The Art of Survivorship

This month the collection, "Mother & Son: The Art of a Mom’s Journey through Childhood Cancer with Her Son" will be on display at Tiny’s Coffee 1412 SE 12th Portland, Oregon.  The artist, April, is an advocate for childhood cancer survivorship, her son now thriving after a challenging period with sarcoma.  The mixed media of paint-on-radiograph is accompanied by the history, from a mother's perspective, of the experience.  

Nanocourse publication

Congratulations to the 2012 Participants of the OHSU Pediatric Cancer Nanocourse whose peer-reviewed commentary, "A Diffuse Intrinsic Pontine Glioma Roadmap: Guiding Research Toward a Cure" is published in the journal, Pediatric Blood & Cancer.  
  
It should be emphasized that this scholarly work is that of members of the community: parents, survivors and students.  We are grateful to have been able to work with this talented and insightful group of individuals.  

New & Improved: Patient & Family Wall

We are grateful to the dozens of families who renewed consent forms for the Patient & Family Wall.  This is a very important aspect of our labs' research culture... seeing first hand, every day, those for whom we work towards new treatments in order to "give back childhood".

Proof-of-concept rare cancers in drug development: the case for rhabdomyosarcoma

We hope you will enjoy this review and commentary as much as we do.  A lot of people in pharma, the community-at-large and scientific thought leaders helped to create this somewhat out of the box concept proposal.  With some additional community volunteers, I think we could really put this plan to action.  Sincerely, Charles
  
[ This review was made possible by a gift from the Ethan Jostad Foundation ].

Dupont creates new opportunities

The recent change in policy by Dupont with regard to the Oncomouse patent opens the door to academic-pharma collaboration.  It may also be possible to streamline development of novel drug testing by creating a non-profit company or organization for this specific purpose.  Rhabdomyosarcoma, Inc?  Would members of the community have interest in such an endeavor?  

Pediatric Cancer Nanocourse 2012

We are grateful and inspired by the 12 participants that came to Portland for the one-week Pediatric Cancer Nanocourse.  The goal was to create science‐informed liaisons between childhood cancer researchers and the community in order to empower the public to drive the cure of rare cancers. We firmly believe liaisons like these dedicated individuals, many of whom experienced unthinkable loss, are needed to speed the development of new and effective childhood cancer treatments.  We welcome the opportunity to work together with these individuals and the community in this shared mission.

[ update 1/31/2014:  see details of the 2012 Nanocourse peer-reviewed publication. ]

(guest entry) Our Hope: “No Curative Measures” Ends Here

by Nettie Boivin

The Team Julian Foundation

   

I had never in my life heard the term “glioma” until this monster swept into our lives and threatened the life of our son. Julian was a healthy, handsome and fun-loving 4-year-old with huge eyes and an even bigger imagination. It was Nov. 29, 2010, that our beautiful boy was, seemingly overnight and out of nowhere, diagnosed with an inoperable brain stem glioma. Gripped by fear but determined to beat the odds, we researched the best doctors in the country and brought him under the care of top pediatric oncologists at St. Jude Children’s Research Hospital in Memphis.

   

Our diagnosis happened to be the deadliest of all brain tumors with “no known cause or cure.” It was unimaginable and impossible to process that we’d most likely lose our first-born within 18 months. Throughout Julian’s treatment, doctors used terms like “palliative measures” and “grim prognosis.” With every blow, we kept waiting for that next line - some promising shred of a breakthrough that may halt the heartbreak to come.  But much to our dismay, we discovered that little research was currently underway for pediatric gliomas and cures were still years away.

   

In only 7 intense months, filled with beautiful and bittersweet moments,  the incurable disease proved too much. We lost our sweet boy, Julian Bradley Boivin, on July 3, 2011, just three weeks after his 5th birthday.

   

Last March while at St. Jude, Julian met a little girl who also had a DIPG, and together they forged a friendship as two 4-year-olds discussing bravery techniques before daily radiation treatments. This girl's mother and I desperately hoped and prayed these two would be exceptions to this dreaded diagnosis. Now, only months after having to say goodbye to both children, we are committed to making sure our two angels help turn the tide on this incurable disease.

