Impact of the introduction of weekly radiotherapy quality assurance meetings at one UK cancer centre.

OBJECTIVE: The complexity of radiotherapy planning is increasing rapidly. Delivery and planning is subject to detailed quality assurance (QA) checks. The weakest link is often the oncologists' delineation of the clinical target volume (CTV). Weekly departmental meetings for radiotherapy QA (RTQA) were introduced into the Royal Wolverhampton Hospital, Wolverhampton, UK, in October 2011. This article describes the impact of this on patient care. METHODS: CTVs for megavoltage photon radiotherapy courses for all radical, adjuvant and palliative treatments longer than five fractions (with the exception of two field tangential breast treatments not enrolled into clinical trials) were reviewed in the RTQA meeting. Audits were carried out in January 2012 (baseline) and September 2013, each over a 4-week period. Adherence to departmental contouring protocols was assessed and the number of major and minor alterations following peer review were determined. RESULTS: There was no statistically significant difference for major alterations between the two study groups; 8 alterations in 80 patients (10%) for the baseline audit vs 3 alterations from 72 patients (4.2%) in the second audit (p = 0.17). A trend towards a reduction in alterations following peer review was observed. There has, however, been a change in practice resulting in a reduction in variation in CTV definition within our centre and greater adherence to protocols. There is increasing confidence in the quality and constancy of care delivered. CONCLUSION: Introduction of a weekly QA meeting for target volume definition has facilitated consensus and adoption of departmental clinical guidelines within the unit. ADVANCES IN KNOWLEDGE: The weakest areas in radiotherapy are patient selection and definition of the CTV. Engagement in high-quality RTQA is paramount. This article describes the impact of this in one UK cancer centre.

Radical chemoradiotherapy for urethral squamous cell carcinoma: two case reports and a review of the literature.

Primary urethral squamous cell carcinoma is rare. Its management is particularly challenging owing to the paucity of evidence from randomised trials to inform practice. We report two male and female cases of squamous cell carcinoma of the urethra, which were treated with concomitant cisplatin and radiotherapy. These cases add to the body of case reports that have shown benefit for concomitant chemoradiotherapy in urethral squamous cell carcinoma. They also illustrate that single agent chemotherapy, namely, cisplatin, may be used successfully with limited toxicities.

Can radiobiological parameters derived from squamous cell carcinoma of the head and neck be used to predict local control in anal cancer treated with chemoradiation?

OBJECTIVES: Parameters have been derived in head and neck cancer to account for the additional biological effective dose provided by synchronous chemotherapy. The purpose of this study was to establish whether such parameters could be used to predict local control differences in anal cancer. METHODS: In anal cancer two randomised trials of radiotherapy vs chemoradiotherapy and two trials randomising between different synchronous chemotherapy regimens were identified. To predict differences in local control between the arms of the first two studies, a global value of 9.3 Gy for the chemotherapy biologically effective dose was employed. For the last two trials, values specific to differing chemotherapy schedules were derived. These values were added to the calculated biological effective dose for the radiotherapy component in order to predict local control outcomes in anal cancer trials. RESULTS: The predicted difference in local control using the global value of 9.3 Gy for the addition of synchronous chemotherapy in the trials of radiotherapy vs radiotherapy and synchronous chemotherapy was 24.6% compared with the observed difference of 21.4%. Using schedule-specific values for the contribution of chemotherapy, the predicted differences in local control in the two trials of differing synchronous chemotherapy schedules were 7.2% and 12% compared with the observed 18% and 0%. CONCLUSION: The methods initially proposed require modification to result in adequate prediction. If the decreased cisplatin dose intensity employed in anal cancer is modelled, more satisfactory predictions for such trials can be achieved. ADVANCES IN KNOWLEDGE: This revised modelling may be hypothesis generating.

The role of somatostatin analogues in the treatment of advanced malignant thymomas: case report and review of the literature.

Thymomas are the most common tumours of the anterior mediastinum; their clinical course is often complicated by accompanying autoimmune and paraneoplastic syndromes. Advanced malignant thymoma is particularly challenging to manage owing to the lack of evidence from randomised trials to guide treatment. Combination first-line chemotherapy has been trialled in several small studies and has been reported to produce a 50-80% response with platinum-containing regimes. Progression following first-line chemotherapy is difficult to manage as most of these patients maintain a good performance status and demand further active palliative treatment. There is no standard second-line treatment. We report a good clinical and radiological response to third-line palliative octreotide therapy in a patient who had a positive octreotide scan.

Value of oral antibiotic prophylaxis in colorectal surgery.

A total of 169 patients undergoing colorectal surgery were randomly allocated to receive either gentamicin plus metronidazole or oral ciprofloxacin plus metronidazole as prophylaxis; they were also allocated to receive cover for 1 or 3 days. Twenty-eight patients (17 per cent) developed postoperative wound infections. The proportion of patients with wound infections and other infective complications was significantly less (P < 0.02) in those receiving oral ciprofloxacin. Cover for 3 days was no better than that for only 1 day. Oral ciprofloxacin for prophylaxis may offer advantages in efficacy and ease of administration compared with parenteral antibiotics.

Oral ciprofloxacin as prophylaxis in gastroduodenal surgery.

