Brachytherapy quality assurance in the PORTEC-4a trial for molecular-integrated risk profile guided adjuvant treatment of endometrial cancer.

OBJECTIVE: The PORTEC-4a trial investigates molecular-integrated risk profile guided adjuvant treatment for endometrial cancer. The quality assurance programme included a dummy run for vaginal brachytherapy prior to site activation, and annual quality assurance to verify protocol adherence. Aims of this study were to evaluate vaginal brachytherapy quality and protocol adherence. METHODS: For the dummy run, institutes were invited to create a brachytherapy plan on a provided CT-scan with the applicator in situ. For annual quality assurance, institutes provided data of one randomly selected brachytherapy case. A brachytherapy panel reviewed and scored the brachytherapy plans according to a checklist. RESULTS: At the dummy run, 15 out of 21 (71.4%) institutes needed adjustments of delineation or planning. After adjustments, the mean dose at the vaginal apex (protocol: 100%; 7 Gy) decreased from 100.7% to 99.9% and range and standard deviation (SD) narrowed from 83.6-135.1 to 96.4-101.4 and 8.8 to 1.1, respectively. At annual quality assurance, 22 out of 27 (81.5%) cases had no or minor and 5 out of 27 (18.5%) major deviations. Most deviations were related to delineation, mean dose at the vaginal apex (98.0%, 74.7-114.2, SD 7.6) or reference volume length. CONCLUSIONS: Most feedback during the brachytherapy quality assurance procedure of the PORTEC-4a trial was related to delineation, dose at the vaginal apex and the reference volume length. Annual quality assurance is essential to promote protocol compliance, ensuring high quality vaginal brachytherapy in all participating institutes.

Management of anal intraepithelial neoplasia and anal squamous cell carcinoma at a tertiary referral centre with a dedicated infectious diseases unit: an 18-year review.

INTRODUCTION: Anal squamous cell carcinoma (ASCC) is a rare malignancy with rising incidence rates. Risk factors include human immunodeficiency virus (HIV) infection, high-risk sexual activity and HPV-related genitourinary dysplasia/neoplasia. There is an overlap between high-risk patients and those attending HIV Medicine/Sexual Health (HMSH) services. We hypothesised that HMSH involvement may facilitate earlier referral to colorectal surgeons, with better outcomes. METHODS: Retrospective review of all ASCC and anal intraepithelial neoplasia (AIN) treated at a tertiary-referral hospital with a dedicated HMSH clinic between 2000 and 2018. Comparative analysis was performed of demographics, management and outcomes between HMSH and non-HMSH patients. RESULTS: One hundred and nine patients had anal pathology, eighty-five with ASCC (78%) and twenty-four with AIN (22%). Seventy (64%) were male. Median (range) age at ASCC diagnosis was 51 years (26-88). Thirty-six percent of all patients attended HMSH services, 28% were HIV positive, and 41% of males were men-who-have-sex-with-men (MSM). Eighty-one ASCC patients (97.5%) were treated with curative intent. Sixty-seven (80%) had primary chemoradiation therapy. Fifteen (17.5%) had primary surgical excision. Twelve (14%) developed recurrent disease. Ultimately, seven required salvage APR. Overall 3-year survival (3YS) was 76%. HMSH patients were significantly younger at ASCC diagnosis (p < 0.001), with a higher prevalence of HIV, HPV and MSM. HMSH attenders also tended to be diagnosed at earlier stages, were less likely to develop recurrence and achieved better overall outcomes, with a superior overall 3YS than non-HMSH patients (92% vs 72%, p = 0.037). CONCLUSION: ASCC incidence is increasing worldwide. The HMSH cohort has emerged as a distinct subpopulation of younger, high-risk, male patients. Collaboration between HMSH and colorectal surgeons offers an opportunity for risk reduction strategies and earlier intervention.

Subjective taste and smell changes in treatment-naive people with solid tumours.

PURPOSE: Taste and smell changes (TSCs) are common in head and neck (H&N) cancer and during and after chemotherapy (CT) and radiotherapy (RT). It is an area that has been under-investigated, particularly in the treatment-naive, but can negatively impact nutritional status. This study examined the prevalence, severity and characteristics of TSCs in people with non-H&N solid tumours, before CT and RT, and their relationship with co-occurring symptoms. METHODS: A prospective, observational study was conducted. Forty consecutive pre-treatment cancer patients, referred to radiation oncology outpatients over 6 weeks, were recruited. Data on TSCs, symptoms and nutritional status were obtained using the 'Taste and Smell Survey' and the 'abridged Patient-Generated Subjective Global Assessment' (abPG-SGA). BMI was measured. SPSS® was used for statistical analysis. Two-sided P values <0.05 were considered statistically significant. RESULTS: Most patients were newly diagnosed (n = 28; 70 %). Nineteen (48 %) reported TSCs; nine noted a stronger sweet and seven a stronger salt taste. Of these, four reported a stronger and four a weaker smell sensation. Those at nutritional risk reported more TSCs (n = 13/20). TSCs were significantly associated with dry mouth (P < 0.01), early satiety (P < 0.05) and fatigue (P < 0.05). CONCLUSIONS: TSCs preceded CT or RT in almost half of treatment-naive patients with solid tumours, notably stronger sweet and salt tastes. Half of the study group were at nutritional risk; the majority of these reported TSCs. TSCs were significantly associated with other symptoms. Future research and clinical guidelines, with a common terminology for assessment, diagnosis and management of cancer TSCs, are needed.

