Electrochemotherapy in the treatment of metastatic malignant melanoma: a prospective cohort study by InspECT.

BACKGROUND: (ECT) is an effective local treatment for cutaneous metastasis. Treatment involves the administration of chemotherapeutic drugs followed by delivery of electrical pulses to the tumour. OBJECTIVES: To investigate the effectiveness of ECT in cutaneous metastases of melanoma and to identify factors that affect (beneficially or adversely) the outcome. METHODS: Thirteen cancer centres in the International Network for Sharing Practices on Electrochemotherapy consecutively and prospectively uploaded data to a common database. ECT consisted of intratumoral or intravenous injection of bleomycin, followed by application of electric pulses under local or general anaesthesia. RESULTS: In total, 151 patients with metastatic melanoma were identified from the database, 114 of whom had follow-up data of 60 days or more. Eighty-four of these patients (74%) experienced an overall response (OR = complete response + partial response). Overall, 394 lesions were treated, of which 306 (78%) showed OR, with 229 showing complete response (58%). In multivariate analysis, factors positively associated with overall response were coverage of deep margins, absence of visceral metastases, presence of lymphoedema and treatment of nonirradiated areas. Factors significantly associated with complete response to ECT treatment were coverage of deep margins, previous irradiation of the treated area and tumour size (< 3 cm). One-year overall survival in this cohort of patients was 67% (95% confidence interval 57-77%), while melanoma-specific survival was 74% (95% confidence interval 64-84%). No serious adverse events were reported, and the treatment was in general very well tolerated. CONCLUSIONS: ECT is a highly effective local treatment for melanoma metastases in the skin, with no severe adverse effects noted in this study. In the presence of certain clinical factors, ECT may be considered for local tumour control as an alternative to established local treatments, or as an adjunct to systemic treatments.

Improved survival prediction for oropharyngeal cancer beyond TNMv8.

PURPOSE: For oropharynx squamous cell carcinoma (OPSCC) this study aimed to: (i) compare 5-year overall survival (OS) stratification by AJCC/UICC TNM versions 7 (TNMv7) and 8 (TNMv8), (ii) determine whether changes to T and N stage groupings improve prognostication and (iii) develop and validate a model incorporating additional clinical characteristics to improve 5-year OS prediction. MATERIAL AND METHODS: All OPSCC treated with curative-intent at our institution between 2011 and 2017 were included. The primary endpoint was 5-year OS. Survival curves were produced for TNMv7 and TNMv8. A three-way interaction between T, N stage and p16 status was evaluated for improved prognostication. Cox proportional hazards modelling was used to derive a new predictive model. RESULTS: Of 750 OPSCC cases, 574 (77%) were p16-positive. TNMv8 was more prognostic than TNMv7 (concordance probability estimate [CPE] ±â€¯SE = 0.72 ±â€¯0.02 vs 0.53 ±â€¯0.02). For p16-positive disease, TNMv8 discriminated stages II vs I (HR 2.32, 95% CI 1.47-3.67) and III vs II (HR 1.75, 95% CI 1.13-2.72). For p16-negative disease, TNMv7 and TNMv8 demonstrated poor hazard discrimination. Different T, N stage and p16-status combinations did not improve prognostication after adjusting for other factors (CPE = 0.79 vs 0.79, p = 0.998). A model for p16-positive and p16-negative OPSCC including additional clinical characteristics improved 5-year OS prediction beyond TNMv8 (c-index 0.76 ±â€¯0.02). CONCLUSIONS: TNMv8 is superior to TNMv7 for p16-positive OPSCC, but both performed poorly for p16-negative disease. A novel model incorporating additional clinical characteristics improved 5-year OS prediction for both p16-positive and p16-negative disease.

Electrochemotherapy and Ablative Therapies in Non-melanoma Skin Cancer.

Although surgery and radiotherapy remain the most commonly used treatments for non-melanoma skin cancer, there are a variety of alternatives. Here we discuss the use of electrochemotherapy and ablative treatments and examine the evidence for their effectiveness against a number of non-melanoma skin cancers.

