Tuesday, April 28, 2015

Clinical trial will use mice to guide treatment choices in soft-tissue sarcoma

Mice in Champions lab.
By Suzie Siegel

Cancer treatments have been tested on mice for years. Now a new technology uses mice to determine which treatments may best fight an individual patient’s sarcoma.

The TumorGraft technology “provides options for patients in difficult situations when, often as doctors, we are not sure how to treat people,” said medical oncologist Justin Stebbing, a professor of cancer medicine and oncology at London’s Imperial College. “In doing so, it advances the frontiers of science and medicine, but in a practical way, giving clinicians information on treatment choices – what is likely to work, and as importantly, what is likely to not work.”

Champions Oncology soon hopes to open a phase II clinical trial of its TumorGrafts for patients with soft-tissue sarcoma, Chief Medical Officer Angela Davies said. About 200 people whose sarcoma has recurred or metastasized will be enrolled at sarcoma centers across the United States and Canada.

“We have plans for clinical trials in many different tumor types,” she said. “We currently are partnering with academic centers conducting a clinical trial in breast cancer and advanced non-small-cell lung cancer, with plans for a trial in head-and-neck cancer and colorectal cancer to start within the next 12 months.”

In the sarcoma trial, she said, patients will start standard treatments while waiting for results from the TumorGraft process, which can take 4-6 months. The trial will accept only patients who are expected to survive at least six months and who are healthy enough to undergo systemic therapy, such as chemo. If the initial treatment fails, the TumorGrafts may help a doctor choose which treatments to try next.

Until a clinical trial validates the process, a U.S. doctor can’t use it to justify delaying or changing treatment in a patient with advanced sarcoma, said Sujana Movva, a sarcoma medical oncologist at Fox Chase Cancer Center in Philadelphia.

Dr. Sujana Movva

Dr. Movva helped design the trial, which was discussed last fall at the annual meeting of the Connective Tissue Oncology Society in Berlin. Other physicians involved in the research were from Massachusetts General Hospital in Boston; University of Michigan, Ann Arbor; Oregon Health & Science University, Portland; Mount Sinai Hospital, New York; Rutgers Cancer Institute of New Jersey, New Brunswick; Johns Hopkins University, Baltimore; M.D. Anderson Cancer Center, Houston; Sarcoma Oncology Center, Santa Monica, Calif.; University of California, Los Angeles; and University of Pennsylvania, Philadelphia.  

Dr. Stebbing serves on Champions’ Scientific Advisory Committee, as does medical oncologist George Demetri, director of the Center for Sarcoma and Bone Oncology at Dana-Farber Cancer Institute in Boston.

Before surgery, patients can ask for a piece of their tumor and its surroundings to be saved for Champions. The fresh tissue will be implanted into one or more immunodeficient mice. If the graft grows, it will be divided again and implanted in more mice. Grafts also will be preserved for future testing.

These grafts are called patient-derived xenografts (PDX) or patient-derived tumor xenografts (PDTX).

“Champions can test chemotherapy, targeted agents, monoclonal antibodies and antiangiogenics as single agents or in combination,” said Dr. Davies, a medical oncologist. Immunotherapies cannot be tested now, but scientists are working on a mouse model with a humanized immune system engrafted.

“No model system is perfect,” Dr. Movva said, “but it is the best ‘in-vivo’ testing available so far.”

The Hackensack, N.J., company began testing different cancers in 2007, with the greatest number of tests in sarcoma, Dr. Davies said. “The rare and heterogeneous nature of sarcomas and the lack of well-defined treatment strategies make sarcoma well-suited to a personalized approach.”

More than 150 sarcoma patients have tried TumorGrafts, she said. “We managed to grow approximately 100 tumors. Currently, we have 60 successful mice models for sarcoma patients.” That translates into a 65-percent success rate for growing sarcomas in mice, she said, “and 67 percent of patients for whom a model was successfully developed decided to proceed with drug sensitivity testing in the model.”

Implantation costs about $2,000, she said. Testing one therapy costs an additional $2,500-$3,000, and the cost mounts as more therapies are tested. The upcoming clinical trial would be free to patients, however. A successful phase III trial could lead to insurance coverage for TumorGrafts.

