She said she had lived a full and adventurous life and seen many countries. She would have liked to have had more time with her horses and visit Japan. She was happy with what she had achieved and had no fear of dying.
Neuroendocrine cancer is often called the secret cancer as it is rarely found before it is in its later stages. It can affect anyone of any age or gender. Our daughter, Miranda, was diagnosed with neuroendocrine tumours (NETs) in 2017, aged 25 years. Irrfan Khan was not diagnosed until he was in his late 50s.
Miranda had experienced crippling stomach pains for several months that had not been attributed to anything specific. The tunnel vision of the specialists consulted did not expect to find cancer in such an apparently vibrant healthy young woman; it is rare to find intermediate grade NETs stage 4 cancer in someone so young and athletic. After several agonising midnight visits to the local Accident & Emergency department, an Indian nurse spotted something on a lung X-ray and insisted that the registrar on duty conduct further investigation. The resulting CT scan highlighted many tumours throughout her lungs, liver, lymph nodes and hilum. This exact diagnosis from a biopsy shocked the living daylights out of our family.
A specialist physician briefed a shell-shocked Miranda on her options and connected her with the prime oncologist, Dr Daniel Krell, and the leading professor in the neuroendocrine field.
Simultaneously, her father, Charles, took advice from the Sloane Kettering, Mayo Clinic and the Royal Marsden Hospital, who unanimously concluded that Professor Martyn Caplin was the foremost expert in Europe for neuroendocrine cancer, which at the moment is an incurable disease unless it is diagnosed in the early stages. Patients typically survive for about a year following a similar diagnosis.
Miranda was a geographer, who loved a chat about tectonic plates or volcanos, and a “researcher” with an MScR in equine hydration, a subject which she made sound surprisingly compelling; but mostly she was an extreme sportswoman: equestrian, cyclist, skier on snow and water, swimmer, runner and lacrosse player; everything she undertook she did enthusiastically, including an episode of rock climbing. She had a cheeky sense of humour and set herself very high standards, which she learnt from her army Dad and which were reinforced during her first position in a professional equestrian yard.
At the time of this life-changing news Miranda was working as “Head Girl” in a professional equestrian eventing establishment, and successfully competing two of her own young horses in British Eventing. As the treatments were likely to be debilitating, Miranda moved back home to have the support of her parents; but no slacking for our girl who immediately embarked on her Masters degree at the Royal Agricultural University, whilst on the chemotherapy drip she would be writing up her notes from her experiments.
Miranda was born with unilateral hearing loss, thus she dreaded losing her hearing and also her very thick long hair during chemotherapy. Carboplatin (FCarboStrep) was selected for the first chemotherapy as she understood it is less likely to induce hearing and hair loss than Cisplatin. Like all chemotherapy, the side effects range between extreme nausea, fatigue, weakness, chills and bruising; Miranda chose to override these symptoms, the best way for her to do this was to get on a horse or two the very and every morning after a treatment. I remember her barely with the strength to mount her beloved Lusitano, but once sitting in the saddle the trust and comfort she found on horseback was there for all to see. With the help of anti-sickness medications and steroids hacking out and schooling her horses sustained her through this first cycle of eight increasingly debilitating treatments.
The next scan results showed the disease had responded, tumours were gone or dormant. As a family we celebrated this period of metabolic remission. Miranda joyfully went back to competing in British Eventing and took over running our yard of horses at home.
Early in 2018, just nine months, later the dreaded disease had remerged in the hilum, liver with new vertebral metastases in the lumbar spine; Peptide Receptor Radionuclide Therapy (PRRT) was prescribed. PRRT was virtually unavailable in UK in 2018, there were only 4-5 people undergoing this treatment for NETs which involves overnight isolation and supervision in hospital. It is a precise form of radio pharmaceutical therapy that targets the hormone receptors on tumours, extreme sickness is a side effect. Miranda showed a good response until in December 2018 on the motorway driving home after one the many scans, Miranda shrieked and thought she had been shot in the back. We made it to a safe place to stop and I examined the car, no bullet holes, but later it transpired, two of her vertebrae had collapsed, causing that acute localised pain. These vertebrae were expertly rebuilt with a cement like substance by neurosurgeon Dan Plev, not once during this terrifying few days did Miranda show any signs of fear or self-pity, her will to live her life was amazing, she was skiing again in February 2019. When Miranda begged Mr Plev to allow her to ski, he told her he had to treat the whole patient, which included her psyche as well as her back, he knew what an athlete Miranda was and how much her sports meant to her, he reassuringly said that if she broke anything he would put her back together again. There followed an oral chemotherapy course of Capecitabine and Temozolomide, and Miranda had a second cycle of PRRT and a series of complex radiotherapies to her lumbar spine, which made her dangerously sick and hospitalised. During all these sessions and their horrible side effects Miranda always had faith she could ride through it. These were the early signs of fortitude and courage that she increasingly showed to the outside world. Very few folks knew of Miranda’s cancer, she absolutely refused to be defined by it. She rarely even told her closest friends when she was in treatment or hospital, most of her friends and ours thought she was “better”. We as her parents witnessed and supported every stage and encouraged her resilience, but we never had a conversation with her about cancer.
