Pathological response calculation assessment remains accurate with reduced tumor bed examination after neoadjuvant immunotherapy in clinically detectable stage III melanoma
Year: 2025
Type: article
Abstract: BACKGROUND: Neoadjuvant immunotherapy produces event-free survival advantage over adjuvant therapy for patients with surgically resectable macroscopic stage IIIB/C/D melanoma. Pathological response, determined as percentage residual viable tumor (% RVT), provides critical prognostic information and informs management decisions. Here, we assessed accuracy of %RVT calculation when reduced tumor bed (TB) was examined and leverage these results proposing streamlined protocols for pathological examination. PATIENTS AND METHODS: Comprehensive histopathological examination was carried out on 134 patient specimens after neoadjuvant immunotherapy with ipilimumab and nivolumab. Impact on %RVT when evaluating less TB than recommended by the initial International Neoadjuvant Melanoma Consortium (INMC) protocol was assessed. Firstly, % RVT of each case was recalculated using seven modified protocols and compared with % RVT obtained under INMC protocol. Next, a simulation study was carried out recalculating % RVT by random sampling 50%, 33%, and 25% of TB slides per specimen. RESULTS: > 0.97) for all the modified protocols and >90% accuracy in five protocols. Accuracy of major pathological response (MPR)/non-MPR and pathological response category classification was ≥96% in six protocols. The decrease in average slides examined per specimen ranged from 9% to 58%. In total, 85%, 79%, and 74% of simulations recalculating %RVT were within 5% of the INMC calculation when 50%, 33%, and 25% of TB slides were examined, respectively. If TB slide examination is capped at 20, %RVT calculation remains 93% accurate. CONCLUSIONS: TB embedded for histopathological examination in neoadjuvant stage IIIB/C/D melanoma specimens can be reduced without significantly compromising accuracy of %RVT calculation. We recommend an updated pathological assessment protocol: lymph nodes ≤3 cm examined in entirety; macroscopically involved lymph nodes >3 cm should have a modified examination protocol of at least a full cross-sectional transverse slice. Capping TB slides examined at 20 appears reasonable. This refined approach results in high accuracy and significant reduction in the slides examined.
Source: Annals of Oncology
Authors: R.V. Rawson, N.G. Maher, A.M. Menzies, S.N. Lo, N. Mesbah Ardakani, L.A. Jackett, I.A. Vergara, T.E. Pennington, K.F. Shannon, S. Ch’ng, M. Gonzalez, E.M. Burton, M.W. Lucas, I.L.M. Reijers, E.A. Rozeman, D.E. Gyorki, S. Sandhu, M.S. Carlino, J. Howle, M. Khattak, A. Van der Westhuizen, M.C. Andrews, V. Atkinson, A.C.J. van Akkooi, A.J. Spillane, R.P.M. Saw, B.A. van de Wiel, C.U. Blank, G.V. Long, M.T. Tetzlaff, R.A. Scolyer
Institutions: The University of Sydney, Royal Prince Alfred Hospital, Melanoma Institute Australia, NSW Health Pathology, Queen Elizabeth II Medical Centre, Pathwest Laboratory Medicine, Peter MacCallum Cancer Centre, The University of Texas MD Anderson Cancer Center, The Netherlands Cancer Institute, The University of Melbourne, Blacktown & Mount Druitt Hospital, Westmead Hospital, Edith Cowan University, Fiona Stanley Hospital, Lake Macquarie Private Hospital, University of Newcastle Australia, The Alfred Hospital, Alfred Health, Monash University, The University of Queensland, Princess Alexandra Hospital, University of California, San Francisco
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,080
Funders: Amgen, Bristol-Myers Squibb, Pfizer, AstraZeneca, GlaxoSmithKline, Sanofi, Melanoma Research Alliance, F. Hoffmann-La Roche, Hexal AG, Array BioPharma, Endocyte, Regeneron Pharmaceuticals, Les Laboratories Pierre Fabre, Australian Government, Menarini Silicon Biosystems, Myriad Genetics, Innovent Biologics, SkylineDx, MacroGenics, British Association of Dermatologists, University of Sydney, Eisai, Melanoma Institute Australia, Qbiotics, NeraCare, Genentech, University of California, San Francisco, Medical Research Council, National Health and Medical Research Council, Daiichi Sankyo Europe
Awards: Deep learning pathology image analysis of neoadjuvant treated melanoma, Towards Zero Deaths from Melanoma: Innovative Clinical Trials with Multi-omics Analyses, Melanoma: Getting the Diagnosis and Treatment Right for Better Patient Outcomes, Androgen disruption as a novel treatment approach in hormone 'insensitive' cancers
OpenAlex ID: W4415760643