Joanne Soo
Resident in OHNS/Otolaryngology/Head & Neck Surgery
All Publications
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Inferring gene expression from cell-free DNA fragmentation profiles.
Nature biotechnology
2022
Abstract
Profiling of circulating tumor DNA (ctDNA) in the bloodstream shows promise for noninvasive cancer detection. Chromatin fragmentation features have previously been explored to infer gene expression profiles from cell-free DNA (cfDNA), but current fragmentomic methods require high concentrations of tumor-derived DNA and provide limited resolution. Here we describe promoter fragmentation entropy as an epigenomic cfDNA feature that predicts RNA expression levels at individual genes. We developed 'epigenetic expression inference from cell-free DNA-sequencing' (EPIC-seq), a method that uses targeted sequencing of promoters of genes of interest. Profiling 329 blood samples from 201 patients with cancer and 87 healthy adults, we demonstrate classification of subtypes of lung carcinoma and diffuse large B cell lymphoma. Applying EPIC-seq to serial blood samples from patients treated with PD-(L)1 immune-checkpoint inhibitors, we show that gene expression profiles inferred by EPIC-seq are correlated with clinical response. Our results indicate that EPIC-seq could enable noninvasive, high-throughput tissue-of-origin characterization with diagnostic, prognostic and therapeutic potential.
View details for DOI 10.1038/s41587-022-01222-4
View details for PubMedID 35361996
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Circulating tumor DNA in head and neck cancer: Early successes and future promise.
Cancer
2022
Abstract
LAY SUMMARY: The genetic components (DNA) of human papillomavirus-related throat cancer (in the oropharynx) might be measured after surgery to help to predict whether treatment has been successful.
View details for DOI 10.1002/cncr.34189
View details for PubMedID 35298053
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Enhanced detection of minimal residual disease by targeted sequencing of phased variants in circulating tumor DNA.
Nature biotechnology
2021
Abstract
Circulating tumor-derived DNA (ctDNA) is an emerging biomarker for many cancers, but the limited sensitivity of current detection methods reduces its utility for diagnosing minimal residual disease. Here we describe phased variant enrichment and detection sequencing (PhasED-seq), a method that uses multiple somatic mutations in individual DNA fragments to improve the sensitivity of ctDNA detection. Leveraging whole-genome sequences from 2,538 tumors, we identify phased variants and their associations with mutational signatures. We show that even without molecular barcodes, the limits of detection of PhasED-seq outperform prior methods, including duplex barcoding, allowing ctDNA detection in the ppm range in participant samples. We profiled 678 specimens from 213 participants with B cell lymphomas, including serial cell-free DNA samples before and during therapy for diffuse large B cell lymphoma. In participants with undetectable ctDNA after two cycles of therapy using a next-generation sequencing-based approach termed cancer personalized profiling by deep sequencing, an additional 25% have ctDNA detectable by PhasED-seq and have worse outcomes. Finally, we demonstrate the application of PhasED-seq to solid tumors.
View details for DOI 10.1038/s41587-021-00981-w
View details for PubMedID 34294911
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Phased variants improve DLBCL minimal residual disease detection at the end of therapy.
LIPPINCOTT WILLIAMS & WILKINS. 2021
View details for DOI 10.1200/JCO.2021.39.15_suppl.7565
View details for Web of Science ID 000708120604161
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Short Diagnosis-to-Treatment Interval Is Associated With Higher Circulating Tumor DNA Levels in Diffuse Large B-Cell Lymphoma.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
2021: JCO2002573
Abstract
Patients with Diffuse Large B-cell Lymphoma (DLBCL) in need of immediate therapy are largely under-represented in clinical trials. The diagnosis-to-treatment interval (DTI) has recently been described as a metric to quantify such patient selection bias, with short DTI being associated with adverse risk factors and inferior outcomes. Here, we characterized the relationships between DTI, circulating tumor DNA (ctDNA), conventional risk factors, and clinical outcomes, with the goal of defining objective disease metrics contributing to selection bias.We evaluated pretreatment ctDNA levels in 267 patients with DLBCL treated across multiple centers in Europe and the United States using Cancer Personalized Profiling by Deep Sequencing. Pretreatment ctDNA levels were correlated with DTI, total metabolic tumor volumes (TMTVs), the International Prognostic Index (IPI), and outcome.Short DTI was associated with advanced-stage disease (P < .001) and higher IPI (P < .001). We also found an inverse correlation between DTI and TMTV (RS= -0.37; P < .001). Similarly, pretreatment ctDNA levels were significantly associated with stage, IPI, and TMTV (all P < .001), demonstrating that both DTI and ctDNA reflect disease burden. Notably, patients with shorter DTI had higher pretreatment ctDNA levels (P < .001). Pretreatment ctDNA levels predicted short DTI independent of the IPI (P < .001). Although each risk factor was significantly associated with event-free survival in univariable analysis, ctDNA level was prognostic of event-free survival independent of DTI and IPI in multivariable Cox regression (ctDNA: hazard ratio, 1.5; 95% CI [1.2 to 2.0]; IPI: 1.1 [0.9 to 1.3]; -DTI: 1.1 [1.0 to 1.2]).Short DTI largely reflects baseline tumor burden, which can be objectively measured using pretreatment ctDNA levels. Pretreatment ctDNA levels therefore have utility for quantifying and guarding against selection biases in prospective DLBCL clinical trials.
