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The Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) burden of care study: Analysis of local treatments for lung metastases and systemic chemotherapy in 220 patients in the PulMiCC cohort.
AimThe aim of this work was to examine the burden of further treatments in patients with colorectal cancer following a decision about lung metastasectomy.MethodFive teams participating in the Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) study provided details on subsequent local treatments for lung metastases, including the use of chemotherapy. For patients in three groups (no metastasectomy, one metastasectomy or multiple local interventions), baseline factors and selection criteria for additional treatments were examined.ResultsThe five teams recruited 220 patients between October 2010 and January 2017. No lung metastasectomy was performed in 51 patients, 114 patients had one metastasectomy and 55 patients had multiple local interventions. Selection for initial metastasectomy was associated with nonelevated carcinoembryonic antigen, fewer metastases and no prior liver metastasectomy. These patients also had better Eastern Cooperative Oncology Group scores and lung function at baseline. Four sites provided information on chemotherapy in 139 patients: 79 (57%) had one to five courses of chemotherapy, to a total of 179 courses. The patterns of survival after one or multiple metastasectomy interventions showed evidence of guarantee-time bias contributing to an impression of benefit over no metastasectomy. After repeated metastasectomy, a significantly higher risk of death was observed, with no apparent reduction in chemotherapy usage.ConclusionRepeated metastasectomy is associated with a higher risk of death without reducing the use of chemotherapy. Continued monitoring without surgery might reassure patients with indolent disease or allow response assessment during systemic treatment. Overall, the carefully collected information from the PulMICC study provides no indication of an important survival benefit from metastasectomy.
Health economic studies of colorectal cancer and the contribution of administrative data: A systematic review.
IntroductionSeveral forces are contributing to an increase in the number of people living with and surviving colorectal cancer (CRC). However, due to the lack of available data, little is known about the implications of these forces. In recent years, the use of administrative records to inform research has been increasing. The aim of this paper is to investigate the potential contribution that administrative data could have on the health economic research of CRC.MethodsTo achieve this aim, we conducted a systematic review of the health economic CRC literature published in the United Kingdom and Europe within the last decade (2009-2019).ResultsThirty-seven relevant studies were identified and divided into economic evaluations, cost of illness studies and cost consequence analyses.ConclusionsThe use of administrative data, including cancer registry, screening and hospital records, within the health economic research of CRC is commonplace. However, we found that this data often come from regional databases, which reduces the generalisability of results. Further, administrative data appear less able to contribute towards understanding the wider and indirect costs associated with the disease. We explore several ways in which various sources of administrative data could enhance future research in this area.
Consultations for clinical features of possible cancer and associated urgent referrals before and during the COVID-19 pandemic: an observational cohort study from English primary care.
BackgroundIt remains unclear to what extent reductions in urgent referrals for suspected cancer during the COVID-19 pandemic were the result of fewer patients attending primary care compared to GPs referring fewer patients.MethodsCohort study including electronic health records data from 8,192,069 patients from 663 English practices. Weekly consultation rates, cumulative consultations and referrals were calculated for 28 clinical features from the NICE suspected cancer guidelines. Clinical feature consultation rate ratios (CRR) and urgent referral rate ratios (RRR) compared time periods in 2020 with 2019.FindingsConsultations for cancer clinical features decreased by 24.19% (95% CI: 24.04-24.34%) between 2019 and 2020, particularly in the 6-12 weeks following the first national lockdown. Urgent referrals for clinical features decreased by 10.47% (95% CI: 9.82-11.12%) between 2019 and 2020. Overall, once patients consulted with primary care, GPs urgently referred a similar or greater proportion of patients compared to previous years.ConclusionDue to the significant fall in patients consulting with clinical features of cancer there was a lower than expected number of urgent referrals in 2020. Sustained efforts should be made throughout the pandemic to encourage the public to consult their GP with cancer clinical features.
Microbiome Analysis of More Than 2,000 NHS Bowel Cancer Screening Programme Samples Shows the Potential to Improve Screening Accuracy.
