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.
Taking the opportunity of World Lung Cancer Day and the World Conference on Lung Cancer, we’re pleased to share some recent updates and achievements by the FT3 community in lung cancer and beyond.
If you missed the most recent Town Hall meeting, you can access the slides here.
Please help us bring our work to the next level by sharing this update with your network, and thank you for your continued support in helping us make precision medicine a more accessible reality for patients!
Building on World Lung Cancer Day
FT3 hosted an open face-to-face session at the World Conference on Lung Cancer on August 6, where FT3 community-created tools to improve access in PM were presented to an international audience, followed by a discussion on local needs in improving access to PM. The slides from the presentation can be found here.
Lung cancer patient support and advocacy charity ALK+ UK used the Biomarker Testing for Cancer Treatment Adaptable Resource to develop their own resource and help their patients find the right information and make informed decisions at the right time. Discover it here. Are you interested in adapting thisresource for your geography and/or other conditions? Please contact:silva@thesynergist.org
Having prototyped the first Country Agnostic Condition Card for colorectal cancer, a second country agnostic card for lung cancer has been developed, aiming to provide advocates with an overview of the general availability of precision medicine tests and treatments for lung cancer in order to support care level improvements and advocacy efforts. Discover it here and share your feedback with maximiliane@thesynergist.org.
Expanding FT3’s reach globally
In a joint session with PFMD, FT3 held an interactive session with the Alliance and Partnerships for Patient Innovation and Solutions (APPIS) on August 2. This workshop brought together over 50 patients and other stakeholders from the Asia Pacific, Middle East and Africa region, representing an important step towards increasing the Program’s visibility globally. Participants were invited to share barriers and best practices in PM in their countries. The recordings and results will be available soon on Precision Medicine Synapse.
We are continuously assessing opportunities to increase the visibility of FT3 at upcoming conferences and events. Please let us know what activities and events you have planned that we can link to, and which events/conferences you will be attending or presenting at this year.
Other Program Highlights
FT3’s first country-level pilots are getting started with intake calls in Spain and Canada. The expression of interest is open for 1-2 other countries until August 22. Champions in PM of all parts of the world are welcome to apply.
Our Library of Patient Stories in PM continues to grow with new stories in Cancer of the Unknown Primary (CUP) and Leiomyosarcoma. The aim of these stories is to capture the patient experience and learnings at the individual and collective level to support care level improvements and advocacy efforts. Access all stories here.
In collaboration with Colorectal Cancer Canada, the Precision Medicine Q&A Builder has been adapted for colorectal cancer, resulting in a series of resources in multiple languages. We would like to thank Maria and Barry for piloting this initiative. Access all adaptable resources here and read more about our collaboration with Colorectal Cancer Canada in our interview with Maria. Are you interested in adapting this resource for your geography and/or other conditions? Please contact silvia@thesynergst.org.
The scoping literature review focused on provider-patient communication is currently underway. Learn more about this initiative in our latest interviews with contributing authors Navdeep Dehar from Queens University in Ontario and Erin Dickman from the Oncology Nursing Society.
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.
Here is an update on latest developments in FT3 including ideas to get involved and engage your network.
The first quarter of 2022 has been very exciting and full of great achievements thanks to the support of the entire From Testing to Targeted Treatments (FT3) Community of Practice. We are thankful to all those who contributed and we are happy to share with you an update of the past few months from the From Testing and Targeted Treatments (FT3) program, including ideas to get involved and engage your network.
We are delighted to confirm the recent addition of two new members to FT3, Colorectal Cancer Canada and Takeda, and warmly welcome Nicole Sheahan (Global Colon Cancer Association), Donatella Decise (Novartis) and James Creeden (Independent Expert), to the Board. Last but not least, we are pleased to announce that Sandra Blum (Roche) will join Andrea Ferris (LUNGevity) and Denis Costello (CML Advocates Network) on the FT3 Executive Committee. We are honored to be able to benefit from their support and expertise as we continue to move forward.
Please help us bring our work to the next level by sharing this update with your network, and thank you for your continued support in helping us make precision medicine a more accessible reality for patients.
