What I’m Grateful For, Thanksgiving 2015

By: Annette McElhiney

I’m grateful to be alive! Seven years ago, I didn’t think I would be. I’m grateful for a husband of 53 years, two wonderful sons and their wives, three delightful grandchildren, a sister, my doctor and her assistant, my scientific advisors and friends at the Clearity Foundation, many other good friends and supporters and my precious Bengal girls (one named Liebee which means love in German, and the other named Hoffiee which means hope.) I wouldn’t be Dancing Joyfully With or Without NED without each of them. 

But, perhaps, I’m most grateful to my grandchildren because they have helped me keep my life in perspective after a diagnosis of Stage III Ovarian Cancer in 2008. Like many other cancer patients, I took chemo which caused me to lose my hair. My first grandchild, Max, was 7 at the time. I was afraid he would sneak up on me some day, see his bald Nana and be frightened. So I warned him I’d be bald.

I told him I would be taking some very strong medicine that would make me better. I asked him, “Until my hair comes back, what color wig should I get?” He laughed and said “Blue.” “Blue?” I asked. “No Nana, I was just kidding. I want you to get a wig the same color your hair was before.” I told him I didn’t think I would tell his 2 years younger cousin because I wasn’t sure how she’d react. Max said “No I wouldn’t either Nana as she might freak out.” I was sure he’d slip and tell her sometime, but he never did. Finally when my hair grew partially back in and I was wearing it in spikes, I told Kenzie the truth and she, too, seemed unconcerned.

Several years later, a week after Thanksgiving my son called me to read me the school assignment that Kenzie, that same grand daughter, had written before Thanksgiving in response to the teacher’s question, “What are you grateful for this Thanksgiving?” I’m not quoting her word for word but she said, “I’m thankful for my Nana because she had cancer and now paints pictures in her studio and writes books to make money to help other cancer patients who can’t afford their medicine.”

As for my youngest grandchild, Kiera, who was born on 08/08/08 (the same week I got out of the hospital) she has finally become my buddy. For her first 18 months, I was on chemo, which made me weak and unbalanced. I couldn’t dance with her, swing her around with my arms, or rough house with her as I had with the other kids. But in the past two years, as I’ve gotten stronger, she has gotten friendlier. All 3 grandchildren love to help me paint occasionally in my studio and are quite comfortable with the big scary word, cancer.

In fact, Kenzie likes the large teal Ovarian Cancer ribbon sticker on the back of my car as she can always find it in the soccer parking lot. Children have a wonderful way of brushing away our obsessive negative thoughts about our diseases. They are so accepting and casual about illness, they have helped me accept it.

This Thanksgiving, in addition to the people I love, I’m grateful for my hair, teeth, hearing, sight, mobility, functioning liver, kidneys, moving fingers, toes, appetite, good digestion, and health! Until I had cancer, I never appreciated how important every cell in my body was. Today I’m amazed that the human body can be exposed to such incredible abuse from the chemo that it can recover at all.

So instead of writing more about me in this post, I’m hoping you will sit down and think of all the things you are thankful for this Thanksgiving. Then I hope you will write your list down and share it with loved ones on Thanksgiving Day. Every day I am alive I am grateful and I hope you are as well.

Also, I made my yearly donation to the Clearity Foundation, a non profit that helps ovarian cancer patients get the best and most personalized treatment available. Their dedication to making life better for ovarian cancer survivors and their families is abundant!

But who describes Thanksgiving better than my favorite poet Emily Dickinson? Help me make Thanksgiving better for all of us!