View details for DOI 10.1200/JCO.20.02573
View details for PubMedID 33909455
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Chromatin accessibility patterns in cell-free DNA reveal tumor heterogeneity
AMER ASSOC CANCER RESEARCH. 2020
View details for DOI 10.1158/1538-7445.AM2020-3388
View details for Web of Science ID 000590059301076
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Deep Sequencing of Viral Cell-Free DNA for Noninvasive Detection of Immunosuppression-Related Lymphoid Malignancies
AMER SOC HEMATOLOGY. 2019
View details for DOI 10.1182/blood-2019-131602
View details for Web of Science ID 000518218500906
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Dynamic Risk Profiling Using Serial Tumor Biomarkers for Personalized Outcome Prediction.
Cell
2019
Abstract
Accurate prediction of long-term outcomes remains a challenge in the care of cancer patients. Due to the difficulty of serial tumor sampling, previous prediction tools have focused on pretreatment factors. However, emerging non-invasive diagnostics have increased opportunities for serial tumor assessments. We describe the Continuous Individualized Risk Index (CIRI), a method to dynamically determine outcome probabilities for individual patients utilizing risk predictors acquired over time. Similar to "win probability" models in other fields, CIRI provides a real-time probability by integrating risk assessments throughout a patient's course. Applying CIRI to patients with diffuse large B cell lymphoma, we demonstrate improved outcome prediction compared to conventional risk models. We demonstrate CIRI's broader utility in analogous models of chronic lymphocytic leukemia and breast adenocarcinoma and perform a proof-of-concept analysis demonstrating how CIRI could be used to develop predictive biomarkers for therapy selection. We envision thatdynamic risk assessment will facilitate personalized medicine and enable innovative therapeutic paradigms.
View details for DOI 10.1016/j.cell.2019.06.011
View details for PubMedID 31280963
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Prognostic Value of Circulating Tumor DNA in Diffuse Large B-Cell Lymphoma Reply
JOURNAL OF CLINICAL ONCOLOGY
2019; 37 (9): 755-+
View details for DOI 10.1200/JCO.18.01907
View details for Web of Science ID 000462408300010
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Reply to J. Wang et al.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
2019: JCO1801907
View details for PubMedID 30753108
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Modified V-Y Fasciocutaneous Flap Reconstruction After Abdominoperineal Resection in Irradiated Patients Prevents Wound Dehiscence and Associated Complications A Retrospective Analysis and Benchtop Confirmation
ANNALS OF PLASTIC SURGERY
2019; 82 (2): 218–23
Abstract
Primary perineal closure following abdominal perineal resection (APR) is reported to have a wound complication rate as high as 66%, whereas flap reconstruction reduces wound complications to 15% to 35%. A modified de-epithelialized V-Y fasciocutaneous flap aims to further improve results in this patient population.To study the breaking force of a simple interrupted suture in either skin or subcutaneous fat, various quantitative assessments were performed in a porcine flap model using uniaxial static tensile testing with an Instron tensiometer, with a single or triple row of 3 Vicryl sutures in both skin and fat.An outcomes analysis was performed in 24 patients who underwent modified V-Y flap reconstruction after APR. Primary outcome was wound complications including infection, dehiscence, seroma, hematoma, and pelvic fluid collections.Tensile strength of sutures anchored in skin was found to be up to 8 times stronger than sutures anchored in subcutaneous fat in a single row and 3 times as strong in 3 rows (breaking force, 500.2 N vs 263.7 N). In our patient cohort of 24 irradiated cancer patients, 10 (42%) had wound healing complications. Wound dehiscence of various degrees accounted for 80% of these complications. Five patients with wound complications (50%) had associated pelvic fluid collections (infection, 1; wound dehiscence, 4). Minor dehiscence was more likely to occur after suture removal and less likely to be associated with pelvic collections compared to patients with major dehiscence. Our study yields total complication rates lower than what is reported in the literature for anterolateral thigh or gracilis flap including much lower infection rates, and almost similar results to the commonly used vertical rectus myocutaneous muscle.Tension-free de-epithelialized V-Y flap use after APR effectively reconstructs the defect while eliminating an additional donor site. Benchtop studies suggest enhanced flap integrity yielded by layered closure. Wound complications can be managed with local care in their majority (90%). Staggering or delaying suture removal can decrease minor dehiscence. Based on analysis of our results, review of the literature and consideration of donor site morbidity, we believe that modified V-Y flap is the best approach for APR reconstruction in irradiated patients.
