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3. Analysis of Circulating Tumor DNA to Predict Risk of Recurrence in Patients With Esophageal and Gastric Cancers

Author

Huffman, Brandon M, Aushev, Vasily N, Budde, Griffin L, Chao, Joseph, Dayyani, Farshid, Hanna, Diana, Botta, Gregory P, Catenacci, Daniel VT, Maron, Steven B, Krinshpun, Shifra, Sharma, Shruti, George, Giby V, Malhotra, Meenakshi, Jurdi, Adham, Moshkevich, Solomon, Aleshin, Alexey, Kasi, Pashtoon M, and Klempner, Samuel J

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Digestive Diseases, Genetics, Clinical Research, Women's Health, Patient Safety, Cancer, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Good Health and Well Being, Humans, Circulating Tumor DNA, Stomach Neoplasms, Retrospective Studies, Esophageal Neoplasms, Oncology and carcinogenesis
Abstract

PurposeCirculating tumor DNA (ctDNA) analyses allow for postoperative risk stratification in patients with curatively treated colon and breast cancers. Use of ctDNA in esophagogastric cancers (EGC) is less characterized and could identify high-risk patients who have been treated with curative intent.MethodsIn this retrospective analysis of real-world data, ctDNA levels were analyzed in the preoperative, postoperative, and surveillance settings in patients with EGC using a personalized multiplex polymerase chain reaction-based next-generation sequencing assay. Plasma samples (n = 943) from 295 patients at > 70 institutions were collected before surgery, postoperatively, and/or serially during routine clinical follow-up from September 19, 2019, to February 21, 2022. ctDNA detection was annotated to clinicopathologic features and recurrence-free survival.ResultsA total of 295 patients with EGC were analyzed, and 212 patients with stages I-III disease were further explored. Pretreatment ctDNA was detected in 96% (23/24) of patients with preoperative time points. Postoperative ctDNA was detected in 23.5% (16/68) of patients with stage I-III EGC within 16 weeks (molecular residual disease window) after surgery without receiving systemic therapy. ctDNA detection at any time point after surgery (hazard ratio [HR], 23.6; 95% CI, 10.2 to 66.0; P < .0001), within the molecular residual disease window (HR, 10.7; 95% CI, 4.3 to 29.3; P < .0001), and during the surveillance period (HR, 17.7; 95% CI, 7.3 to 50.7; P < .0001) was associated with shorter recurrence-free survival. In multivariable analysis, ctDNA status and clinical stage of disease were independently associated with outcomes.ConclusionUsing real-world data, we demonstrate that postoperative tumor-informed ctDNA detection in EGC is feasible and allows for enhanced patient risk stratification and prognostication during curative-intent therapy.

Published
2022

4. Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer

Author

Kotani, Daisuke, Oki, Eiji, Nakamura, Yoshiaki, Yukami, Hiroki, Mishima, Saori, Bando, Hideaki, Shirasu, Hiromichi, Yamazaki, Kentaro, Watanabe, Jun, Kotaka, Masahito, Hirata, Keiji, Akazawa, Naoya, Kataoka, Kozo, Sharma, Shruti, Aushev, Vasily N., Aleshin, Alexey, Misumi, Toshihiro, Taniguchi, Hiroya, Takemasa, Ichiro, Kato, Takeshi, Mori, Masaki, and Yoshino, Takayuki

Published
2023
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7. Perioperative Modified FOLFIRINOX for Resectable Pancreatic Cancer: A Nonrandomized Clinical Trial

Author

Cecchini, Michael, Salem, Ronald R., Robert, Marie, Czerniak, Suzanne, Blaha, Ondrej, Zelterman, Daniel, Rajaei, Moein, Townsend, Jeffrey P., Cai, Guoping, Chowdhury, Sumedha, Yugawa, Deanne, Tseng, Robert, Mejia Arbelaez, Carlos, Jiao, Jingjing, Shroyer, Kenneth, Thumar, Jaykumar, Kortmansky, Jeremy, Zaheer, Wajih, Fischbach, Neal, Persico, Justin, Stein, Stacey, Khan, Sajid A., Cha, Charles, Billingsley, Kevin G., Kunstman, John W., Johung, Kimberly L., Wiess, Christina, Muzumdar, Mandar D., Spickard, Erik, Aushev, Vasily N., Laliotis, George, Jurdi, Adham, Liu, Minetta C., Escobar-Hoyos, Luisa, and Lacy, Jill

