A Qualitative Assessment of Radiotherapy Training at a UK Regional Cancer Centre.

AIMS: Specialty trainees in clinical oncology must be competent in the coordination of both radiotherapy and systemic therapy at the completion of their training. Radiotherapy technology and postgraduate medical education have evolved significantly over the last two decades, but little is known of the educational impact of those changes within the dual training of the clinical oncology programme. A qualitative assessment of the radiotherapy component of training was undertaken at a single regional cancer centre in order to identify potential areas for improvement. MATERIALS AND METHODS: Consultants and trainees (n = 10) at a regional cancer centre underwent semi-structured interviews regarding their lived experience of learning radiotherapy skills and knowledge. As consultants and trainees can be considered equal co-investors in the process of radiotherapy learning, the same question stems were used for both groups. An interpretative phenomenological analysis was undertaken by the investigators to elicit the perception of both groups. RESULTS: Consultant and trainee assessments of current radiotherapy learning standards differ for several aspects of training, as do their expectations of the other in learning processes. A lack of time is a major barrier in modern practice, and both groups can propose novel measures to improve learning locally. CONCLUSIONS: Arrangements for learning radiotherapy have not kept pace with the rate of change in the clinical oncology discipline. Trainees and consultants have contrasting views on the state of training, its strengths and weaknesses, and pathways to improvement, which should be reconciled by programme coordinators charged with upgrading the training system.

Unintended cardiac irradiation during left-sided breast cancer radiotherapy.

OBJECTIVE: Cardiac irradiation during left-sided breast radiotherapy may lead to deleterious cardiac side effects. Using image guided radiotherapy, it is possible to exclude the heart from treatment fields and monitor reproducibility of virtual simulation (VS) fields at treatment delivery using electronic portal imaging (EPI). Retrospectively, we evaluate the incidence of cardiac irradiation at VS and subsequent unintended cardiac irradiation during treatment. METHODS: Patients receiving left-sided radiotherapy to the breast or chest wall, treated with a glancing photon field technique during a four-month period, were included. VS images and EPIs during radiotherapy delivery were visually assessed. The presence of any portion of the heart within the treatment field at VS or during treatment was recorded. Central lung distance and maximum heart distance were recorded. RESULTS: Of 128 patients, 45 (35.1%) had any portion of the heart within the planned treatment field. Of these, inclusion of the heart was clinically unavoidable in 25 (55.6%). Of those with no heart included in the treatment fields at VS, 41 (49.4%) had presence of the heart as assessed on EPI during treatment. CONCLUSION: Unintended cardiac irradiation during left-sided breast radiotherapy treatment occurs in a sizeable proportion of patients. ADVANCES IN KNOWLEDGE: Despite the use of three-dimensional computed tomography simulation and cardiac shielding, sizeable proportions of patients receiving left-sided breast cancer radiotherapy have unintended cardiac irradiation.

The introduction of single best answer questions as a test of knowledge in the final examination for the fellowship of the Royal College of Radiologists in Clinical Oncology.

AIMS: The single best answer (SBA) format of multiple choice questions (MCQ) is recognised to be better suited to the assessment of the higher levels of knowledge essential for clinical practice, such as data interpretation, problem solving and decision making, than traditional true/false MCQ. In autumn 2006, the Royal College of Radiologists (RCR) introduced SBA questions as its sole written test of knowledge for the Final Fellowship Examination in Clinical Oncology (Final FRCR Examination). This article reviews the application of SBA questions to clinical oncology and analyses the first year's experience of the new examination format. METHODS: The results of the last two true/false MCQ examinations (autumn 2005 and spring 2006) and the first two SBA examinations (autumn 2006 and spring 2007) were analysed. The predictive values of the different components of the Final FRCR Examination (SBA, true/false MCQ, case orientated questions COQ, clinical and oral examinations) were compared. RESULTS: In autumn 2005, 86% of candidates passed the true/false MCQ paper but only 48% passed the examination overall. In spring 2006, 91% of candidates passed the true/false MCQ paper but the overall pass rate was only 36%. In contrast, the pass rate for the SBA papers was 66% for both autumn 2006 and spring 2007, which was comparable to the overall pass rate of 53% and 52% respectively. All the components of the examination (SBA, true/false MCQ, COQ, clinical and oral examinations) had similar negative predictive values of between 80% and 90% (p = 0.3, chi-square test). However, the positive predictive value of true/false MCQ was inferior to the other sections of the examination (46% compared to 74%, 80%, 74% and 72% for SBA, COQ, clinicals and orals respectively, p < 0.001, chi-square test). CONCLUSION: The new format SBA questions are more reliable than the previous true/false MCQ in discriminating between knowledgeable and unknowledgeable candidates in the Final FRCR Examination in Clinical Oncology.

