Browsing by Author "Brohl, Andrew S."

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    Cetuximab for Immunotherapy-Refractory/Ineligible Cutaneous Squamous Cell Carcinoma
    (MDPI, 2023-06-14) Marin-Acevedo, Julian A.; Withycombe, Bethany M.; Kim, Youngchul; Brohl, Andrew S.; Eroglu, Zeynep; Markowitz, Joseph; Tarhini, Ahmad A.; Tsai, Kenneth Y.; Khushalani, Nikhil I.; Medicine, School of Medicine
    Anti-PD1 therapy demonstrated impressive, prolonged responses in advanced cutaneous squamous cell carcinoma (CSCC). Therapy for ICI-refractory/ineligible disease remains unclear. We performed a retrospective analysis in locally-advanced/metastatic CSCC using cetuximab across three cohorts: immediately after ICI failure (A), not immediately following ICI failure (B), or without prior ICI (C). The primary endpoint was the overall response rate (ORR). Secondary endpoints included disease-control rate (DCR), progression-free survival (PFS), overall survival (OS), time-to-response (TTR) and toxicity. Twenty-three patients were included. In cohort A (n = 11), the ORR was 64% and DCR was 91%, with six ongoing responses at data cutoff. In cohort B (n = 2), all patients had progression as the best response. At a median follow-up of 21 months for A and B, TTR and PFS were 2.0 and 17.3 months, respectively. The median OS was not reached. In cohort C (n = 10), the ORR and DCR were 80%, including five ongoing responses at the data cutoff. At a median follow-up of 22.4 months, the TTR, PFS and OS were 2.5, 7.3 and 23.1 months, respectively. Cetuximab was well tolerated in all cohorts. In summary, cetuximab is effective in patients with failure/contraindications to ICI. Cetuximab immediately after ICI failure yielded particularly fast, durable responses. If confirmed, this could be the preferred therapy following ICI failure.
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    Genomic, transcriptomic, and immunogenomic landscape of over 1300 sarcomas of diverse histology subtypes
    (Springer Nature, 2025-05-06) Soupir, Alex; Ospina, Oscar E.; Hampton, Oliver; Churchman, Michelle; Radmacher, Michael; Hedges, Dale; McKean, David; Agius, Phaedra; Zeeshan, Saman; Seligson, Nathan D.; Pollock, Raphael; Liebner, David; Chen, James L.; Tinoco, Gabriel; Salhia, Bodour; McCarter, Martin; Wilky, Breelyn A.; Miller, Benjamin J.; Cavnar, Michael J.; Groundland, John S.; Schneider, Bryan P.; Riedlinger, Gregory; Edge, Stephen B.; Moskaluk, Christopher A.; Cardona, Kenneth; Naqash, Abdul Rafeh; Gonzalez, Ricardo J.; Mullinax, John E.; Joyce, David M.; Binitie, Odion; Letson, G. Douglas; Naghavi, Arash O.; Druta, Mihaela; Reed, Damon R.; Siegel, Erin M.; Teer, Jamie K.; Fridley, Brooke L.; Brohl, Andrew S.; Medicine, School of Medicine
    Given their rarity and diversity, a fundamental understanding of the genomic underpinnings for many sarcoma subtypes is still lacking. To better define the molecular landscape of this group of diseases, we perform matched whole exome sequencing and RNA sequencing on a cohort of 1340 sarcoma tumor specimens. We identify recurrent somatic mutations and observe an increased mutational burden in metastatic vs. primary samples (p < 0.001). We observe frequent copy number alterations including whole genome doubling, with this feature being more common in metastatic tumors (p = 0.026). Estimation of immune cell abundances followed by hierarchical clustering identifies five immune subtypes ranging from low to high and we observe inferior overall survival in immune deplete clusters compared to immune enriched (p < 0.01). Interestingly, GIST predominantly form a distinct "immune intermediate" cluster that is marked by a specific enrichment for NK cells (FDR < 0.01).