Program highlights
Building greater awareness around all the work underway is an important focus in 2022. Ben (Comprehensive Cancer Center Munich), Andrea (LUNGevity) and Denis (CML Advocates) represented FT3 in a multistakeholder panel at the Festival of Genomics & Biodata on the 28th of January. The event was founded on the social mission to bring the benefits of omics to patients faster and reached over 7000 participants. We are continuing to assess different opportunities to increase the visibility of FT3 at upcoming conferences and events. Please let us know what activities and events you have planned that we can link to, and which events/conferences you will be attending or presenting at this year.
Following 2 public consultations, the Precision Medicine Q&A Builder and the Patient Information Needs Map are now being piloted in colorectal cancer in collaboration with DiCE, GCCA, and Colorectal Cancer Canada. Maria and Barry from Colorectal Cancer Canada, Marianna from DiCE, and Nicole from GCCA are helping us make great progress with the colorectal cancer pilot. We will begin by testing a Q&A resource builder for colorectal cancer and a first draft of a country agnostic colorectal cancer condition card.
The latest adaptable tool for PM champions, the biomarker testing for cancer treatment adaptable resource, is now available for feedback. We thank Jean Jenkins, Karen Wood, Christine Ghione, Krystin Larkin, Lisa Giuroiu, Maria Watson, Susan McClure and others for their expertise and hard work in putting this resource together. You can find the resource and access the public consultation here.Share with us your feedback and help us bring this resource to the next level of maturity.
Over 110+ advanced precision medicine educational resources have been mapped and are now available on Precision Medicine Synapse. These resources aim to help patient advocates and POs better navigate the field of precision medicine. Please refer us to other advanced resources and tools designed to support patient advocates and patient organizations so they can be included.
We are continuing the engagement and collaboration around Tell the Story of Precision Medicine, where we are co-creating a storyline that explains what precision medicine is, with its promises and challenges, from the lens and experience of patients. We thank all the contributors that worked hard for the refinement of the current draft v.04. This is expected to be hosted in the FT3 website: the wireframe and mockup are also being co-created and will be shared for feedback in May. Please review the current draft and share it with your colleagues and network to gather inputs and ideas.
We have kick-started an analysis of good practice resources aroundtargeted therapies to build on them and co-create a new adaptable resource for PM champions. In order to develop a first outline, please share with us your interest in this workstream so that we can include you in upcoming calls.
We have kick-started a narrative literature review focused on provider-patient communication. We aim to shed light on research that has explored the complexities of communication in precision medicine, including aspects such as shared decision making, expectations and psychological impact. The publication will deliver conclusions from previous research on how healthcare teams can support and be supported in managing these considerations.
A second version of the visualization of patient stories for the library of patient stories in precision medicine has been developed. Moving forward, the focus will be on adding more stories to the library and improving on the actionability of the stories, aligning with upcoming disease awareness days and piloting opportunities.
The FT3 community members have stressed that data education in PM is an important area, including the ability of patients & healthcare professionals to understand, interpret and discuss biomarker test results, enabling informed decisions as well as better management of expectations. We are forming a Data Education sub-working group to address these barriers. Please contact vincent@thesynergist.org if you are interested in being involved in this project.
The Stakeholder Expectations Matrix was completed and findings were presented to the FT3 community members. The interviews generated important insights on expectations of different stakeholders of each other in PM and priority actions by stakeholder group, and confirmed the need for cross-stakeholder collaboration to bring together current programs and best practices to support more universal access to PM globally. We thank Andrea Ferris (LUNGevity), Jo Gumbs (OcuMel UK), Julia Barenghi (DiCE), Andrea Stevens (Janssen), James Creeden (FMI), Peter Krein (Loxo Oncology) and Benjamin Horbach (Roche) and many others for their expertise and leadership in guiding this effort. As a next step, we are discussing a potential publication of findings with the sub-group.
A new Country & Condition Card has been developed for Germany, starting in lung cancer, and cards in other countries including the U.K. are being developed. We are working on a prototype card for Ontario, Canada which would be our first regional card, enabling comparisons of PM availability within countries. . We have also drafted the first country agnostic card for colorectal cancer, which would provide advocates with a snapshot of the general availability of precision medicine tests and treatments for colorectal cancer irrespective of geography. We plan on completing more country agnostic condition cards throughout the year. Let us know if you would be interested in developing a Country & Condition Card for a given geography or condition.