Primary radical radiotherapy for squamous cell carcinoma of the middle ear and external auditory cana--an historical series.

AIMS: To evaluate patients treated with radical radiotherapy alone for squamous cell carcinoma of the middle ear (MEC) and external auditory canal (EAC) in terms of freedom from local recurrence, cancer-specific survival and morbidity. MATERIALS AND METHODS: Between 1965 and 1988, 123 patients were treated, 70 with MEC and 53 with EAC. The median age was 64 years (range 21-86) and 78% presented as late stage. The median dose was 55 Gy (range 39-55) in 16 once daily fractions (range 13-21). RESULTS: At 5 and 10 years, respectively, freedom from local recurrence was 56 and 56%, disease-free survival was 45 and 43%, cancer-specific survival was 53 and 51%, and overall survival was 40 and 21%. Cancer-specific survival was significantly worse with late stage as opposed to early stage (P = 0.0026), as was local recurrence (P = 0.0088). No differences in survival and local control were seen according to site. Radionecrosis developed in 6% of patients. CONCLUSIONS: Combined treatment using radiotherapy and radical surgery is often favoured. This large series shows that radical radiotherapy achieves comparable results in terms of local control and cancer-specific survival. Our radiotherapy regimen is now 55 Gy in 20 daily fractions to reduce late morbidity. Radiotherapy alone remains a viable option, especially as morbidity can be minimised and target volume delineation optimised using computer planning in the future.

331 cases of clinically node-negative supraglottic carcinoma of the larynx: a study of a modest size fixed field radiotherapy approach.

PURPOSE: For node-negative supraglottic carcinoma of the larynx, radiotherapy with surgery in reserve commonly provides very good results in terms of both local control and survival, while preserving function. However uncertainty exists over the treatment of the node-negative neck. Elective whole neck radiotherapy, while effective, may be associated with significant morbidity. The purpose of this study was to examine our practice of treating a modest size, fixed field to a high biologically effective dose and compare it with the patterns of recurrence from other centers that use different dose/volume approaches. METHODS AND MATERIALS: Over a 10-year period 331 patients with node-negative supraglottic carcinoma of the larynx were treated with radiotherapy at the Christie Hospital Manchester. Patients were treated with doses of 50-55 Gy in 16 fractions over 3 weeks. Data were collected retrospectively for local and regional control, survival, and morbidity. RESULTS: Overall local control, after surgical salvage in 17 cases, was 79% (T1-92%, T2-81%, T3-67%, T4-73%). Overall regional lymph node control, after surgical salvage in 13 cases, was 84% (T1-91%, T2-88%, T3-81%, T4-72%). Five-year crude survival was 50%, but after correcting for intercurrent deaths was 70% (T1-83%, T2-78%, T3-53%, T4-61%). Serious morbidity requiring surgery was seen in 7 cases (2.1%) and was related to prescribed dose (50 Gy-0%, 52.5 Gy-1. 3%, 55 Gy-3.4%). DISCUSSION: Our results confirm that treating a modest size, fixed field to a high biologically effective dose is highly effective. It enables preservation of the larynx in most cases, with acceptable regional control and no loss of survival compared to whole neck radiotherapy regimes.

Definitive radiotherapy for 114 cases of T3N0 glottic carcinoma: influence of dose-volume parameters on outcome.

