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28 November 2023

6 minutes read

Crafting an Outstanding UCL Personal Statement: A Comprehensive Guide with Examples

Dirghayu Kaushik

Gaining admission to University College London (UCL) is a dream for many, but achieving this goal requires more than just academic excellence.

Your UCL personal statement plays a pivotal role in your application, serving as a unique opportunity to showcase your aspirations, achievements, and individuality.

This article provides essential insights and examples to assist you in creating a personal statement that captures the essence of your academic and personal journey, tailored to resonate with UCL’s admissions committee.

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The Role of a Personal Statement in Your UCL Application

Understanding the Significance

Your personal statement is a critical element of your UCAS application to UCL. It’s your chance to convey your enthusiasm, experiences, and suitability for your chosen course.

This narrative helps the admissions team to understand who you are beyond your grades and test scores. It’s about making a compelling case for why you are an ideal candidate for UCL and how the university fits into your academic and career aspirations.

What UCL Looks For

UCL, being a prestigious and competitive institution, seeks candidates who demonstrate intellectual curiosity, a commitment to their field of study, and the potential to contribute meaningfully to the university community.

Your personal statement should reflect these qualities, showcasing your passion for learning, your understanding of the course content, and your readiness for the challenges of university life.

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Crafting a Winning Personal Statement for UCL

Creating a personal statement for University College London (UCL) is a crucial step in your application process. Your statement should stand out, reflecting your unique qualifications and enthusiasm for your chosen course. Here are key points to help you craft a winning personal statement for UCL:

Understand UCL’s Values and Course Requirements : Before you begin, research UCL’s ethos, values, and specific requirements for your chosen course. Understanding what UCL looks for in its students can help tailor your statement to resonate with the admissions committee.
Start with a Compelling Introduction : Your opening lines should grab the reader’s attention. Start with a personal anecdote, a provocative question, or a statement that clearly expresses your passion for the subject.
Showcase Your Academic Strengths : Highlight your academic achievements that are relevant to the course. Include any awards, high grades in related subjects, or participation in relevant academic competitions or projects.
Demonstrate Interest and Knowledge in the Subject : Show that you have a deep understanding of and a genuine interest in the field. Discuss any books, articles, or research that have inspired you and shaped your desire to study this subject at UCL.
Reflect on Relevant Experiences : Include work experience, internships, volunteering, or extracurricular activities that have helped develop skills and qualities relevant to the course. Explain what you learned from these experiences and how they have prepared you for university-level study.
Discuss Your Career Aspirations : Clearly articulate how the course at UCL fits into your long-term career goals. This shows admissions tutors that you have a clear direction and motivation for your studies.
Exhibit Your Skills and Qualities : Highlight personal skills and qualities that make you a suitable candidate for the course. These might include problem-solving, critical thinking, leadership, teamwork, or communication skills.
Explain Why UCL Is the Right Choice for You : Discuss specific aspects of UCL and its course offerings that appeal to you. This could be particular modules, the teaching methodology, research opportunities, or the campus environment.
Make It Personal and Authentic : Your statement should be personal and reflect your true self. Avoid clichés and generic statements. Admissions tutors want to hear your voice and understand who you are.
Conclude with a Strong Closing Statement : End your personal statement on a high note, reemphasizing your enthusiasm and readiness for the course and how you look forward to contributing to the UCL community.
Proofread and Edit : Ensure your statement is free of grammatical errors and typos. A well-written, error-free statement demonstrates your attention to detail and commitment to excellence.
Seek Feedback : Before finalizing, get feedback from teachers, mentors, or those who know you well. They can provide valuable insights and help you refine your statement.

By following these points, you can craft a personal statement that not only meets the standards of UCL but also truly represents your academic ambitions and personal journey, significantly boosting your chances of admission.

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Personal Statement Examples for Different UCL Courses

Example of UCL Medicine Program

Medicine applicants need to demonstrate a passion for the field, empathy, and a strong academic background in sciences. An effective personal statement for a UCL medicine course might begin with a personal anecdote or experience that sparked your interest in medicine.

Follow this with details of your academic journey in sciences, any relevant work experience, and extracurricular activities. Conclude by discussing your career aspirations in medicine and how UCL’s program aligns with these goals.

Example for UCL Economics Program

For an economics course, your statement should reflect your understanding of economic principles and your ability to think critically about economic issues. Start by explaining why you are interested in economics, possibly by citing a current issue or personal experience.

Include your academic achievements in mathematics and related subjects, and any relevant extracurricular activities, like participating in economics clubs or competitions. Finally, express how UCL’s economics program will help you achieve your career objectives.

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Key Dos and Don’ts in Writing Your Personal Statement

Final Steps Before Submission

Review and Feedback

Before submitting your personal statement, it’s crucial to review it thoroughly. Seek feedback from teachers, mentors, or peers who can provide constructive criticism. Their insights can help refine your statement, ensuring it’s compelling and error-free.

Aligning Your Statement with UCL’s Values

Research UCL’s values and ethos, and subtly align your statement with these. Show how you embody qualities valued by UCL, such as intellectual curiosity, global perspective, and a commitment to impact society positively. This alignment demonstrates that you are not only a good fit academically but also culturally for UCL.

Your UCL personal statement is a vital part of your application. It’s an opportunity to showcase your unique qualifications, experiences, and aspirations.

By following the guidelines and examples provided in this guide, you can create a statement that captures your individuality and suitability for UCL.

Remember, this is your chance to make a lasting impression on the admissions committee, so take the time to craft a personal statement that truly reflects who you are and why you are the perfect candidate for UCL.

Q1: How important is it to relate my personal statement to my future career goals?

It’s very important. Relating your course of study to your future career goals shows foresight and a clear understanding of how UCL will help you achieve your aspirations.

Q2: Can I include quotes in my personal statement?

While a well-chosen quote can be impactful, it’s generally better to use your own words to ensure your personal statement is truly personal and unique.

Q3: How can I ensure that my personal statement stands out?

To make your personal statement stand out, focus on unique experiences, present your content in a structured and coherent manner, and infuse your personal voice and enthusiasm throughout the text.

Q4: Is it okay to share personal challenges in my statement?

Yes, sharing personal challenges can be powerful, especially if you can demonstrate how they have shaped your character and academic journey. However, ensure that the overall tone remains positive and forward-looking.

Key Dos and Don'ts in Writing Your Personal Statement

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• The Role of a Personal Statement in Your UCL Application
• Crafting a Winning Personal Statement for UCL
• Personal Statement Examples for Different UCL Courses
• Key Dos and Don'ts in Writing Your Personal Statement
• Final Steps Before Submission
• Conclusion

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Medicine Personal Statement Inspiration – James (UCL)

Home » Application Guide » Medicine Personal Statement Inspiration – James (UCL)

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Awesome ps resources., awesome resources + course.

This is part of a series of blog posts wherein members of the 6med team attach and comment on their own medicine personal statements. James shares his personal statement that helped him successfully gain an offer from UCL to study Medicine.

Please be aware that these examples are meant purely for the sake of inspiration, and should absolutely NOT be used as a model around which to base your own personal statement. UCAS have a rather strict system that detects plagiarism .

Successful UCL Medicine Personal Statement

First, take a read through this successful UCL personal statement and then we will break down each section and analyse it.

“For several months this year, I volunteered at a school for children with mental and physical disabilities. One particular student caught my attention, a violent and withdrawn boy. By patiently encouraging him to engage in activities through a toy caterpillar, I found a way to connect with him. The experience highlighted the importance and value of every human life, of having compassion for others, and of being aware of other people’s needs and problems aside from our own. Medicine is a lifelong endeavour; it is an opportunity for me to contribute to an expanding scientific field, as well as confront the physical, social and emotional challenges that face humanity.

As a naturally inquisitive person, my fascination with science has led to a profound interest in the human body. My wider reading included “The Music of Life” by Denis Noble, which gave me a better understanding of the physiological functions within the body and the interaction of genes with the environment, cells and organs. Further study of the applications of genetic engineering resulted in me writing a paper on the use of nanotechnology in Medicine. This discussed the relation of current scientific research to the management of various pathologies; the task required me to scrutinize secondary sources and gave me stronger analytical skills. Realising that this combination of science and practical undertaking appealed hugely, I sought some real world experiences to confirm my career choice.

Earlier this year, I undertook work experience in a Renal Unit of my local hospital. This gave me the opportunity to attend ward rounds and clinics, as well as observe dialysis and venous catheter insertion. Through talking to patients, the physical, and at times, mental fragility of some individuals surprised me. The empathy shown by the doctors inspired me deeply. A junior doctor recounted her tough experiences; there were instances where she was confined to a desk organising paperwork, and occasions where she didn’t get any sleep. However, her involvement with patients was satisfying, and seeing them progressively improve motivated her. From these experience, I appreciate how being a doctor can be gruelling, but also very gratifying. Above all, I realise the importance in having moral fibre, perseverance and humility.

