Newly Diagnosed With Ovarian Cancer? Take a Breath, Then Follow These Steps

BY Jason Harris
The first thing a woman should do after receiving a diagnosis of ovarian cancer, according to Teresa P. Díaz-Montes, M.D., M.P.H., is nothing. At least not right away.

“You feel lost and confused, and everybody is going to give you advice, and everybody is an expert. And you just want somebody to tell you where you have to go,” she said. “I usually tell patients, ‘You have to keep calm and breathe, and you will get an answer at some point.’ I would not recommend taking months to figure this out, but you have a window of time. You don’t have to rush things.”

Ovarian Cancer: Clot Risk High in All Phases of TreatmentDíaz-Montes, associate director of the Lya Segall Ovarian Cancer Institute at Mercy Medical Center in Baltimore, delivered her presentation for women with newly diagnosed disease July 14 at the 2018 Ovarian Cancer National Conference in Washington, D.C. The time after a diagnosis is confusing and scary, but there’s no reason to panic, she told her audience at the event, sponsored by the Ovarian Cancer Research Fund Alliance.

She recommended finding a partner, such as a close friend or a family member, who can act as a sounding board for serious issues. Then, she said, get organized and informed. A patient will have a lot of information that she needs to keep track of and a lot to learn about this serious but treatable disease. The doctor recommended getting a second opinion before making any decisions, and then trying to get back to normal.

“You should keep your life as normal as possible,” she said. “Try not to isolate yourself. If you’re doing that, your mind is going to go crazy and you’re not going to be able to focus on the important things.”

Staying positive can be a challenge, she said, but it’s necessary for mental health, and also because studies have shown that a person’s emotional state can affect his or her immune system. She warned that staying positive doesn’t mean that a newly diagnosed woman should ignore negative emotions like anger, sadness or fear. A mental health professional can help patients understand and manage the complex mix of emotions they’re likely to be feeling.

“This is a stressful period. It doesn’t mean that you’re depressed,” she said. “We go through all these emotions and sometimes we have to talk about it. Sometimes we need somebody else to give us some light or give us some tool to channel us and help us decide, ‘OK, this is the way I want to go.'”

Díaz-Montes said that cancer treatment is a group activity. Care teams can improve efficiency, effectiveness and coordination of care, resulting in a better experience for both the patient and the caregiver. But there is no formula for choosing the providers. She recommended that patients find health care practitioners — such as an oncologist, primary care physician, social worker, physical therapist and/or palliative care expert — with whom they feel comfortable.

“Life is a journey,” she said. “You can choose to take a bumpy road or a very dark road. The most important thing is that you have the capacity to decide. You just have to take time to think what you want to accomplish.”

Being A Self-Advocate

Below is a brief sample of questions from Teresa P. Díaz-Montes, M.D., M.P.H., associate director of the Lya Segall Ovarian Cancer Institute at Mercy Medical Center in Baltimore, that patients can ask as active participants in their own care.

  • General
    • What lifestyle changes do you recommend so that I can stay as healthy as possible before, during and after treatment?
    • Where can I find more information about my cancer?
  • Staging
    • What is the stage and location of my cancer?
    • What is my prognosis?
  • Treatment
    • What are my treatment options?
    • What treatment, or combination of treatments, do you recommend?
    • What are the potential short- and long-term side effects?
  • Clinical trials
    • What are clinical trials?
    • How do trials help people with cancer?
    • Am I a candidate for a trial?
  • Support
    • What kinds of support services are available to me?
    • Where can I find information about managing the cost of treatment?
    • Who handles health insurance questions in your office?
  • Follow-up care
    • What follow-up tests do I need and how often will I need them?
    • Is there anything else I need to know?

This article was published by Cure Today.

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Triggering an Immune Response in Ovarian Cancer

by Mark L. Fuerst

A novel personalized vaccine made from an ovarian cancer patient’s tumor tissue and immune cells was found in early research to stimulate potent therapeutic immune responses, extending overall survival for patients with recurrent disease.

The vaccine, made from a processed sample of the tumor and delivered via a patient’s own immune cells, was well tolerated and safely administered and can be made in sufficient quantities with relative ease, the researchers said. The immune responses elicited were “vigorous” and targeted both known cancer antigens as well as a broad variety of neoantigens expressed by cancer cells.

“This study clearly proved that whole-tumor vaccination effectively mobilizes antitumor T-cell immunity in ovarian cancer. The vaccination itself amplified T-cell responses against mutated neoantigens derived from individual somatic tumor mutations, and this included stimulating the T cells against previously unrecognized neoantigens, as well as novel T-cell clones of markedly higher activity against previously recognized neoantigens,” the study’s lead author, Janos Tanyi, MD, of the Perelman School of Medicine at the University of Pennsylvania, told MedPage Today.

