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Pathological response and tumour bed histopathological features correlate with survival following neoadjuvant immunotherapy in stage III melanoma.
Rawson, R V; Adhikari, C; Bierman, C; Lo, S N; Shklovskaya, E; Rozeman, E A; Menzies, A M; van Akkooi, A C J; Shannon, K F; Gonzalez, M; Guminski, A D; Tetzlaff, M T; Stretch, J R; Eriksson, H; van Thienen, J V; Wouters, M W; Haanen, J B A G; Klop, W M C; Zuur, C L; van Houdt, W J; Nieweg, O E; Ch'ng, S; Rizos, H; Saw, R P M; Spillane, A J; Wilmott, J S; Blank, C U; Long, G V; van de Wiel, B A; Scolyer, R A.
Afiliação
  • Rawson RV; Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; Departments of Tissue Pathology and Diagnostic Oncology, Sydney, Australia; Department of Melanoma Surgical Oncology, Royal Prince Alfred Hospital,
  • Adhikari C; Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; Departments of Tissue Pathology and Diagnostic Oncology, Sydney, Australia; Department of Melanoma Surgical Oncology, Royal Prince Alfred Hospital,
  • Bierman C; The Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • Lo SN; Melanoma Institute Australia, The University of Sydney, Sydney, Australia.
  • Shklovskaya E; Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, Australia.
  • Rozeman EA; The Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • Menzies AM; Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; Royal North Shore Hospital, Sydney, Australia; Mater Hospital, Sydney, Australia.
  • van Akkooi ACJ; The Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • Shannon KF; Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; Departments of Tissue Pathology and Diagnostic Oncology, Sydney, Australia; Department of Melanoma Surgical Oncology, Royal Prince Alfred Hospital,
  • Gonzalez M; Melanoma Institute Australia, The University of Sydney, Sydney, Australia.
  • Guminski AD; Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Royal North Shore Hospital, Sydney, Australia; Mater Hospital, Sydney, Australia.
  • Tetzlaff MT; Department of Pathology, Dermatopathology and Oral Pathology Unit, The University of California, San Francisco, San Francisco, USA; Department of Dermatology, Dermatopathology and Oral Pathology Unit, The University of California, San Francisco, San Francisco, USA.
  • Stretch JR; Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; Departments of Tissue Pathology and Diagnostic Oncology, Sydney, Australia; Department of Melanoma Surgical Oncology, Royal Prince Alfred Hospital,
  • Eriksson H; Theme Cancer, Skin Cancer Center/Department of Oncology, Karolinska University Hospital, Stockholm, Sweden; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
  • van Thienen JV; The Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • Wouters MW; The Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands.
  • Haanen JBAG; The Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • Klop WMC; The Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • Zuur CL; The Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • van Houdt WJ; The Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • Nieweg OE; Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; Departments of Tissue Pathology and Diagnostic Oncology, Sydney, Australia; Department of Melanoma Surgical Oncology, Royal Prince Alfred Hospital,
  • Ch'ng S; Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; Departments of Tissue Pathology and Diagnostic Oncology, Sydney, Australia; Department of Melanoma Surgical Oncology, Royal Prince Alfred Hospital,
  • Rizos H; Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, Australia.
  • Saw RPM; Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; Departments of Tissue Pathology and Diagnostic Oncology, Sydney, Australia; Department of Melanoma Surgical Oncology, Royal Prince Alfred Hospital,
  • Spillane AJ; Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; Royal North Shore Hospital, Sydney, Australia; Mater Hospital, Sydney, Australia.
  • Wilmott JS; Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
  • Blank CU; The Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • Long GV; Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; Royal North Shore Hospital, Sydney, Australia; Mater Hospital, Sydney, Australia.
  • van de Wiel BA; The Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • Scolyer RA; Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; Departments of Tissue Pathology and Diagnostic Oncology, Sydney, Australia; Department of Melanoma Surgical Oncology, Royal Prince Alfred Hospital,
Ann Oncol ; 32(6): 766-777, 2021 06.
Article em En | MEDLINE | ID: mdl-33744385
ABSTRACT

BACKGROUND:

Guidelines for pathological evaluation of neoadjuvant specimens and pathological response categories have been developed by the International Neoadjuvant Melanoma Consortium (INMC). As part of the Optimal Neo-adjuvant Combination Scheme of Ipilimumab and Nivolumab (OpACIN-neo) clinical trial of neoadjuvant combination anti-programmed cell death protein 1/anti-cytotoxic T-lymphocyte-associated protein 4 immunotherapy for stage III melanoma, we sought to determine interobserver reproducibility of INMC histopathological assessment principles, identify specific tumour bed histopathological features of immunotherapeutic response that correlated with recurrence and relapse-free survival (RFS) and evaluate proposed INMC pathological response categories for predicting recurrence and RFS. PATIENTS AND

METHODS:

Clinicopathological characteristics of lymph node dissection specimens of 83 patients enrolled in the OpACIN-neo clinical trial were evaluated. Two methods of assessing histological features of immunotherapeutic response were evaluated the previously described immune-related pathologic response (irPR) score and our novel immunotherapeutic response score (ITRS). For a subset of cases (n = 29), cellular composition of the tumour bed was analysed by flow cytometry.

RESULTS:

There was strong interobserver reproducibility in assessment of pathological response (κ = 0.879) and percentage residual viable melanoma (intraclass correlation coefficient = 0.965). The immunotherapeutic response subtype with high fibrosis had the strongest association with lack of recurrence (P = 0.008) and prolonged RFS (P = 0.019). Amongst patients with criteria for pathological non-response (pNR, >50% viable tumour), all who recurred had ≥70% viable melanoma. Higher ITRS and irPR scores correlated with lack of recurrence in the entire cohort (P = 0.002 and P ≤ 0.0001). The number of B lymphocytes was significantly increased in patients with a high fibrosis subtype of treatment response (P = 0.046).

CONCLUSIONS:

There is strong reproducibility for assessment of pathological response using INMC criteria. Immunotherapeutic response of fibrosis subtype correlated with improved RFS, and may represent a biomarker. Potential B-cell contribution to fibrosis development warrants further study. Reclassification of pNR to a threshold of ≥70% viable melanoma and incorporating additional criteria of <10% fibrosis subtype of response may identify those at highest risk of recurrence, but requires validation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Cutâneas / Melanoma Tipo de estudo: Guideline / Prognostic_studies Limite: Humans Idioma: En Revista: Ann Oncol Assunto da revista: NEOPLASIAS Ano de publicação: 2021 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Cutâneas / Melanoma Tipo de estudo: Guideline / Prognostic_studies Limite: Humans Idioma: En Revista: Ann Oncol Assunto da revista: NEOPLASIAS Ano de publicação: 2021 Tipo de documento: Article