In the Journals

Comprehensive screening fails to increase occult cancer detection after unprovoked VTE

The addition of 18F-fluorodeoxyglucose PET/CT scans to limited screening did not appear to significantly increase the rate of occult cancer detection in patients who experienced an unprovoked venous thromboembolism, according to the results of a randomized controlled trial.

However, the risk for subsequent cancer diagnoses appeared lower in patients with a negative initial screening that included 18F-fluorodeoxyglucose PET/CT scans compared with patients who had negative results only from limited screening.

Although the incidence of undiagnosed cancer in the year after an unprovoked VTE ranges from 6% to 15%, no clear guidelines exist to screen for occult malignancy in these patients, according to study background. However, clinicians previously surmised that 18F-fluorodeoxyglucose PET scanning, combined with low-dose CT (18F-FDG PET/CT), could serve as a comprehensive screening strategy for occult disease.

Thus, Pierre-Yves Salaun, MD, of the department of nuclear medicine at University of Western Brittany in Brest, France, and colleagues sought to evaluate the addition of 18F-FDG PET/CT to a limited screening strategy for the detection of malignant disease in patients with an unprovoked VTE.

Salaun and colleagues evaluated data from 394 patients (median age, 63 years; interquartile range, 49-76) with unprovoked VTE — defined as an incident not provoked by a major inherited or acquired risk factor — from four academic medical centers in France. Researchers randomly assigned patients 1:1 to a limited screening strategy, defined as a physical examination, usual laboratory tests and basic radiography, alone (n = 197) or with 18F-FDG PET/CT (n = 197).

Follow-up continued for up to 2 years.

The proportion of patients diagnosed with cancer in each arm following the initial assessment served as the primary endpoint. Secondary endpoints included subsequent diagnosis of cancer in patients with negative initial screening, the proportion of early-stage vs. advanced tumors at initial screening and during follow-up, overall mortality and cancer-related mortality during follow-up.

During initial screening, the researchers diagnosed cancer in 11 patients in the 18F-FDG PET/CT group (5.6%) and four patients (2%) in the limited screening group (absolute risk difference = 3.6%; 95% CI, –0.4 to 7.9).

Sixty-four percent of cancers (n = 7) in the 18F-FDG PET/CT group and 50% (n = 2) of cancers diagnosed in the limited screening group were early-stage tumors.

Patients in the 18F-FDG PET/CT group appeared at lower risk for a subsequent cancer following initial negative screening. One subsequent diagnosis occurred among 186 patients with negative initial results in the 18F-FDG PET/CT group, compared with nine diagnoses among 193 patients in the limited screening group (absolute risk difference = 4.1%; 95% CI, 0.8-8.4).

Of the 12 cancers total detected in the 18F-FDG PET/CT group, five (42%) were detected at an advanced stage. Of the 13 total cancers detected in the limited screening group, seven (54%) were at an advanced stage.

Sixteen patients — eight in each arm — died during follow-up. The researchers deemed two deaths in the 18F-FDG PET/CT group and five deaths in the limited screening group to be cancer related.

The researchers acknowledged the open-label study design and the low incidence of cancer in both arms as study limitations. They further acknowledged that 12% of patients assigned to the 18F-FDG PET/CT group did not receive their allocated imaging intervention.

“Whether or not 18F-FDG PET/CT might be useful in a more selected population of patients with a high risk [for] cancer remains to be determined,” Salaun and colleagues wrote.

In an accompanying editorial, Ramón Lecumberri, MD, PhD, and Ana Alfonso, MD, both hematologists at Clinical University of Navarra in Pamplona, Spain, wrote that older patients may benefit from 18F-FDG PET/CT screening.

“Hopefully, future studies will help to clarify the role of 18F-FDG PET/CT in this setting,” Lecumberri and Alfonso wrote. “Indeed, cost analysis will also be welcome. Until then, it seems reasonable to proceed with a limited screening strategy in younger patients with unprovoked VTE and offer a more extensive screening (perhaps with 18F-FDG PET/CT, if available) to those older than 50 years.” – by Cameron Kelsall

References:

Lecumberri R and Alfonso A. Lancet Oncol. 2015;doi:10.1016/S1470-2045(15)00535-5.

Robin P, et al. Lancet Oncol. 2015;doi:10.1016/S1470-2045(15)00480-5.

Disclosure: One study researcher reports grants, personal fees and nonfinancial support from Actelion, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Daiichi Sankyo and GlaxoSmithKline. Salaun and the other study researchers report no relevant financial disclosures. Lecumberri and Alfonso report no relevant financial disclosures.

