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MB Sample ID: SA202365
Local Sample ID: | BW45-37 |
Subject ID: | SU002194 |
Subject Type: | Human |
Subject Species: | Homo sapiens |
Taxonomy ID: | 9606 |
Select appropriate tab below to view additional metadata details:
Subject:
Subject ID: | SU002194 |
Subject Type: | Human |
Subject Species: | Homo sapiens |
Taxonomy ID: | 9606 |
Factors:
Local Sample ID | MB Sample ID | Factor Level ID | Level Value | Factor Name |
---|---|---|---|---|
BW45-37 | SA202365 | FL024606 | NA | Phenotype |
BW45-37 | SA202365 | FL024606 | Pre | Treatment |
Collection:
Collection ID: | CO002187 |
Collection Summary: | This was a multi-center, prospective, single-arm phase I/Ib safety trial. Patients eligible for treatment had to be diagnosed with non-metastatic, biopsy-proven p16-negative histology squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx, and had to be eligible and amenable to surgical resection. This study enrolled using a 3+3 model. Patients received one dose of neoadjuvant Durvalumab 1500 mg approximately 3-6 weeks before standard-of-care surgery given concurrently with the first dose of radiation (RT). The starting RT dose level was 6 Gy for 2 fractions (12 Gy total) every other day over approximately one week to sites of gross disease (Table 1) to minimize exposure to normal tissue. If toxicity developed and surgery was delayed by more than 6 weeks due to treatment toxicity (qualifying as a DLT), the radiation dose was set to be dropped per protocol for the next set of patients. If this dose was tolerated, the dose was increased to 6 Gy for 3 fractions (18 Gy total) for the next 3 patients. Patients proceeded to surgical resection approximately 3-6 weeks after radiation as recommended by the ENT surgeon. Post-operatively, pathology was reviewed at the multi-disciplinary head and neck conference, and the need for adjuvant therapy was discussed. For the first 8 patients, all patients were given adjuvant therapy based on presenting features. However, after patient 8, adjuvant therapy was dictated based on high-risk pathologic features as per the NCCN guidelines and treating physician recommendations. Adjuvant radiation included intensity-modulated radiation therapy of 60 Gy in 2 Gy once-daily fraction size once-daily fraction size (total of 30 fractions). If indicated, adjuvant systemic therapy included cisplatin or other cytotoxic chemotherapy or targeted biologics (Cetuximab) per physician discretion. All patients received adjuvant durvalumab to be initiated approximately 6-12 weeks post-surgery. It was given as 1500 mg intravenously once every 4 weeks for a maximum of 6 doses, or until progression, toxicity, or withdrawal from study. This was delivered either as monotherapy or concurrently with adjuvant radiation +/- systemic therapy for high-risk patients. Safety and toxicity evaluations were done throughout the study process. DLTs and adjustment of radiation doses were done during the neoadjuvant period. |
Sample Type: | Blood (plasma) |
Treatment:
Treatment ID: | TR002206 |
Treatment Summary: | This was a multi-center, prospective, single-arm phase I/Ib safety trial. Patients eligible for treatment had to be diagnosed with non-metastatic, biopsy-proven p16-negative histology squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx, and had to be eligible and amenable to surgical resection. This study enrolled using a 3+3 model. Patients received one dose of neoadjuvant Durvalumab 1500 mg approximately 3-6 weeks before standard-of-care surgery given concurrently with the first dose of radiation (RT). The starting RT dose level was 6 Gy for 2 fractions (12 Gy total) every other day over approximately one week to sites of gross disease (Table 1) to minimize exposure to normal tissue. If toxicity developed and surgery was delayed by more than 6 weeks due to treatment toxicity (qualifying as a DLT), the radiation dose was set to be dropped per protocol for the next set of patients. If this dose was tolerated, the dose was increased to 6 Gy for 3 fractions (18 Gy total) for the next 3 patients. Patients proceeded to surgical resection approximately 3-6 weeks after radiation as recommended by the ENT surgeon. Post-operatively, pathology