Broadcast quality teleconferencing for oncology.

The National Cancer Institute (NCI) in Bethesda, Maryland has developed a broadcast-quality teleconferencing system known as the Telesynergy system to address the need to convey expert information between larger cancer centers and their remote counterparts. This system is available to "Partnerships in Science Program" partners across the U.S. Recently, it has been made available in Ireland under a "Memorandum of Understanding" among the Department of Health and Children of Ireland, the Department of Health and Social Services in Northern Ireland, and the NCI. The Telesynergy system is capable of transmitting not only broadcast-quality teleconferencing among several different sources, but also diagnostic-quality radiology and pathology images. Remote operated microscopes and video cameras allow biopsy specimens to be discussed and manipulated from several different locations. Smear preparations of blood, bone marrow, and other cytological specimens can be examined in detail by a remote operator. The system can also transmit conventional x-ray images and paper documents. The Telesynergy system ensures that each patient, regardless of location, will receive an expert assessment and be given optimal therapy. While the system is currently being developed in Ireland for use in oncology, it is hoped that other specialties can benefit from it in the future.

Radiation recall dermatitis in a patient treated with dacarbazine.

Radiation recall describes an inflammatory reaction at a previously irradiated site associated with the use of chemotherapeutic agents. Dacarbazine, a tetrazine cytotoxic drug, has not been noted to cause this phenomenon. We report the case history of a 44-year-old female patient who developed a recall dermatitis due to dacarbazine in a site previously irradiated for the treatment of malignant melanoma. The skin erythema responded quickly to oral corticosteroid treatment. Further cycles of dacarbazine were facilitated with oral corticosteroid premedication. We conclude that dacarbazine should be considered as a potential cause of radiation recall dermatitis and that this can be managed and prevented with oral corticosteroids.

Radical radiotherapy for inoperable non-small cell lung cancer: what factors predict prognosis?

We set out to determine the factors that predict the outcome of conventional radical radiotherapy for inoperable non-small cell lung cancer. A retrospective casenote review was carried out of all 69 patients treated between 1986 and 1992 at the Northern Ireland Centre for Clinical Oncology, Belfast, with radical radiotherapy for inoperable non-small cell lung cancer. The tumour dose ranged from 45 Gy to 67.5 Gy, delivered in 15-30 fractions, 5 days per week over 3-6 weeks. All patients were followed up for 5 years. The disease was TNM Stage T1-T4N0-N2M0. The majority of tumours (51) were squamous. Overall survival was 63.8% (44-patients; 95% confidence interval (CT) 51.3-75.2) at one year; median survival was 16 months and 5-year survival was 13% (nine patients; 95% CI 6.1-23.3). Five-year survival for the 36 patients with stage T1 or T2 disease was 5.6% (2 patients). Five-year survival for the 33 patients with stage T3 or T4 disease, all with tumours at or near the carina, was 21.2% (seven patients). A WHO performance status of 0 or 1 (P = 0.03, Cox proportional hazards model) was associated with a better chance of survival.

Pathology of rectal adenocarcinoma following preoperative adjuvant radiotherapy and chemotherapy.

The study group comprised 13 patients (mean age 68 years) with clinically fixed and biopsy proven moderately differentiated rectal adenocarcinoma (8 high rectal, 5 low-mid rectal) who received synchronous courses of preoperative combination chemotherapy and pelvic radiotherapy (radiotherapy alone in 3 cases) over a period of 8-20 weeks prior to surgical resection. All cases showed varying degrees of mural and mesorectal fibrosis. Three cases did not differ otherwise from usual rectal adenocarcinoma while 4 had a 20-30% diminution in expected tumour area. In 6 cases tumour could not be definitely identified grossly--1 showed a 50% reduction in tumour bulk while 5 had only residual microscopic foci from 0.6-4 mm in maximum dimensions. Only 3 cases had involvement of the mesorectal circumferential radial margin. Four involved lymph nodes in 2 cases were partially hyalinised and calcified. Preoperative combination adjuvant therapy can produce marked regressive morphological changes in rectal adenocarcinoma. The implications of this are discussed.