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.”
Patient story: A cutting-edge DNA test put Inke Logtenberg on the right treatment path. Now she hopes others with Cancer of Unknown Primary (CUP) will have swift access to personalized care
Inke knew something wasn’t right. She had some swelling in a lymph node in her groin, prompting a trip to the doctor. After a physical examination, the doctor was not very concerned and recommended a ‘wait and soon’ approach.
‘One month later, it hadn’t gone away, so I went back to the doctor because I was worried that it might be more serious,’ Inke recalls. ‘I was referred to the regional hospital where I had blood tests and was given another appointment.’
In the meantime, while waiting for her next hospital visit, things went downhill. Swelling spread to Inke’s neck and she began to feel quite ill. ‘I was really unwell. At one point, I thought that I might collapse if I didn’t sit down immediately. Inside, I knew this was serious.’
That was mid-January 2021. The next time she saw a doctor, they could see that Inke’s condition had deteriorated. A series of blood tests and biopsies revealed metastatic cancer in the lymph nodes, but the original source was unclear.
‘After a while, the doctors said the cancer did not originate in the lymph. It was a mystery,’ she says. ‘I learned a new term: I had Cancer of Unknown Primary.’
Diagnosis guides treatment
For patients and doctors alike, this is often a diagnostic cul de sac. Without knowing where the cancer began, there is no off-the-shelf guideline to tell clinicians how to proceed. This can be dispiriting for doctors and deeply distressing for the person with CUP.
But Inke was in luck. She was referred to a specialist CUP clinic in Amsterdam where the latest advances in cancer testing are changing the prognosis for patients.
‘I went from the GP to the regional hospital and then to a specialist centre and it was frustrating to find that my personal health information sometimes took a week to follow me to a new doctor,’ she says. ‘It was ridiculous in the age of the internet.’
When she was eventually connected with the right specialists and offered access to appropriate testing, everything began to move more quickly. ‘The most important aspect of my story is a DNA test they did in Amsterdam. This led them to conclude that I most likely had cancer of the cervix.’
Without the DNA test, there would have been no such diagnosis. Inke showed no sign of cervical cancer, but by sequencing the genome of cancer cells found in her lymphatic system, doctors could proceed with a specific course of chemotherapy.
‘I feel lucky’
For six weeks, she had treatment three times a week as part of a clinical trial for CUP patients. Having finished this line of therapy in July, Inke is now feeling better and is in good spirits. Her cancer is stable and doctors are working to ensure it remains that way.
While the two-month wait for a diagnosis felt like an eternity at the time, Inke says she feels lucky to have had access to testing and treatment. ‘When you’re waiting from January to March for something to happen, it’s really difficult. There’s so much uncertainty,’ she says.
One month after Inke’s diagnosis, a new policy passed by Dutch lawmakers ensured that the whole genome sequencing (WGS) testing that put her on the path to treatment would be more widely available. The first centres are now offering this technique, and a growing number of other centres across the country are preparing to offer this test to people with CUP. This can help to end the uncertainty patients have faced in the past and give unprecedented hope.
‘I know not everyone has been lucky enough to have the tests and treatment that I had,’ Inke says. ‘By speaking about this, I hope it will help more people to access the right care for CUP.’
Warnyta Minnaard lost her partner, Hederik, to Cancer of Unknown Primary (CUP). Heartbreak inspired her to spearhead a campaign for the reimbursement of whole genome sequencing in the Netherlands so that others might be spared the same fate
Hederik was just 32 when he became ill three years ago. It began with a drooping eyelid and prompted him to go to hospital in search of answers. Doctors were able to confirm after several months that he had cancer, but could not determine where it began. This matters because diagnosis informs treatment.
‘Unfortunately, he passed away in early January 2019 and I became a widow at age 29,’ Warnyta recalled. ‘Even though he was severely ill, we had no idea he was going to die as we were in the midst of an ongoing diagnostic trajectory that already took seven months.’