PurposeThere is potential for fecal microbiome profiling to improve colorectal cancer screening. This has been demonstrated by research studies, but it has not been quantified at scale using samples collected and processed routinely by a national screening program.Experimental designBetween 2016 and 2019, the largest of the NHS Bowel Cancer Screening Programme hubs prospectively collected processed guaiac fecal occult blood test (gFOBT) samples with subsequent colonoscopy outcomes: blood-negative [n = 491 (22%)]; colorectal cancer [n = 430 (19%)]; adenoma [n = 665 (30%)]; colonoscopy-normal [n = 300 (13%)]; nonneoplastic [n = 366 (16%)]. Samples were transported and stored at room temperature. DNA underwent 16S rRNA gene V4 amplicon sequencing. Taxonomic profiling was performed to provide features for classification via random forests (RF).ResultsSamples provided 16S amplicon-based microbial profiles, which confirmed previously described colorectal cancer-microbiome associations. Microbiome-based RF models showed potential as a first-tier screen, distinguishing colorectal cancer or neoplasm (colorectal cancer or adenoma) from blood-negative with AUC 0.86 (0.82-0.89) and AUC 0.78 (0.74-0.82), respectively. Microbiome-based models also showed potential as a second-tier screen, distinguishing from among gFOBT blood-positive samples, colorectal cancer or neoplasm from colonoscopy-normal with AUC 0.79 (0.74-0.83) and AUC 0.73 (0.68-0.77), respectively. Models remained robust when restricted to 15 taxa, and performed similarly during external validation with metagenomic datasets.ConclusionsMicrobiome features can be assessed using gFOBT samples collected and processed routinely by a national colorectal cancer screening program to improve accuracy as a first- or second-tier screen. The models required as few as 15 taxa, raising the potential of an inexpensive qPCR test. This could reduce the number of colonoscopies in countries that use fecal occult blood test screening.
The impact of the COVID-19 pandemic on radiotherapy services in England, UK: a population-based study.
BackgroundThe indirect impact of the COVID-19 pandemic on cancer outcomes is of increasing concern. However, the extent to which key treatment modalities have been affected is unclear. We aimed to assess the impact of the pandemic on radiotherapy activity in England.MethodsIn this population-based study, data relating to all radiotherapy delivered for cancer in the English NHS, between Feb 4, 2019, and June 28, 2020, were extracted from the National Radiotherapy Dataset. Changes in mean weekly radiotherapy courses, attendances (reflecting fractions), and fractionation patterns following the start of the UK lockdown were compared with corresponding months in 2019 overall, for specific diagnoses, and across age groups. The significance of changes in radiotherapy activity during lockdown was examined using interrupted time-series (ITS) analysis.FindingsIn 2020, mean weekly radiotherapy courses fell by 19·9% in April, 6·2% in May, and 11·6% in June compared with corresponding months in 2019. A relatively greater fall was observed for attendances (29·1% in April, 31·4% in May, and 31·5% in June). These changes were significant on ITS analysis (p<0·0001). A greater reduction in treatment courses between 2019 and 2020 was seen for patients aged 70 years or older compared with those aged younger than 70 years (34·4% vs 7·3% in April). By diagnosis, the largest reduction from 2019 to 2020 in treatment courses was for prostate cancer (77·0% in April) and non-melanoma skin cancer (72·4% in April). Conversely, radiotherapy courses in April, 2020, compared with April, 2019, increased by 41·2% in oesophageal cancer, 64·2% in bladder cancer, and 36·3% in rectal cancer. Increased use of ultra-hypofractionated (26 Gy in five fractions) breast radiotherapy as a percentage of all courses (0·2% in April, 2019, to 60·6% in April, 2020; ITS p<0·0001) contributed to the substantial reduction in attendances.InterpretationRadiotherapy activity fell significantly, but use of hypofractionated regimens rapidly increased in the English NHS during the first peak of the COVID-19 pandemic. An increase in treatments for some cancers suggests that radiotherapy compensated for reduced surgical activity. These data will assist health-care providers in understanding the indirect consequences of the pandemic and the role of radiotherapy services in minimising these consequences.FundingNone.
Power of big data to improve patient care in gastroenterology.