Abstract

IMPORTANCE: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignant tumor, and durable disease control is rare with the current standard of care, even for patients who undergo surgical resection. OBJECTIVE: To assess whether neoadjuvant modified 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (mFOLFIRINOX) leads to early control of micrometastasis and improves survival. DESIGN, SETTING, AND PARTICIPANTS: This open-label, single-arm, phase 2 nonrandomized clinical trial for resectable PDAC was conducted at the Yale Smilow Cancer Hospital from April 3, 2014, to August 16, 2021. Pancreatic protocol computed tomography was performed at diagnosis to assess surgical candidacy. Data were analyzed from January to July 2023. INTERVENTIONS: Patients received 6 cycles of neoadjuvant mFOLFIRINOX before surgery and 6 cycles of adjuvant mFOLFIRINOX. Whole blood was collected and processed to stored plasma for analysis of circulating tumor DNA (ctDNA) levels. Tumors were evaluated for treatment response and keratin 17 (K17) expression. MAIN OUTCOMES AND MEASURES: The primary end point was 12-month progression-free survival (PFS) rate. Additional end points included overall survival (OS), ctDNA level, tumor molecular features, and K17 tumor levels. Survival curves were summarized using Kaplan-Meier estimator. RESULTS: Of 46 patients who received mFOLFIRINOX, 31 (67%) were male, and the median (range) age was 65 (46-80) years. A total of 37 (80%) completed 6 preoperative cycles and 33 (72%) underwent surgery. A total of 27 patients (59%) underwent resection per protocol (25 with R0 disease and 2 with R1 disease); metastatic or unresectable disease was identified in 6 patients during exploration. Ten patients underwent surgery off protocol. The 12-month PFS was 67% (90% CI, 56.9-100); the median PFS and OS were 16.6 months (95% CI, 13.3-40.6) and 37.2 months (95% CI, 17.5-not reached), respectively. Baseline ctDNA levels were detected in 16 of 22 patients (73%) and in 3 of 17 (18%) after 6 cycles of mFOLFIRINOX. Those with detectable ctDNA levels 4 weeks postresection had worse PFS (hazard ratio [HR], 34.0; 95% CI, 2.6-4758.6; P = .006) and OS (HR, 11.7; 95% CI, 1.5-129.9; P = .02) compared with those with undetectable levels. Patients with high K17 expression had nonsignificantly worse PFS (HR, 2.7; 95% CI, 0.7-10.9; P = .09) and OS (HR, 3.2; 95% CI, 0.8-13.6; P = .07). CONCLUSIONS AND RELEVANCE: This nonrandomized clinical trial met its primary end point, and perioperative mFOLFIRINOX warrants further evaluation in randomized clinical trials. Postoperative ctDNA positivity was strongly associated with recurrence. K17 and ctDNA are promising biomarkers that require additional validation in future prospective studies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02047474

Published
2024
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9. Circulating tumor DNA (ctDNA) for informing adjuvant chemotherapy (ACT) in stage II/III colorectal cancer (CRC): Interim analysis of BESPOKE CRC study.

Author

Kasi, Pashtoon Murtaza, primary, Aushev, Vasily N., additional, Ensor, Joe, additional, Langer, Nathan, additional, Wang, Christopher Gene, additional, Cannon, Timothy Lewis, additional, Berim, Lyudmyla Derby, additional, Feinstein, Trevor, additional, Grothey, Axel, additional, McCollom, Joseph William, additional, Kalmadi, Sujith R., additional, Zakari, Ahmed, additional, Dayyani, Farshid, additional, Gravenor, Donald, additional, Meyer, Janelle Marie, additional, Sharif, Saima, additional, Jurdi, Adham A, additional, Liu, Minetta C., additional, Aleshin, Alexey, additional, and Kopetz, Scott, additional

Published
2024
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10. Patient-reported outcomes from the BESPOKE CRC study.

Author

Kasi, Pashtoon Murtaza, primary, Rivero, Samuel, additional, Aushev, Vasily N., additional, Langer, Nathan, additional, Wang, Christopher Gene, additional, Cannon, Timothy Lewis, additional, Berim, Lyudmyla Derby, additional, Feinstein, Trevor, additional, Grothey, Axel, additional, McCollom, Joseph William, additional, Kalmadi, Sujith R., additional, Zakari, Ahmed, additional, Dayyani, Farshid, additional, Gravenor, Donald, additional, Meyer, Janelle Marie, additional, Sharif, Saima, additional, Jurdi, Adham A, additional, Liu, Minetta C., additional, Aleshin, Alexey, additional, and Kopetz, Scott, additional

Published
2024
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11. Prognostic value of circulating tumor DNA (ctDNA) testing in patients (pts) with rectal cancer after neoadjuvant therapy (NAT) and surgery.

Author

Chakrabarti, Sakti, primary, Cohen, Stacey A., additional, Tin, Antony, additional, Dangl, Autumn, additional, Aushev, Vasily N., additional, Tejani, Mohamedtaki Abdulaziz, additional, Chandana, Sreenivasa R, additional, Malla, Midhun, additional, Landmann, Ron G., additional, Sharma, Vivek R., additional, Botta, Gregory P., additional, Nagarajan, Arun, additional, Azzi, Georges, additional, Cho, May Thet, additional, Dayyani, Farshid, additional, Hanna, Diana L., additional, Jurdi, Adham A, additional, Liu, Minetta C., additional, Dasari, Arvind, additional, and Kasi, Pashtoon Murtaza, additional

Published
2024
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12. Comparison of colorectal cancer (CRC) characteristics across genetic ancestries: Implications for early cancer detection (ECD).

