Nerina Denaro

State-of-the-art and emerging treatment options in the management of head and neck cancer: news from 2013.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cause of cancer death worldwide. Its treatment is complex and evolving. In general, early-stage disease may be managed with single-modality treatment while an advanced stage (about 60% of clinical presentation) needs a multidisciplinary approach. In this setting concurrent chemoradiation has been associated with improvement in locoregional control and organ preservation, but at the cost of significant acute and chronic toxicity. Molecular target therapies specially directed to epidermal growth factor receptor (EGFR) might improve the outcomes and reduce toxicities. In recurrent-metastatic (R/M) HNSCC, cetuximab, a monoclonal antibody against EGFR, plus platinum-based chemotherapy (CT) allow an overall survival (OS) of about 10 months. However, the prognosis for R/M-HNSCC remains dismal and additional efforts are needed. At the 2013 American Society of Clinical Oncology (ASCO) Meeting, data on induction CT, anti-EGFR inhibitors, innovative molecular targets and predictor factors were reported. Further results on target therapies were presented at the European Cancer Congress (ECC) 2013, where a large study also showed that hyperfractionated radiotherapy (RT) improve OS rates compared with standard RT. The aim of this review is to discuss current standards and emerging therapies by considering recent new updates.

Dysphagia in Head and Neck Cancer Patients: Pretreatment Evaluation, Predictive Factors, and Assessment during Radio-Chemotherapy, Recommendations

Progress in head and neck cancer (HNC) therapies has improved tumor response, loco-regional control, and survival. However, treatment intensification also increases early and late toxicities. Dysphagia is an underestimated symptom in HNC patients. Impairment of swallowing process could cause malnutrition, dehydration, aspiration, and pneumonia. A comprehensive literature review finalized in May 2012 included searches of electronic databases (Medline, Embase, and CAB abstracts) and scientific societies meetings materials (American Society of Clinical Oncology, Associazione Italiana Radioterapia Oncologica, Associazione Italiana di Oncologia Cervico-Cefalica, American Head and Neck Society, and European Society for Medical Oncology). Hand-searches of HNC journals and reference lists were carried out. Approximately one-third of dysphagia patients developed pneumonia requiring treatment. Aspiration pneumonia associated mortality ranged from 20% to 65%. Unidentified dysphagia caused significant morbidity, increased mortality, and decreased the quality of life. In this review we underline definition, causes, predictive factors of dysphagia and report on pretreatment and on-treatment evaluation, suggesting some key points to avoid underestimation. A multi-parameter assessment of swallowing problems may allow an earlier diagnosis. An appropriate evaluation might lead to a better treatment of both symptoms and cancer.

Dysphagia in head and neck cancer patients treated with radiotherapy and systemic therapies: Literature review and consensus.

BACKGROUND Head and neck cancer (HNC) and its therapy are associated with acute and late swallowing dysfunction. Consensus guidelines regarding evaluation and management are lacking. To address this gap, a multidisciplinary team of experts (oncologists, practitioners, deglutologists, etc.) met in Milan 17-18 February 2013 with the aim of reaching a consensus on the management of swallowing difficulties in HNC patients treated with radiotherapy with or without systemic therapies (such as chemotherapy and targeted agents). The consensus was focused particularly on those statements with limited evidence. The results of the literature review and the statements that obtained a consensus are reported and discussed in this paper. MATERIALS AND METHODS The Delphi Appropriateness Method was used for this consensus. External expert reviewers then evaluated the conclusions carefully according to their area of expertise. RESULTS This paper contains 6 clusters of statements about the management of swallowing problems in radio-treated HNC patients and a review of the recent literature on these topics. CONCLUSIONS Dysphagia assessment and its management are difficult and require a multi-team cooperation (ENT specialists, radiation and medical oncologists, deglutologists, etc.).

The role of chemotherapy and latest emerging target therapies in anaplastic thyroid cancer.

Anaplastic thyroid cancer represents 1%–2% of thyroid cancers. For its aggressiveness, it is considered a systemic disease at the time of diagnosis. Surgery remains the cornerstone of therapy in resectable tumor. Traditional chemotherapy has little effect on metastatic disease. A multimodality approach, incorporating cytoreductive surgical resection, chemoradiation, either concurrently or sequentially, and new promising target therapies is advisable. Doxorubicin is the most commonly used agent, with a response rate of 22%. Recently, other chemotherapy agents have been used, such as paclitaxel and gemcitabine, with superimposable activity and response rates of 10%–20%. However, survival of patients with anaplastic thyroid cancer has changed little in the past 50 years, despite more aggressive systemic and radiotherapies. Several new agents are currently under investigation. Some of them, such as sorafenib, imatinib, and axitinib have been tested in small clinical trials, showing promising disease control rates ranging from 35%–75%. Referral of patients for participation in clinical trials is needed.

