Pre-treatment tumour perfusion parameters and initial RECIST response do not predict long-term survival outcomes for patients with head and neck squamous cell carcinoma treated with induction chemotherapy.

OBJECTIVES: Previously, we showed that pre-treatment tumour plasma perfusion (Fp) predicts RECIST response to induction chemotherapy (ICT) in locoregionally advanced head and neck squamous cell carcinoma (HNSCC). The aim here was to determine whether the pre-treatment tumour Fp estimate, changes in tumour Fp or RECIST response post 2 cycles of ICT were prognostic for long-term survival outcomes. METHODS: A prospective study enrolled patients with high stage HNSCC treated with docetaxel (T), cisplatin (P) and 5-fluorouracil (F) (ICT) followed by synchronous cisplatin and intensity modulated radiotherapy. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) before and after two cycles of ICT was used to measure Fp and RECIST response. RESULTS: Forty-two patients were recruited and 37 underwent two scans. The median follow-up was 36 (range 23-49) months. Pre-treatment tumour Fp (stratified by median) was not prognostic for overall survival (p = 0.42), disease specific survival (p = 0.20) and locoregional control (p = 0.64). Neither change in tumour Fp nor RECIST response post two cycles of ICT was prognostic for any outcome (p>0.21). CONCLUSION: DCE-MRI parameters do not predict long-term survival outcomes following ICT and RECIST response to ICT may not be an appropriate endpoint to determine early efficacy of a treatment in HNSCC patients.

Taxane, platinum and 5-FU prior to chemoradiotherapy benefits patients with stage IV neck node-positive head and neck cancer and a good performance status.

PURPOSE: The benefit of adding docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy to chemoradiotherapy (CRT) in head and neck squamous cell carcinoma (HNSCC) remains uncertain. We aimed to investigate whether ICT is well tolerated when given with prophylactic treatment against predicted adverse effects and which patients benefit most. METHODS: A single-centre audit identified 132 HNSCC patients with stage IVa/b neck node-positive disease, prescribed TPF followed by CRT. TPF involved three cycles of docetaxel (75 mg/m2 IV) and cisplatin (75 mg/m2 IV) on day 1 plus 5-FU (750 mg/m2 IV) on days 2-5. Planned CRT was 66 Gy in 30 fractions of intensity-modulated radiotherapy with concurrent cisplatin (100 mg/m2 IV) at the beginning of week 1 and 4 (days 1 and 22). All patients received prophylactic antibiotics and granulocyte colony-stimulating factor. RESULTS: Median follow-up was 39.5 months. 92.4% of patients completed three cycles of TPF; 95.5% of patients started chemoradiotherapy. Grade 3/4 adverse events were low (febrile neutropenia 3.0%), with no toxicity-related deaths. 3-year overall survival was 67.2%; disease-specific survival was 78.7%; locoregional control was 78.3%. Distant metastases rate was 9.8% (3.0% in those without locoregional recurrence). Good performance status (p = 0.002) and poor tumour differentiation (p = 0.018) were associated with improved overall survival on multivariate analysis. CONCLUSION: With prophylactic antibiotics and granulocyte colony-stimulating factor TPF was well tolerated with good survival outcomes. TPF should remain a treatment option for stage IV neck node-positive patients with a good performance status. The use of tumour grade to aid patient selection for TPF warrants investigation.

Dose intensified hypofractionated intensity-modulated radiotherapy with synchronous cetuximab for intermediate stage head and neck squamous cell carcinoma.

BACKGROUND: For stage II and III head and neck squamous cell carcinoma (HNSCC) treated with radiotherapy alone, loco-regional recurrence is the main cause of treatment failure. Strategies to improve loco-regional control should not be at the expense of increased late normal tissue toxicity. We investigated dose-intensified hypofractionated intensity-modulated radiotherapy (IMRT) with synchronous cetuximab. MATERIAL AND METHODS: In a phase I/II trial, 27 patients with stage III or high risk stage II HNSCC were recruited. They received three dose level simultaneous integrated boost IMRT, 62.5 Gy in 25 daily fractions to planning target volume one over five weeks with synchronous cetuximab. The primary endpoint was acute toxicity. Secondary endpoints included: late toxicity and quality of life; loco-regional control, cause-specific and overall survival. RESULTS: Radiotherapy was completed by 26/27 patients; for one (4%) the final fraction was omitted due to skin toxicity. All cycles of cetuximab were received by 23/27 patients. Grade 3 acute toxicities included: pain (81%), oral mucositis (78%) and dysphagia (41%). There were few grade 3 physician-recorded late toxicities, including: pain (11%), problems with teeth (8%) and weight loss (4%). At 12 months, only one (4%) patient required a feeding tube, inserted prior to treatment due to dysphagia. The maximal/peak rates of patient-reported late toxicities included: severe pain (11%), any dry mouth (89%) and swallowing dysfunction that required a soft/liquid diet (23%). At 12 months, all quality of life and most symptoms mean scores had resolved to baseline or were only a little worse; dry mouth, sticky saliva and dentition scores remained very much worse. At a median follow-up of 47 months, there were five (18.5%) loco-regional recurrences and the overall cause-specific survival was 79% (95% CI 53-92). CONCLUSIONS: This regimen is safe with acceptable acute toxicity, low rates of late toxicity and impact on quality of life at 12 months following treatment. Further evaluation is recommended.