Every Wednesday for four months I shadowed my local GP. Watching him give both medical and social advice with such understanding and clinical skill to people from every race, culture and faith made me realise the importance of primary care, good communication and careful allocation of resources.

As a concert pianist, I have gained experience in handling stress and performance anxiety. I perform at a local hospice every week and through successful piano competitions, I had the honour of playing at the Jacqueline De Pre Hall in Oxford. I enjoy conveying the emotion of a piece of music in a beautiful and hopefully profound way. As a school mentor and piano teacher for younger students, I developed skills in passing on information effectively and in listening to others with patience and respect. My experience in representing the school in badminton and hockey has given my stronger teamwork abilities, which I was able to apply in helping organise the school charity week, in which we raised £16,000. I hold positions of responsibility as a school prefect and founder of two societies, where I teach students musical theory and philosophy. Having also been a St John first aider for three years, I gained experience in making others feel comfortable in times of close contact and in assessing situations quickly and effectively. I also enjoy helping out at community events. Finally, I enjoy acting, and also performing magic; being able to instil wonder and joy in others is priceless.

I believe I have the humility, scientific acuity and empathy to become a committed doctor and to face the challenges ahead in my chosen career.”

Now, we’re going to take apart this personal statement and have a look at what makes it work.

Remember, though, we’re not going to teach a set formula, but instead, instil some general principles you can use when you’re writing your own.

Personal statements are ‘personal’ after all, so try not to put across things that don’t faithfully reflect your own experiences, understanding and individuality.

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UCL Medicine Personal Statement Analysis

The first paragraph is often the hardest the write, and there are a number of ways you can go about it.

Whatever you write, always try to captivate the reader – although sometimes unavoidable, the first few sentences run a high risk of being clichéd. One possible way to sound more gripping is by richly conveying a personal experience, either as a volunteer or during your work experience.

Of course, this isn’t the only way: if you have a strong personal reason for studying medicine (which is actually quite rare among students) or just a strong interest in the sciences, make sure it comes across in the first paragraph, phrasing it in a more interesting and unique manner if possible; remember though, it’s important to always favour a more introspective and honest account of your experiences instead of something unrealistic and unnecessarily flamboyant.

“The experience highlighted the importance and value of every human life, of having compassion for others, and of being aware of other people’s needs and problems aside from our own.”

Following the purely descriptive account of the boy, the model statement goes on to reveal what the writer learnt from the experience.

This is an important point: it’s never about what you did, it’s about what you gained from the experience . Many students make the mistake of simply describing all the things they did during their hospital placement or whilst volunteering.

Instead, medical schools are looking for students that are able to reflect upon their experiences , and you’ll be doing this for the rest of your career as you input reflections onto your NHS ePortfolio.

“Medicine is a lifelong endeavour; it is an opportunity for me to contribute to an expanding scientific field, as well as confront the physical, social and emotional challenges that face humanity.”

Throughout the application process, medical schools are looking not just for an understanding of the medical course, but medicine as a career.

The writer here shows an awareness of medicine as a profession that requires continuous learning and growth, as well as an opportunity to do good in the world. Of course, there is some flowery language here, but the writer carefully chose this sentence to offer a convincing ending to the opening paragraph.

“As a naturally inquisitive person, my fascination with science has led to a profound interest in the human body.”

The next paragraph begins with one aspect of the writer’s desire to study medicine: scientific interest. Ultimately, no matter how much you want to care for people, studying medicine requires some degree of interest in the biological sciences, otherwise, you may as well serve people through a number of other fulfilling career paths, as a social worker, for example.

Note how this opening sentence sets the scene for the paragraph to come – it clearly marks a scientific theme. The language used is also richly descriptive, with words and phrases such as ‘naturally inquisitive’, ‘fascination’, and ‘profound’ adding colour to the sentence. Too often students fail to pick up a thesaurus and can end up sounding grey, unexciting and almost apathetic towards the things they talk about in some areas of their statement.

Never underestimate how the careful choice of language can add a new dimension to your personal statement.

“My wider reading included “The Music of Life” by Denis Noble, which gave me a better understanding of the physiological functions within the body and the interaction of genes with the environment, cells and organs. Further study of the applications of genetic engineering resulted in me writing a paper on the use of nanotechnology in Medicine. This discussed the relation of current scientific research to the management of various pathologies; the task required me to scrutinize secondary sources and gave me stronger analytical skills.”

The next few sentences provide support for the natural inquisitiveness and scientific interest the writer claimed to have.

Wider reading isn’t always necessary, but rather a nice addition to more academic personal statements. It’s usually the case that students applying to the more traditional and research-orientated universities (Oxbridge, UCL, Imperial, etc.) offer a few sentences showcasing their interest in scientific research and topics outside of their science curriculum.

If do you want to include a book you’ve read, make sure you know what it’s about so that you can write a concise, perceptive description about it in your PS, just like the writer has done here. We would advise against emphasising A-level choices too much and focus on things you’ve read or done outside the curriculum; certainly avoid talking about how high your grades are as this is a prerequisite for studying medicine anyway.

If scientific research plays a lesser role in your reasons for applying to medicine, then dedicate more space for work experience, volunteering and extra-curricular activities.

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“Realising that this combination of science and practical undertaking appealed hugely, I sought some real world experiences to confirm my career choice.”

Flow is important when it comes to writing your personal statement – don’t make the mistake of making the act of writing your personal statement a listing exercise, like you would for a curriculum vitae.

There should be some hint of an underlying narrative or flow to your writing; in terms of structure, each paragraph should have some theme – in this model statement, the writer has a paragraph on science, hospital work experience and volunteering, for example.

If you’re a fantastic writer (and most of us aren’t), then you may have already put together a beautiful story of how you discovered your passion for medicine and feel comfortable not sticking with a more conventional structure. If you’re not a strong writer, then we recommend you make your personal statement very thematic and simply use nice ‘linking sentences’ that bring together different themes between paragraphs. For example, the writer here draws the scientific paragraph to a close and links to the next paragraph, which talks about work experience.

“Earlier this year, I undertook work experience in a Renal Unit of my local hospital.”

Your description of where and when you did work experience should be short and snappy. There’s no need to give the full name of the hospital, and as a quick writing tip, try to avoid starting sentences with ‘I’.

“This gave me the opportunity to attend ward rounds and clinics, as well as observe dialysis and venous catheter insertion.”

You should then move on to what you actually did, keeping the descriptions as concise as possible.

Remember, medical schools don’t care how many ward rounds you’ve been on or that you’ve even worked at a hospital (although hospital experience is rather important). What is important is that you explain the things you’ve picked up and realized as a result of your experience.

“Through talking to patients, the physical, and at times, mental fragility of some individuals surprised me.”

The writer here first demonstrates they took opportunities to speak to patients, which is one of the most important things you can take away from a hospital placement.

Medical schools want to know you’re able to communicate with real patients and reflect upon your conversations with them. In this case, the writer succinctly reveals a first-hand experience of how patients can be weak, fragile and utterly dependent on doctors and others to support them.

“The empathy shown by the doctors inspired me deeply.”

The writer then goes on to reflect on how the doctors treated these patients and offers one of the most important qualities needed in all doctors , that is empathy .

Note again how this sentence is phrased – it sounds more genuine and meaningful than a sentence such as ‘Empathy is important in doctors’, which is something a lot of students would write.

Always write about what you learnt and realized through your experiences in an authentic manner, it’s much more powerful than phrasing things in a way that suggests you’re just saying it to earn points.

“A junior doctor recounted her tough experiences; there were instances where she was confined to a desk organising paperwork, and occasions where she didn’t get any sleep. However, her involvement with patients was satisfying, and seeing them progressively improve motivated her. From these experiences, I appreciate how being a doctor can be gruelling, but also very gratifying.”

At the same time, you should also be aware that personal statements can be a checklist exercise, with medical schools scrutinizing every sentence you write in order to determine whether you understand what being a doctor is about.

One of the important things you should include is the realities of being a doctor. All too often doctors are over-glamourized by students in their personal statements, with some going as far as saying doctors are trained to deal with all complications, which clearly isn’t true.

Instead, dedicate one or two sentences to the less attractive side of medicine, as the writer has done here. Examples of areas you could talk about may include the stress of long hours or having to break bad news to patients . Of course, you don’t want to leave any negative sentences hanging, so tactfully counter them by adding on positives that more than make up for some of the downsides of being a doctor.

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“Above all, I realise the importance in having moral fibre, perseverance and humility.”

As you’ll come to realize when writing your personal statement, fitting everything you want to mention into 4,000 characters isn’t easy.

