Immunocompetent murine model of cancer cachexia for head and neck squamous cell carcinoma

BACKGROUND: Muscle wasting and weight loss were observed when carcinomas were induced in a murine model of head and neck squamous cell carcinomas. Our hypothesis was C3H/HeN mice would develop evidence of cachexia when injected with tumor cells METHODS: Age- and weight-matched female mice were injected with SCCF/VII cells. Daily food intake and weights were measured. Body composition and analysis of circulating cytokines was performed. At the completion of experiments, hind legs were weighed. Muscle atrophy was detected using analysis for muscle ring finger 1 (MuRF1). The tumor-derived lipid mobilizing factor (LMF) was measured. RESULTS: Despite increased food intake, tumor-bearing mice lost weight and experienced reduced hind leg weights. Interleukin-1beta (IL-1beta) was increased and MuRF1 was present in tumor-bearing mice but not controls. LMF was present in SCCF/VII cells. CONCLUSION: In this immunocompetent murine model, we demonstrated the development of cancer cachexia in mice inoculated with SCCF cells, which express LMF. There was increased serum IL-1beta, weight loss, and muscle wasting and atrophy in tumor-bearing mice.     

Designing biomarker studies for head and neck cancer

Although there is ample literature reporting on the identification of molecular biomarkers for head and neck squamous cell carcinoma, none is currently recommended for routine clinical use. A major reason for this lack of progress is the difficulty in designing studies in head and neck cancer to clearly establish the clinical utility of biomarkers. Consequently, biomarker studies frequently stall at the initial discovery phase. In this article, we focus on biomarkers for use in clinical management, including selection of therapy. Using several contemporary examples, we identify some of the common deficiencies in study design that hinder success in biomarker development for this disease area, and we suggest some potential solutions. The purpose of this article is to provide guidance that can assist investigators to more efficiently move promising biomarkers in head and neck cancer from discovery to clinical practice. © 2013 Wiley Periodicals, Inc. Head Neck 36: 1069–1075, 2014     

Postimplantation radiation therapy in head and neck cancer patients: Literature review

There is no recommendation regarding the timing for implant surgery in patients with head and neck cancer (HNC) who require postoperative radiation therapy (RT). This systematic review focused on the literature about the outcomes of implants placed during ablative surgery in patients with HNC who underwent postoperative RT. Implants placed after radiation therapy and implants placed in reconstructed jaws were excluded. Four comparative studies involving 755 native mandible primary implants were analyzed. The survival rate with postimplantation RT was 89.6% vs 98.6% in patients with no additional radiation. The overall success of implant‐retained overdenture in patients with RT performed postimplantation was 67.4% vs 93.1% in patients with implant surgery that was carried out 1 year after the completion of radiation therapy. Only five cases of osteoradionecrosis (ORN) of the jaw were reported. The outcomes for implant survival rates appear to be positive for irradiated implants.     

Cancer stem cells in head and neck squamous cell carcinoma: a review of current knowledge and future applications

Head and neck squamous cell carcinoma (HNSCC) is a major cause of morbidity and mortality, and the alleviation thereof requires greater understanding of the pathobiologic behavior of HNSCC. Although the existence of cancer stem cells (CSCs) in most solid tumors has not been formally proven, application of the CSC concept has certainly enhanced understanding of HNSCC heterogeneity and progression. Recent data support the role of ALDH1(+) CD44(+) CSC in HNSCC, since the implantation of a few ALDH1(+) CD44(+) cells consistently gives rise to tumors that can be serially passaged in vivo. In addition to CSC biomarkers, recent explorations of CSC signaling pathways, gene expression, and localization in HNSCC carry significant clinical and therapeutic implications. Identification and characterization of CSC populations that regulate HNSCC growth, metastasis, and treatment resistance will facilitate development of novel diagnostic, therapeutic, and prognostic strategies. Furthermore, advances in multimodal imaging and nanotechnology, in conjunction with CSC models, may better elucidate the regulatory mechanisms that govern CSC biology in vivo, as well as develop platforms for targeted theragnostics. It is hoped that the promising applications of the CSC model in HNSCC will eventually alleviate the morbidity and mortality of this pervasive disease.     

Selective neck dissection in the management of the neck after (chemo)radiotherapy for advanced head and neck cancer. Proposal for a classification update

For patients with advanced regional disease, neck dissection following (chemo)radiotherapy remains controversial. Selective neck dissection (SND) was reported as suitable after chemoradiation in patients with advanced regional disease. Reduced morbidity represents the major advantage of SND. In a situation in which there is a major fibrosis around the previously invaded nodes, resection of 1 or more nonlymphatic structures may be required. The current classification of SND could be implemented by the addition of extended selective neck dissection (ESND). The standard basic procedures for SND spare the sternocleidomastoid muscle (SCM), the internal jugular vein (IJV), and the spinal accessory nerve (SAN). When an SND is associated with the resection of 1 or more nonlymphatic structures, it should be termed ESND. All additional nonlymphatic structure(s) removed should be identified in parentheses. The proposal to subclassify SND not only in accord with the resected lymph node levels but also upon the nonlymphatic structures removed may be of some help to avoid potential misinterpretation. © 2010 Wiley Periodicals, Inc. Head Neck, 2010     

Isolated neck recurrence after definitive radiotherapy for node-positive head and neck cancer: salvage in the dissected or undissected neck

BACKGROUND: The role of salvage neck dissection for isolated regional recurrences after definitive radiotherapy (RT) is ill-defined. METHODS: Five-hundred fifty patients were treated with RT for lymph node-positive head and neck cancer. RT consisted of a median dose of 74.4 Gy. Chemotherapy was administered in 133 patients (24%). Patients were followed for neck failure after planned neck dissection (n = 341) or observation (n = 209). Salvage therapy was offered to those with isolated neck recurrences. RESULTS: There were 54 (10%) failures in the neck at a median 3.7 months after RT (range, 0 to 17 months). Thirteen patients had isolated recurrences after receiving definitive RT with (n = 11) or without (n = 2) neck dissection. Nine patients underwent attempted surgical salvage with or without re-irradiation and 4 were successfully salvaged without major complications. CONCLUSIONS: Patients with neck failure after definitive therapy usually have poor outcomes, but salvage attempts may be successful in selected patients with an isolated neck recurrence.