Big data is defined as being large, varied or frequently updated, and usually generated from real-world interaction. With the unprecedented availability of big data, comes an obligation to maximise its potential for healthcare improvements in treatment effectiveness, disease prevention and healthcare delivery. We review the opportunities and challenges that big data brings to gastroenterology. We review its sources for healthcare improvement in gastroenterology, including electronic medical records, patient registries and patient-generated data. Big data can complement traditional research methods in hypothesis generation, supporting studies and disseminating findings; and in some cases holds distinct advantages where traditional trials are unfeasible. There is great potential power in patient-level linkage of datasets to help quantify inequalities, identify best practice and improve patient outcomes. We exemplify this with the UK colorectal cancer repository and the potential of linkage using the National Endoscopy Database, the inflammatory bowel disease registry and the National Health Service bowel cancer screening programme. Artificial intelligence and machine learning are increasingly being used to improve diagnostics in gastroenterology, with image analysis entering clinical practice, and the potential of machine learning to improve outcome prediction and diagnostics in other clinical areas. Big data brings issues with large sample sizes, real-world biases, data curation, keeping clinical context at analysis and General Data Protection Regulation compliance. There is a tension between our obligation to use data for the common good and protecting individual patient's data. We emphasise the importance of engaging with our patients to enable them to understand their data usage as fully as they wish.
Pulmonary metastasectomy in colorectal cancer: health utility scores by EQ-5D-3L in a randomized controlled trial show no benefit from lung metastasectomy.
AimThe aim was to assess the health utility of lung metastasectomy in the treatment of patients with colorectal cancer (CRC) using the EQ-5D-3L questionnaire.MethodsMultidisciplinary CRC teams at 14 sites recruited patients to a two-arm randomized controlled trial-Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC). Remote randomization was used, stratified by site and with minimization for seven known confounders. Participants completed the EQ-5D-3L questionnaire together with other patient reported outcome measures at randomization and then again at 3, 6, 12 and 24 months. These were returned by post to the coordinating centre.ResultsBetween December 2010 and December 2016, 93 participants were randomized, 91 of whom returned questionnaires. Survival and patient reported quality of life have been published previously, revealing no significant differences between the trial arms. Described here are patient reported data from the five dimensions of the EQ-5D-3L and the visual analogue scale (VAS) health state. No significant difference was seen at any time point. The estimated difference between control and metastasectomy patients was -0.23 (95% CI -0.113, 0.066) for the composite 0 to 1 index scale based on the descriptive system and 0.123 (95% CI -7.24, 7.49) for the 0 to 100 VAS scale.ConclusionsFollowing lung metastasectomy for CRC, no benefit was demonstrated for health utility, which alongside a lack of a survival or quality of life benefit calls into question the widespread use of the procedure.
The incidence, characteristics and outcomes of pregnant women hospitalized with symptomatic and asymptomatic SARS-CoV-2 infection in the UK from March to September 2020: A national cohort study using the UK Obstetric Surveillance System (UKOSS).
BackgroundThere is a lack of population level data on risk factors, incidence and impact of SARS-CoV-2 infection in pregnant women and their babies. The primary aim of this study was to describe the incidence, characteristics and outcomes of hospitalized pregnant women with symptomatic and asymptomatic SARS-CoV-2 in the UK compared to pregnant women without SARS-CoV-2.Methods and findingsWe conducted a national, prospective cohort study of all hospitalized pregnant women with confirmed SARS-CoV-2 from 01/03/2020 to 31/08/2020 using the UK Obstetric Surveillance System. Incidence rates were estimated using national maternity data. Overall, 1148 hospitalized women had confirmed SARS-CoV-2 in pregnancy, 63% of which were symptomatic. The estimated incidence of hospitalization with symptomatic SARS-CoV-2 was 2.0 per 1000 maternities (95% CI 1.9-2.2) and for asymptomatic SARS-CoV-2 was 1.2 per 1000 maternities (95% CI 1.1-1.4). Compared to pregnant women without SARS-CoV-2, women hospitalized with symptomatic SARS-CoV-2 were more likely to be overweight or obese (adjusted OR 1.86, (95% CI 1.39-2.48) and aOR 2.07 (1.53-2.29)), to be of Black, Asian or Other minority ethnic group (aOR 6.24, (3.93-9.90), aOR 4.36, (3.19-5.95) and aOR 12.95, (4.93-34.01)), and to have a relevant medical comorbidity (aOR 1.83 (1.32-2.54)). Hospitalized pregnant women with symptomatic SARS-CoV-2 were more likely to be admitted to intensive care (aOR 57.67, (7.80-426.70)) but the absolute risk of poor outcomes was low. Cesarean births and neonatal unit admission were increased regardless of symptom status (symptomatic aOR 2.60, (1.97-3.42) and aOR 3.08, (1.99-4.77); asymptomatic aOR 2.02, (1.52-2.70) and aOR 1.84, (1.12-3.03)). The risks of stillbirth or neonatal death were not significantly increased, regardless of symptom status.ConclusionsWe have identified factors that increase the risk of symptomatic and asymptomatic SARS-CoV-2 in pregnancy. Clinicians can be reassured that the majority of women do not experience severe complications of SARS-CoV-2 in pregnancy.