Author

Myer, Parvathi, primary, Srinivasan, Preethi, additional, Bristow, Sara L., additional, Krinshpun, Shifra, additional, Solari, Omid, additional, Aushev, Vasily N., additional, Jurdi, Adham A, additional, Liu, Minetta C., additional, Mitchell, Breeana L., additional, Aleshin, Alexey, additional, Reiter, Johannes G., additional, Weitzel, Jeffrey N., additional, Nakamura, Yoshiaki, additional, Yoshino, Takayuki, additional, Wall, Jeffrey, additional, Ioannidis, Alexander, additional, and Bustamante, Carlos, additional

Published
2024
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13. Abstract A002: A phase II study of peri-operative modified FOLFIRINOX in localized pancreatic ductal adenocarcinoma (PDAC)

Author

Cecchini, Michael, primary, Salem, Ronald, additional, Robert, Marie, additional, Czerniak, Suzanne, additional, Rajaei, Moein, additional, Townsend, Jeffrey, additional, Blaha, Ondrej, additional, Zelterman, Daniel, additional, Thumar, Jaykumar, additional, Kortmansky, Jeremy, additional, Zaheer, Wajih, additional, Fischbach, Neal, additional, Persico, Justin, additional, Stein, Stacey, additional, Khan, Sajid, additional, Cha, Charles, additional, Billingsley, Kevin, additional, Kunstman, John, additional, Chowdhury, Sumedha, additional, Tseng, Robert, additional, Mauricio, Carlos, additional, Yugawa, Deanne, additional, Escobar-Hoyos, Luisa, additional, Johung, Kimberly, additional, Wiess, Christina, additional, Spickard, Erik, additional, Aushev, Vasily N., additional, Laliotis, George, additional, Jurdi, Adham, additional, Liu, Minetta C., additional, and Lacy, Jill, additional

Published
2024
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14. Impact of Circulating Tumor DNA–Based Detection of Molecular Residual Disease on the Conduct and Design of Clinical Trials for Solid Tumors

Author

Kasi, Pashtoon M., Fehringer, Gordon, Taniguchi, Hiroya, Starling, Naureen, Nakamura, Yoshiaki, Kotani, Daisuke, Powles, Thomas, Li, Bob T., Pusztai, Lajos, Aushev, Vasily N., Kalashnikova, Ekaterina, Sharma, Shruti, Malhotra, Meenakshi, Demko, Zachary P., Aleshin, Alexey, Rodriguez, Angel, Billings, Paul R., Grothey, Axel, Taieb, Julien, Cunningham, David, Yoshino, Takayuki, and Kopetz, Scott

Published
2022
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15. Molecular residual disease detection in resected, muscle-invasive urothelial cancer with a tissue-based comprehensive genomic profiling–informed personalized monitoring assay

Author

Powles, Thomas, primary, Young, Amanda, additional, Nimeiri, Halla, additional, Madison, Russell W., additional, Fine, Alexander, additional, Zollinger, Daniel R., additional, Huang, Yanmei, additional, Xu, Chang, additional, Gjoerup, Ole V., additional, Aushev, Vasily N., additional, Wu, Hsin-Ta, additional, Aleshin, Alexey, additional, Carter, Corey, additional, Davarpanah, Nicole, additional, Degaonkar, Viraj, additional, Gupta, Pratyush, additional, Mariathasan, Sanjeev, additional, Schleifman, Erica, additional, Assaf, Zoe June, additional, Oxnard, Geoffrey, additional, and Hegde, Priti S., additional

Published
2023
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17. Circulating tumor DNA (ctDNA) dynamics in patients with colorectal cancer (CRC) with molecular residual disease: Updated analysis from GALAXY study in the CIRCULATE-JAPAN.

Author

Yukami, Hiroki, Nakamura, Yoshiaki, Mishima, Saori, Ando, Koji, Bando, Hideaki, Watanabe, Jun, Hirata, Keiji, Akazawa, Naoya, Ikeda, Masataka, Yokota, Mitsuru, Kato, Kentaro, Laliotis, George, Aushev, Vasily N., Jurdi, Adham A, Liu, Minetta, Kotani, Daisuke, Oki, Eiji, Takemasa, Ichiro, Kato, Takeshi, and Yoshino, Takayuki

Published
2024
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18. Correlation between variant allele frequency and mean tumor molecules with tumor burden in patients with solid tumors.