This model statement clearly makes sacrifices with the content it includes – in this hospital placement paragraph, only two main qualities are covered: empathy and the realities of being a doctor.

There is no doubt that the writer could have included much more – but it’s more effective to go into detail on one or two of the most significant themes, and then just list or briefly talk about other things that the writer picked up from his experiences. In a nutshell, you should sit down and have a think about which of the most important qualities you can and want to portray through your work experience, and sacrifice the less powerful content.

In terms of writing tips here, the writer uses the rule of three (and this technique is used throughout this model statement) when listing: this is a way of making things sound nicer, but also allows the writer to include more high-yield content.

“Every Wednesday for four months I shadowed my local GP.”

The writer starts a new and shorter paragraph here, and this is purely for the sake of clarity. Do avoid writing long paragraphs and aim to split them into organized chunks if possible.

“Watching him give both medical and social advice with such understanding and clinical skill to people from every race, culture and faith made me realise the importance of primary care, good communication and careful allocation of resources.”

Again, the writer doesn’t give much of a description of what he did at the GP surgery, and neither is there much space to do so. Instead, it is more important to reflect on what you learnt and realized through whatever experiences you have undertaken.

“As a concert pianist, I have gained experience in handling stress and performance anxiety. I perform at a local hospice every week and through successful piano competitions, I had the honour of playing at the Jacqueline De Pre Hall in Oxford. I enjoy conveying the emotion of a piece of music in a beautiful and hopefully profound way.”

The penultimate paragraph talks about the writer’s extra-curricular skills and qualities developed through such activities. Never just list a bunch of hobbies you do – instead, always reflect on how you’ve developed your skills, making sure the qualities and skills you talk about are relevant to a future career in medicine.

The writer here uses the word ‘profound’ again – as a writing tip, it is good practice to avoid using the same adjectives or verbs again or close to each other in a piece of prose; ‘powerful’ may be a more suitable word here.

“As a school mentor and piano teacher for younger students, I developed skills in passing on information effectively and in listening to others with patience and respect. My experience in representing the school in badminton and hockey has given my stronger teamwork abilities, which I was able to apply in helping organise the school charity week, in which we raised £16,000. I hold positions of responsibility as a school prefect and founder of two societies, where I teach students musical theory and philosophy. Having also been a St John first aider for three years, I gained experience in making others feel comfortable in times of close contact and in assessing situations quickly and effectively. I also enjoy helping out at community events. Finally, I enjoy acting, and also performing magic; being able to instil wonder and joy in others is priceless.”

It’s important to watch out in this section of the personal statement: many extremely talented students apply for medical school, and it’s easy to run the risk of sounding arrogant if the way you phrase things isn’t carefully considered. In fact, this is a risk for all stages of the application !

One way to avoid sounding arrogant is to talk about how you ‘developed’ your skills, opposed to you already possessing them. For example, there’s a subtle difference between ‘I was given the responsibility to be a school mentor due to my strong communication skills’ and ‘I’ve developed strong communication skills through being a school mentor’.

Although the difference is certainly subtle, it can give you a sense of being humble, especially if you have impressive traits.

“I believe I have the humility, scientific acuity and empathy to become a committed doctor and to face the challenges ahead in my chosen career.”

The ending of this model statement isn’t particularly novel and many personal statements finish with something similar. It is important though to have a closing paragraph that links together your principal themes and affirms your suitability for medicine: in this case, the writer chooses scientific acuity, empathy and humility to be his big three qualities; moreover, the writer also slips in a few other qualities expected in medics, emphasising a commitment and readiness to overcome the challenges that are sure to come in the future.

Although simple, short and nothing original, the content in the closing paragraph was carefully chosen – it does the job and most importantly leaves a positive impression, which is the aim of the game.

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UCL University Personal Statements

These UCAS personal statements have been kindly provided by students applying to University College London. You can click on one of the links below to view the entire statement and find out if the applicant was offered a place.

You can also view our entire collection of personal statements or view personal statements for application at other universities .

Linguistics Personal Statement Example 1 My most memorable Christmas came with a parcel of Harry Potter audio books and this was where my quest to understanding language began. The moment Stephen Fry started to narrate chapter one, I fell in love with words and all they could achieve...

History Personal Statement Example 3 Recently, I found out that my grandma was gambled into slavery for seven years. She escaped her prison and made her way back to Hong Kong, 300 miles south. I was amazed at how courageous she was. This personal discovery led me to read Jung Chang's 'Wild Swans' which made me both proud and ashamed of my heritage...

Mathematics and Economics Personal Statement Example 1 As Pythagoras may have said, (Ambitious)2 + (Bold)2 = (Critical thinker)2 makes a perfect student and is what I strive to be. From the simple Pythagorean to the complex Fermat's Last Theorem, mathematics is a never ending branch of study which I enthusiastically enjoy studying and why I wish to pursue it even further at university...

Mathematics and Physics Personal Statement Example 1 Mathematics is a fundamental tool for understanding our world: it can be used to define the symmetry of flowers or to manage global companies. What is so appealing about mathematics is the opportunity of applying it in the physical world...

Maths and Spanish Personal Statement Example For as long as I have recognised words and numbers, I have seen a connection between the two. As I progressed in the AS Mathematics course I realised how drawn I was to the subject, motivating me to spend 2 weeks at school over the summer holidays learning 2 entire AS Further Maths modules, in order to take the full A-level course in one year...

Electrical and Electronic Engineering Personal Statement Example 1 I have always had a creative ability and a fascination with how things work. The challenge of solving practical problems inherent in the field of engineering appeals directly to these traits. I am particularly interested in electrical and electronic engineering (EEE) because it is such a rapidly evolving discipline...

Economics and Politics Personal Statement Example 1 "I killed the bank": the last words of Andrew Jackson, former president of the US, after he had vetoed to renew the charter and withdraw all federal deposits from banks causing them to bust. Real money was backed with gold shortly after, causing the greatest economic boom in history for the US where no income tax was implemented...

Spanish and Economics Personal Statement Example My aspiration to study Spanish and Economics has not only been influenced by my curricular education but also from experiences I have had throughout life. I am intrigued in the effects caused by the failing Euro zone, and I consider communication among speakers of different languages essential in progressing forward...

Economics Personal Statement Example 5 Choosing an undergraduate degree in economics is a result of my deep seated curiosity to know why economies are they way they are; why oil prices in my country, Pakistan, rapidly fluctuate whereas economies like USA and China continue to strengthen despite recessions...

Anthropology Personal Statement Example 2 My fascination with human behaviour and the motivations behind human actions has existed for most of my adult life, to determine a cause however I would accredit this to the voluntary work I participated in with Crisis Single Persons Homeless charity...

Geography Personal Statement Example 2 In a dynamic world, the study of geography is increasingly important. The diversity of the subject and the interaction between the physical environment and human population is becoming even more evident with climate change and globalisation influencing our everyday lives...

Psychology Personal Statement Example 11 “If she’s smart she will study Medicine.” This is an unwritten rule in my culture - all Nigerian parents want their children to become doctors. What becomes of the aspiring psychologist in the family? I met a junior doctor, at an educational conference, who wanted to specialise in psychiatry...

Architecture Personal Statement Example 3 Growing up in post-soviet Belarus I wasn't surrounded by the architectural wonders - all the buildings were dull and grey, therefore from early childhood I started drawing and making houses of my dreams...

Mathematics and Economics Personal Statement Example 2 Every day we make decisions and interact with others; the laws of economics help us make rational choices and consider the irrationality of others, as well as understand the world better. Maths and statistics are the necessary tools for me to understand the modern economics...

Anthropology and Archaeology Personal Statement Example My interest in culture first started when I began to attend my local Hindu Temple with my friend in primary school. I was highly interested in how her surroundings differed from my own and enjoyed immersing myself in her way of life...

English and History Personal Statement Example 1 I believe history inspires optimism. With the state being cut and our economy weakening we could easily fall to pessimism. I just have to look within history to see that just over 400 years ago Queen Mary I killed 'rebels' for heresy when they protested, whereas Modern freedoms have allowed me to protest openly in several Unite marches...

English Personal Statement Example 23 My love of literature is rooted in the connection it gives us to centuries of ideas, giving us the ability to converse with ghosts, linking us with the greatest and most eloquent minds in history; as Bovee puts it, “books are embalmed minds”...

Pharmacology and Human Sciences Personal Statement Example From the race to find a vaccine for the H1N1 virus to the almost daily reports of breakthroughs in the field of cancer research, science has always fascinated me.On a more personal note, my interest has largely stemmed from school, work experiences, and science in the news...

Biomedical Engineering Personal Statement Example 2 Thanks to my mother's profession, I have had a front row seat in observing the radical changes made in the medical field with the introduction of new devices. I have also seen the beneficial effects these developments have had on the lives of people living in the less affluent countries in the Middle East; these observations coupled with my interest in mechanics have inspired me to pursue a career in biomedical engineering...

