An 81-year-old former minor league baseball player with a history of cancer arrived at the emergency department with a fractured forearm and leg pain after a fall at home.
Ironically that fracture, and the cutting-edge diagnostic testing that followed, would save his life, and allow the patient to have a remarkable response to treatment. This case was recently highlighted in a Frontiers in Oncology paper.
The patient had been diagnosed two years ago with urothelial cancer. And after surgery from his fall, circulating DNA in his blood showed a return of cancer. A CT scan showed what was presumed to be metastatic disease in the lung and he began chemotherapy, but he didn’t respond to treatment and was in declining health.
The result of additional molecular testing found the smoking gun. “He had a KRAS mutation. HRAS can be seen in bladder cancer, but you rarely if ever see KRAS, so that was unusual. And we know that KRAS is common in lung cancer,” said Dr. David Nanus, Associate Director, Network Integration at Weill Cornell Medicine’s Meyer Cancer Center.
Clinicians at Weill Cornell Medicine, working on a study of Carcinoma of Unknown Primary (CUP) with Next Generation Sequencing (NGS) used an algorithm developed by a company and determined the patient indeed had lung cancer. “This approach helped our clinicians identify a molecular target, characterize the tumor expression profile and tumor microenvironment, and analyzed the origin of the tumor. This led to a tailored treatment that made his lesions disappear, and there is now no evidence of disease. He is doing well,” added Dr. Nanus.
“It’s interesting the way in which new DNA screening tests for cancer take a blood sample and analyze a tissue biopsy and are able to sequence it,” said Dr. Nanus. “The idea is that if they see a certain mutation pattern, it can be very beneficial for determining the right therapy.”
“These CUP patients present unique and challenging cases for clinicians,” said EIPM Clinical Director Dr. Cora N. Sternberg, who has written the protocol that was used for patients with CUP. “Successful treatment often requires us to determine the original source of a cancer, and to do so requires novel genomic analysis leveraging whole-exome sequencing and RNA sequencing.”
“The learning point from these studies is that you should always do molecular testing,” added Drs. Sternberg and Nanus, “especially when you have available tissue. And since he broke his arm and had surgery that removed tumor tissue, we had plenty of tissue available for testing and sequencing.”
“CUP is not uncommon and represents 3-5% of patients with metastatic disease,” said Dr. Juan Miguel Mosquera from WCM’s Pathology and Laboratory Medicine department and an EIPM Member. “Despite extensive pathology studies, the site of origin can remain unknown. However, with current genomic sequencing tools, not only the tumor type can be predicted with high accuracy, but also actionable events can be identified. As illustrated in this case, the integration of these molecular-based algorithms in the routine pathology work-up of CUP patients is critical and a powerful diagnostic tool.”
This comprehensive genomic and molecular profiling approach can provide a more definitive, personalized treatment strategy for other patients, overcoming the limitations of current predictive analyses. It also offers a potential solution to the unmet need for a standardized approach to identifying the tumor origin for the effective management of these types of CUP cases.
“At most major cancer centers, this type of collaborative approach between departments is increasingly common,” concluded Dr. Nanus. “But at Weill Cornell Medicine, my close relationship here over many years with co-investigators, including Drs. Sternberg and Mosquera, really helps facilitate the process. We communicate very frequently, support each other, work closely together, and act quickly to benefit of the patient.”
The Englander Institute for Precision Medicine (EIPM) Director Olivier Elemento, Ph.D. agrees, "At the EIPM, our researchers collaborate across disciplines to accelerate scientific discoveries and bring innovative treatments to patients sooner."
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