Abstract Background Over 10% of patients with metastatic breast cancer develop symptomatic brain metastases. Limited treatment options can result in significant morbidity and a dismal prognosis. Little is known about the molecular profile of brain secondaries, differences compared with the patient's breast primary and whether any changes impact on prognosis. Methods Patients with resected or biopsied brain metastases from a breast cancer were identified from an electronic database, with clinical data collected from hospital notes for patients in the south west of the UK. Patients were included if tissue from the primary breast cancer and brain metastasis were available for testing. Immunohistochemical analysis was performed for oestrogen receptor (ER), progesterone receptor (PR), p27kip1, cyclin D1, epidermal growth factor receptor (EGFR), insulin like growth factor 1 (IGF1) and receptor (IGF1-R), vascular endothelial growth factor A (VEGF A), vascular endothelial growth factor receptor (VEGFR-2), transforming growth factor beta (TGFB) and Her 2 receptor on both the brain and breast samples. Borderline Her 2 results were analysed by fluorescent in situ hybridisation. Results 41 patients were identified. Median age of patients was 49, with a 26 month interval between breast cancer diagnosis and development of brain metastases. Median time from brain metastases to death was 15 months. 13 patients (32%) had a HER2 positive breast primary, 12 receiving HER2 directed therapy prior to development of brain metastases. 15 patients (37%) had an ER positive breast cancer at initial diagnosis. 11 patients had a biopsy of their brain secondary, 30 more extensive surgical resection. 28 patients received whole brain radiotherapy (WBRT), 1 patient stereotactic radiotherapy (SRT) alone, 6 patients both WBRT and SRT, 6 unknown. Changes in the molecular profile of the breast primary compared with the brain secondary are illustrated in Table 1. Number of patients with a change in molecular profile from breast primary to brain metastasis Breast positive to brain negativeBreast negative to brain positiveER03PR01Her214EGFR16IGF 1312IGF1-R34TGFB11p27 kip 1515cyclin D1312VEGF00VEGFR-211 There was a change in more than 10% of patients from a positive breast primary to a negative brain secondary for p27kip1 and from a negative breast cancer to a positive brain metastasis for EGFR, IGF1, cyclin D1 and p27kip1. These alterations did not have a significant impact on time from brain metastasis to death. However, there was a significant improvement in survival from brain metastasis diagnosis for secondary lesions that were ER positive (p=0.005) or PR positive (p=0.013). Survival from time of brain metastasis improved with a longer time to brain metastasis from initial diagnosis (p=0.001). Conclusions In this cohort there were demonstrable phenotypic differences in the expression levels of EGFR, IGF1, p27Kip1 and cyclin D1 in metastatic brain tumours compared with primary breast tumours of the same patient, although survival was not affected. 8 patients (20%) had a change in ER or Her 2 that could impact on current therapeutic decisions. Hormone receptor positive brain metastases had superior survival compared with negative lesions. Citation Format: Thomson AH, Purvis G, McGrane J, Palmer J, Jenkins R. Changing molecular profile of brain metastases compared with matched breast primaries and impact on clinical outcomes. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-17-07.
BACKGROUND:Breast cancer commonly metastasises to the brain, but little is known about changes in the molecular profile of the brain secondaries and impact on clinical outcomes.METHODS:Patients with samples from brain metastases and matched breast cancers were included. Immunohistochemical analysis for oestrogen receptor, progesterone receptor, p27kip1, cyclin D1, epidermal growth factor receptor, insulin like growth factor 1, insulin like growth factor 1 receptor, vascular endothelial growth factor A, transforming growth factor-β and HER2 receptor was performed. Borderline HER2 results were analysed by fluorescent in situ hybridisation. Levels of expression were compared, with review of effect on clinical outcomes.RESULTS:A total of 41 patients were included. Of the patients, 20% had a change in oestrogen receptor or HER2 in their brain metastasis that could affect therapeutic decisions. There were statistically significant rises in brain metastases for p27kip1 (P=0.023) and cyclin D1 (P=0.030) and a fall in vascular endothelial growth factor A (P=0.012). Overall survival from the time of metastasis increased significantly with oestrogen receptor-positive (P=0.005) and progesterone receptor-positive (P=0.013) brain lesions and with a longer duration from diagnosis of the breast primary (P<0.001).CONCLUSIONS:In this cohort there were phenotypic differences in metastatic brain tumours compared with matched primary breast tumours. These could be relevant for aetiology, and have an impact on prognostication, current and future therapies.
