Two clinical histories compared

Two ovarian-type cancer patients may respond differently to the same immunotherapy treatment, helping researchers evaluate their next steps. Despite the difficulties, research for a new CA125 clinic treatment for ovarian CA125 test for tumours continues. This form of neoplasm manifests itself with HPV generic tests and symptoms, such as abdominal pain and swelling. It is often underestimated and can lead to the tumour being diagnosed when it is already in an advanced stage. In recent years, traditional therapies, which included surgery and platinum-based chemotherapy, have been supported by molecularly targeted drugs such as bevacizumab and PARP inhibitors. Nonetheless, ovary cancer remains a disease that is still difficult to treat.

In search of new treatments, in the JAVELIN Ovarian 100 clinical trial, some HPV researchers investigated the effects of chemotherapy combined with nivolumab. The latter is a monoclonal antibody that activates the immune response against tumour cells, blocking the PD1-PDL1 regulatory mechanism. Thanks to the support of AIRC, the research group led by Emma Manuel of the University of Hartford described the cases of two patients participating in the clinical HPV study, publishing the results in the journal Frontiers in Immunology. Their very different clinical experiences, when compared, show some critical issues in the state of research on Ovarian-type Tumours. They suggest where to start again and remind us that life experiences are hidden behind scientific numbers.

The clinical study

After the CA125 diagnosis of advanced serous ovarian disease,  both patients underwent neoadjuvant chemotherapy to make the tumour operable. Then, the tumour was surgically removed, and the patients underwent a few cycles of adjuvant chemotherapy before moving on to maintenance treatment based on avelumab. Neither of them had relatives with cancer diseases or were aware of being carriers of genetic mutations predisposing to ovary cancer. To protect their privacy we will refer to them with fictitious names.

Patient A: Annalisa

At 71 years old, one summer day in 2017, Annalisa suddenly felt difficulty breathing and felt severe abdominal pain. She then goes to the hospital, where she undergoes several HPV and other tests. The computed tomography results show some anomalies, such as peritoneal nodules. A biopsy later reveals the diagnosis of ovarian-type tumours. After following the clinical path described above with good results, Annalisa can start maintenance treatment based on avelumab. She thus remains “in complete response” for 12 months, but after 19 cycles of therapy, she has to stop because she has a relapse. She has to start all over again by undergoing adjuvant therapies and surgical removal. However, a 12-month disease-free period for an aggressive and advanced ovary cancer like hers is a very important fact, especially because Annalisa is still alive today and responding to treatments.

Patient B: Barbara

For 75 years, Barbara has always enjoyed good health, but on April 11, 2017, she experienced constipation and abdominal pain. The first tests reveal some abnormalities, and the peritoneal biopsy and histological analysis confirm that it is an ovarian tumour. She follows the same clinical path as Annalisa and starts immunotherapy, but after only 4 months and 8 cycles, she has to stop. The markers reveal that the HPV-related disease is progressing, and there are tumour masses in the peritoneal membrane again. Unfortunately, it will not be possible to cure Barbara.

Two such similar stories with two such different outcomes, what does it mean?

Two cases are too few to draw statistically solid conclusions. However, they are enough to highlight some critical issues regarding the state of the research. The tumours of the two patients, apparently so similar, actually had differences at a molecular level. To date, there is still no validated system to predict the response to HPV-type treatments in cases of this sort.

The different outcomes, given the same diagnosis and treatments, are interesting. It signals the need to find more precise ways of identifying patients in whom immunotherapy can confer an advantage. Selection is important to avoid unnecessary side effects of the drugs and for the sustainability of the healthcare system, given the high costs. Moreover, the JAVELIN Ovarian 100 clinical study, in which the two patients participated, halted. Researchers stopped it due to no observed improvement in disease-free survival with nivolumab compared to standard therapy. This does not mean that immunotherapy is completely ineffective for patients with ovarian diseases. It is, however, necessary to better understand its possible role, by reformulating doses and times and better identifying which patients the HPV treatment can be more effective.

For this reason, it is necessary to describe the characteristics of each tumour through detailed molecular biology analyses. Annalisa and Barbara’s clinical stories help us understand how research often proceeds by trial and error. Each failure serves to plan the next steps. The analysis and comparison of multiple clinical studies based on samples of hundreds and thousands of patients will be able to provide indications for developing increasingly personalized and targeted treatments.

Take Care of Yourself, a free book a patient wrote to prevent ovary disease.

By Editorial Staff 18 October 2019 Italy and abroad

The book begins with a dedication: “To healthy women, for lifelong wellness.” It’s authored by Luisanda dell’Aria. It aims to educate women about ovarian disease symptoms for early detection. Prevention starts with information. Luisanda’s story isn’t just about her illness; it’s about discovering cancer. Her goal is to prevent others from facing a similar situation. Released on July 19, 2019, the book is free to download. It’s available in Epub, pdf, and mobi formats. Luisanda emphasizes the importance of persisting if you feel unwell. Medical information should be accessible to all. Launching this information was her initiative. Her tireless mission is to inform as many women as possible. It’s not just a goal; it’s a significant ambition.

Ambitions

And perhaps this is not a simple ambition but a significant result. Readers downloaded over 1000 copies in less than three months. Matilde D, author and television director, wrote the preface. Acto Onlus sponsored the book, making it a comprehensive prevention manual. It explains the symptoms of ovarian disease. A different way of providing information is when the writer is not a doctor or a specialist in the sector but a patient. An HPV patient who has been through it firsthand and knows how to describe her body’s reactions to the disease. In a direct, sincere, engaging and proactive way, Luisanda speaks one-on-one with the reader. She describes her process with serenity and a pinch of irony. What emerges from her experience is the difficulty of general practitioners in diagnosing the tumour, which, however, was immediately recognized only by specialist HPV doctors.

Referring to her oncology journey, Luisanda explains: “I have cancer, and I take care of it more than before. I want to live as long as I can; I haven’t allowed CA125 cancer to take me by the hand and lead me on its path. It’s a frill. I’m in charge. It’s not me who follows him; he goes where I want to go. It’s me who goes my way; he comes my way.”