Selective arterial embolisation for intractable vaginal haemorrhage in genital tract malignancies.

PURPOSE OF INVESTIGATION: Embolisation of the internal iliac artery has been described as an effective and safe method of treating massive vaginal haemorrhage in small series of advanced uterine cancer and case reports of cervical cancer. Selective embolization of the bleeding vessel is potentially less morbid. The aim of this study was to assess the efficacy of selective arterial embolisation (SAE) in controlling intractable haemorrhage due to gynaecological malignancy. MATERIALS AND METHODS: This retrospective observational study comes from in a tertiary cancer center with 300 new gynecologic cancers per annum. The authors reviewed all gynecology cancer patients who had intractable major vaginal haemorrhage in the first five years following the introduction of selective arterial embolisation at their unit. The outcomes measured were the control of acute haemorrhage and discharge to planned pathway of treatment. RESULTS: SAE was successful in all cases. Identification of the bleeding point facilitated highly selective embolisation in more than half of the patients. The uterine arteries were embolised in the remaining cases. Bleeding stopped immediately. The expedient control of haemorrhage facilitated early discharge to commencement/continuation of radiation treatment or palliative care as appropriate. CONCLUSIONS: Since the introduction of SAE the authors have avoided emergency radiotherapy, surgery, and repeat vaginal packing in patients with intractable vaginal bleeding due to gynaecological cancer. Patients were discharged to their appropriate treatment pathways in a timely manner. The authors recommend the application of SAE.

Quality of life and survival in patients treated with radical chemoradiation alone for oesophageal cancer.

AIMS: To report cancer-specific and health-related quality-of-life outcomes in patients undergoing radical chemoradiation (CRT) alone for oesophageal cancer. MATERIALS AND METHODS: Between 1998 and 2005, 56 patients with oesophageal cancer received definitive radical CRT, due to local disease extent, poor general health, or patient choice. Data from European Organization for Research and Treatment of Cancer quality-of-life questionnaires QLQ-30 and QLQ-OES24 were collected prospectively. Questionnaires were completed at diagnosis, and at 3, 6 and 12 months after CRT where applicable. RESULTS: The median follow-up was 18 months. The median overall survival was 14 months, with a 51, 26 and 13% 1-, 3- and 5-year survival, respectively. At 12 months after treatment there was a significant improvement compared with before treatment with respect to dysphagia and pain. Global health scores were not significantly affected. CONCLUSIONS: Considering the relatively short long-term survival for this cohort of patients, maximising the quality of those final months should be very carefully borne in mind from the outset. The health-related quality-of-life data reported herein helps to establish benchmarks for larger evaluation within randomised clinical trials.

Comparison of two fractionation regimens in the multimodal therapy of cancer of the esophagus.

Multimodal therapy is increasingly utilized in the management of esophageal cancer. The optimum dose and fraction is unclear, and this retrospective analysis compared two radiation regimens in multimodality regimens where the chemotherapy arm and the type and magnitude of surgery was constant. Ninety-three consecutive patients with squamous cell carcinoma or adenocarcinoma of the esophagus were reviewed. Forty patients received the conventional unit regimen of 44 Gy in 22 daily fractions (2 Gy/fraction), and 40 patients received an increased dose per fraction (40 Gy in 15 daily fractions [2.67 Gy/fraction]). All patients received two courses of 5-fluorouracil and cisplatin and surgery was carried out within 8 weeks of completing therapy. The median overall survival in the group receiving the increased dose per fraction group was 25 months compared with 17 months in the conventional dose per fraction group (P=0.08). At 1, 3, and 5 years, 66%, 38%, and 38%, of patients in the increased dose per fraction group were alive, compared with 65%, 18%, and 15% in the conventional dose per fraction group (P=0.13), respectively. In the conventional dose per fraction group, two patients developed esophageal fistulae and one patient died postoperatively due to hemorrhage from an aorto-enteric fistula. There were no significant differences observed between treatment groups, but a trend toward improved efficacy appeared with the increased dose per fraction.

The effects of high shear blending on alpha-lactose monohydrate.

alpha-Lactose monohydrate is an important pharmaceutical excipient used extensively in dry powder inhaler (DPI) formulations. The ways in which a high shear blending process affect this material have been investigated and important process parameters have been identified. Total energy input (kJ/kg), blade design and the conditions in which lactose was stored prior to blending were found to have the most significant effect on the apparent particle size distribution of the processed material, which may subsequently affect the performance of DPI formulations. The power conditions used during blending, equipment temperature and humidity of the headspace above the powder were found to be less important in this respect. Additionally, it was found that high energy blending could induce changes in the water sorption characteristics of the material, although the formation of amorphous material could not be confirmed.

