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Association of a 40-Gene Expression Profile With Risk of Metastatic Disease Progression of Cutaneous Squamous Cell Carcinoma and Specification of Benefit of Adjuvant Radiation Therapy.
- Source :
-
International journal of radiation oncology, biology, physics [Int J Radiat Oncol Biol Phys] 2024 Nov 01; Vol. 120 (3), pp. 760-771. Date of Electronic Publication: 2024 May 27. - Publication Year :
- 2024
-
Abstract
- Purpose: Adjuvant radiation therapy (ART) for cutaneous squamous cell carcinoma is recommended based on a number of wide-ranging clinicopathologic features, which encompass a broad array of patients. The 40-gene expression profile (GEP) test classifies cutaneous squamous cell carcinoma tumors into low (class 1), higher (class 2A), or highest (class 2B) risk of nodal and/or distant metastasis. This study's hypotheses are as follows: (1) local recurrence is associated with metastatic disease progression and (2) 40-GEP, by identifying high risk for metastasis, could predict a metastasis-specific benefit from ART.<br />Methods and Materials: Samples were obtained from 920 patients (ART-untreated: 496 class 1, 335 class 2A, and 33 class 2B; ART-treated: 11 class 1, 35 class 2A, and 10 class 2B) who were matched on clinical risk factors and stratified by ART status to create 49 matched patient strata. To control for the variety of characteristics and treatment selection bias, randomly sampled pairs of matched ART and non-ART patients comprising 10,000 resampled cohorts were each analyzed for 5-year metastasis-free survival and predicted time to metastatic event.<br />Results: Of 96 patients experiencing local recurrence, 56.3% experienced metastasis; of those experiencing both, 88.9% experienced local recurrence before (75.9%) or concurrently (13.0%) with metastasis. After matching for clinicopathologic risk, median 5-year disease progression rates for resampled cohorts demonstrated approximately 50% improvement for class 2B ART-treated compared with ART-untreated cohorts. ART-treated class 2B cohorts had a 5-fold delay in predicted time to metastatic event and deceleration of disease progression compared with ART-untreated cohorts (Kolmogorov-Smirnov test, P < .01); this was not observed for patients with class 1 or 2A cSCC (P > .05 for each). No risk factor or staging system combined with ART status identified groups that would benefit from ART as well as 40-GEP.<br />Conclusions: Forty-GEP identifies patients at the highest risk of nodal/distant metastasis who may derive the greatest benefit from ART, as well as patients who may have clinical indications for ART but are at low risk of metastasis. Compared with current guidelines, 40-GEP could provide greater specificity concerning the benefit of ART in individual patients.<br /> (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Humans
Male
Female
Radiotherapy, Adjuvant
Aged
Middle Aged
Aged, 80 and over
Neoplasm Metastasis
Gene Expression Profiling
Transcriptome
Skin Neoplasms pathology
Skin Neoplasms genetics
Skin Neoplasms radiotherapy
Carcinoma, Squamous Cell genetics
Carcinoma, Squamous Cell radiotherapy
Carcinoma, Squamous Cell pathology
Carcinoma, Squamous Cell secondary
Carcinoma, Squamous Cell mortality
Disease Progression
Neoplasm Recurrence, Local genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1879-355X
- Volume :
- 120
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- International journal of radiation oncology, biology, physics
- Publication Type :
- Academic Journal
- Accession number :
- 38810706
- Full Text :
- https://doi.org/10.1016/j.ijrobp.2024.05.022