Anders Bergström

Background/Objectives: Histological assessment of the response to neoadjuvant immunotherapy in stage IIIB/C cutaneous melanoma is commonly performed using the INMC recommendations, which advocate embedding the entire tumour bed. However, this approach is highly resource-intensive. The original Swedish National Clinical Cancer Care Guidelines for Melanoma recommend a reduced embedding strategy, but its diagnostic performance in comparison with full embedding has not been systematically evaluated. We aimed to assess whether a reduced sampling approach based on selecting representative tumour bed slices provides comparable response classification to comprehensive embedding according to the INMC protocol. Methods: Ten consecutive patients with stage IIIB/C melanoma treated with neoadjuvant immunotherapy and subsequent lymph node dissection were included. All lymph node material was completely embedded, and the pathological response was evaluated using INMC criteria. Response classification based on the full embedding of the tumour bed was compared with reduced-sampling approaches that simulate the Swedish National Clinical Cancer Care Guidelines for Melanoma. Agreement between sampling methods was analyzed. Results: Targeted reduced sampling of two slices per lymph node demonstrated complete agreement with the full embedding for the INMC response category. Conclusions: In our study, a targeted reduced-embedding strategy focusing on slices with the largest area of tumour bed enables accurate histological assessment of response to neoadjuvant immunotherapy in stage IIIB/C melanoma while substantially reducing workload. These findings support the feasibility of targeted reduced embedding of instructions in the Swedish National Clinical Cancer Care Guidelines for Melanoma as an efficient alternative to full embedding of the lymphadenectomy specimens.

(1) Purpose: Small intestinal neuroendocrine tumors (SI-NETs) often present with distant metastases at diagnosis. Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogues is a systemic treatment that increases overall survival (OS) in SI-NET patients with stage IV disease. However, the treatment response after PRRT, which targets somatostatin receptor 2 (SSTR2), is variable and predictive factors have not been established. This exploratory study aims to evaluate if SSTR2 expression in SI-NETs could be used to predict OS after PRRT treatment. (2) Methods: Using a previously constructed Tissue Micro Array (TMA) we identified tissue samples from 42 patients that had received PRRT treatment during 2006–2017 at Sahlgrenska University hospital. Immunohistochemical expression of SSTR2, Ki-67 and neuroendocrine markers synaptophysin and Chromogranin A (CgA) were assessed. A retrospective estimation of ¹⁷⁷Lu-DOTATATE uptake in 33 patients was performed. Data regarding OS and non-surgical treatment after PRRT were collected. Another subgroup of 34 patients with paired samples from 3 tumor sites (primary tumor, lymph node and liver metastases) was identified in the TMA. The SSTR2 expression was assessed in corresponding tissue samples (n = 102). (3) Results: The patients were grouped into Low SSTR2 or High SSTR2 groups based upon on levels of SSTR2 expression. There was no significant difference in ¹⁷⁷Lu-DOTATATE uptake between the groups. The patients in the Low SSTR2 group had significantly longer OS after PRRT than the patients in the High SSTR2 group (p = 0.049). PRRT treated patients with low SSTR2 expression received less additional treatment compared with patients with high SSTR2 expression. SSTR2 expression did not vary between tumor sites but correlated within patients. (4) Conclusion: The results from the present study suggest that retrospective evaluation of SSTR2 expression in resected tumors cannot be used to predict OS after PRRT.