Study finds CT scans predict chemotherapy response in pancreatic cancer

March 11, 2014

Computed tomography (CT) scans routinely taken to guide the treatment of pancreatic cancer may provide an important secondary benefit. According to new research from The University of Texas MD Anderson Cancer Center, the scans also reflect how well chemotherapy will penetrate the tumor, predicting the effectiveness of treatment.

The research, published in the Journal of Clinical Investigation, is the first human study to address the issue of chemotherapy delivery to pancreatic tumors, a problem previously shown in animal studies.

"We found that the distribution of intravenous dye used in CT scans is a surrogate for chemotherapy delivery in the tumor," said Jason Fleming, M.D., professor in Surgical Oncology and corresponding author of the study. "Our results indicate that combining data from routine CT scans and using a mathematical formula developed by our team can predict response, guide patient treatment and lead to efforts to improve drug delivery."

Pancreatic tumors contain disorganized or nonfunctional blood vessels, high proportions of fibrotic tissue and molecular variations that create barriers for a drug to reach its target. It's a disease with a poor prognosis and the American Cancer Society estimates more than 39,000 people will die in 2014 as a result.

"Chemotherapy is used every day, however we've done very little to demonstrate that the drug actually reaches the tumor efficiently," Fleming said. "Results from our previous clinical trials at MD Anderson taught us that when chemotherapy kills most of a patient's tumor, the patient has a better chance of being a long-term survivor."

Researchers first enrolled 12 patients with primary pancreatic disease who would undergo a surgical resection. During surgery, each patient received an infusion of the chemotherapy drug gemcitabine. After surgery, the tumor DNA was analyzed for penetration of gemcitabine.

Gemcitabine is delivered to tumor DNA primarily through a protein called the human equilibrative nucleoside transporter (hENT1). Previous studies have shown its expression varies in pancreatic tumors, linking the protein to drug response.

For patients in the study with dense, fibrotic tumors and not much hENT1 protein, the chemotherapy was delivered constantly but its uptake was minimal since the drug was not reaching cancer cells, Fleming said.

Researchers found gemcitabine penetrated tumors at varying levels in the group of 12 patients and those with greater gemcitabine levels responded better to therapy and had improved outcomes. After seeing this difference, the team examined past CT scans from another group of patients to compare how the drug reached tumor cells.

The research team analyzed scans from 176 patients (12 who received gemcitabine infusion during surgery, 110 who received presurgical gemcitabine-based chemoradiation and 55 who received upfront surgery to remove the tumor).

Results show striking differences

After reviewing the data, researchers noticed visual differences in tumors as a result of the CT contrast being absorbed differently. Based on these observations, Fleming and his colleagues began to question whether the intravenous contrast used for CT scans predicted the path and absorption of gemcitabine . It turned out this theory was true.

By employing models to measure factors that influence drug delivery, researchers found resected tumors showed up to 6-fold differences in gemcitabine incorporation.

"This work is showing that solid tumors are much more heterogeneous than we thought with respect to drug delivery," Fleming said. "Going forward the implication is that molecular information from a biopsy of the tumor can be combined with data from a standard CT scan to place patients into categories that predict their response to therapy."

Additionally, Fleming said the trial implications are broad and could apply to other solid tumors. Researchers are beginning to look at existing drugs, such as losartan, a drug for high blood-pressure, as it could change the makeup of dense tumors, allowing better delivery of chemotherapy for patients who otherwise would have a poor response.

"The nice thing is that we can measure the effect of these new and repurposed drugs by using intravenous contrast in CT scans as a surrogate, so we don't have to commit a patient to receive a cancer drug until we know it improves the tumor characteristics," he added.

Future research is required to standardize this method of matching patients' tumors to the most promising drugs.
-end-
This research was primarily supported through grants from the Lustgarten Foundation (989161), the Methodist Hospital Research Institute, including the Ernest Cockrell Jr. Distinguished Endowed Chair and the National Institutes of Health Physical Sciences Oncology Centers (U54CA151668, U54CA149196 and U54CA143837).

The authors have no conflicts to declare.

In addition to Fleming, other MD Anderson authors include: Eugene Koay, M.D., Ph.D., Christopher Crane, M.D., William Plunkett, Ph.D., Robert Wolff, M.D., Jeffrey Lee, M.D., Huamin Wang, M.D., Ph.D., Gauri Varadhachary, M.D., Vijava Gottumukkala, M.D., Marc Rozner, M.D., Yuling Chen, M.D., Eric Tamm, M.D., Matthew Katz, M.D., Milind Javle, M.D., Priya Bhosale, M.D., Ya'an Kang, M.D., Ph.D., Deyali Chatterjee, M.D. and Rong Chen, M.D. Other non-MD Anderson authors include: Mauro Ferrari, Ph.D. and Haifa Shen, M.D., Houston Methodist Research Institute; James Abbruzzese, M.D., Duke Cancer Institute; Ryan Thomas, M.D., University of Florida College of Medicine; Mark Truty, M.D., Mayo Clinic College of Medicine; and Vittorio Cristini, Ph.D., University of New Mexico.

University of Texas M. D. Anderson Cancer Center

Related Chemotherapy Articles from Brightsurf:

Chemotherapy is used to treat less than 25% of people with localized sarcoma
UCLA researchers have found that chemotherapy is not commonly used when treating adults with localized sarcoma, a rare type of cancer of the soft tissues or bone.

Starved cancer cells became more sensitive to chemotherapy
By preventing sugar uptake, researchers succeeded in increasing the cancer cells' sensitivity to chemotherapeutic treatment.

Vitamin D could help mitigate chemotherapy side effects
New findings by University of South Australia researchers reveal that Vitamin D could potentially mitigate chemotherapy-induced gastrointestinal mucositis and provide relief to cancer patients.

Less chemotherapy may have more benefit in rectal cancer
GI Cancers Symposium: Colorado study of 48 patients with locally advanced rectal cancer receiving neoadjuvant chemotherapy, found that patients receiving lower-than-recommended doses in fact saw their tumors shrink more than patients receiving the full dose.

Male fertility after chemotherapy: New questions raised
Professor Delb├Ęs, who specializes in reproductive toxicology, conducted a pilot study in collaboration with oncologists and fertility specialists from the McGill University Health Centre (MUHC) on a cohort of 13 patients, all survivors of pediatric leukemia and lymphoma.

'Combo' nanoplatforms for chemotherapy
In a paper to be published in the forthcoming issue in NANO, researchers from Harbin Institute of Technology, China have systematically discussed the recent progresses, current challenges and future perspectives of smart graphene-based nanoplatforms for synergistic tumor therapy and bio-imaging.

Nanotechnology improves chemotherapy delivery
Michigan State University scientists have invented a new way to monitor chemotherapy concentrations, which is more effective in keeping patients' treatments within the crucial therapeutic window.

Novel anti-cancer nanomedicine for efficient chemotherapy
Researchers have developed a new anti-cancer nanomedicine for targeted cancer chemotherapy.

Ending needless chemotherapy for breast cancer
A diagnostic test developed at The University of Queensland might soon determine if a breast cancer patient requires chemotherapy or would receive no benefit from this gruelling treatment.

A homing beacon for chemotherapy drugs
Killing tumor cells while sparing their normal counterparts is a central challenge of cancer chemotherapy.

Read More: Chemotherapy News and Chemotherapy Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.