Computer Science Personal Statement Example 45 Advances in computer and information technology over the past few decades have brought about revolution in science, medicine, education, business, and entertainment. I wish to be part of the future revolution and that is why I want to study computer science...

Maths & Actuarial Science Personal Statement Example 1 "It has become a very strange and perhaps frightening subject from the ordinary point of view,but anyone who penetrates into it will find a veritable fairyland"( Kasner E and Newman J).This saying is perhaps the most fitted to describe my enthusiasm for Maths...

Psychology Personal Statement Example 48 Since embarking on the A level course 16 months ago I have decided to devote my life to working in psychology. I am struck by the way Psychological research has impacted all areas of life, but also how much there is yet to understand...

Economics Personal Statement Example 23 It would not be foolish to contemplate the possibility of a far greater progress still. John Maynard Keynes From childhood I was bred to learn and the passion to understand has become a trait of my character...

Anthropology Personal Statement Example 5 I realised that I wanted to study Anthropology in 2005 after picking up a book called ''Mapping Human History'' by Steve Olson. I read the book cover to cover a number of times, and knew that I had discovered a subject that I was not only interested in learning but wanted to investigate for myself...

Postgraduate Linguistics Personal Statement Example My interest in linguistics was gradually shaped throughout my life by all the different ways in which I have experienced languages: as a learner, translator, and as a teacher. However, it was the times spent living in Russia and later in the UK that made me fully understand that language can be a means of conveying much more than just our thoughts...

European Social & Political Studies Personal Statement Example In my opinion, the problems societies face today deserve an in-depth analysis which draws on different disciplines of thought for its relevance; furthermore the implementations of strategies to combat problems must take into account more than one academic approach if they are going to be positively effective...

Human Sciences Personal Statement Example Perhaps what makes me different from other University applicants is that I have ambition to understand multidimensional human life. It is not the appeal of a top qualification or the zesty student lifestyle that attracts me to this course; but it is the long-term knowledge and answers to interdisciplinary human problems, and the enigmas that I will commit a lifetime investigating with perhaps no solution, that inspires me to apply...

Psychology Personal Statement Example 51 There is a reason behind everything we do, a purpose to our actions. The cognition behind any decision that we make is one of the many aspects of psychology that I am fascinated by. The following five words, as said by the Prophet Muhammad, I believe explain such a suggestion: "Actions are but by intentions"...

Archaeology and Anthropology Personal Statement Example 2 As an immigrant living in Spain, I am constantly reminded of the importance social and cultural factors have on my daily life, the language I speak, and the difference between the relationships I maintain with people from my own country and those I encounter here on a daily basis...

Mathematics Personal Statement Example 12 Mathematics is at the root of many academic subjects, such as mechanics in Physics, organic Chemistry and even Music and this is why I find it so fascinating. The process of starting from a simple set of formulae and deriving nearly all mathematical truth from these is what makes Mathematics a leading academic subject...

Creative Writing Personal Statement Example 2 To me, fiction is like the magic carpet of Aladdin. It takes me to travel through time and space and explore the slices of human experience. In the wonderful trips, I am guided by the author and accompanied by the characters...

Economics and Management Personal Statement Example 2 My interest in Economics goes beyond an appreciation of statistics and profit margins. In my mind, economics represents the relationship between people and their money – a relationship that dates back to the history of mankind...

Medicine Personal Statement Example 61 While the idea to care for others is appealing to me, the applications of medicine for finding remedies to the complexities of the human body fascinates me even more. Studying medicine opens several career options from general practice to clinical research! Having the interest and aptitude for scientific knowledge and the awareness to promote health safety, it encourages me to choose this highly rewarding and satisfying course...

Chemical Engineering Personal Statement Example 10 Chemical engineering is a most fascinating field of all the branches of science and engineering. To me it truly reflects human endeavour and spirit through means such as the exploration of unknown substances, and making something of worth and value out of mere raw materials...

Maths Personal Statement Example 12 Mathematics dictates our understanding of the universe; the sciences that the world depends on today are founded and dependant on maths. Scientists and mathematicians spend their lives making remarkable discoveries contributing to the development of humanity, the findings we have been making in fields like quantum mechanics would be completely impossible without maths...

Medicine Personal Statement Example 66 White coats, stethoscopes hung around necks and the sense of playing hero were popular amongst childhood dreams. However, unlike others around me, this dream was not lost when I realised reality paved a much tougher road- instead, it grew to become a fierce ambition...

Psychology Personal Statement Example 64 Psychology is ubiquitous in society. Because of the mercurial nature of humans, there is always something different to study and analyse. I find this exciting. Part of what draws me to psychology is how the dynamics of it affect daily life and behaviour...

Economics Personal Statement Example 30 The ever-changing nature of the human science intrigues me. Newton’s laws of motion will never change, from wherever ‘the ball is dropped’. However, different strategies and policies have to be framed and implemented for each economic problem...

Psychology Personal Statement Example 67 I first became interested in psychology whilst discussing the underlying causes of criminal behaviour and non-conformity with my father. The nature-nurture debate gave me a huge desire to increase my knowledge and understanding of the human condition...

Physics Personal Statement Example 15 I have always been intrigued by the world of physics. From everyday experiences to the most extreme boundaries of today's knowledge, I have always voraciously searched for answers to my questions. As I grew up, the elegance of mathematical demonstrations and of physical theorems fascinated me, and I have often dreamt of making contributions to the unification theory and of improving and simplifying the Navier-Stokes equations...

Natural Sciences Personal Statement Example 4 Why and How? I believe these are the two most important question words as they express mankind’s unquenchable thirst for knowledge, and they have lain the foundation of sciences and have helped us find answers and solutions to problems throughout history from the domestication of fire to Darwin’s theory of evolution, to landing on the moon and so on...

Electrical Engineering Personal Statement Example 2 The defining wonder of today’s age is electricity. In just two centuries, we have come from Faraday’s crude but prophetic experiments to devices just a square inch that can calculate in seconds what the most gifted of human minds might take days...

Biological Sciences Personal Statement Example 3 When I was in primary school I would take pens apart to put them back together, so that I could see how every small piece fits together to create a whole working object, and as I furthered my education my focus shifted to the w orld around me...

Linguistics Personal Statement Example 3 Have you ever heard the Tuvan throat singing technique? Beautiful and intriguing at the same time. The question that's bound to accompany a throat singing performance is how the human voice could possibly produce such a sound...

Anthropology Personal Statement Example 7 Coming from a mixed religious background, the comparison between cultural practices has touched me deeply, personally and profoundly. I have been able to observe the influence of culture on people's perspectives and world views...

Civil Engineering Personal Statement Example 17 My decision to study engineering stems from a desire to contribute to the evolution of society through a process that does not just define our environment but our era. My personal inspiration is the Segovia aqueduct, an 800m long, 30 metre high Roman marvel which still stands today...

PPE/Economics Personal Statement Example Humanity today stands at the intersection of the most significant questions facing the world today: if democracy leads to political infighting, should it be sacrificed in the interest of economic well-being? Does religious fundamentalism provide a way for countries in the developing world to assert their identity in the face of Western hegemony? Does the entry of Western consumer goods threaten a country’s economic self-sufficiency? The answers of these questions will determine what the nature of our world is in the twenty-first century...

History Personal Statement Example (Oxbridge) 2 Whether considering the real world applications of Bentham's utilitarianism in Religious Studies, analysing the context of a changing Victorian society in English Literature, or debating the evolving ideology of the Labour Party in Politics, there is one common thread connecting what I enjoy most about my studies: history...

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Climate change likely to aggravate brain conditions

16 May 2024

Climate change, and its effects on weather patterns and adverse weather events, is likely to negatively affect the health of people with brain conditions, argue a UCL-led team of researchers.

Forest shaped like a brain in the middle of cracked dry land

In a Personal View article, published in The Lancet Neurology , the team emphasise the urgent need to understand the impact of climate change on people with neurological conditions – in order to preserve their health and prevent worsening inequalities.

Following a review of 332 papers published across the world between 1968 and 2023, the team, led by Professor Sanjay Sisodiya (UCL Queen Square Institute of Neurology), said they expect the scale of the potential effects of climate change on neurological diseases to be substantial.

They considered 19 different nervous system conditions, chosen on the basis of the Global Burden of Disease 2016 study, including stroke, migraine, Alzheimer’s, meningitis, epilepsy and multiple sclerosis.

The team also analysed the impact of climate change on several serious but common psychiatric disorders, including anxiety, depression and schizophrenia.

