Tuesday, March 17, 2020

Emergency Room Doctor: How We Treat Cancer Patients With Coronavirus Symptoms

This article appeared on the SurvivorNet.com website today. I'm reprinting it here. I hope that this information is helpful.

So what happens when a person undergoing cancer treatment goes to the emergency room worried they might have coronavirus? As many people in the SurvivorNet community are concerned, the editors thought it could be helpful for me to explain how we take care of these patients. Hopefully, knowing the specific medical protocol can help demystify the process, and maybe lessen the anxiety.

Most Emergency Departments, which is where I work as a doctor, have protocols on what to do with a feverish person undergoing chemo.

First Step On Arriving At The ER

When you arrive in the ER, you’ll likely be screened with questions first. If the staff is concerned you might have Coronavirus, you’ll likely be given a  mask and hand sanitizer.
Your vital signs will checked: the temperature, heart rate, blood pressure and how much the oxygen saturation is. Vital signs offer a clue if something is off in the body. After a physical exam, a series of tests are ordered: a chest x-ray to see if there is a pneumonia, a urine test to see if there is a urinary tract infection. Blood work, like the following, is also ordered:
  • CBC ( complete blood count) with differential: this tells the white blood cell count ( is there leukopenia or neutropenia?), if the person is anemic (does the person need a blood transfusion?) and if the ability to clot blood is ok ( is the person bleeding easily?).
  • Complete Metabolic Panel (CMP): this checks all the electrolytes (like sodium, potassium, kidney function and blood sugar) as well as liver function.
  • Blood and urine cultures: Bottles and vials of blood and urine are sent to the lab to see if any bacteria are growing in them that might be responsible for an infection. If bacteria is found, tests are run on it to see what specific antibiotics works against it. Cultures can take a few days to grow; it is not a same day test.
  • Other tests can be added on like a flu swab, stool tests, etc. COVID-19 cultures are sent based on whether a person meets testing criteria by the CDC. The purpose of this work up is to find the fever source. Sometimes, the answer is not immediate. So, many protocols include giving a dose of broad-spectrum, intravenous (IV) antibiotics. Broad-spectrum antibiotics cover a broad range of bacteria to treat everything that it could be. The antibiotics can be narrowed down or stopped once the culture results are known.
We understand a hospital is the last place a person dealing with cancer wants to be. Between frequent hospital visits, the desire to spend time with loved ones and simply missing home, people do not want to stay in the hospital.

Admission vs Discharge?

The decision of admission versus discharge depends on certain factors:
  • If the person is sick ( very weak, dehydrated, can’t keep down medications because he or she will vomit so IV treatment is needed) or unstable     (vital signs are abnormal, or a person’s mental status is off, or not breathing properly) the concern is, if sent home, the person can deteriorate. People meeting these criteria should be admitted. People who have normal vital signs and are otherwise well, may be admitted until the cultures come back negative, or sent home after a discussion with the oncologist. In cases of discharging home, it is essential that the oncologist is following the culture results. If a person is going home, it is helpful to obtain a copy of the test results for home records and to share with other health providers. It is important to also know what to return to the hospital for.
  • The whole goal, from the ED, is to make sure that the person is safe, monitored and treated appropriately so that he or she can either go home or continue the treatment process upon admission. There should always be discussion between you and your healthcare providers and, please, ask questions freely. That said, we might not have all the answers right then and there. This is especially true in the ED where tests are still running, there is a limited amount of time to talk, or the environment is hectic.  However, remember, this is an ongoing and dynamic process involving a lot of discussions, fighting and hope- and we as your health care providers want to support you through all of that.

What We Worry About With Cancer Patients & Coronavirus

Chemotherapy continues to be a typical treatment for many cancers.  However, “living life” while on chemo can be anything but typical. Mundane tasks such as running errands, preparing meals and self-care can be challenged by chemo’s side effects, such as fatigue, nausea, vomiting and a weakened immune system.
  • Weakened immune systems due to chemo can present itself in blood work through leukopenia. Leukopenia is a low white blood cell count- the cells that help the body fight infection. Sometimes, white blood cell numbers can go so low that it can shift to neutropenia- which is when then main white blood cell that fights infection, the neutrophil, is super low.
  • The weakened immune system complicates what were formerly simple issues. A fever that could have just been treated with medicine and some rest becomes an event. What does fever while on chemo and/or a low white blood cell count mean? To medical professionals, it can mean different things.
  • It can mean it’s a reaction to the treatment. It can also mean there is an underlying infection that is taking advantage of the body’s compromised defenses and is causing the fever. The infection can be viral like a cold, or bacterial like a urinary tract infection. It could be simple and go away with medications or it can get complicated and require further in-hospital treatment. Either way, healthcare providers are conservative with treating fevers in people undergoing chemo because a person can get sicker quicker and, sometimes, in a bigger way.


