Harano K, et al. J Gynecol Oncol. 2025 Apr;36:e117. https://doi.org/10.3802/jgo.2025.36.e117

To evaluate the rate of early breast cancer (EBC) patients treated with neoadjuvant systemic therapy (NAT) in Italy, criteria of patient selection and types of therapies delivered, an analysis of 1276 patients with stage I-II-III was conducted out of 1633 patients enrolled in the multicenter prospective observational BRIDE study. A total of 177 patients (13.9%) were treated with NAT and 1099 (85.9%) with surgery; in multivariate analysis, menopausal status, cT, cN, grade, HER2-positive and Triple negative (TN) subgroups were significantly associated with the decision to administer NAT. The type of NAT delivered was influenced by EBC subtype. NAT was administered to 53.2% of HER2+/HR-negative, 27.9% of HER2+/HR+, 7.1% of HER2-negative/HR+ and 30.3% of TN EBC patients. The pCR rates were similar to the ones reported in the literature: 74.2% in HER2+/HR-negative, 52.3% in HER2+/HR+, 17.2% in HER2-negative/HR+ and 37.9% in TN. In clinical practice, patient and tumor characteristics influenced oncologists in the decision to administer NAT in EBC and in the choice of the type of systemic therapy, according to ESMO and AIOM Guidelines. Currently, it is recommended always to evaluate the use of NAT in EBC, mainly in HER2+ and TN patients, considering that pCR is associated with significantly better survival of the patient and that effective therapies are now available for residual disease.

Background: the prognostic significance of tumor infiltrating lymphocytes (TILs) in intermediate/thick primary cutaneous melanoma (PCM) remains controversial, partially because conventional evaluation is not reliable, due to inter-observer variability and diverse scoring methods. We aimed to assess the prognostic impact of the density and spatial distribution of immune cells in early stage intermediate/thick PCM. Materials and Methods: digital image acquisition and quantitative analysis of tissue immune biomarkers (CD3, CD4, CD8, CD68, PD-L1, CD163, FOX-P3, and PD-1) was carried out in a training cohort, which included patients with primary PCM ≥ 2 mm diagnosed, treated, and followed-up prospectively in three Italian centers. Results were validated in an independent Italian cohort. Results: in the training cohort, 100 Stage II–III melanoma patients were valuable. At multivariable analysis, a longer disease free survival (DFS) was statistically associated with higher levels of CD4⁺ intratumoral T-cells (aHR [100 cell/mm² increase] 0.98, 95%CI 0.95–1.00, p = 0.041) and CD163⁺ inner peritumoral (aHR [high vs. low] 0.56, 95%CI 0.32–0.99, p = 0.047). A statistically significant longer DFS (aHR [high-high vs. low-low] 0.52, 95%CI 0.28–0.99, p = 0.047) and overall survival (OS) (aHR [high-high vs. low-low] 0.39, 95%CI 0.18–0.85, p = 0.018) was found in patients with a high density of both intratumoral CD8⁺ T-cells and CD68⁺ macrophages as compared to those with low density of both intratumoral CD8⁺ T-cells and CD68⁺ macrophages. Consistently, in the validation cohort, patients with high density of both intratumoral CD8⁺ and CD3⁺ T-cells were associated to a statistically better DFS (aHR[high-high vs. low-low] 0.24, 95%CI 0.10–0.56, p < 0.001) and those with high density of both intratumoral CD8⁺ and CD68⁺ were associated to a statistically longer OS (aHR[high-high vs. low-low] 0.28, 95%CI 0.09–0.86, p = 0.025). Conclusion: our findings suggest that a specific preexisting profile of T cells and macrophages distribution in melanomas may predict the risk of recurrence and death with potential implications for the stratification of stage II–III melanoma patients.

Although it is a disease that occurs mainly in the Caucasian population, uveal melanoma (UM) is the most common primary intraocular tumor in adults. Here, we used digital pathology and image analysis for the diagnosis of UM and the prediction of the prognosis. Our retrospective study included a total of 404 histopathological slides from 101 patients. A digital image acquisition and quantitative analysis of tissue immune biomarkers (CD4, CD8, CD68, CD163) were performed. A negative impact of the intratumoral CD8 positive cell density higher than 13.3 cells/mm² was detected for both RFS (HR 2.08, 95% Cl 1.09 to 3.99, p = 0.027) and OS (HR 3.30, 95% CI 1.58 to 6.88, p = 0.001). Moreover, we confirmed that older age and stage III were independent negative prognostic factors for both RFS and OS. Our results suggest that a specific distribution profile of CD8 in UM might predict the risk of relapse and death, with potential implications for determining which subgroups of UMs are amenable to specific pharmacological treatment regimens.