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University of Pittsburgh

Summer 2015

Chordoma Contained — Life Radiates Chordoma is rare. . Chordoma is tough. . Chordoma, meet Joey Rodriguez. “On November 18, 2005, at roughly 3:00 in the afternoon, Dr. Donna Hill at Emory University Medical Center, called to tell me that I had a brain tumor. She told me that I had a very rare type of cancerous brain tumor called a clival chordoma and that I would need brain surgery immediately. I wondered to myself, ’How bad is a clival chordoma?’ Available research at the time suggested that the average life expectancy of a person diagnosed with a clival chordoma is approximately 3 to 5 years from diagnosis to death. ’Well, that’s that,’ I thought.” “In May 2006, I flew to Pittsburgh to have brain surgery at the University of Pittsburgh Medical Center. I spent over 12 hours in the operating room; they used the endoscopic endonasal approach, where they enter the skull and remove the tumor via the nose — the one and only time that the family schnoz has paid off.” “In August 2006, I began radiation therapy. It took a full year to recover from the radiation. Sometime in 2007, I was told the tumor was in remission.” Joey decided not to be defined by his cancer. “Since achieving remission,” he says, “I’ve.         

..

Swam in the ocean below the Mayan temples of Mexico Walked along the blooming cherry trees that shade “The Philosopher’s Path” in Japan Received a Swedish massage from a grumpy Hungarian in Budapest Rode a Harley 30 miles on a dirt road into the wilds of Arizona to spend a night on a mountain top Fallen out of love, fallen in love Felt humbled and small at Anne Frank’s house Said a prayer for the dead at Hiroshima Worked with the Metropolitan Museum of Art, Art Institute of Chicago, The LA County Museum of Art…. Held my baby niece and nephew when they were born

“In short, I’ve lived more of my life in the past 11 years than I did in the first 35. I’ve had more good days than bad and having brain cancer gave me opportunity to learn more about myself and the world around than anything else I might have gone through or done. It was a terribly difficult event - but a profoundly meaningful and positive experience. I am thankful for it and thankful to those who were there with me through it all.” Joey is a survivor. He loves being part of the Chordoma Support Group on Facebook while getting serious about his new career in acting. He has roles on television shows Homicide Hunter and The Walking Dead. Check out season 6, episode 9 of The Walking Dead to see Joey, resplendent in black leather, lots of hair, and lots of menace, up front in a group of bad-guy bikers. While casting agents typically tap him for the role of “biker, criminal, or thug,” the real-life role for Mr. Joey Rodriguez would, undoubtedly, be alongside the good guys, fighting the evil villain chordoma.

What is chordoma?

Chordoma

is a

type of bone cancer usually found in the skull base or spine. These often slowgrowing tumors are rare, accounting for only 1% of central nervous system cancers. They often recur after treatment, and can occur in people of all ages, from infants to the elderly. Chordomas are thought to arise from remnants of the embryonic notochord, a structure that serves as scaffold in the formation of the spinal column. Notochord cells normally persist after birth inside the spine and skull; rarely, these cells undergo a transformation that leads to the formation of chordoma. Tumors at the base of the skull (the clivus) are referred to as clival chordomas.


Skull Base Center Research Updates: Chordoma

Everyone

Patients

UPMC researchers

The Chordoma Genome Project The goal of the Chordoma Genome Project is to identify new targets for treatment of patients with chordoma tumors by revealing genetic changes that drive chordoma. With each new patient, precious tumor tissue is saved in a tissue bank for analysis . Dr. Paul Gardner and the research team of Eric Wang MD, George Zenonos MD, and William LaFramboise PhD then evaluate the chordoma tissue for tumor mutations, comparing them to the known human genome. Dr. Zenonos, who is currently doing a fellowship in skull base surgery at UPMC, and Dr. Wang and Dr. Gardner of the Center for Skull Base Surgery collaborate with Dr. LaFramboise, who directs the Genomics Division of the Cancer Biomarker Facility in the Pathology Department of UPMC. Continued on facing page

Key researchers for the Chordoma Genome Project

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Paul Gardner, MD

Eric Wang, MD

William LaFramboise, PhD

Georgios Zenonos, MD


The Chordoma Genome Project . . continued Dr. LaFramboise uses a pathway concept to describe the research process (graphic on right). “We are currently completing step 3 in my lab now, “ says Dr. LaFramboise; “Future goals are to expand the numbers of samples, perform whole transcriptome RNA sequencing, deposit these data, and correlate current findings with genomic data in other chordoma databases.”

