Introducing the Intergroup 0116 protocol of adjuvant chemo-radiotherapy in gastric cancer into clinical practice.

AIMS: The results of techniques from a well-conducted clinical trial are often difficult to reproduce when implemented in community oncology practice. The U.S. Intergroup 0116 protocol of adjuvant chemo-radiotherapy in gastric cancer presented in mid-2000 produced a survival advantage over surgery alone. The current study aims to determine the adherence with protocol design and delivery of radiation therapy (radiotherapy) in the initial 20 patients managed with the Intergroup 0116 protocol at The National University Hospital, Singapore. MATERIALS AND METHODS: A formal quality assurance audit was performed on clinical features, radiotherapy treatment charts and simulation films of the first 20 patients treated with the Intergroup 0116 protocol from July 2000 to September 2001. Specific details were audited for their consistency with described protocol in domains of eligibility criteria, radiotherapy prescription, target volume coverage and adherence to dose-limiting normal tissue tolerances. Compliance and toxicity with the protocol was assessed by audit of delivered radiotherapy dose, treatment interruptions, inpatient admissions and weight loss during radiotherapy. RESULTS: The 20 audited patients were appropriately selected on the basis of eligibility criteria of Intergroup 0116 protocol. There was only one minor variation of radiotherapy target volume coverage resulting from marginal coverage of the porta hepatis region. Adherence to the protocol was satisfactory, with 19 patients completing the radiotherapy protocol as planned and only one major variation in treatment delivery resulting from gastrointestinal toxicity. One major and one minor variation in normal tissue-dose constraints occurred on the heart and spinal cord, respectively. Compliance with treatment delivery was good, with only one patient failing to complete the prescribed radiotherapy dose owing to toxicity, although seven patients required treatment interruption. CONCLUSION: This audit showed good compliance with radiotherapy design and delivery. A formal medical quality assurance audit may provide a useful tool to assess complex new protocols introduced into routine departmental practice.

Treatment and planning decisions in non-small cell carcinoma of the lung: an Australasian patterns of practice study.

Fourteen practising radiation oncologists were surveyed to assess their treatment and planning habits utilizing six sample cases of non-small cell carcinoma of the lung. Respondents were first given a general questionnaire, designed to evaluate their theoretical treatment and planning recommendations based on various tumour and patient related variables. Respondents then undertook a practical planning exercise utilizing planning CT and simulator radiographs for each of the six sample cases. Each case was accompanied by a brief history and report outlining specific tumour stage and non-stage related variables. The practical planning exercise was repeated on the second day of the survey utilizing different non-stage related variables but identical radiology and stage-related information. This design enabled firstly, a comparison of clinicians' intended policy and planning methods with actual policy and planning decisions, and secondly, an assessment of intra-clinician variability in decision making and planning practice. Good agreement was evident among clinicians with respect to general, non-case specific treatment policies; however, very significant variation occurred at an inter- and intra-clinician level and involved the entire treatment and planning process for individual cases. Despite identical treatment intent across identical radiological case pairings, clinicians chose widely differing margins and target volumes in their planning exercise. Treatment intent appeared to be influenced more by non-stage related variables rather than stage related information and radiological appearances per se. We have shown that experienced radiation oncologists do not adhere to stated case selection criteria and show inconsistencies in their treatment planning for non-small cell carcinoma of the lung.

Carcinoma of the glottic larynx: the Christchurch experience.

AIMS: to establish the local control and survival rates for glottic laryngeal cancer, and to determine the incidence of second primary cancers after treatment of the original tumour. METHODS: a retrospective review of all patients with glottic cancers treated in Christchurch over a five year period, with a minimum follow up of five years. RESULTS: between 1979 and 1984, 83 patients with laryngeal cancer were treated in Christchurch Hospital. Forty-seven of these patients had cancers of the glottic larynx. Overall, 39 of 45 patients were free of their laryngeal cancer at five years (two were lost to follow up). Eight of 45 developed a second primary cancer, usually lung or oesophagus, and this was invariably fatal. CONCLUSION: with multidisciplinary management of head and neck cancers satisfactory control rates can be achieved, but since these patients are usually heavy smokers and drinkers, they are at high risk of developing a second primary cancer. The use of chemopreventative agents is mentioned.

Total skin electron therapy at two energies on a linear accelerator.

We have implemented the AAPM Task Group 30 recommendations with respect to Total Skin Electron Therapy (TSET) for the treatment of Mycosis Fungoides. Extensive measurements have been performed on the Varian 2100c linear accelerator with a water equivalent phantom, cylindrical phantoms and an anthropomorphic phantom to validate the 12 beam technique and to measure calibration factors. The technique was developed at 2.5 MeV and 3.5 MeV (mean energy at the surface) with the energy degrading screen at 30 cm from the patient. Field flatness over the treatment area was within +/- 3% with no significant regional variation of energy. The bremstrahlung contamination was .06-1.2%. The absolute calibration of absorbed dose to the patient required the measurement of the ratio "skin dose to calibration point dose", this was confirmed by measurements with a parallel plate ionization chamber and thermoluminescence dosimetry. The results indicate the care that must be taken with ionization chamber measurements under TSET condition to avoid erroneous readings due to the "polarity effect". A protocol is suggested for the practical implementation and quality assurance of the technique. The results of two successful treatments are presented and compared with the predicted results from phantoms.