Professor Sisodiya, who is also Director of Genomics at the Epilepsy Society and a founding member of Epilepsy Climate Change, said: “There is clear evidence for an impact of the climate on some brain conditions, especially stroke and infections of the nervous system.

“The climatic variation that was shown to have an effect on brain diseases included extremes of temperature (both low and high), and greater temperature variation throughout the course of day – especially when these measures were seasonally unusual.

“Nighttime temperatures may be particularly important, as higher temperatures through the night can disrupt sleep. Poor sleep is known to aggravate a number of brain conditions.”

The researchers found that there was an increase in admissions, disability or mortality as a result of a stroke in higher ambient temperatures or heatwaves.

Meanwhile, the team state that people with dementia are susceptible to harm from extremes of temperature (e.g. heat-related illness or hypothermia) and weather events (e.g. flooding or wildfires), as cognitive impairment can limit their ability to adapt behaviour to environmental changes.

They write: “Reduced awareness of risk is combined with a diminished capacity to seek help or to mitigate potential harm, such as by drinking more in hot weather or by adjusting clothing.

“This susceptibility is compounded by frailty, multimorbidity, and psychotropic medications. Accordingly, greater temperature variation, hotter days, and heatwaves lead to increased dementia-associated hospital admissions and mortality.”

In addition, incidence, hospital admissions, and mortality risk for many mental health disorders are associated with increased ambient temperature, daily fluctuations in temperature, or extreme hot and cold temperatures.

The researchers note that as adverse weather events increase in severity and global temperatures rise, populations are being exposed to worsening environmental factors that may not have been severe enough to affect brain conditions in some of the earlier studies they reviewed as part of the analysis.

As a result, they say it’s important to ensure that research is up to date and considers not only the present state of climate change but also the future.

Professor Sisodiya said: “This work is taking place against a worrying worsening of climatic conditions and it will need to remain agile and dynamic if it is to generate information that is of use to both individuals and organisations.

“Moreover, there are few studies estimating health consequences on brain diseases under future climate scenarios, making forward planning challenging.”

He added: “The whole concept of climate anxiety is an added, potentially weighty, influence: many brain conditions are associated with higher risk of psychiatric disorders, including anxiety, and such multimorbidities can further complicate impacts of climate change and the adaptations necessary to preserve health. But there are actions we can and should take now.”

The new article is published ahead of The Hot Brain 2: climate change and brain health event, which is led by Professor Sisodiya and jointly organised by UCL and The Lancet Neurology.

The aims of the meeting are to raise awareness about the risks of climate change for the brain and neurological healthcare, to nurture global collaborative research, and to promote action against climate change and foster adaptation strategies.

The research was funded by the Epilepsy Society and the National Brain Appeal Innovation Fund.

Article in The Lancet Neurology
Professor Sanjay Sisodiya's academic profile
UCL Queen Square Institute of Neurology
UCL Brain Sciences
The Hot Brain 2: climate change and brain health
Credit: Alones Creative on iStock

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Poppy tombs.

E: p.tombs [at] ucl.ac.uk

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Juventus sack manager Massimiliano Allegri following Coppa Italia outburst, with two games remaining in season

Allegri's contract was due to expire on june 30, 2025 but he was expected to leave at season's end.

Juventus have sacked coach Massimiliano Allegri. The decision was expected, but the timing was definitely surprising as the club won the Coppa Italia on Wednesday after beating Atalanta 1-0 at the Stadio Olimpico of Rome. The news arrived after the 56-year-old won his fifth Coppa Italia, most for any manager in the history of the tournament. However, Juventus decided to part ways with Allegri after some episodes that happened after the Atalanta game, according the multiple reports.

Juventus released the following statement.

"Juventus announces that it has relieved Massimiliano Allegri of his role as coach of the men's first team. The dismissal follows certain behaviors during and after the Italian Cup final which the club deemed incompatible with the values of Juventus and with what those who represent it must behave. A period of collaboration ends, which began in 2014, restarted in 2021 and ended after the last 3 seasons together with the Coppa Italia Final. The club wishes Massimiliano Allegri good luck in his future projects."

Massimiliano Allegri non è più l’allenatore della Juventus F.C. — JuventusFC (@juventusfc) May 17, 2024

Allegri was spotted during the Coppa Italia celebrations having a verbal altercation with Juventus sport director Cristiano Giuntoli, despite denying the allegations during the post-game interview to Mediaset. According to Italian agency LaPresse, Allegri also lashed out at a federal prosecutor and kicked out, irreparably damaging lights on a set. Juventus then inquired about reimbursement for the damages, according to the same agency.

On top of this, Italian newspaper Tuttosport director Guido Vaciago accused Allegri of confronting him as well.

"After the game, Allegri told me: you're a shitty director! Write the truth in your newspaper, not what the club tells you. Look, I know where to come and get you. I know where to wait for you. I'll come and rip off both your ears. I'll come and hit you in the face. Write the truth in your newspaper." Allegri denied the allegations in a statement on Thursday.

Allegri coached Juventus from 2014 to 2019 and again from 2021 to 2024. Former Juventus president Andrea Agnelli, one of the masterminds behind the first Super League project in 2021 , was the one that in that summer called Allegri back to the club, two years after his departure. Allegri became a more crucial figure for the club after signing a long term deal until 2025, with more power inside the club especially after former director Fabio Paratici left the club to sign with Tottenham. Allegri obtained what he wanted and ended up fourth in the league in his first season in charge, but things changed dramatically in November 2022 when the whole club's board resigned after Juventus went under scrutiny by prosecutors for false accounting and market manipulation.

With multiple off-the pitch scandals, Juventus qualified for European competition again in his second season at the club despite a 10-point deduction on the table, but the club agreed with UEFA to not participate in their competition for one season. In his third and last season at the club Juventus ended up again to qualify for the Champions League and won the Coppa Italia for the 15th time in their history.

Thiago Motta will most likely be the replacement starting from next season after the manager qualified with Bologna for the Champions League's group stages. Bologna will host Juventus for the second last matchday of the Serie A 2023-24 season on Monday,

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http://orcid.org/0000-0002-7262-6227 Agnieszka Michael 1 ,
William Wilson 2 ,
Sunny Sunshine 1 ,
Nicola Annels 1 ,
Richard Harrop 3 ,
Daniel Blount 4 ,
Hardev Pandha 1 ,
http://orcid.org/0000-0003-1544-8396 Rosemary Lord 5 ,
Yen Ngai 2 ,
Shibani Nicum 6 ,
Laura Stylianou 2 ,
Stephen Gwyther 7 ,
Iain A McNeish 8 ,
Allan Hackshaw 9 and
http://orcid.org/0000-0003-3799-3539 Jonathan Ledermann 9
1 Department of Clinical and Experimental Medicine , University of Surrey , Guildford , UK
2 Cancer Research UK and UCL Cancer Trials Centre , University College London , London , UK
3 Oxular , Oxford , Oxfordshire , UK
4 Barinthus Biotherapeutics (UK) Ltd , Oxford , Oxfordshire , UK
5 Department of Medical Oncology , Clatterbridge Cancer Centre NHS Foundation Trust , Bebington , UK
6 University College London , London , UK
7 Surrey and Sussex NHS Healthcare Trust , Redhill , UK
8 Department of Surgery and Cancer , Imperial College London , London , UK
9 UCL Cancer Institute , University College London , UK
Correspondence to Professor Agnieszka Michael, Department of Clinical and Experimental Medicine, University of Surrey, Guildford W1T 4TJ, UK; A.Michael{at}surrey.ac.uk

Background Immunotherapy directed at 5T4 tumor antigen may delay the need for further chemotherapy. An attenuated modified vaccinia Ankara virus containing the gene encoding for 5T4 (MVA-5T4) was studied in asymptomatic relapsed ovarian cancer.

Objective To assess the effectiveness and safety of MVA-5T4 as treatment for asymptomatic relapsed ovarian cancer.

Methods TRIOC was a phase II randomized (1:1), placebo-controlled, double-blind multicenter study. The primary aim was to assess the effectiveness and safety of MVA-5T4 as a treatment for asymptomatic patients with relapsed ovarian cancer. Eligible patients had International Federation of Gynecology and Obstetrics (FIGO) stage IC1–III or IVA epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, Eastern Cooperative Oncology Group (ECOG) 0–1, with relapse defined by a rise in CA-125 to twice the upper limit of normal or low-volume disease on CT scan. The primary endpoint was disease progression (including deaths from ovarian cancer) at 25 weeks. Following a brief suspension, the trial restarted as a single-arm study. The revised single-arm design required 45 evaluable patients treated with MVA-5T4 to detect a 25-week progression rate of 50%, assuming an expected 70% rate without MVA-5T4; 85% power with one-sided 5% significance.

