Pros and Cons of the New Edition of TNM Classification of Head and Neck Squamous Cell Carcinoma.

The TNM classification is a worldwide standard staging system used to define the extent of cancer and is a major prognostic factor in predicting the outcome of patients. The TNM Classification of Malignant Tumours, 8th edition, has been used since January 1, 2018. In the area of head and neck cancer major modifications were produced: important updated T and N modification for oral cavity and nasopharyngeal cancer, the introduction of clinical and pathological stages for neck disease, and a new HPV-16-positive HNSCC classification. While until a few years ago the TNM staging system classified prognostic risk groups based on tumour size, the 8th edition responds to the need to categorize the prognosis of patients with similarly sized tumours but with very different clinical and biological behaviour. This review details TNM changes and the clinical need for these modifications, valuating possible limits in daily applicability.

A comparison of swallowing dysfunction after three-dimensional conformal and intensity-modulated radiotherapy : A systematic review by the Italian Head and Neck Radiotherapy Study Group.

PURPOSE: Dysphagia is one of the most important treatment-related side effects in head and neck cancer (HNC), as it can lead to severe life-threating complications such as aspiration pneumonia and malnutrition. Intensity-modulated radiotherapy (IMRT) could reduce swallowing dysfunction by producing a concave dose distribution and reducing doses to the swallowing-related organs at risk (SWOARs). The aim of this study was to review the current literature in order to compare swallowing outcomes between IMRT and three-dimensional conformal radiotherapy (3DCRT). METHODS: A search was conducted in the PubMed and Embase databases to identify studies on swallowing outcomes, both clinically and/or instrumentally assessed, after 3DCRT and IMRT. Dysphagia-specific quality of life and objective instrumental data are summarized and discussed. RESULTS: A total of 262 papers were retrieved from the searched databases. An additional 23 papers were retrieved by hand-searching the reference lists. Ultimately, 22 papers were identified which discussed swallowing outcomes after 3DCRT and IMRT for HNC. No outcomes from randomized trials were identified. CONCLUSION: Despite several methodological limitations, reports from the current literature seem to suggest better swallowing outcomes with IMRT compared to 3DCRT. Further improvements are likely to result from the increased use of IMRT plans optimized for SWOAR sparing.

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. © 2014 S. Karger AG, Basel.

Management of 'in-field' skin toxicity in head and neck cancer patients treated with combined cetuximab and radiotherapy.

It is well known that the cetuximab (Cet) epidermal growth factor receptor (EGFR) antibody enhances the sensitivity of tumour cells to radiation, and it is likely that the concurrent administration of Cet and radiotherapy (RT) results in some degree of interplay between the effects of the individual agents on the skin and in the exacerbation of reactions normally seen with these individual agents. In this paper, we present a concise review of Cet/RT-related skin toxicity, focusing on mechanisms and pathogenesis, clinical presentation and scoring systems and, finally, therapeutic management.

Management of skin toxicity associated with cetuximab treatment in combination with chemotherapy or radiotherapy.

BACKGROUND: Cetuximab was demonstrated by clinical trials to improve response rate and survival of patients with metastatic and nonresectable colorectal cancer or carcinoma of the head and neck. Appropriate management of skin toxicity associated with epidermal growth factor receptor inhibitor (EGFR-i) therapy is necessary to allow adequate drug administration and to improve quality of life and outcomes. METHODS: A group of Italian Experts produced recommendations for skin toxicity management using the RAND/UCLA Appropriateness Method. Statements were generated on the basis of a systematic revision of the literature and voted twice by a panel of 40 expert physicians; the second vote was preceded by a meeting of the panelists. RESULTS: Skin toxicity included skin rash, skin dryness, pruritus, paronychia, hair abnormality, and mucositis. Recommendations for prophylaxis and therapeutic interventions for each type of toxicity were proposed. CONCLUSIONS: Interventions that were considered appropriate to improve compliance and outcomes of cancer patients treated with EGFR-i were identified.

What is the role of postoperative re-irradiation in recurrent and second primary squamous cell cancer of head and neck? A literature review according to PICO criteria.

Re-irradiation has been increasingly offered as a potential effective treatment for head and neck squamous cell carcinoma (HNSCC) loco-regional recurrence as well as second primary tumor in previously irradiated area. This review focused on the role of postoperative re-irradiation (POreRT) in terms of feasibility, toxicity and long-term outcomes in HNSCC patients. The key issue for the research was formulated in two questions according to the PICO (population, intervention, control, and outcomes) criteria. A total of 16 publications met the inclusion criteria for a total of 919 patients; in 522 patients POreRT was performed. POreRT in recurrent and second primary HNSCC seems to be feasible in highly selected patients with the intent to guarantee an acceptable LC compared to surgery alone. The optimal RT schedule remains unclear due to the heterogeneity of literature data.

