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Diffusion-weighted MRI characteristics of the cerebral metastasis to brain boundary predicts patient outcomes.

Zakaria R, Das K, Radon M, Bhojak M, Rudland PR, Sluming V, Jenkinson MD - BMC Med Imaging (2014)

Bottom Line: Patient outcomes were overall survival and time to local recurrence.This was not simply due to differences between the types of primary cancer because the effect was observed even in a subgroup of 36 patients with the same primary, non-small cell lung cancer.The ATC was the only imaging measurement which independently predicted overall survival in multivariate analysis (hazard ratio 0.54, 95% CI 0.3 - 0.97, p = 0.04).

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurosurgery, The Walton Centre NHS Foundation Trust, Liverpool, UK. rzakaria@nhs.net.

ABSTRACT

Background: Diffusion-weighted MRI (DWI) has been used in neurosurgical practice mainly to distinguish cerebral metastases from abscess and glioma. There is evidence from other solid organ cancers and metastases that DWI may be used as a biomarker of prognosis and treatment response. We therefore investigated DWI characteristics of cerebral metastases and their peritumoral region recorded pre-operatively and related these to patient outcomes.

Methods: Retrospective analysis of 76 cases operated upon at a single institution with DWI performed pre-operatively at 1.5T. Maps of apparent diffusion coefficient (ADC) were generated using standard protocols. Readings were taken from the tumor, peritumoral region and across the brain-tumor interface. Patient outcomes were overall survival and time to local recurrence.

Results: A minimum ADC greater than 919.4 × 10(-6) mm(2)/s within a metastasis predicted longer overall survival regardless of adjuvant therapies. This was not simply due to differences between the types of primary cancer because the effect was observed even in a subgroup of 36 patients with the same primary, non-small cell lung cancer. The change in diffusion across the tumor border and into peritumoral brain was measured by the "ADC transition coefficient" or ATC and this was more strongly predictive than ADC readings alone. Metastases with a sharp change in diffusion across their border (ATC >0.279) showed shorter overall survival compared to those with a more diffuse edge. The ATC was the only imaging measurement which independently predicted overall survival in multivariate analysis (hazard ratio 0.54, 95% CI 0.3 - 0.97, p = 0.04).

Conclusions: DWI demonstrates changes in the tumor, across the tumor edge and in the peritumoral region which may not be visible on conventional MRI and this may be useful in predicting patient outcomes for operated cerebral metastases.

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ADC of the metastasis predicts subsequent patient outcomes. Cases such as that in A. an enhancing lesion with hypo-intense DWI signal and higher than median ADC were compared to those such as B. an enhancing lesion but with hyper-intense DWI signal and corresponding low readings on ADC map. C. The largest group of metastases (n = 36) from a single primary - lung non-small cell carcinoma – were stratified into two groups by these readings of tumor ADC. Overall survival was significantly longer for cases with a high tumor ADCmean (10.5 months, CI 7.7 – 13.2) versus a low tumor ADCmean (5.8 months, CI 3.2 – 8.4, Log rank = 4.135, p = 0.042). D. For the 66 cases where gross total resection was performed, local recurrence in the brain occurred in 16. Metastases with a higher ADC showed significantly longer progression free survival, 18.4 months (95% CI 11.6 – 25.1) versus 11.3 months (95% 5.8 – 16.8) in those with a low ADCmean (Log rank test, Chi Square 4.263, p = 0.039).
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Figure 4: ADC of the metastasis predicts subsequent patient outcomes. Cases such as that in A. an enhancing lesion with hypo-intense DWI signal and higher than median ADC were compared to those such as B. an enhancing lesion but with hyper-intense DWI signal and corresponding low readings on ADC map. C. The largest group of metastases (n = 36) from a single primary - lung non-small cell carcinoma – were stratified into two groups by these readings of tumor ADC. Overall survival was significantly longer for cases with a high tumor ADCmean (10.5 months, CI 7.7 – 13.2) versus a low tumor ADCmean (5.8 months, CI 3.2 – 8.4, Log rank = 4.135, p = 0.042). D. For the 66 cases where gross total resection was performed, local recurrence in the brain occurred in 16. Metastases with a higher ADC showed significantly longer progression free survival, 18.4 months (95% CI 11.6 – 25.1) versus 11.3 months (95% 5.8 – 16.8) in those with a low ADCmean (Log rank test, Chi Square 4.263, p = 0.039).

