New radiotracer shows early treatment response for patients with lung cancer

PET scanning with FDG has proved its mettle as a way to judge tumor response to treatment. Now Australian researchers are going one step further and working with another radiotracer, which they have determined can monitor the response of non-small-cell lung cancer and normal tissue changes during radical chemoradiotherapy.

Sarah Everitt, a research radiation therapist from Radiation Therapy Services at Peter MacCallum Cancer Centre and a final year PhD candidate at Monash University in Melbourne, and her colleagues enrolled five NSCLC patients in their proof of concept study, with each patient receiving F-3′-deoxy-3′-fluoro-L-thymidine (F-FLT) with PET/CT as well as FDG on PET/CT (Int J Radiat Oncol Biol Phys 75:1098-1104, 2009).

The researchers explored whether F-FLT uptake could be seen at all in patients and at which time-points during their course of treatment the most informative measurements could be taken.

In all patients, baseline lesion uptake of F-FLT on PET/CT was concordant with the staging FDG PET/CT. Uptake at both the primary site and in metastatic lymph nodes was previously identified. The biodistribution uptake of F-FLT was heterogeneous within all lesions, according to the researchers.

The maximum standard uptake value (SUVmax) of the primary tumor was on average 2.2 times greater on baseline F-FDG scans than on baseline F-FLT scans. Similarly, the SUVmax of lymph nodes was on average 2.3 times greater on F-FDG scans than on F-FLT scans. F-FLT uptake in tumors was observed on five of nine on-treatment scans on days 2, 8, and 29. A “flare” of F-FLT uptake in the primary tumor of one patient was observed after 2 Gy of radiation. The remaining eight on-treatment scans demonstrated a mean reduction in F-FLT tumor uptake of 0.58 × baseline. A marked reduction of F-FLT uptake in irradiated bone marrow was observed for all patients. This reduction was observed even after only 2 Gy, and all patients demonstrated a complete absence of proliferating marrow after 10 Gy.

Individualized treatment
“While a complete proliferative response was observed in some cases, other tumors demonstrated persistent FLT activity throughout the course of therapy. We believe that the treatment of patients in the latter category could potentially be adapted based on the individual’s biological tumor response,” she said. Individualized treatment could include accelerating the delivery of therapy and escalating the dose to hyperproliferative subvolumes of tumor.

At this point, it is too early to assess the implications of this study. Many institutions have a standard of care for NSCLC, but survival remains poor and there is scope to improve local tumor control and long-term outcomes, said Ms. Everitt. Being able to indicate how the tumors are responding, however, is invaluable.

“This may save patients from having to wait weeks and months after treatment is complete to confirm its effectiveness. Patients have informed me that it is very encouraging to know their tumors are responding, based on FLT PET/CT, and that this information has motivated them to complete the prescribed course of therapy,” she said.

The study also confirms that F-FLT clearly shows areas of irradiated bone marrow and that bone marrow is affected by only one 2 Gy fraction of radiation therapy.

“The sensitivity of FLT to detect changes after this small dose could be useful in monitoring patients receiving treatment with larger radiation portals and in individuals affected by accidental radiation exposure,” she said.

“There obviously remains a great deal of work to validate these observations and to assess the reproducibility of proliferative subvolumes over time,” she added. “Hopefully in the future, this strategy could be tested in a clinical trial of adaptive therapy based on FLT PET/CT, which also assesses the value of this tracer as a prognostic marker.”

Ms. Everitt is currently leading a multidisciplinary team to validate the preliminary findings of the study. The researchers hope to finish recruiting patients by the end of 2010.

VANTAGE POINT
Small study still ofers noteworthy results
Stephan M. Hahn, MD

Although this is a proof of concept study, the fact that it got published shows its potential importance, according to Dr. Hahn, a professor and chair of radiation oncology at the University of Pennsylvania in Philadelphia.

“I think what they’re measuring is a potentially very important parameter that could help us make treatment decisions. This is a really important part of oncologic imaging that a lot of us are going to move into in the future,” he said.

FDG-PET has already established its usefulness in imaging tumors, but this study shows there are techniques beyond FDG that assess early treatment response. F-FLT could help determine after a week or two of treatment whether or not a patient is responding, he said.

“I think what this study really means is that there’s more targeting of appropriate treatment for patients. This gives me hope that we might be able to use this approach in the future. It doesn’t prove it but it’s a really interesting trial,” he said.

While it’s too early to tell the implications of this study for the community oncologist, in the next few years, physicians may start to see the increasing use of agents in exactly this setting, Dr. Hahn said.