Some sarcoma patients choose to do chemosensitivity or chemoresistance tests in which their cancer cells are grown in a Petri dish. TumorGrafts have an advantage because they preserve the biological characteristics of the original human tumor, Dr. Davies said.

“Previous work has shown that implanted tumors are able to spontaneously metastasize,” Dr. Movva said. “This suggests that there is interaction between the tumor and its microenvironment, which may therefore mimic the patient response better.”

Genetic testing can help people with certain cancers, but researchers have found few targeted therapies for people with sarcoma, she said. There are more than 70 subtypes of sarcoma, and chemo is less effective in many of them than in more common cancers.

“A recent paper by Stebbing et al. summarizes the clinical experience of 29 patients,” she said. “A few of these patients did have DNA sequencing of their tumors, which guided the physician in selection of drugs for the sensitivity testing.”

In 13 cases, treatments that worked in the mice also helped the patients. “A few patients derived benefit from drugs not normally prescribed for patients with soft-tissue sarcoma,” Dr. Movva said. Grafts failed for seven patients. Six died before data from the mice became available. In three cases, there was no correlation between the mice and the patients.

“It is unclear, therefore, if this approach (using a PDX model to direct care) is better than participating in a phase I trial, for example,” Dr. Movva said. Nevertheless, “patients should definitely consider participating in the TumorGraft clinical trial when it becomes available. This will help determine how well the PDX model predicts patient response and also help sort out some of the issues related to engraftment rates and feasibility.”

Other companies have developed PDX models for research. But Champions is the only one that sells them to individual patients, Dr. Davies said.

Tuesday, April 7, 2015

Treating Cancer with Viruses: What about Sarcoma?

Everyone is talking about the recent television reports on the use of viruses to treat cancer. The very general concept behind these treatments is that viruses can be adapted to kill cancerous cells while leaving healthy cells unaffected. This field of treatment is called Oncolytic Virotherapy. But if you've found your way to this article, you’re most likely thinking: “This is great… but what about sarcoma?”

The Sarcoma Alliance has put together this blog post as a way to provide a general overview of what oncolytic virotherapy is and how it is being studied in sarcoma. This is not a comprehensive look at all of the research that has been done pertaining to sarcoma, nor is it intended to reach conclusions about the future of oncolytic virotherapy as a sarcoma treatment. If you are interested in the studies listed below or want to learn more, we encourage you to speak with your or your loved one's treating sarcoma specialist.

While some research has been performed on sarcoma oncolytic virotherapy, there are still many challenges to developing these treatments. For example, viruses are attracted to cells with certain specific markers, so if a sarcoma cell does not have the marker for a specific virus, it won’t be attacked.  Additionally, many tumor cells mutate rapidly, which can lead to markers on only some of a tumor’s cells.  Conversely, if the sarcoma cells have the same type of cell markers that normal cells have, the virus might attack too many healthy cells. However, in spite of these potential complications, some preliminary studies on the efficacy of oncolytic virotherapy as a sarcoma treatment show promise. 

Several types of virotherapy have been studied in sarcomas, including:
  • Using viruses to directly attack the sarcoma.  Since viruses kill cells, if they can be genetically “tweaked” to attack only a sarcoma, this may work well.
  • Using vaccine viruses to attack the sarcoma. Vaccine viruses won’t cause disease, and since they have been used in vaccines they are known to be safe.  They may kill cancer cells directly, or have the immune system attack the cells.
  • Using viruses to make the immune system do a better job of attacking the sarcoma cell.  In some cases, the immune system cells that attack cancer cells remain in the body only a short time, thus cancer can recur.  Tying the immune response to a viral infection seems to keep these immune cells around far longer, thus preventing tumor recurrence.
  •  Developing drugs that attack cancer cells the same way that viruses attack cells.  These drugs mimic the ways that viruses kill cells, and thus may be able to be very specific for types of cancers, as well as “recognizing” mutated tumor cells.