Mentions: For survival analysis, the patients were grouped based on each of the DWI characteristics of their cerebral metastases and the two groups compared. The cases having a higher than median ADCmin (>919.4 × 10-6 mm2/s) showed a longer overall survival, median 9.7 months (95% CI: 8.5 – 11.0) versus those with a lower ADCmin (median survival 6.2 months, 95% CI: 3.7 – 8.8, Breslow Chi square 3.87, p = 0.049). There was no difference in the proportion of patients receiving WBRT in the high versus the low ADCmin groups that would confound the effect on survival (Chi square = 3.49, p =0.062). The effect was also seen if the median ADCmean was used as the cutoff to define the two groups but was not statistically significant: OS 9.7 months, 95% CI 7.9 – 11.5 for patients with metastases having a higher ADCmean (>1148.1 × 10-6 mm2/s) versus 6.7 months for lower ADCmean, 95% CI 4.9 – 8.5, Breslow Chi square = 2.83, p = 0.093.Regarding local control, the median progression free survival was 11.3 months (95% 5.8 – 16.8) in those cases with a low ADCmean reading versus 18.4 months (95% CI 11.6 – 25.1) in those with a high ADCmean (Log rank test, Chi Square 4.263, p = 0.039). This is illustrated in Figure 4. This effect was also seen when the median ADCmin was used as the cutoff to define the two groups but did not reach statistical significance (high ADCmin, progression free survival 18.4 months, 95% CI 13.2 – 23.6 versus low ADCmin, progression free survival 11.3 months, 95% CI 8.4 – 14.3, Log rank = 2.93, p = 0.087).


Diffusion-weighted MRI characteristics of the cerebral metastasis to brain boundary predicts patient outcomes.

Zakaria R, Das K, Radon M, Bhojak M, Rudland PR, Sluming V, Jenkinson MD - BMC Med Imaging (2014)