View details for DOI 10.1097/SAP.0000000000001672
View details for Web of Science ID 000459895800019
View details for PubMedID 30557183
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Towards Non-Invasive Classification of DLBCL Genetic Subtypes By Ctdna Profiling
American Society of Hematology
2019
View details for DOI 10.1182/blood-2019-132069
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Interim Circulating Tumor DNA As a Prognostic Biomarker in the Setting of Interim PET-Based Adaptive Therapy for DLBCL
American Society of Hematology
2019
View details for DOI 10.1182/blood-2019-131278
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Short Diagnosis-to-Treatment Interval Is Associated with Higher Levels of Circulating Tumor DNA in Aggressive B-Cell Non-Hodgkin Lymphoma
American Society of Hematology
2019
View details for DOI 10.1182/blood-2019-129283
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Phased Variant Enrichment for Enhanced Minimal Residual Disease Detection from Cell-Free DNA
American Society of Hematology
2019
View details for DOI 10.1182/blood-2019-131267
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Lymphoma Virome Dynamics Revealed By Cell-Free DNA Sequencing
AMER SOC HEMATOLOGY. 2018
View details for DOI 10.1182/blood-2018-99-119905
View details for Web of Science ID 000454842800062
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Distinct Chromatin Accessibility Profiles of Lymphoma Subtypes Revealed By Targeted Cell Free DNA Profiling
AMER SOC HEMATOLOGY. 2018
View details for DOI 10.1182/blood-2018-99-119361
View details for Web of Science ID 000454837602050
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Noninvasive Genotyping and Monitoring of Classical Hodgkin Lymphoma
AMER SOC HEMATOLOGY. 2018
View details for DOI 10.1182/blood-2018-99-119140
View details for Web of Science ID 000454842800039
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Circulating Tumor DNA Measurements As Early Outcome Predictors in Diffuse Large B-Cell Lymphoma
JOURNAL OF CLINICAL ONCOLOGY
2018; 36 (28): 2845-+
View details for DOI 10.1200/JCO.2018.78.5246
View details for Web of Science ID 000451485300005
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Circulating Tumor DNA Measurements As Early Outcome Predictors in Diffuse Large B-Cell Lymphoma.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
2018: JCO2018785246
Abstract
Purpose Outcomes for patients with diffuse large B-cell lymphoma remain heterogeneous, with existing methods failing to consistently predict treatment failure. We examined the additional prognostic value of circulating tumor DNA (ctDNA) before and during therapy for predicting patient outcomes. Patients and Methods We studied the dynamics of ctDNA from 217 patients treated at six centers, using a training and validation framework. We densely characterized early ctDNA dynamics during therapy using cancer personalized profiling by deep sequencing to define response-associated thresholds within a discovery set. These thresholds were assessed in two independent validation sets. Finally, we assessed the prognostic value of ctDNA in the context of established risk factors, including the International Prognostic Index and interim positron emission tomography/computed tomography scans. Results Before therapy, ctDNA was detectable in 98% of patients; pretreatment levels were prognostic in both front-line and salvage settings. In the discovery set, ctDNA levels changed rapidly, with a 2-log decrease after one cycle (early molecular response [EMR]) and a 2.5-log decrease after two cycles (major molecular response [MMR]) stratifying outcomes. In the first validation set, patients receiving front-line therapy achieving EMR or MMR had superior outcomes at 24 months (EMR: EFS, 83% v 50%; P = .0015; MMR: EFS, 82% v 46%; P < .001). EMR also predicted superior 24-month outcomes in patients receiving salvage therapy in the first validation set (EFS, 100% v 13%; P = .011). The prognostic value of EMR and MMR was further confirmed in the second validation set. In multivariable analyses including International Prognostic Index and interim positron emission tomography/computed tomography scans across both cohorts, molecular response was independently prognostic of outcomes, including event-free and overall survival. Conclusion Pretreatment ctDNA levels and molecular responses are independently prognostic of outcomes in aggressive lymphomas. These risk factors could potentially guide future personalized risk-directed approaches.
