Kate Johnson

May 21, 2012

May 21, 2012 (Barcelona, Spain) — Three blood biomarkers are strong predictors of response to chemoradiation therapy for rectal cancer and could be used with other predictors to tailor treatment, reported Jeroen Buijsen, MD, at the European Society for Radiotherapy and Oncology 2012 Annual Conference (ESTRO 31).

Patients with these biomarkers "may be offered less invasive surgical treatments like sphincter-saving surgery, TEMS surgery [transanal endoscopic microsurgery] or a wait-and-see policy," suggested Dr. Buijsen, from the Maastro Clinic in Maastricht, the Netherlands.

"Blood markers are attractive because they are easy to collect, it's cheap to measure them, and they may get information about different aspects of tumor biology," he added.

His prospective study included 260 patients scheduled for chemoradiation therapy for locally advanced rectal cancer.

Blood was drawn before therapy and tested for 9 biomarkers.

"CEA and CA19-9 can be seen as markers of tumor volume, IL-6, IL-8, and CRP are related to inflammation processes, LDH can been seen as a marker of cell death, CAIX and osteopontin are correlated to hypoxia and angiogenesis, and vitamin D25 is related to growth arrest and apoptosis," he said.

The patients were treated with 28 fractions of chemoradiation at 1.8 Gy each plus capecitabine (Xeloda, Genentech), and those with pathological complete response (pCR) or good response were compared with nonresponders.

"Responders were defined as either pCR but also patients with tumor confined to the bowel wall," he explained. "We think this makes sense because this is a patient group that can be suitable for TEMS surgery."

Multivariate analysis showed that for pCR, only 1 biomarker, osteopontin, showed a significantly predictive value (P = .03); for good response, both CEA (P = .03) and IL-8 (P = .02) were significant predictors.

Dr. Buijsen's group has recently shown that positron emission tomography (PET)–based parameters are also helpful in predicting response to chemoradiation in this patient population (Int J Radiat Oncol Biol Phys 2012;82:871-6).

He showed that both blood biomarkers and PET parameters offer similar predictive value, but a model that combines both offers even stronger prediction.

Asked to comment, Vincenzo Valentini, MD, president of ESTRO and a radiation oncologist at Policlinico Universitario A. Gemelli in Rome, Italy, told Medscape Medical News, "the more we know, the more we can tailor treatment — either intensify or de-escalate it."

He agreed that "for rectal cancer, if you have a good prediction model using biomarkers and other data from imaging or clinical factors, you can go to an organ-sparing surgical approach."

But the challenge for the field is in learning how to combine information about many different biomarkers, he said.

"What is unfortunately the reality is that at the moment, no biomarkers can provide a clear separation of the good from the ugly. They will show a difference of 10% to 20%."

"What's easy to predict is that in a few years, on the desk of clinicians, we could have hundreds or maybe thousands of reports of different biomarkers — all of them indicating some survival impact of 8% to 10%. But how to combine all this information together? We need some decision-management tools that provide the best navigation inside this important but complex new scenario."

Dr. Buijsen and Dr. Valentini have disclosed no relevant financial relationships.

ESTRO 31: European Society for Radiotherapy and Oncology 2012 Annual Conference. Abstract #OC-0454. Presented May 12, 2012.


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