Friday, March 13, 2020

CoVid 19 and Cancer

This is reprinted from an article sent by Diane Riche, New England Coordinator for the Ovarian Cancer National Alliance's Program, "Survivors Teaching Students". 

From Fred Hutch Cancer Research Center…

The spread of COVID-19 across the U.S. is looking increasingly likely, even as researchers and public health officials work to distribute information, ramp up testing and enact measures to slow and eventually stop this new coronavirus.

Not everyone will get sick. But like the flu virus, there are definitely people who are more at risk.

With COVID-19, people who are older (particularly over 70) and people with underlying health conditions, such as chronic lung disease (think COPD), cardiovascular disease, diabetes, chronic kidney disease and cancer appear to be at higher risk for major complications. That includes admission to intensive care and even death.

“The early data from China, and reports from the ground in Italy and other sites of local transmission is that our cancer patients are going to be at increased risk,” said Dr. Steve Pergam, a clinical and infectious disease researcher at Fred Hutchinson Cancer Research Center.

Who’s most at risk?

“Patients with hematologic [blood] malignancies we believe will have the biggest risk,” he said. “Also, patients who are in active chemotherapy and bone marrow transplant patients. Those are the ones with the most profound immune deficits.”

What else should cancer patients and survivors keep in mind as they navigate yet another new normal, in this case the introduction of a completely novel viral pandemic to the human race?

We turned to our cancer and infectious disease experts for answers. Wash your hands and read on.

Are all cancer patients at risk? Or just those currently getting treatment?
Pergam, the medical director of infection prevention at Seattle Cancer Care Alliance, said patients with blood malignancies such as non-Hodgkin lymphoma, chronic lymphocytic leukemia, acute myeloid leukemia, acute lymphoblastic leukemia and multiple myeloma are most at risk.

Also at risk: those in active treatment for any type of cancer and those who’ve undergone bone marrow transplants. (Active treatment is usually defined as surgery, radiation, chemotherapy and other treatments such as immunotherapies.)

Dr. Gary Lyman, an oncologist and health policy expert at the Hutch, added that even those out of treatment may want to be extra cautious.

“The risk extends beyond the period of active treatment,” he said. “The after-effects of treatment don’t end when people finish their last course of therapy or leave the hospital after surgery. The after-effects of cancer and the immunosuppressive effects of treatment can be long term.”

Can patients and survivors get tested to see if they’re immunosuppressed?
Pergam said there’s no easy blood test to check someone’s level of immune suppression, but being in active chemotherapy, having low white-cell or low lymphocyte counts and/or taking immune-suppressive agents (such as prednisone) are all associated with immune suppression and increased risk of infection.

“We don’t know all the details on this yet but if you’ve been told you’re immunosuppressed by your provider, then you should be extra cautious,” he said.

Can patients and survivors get tested to see if they’re immunosuppressed?
Pergam said there’s no easy blood test to check someone’s level of immune suppression, but being in active chemotherapy, having low white-cell or low lymphocyte counts and/or taking immune-suppressive agents (such as prednisone) are all associated with immune suppression and increased risk of infection.

“We don’t know all the details on this yet but if you’ve been told you’re immunosuppressed by your provider, then you should be extra cautious,” he said.

What data do we have on how the coronavirus affects cancer patients?
Not a lot, Lyman said.

“But there was an early study from China published in a major medical journal, The Lancet, that shows both current and former cancer patients are at greater risk from COVID-19.”

Published mid-February, the study looked at 2,007 cases of hospitalized COVID-19 patients from 575 hospitals in China. Out of that group, they found 18 patients with a history of cancer they could track — some currently in treatment, some years out. Nearly half of those patients had a higher risk of “severe events” (defined as admission to the ICU, the need for ventilation or death).

