Sentinel lymph node biopsy in Merkel cell carcinoma: a 15-year institutional experience and statistical analysis of 721 reported cases.

Merkel cell carcinoma (MCC) is a rare aggressive cutaneous neuroendocrine malignancy that frequently metastasizes to the regional lymphatic basin. Pathological assessment of regional lymph nodes with sentinel lymph node biopsy (SLNB) in patients without clinical involvement has permitted more accurate staging and more appropriate management. Nonetheless, concerns have been raised regarding the accuracy of this technique and its prognostic implications. We conducted a review of previously published data analysing the positive and false negative rates of SLNB in MCC. A search of the Medline and Embase databases to April 2015 identified 36 published studies between 1997 and 2015 comprising 692 patients. With the addition of 29 patients treated at our own institution, we conducted an analysis of 721 patients. Among this cumulative cohort, SLNBs were performed from 736 regional sites with 29·6% recorded as positive. Regional metastasis occurred in 45 cases following a negative SLNB, for a false negative rate of 17·1%. Adjuvant regional radiotherapy in the setting of a negative SLNB did not affect regional recurrence (P = 0·31), providing credence to emerging evidence that regional therapy can be safely omitted in the setting of a negative SLNB. Distant relapse was noted far more frequently following a positive rather than negative SLNB (17·6% vs. 7·3%, P < 0·001).

Current Role of Radiotherapy in Non-melanoma Skin Cancer.

Non-melanoma skin cancer (NMSC) represents the most frequently diagnosed malignancy worldwide, most being cutaneous basal cell and squamous cell carcinoma. The global incidence of NMSC continues to increase as the global population ages. Numerous treatment options are available for NMSC patients, with radiotherapy an efficacious and tissue-preserving non-surgical option. External beam radiotherapy and brachytherapy are modalities with specific indications and advantages in treating NMSC. Where excision is not an option (medically/technically inoperable) or considered less ideal (e.g. cosmetic or functional outcome), radiotherapy offers an excellent alternative. Inoperable elderly and/or co-morbid patients of poor performance status can benefit from short-course hypofractionated radiotherapy, with very acceptable toxicity. Adjuvant radiotherapy in patients with unfavourable pathology can decrease the risk of local and regional recurrence and associated morbidity and mortality. Radiotherapy has advantages and disadvantages and it is important for clinicians to understand these. Managing patients with NMSC is carried out by clinicians from multiple disciplines but it is imperative that they are all aware of the role of radiotherapy in their patients in various clinical settings. Here we aim to discuss the role and indications for recommending radiotherapy in patients with NMSC.

Role of combined modality treatment of buccal mucosa squamous cell carcinoma.

BACKGROUND: Squamous cell carcinoma of the buccal mucosa is an oral cancer reported as having a poor prognosis. In many patients combined modality treatment incorporating surgery and adjuvant radiotherapy should be considered best practice. METHODS: Patients treated for buccal mucosa squamous cell carcinoma were identified through the computer database in the Department of Radiation Oncology, Westmead Hospital, Sydney. All eligible patients were treated with curative intent. Survival was calculated using the Kaplan-Meier product limit method. RESULTS: A total of 32 eligible patients were identified. There were 20 males and 12 females. Median age at diagnosis was 67 years (range 44-82 years). Median duration of follow-up was 42 months (6-205 months). More than half (59 per cent) presented with early stage disease (stage I/II) with 35 per cent presenting with advanced (stage III/IV) disease. Most patients (28/32; 88 per cent) underwent surgery with eight patients also undergoing adjuvant radiotherapy. Four patients underwent definitive radiotherapy alone. A total of 15/32 (47 per cent) patients developed recurrence: four locally, eight regionally and three with locoregional recurrence. Patients treated with surgery and adjuvant radiotherapy had the lowest rate of recurrence. Median time to recurrence was five months. The three-year overall and disease free survival was 55 and 47 per cent, respectively. CONCLUSION: Buccal mucosa squamous cell carcinoma is an aggressive squamous cell carcinoma of the oral cavity. Despite treatment patients remain at risk of locoregional recurrence especially in the untreated ipsilateral neck. In many cases patients will benefit from multimodality treatment.

Cardiac transplant-related cutaneous malignancies in an Australian recipient: immunosuppression, friend or foe?