Multiple cranial nerve palsies as the presenting features of prostate carcinoma.

Cranial nerve palsies have previously been reported in metastatic prostate carcinoma, usually occurring late in the course of the disease. We describe the case of a 55-year-old man whose diagnosis of prostate cancer was made following investigation of multiple cranial nerve palsies.

Does the implementation of radiation oncology outpatient infection control measures adversely affect patient satisfaction with doctor-patient interaction?

INTRODUCTION: There are worldwide concerns of an impending avian influenza outbreak, with nations formulating infection control strategies to prepare for such an event. Little evidence exists for how infection control measures impact on the provision of cancer services, or how patient experience would be affected. Our aim was to compare patient satisfaction with doctor-patient interaction, during and following a period of infection control measures. METHODS: We measured patient satisfaction using a validated 29-question instrument for two weeks during the implementation of strict infection control measures as a result of the severe acute respiratory syndrome outbreak (T1), and compared results with a two-week period after measures had been lifted (T2). RESULTS: A total of 296 patients were surveyed, 149 at T1 and 147 at T2. Most patients indicated overall satisfaction, with 92.3 percent and 86.9 percent satisfied at T1 and T2, respectively (p-value is not significant). Mean satisfaction index was 3.02 and 3.04 out of 4 at T1 and T2, respectively (p-value is not significant). However, the responses for several individual questions did differ significantly between time points. At T1 more patients indicated satisfaction for understanding the doctor's plans (p-value is 0.001), while at T2, more patients indicated satisfaction for being told how to care for their condition (p-value is 0.04). CONCLUSION: The study demonstrated high patient satisfaction at both time points. Similar levels of satisfaction despite infection control measures may be due to patients being more tolerant of problems in doctor-patient interactions during the outbreak due to media campaigns. This research may facilitate those healthcare services planning to minimise the impact of infection control measures on patient care.

Patient satisfaction with doctor-patient interaction in a radiotherapy centre during the severe acute respiratory syndrome outbreak.

An outpatient radiotherapy department assessed how precautions implemented during the severe acute respiratory syndrome (SARS) outbreak affected patient satisfaction with doctor-patient interaction and explored variables potentially influencing satisfaction. The information obtained would help prepare us for future infectious disease outbreaks. Outpatients seen during the outbreak completed a validated questionnaire assessing satisfaction with doctor-patient interaction. Additional items assessed included patients' perception of SARS measures and patient demographics. Of 149 patients, 97% had heard of SARS, 92% believed SARS precautions necessary, and 54% believed contracting SARS was possible despite the precautions. Patients were satisfied with doctors wearing masks (97%), temperature checks (97%), and patients wearing masks (96%). Despite the high satisfaction levels with SARS precautions, 24% believed it had adversely affected doctor-patient interaction. With regards to doctor-patient interaction, 94% of patients were satisfied. Patients were most satisfied with the 'information exchange' domain (mean score 3.23 out of 4) compared to other domains (P < 0.0001, 100.00% confidence) and were less satisfied with the 'empathy' domain compared to other domains (P < 0.0001, 100.00% confidence). Patients were most satisfied with understanding their treatment plan (100%), doctor being honest (97%) and being understood (96%). Patients were least satisfied with information about caring for their illness (61%), that the visit could be better (59%), and the doctor showing more interest (58%). On multivariate analysis, patients who were less satisfied with SARS measures were significantly less satisfied with doctor-patient interaction (P = 0.0001). Dissatisfaction with SARS measures was associated with significant dissatisfaction for questions in all domains. Older age and non-breast cancer patients were also less satisfied with doctor-patient interaction. Most (94%) of patients were satisfied with doctor-patient interaction, despite implementation of infectious disease prevention measures. However, patients who were dissatisfied with the SARS precautions had poorer satisfaction. In particular, physician empathy appeared to be most adversely affected. The results have relevance to any radiotherapy department preparing contingency plans in the event of infectious disease outbreaks.

Merkel cell tumor. A chemosensitive skin cancer.

The clinical courses of six patients treated with cytotoxic chemotherapy for recurrent Merkel cell tumor of the skin are reported. All patients experienced prompt clinical responses to chemotherapy (five complete response [CR], one partial response [PR]) and three patients (50%) have achieved long-term disease-free remission. The report highlights (1) the aggressive nature of Merkel cell skin cancer, (2) the highly chemosensitive nature of the disease, and (3) some practical problems in administering chemotherapy to elderly patients.

Radiotherapy planning for lung cancer: can we do better?