Published studies using viruses in a laboratory setting, both in vitro and in vivo (in these cases, mouse models), show some positive results. Below is a brief overview of some of these most recent studies:
  • The measles vaccine virus has been studied and shown some promise in treating various subtypes of sarcoma.[i][ii]
  • The vaccina virus (similar to cowpox, used in the vaccine for smallpox) has also been studied in advanced extremity sarcoma, which reported some positive results.[iii]
  • Vesicular stomatitis virus was studied in metastatic Ewing's sarcoma mouse models, and was shown to have “selectively infected and killed EWS" and delayed tumor growth.”[iv]

Due to the nature of drug development and the potential for differing results as studies continue, it’s impossible to say whether any of these studies will lead to treatments, but we will continue to monitor these and other early developments in oncolytic virotherapies.

In addition to laboratory studies, a few clinical trials using oncolytic virotherapies for sarcoma have been completed or are underway. Below is a brief overview of some of the most recent studies:
  • A handful of clinical trials of Reovirus (Reolysin) have taken place, both for pediatric and adult sarcomas.[v][vi]While previous laboratory studies showed that Reolysin may be effective therapy in sarcomas,[vii] these clinical trials had mixed results. 
  • A trial looking at varicella zoster virus (chicken pox) in combination with immunotherapy is currently open for osteosarcoma patients who meet certain criteria.  For more information about this trial visit: https://www.clinicaltrials.gov/ct2/show/NCT01953900?term=sarcoma+virus&recr=Open&rank=8
  • A Phase II clinical trial that just opened in March testing pembrolizumab in both soft tissue sarcoma and bone sarcoma patients who meet certain criteria. While not a virotherapy, Pembrolizumab (Keytruda) is a promising drug that works similarly to virotherapies, and is already approved to treat melanoma.   For more information about this trial visit: https://clinicaltrials.gov/ct2/show/NCT02301039?term=pd1+and+sarcoma&rank=1

In summary, while some studies have shown promise, it is still unclear what the future holds for treating sarcomas with oncolytic virotherapies. We will continue to follow these and other potential treatments for this rare disease.

Monday, October 27, 2014

How the LA support group began


The late Suzanne Leider, co-founder of the Sarcoma Alliance, holds a poster at the first meeting. Dave Murphy is on the left.  In back, from left, are board member Marita Tullius and Brian and Kendra Krause. Can you help us identify the man and woman on the right?

By Dave Murphy

After my wife was diagnosed with leiomyosarcoma in 1998, I joined the Association of Cancer Online Resource’s LMS listserv. She died the next year, after her diagnosis was switched to malignant fibrous histiocytosis, and I joined ACOR’s Sarcoma list.

Also in 1999, Suzanne Leider founded the Sarcoma Alliance. I first met her online and then in person. I began to meet other patients and their families and friends.

The Orthopaedic Institute for Children in Los Angeles let us have a sarcoma support group in the spring of 2001. After two monthly meetings, sarcoma survivor Kirk Souder said we could meet at his office in Marina del Rey. We met several times there.

Kirk, who had a marketing company, had done some work for the Wellness Community (a cancer-support organization now called the Cancer Support Community. He contacted the organization to see if we could meet there. A local branch didn’t think we could get enough participants, but the South Bay Cities Wellness Community in Redondo Beach gave us a chance.

Sarcoma support group in Redondo Beach in 2003.
Our first meeting there was in 2002, the year I joined the Sarcoma Alliance's board of directors. The meeting attracted only three people, but by the end of 2003, we were well on our way to establishing a monthly group for support and information exchange. Networking is crucial for a rare cancer, especially in the days when so little information was online.

In 2004 I attended the American Association for Cancer Research  conference as part of the Scientist-Survivor Advocate Program (SSP). Dr. Karen Antman, a sarcoma specialist who is now dean of Boston University Medical School, was AACR president that year. Her address was: “Sarcomas, A Model for Research of Less Common Malignancies.”

In 2005 I was accepted to AACR’s SSP program again, and my scientist mentor was Dr. Lee Helman, a sarcoma specialist who now heads the Pediatric Oncology Branch of the National Cancer Institute. I came back from the AACR conferences able to tell sarcoma patients that research is being done to benefit them. I could give them hope.

I waited another 10 years before reapplying to AACR. After the 2014 conference, I reported back on how whole genomic sequencing was changing research.