“We found that patients with cancer might have a higher risk of COVID-19 than individuals without cancer,” the study authors wrote. “Additionally, we showed that patients with cancer had poorer outcomes from COVID-19, providing a timely reminder to physicians that more intensive attention should be paid to patients with cancer, in case of rapid deterioration.”

Pergam acknowledged the study, but said it was hard to make assumptions based on just 18 patients. Also, it was a mixed group of survivors and current patients with different cancers and a variety of therapies. Some of them smoked and/or had other health issues like high blood pressure, diabetes or COPD, all of which make people more susceptible to infection.

“The message that’s very clear,” Pergam said, “is that those who have comorbidities are at an increased risk from this infection. We have a lot of concerns both from this paper and another one that suggest there are increased rates of major complications, including the need for ICU, intubation and death in cancer patients — as many are double and triple hits. They not only have cancer but respiratory, cardiac or other organ dysfunction, as well.”

People over the age of 70 also face more of a risk. The fatality rate is nearly 15% for people 80 and over (more here on who exactly is getting sick). Pergam said that when elderly people don’t do well with a virus, it’s often “a litmus test of sorts” for infections that might cause more complications in immunosuppressed patients. 

“Immunosuppressed and cancer patients should be extra cautious and treat this like a really bad flu season,” he said.

Should I cancel my treatment or follow-up appointments?  
Experts at SCCA, Fred Hutch’s clinical care partner, said cancer patients with scheduled appointments should keep them, unless they’re experiencing coronavirus symptoms.

The facility is currently screening everyone for respiratory symptoms. Those with symptoms are asked to wear a mask, which decreases the spread of viruses and bacteria.  

More advice for SCCA cancer patients can be found here. The American Cancer Society offers this guidance for cancer  patients with questions about COVID-19.

What should I do if I have symptoms?
If you develop symptoms of coronavirus (such as high fever, a deep dry cough, fatigue and shortness of breath), call your provider.

“What’s really important is if you get sick, let someone know,” Pergam said. “Call your provider and tell them if you have respiratory symptoms. Sometimes, they may advise you to stay home. If you’re feeling that you need to go to an ER because you’re feeling very ill, call ahead and let them know you have respiratory symptoms. They can provide guidelines and protect you when you walk in the door.”

And if the symptoms are minor, Pergam said, just stay home. Remember, it’s still flu and cold season.

“We don’t want to overburden the health care system with the worried well,” he said. “It’s a balance. We want to be prepared but also make sure people don’t panic. If we panic, there will be a run on the health care system.”

Testing for COVID-19 in Seattle has been greatly aided by the UW Medicine Clinical Virology Lab, which started testing people immediately after the U.S. Food and Drug Administration gave its OK. The lab anticipates it will soon be able to test more than 1,000 samples a day; researchers said eventually they will be able to test 4,000 and perhaps even 5,000 samples a day.

Currently, a doctor’s recommendation is the only requirement for the COVID-19 test.

What if a family member develops symptoms?  
“Your family is important and you don’t want to avoid them, but if someone in your household gets sick, use some social distancing,” Pergam said. “Wear gloves, have them sleep in a different room if you can, make sure you wipe down areas with some sort of bleach wipes and keep washing your hands regularly. That’s really important.”  

It’s also crucial not to bring a sick family member into your cancer treatment center.

“We need less people who are ill, not more,” Pergam said. “You don’t want someone going in with you even if they only have minor symptoms.”

Finally, he said it’s important to bring just one caregiver with you to treatment, not your entire family.

Should cancer patients (and survivors) avoid public transportation and events?
Pergam said people currently in treatment, if at all possible, should avoid taking public buses or trains. But he also acknowledged not every patient can afford Lyft or Uber or some other rideshare service.

“Talk to your care team about what options exist to support you getting there without taking public transportation,” Pergam said. “Some hospital systems have services set up for patients.”

If you have no choice but to use the bus or a train, take precautions and distance yourself from others.

“Protect yourself,” Pergam said. “Sit in the back of the bus or other areas with less exposures and if you see someone who seems ill, coughing, move away.”

Pergam said cancer patients a few years out of treatment “should be OK,” but whenever possible should also avoid crowded buses or trains.

