Claudia Kouwenberg died from an aggressive form of cancer known as cancer of unknown primary (CUP). As CUP Awareness Week approaches, her husband Peter is telling their story in a bid to educate the public – as well as medical professionals – about why access to molecular diagnostics would have given them the answers they deserved
In March 2020, the world was coming to terms with the threat posed by the coronavirus pandemic, and in the Netherlands, Claudia Kouwenberg was dealing with a mild but troublesome case of eczema. Within weeks the world would be in lockdown and Claudia would be in a wheelchair, no longer able to walk unassisted. Within 6 months, she died.
The cause of Claudia’s death was cancer of unknown primary (CUP), an advanced/metastatic form of cancer which affects at least two areas of the body, but this was not realized for many months. Although more than 1,500 people in the Netherlands will be diagnosed with this form of cancer in a given year, a lack of awareness and access to cutting-edge molecular diagnostics means that diagnosis is often delayed or even missed. World CUP Awareness Week takes place every September in a bid to increase awareness of the cancer as well as imbue the public and medical community with a sense of urgency when it comes to its diagnosis.
Peter Kouwenberg is 55 and has decided to tell the story of Claudia’s final months. The eczema, in hindsight, was an initial sign, but the following month Claudia began to have trouble walking. An incorrect diagnosis of bursitis in the hip was offered, and physio and antibiotics were given, to no avail. Within a matter of weeks, her mobility was severely impaired and she began using a wheelchair. Peter’s frustration even at this early stage is palpable.
“We had already urged the GP several times for a referral to the hospital for further examinations,” Peter explains. “We also insisted on a blood test… Again and again, there was no response to our requests. We were worried because she wasn’t recovering and we wondered what was going on.”
Their GP’s uncertainty compounded the delays caused by the ongoing pandemic. When Claudia was no longer able to sleep because of her pain, she finally received a neurology referral, but during the appointment, her hip suddenly broke when she was trying to get up from the examination table.
“An upper leg does not just break, we soon took cancer into account,” Peter admits. “After a few nerve-wracking days, we were told that it was indeed cancer, but it was not clear what the primary location was and the tissue taken was no longer usable for research because it had already died.”
A host of examinations followed, including CT scans, PET scans, MRI scans, mammography, ultrasound, lung X-rays and blood tests. Once again, they were told it was cancer but the primary source was not known. As the investigations continued, Peter said he was almost overcome with feelings of despair. “You are powerless. You stand there but can’t do anything. Really powerless.”
This is unfortunately a typical journey for patients with CUP. While the eventual outcome may not have been different, Claudia’s last months were spent in grave pain as her condition deteriorated rapidly. She had swallowing problems, a rapidly deteriorating appetite which made supplementation with a protein drink and nutridrink necessary, rapidly deteriorated vision, presumably due to medication. Bladder infections were also common. By August 2020, they had been told that Claudia was too weak for an experimental clinical trial, and standard treatment was not possible as it was unclear what to focus on as the primary tumor was still unknown. She passed away weeks later.
For CUP patients like Claudia, battling to receive a diagnosis wastes precious time. The advent of whole genome sequencing (WGS) of tumors is promising and could help transform their care, as instead of treating cancer based on where it originated, doctors would instead devise a treatment regime based on the genetic characteristics of the tumor. This personalized approach is being rolled out for many cancer types, but access is patchy – or even non-existent. It is also critical that it is carried out early in the diagnostic process so as to improve outcomes.
Peter admits that while this may not have made a difference in his wife’s case, the answers it would have provided would have been invaluable.
“It takes six weeks until the results are available, so we probably would have had a diagnosis only after death. This could have eased the frustration of not knowing what it is, even though there was probably no treatment for Claudia as she was already too weak.”
Since then, the Dutch Parliament unanimously added extensive DNA-testing to the basic package of care that must be covered by health insurers and WGS has been reimbursed for CUP patients from April 2021. Yet it is not always a given that patients will receive prompt access to this testing, and in many countries around the world it is not offered at all.