Impact of age on acute toxicity induced by bio- or chemo-radiotherapy in patients with head and neck cancer.

INTRODUCTION The purpose of this study is to retrospectively analyze acute toxicity encountered in young and old patients treated with chemo-radiation or bio-radiation at the S. Croce General Hospital between 1997 and 2008, in daily clinical practice. MATERIAL AND METHODS Three hundred and seventeen patients were allocated into two groups according to age (cut-off 65 years). The two groups were compared in terms of treatment related toxicities, treatment activity and efficacy. Epidermal Growth factor receptor (EGFr), Human papillomavirus (HPV) and p53 status were also considered. RESULTS As expected, overall survival was significantly worse in elderly patients (p=0.005), but response rate, including complete response rate, was similar between the two age groups, as were most of the side effects analyzed. However, infections (p=0.011) and in particular pneumonias (p=0.002) were significantly more represented in elderly patients. CONCLUSION Elderly patients treated with chemo-radiation or bio-radiation in our centre had a higher risk of infection and in particular, pneumonia. These data suggest a more careful follow-up, but age alone does not justify their exclusion from treatment.

A systematic review of current and emerging approaches in the field of larynx preservation

Treatment options targeting laryngeal preservation include conservative surgery, concurrent chemo-radiotherapy, induction chemotherapy (IC) followed by radiotherapy (RT), and alternating chemo-radiation. The goal of this paper was to perform a systematic review of randomized clinical trials (RCTs) on current and emerging approaches in the field of larynx preservation. The search identified 36 papers of which 27 did not fall within the inclusion criteria (i.e. non-RCTs). IC followed by RT has been shown to allow laryngeal preservation in about two-thirds of pts with locally advanced laryngeal or hypopharyngeal cancer without compromising survival. IC is regarded as the landmark treatment of non-surgical larynx preservation approaches. Concomitant and alternating chemoradiotherapy treatments are also acceptable in larynx preservation.

Follow-up in Head and Neck Cancer: Do More Does It Mean Do Better? A Systematic Review and Our Proposal Based on Our Experience

As the patients population ages, cancer screening increases, and cancer treatments improve, millions more head and neck carcinoma (HNC) patients will be classified as cancer survivors in the future. Change in epidemiology with human papillomavirus related HNC leads to a number of young treated patients. After treatment for HNC intensive surveillance, including ear, nose and throat (ENT) endoscopy, imaging, and serology, confers a survival benefit that became less evident in unresectable recurrence. We performed a comprehensive revision of literature and analyzed the experience of our centre. We revised publications on this topic and added data derived from the interdisciplinary work of experts within medical oncology, ENT, and radiation oncology scientific societies. We retrospectively collected local and distant recurrence of chemoradiation treated patients at Santa Croce and Carle University Hospital. A HNC follow-up program is not already codified and worldwide accepted. There is a need of scheduled follow-up. We suggest adopting a standardized follow-up guideline, although a multidisciplinary approach is frequently requested to tailor surveillance program and treatment on each patient.

Sepsis in head and neck cancer patients treated with chemotherapy and radiation: Literature review and consensus.

The reporting of infection/sepsis in chemo/radiation-treated head and neck cancer patients is sparse and the problem is underestimated. A multidisciplinary group of head and neck cancer specialists from Italy met with the aim of reaching a consensus on a clinical definition and management of infections and sepsis. The Delphi appropriateness method was used for this consensus. External expert reviewers then evaluated the conclusions carefully according to their area of expertise. The paper contains seven clusters of statements about the clinical definition and management of infections and sepsis in head and neck cancer patients, which had a consensus. Furthermore, it offers a review of recent literature in these topics.

The Role of p53 and MDM2 in Head and Neck Cancer

Head and neck cancer is a complex disorder that includes mostly squamous cell carcinomas that can develop in the throat, larynx, nose, sinuses, and mouth. Etiopathogenesis is due to tobacco and alcohol consumption and to infection by human papillomavirus (HPV) type 16/18. Tumors often develop within preneoplastic fields of genetically altered cells. Most head and neck cancers result from multistep accumulation of genetic alterationsm resulting in clonal outgrowth of transformed cells. These DNA changes are caused by a variety of mechanisms like endogenous mutations and exogenous mutations. Dysregulated molecular pathway includes alterations of critical inhibitor of cyclin CDK complexes, inactivating mutations of p53 gene, and activation of oncogenes and growth factors. This paper attempts to review the role of p53 and MDM2 genetic aberrations and pathways in head and neck cancer.

Cancer and stress: what’s matter? from epidemiology: the psychologist and oncologist point of view

Abstract Collective evidence points to a prominent role of stress in cancer growth and metastasis. Despite these results an etio-pathogenetic role has not been widely accepted. Reasons of controversies are the coexistence in stressed