“If you have to get on a bus, practice distancing,” he said. “Or stay home if you can. It increases your risk when you are in public spaces.”

As for other public gathering places, Pergam again advised caution. Instead of going out to a movie, watch something at home instead, he said. Get take-out or delivery from your favorite restaurant instead of showing up in person. Or cook at home. Many grocery stores offer delivery service. You can even ask your pastor if they can set up a computer so you can go to “virtual church.”

“This doesn’t mean you have to be a hermit, just limit close interactions, particularly in public spaces,” he said.

Are there ways to keep your immune system strong?
Both Lyman and Pergam stressed the importance of sleep in recharging the immune system.

“Sleep deprivation is one of the most potent ways of suppressing the immune system,” Lyman said. “Everybody has a different threshold but if you’re not getting a minimum of six or seven or, ideally, eight hours of sleep a night, there’s demonstrable scientific evidence that the immune system may be compromised.”

Also helpful: exercise, preferably something aerobic, like walking or jogging, that will get the heart pumping.

“Take a walk outside in the fresh air; that’s really good for you,” said Pergam, who’s also at risk as a kidney transplant recipient and cancer survivor. “Right now, that’s better than going to the gym.”

Another step to staying strong and healthy through the COVID-19 crisis: getting good nutrition.

“It appears that 70%-80% of our immune system is in the gastrointestinal tract,” Lyman said. “And [it is] directly impacted by the food we eat and the microbes that thrive in our gut. A balanced diet, eating fruits and vegetables, is very important.”

As is staying up to date on vaccinations, including the flu vaccine; avoiding smoke or smoking (cancer patients can get smoking-cessation help here) and making sure you have any and all other medical conditions (high blood pressure, lung disease, diabetes, etc.) under control, he said.

Stress also appears to be bad for the immune system. Although both researchers admitted it’s not easy to stay relaxed at a time like this.  

“Some things we cannot control,” said Lyman, whose age and health issues put him at risk, as well. “But you can control what you eat, whether you exercise and how much you sleep. These are definitely the things I’m doing.”

Monday, February 24, 2020

Crispr Technology Used in First Human Study

Crispr technology has been around for several years. Essentially, Crispr is a “cut-and-paste” tool used in gene editing – especially useful when scientists have pinpointed specific disease-causing genes. 

Fast forward to a very small study (3 people) released this week from the University of Pennsylvania and Stanford research teams that has cleared the first hurdle related to safety. 

These cancer patients received their own genetically modified T cells – to make them more powerful hunters and killers of cancer cells. The T-cells were bathed in a special growing solution until they had increased to about a 100 million at which time they were infused back into the patient. The biggest concern was that once these cells were released back into the body, would they be too hyper-active, that is, trigger a massive deadly immune response. Instead, these gene edited immune cells lived and appeared to fit right back into the body’s immune system.

Results have been mixed: of the three patients, one woman with multiple myeloma died seven months after receiving the treatment and the other two, another with multiple myeloma and a man with sarcoma, have had their cancers return. A few other trials are getting underway. Overall, this promises to be an invaluable tool perhaps used in conjunction with other therapies. 

To read more about this particular research, follow this link

To read more about Crispr technology, read this article.

Friday, February 21, 2020

Ovarian Cancer Thriver Seminar: The Julie Fund

A shout out to Betsy who sent me this information today about this seminar scheduled for April 4, 2020 from 8:30am to 2:00pm at the Wyndham Boston Beacon Hill.

The seminar is FREE to women and their caregivers and includes lunch.

The topics, presented by the gyn/onc doctors from MGH - who I can't speak highly enough about - cover biology, surgery, personalized medicine, immunotherapy, advances in management of disease recurrence/clinical trials and other relevant and interesting topics.

Of course, there will also be time for Q&A. Parking is only $5 for all attendees with validation.

To register for this free event, follow this link.

Monday, February 17, 2020

Genetic Links to Ovarian Cancer

I stumbled across this interesting and informative   website during a recent on-line search. Published by the National Institutes of Health (NIH)/Genetics Home Reference section, the article gives a basic overview of the origins, frequency, causes, inheritance patterns, diagnosis and treatment options etc. of ovarian cancer.