SJK Foundation (Ireland) and Missie Tumor Onbekend (the Netherlands), are two national patient organizations dedicated to improving quality of care & life and providing information and support for patients. World CUP Awareness Week runs from 19-23 September 2022. Peter is a volunteer at Missie Tumor Onbekend.
This story is also part of the From testing to Targeted Treatments Precision Medicine Patient Stories Library, a repository of stories that aim to visualize each patient’s pathway according to a common framework, and highlight learnings and best practices. Discover the visual version of this story here.
The role of the oncology nurse in supporting patients and genomic education is a pivotal one, Oncology Clinical Specialist Erin Dickman, MS, RN, OCN tells Danielle Barron
Oncology nurses have a very specific, very important role when it comes to supporting patients through what can be a complex treatment journey. Can you elaborate on this?
Oncology nurses have an essential role on the healthcare team to support their patient through their cancer journey which includes any genomic-informed care. The application of genomics to oncology nursing includes adopting consistent and accurate genomic terminology, educating patients and family members about the biomarker testing process and participating in the process, understanding possible outcomes of biomarker testing and implications for cancer care, translating complex findings through patient and family education, identifying when a patient should be referred to a genetics professional, providing emotional support to patients and family through the testing process, and advocate for a precision medicine approach
Genomics and precision oncology is a relatively new field that is of increasing importance in the oncology community. How has it changed practice?
The utilization of biomarker testing to inform diagnosis, prognosis, treatment decisions, symptom management, and monitoring response to therapy has shifted many parts of cancer care and in response, the workflow and scope of the oncology nurse. For example, in some cases, biomarker testing results are part of the workup for a person newly diagnosed with cancer. It can be emotional waiting for testing results before starting treatment and the nurse is there to guide, educate, and support the patient through that time. Another example is genomic testing technologies, which has led to novel therapy advancements and additional treatment options for patients who are now living longer. Nurses are now supporting people with longer survival times and different symptom profiles.
What are the challenges in educating patients on these developments? What are the opportunities?
Genomics is complex and the rapid advancements and application of this science into practice is evolving by the day. This makes it challenging for nurses to keep up with the correct terminology and integrate the most up to date information into their practice. Many nurses lack confidence and knowledge about genomics concepts because they did not get the content in their educational preparation. ONS is working to fill this practice gap through an extensive Genomics and Precision Oncology Learning Library that includes genomics taxonomy and on-demand education that spans from 5 mins – one hour depending on the time that you have. We have also developed clinical practice resources to be used at the point-of-care to inform conversations with patients or show them a video to prepare for their genetic counseling appointment. A clinical decision support tool, the ONS Biomarker Database, was just launched to bring precision medicine to the point-of-care for oncology nurses. It will help nurses better understand biomarker testing reports and much more.
Why did the ONS develop the Learning Library? Who is it aimed at and what kind of information does it include?
The Library of resources was created to support the oncology nurse that cares for patients that would benefit from genomic-informed care. It provides ONS developed patient education, clinical practice resources to have at your fingertips for reference in daily practice, learning activities that include bite and snack size videos, podcasts, and a free basics course that takes about one-hour – this course will launch in mid-July. All of the resources provided in the learning library were built through collaboration of nurses from a variety of backgrounds and experiences with expertise in genomics. We have an avid review process to ensure the content is up to date and reflects the current state of the science.
How important is provider-patient communications when it comes to a complex topic such as genomics and precision medicine? How can it help improve access?
Consistent communication of genomic information among healthcare professionals and between the healthcare professional and patient/caregiver is extremely important to build trust and deter misconceptions of the patient. Shared decision-making cannot occur if anyone in the decision-making has different information than another or lacks understanding. It is imperative that time is spent as healthcare providers using the same language and being knowledgeable of precision medicine offerings and then translating that information to the patient so they can make informed decisions about their care. In addition, it may provide them broader access to care and novel treatments through clinical trial eligibility.