   

An autopsy to resect and study Julian’s tumor wasn't possible when he died over the 4th of July holiday weekend. However the little girl's doctors were able to remove her entire tumor after she passed on in late 2011. Through The Team Julian Foundation’s support of CureSearch for Children’s Cancer, we were told about an important opportunity to partner with Dr. Keller’s Lab and the DIPG Consortium to find chemo agents that would finally combat this sly disease. So, between funding through Julian's foundation and the donation of this little girl's tumor sample, we believe this is Julian’s and the little girl's way of having a big impact on a world they were a part of for such a short but wonderful time.

   

By supporting the DIPG Consortium, we hope to see a day very soon when other children and their families facing this disease won’t ever have to hear the words “no curative measures” again.

Whose data?

For an interesting concept, see Sage Bionetwork's website on a new trend for patients to have access to data generated from their own samples.  Quoting, "Key objectives: Enable patients to obtain their own data back from samples they donate to trials".  A very provocative idea! 
  
  

Leaving a Legacy - the value of tumor tissue from Autopsy

While a difficult topic, there may be times where a cancer death can have more meaning by improving knowledge of the disease through tissue donations after life.  For the first in a series of publications related to childhood cancer 'Legacy Gifts', see our co-authored paper in the journal Cancer entitled, "The clinical, research, and social value of autopsy after any cancer death: A perspective from the Children's Oncology Group Soft Tissue Sarcoma Committee".

More information can also be found at www.ccurefast.org or our partner website at the Northwest Sarcoma Foundation.  See also our PCB related blog entries on this topic.  




OPEN SCIENCE FORUM:   (updated 04/05/2012, with comments welcome!) 
Below are our academic-community team's intended project milestones for defining a path to survival for the most incurable childhood cancers:
     

• begin national dialogue with pediatric oncologists about the topic. 
• Legacy Gift Workshop presented at Fall 2011 Children’s Oncology Group (COG) meeting, in partnership with two Sandy Smith and Kim Spady, who themselves are cancer survivors presented their families experiences with tissue donation after their sons passed away from brainstem gliomas.  Sandy and Kim are passionate supporters of families on this topic, and have first-hand experience facilitating these types of tissue donations after life (at autopsy).  
• understand and publish the potential barriers to autopsy as understood from interviews of families conducted under our NCI-funded project, NIH/NCI R01CA133229-04S2.
• This study is the successor to the position paper we published for the COG Soft Tissue Sarcoma committee:
• Sheri L. Spunt, Sara O. Vargas, Cheryl M. Coffin, Stephen X. Skapek, David M. Parham, Joan Darling, Douglas S. Hawkins, Charles Keller.  The Clinical, Research, and Social Value of Autopsy after Any Cancer Death:  A Perspective from the Children’s Oncology Group Soft Tissue Sarcoma Committee.  Cancer, 2011 Oct 17 epub [PMID 22006470]
• create a shift in culture among medical care providers by seeking to have an educational session on how to approach the topic of autopsy with families at the COG Fall 2012 meeting.
• This is a successor to the Fall COG 2010 workshop, OVERCOMING AUTOPSY BARRIERS IN PEDIATRIC CANCER RESEARCH: Providing Hope For Tomorrow’s Cures described above.
• optimize www.ccurefast.org to work in parallel with other websites such as kidsvcancer.org, having peer education & caregiver guidelines as well as assistance for families via an online single-point-of-contact.
• write a Children’s Oncology Group autopsy banking protocol for all childhood cancers by multi-institutional collaboration by Spring 2012.
• All specimens would be sent to the COG Biorepository in Columbus, Ohio.
• Access to any specimen in the COG Biorepository would require COG disease subcommittee scientific peer review to ensure the study request was scientifically rigorous and used only the amount of sample absolutely required (in order to increase the number of studies per tissue collection).
• seek a foundation that would help fund the costs of autopsy collection kits, as well as a reimbursement to COG institutions for the logistics of packaging and shipping autopsy collections by Summer 2012.
• encourage broad use of these highly valuable, high informative tissue specimens starting Fall 2012 so that the 1 in 5 children not cured of cancer may someday survive his/her cancer.