Report: Heterogeneity Of Ovarian Cancer Should Drive Research, Treatment

He explained that although ovarian tumor cells are known to express neoantigens, the malignancy has so far proved largely resistant to immunotherapies, including traditional cancer vaccines that stimulate an attack by killer T cells. Ovarian tumors also harbor T regulatory cells, whose job it is to suppress killer T cells.

“The key finding was that an individualized dendritic cell vaccine was able to initiate T-cell response against neoantigens, which otherwise was completely unrecognized by the immune system before vaccination.”

Earlier research by the team showed that production of oxidized lysate-pulsed dendritic cells and intranodal injection of a vaccine was feasible in ovarian cancer, and the new study builds on that data. The investigators made personalized vaccines by sifting through a patient’s peripheral blood mononuclear cells for suitable precursor cells. The cells were grown in the laboratory into a large population of dendritic cells, which are essential for an effective T-cell immune response. The dendritic cells were exposed to prepared extracts of the patient’s tumor, activated with interferon gamma, and then injected into the patient’s lymph nodes in order to prime a T-cell response.

The oxidized autologous whole-tumor cell lysate was given alone to five patients, in combination with bevacizumab to 10 patients, and with bevacizumab plus low-dose intravenous cyclophosphamide in 10 patients, until disease progression or vaccine exhaustion. A total of 392 vaccine doses were administered without serious adverse events, the researchers reported.

Vaccination induced T-cell responses to autologous tumor antigen, which were associated with significantly prolonged survival. At 1 year, all of the patients who received the whole-tumor lysate plus the two drugs were alive, compared with 60% of patients who received just bevacizumab and cyclophosphamide without the vaccine. Vaccination also amplified T cell responses against mutated neo-epitopes.

The whole-tumor lysate contains all the neo-epitope peptides characteristic for the actual patient, Tanyi explained. “This could lead to a cost-effective way of producing an individualized cancer vaccine. The individual patient’s tumors are not needed to be sequenced in order to identify and create these neo-epitope peptides, which otherwise is a very expensive procedure. Instead, neo-epitopes in the lysate from the actual patient can be used to generate an immune response because they are already in the whole tumor lysate.”

The personalized vaccine produces immune responses against neoantigens, which is important in ovarian cancer because each patient’s cancer is different and changes even further during disease progression, he said. “Targeting these neoantigens can cover most of the tumor cells in the patient, as this vaccine targets thousands or even more neoantigens.”

Tanyi noted that the study used two potentially synergistic immunomodulatory drugs that are commonly used in advanced recurrent ovarian cancer patients as adjuvants to increase the effectiveness of the vaccine: Cyclophosphamide is known to decrease the CD25 regulatory T-cell activity, which “otherwise would shoot down the generated immune response, and bevacizumab as an anti-angiogenic agent decreases the endothelial barrier and makes it more penetrable for CD8-positive cytotoxic T lymphocytes.”

In the future, additional combinations with checkpoint inhibitors will further increase the T cell responses, he said, noting that the team had previously shown that the combination of a whole-tumor antigen vaccine markedly increased the efficacy of checkpoint blockade immunotherapy.

The next step is to test this personalized vaccine concept earlier in the disease process as a maintenance treatment in patients who have just finished first-line therapy. “Many of these patients reach ‘no evidence of disease’ [status] just when completing first-line therapy. Unfortunately, most of them recur. We propose that if dendritic cell vaccine immunotherapy can be started much earlier, during or immediately after the first-line treatment, it might decrease the recurrence rate or increase the disease-free interval of this devastating disease.

“Individualized immunotherapy is the future, as each patient’s disease has unique features and nonsynonymous mutations that can be targeted,” Tanyi continued. “We need to help the immune system to overcome immune resistance and define these neoantigens as foreign and initiate an antitumor immune attack. This whole tumor lysate-induced dendritic cell vaccine proved to be an effective method to alert the immune system against these neoantigens.”

This article was published by MedPage Today.

Study does not find causal association between assisted reproduction and ovarian cancer risk

Following concerns over many years that hormonal stimulation of the ovaries necessary for IVF may increase the risk of ovarian cancer, a nationwide cohort study from Denmark has now concluded that any perceived increase in risk is actually a statistical bias resulting from vigilant diagnosis at the time of treatment. The investigators were unable to make any causal association between the treatment and fertility drugs used and any excess risk of ovarian cancer.

Paradigm Shift in Ovarian Cancer Points to Fallopian Tube as Site of OriginThe study matched every woman having IVF in Denmark between 1994 and 2015 with ten women from the background population and in its analysis found that assisted reproduction treatment (ART) “was not associated with a long-term increased risk of ovarian cancer which would be expected if caused by ovarian stimulating hormones”.

