Sarcomas constitute a large group of cancers that can occur anywhere in the body, either on the skeleton (e.g., osteosarcoma, chondrosarcoma, Ewing sarcoma) or on connective tissue, including fat, blood vessels, fibrous and nerve tissue, tendons, skeletal and smooth muscle, and the lining of joints.
The connective tissue cancers are collectively called soft tissue sarcomas (STS). There are approximately 100 subtypes of STS characterized by site of origin, genetic alterations, behavior, metastatic mechanisms and response to therapy.
Sarcomas are more prevalent among children and adolescents than adults, making up some 10 percent of childhood cancers but less than 1 percent of adult malignancies.
The Ohio State University’s cancer program has a history of science-based patient care in adult and pediatric sarcomas. The program encompasses one of the most complete continuum's of sarcoma research and clinical faculty in the United States, featuring experts from the OSUCCC – James, Nationwide Children’s Hospital (NCH) in Columbus, and the University’s College of Veterinary Medicine.
- Exploring the origins of sarcoma at the genetic level
- Testing new drugs aimed at slowing or halting the progress of sarcomas
- Developing treatment strategies with available drugs
- Finding ways to help the body’s immune system subdue sarcoma cancer cells
Ohio State is one of two academic institutions in the nation to have principal investigators for both a Specialized Programs of Research Excellence (SPORE) grant and a pediatric Program Project Grant (PPG) from the NCI to study sarcoma. By leading both grants, Ohio State’s cancer program can use molecular advances in medicine to help change the global paradigm of sarcoma care.
SARC Sarcoma SPORE (CA168512)
In 2012, the NCI awarded a five-year, $11.5 million SPORE grant to the Sarcoma Alliance for Research through Collaboration (SARC), a not-for-profit consortium representing physician clinician-scientists from several institutions who are dedicated to cooperative research leading to new sarcoma treatments. It was only the second SPORE ever awarded for studying this disease.
Raphael Pollock, MD, PhD, director of Ohio State’s Division of Surgical Oncology and chief of surgical services at the OSUCCC – James, is principal investigator (PI) for the SPORE, a multi-institutional collaboration that contains four research projects along with separate cores for administration, tissue and pathology, clinical trials and biostatistics. It also has a Career Development Program and a Developmental Research Program. Besides serving as overall PI, Pollock is co-PI for one of the four research projectsand leads the administrative core.
- Provide the infrastructure for collaboration on translational research for sarcoma
- Determine the biological basis for observations made in individuals with sarcoma
- Develop novel treatments to improve sarcoma outcomes
Studies of Childhood Sarcoma (P01 CA165995)
In 2013, the NCI awarded a five-year, $7.8 million Program Project Grant (PPG) for Studies of Childhood Sarcoma to a team led by PI Peter Houghton, PhD, who directs the Center for Childhood Cancer and Blood Diseases at The Research Institute at NCH and is a member of the OSUCCC – James. The grant funds three separate but related research projects.
- Characterize the interrelationship of three integrated molecular signaling pathways that are active in childhood sarcomas
- Identify combinations of inhibitors that target these pathways and are likely to improve patient outcomes
- Develop novel therapeutic strategies for treating advanced childhood sarcoma
Examples of sarcoma clinical trials under way at the OSUCCC – James:
(OSU-12067) Decision Impact Analysis of Foundation Medicine's Next Generation Sequencing Test in Advanced Solid Tumor Malignancies
PI: Erin Macrae, MD
- Assess the feasibility and logistics associated with a clinical trial utilizing the Foundation Medicine Incorporated (FMI) test in an academic therapeutic setting
- Determine the proportion of patients who will receive a cancer-related therapy based on results provided by the FMI test
- Explore and report estimates of progression-free-survival (PFS) of the regimen administered after the FMI test results are revealed and the PFS of the most recent regimen administered before the FMI test results were received
- Determine the feasibility of performing Next Generation Sequencing (NGS) on metastatic tumor tissue
- Determine the feasibility of administering cancer-related drugs that are proposed by the results of NGS that are not Food and Drug Administration (FDA)-approved for a patient's specific cancer diagnosis
(OSU-12211) A Study of the Safety and Efficacy of the Combination of Gemcitabine and Docetaxel in Metastatic Soft Tissue Sarcoma
PI: Arvinder Bhinder, MBBS
- Determine whether MORAb-004 increases effectiveness of the chemotherapies gemcitabine and docetaxel in people with metastatic soft tissue sarcoma
(OSU-12066) Phase I Trial of Dabrafenib (BRAFi) and Pazopanib in Patients with BRAF-Mutated Advanced Malignant Tumors
PI: Minisha Shah, MD
- Assess the safety and tolerability of GSK2118436 (dabrafenib) given with pazopanib (pazopanib hydrochloride) and determine the maximum tolerated dosing regimen in patients with BRAF-mutated advanced malignant tumors
- Evaluate pharmacokinetics of the two study drugs and identify potential drug-drug interactions
- Determine pharmacogenomics with microarray testing
- Perform genotyping of tumors and see if objective tumor response rates are identified
Recent Clinical Research Accomplishments
Loss of microRNA Decoy May Contribute to Development of Soft Tissue Sarcoma. OSUCCC – James researchers discovered a mechanism responsible for the loss of a critical tumor-suppressor gene in rhabdomyosarcoma and other soft-tissue sarcomas. The discovery could lead to more effective therapies for these malignancies, whose cause is largely unknown, says principal investigator Denis Guttridge, PhD, of the OSUCCC – James. The study was published in the journal Science Signaling.
False Pedicle Surgery Allows for Advanced Spinal/Pelvic Reconstruction. A multidisciplinary team at the OSUCCC – James pioneered a surgical technique that used false pedicles to reconstruct a load-bearing pelvic-spine structure to support and protect the spine following a complex cancer surgery. Ehud Mendel, MD, a neurosurgeon and director of Ohio State’s Spine Oncology Program, and colleagues detailed the creation of false pedicles and a neo-pelvis for lumbopelvic reconstruction following en bloc resection of iliosacral chondrosarcoma with lumbar spine in a paper published in the March 2014 issue of the Journal of Neurosurgery: Spine.
Ohio State Surgeon Performs Rare Rotation Surgery on Young Cancer Patien. When athletic fourth-grader Dugan Smith fell and broke his femur, doctors found a softball-sized tumor just above his knee. It was an osteosarcoma, a rare primary bone cancer. But two years later, after undergoing an unusual rotationplasty surgery in which his lower leg was amputated, the tumor removed, and the leg rotated and reattached so that his ankle functions as his knee, the boy was cancer-free and back to playing sports. The surgery was performed at Nationwide Children’s Hospital by Joel Mayerson, MD, an orthopaedic surgeon and director of the Division of Musculoskeletal Oncology at Ohio State. Mayerson also is medical director of the sarcoma service for Ohio State’s James Cancer Hospital and Solove Research Institute.