“One Day Is There Of The Series” — By: Emily Dickinson (1830 – 1886)

One day is there of the series

Termed “Thanksgiving Day”

Celebrated part at table

Part in memory –

Neither Ancestor nor Urchin

I review the Play –

Seems it to my Hooded thinking

Reflex Holiday

Had There been no sharp subtraction

From the early Sum –

Not an acre or a Caption

Where was once a Room

Not a mention whose small Pebble

Wrinkled any Sea,

Unto such, were such Assembly,

‘Twere “Thanksgiving day”

Researchers Find Experimental Drug Can Help Fight Debilitating Side Effect Of Ovarian Cancer

Women who have ovarian cancer often develop a condition called ascites, which is a buildup of fluids in the abdomen. The most common treatment for ascites is puncturing the abdomen and manually draining the fluid, which is painful and risky and must be repeated every few weeks.

UCLA researchers have found that a drug that inhibits a receptor called the Colony-Stimulating-Factor-1 Receptor, or CSF1R, reduces ascites with minimal side effects. This inhibition therapy targets not cancer cells but macrophages, a special type of immune cell, in order to prevent them from helping the cancer take root in the abdomen.

In effect, the drug makes the abdominal cavity — where ovarian cancers often spread — into an environment less conducive to cancer growth. It may prove to be an effective treatment in combination with conventional cancer treatments such as chemotherapy.

The findings, published in the peer-reviewed journal Cancer Research, may lead to a clinical trial of the drug in patients with epithelial ovarian cancer, said Dr. Lily Wu, the study’s senior author and a professor of pharmacology, pediatrics and urology at UCLA.

Wu said 50 to 70 percent of the approximately 22,000 women diagnosed with epithelial ovarian cancer in the United States each year will also develop ascites. “Trying to fight a battle on two fronts can seem hopeless, and patients fighting ascites while trying to survive a particularly deadly cancer is unacceptable,” said Wu, who is also a member of UCLA’s Jonsson Comprehensive Cancer Center.

Ascites is not exclusive to epithelial ovarian cancer, said Diana Moughon, the study’s first author and a graduate student in pharmacology at UCLA.

“Some other cancers of the abdomen such as liver and pancreatic cancers and some highly invasive and metastatic cancers from elsewhere, such as breast cancer, can also cause ascites,” Moughon said. “Macrophages have also been shown to assist in these aggressive malignancies and be a mechanism of their ascites accumulation. We are hopeful that our therapeutic strategy can eventually be broadened to include ascites induced by other cancers.”

Ascites is caused by a problem with the abdominal blood and lymphatic vessels that causes the blood vessels to “leak” and the lymphatic vessels, which would otherwise drain the excess fluid, to become “plugged” with cancer cells. Previous research has focused on inhibiting a protein called VEGF, which promotes the growth of blood vessels. However, Wu said, that treatment is risky and has been reported to cause catastrophic intestinal perforation in up to 10 percent of patients in clinical trials. By contrast, people treated with CSF1R inhibitors experienced no major side effects. “Specifically targeting the cells with CSF1R inhibitors lessens the number of pro-tumor macrophages and allows the vessels in the abdomen to become normal again, easing ascites accumulation,” Wu said. “All of this is accomplished without dangerous side effects or pain.”

One of the ways tumors recruit and change macrophages is through a long-distance signaling mechanism. Tumors pump out a protein called CSF-1, which floats around until it finds the receptor it is looking for — in this case CSF1R. When the signal meets the receptor, the cell in contact with the receptor receives the message from the tumor. Macrophages express CSF1R and respond to the signaling by traveling toward the tumor and becoming pro-tumor. When CSF1R was inhibited, the number of macrophages in the ascites around the tumor was vastly reduced, which, in turn made the ascites environment much less favorable to the tumor.

After just two weeks of treatment, the animals’ blood vessels carried blood normally instead of leaking it. Wu said this caused the ascites to at least stop accumulating, and in many cases to regress.

Going forward, Wu and her team want to try the therapy in a clinical trial. They also will explore whether the CSF1R inhibition therapy can be combined with standard ovarian cancer treatments to fight both the ascites and the cancer.

Read this research article by UCLA on Science Daily by clicking here.