Precision medicine is here and ready to improve outcomes, yet patients cannot access the necessary tools and supports, the recent PEOF heard
Precision medicine represents a paradigm shift in the treatment of many of the most serious diseases, with the promise of tailored therapies and much-enhanced outcomes. Yet global access to this approach remains patchy and inconsistent, and inequality dominates.
This was the focus of an eagerly awaited session at the recent Autumn sessions of the Patient Engagement Open Forum. Entitled “Visualising the patient pathway in precision medicine: the identification of barriers and best practices across different stakeholder groups”, as with previous PEOF sessions, a broad spectrum of multi stakeholder involvement gathered to offer an holistic overview of the problems and endeavour to co-create potential solutions.
Helena Harnik, executive director of FT3, outlined the goals and objectives of the unique initiative. A “global collaborative program to make precision medicine an accessible reality for all those who could benefit from it”
“The FT3 members and community believe that a true multi stakeholder program, one that involved diverse stakeholders is the best way to address this complex issue,” she told the virtual audience. Initially focusing on cancer and testing, FT3 is striving to develop practical solutions to making precision medicine “a reality on the ground”. Immediate action is being taken to accelerate existing efforts in precision medicine and scale best practices, she added.
Yet this remains a “complex topic and fragmented landscape”, she reminded attendees; despite the rapid speed of change in the area, it is fundamentally fragmented in terms of the actors and organizations involved. “Hence the need for a whole health system view,” she advised. This is why FT3 is taking a unique approach, acting as a global catalyst identifying and sharing translatable good practices and learnings, developing practical resources and support for PM champions and identifying good practices but also co-creating solutions for unmet needs by drawing on existing knowledge.
Attendees of a previous PEOF session, back in September 2020, had direct input into this work, Harnik explained. Some 85 attendees had helped to identify over 220 patient support and information needs in precision medicine. These included issues pertaining to access, clinical trials, and testing, as well as understanding the patient experience and access barriers at all levels.
Andrea Ferris, President and CEO of LUNGevity Foundation, then delivered a presentation on the patient pathway in non small cell lung cancer (NSCLC). A lung cancer advocacy group, LUNGevity defines precision medicine as “biomarker-driven care” across the entire spectrum of a disease, Ferris explained. LUNGevity is involved in funding translational research, providing education and outreach, as well as promoting precision medicine and advocating for public policy reform.
“Every patient has access to the right test and the right treatment at the right time,” she said, adding that this is particularly important in lung cancer as advances in the area are being predominantly driven by precision medicine and immunotherapy.
Ferris outlined the biomarker testing journey of NSCLC; looking at it from different perspectives, she explained, including the patient, the healthcare provider, the payer, helped to identify the key barriers at all levels of stakeholder involvement.
There were “issues along the entire journey” – from the tissue acquisition to diagnostic testing, all the way through to how doctors were using the test results, educating patients on waiting for their test results and reimbursement of the eventual therapy. LUNGevity then explored interventions that would help to address the various barriers on this journey. “This is a tool that could be applied in many other diseases,” Ferris concluded.
FT3 were struck by the simplicity and effectiveness of LUNGevity’s approach, Helena explained, and also sought to map out the patient experience, as well as access barriers and solutions across the patient pathway. In the course of doing this, they also found similar approaches being taken elsewhere and elements of these were incorporated.
She presented a draft version of the resulting Access Barrier Cause-Effect Canvas, which aims to be a practical tool for precision medicine champions, enhancing best practice.
Tanya Knott established the SJK Foundation following the death of her sister Sarah Jennifer Knott from cancer of unknown primary (CUP) in direct response to the lack of specific supports for the disease, despite it being the fourth most common cause of cancer death worldwide. Embracing precision medicine is “critical” as it may allow CUP patients to be identified earlier and ultimately achieve better outcomes, Tanya told attendees. Significant advances have been made in not only awareness of CUP, but also in terms of diagnosis and treatment, with genomic advances crucial in achieving this. Tanya also outlined how genomic profiling will allow for targeted, personalized treatment, yet she reiterated that patients often cannot access these sophisticated but essential tests.
