Surveillance of Regional Nodal Basins and Gene Expression Profiling in Patients With Primary High Risk Cutaneous Squamous Cell Carcinoma of the Head and Neck

Sponsor

Johns Hopkins University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05956795

Collaborator

Castle Biosciences Incorporated (Industry)

470

Enrollment

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

In this prospective cohort study, investigators will conduct ultrasound surveillance of the nodal basins of patients with head and neck cutaneous squamous cell carcinoma (cSCC) whose tumors are considered high risk and staged by the Brigham and Women's Hospital (BWH) tumor staging system. The study will enroll patients with tumors staged T2a and who are also immunosuppressed (from solid organ transplant, hematologic malignancy or autoimmune disease), T2b (sentinel lymph node negative), and T3 (sentinel lymph node negative). After two years of surveillance, outcomes regarding local recurrence, nodal metastasis, disease specific death, and overall survival will be compared with historical controls with the overall hypothesis that ultrasound surveillance will detect subclinical disease earlier and help improve outcomes. Investigators will also submit tissue samples from excised tumor (from both prospective and retrospective groups) for gene expression profiling (GEP) to see if 40-GEP Class 2 and Class 2B tumors are associated with a higher incidence of subclinical disease.

Condition or Disease	Intervention/Treatment	Phase
Cutaneous Squamous Cell Carcinoma of the Head and Neck	Diagnostic Test: Ultrasound Diagnostic Test: 40-GEP

Study Design

Study Type:

Observational

Anticipated Enrollment :

470 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Surveillance of Regional Nodal Basins and Gene Expression Profiling in Patients With Primary High Risk Cutaneous Squamous Cell Carcinoma of the Head and Neck

Anticipated Study Start Date :

Aug 1, 2023

Anticipated Primary Completion Date :

Aug 14, 2028

Anticipated Study Completion Date :

Dec 31, 2028

Arms and Interventions

Arm	Intervention/Treatment
BWH stage T2a tumors in patients who are on chronic immunosuppression Patient's whose cutaneous squamous cell carcinoma is BWH stage T2a and also have a history of organ transplant, hematologic malignancy, autoimmune disease. After these participants are diagnosed, the participants are entered into the study without any further imaging or sentinel lymph node biopsy. The participants will have ultrasound surveillance every 6 months and regular visits every 3 months throughout the duration of the study (2 years). Tissue samples from excised tumor will be submitted to Castle Biosciences for 40-gene expression profiling.	Diagnostic Test: Ultrasound Sonographic imaging will be performed of lymph node basins Diagnostic Test: 40-GEP DecisionDx®-SCC, is a 40-gene expression profile (40-GEP) test recently developed and validated to improve metastasis risk prediction in cSCC patients with one or more risk factors using archival, formalin-fixed paraffin-embedded (FFPE) primary cSCC tissue. Other Names: CastleBiosciences 40-gene expression profile DecisionDx®-SCC
BWH stage T2b Participants whose cutaneous squamous cell carcinoma is BWH stage T2b. Participants will initially undergo CT imaging of the nodal basin immediately after diagnosis. If the CT is positive, the participants will be excluded from the study. If the CT is unremarkable, patients will undergo sentinel lymph node biopsy (SLNB), which has a higher sensitivity to detect occult micro-metastases. If the SLNB is negative, the participants are entered into the study. The participants will have ultrasound surveillance every 6 months and regular visits every 3 months throughout the duration of the study (2 years). Tissue samples from excised tumor will be submitted to Castle Biosciences for 40-gene expression profiling.	Diagnostic Test: Ultrasound Sonographic imaging will be performed of lymph node basins Diagnostic Test: 40-GEP DecisionDx®-SCC, is a 40-gene expression profile (40-GEP) test recently developed and validated to improve metastasis risk prediction in cSCC patients with one or more risk factors using archival, formalin-fixed paraffin-embedded (FFPE) primary cSCC tissue. Other Names: CastleBiosciences 40-gene expression profile DecisionDx®-SCC
BWH stage T3 Participants whose cutaneous squamous cell carcinoma is BWH stage T3. Participants will initially undergo CT imaging of the nodal basin immediately after diagnosis. If the CT is positive, The participants will be excluded from the study. If the CT is unremarkable, patients will undergo sentinel lymph node biopsy (SLNB), which has a higher sensitivity to detect occult micro-metastases. If the SLNB is negative, the participants are entered into the study The participants will have ultrasound surveillance every 6 months and regular visits every 3 months throughout the duration of the study (2 years). Tissue samples from excised tumor will be submitted to Castle Biosciences for 40-gene expression profiling.	Diagnostic Test: Ultrasound Sonographic imaging will be performed of lymph node basins Diagnostic Test: 40-GEP DecisionDx®-SCC, is a 40-gene expression profile (40-GEP) test recently developed and validated to improve metastasis risk prediction in cSCC patients with one or more risk factors using archival, formalin-fixed paraffin-embedded (FFPE) primary cSCC tissue. Other Names: CastleBiosciences 40-gene expression profile DecisionDx®-SCC