BACKGROUND AND PURPOSE: Assuming that the dose-response curve for T3N0M0 glottic carcinoma is steep and that the rate of occult lymph node metastases is low, it should be possible to employ high biological tumour doses to modest target volumes and thereby maximise laryngeal control without compromising final neck control. Within the constraints of a retrospective study we aim to examine this policy with respect to local control, incidence of nodal relapse and late complications. MATERIALS AND METHODS: One hundred and fourteen patients with T3N0M0 glottic carcinoma who received a 3-week schedule of radical radiotherapy between 1986 and 1994 were analysed. The median age was 67 years (range, 34-85 years) and the median follow-up for living patients was 4.8 years (1.9-8.9 years). There were no strict selection criteria for those patients treated with radiotherapy. RESULTS: The 5-year overall survival was 54%. The 5-year local control with radiotherapy and the ultimate loco-regional control following salvage laryngectomy were 68 and 80%, respectively. Nine patients (8%) suffered a regional nodal relapse but only three of these (3% overall) occurred in the absence of local failure. Four patients (3.5%) developed serious late complications requiring surgical intervention (three received 55 Gy and one 52.5 Gy). CONCLUSIONS: It is possible to employ maximum tolerable doses to specific target volumes and thereby exploit the dose response demonstrated and minimise major late effects. The use of modest target volumes resulted in only 3% of patients requiring surgery that might have been avoided had prophylactic neck irradiation been employed.

Radical radiotherapy for carcinoma of the oesophagus: an effective alternative to surgery.

BACKGROUND AND PURPOSE: Despite advances in operative and postoperative care, long term survival rates following radical oesophagectomy are poor. Surgery remains the mainstay of radical treatment despite various series reporting similar results for treatment with radiotherapy, in particular in the upper third of the oesophagus. We have studied a cohort of patients treated with definitive radiotherapy to examine the influence on survival of changes in diagnostic scanning and radiotherapy computer planning as well as various patient and disease related prognostic factors. PATIENTS AND METHODS: From 1985 to 1994, 101 patients with clinically localised carcinoma of the oesophagus were treated at the Christie Hospital with definitive radiotherapy. This included 11 patients with oesophageal adenocarcinoma. Diagnostic and planning techniques changed over the period studied, with increasing use of both diagnostic and radiotherapy planning CT scanning. Radiotherapy doses ranged from 45 to 52.5 Gy in 15 or 16 fractions over 3 weeks. RESULTS: The 3- and 5-year survival figures were 27% and 21%, respectively, corrected for intercurrent deaths. Survival was better for adenocarcinoma than squamous cell carcinoma, though not statistically significantly. The only significant prognostic factor (P = 0.01) was the use of diagnostic CT scanning (42% versus 13% 5-year survival with or without diagnostic CT scanning, respectively) which was associated with an increase in field size. Radiotherapy was well tolerated with no acute mortality or significant morbidity. Late stenosis requiring oesophageal was seen in five of 20 patients surviving 3 years or more. CONCLUSIONS: Survival following well planned radiotherapy is an effective alternative to surgery for both squamous cell and adenocarcinoma. Advances in staging and three-dimensional planning and the use of multimodality treatment may further improve survival.

Small cell carcinoma of the uterine cervix: a clinicopathological review.

Small cell carcinoma of the cervix is rare, with an aggressive natural history. We report on a series of 11 patients treated at the Christie Hospital, Manchester and examine their treatment and survival. Eleven patients with small cell carcinoma of the cervix were identified retrospectively from patient case notes. Treatment was individualised and included a variety of combinations of surgery radiotherapy and chemotherapy. Four patients were disease-free between 21 and 108 months (crude disease-free survival 36%). They presented with earlier disease and were older than the average for the group. They were all initially treated with radical radiotherapy. 7 patients died between 7 and 25 months. Despite combination chemotherapy, survival with advanced disease was poor. Published studies are small and fail to provide definitive answers on the best management of small cell carcinoma of the cervix. Drawing on the experience of small cell carcinoma of the lung however, combination therapy with radiotherapy, chemotherapy and possibly surgery requires careful assessment by an oncologist.

Radiotherapy for carcinoma of the posterior pharyngeal wall.

