29 A number of biological factors may modulate GR and add confusion to the utility of GR in observing patients with SRMs. For instance, in the prospective study by Mason and colleagues, larger tumors (> 2.45 cm) demonstrate a faster GR than smaller tumors.8 However, several retrospective analyses have failed to find a relationship between primary tumor size and GR.6,20 Kouba and colleagues Palbociclib PD 0332991 demonstrated that patients aged < 60 years Inhibitors,research,lifescience,medical had more rapidly growing tumors than those aged > 60 years.9 Finally, changes in tumor volume have been touted as more accurately reflecting

growth kinetics and the biologic aggressiveness of an SRM; however, consistent with Gompertzian growth kinetics, smaller tumors are demonstrated to grow faster volumetrically.30 A recent pooled

analysis of the AS literature demonstrated increased age, larger greatest initial tumor dimension and estimated Inhibitors,research,lifescience,medical volume, and higher linear and volumetric GR to predict metastatic progression.7 Although a number of important factors may indicate the malignant potential of an SRM, it is clear that progression to metastatic disease is exceptionally low in tumors that demonstrate slow or no GR and remain Inhibitors,research,lifescience,medical < 3 cm. Conversely, although tumors may demonstrate variable GR, the majority that progress to metastasis exceed 3 cm and often become cT1b (> 4 cm) tumors prior to or at the diagnosis of metastasis. In the retrospective literature, on average, patients undergo five to six imaging evaluations over a period of 29 to 41 months yielding an approximate average rate Inhibitors,research,lifescience,medical of imaging every 6 months.7 The majority of retrospective studies use computed tomography (CT) and magnetic resonance

imaging (MRI), with ultrasonography (US) used sparingly. The Inhibitors,research,lifescience,medical prospective study by Mason and colleagues recommended CT, MRI, or US imaging every 6 months.8 The DISSRM protocol recommends a high-quality axial image (CT or MRI with contrast) at enrollment to be followed by CT, MRI, or US every 4 to 6 months for 2 years and then every 6 to 12 months thereafter (Figure 1).10 It is our experience GSK-3 that, given conflicting reports regarding the risk of secondary malignancy,31 few patients are willing to undergo serial exposure to ionizing radiation in the form of CT scan. As GR is the main trigger for delayed intervention, we approve of serial US examination with confirmation of a change in growth with axial imaging if indicated. To better determine the aggressiveness of a new lesion, we recommend the first serial image be performed within 4 to 6 months with the caveat that GR may be exacerbated by even a small change in tumor diameter seen over a short period of time. It is known that tumor diameter measurements may vary by up to 3 mm between and among but observers.32 Consequently, wide fluctuation is seen and little prognostic value is gained by small changes in tumor diameter seen on the first surveillance image.

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