“Being a part of the FT3 group means we can work together with all the different countries to find the best practices and try bring them to the countries that don’t necessarily have them while learning from best examples,” she said.
Following Tanya was Warnyta Minnaard, who is one of the founders of Missie Tumor Onbekend, the Dutch advocacy and patient organization for patients with cancer of unknown primary (CUP). Outlining her own personal family experience of the disease, she reiterated Tanya’s points about the unsatisfactory nature of the patient pathway in CUP, as well as the barriers patients face in obtaining a timely diagnosis and effective treatment. Warnyta emphasized the aggravated emotional impact of
“every cancer or challenging diagnosis”. “It is especially challenging to grasp what is happening if you have cancer but they cannot locate the primary site and they don’t know what to do.” Yet she also stressed the enormous potential in this area because of increasing focus and enhanced possibilities around precision diagnosis and treatment.
As the diagnosis in CUP is based on a diagnosis of exclusion, discrete differences in the diagnostic workup between countries means there is no reliable comparison data, and no understanding why specific treatments are given to CUP patients, Caroline explained.
“Mostly we miss out on the possibility of learning from each other and improving healthcare for CUP worldwide”. A national and international consensus on diagnostic techniques must be achieved but this is easier said than done, she warned. “Together is the only way we can move forward.”
As with all PEOF sessions, its interactive nature meant that the feedback of the audience was eagerly gathered; Helena outlined the questions they were hoping to answer such as identifying access barriers, how best to represent the patient experience and which critical stakeholders were missing from the draft Access Barrier Cause-Effect Canvas. She also asked their input on how the canvas could be employed in a real-life scenario – this will allow the first draft to be refined and tested.
Feedback was plentiful: among the access barriers highlighted by the online attendees were the limited availability of tests, deficiencies in health literacy, delayed referrals by primary care physicians, and geographical issues. It was also suggested that the canvas could be used to help compare and contrast the experiences of patients in different jurisdictions to see where they diverge or converge.
Ultimately what the session had proven was that access challenges are “complex and interconnected” said Helena. “A whole system approach, starting with the patient experience is needed.”
Cancer will only be beaten when the genomic drivers of a person’s cancer are understood and targeted, according to Brian Tomlinson of Foundation Medicine
Tell me about yourself and your organization
Brian Tomlinson – Medicine Foundation
Foundation Medicine is a molecular information company dedicated to transforming cancer care through a deep understanding of the genomic changes that contribute to each patient’s unique cancer. The company offers a full suite of comprehensive genomic profiling assays to identify the molecular alterations in a patient’s cancer and match them with relevant targeted therapies, immunotherapies and clinical trials.
I joined Foundation Medicine after working for two national cancer patient advocacy Organizations for nearly 18 years. In my role at Foundation Medicine, I lead our external engagement efforts with our patient advocacy partners in the US.
What does personalized medicine mean to you?
Personalized medicine involves providing treatment based on the unique drivers of disease at a molecular level. In cancer, this starts with comprehensive genomic testing to understand what’s driving a patient’s cancer at a molecular level. This gives oncologists and patients the information they need to make informed treatment decisions.
We’re at a critical moment for precision medicine in cancer care. To me, it means finding the right treatment, for the right patient and the right time.
Why do you believe this topic is important?
I am motivated every day by the patients we serve now and the opportunity we have to impact cancer care in the future. Unfortunately, many patients right now do not have access to genomic testing. We have an opportunity to extend lives or even manage cancer as a chronic condition for certain patients today using these breakthrough therapies, but we can only do this when physicians understand the genomic drivers of a patients’ cancer.