BACKGROUND:Penis cancer is rare and clinical trial evidence on which to base treatment decisions is limited. Case reports suggest that the combination of docetaxel, cisplatin and 5-flurouracil (TPF) is highly active in this disease. METHODS:Twenty-nine patients with locally advanced or metastatic squamous carcinoma of the penis were recruited into a single-arm phase II trial from nine UK centres. Up to three cycles of chemotherapy were received (docetaxel 75 mg m(-2) day 1, cisplatin 60 mg m(-2) day 1, 5-flurouracil 750 mg m(-2) per day days 1-5, repeated every 3 weeks). Primary outcome was objective response (assessed by RECIST). Fourteen or more responses in 26 evaluable patients were required to confirm a response rate of 60% or higher (Fleming-A'Hern design), warranting further evaluation. Secondary endpoints included toxicity and survival. RESULTS:10/26 evaluable patients (38.5%, 95% CI: 20.2-59.4) achieved an objective response. Two patients with locally advanced disease achieved radiological complete remission. 65.5% of patients experienced at least one grade 3/4 adverse event. CONCLUSION:Docetaxel, cisplatin and 5FU did not reach the pre-determined threshold for further research and caused significant toxicity. Our results do not support the routine use of TPF. The observed complete responses support further investigation of combination chemotherapy in the neoadjuvant setting.
Aims: To assess the influence of the type of breast conserving surgery on postoperative clinical target volume (CTV) and the implications for breast radiotherapy planning.
Prostate cancer is the most common male malignancy in the UK, with over 25 000 cases diagnosed in 2000 [ 1 National Statistics Cancer statistics registrations. Office for National Statistics, London2003 Google Scholar ]. National Institute for Health and Clinical Excellence (NICE) guidance and a Cochrane Database Systematic Review support cryotherapy as a primary treatment option for prostate cancer [ 2 Shelley M. Wilt T.J. Coles B. Mason M.D. Cryotherapy for localized prostate cancer. Cochrane Database Syst Rev. 2007; : CD005010 PubMed Google Scholar ]. There is little information on the management of relapses after primary cryotherapy, a scenario that may become increasingly common after the NICE endorsement.
BACKGROUND: Transfusion of the incorrect blood component is a frequent serious incident associated with transfusion and often involves misidentification of the patient and/or the unit of blood. The objective of this study was to assess the effect of a simple intervention designed to improve performance of the bedside check and to observe the durability of any effect. The intervention was a tag on blood bags reminding staff to check the patient's wristband. The tag was positioned in such a way that the transfusionist was required to remove the tag to spike the unit.STUDY DESIGN AND METHODS: The intervention was tested in a multicenter cluster-randomized controlled trial incorporating short-term and long-term follow-up periods. The primary endpoint was the proportion of patients transfused with red cell units for whom the key elements of the bedside check were all correctly completed.RESULTS: Fifteen matched-paired clinical areas at 12 participating hospitals in six countries were included in the trial. Combining data from all participating hospitals, the bedside check was correctly performed in 37 percent of transfusions during the baseline audit period. There was no evidence of a favorable effect of the intervention immediately after its introduction (pooled odds ratio, 1.09; 95% confidence interval, 0.54-2.17). There was similarly no evidence of a favorable effect after continued use of the intervention for an additional 8 weeks.CONCLUSIONS: A simple intervention in the form of a barrier warning label on blood bags reminding staff to check the patient's wristband failed to improve bedside transfusion practice. The robust study design developed for this study could be applied to investigate other interventions to improve the safety of bedside transfusion practice.