What makes this website unique are the sidebars associated with each section providing informational links. For example, one link connects to a new page explaining why some genetic conditions are found more often in particular ethnic groups. There were also over 20 additional links to further resources.

To find out more about this website, follow this link.


Monday, February 10, 2020

Endometriosis Appears to Have No Effect on Ovarian Cancer Outcomes, But More Research Needed, Study Says

This was a small study that examined the link between endometriosis and ovarian cancer. It appeared on the Clearity Foundation website.


Endometriosis does not seem to significantly affect ovarian cancer prognosis and survival in patients of reproductive age, a small study suggests.

However, more research is needed to identify factors associated with the progression of endometriosis to cancer and also to identify women who would benefit from more aggressive endometriosis treatment.
Ovarian cancer risk factors include a number of variables, such as age, weight, menstrual history, pregnancy history, smoking, inheritance of certain mutations, and benign gynecological conditions, including endometriosis.
Specific risk incidences vary depending on the type of cancer, but according to a study published in The Lancet, overall, endometriosis was estimated to increase ovarian cancer risk by nearly 50%.
However, it remains unclear whether there is a meaningful clinical difference between ovarian cancer in a person with endometriosis (endometriosis-associated ovarian carcinoma, EAOC) and the same type of cancer in a person without endometriosis (non-endometriosis-associated ovarian cancer, non-EAOC).
This is of particular interest in younger individuals, since age itself is independently associated with different ovarian cancer prognoses (younger age seems to be a prognostic factor for improved survival). Moreover, endometriosis is most common in people between 25 and 35 years old, according to the authors of the study.
The researchers analyzed medical records of people 40 years of age or younger who were treated for ovarian cancer at the Peking Union Medical College Hospital in China between 2006 and 2017.
Specifically, the researchers compared cases of EAOC, comprising either ovarian endometrioid carcinoma (OEC) or ovarian clear cell carcinoma (OCCC), with non-EAOC cases.
The studied group included 94 people with ovarian cancer — 40 with endometriosis (EAOC group) and 54 without (non-EAOC group). All of them were treated surgically; most also received chemotherapy.
In terms of outcomes, “a total of 77 (81.9%) patients were alive with no evidence of residual tumour at the time of the last visit, 4 (4.3%) patients were alive with the recorded disease, and 13 (13.8%) were dead of the recorded disease. There were no obvious differences between the two groups in terms of these variables,” the researchers wrote.
Further statistical analyses demonstrated that endometriosis was not significantly associated with an altered risk of disease progression or death. Another factor was, most notably, whether there was residual disease after initial treatment.
On the whole, there were “no differences in clinicopathological [disease-causing] or prognostic features,” between ovarian cancer in people with or without endometriosis, according to the researchers.
There was one exception: painful periods, or dysmenorrhea, which was reported by a much higher percentage of people with endometriosis than without (45% vs. 3.7%). But, the researchers said, this “is a typical symptom of patients with endometriosis,” and, as a result, most likely isn’t tied to the ovarian cancer.
This was a fairly small study of patients treated at a single center, so the results shouldn’t be generalized yet — there is still a need for further research to understand both endometriosis and ovarian cancer, and the intersection of both diseases.
“Endometriosis is not an independent prognostic predictor in patients with OCCC and OEC when age is confined to under 40 years. It is premature to consider ovarian cancers arising from endometriosis as a distinct entity,” the researchers concluded.
“This analysis also suggests that reproductive-aged women with early-stage OEC and OCCC should be offered conservative treatment,” they said. “Future research should focus on the identification of factors that are associated with the malignant transformation of endometriosis and how to identify women for whom more definitive endometriosis treatment would be appropriate to prevent ovarian cancer.”



Monday, February 3, 2020

Weekly Dose-Dense Chemo Not Recommended in First-Line Epithelial Ovarian Cancer Treatment

This article, by Matthew Fowler was orginally published published by the Clearity Foundation.

