The Impact of Centralised Services on Metric Reflecting High-quality Performance: Outcomes from 1110 Consecutive Radical Cystectomies at a Single Centre.

BACKGROUND: The 2002 National Institute for Health and Care Excellence guidance on centralisation of radical cystectomy (RC) coincided with changes in practice: use of neoadjuvant chemotherapy (NAC) and pelvic lymph node dissection (PLND), and RC for high-risk non-muscle-invasive bladder cancer (HR-NMIBC). OBJECTIVE: To report the outcomes of RC at a single centre and to compare trends in survival with respect to centralisation and change in RC practice. DESIGN, SETTING, AND PARTICIPANTS: Data were collected retrospectively between 1 January 1994 and 31 December 2016. Patients with urothelial cell carcinoma (UCC) were selected. Outcomes from 1994 to 2007 (before centralisation, era 1) were compared with those from 2008 to 2016 (after centralisation, era 2). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was disease-specific mortality. Secondary outcomes were survival and use of NAC and PLND. RESULTS AND LIMITATIONS: Overall, 1100 RCs (era 1, 316; era 2, 794) were performed for UCC. Median (interquartile range [IQR]) follow-up was 28.5 (11.9-57.4) mo. RC for NMIBC was 36.2% versus 51.3% (p<0.001), NAC use was 2.2% versus 31.6% (p<0.001), and PLND use was 59.7% versus 76.4% (p<0.001) in era 1 versus era 2. The 30-d (1.6% [era 1] vs 0.8% [era 2], p=0.21) and 90-d (4.1% vs 2.6%, p=0.2) mortality rates did not differ with respect to RC year. Five-year disease-specific survival (DSS) was 56.0% in era 1 versus 79.0% in era 2 (p<0.001). RC for patients aged ≥75 yr was 13.9% versus 28.1% (p<0.001) and 30-d mortality in this group was 4.5% versus 0% (p=0.001) in era 1 versus era 2. The study is limited by its retrospective design. CONCLUSIONS: Centralisation was associated with higher rates of NAC and PLND use, and increased RC performed for older patients and patients with HR-NMIBC. DSS was higher and RC appeared to be safer for older patients (fewer postoperative mortalities) after centralisation. PATIENT SUMMARY: We looked at outcomes from bladder removal for bladder cancer. Survival outcomes improved following centralisation of services. Surgery appeared to be safer for older patients, as there were fewer postoperative mortalities after centralisation. Centralisation of radical cystectomy (RC) services was associated with higher rates of neoadjuvant chemotherapy and pelvic lymph node dissection use, and increased usage of RC for older patients with high-risk non-muscle-invasive bladder cancer. Survival outcomes from RC were superior after centralisation and safer for older patients undergoing RC (fewer postoperative mortalities).

Aromatase inhibitor-induced arthralgia in early breast cancer: what do we know and how can we find out more?

Aromatase inhibitors (AIs) are a standard of care for the adjuvant treatment of hormone responsive early carcinoma of the breast as demonstrated in a number of large international phase III randomised trials. Arthralgia was a somewhat unexpected side effect of this class of agents and has proven to be potentially problematic in clinical practice. Although rates of up 35% have been reported in the randomised trials, the figure has been much higher in subsequent case series. There is concern that these symptoms are significant and may affect compliance and thus the overall efficacy of treatment. It is therefore extremely important that we evaluate this syndrome with a view to gaining more information regarding its clinical features and possible aetiological mechanism. The potential aetiological mechanisms and evidence for aromatase inhibitor-induced arthralgia (AIA) are reviewed in this article. Looking forward, it is now important that prospective clinical trials are well designed to evaluate this syndrome and potential therapeutic strategies to circumvent it. Radiological imaging and biochemical analyses may help our understanding of AIA and these are discussed.

Accelerated hypo-fractionated radiotherapy for non small cell lung cancer: results from 4 UK centres.

BACKGROUND AND PURPOSE: A variety of radiotherapy fractionations are used as potentially curative treatments for non-small cell lung cancer. In the UK, 55 Gy in 20 fractions over 4 weeks (55/20) is the most commonly used fractionation schedule, though it has not been validated in randomized phase III trials. This audit pooled together existing data from 4 UK centres to produce the largest published series for this schedule. MATERIALS AND METHODS: 4 UK centres contributed data (Cambridge, Cardiff, Glasgow and Sheffield). Case notes and radiotherapy records of radically treated patients between 1999 and 2007 were retrospectively reviewed. Basic patient demographics, tumour characteristics, radiotherapy and survival data were collected and analysed. RESULTS: 609 patients were identified of whom 98% received the prescribed dose of 55/20. The median age was 71.3 years, 62% were male. 90% had histologically confirmed NSCLC, 49% had stage I disease. 27% had received chemotherapy (concurrent or sequential) with their radiotherapy. The median overall survival from time of diagnosis was 24.0 months and 2 year overall survival was 50%. CONCLUSION: These data show respectable results for patients treated with accelerated hypo-fractionated radiotherapy for NSCLC with outcomes comparable to those reported for similar schedules and represent the largest published series to date for 55/20 regime.

Detection of radiation-induced lung injury in non-small cell lung cancer patients using hyperpolarized helium-3 magnetic resonance imaging.