Results of this study, which finally included 58,472 women treated with IVF or ICSI and 549,210 non-treatment women, are presented today at the 34th Annual Meeting of ESHRE in Barcelona by gynaecologist Professor Anja Pinborg of the Fertility Department at Rigshospitalet, Copenhagen University Hospital, in Denmark. Each of the women were followed-up until a first cancer diagnosis, death or end of study period in 2015.

Results did show a slightly higher overall risk of ovarian cancer among the ART women (0.11%) than among the non-ART controls (0.06%). However, the analysis also showed comparably higher rates of ovarian cancer in women who were nulliparous and in the ART women who had a female cause of infertility. By contrast, ART treatment where the cause of infertility was in the male partner (or even unexplained) was associated with a lower risk of ovarian cancer. It was these anomalies in the analysis which indicated that any observed increase in risk was not associated with stimulation of the ovaries per se but more with parity status, cause of infertility and vigilance.

There has long been a concern that the fertility drugs used in assisted reproduction were a risk factor for ovarian cancer, though any causal biological mechanism was never fully explained. This view is based on an observation that increased ovarian activity (such as in nulliparity or a late menopause) increases the risk. By contrast, pregnancy or use of oral contraceptives, which both inhibit ovarian activity, have been shown to reduce the risk. Nevertheless, and despite these proposals, increasing age and genetic factors (such as an inherited mutation of the two BRCA genes) remain the most clearly associated risk factors, although the disease remains complex in its cause and late in its diagnosis.

This population study, which cross-linked the comprehensive national cancer and reproductive health registries of Denmark, found that any excess risk in the ART women was at its highest in the first two years after treatment but this excess risk gradually declined over the study period – and at 12 years after treatment was similar to that of the general population background group. “This pattern,” say the authors, “suggests an influence of detection bias while undergoing ART treatment.”

“We found that the higher risk of ovarian cancer among women having assisted reproduction treatment was only present among those with diagnosed female infertility,” said Pinborg. “And in a general population we saw that ovarian stimulation does not seem to increase the risk of ovarian cancer.”

She described the results as “reassuring”, adding: “I would advise infertile women contemplating ART treatment to go ahead. Ovarian stimulation itself is not introducing any excess risk of ovarian cancer.” She also noted that, while the relative risks appear high among some groups of women, the absolute risk of being diagnosed with ovarian cancer remain small.

This article was published by News-Medical.Net

Engineering Plant Cells to Speed the Production of a Widely Used Cancer Drug

This article was published by Worcester Polytechnic Institute

Can a personalized cancer vaccine effectively treat ovarian cancer?

In recent study published in Science Translational Medicine, researchers tested a personalized cancer vaccine for treating ovarian cancer.

For most advanced ovarian cancers, the current treatment is a combination of surgery and chemotherapy. Initially, patient response to this treatment is good, but most patients relapse and eventually develop a resistance to platinum-based chemotherapy. At this stage, there are no other curative therapeutic options for these patients.cancer-vaccine-min

Researchers recently carried out a pilot clinical trial testing a personalized cancer vaccine, and published their results in Science Translational Medicine.

The vaccine they tested was a dendritic cell-based vaccine. Dendritic cells are responsible for presenting foreign material, such as cancer cells, to the immune system. It is these dendritic cells that are taken from the cancer patient and are then exposed to the patient’s own cancer cells by a specified process. This essentially primes the dendritic cells so that when they are reintroduced into the cancer patient via a vaccine, it facilitates a broader, more effective immune response to treat the cancer.

During the clinical trial, patients received the vaccine in combination with established cancer treatments of bevacizumab and/or cyclophosphamide. Researchers chose cyclophosphamide as they believe it would enhance vaccination, and bevacizumab was thought to be a good addition for immunotherapy. The researchers specifically designed this study to assess the feasibility and safety of this personalized vaccine in ovarian cancer patients.

The study found that patients who received the vaccine in combination with cyclophosphamide and bevacizumab demonstrated a longer overall survival than those patients who received the vaccine and bevacizumab alone. The researchers highlight that these results support their hypothesis that cyclophosphamide allowed better immunization—that is, it allowed the vaccine to work more effectively.

There are many limitations associated with these dendritic cell-based vaccines. One of the limitations is the difficulty in obtaining enough tumour material to produce the vaccine and the difficulty in manufacturing the vaccine itself.

However, the data from this study is encouraging and it emphasizes the need for further research on these personalized vaccines that can be used in combination with other treatments to facilitate a broader anti-tumour immune response.