Author

Kalashnikova, Ekaterina, Aushev, Vasily N., Malashevich, Allyson Koyen, Tin, Antony, Krinshpun, Shifra, Salari, Raheleh, Scalise, Carly Bess, Ram, Rosalyn, Malhotra, Meenakshi, Ravi, Harini, Sethi, Himanshu, Sanchez, Stephanie, Hagelstrom, Robert Tanner, Brevnov, Maxim, Rabinowitz, Matthew, Moshkevich, Solomon, Zimmermann, Bernhard G., Liu, Minetta C., and Aleshin, Alexey

Abstract

Several studies have demonstrated the prognostic value of circulating tumor DNA (ctDNA); however, the correlation of mean tumor molecules (MTM)/ml of plasma and mean variant allele frequency (mVAF; %) with clinical parameters is yet to be understood. In this study, we analyzed ctDNA data in a pan‐cancer cohort of 23 543 patients who had ctDNA testing performed using a personalized, tumor‐informed assay (Signatera™, mPCR‐NGS assay). For ctDNA‐positive patients, the correlation between MTM/ml and mVAF was examined. Two subanalyses were performed: (a) to establish the association of ctDNA with tumor volume and (b) to assess the correlation between ctDNA dynamics and patient outcomes. On a global cohort, a positive correlation between MTM/ml and mVAF was observed. Among 18 426 patients with longitudinal ctDNA measurements, 13.3% had discordant trajectories between MTM/ml and mVAF at subsequent time points. In metastatic patients receiving immunotherapy (N = 51), changes in ctDNA levels expressed both in MTM/ml and mVAF showed a statistically significant association with progression‐free survival; however, the correlation with MTM/ml was numerically stronger. [ABSTRACT FROM AUTHOR]

Published
2023
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20. Table S2 from Novel Predictors of Breast Cancer Survival Derived from miRNA Activity Analysis

Author

Aushev, Vasily N., primary, Lee, Eunjee, primary, Zhu, Jun, primary, Gopalakrishnan, Kalpana, primary, Li, Qian, primary, Teitelbaum, Susan L., primary, Wetmur, James, primary, Degli Esposti, Davide, primary, Hernandez-Vargas, Hector, primary, Herceg, Zdenko, primary, Parada, Humberto, primary, Santella, Regina M., primary, Gammon, Marilie D., primary, and Chen, Jia, primary

Published
2023
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21. Figure S7 from Novel Predictors of Breast Cancer Survival Derived from miRNA Activity Analysis

Author

Aushev, Vasily N., primary, Lee, Eunjee, primary, Zhu, Jun, primary, Gopalakrishnan, Kalpana, primary, Li, Qian, primary, Teitelbaum, Susan L., primary, Wetmur, James, primary, Degli Esposti, Davide, primary, Hernandez-Vargas, Hector, primary, Herceg, Zdenko, primary, Parada, Humberto, primary, Santella, Regina M., primary, Gammon, Marilie D., primary, and Chen, Jia, primary

Published
2023
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22. Legends for Supplemental Figures from Novel Predictors of Breast Cancer Survival Derived from miRNA Activity Analysis

Author

Aushev, Vasily N., primary, Lee, Eunjee, primary, Zhu, Jun, primary, Gopalakrishnan, Kalpana, primary, Li, Qian, primary, Teitelbaum, Susan L., primary, Wetmur, James, primary, Degli Esposti, Davide, primary, Hernandez-Vargas, Hector, primary, Herceg, Zdenko, primary, Parada, Humberto, primary, Santella, Regina M., primary, Gammon, Marilie D., primary, and Chen, Jia, primary

Published
2023
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23. Data from Small-molecule inhibitor of USP7/HAUSP ubiquitin protease stabilizes and activates p53 in cells

Author

Colland, Frédéric, primary, Formstecher, Etienne, primary, Jacq, Xavier, primary, Reverdy, Céline, primary, Planquette, Cécile, primary, Conrath, Susan, primary, Trouplin, Virginie, primary, Bianchi, Julie, primary, Aushev, Vasily N., primary, Camonis, Jacques, primary, Calabrese, Alessandra, primary, Borg-Capra, Catherine, primary, Sippl, Wolfgang, primary, Collura, Vincent, primary, Boissy, Guillaume, primary, Rain, Jean-Christophe, primary, Guedat, Philippe, primary, Delansorne, Rémi, primary, and Daviet, Laurent, primary

Published
2023
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24. Supplementary Data from Small-molecule inhibitor of USP7/HAUSP ubiquitin protease stabilizes and activates p53 in cells

Author

Colland, Frédéric, primary, Formstecher, Etienne, primary, Jacq, Xavier, primary, Reverdy, Céline, primary, Planquette, Cécile, primary, Conrath, Susan, primary, Trouplin, Virginie, primary, Bianchi, Julie, primary, Aushev, Vasily N., primary, Camonis, Jacques, primary, Calabrese, Alessandra, primary, Borg-Capra, Catherine, primary, Sippl, Wolfgang, primary, Collura, Vincent, primary, Boissy, Guillaume, primary, Rain, Jean-Christophe, primary, Guedat, Philippe, primary, Delansorne, Rémi, primary, and Daviet, Laurent, primary

Published
2023
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25. Legends for Supplemental Tables from Novel Predictors of Breast Cancer Survival Derived from miRNA Activity Analysis

