Thinking Beyond Survival – Cerebrovascular Complications of Cancer

Babak Navi_headshotBabak B. Navi, MD, MS
Stroke Center Director
Assistant Professor of Neurology
Weill Cornell Medicine | NewYork-Presbyterian

Over the past decade, there has been tremendous progress in cancer therapeutics. This includes targeted agents that act on specific receptors in cancer cells, immunotherapy which harnesses the body’s immune system to attack cancer cells, and personalized medicine whereby oncologists use different combinations of cancer drugs to optimize the chance of success based on the molecular profile of the tumor. These amazing scientific advances have led to prolonged survival for people with several cancer types, and it is possible that in the not-too-distant future, cancer will become more of a chronic disease with periodic flare-ups similar to what has occurred with diabetes and HIV. However, with this paradigm shift, long-term quality of life and well-being has become more important, and preventing diseases and complications that can affect these factors is paramount.

Stroke is the leading cause of disability in the United States. In addition, in many parts of the world, including Asia, it is the leading cause of death. In the United States alone, 800,000 people each year suffer stroke and this number is expected to rise as average life expectancy increases. Many factors can increase a person’s risk for stroke including age, hypertension, diabetes, high cholesterol, obesity, and smoking. Besides these traditional stroke risk factors, we now know that cancer and its treatments also increase the risk of stroke. In particular, patients with certain types of cancer, such as lung, pancreatic, and bladder cancers, as well as patients with metastatic disease, tend to have the highest risk. For instance, elderly patients with newly-diagnosed lung cancer face roughly an 8% risk of stroke in the first year after being diagnosed with cancer. In addition, cancer patients’ stroke risk varies with time and is highest in the first 3 months after diagnosis, when some cancer patients face up to a 3-fold higher risk of stroke than usual. It also turns out that certain necessary and potentially life-saving cancer treatments, including some forms of chemotherapy and radiation, can increase stroke risk.

At the moment, the exact reasons why cancer patients face a heightened risk of stroke are unclear. It is well known that circulating cancer cells can alter individuals’ clotting systems to promote clot formation but exactly how they do this is uncertain. Furthermore, doctors know that certain chemotherapy and radiotherapy treatments can damage blood vessels, but once again, the exact mechanisms underlying these processes are poorly understood.

At Weill Cornell Medicine and NewYork-Presbyterian, my team is actively working to determine what the exact risks of stroke are in people with newly diagnosed cancer, what clinical factors and biomarkers in blood can help doctors identify high-risk patients, and what the optimal strategies are to prevent and treat stroke in cancer patients. One particular study that we are currently enrolling into is entitled MOST-Cancer. This study uses cutting-edge ultrasound and blood tests to evaluate the predictors and mechanisms of stroke in people with cancer. If you or a loved one has cancer and are interested in learning more about these studies, please email our team at stroketrials@med.cornell.edu or call 212-746-6757.

May is National Stroke Awareness Month. The main intent of this campaign is to raise awareness about the symptoms and signs of stroke and to educate the public to call 911 if they suspect stroke. The most popular campaign is FAST, which stands for Face, Arm, Speech, and Time – Time to call 911.

If you or a companion develops unexplained facial asymmetry, arm weakness, or speech changes, you should call 911 immediately so that an ambulance is activated to provide rapid delivery to the closest stroke center. This is imperative as there are medicines and surgical procedures that have been proven to improve outcomes after stroke but these are only effective in the first few hours after stroke onset. Therefore, if stroke is suspected, do not hesitate, call 911, as it could be life saving!

Furthermore, I recommend that cancer patients have a frank discussion with their doctors about their individual risks for stroke and other cardiovascular diseases, as well as potential strategies to reduce their risks through medicines and lifestyle modifications.

We’ve made great strides in oncological care so that patients routinely get cured or live many years with their disease. Therefore, it is now time that we turn our attention to long-term quality of life, and in particular, to preventing stroke and the other secondary complications of cancer.

Stroke_BE FAST SIGN NEW

AACR 2017: Organoids & Neuroendocrine Prostate Cancer

nepc organoidsAt the American Association for Cancer Research (AACR) 2017 Annual Meeting, researchers and physicians from Weill Cornell Medicine and NewYork-Presbyterian presented updates on the use of organoids in neuroendocrine prostate cancer.

Dr. Mark Rubin, Director of the Englander Institute for Precision Medicine, spoke about functional testing to use organoids to determine drug sensitivity or resistance. We have previously shown the power of sophisticated genomic analysis, but the information obtained by extracting DNA or RNA from a sample is fixed in time. Organoids allow for testing of many different types of tumor processes or properties, including the examination of important cellular pathways and treatment sensitivity and resistance. For example, we can test certain drugs or drug combinations to see how well they work or don’t work on a specific tumor or tumor type. For instance, in a clinical trial to examine the response of men with neuroendocrine prostate cancer (NEPC) to a drug called alisertib, we took tissue biopsies before the patients started treatment. From these tissues, we developed organoids. We then used these organoids to test response to alisertib. Treating the organoids with the drug showed the same results as in the patients (one with an exceptional response and the other with treatment resistance).