“Unfortunately, very little is known about the DNA and other molecular changes that result in a clival chordoma, says Dr. Wang. Taking advantage of ever improving DNA sequencing technologies and advancing computing algorithms, we can compare the DNA in clival chordomas with the DNA in a patient’s blood. This comparison of DNA from the same patient may allow for identification of key mutations that can be exploited to develop new therapies for this disease,” concludes Wang. To date, Dr. Zenonos and Dr. Gardner have evaluated the known molecular changes of 92 chordomas, comparing these changes to patient outcomes. This has allowed them to develop a molecular prognostication panel, which is the first of its kind. Think of it as a “Prediction” or “Forecast” that enables physicians to individualize treatment for each patient. From this initial research:   

Molecular markers (generally higher rates of genetic mutations) were identified that were predictive of faster tumor progression. A subgroup of patients was identified that had long-term survival. The extent to which cells containing the identified molecular aberrations were removed correlated with progression-free survival.

Chordoma, with characteristics of being both rare and widely divergent in its behavior, presents multiple challenges. Few institutions have the volume to do these kinds of studies. The research team works with the same goal in sight: “Our work in developing a molecular model for progression of chordoma holds potential to provide a targeted approach with more effective treatments.”

FROZEN TISSUE BANK

Sinonasal Malignancy Tissue Bank In addition to chordomas, the skull base team deals with a multitude of rare sinus cancers. “As with chordoma,” says Carl Snyderman, MD, “the rarity of these tumors makes it difficult for any one institution to develop a sufficient experience to answer questions regarding the behavior and treatment of these cancers.” (see box for types of sinus cancers)

“To understand and treat these malignancies requires a commitment to follow clinical outcomes data and awareness of key DNA alterations that cause these cancers to grow,” says Eric Wang, MD. “Similar to our study of chordoma, we collect tumor tissue samples that can be studied with a combination of advanced molecular sequencing and data analysis tools to investigate these questions. We are one of 7 universities across the United States who enroll patients with sinonasal malignancy into a registry that measures both traditional cancer outcomes as well as quality of life measures.”

Sinonasal malignancies include: Adenoid cystic carcinoma Adenocarcinoma Chondrosarcoma Esthesioneuroblastoma Hemangiopericytoma Melanoma Metastasis Mucoepidermoid carcinoma Nasopharyneal carcinoma Neuroendocrine carcinoma Sarcoma Sinonasal undifferentiated carcinoma Squamous cell carcinoma

These tumor tissues will be made available to researchers who are trying to unlock the secrets of these tumors. 3


Chordoma Foundation International Community Conference and Research Workshop As mission statements go, the Chordoma Foundation’s seems simple: “To improve the lives of those affected by chordoma and to lead the search for a cure.” Though seemingly “simple,” a deeper acquaintance with the Foundation and its achievements tells a story that is inspirational. From its beginnings in 2008 around a dining room table, the Foundation has fostered progress in the understanding of chordoma and its treatment at speeds not typical in science and medical research. The Director of the Chordoma Foundation is Josh Sommer, a chordoma survivor. To learn more about Josh’s story and the Chordoma Foundation, please see Winter 2016 issue, which can be found online (https://eyeandear.org > Media > Center for Skull Base Surgery). Dr. Paul Gardner of the UPMC Center for Skull Base Surgery was a panelist on “Ask the Experts” at the Summer 2016 Chordoma Foundation Community Conference. Surgeons, oncologists, and researchers analyzed and debated hormonal therapies, proton beam therapy, targeted therapies, systemic therapies, chordoma recurrence, metastasis, biopsy for chordoma, tumor behavior, pediatric chordoma, and research advances. Patients and physicians in attendance posed questions and challenges to the panel at the conclusion of the nonstop, hour-and-a-half session.