Author

Aushev, Vasily N., primary, Lee, Eunjee, primary, Zhu, Jun, primary, Gopalakrishnan, Kalpana, primary, Li, Qian, primary, Teitelbaum, Susan L., primary, Wetmur, James, primary, Degli Esposti, Davide, primary, Hernandez-Vargas, Hector, primary, Herceg, Zdenko, primary, Parada, Humberto, primary, Santella, Regina M., primary, Gammon, Marilie D., primary, and Chen, Jia, primary

Published
2023
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26. Supplemental Methods from Novel Predictors of Breast Cancer Survival Derived from miRNA Activity Analysis

Author

Aushev, Vasily N., primary, Lee, Eunjee, primary, Zhu, Jun, primary, Gopalakrishnan, Kalpana, primary, Li, Qian, primary, Teitelbaum, Susan L., primary, Wetmur, James, primary, Degli Esposti, Davide, primary, Hernandez-Vargas, Hector, primary, Herceg, Zdenko, primary, Parada, Humberto, primary, Santella, Regina M., primary, Gammon, Marilie D., primary, and Chen, Jia, primary

Published
2023
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27. Data from Novel Predictors of Breast Cancer Survival Derived from miRNA Activity Analysis

Author

Aushev, Vasily N., primary, Lee, Eunjee, primary, Zhu, Jun, primary, Gopalakrishnan, Kalpana, primary, Li, Qian, primary, Teitelbaum, Susan L., primary, Wetmur, James, primary, Degli Esposti, Davide, primary, Hernandez-Vargas, Hector, primary, Herceg, Zdenko, primary, Parada, Humberto, primary, Santella, Regina M., primary, Gammon, Marilie D., primary, and Chen, Jia, primary

Published
2023
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28. Circulating tumor DNA as a marker of recurrence risk in locoregional esophagogastric cancers with pathologic complete response.

Author

Lander, Eric Michael, primary, Huffman, Brandon, additional, Klempner, Samuel J, additional, Aushev, Vasily N., additional, Izaguirre Carbonell, Jesus, additional, Ferguson, Jenifer, additional, Sharma, Shruti, additional, Jurdi, Adham A, additional, Liu, Minetta C., additional, Eng, Cathy, additional, and Gibson, Michael K., additional

Published
2023
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29. Circulating tumor DNA (ctDNA) informs clinical practice in patients with recurrent/metastatic gastroesophageal cancers.

Author

Mehta, Rutika, primary, Rivero-Hinojosa, Samuel, additional, Dayyani, Farshid, additional, Chao, Joseph, additional, Izaguirre Carbonell, Jesus, additional, Ferguson, Jenifer, additional, Shariff, Bushra, additional, Aushev, Vasily N., additional, Budde, Griffin, additional, Sharma, Shruti, additional, Malhotra, Meenakshi, additional, Jurdi, Adham A, additional, Liu, Minetta C., additional, Klempner, Samuel J, additional, and Huffman, Brandon, additional

Published
2023
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30. Kinetics of postoperative circulating cell-free DNA and impact on minimal residual disease detection rates in patients with resected stage I-III colorectal cancer.

Author

Cohen, Stacey A., primary, Kasi, Pashtoon Murtaza, additional, Aushev, Vasily N., additional, Hanna, Diana L., additional, Botta, Gregory P., additional, Sharif, Saima, additional, Laliotis MD, PhD, Georgios I., additional, Sharma, Vivek R., additional, Alqahtani, Ali, additional, Chandana, Sreenivasa R, additional, Kang, Sandra, additional, Chakrabarti, Sakti, additional, Somer, Bradley G., additional, Kasi, Anup, additional, Dayyani, Farshid, additional, Malla, Midhun, additional, Jurdi, Adham A, additional, Liu, Minetta C., additional, Aleshin, Alexey, additional, and Kopetz, Scott, additional

Published
2023
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31. ctDNA-based molecular residual disease and survival in resectable colorectal cancer

Author

Nakamura, Yoshiaki, Watanabe, Jun, Akazawa, Naoya, Hirata, Keiji, Kataoka, Kozo, Yokota, Mitsuru, Kato, Kentaro, Kotaka, Masahito, Kagawa, Yoshinori, Yeh, Kun-Huei, Mishima, Saori, Yukami, Hiroki, Ando, Koji, Miyo, Masaaki, Misumi, Toshihiro, Yamazaki, Kentaro, Ebi, Hiromichi, Okita, Kenji, Hamabe, Atsushi, Sokuoka, Hiroki, Kobayashi, Satoshi, Laliotis, George, Aushev, Vasily N., Sharma, Shruti, Jurdi, Adham, Liu, Minetta C., Aleshin, Alexey, Rabinowitz, Matthew, Bando, Hideaki, Taniguchi, Hiroya, Takemasa, Ichiro, Kato, Takeshi, Kotani, Daisuke, Mori, Masaki, Yoshino, Takayuki, and Oki, Eiji