PURPOSE: To compare hyperpolarized helium-3 magnetic resonance imaging ((3)He-MRI) acquired from non-small cell lung cancer (NSCLC) patients before and after external beam radiotherapy (EBRT). METHODS AND MATERIALS: In an Ethics Committee-approved prospective study, five patients with histologically confirmed NSCLC gave written informed consent to undergo computed tomography (CT) and (3)He-MR ventilation imaging 1 week prior to and 3 months after radiotherapy. Images were registered to pre-treatment CT using anatomical landmark-based rigid registration to enable comparison. Emphysema was graded from examination of the CT. MRI-defined ventilation was calculated as the intersection of (3)He-MRI and CT lung volume as a percentage of the CT lung volume for the whole lung and regions of CT-defined pneumonitis. RESULTS: On pre-treatment images, there was a significant correlation between the degree of CT-defined emphysema and (3)He-MRI whole lung ventilation (Spearman's rho=0.90, p=0.04). After radiation therapy, pneumonitis was evident on CT for 3/5 patients. For these cases, (3)He-MRI ventilation was significantly reduced within the regions of pneumonitis (pre: 94.1±2.2%, post: 73.7±4.7%; matched pairs Student's t-test, p=0.02, mean difference=20.4%, 95% confidence interval 6.3-34.6%). CONCLUSIONS: This work demonstrates the feasibility of detecting ventilation changes between pre- and post-treatment using hyperpolarized helium-3 MRI for patients with NSCLC. Pre-treatment, the degree of emphysema and (3)He-MRI ventilation were correlated. For three cases of radiation pneumonitis, (3)He-MRI ventilation changes between pre- and post-treatment imaging were consistent with CT evidence of radiation-induced lung injury.

Palliative prostate radiotherapy for symptomatic advanced prostate cancer.

BACKGROUND AND PURPOSE: To report the results for the use of short-course palliative radiotherapy to the prostate for localised symptoms. MATERIALS AND METHODS: Fifty-eight patients were identified from radiotherapy records between 2003 and 2007. Data were collected retrospectively on patients' demographics, radiotherapy details and response. Symptoms and toxicity were scored, retrospectively, according to the following scale: 0=no symptoms, 1=mild symptoms, 2=moderate symptoms, and 3=severe symptoms. RESULTS: All the 58 patients had advanced prostate carcinoma. The median age at radiotherapy was 76.6 years (range 54-91). Fifty-six patients (97%) had hormone refractory disease. Twenty-seven patients (47%) had evidence of metastatic disease. 20 Gy in 5 fractions was the most commonly used fractionation. The most frequent baseline symptom was haematuria (54%). Eighty-nine percent (31/35) of the patients had a complete or partial resolution of symptoms at 4 months. Response rates for individual symptoms (including unknown responses) were: rectal symptoms (75%), pelvic pain (69%), urinary obstruction (54%) and haematuria (42%). A >50% reduction in PSA occurred in five patients. Toxicity was mild to moderate only and was self-limiting. CONCLUSION: Palliative radiotherapy to the prostate gland for local symptoms appears to be an effective means of palliation with minimal toxic side effects. Prospective studies are now required to assess its benefits in more detail.

Treatment of gastrointestinal stromal tumor: focus on imatinib mesylate.

Gastrointestinal stromal tumor (GIST) is a rare primary neoplasm of the gastrointestinal tract, mesentery, or omentum. In the past, surgery has been the only effective treatment. The diagnosis and treatment of GIST has been revolutionized over the past decade, since expression of the receptor tyrosine kinase KIT was shown to occur on these tumors. Mutations in this proto-oncogene commonly cause constitutive activation of the KIT tyrosine kinase receptor, an important factor in the pathogenesis of the disease. The development of specific tyrosine kinase inhibitors, such as imatinib mesylate, has led to a breakthrough in the treatment of advanced GIST. Treatment with this drug has led to significant improvements in survival, with overall response rates in excess of 80%. Side effects are common, but usually manageable. The success of this drug has led to further trials investigating its use in the pre- and postoperative situation. This review summarizes the current knowledge of GIST and imatinib treatment and possible future developments.

Routine use of continuous, hyperfractionated, accelerated radiotherapy for non-small-cell lung cancer: a five-center experience.

PURPOSE: To report the results from continuous, hyperfractionated, accelerated radiotherapy (CHART) used as the standard fractionation for radical RT in the management of non-small cell lung cancer (NSCLC) in five United Kingdom centers. METHODS AND MATERIALS: In 2005, the CHART consortium identified six U.K. centers that had continued to use CHART after the publication of the CHART study in 1997. All centers had been using CHART for >5 years and agreed to use a common database to audit their results. Patients treated with CHART between 1998 and December 2003 were identified to allow a minimum of 2 years of follow-up. Patient demographics, tumor characteristics, treatment details, and survival were recorded retrospectively. Five centers completed the data collection. RESULTS: A total of 583 patients who had received CHART were identified. Of these patients, 69% were male, with a median age of 68 years (range, 31-89); 83% had performance status 0 or 1; and 43% had Stage I or II disease. Of the 583 patients, 99% received the prescribed dose. In only 4 patients was any Grade 4-5 toxicity documented. The median survival from the start of RT was 16.2 months, and the 2-year survival rate of 34% was comparable to that reported in the original study. CONCLUSION: The results of this unselected series have confirmed that CHART is deliverable in routine clinical practice, with low levels of toxicity. Importantly, this series has demonstrated that the results of CHART reported from the randomized trial can be reproduced in routine clinical practice.