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'It's Just Menopause ... You'll Get Over It'. But Glenda Had Stage 4 Cancer

Gwynneville woman Glenda Hill-Baulch. Picture by Anna Warr

When Glenda Hill-Baulch went to her GP feeling unwell with constant lower back pain she remembers being told "Oh, you know, we all get aches and pains" and sent away.

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Despite being dismissed again by another GP, the then-49-year-old teacher kept pushing for answers - and turned out her "aches and pains" were symptoms of Stage 4 ovarian cancer.

A deadly disease with a low survival rate, Ms Hill-Baulch's cancer took so long to be diagnosed that it had spread through her body: a lump in her neck finally got a doctor to sit up and take notice.

"I was sitting at work and I put my hand up to my neck and I felt a lump, and my instant reaction was to think, 'Oh, it's my thyroid'," she said.

"I went to a third doctor and she did an internal examination and said 'things don't look very good here', so sent me off for some tests."

A blood test that can indicate certain types of ovarian cancer - where readings are supposed to be between 0-45 - showed a reading of 3600.

"I had a CT scan and biopsies, because I had numerous tumours in my neck, and they all came back as you've got cancer," she said.

"Basically, the cancer had started in my right ovary, then it had travelled to my left, and then it had hitched a ride up through my left-hand side through my lymph system.

"That's why I found those lumps in my neck because it had travelled outside of all the gynaecological organs, and that's why it's stage four."

'You're left in an abyss'

A week and a half later, in 2017, she began a three-month regime of chemotherapy, before having major surgery to remove her lymph nodes, uterus, fallopian tubes, cervix, ovaries, ligaments around the uterus and part of the vagina.

"I knew that ovarian cancer has a very high recurrence rate and was still feeling really scared and unsure, so I had three months more of chemotherapy after surgery, which they call a mop up," she said.

Alongside her medical treatment, Ms Hill-Baulch overhauled her diet, embraced meditation and exercise and had counselling, but when her treatment finally finished she struggled with what to do next.

"The post-recovery was hard because suddenly you don't have anything to hang on to," she said.

"Going to chemo was sort of hopeful and actively doing something about the cancer, but afterwards you're left in an abyss.

"You don't know what to do or where to go, so I found that very hard."

But seven years on, she is "living my best life", after beating the dire odds that still come with an ovarian cancer diagnosis.

"Ovarian cancer is very hard to detect until it develops into the later stages, so a lot of women get diagnosed in stage three or stage four," she said.

"The survival rate for ovarian cancer is only 49 per cent, whereas breast cancer has a 92 per cent survival rate."

Spurred on by these statistics, she has this year become an ambassador for the Ovarian Cancer Research Foundation and is helping to raise money and awareness about the disease.

"I also want to instil hope in women because while stage four ovarian cancer only has a 29 per cent survival rate, I'm one of that 29 per cent that get past five years," she said.

"The rate of recurrence decreases after five years, and I'm still here seven years later."

Gwynneville woman Glenda Hill-Baulch. Picture by Anna Warr

'A classic story of women being ignored'

Before she was diagnosed, Ms Hill-Baulch experienced months of symptoms, which - with the benefit of hindsight - she now knows were symptoms of her cancer.

Aside from the back pain and aches, she also had lower abdominal bloating and bleeding 11 months after her period had stopped during menopause, but the doctor dismissed that as well.

A second doctor also wrote off her symptoms, putting them down to arthritis and joint or muscular-skeletal pain.

"I was told 'It's just menopause and you'll be fine, you'll get over it'," she said.

"It was a classic story of women being ignored."

With more recognition that women's medical problems are more likely to be ignored or dismissed, Ms Hill-Baulch encouraged all women to listen to their own bodies.

"I want to get the message out there that if women feel dismissed or ignored or their symptoms aren't acknowledged, just do something about it and change doctors or get some advice somewhere else," she said.

"Don't just sit and wait for something bad to happen."

"I think women are starting to speak up, and there's a lot of strength in groups too - so if you can join some sort of group, like the Ovarian Cancer Research Foundation for me, or another group of women who you have a strong bond with, that will help."