Abstract

The interim analysis of the CIRCULATE-Japan GALAXY observational study demonstrated the association of circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) detection with recurrence risk and benefit from adjuvant chemotherapy (ACT) in resectable colorectal cancer (CRC). This updated analysis with a 23-month median follow-up, including 2,240 patients with stage II–III colon cancer or stage IV CRC, reinforces the prognostic value of ctDNA positivity during the MRD window with significantly inferior disease-free survival (DFS; hazard ratio (HR): 11.99, P< 0.0001) and overall survival (OS; HR: 9.68, P< 0.0001). In patients who experienced recurrence, ctDNA positivity correlated with shorter OS (HR: 2.71, P< 0.0001). The significantly shorter DFS in MRD-positive patients was consistent across actionable biomarker subsets. Sustained ctDNA clearance in response to ACT was an indicator of favorable DFS and OS compared to transient clearance (24-month DFS: 89.0% versus 3.3%; 24-month OS: 100.0% versus 82.3%). True spontaneous clearance rate with no clinical recurrence was 1.9% (2/105). Overall, our findings provide evidence for the utility of ctDNA monitoring for post-resection recurrence and mortality risk stratification that could be used for guiding adjuvant therapy.

Published
2024
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32. Using Tumor-Informed Circulating Tumor DNA (ctDNA)-Based Testing for Patients with Anal Squamous Cell Carcinoma

Author

Azzi, Georges, primary, Tavallai, Mehrad, additional, Aushev, Vasily N, additional, Koyen Malashevich, Allyson, additional, Botta, Gregory P, additional, Tejani, Mohamedtaki A, additional, Hanna, Diana, additional, Krinshpun, Shifra, additional, Malhotra, Meenakshi, additional, Jurdi, Adham, additional, Aleshin, Alexey, additional, and Kasi, Pashtoon M, additional

Published
2022
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33. Circulating tumor DNA monitoring for early recurrence detection in epithelial ovarian cancer

Author

Hou, June Y., primary, Chapman, Jocelyn S., additional, Kalashnikova, Ekaterina, additional, Pierson, William, additional, Smith-McCune, Karen, additional, Pineda, Geovanni, additional, Vattakalam, Reena Marie, additional, Ross, Alexandra, additional, Mills, Meredith, additional, Suarez, Carlos J., additional, Davis, Tracy, additional, Edwards, Robert, additional, Boisen, Michelle, additional, Sawyer, Sarah, additional, Wu, Hsin-Ta, additional, Dashner, Scott, additional, Aushev, Vasily N., additional, George, Giby V., additional, Malhotra, Meenakshi, additional, Zimmermann, Bernhard, additional, Sethi, Himanshu, additional, ElNaggar, Adam C., additional, Aleshin, Alexey, additional, and Ford, James M., additional

Published
2022
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34. Feasibility of disease recurrence monitoring in liver post-transplantation for patients with hepatocellular carcinoma via personalized and tumor-informed ctDNA test.

Author

Abdelrahim, Maen, primary, Esmail, Abdullah, additional, Saharia, Ashish, additional, McMillan, Robert, additional, He, Aiwu Ruth, additional, Starr, Jason S., additional, Dhani, Harmeet, additional, Aushev, Vasily N., additional, Koyen Malashevich, Allyson, additional, Rattigan, Nicole Hook, additional, Gauthier, Phil, additional, Jarudi, Adham, additional, and Ghobrial, Rafik Mark, additional

Published
2022
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35. Sa1175 COMPARISON OF COLORECTAL CANCER (CRC) CHARACTERISTICS ACROSS GENETIC ANCESTRIES: IMPLICATIONS FOR EARLY CANCER DETECTION

Author

Myer, Parvathi A., Srinivasan, Preethi, Bristow, Sara L., Krinshpun, Shifra, Solari, Omid Shams, Aushev, Vasily N., Jurdi, Adham, Liu, Minetta C., Mitchell, Breeana L., Aleshin, Alexey, Reiter, Johannes G., Weitzel, Jeffrey N., Nakamura, Yoshiaki, Yoshino, Takayuki, Wall, Jeffrey, Ioannidis, Alexander, and Bustamante, Carlos

Published
2024
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36. Using Tumor-Informed Circulating Tumor DNA (ctDNA)-Based Testing for Patients with Anal Squamous Cell Carcinoma.

Author

Azzi, Georges, Tavallai, Mehrad, Aushev, Vasily N, Malashevich, Allyson Koyen, Botta, Gregory P, Tejani, Mohamedtaki A, Hanna, Diana, Krinshpun, Shifra, Malhotra, Meenakshi, Jurdi, Adham, Aleshin, Alexey, and Kasi, Pashtoon M

Subjects
EPITHELIAL cell tumors, DISEASE progression, SEQUENCE analysis, GENETIC mutation, CANCER relapse, METASTASIS, ANAL tumors, GENES, EXTRACELLULAR space, TUMOR markers, NUCLEIC acids
Abstract