Meanwhile, our L.A. area sarcoma support group continues to thrive. The last meeting, on Sept. 13, had eight people with sarcoma and eight caregivers or family members. The Sarcoma Alliance continues to promote in-person meetings with others. To quote our mission statement: “The Sarcoma Alliance strives to improve the lives of people affected by sarcoma through accurate diagnosis, improved access to care, guidance, education and support.”

Friday, September 19, 2014

A Parent's Story: Heather Patryas-Valentin (Baby Olivia)


Heather Patryas-Valentin is Olivia’s mom. Olivia was diagnosed with embroynal rhabdomyosarcoma at just six months of age.

 This is their story . . .
 I have two stepchildren - 14 and 12 years old, both boys. We have two Jack Russell dogs. Before Olivia’s diagnosis, we were your average family.

Diagnosis and Treatment...
My husband was changing Olivia's diaper and noticed a egg shaped lump on the right side, above her lady parts. Olivia was two months old at the time.




Were you immediately referred to a specialist?
No, we went to an overnight pediatrician and they referred us to Nemours Hospital because they were thinking it was a hernia and an ovary had popped out of place.

Nemours fixed the hernia the next day, but her ultrasound showed two normally placed ovaries. They thought maybe she had a third ovary.  

A month later after a follow-up ultrasound, they discovered this lump had moved to the left side. The doctors didn’t know what it was. Nemours planned to remove this lump but our insurance wouldn't cover it and we couldn't use Nemours Hospital anymore.

A month later we found another doctor affiliated with Arnold Palmer Hospital. He wanted to watch the lump to see if it grew or shrunk. By this time Olivia was four months old.

We followed the doctor’s suggestion and waited to watch the mystery lump.



 Olivia was now six months old and the time came to see if the lump grew or shrunk. The ultrasound showed that it had tripled in size in just two months.

The doctor decided to operate right away and take the growth out. He assured us this is common and not to worry. It wasn't even 24 hours after we were released from the hospital that the doctor wanted us back at his office to discuss something.

I wasn't thinking it was going to be anything bad, so I took Olivia by myself to that appointment. As soon as the doctor came in he asked where my husband was and I knew something was wrong. He said the tumor they removed was cancerous and it was the size of an orange.

That same day we met with our oncologist and that next week Olivia started chemotherapy. 




She has had three surgeries and just finished chemo this month.

Let’s Get Personal
I want parents to be aware of their babies bodies and how they act. It’s better to be overly cautious than to be too late.  

Being a first time mom, this has been really rough. I knew I was always meant to be a mom. Ask any women through pregnancy what they want and most common answer is a healthy baby. That's all I wanted and then when you find out your baby is sick and has only been in your life for such a short period of time, it crushes you.

I’ve never been sick or broken any bones, and my child is born with cancer. All you think is how you would give anything to trade places with them.

When I first found out all I could do is cry and think, “Oh, my god, people die from cancer. What am I going to do?”



I was like this for probably the first week and finally I had my breaking point. I broke down and had to accept our new life. After seeing Olivia’s smiles after each surgery, I thought, “Why am I crying if she’s not. If she can smile so can I and ever since then we have been going with the flow and smiling everyday.”

We thought about going to counseling. To be honest, my relationship with my husband wasn't doing to good before this happened. We had looked into getting marriage counseling. Since all this started our relationship has gotten so strong we didn't feel the need for it.

When your child is sick nothing else matters and eventually things just worked out and fell into place. We are strong for Olivia and lean on each other now more then ever. I couldn't go through this without him and vice versa.




On Religion . . .
I am a Catholic but do not go to church on a regular basis. I have always believed in God and doing what’s right. After Olivia’s diagnosis, I really began to question everything. I was mad and angry as to why God would do this to me and my family. A family I had always asked for. I never did anything bad in my life. I’m not perfect, but morally I’ve always tried to make the right choices. So I questioned my faith a lot and still do. But that's life.

No one asks for cancer or anything bad to happen. I just figure He is challenging me and I’m up for the challenge. If I love my daughter as much as I say I do, then I will do anything and everything for her and fight this battle with her. I will only come out a stronger person after all this and so will Olivia.

