Optimising CT-guided biopsies of sclerotic bone lesions in cancer patients

In this study, we found that in cancer patients, CT-guided bone biopsies of predominantly mild sclerosis and lower CT attenuation lesions result in significantly greater tumour-positive and NGS feasibility rate, when compared with biopsies of dense sclerosis and higher attenuation lesions. Regarding a tumour-positive biopsy outcome, we found 610 HU as an optimal threshold with a PPV of 89% for lesions with smaller mean HU. With regards to NGS feasibility in prostate cancer patients, the optimised threshold was 370 HU, resulting in 94% PPV for lesions with smaller mean HU. By contrast, most laboratory or procedure-related parameters had no significant impact on the biopsy results.

LDH was the only laboratory blood parameter that showed a statistical significant correlation with the bone biopsy outcome, with higher LDH levels found in cancer patients with a positive bone biopsy. Although LDH is an established parameter for monitoring malignant disease [16], linking a systemic blood parameter to the success of local tissue sampling is questionable. Overall, the lack of correlation between the remaining blood parameter levels and bone biopsy results is in keeping with earlier observations [15]. Thus, systemic laboratory measurements may have limited implications for individual bone lesions.

Neither lesion size nor lesion-to-cortex distance differed significantly between tumour-positive and negative nor NGS feasible and non-feasible biopsies. This is in keeping with the published literature [6, 11].

Targeting lytic bone lesions for CT-guided bone biopsies is established as a general recommendation [4,5,6, 10, 13,14,15, 17]. However, in some patients, lytic disease is absent and sclerotic bone lesions are the only available biopsy targets. For these patients, target selection support criteria are required. Validating previous researchers, we found that areas of visually mild sclerosis should be favoured as biopsy targets over the densely sclerotic bone to improve tumour-tissue yield [6]. This subjective finding is supported by our quantitative analysis, as significantly lower lesion NC-CT HU values were found for successful biopsies. We identified 610 HU as the optimal threshold for identification of sclerotic bone lesions with a tumour-positive bone biopsy result, with lower values indicating bone disease suitable for biopsy. In prostate cancer patients, 370 HU was identified as the optimised threshold for the identification of bone biopsy targets resulting in NGS feasible results in our cohort. The discrepancy between the 610 HU diagnostic and 370 HU NGS threshold may be explained by the fact that significantly more tumour tissue is required for NGS compared with a histopathological tumour diagnosis. It can be hypothesised that mildly sclerotic, lower HU lesions contain more viable tumour than sclerotic, higher CT-attenuation bone marrow. Previously defined thresholds for the identification of tumour-positive biopsies range between 400 and 500 HU [6, 10, 18]. Improved tumour-positive bone biopsy rates of 70–79% in lower HU lesions compared with higher CT-attenuation lesions (33–40%) were also described [6, 18]. These thresholds included lytic or mixed-lytic lesions, while our study exclusively focussed on sclerotic bone, which may account for the HU difference. Optimised HU thresholds focussed on NGS feasibility from sclerotic bone lesion biopsies were not previously published.

Within the available data, differences in procedure-related parameters, including needle diameter, biopsy tract length, and number of core samples taken were not associated with a tumour-positive or NGS feasible result. Similar findings were made by previous researchers, who analysed the role of needle diameter, lesion-to-cortex distance, skin-to-lesion distance, tract length, and number of cores obtained [6, 10,11,12].

The overall tumour-positive rate of 74% in our study is within the pooled range of 62–82% and equal to the mean calculated across 13 studies analysed in a contemporary meta-analysis of CT-guided sclerotic bone biopsies [3]. The 73% NGS feasibility rate is within the range of previously published results, which included lytic and sclerotic bone lesions [6, 11, 12, 15, 17]. This should allow for the general applicability of our findings outside of our own institution, to improve CT-guided bone biopsy success rates in cancer patients with sclerotic bone disease. Although the threshold values need further validation in larger cohorts, our results suggest that for diagnostic biopsies bone lesions with mean values < 610 HU and for NGS in prostate cancer lesions < 370 HU should be targeted.

Our study has limitations. First, in this small, retrospective and single-centre cohort, all lesions had already undergone a selection process by the executing interventional radiologist, creating inclusion bias. Second, there was no histopathologic prove that negative biopsies targeted malignant lesions. Imaging suggested malignancy, and this study deliberately aimed to identify parameters that discriminate tumour-positive from tumour-negative and NGS feasible from non-feasible biopsies. Third, only a limited variety of bone biopsy needles are used in our department. Hence, the full scope of the hardware influence, including different biopsy systems and a wide range of needle diameters, on biopsy outcome cannot be evaluated. Moreover, the impact of electrical powered drills, which were suggested to give superior results was not assessed [3]. Fourth, NGS was only performed in prostate cancer patients. Thus, results can only be applied to this patient group. Moreover, the number of obtained samples was significantly higher for NGS than diagnostic biopsies, as patients were included in multiple trials, requiring separate specimens. Finally, PET/CT and especially PSMA PET/CT, which was previously shown to improve bone biopsy success in prostate cancer patients [15, 17], were available only in a small number of patients. As such, the presented study likely underestimates the value of PET/CT for bone biopsy target selection.

Concluding, in cancer patients with sclerotic bone disease, targeting areas of predominantly mild sclerosis in lower CT-attenuation lesions can improve tumour tissue yield and NGS feasibility. NC-CT sclerotic bone target lesion mean HU should preferably be less than 610 HU for diagnostic biopsies and less than 370 HU when biopsies are performed for NGS in prostate cancer patients.

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