Cardiac transplantation now offers hope to those diagnosed with end stage cardiac failure. The consequences of such transplantation include the need for lifelong immunosuppression to avoid life-threatening rejection. The subsequent development of secondary malignancies and opportunistic infections often leads to significant morbidity and mortality. Cutaneous malignancies in particular represent a major concern to Australian transplant recipients. The case history is presented of a cardiac transplant recipient who developed multiple recurrent aggressive cutaneous squamous cell carcinomas of the head and neck. Despite surgery and radiotherapy, he experienced explosive in-field and distant relapse. The aggressiveness and atypical natural history of this disease, driven by the need for ongoing immunosuppression, highlights the inadequacies of current treatment approaches.

Minor salivary gland carcinoma involving the oral cavity or oropharynx.

BACKGROUND: Minor salivary gland carcinomas are uncommon but most often occur in the oral cavity, particularly the hard palate. Dental examination may provide an opportunity for early detection. METHODS: Patients referred to the multidisciplinary head and neck clinic at Westmead Hospital between 1980-2002 with a diagnosis of minor salivary gland carcinoma of the oral cavity or oropharynx were retrospectively identified. Data were collected on histology, treatment, outcome and the referring practitioner. RESULTS: A total of 30 patients diagnosed with a malignant minor salivary gland carcinoma were identified. Many patients, 16/30 (53 per cent), were referred by dentists. There were 15 males and 15 females with a mean age of 62 years (range, 22-86 yrs). Most (73 per cent) presented with early stage disease (stage 1/11). Adenoid cystic carcinoma was the most common histological subtype (40 per cent) followed by mucoepidermoid carcinoma (30 per cent) and polymorphous low-grade adenocarcinoma (20 per cent). All but two patients underwent surgery with 12/30 (40 per cent) also receiving adjuvant radiotherapy usually in the setting of an incomplete/close margin. One patient developed local recurrence and one developed widespread metastatic disease. At last follow-up 83 per cent of patients were alive and disease free. CONCLUSIONS: Early diagnosis and treatment of minor salivary gland carcinoma is likely to lead to a better outcome. In our study dentists were responsible for half of all referrals to our multidisciplinary head and neck clinic. Awareness of this uncommon entity is important for dental practitioners.

Tongue cancer: do patients younger than 40 do worse?

BACKGROUND: Debate continues as to whether being young confers a worse prognosis for patients with squamous cell carcinoma of the tongue. Recent papers have provided conflicting views in this debate. In this study we aimed to investigate if young age at the time of diagnosis of squamous cell carcinoma of the tongue confers a worse prognosis. METHODS: Eligible patients were identified through the computer database of the Department of Radiation Oncology, Westmead Hospital, Sydney. All eligible patients were treated with radical intent. Using age 40 as a cut off multivariate and survival analysis was undertaken to compare age groups. RESULTS: Median age at diagnosis was 60 years (range, 19-86 years) in 84 males (65 per cent) and 45 females (35 per cent). Median follow-up time was 43 months (range, 2.3-203 months). Fifteen patients (12 per cent) were aged <40 years. On univariate analysis stage and age were significant determinants of disease-specific survival. There was no difference in overall survival between the young (<40 years) and middle-aged groups (40-60 years). However, the young and the middle aged were both more likely to survive than the older age group (>60 years). On multivariate analysis age remained a significant factor for determining disease-specific survival, with the older age group 2.9 times more likely to die than the younger groups. CONCLUSION: Young age (<40 years) did not portend to worse survival in comparison to older tongue cancer patients.

Quality of life assessment in patients treated for metastatic cutaneous squamous cell carcinoma of the head and neck.

BACKGROUND: Treatment for metastatic cutaneous head and neck squamous cell carcinoma is usually multimodal and associated with morbidity. This study aimed to evaluate the impact of treatment on patients' quality of life. METHOD: Cross-sectional survey of 42 patients (35 men, 7 women) at least 6 months after metastatic cutaneous head and neck squamous cell carcinoma treatment, using two standardised quality of life questionnaires: the Functional Assessment of Cancer Therapy - Head and Neck questionnaire and the Facial Disability Index, with statistical analysis to identify potential predictors of outcome. RESULTS: Female gender correlated with significantly lower Facial Disability Index physical function scores (p = 0.017). Alcohol consumption correlated with significantly better scores for Functional Assessment social well-being (p = 0.016), general total score (p = 0.041) and overall total score (p = 0.033), and for Facial Disability Index physical function (p = 0.034). Marital status, education, employment, chemotherapy, time from last treatment, parotidectomy and facial nerve sacrifice did not affect quality of life. The commonest patient complaints were dry mouth (76 per cent), altered voice quality and strength (55 per cent), and physical appearance (45 per cent). CONCLUSION: Female gender predicts worse quality of life, while alcohol consumption (versus none) predicted for better quality of life.