The addition of 18F-fluorodeoxyglucose PET/CT scans to limited screening did not appear to significantly increase the rate of occult cancer detection in patients who experienced an unprovoked venous thromboembolism, according to the results of a randomized controlled trial.

However, the risk for subsequent cancer diagnoses appeared lower in patients with a negative initial screening that included 18F-fluorodeoxyglucose PET/CT scans compared with patients who had negative results only from limited screening.

Although the incidence of undiagnosed cancer in the year after an unprovoked VTE ranges from 6% to 15%, no clear guidelines exist to screen for occult malignancy in these patients, according to study background. However, clinicians previously surmised that 18F-fluorodeoxyglucose PET scanning, combined with low-dose CT (18F-FDG PET/CT), could serve as a comprehensive screening strategy for occult disease.

Thus, Pierre-Yves Salaun, MD, of the department of nuclear medicine at University of Western Brittany in Brest, France, and colleagues sought to evaluate the addition of 18F-FDG PET/CT to a limited screening strategy for the detection of malignant disease in patients with an unprovoked VTE.

Salaun and colleagues evaluated data from 394 patients (median age, 63 years; interquartile range, 49-76) with unprovoked VTE — defined as an incident not provoked by a major inherited or acquired risk factor — from four academic medical centers in France. Researchers randomly assigned patients 1:1 to a limited screening strategy, defined as a physical examination, usual laboratory tests and basic radiography, alone (n = 197) or with 18F-FDG PET/CT (n = 197).

Follow-up continued for up to 2 years.

The proportion of patients diagnosed with cancer in each arm following the initial assessment served as the primary endpoint. Secondary endpoints included subsequent diagnosis of cancer in patients with negative initial screening, the proportion of early-stage vs. advanced tumors at initial screening and during follow-up, overall mortality and cancer-related mortality during follow-up.

During initial screening, the researchers diagnosed cancer in 11 patients in the 18F-FDG PET/CT group (5.6%) and four patients (2%) in the limited screening group (absolute risk difference = 3.6%; 95% CI, –0.4 to 7.9).

Sixty-four percent of cancers (n = 7) in the 18F-FDG PET/CT group and 50% (n = 2) of cancers diagnosed in the limited screening group were early-stage tumors.

Patients in the 18F-FDG PET/CT group appeared at lower risk for a subsequent cancer following initial negative screening. One subsequent diagnosis occurred among 186 patients with negative initial results in the 18F-FDG PET/CT group, compared with nine diagnoses among 193 patients in the limited screening group (absolute risk difference = 4.1%; 95% CI, 0.8-8.4).

Of the 12 cancers total detected in the 18F-FDG PET/CT group, five (42%) were detected at an advanced stage. Of the 13 total cancers detected in the limited screening group, seven (54%) were at an advanced stage.

Sixteen patients — eight in each arm — died during follow-up. The researchers deemed two deaths in the 18F-FDG PET/CT group and five deaths in the limited screening group to be cancer related.

The researchers acknowledged the open-label study design and the low incidence of cancer in both arms as study limitations. They further acknowledged that 12% of patients assigned to the 18F-FDG PET/CT group did not receive their allocated imaging intervention.

“Whether or not 18F-FDG PET/CT might be useful in a more selected population of patients with a high risk [for] cancer remains to be determined,” Salaun and colleagues wrote.

In an accompanying editorial, Ramón Lecumberri, MD, PhD, and Ana Alfonso, MD, both hematologists at Clinical University of Navarra in Pamplona, Spain, wrote that older patients may benefit from 18F-FDG PET/CT screening.

“Hopefully, future studies will help to clarify the role of 18F-FDG PET/CT in this setting,” Lecumberri and Alfonso wrote. “Indeed, cost analysis will also be welcome. Until then, it seems reasonable to proceed with a limited screening strategy in younger patients with unprovoked VTE and offer a more extensive screening (perhaps with 18F-FDG PET/CT, if available) to those older than 50 years.” – by Cameron Kelsall

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References:

Lecumberri R and Alfonso A. Lancet Oncol. 2015;doi:10.1016/S1470-2045(15)00535-5.

Robin P, et al. Lancet Oncol. 2015;doi:10.1016/S1470-2045(15)00480-5.

Disclosure: One study researcher reports grants, personal fees and nonfinancial support from Actelion, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Daiichi Sankyo and GlaxoSmithKline. Salaun and the other study researchers report no relevant financial disclosures. Lecumberri and Alfonso report no relevant financial disclosures.