As part of our efforts to expand access to genomic testing, we engage with advocacy groups and patients across indications to share scientific insights and serve as a resource on CGP with the goal of expanding overall education and awareness. I have dedicated my career to supporting cancer patients and their families. Having comprehensive testing provides access to really important information about treatment planning and shared decision making.
Why is your organization interested in participating in this multi-stakeholder collaboration? What has your organization been doing in this space?
We believe that transforming cancer care and ensuring all patients can benefit from precision medicine cannot be done alone, which is why we believe collaboration across the ecosystem is so critical. Over the past almost 10 years we’ve established deep partnerships with organizations across academia, industry, biopharma and advocacy.
What makes this collaboration unique?
I think the global focus and the comprehensive external stakeholder engagement make this collaboration a first of its kind and quite unique.
What are your ultimate expectations from the project?
We know expanding access to CGP is critical to increasing the number of patients who can benefit from precision medicine. We’re committed to working across the ecosystem to ensure all patients can benefit from the latest science at the time of care and that oncologists have the tools to make informed treatment decisions. We’re at a true turning point for precision medicine in many regions – including Europe. The healthcare ecosystem has made incredible progress in recent years but there is more work to be done.
Begonya Nafria Escalera of Sant Joan de Déu Children’s Hospital in Barcelona has both a professional and personal interest in ensuring that patients’ needs are met by personalized medicine
Tell me about yourself and your organization
Begonya Nafria Escalera – Sant Joan de Déu Research Foundation
I’m working at Sant Joan de Déu Children’s Hospital as Patient Engagement in Research Coordinator. My area of responsibility is to ensure that the patients and families have an active role, as experts, in any of the research and innovation projects in which our institution is involved. Sant Joan de Déu Children’s Hospital is the largest paediatric hospital in Spain. My background is in social sciences and working in the defence of the patients’ rights for more than 10 years. Also I have a personal story linked with my area of expertise, as I’m caregiver of an adult with cerebral palsy, my brother. In recent years I have also been volunteering with several patient organizations.
What does personalized medicine mean to you?
For me it means the opportunity to offer a treatment for a huge group of complex conditions, the genetic diseases. Most of these conditions affect paediatric patients and there is no cure for them, only in some cases palliative treatments. PM from the patient side means hope but also uncertainty. At this moment, few conditions have the opportunity of these innovative treatments, this means that we need to inform and educate the patients/families about this type of treatment, how it works and what it means to be involved in a clinical trial.
Why do you believe this topic is important?
Because research in new treatments is moving to this direction: try to provide the best and most accurate treatment for the patients. Society and specifically the patients/caregivers need also to move in this direction, knowing what a therapy means, when it works and also the status of research according to the different genetic conditions.
Why is your organization interested in participating in this multi-stakeholder collaboration?
We are increasing our activity in the field of clinical trials in paediatric conditions, as most of these diseases are genetic. For our patients this really can be an opportunity for treatment in the future, considering that probably at the present we don’t have therapeutic options to offer to them. In parallel, in our institution the research model is based on a patient-centric approach, ensuring that in any project in which our institution will be involved patients/families can take part as advisors and/or part of the research team. We have a young person’s advisory group helping in many projects, a board of parents, and according to the needs of every initiative we set up a specific group of patients/parents to help in the design and development of the project. We don’t envision clinical research without the involvement of patients and parents.
What makes this collaboration unique?
For me, it’s the 360 degree approach with a pillar being patient involvement and the issues that need to be addressed to ensure the best quality of life, disease management and empowerment. The activities around health literacy are essential to ensure that any initiative about personalized medicine will be patient-centric, providing patients with the right information to make decisions about their health and treatments.
What are your ultimate expectations from the project?
I am happy to contribute to a global initiative in which patient engagement will be an essential part of the framework, while increasing awareness about health literacy in this field and providing the expertise of working with paediatric patients. As clinical trials in children and young people are global, we need truly collaborative initiatives involving different stakeholders in order to provide the best treatments for the patients, always considering the unmet and specific needs of the most vulnerable groups of patients.