Hederik was one of about 1,500 Dutch people each year who are diagnosed with Cancer of Unknown Primary (CUP). For patients with CUP – an advanced/metastatic form of cancer which affects at least two areas of the body – time is of the essence. However, lack of access to cutting-edge diagnostics is a barrier to diagnosis and effective treatment which could prolong and improve lives.
The advent of whole genome sequencing (WGS) of tumours promises to transform cancer care, making it more personalized and more effective. Instead of treating cancer based on where in the body it began, doctors would select a treatment based on the genetic characteristics of the tumour.
Policy influencers
Warnyta co-founded Missie Tumor Onbekend, a patient support and advocacy organization for patients with CUP in the Netherlands. The charity advocates for a specialized diagnostic and improved care pathways for CUP patients, better access to innovative diagnostics, and better treatment. The organization also offers support to patients, clinical research and awareness raising campaigns.
Legislators in the Dutch Parliament had been working on personalized medicine for some time in an attempt to update health insurance rules to keep pace with rapid advances in medical science. Warnyta and colleagues saw an opportunity to ensure that the interests of CUP patients were reflected in any legislation agreed by policymakers.
Following a series of events to engage with experts and members of Parliament and key decision-makers, Missie Tumor Onbekend and a team of clinical experts helped to secure a significant amendment to proposed legislation which has now come into force.
Petur Snaebjornsson, a clinical pathologist at the Netherlands Cancer Institute, helped to make the case to policymakers by explaining the technology and sharing early data from a large study. He argues that WGS is better than routine DNA testing which can sometimes leave out rare but relevant biomarkers.
‘WGS offers two main advantages. Firstly, in this all-in-one DNA test you can detect all genetic biomarkers that are used to guide so-called targeted treatment or immunotherapy, which are new types of cancer treatment compared to chemotherapy,’ he said.
‘Secondly, WGS can be used to predict the location of the primary tumour. Finding the primary tumour location is of importance because it guides the choice of chemotherapy. So WGS represents a win-win test for patients with cancer of unknown primary.’
Insurance coverage
In February 2021, the Parliament unanimously added extensive DNA-testing to the basic package of care that must be covered by private health insurers as part of their mandatory offering available to each citizen in the country. This led to WGS being reimbursed for CUP patients from 24 April 2021.
Petur said the campaign and subsequent changes to reimbursement rules have increased awareness of CUP, raised the profile of patient advocates, and prompted the establishment of a Dutch expert platform called CUPP-NL. ‘The platform aims to raise awareness and collaboration, pool current knowledge, stimulate research and improve diagnostics and treatment options for patients with CUP,’ he added.
It was a remarkable achievement for the small group of activists behind a relatively new advocacy organization. However, campaigners are not yet ready to celebrate as there is still work to do before the new rules have the desired impact. Some patients have reported a slow response to the new rules, with families struggling to access the testing they need.
Petur said performing WGS early in the diagnostic process is vital to improving outcomes. Some hospitals have opened CUP clinics and access would improve if more hospitals followed this example.
For Warnyta, this cannot come quickly enough: action must follow the policy shift announced in April. ‘We are now strong on policy but the coordination to reflect the policy change in care pathways is still missing at a central level. In specific parts of the country, hospitals are now taking a coordinator role for patients in their catchment areas but access needs to be arranged at a country-wide level so that it does not matter where you live,’ she said.
This is a source of deep frustration and sadness for campaigners and people living with CUP. As time ticks on, lives are lost. And that motivates Warnyta and other CUP patient advocates to continue to strive for more awareness and support for CUP.
World CUP Week: Researchers are screening hundreds of tumour genes in search of drug targets that could open the door to more personalised cancer care
Most cancers are named – and treated – according to where the first tumour is found. But for some patients, tumours are detected in various organs of the body but the origin of the disease remains a mystery.
People with Cancer of Unknown Primary (CUP) are up against it. Their disease is advanced at the time of diagnosis and there are no specific treatment options available. As time is of the essence, they are usually offered several drugs at once – an approach known as polychemotherapy – in the hope that one of them may work. The outcomes are often poor and therapies affecting all of the body’s cells can make patients feel very unwell.
‘We would like to see a more personalised approach to therapy in patients with CUP,’ explained Dr Manel Esteller, Director of the Josep Carreras Leukaemia Research Institute (IJC) in Barcelona. ‘For common cancer types, such as colon cancer and lung cancer, some hospitals screen patients for genes which help them select a targeted therapy. In CUP, we don’t yet know which genes to look for.’