One hundred and fifty patients undergoing gastroduodenal surgery were randomly allocated to receive intravenous (iv) cefuroxime, iv ciprofloxacin or oral ciprofloxacin as prophylaxis. There were no differences in the incidence of postoperative infection complications or duration of stay among the three groups. Oral ciprofloxacin offers obvious advantages in terms of ease of administration and cost.

A dramatic change in the interaction of Cu(II) with bio-peptides promoted by SDS--a model for complex formation on a membrane surface.

The extent of complex formation between Cu(II) and many biologically active oligopeptides has been shown to change significantly in the presence of SDS micelles, a recognized model for cell lipid membranes. Protonation constants of peptides can be increased by up to 2 log unit, especially when they contain hydrophobic side chains. Metal complex formation is generally less extensive and the conformations of peptides can be altered dramatically when compared to those in simple aqueous solution.

The coordination of copper(II) to 1-hydroxy-4-(glycyl-histidyl-lysine)-anthraquinone; a synthetic model of anthraquinone anti-cancer drugs.

Results are reported of a pH-metric and spectroscopic (CD and ESR) study of the complexes formed between the pseudo-peptide 1-hydroxy-4-(Gly-His-Lys)-anthraquinone (Q-GHK) since, when complexed to copper ions, Q-GHK has been shown to be very effective in promoting the formation of free radicals and inducing DNA cleavage. Q-GHK forms very stable complexes with copper, the major species being bonded to three nitrogen donors in the coordination plane: an imidazole-N of the His residue and the peptide nitrogens of the Gly and His residues. This species is probably stabilized through bonding of the fourth planar coordination site of Cu(II) to the 9-anthraquinone oxygen. At high Q-GHK:copper ratios a second Q-GHK molecule is coordinated through its imidazole-N donor.

The value of oral antibiotic prophylaxis in biliary tract surgery.

In this study the relationship between the presence or absence of organisms in bile or on closing wound swabs and the subsequent development of wound sepsis was confirmed. There was no significant difference in the incidence of septic complications among three treatment groups in which cefuroxime (iv) and ciprofloxacin (iv or oral) were administered. Consideration of costs attributable to the choice of antibiotic prophylaxis suggests that oral ciprofloxacin in biliary tract surgery may offer significant advantages.

Mitomycin C-loaded microcapsules in the treatment of colorectal liver metastases. Pharmacokinetics of regionally administered particulate chemotherapy.

Microencapsulated mitomycin C has been used for the treatment of intrahepatic tumors in Japan, but there have been no reports of its use in western countries. In this study, the pharmacokinetic profile of intrahepatic arterial mitomycin C microcapsules is reported. Regional mitomycin C was administered to six patients, both in the microencapsulated form and in solution. The clearance (140 +/- 31 1/hour, mean +/- SD) and half-life of drug in plasma (0.39 +/- 0.03 hours), and volume distribution (246 +/- 23 1) were significantly higher, and peak drug concentrations (80 +/- 75 ng/ml) significantly lower with the microencapsulated preparation than with the free drug (clearance, 46 +/- 8 1/hour; half-life, 0.11 +/- 0.02 hours; volume distribution, 33 +/- 4; peak drug concentration, 812 +/- 423 ng/ml), on Student's t testing (P less than 0.05). The results show that very little systemic exposure is associated with the microencapsulated form of mitomycin C. Dose escalation should be feasible without increasing systemic toxicity.

Complexes of zinc, copper, and nickel with the nonprotein amino acid L-alpha-amino-beta-methylaminopropionic acid: a naturally occurring neurotoxin.

The non-protein amino acid L-alpha-amino-beta-methylaminopropionic acid (L-MeDAP) causes motor neuron dysfunction in macaques. The amino acid is a potent chelator of divalent metal ions such as copper and zinc. Binding constants nickel(II) for copper(II) and zinc(II) with L-MeDAP have been measured. Some copper(II) complexes of L-MeDAP have been synthesized and characterized by their electronic, infrared, and epr spectra. These results are used to comment on the possibility that metal ion complexation in the central nervous system is involved in the expression of the meurotoxicity of L-MeDAP.

Metal complexes of luteinizing hormone-releasing hormone (LHRH). potentiometric and spectroscopic studies.

The results are reported of a potentiometric and spectroscopic study of the H+, Cu2+, and Ni2+ complexes of luteinizing hormone-releasing hormone (LHRH, HL) at 25 degrees C and an ionic strength 0.10 mol dm-3 (KNO3), since there is much evidence that the in vivo release of LHRH is influenced by the concentration of copper ions. With Cu2+ the hormone has been shown to behave similarly to the thyrotropin releasing factor, forming a very stable [CuH-1L] complex involving coordination of three nitrogen donors: the Nim atom of the imidazole side chain and the two amido-N atoms of the pyroglutamylhistidyl unit. With Ni2+, coordination proceeds differently to give four nitrogen coordination.

The proton and metal complexes of adenyl-5'-yl imidodiphosphate.

The formation constants of the complexes of adenyl-5'-yl imidodiphosphate with H+ Mg2+, Ca2+ and a number of bivalent transition-metal ions were measured potentionmetrically. The complexes are generally a little more stable than the analogous complexes of ATP. By measuring the formation constants at two temperatures, this increase in stability was shown to result from an increased enthalpy change on complex-formation.