Weekly dose-dense paclitaxel as a frontline treatment for patients with epithelial ovarian cancer was not found to significantly improve progression-free survival (PFS) compared to the standard 3-weekly chemotherapy, according to results from the ICON8 study published in The Lancet.1

The results of the ICON8 trial show that it is feasible to deliver weekly dose-dense paclitaxel in combination with either 3-weekly or weekly carboplatin in the first-line treatment of high-risk ovarian cancer,” Andrew Clamp, PhD, of The Christie NHS Foundation Trust, and colleagues wrote. “However, neither of these regimens is associated with an improvement in survival outcomes compared with standard 3-weekly carboplatin–paclitaxel treatment in the predominantly European population treated on this trial.”
The phase III ICON8 trial randomly assigned predominantly European women with newly diagnosed International Federation of Gynecology and Obstetrics stage IC–IV epithelial ovarian cancer to 3 groups.
1,566 women from June 2011 to November 2014 were recruited for treatment as a part of the ICON8 study. In this 3 arm trial, patients in group 1 received carboplatin AUC5 or AUC6 and 175 mg/m2paclitaxel once every 3 weeks; patients in group 2 received carboplatin as in group 1 and dose-fractionated 80 mg/m2paclitaxel weekly; and patients in group 3 received carboplatin AUC2 and 80 mg/m2paclitaxel weekly.
Primary endpoints for the study were PFS and overall survival (OS). Both groups 2 and 3 were individually compared with group 1 (control group) to determine primary endpoint results. Secondary endpoints included safety, quality of life, and health economics.
The median PFS was 17.7 months for the control group (group 1), 20.8 months in group 2, and 21.0 months in group 3.
After a 9-month cross-analysis of the results, the study determined there was no significant difference between the groups with regards to quality of life. As for toxic effects, both group 2 and group 3 treatments were associated with increased instances of grade 3 or higher toxic effects, but these effects were deemed “uncomplicated.”
“Although most patients were able to complete 6 chemotherapy cycles, both weekly treatments were associated with more treatment modifications and a higher incidence of grade 3 or higher toxic effects,” stated in a press issued by the European Society for Medical Oncology (ESMO). “Although grade 3 or 4 toxic effects increased with weekly treatment, these effects were predominantly uncomplicated.”2
The population included both patients who underwent primary cytoreductive surgery (IPS) and those who chose delayed primary cytoreductive surgery (DPS) options. The results from each of these populations also stood as a secondary point of intrigue for the researchers. No significant relationship between surgical decision and treatment schedule was detected.
The ICON8 study was a large, international process including a variety of different patient variables, including demographic, surgery selection and treatment schedule. The study also yielded an 85% chemotherapy completion rate, allowing for valuable results to be drawn from the process. Even more, although the results did not yield a positive development for European women, the weekly-dose treatment can still be an option for Japanese women with epithelial ovarian cancer, who previously demonstrated a superior benefit to the regimen.2
“Weekly dose-dense paclitaxel treatment could still be considered as a first-line treatment option for Japanese women with epithelial ovarian cancer,” said in an ESMO press release. “But the weekly dose-dense paclitaxel should not be recommended as a component of first-line epithelial ovarian cancer treatment for women of non-Japanese ethnic origin.”
Two further studies have been done analyzing weekly dose-dense chemotherapy treatment within the lifetime of the ICON8 study, but the researchers recommend even more investigation into this treatment among different ethnic groups.
This article was published by Cancer Network.

Monday, January 27, 2020

Niraparib in Patients With Newly Diagnosed Ovarian Cancer

This article appeared in the New England Journal of Medicine (NEJM). The conclusion showed that women with newly diagnosed OC who were not platinum resistant had a longer progression free survival - regardless of their BRCA status - than those on placebo.

Here's the abstract to the study:

Abstract

BACKGROUND

Niraparib, an inhibitor of poly(adenosine diphosphate [ADP]–ribose) polymerase (PARP), has been associated with significantly increased progression-free survival among patients with recurrent ovarian cancer after platinum-based chemotherapy, regardless of the presence or absence of BRCA mutations. The efficacy of niraparib in patients with newly diagnosed advanced ovarian cancer after a response to first-line platinum-based chemotherapy is unknown.

METHODS

In this randomized, double-blind, phase 3 trial, we randomly assigned patients with newly diagnosed advanced ovarian cancer in a 2:1 ratio to receive niraparib or placebo once daily after a response to platinum-based chemotherapy. The primary end point was progression-free survival in patients who had tumors with homologous-recombination deficiency and in those in the overall population, as determined on hierarchical testing. A prespecified interim analysis for overall survival was conducted at the time of the primary analysis of progression-free survival.