To rectify this, Dr Esteller is running the CUPP-On project which will analyse samples from 50 patients with CUP. The team are looking for up to 500 genetic mutations or copy number variations (CNV) frequently observed in solid tumours, for which there are already approved therapies available.
‘In selected cases, we will take a sample of the patient’s tumour and grow it in mice where we can then test existing therapies to establish whether it reduces tumour growth,’ Dr Esteller said.
Clinicians may consider using this information to change their patients’ treatment plan. Looking at the bigger picture, the study could offer clues about the origins of CUPs. ‘Is the original tumour small or hidden? Is there something special about these tumour types? Are certain genes responsible for a proportion of CUP cases? We hope to find out,’ said Dr Esteller.
Other advances could flow from the project, such as the inclusion of CUP patients in so-called basket trials where patients are recruited to clinical studies based on having a tumour with a specific mutation which can be targeted by a drug.
‘Basket trials don’t care about tumour type or location – they include patients based on the presence of certain mutations,’ Dr Esteller said. ‘If we show that some CUP patients have mutations that are actionable by a drug, it becomes possible to join these kinds of trials.’
He said targeted therapy also brings benefits beyond survival as treatment tends to be well tolerated, helping to preserve quality of life. If the study proves successful, the results could be translated into clinical practice relatively swiftly as the drugs are already approved for human use. What’s more, as the cost of gene sequencing is much lower than it was a decade ago, there are fewer barriers to access in hospitals with sufficient lab capacity.
The CUP-On project is supported by the Sarah Jennifer Knott Foundation, a charitable organisation devoted to promoting awareness, education and research of CUP. ‘Support from charitable foundations is critical right now as it can be challenging to attract large grants from public agencies for rare tumours,’ Dr Esteller said. ‘Foundations can make a big difference by jump-starting research initiatives like this one.’
Tanya Knott, Director of the Sarah Jennifer Knott Foundation said patients diagnosed with cancer of unknown primary desperately need greater access to genomic profiling and potential targeted treatments. ‘The potential diagnostic and treatment opportunities that Dr Esteller’s research study will bring for CUP patients is incredible and we feel honoured to contribute to his amazing work.’
Here is an update on latest developments in FT3 including ideas to get involved and engage your network.
At the last Board meeting, FT3 members clarified our unique role as a global catalyst to identify and share translatable good practices & learnings in precision medicine (PM) across our 3 strategic pillars: Support Data & Evidence Development, Provide Education & Tools, and Build the Accessibility Conditions for PM.
Building on the gaps and shared needs that the FT3 community identified, we are developing tools and resources for key stakeholder champions in PM, designed to be adapted to the local context. There are 4 groups of resources: resources for patient organizations and support for HCPs, a library of patient stories and evidence, advocacy tools, and capacity building resources. We aim to develop the first testable resources this year.
Thanks to the hard work and expertise contributed by FT3 collaborators, we now have several resources in production. Highlights include a draft Patient Information Needs Map resource, a draft Q&A resource tool, and a draft Access Barrier Cause-Effect Canvas ready for feedback. Help us bring these resources to the next level of maturity by sharing your feedback and sharing this update with your network.
First tools and resources for PM champions now available for further development with the FT3 community
The PM champion toolbox is a suite of resources for key stakeholders in PM (e.g. patient organizations, key HCPs, key health system actors) across the 3 strategic areas of FT3 that build on existing learnings and good practices.
Draft Patient Information Needs Map: This co-created tool aims to help PM stakeholders develop informational resources and strategies that meet individual patients where they are in the patient pathway. The map provides an overview of the key decision points and information needs. Please share the Patient Information Needs Map with your colleagues and networks for feedback and share any ideas or opportunities to apply it.
Parallel Q&A resource tool to target individual Patients: The draft Q&A builder for PM advocates and champions, co-created by working group contributors, is composed of questions that individual patients can ask their HCP in order to guide shared decision-making, leading to better health outcomes, with a particular focus on genomic testing and biomarker-driven care. This patient-facing part of the resource is currently being reviewed with the HCP community. Please share your feedback and connect us with HCPs who could help us define HCP support needs.