(18)FDG uptake during induction chemoradiation for oesophageal cancer fails to predict histomorphological tumour response.

To determine whether [(18)F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) could predict the pathological response in oesophageal cancer after only the first week of neoadjuvant chemoradiation. Thirty-two patients with localised oesophageal cancer had a pretreatment PET scan and a repeat after the first week of chemoradiation. The change in mean maximum standardised uptake value (SUV) and volume of metabolically active tissue (MTV) was compared with the tumour regression grade (TRG) in the final histology. Those who achieved a TRG of 1 and 2 were deemed responders and 3-5 nonresponders. In the responders (28%), the SUV fell from 12.6 (+/-6.3) to 8.1 (+/-2.9) after 1 week of chemoradiation (P=0.070). In nonresponders (72%), the results were 9.7 (+/-5.4) and 7.1 (+/-3.8), respectively (P=0.003). The MTV in responders fell from 36.6 (+/-22.7) to 22.3 (+/-10.4) cm(3) (P=0.180), while in nonresponders, this fell from 35.9 (+/-36.7) to 31.9 (+/-52.7) cm(3) (P=0.405). There were no significant differences between responders and nonresponders. The hypothesis that early repeat FDG-PET scanning may predict histomorphologic response was not proven. This may reflect an inflammatory effect of radiation that obscures tumour-specific metabolic changes at this time. This assessment may have limited application in predicting response to multimodal regimens for oesophageal cancer.

Nuchal aggressive fibromatosis in childhood: two instructive case reports.

Aggressive fibromatosis is a rare, benign tumour with a capacity for infiltration of surrounding structures and a propensity for local recurrence. The cornerstone of therapy is surgery, with various other treatment modalities having ill-defined roles. Assessment of the efficacy of these interventions is difficult. The natural history of the condition is variable and different treatment modalities are often used concurrently. Childhood cases pose particular management problems because of their tendency to occur in the head and neck region and the potential for treatment-related morbidity. Two children presented after surgery with recurrent disease threatening the airway. One remitted spontaneously and remains disease free at 20 years. The other achieved a complete remission with radiotherapy and toremifene. The role of non-surgical treatment, particularly radiotherapy, is reviewed.

Public health. Roads to poor health.

Simon P Wolff and Carola J Gillham highlight the negative health consequences of the motor car and argue that these are not inevitable. A land-use and transport policy which will protect and improve public health is not only possible but an urgent necessity.

Public health versus public policy? An appraisal of British urban transport policy.

The most visible aspect of the relationship between transport and health is in the realm of road traffic accidents (RTAs). But the effects of transport policy upon the public health are much wider-ranging. They include exacerbation of social and health inequalities, separation from directly health-protective amenities and social isolation, as well as health damage by physico-chemical pollution. It is arguable that these factors may account for more years of life lost annually than do RTAs. The current focus on accident reduction as the sole means of avoiding adverse health effects of transport distracts attention from the wide health erosive effects of road traffic. Universal mobility and accessibility, independent of the car, is required for public health protection and advancement, since private transport carries many external, and poorly recognised health costs.

Trace element and vitamin deficiency in alcoholic and control subjects.

A wide range of trace elements and vitamins was studied in alcoholic patients admitted for detoxification and in healthy controls. Alcoholic subjects were found to be deficient relative to controls in magnesium and vitamin E, while a relative excess of serum iron and copper, and sweat nickel, was noted. A surprisingly wide range of deficiencies, as compared with standard laboratory ranges, was seen in the control group. This finding emphasizes the need for adequate control groups in nutritional studies of alcoholism, the insufficiency of an adequate diet alone to guarantee adequate nutrition, and the likely high prevalence of undetected nutritional deficiency in the general population. Further research is required on the clinical benefits of nutritional supplementation as part of the treatment of alcoholism, and the value of conventional supplements as a routine treatment is questioned.

A log-dose-response study of xipamide and its effect on metabolic parameters.

An extended dose-response study with xipamide, using seven doublings of the dose, from 0.3125 to 40 mg/day at 4-week intervals, was carried out in 12 hypertensive patients. Blood pressure showed a progressive decline with doses from 5 to 20 mg, and 40 mg xipamide produced no greater fall. Some subjects showed a maximum fall in blood pressure with a single dose increase but most showed a declining blood pressure over two or more dose increases. Plasma urea increased with doses of 5-40 mg to a similar extent, but there was no fall in the mean potassium level except with the 40-mg dose. Urinary calcium was reduced (from 4.2 to 1.7 mmol/24 h) on the 40-mg dose and the corrected plasma calcium level rose from 2.28 to 2.32 mmol/l. Triglycerides, very-low-density lipoprotein cholesterol and plasma aldosterone increased at the maximum dose; the cholesterol ratio, however, was unchanged.