ADC of the metastasis predicts subsequent patient outcomes. Cases such as that in A. an enhancing lesion with hypo-intense DWI signal and higher than median ADC were compared to those such as B. an enhancing lesion but with hyper-intense DWI signal and corresponding low readings on ADC map. C. The largest group of metastases (n = 36) from a single primary - lung non-small cell carcinoma – were stratified into two groups by these readings of tumor ADC. Overall survival was significantly longer for cases with a high tumor ADCmean (10.5 months, CI 7.7 – 13.2) versus a low tumor ADCmean (5.8 months, CI 3.2 – 8.4, Log rank = 4.135, p = 0.042). D. For the 66 cases where gross total resection was performed, local recurrence in the brain occurred in 16. Metastases with a higher ADC showed significantly longer progression free survival, 18.4 months (95% CI 11.6 – 25.1) versus 11.3 months (95% 5.8 – 16.8) in those with a low ADCmean (Log rank test, Chi Square 4.263, p = 0.039).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 4: ADC of the metastasis predicts subsequent patient outcomes. Cases such as that in A. an enhancing lesion with hypo-intense DWI signal and higher than median ADC were compared to those such as B. an enhancing lesion but with hyper-intense DWI signal and corresponding low readings on ADC map. C. The largest group of metastases (n = 36) from a single primary - lung non-small cell carcinoma – were stratified into two groups by these readings of tumor ADC. Overall survival was significantly longer for cases with a high tumor ADCmean (10.5 months, CI 7.7 – 13.2) versus a low tumor ADCmean (5.8 months, CI 3.2 – 8.4, Log rank = 4.135, p = 0.042). D. For the 66 cases where gross total resection was performed, local recurrence in the brain occurred in 16. Metastases with a higher ADC showed significantly longer progression free survival, 18.4 months (95% CI 11.6 – 25.1) versus 11.3 months (95% 5.8 – 16.8) in those with a low ADCmean (Log rank test, Chi Square 4.263, p = 0.039).
Mentions: For survival analysis, the patients were grouped based on each of the DWI characteristics of their cerebral metastases and the two groups compared. The cases having a higher than median ADCmin (>919.4 × 10-6 mm2/s) showed a longer overall survival, median 9.7 months (95% CI: 8.5 – 11.0) versus those with a lower ADCmin (median survival 6.2 months, 95% CI: 3.7 – 8.8, Breslow Chi square 3.87, p = 0.049). There was no difference in the proportion of patients receiving WBRT in the high versus the low ADCmin groups that would confound the effect on survival (Chi square = 3.49, p =0.062). The effect was also seen if the median ADCmean was used as the cutoff to define the two groups but was not statistically significant: OS 9.7 months, 95% CI 7.9 – 11.5 for patients with metastases having a higher ADCmean (>1148.1 × 10-6 mm2/s) versus 6.7 months for lower ADCmean, 95% CI 4.9 – 8.5, Breslow Chi square = 2.83, p = 0.093.Regarding local control, the median progression free survival was 11.3 months (95% 5.8 – 16.8) in those cases with a low ADCmean reading versus 18.4 months (95% CI 11.6 – 25.1) in those with a high ADCmean (Log rank test, Chi Square 4.263, p = 0.039). This is illustrated in Figure 4. This effect was also seen when the median ADCmin was used as the cutoff to define the two groups but did not reach statistical significance (high ADCmin, progression free survival 18.4 months, 95% CI 13.2 – 23.6 versus low ADCmin, progression free survival 11.3 months, 95% CI 8.4 – 14.3, Log rank = 2.93, p = 0.087).

Bottom Line: Patient outcomes were overall survival and time to local recurrence.This was not simply due to differences between the types of primary cancer because the effect was observed even in a subgroup of 36 patients with the same primary, non-small cell lung cancer.The ATC was the only imaging measurement which independently predicted overall survival in multivariate analysis (hazard ratio 0.54, 95% CI 0.3 - 0.97, p = 0.04).

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurosurgery, The Walton Centre NHS Foundation Trust, Liverpool, UK. rzakaria@nhs.net.

ABSTRACT

Background: Diffusion-weighted MRI (DWI) has been used in neurosurgical practice mainly to distinguish cerebral metastases from abscess and glioma. There is evidence from other solid organ cancers and metastases that DWI may be used as a biomarker of prognosis and treatment response. We therefore investigated DWI characteristics of cerebral metastases and their peritumoral region recorded pre-operatively and related these to patient outcomes.

Methods: Retrospective analysis of 76 cases operated upon at a single institution with DWI performed pre-operatively at 1.5T. Maps of apparent diffusion coefficient (ADC) were generated using standard protocols. Readings were taken from the tumor, peritumoral region and across the brain-tumor interface. Patient outcomes were overall survival and time to local recurrence.

Results: A minimum ADC greater than 919.4 × 10(-6) mm(2)/s within a metastasis predicted longer overall survival regardless of adjuvant therapies. This was not simply due to differences between the types of primary cancer because the effect was observed even in a subgroup of 36 patients with the same primary, non-small cell lung cancer. The change in diffusion across the tumor border and into peritumoral brain was measured by the "ADC transition coefficient" or ATC and this was more strongly predictive than ADC readings alone. Metastases with a sharp change in diffusion across their border (ATC >0.279) showed shorter overall survival compared to those with a more diffuse edge. The ATC was the only imaging measurement which independently predicted overall survival in multivariate analysis (hazard ratio 0.54, 95% CI 0.3 - 0.97, p = 0.04).

Conclusions: DWI demonstrates changes in the tumor, across the tumor edge and in the peritumoral region which may not be visible on conventional MRI and this may be useful in predicting patient outcomes for operated cerebral metastases.

Show MeSH
Related in: MedlinePlus