The Draft Access Barrier Cause-Effect Canvas aims to help identify the patient pathway in a given focus area, as well as access barriers and good practices experienced by different stakeholders at each step. The first draft is now available here for feedback and an interactive session on the canvas is planned at the Patient Engagement Open Forum on October 6.
Also in the pipeline
Country & Condition Cards: The availability of PM varies from country to country, making it hard to make comparisons and share best practices. Policy makers are often not aware of the current situation and potential advocates working towards advancing access to PM do not have easy facts at their disposal. The country and condition cards aim to fill that gap. Currently, we are finalising our first country card prototypes using the Netherlands and Ireland as a starting point. Look out for an update in the next few weeks to share your feedback and tell us if you are interested in helping us prototype the Cards in your area of work.
Adaptable patient information resources for Patient Organizations: to support FT3’s mission to bring together learnings and good practices in PM, the sub-working group has identified the first good practice resources that are now being converted into adaptable formats. Tell us about any other good practice resources in PM that could be a model for other users.
Tell the story of PM: this sub-working group is focused on developing an approach and storytelling materials to tell the story of PM and why it matters, for different stakeholder groups. This is a tool that various stakeholders can use and adapt to get exactly what they need to advocate for PM in various environments and locations.
Library of patient stories & evidence: contributors have identified an opportunity to bring together and link existing patient stories and evidence across PM. We are now using the first patient stories proposed by the FT3 community to try to develop a common framework for sharing patient stories. Share your patient stories and let us know if you want to be involved.
The Precision Medicine Synapse (in beta) supports FT3’s mission to defragment the PM ecosystem, facilitate collaboration and share best practices to drive change. It is an interconnected and dynamic repository of precision medicine experts, activists, initiatives and resources that is focused on building a crowdsourced global actionable community on precision medicine. To date there are over 279 resources, 269 organizations, 111 events and 46 people mapped in the PM environment.
Call-To-Action publication: FT3 members have been working on a “Call to Action” publication to create the right context for the program to succeed, build awareness of the program and approach, and to build a wider support network to develop and disseminate our activities. We are now in the last stages of finalizing the manuscript and aim for publication in early 2022.
Building an influence network to engage, cocreate and cascade outputs
The complex challenges of PM can only be sustainably addressed through close multi-stakeholder collaboration across the whole PM ecosystem. An important FT3 strategic driver is to connect and cascade through ambassadors in the wider PM community.
Extending the FT3 community through disease awareness days
Disease awareness days are an opportunity to raise awareness of PM, identify challenges, and bubble up good practices, as well as engage stakeholders to support FT3 activities. It is also part of FT3’s mission to support ongoing efforts in PM. These efforts will continue in September, starting with CUP World Awareness Week and Thyroid Cancer Awareness Month. Please share and engage with our social media channels (on Twitter, LinkedIn and Facebook) and use the suggested messages and visuals provided in the social media toolkit which will be updated on an ongoing basis. Tell us about your disease awareness activities or any other campaigns that we can connect to and support.
Latest storytelling content to share with your network
This blog, with contributions from Tanya Knott of the Sarah Jennifer Knott Foundation, Dr John Symons of the Cancer of Unknown Primary Foundation and Warnyta Minnaard of Missie Tumor Onbekend, brings together different perspectives on CUP and sets the scene for the upcoming World Awareness Week.
This interview with FT3 member Brian Tomlinson of Foundation Medicine highlights the importance of understanding the genomic drivers of a person’s cancer in order to impact cancer care in the future.
CUP Awareness Week: connecting researchers, clinicians and patient advocates
Cancer is usually diagnosed and treated based on where it began. If the disease originates in the lung, it is called lung cancer even if it spreads to the bones or the liver. This matters because it informs treatment decisions, prompting oncologists to follow standard pathways of care.
However, the primary site of cancer is not always easily determined. This results in people being told that they have Cancer of Unknown Primary (CUP), leaving them without a clear treatment trajectory. In some cases, this translates into poor outcomes: mortality rates in CUP are among the highest in the field of oncology. CUP accounts for between 3% and 5% of cancers and is the sixth most cause of death in the UK, making it more common than cervical cancer and more deadly than kidney cancer. One in 64 people will be diagnosed with CUP during their lifetime (UK data).