In patients with metastatic cutaneous head and neck squamous cell carcinoma to cervical lymph nodes, the extent of neck dissection does not influence outcome.

BACKGROUND: This study aimed to compare recurrence and survival in patients undergoing either selective neck dissection or modified radical neck dissection to treat metastatic cutaneous head and neck squamous cell carcinoma to the cervical lymph nodes (levels I-V) only. METHODS: Twenty-eight year, retrospective analysis of a prospectively maintained database from a tertiary referral hospital, with a minimum follow up of two years. RESULTS: There were 122 eligible patients: 96 males (79 per cent) and 26 (21 per cent) females (median age, 66 years). Sixty-six patients (54 per cent) underwent selective neck dissection and 56 (46 per cent) modified radical neck dissection. The former patients had a lower rate of regional recurrence compared with the latter (17 vs 23 per cent, respectively). There was no significant difference in five-year overall survival (61 vs 57 per cent, respectively) or five-year disease-free survival (74 vs 60 per cent, respectively), comparing the two groups. Overall survival and disease-free survival were significantly improved by the addition of adjuvant radiotherapy. CONCLUSION: We found no difference in outcome in patients undergoing selective versus modified radical neck dissection. Adjuvant radiotherapy significantly improved outcome.

Metastatic cutaneous squamous cell carcinoma of the external ear: a high-risk cutaneous subsite.

INTRODUCTION: Patients with cutaneous squamous cell carcinoma of the external ear may develop metastatic spread to the nearby ipsilateral parotid and/or upper cervical lymph nodes. The literature suggests that the external ear is a high-risk subsite for such tumours, due to nodal metastasis and its associated morbidity and mortality. METHODS: Between 1980 and 2007, 43 patients with a diagnosis of metastatic cutaneous squamous cell carcinoma of the external ear were treated with surgery alone, surgery plus adjuvant radiotherapy, or radiotherapy alone. RESULTS: Patients comprised 39 men and four women. Their median age at diagnosis was 72 years, with a median follow up of 35 months. The median size of the primary lesion was 21 mm, with a median thickness of 7 mm. Fifteen patients presented concurrently with nodal metastases. Thirty patients developed parotid metastases (with positive cervical nodes in six patients), while 13 developed cervical metastases only. Eight patients underwent surgery alone, 32 underwent surgery plus adjuvant radiotherapy, and three received radiotherapy alone. At the last follow up, 15 patients had relapsed and nine had died of their disease, with a median survival after relapse of 5.5 months. CONCLUSION: Patients with metastatic cutaneous squamous cell carcinoma of the external ear have a relatively poor outcome, with a significant number of patients experiencing nodal relapse and death after treatment.

The important role of radiotherapy in patients with non-melanoma skin cancer and other cutaneous entities.

Non-melanoma skin cancer is the commonest malignancy worldwide and a significant public health issue. Although most non-melanoma skin cancers are small and easily excised or ablated, a recommendation of definitive radiotherapy is often made in patients where the outcome (cosmetic and/or functional) will probably be better with radiotherapy compared to surgery. The aim of adjuvant radiotherapy is to reduce the risk of loco-regional recurrence and the role of palliative radiotherapy is important in improving the quality of life in patients with advanced and/or incurable disease. The aim of this review article is to broadly discuss the various clinical settings in which a recommendation of radiotherapy may be made and also includes a discussion on less frequently encountered cutaneous entities (e.g. in situ squamous cell carcinoma, keratocanthoma, lentigo maligna, cutaneous lymphomas and malignant fibrous tumours).

Basal cell carcinoma of the nose: an Australian and New Zealand radiation oncology patterns-of-practice study.

Patients with a basal cell carcinoma (BCC) of the nose may be recommended radiotherapy (RT) with a wide variation in techniques and prescribed dose fractionation schedules between clinicians. The aim of this study was to ascertain variability in the patterns of practice among Australian and New Zealand radiation oncologists (ROs) when treating BCC arising on the nose. A postal survey was sent to 222 practising ANZ ROs detailing 12 different clinical scenarios of a BCC arising on the nose. The treatment selected for each scenario was analysed according to clinician's attitudes, training, experience and the availability of resources. The response rate was 74% (165/222) with 90 respondents treating non-melanoma skin cancer. Training was perceived to have a marked influence on treatment practice by most (79%). In total, 72% of ROs were 'very certain' in their choice of a dose fractionation schedule for obtaining local control and 61% for a satisfactory cosmetic outcome, respectively. Most (76%) favoured low-voltage photons over electrons as the optimal method of treatment, although for certain clinical scenarios most would use electrons. Dose fractionation schedules were highly variable with a lower total dose and hypofractionation favoured for older patients. Low-voltage photons were favoured for the T1 BCC and electrons for the T2 and T4 BCC. Nearly one-third of the ROs chose megavoltage photons for the T4 lesion. There is marked variation in treatment practices in terms of recommending RT over other treatment options, the choice of RT method, the dose fractionation schedule, the extent of field margins and the point of dose prescription.