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.

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.

An Incidental Finding of Mucinous Colon Cancer by (18)F-Choline PET/CT Determining a Change in Clinical Management of a Patient with Recurrent Prostate Adenocarcinoma.

A 66-year-old-man underwent a PET/CT scan after a biochemical relapse for a prostate cancer previously treated with a laparoscopic surgical procedure which revealed a focal uptake in the posterior wall of sigmoid colon. The biopsy demonstrated a colon cancer with mucinous differentiation producing a shift in clinical priority. To the best of our knowledge this is the first report in the English literature describing the detection by (18)F-choline PET/CT of a colorectal cancer with mucinous differentiation.

Non coding RNAs in head and neck squamous cell carcinoma (HNSCC): a clinical perspective.

BACKGROUND: Head and neck squamous cell carcinoma is a common cause of cancer death. Despite decades of clinical studies exploring new treatments and considerable advance in multimodality treatment, satisfactory curative rates have not yet been reached. In the last few decades the emerging data from both tumor biology and clinical trials led to growing interest for research of predictive biomarkers. However, no molecular markers were discovered to improve clinical outcomes and to be used as new anticancer agents. Non coding RNAs (ncRNAs) are promising biomarkers. They are important regulators both in normal biological process and in proliferation, metastasis, chemo-radioresistance. MATERIALS AND METHODS: We revised the literature on this topic to summarize current findings on ncRNAs. RESULTS: Several studies reported an altered regulation of ncRNAs and a specific cancer site signature has also been described among different primary head and neck squamous cell carcinomas (HNSCC). Moreover, expression of ncRNAs correlates with poor prognosis and resistance to treatment. CONCLUSION: ncRNAs are emerging potential molecular markers and anticancer agents.

EGFR status and prognosis of patients with locally advanced head and neck cancer treated with chemoradiotherapy.

BACKGROUND: Overexpression of epidermal growth factor receptor (EGFR) is related to poor prognosis in patients with head and neck cancer (HNC) treated with surgery or radiotherapy. We assessed the relationship between EGFR status and outcome in patients treated with concurrent chemoradiotherapy. PATIENTS AND METHODS: Among 149 patients with unresectable HNC treated with chemoradiotherapy, immunohistochemistry was performed on 122 available tumor specimens. The following factors were included in the analysis: age at diagnosis, gender, performance status, site of primary tumor, T- and N-stage, grading, pretreatment, treatment protocol and EGFR staining. RESULTS: Overall, 43/122 (35%) were considered positive. At a median follow-up of 45 months, 5-year survival did not differ between positive and negative cases (42.1% vs. 48.0% respectively: hazard ratio for death 1.23; 95% confidence interval 0.70 to 2.17, p=0.45) nor was 5-year progression-free survival and 5-year locoregional control. Only when a smaller subgroup of tumors showing the strongest EGFR expression was considered, was any difference in 5-year overall survival detected (33.6% vs. 50.1%, p=0.009). CONCLUSION: EGFR appears to have no prognostic value when chemoradiotherapy is used. Possibly a small subgroup of cases with stronger positivity and worse prognosis can be identified.

The cisplatin-irradiation combination suggests that apoptosis is not a major determinant of clonogenic death.

It is commonly believed that tumor cells treated with anticancer agents, chemotherapy and/or radiation, die by apoptosis and that tumors which do not undergo apoptosis are resistant to treatment. In this study, we investigated the molecular basis underlying cisplatin cytotoxicity in the murine teratocarcinoma F9 cell line to see whether irradiation enhances cisplatin-induced cytotoxicity. We compared the apoptosis induced by chemo and/or radiotherapy with other cellular effects such as cell survival, clonogenic capability, cell cycle perturbation, expression of p53 and p53-related mRNAs, and necrosis. When combined with radiation, a clear additive cytotoxic effect of cisplatin was demonstrated. We found that both cisplatin and radiation induced cell death, but the level of induced apoptosis was low and there was no correlation with the results of the clonogenic assays: we noted a difference between cytotoxic effects in the clonogenic assay and the extent of apoptosis by fluorescence-activated cell sorter analysis, suggesting that cell killing reflected not only apoptosis but also cell cycle arrest, and that apoptosis, cell kinetics and clonogenicity suppression were independent processes.