New Insights in the Pathophysiology of Ovarian Cancer and Implications For Screening and Prevention

The American Cancer Society estimated that 21,290 new cases of ovarian cancer will be diagnosed, and 14,180 deaths from ovarian cancer will occur during 2015.[1] A woman has a 1:70 lifetime risk of being diagnosed with ovarian cancer, the second most common gynecologic malignancy, with the highest mortality rate.[2] Early-stage cancer is associated with vague, nonspecific symptoms, and therefore most cases are diagnosed at an advanced stage when treatments are less successful. A woman’s risk for ovarian cancer typically takes known risk factors into account. Certain reproductive and other factors (early menarche, late menopause, nulliparity, contraceptive pill use, family history, carriers of genetic mutations, etc.) are known to modify individual risk.[3] Several screening tests (ultrasound, tumor markers) have been evaluated, but none has proved to be sufficiently effective.[2]

Various theories about the etiology of ovarian cancer have been proposed, and each histologic type probably has a specific etiology.[4] Most ovarian cancers are epithelial in origin, and within this group the serous type is the most frequent. One of the most widely accepted theories is that epithelial surface injury occurs with each ovulation. This theory holds that serous ovarian cancer begins in the Fallopian tube from where it spreads onto the ovarian surface.[5] The site of ovulation is affected by intensive repair mechanisms involving inflammatory processes. The cyclic secretion of high concentrations of steroid hormones (estrogen, progesterone, and androgens) may also have a carcinogenic effect, as do carcinogens ascending through the genital tract. Furthermore, when the tumor spreads to the ovary, it seeds the peritoneum as well. Thus, by the time ovarian cancer is diagnosed, it is already at an advanced stage. If this theory proves correct, we may have an opportunity to reduce the frequency of epithelial ovarian cancer and may actually have something to offer in terms of prevention, at least to women at higher risk.

A New Paradigm for Pathogenesis of Ovarian Cancer

Nezhat and colleagues classify ovarian cancers on the basis of etiology into two groups. Type I cancers originate from various ovarian pathologies (borderline ovarian tumors, endometriomas). These cancers typically have a more favorable prognosis because they are diagnosed at an earlier stage and metastasize more slowly. The more frequent type II tumors originate from the fimbriated end of the Fallopian tube and have a less favorable prognosis because they are often diagnosed at an advanced stage.

Cancers associated with endometriosis are accompanied by typical symptoms of endometriosis (pain, dysmenorrhea, dyspareunia), whereas type II cancers are associated with nonspecific, vague gastrointestinal symptoms.

Few effective preventive measures can be offered. Contraceptive pills are known to lower the risk for ovarian cancer, most likely by reducing ovulation and gonadotropin levels as well as reducing blood flow at menstruation. This positive effect can be seen for both epithelial and nonepithelial cancers.

Tubal ligation (most likely by eliminating retrograde menstruation) is known to reduce the risk primarily for clear cell and endometrioid cancers. More recently, the benefits of salpingectomy have been discussed. Bilateral salpingo-oophorectomy upon completing childbearing is already recommended to women carrying risk-increasing mutations (BRCA1 and BRCA2). Bilateral salpingectomy, when pregnancy is no longer desired, should be considered at the time of surgery for benign diseases even for women who are not at high risk for ovarian cancer. On the other hand, the immediate surgical risks as well as the potential impact of bilateral salpingectomy on ovarian function must be considered.

Viewpoint

In recent years, the potential role of the Fallopian tube in the etiology of ovarian cancer has been proposed.[5] It is believed that the most common, serous epithelial cancer may actually develop in the Fallopian tube and spread from there onto the ovary. Not surprisingly, it may spread to any other adjacent organ or to the peritoneum as well. The problem with this type of cancer is that it is mostly asymptomatic early on. The nonspecific abdominal pain, feeling bloated, fullness, lack of appetite, slowly changing bowel habits, etc., often do not point in this direction. Other screening measures (use of ultrasound for diagnosis, checking tumor markers) have not been successful as neither of them is specific enough to warrant surgery.

