ACR Appropriateness Criteria® Locoregional therapy for resectable oropharyngeal squamous cell carcinomas

BackgroundThere are no level I studies to guide treatment for resectable oropharyngeal squamous cell carcinoma (SCC). Treatment toxicities influence management recommendations. Ongoing investigations are examining deintensified treatments for human papillomavirus (HPV)‐associated oropharyngeal SCC.MethodsThe Appropriateness Criteria panel, using modified Delphi methodology, produced a literature summary, an assessment of treatment recommendations, and cases to illustrate their use.ResultsA multidisciplinary team produces optimum results. Based on HPV status, smoking history, and staging, patients are divided into groups at low, intermediate, and high‐risk of death. In the future, treatment recommendations may be influenced by HPV status, which has changed the epidemiology of oropharyngeal SCC.ConclusionT1 to T2N0M0 resectable oropharyngeal SCC can be treated with surgery or radiation without chemotherapy. Patients with T1‐2N1‐2aM0 disease can receive radiation, chemoradiation, or transoral surgery with neck dissection and appropriate adjuvant therapy. Patients with T1‐2N2b‐3M0 disease should receive chemoradiation or transoral surgery with neck dissection and appropriate adjuvant therapy. Concurrent chemoradiation is preferred for T3 to T4 disease. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1299–1309, 2016Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/133590/1/hed24447.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/133590/2/hed24447_am.pd

Current trends in initial management of hypopharyngeal cancer: The declining use of open surgery

Squamous cell carcinoma of the hypopharynx represents a distinct clinical entity. Most patients present with significant comorbidities and advanced‐stage disease. The overall survival is relatively poor because of high rates of regional and distant metastasis at presentation or early in the course of the disease. A multidisciplinary approach is crucial in the overall management of these patients to achieve the best results and maintain or improve functional results. Traditionally, operable hypopharyngeal cancer has been treated by total (occasionally partial) laryngectomy and partial or circumferential pharyngectomy, followed by reconstruction and postoperative radiotherapy in most cases. Efforts to preserve speech and swallowing function in the surgical treatment of hypopharyngeal (and laryngeal) cancer have resulted in a declining use of total laryngopharyngectomy and improved reconstructive efforts, including microvascular free tissue transfer. There are many surgical, as well as nonsurgical, options available for organ and function preservation, which report equally effective tumor control and survival. The selection of appropriate treatment is of crucial importance in the achievement of optimal results for these patients. In this article, several aspects of surgical and nonsurgical approaches in the treatment of hypopharyngeal cancer are discussed. Future studies must be carefully designed within clearly defined populations and use uniform terminology and standardized functional assessment and declare appropriate patient or disease endpoints. These studies should focus on improvement of resultsx, without increasing patient morbidity. In this respect, technical improvements in radiotherapy such as intensity‐modulated radiotherapy, advances in supportive care, and incorporation of newer systemic agents such as targeted therapy, are relevant developments. © 2010 Wiley Periodicals, Inc. Head Neck, 2012Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90087/1/21613_ftp.pd

Evidence‐based review of treatment options for patients with glottic cancer

Evidence‐based medicine integrates the best available data in decision making, with the goal of minimizing physicians' and patients' subjectivity. In 2006, the American Society of Clinical Oncology edited clinical practice guidelines for the use of larynx preservation strategies. The objective of this review was to evaluate the current levels of evidence for glottic squamous cell carcinoma. Current guidelines for early stage glottic cancer are based on low‐level evidence. Conservation surgery (open or transoral) and radiation therapy are all valid options for T1 and selected T2 lesions. For advanced lesions, surgery and combined chemotherapy and radiation are options. High‐level evidence favors combined chemotherapy and radiation therapy or altered fractionation radiation therapy as nonsurgical strategies for organ preservation, compared with radiation therapy alone. The optimal combination of chemotherapy, targeted therapy, and radiation therapy remains to be demonstrated, however, and for high‐volume tumors, total laryngectomy may still be warranted. © 2011 Wiley Periodicals, Inc. Head Neck, 2011Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87151/1/21528_ftp.pd