Role of radiotherapy in the management of organ transplant recipients diagnosed with non-melanoma skin cancers.

Organ transplantation has had a major effect on the lives of thousands of patients worldwide. In Australia and New Zealand, over 13 000 patients have become organ transplant recipients (OTR). Following transplantation, patients require lifelong immunosuppression to prevent organ rejection. The loss of immune surveillance results in OTR experiencing a higher incidence of infection and malignancy in comparison with the general (immunocompetent) population. Non-melanoma skin cancer (NMSC) is the most common malignancy worldwide, arising most often on the sun-exposed head and neck. Organ transplant recipients experience a higher incidence of NMSC when compared with the general population and a higher incidence of squamous cell carcinoma compared with basal cell carcinoma. Organ transplant recipients also develop NMSC at a younger age and experience multiple new NMSC. Australians experience the highest incidence of NMSC in the world with a consequence that NMSC arising in OTR can lead to significant morbidity and even mortality. Radiation oncologists treating patients with skin cancer will almost certainly make recommendations in the setting of NMSC arising in OTR. The aim of this article is to discuss the role of radiotherapy in the management of OTR diagnosed with NMSC. The emphasis will be on the treatment of patients with a high-risk NMSC (e.g. squamous cell carcinoma, Merkel cell carcinoma, unfavourable basal cell carcinoma) because this reflects the most common clinical scenario in which a recommendation of radiotherapy, usually adjuvant, may be considered.

Use of topical misoprostol to reduce radiation-induced mucositis: results of a randomized, double-blind, placebo-controlled trial.

Radiation-induced mucositis is an acute reaction of the mucosa of patients undergoing head and neck radiotherapy. It can have debilitating and dose-limiting consequences. There is no consensus on an accepted intervention that significantly reduces its severity. Misoprostol is a synthetic prostaglandin E1 analogue, with properties of a mucosal cytoprotectant. We designed a randomized, double-blind, placebo-controlled trial of misoprostol in patients with head and neck cancer. The aim of this study was to determine if topical misoprostol was effective in reducing the severity of radiation-induced mucositis in patients receiving radical dose radiotherapy. The effect of this intervention on a patient's general well-being was also investigated. The primary end-point of the study was the incidence of Radiation Therapy Oncology Group grade 3 mucositis. Between 1999 and 2002, 83 patients were recruited into the study at Westmead and Nepean Hospitals, Sydney. Forty-two patients were randomized to receive misoprostol and 41 to receive a placebo. Most patients received radiotherapy in the adjuvant setting (52 of the 83) and had either an oral cavity (42 of the 83) or an oropharyngeal (16 of the 83) cancer. We could not identify any significant difference in the incidence of severe mucositis based on whether patients were allocated to receive misoprostol or placebo. There was no significant difference in the mean area under the mucositis curve (13.2 vs 16.6; P = 0.1). Patients allocated to misoprostol did report slightly increased soreness (7.6 vs 6.9; P = 0.04) and a greater use of analgesics. However, this difference did not translate into a worse feeling of general well-being as measured by a simple visual analogue scale (5.8 vs 5.2; P = 0.3). In conclusion, we were unable to identify a reduction in radiation-induced mucositis in patients receiving misoprostol. There is a paucity of high-level evidence on potentially useful interventions and a continued need for new and innovative research, incorporating quality-of-life measurements, in patients experiencing radiation-induced mucositis.

Treatment recommendations in patients diagnosed with high-risk cutaneous squamous cell carcinoma.