Written by Jade Marie Evans, MPharm, Medical Writer

Reference: Tanyi JL et al. (2018). Personalized cancer vaccine effectively mobilizes antitumor T cell immunity in ovarian cancer. Available: https://www.ncbi.nlm.nih.gov/pubmed/29643231.

This article was published by Medical News Bulletin.

The Future of Ovarian Cancer: PARP Inhibition ‘Leading the Way’

BY Brielle Urciuoli

PARP inhibitors have made for new and exciting treatment options for ovarian cancer, but there is still much more work to be done, according to Dennis J. Slamon, M.D., Ph.D.

Slamon, who is the director of both Clinical/Translational Research and the Revlon/UCLA Women’s Cancer Research Program at Jonsson Comprehensive Cancer Center, sat down with OncLive, a sister publication of CURE, to discuss next steps and new discoveries in ovarian cancer.

“PARP inhibitors will lead the way, but the landscape is by no means restricted to PARP inhibition,” he said.

One frustration in this field, Slamon says, is that the treatments that are being used for ovarian cancer today are the same ones that were being used more than four decades ago.

“We need to come up with something more effective,” he added. “We are using the laboratory preclinical models to try and understand that and develop rational clinical trials based on that molecular information.”

Admittedly, though, the “hottest thing in ovarian cancer right now” is, of course, PARP inhibitors. These were initially developed – and appear to work well – for patients with BRCA mutations.

However, the benefit of PARP inhibition is being seen even in women who do not have this mutation. For example, previous data have shown that Zejula (niraparib) is effective in non-BRCA-positive patients who either have homologous repair deficiency (HRD) or another DNA repair deficiency, and even for those who do not have a deficiency.

Now, it is time to determine how to best use these agents, according to Slamon.

One possibility of this is using PARP inhibitors to their “fullest potential,” meaning that they should be given at or near full dose, unless they are being used in a cytotoxic combination, where they should be given at minimal dose (10-15 percent of the standard dose).

“If you have full-dose PARP inhibition on board and you have knocked that pathway out with minimal DNA damage, you can have profound clinical impact on their tumor,” Slamon said. “You can also spare normal tissues.”

To date, PARP inhibitors have only been evaluated in the relapsed or refractory setting. Although, Slamon is hoping future studies will test these agents as a frontline therapy.

“It does not necessarily need to be moved to the initial disease setting, although it can potentially be moved there,” he said. “Now, it needs to be tested in the first-line recurrences, as opposed to giving our best approved standard care treatments because they have not resulted in a significant increase in cures.”

Looking even further ahead to the next five or 10 years, Slamon predicts that PARP inhibitors will be combined with cytotoxics, as well as combinations of novel targeted therapies.

“This means that we may have PARP and other targeted pathways where there is a clear molecular interaction. If we knock out both pathways, we can get very important synergistic effects,” Slamon said.

Some of these targets include ATM and ATR kinases, as well as CDK4/6 inhibitors. “There are some very interesting preliminary data with checkpoint inhibitors in combination with PARP. There are a lot of options that are happening out there,” Slamon said.

Regardless of what the treatment landscape may look like, patients with ovarian cancer ultimately need newer therapies.

“Ovarian cancer is a disease where we really need new therapeutic interventions,” Slamon said, mentioning that once a woman fails on chemotherapy, there are limited options for her. “There is going to be a lot that will begin to be put out there in the next 24 to 36 months, which will look pretty exciting.”

This article was published by Cure Today.

Infertility linked to increased risk for ovarian cancer

Fertility drugs do not increase a woman’s risk of ovarian cancer, a new study suggests.

It did find that infertility itself is associated with an increased risk of ovarian cancer.59285

The researchers examined data from more than 58,000 women in Denmark who had infertility treatments (ART, or assisted reproduction technology) between 1994 and 2015. The investigators then compared them with more than 549,000 women who did not undergo ART.

“We found that the higher risk of ovarian cancer among women having assisted reproduction treatment was only present among those with diagnosed female infertility,” said study author Anja Pinborg. She is a professor in the fertility department at Rigshospitalet, Copenhagen University Hospital, in Denmark.

“And in a general population we saw that ovarian stimulation does not seem to increase the risk of ovarian cancer,” she added.

The findings were presented July 3 at a meeting of the European Society of Human Reproduction and Embryology, in Barcelona. The study addresses long-held concerns that the fertility drugs could be a risk factor for ovarian cancer.

In a meeting news release, Pinborg said the results are “reassuring,” and added that she “would advise infertile women contemplating ART treatment to go ahead. Ovarian stimulation itself is not introducing any excess risk of ovarian cancer.”

Research presented at meetings is considered preliminary until published in a peer-reviewed journal.

This article was published by Healthday.