was reviewed at the multi-disciplinary head and neck conference, and the need for adjuvant therapy was discussed. For the first 8 patients, all patients were given adjuvant therapy based on presenting features. However, after patient 8, adjuvant therapy was dictated based on high-risk pathologic features as per the NCCN guidelines and treating physician recommendations. Adjuvant radiation included intensity-modulated radiation therapy of 60 Gy in 2 Gy once-daily fraction size once-daily fraction size (total of 30 fractions). If indicated, adjuvant systemic therapy included cisplatin or other cytotoxic chemotherapy or targeted biologics (Cetuximab) per physician discretion. All patients received adjuvant durvalumab to be initiated approximately 6-12 weeks post-surgery. It was given as 1500 mg intravenously once every 4 weeks for a maximum of 6 doses, or until progression, toxicity, or withdrawal from study. This was delivered either as monotherapy or concurrently with adjuvant radiation +/- systemic therapy for high-risk patients. Safety and toxicity evaluations were done throughout the study process. DLTs and adjustment of radiation doses were done during the neoadjuvant period. |
Sample Preparation:
Sampleprep ID: | SP002200 |
Sampleprep Summary: | Metabolomics analyses were performed as extensively described in previous studies (Issaian et al., Hematologica 2021). A volume of 20μl of frozen plasma was extracted in either 480μl of methanol:acetonitrile:water (5:3:2, v/v/v) (D'Alessandro et al. JCI Insight 2021). After vortexing at 4°C for 30 min, extracts were separated from the protein pellet by centrifugation for 10 min at 10,000g at 4°C and stored at −80°C until analysis. Ultra-High-Pressure Liquid Chromatography-Mass Spectrometry analyses were performed using a Vanquish UHPLC coupled online to a Q Exactive mass spectrometer (Thermo Fisher, Bremen, Germany) (Nemkov et al. Methods Mol Bio 2019). Samples were analyzed using a 5-minute gradient as described ( Nemkov et al. Methods Mol Bio 2019, Nemkov et al. JCI Insight 2020). Solvents were supplemented with 0.1% formic acid for positive mode runs and 1 mM ammonium acetate for negative mode runs. MS acquisition, data analysis and elaboration were performed as described. |
Combined analysis:
Analysis ID | AN003450 | AN003451 |
---|---|---|
Analysis type | MS | MS |
Chromatography type | Reversed phase | Reversed phase |
Chromatography system | Thermo Vanquish | Thermo Vanquish |
Column | Phenomenex Kinetex C18 (150 x 2.1mm,2.6um) | Phenomenex Kinetex C18 (150 x 2.1mm,2.6um) |
MS Type | ESI | ESI |
MS instrument type | Orbitrap | Orbitrap |
MS instrument name | Thermo Q Exactive Orbitrap | Thermo Q Exactive Orbitrap |
Ion Mode | NEGATIVE | POSITIVE |
Units | Relative Abundance | Relative Abundance |
Chromatography:
Chromatography ID: | CH002548 |
Chromatography Summary: | Negative Mode: Samples were analyzed using a 5-minute gradient as described (Nemkov et al. Methods Mol Bio 2019, Nemkov et al. JCI Insight 2020). Solvents were supplemented with 1 mM ammonium acetate for negative mode runs. |
Instrument Name: | Thermo Vanquish |
Column Name: | Phenomenex Kinetex C18 (150 x 2.1mm,2.6um) |
Chromatography Type: | Reversed phase |
Chromatography ID: | CH002549 |
Chromatography Summary: | Positive Mode: Samples were analyzed using a 5-minute gradient as described (Nemkov et al. Methods Mol Bio 2019, Nemkov et al. JCI Insight 2020). Solvents were supplemented with 0.1% formic acid for positive mode runs. |
Instrument Name: | Thermo Vanquish |
Column Name: | Phenomenex Kinetex C18 (150 x 2.1mm,2.6um) |
Chromatography Type: | Reversed phase |
MS:
MS ID: | MS003213 |
Analysis ID: | AN003450 |
Instrument Name: | Thermo Q Exactive Orbitrap |
Instrument Type: | Orbitrap |
MS Type: | ESI |
MS Comments: | MS acquisition, data analysis and elaboration were performed as described. (Nemkov et al. Methods Mol Bio 2019). |
Ion Mode: | NEGATIVE |
MS ID: | MS003214 |
Analysis ID: | AN003451 |
Instrument Name: | Thermo Q Exactive Orbitrap |
Instrument Type: | Orbitrap |
MS Type: | ESI |
MS Comments: | MS acquisition, data analysis and elaboration were performed as described. (Nemkov et al. Methods Mol Bio 2019). |
Ion Mode: | POSITIVE |