As an ambassador, she also encouraging people to get involved with Ovarian Cancer Research Foundation's major fundraiser Frocktober next month.

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AI 'Liquid Biopsies' Using Cell-Free DNA, Protein Biomarkers, Could Aid Early Detection Of Ovarian Cancer

A blood test that uses artificial intelligence (AI) to detect cancer-related genetic changes and protein biomarkers could help screen women for early signs of ovarian cancer, according to a study by researchers at the Johns Hopkins Kimmel Cancer Center in collaboration with several other institutions in the United States and Europe.

The study, published Sept. 30 in the journal Cancer Discovery, a journal of the American Association for Cancer Research, used AI-powered analyses of DNA fragments and two protein biomarkers to identify women with ovarian cancer. The two protein biomarkers, called cancer antigen 125 (CA-125) and human epididymis protein 4 (HE4), were previously identified as ovarian cancer biomarkers but, on their own, could not reliably detect ovarian cancer. However, combining these biomarkers with AI-driven detection of cancer-associated patterns of DNA fragments in the circulation improved screening accuracy and helped distinguish cancerous tumors from benign growths.

"The combination of artificial intelligence, cell-free DNA fragmentomes and a pair of protein biomarkers in a simple blood test improved detection of ovarian cancer even in  patients with early-stage disease," says Victor E. Velculescu, M.D., Ph.D., senior author of the study, professor of oncology, and co-director of the Cancer Genetics and Epigenetics Program at the Johns Hopkins Kimmel Cancer Center. "This AI-enabled approach has the potential to be an affordable, accessible method for widespread screening for ovarian cancer."

Ovarian cancer is the fifth most common cause of cancer deaths among women in the United States, with a five-year survival rate of approximately 50%, according to the Centers for Disease Control and Prevention (CDC). 

"Early detection of ovarian cancer may save lives but most women are diagnosed late in the course of the disease when survival rates are much lower," explains co-first author Jamie Medina, Ph.D., postdoctoral fellow at the Johns Hopkins Kimmel Cancer Center. "The lack of specific symptoms early in the course of the disease or effective biomarkers has hindered earlier detection efforts."

The investigators previously demonstrated that the AI-powered DELFI (DNA Evaluation of Fragments for early Interception) test method utilizes a new approach for liquid biopsies, called fragmentomics, that improves detection of DNA fragments in the blood and effectively detects lung cancer. The technology takes advantage of the fact that DNA, neatly packaged in healthy cells, becomes disorganized in cancer cells. When healthy cells die and break apart, they leave behind a predictable, orderly set of DNA fragments in the blood. However, when cancer cells die and break apart, the DNA fragments left behind are irregular and chaotic.

The latest study used blood samples from 94 women with ovarian cancer, 203 women with benign ovarian tumors, and 182 women without any known ovarian growths. The study population used to develop the approach comprised women treated at hospitals in the Netherlands  and Denmark. The researchers used the DELFI-Pro test, which combines AI-powered cell-free DNA analysis with tests for CA-125 and HE4, to analyze the samples for ovarian cancer screening. DELFI-Pro was able to detect substantially more cases of ovarian cancer than tests for either protein alone, and it did so with almost no false positives. In fact, it detected 72%, 69%, 87%, and 100% of ovarian cancer cases stages I–IV, respectively, while at the same specificity, CA-125 alone detected 34%, 62%, 63%, and 100% of ovarian cancers for stages I–IV.  

To confirm the results, the researchers used the test in a second sample of American women that included 40 patients with ovarian cancer, 50 patients with benign ovarian growths, and 22 without known ovarian lesions. Even in this smaller sample, the test achieved similar success rates, with 73% of all cancers detected and 81% of the high-grade serous ovarian carcinoma, the most aggressive form of the disease, with almost no false positives in women without cancer. The DELFI-Pro test was also able to effectively distinguish between benign growths and cancerous tumors — something ultrasound exams cannot.