Modern radiotherapy planning and treatment techniques allow the delivery of treatment with considerable geographic and dosimetric precision. Uncertainties and variability in the radiotherapy process prior to this stage, that is, localization of the target volume, has received little systematic study. The results of a planning study in non-small cell carcinoma of the lung are presented to highlight the possible variability in the planning process, both at an inter-clinician and intra-clinician level. The implications of this survey, both in terms of treatment outcome and training issues, are discussed.

Covering the CSF space: does teaching make a difference?

Following a paediatric teaching course for radiation oncology registrars which specifically addressed the method for planning cranial irradiation, a lateral skull simulation film was sent to all attendees to assess the effect of the teaching. To assess current clinical practice in New Zealand, a copy of the same radiograph was sent to radiation oncologists who had not attended the course. Recommendations from the course were that 10-mm margins should be placed in the regions of the cribiform plate and the floor of the middle cranial fossa. However, only 6.9% of the attendees marked the film with the recommended 10-mm margins. Dose profiles are also presented to support the use of 10-mm margins.

A very unusual breast lump.

A 77 year old woman presenting with a malignant phyllodes tumour of of the right breast with exclusively stromal metastases to axillary lymph nodes refractory to both radiotherapy and chemotherapy.

Hiding in the bunker: Challenges for a radiation oncology department operating in the Severe Acute Respiratory Syndrome outbreak.

In February 2003, one woman returned from Hong Kong to Singapore with a previously undescribed atypical pneumonia. Two months later, Singapore is facing its greatest ever threat to its population's health and the country's economy. The government has taken strong action to break the chain of infection of Severe Acute Respiratory Syndrome (SARS). As a radiation oncology department in Singapore, we have faced challenges in keeping staff and patients safe while continuing to provide a service to our patients. In this article, we outline the measures taken to curb SARS in Singapore and discuss the implications for Australasian radiation oncology departments.

Studies on the catalytic mechanism of pig purple acid phosphatase.

Several independent experiments failed to reveal any evidence in support of the involvement of a phosphoryl-enzyme intermediate in the catalytic mechanism of pig allantoic fluid purple acid phosphatase: (i) attempts to label enzyme with phosphate derived from [32P]p-nitrophenyl phosphate were unsuccessful; (ii) values of kcat for a series of phosphate derivative varied over a wide range, with the enzyme showing a marked preference for activated ester and anhydride substrates over those with a stable leaving group; (iii) burst titrations revealed a "burst" of p-nitrophenol from p-nitrophenyl phosphate only when the enzyme was added after the substrate, suggesting that this result was an artifact of the order of addition of reagents; (iv) transphosphorylation from p-nitrophenyl phosphate to acceptor alcohols could not be detected, even under conditions where a transphosphorylation to hydrolysis ratio as low as 0.015 could have been measured; (v) enzyme-catalyzed exchange of 180 between phosphate and water was demonstrated, although at a rate much slower than that observed for other phosphatases where the involvement of a phosphoryl-enzyme intermediate in the mechanism has been clearly established. The present results are compared with those obtained in similar studies on other phosphatases, particularly the highly homologous beef spleen purple acid phosphatase, and their implications for the catalytic mechanism of the purple acid phosphatases are discussed.

Binuclear metal centers in plant purple acid phosphatases: Fe-Mn in sweet potato and Fe-Zn in soybean.

Purple acid phosphatases comprise a family of binuclear metal-containing acid hydrolases, representatives of which have been found in animals, plants, and fungi. The goal of this study was to characterize purple acid phosphatases from sweet potato tubers and soybean seeds and to establish their relationship with the only well-characterized plant purple acid phosphatase, the FeIII-ZnII-containing red kidney bean enzyme. Metal analysis indicated the presence in the purified sweet potato enzyme of 1.0 g-atom of iron, 0.6-0.7 g-atom of manganese, and small amounts of zinc and copper. The soybean enzyme contained 0.8-0.9 g-atom of iron, 0.7-0.8 g-atom of zinc per subunit, and small amounts of manganese, copper, and magnesium. Both enzymes exhibited visible absorption maxima at 550-560 nm, with molar absorption coefficients of 3200 and 3300 M(-1) cm(-1), respectively, very similar to the red kidney bean enzyme. Substrate specificities were markedly different from those of the red kidney bean enzyme. A cloning strategy was developed based on N-terminal sequences of the sweet potato and soybean enzymes and short sequences around the conserved metal ligands of the mammalian and red kidney bean enzymes. Three sequences were obtained, one from soybean and two from sweet potato. All three showed extensive sequence identity (>66%) with red kidney bean purple acid phosphatase, and all of the metal ligands were conserved. The combined results establish that these enzymes are binuclear metalloenzymes: Fe-Mn in the sweet potato enzyme and Fe-Zn in soybean. The sweet potato enzyme is the first well-defined example of an Fe-Mn binuclear center in a protein.