Background: Previous work on the impact of waiting times for patients with high grade glioma found that the hazard of death increased by 2% per day from oncological presentation to commencement of radiotherapy. However, this was a heterogenous group of tumours with data collated over 20 years. Use of CT planned radiotherapy was limited and doses varied (50–70 Gy). No chemotherapy was given.
This study aimed to compare the confidence of oncology consultants and specialist registrars (SpRs) in the performance of practical procedures, to contrast this with confidence in other areas of practice and to determine at what grade they felt most confident. Questionnaires were sent to all 57 oncology consultants and SpRs in the South-West region. Respondents scored confidence on a five-point Likert scale. The response rate was 70%. SpRs were significantly more confident in cardiopulmonary resuscitation (p = 0.003) and central line insertion (p = 0.006). Consultants were significantly more confident in developing management plans (p = 0.001) and performing committee work (p = 0.002). Only 6% of consultants felt most confident performing practical procedures as a consultant, and were less confident about these than other tasks (p = 0.001). Some 86% of SpRs considered they were more confident performing practical procedures as senior house officers (SHOs). In conclusion, self-reported confidence in performing practical procedures declines during career progression in oncology. This raises questions about the teaching and supervision of these procedures. If there is a greater emphasis on a consultant-provided service, their educational needs will need to be recognized and retraining or outsourcing of these procedures to other specialties may be necessary.
We read with interest the work of Barnett et al. [ 1 Barnett G.C. Charman S.C. Sizer B. Murray P.A. Information given to patients about adverse effects of radiotherapy: a survey of patients' views. Clin Oncol. 2004; 16: 479-484 Abstract Full Text Full Text PDF Scopus (25) Google Scholar ], who investigated the views of patients on the adverse events of radiotherapy. Although opinions varied, it was concluded that many patients required information on side-effects, even if these events were relatively uncommon. It was also noted that recall of information on adverse events after initial discussion is poor, and that the information needs of people with cancer fluctuate throughout their illness [ 2 Lloyd A.J. Hayes P.D. London N.J.M. Bell P.R.F. Naylor A.R. Patient ability to recall risk associated with treatment options. Lancet. 1999; 353: 645 Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar , 3 Kriwanek S. Armbuster C. Beckerhinn P. Blauensteiner W. Gschwantler M. Patients' assessment and recall of surgical information after laparoscopic cholecystectomy. Dig Surg. 1998; 15: 669-673 Crossref PubMed Scopus (62) Google Scholar , 4 Leydon G.M. Boulton M. Moynihan C. et al. Cancer patients' information needs and information seeking behaviour: in depth interview study. BMJ. 2000; 320: 909-913 Crossref PubMed Scopus (660) Google Scholar ].
Chylothorax is the presence of lymphatic fluid in the pleural space caused by a leak of the thoracic duct or one of its divisions. Causative factors include congenital abnormalities, trauma, surgery, and neoplastic processes. Tumour-related chylothorax can occur by direct invasion and erosion of the thoracic duct by the primary tumour or a tumour embolus, or by an indirect effect of back pressure and rupture of distended tributaries. Radiotherapy can cause narrowing of lymph vessels and consequent impaired lymph flow, but this mechanism is rarely described as a cause of chylothorax. 1 McWilliams A Gabbay E Chylothorax occurring 23 years post irradiation: literature review and management strategies. Respirology. 2000; 5: 301-303 Crossref PubMed Scopus (25) Google Scholar , 2 Zoetmulder F Rutgers E Baas P Thoracoscopic ligation of a thoracic duct leakage. Chest. 1994; 106: 1233-1234 Summary Full Text Full Text PDF PubMed Scopus (39) Google Scholar , 3 Lee YC Tribe AE Chylothorax from radiation induced mediastinal fibrosis. Aust NZ J Med. 1998; 28: 667-668 Crossref PubMed Scopus (7) Google Scholar