AQ4N: an alkylaminoanthraquinone N-oxide showing bioreductive potential and positive interaction with radiation in vivo.

AQ4N (1,4-bis([2-(dimethylamino-N-oxide)ethyl]amino)5,8-dihydroxy- anthracene-9,10-dione) is a novel alkylaminoanthraquinone N-oxide which, on reduction, forms a stable DNA affinic cytotoxic compound AQ4. The in vivo anti-tumour efficacy of AQ4N was investigated in B6D2F1 mice bearing the T50/80 mammary carcinoma. The effect of the drug was evaluated in combination with hypobaric hypoxia and with radiation (single and multiple fractions). Systemic toxicity was assessed by weight loss post treatment. This was low for AQ4N and was less than that obtained with the bioreductive drugs, RSU 1069 (1-[3-aziridinyl-2-hydroxypropyl]-2-nitroimidazole) and SR 4233 (Tirapazamine, 3-amino-1,2,4-benzotriazine-1,4-dioxide). The anti-tumour effect of AQ4N was potentiated in vivo by combination with hypobaric hypoxia with a dose enhancement ratio of 5.1. This is consistent with the proposal that AQ4N was reduced in vivo to AQ4, resulting in enhanced anti-tumour toxicity. When AQ4N (200 mg kg-1) was combined with single dose radiation (12 Gy) the drug was shown to have an additive interaction with radiation. This was obtained even if the drug was administered from 4 days before to 6 h after radiation treatment. Equivalent anti-tumour activity was also shown when both AQ4N (200 mg kg-1) and radiation (5 x 3 Gy) were administered in fractionated schedules. In conclusion, AQ4N shows significant potential as a bioreductive drug for combination with fractionated radiotherapy.

Malignant anal tumours.

Anal tumours represent 5 per cent of anorectal cancers and exist as two clinical entities: tumours of the anal canal and those of the anal margin. Smoking and sexual behaviour, particularly homosexual anal intercourse, are important aetiological factors. This association is related to anal warts and human papillomavirus infection, notably type 16, which is found in around 70 per cent of warts. Symptoms are non-specific and are frequently attributed to benign conditions. Rectal examination reveals a characteristically infiltrating lesion and any suspicious anal area should be biopsied. There are two histological types. Squamous carcinoma comprises approximately 95 per cent of anal tumours and includes the 35 per cent of tumours derived from the anal transition zone (cloacogenic tumours), containing a mixture of squamous and mucinous elements. The remaining 5 per cent of anal tumours are adenocarcinoma. Squamous cell tumours of the anal canal are probably best treated using radiotherapy (with chemotherapy) as complete response rates, 5-year survival rates, and incidences of normal sphincter function and significant toxicity are around 80, 70, 75 and 20 per cent respectively. Treatment failures may be salvaged by surgery. The 5-year survival and local recurrence rates for radical surgery are around 60 and 25 per cent respectively; there are few indications for local excision. In contrast, 60 per cent of anal margin tumours are suitable for local excision, the 5-year survival rate being in excess of 80 per cent. Combining radiotherapy with surgery may give additional benefit. Current randomized controlled trials should further clarify the relative merits and demerits of the treatment options.

The effect of recombinant human erythropoietin treatment on tumour radiosensitivity and cancer-associated anaemia in the mouse.

Recombinant human erythropoietin (rHuEpo) has recently become available for the treatment of chronic anaemia, including that associated with cancer. Carcinoma NT in CBA mice causes a progressive anaemia which can be overcome by daily injections of recombinant human erythropoietin (rHuEpo). This model was used to study the effect of haematocrit on tumour blood flow, growth rate and radiosensitivity, in mice with haematocrits ranging from approximately 38% (control) to 65% (20 U/day rHuEpo). Tumours showed a small but significant slowing in growth rate with higher haematocrit. In vitro studies showed rHuEpo had no direct effect on the growth of NT cells. Tumour blood flow was measured by two methods in each mouse (133Xe clearance and 86Rubidium uptake). Blood flow showed a tendency to decrease with increasing blood viscosity although this effect was not significant despite the large differences in haematocrit. Although tumour doubling time was prolonged despite the large differences in haematocrit. Although tumour doubling time was prolonged with increasing radiation dose, from 0 (sham irradiated) to 35 Gy, haematocrit was not found to influence the growth delay. This was attributed to adaptation of the tumour during the relatively slow change in the haematocrit. rHuEpo is being considered for clinical use in anaemic cancer patients. Our data suggest that this treatment will correct haematocrit with no effect on tumour radiosensitivity.