Arm

Intervention/Treatment

BWH stage T2a tumors in patients who are on chronic immunosuppression

Patient's whose cutaneous squamous cell carcinoma is BWH stage T2a and also have a history of organ transplant, hematologic malignancy, autoimmune disease. After these participants are diagnosed, the participants are entered into the study without any further imaging or sentinel lymph node biopsy. The participants will have ultrasound surveillance every 6 months and regular visits every 3 months throughout the duration of the study (2 years). Tissue samples from excised tumor will be submitted to Castle Biosciences for 40-gene expression profiling.

Diagnostic Test: Ultrasound

Sonographic imaging will be performed of lymph node basins

Diagnostic Test: 40-GEP

DecisionDx®-SCC, is a 40-gene expression profile (40-GEP) test recently developed and validated to improve metastasis risk prediction in cSCC patients with one or more risk factors using archival, formalin-fixed paraffin-embedded (FFPE) primary cSCC tissue.

Other Names:

CastleBiosciences 40-gene expression profile

DecisionDx®-SCC

BWH stage T2b

Participants whose cutaneous squamous cell carcinoma is BWH stage T2b. Participants will initially undergo CT imaging of the nodal basin immediately after diagnosis. If the CT is positive, the participants will be excluded from the study. If the CT is unremarkable, patients will undergo sentinel lymph node biopsy (SLNB), which has a higher sensitivity to detect occult micro-metastases. If the SLNB is negative, the participants are entered into the study. The participants will have ultrasound surveillance every 6 months and regular visits every 3 months throughout the duration of the study (2 years). Tissue samples from excised tumor will be submitted to Castle Biosciences for 40-gene expression profiling.

Diagnostic Test: Ultrasound

Sonographic imaging will be performed of lymph node basins

Diagnostic Test: 40-GEP

Other Names:

CastleBiosciences 40-gene expression profile

DecisionDx®-SCC

BWH stage T3

Participants whose cutaneous squamous cell carcinoma is BWH stage T3. Participants will initially undergo CT imaging of the nodal basin immediately after diagnosis. If the CT is positive, The participants will be excluded from the study. If the CT is unremarkable, patients will undergo sentinel lymph node biopsy (SLNB), which has a higher sensitivity to detect occult micro-metastases. If the SLNB is negative, the participants are entered into the study The participants will have ultrasound surveillance every 6 months and regular visits every 3 months throughout the duration of the study (2 years). Tissue samples from excised tumor will be submitted to Castle Biosciences for 40-gene expression profiling.

Diagnostic Test: Ultrasound

Sonographic imaging will be performed of lymph node basins

Diagnostic Test: 40-GEP

Other Names:

CastleBiosciences 40-gene expression profile

DecisionDx®-SCC

Outcome Measures

Primary Outcome Measures

Number of participants with Nodal metastasis [From diagnosis up to 2 years]
Metastatic squamous cell carcinoma to lymph node basins will be assessed through regular US surveillance of each cohort group along with review of respective medical records for any subsequent studies that were performed to confirm metastasis during routine care. Review of medical records will be conducted for historical controls. Investigators will then compare time to nodal metastasis between the US surveillance group and the historical controls using Kaplan-Meier estimates of the survivor function and a log-rank test. The investigators will also use Cox proportional-hazards regression to estimate the hazard ratio of nodal metastasis between these two group while adjusting for the covariates of age, sex, stage, etc.

Secondary Outcome Measures

Number of participants with local recurrence of squamous cell carcinoma [From diagnosis up to 2 years]
Recurrent squamous cell carcinoma in the original excision site will be confirmed by review of respective medical records/charts for subsequent confirmation studies performed during routine care. Investigators will use Kaplan-Meier estimates, a log-rank test, and Cox proportional-hazards to compare time to local recurrence between groups
Disease specific death [From diagnosis up to 2 years]
Death from cutaneous squamous cell carcinoma will be determined by review of medical records. Investigators will compare two-year disease-specific mortality rates between groups using a test of two proportions followed by logistic regression to allow adjustment for covariates.
Overall survival rate [From diagnosis up to 2 years]
The percentage of participants in each cohort who are still alive at the end of the study. Investigators will compare two-year overall mortality rates between groups using a test of two proportions followed by logistic regression to allow adjustment for covariates

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

All cSCC must be on the head or neck
All cSCC must be primary tumors.
BWH stage T2a tumors in patients who are on chronic immunosuppression (organ transplant, hematologic malignancy, autoimmune disease)
All BWH T2b or T3 tumors with a negative CT of the nodal basin AND a negative SLNB