RESULTS

Of the 733 patients who underwent randomization, 373 (50.9%) had tumors with homologous-recombination deficiency. Among the patients in this category, the median progression-free survival was significantly longer in the niraparib group than in the placebo group (21.9 months vs. 10.4 months; hazard ratio for disease progression or death, 0.43; 95% confidence interval [CI], 0.31 to 0.59; P<0.001). In the overall population, the corresponding progression-free survival was 13.8 months and 8.2 months (hazard ratio, 0.62; 95% CI, 0.50 to 0.76; P<0.001). At the 24-month interim analysis, the rate of overall survival was 84% in the niraparib group and 77% in the placebo group (hazard ratio, 0.70; 95% CI, 0.44 to 1.11). The most common adverse events of grade 3 or higher were anemia (in 31.0% of the patients), thrombocytopenia (in 28.7%), and neutropenia (in 12.8%). No treatment-related deaths occurred.

CONCLUSIONS

Among patients with newly diagnosed advanced ovarian cancer who had a response to platinum-based chemotherapy, those who received niraparib had significantly longer progression-free survival than those who received placebo, regardless of the presence or absence of homologous-recombination deficiency. (Funded by GlaxoSmithKline; PRIMA/ENGOT-OV26/GOG-3012 ClinicalTrials.gov number, NCT02655016. opens in new tab.)

Monday, January 20, 2020

Where Does Ovarian Cancer Originate?

It used to be thought that the ovaries were the origin of high grade serous ovarian cancer - certainly the name of the cancer suggests its origins. However research at multiple health centers points to another source: the fallopian tubes.

The consortium of centers included Johns Hopkins University, Toronto University Health Network, Yale University and Memorial Sloan-Kettering Cancer Center. Using molecular profiling, researchers were able to show that the cellular origin of the cancer was most closely aligned to the fallopian tube region rather than the ovaries. This is significant because in high-risk women, currently the ovaries and the fallopian tubes are generally removed. The ability to preserve the ovaries could reduce the risk of heart disease, osteoporosis and other diseases associated with ovarian resection.

To read more about this study, follow this link.  



Monday, January 13, 2020

SCIENTISTS DEVELOP PROMISING DRUG FOR TREATING OVARIAN AND PANCREATIC CANCERS

As we know, ovarian and pancreatic cancer are very difficult to treat because by the time they are diagnosed, they are often late stage.

Houston Methodist and MD Anderson have filed a joint patent for a new monoclonal antibody. (Monoclonal antibodies are cloned from a single parent cell and can mimic a variety of immune functions in cancer treatment.)

MFAP5, a protein secreted in high levels in both these cancers, is a marker of poorer survival rates. Researchers have developed a monoclonal antibody that blocks MFAP5 found in the areas surrounding the tumor cells that feed and support the tumor. Blocking MFAP5 effectively starves the tumor since MFAP5 is associated with sustaining the tumor with nutrients. Without this, these cells are more sensitive to chemo. Phase 1 clinical trials will hopefully start in 2020.

You can read more about this by following this link

Monday, January 6, 2020

OUT OF MANY OVARIAN PRECANCEROUS LESIONS, ONE BECOMES CANCER

Turns out there is not just one smoking gun in pre-cancerous lesions that lead to ovarian cancer. Instead, researchers at Johns Hopkins discovered that some women can have multiple pre-cancerous lesions which are not driven by one specific set of mutations. Many of these pre-cancerous lesions simply remain dormant. Additionally, it can take decades before some of these lesions develop into OC.

Now researchers need to determine which of these precursors will go on to become ovarian cancers as well as how to detect them.

This article first appeared on the Johns Hopkins Institute for Clinical and Translational Research website.