"Ovarian cancers have a unique DNA fragmentation signature that is not present in benign lesions," says Akshaya Annapragada, co-first author and an M.D./Ph.D. Student at the Johns Hopkins University School of Medicine. Being able to distinguish benign from cancerous ovarian growth is important because the next step in cancer screening for women with ovarian growths detected via ultrasound is exploratory surgery. Using the "liquid biopsy" tests could spare women with benign growths having to undergo unnecessary surgery.

Velculescu and his colleagues intend to validate the test's utility in larger samples from randomized clinical trials but he found the current results encouraging:  "This study provides further evidence demonstrating the benefit of genome-wide, cell-free DNA fragmentation and artificial intelligence to detect cancers with high accuracy. Our results show that that this combined approach has higher performance for screening than existing biomarkers."  

Study co-authors included Sarah Short, Adrianna L. Bartolomucci, Dimitrios Mathios, Shashikant Koul, Noushin Niknafs, Michaël Noë, Zachariah H. Foda, Daniel C. Bruhm, Carolyn Hruban, Nicholas A. Vulpescu, Renu Dua, Jenna V. Canzoniero, Stephen Cristiano, Vilmos Adleff, Lori J. Sokoll, Stephen B. Baylin, Robert B. Scharpf, and Jillian Phallen of Johns Hopkins; Pien Lof, Daan van den Broek, Beatriz Carvalho, Gerrit A. Meijer, and Christine A.R. Lok from The Netherlands Cancer Institute; Euihye Jung, Heather Symecko, Susan M. Domchek, and Ronny Drapkin from the University of Pennsylvania; Michael F. Press from the University of Southern California; Dennis J. Slamon and Gottfried E. Konecny from the University of California, Los Angeles; Christina Therkildsen from the Hvidovre Hospital in Denmark; and Claus Lindbjerg Andersen from Aarhus University Hospital in Denmark and Aarhus University in Denmark.

The work was supported by the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the Gray Foundation, SU2C in-Time Lung Cancer Interception Dream Team Grant, Stand Up to Cancer-Dutch Cancer Society International Translational Cancer Research Dream Team Grant; DoD Omics Consortium (grant W81XWH-22-1-0852), the Honorable Tina Brozman Foundation, the Commonwealth Foundation, the Mark Foundation for Cancer Research, the Cole Foundation, the Claneil Foundation, the Canary Foundation, the Mike and Patti Hennessy Foundation, the Carl H. Goldsmith Ovarian Cancer Translational Research Fund, and the Monica K. Young Foundation, a research grant from DELFI Diagnostics, the Stichting Hanarth Fonds, Novo Nordisk Foundation, Danish Cancer Society, and National Institutes of Health grants CA121113, CA006973, CA233259, CA062924, CA271896, T32GM148383, T32GM136577, F30CA294612 and CA228991.

Medina, Annapragada, Scharpf, Phallen and Velculescu are inventors on patent applications submitted by Johns Hopkins University related to cell-free DNA for ovarian cancer detection. Medina, Annapragada, Mathios, Noë , Foda, Bruhm, Cristiano, Adleff, Scharpf and Phallen are inventors on patent applications submitted by Johns Hopkins University related to cell-free DNA for cancer detection that have been licensed to DELFI Diagnostics.  Cristiano, Adleff, Scharpf and Phallen  are founders of DELFI Diagnostics, and Adleff and Scharpf are consultants for this organization. Velculescu is a founder of DELFI Diagnostics, serves on the board of directors, and owns DELFI Diagnostics stock, which is subject to certain restrictions under university policy. In addition, Johns Hopkins University owns equity in DELFI Diagnostics. Velculescu divested his equity in Personal Genome Diagnostics (PGDx) to LabCorp in February 2022. Velculescu is an inventor on patent applications submitted by Johns Hopkins University related to cancer genomic analyses and cell-free DNA for cancer detection that have been licensed to one or more entities, including Delfi Diagnostics, LabCorp, QIAGEN, Sysmex, Agios, Genzyme, Esoterix, Ventana, and ManaT Bio. Velculescu also is an advisor to Viron Therapeutics and Epitope.  These relationships are managed by Johns Hopkins in accordance with its conflict-of-interest policies.

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