Despite this, and the heavy toll it takes on patients and their families, the burden of the disease is underappreciated by the public, policymakers and many clinicians. Unlike breast cancer or bowel cancer, CUP is an area that has not traditionally been a hive of research activity and rarely makes the news headlines.
Information hub & patient support
CUP Awareness Week aims to change all of this. Running through the last full week of September (20-26 September 2021), it seeks to build momentum behind a shift towards treating cancer based on genomic information rather than solely on the initial location of a tumour. The first event of its kind, the awareness week will help to connect researchers and clinicians in this fast-moving field, while keeping patients at the centre of the conversation.
‘Access to information and support can be a real challenge for patients with CUP. This need will be highlighted by CUP Awareness Week through the World CUP Awareness website. It aims to serve as a hub for all information regarding CUP for healthcare professionals, researchers, industry, patients, patient organisations and all those with an interest in CUP,’ said Tanya Knott of the Sarah Jennifer Knott Foundation, an advocacy group supporting education and research. ‘We will run webinars which are open to the public and allow experts and patients alike to learn more about CUP.’
Redefining cancer based on genomics
The practice of classifying cancers based on their anatomical location is a legacy of the pre-genomic era: physicians labelled cancers according to the organ they first affected because it was the only information available. That has been changing, with genomics opening the door to a more precise approach to classifying and treating disease based on the genomics of a tumour.
While scientific advances take time to filter down into daily practice, there are some positive signs that progress may be under way. Dr John Symons, who founded the Cancer of Unknown Primary Foundation in 2007, sees the 2010 publication of NICE Guidelines as a pivotal moment in England.
‘In the 10 years prior to that, progress had been slow, despite advances in genomics,’ he recalls. ‘Frankly clinicians were not terribly interested in CUP: there was no solution, no guidelines, and it was not a major research area. Treatment was ad hoc and the outlook for patients was poor.’
The NICE Guidelines offered evidence-based treatment pathways which boosted recognition of CUP among clinicians, creating a managed pathway for patients to take. Perhaps unsurprisingly, not every doctor in every hospital follows – or is aware of – the guidelines. ‘We have seen some enlightened scientists come to view cancer as a disease of the genome rather than a disease of the anatomy, but healthcare systems lag science by a long way,’ John said. ‘We speak about it at conferences and it gradually filters into the health service, but it’s not there yet.’
Test, test, test
Central to the changes required to turn this approach to cancer into better outcomes is the use of molecular profiling which would inform treatment decisions. Some hospitals in the UK routinely run whole genome sequencing on tumour samples for research purposes but the practice is far from widespread. Indeed, testing is usually paid for privately rather than through centrally-funded health services.
‘Molecular profiling is available in Ireland where there is a therapeutic indication for example in breast and lung cancer, however for other cancers genomic testing is hugely under-resourced,’ Tanya explained. ‘Ireland has fallen behind and the gap is widening. Ireland needs a formalised national policy in genomic testing.’
In the Netherlands, the Parliament passed legislation in February 2021 which added extensive DNA-testing to the basic package of care that must be covered by private health insurers. This led to Whole Genome Sequencing (WGS) being reimbursed for CUP patients specifically from April and followed a vigorous campaign led by Warnyta Minnaard, co-founder of Missie Tumor Onbekend, a support and advocacy organization for CUP patients.
Despite this, some patients have been frustrated to find that the policy change has not yet been matched with action countrywide. ‘We are now strong on policy but the practicality to make the test readily available to all patients everywhere in the country is missing,’ she said. ‘Patients are still faced with bureaucracy when they try to get tested. Meanwhile, time will pass and people will die of CUP. That is why we need awareness of the urgency of the situation.’
Warnyta also hopes to see greater standardisation in care within and between countries, with more hospitals following best practice and applying the latest tools to diagnose and treat CUP. ‘I hope CUP Awareness Week can prompt more people to reach out to us, to talk to their doctor, and to get tested,’ she said. ‘And, ultimately, I hope it gives more people a clear pathway and a better chance of survival.’
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.