Below, left to right: Paul Gardner MD, Silvia Stacchiotti MD, Chris Heery MD

A sampling of the thought-provoking discussions in the session:

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Josh Sommer, above, is founder of the Chordoma Foundation - a chordoma survivor and unflinching advocate for scientific advancement in understanding this disease.

“One of the limitations with preoperative radiation of a skull base tumor is how close it is to the brain or brainstem.”

“The surgeon might need a very specific sequence of images or specific contrast agents prior to tumor removal.”

“Hormones depleted by radiation must always be replaced.”

“Among the experts there is not yet complete agreement on the best follow up approach after treatment.”

“In pediatric chordoma, you want a specialist who understands the disease along with a specialist who understands the child.”

“The risk of tumor seeding is very low in skull base tumor surgery with the endoscopic endonasal approach.”


Chordoma Foundation Conference .. continued Chordoma patient attendees had the opportunity to hear directly from doctors and leading researchers about the latest advances in chordoma research and treatment. “Empowered” is a term the Foundation uses to describe one of the goals of the conferences. Anyone participating in these conferences — patients, clinicians, researchers— contributes their expertise, whether it is researchers sharing data in a chordoma global database, or patients sharing their test results and their state of health. The University of Pittsburgh Medical Center is a “partner site” with the Chordoma Foundation. Surgeons, pathologists, and staff at UPMC ensure that patients’ precious chordoma tissue is saved for use in research at UPMC and in the global chordoma database (see pages 2 and 3). The determined little group who gathered at that dining table 9 years ago to “improve the lives of those affected by chordoma and to lead the search for a cure” can count its accomplishments today in 4 clinical trials, 5 research workshops, 10 community conferences, 19 research seed grants, and support of 32 academic publications related to chordoma research. According to Dr. Paul Gardner, “what we know today is a million times more than we knew 5 years ago because of the Chordoma Foundation.” Watch Dr. Gardner’s video interview discussing Chordoma in this publication online at https://eyeandear.org > Media > Center for Skull Base Surgery.

ONLINE access to all links in this publication via https://eyeandear.org

First Advanced Endoscopic Endonasal Surgery Course The UPMC Center for Skull Base Surgery hosted more than 50 advanced surgeons and visiting scholars from around the world at their first advanced endoscopic endonasal surgery course in August 2016. All participants had previously attended the Center’s comprehensive endoscopic endonasal surgery course which has trained more than 1,000 skull base surgeons since 2005. This advanced course highlighted both surgical decision making and advanced techniques in endoscopic endonasal skull base surgery. Sessions included interacti ve casebased discussions on the indications, limitations, and technical nuances of the procedures. Additionally, anatomical and technical aspects of these interventions were demonstrated in lectures, anatomical prosections, and illustrative live surgery. The next Advanced Course presented by the Center for Skull Base Surgery is August 16-19, 2017.

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Center for Skull Base Surgery UPMC 203 Lothrop Street Suite 500 Pittsburgh, PA 15213 Directors: Paul A. Gardner, MD gardpa@upmc.edu Carl H.Snyderman, MD snydermanch@upmc.edu

This publication is accessible online at https://eyeandear.org In future newsletters, you will continue to hear about the exciting educational projects underway at the Center for Skull Base Surgery. Your support is essential.

If you would like to learn more about our activities or sponsor a project, please contact the Eye & Ear Foundation.* To support the Center for Skull Base Surgery, please use the enclosed envelope or visit eyeandear.org. If sending a check, please make payable to the Eye & Ear Foundation.

The UPMC Skull Base Team Additional information about the educational and clinical work of the surgeons of the Center for Skull Base Surgery is found at: UPMC.com/skullbasesurgery.

www.eyeandear.org 203 Lothrop Street Suite 251 EEI Pittsburgh, Pennsylvania 15213 Tel: 412 864 1300 *The Eye & Ear Foundation is a non-profit (C)(3) organization created

Nationally and internationally recognized as one of the leading centers for skull base surgery, we receive consultations and patient referrals from all parts of North America as well as other continents.

solely to support the educational and research efforts of the Departments of Otolaryngology and Ophthalmology at the University of Pittsburgh.

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Center for Skull Base Surgery: Winter 2017  

Chordoma

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