LoredanaLoredana Puca, PhD, a postdoctoral associate mentored by Drs. Beltran and Rubin, highlighted the similarities in the microscopic anatomy of the cells and tissues (also referred to as the histology) between the organoids and the original biopsy tissue at the 2017 AACR meeting. Additionally, she presented results showing how the tumor’s DNA (also referred to as the genomics), as well as way the cells encode RNA to create proteins (also referred to as transcriptomics) – both of which are integral to the tumor’s ability to grow and mutate – are similar between organoids and biopsy. This sets the stage to utilize organoids for diagnostic and treatment testing in the hopes that the results will be more analogous to human tumors than traditional cell-line work.

Learn more about this research by visiting Dr. Beltran’s lab website. For additional information about organoids and how they work check out this recent blog post.

2017 Genitourinary Cancers Symposium

gu_symposium_2017_img_3054The 2017 Genitourinary (GU) Cancer Symposium kicked off on February 16th in Orlando, Florida, bringing together more than 3,000 attendees from all over the world. At this annual conference, clinicians from a wide range of disciplines treating people with prostate cancer, kidney cancer, bladder cancer, and testicular cancer come together to hear from experts on the latest scientific discoveries and how they impact clinical care for patients.

The Weill Cornell Medicine (WCM) and NewYork-Presbyterian (NYP) GU Oncology team is down in the Sunshine State highlighting the cutting-edge research and patient care that has been taking place back on campus in New York City.

twitter-iconTeam member Dr. Bishoy Faltas was selected by the conference to be a “Featured Voice” on Twitter, so be sure to follow him (@DrFaltas) for updates in real-time. Dr. Scott Tagawa (@DrScottTagawa) is now on Twitter too and also tweeting live from the symposium. The official conference hashtag is #GU17.

Some #GU17 highlights

Day 1 – The initial session focused on active surveillance for prostate cancer, including using both imaging as well as tissue biomarkers to help select optimal patients for surveillance versus those who should undergo surgery or radiation. A subsequent session focused on prostate cancer that progresses despite therapy and the pathways of resistance that can develop. This included a discussion of prostate cancer subtypes that become independent of the androgen-receptor (hormonal) pathway, including aggressive variant and neuroendocrine prostate cancer (NEPC). Neuroendocrine prostate cancer is one of the most aggressive and treatment-resistant types of prostate cancer that most often evolves from prior hormonal therapy.

beltran-attard
Dr. Misha Beltran and Dr. Gerhardt Attard are two of the primary investigators for the 2016-2018 Movember Foundation-PCF Challenge Award

Dr. Gerhardt Attard at the Institute of Cancer Research in London, gave a great talk on the value of circulating tumor DNA in prostate cancer. He spoke about the collaborative grant from the Movember Foundation and the Prostate Cancer Foundation (PCF) that he, Dr. Misha Beltran and others have used to develop signature ways to confirm neuroendocrine prostate cancer with a blood test. An additional collaborative grant will allow optimization of this technology across a larger number of centers. Learn more about this prestigious Movember Foundation-PCF Challenge Award and how we’re using genomic characterization of tumors in less invasive ways in order to bring precision medicine – or narrowly tailored, personalized treatment – to more patients.

evi_taxynergy_gu-symposium_jpgDr. Evi Giannakakou explains to a crowd of physician-scientists results from our TAXYNERGY clinical trial showing additional evidence of using cancer cells circulating in the blood, also referred to as circulating tumor cells or CTCs, as a primary biomarker for chemotherapy response. This research validated prior work regarding the mechanism of action of chemotherapy in prostate cancer and demonstrates that using a simple blood draw, within one week of first chemotherapy treatment, we’re able to determine whether men with metastatic prostate cancer have a higher chance of responding. In the future, this might spare men from additional treatment (with associated side effects) with a drug that has a lower chance of working. For additional background information on this research, check out our prior in-depth blog post on the topic.

jok9106Dr. Josephine Kang, a radiation oncologist at WCM/NYP, presented a poster on Stereotactic Body Radiotherapy (SBRT), which is an emerging treatment modality with excellent control rates for low- and intermediate-risk prostate cancer. The role of SBRT for high-risk prostate cancer has not been studied as closely, but this trial showed encouraging results for those with high-risk disease. These results are very encouraging, as the treatment can be completed in 5 treatments. Additionally, this data longitudinally followed men treated with this modality for 7 years, and it appears to be a safe and effective treatment for high-risk prostate carcinoma. SBRT may be a good treatment alternative particularly for patients unable to undergo hormonal therapy (androgen receptor therapy/ADT) or unwilling to receive standard 8-9 week radiation therapy. More research is ongoing. Learn more about our open clinical trial using this modality. Another study will soon be opening.

In the oral abstract session, data was presented from a cooperative group trial that the older chemotherapy drug mitoxantrone should not be used immediately following surgery. Assays from biopsy material can separate different classes of prostate cancer with different risk for inferior outcomes. Blood biomarkers utilizing circulating tumor cells appear to be prognostic and potentially predictive of response to certain drugs. We are currently participating in a study to validate this data across multiple institutions and technology platforms.

In the keynote lecture, Dr. Charles Drake who recently joined the NYP family at Columbia discussed the current status and future directions of immunotherapy for prostate cancer.

Stay tuned for additional updates throughout the symposium!