01/09/2012:  manuscript for the NCI-funded study of autopsy barriers to be submitted today.
03/28/2012:  Effort to create an autopsy educational session for the Fall COG session instead suggested to be made an educational session at the ASPHO conference.
04/05/2012:  Consortium grant for COG-based autopsy program submitted today to St Baldrick's Foundation.
05/17/2012:  Jen presents Legacy Gift study at APOSW national conference in Portland.  
06/26/2012:  Consortium grant for COG-based autopsy program received 2 overwhelmingly positive reviews, and one very brief non-positive review.  Project will not be funded.  Effort will be revised and resubmitted for funding elsewhere.  Copy of the submitted grant and reviews are available on request.  
06/27/2012:  Manuscript submitted to a scientific journal is now in revision, and will be resubmitted within the week.
08/16/2012:  Manuscript accepted to Pediatric Blood & Cancer, the leading journal in pediatric hematology-oncology.  Congratulations to Jen and all co-authors!
09/06/2012:  Rally Foundation takes a bold new step to bring this effort to a national level!
09/26/2012:  paper is now published online here.
02/01/2013:  See the editorial, "Pediatric autopsy consent: Helping families create hope out of despair", written in Pediatric Blood & Cancer here (it accompanies our paper's print version is the same issue).  

our approach to Personalized Cancer Therapy

Many thanks to the team and to the patients that helped created this first video version of our vision for personalized cancer therapy.  The approach will probably be moved from canine patients to human patients in the context of relapsed disease.  It's certainly something we are moving ahead as quickly and as carefully as we can.  A high resolution of our video can also be found here.  
  

Collaborator, Dr. John Ohlfest

For a summary from Minnesota Public Radio on the promising tumor immunology approach of brain tumor researcher, Dr. John Ohlfest, click here.  

Legislation and Childhood Cancer

Groups like CureSearch, foundations and individuals approach childhood cancer advocacy through hard work in lobbying for executive and legislative initiative that improve the research and care of childhood cancer patients.  One example is that September is "Childhood Cancer Awareness Month" by Presidential Proclamation.  Nancy Goodman is a childhood cancer parent and founder of KidsvCancer.org who regularly lobbies on behalf of childhood cancer causes.  Another advocacy group for increasing drug availability for cancer patients is the Abigail Alliance.  These groups certainly deserve our thanks and support in their efforts.  
  
  
  
[ 9/15/10   For a touching story about a little girl named Joanna whose memory is bringing awareness and rallying a community around childhood cancer patients, click here.  ]
  
[ 9/16/10   See Nancy Goodman's testimony before the House at  http://www.kidsvcancer.org/pediatric-cancer-caucus/ ]

   

Tissue Banking - Demystified

A question sometimes asked is how research can be advanced, and contributing tissue to a tumor bank for research is a key element (money, yes, is nice... but high quality tissue from patients with tumors for which little is know is more valuable).  And if it can be put in a gentle way, tumor tissue from the patients that researchers and clinicians so far have failed is the most valuable.  That is, tissue from patients with relapses... even post-mortem biopsies from patients that have failed our best treatments.


How does one enroll to give tissue? In the case of soft tissue sarcomas, the Children's Oncology Group (COG) has had a tumor bank protocol called "D9902" open since March 1999.  The consent form for this study is usually presented to families at the time a child is diagnosed and is being considered for a COG treatment study.  Most people think of D9902 as a study for collecting tissue from the original untreated tumor, but... the protocol does already allow tissue to be collected from biopsies done at the time of relapse, as well as tissue taken after death (autopsies, partial autopsies and post-mortem biopsies).  In practice, relapse samples rarely are collected (there are practical reasons not to subject children to extra procedures).  Post-mortem samples are scarce... maybe none, with recent notable exceptions.


Where does the tissue go?  well, a really good tumor bank!  The COG contracts the Pediatric Cooperative Human Tissue Network (pCHTN) to store COG sample studies.  Their Director is Dr. Nilsa C. Ramirez, and she and the Biopathology Center for the pCHTN are at the Nationwide Children's Hospital in Columbus, Ohio.  Nilsa succeeds the late Dr. Stephen Qualman, who himself was taken by pancreatic cancer.  Dr. Qualman was a leader in rhabdomyosarcoma pathology research, but Nilsa keeps this tradition in sarcomas strong, and she was recently joined by rhabdomyosarcoma researcher Dr. Peter Houghton who is building an exciting pediatric cancer research program at Nationwide.