Environmental and Molecular Drivers of the α-Gal Syndrome

The α-Gal syndrome (AGS) is a type of allergy characterized by an IgE antibody (Ab) response against the carbohydrate Galα1-3Galβ1-4GlcNAc-R (α-Gal), which is present in glycoproteins from tick saliva and tissues of non-catarrhine mammals. Recurrent tick bites induce high levels of anti-α-Gal IgE Abs that mediate delayed hypersensitivity to consumed red meat products in humans. This was the first evidence that tick glycoproteins play a major role in allergy development with the potential to cause fatal delayed anaphylaxis to α-Gal-containing foods and drugs and immediate anaphylaxis to tick bites. Initially, it was thought that the origin of tick-derived α-Gal was either residual blood meal mammalian glycoproteins containing α-Gal or tick gut bacteria producing this glycan. However, recently tick galactosyltransferases were shown to be involved in α-Gal synthesis with a role in tick and tick-borne pathogen life cycles. The tick-borne pathogen Anaplasma phagocytophilum increases the level of tick α-Gal, which potentially increases the risk of developing AGS after a bite by a pathogen-infected tick. Two mechanisms might explain the production of anti-α-Gal IgE Abs after tick bites. The first mechanism proposes that the α-Gal antigen on tick salivary proteins is presented to antigen-presenting cells and B-lymphocytes in the context of Th2 cell-mediated immunity induced by tick saliva. The second mechanism is based on the possibility that tick salivary prostaglandin E2 triggers Immunoglobulin class switching to anti-α-Gal IgE-producing B cells from preexisting mature B cells clones producing anti-α-Gal IgM and/or IgG. Importantly, blood group antigens influence the capacity of the immune system to produce anti-α-Gal Abs which in turn impacts individual susceptibility to AGS. The presence of blood type B reduces the capacity of the immune system to produce anti-α-Gal Abs, presumably due to tolerance to α-Gal, which is very similar in structure to blood group B antigen. Therefore, individuals with blood group B and reduced levels of anti-α-Gal Abs have lower risk to develop AGS. Specific immunity to tick α-Gal is linked to host immunity to tick bites. Basophil activation and release of histamine have been implicated in IgE-mediated acquired protective immunity to tick infestations and chronic itch. Basophil reactivity was also found to be higher in patients with AGS when compared to asymptomatic α-Gal sensitized individuals. In addition, host resistance to tick infestation is associated with resistance to tick-borne pathogen infection. Anti-α-Gal IgM and IgG Abs protect humans against vector-borne pathogens and blood group B individuals seem to be more susceptible to vector-borne diseases. The link between blood groups and anti-α-Gal immunity which in turn affects resistance to vector-borne pathogens and susceptibility to AGS, suggests a trade-off between susceptibility to AGS and protection to some infectious diseases. The understanding of the environmental and molecular drivers of the immune mechanisms involved in AGS is essential to developing tools for the diagnosis, control, and prevention of this growing health problem

Study of sources of variability in terms of efficacy and adverse side effects of cetuximab in patients treated for head and neck squamous cell carcinoma

Le cetuximab (CTX) est un anticorps monoclonal anti-EGFR indiqué dans les cancers ORL dont les modalités de prescription pourraient être améliorées. Après chimiothérapie d’induction (étude Tremplin), en comparaison au cisplatine, il était moins toxique mais sans améliorer la préservation laryngée. À la première injection, le CTX peut déclencher un choc anaphylactique lié à la préexistence d’IgE anti-αGal. Des tests prédictifs détectant ces IgE ont été développés et réalisés chez 41 patients avec une sensibilité et une valeur prédictive négative de 100%. La relation entre concentrations sériques et efficacité/toxicité a été étudiée chez 34 patients. La pharmacocinétique a été décrite à l’aide d’un modèle combinant des mécanismes d’élimination non saturable (CL) et saturable (k0). La clairance globale du CTX, reflet de l’exposition des patients, était reliée aux survies sans progression et globale (SG). Le grade de radiodermite était associé à la SG. Une simulation pharmacocinétique suggère, qu’en comparaison à l’injection standard de CTX, une injection toutes les trois semaines entrainera des AUC proches mais des concentrations résiduelles différentes.Cetuximab (CTX) is an anti-EGFR monoclonal antibody approved in head and neck cancer, which prescription modalities may be improved. After induction chemotherapy (Tremplin study), compared to cisplatin, CTX was less toxic but did not improve larynx preservation. During first infusion, CTX can induce an anaphylaxis reaction due to the presence of preexisting anti-αGal IgE. Predictive assays detecting these IgE were developed and tested in 41 patients, with sensitivity and negative predictive values of 100%. Relationship between serum concentrations and efficacy/toxicity was studied in 34 patients. CTX pharmacokinetics was described using a model combining non-saturable (CL) and saturable (k0) eliminations. Global clearance, which reflects patient exposure, was related to progression free and overall (OS) survivals. Severe radiation dermatitis was also associated with OS. A pharmacokinetic simulation suggests that, in comparison to standard CTX infusion, an infusion every three weeks will lead to similar AUC but to different residual concentrations

SFRO 2010: congress highlights

National audienceThe 21(st) SFRO Congress during October 2010 focused on three main topics: prostate, radiotherapy technical innovations (including reirradiation) and quality of life. The pitfalls of IMRT (treatment time, number of monitor unit, low doses) are in competition with arctherapy dynamic techniques that offer reduction treatment time for an equivalent ballistic. These techniques with high dose gradient should be coupled with the better imagery of repositioning (IGRT) to ensure benefice. A prospective evaluation of toxicity, clinical benefit on tumor control but also on quality of life of patients is necessary. In many current and future clinical trials, quality of life related to health will be a relevant outcome measurement to secure the importance of treatment for the patient and the health system. (C) 2011 Societe francaise de radiotherapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved

SFRO 2010: congress highlights

National audienceThe 21(st) SFRO Congress during October 2010 focused on three main topics: prostate, radiotherapy technical innovations (including reirradiation) and quality of life. The pitfalls of IMRT (treatment time, number of monitor unit, low doses) are in competition with arctherapy dynamic techniques that offer reduction treatment time for an equivalent ballistic. These techniques with high dose gradient should be coupled with the better imagery of repositioning (IGRT) to ensure benefice. A prospective evaluation of toxicity, clinical benefit on tumor control but also on quality of life of patients is necessary. In many current and future clinical trials, quality of life related to health will be a relevant outcome measurement to secure the importance of treatment for the patient and the health system. (C) 2011 Societe francaise de radiotherapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved