Is sentinel lymph node biopsy the standard of care for cutaneous head and neck melanoma?

OBJECTIVES/HYPOTHESIS: Sentinel lymph node biopsy (SLNB) is considered one of the most important melanoma advancements to date. Since its inception in 1992, a plethora of data and associated controversies has emerged leading to the question: Is SLNB considered the standard of care for head and neck (HN) cutaneous melanoma? STUDY DESIGN: English literature (1990-2014) review. METHODS: The PubMed database search was conducted using key terms "melanoma" and "sentinel node." This review included both dedicated HN SLNB studies and larger prospective SLNB studies, in which HN patients were included among the cohort. Bibliography cross-referencing was conducted to ensure a comprehensive search. RESULTS: SLNB is safe and accurate in the HN region. Review of large prospective SLNB trials identified the pathologic status of the SLN as the most important prognostic factor for recurrence and survival. Early lymphadenectomy following a positive SLNB imparts a survival benefit. CONCLUSIONS: Our review of the current literature suggests that SLNB is the standard of care for selected cases of HN cutaneous melanoma. It is now incorporated into the American Joint Committee on Cancer staging system, the National Comprehensive Cancer Network practice guidelines, and numerous national and international consensus statements.

Concomitant chemoradiotherapy versus induction chemotherapy followed by chemoradiotherapy as definitive, first line treatment of squamous cell carcinoma of the head and neck. A retrospective single center analysis.

PURPOSE: Despite the lack of evidence to support its implementation in the clinical practice, induction chemotherapy (IC) before chemoradiotherapy (CRT) is often used in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). We retrospectively examined the tolerability, feasibility, and clinical outcome of both concepts in a single center analysis. PATIENTS AND METHODS: In all, 83 patients were treated between 2007 and 2010 with IC + CRT (n = 42) or CRT alone (n = 41). IC consisted of docetaxel, cisplatin and 5-fluorouracil (TPF), or cisplatin and 5-fluorouracil (PF). All patients were scheduled to receive 2 cycles of PF during concurrent CRT. Adverse events were assessed according to the common toxicity criteria of adverse events (CTCAE v. 3.0). Associations were tested using the χ² test, and survival estimates were calculated according to Kaplan-Meier. RESULTS: The median follow-up was 30.35 months (range 2.66-61.25 months). At 2 years, the overall survival rate was significantly higher for primary CRT compared to IC + CRT group (74.8 % vs. 54 %, respectively; p = 0.041). Significantly more treatment-related overall grade 4 toxicities were documented in the IC + CRT group compared to the CRT group (42.9% vs. 9.8%; p = 0.001). Renal toxicity ≥ grade 2 occurred in 52.4 % vs. 7.3 % (p < 0.001), respectively. In all, 93 % of the patients with primary CRT compared to 71 % with IC + CRT received the planned full radiotherapy dose (p = 0.012). CONCLUSION: This is, to our knowledge, the largest retrospective study to compare IC + CRT with primary CRT. IC showed high acute toxicity, compromised the feasibility of concurrent CRT, and was associated with reduced overall survival rates compared to primary CRT. The lack of clinical benefit in conjunction with the increased toxicity does not support implementation of IC.

Selective neck dissection as a therapeutic option in management of squamous cell carcinoma of unknown primary.

Carcinoma of unknown primary of the neck (CUP) is a metastasis presenting in one or more cervical lymph nodes, with no primary mucosal site identified. Retrospective case notes review of 25 consecutive patients (median age 55, 72% males) diagnosed as CUP who underwent neck dissection in a UK tertiary referral comprehensive cancer centre between 2000 and 2011. Median follow-up was 33 months. Nineteen patients underwent comprehensive neck dissections (six extended), six patients had selective neck dissection. Five year disease specific survival and regional recurrence free survival were 76 and 80% respectively. The overall rate of occult disease (disease not identified on preoperative evaluation, but found on histopathologic examination) was 8%, with rates of 0% in level I and 6% in level V. Our study suggests that in patients without preoperative evidence of disease in levels I or V selective neck dissection might be considered as an option, to facilitate preservation of the submandibular gland and accessory nerve without compromising oncological outcome. Larger studies should be performed before a change in practice can be advised.

[Advances in head and neck cancers on behalf of the French Intergroup ORL and GORTEC]. / Évolution des concepts dans les cancers des voies aérodigestives supérieures, sous l'égide de l'Intergroupe ORL (GORTEC, GETTEC, GERCOR).

Head and neck cancers are the fifth among the most common cancers in France. Two thirds of cases occur at an advanced stage. For advanced disease, progression-free survival, despite undeniable progress, remains below 50% at three years. The last 20 years have been marked by the necessity to identify situations where less intense surgery and/or radiotherapy and/or chemotherapy is possible without jeopardizing the prognosis, and situations where a therapeutic intensification is necessary and results in a gain in survival while better preserving function with less toxicity. French cooperative groups gathering radiation oncologists (GORTEC), surgeons (GETTEC) and medical oncologists or physicians involved in the management of systemic treatments in head and neck cancers (GERCOR) are now belonging to the INCa-labelled Intergroup ORL to deal with the challenges of head and neck cancers.

[Diagnosis and therapeutic pathways in head and neck cancers]. / Parcours de soins du patient présentant un carcinome epidermoïdes des voies aéro-digestives supérieures.

BACKGROUND: Cancers of uppers aero-digestives tracts represent, infrequency, the 5th cancer in the French population. Most of them (about 70%) are diagnosed at an advanced stage (stage III or IV) while they are associated with a poor prognosis (only 40% five year survival). The objective of our study was to analyze the care pathway of patients with cancers of uppers aero-digestives tracts in order to target efforts to improve the survival of these patients. METHODS: It was a descriptive and retrospective study, on medical files, on the health care pathway of patients with cancers of uppers aero-digestives tracts cared in the Head and Neck surgery department of Val de Grâce in Paris and Percy in Clamart between January 2004 and December 2006. The patients were adults with squamous cell carcinoma of uppers aero-digestives tracts. RESULTS: One hundred thirty-eight files of patients were analyzed. Fifty-five percent of patients were diagnosed at an advanced stage. On average patients have waited two months and twenty-one days before consulting a doctor for the first time. The time interval between the specialist consultation and the start of treatment was on average 7 weeks. The overall 5-year survival rate was 61%. CONCLUSION: Squamous cell carcinoma of uppers aero-digestives tracts remains serious and has a poor diagnosis, even in a population with a high social-cultural level. The long time interval before the first consultation may be reduced by improving health education among the general practitioner (primary and secondary prevention), and by establishing health care public campaigns. This would allow earlier diagnosis, more conservative therapeutic opportunities and therefore a better prognosis.

Assessment of nutritional status at the time of diagnosis in patients treated for head and neck cancer.

OBJECTIVE: To evaluate the nutritional status at the time of diagnosis of patients treated for head and neck cancer. MATERIAL AND METHODS: Single-centre prospective study. Nutritional assessment comprised: clinical interview, physical examination, and a laboratory work-up. Clinical interview assessed: reference weight, diet, calorie intake, causes of weight loss, use of dietary supplements. A subjective global assessment of nutritional status (Detsky index) was established on the basis of clinical interview. The patient's height and weight were determined and serum albumin was assayed. Weight loss, body mass index, and Buzby index were then calculated. Two groups of malnourished patients were distinguished: moderately malnourished (group 1), severely malnourished (group 2). Variables were compared between the two groups by Chi(2) test. RESULTS: One hundred and sixty-nine patients were included in the study: 145 had a history of smoking and alcohol abuse, 82 (48.5%) were malnourished and 47 of them were classified in group 1. All patients of group 1 had a normal or pureed diet. 21 (69%) patients of group 2 had a pureed or liquid diet. The mean daily calorie intake was 31kcal/kg/24h for group 1 and 20kcal/kg/24h for group 2. The main causes of weight loss were pain and dysphagia. Dietary supplements were not used by any of the patients in group 1 and by four (13%) patients in group 2. The concordance between the Detsky index and objective nutritional status was 92% for the overall population. Malnutrition was significantly more frequent among males (P=0.01), alcohol users (P=0.02), elderly subjects (P=0.01), patients with pharyngeal tumour (P=0.03), and patients with advanced tumour stage (P=0.01). CONCLUSION: The prevalence of malnutrition among patients with head and neck cancer is high. Assessment of nutritional status and appropriate management must be part of the initial work-up of these patients.

Surveillance low-dose chest computed tomography for head and neck cancer patients.

Based on the recent results of the National Lung Cancer Screening Trial, the National Comprehensive Cancer Network now recommends annual screening with low-dose computed tomography for high-risk individuals (generally defined as 45- to 60-year-old current or former smokers). As head and neck cancer patients are at a high risk for (second) lung cancers, annual surveillance computed tomography should be considered for head and neck cancer patients.

[Current advances in diagnosis and surgical treatment of lymph node metastasis in head and neck cancer]. / Aktuelle Fortschritte in der Diagnostik und chirurgischen Therapie der Halslymphknotenmetastasen bei Kopf-Hals-Karzinomen.

Still today, the status of the cervical lymph nodes is the most important prognostic factor for head and neck cancer. So the individual treatment concept of the lymphatic drainage depends on the treatment of the primary tumor as well as on the presence or absence of suspect lymph nodes in the imaging diagnosis. Neck dissection may have either a therapeutic objective or a diagnostic one. The selective neck dissection is currently the method of choice for the treatment of patients with advanced head and neck cancers and clinical N0 neck. For oncologic reasons, this procedure is generally recommended with acceptable functional and aesthetic results, especially under the aspect of the mentioned staging procedure. In this review article, current aspects on pre- and posttherapeutic staging of the cervical lymph nodes are described and the indication and the necessary extent of neck dissection for head and neck cancer is discussed. Additionally the critical question is discussed if the lymph node metastasis bears an intrinsic risk of metastatic development and thus its removal in a most possible early stage plays an important role.

The impact of early percutaneous endoscopic gastrostomy placement on treatment completeness and nutritional status in locally advanced head and neck cancer patients receiving chemoradiotherapy.

To investigate the impact of early insertion of percutaneous endoscopic gastrostomy-tube on nutritional status and completeness of concurrent chemotherapy in locally advanced head and neck cancer patients treated with chemoradiotherapy. Twenty-three patients were enrolled into this prospective study. Gastrostomy-tube was inserted in patients before the initiation of chemoradiotherapy. There was not any significant change in nutritional parameters of patients that used their tube during treatment. Despite the grade 3 mucositis, the planned concurrent chemotherapy could be given in 70% of the patients. However, nine patients had weak compliance and their body weight (P = 0.01) and body mass index (P = 0.01) deteriorated in the first 4 weeks of chemoradiotherapy. The completeness of concurrent chemo-rate was 44% in these patients. Toxicity, requiring aggressive supportive care, may limit the chemotherapy part of curative concomitant chemoradiotherapy. By providing adequate enteral nutrition the insertion of gastrostomy-tube can increase the completeness rate of concurrent chemotherapy.

When to manage level V in head and neck carcinoma?

OBJECTIVES/HYPOTHESIS: As superselective neck dissection strategy is gaining popularity to minimize postoperative morbidity and better life quality, we investigated the metastatic nodal status of level V neck lymph node group for head and neck squamous cell carcinoma in various primary sites. We have also aimed to display the impact of involvement of other nodal groups on level V. STUDY DESIGN: Retrospective review of histopathologic examination of case series at a comprehensive cancer center. METHODS: The study group was composed of 107 patients who underwent a type of neck dissection including level V among 243 patients. The impact of primary site and metastatic nodal status of other levels on metastasis to level V involvement were evaluated. RESULTS: The most common primary tumor site was oropharynx (n = 43), followed by oral cavity (n = 32), larynx (n = 16), carcinoma of unknown primary (n = 10), and hypopharynx (n = 6). General pathologic N positivity for all levels was 78.3% (76 of 97) when 10 carcinoma of unknown primary patients were excluded. Level V was involved in 13 of 107 (12.1%) patients. Level V was not involved in any patient when the other levels were not involved (0 of 21). Even when considering only N+ patients, the ratio of N positivity for level V is still <20% (13 of 86, 15.1%). CONCLUSIONS: Because level V was not involved in any patient when the other levels were not involved, it might be reasonable to preserve level V especially in clinically and intraoperatively N0 patients.

Treatment of locally advanced carcinomas of head and neck with intensity-modulated radiation therapy (IMRT) in combination with cetuximab and chemotherapy: the REACH protocol.

BACKGROUND: Primary treatment of carcinoma of the oro-/hypopharynx or larynx may consist of combined platinum-containing chemoradiotherapy. In order to improve clinical outcome (i.e. local control/overall survival), combined therapy is intensified by the addition of the EGFR inhibitor cetuximab (Erbitux®). Radiation therapy (RT) is carried out as intensity-modulated RT (IMRT) to avoid higher grade acute and late toxicity by sparing of surrounding normal tissues. METHODS/DESIGN: The REACH study is a prospective phase II study combining chemoradiotherapy with carboplatin/5-Fluorouracil (5-FU) and the monoclonal epidermal growth factor-receptor (EGFR) antibody cetuximab (Erbitux®) as intensity-modulated radiation therapy in patients with locally advanced squamous-cell carcinomas of oropharynx, hypopharynx or larynx.Patients receive weekly chemotherapy infusions in the 1st and 5th week of RT. Additionally, cetuximab is administered weekly throughout the treatment course. IMRT is delivered as in a classical concomitant boost concept (bid from fraction 16) to a total dose of 69,9 Gy. DISCUSSION: Primary endpoint of the trial is local-regional control (LRC). Disease-free survival, progression-free survival, overall survival, toxicity, proteomic and genomic analyses are secondary endpoints. The aim is to explore the efficacy as well as the safety and feasibility of this combined radioimmunchemotherapy in order to improve the outcome of patients with advanced head and neck cancer. TRIAL REGISTRATION: ISRCTN87356938.

Radiochemotherapy including cisplatin alone versus cisplatin + 5-fluorouracil for locally advanced unresectable stage IV squamous cell carcinoma of the head and neck.

BACKGROUND AND PURPOSE: The optimal radiochemotherapy regimen for advanced head-and-neck cancer is still debated. This nonrandomized study compares two cisplatin-based radiochemotherapy regimens in 128 patients with locally advanced unresectable stage IV squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Concurrent chemotherapy consisted of either two courses cisplatin (20 mg/m(2)/d1-5 + 29-33; n = 54) or two courses cisplatin (20 mg/m(2)/d1-5 + 29-33) + 5-fluorouracil (5-FU; 600 mg/m(2)/d1-5 + 29-33; n = 74). RESULTS: At least one grade 3 toxicity occurred in 25 of 54 patients (46%) receiving cisplatin alone and in 52 of 74 patients (70%) receiving cisplatin + 5-FU. The latter regimen was particularly associated with increased rates of mucositis (p = 0.027) and acute skin toxicity (p = 0.001). Seven of 54 (13%) and 20 of 74 patients (27%) received only one chemotherapy course due to treatment-related acute toxicity. Late toxicity in terms of xerostomia, neck fibrosis, skin toxicity, and lymphedema was not significantly different. The 2-year locoregional control rates were 67% after cisplatin alone and 52% after cisplatin + 5-FU (p = 0.35). The metastases-free survival rates were 79% and 69%, respectively (p = 0.65), and the overall survival rates 70% and 51%, respectively (p = 0.10). On multivariate analysis, outcome was significantly associated with performance status, T-category, N-category, hemoglobin level prior to radiotherapy, and radiotherapy break > 1 week. CONCLUSION: Two courses of fractionated cisplatin (20 mg/m(2)/day) alone appear preferable, as this regimen resulted in similar outcome and late toxicity as two courses of cisplatin + 5-FU, but in significantly less acute toxicity.

Life after cancer in India: coping with side effects and cancer pain.

The article aims to understand the coping strategies of postsurgery head and neck cancer patients in Mumbai, India. A descriptive research design with a sample of 80 patients suffering from head and neck cancer was selected to analyze their coping strategies in relation to sociodemographic profile and illness characteristics. The findings of the study highlighted that the spiritual methods of coping (such as prayer and meditation, adopting a positive attitude) were the most frequently used mainstream coping strategy, apart from other traditional methods (such as taking medications, indulging in exercise and activities to divert one's attention, etc.) of coping. The findings of the study help to broaden the understanding of various psychosocial aspects faced by the patient in India and provide progressive recommendations to improve the quality of life of the patient suffering from cancer.

Selenium levels during the course of radiotherapy. No influence of irradiation on blood selenium concentration.

PURPOSE: To evaluate the influence of tumor characteristics and irradiation on blood selenium concentrations and their course during radiotherapy. MATERIAL AND METHODS: Selenium Levels were determined at various times during radiotherapy (I: beginning, II: mid, III: end, IV: 6 weeks after) by atomic absorption spectrometry in whole blood. The values were correlated with patient-, tumor- and irradiation-related parameters. RESULTS: A total of 690 samples were analyzed in 224 patients. The mean selenium value was 75.64 microg/l at the beginning of radiotherapy. 170 patients (77%) had reduced selenium Levels < 89 microg/l. Twelve patients (5.4%), mostly with head-and-neck cancer, had critically low values which need to be controlled and monitored. Three patients (1.3%) with breast cancer had critically increased values. Female patients showed higher seLenium concentrations than male patients (p = 0.0404). Patients diagnosed for head-and-neck cancer had significantly lower seLenium values than breast cancer patients (p = 0.016). Previous treatment by surgery and/or chemotherapy was correlated with lower selenium concentrations compared with irradiation as primary treatment (p = 0.039). According to analysis of variance, there was no significant change of the selenium concentration during the course of radiotherapy (p > 0.05). CONCLUSION: A preexisting selenium deficiency could be diagnosed in the broad majority of cancer patients undergoing radiotherapy. In contrast to the widely held opinion, it was not further aggravated by standard radiotherapy protocols.

Induction of cell cycle arrest and apoptosis by a combined treatment with 13-cis-retinoic acid, interferon-alpha2a, and alpha-tocopherol in squamous cell carcinoma of the head and neck.

BACKGROUND: We have previously conducted phase II trials with a combination of 13-cis-retinoic acid (13-cRA), interferon-alpha2a (IFN-alpha2a), and alpha-tocopherol (alpha-TF) in patients with advanced oral premalignant lesions and locally advanced head and neck cancer in the adjuvant settings and achieved promising outcomes. The present study was conducted in vitro to elucidate the mechanisms of anti-tumor activity of this 3-drug combination in squamous cell carcinoma of the head and neck (SCCHN). METHODS: Five SCCHN cell lines were treated with 13-cRA, IFN-alpha2a, and alpha-TF as single agents or 2- to 3-drug combinations for 72 hours. Inhibition of cell growth and cell cycle progression and induction of apoptosis by the treatments were evaluated. RESULTS: Our results demonstrated that although each single-agent and 2-drug combination showed a certain level of cell growth inhibition, the 3-drug combination apparently further inhibited cell growth in comparison to any single agents and 2-drug combinations in the 5 SCCHN cell lines. Cell cycle analysis on Tu212 and 886LN cells by flow cytometry exhibited significant accumulation of the cells at S phase in the 3-drug combination. On the other hand, Annexin-V binding assay demonstrated that the 3-drug combination induced more profound apoptosis than any of the single agents or 2-drug combinations. In parallel, proteolytic cleavages of pro-caspase-8, -9, -3 and poly (ADP ribose) polymerase as well as caspase-3 activity induced by the 3-drug treatment were observed. CONCLUSIONS: Our data suggests that 3-drug combination biochemopreventive regimen has cooperative inhibitory effect on the growth of SCCHN cells. Both cell cycle arrest and apoptosis contribute to cell growth inhibition of this 3-drug combination therapy.

[Status of essential trace elements in untreated carcinomas of the head and neck]. / Status essenzieller Spurenelemente bei unbehandelten Kopf-Hals-Karzinomen.

BACKGROUND: The changed mineral status is well known in different tumor types. This phenomenon has influenced the redox potential of patients suffering from solid cancers. A prospective trial was conducted to evaluate the specifics for untreated head and neck cancer patients. MATERIAL AND METHODS: We included 100 patients with advanced squamous cell carcinoma of the head and neck region before each kind of treatment. Following serum-concentrations were measured by atom absorption spectrometry: selenium, copper, zinc, and ferrum. Additionally we evaluated the activity of glutathion peroxidase and the concentration of malondialdehyde of the serum. RESULTS: 66 % of all patients have shown a decreased serum-concentration of selenium. These patients were additionally characterized by decreased activities of endogenous glutathionperoxiase. A third of all patients had decreased zinc and iron levels. Copper was found enhanced in 30 %. In trend the malondialdehyde was increasing due to decreasing selenium levels. CONCLUSIONS: Head neck cancer patients show the same characteristic trace element status as other solid tumors: decreased selenium, zinc and iron, increased copper. The therapeutic consequences of these observations are still unclear.

[Diagnosis of a metastatic valvular tumor in a living patient]. / Tumeur métastatique valvulaire diagnostiquée du vivant du malade.

INTRODUCTION: The discovery of an endocardial mass always raises the question of its nature. Infectious endocarditis is the most frequent cause, but others diagnoses must be considered. EXEGESIS: We report a case of endocardial metastasis originating from an upper respiratory tract epidermoid carcinoma in a 48-years-old man. The diagnosis was established while the patient was alive, and survival at the time of writing is 8 months. This case report provides an opportunity for discussion of the differential diagnosis when confronted with an endocardial tumor, i.e. bacterial endocarditis, non-bacterial thrombotic endocarditis, primary cardiac tumors, metastatic osteogenic sarcoma and Libman-Sachs endocarditis. CONCLUSION: Non bacterial thrombotic endocarditis and valvular metastasis should be considered upon discovery of a valvular tumor, in the context of neoplastic disease. The prognosis of endocardial metastasis is poor, but early diagnosis and appropriate management should eventually prolong survival.

Intraindividual comparison of two different skin care conceptions in patients undergoing radiotherapy of the head-and-neck region. Creme or powder?

OBJECTIVES: This study evaluated for the first time in intraindividual comparison the conception of care with creme or powder. Acute skin reactions on the left and right side of the neck during symmetrically performed radiotherapy and subjective impairment were assessed. PATIENTS AND METHODS: Twelve patients receiving radiotherapy of the head-and-neck region up to 50, 60, 66 and 72 Gy, respectively, were asked to treat one side of the neck with creme, the contralateral side with powder after random assignment. Objective and subjective assessment and photodocumentation were performed at therapy onset and weekly during therapy. The photodocumentation provides an impressive course of acute skin reactions under these care concepts. RESULTS: Altogether we saw no relevant difference in favor of care with creme or powder according to objective as well as subjective assessment criteria (Figure 2 and 3). In this intraindividual comparison the results are independent from interindividual different sensitivity to radiotherapy, total dose or fractionation. Therefore the small patient number is a minor limitation for evidence. Our results are in accordance to trials comparing other care concepts. CONCLUSIONS: A relevant effect concerning onset and degree of acute skin reactions or differences in symptom relief could not be demonstrated. Both conceptions are to be regarded equal in terms of subjective symptom relief and in extent of acute skin reactions. The lack of differences may be explained by the fact that the underlying pathophysiological processes cannot be influenced by topical agents.

Hypothyroidism after treatment for nonthyroid head and neck cancer.

OBJECTIVES: To determine the incidence of posttreatment hypothyroidism in patients treated with surgery with or without radiotherapy for advanced-stage nonthyroid head and neck cancer and to make recommendations for its detection. DESIGN: A prospective study to assess the incidence and time frame of occurrence of hypothyroidism in patients by primary tumor site and treatment modality. Thyroid function tests were performed preoperatively, at the first postoperative visit, and then approximately every 6 months. Patients were followed up for up to 3 years. SETTING: Arthur G. James Cancer Hospital and Research Institute, Columbus, Ohio. PATIENTS: A total of 251 patients with nonthyroid head and neck cancer were originally enrolled; 198 patients with evaluable data were studied to determine the incidence of posttreatment hypothyroidism. Approximately 80% of the patients had advanced stage (III or IV) or recurrent cancer. RESULTS: The overall incidence of posttreatment hypothyroidism was 15% in 198 patients followed up for a mean of approximately 12 months. Hypothyroidism developed in 12% of patients treated with nonlaryngeal surgery and radiotherapy. The group undergoing total laryngectomy (with thyroid lobectomy) and radiotherapy had a 61% incidence of hypothyroidism. The average time to detection of hypothyroidism was 8.2 months. CONCLUSIONS: Approximately 15% of patients treated for advanced head and neck cancer with surgery and radiotherapy will develop hypothyroidism. Those treated with total laryngectomy and radiotherapy are at greatest risk.