A double-blind, placebo-controlled, randomised trial of active manuka honey and standard oral care for radiation-induced oral mucositis.

Our aim was to investigate the effect of active manuka honey on radiation-induced mucositis. A total of 131 patients diagnosed with head and neck cancer who were having radiotherapy to the oral cavity or oropharyngeal area were recruited into the study, and were randomly allocated to take either manuka honey or placebo (golden syrup) 20 ml 4 times daily for 6 weeks. Mucositis was assessed according to the Radiation Therapy Oncology Group (RTOG) scale at baseline, weekly during radiotherapy, and twice weekly thereafter until the mucositis resolved. The patient's weight was recorded at the same time as the mucositis was assessed. Throat swabs to identify bacterial or fungal infections were taken at baseline, and during and after radiotherapy. There was no significant difference between honey and golden syrup in their effects on mucositis. Active manuka honey did not improve mucositis, but both the honey and the syrup seemed to be associated with a reduction in bacterial infections. Compliance was a problem after the onset of mucositis, which may have affected the findings.

Phase II study of cisplatin and imatinib in advanced salivary adenoid cystic carcinoma.

Patients with adenoid cystic carcinoma of the salivary glands show over-expression of KIT in a high proportion of cases. Options for systemic treatment are limited in locally advanced and metastatic disease. We explored the efficacy of imatinib and cisplatin combined in this group of patients. A Gehan's two-stage, phase II trial was conducted on 28 patients. Those with progressive, locally advanced, and metastatic disease with an over-expression of KIT were treated with single agent imatinib 800 mg daily for two months, followed by a combination of imatinib 400mg daily and cisplatin 80 mg/m(2) at four-weekly intervals for six cycles. This was followed by maintenance single agent imatinib 400mg daily until the disease progressed. Response was monitored using fluorodeoxyglucose positron emission tomography (FDG-PET) and morphological imaging using computed tomography, magnetic resonance, and chest radiographs (CT/MRI/CXR). Morphological imaging showed partial response in three of 28 patients, and five patients showed a response on FDG-PET. In addition, 19 patients had useful stabilisation of disease. The median time to progression and overall survival was 15 months (range 1-43) and 35 months (range 1-75), respectively. The combination of imatinib and cisplatin was reasonably well tolerated. This combination may provide stabilisation in locally advanced and metastatic adenoid cystic carcinoma of the salivary glands.

A systematic review of honey uses and its potential value within oncology care.

AIM: To synthesise the evidence regarding honey's role in health care and to identify whether this evidence applies more specifically to cancer care. DESIGN: Systematic review. METHODS: The inclusion and exclusion criteria were agreed by two reviewers and a keyword strategy was developed. EMBASE, CINAHL, AMED, MEDLINE, COCHRANE and PUBMED databases were screened to identify suitable articles. The citation list from each included study was also screened for potentially suitable papers. The key findings from each study were entered onto a data extraction sheet. RESULTS: In total, 43 studies were included in the systematic review, which included studies in relation to wounds (n = 19), burns (n = 11), skin (n = 3), cancer (n = 5) and others (n = 5). In addition, a systematic review regarding honey use in wound care was also included. While the majority of studies noted the efficacy of honey in clinical use, five studies found honey to be equally as effective as the comparator and three found honey to be less effective than the comparator treatment. Other research did not illustrate any significant difference between standard treatment regimes vs. honey treatment. Studies were generally poor in quality because of small sample sizes, lack of randomisation and absence of blinding. CONCLUSIONS: Honey was found to be a suitable alternative for wound healing, burns and various skin conditions and to potentially have a role within cancer care. RELEVANCE TO CLINICAL PRACTICE: In the cancer setting, honey may be used for radiation-induced mucositis, radiotherapy-induced skin reactions, hand and foot skin reactions in chemotherapy patients and for oral cavity and external surgical wounds.