If, however, the type of cancer with the least favorable prognosis indeed originates from the Fallopian tube, we may have a way to prevent such cancers. Ovarian cancer typically is diagnosed in the fifth or sixth decade of life when women no longer plan on or are able to have children. Therefore, the tube no longer plays an important role for them. If these women (especially those at higher risk) undergo elective salpingectomy, then a good proportion of the cancers could be prevented.[6] It also has to be considered that the surgical procedure itself is not without immediate procedure-related risks. Furthermore, the removal of the tube may adversely affect blood flow to the ovaries and therefore may compromise their activity. The full impact of surgery likely depends on the patient’s age, however. If it is done after age 40 years, the long-term health risks associated with some compromise in ovarian function are likely to be minimal. If the procedure is done at a younger age, it may be associated with significant long-term health risks. In the case of younger women, the resulting infertility or the inability to reverse the procedure also need to be considered. The patient has to be counseled that a salpingectomy is not reversible, should she change her mind later on. Such a definite surgical approach could still be recommended to those at high risk for cancer (strong family history, carrier of genetic mutations).

In this review, the role of endometriosis was emphasized. Women with endometriosis are known to be at higher risk for ovarian cancer.[4] Endometriosis affects 10%-15% of women, and management requires an individualized approach. The desire for future fertility, risk factors for ovarian cancer, and age, for example, must be considered when making a recommendation for medical or surgical treatment, especially if the surgical treatment is radical, such as oophorectomy/hysterectomy. Only around 1% of women with endometriosis will develop ovarian cancer; therefore, surgery for all as a “general rule” cannot be recommended.[7] However, long-term medical treatment (eg, contraceptive pills) to suppress endometriosis can be suggested to women diagnosed with the disease. Regular ultrasound evaluation for changes in size and appearance of endometriomas and surgery for those with worsening symptoms or growing adnexal masses could be considered.

Many questions must still be answered before general recommendations can be made. For now, however, it seems that we may have tools in the future to combat a disease with a high mortality rate.

To read this article and viewpoint on Medscape, click here.

Ovarian Cancer Drug Approved For Use On NHS

Scotland has become the first part of the UK to approve a new treatment on the NHS for women with incurable ovarian cancer.The Scottish Medicines Consortium said Avastin can be prescribed on the NHS for patients with advanced ovarian cancer

Scotland has become the first part of the UK to approve a new treatment on the NHS for women with incurable ovarian cancer.

The Scottish Medicines Consortium (SMC) has given the go ahead for the drug Avastin – also known as bevacizumab – to be used to help patients whose disease is at an advanced stage.

Both doctors and patients’ groups had urged the SMC to make the drug, which has been shown to increase the time people live without their disease worsening, available on the NHS.

The decision means that Scotland is the first part of the UK where ovarian cancer sufferers will have routine access to the treatment, which works by starving tumours of their blood supply.

Approximately 7,000 women in the UK are diagnosed with ovarian cancer every year, including about 615 in Scotland.

It is often not diagnosed until a late stage, after the cancer has spread, with survival rates in the UK the worst in Europe.

Professor Nick Reed, consultant clinical oncologist at the Beatson Oncology Centre in Glasgow, said: “Ovarian cancer is a relapsing and remitting disease and, in its advanced form, is associated with a poor quality of life and outlook.

“Avastin, when given as a front-line treatment, can help to delay the recurrence of the cancer and marks a much needed significant step forward in the treatment of ovarian cancer in Scotland.

“It’s encouraging to see that the Pace (Patient And Clinician Engagement) process has allowed Scottish patients to access this treatment on the NHS.”

The treatment is the first new medicine developed for women with advanced ovarian cancer for 10 years.

Richard Erwin, managing director of the drug manufacturer Roche UK, said: “This is really good news for patients with ovarian cancer in Scotland. The flexibility demonstrated by the SMC has ensured sustainable access for patients in Scotland.”