Background Anal squamous cell carcinoma (SCCA) is an uncommon malignancy with a rising incidence that has a high cure rate in its early stages. There is an unmet need for a reliable method to monitor response to treatment and assist in surveillance. Circulating tumor DNA (ctDNA) testing has shown great promise in other solid tumors for monitoring disease progression and detecting relapse in real time. This study aimed to determine the feasibility and use of personalized and tumor-informed ctDNA testing in SCCA. Patients and Methods We analyzed real-world data from 251 patients (817 plasma samples) with stages I-IV SCCA, collected between 11/5/19 and 5/31/22. The tumor genomic landscape and feasibility of ctDNA testing was examined for all patients. The prognostic value of longitudinal ctDNA testing was assessed in patients with clinical follow-up (N = 37). Results Whole-exome sequencing analysis revealed PIK3CA as the most commonly mutated gene, and no associations between mutations and stage. Anytime ctDNA positivity and higher ctDNA levels (MTM/mL) were associated with metastatic disease (P =. 004). For 37 patients with clinical follow-up, median follow-up time was 21.0 months (range: 4.1-67.3) post-diagnosis. For patients with stages I-III disease, anytime ctDNA-positivity after definitive treatment was associated with reduced DFS (HR: 28.0; P =. 005). Conclusions Our study demonstrates the feasibility of personalized and tumor-informed ctDNA testing as an adjunctive tool in patients with SCCA as well as potential use for detection of molecular/minuteimal residual disease, and relapse during surveillance. Prospective studies are needed to better evaluate the use of ctDNA testing in this indication. [ABSTRACT FROM AUTHOR]

Published
2023
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37. Molecular residual disease (MRD) detection with a tissue comprehensive genomic profiling (CGP)-informed personalized monitoring assay: An exploratory analysis of the IMvigor-010 observation arm.

Author

Young, Amanda, primary, Nimeiri, Halla, additional, Madison, Russell, additional, Fine, Alexander D., additional, Zollinger, Daniel, additional, Gjoerup, Ole, additional, Aushev, Vasily N., additional, Wu, Hsin-Ta, additional, Aleshin, Alexey, additional, Davarpanah, Nicole N., additional, Assaf, Zoe, additional, Mariathasan, Sanjeev, additional, Oxnard, Geoffrey R., additional, Renkonen, Elise, additional, Powles, Thomas, additional, and Hegde, Priti, additional

Published
2022
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38. Circulating tumor DNA-based molecular residual disease detection and recurrence monitoring in patients with advanced or metastatic anal squamous cell carcinoma.

Author

Azzi, Georges, primary, Tavallai, Mehrad, additional, Botta, Gregory P., additional, Tejani, Mohamedtaki Abdulaziz, additional, Hanna, Diana L., additional, Jurdi, Adham Adel, additional, Budde, Griffin, additional, Krinshpun, Shifra, additional, Maninder, Minu, additional, Aushev, Vasily N., additional, Olshan, Perry, additional, Billings, Paul R., additional, Aleshin, Alexey, additional, and Kasi, Pashtoon Murtaza, additional

Published
2022
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39. Association of personalized and tumor-informed ctDNA with patient survival outcomes in pancreatic adenocarcinoma.

Author

Botta, Gregory P., primary, Abdelrahim, Maen, additional, Aushev, Vasily N., additional, Esmail, Abdullah, additional, Drummond, Bridgette, additional, Sharma, Shruti, additional, Kalashnikova, Ekaterina, additional, Hook, Nicole, additional, Chandana, Sreenivasa R, additional, Tejani, Mohamedtaki Abdulaziz, additional, Malla, Midhun, additional, Schafer, Liudmila N., additional, Kasi, Pashtoon Murtaza, additional, George, Giby V., additional, Aleshin, Alexey, additional, Dayyani, Farshid, additional, and Hanna, Diana L., additional

Published
2022
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40. Circulating tumor DNA (ctDNA) serial analysis during progression on PD-1 blockade and later CTLA-4 rescue in patients with mismatch repair deficient metastatic colorectal cancer

Author

Kasi, Pashtoon Murtaza, primary, Budde, Griffin, additional, Krainock, Michael, additional, Aushev, Vasily N, additional, Koyen Malashevich, Allyson, additional, Malhotra, Meenakshi, additional, Olshan, Perry, additional, Billings, Paul R, additional, and Aleshin, Alexey, additional

Published
2022
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43. Tumor-informed assessment of circulating tumor DNA and its incorporation into practice for patients with hepatobiliary cancers.