Non-melanoma cutaneous cancers occur at an epidemic rate in Australia. With an ageing population, more Australians will develop these cancers and at an increasing rate. In the majority of cases local treatment is highly curative. However, a subset of the population will be diagnosed with a high-risk cutaneous squamous cell carcinoma. These can be defined as patients at risk of having subclinical metastases to regional lymph nodes based on unfavourable primary lesion features (including inadequately excised and recurrent lesions), patients with metastatic squamous cell carcinoma to regional lymph nodes, and squamous cell carcinoma in immunosuppressed patients. The mortality and morbidity associated with high-risk cutaneous squamous cell carcinoma is usually as a consequence of uncontrolled metastatic nodal disease and, to a lesser extent, distant metastases. Radiotherapy has an essential role in treating these patients and in many cases the addition of adjuvant radiotherapy may be life saving. It is therefore important that all clinicians treating skin cancers have an understanding and awareness of the optimal approach to these patients. The aim of this article is to present treatment recommendations based on an overview of the current published literature.

Perineural spread in head and neck skin cancer.

Perineural spread (PNS) in the head and neck is an infrequent but aggressive manifestation of skin cancer. As such, it can provide access to the intracranial cavity. Squamous cell carcinoma is the most common histology with the facial and trigeminal nerves most often involved. Orbital invasion is an uncommon but devastating result of PNS located around the orbit, particularly the forehead. Diagnosis can be difficult and initial investigations are often unhelpful. Treatment should ideally be directed at preventing further spread before it develops. Adjuvant radiotherapy is often recommended. The disease may present at an advanced state within the orbit or parotid gland or even within the intracranial cavity. Clinicians need to be aware of the potential for PNS because a group of these patients will die from this potentially preventable and treatable form of metastatic skin cancer.

Aggressive skin cancers in a cardiac transplant recipient.

Skin cancers following cardiac transplantation are a serious problem that may lead to significant morbidity and mortality. While the majority of skin cancers represent minimally invasive lesions that are treated adequately by local means, a small subset exhibits a potentially life-threatening natural history. The aggressiveness of these skin cancers, despite standard treatment, is indicative of the aggressive nature displayed by a subset of secondary malignancies following cardiac transplantation. The need for lifelong maintenance immunosuppression after transplantation is a major factor in the development of these secondary malignancies. Presented here is the case study of a cardiac transplant recipient who developed multiple aggressive squamous and non-squamous cell scalp skin cancers.

Tongue cancer in younger patients.

Tongue cancer involving the anterior tongue often presents at an early stage. The aetiology is strongly associated with smoking and alcohol abuse similar to other squamous cell carcinomas (SCC) of the head and neck (HN). Surgery and radiotherapy, either alone or together, offer the prospect of cure in the majority of patients. However, there remains a group of younger patients less than 40 years old for whom outcome is often poor. Presented here is the case of a 24-year-old woman who developed SCC of the anterior tongue. Despite treatment, loco-regional relapse occurred resulting in death. The literature identifies a distinct subgroup of younger patients who develop HN SCC, particularly of the oral cavity. The aetiology remains unclear. Recent studies have looked at the prognostic significance of various new non-clinico-pathological markers in HN SCC (including p53 tumour suppressor gene, cyclin D1 protein, Ki 67 antigen and tumour angiogenesis). The majority of these studies, as expected, have involved the typical HN patient (male, aged > 60 years old). However, the relevance of these studies is of likely importance to all patients diagnosed with HN SCC. The recent use of these non-clinical-pathological markers in HN SCC, including reference to such studies in younger patients, is discussed. The English literature during the past 30 years is reviewed with reference to the diagnosis of tongue SCC in younger patients.

Perineural spread leading to orbital invasion from skin cancer.

Orbital and intracranial invasion from skin cancer is an uncommon but serious consequence of skin cancer located around the orbit, particularly the forehead. Perineural spread is an aggressive manifestation of skin cancer similar to lymph node metastases. Such spread can provide access to the orbit and squamous cell carcinoma is the most common histology reported. Treatment should be directed at preventing such orbital spread. Adjuvant radiotherapy is strongly recommended. Disease may present in an advanced state within the orbit or beyond the orbital apex and involve the cavernous sinus. Palliative radiotherapy should be considered in such advanced cases. Presented are the cases of four patients treated for advanced orbital and intracranial spread from periorbital skin cancer.

Erythema multiforme-like reaction associated with radiotherapy.

Generalized cutaneous reactions in association with radiotherapy have in the past been grouped into erythema multiforme (EM) and erythema multiforme-like reactions, the latter being reactions that do not strictly fit the accepted clinical and/or histological criteria for EM, yet have similar findings or presentations. Though usually benign and self-limiting, the progression to Stevens-Johnson syndrome, a potentially fatal form of erythema multiforme, has been reported. Presented here is a case study of a less severe radiation-induced erythema-like reaction.