Results A total of 94 eligible patients were recruited, median age was 65 years (range 42–82), median follow-up 34 months (range 2–46). Overall, 59 patients received MVA-5T4 and 35 patients received placebo. The median number of MVA-5T4 injections received was 7 (range 0–9), compared with a median of 6 (range 1–12) for patients receiving placebo. Median progression-free survival was the same in both arms (3.0 months). The 25-week progression rate was similar in both arms: 80.0% for patients treated with MVA-5T4 and 85.7% for those receiving placebo (risk difference −5.7%, 95% CI −21.4% to 10.0%). Median time to clinical intervention was improved with MVA-5T4: 7.6 months (range 6.7–9.5) vs 5.6 (range 4.9–7.6),

Conclusion MVA-5T4 vaccination in patients with asymptomatic relapse was well-tolerated but did not improve the progression rate at 25 weeks. The majority of patients who received MVA-5T4 had clinical intervention later than those assigned to placebo.

Trial registration number NCT01556841 .

Carcinoma, Ovarian Epithelial

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

https://doi.org/10.1136/ijgc-2023-005200

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WHAT IS ALREADY KNOWN ON THIS TOPIC

Immunotherapy in ovarian cancer has a limited role despite the evidence of immune activation. Many patients have a relapse, with an asymptomatic slowly progressive disease. Those whose relapse occurs after a long disease-free interval with a low bulk of cancer or those who have CA-125-only relapse are ideally suited for evaluation of immune-based strategies. 5T4 is an oncofetal antigen that is expressed on the cell surface and has been identified as a target for immunotherapy. This study was the first study targeting 5T4 in patients with low-volume, asymptomatic relapsed ovarian cancer.

WHAT THIS STUDY ADDS

This is a clinical trial of MVA-5T4 vaccine that consists of a highly attenuated vaccinia virus containing the gene encoding for the human tumor-associated antigen 5T4. The trial was designed for patients with relapsed asymptomatic ovarian cancer with CA-125 relapse and/or low volume on imaging. Although it shows limited activity of the vaccine, the majority of patients in the MVA-5T4 arm received clinical intervention later than those assigned to placebo.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

The results of the study will encourage trials of a combination immunotherapy as vaccines alone are unlikely to have an effect on progression-free and overall survival.

INTRODUCTION

Ovarian cancer is the second most common gynecological malignancy in the Western world. There is evidence that ovarian cancer is under immune surveillance. 1 A study reported by Zhang et al in 2003 showed that 5-year overall survival correlates with the presence or absence of tumor-infiltrating lymphocytes in favor of patients who show an immune response (38% vs 4.5%, respectively, p<0.001). 1 The Cancer Genome Atlas Network reported the presence of an immunoreactive molecular subtype of ovarian tumors, which displayed an enrichment of genes and signaling pathways associated with immune cells and longer overall survival. 2

Despite the signs of immune activation, immunotherapy in ovarian cancer has a limited role due to many immunosuppressive mechanisms. With cancer progression, the tumor microenvironment becomes increasingly immunosuppressive due to the development of immune tolerance, propagation of immunosuppressive regulatory T cells, secretion of immunosuppressive cytokines, and exhaustion of pro-inflammatory T cells. 3 Welters et al demonstrated that the success of vaccination in vulvar cancer correlates with the frequency of specific regulatory cells residing in the tumor, and that these suppressive cells were more prevalent in larger lesions than smaller tumors, resulting in a worse response to vaccination. 4 Patients with ovarian cancer, who relapse after a long disease-free interval with a low bulk of cancer, who are not suitable for secondary cytoreductive surgery, or those who have CA-125-only relapse, may be ideal candidates for evaluation of immune-based strategies.

5T4 is an oncofetal antigen that is expressed on the cell surface and has been identified as a target for immunotherapy. 5T4 is expressed on human trophoblast cells and most human tumors, including ovarian cancer. 2 5 5T4 is absent in most normal tissues, but it is expressed in ovarian cancer, where its expression correlates with advanced stage of disease (International Federation of Gynecology and Obstetrics (FIGO) stages III and IV) (p=0.033). 6 To date, MVA-5T4, a vaccine that consists of an attenuated vaccinia virus (MVA) containing the gene encoding for the human tumor antigen (5T4) under transcriptional control of a modified VV promoter, mH5, has been tested in a total of 580 patients in 11 phase I/II and II clinical trials and one phase III clinical trial in subjects with colorectal, renal, and prostate cancer. Across these trials the safety profile was consistent and there was evidence of strong immunological response to MVA-5T4. 7–15

Here we conducted a clinical trial of MVA-5T4 (TroVax), in patients with asymptomatic relapsed ovarian cancer with CA-125-only relapse and/or low-volume disease on imaging to assess the clinical efficacy and immunological responses to MVA-5T4. The vaccine was designed to induce T-cell specific response as well as antibody response to 5T4 antigen and MVA.

Trial Design

TRIOC was originally designed as a phase II randomized (1:1), placebo-controlled, double-blind multicenter study. The primary aims were to assess the effectiveness and safety of MVA-5T4 as a treatment for asymptomatic patients with relapsed ovarian cancer. The study was sponsored by University College London. Ethical (Gene Therapy Advisory Committee 182) and Regulatory Clinical Trials Agreement (2011-001836-44) approvals were obtained, and all participants gave written informed consent.

Patients were randomized (1:1) to receive MVA-5T4 at a dose of 1×10 9 tissue culture infection dose—TCID 50 /mL in 1 mL or matching placebo by intramuscular injection. Injections were scheduled for weeks 1, 2, 4, 7, 10, 13, 19, and 25. The schedule was based on previously published clinical trials of 5T4-based vaccination. 10 12 13 No dose modifications were permitted. Treatment was discontinued in the event of confirmed progression or a grade ≥3 toxicity thought to be related to treatment.

Patients were followed up for a maximum of 2 years. A CT or MRI scan of the abdomen and pelvis and CT scan of the chest was performed at weeks 13 and 25 and then at 2 months after treatment completion, and thereafter 3-monthly until 1 year after the end of treatment. All scans were assessed using RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 and immune-related response criteria. 16 Progressive disease by RECIST 1.1 was confirmed by a repeat scan 8 weeks after to assess response by immune-related response criteria.

Quality of life was assessed by the EORTC (European Organization for Research and Treatment of Cancer) quality-of-life questionnaires C-30 and OV-28 at baseline, at each vaccination visit, at the first post-treatment visit, and at 5- and 11-month visits.

Change of Trial Design

Recruitment started in December 2013. However, the trial was suspended in August 2016 owing to an issue over the quality control of two MVA-5T4 vaccine vials containing tiny particles. The patient who received this vaccine from these vials was unblinded, and no further patients received this batch of vaccine. In total 11 patients who had already started MVA-5T4 did not receive a further dose while the manufacturing process was investigated. A total of 18 patients (including seven patients receiving placebo) were withdrawn during the trial suspension, but outcome data (including safety data) were still collected from them. A full investigation confirmed that the product was safe. However, due to limited allocated drug supply, and a fixed expiration date, the trial was redesigned as a single-arm open-label study, to maximize the number of patients given MVA-5T4. Recruitment restarted in May 2017 after patients reconsented using the revised patient information sheet. All patients randomized before the suspension remained blinded, except for the single patient whose treatment triggered the investigation.

Patients were enrolled at hospital sites and randomized using a third-party interactive web response system with a minimization approach stratified by radiological disease, relapse status (first vs second), histological subtype, and hospital site. Investigators and patients were blinded to the assignment interventions.

Participants

Eligible patients had stage IC1–III or IVA epithelial ovarian, fallopian tube, or primary peritoneal carcinoma (high-grade serous, endometroid, clear cell, and mucinous histology). They were ECOG 0–1, had asymptomatic platinum-sensitive relapse, as defined by asymptomatic CA-125 rise to ≥2 x upper limit of normal, or low-volume disease on CT scan (defined as radiologically visible disease, excluding intra-hepatic, parenchymal liver, or splenic metastases, ascites, or pleural effusion thought to require drainage within the next 2 months). All patients had cytoreductive surgery as part of their first-line treatment and ≥6-month period between completion of last platinum-based chemotherapy and relapse. Maintenance treatment was permitted but discontinued on entry to the trial.

Primary Endpoints

The primary endpoint was disease progression (including deaths from ovarian cancer) rate at 25 weeks. The date of progression was taken as the earliest occurrence of the following: (i) progression by RECIST 1.1 with confirmatory immune-related response criteria 8 weeks later, (ii) progression by immune-related response criteria with confirmatory immune-related response criteria 8 weeks later, or (iii) clinical intervention required for symptoms of progression.

Secondary endpoints were immune-related response criteria response at 25 weeks, progression-free survival, time to clinical intervention, incidence of clinical intervention at 25 weeks, CA-125 doubling time, overall survival, and quality of life. Immunological endpoints included antibody and cellular responses against both 5T4 and the MVA viral vector.