Cancer Trial Impact: Understanding Implementation of the Short Course Oncology Treatment Trial Findings at a National Level.
AimsThe Short Course Oncology Treatment (SCOT) trial indicated that 3 months of adjuvant doublet chemotherapy was non-inferior to 6 months of treatment for patients with colorectal cancer, with considerably less toxicity. The SCOT trial results were disseminated in June 2017. The aim of this study was to understand if SCOT trial findings were implemented in Scotland.Materials and methodsA retrospective analysis was carried out on a dataset derived from a source population of 5.4 million people. Eligible patients were those with stage II or III colorectal cancer who received adjuvant chemotherapy. Logistic regression was applied to understand the extent of practice change to a 3-month adjuvant chemotherapy duration after the SCOT trial results were disseminated. Interrupted time series analysis was used to visualise differences in prescribing trends before and after June 2017 for the overall cohort, and by SCOT trial eligibility.ResultsIn total, 2310 patients were included in the study; 1957 and 353 treated pre- and post-June 2017, respectively. The median treatment duration decreased from 21 weeks (interquartile range 14-24) prior to June 2017 to 12 weeks (interquartile range 12-21 weeks) after June 2017 (P < 0.001). The proportion of patients receiving over 3 months of adjuvant treatment decreased from 75% to 42% (P < 0.001). This change was most noticeable for patients who met the SCOT trial eligibility criteria, and specifically for those with low-risk stage III disease and those treated with capecitabine and oxaliplatin (CAPOX). Although practice change occurred in all locations, there were differences between regions that could be explained by pre-SCOT trial prescribing trends.DiscussionA significant change in chemotherapy prescribing occurred after dissemination of the SCOT trial results. National, real-world data can be used to capture the extent of implementation of clinical trial results. In this case, implementation was aligned with clinical trial subgroup findings. This type of analysis could be conducted to evaluate the impact of other clinical trials.
Creation of the first national linked colorectal cancer dataset in Scotland: prospects for future research and a reflection on lessons learned.
IntroductionCurrent understanding of cancer patients, their treatment pathways and outcomes relies mainly on information from clinical trials and prospective research studies representing a selected sub-set of the patient population. Whole-population analysis is necessary if we are to assess the true impact of new interventions or policy in a real-world setting. Accurate measurement of geographic variation in healthcare use and outcomes also relies on population-level data. Routine access to such data offers efficiency in research resource allocation and a basis for policy that addresses inequalities in care provision.ObjectiveAcknowledging these benefits, the objective of this project was to create a population level dataset in Scotland of patients with a diagnosis of colorectal cancer (CRC).MethodsThis paper describes the process of creating a novel, national dataset in Scotland.ResultsIn total, thirty two separate healthcare administrative datasets have been linked to provide a comprehensive resource to investigate the management pathways and outcomes for patients with CRC in Scotland, as well as the costs of providing CRC treatment. This is the first time that chemotherapy prescribing and national audit datasets have been linked with the Scottish Cancer Registry on a national scale.ConclusionsWe describe how the acquired dataset can be used as a research resource and reflect on the data access challenges relating to its creation. Lessons learned from this process and the policy implications for future studies using administrative cancer data are highlighted.
Influence of age on surgical treatment and postoperative outcomes of patients with colorectal cancer in Denmark and Yorkshire, England.
