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Browsing by Subject "Cutaneous squamous cell carcinoma"
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Item 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 MedicineAnti-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.Item Clinical Utility of the 40-Gene Expression Profile (40-GEP) Test for Improved Patient Management Decisions and Disease-Related Outcomes when Combined with Current Clinicopathological Risk Factors for Cutaneous Squamous Cell Carcinoma (cSCC): Case Series(Springer, 2022-02) Au, Jeremiah H.; Hooper, Perry B.; Fitzgerald, Alison L.; Somani, Ally-Khan; Dermatology, School of MedicineIntroduction While improvements have been made to risk assessment of cutaneous squamous cell carcinoma (cSCC) patients, there is a critical need for a uniform and more precise stratification system of their care. To address this unmet clinical need, a prognostic 40-gene expression profile (40-GEP) test has recently been developed and independently validated to show improved stratification of metastatic risk in high-risk cSCC patients compared with current staging systems. Methods Two cSCC cases, both male with similar patient profiles and the same staging status across two different staging systems, yet with opposing outcomes, were chosen for retrospective review of their primary biopsy using the 40-GEP test. Results Case 1 declined further treatment, even when presented with evidence of a small focus of cSCC found in the last layer of nonmarginal tissue obtained from Mohs micrographic surgery (MMS). Case 1 remained recurrence free, and retrospective analysis of the initial biopsy with the 40-GEP test provided a Class 1 result (low likelihood of metastasis). Case 2, even with subsequent clearing of the primary cSCC with MMS, noted another metastatic cSCC 3 months later. Case 2, after multimodal adjuvant treatments, died due to disease progression. Retrospective analysis of the initial biopsy with the 40-GEP test provided a Class 2B result (high likelihood of metastasis). Conclusions The cases discussed highlight the utility in 40-GEP to provide additional information to guide treatment decisions and improve outcomes. Integrating novel molecular prognostication with traditional clinicopathological risk factors can improve stratification of high-risk cSCC patients and may inform selection of risk-appropriate treatment and surveillance strategies.Item Facial Nerve Sacrifice During Parotidectomy for Metastatic Cutaneous Squamous Cell Carcinoma(Sage, 2021-02-25) Yesensky, Jessica; Solis, Roberto N.; Bewley, Arnaud; Otolaryngology -- Head and Neck Surgery, School of MedicineObjective: We analyzed the incidence of facial nerve sacrifice during parotidectomy for metastatic cutaneous squamous cell carcinoma (CSCC). Study design: We retrospectively reviewed the charts of patients with cutaneous squamous cell carcinoma. Setting: We used our CSCC institutional database, which includes patients treated at the University of California-Davis from 2001 to 2018. Methods: We evaluated patients who presented with biopsy-proven head and neck CSCC who underwent parotidectomy as a part of surgical treatment. We assessed the frequency of facial nerve sacrifice required in patients with normal preoperative facial nerve function with metastatic disease to the parotid. We evaluated the association between sacrifice and high-risk tumor variables using multivariate analysis. Results: We identified 53 patients with parotid metastasis and normal preoperative facial nerve function. Thirteen percent of patients required sacrifice of the main trunk of the facial nerve and 27% required sacrifice of a branch of the facial nerve. All patients who underwent facial nerve sacrifice had extracapsular spread (ECS). Perineural invasion (PNI) in the primary tumor (odds ratio [OR], 9.11; P = .041) and location of metastasis within the parotid body (OR, 6.6; P = .044) were independently associated with facial nerve sacrifice. Conclusion: Patients with regionally metastatic CSCC to the parotid gland frequently require sacrifice of all or a component of the facial nerve despite normal preoperative function. The likelihood of nerve sacrifice is highest for tumors with PNI and metastatic disease within the body of the parotid.Item Genome-wide association study identifies novel susceptibility loci for cutaneous squamous cell carcinoma(SpringerNature, 2016-07-18) Chahal, Harvind S.; Lin, Yuan; Ransohoff, Katherine J.; Hinds, David A.; Wu, Wenting; Dai, Hong-Ji; Qureshi, Abrar A.; Li, Wen-Qing; Kraft, Peter; Tang, Jean Y.; Han, Jiali; Sarin, Kavita Y.; Department of Epidemiology, Richard M. Fairbanks School of Public HealthCutaneous squamous cell carcinoma represents the second most common cutaneous malignancy, affecting 7-11% of Caucasians in the United States. The genetic determinants of susceptibility to cutaneous squamous cell carcinoma remain largely unknown. Here we report the results of a two-stage genome-wide association study of cutaneous squamous cell carcinoma, totalling 7,404 cases and 292,076 controls. Eleven loci reached genome-wide significance (P<5 × 10(-8)) including seven previously confirmed pigmentation-related loci: MC1R, ASIP, TYR, SLC45A2, OCA2, IRF4 and BNC2. We identify an additional four susceptibility loci: 11q23.3 CADM1, a metastasis suppressor gene involved in modifying tumour interaction with cell-mediated immunity; 2p22.3; 7p21.1 AHR, the dioxin receptor involved in anti-apoptotic pathways and melanoma progression; and 9q34.3 SEC16A, a putative oncogene with roles in secretion and cellular proliferation. These susceptibility loci provide deeper insight into the pathogenesis of squamous cell carcinoma.Item Integrating the 40-Gene Expression Profile (40-GEP) Test Improves Metastatic Risk-Stratification Within Clinically Relevant Subgroups of High-Risk Cutaneous Squamous Cell Carcinoma (cSCC) Patients(Springer, 2024) Wysong, Ashley; Somani, Ally-Khan; Ibrahim, Sherrif F.; Cañueto, Javier; Fitzgerald, Alison L.; Siegel, Jennifer J.; Prasai, Anesh; Goldberg, Matthew S.; Farberg, Aaron S.; Regula, Christie; Bar, Anna; Kasprzak, Julia; Brodland, David G.; Koyfman, Shlomo A.; Arron, Sarah T.; Dermatology, School of MedicineIntroduction: The validated 40-gene expression profile (40-GEP) test independently stratifies risk of regional or distant metastasis for cutaneous squamous cell carcinoma (cSCC) tumors with high-risk clinicopathologic features. This study evaluated the stratification of risk by the 40-GEP test in a large cohort of tumors with one or more high-risk factors and in clinically relevant subgroups, including tumors within National Comprehensive Cancer Network (NCCN) high- and very-high-risk groups, lower-stage BWH T1 and T2a tumors, and patients > 65 years old. Methods: This multicenter (n = 58) performance study of the 40-GEP included 897 patients. Kaplan-Meier analyses were performed to assess risk stratification profiles for 40-GEP Class 1 (low), Class 2A (higher) and Class 2B (highest) risk groups, while nested Cox regression models were used to compare risk prediction of clinicopathologic risk classification systems versus risk classification systems in combination with 40-GEP. Results: Patients classified as 40-GEP Class 1, Class 2A, or Class 2B had significantly different metastatic risk profiles (p < 0.0001). Integrating 40-GEP results into models with individual clinicopathologic risk factors or risk classification systems (Brigham and Women's Hospital, American Joint Committee on Cancer Staging Manual, 8th Edition) and NCCN demonstrated significant improvement in accuracy for prediction of metastatic events (ANOVA for model deviance, p < 0.0001 for all models). Conclusion: The 40-GEP test demonstrates accurate, independent, clinically actionable stratification of metastatic risk and improves predictive accuracy when integrated into risk classification systems. The improved accuracy of risk assessment when including tumor biology via the 40-GEP test ensures more risk-aligned, personalized patient management decisions.