Hypobaric hypoxia: a method for testing bioreductive drugs in vivo.

Hypobaric hypoxia has been used to induce tumor hypoxia for in vivo comparison of the anti-tumor effects of the bioreductive agents SR 4233 (3-amino-1,2,4-benzotriazine-1,4-dioxide), RSU 1069 (1(2-nitro-1-imidazolyl)-3-aziridino-2-propanol), and Nitromin (methylbis(2-chloroethyl)amine N-oxide). BDF mice bearing the T50/80 mammary carcinoma were treated with these agents over a range of doses under normobaric (oxic) and hypobaric (hypoxic) conditions. The time taken for the tumor to double treatment volume (volume doubling time) was used as a measure of anti-tumor effect. Volume doubling time was plotted against log dose and dose response curves were fitted. A dose enhancement ratio (the ratio of drug doses required to give an equivalent anti-tumor effect under oxic and hypoxic conditions) was determined. The dose enhancement ratios for SR 4233 and RSU 1069 were 8.8 and 8.5, respectively, showing that these agents had an equivalent and substantial enhancement of their cytotoxicity when combined with hypobaric hypoxia. For Nitromin, no significant dose response effect was obtained under oxic conditions precluding the calculation of the dose enhancement ratio. SR 4233 was found to have increased systemic toxicity when combined with hypobaric hypoxia, suggesting that it is more readily activated than the other drugs tested. This in vivo test system will allow determination of the dose enhancement ratio for novel bioreductive agents and facilitate their comparison.

Does extragonadal presentation impart a worse prognosis to abdominal germ-cell tumours?

The prognostic significance of extragonadal rather than gonadal presentation of germ-cell tumour in 51 patients presenting between 1979 and 1988 with abdominal tumours was compared with that of 51 control patients with testicular primary tumours matched for bulk fo disease, serum tumour marker concentration, age and year of treatment. Very large volume tumour was found at initial staging in 24 extra-gonadal cases (47%) and high tumour markers in 29 (57%). Actuarial survival at 2 and 5 years was 82% and 70% for cases and 78% and 63%, respectively, for controls. These outcomes were not significantly different and the relative hazard of death for cases compared with controls was 0.7 (95% confidence intervals 0.3-1.5). Thus the presentation of germ-cell tumours with a retroperitoneal mass does not itself adversely influence prognosis compared with testicular presentation with equivalent disease extent. However it is rare for extragonadal presentation to be associated with small volume disease.

The nicotinic acid provocation test and unconjugated hyperbilirubinaemia.

It has been suggested that the nicotinic acid provocation test is useful in the diagnosis of Gilbert's syndrome. We compared the response to intravenous nicotinic acid of patients with Gilbert's syndrome and with chronic liver disease. There was no significant difference in the mean rise in unconjugated serum bilirubin between the two groups. A sensitivity of 70% and specificity of 60% were obtained. All of 5 patients with chronic liver disease and a raised fasting unconjugated serum bilirubin had positive tests. We suggest that the nicotinic acid test is positive in unconjugated hyperbilirubinaemia regardless of cause. It is of no value in differentiating Gilbert's syndrome from liver disease.

Delayed sudden death after ingestion of MCPP and ioxynil: an unusual presentation of hormonal weedkiller intoxication.

A patient who died in asystole less than 18 h after ingestion of 'Clovercide Extra', a combination hormonal weedkiller containing ioxynil and 4-chloro-2-methyl phenoxypropionic acid, is described. Previous reports describe coma as an early event following ingestion of these herbicides. In contrast our patient, although showing other characteristic features, including metabolic acidosis, tachycardia, pupillary constriction and pyrexia, remained conscious until the terminal event. Absence of coma does not appear to be related to a more favourable outcome.