Posterior pharyngeal carcinoma has an extremely poor prognosis regardless of the method of treatment. The purpose of this study was to assess the local control and survival in patients with carcinoma of the posterior pharyngeal wall treated with definitive radiotherapy and to determine prognostic factors which may be relevant to the current UICC staging classification. Between January 1991 and December 1995, 22 patients with a mean age of 60 years (range 44-82) received definitive radiotherapy, using a homogeneous technique, for carcinoma of the posterior pharyngeal wall. The median follow-up was 42 months (range 25-66). The overall 3-year survival and local control for the whole group was 50% and 73% respectively. Patients with early stage (T1 and T2) disease had a significantly better overall 3-year survival rate of 77% compared to 11% for patients with advanced stage (T3 and T4) disease (p=0.0010). Similarly, patients with early stage disease had a significantly improved 3-year local control rate compared to patients with more advanced stage disease (92% and 44% respectively, p=0.0080). Patients with node positive disease had an inferior survival rate of 29% compared to 60% for those with node negative disease though the difference did not reach statistical significance. In addition only one patient with initial node negative disease had isolated nodal relapse. There was no significant late morbidity. For patients with early stage disease we have obtained local control and survival rates comparable to other groups with a once daily, short fractionation radiotherapy scheme but with reduced morbidity. In late stage disease altered fractionation schemes should be considered in order to achieve better local control and survival. Isolated nodal relapse was not a significant problem in this cohort of patients. Outcome correlates with primary tumour size and this is reflected in the current UICC staging classification.

Carcinoma of the hard palate treated with radiotherapy: a retrospective review of 31 cases.

There are few studies reporting the results of radical radiotherapy for carcinoma of the hard palate. We have examined our results of patients treated within a single institution, and assessed survival, local control and morbidity. A retrospective analysis was made on 31 patients with hard palate carcinoma treated with external beam radiotherapy at the Christie Hospital between 1990 and 1997. Twenty-six patients received radiotherapy alone and five were treated for post-operative positive surgical margins. The 5-year actuarial survival rate was 55%. The actuarial 5-year local control rate was 53%, rising up to 69% after salvage surgery. Survival was 48% for squamous cell carcinomas and 63% for salivary gland carcinomas, the difference was not significant. The only significant predictor of local control was T-stage, with 80% 5-year local control of T1-2 lesions and 24% control of T3-4 lesions. N-stage was the only significant factor predicting for survival. Radiation necrosis occurred in one patient. Radical radiotherapy for carcinoma of the hard palate is safe and well tolerated. It is an effective treatment for both squamous cell carcinoma and salivary gland carcinoma.

Submandibular gland carcinoma; an audit of local control and survival following adjuvant radiotherapy.

Carcinoma of the submandibular gland is a rare diagnosis, accounting for less than 2% of cases of salivary gland tumours. We have examined the treatment and outcome of a total of 30 patients treated with radiotherapy at the Christie Hospital, Manchester between 1980 and 1993. In most cases this followed radical surgery, though 12 patients were referred following either incomplete excision or biopsy only. Adenoid-cystic histology accounted for 19 cases (63%). Standard radiotherapy was delivered using a beam directed technique to treat the whole submandibular compartment. Doses prescribed were most commonly from 50 to 55 Gy in 16 fractions over three weeks. Cancer specific survival was 79% and 57% at 5 and 10 yr respectively, the continued fall at 10 yr reflected late recurrence seen in patients with adenoid-cystic histology. Local control was 85% and 73%, respectively. Nine of twelve patients with incomplete excision or biopsy only had local control with radiotherapy. Six patients developed lung metastases, all of whom had adenoid-cystic histology. Radiotherapy was well-tolerated acutely, and only one patient experienced osteoradionecrosis requiring surgical intervention. The incidence of adenoid-cystic carcinoma is higher in the submandibular than the parotid gland. This typically results in late recurrence, and a high incidence of lung metastases and this was confirmed in our study. However, overall survival was very similar to that of parotid carcinoma.

Squamous cell carcinoma of the lip: the role of electron treatment.