Statistical Methods

The initial trial was designed as a two-arm study, to directly compare endpoints between the MVA-5T4 and placebo groups. At 25 weeks, 70% were expected to progress or die from ovarian cancer (RECIST-defined progression) in the placebo group. 17 We aimed to detect a progression rate of 50% in the MVA-5T4 group. Based on a direct comparison of proportions (using 70% vs 50%), 80% power, and one-sided test of statistical significance of 15%, we required 42 patients per group. To allow for non-evaluable patients and loss to follow-up, 50 women needed to be recruited per group (100 in total)

Following the trial suspension, the primary design was changed to a single-arm trial. For the revised single-arm design, we required 45 evaluable patients treated with MVA-5T4 to detect a progression rate of 50%, assuming an expected 70% rate without MVA-5T4 (A’Hern design: 85% power with one-sided 5% significance). 18 As well as analyzing all patients treated, additional analyses were performed on the subset of patients whose treatment was not affected by the trial suspension, and on the subset treated as per the final protocol. Analyses comparing the outcomes of randomized patients with those recruited to the single-arm study were also performed.

Progression-free survival, overall survival, and time to clinical intervention were assessed using Kaplan-Meier methods, measured from registration until protocol-defined progression, clinical intervention (time to clinical intervention), or death from any cause. Patients who did not experience an event of interest were censored at the date last seen. Health-related quality of life was analyzed used repeated measures regression, with adjustment for baseline scores. To account for multiple scales being tested, only p values <0.01 were considered statistically significant in quality-of-life analyses. Analyses comparing the outcomes of randomized patients with those recruited to the single-arm study were performed.

Immunological endpoints included antibody and cellular responses against both 5T4 and the MVA viral vector. The interferon-γ enzyme-linked immunosorbent spot assay was used to monitor T-cell responses, as previously described. 9 11 Flow cytometry was performed using a FACSCalibur flow cytometer. T-cell function was tested by mixed lymphocyte proliferation assay, as previously described. 1 9 15 MVA-specific and 5T4-specific antibody titers were determined by enzyme-linked immunosorbent assay, as described previously. 15

Further exploratory analyses investigated potential pre-treatment predictors of treatment benefit: hemoglobin, hematocrit, mean corpuscular hemoglobin concentration, baseline 5T4 antibody, serum C-reactive protein, platelets, neutrophils, lymphocytes, 5T4 immune response surrogate, and neutrophil to lymphocytes ratio, as well as Glasgow Prognostic Index. 19

To assess 5T4 expression in archival tissue, we followed a previously published protocol using deparaffinization, horse serum, and an avidin–biotin block before incubation with an anti-5T4 antibody produced in rabbit (HPA010554; Sigma-Aldrich). Detection of the primary antibody was performed using Vectastain Elite ABC-HRP Kit, Peroxidase (Vector Laboratories) with a diaminobenzidine reaction and hematoxylin counterstaining. For 5T4 immunohistochemistry expression, human placenta, and kidney formalin-fixed paraffin-embedded tissue with and without primary antibody were used as positive and negative controls.

For the antibody response and potential predictors of treatment benefit, the association between pre-treatment variables and maximum absolute responses were reported as Spearman’s correlation coefficients (with corresponding p values). Associations between pre-treatment variables and responder categories were reported as odds ratios (with corresponding 95% confidence intervals) from logistic regression models.

A total of 94 patients were recruited from 12 centers in the UK between December 2013 and October 2017, 59 received MVA-5T4 and 35 placebo. Overall, 69 patients were randomized prior to the change in the design of the study and an additional 25 patients were enrolled in the single-arm study. Median age was 65 (range 42–82), and median time since completion of prior chemotherapy was 18 months (range 7–86). The characteristics of the patients given MVA-5T4 as part of the randomized phase were similar to those in the single-arm study ( Table 1 ). The median follow-up was 34 months (range 2–46).

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Baseline characteristics of eligible patients (n=94)

The median number of MVA-5T4 injections received was 7 (range 0–9), compared with a median of 6 (range 1–12) for patients receiving placebo. The most common reason for stopping treatment before the eighth injection was disease progression (40.7% MVA-5T4; 54.3% placebo), followed by trial suspension (13.6%; 14.3%) and unacceptable toxicity (8.5%; 2.9%). Toxicity that resulted in discontinuation of treatment was due to adverse and serious adverse events such as fatigue, vomiting, arthralgia, myalgia, dizziness, and headache ( Online supplemental table 1 ).

Supplemental material

The 25-week progression rate (primary outcome) was similar in both arms: 80.0% for patients treated with MVA-5T4 and 85.7% for those receiving placebo (risk difference −5.7%, 95% CI −21.4% to 10.0%). Excluding those whose MVA-5T4 treatment was affected by the trial suspension gave a risk difference of −0.9% (−16.5% to 14.6%), while for the pre-specified per protocol analysis (patients who had five or more treatment injections unaffected by trial suspension) it was −12.1% (−30.5% to 6.3%). Median progression-free survival was 3.0 months in both treatment arms.

Clinical intervention was defined by symptoms that required systemic treatment: ascites, pleural effusion, malignant bowel obstruction, or other symptoms related to progressive disease demonstrated on imaging ( Table 2 ). There was a lower proportion of patients requiring clinical intervention by week 25 in the MVA-5T4 arm (29% vs 51% placebo, p=0.03). However this did not translate to a significant improvement in time to clinical intervention (hazard ratio-HR=0.74, 95% CI 0.47 to 1.15, p=0.17); Figure 1 . A total of 44 deaths were reported during follow-up, all attributed to disease progression. The median overall survival was 30.6 months in the MVA-5T4 arm vs 39.7 months with placebo (HR=1.58, 95% CI 0.84 to 2.95, p=0.15); Figure 2 .

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Time to clinical intervention by treatment arm for (A) all patients and (B) per protocol population (≥5 injections and unaffected by trial suspension). ITT, intention to treat.

Overall survival for all patients by treatment arm. ITT, intention to treat; OS, overall survival.

Clinical intervention at 25 weeks by treatment arm (n=90)

The safety population included all patients who received at least one injection. Treatment with MVA-5T4 was well tolerated ( Online supplemental table 2 ). The most frequent grade 3/4 toxicities were gastrointestinal disorders (5.2% in MVA-5T4 vs 11.4% in placebo), including abdominal pain, bloating, constipation, diarrhea, dyspepsia, flatulence, and nausea; as well as nervous system disorders (8.6% vs 2.9%), such as lethargy, headache, dizziness, peripheral sensory neuropathy, dysgeusia, and amnesia. The incidence of any grade 3/4 toxicity in the MVA-5T4 arm was 27.6% compared with 22.9% in the placebo arm. Quality of life was generally similar between the two treatment arms—with no significant differences between treatment arms for the quality-of-life questionnaire C-30 functional scales or symptom scales and no significant differences in the quality-of-life questionnaire OV-28 symptom scales over the duration of the study ( Online supplemental table 3 ).

A total of 94 patients were assessed for immune response. Overall, 72 archival tumor blocks were available for analysis, of which 54 were evaluable (those with ≤10% tumor content were excluded). Of the 54 tumors, 11 (20%) did not show any 5T4 expression and of the blocks that showed 5T4 staining, 21 (39%) showed weak expression. Patients were more likely to have a positive antibody response if they received the active treatment compared with patients who received placebo; 5T4 (53/57 (93%) MVA-5T4 vs 12/34 (35%) placebo, p<0.001) and MVA (54/57 (95%) MVA-5T4 vs 1/34 (3%) placebo, p<0.001).

There was no evidence that MVA-5T4-treated patients were more likely to have a positive 5T4 cellular response than those receiving placebo (6/57 (11%) MVA-5T4 vs 2/34 (6%) placebo, p=0.5). There was also no evidence that antibody response to either 5T4 or MVA was associated with a significant benefit in terms of progression-free survival or time to clinical intervention. There was, however, evidence to suggest that patients who achieved higher maximum MVA cellular responses, had significantly better time to clinical intervention (HR for 100 unit increase in maximum cellular response 0.92, 95% CI 0.88 to 0.97, p<0.01) ( Figure 3 ). 5T4 cellular response was not associated with clinical benefit. Figure 3 shows the time to clinical intervention in patients who developed a high MVA cellular response as compared with patients who had a low response.

Time to clinical intervention split by median maximum MVA cellular frequency (low <376.7, high ≥376.7).