Denmark and Yorkshire are demographically similar and both have undergone changes in their management of colorectal cancer to improve outcomes. The differential provision of surgical treatment, especially in the older age groups, may contribute to the magnitude of improved survival rates. This study aimed to identify differences in the management of colorectal cancer surgery and postoperative outcomes according to patient age between Denmark and Yorkshire. This was a retrospective population-based study of colorectal cancer patients diagnosed in Denmark and Yorkshire between 2005 and 2016. Proportions of patients undergoing major surgical resection, postoperative mortality and relative survival were compared between Denmark and Yorkshire across several age groups (18-59, 60-69, 70-79 and ≥80 years) and over time. The use of major surgical resection was higher in Denmark than in Yorkshire, especially for patients aged ≥80 years (70.5% versus 50.5% for colon cancer, 49.3% versus 38.1% for rectal cancer). Thirty-day postoperative mortality for Danish patients aged ≥80 years was significantly higher than that for Yorkshire patients with colonic cancer [OR (95% CI) = 1.22 (1.07, 1.38)] but not for rectal cancer or for 1-year postoperative mortality. Relative survival significantly increased in all patients aged ≥80 years except for Yorkshire patients with colonic cancer. This study suggests that there are major differences between the management of elderly patients with colorectal cancer between the two populations. Improved selection for surgery and better peri- and postoperative care in these patients appears to improve long-term outcomes, but may come at the cost of a higher 30-day mortality.
Improving the management of early colorectal cancers (eCRC) by using quantitative markers to predict lymph node involvement and thus the need for major resection of pT1 cancers.
Since implementing the NHS bowel cancer screening programme, the rate of early colorectal cancer (eCRC; pT1) has increased threefold to 17%, but how these lesions should be managed is currently unclear. To improve risk stratification of eCRC by developing reproducible quantitative markers to build a multivariate model to predict lymph node metastasis (LNM). Our retrospective cohort of 207 symptomatic pT1 eCRC was assessed for quantitative markers. Associations between categorical data and LNM were performed using χ2 test and Fisher's exact test. Multivariable modelling was performed using logistic regression. Youden's rule gave the cut-point for LNM. All significant parameters in the univariate analysis were included in a multivariate model; tumour stroma (95% CI 2.3 to 41.0; p=0.002), area of submucosal invasion (95% CI 2.1 to 284.6; p=0.011), poor tumour differentiation (95% CI 2.0 to 358.3; p=0.003) and lymphatic invasion (95% CI 1.3 to 192.6; p=0.028) were predictive of LNM. Youden's rule gave a cut-off of p>5%, capturing 18/19 LNM (94.7%) cases and leading to a resection recommendation for 34% of cases. The model that only included quantitative factors were also significant, capturing 17/19 LNM cases (90%) and leading to resection rate of 35% of cases (72/206). In this study, we were able to reduce the potential resection rate of pT1 with the multivariate qualitative and/or quantitative model to 34% or 35% while detecting 95% or 90% of all LNM cases, respectively. While these findings need to be validated, this model could lead to a reduction of the major resection rate in eCRC.
Impact of the SARS-CoV-2 pandemic on female breast, colorectal and non-small cell lung cancer incidence, stage and healthcare pathway to diagnosis during 2020 in Wales, UK, using a national cancer clinical record system.
COVID-19 pandemic responses impacted behaviour and health services. We estimated the impact on incidence, stage and healthcare pathway to diagnosis for female breast, colorectal and non-small cell lung cancers at population level in Wales. Cancer e-record and hospital admission data linkage identified adult cases, stage and healthcare pathway to diagnosis (population ~2.5 million). Using multivariate Poisson regressions, we compared 2019 and 2020 counts and estimated incidence rate ratios (IRR). Cases decreased 15.2% (n = -1011) overall. Female breast annual IRR was 0.81 (95% CI: 0.76-0.86, p
International trends in cancer incidence in middle-aged and older adults in 44 countries
Objective: We examine international incidence trends of lung, colorectal, prostate, and breast cancers, as well as all cancers combined excluding non-melanoma skin cancer (NMSC) in adults aged 50 and older, over a fifteen-year period using data from 113 high quality population-based cancer registries included in the Cancer in Five Continents (CI5) series and NORDCAN. Materials and methods: We calculated annual incidence rates between 1998 and 2012 for ages 50–64, 65–74, and 75+, by sex and both sexes combined. We estimated average annual percentage change (AAPC) in rates using quasi-Poisson regression models. Results: From 1998 to 2012, incidence trends for all cancers (excluding NMSC) have increased in most countries across all age groups, with the greatest increase observed in adults aged 75+ in Ecuador (AAPC = +3%). Colorectal cancer incidence rates increased in the majority of countries, across all age groups. Lung cancer rates among females have increased but decreased for males. Prostate cancer rates have sharply increased in men aged 50–64 with AAPC between 5% and 15% in 24 countries, while decreasing in the 75+ age group in 21 countries, by up to −7% in Bahrain. Female breast cancer rates have increased across all age groups in most countries, especially in the 65–74 age group and in Asia with AAPC increasing to 7% in the Republic of Korea. Conclusions: These findings assist with anticipating changing patterns and needs internationally. Due to the specific needs of older patients, it is urgent that cancer systems adapt to address their growing number.