Evaluating predictive factors for determining enteral nutrition in patients receiving radical radiotherapy for head and neck cancer: a retrospective review.

BACKGROUND AND PURPOSE: To identify objective pre-treatment clinical parameters that could be used to predict for patients at high risk of requiring enteral tube feeding prior to head and neck radiotherapy. PATIENTS AND METHODS: A retrospective study was conducted on 160 consecutive patients attending for radiotherapy assessment. Regression analysis was used to determine various pre-treatment nutritional and tumour specific parameters associated with the use of enteral nutrition either before (prophylactic) or during (reactive) radiotherapy (RT). The significant parameters identified were then selected into categorical variables and compared between those who needed reactive enteral nutrition and the remainder of the group who did not. These results were used to generate predictive factors that could be used to identify those at high risk of malnutrition during RT for whom early or prophylactic enteral nutrition should be considered. RESULTS: Fifty patients required enteral feeding of which 60% required this prior to radiotherapy. Multivariate analysis identified the following factors to be significant--body mass index, performance status (PS), advanced stage, pre-treatment weight loss, low serum albumin and protein, age, and smoking. The most significant categorical predictive parameters for reactive enteral feeding were stage 3-4 disease, PS 2-3, and smoking >20/day. The combination of these factors predicted a 75% chance of needing enteral nutrition. CONCLUSION: Nutritional assessment is important prior to radiotherapy and is multifactorial. Using a combination of relatively simple and objective parameters, (performance status, smoking and disease stage) it is possible to identify those at high risk of needing enteral nutrition prior to starting RT.

Results of a phase I study to determine the maximum tolerated dose of capecitabine when given concurrently with radical radiotherapy in the treatment of squamous cell carcinoma of the head and neck.

Capecitabine is preferentially converted to 5-fluorouracil within tumours, exploiting the higher levels of thymidine phosphorylase (TP) found in areas of poor perfusion and hypoxia. In addition radiation leads to up regulation of TP expression. To exploit these advantages of capecitabine as a synchronous chemoradiotherapy agent patients with advanced squamous cell carcinoma of the head and neck were recruited into a phase I non-randomised dose finding study. Capecitabine was given twice daily, 7 days a week at a dose starting at 350 mg/m(2) bid. Radiotherapy using a beam directed technique was prescribed to 55 Gy in 20 fractions over 4 weeks. A total of 24 patients were treated. Dose-limiting toxicity (grade IV mucositis) was reached at a capecitabine dose of 550 mg/m(2) bid. Radiotherapy was completed without delay in all cases. There was no systemic drug related toxicity. Capecitabine offers the prospect of an orally administered drug for use synchronously with radiotherapy, which in doses up to 500 mg/m(2) bid is well tolerated.

Three weeks radiotherapy for T1 glottic cancer: the Christie and Royal Marsden Hospital Experience.

BACKGROUND AND PURPOSE: Radiotherapy for laryngeal carcinoma is conventionally given over a 6-7-week period. However, in a number of UK centres early lesions are treated over 3 weeks. We review recent results of this policy and discuss the reasons why short treatment times may be advantageous. MATERIALS AND METHODS: Two hundred patients (100 from each centre) with T1 glottic invasive squamous cell carcinoma treated with definitive radiotherapy between 1989 and 1997 were analysed. The median age was 68 years. All patients received once daily fractionation, 5 days a week to a total tumour dose of 50.0-52.5 Gy in 16 fractions over 21 days; the fraction size ranged from 3.12 to 3.28 Gy. The median follow-up period was 5 years and 10 months. RESULTS: The 5-year local control rates with radiotherapy for the whole group was 93%; there were 14 recurrences of which seven were salvaged by laryngectomy giving an ultimate local control of 96%. The 5-year overall survival was 80% and cause specific survival at 5 years was 97%. Univariate analysis revealed that T1 substaging (P=0.82) and anterior commissure involvement (P=0.47) did not significantly influence local control. A severe late radiation complication was seen in only one patient who continued to smoke heavily after treatment. There were no severe acute complications. CONCLUSIONS: Once daily radiotherapy over 3 weeks gives excellent local control in patients with T1 glottic squamous-cell carcinoma and has a low rate of severe complications. The short overall treatment time and large fraction size may be advantageous in radiotherapy of these well-differentiated tumours.