What happens with the tissue?  It gets used, hopefully!  Dr. Stephen Skapek at the University of Chicago leads the Soft Tissue Sarcoma Biology subcommittee of the COG.  Researchers send the pCHTN/COG applications to use the tissue. The applications are reviewed by Steve and others on his committee (such as myself).  If the study looks promising, a few samples are sent.  If the researcher shows promising results, many more samples can be sent.  In fact, for the best studies we even consider, "emptying the bank".  (important notes:  the researchers only have de-identified samples... they won't know each patient's name.  Also, statistical rigorousness is another important judging criteria for proposed studies).  


How much does it cost?  In theory, it shouldn't.... the tissue collection kits are meant to be a part of the existing COG D9902 protocol.  However, there have been cutbacks in what the NIH/NCI gives COG for its studies. If there were a sudden 'flood' of samples, the pCHTN and I estimate it would cost  $150 total (70 for the kit, 30 to ship the kit to the child's hospital, 50 to ship it back on dry ice).  I've talked with a few foundations on whether they'd sponsor kits, and while we don't have any definite commitments, I think if the need arose we could find a way that patients wouldn't need to use their own money to contribute to research through the tumor bank.


I hope this helps with some of the questions arising lately. Feel free to comment on this blog or email me for more information.  


Sincerely,
Charles




   

an informal word on our lab's research

Our laboratory focuses on long term and near-term treatments for the childhood muscle cancer, rhabdomyosarcoma, and the childhood brain tumor, medulloblastoma. To say long term, we mean basic science investigation of how these tumors work – such things as what kind of normal cell gives rise to one particular kind of cancer. And in saying near-term, we mean finding molecules in these cancers to directly turn off or turn on by drugs so that the tumor stops growing. Behind both approaches are some rather exciting genetically-engineered mice… modified from before birth so that at a certain age, and in a certain tissue, the same mutations found in a child’s cancer are activated in the mouse. Then the tumor can be followed to see how it grows and spreads… even to test a treatment to see whether the tumor growth can be reversed. That these mice have normal immune systems is a real plus, too, because white blood cells play an important role in how tumors evolve and respond to therapy.

While this use of mouse models makes our lab slightly unique, our greatest asset is that we have a very multi-disciplinary team. Biomedical engineers for building and operating imaging and diagnostic instruments, biochemists for understanding the molecules, molecular biologists and electrical engineers for understanding how tumors express genes in certain ways, and me (the board-certified pediatric oncologist) helping bring it all together in a focused way. Sometimes we venture beyond the ordinary, such as the use of 26¢ fertilized quail eggs (instead of mice or petri dish experiments) to study anti-cancer drugs. That last project is one graciously sponsored by the Alex’s Lemonade Stand Foundation. We’re even the first to work with the National Cancer Institute’s Pediatric Preclinical Testing Program to try exciting new drugs right out of the pharmaceutical development pipeline in genetically-engineered mouse models of childhood cancer.

I’d like to think that tangibly better treatments for rhabdomyosarcoma and medulloblastoma can be found in a matter of years, instead of tens of years. I go to a fundraiser golf tournament for the Scott Carter Foundation every year. They sponsored my research training in Mario Capecchi’s lab years ago, and now sponsor our pediatric cancer researcher in training, Nicolle Hoffman. Standing at the 18th hole every year, I get the same question about every 5 minutes, “Doctor, do you have anything new for these kids yet?” These questions led my lab to put a heavy emphasis on therapeutics about 4 years ago. As a result, we’re finding drug targets, as well as drugs to hit those targets that are less inclined to result in relapse for our patients (ok – yes, it’s just mice so far, but I also am a member of the Children’s Oncology Group committee that designs COG trial for rhabdomyosarcoma).

What's on the horizon?  A lot!  In moving to OHSU in Portland we're now teaming with Dr. Brian Druker to develop personalized targeted therapies (of the non-chemotherapy variety) for children with cancer.  Our results can move faster than ever from the bench to the bedside with the COG Phase I pediatric oncology program here at our Doernbecher Children's Hospital, and with the leadership opportunity of building a de novo Pediatric Cancer Biology Program at OHSU, there's tremendous potential to build a focused team of laboratories that share a common goal of doing the best research and moving making results relevant to patients in the here and now.