After skin cancer, squamous cell carcinoma (SCC) of the lip is the most common cancer of the head and neck. It can be treated in a variety of ways, including both surgery and radiotherapy. Many centres have reported excellent cure and local control rates for their chosen treatment method. Electron beam treatment is recognized as a method of treatment and has theoretical advantages related to its depth-dose characteristics. We report a retrospective study of the treatment with electrons of 26 patients with Stage T1-2 SCCs of the lip. With a median follow-up period of 31 months (range 1.5-60) 100% local control was obtained, although two patients required surgical salvage, one for a geographical miss. One patient presented with metastatic neck nodes, and one relapsed in the neck, but both were treated with a combination of surgery and radiotherapy and were free of disease at follow-up. Patients tolerated the acute radiation reaction well and the long term cosmetic and functional results were good. Two patients experienced minor soft tissue necrosis, one of whom required surgical treatment. Electron treatment for T1-2 SCC of the lip is an effective, well tolerated treatment for these patients, many of whom are elderly and frail.

An analysis of radiotherapy in the management of 104 patients with parotid carcinoma.

A retrospective analysis was made of 104 patients with parotid carcinoma treated with radical radiotherapy between 1977 and 1986. Eighty-seven patients received postoperative radiotherapy and 17 had radiotherapy alone. The 5- and 10-year survival figures, corrected for intercurrent deaths, were 60% and 49% respectively, with primary control rates of 68% and 58%. Local control was significantly better for patients initially presenting with T1/T2 disease, but local relapse still occurred in 23% of these patients. Of 13 patients with acinic cell tumours, four developed local recurrence and a further two had metastatic disease. These patterns of relapse suggest that patients with parotid carcinoma should receive postoperative radiotherapy irrespective of disease stage or histological type.

Radiotherapy treatment of non-melanoma skin cancer: a survey of current UK practice and commentary.

OBJECTIVE: In the ongoing absence of available trial data, a national survey was carried out to provide details on radiotherapy treatment strategy for non-melanoma skin cancer (NMSC). METHODS: A survey of clinical oncologists treating NMSC was performed. The respondents were asked for basic information on workload as well as a proposed treatment strategy for various clinical scenarios for patients of varying fitness. RESULTS: A total of 43 completed and 20 partially completed surveys were received. There was a wide variation in the workload and additional disease sites that respondents had responsibility for. Kilovoltage radiotherapy was available to 81% of responders. The respondents' approach was affected by the fitness of patients, with longer fractionation regimes proposed for younger, fitter patients and shorter or non-standard fractionations more likely for the infirm elderly. Four daily fractionation regimes (18-20 Gy in 1 fraction, 35 Gy in 5 fractions, 45 Gy in 10 fractions and 55 Gy in 20 fractions) were most commonly suggested. There was a large degree of variation in non-standard fractions proposed with significant potential differences in radiobiological effect. Concern over the use of kilovoltage photons on skin over cartilage was apparent, as was a reluctance to use radiotherapy in areas of increased risk of poor wound healing. CONCLUSION: The survey results largely showed practice to be in line with available published evidence. The variation seen in some areas, such as non-standard fractionation, would benefit from the publication of local outcomes to achieve a more consistent approach. ADVANCES IN KNOWLEDGE: This study provides information on national practices and identifies variations, particularly within widespread use of non-standard fractionation.

Value of the Hospital Anxiety and Depression Scale in the follow up of head and neck cancer patients.

BACKGROUND: Few studies have prospectively investigated psychological morbidity in UK head and neck cancer patients. This study aimed to explore changes in psychological symptoms over time, and associations with patients' tumour and treatment characteristics, including toxicity. METHODS: Two hundred and twenty patients were recruited to complete the Hospital Anxiety and Depression Scale and the Late Effects on Normal Tissue (Subjective, Objective, Management and Analytic) ('LENT-SOMA') questionnaires, both pre- and post-treatment. RESULTS: Anxiety was highest pre-treatment (38 per cent) and depressive symptoms peaked at the end of treatment (44 per cent). Anxiety significantly decreased and depression significantly increased, comparing pre- versus post-treatment responses (p < 0.001). Hospital Anxiety and Depression Scale scores were significantly correlated with toxicity, age and chemotherapy (p < 0.01 for all). CONCLUSION: This is the first study to analyse the relationship between Hospital Anxiety and Depression Scale scores and toxicity scores in head and neck cancer patients. It lends support for the use of the Hospital Anxiety and Depression Scale and the Late Effects on Normal Tissue (Subjective, Objective, Management and Analytic) questionnaire in routine clinical practice; furthermore, continued surveillance is required at multiple measurement points.