Early in 2020, Miranda agreed to two trans arterial embolizations in her liver. This involves placing a bead to block the blood supply to the tumours, nothing prepared her for the pain in the aftermath, which she described as if her “veins were on fire”, and deep breaths were painful as the diaphragm was compressed above the liver. In May 2020, scans revealed disease progression in liver, bone and lymph nodes. By summer, this resulted in bone tumours pressing against nerves in Miranda’s groin, causing excruciating bone and nerve pain in the pelvic area. During this period, Miranda lost the use of her right leg and was unable to ride for a period as she was on crutches. This was devastating for her. Tragically her Lusitano sustained an injury whilst not in our care; after the horse came out of surgery and after her pelvic radiotherapy Miranda nursed the horse lovingly, and was literally heartbroken at its eventual loss. She commenced Everolimus, Denosumab and Lanreotide, in August began another 6 cycles of F-Carbo Strep.
Meanwhile, the lockdowns were a difficult time for her. Like everyone, she was separated from her network of friends; this gang of friends had been accumulated through sport, they were a lifeline for each other. During the UK lockdown, Miranda rode, cycled and completed her Masters, then began looking for a job. Zoom interviews were a new challenge to overcome but she got the job of her dreams for Anderson & Co Publishing, working in the international horse racing and bloodstock world, for a once in a lifetime boss, Giles Andersen, who gave her increasing responsibilities, to which Giles said she rose to on every occasion. At this stage she had not yet told her boss she was desperately ill, she did not want him or anyone else to treat her differently.
In the hope of finding a rhyme or reason or a treatment that would explain Miranda’s NETs, she agreed to genetic profiling, which showed nothing interesting. During 2021, she swallowed various oral chemotherapies. They held the beast at bay for a bit, but Miranda developed disease progression on lungs, spine, pelvis, lymph and most worryingly of all, in the liver. Towards the end of 2021, she began losing weight and developed a small resistance to swallowing and an examination of her thyroid began. The above are just a snippet of why we admire our daughter so greatly.
In January 2022, Miranda began planning her competitions to begin in March. She had big ambitions for her new Irish thoroughbred and was excited at the prospect of taking him cross country training. Before training began, her father took her on a skiing holiday in February, where she insisted on skiing black runs to her limits. In the past, her fitness had been credited with her resilience to treatment. In 2022, Miranda began I/V chemo at home, as travelling to London was too exhausting and she was weak from still losing weight. In April, a biopsy showed the tumours in her liver had changed their structure and become high grade and extremely aggressive; treatments were being contemplated. There was one last treatment to try, a trial combining Immunotherapy Nivolumab and Ipilimumab. Miranda agreed to have this in London in early May. She was already weak and very thin and she did have debilitating side effects after this treatment.
Miranda’s swallowing had now become a problem, she was experiencing severe abdominal pain and was hospitalised in the middle of May, her kidneys were also not functioning properly. Miranda was still intermittently working for Anderson & Co on her laptop in the hospital.
Miranda clung to a last vestige of hope that her doctors would find a treatment to “fix her”, as they had on so many occasions before. Miranda returned home on 1 June. A few days later she was told there was nothing that could fix her. The very practical hemisphere of her brain kicked in and we had a few conversations with her about dying; she left us some instructions to live life fully, carry on with everything that we had enjoyed together as a family, and not to collapse in an inconsolable heap. She said she had lived a full and adventurous life and seen many countries, she would have liked to have had more time with her horses and to visit Japan, she was happy with what she had achieved and she had no fear of dying. Miranda was so philosophical, gracious and grateful while she was at home; she messaged her friends who came home to say goodbye, there were oceans of tears. This was our brave girl’s spirit and stoicism, she fought her battle like a lioness for five years, in spite of weakness and pain she was competing her horse and in the ribbons just 3 weeks before she died, on 10 June.
Antonia and Charles Filmer have set up a research project with The Royal Free Charity and Professor Caplin to advance the use genomic profiling and the impact of the heterogeneity to treat neuroendocrine tumours. Genomic profiling helps researchers understand the genes in a person or a cell type, and how they interact with one another and their environment. This could help reveal why tumours present more aggressively in some patients and lead to more efficient personalised treatments.