But Mr Erwin said more must be done “as a matter of urgency” to ensure cancer patients across the UK have access to the same level of treatment.

The SMC also approved the drug pembrolizumab for the treatment of advanced skin cancer for those patients who have not been treated with ipilimumab.

SMC chair Professor Jonathan Fox said: “We know from the testimonies given by patient groups through both the Pace process and patient group submissions that patients and clinicians will welcome these medicines being made routinely available in NHS Scotland.”

To read this entire in full, click here.

New Method Enables The Early Detection Of Ovarian Cancer

Every year, around 1,000 women in Austria develop the extremely aggressive condition known as ovarian cancer. Around 75 per cent of these tumours arise from the fallopian tube. There are currently no options for detecting this condition early or preventing it. With the help of an innovative, “three-way” catheter developed by Paul Speiser from the University Department of Gynaecology at the MedUni Vienna and the Molecular Oncology working group, along with a new investigation concept associated with it, this situation may be different in the future. This is the hope from the first results of a study, which has now been published in the highly respected Journal of Clinical Oncology

“Currently there are only two types of cancer in which the early detection methods of the American Prevention Task Force can be rated with an ‘A’ for ‘extremely’ targeted”, says Speiser, who is also a member of the Comprehensive Cancer Centre (CCC) at the MedUni Vienna and the Vienna General Hospital, “Namely cervical cancer and . Our development could add a third type of cancer to this list”.

Speiser has developed a catheter which prevents irrigation liquid from draining into the abdominal cavity and which can be harvested virtually painlessly.

The recently published study showed that, when ovarian cancer was present, tumour cells were found in the irrigation fluid in 80 per cent of cases. For one test subject who had already decided to have prophylactic removal of her ovaries, a type of next-generation sequencing (“smart sequencing” / analysis of genetic changes in DNA) performed on the irrigation fluid obtained was able to detect an occult, or hidden, carcinoma. “These results encourage the hope that at least early detection will soon be possible,” explains Speiser.

This is an important development, since ovarian cancer has virtually no symptoms and is only discovered very late in around three-quarter of all cases. At a late stage, is associated with a very poor prognosis in terms of the patient’s life expectancy.

The study was initiated and managed by the MedUni Vienna and organised in cooperation with centres in London, Dublin, Milan, Graz, Berlin, Hamburg, Prague, Pilsen, Leuven and Essen. This and other studies are also being carried out in close collaboration with Bert Vogelstein from the Johns Hopkins University in Baltimore. The scientists’ aim is to develop the removal of irrigation fluid and its analysis so that it “can be easily used in every hospital and in every gynaecology department”, says Speiser. Other studies are also expected to show whether it is possible to detect tumours or their early stages (STIC) using this method and to possibly prevent the disease from progressing at all.

To read this article in its entirety on Medical Press by clicking here.

Immunotherapy Not Yet Ready for Ovarian Cancer

Immune checkpoint inhibitors have shown early promise for patients with ovarian cancer; however, these findings will still need to be validated by larger randomized trials before these agents are ready for widespread use, said Maurie Markman, MD, at the 33rd Annual Chemotherapy Foundation Symposium.

“The checkpoint inhibitors are not ready for prime time yet in ovarian cancer. It’s not because there’s evidence that they don’t work—it’s just that there’s no evidence at all,” said Markman, president of Medicine and Science at the Cancer Treatment Centers of America. “You could not think of a more appropriate tumor type to explore the concept of immunotherapy than ovarian cancer. Unfortunately, as we’ve all learned, it’s much more complicated.”

While early studies have suggested that ovarian cancer may be highly susceptible to immunotherapy, larger trials investigating numerous agents have not yet panned out. Markman said in most situations, the agents showed an even response rate of 10% to 20% in phase II studies and proceeded to fail to better those outcomes in confirmatory trials.