Of the pre-treatment factors analyzed, only Glasgow Prognostic Index and 5T4 immune response surrogate had a predictive value of clinical benefit. 20 Patients with a high Glasgow Prognostic Index (defined as ≥1) had worse progression-free survival in the MVA-5T4 arm (HR=2.66 (95% CI 1.18 to 6.01), p=0.02), but not in the placebo arm (HR=0.71 (95% CI 0.27 to 1.91) p=0.5) (interaction p=0.04). A similar pattern was seen for time to clinical intervention: for patients in the MVA-5T4 arm the HR was 2.58 (95% CI 1.13 to 5.89, p=0.02), compared with a HR of 0.6 (95% CI −0.23 to 1.59, p=0.3) in the placebo arm (interaction p=0.03). The 5T4 immune response surrogate predicted patients who derive benefit from MVA-5T4 in terms of time to symptomatic progression (HR=0.99 (95% CI 0.98 to 1.00) p=0.05), but not progression-free survival.

Summary of Main Results

Disease progression at 25 weeks did not differ between the two arms and there was no evidence of an overall survival benefit with the vaccine. However, although, not statistically significant, there was a trend towards improvement in time to clinical intervention with MVA-5T4 treatment (HR=−0.74), with fewer patients requiring clinical intervention by week 25 than those given placebo (29% vs 51%). Vaccination with MVA-5T4 resulted in measurable immunological responses with increased levels of antibodies against 5T4 and MVA. Interestingly the cellular responses were mainly directed at MVA and there was no evidence that MVA-5T4 patients were more likely to mount a positive 5T4 cellular response (p=0.5).

Results in the Context of Published Literature

The results of immunotherapy trials in ovarian cancer have so far been disappointing. Some studies looking at the immune environment show promising results with evidence of immune activation, but with low rates of clinical response. 21 22 Based on pre-clinical and clinical results demonstrating a good immunological response to 5T4, 7–9 12 13 expressed in many solid tumors, we conducted a trial in ovarian cancer using a genetically modified vaccinia Ankara virus, encoding the human tumor-associated antigen, 5T4. Only patients who had no symptoms relating to their relapsing cancer were eligible for the study. This study captured patients who did not immediately require chemotherapy or surgery and could potentially benefit from an immunological treatment approach.

Our results can potentially be explained by the low immunogenicity of 5T4 and high immunogenicity of the MVA vector in patients with ovarian cancer. Interestingly, several trials that looked at MVA-5T4 vaccination in other tumor types reported a better cellular response to MVA-5T4 vaccination. 7 9–11 13 23 A trial of vaccination of patients with colorectal cancer showed that most patients developed 5T4-specific cellular responses, and there was a positive association between the development of a 5T4 (but not MVA) antibody response and patient survival or time to disease progression. 11 Similarly, in a trial of patients with renal cancer, many patients developed a high 5T4 antibody response, which was associated with longer survival within the MVA-5T4-treated group. 13 The nature of immune response development in ovarian cancer is perhaps more complex and evaluation of tumor tissue prior to immunotherapy trial enrollment may be the key to a better clinical response. The inclusion of only women with asymptomatic recurrence did not permit taking biopsies at the time of the trial enrollment.

Several clinical trials have combined immunotherapy agents with other agents—for example, bevacizumab, atezolizumab, and chemotherapy or poly-(ADP-ribose)-polymerase (PARP) inhibitors, and the response rates are encouraging, with some women achieving complete remission and high rates of clinical benefit (up to 95% in platinum-sensitive relapse) (reviewed in the article by Muaibati et al). 24 However, data are awaited from the large, randomized phase III trials that investigate whether the addition of PARP inhibitors and/or bevacizumab to immune checkpoint inhibitor maintenance therapy can extend progression-free survival in first-line, advanced ovarian cancer. We have found that some previously described clinical indicators of immune response can offer valuable predictive information. Patients with a high Glasgow Prognostic Index had a worse progression-free survival in the MVA-5T4 arm and those patients developed symptoms sooner than patients who had a low Glasgow Prognostic Index. This correlation was previously published, and it should be used in future clinical trials and in clinical practice. 19

Strengths and weaknesses

This study explored an immune treatment approach in a group of women who are not normally offered clinical trials of novel agents. The women in this study did not have cancer-related symptoms, and some had no measurable disease, but CA-125 progression only. Patients in this clinical scenario might be better suited for an immunotherapy-based approach, and this is a strength of the study.

The limitations of the study include a change of the design to a single-arm study, as well as lack of fresh tumor tissue, which is a frequent hurdle in clinical trials, and it often limits our understanding of the tumor environment and how it evolves with cancer progression. Also, some patients had to discontinue treatment during the trial suspension, but this was unavoidable given the potential safety concern.

Implications for Practice and Future Research

The change in clinical practice over the last few years and the use of PARP inhibitors in the maintenance setting has altered the clinical picture and future immunotherapy trials in ovarian cancer. We are unlikely to have many women with asymptomatic relapse who are not receiving treatment, as most of those women will be on maintenance therapy. Combining immunotherapy agents might offer more effective treatment options in recurrent ovarian cancer. The molecular and immune heterogeneity of ovarian cancer indicates that the combination of immunotherapy treatment together with targeted agents such as PARP inhibitors, as well as drugs that target the immune suppressors, like transforming growth factor β or interleukin-10 might be the way forward. The idea of immune stimulation in low-volume relapsed disease might be explored further with new approaches and combinations of targeted therapy and immunotherapy.

Recent studies with vaccines in the adjuvant setting, targeting tumor antigens such as NY-ESO-1 have suggested a survival benefit, 21 but these may well be overtaken by checkpoint inhibitors in combination with targeted agents such as PARP inhibitors. Studies such as KEYNOTE-162 (niraparib/pembrolizumab) and MEDIOLA (olaparib/durvalumab with or without bevacizumab) combining PARP inhibitors and checkpoint inhibitors show promising results, with the latter demonstrating overall response rate of 74.2% in the non-BRCA patients and over 90% in patients with BRCA mutation. 25 26 Targeting early relapsed disease in patients receiving treatment with PARP inhibitors by adding immunomodulating agents may be an attractive option to explore. Access to fresh tissue to evaluate the immune microenvironment and better ways to assess immune activation using peripheral blood will help us to understand the dynamic changes that occur during immune modulation.

In summary, our trial did not demonstrate an improvement in cancer progression at 25 weeks but MVA-5T4 was a safe and well-tolerated treatment that showed some evidence of immune activation that might influence the development of clinical symptoms. Therefore, there may still be a role for using anti-cancer vaccines in advanced ovarian cancer.

Ethics statements

Patient consent for publication.

Not applicable.

Ethics approval

This study involves human participants and was approved by Gene Therapy Advisory Committee -GTAC182. Participants gave informed consent to participate in the study before taking part.

Acknowledgments

The authors are grateful to all the patients who agreed to participate in this study and to the participating sites, principal investigators and their coordinating and clinical research teams. We also thank members of the Trial Steering Committee and Independent Data Monitoring Committee for their guidance throughout the course of the trial. The Cancer Research UK and UCL Cancer Trials Centre managed and coordinated the trial and acknowledge the support of the National Institute for Health Research, through the National Cancer Research Institute (particularly the Ovarian subgroup within the Gynaecological Cancer Clinical Studies Group), and the charity OVACOME, which kindly reviewed the patient information. JL and AH acknowledge support from the University College London and University College London Hospitals Biomedical Research Centre. AM acknowledges the University of Surrey for support in the analysis of the immunological endpoints. IAM acknowledges support from the Imperial NIHR Biomedical Research Centre, the Imperial Experimental Cancer Medicine Centre, and an NIHR Senior Investigator Award. The Cancer Research UK and UCL Cancer Trials Centre is grateful for the support of the following who assisted in the conduct of the research – Laura Farrelly, Kate Frost, Richard Jenner, Gita Parmar, Oliver Pressie, and Christina Wadsworth.

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Supplementary materials

Supplementary data.

This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

Data supplement 1
Data supplement 2
Data supplement 3

X @AgnMichael

Contributors AM: chief investigator for the study, overall study guarantor, study design and grant submission, oversight of recruitment, data analysis, manuscript writing. WW and AH: statistical study design, data analysis, manuscript writing, data oversight. SS, NA, and HP: immunological and translational analysis and writing support. RH, DB: Oxford Biomedica study development support, immunological and translational analysis of samples. RL, SN, SG, and IAM: patient recruitment, study design support, data analysis support, manuscript writing support. LS and YN: project manager, patients’ recruitment oversight, study conduct support, data analysis support, manuscript writing support. JL: overall study design and conduct oversight on behalf of the study sponsor.

Funding The TRIOC trial was funded by Oxford Biomedica who supplied the MVA-5T4 (TroVax) and placebo as well as providing funding for trial-associated costs. Cancer Research UK provided endorsement for the trial (grant reference C34426/A15045).

Competing interests None declared.

Provenance and peer review Not commissioned; externally peer reviewed.

Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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