View details for PubMedID 30125215
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Early detection of post-transplant lymphoproliferative disorder using circulating tumor DNA.
AMER SOC CLINICAL ONCOLOGY. 2018
View details for DOI 10.1200/JCO.2018.36.15_suppl.7572
View details for Web of Science ID 000442916003038
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Post-transplant head and neck cancers: A prospective analysis of clinical factors for risk stratification.
AMER SOC CLINICAL ONCOLOGY. 2018
View details for DOI 10.1200/JCO.2018.36.15_suppl.e18051
View details for Web of Science ID 000442916005614
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Development of a Dynamic Model for Personalized Risk Assessment in Large B-Cell Lymphoma
AMER SOC HEMATOLOGY. 2017
View details for Web of Science ID 000432419402076
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Hierarchy in Somatic Mutations Detected in Circulating and Tissue-Resident Follicular Lymphoma Precursors before Clinical Diagnosis
AMER SOC HEMATOLOGY. 2017
View details for Web of Science ID 000432419400363
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Circulating Tumor DNA Is a Reliable Measure of Tumor Burden at Diagnosis of Diffuse Large B Cell Lymphoma: An International Reproducibility Study
AMER SOC HEMATOLOGY. 2017
View details for Web of Science ID 000432419400365
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Determinants of Circulating Tumor DNA Levels across Lymphoma Histologic Subtypes
AMER SOC HEMATOLOGY. 2017
View details for Web of Science ID 000432419703029
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Comparison of Circulating Tumor DNA Recovery from Plasma and Serum
AMER SOC HEMATOLOGY. 2017
View details for Web of Science ID 000432419406389
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Reproducibility of m7-FLIPI Risk Scores in Follicular Lymphoma Using Tumor Biopsies and Blood Specimens
AMER SOC HEMATOLOGY. 2017
View details for Web of Science ID 000432419403290
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Clinical Impact of Somatic Copy Number Alterations in Circulating Tumor DNA from Diverse Lymphoma Subtypes
AMER SOC HEMATOLOGY. 2017
View details for Web of Science ID 000432419406380
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Noninvasive detection of clinically relevant copy number alterations in diffuse large B-cell lymphoma.
AMER SOC CLINICAL ONCOLOGY. 2017
View details for DOI 10.1200/JCO.2017.35.15_suppl.7507
View details for Web of Science ID 000411931708176
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Elucidation of distinct mutational patterns between diffuse large B cell lymphoma subtypes utilizing circulating tumor DNA.
AMER SOC CLINICAL ONCOLOGY. 2017
View details for DOI 10.1200/JCO.2017.35.15_suppl.7538
View details for Web of Science ID 000411931709025
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A Rare Case of Malignant Transformation of Oral Lichen Planus of the Mandible.
Plastic and reconstructive surgery. Global open
2016; 4 (12): e1070
Abstract
Oral lichen planus (OLP) is an immune-mediated mucocutaneous disease associated with an increased risk in oral squamous cell carcinoma (OSCC). Nearly all cases of malignant transformation have been reported in patients >40 years old. We report the case of a 37-year-old woman with a 5-year history of erosive OLP who presented with malignant transformation to OSCC. Delineating the margins of the disease was impossible at presentation given her OLP, and she was initially treated with concurrent chemoradiation therapy. She then developed a recurrence of the mandibular alveolar ridge. The patient was successfully treated with a composite resection including a segmental mandibulectomy, buccal mucosa resection, partial glossectomy, and ipsilateral neck dissection. This was reconstructed with a free fibula osteo-septo-cutaneous flap. Mandibular OSCC is a rare complication of OLP with few reports on effective reconstructive interventions. The case represents the youngest reported patient with mandibular OSCC arising in the context of OLP and highlights the utility of the free vascularized fibula graft in the treatment of these patients.
View details for DOI 10.1097/GOX.0000000000001070
View details for PubMedID 28293492
View details for PubMedCentralID PMC5222637