Age disparities in lung cancer survival in New Zealand: The role of patient and clinical factors.
ObjectiveAge is an important prognostic factor for lung cancer. However, no studies have investigated the age difference in lung cancer survival per se. We, therefore, described the role of patient-related and clinical factors on the age pattern in lung cancer excess mortality hazard by stage at diagnosis in New Zealand.Materials and methodsWe extracted 22 487 new lung cancer cases aged 50-99 (median age = 71, 47.1 % females) diagnosed between 1 January 2006 and 31 July 2017 from the New Zealand population-based cancer registry and followed up to December 2019. We modelled the effect of age at diagnosis, sex, ethnicity, deprivation, comorbidity, and emergency presentation on the excess mortality hazard by stage at diagnosis, and we derived corresponding lung cancer net survival.ResultsThe age difference in net survival was particularly marked for localised and regional lung cancers, with a sharp decline in survival from the age of 70. No identified factors influenced age disparities in patients with localised cancer. However, for other stages, females had a greater difference in survival between middle-age and older-age than males. Comorbidity and emergency presentation played a minor role. Ethnicity and deprivation did not influence age disparities in lung cancer survival.ConclusionSex and stage at diagnosis were the most important factors of age disparities in lung cancer survival in New Zealand.
Age disparities in lung cancer survival in New Zealand: the role of patient and clinical factors
Background Age is an important prognostic factor for lung cancer. However, no studies have investigated the age difference in lung cancer survival per se. We, therefore, described the role of patient-related and clinical factors on the age pattern in lung cancer excess mortality hazard by stage at diagnosis in New Zealand. Methods We extracted 22 487 new lung cancer cases aged 50-99 (median age = 71, 47.1% females) diagnosed between 1 January 2006 and 31 July 2017 from the New Zealand population-based cancer registry and followed up to December 2019. We modelled the effect of age at diagnosis, sex, ethnicity, deprivation, comorbidity, and emergency presentation on the excess mortality hazard by stage at diagnosis, and we derived corresponding lung cancer net survival. Results The age difference in net survival was particularly marked for localised and regional lung cancers, with a sharp decline in survival from the age of 70. No identified factors influenced age disparities in patients with localised cancer. However, for other stages, females had a greater age difference in survival between middle-aged and older patients with lung cancer than males. Comorbidity and emergency presentation played a minor role. Ethnicity and deprivation did not influence age disparities in lung cancer survival. Conclusion Sex and stage at diagnosis were the most important factors of age disparities in lung cancer survival in New Zealand. Key messages What is the key question? How do patient-related and clinical factors influence age pattern in lung cancer survival? What is the bottom line? Age disparities in lung cancer survival were strongest for females and non-advanced disease. Deprivation, ethnicity, comorbidity, and emergency presentation did not influence age disparities. Why read on? Our findings reinforce the call for a better representation of older adults in clinical trials and a wider use of geriatric assessment to identify patients who will benefit treatment.
Multi-Facet Clustering Variational Autoencoders
Work in deep clustering focuses on finding a single partition of data. However, high-dimensional data, such as images, typically feature multiple interesting characteristics one could cluster over. For example, images of objects against a background could be clustered over the shape of the object and separately by the colour of the background. In this paper, we introduce Multi-Facet Clustering Variational Autoencoders (MFCVAE), a novel class of variational autoencoders with a hierarchy of latent variables, each with a Mixture-of-Gaussians prior, that learns multiple clusterings simultaneously, and is trained fully unsupervised and end-to-end. MFCVAE uses a progressively-trained ladder architecture which leads to highly stable performance. We provide novel theoretical results for optimising the ELBO analytically with respect to the categorical variational posterior distribution, correcting earlier influential theoretical work. On image benchmarks, we demonstrate that our approach separates out and clusters over different aspects of the data in a disentangled manner. We also show other advantages of our model: the compositionality of its latent space and that it provides controlled generation of samples.