The Future . . .
I worry all the time. Telling me not to worry is like telling me not to breathe. I cant. I stay focused by taking care of Olivia like I would cancer or not. She is hitting all her milestones and I couldn't be happier. We try not to shelter her and just be a normal baby. We go to work and have a routine like anyone else. Except our routine involves hospitals and chemo.



About Olivia . . .
Olivia smiles through everything. When all this started I was so worried she wouldn't be a happy baby. But I don't even think about that now because her laugh and smile remind me everyday that she is happy and is going to be ok. Everyone that meets her instantly falls in love. Even nurses and doctors that aren't with Olivia come by her room cause they hear Princess Olivia is here and they have to see her.

I couldn't have asked for a better baby.


Olivia has completed all of her scheduled treatments. She will have scans in a few weeks and if all is well, her port will be removed.

Today is Olivia's first birthday. Happy Birthday, baby.


To learn more about sarcoma and how you can help, please visit our website.


Monday, September 15, 2014

SURVIVOR INTERVIEW: Rob Ambrose


Rob Ambrose is a 36 year old middle school science teacher.  He lives in Somerville, New Jersey with his beautiful wife Kate and their two cats.  In May of this year, Rob was diagnosed with myxoid liposarcoma. 

This is Rob’s story . . . 

How were you diagnosed?
In February 2014, I injured my lower left leg while training for the NYC half marathon.  I began physical therapy shortly after the injury.  The physical therapist that was seeing me took notice of my extremely tight left hamstring and mentioned that she could feel a lot of knots.  I had been told something similar when I received a massage earlier that winter.  It turned out that my injury was a stress fracture in my left fibula so there was no need for further physical therapy, and there was no follow-up on the tight hamstring.
On May 3, 2014, my wife and I were at Macy's shopping for new jeans.  The first pair of jeans I tried on fit very strangely - they were very tight around my left thigh but not so tight around the right.  I noticed the same thing with other pairs that I tried on.  I became very concerned and my wife, Kate, took a closer look at my thigh when we got home.  We measured my two thighs for comparison and the left one was definitely larger than the right.  Kate also noticed that it looked swollen in comparison to the right leg.  Since it was a Saturday evening and our primary doctor's office was not open, we went to the emergency room at our local hospital.   
The hospital took an x-ray and CAT scan of my leg, which revealed a large mass.  Kate and I were shocked by this - neither of us expected the swelling to be anything serious.  The doctor who came in to see us mentioned that the initial radiology report suspected a possible sarcoma.  I was admitted to the oncology floor of the hospital that evening.  The next day a more in-depth radiology report confirmed the suspicion of sarcoma.  The hospital staff informed me that their facilities were not equipped to provide me with the treatment I would need and referred me to Robert Wood Johnson University Hospital in New Brunswick, New Jersey.  
Kate and my parents brought me to Robert Wood Johnson on May 4th, where I received a series of MRI scans.  The MRI reports revealed similar findings, that the mass was likely a sarcoma.  Since the mass was so large, no biopsy was going to be performed, as it would need to come out regardless of whether or not it was sarcoma.  
It seemed surreal. Time seemed to slow down all of a sudden - seconds felt like agonizingly long hours and I felt like I was in some sort of limbo.  I wanted somebody to immediately tell me exactly what was wrong and exactly how it was going to be solved.  My emotions went through a pretty wide range, but the one I most specifically remember feeling was fear.  I have never been more frightened in my entire life and all I wanted was to be with my wife and to hold her in my arms.  

I remember immediately thinking I didn't want to die and I realized that any hardships or complaints I had about my life up to that point didn't matter any more.

I began reading about sarcoma on the internet during my initial stay in the hospital and quickly found out this was not a good idea.  I was still in the initial shock of being told I had cancer and was not mentally or emotionally ready to take in more information.  During this time, my wife and mother were both extremely helpful and did all of my information-gathering for me.  They helped come up with questions for me to ask the doctors so we could all be more well-informed of the treatment plan.   





What would you tell someone else who is newly diagnosed?
You are going to be amazed with how many people out there love you and are willing to do anything for you.  Don't hesitate to lean on people for help.  