Nasopharyngeal carcinoma: a retrospective review of demographics, treatment and patient outcome in a single centre.

AIMS: Nasopharyngeal cancer (NPC) is relatively uncommon, especially in the Western world. We report our single institution experience of 20 years of data in 128 patients with NPC, including responses to different treatment modalities and outcomes by histological subtype. MATERIALS AND METHODS: NPC patients presenting from 1992 to 2005 were located on the cancer registry database. Demographic data included age, gender, length of presenting symptoms and stage. World Health Organization classification (2005) was used for histological subtyping. The date of recurrence and survival outcomes were analysed using Kaplan-Meier curves. RESULTS: Presentation data were analysed from 128 patients; the survival analysis included 123 patients. The median age at presentation was 57.7 years. Stage III and IV presentation rates were 34 and 38%, respectively. The most common presenting symptom was a palpable neck lump (55%) and the median duration of symptoms was 16 weeks. Forty-eight patients received radiotherapy alone and 75 received chemoradiotherapy. The median overall survival in chemoradiotherapy patients was 80.3 months versus 28.5 months with radiotherapy alone (P = 0.003). A significant difference was also seen with recurrence-free survival (RFS) (P = 0.017). Type 1 keratinising carcinoma had a significantly worse overall survival (P = 0.04) and a similar but non-statistically significant trend was seen for RFS (P = 0.051). The multivariate analysis for overall survival showed that histological subtype (hazard ratio 2.7, 95% confidence interval 1.3-5.5, P = 0.034), age (hazard ratio 2.3, 95% confidence interval 1.1-4.9, P = 0.018) and N stage (hazard ratio 3.7, 95% confidence interval 1.4-9.4, P = 0.024) were prognostic factors. CONCLUSIONS: We present the first large-scale, single-centre retrospective review of NPC in a UK-based population. Demographic data were similar to that in other Western populations, with a significantly worse survival outcome in the keratinising group. Further prospective study of outcome in Western populations accounting for newer radiotherapy techniques such as intensity-modulated radiotherapy and dose escalation, particularly in the keratinising population who were more likely to present with an isolated local recurrence, is recommended.

Primary radiotherapy for carcinoma of the retromolar trigone: a useful alternative to surgery.

AIMS: Squamous cell carcinoma of the retromolar trigone is uncommon. The standard initial treatment is primary surgery, which usually involves microvascular reconstruction with a composite flap. Some patients are considered unsuitable for this procedure. This retrospective study examined the outcome and toxicity for patients with squamous cell carcinoma of the retromolar trigone treated with definitive radiotherapy in a single centre. MATERIALS AND METHODS: Between 1991 and 2000, 43 patients were treated with definitive radiotherapy with a median dose of 50Gy in 16 fractions over 21 days. Hospital case notes and radiotherapy records were analysed. RESULTS: The median age was 66 years (range 39-84 years). Nodal disease was evident in 13 (30.2%) patients. Twenty-one patients (51.2%) had stage I/II disease and 20 patients (48.8%) had stage III/IV disease. After a median follow-up of 59 months, 13 (30.2%) patients were alive and well, nine (20.9%) patients had died of an intercurrent illness and 21 (48.8%) had died of their disease. Five-year locoregional control was 46.5% (95% confidence interval 29.7-61.7), cause-specific survival was 45.7% (95% confidence interval 29.1-60.8) and overall survival was 30.9% (95% confidence interval 17.5-46.3). Osteoradionecrosis was documented in two patients. DISCUSSION: This hypofractionated regimen is convenient for this patient population and produced comparable outcomes to longer fractionation schedules without an increase in late toxicity.