Breslow Density Is a Novel Prognostic Feature That Adds Value to Melanoma Staging

Abstract

Histomorphologic prognostic biomarkers that can be measured using only an hematoxylin and eosin stain are very attractive because they are simple and cheap. We conceived an entirely novel biomarker of this type, the Breslow density (BD), which measures invasive melanoma cell density at the site where Breslow thickness (BT) is measured. This study assessed BD's prognostic value. In this study, BD was measured in 1329 melanoma patients. Measurement accuracy and precision was assessed using intraclass correlation coefficient (ICC). Survival was assessed with a primary end-point of melanoma-specific survival (MSS) and also overall survival and metastasis-free survival. We found that BD measurement was accurate compared with gold standard image analysis (ICC, 0.84). Precision was excellent for 3 observers with different experience (ICC, 0.93) and for an observer using only written instructions (ICC, 0.93). BD was a highly significant predictor in multivariable analysis for overall survival, MSS, and metastasis-free survival (each, P<0.001) and it explained MSS better than BT, but BT and BD together had best explanatory capability. A BD cut point of ≥65% was trained in 970 melanomas and validated in 359. This cut point showed promise as a novel way to upstage melanoma from T stage "a" to "b." BD was combined with BT to create a targeted burden score. This was a validated as an adjunct to American Joint Committee on Cancer stage. In summary, BD can be measured accurately and precisely. It demonstrated independent prognostic value and explained MSS better than BT alone. Notably, we demonstrated ways that BD could be used with American Joint Committee on Cancer version 8 staging.

Development and Initial Validation of Calculated Tumor Area as a Prognostic Tool in Cutaneous Malignant Melanoma

“…Targeted burden score was entered into Cox proportional hazards regression models with a natural logarithm transformation, as done previously. 22 The BIC of a CTA-only model was 2054.3; BIC of TBS only, 2061.1 (difference, 6.8), showing strong evidence for the CTA model. 21 In addition, a multivariable model was created in which both CTA and TBS were entered.…”

Optimal surveillance strategies for patients with stage 1 cutaneous melanoma post primary tumour excision: three systematic reviews and an economic model

“…A total of 11 articles reporting 11 different risk prediction models met the full inclusion criteria of this review. [105][106][107][108][109][110][111][112][113][114][115] A total of 101 studies were reviewed fully and excluded for the following reasons: used single prognostic factors for model development (21%), combined stages of the disease (28%) or were not validated (51%). Details of the excluded studies are presented in Appendix 4.…”

“…A summary of the studies and patient characteristics is presented in Table 7. Eight of the studies were conducted in the USA, [106][107][108][109]111,[113][114][115] one in the UK, 112 one in Australia 105 and one in Italy. 110 Seven studies used a retrospective cohort design, [105][106][107][108][109]112,115 three used a prospective design 111,113,114 and one used a retrospective cohort of prospectively collected data.…”

Global and mitosis‐specific interobserver variation in mitotic count scoring and implications for malignant melanoma staging

“…For Kaplan-Meier analysis of a single mitosis in pT1 melanoma a starting cohort of 970 cutaneous melanoma from the archives of the University Hospitals of Leicester NHS trust was used representing cases diagnosed between January 1st 2004 and December 31st 2011. The cases have been described previously 9 . From these, a set of 476 was identified that were ≤ 1 mm thick, with either 0 or 1 mitoses per mm 2 and without ulceration.…”