“The 10% to 20% response rate is basically seen in all phase II studies for patients with ovarian cancer. Clearly, some of those responses are ultimately turned into results that are positive in phase III trials, but you have a lot of 20% responses that turn out to be nothing,” Markman said. “We have to be very cautious when we look at objective responses, based on our historical data.”

Findings for the PD-1 inhibitor pembrolizumab (Keytruda) were presented at the 2015 ASCO ANnual Meeting, as well as findings from a study exploring the PD-1 inhibitor nivolumab (Opdivo), which were recently published in the Journal of Clinical Oncology. In the pembrolizumab study, 26 evaluable patients were treated with pembrolizumab, with a confirmed response rate of 11.5%. Additionally, six patients (23.1%) had stable disease which resulted in a disease control rate of 34.6%.

“PD-1 blockade with pembrolizumab is well tolerated and has antitumor activity in patients with advanced ovarian cancer,” Markman said. “But clearly, this response rate is not a home run.”

For the nivolumab study, 20 patients with platinum-resistant ovarian cancer were treated with the agent at 1 mg/kg (n = 10) or 3 mg/kg (n = 10) every 2 weeks for up to 6 cycles. The response rate for the overall study population was 15% and the disease control rate was 45%. Median progression-free survival (PFS) was 3.5 and 3.0 months in the 1-mg/kg and 3-mg/kg cohorts, respectively.

Median overall survival (OS) was 16.1 months in the low-dose arm. OS data were not yet mature for those treated with the higher dose. The median OS for the full population was 20 months.

“The PFS was short overall. The median survival was 20 months, although the time of the report was 2014 and some of the responses were continuing,” Markman noted.

Results from larger phase III studies are still needed to validate early findings for checkpoint inhibition, particularly with regard to the duration of response seen with these agents, said Markman. Moreover, work is needed to uncover a biomarker of response and effective combination strategies.

“We have to look for clinically validated biomarkers,” Markman said. “For the one patient who responds for 4 years, wouldn’t it be wonderful today to know if there was something unique in her tumor or in her normal genetic makeup that allowed that to happen.”

In addition to checkpoint inhibition, other immunotherapy approaches explored included interferon, interleuken-2, and a variety of tumor antigen specific vaccines. Despite the lack of success for these many approaches, Markman does not anticipate a stall in research.

“Vaccine studies will likely continue, because there is tremendous interest in vaccines,” Markman said. “I have to conclude that utility, based on existing experience, is questionable. I would not look at an immune response as any indication that there will be any kind of benefit.”

Read this entire article on Targeted Oncology by clicking here.

Factors Predictive of Improved Survival in Patients With Brain Metastases From Gynecologic Cancer: A Single Institution Retrospective Study of 47 Cases and Review of the Literature

Objective: The reported incidence of brain metastasis from epithelial ovarian cancer (EOC), endometrial cancer (EC), and cervical cancer (CC) is exceedingly rare. As the long-term survival for patients with gynecologic cancer increases, there has been a corresponding increase in the number of diagnosed intracranial metastases. We seek to report our experience with managing brain metastatic disease (BMD) in patients with gynecologic cancer.

Methods: A retrospective review of all patients with EOC, EC, and CC at our institution revealed 47 patients with concurrent BMD between 2000 and 2013. Demographic data, risk factors, treatment modalities, progression-free data, and overall survival data were collected.

Results: Median survival time in patients with brain metastasis from EOC, EC, and CC was 9.0, 4.5, and 3.0 months, respectively. Two-year overall survival rates were 31.6%, 13.6%, and 0%, respectively. Patients received surgery, radiation therapy alone, palliative care, or radiation plus surgery. Radiation combined with surgical resection resulted in a significant hazards ratio of 0.36 (95% confidence interval, 0.15–0.86), compared with radiation alone.

Conclusions: Our report provides a large single-institution experience of brain metastases from gynecologic cancer. Patients with BMD have poor prognoses; however, treatment with multimodal therapy including surgical resection and radiation may prolong overall survival.

To read the full article on the International Journal of Gynecological Cancer, click here.