August 25, 2015 | Patti Wieser
Loren Mell, MD, wanted to test a hypothesis in an international phase II trial: If an advanced type of radiation therapy called IMRT was used to treat patients with cervical cancer, then it would result in fewer side effects and enable the delivery of more intensive chemotherapy.
"Multiple preliminary studies indicate that intensity modulated radiation therapy (IMRT) can significantly reduce toxicity of chemoradiotherapy and improve chemotherapy delivery, but this hypothesis had not been tested in clinical trials," said Mell, an associate professor in the Department of Radiation Medicine and Applied Sciences at UC San Diego.
With support from the UC San Diego Clinical and Translational Research Institute (CTRI) through the KL2 program, Mell organized the International Evaluation of Radiotherapy Technology Effectiveness in Cervical Cancer (INTERTECC) trial to assess the toxicity, feasibility and quality of IMRT in the treatment of cervical cancer. Phase II trials use a larger group of individuals to test the effectiveness of a medical intervention and further evaluate its safety.
According to the World Health Organization, cervical cancer is one of the world's deadliest – but most preventable – forms of cancer for women, responsible for more than 270,000 deaths annually, 85 percent of which occur in developing countries.
The standard treatment for advanced cervical cancer is pelvic radiation therapy combined with a chemotherapy drug called cisplatin, which often results in toxicity and failure, Mell said. IMRT, he added, differs from conventional radiation therapy by using multiple beam angles and computerized planning algorithms to conform radiation dose to the target. This causes less collateral damage to nearby tissue and organs and enables a more focused dose to the tumor.
"The K grant was designed to support a phase II trial, so that allowed me to organize the INTERTECC trial," said Mell, an expert in radiation technology and clinical trial design. Collaborating with seven other centers globally, the INTERTECC team is comparing toxicity levels of patients at centers that treat with IMRT with levels at centers that don't.
Mell has submitted INTERTECC phase II trial results as a late-breaking abstract to the American Society of Radiation Oncology (ASTRO) meeting in San Antonio, Texas, in October. The abstract is titled, International Multi-Center Phase II Clinical Trial of Intensity Modulated Radiation Therapy with Concurrent Cisplatin for Locoregionally Advanced Cervical Cancer.
Promising results from his three-year KL2 project helped Mell land a $500,000 R01 grant from the National Institutes of Health to lead a cooperative group investigation of IMRT as an effective and safe therapy to treat advanced cervical cancer.
"Through the R01 project, we will be better able to test the hypothesis that IMRT can reduce side effects and permit more intensive chemotherapy. This will be the first trial in a cooperative group to really test IMRT in advanced cervix cancer," he said. Cooperative research and multi-institution trials – despite being challenging – can have a significant impact on practice. "There's not a better way to have an evidence-based avenue to alter standard of care than through a multi-institution cooperative." Mell is also the recipient of an R21 grant, awarded between his KL2 and R01 grants to support the INTERTECC trial.
Mell received bachelor's degrees in mathematics and economics from Stanford University in 1996 and completed his medical school and residency at the University of Chicago before joining UC San Diego in 2008. Medicine, he said, offered a way to solve challenging problems while helping people. Arno Mundt, MD, Chair of the Department of Radiation Medicine and Applied Sciences, and Mell's mentor at the University of Chicago and later at UC San Diego, influenced his research focus. "Dr. Mundt was studying new technologies – IMRT – to reduce side effects in patients with gynecological cancers," Mell said. "My experience with him convinced me I wanted to do radiation oncology."
"I immediately knew when I first met Loren when he was a senior medical student at the University of Chicago, he would develop into an outstanding academic researcher," said Mundt. "His career thus far, however, has exceeded all of my expectations. I know few other radiation oncologists his age who have made as many impactful and novel contributions to our field as he has."
Mell is especially interested in studying how IMRT could help spare bone marrow, and the R01 grant builds on this research. Standard radiation therapy techniques tend to irradiate everything in a region, but if the dose is reduced, physicians could miss the tumor. The KL2 and R01 support studies if IMRT can deliver enough radiation to a smaller target and lessen the impact on surrounding tissue and organs, while still being effective. Less radiation could enable additional chemotherapy, which augments radiation therapy, but overlapping toxicities from the combined therapies pose challenges to patients. "Much work needs to be done to figure out how much radiation reduction is possible. Most importantly we have to figure out the dose-toxicity tradeoff," Mell said. "We want to spare normal tissue surrounding the cancer while at the same time intensifying radiation to a specific area."
Mell said he enjoys his dual role as physician-researcher, and quips that he spends 50 percent of his time doing research, 50 percent seeing patients, and 50 percent completing administrative tasks. Time with patients often stimulates his research – an approach he calls "bedside to bench," a twist to the "bench to bedside" approach that takes lab discoveries to the patient.
While screening programs for cervical cancer are one of the most successful health interventions in the U.S. and other developed countries, cervical cancer persists in developing nations and underserved populations here.
"I want to help people who have come from socio-economically disadvantaged backgrounds," Mell said. "They get less, but need more of our resources."