April 17, 2009 — The effectiveness of chemotherapy can be accurately determined in sarcoma patients — after only 1 treatment cycle, according to investigators at the University of California at Los Angeles (UCLA).
In a single-center study, imaging of tumor metabolic activity with a combination positron emission tomography/computed tomography (PET/CT) scanner predicted histopathologic response to neoadjuvant chemotherapy in high-grade sarcoma patients — about a week after the first treatment cycle.
"I was surprised that we could tell that early," study senior author Frtiz C. Eilber, MD, told Medscape Oncology. Dr. Eilber is director of the Sarcoma Program at UCLA's Jonsson Cancer Center.
Being able to identify responders and nonresponders to a chemotherapy regimen early on is of great importance, he said. "Neoadjuvant therapy is highly toxic and frequently ineffective. This approach accelerates the identification of the correct therapy for patients and reduces morbidity from chemotherapy," he said.
Patients who are not responders to therapy could also potentially undergo surgery earlier, he added.
The new study was published April 7 in Clinical Cancer Research.
Dr. Eilber is part of a group of UCLA researchers who at the forefront of using PET/CT imaging and biological probes to more quickly and accurately assess the effectiveness of chemotherapy.
"Noninvasive molecular evaluations of treatment effectiveness are part of the future of oncology," he said.
In the current study, the PET portion of the PET/CT scanner is used in conjunction with a glucose-uptake probe called fluorodeoxyglucose (FDG), which allows the investigators to see how much sugar is being consumed by the cancer cells. This metabolic activity makes cancer cells light up under PET scanning.
All 8 of the 50 patients in the study who had eventual histopathologic evidence of a response to therapy had a 35% or greater reduction in their glucose metabolism after their first cycle of chemotherapy.
The histopathologic response to chemotherapy was defined as 95% or greater necrosis in tumor tissue when the tumor was surgically removed at the end of the regimen.
"If you did not get an initial 35% or greater reduction in activity of the tumor, then the chemotherapy was not working," Dr. Eilber said, explaining that 28 patients in the study did not reach this level of tumor-activity reduction.
The remaining 14 patients in the study had a 35% or greater reduction in tumor activity but the necrosis in their tumor tissue was less than 95%; thus, they were not considered responders to chemotherapy.
"Using a 35% or greater reduction in FDG uptake as an early metabolic response threshold resulted in a sensitivity and specificity of FDG-PET for histopathologic response of 100% and 67%, respectively," conclude the study authors.
The investigators are now following the patients to see how those with tumor-activity reduction fare in terms of survival, compared with the patients who did not meet the cut-off level of activity reduction.
The study and its methods are not novel. Glucose metabolic imaging has been used successfully in patients with esophageal cancer to determine whether neoadjuvant treatment should be continued or discontinued, noted Dr. Eilber.
Standard for Evaluation is Tumor Size
Currently, sarcoma patients are typically evaluated after 2 or 3 cycles of chemotherapy by PET, said Dr. Eilber. However, metabolic activity of tumor cells is not measured — the size of the tumor is. The guidelines for this evaluation are known as RECIST (Response Evaluation Criteria in Solid Tumors). In brief, if the tumor shrinks, compared with the baseline PET, the therapy is deemed to be working in this standard of care.
In a previous study (Clin Cancer Res. 2008;14:715-720), Dr. Eilber and colleagues showed that changes in glucose metabolic activity were more accurate than tumor size in predicting the histopathologic response of tumors to chemotherapy.
"We've known for a long time that change in tumor size does not correlate well with outcomes," he said.
The insufficiency of the standard approach and the results of the new research have led to a change in practice for Dr. Eilber, who now employs FDG-PET in his clinic.
"We are already using this in the clinic. For example, we had a woman with a breast sarcoma who did not have a change in tumor activity after the first cycle of a taxane regimen. So we switched the regimen and saw a metabolic activity decrease well over the 35% cut-point. We subsequently excised the tumor and she was a pathologic responder," he said.
Dr. Eilber believes that moving up the assessment of chemotherapy in a wide variety of oncology patients is key to improving treatment. For example, the early metabolic activity assessment of tumors could be used in metastatic colon cancer and gastric cancer, he said.
He also pointed out that many community hospitals have PET/CT technology and could be trained to use FDG, the glucose-uptake probe.
According to Dr. Eilber, there are also other noninvasive methods for assessing tumor response to therapy in development, including the thymidine analog 18F-3'-deoxy-3'-fluorothymidine, which is being used clinically for PET imaging of tumor proliferation.
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