Tell us about your treatment? 
My surgery was on May 22, 2014.  A large tumor measuring 10.6 inches X 5.3 inches X 3.1 inches was removed from my posterior left thigh.  I was actually up and moving much faster than I thought I would - I was only kept in the hospital for one night after they saw I could move relatively well around the floor and even make way up and down stairs.  The main side effect I had from the surgery was accumulation of fluid in the area where the tumor was removed.  It wasn't painful, just very uncomfortable - it felt like a very large water balloon was sloshing around in my thigh and made it feel very numb.  I had a JP Drain to initially remove the fluid but it was taken out after a week.  After that the fluid continued to build up so I had to go in to have my surgeon drain my leg once.  About three months after the surgery, the fluid was completely gone and I felt a lot better.
I started 6 1/2 weeks of radiation treatments on July 2, 2014, and finished on August 18.  I went in five days a week and the sessions lasted about a half hour.  Throughout the course of my treatments I felt increasing fatigue. Near the end of treatments, the skin in the treated area started turning darker and more red than normal. Since the treatments have concluded, the skin has become more irritated and it can quite painful at times – like a very strong sunburn.
I should also mention that since the initial finding in early May and until very recently, my sleep schedule was a wreck and I had only a handful of nights of uninterrupted sleep.




  
How did friends and family react?
Kate let both of our parents and siblings know right away.  She was also very good in notifying my close friends and our school's principal right away.  

I can honestly say that I have had the most amazingly supportive group of friends and family throughout all of this.  Whatever support I have asked for, they have given me that and so much more.  I could not ask or expect them to do better.  It feels amazing to know that I am so loved and that I have so many incredible people in my life.  
Throughout my radiation treatments, I had someone accompany me every single day. My wife, parents, brother, and in-laws all took turns going in with me and were there to greet me with a smile and a hug when I was ready to leave each day. The radiation therapists actually commented on how great it was that I had so many people to support me through this and I completely agree. It made it much easier to go to the hospital every day with someone else.

Do you ever feel alone – even though you have people around you?
Yes.  This is one of the most difficult things for me to explain.  I would say that in some way, shape, or form, this cancer is on my mind all of the time.  It feels like a burden I can't escape or relieve myself from.  That feeling of burden sometime leads to intense sadness and a sense of isolation.  I remember how it felt to know that cancer was inside my body and the fear of it ever returning and having to feel that again is something I could not expect or want others to understand.  
  

Do/did you feel like your life is on hold while you deal with sarcoma?
I try to not let it be on hold, but as I mentioned before, this is on my mind all of the time and in that sense, it has put my emotional and mental state in a deep hole that has been very hard to climb out of.  In that sense even if I am physically trying to experience as much of a "normal" life as I can, many times I am mentally / emotionally in an entirely different place.  I have tried to cope with this by seeing my therapist regularly and not hesitating to talk about my feelings with my wife, who is the best friend and best listener I could ever hope for.  
How has your day-to-day life changed since your diagnosis? What can’t you do that you could before?
I have always been a very physically active person with exercise and fitness and since my diagnosis that has somewhat slowed down.  I did buy a new bicycle, which allows me to engage in a low-impact form of exercise that I could handle.  
What is your prognosis?

I handled the surgery very well and the pathology report revealed a myxoid liposarcoma with no definite round cell component. I was referred to Memorial Sloan Kettering Cancer Center in New York for a second opinion on whether or not chemotherapy would be needed following radiation. On August 5, I went there and met with a sarcoma specialist. I was extremely relieved to hear that chemotherapy would not be needed and I was even more relieved when I was told that my outlook for the future is very good.
There is a very low chance of the cancer spreading and with the radiation treatments the chance of recurrence is also very low.

What keeps you inspired / motivated?
Kate.  She is the love of my life and my best friend.  I aspire to be cancer-free and live a long, fulfilling life together with her.  That motivates me to do whatever is needed to win this fight.
And, finally, a bonus question – what is your hidden talent?

I would like to think it is one I am not even aware of yet.  I try to make myself open to new experiences and am constantly developing new interests and skills.  Over the past few years alone, I have developed a love for studying local history, practicing yoga, and gardening - things that I could never have seen myself enjoying when I was younger.    
As with all of our personal stories, please keep in mind that nothing here is meant to be medical advice. Thank you, Rob, for sharing your story.