced recovery after surgery (ERAS) protocols in non-head and neck disciplines and to describe early implementation efforts in major head and neck surgeries. Recent findings Several groups have adopted ERAS protocols for major head and neck surgery and demonstrated its feasibility and effectiveness. Summary There is growing evidence that clinical and financial outcomes for patients undergoing major head and neck surgery rehabilitation can be significantly improved by standardizing preoperative, intraoperative, and postoperative treatment protocols. Current experience is limited to single centers. A future goal is to broaden the adoption of ERAS in head and neck surgical oncology to include national and international collaboration, data sharing, and learning. Correspondence to Gerhard F. Huber, MD, MSc, Lead Head & Neck surgical oncology, ENT clinic, University Hospital of Zurich, Frauenklinikstrasse 24, 8091 Zurich, Switzerland. Tel: +41 71 494 6433; fax: +41 71 494 2888; e-mail: gerry.huber@usz.ch; Surgical oncology, ENT clinic, Kantonsspital St. Gallen, Rorschacher Strasse 95, 9007 St. Gallen, Switzerland. E-mail: gerhard.huber@kssg.ch Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2BmKZm6

Phacomatosis pigmentokeratotica: a case of HRAS mosaicism causing rhabdomyosarcoma

Abstract

A 17-year-old male presented with a large sebaceous naevus (SN) comprising part of his left face and scalp and a speckled lentiginous naevus (SLN) on his right trunk, hip, neck and scalp with a checkerboard pattern. His right oral hemimucosa showed extensive papillomatous lesions which were contiguous to the upper lip SN lesions. As for extracutaneous manifestations he suffered from cardiac, musculoskeletal and ocular alterations. On the other hand, he developed two primary rhabdomyosarcomas. DNA samples of the SN, SLN, the oral papillomatous hyperplasia and both rhabdomyosarcomas were analyzed by Sanger sequencing. A HRAS c.37G>C mutation was detected in all of them. Skin and blood DNA resulted wild type. PPK is characterized by the association of a sebaceous naevus with a papular naevus spilus and extracutaneous manifestations. Until not long ago, the etiopathogenetical hypothesis of didymosis was accepted. However, in 2013 Groesser et al. proved the existence of an activating HRAS mutation as the cause of this syndrome. A higher incidence of cancer has been observed in germline RASophaties. Furthermore, up to 30% of human cancers show dysregulation of the Ras-Raf-MEK-ERK pathways. In our patient, a HRAS mosaic mutation explains not only the cutaneous but also the extracutaneous manifestations. To our knowledge this is the first described case of PPK in which the existence of a HRAS mosaic mutation is the confirmed cause of rhabdomyosarcoma. Besides the HRAS 37G>C mutation has never been related to any type of rhabdomyosarcoma. Mosaicisms could be underdiagnosed causes of childhood tumours. As dermatologists we stand on a privileged position for the detection of these alterations.

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Patient, Surgeon, and Anesthesiologist Satisfaction: Who has the Priority?

No abstract available

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