Where there is a will, there is a way. Change can be tangible.  And we are accountable.

Charles Keller, MD
keller@ohsu.edu

The “Creating Hope Act of 2010” S.3697

This important proposed bipartisan legislature by Senators Sam Brownback (R-KS), Sherrod Brown (D-OH), and Al Franken (D-MN) would encourage pharmaceutical companies to develop new drugs for rare childhood diseases, including cancer.  Essentially, the pharmaceutical companies would receive a voucher to expedite FDA approval.


For more details, visit Nancy Goodman's website for KIDS V CANCER.     
  
  

an informal word on the research in the Keller Laboratory

Our laboratory focuses on long term and near-term treatments for the childhood muscle cancer, rhabdomyosarcoma, and the childhood brain tumor, medulloblastoma. To say long term, we mean basic science investigation of how these tumors work – such things as what kind of normal cell gives rise to one particular kind of cancer. And in saying near-term, we mean finding molecules in these cancers to directly turn off or turn on by drugs so that the tumor stops growing. Behind both approaches are some rather exciting genetically-engineered mice… modified from before birth so that at a certain age, and in a certain tissue, the same mutations found in a child’s cancer are activated in the mouse. Then the tumor can be followed to see how it grows and spreads… even to test a treatment to see whether the tumor growth can be reversed. That these mice have normal immune systems is a real plus, too, because white blood cells play an important role in how tumors evolve and respond to therapy.

While this use of mouse models makes our lab slightly unique, our greatest asset is that we have a very multi-disciplinary team. Biomedical engineers for building and operating imaging and diagnostic instruments, biochemists for understanding the molecules, molecular biologists and electrical engineers for understanding how tumors express genes in certain ways, an orthopedic oncologist and me (the board-certified pediatric oncologist) helping bring it all together in a focused way. Sometimes we venture beyond the ordinary, such as the use of 25¢ fertilized chicken eggs (instead of mice or petri dish experiments) to study anti-cancer drugs. That last project is one graciously sponsored by the Alex’s Lemonade Stand Foundation. We’re even starting to work with the National Cancer Institute’s Pediatric Preclinical Testing Program to try exciting new drugs right out of the pharmaceutical development pipeline in our novel mice.

I’d like to think that tangibly better treatments for rhabdomyosarcoma and medulloblastoma can be found in a matter of years, instead of tens of years. I go to a fundraiser golf tournament for the Scott Carter Foundation every year. They sponsored my research training in Mario Capecchi’s lab years ago, and now sponsor my postdoctoral fellow, Koichi Nishijo. Standing at the 18th hole every year, I get the same question about every 5 minutes, “Doctor, do you have anything new for these kids yet?” These questions led my lab to put a heavy emphasis on therapeutics about 3 years ago. As a result, we’re finding drug targets, as well as drugs to hit those targets that are less inclined to result in relapse for our patients (ok – yes, it’s just mice so far, but we did present our results at a Children’s Oncology Group symposium a few weeks ago to help select a non-chemotherapy drug to add to the next COG trial for rhabdomyosarcoma).

We’re fortunate that despite the economic downturns that we’re doing pretty well so far… R01 funding from the National Cancer Institute, grants from the ALSF, the St Baldrick’s Foundation, the National Brain Tumor Society, the Joanna McAfee Foundation and more. Seven publications in print or accepted in 2008. This are truly exciting times. On top of all this is our mouse drug testing program mentioned above, which is open to public participation (for more details, see the left column of our blog). And just to put a plug in for a colleague’s new lab, try visiting Dr. David Langenau’s website . David has made a zebrafish model of embryonal rhabdomyosarcoma. He treats these little fish with drugs, right in the tank water. Also see Dr. Rene Galindo's website on using fruitflies to understand rhabdomyosarcoma. It will probably take a lot of new approaches and cooperation between groups to make the big impact we’re all hoping for, but it can be done.

Where there is a will, there is a way. Change can be tangible.

Charles Keller, MD
kellerc2@uthscsa.edu    keller@ohsu.edu

[ many thanks to collaborator Dr. Bryan W. Jones who took this picture on a hike in Utah. ]