Some deadly ovarian cancers arise from lesions genetically unrelated to each other.
In a novel study of cancer genetics using fallopian tube tissue from 15 women, researchers at the Johns Hopkins Kimmel Cancer Center say they have found evidence that the most common and lethal type of ovarian cancer arises not from a uniform group of precancerous lesions, but from individual growths found in groups genetically unrelated to each other.
If confirmed in further studies, the discovery, described in the May issue of the Journal of Pathology, would go a long way towards upending a longstanding cancer dogma dictating that cancer steadily progresses from any and all precancerous lesions, and could lead to new ways to fight this deadly disease.
“We’re finding that it’s not a straight line progress from precancerous lesions to cancer in these tumors,” says Ren-Chin Wu, Ph.D., first author and associate professor at Chang Gung University School of Medicine in Taiwan  “If we can find a way to eradicate just the ones that progress, and distinguish them from those that maintain dormancy forever, we likely can make treatments more effective and save more women’s lives,” he adds.Up to 70 percent of all ovarian cancers are so-called high-grade serous carcinomas (HGSCs) and account for the vast majority of the 14,000 women who die of ovarian cancer each year in the U.S., explains study leader Tian-Li Wang, Ph.D., director of the Molecular Genetics Laboratory of Female Reproductive Cancer and professor of pathology, oncology, and gynecology and obstetrics at the Johns Hopkins University School of Medicine. “This cancer is incredibly hard to beat because it’s usually diagnosed at a late stage since earlier stages have few to no symptoms,” says Wang.
Recent studies, Wang notes, suggest that these ovarian cancers arise from precancerous lesions in the fallopian tubes, a pair of organs that carry eggs from the ovaries to the uterus. But how this progression proceeds from precancerous lesions to active cancer has been unclear.
To investigate this biological path, Wang and her colleagues, including first author Wu, studied fallopian tube and ovarian tissue from 15 women seen at the Johns Hopkins Hospital.
Eleven of these women had no evidence of cancer when these organs were removed prophylactically to reduce their cancer risk. The other four already were diagnosed with HGSCs.
Using high-powered microscopes, the researchers first identified a variety of different precancerous lesions clustered in three groups according to pathological diagnostic markers on the women’s fallopian tubes. They then removed cells from these lesions using a technique called laser capture microdissection to determine how fast the cells in each of the lesions were dividing, and to enable analysis of their genetic mutations.
The researchers say they found these precancerous lesions were in a variety of stages of activity. Some were dormant and not actively proliferating. Others were proliferating but weren’t yet cancer.
Overall, their genetic analyses on 24 lesions in 11 women identified mutations in 12 different cancer-related genes. Surprisingly, they say, one cancer-free woman had multiple precursor tubal lesions and each appeared to be driven by different sets of mutations, suggesting that they weren’t derived from a common primary lesion and had each arisen independently.
In three of the four women with active ovarian cancer, the researchers were able to link their tumors genetically with a primary precursor lesion on their fallopian tubes. However, for one of the women, the researchers couldn’t find a genetic link with co-existing precancerous lesions—reinforcing the idea that while many precancerous lesions arise in women at risk for ovarian cancer, only some progress to active cancers.
Further experiments that modeled mutation progression in these tumors suggest that it may take decades for tumors to progress from precancerous lesions to HGSCs, says co-lead author Cristian Tomasetti, Ph.D., associate professor of oncology. This potentially offers a large window of time to intervene before cancers become advanced and difficult to treat, but he says researchers will first need to find ways to detect cancer precursors that are dangerous from those unlikely to cause any harm.”
“Unlike prior studies that analyzed precursors and cancers from the same patients, this study includes many precursor lesions without cancer present, and provides a unique molecular landscape of ovarian cancer precursors in place before ovarian cancer actually develops,” says Ie-Ming Shih, M.D., Ph.D., study co-author, Richard W. TeLinde Distinguished Professor, Department of Gynecology and Obstetrics and co-director of the Johns Hopkins Kimmel Cancer Center Women’s Malignancies Program.
Other Johns Hopkins researchers who participated in this study include Shiou-Fu Lin, Ming Zhang, Tiffany Chu, Robert J. Kurman, Russell Vang and Kenneth Kinzler.
This study was supported by funding from the US Department of Defense CDMRP (grant number W81XWH-11-2-0230); the National Institutes of Health/National Cancer Institute (grant numbers UO1CA200469, RO1CA215483, P50CA228991, P30CA006973); the Honorable Tina Brozman Foundation, Ovarian Cancer Research Fund Alliance, Roseman Foundation; Teal Award, and Gray Foundation; the John Templeton Foundation; the Richard W. TeLinde Endowment from the Johns Hopkins University.