M T Tetzlaff1, J L Messina2, J E Stein3, X Xu4, R N Amaria5, C U Blank6, B A van de Wiel6, P M Ferguson7, R V Rawson7, M I Ross8, A J Spillane9, J E Gershenwald10, R P M Saw7, A C J van Akkooi6, W J van Houdt6, T C Mitchell11, A M Menzies9, G V Long12, J A Wargo13, M A Davies14, V G Prieto15, J M Taube3, R A Scolyer7. 1. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA; Department of Translational and Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA. Electronic address: mtetzlaff@mdanderson.org. 2. Departments of Anatomic Pathology and Cutaneous Oncology, Moffitt Cancer Center, Tampa, USA. 3. Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, USA. 4. Department of Pathology and Laboratory Medicine, The Hospital of the University of Pennsylvania, Philadelphia, USA. 5. Melanoma Medical Oncology Department, The University of Texas MD Anderson Cancer Center, Houston, USA. 6. The Netherlands Cancer Institute, Amsterdam, Netherlands. 7. Melanoma Institute of Australia, The University of Sydney and Royal Prince Alfred Hospital, Sydney, Australia. 8. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. 9. Melanoma Institute of Australia, The University of Sydney, Royal North Shore and Mater Hospitals, Sydney, Australia. 10. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, USA. 11. Department of Medicine, The Hospital of the University of Pennsylvania, Philadelphia, USA. 12. Melanoma Institute of Australia, The University of Sydney, Royal North Shore Hospital, Sydney, Australia. 13. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA. 14. Department of Translational and Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA; Melanoma Medical Oncology Department, The University of Texas MD Anderson Cancer Center, Houston, USA; Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, USA. 15. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA; Dermatology, The University of Texas MD Anderson Cancer Center, Houston, USA.
Abstract
Background: Clinical trials have recently evaluated safety and efficacy of neoadjuvant therapy among patients with surgically resectable regional melanoma metastases. To capture informative prognostic data connected to pathological response in such trials, it is critical to standardize pathologic assessment and reporting of tumor response after this treatment. Methods: The International Neoadjuvant Melanoma Consortium meetings in 2016 and 2017 assembled pathologists from academic centers to develop consensus guidelines for pathologic examination and reporting of surgical specimens from AJCC (8th edition) stage IIIB/C/D or oligometastatic stage IV melanoma patients treated with neoadjuvant-targeted or immune therapy. Patterns of pathologic response are provided context to inform these guidelines. Results: Based on our collective experience and guided by efforts in well-established neoadjuvant settings like breast cancer, procedures directing handling of pre- and post-neoadjuvant therapy-treated melanoma specimens are provided to facilitate comparison of findings across different trials and centers. Definitions of pathologic response are provided together with guidelines for reporting and quantifying the extent of pathologic response. Finally, the spectrum of histopathologic responses observed following neoadjuvant-targeted and immune-checkpoint therapy is described and illustrated. Conclusions: Standardizing pathologic evaluation of resected melanoma metastases following neoadjuvant-targeted or immune-checkpoint therapy allows more robust stratification of patient outcomes. This includes recognizing the spectrum of histopathologic response patterns to neoadjuvant therapy and a standard approach to grading pathologic responses. Such an approach will facilitate comparison of results across clinical trials and inform ongoing correlative studies into the mechanisms of response and resistance to agents applied in the neoadjuvant setting.
Background: Clinical trials have recently evaluated safety and efficacy of neoadjuvant therapy among patients with surgically resectable regional melanoma metastases. To capture informative prognostic data connected to pathological response in such trials, it is critical to standardize pathologic assessment and reporting of tumor response after this treatment. Methods: The International Neoadjuvant Melanoma Consortium meetings in 2016 and 2017 assembled pathologists from academic centers to develop consensus guidelines for pathologic examination and reporting of surgical specimens from AJCC (8th edition) stage IIIB/C/D or oligometastatic stage IV melanomapatients treated with neoadjuvant-targeted or immune therapy. Patterns of pathologic response are provided context to inform these guidelines. Results: Based on our collective experience and guided by efforts in well-established neoadjuvant settings like breast cancer, procedures directing handling of pre- and post-neoadjuvant therapy-treated melanoma specimens are provided to facilitate comparison of findings across different trials and centers. Definitions of pathologic response are provided together with guidelines for reporting and quantifying the extent of pathologic response. Finally, the spectrum of histopathologic responses observed following neoadjuvant-targeted and immune-checkpoint therapy is described and illustrated. Conclusions: Standardizing pathologic evaluation of resected melanoma metastases following neoadjuvant-targeted or immune-checkpoint therapy allows more robust stratification of patient outcomes. This includes recognizing the spectrum of histopathologic response patterns to neoadjuvant therapy and a standard approach to grading pathologic responses. Such an approach will facilitate comparison of results across clinical trials and inform ongoing correlative studies into the mechanisms of response and resistance to agents applied in the neoadjuvant setting.
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