Author

Kasi, Pashtoon Murtaza, primary, Budde, Griffin, additional, Dayyani, Farshid, additional, Botta, Gregory P., additional, Diehl, Adam, additional, King, Gentry Teng, additional, Malla, Midhun, additional, Abdelrahim, Maen, additional, Hanna, Diana L., additional, Schafer, Liudmila N., additional, Tejani, Mohamedtaki Abdulaziz, additional, Krainock, Michael, additional, Billings, Paul R., additional, Olshan, Perry, additional, Aushev, Vasily N., additional, and Aleshin, Alexey, additional

Published
2021
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44. Exosomal miRNAs in urine associated with children's cardiorenal parameters : A cross-sectional study

Author

Levin-Schwartz, Yuri, Curtin, Paul, Flores, Daniel, Aushev, Vasily N., Tamayo-Ortiz, Marcela, Svensson, Katherine, Pantic, Ivan, Estrada-Gutierrez, Guadalupe, Pizano-Zarate, Maria L., Gennings, Chris, Satlin, Lisa M., Baccarelli, Andrea A., Tellez-Rojo, Martha M., Wright, Robert O., Sanders, Alison P., Levin-Schwartz, Yuri, Curtin, Paul, Flores, Daniel, Aushev, Vasily N., Tamayo-Ortiz, Marcela, Svensson, Katherine, Pantic, Ivan, Estrada-Gutierrez, Guadalupe, Pizano-Zarate, Maria L., Gennings, Chris, Satlin, Lisa M., Baccarelli, Andrea A., Tellez-Rojo, Martha M., Wright, Robert O., and Sanders, Alison P.

Abstract

Aims: The authors sought to examine associations between urinary exosomal miRNAs (exo-miRs), emerging biomarkers of renal health, and cardiorenal outcomes in early childhood. Materials & Methods: The authors extracted exo-miRs in urine from 88 healthy Mexican children aged 4-6 years. The authors measured associations between 193 exo-miRs and cardiorenal outcomes: systolic/diastolic blood pressure, estimated glomerular filtration rate and urinary sodium and potassium levels. The authors adjusted for age, sex, BMI, socioeconomic status, indoor tobacco smoke exposure and urine specific gravity. Results: Multiple exo-miRs were identified meeting a false discovery rate threshold of q < 0.1. Specifically, three exo-miRs had increased expression with urinary sodium, 17 with urinary sodium-to-potassium ratio and one with decreased estimated glomerular filtration rate. Conclusions: These results highlight urinary exo-miRs as early-life biomarkers of children's cardiorenal health.

Published
2021
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45. Exosomal miRNAs in urine associated with children's cardiorenal parameters: a cross-sectional study

Author

Levin-Schwartz, Yuri, primary, Curtin, Paul, additional, Flores, Daniel, additional, Aushev, Vasily N, additional, Tamayo-Ortiz, Marcela, additional, Svensson, Katherine, additional, Pantic, Ivan, additional, Estrada-Gutierrez, Guadalupe, additional, Pizano-Zárate, María L, additional, Gennings, Chris, additional, Satlin, Lisa M, additional, Baccarelli, Andrea A, additional, Tellez-Rojo, Martha M, additional, Wright, Robert O, additional, and Sanders, Alison P, additional

Published
2021
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49. STK 38 kinase acts as XPO 1 gatekeeper regulating the nuclear export of autophagy proteins and other cargoes

Author

Martin, Alexandre PJ, primary, Jacquemyn, Maarten, additional, Lipecka, Joanna, additional, Chhuon, Cerina, additional, Aushev, Vasily N, additional, Meunier, Brigitte, additional, Singh, Manish K, additional, Carpi, Nicolas, additional, Piel, Matthieu, additional, Codogno, Patrice, additional, Hergovich, Alexander, additional, Parrini, Maria Carla, additional, Zalcman, Gerard, additional, Guerrera, Ida Chiara, additional, Daelemans, Dirk, additional, and Camonis, Jacques H, additional

Published
2019
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50. Different metastasis promotive potency of small G-proteins RalA and RalB in in vivo hamster tumor model

Author

Trukhanova Lyubov S, Aushev Vasily N, Komelkov Andrei V, Knizhnik Anna V, Rybko Vera A, and Tchevkina Elena M

Subjects
metastasis, Ral proteins, invasion, Ral effector mutants, tumor growth, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Cytology, QH573-671
Abstract

Abstract Background Previously we have shown that oncogenic Ha-Ras stimulated in vivo metastasis through RalGEF-Ral signaling. RalA and RalB are highly homologous small G proteins belonging to Ras superfamily. They can be activated by Ras-RalGEF signaling pathway and influence cellular growth and survival, motility, vesicular transport and tumor progression in humans and in animal models. Here we first time compared the influence of RalA and RalB on tumorigenic, invasive and metastatic properties of RSV transformed hamster fibroblasts. Methods Retroviral vectors encoding activated forms or effector mutants of RalA or RalB proteins were introduced into the low metastatic HET-SR cell line. Tumor growth and spontaneous metastatic activity (SMA) were evaluated on immunocompetent hamsters after subcutaneous injection of cells. The biological properties of cells, including proliferation, clonogenicity, migration and invasion were determined using MTT, wound healing, colony formation and Boyden chamber assays respectively. Protein expression and phosphorylation was detected by Westen blot analysis. Extracellular proteinases activity was assessed by substrate-specific zymography. Results We have showed that although both Ral proteins stimulated SMA, RalB was more effective in metastasis stimulation in vivo as well as in potentiating of directed movement and invasion in vitro. Simultaneous expression of active RalA and RalB didn't give synergetic effect on metastasis formation. RalB activity decreased expression of Caveolin-1, while active RalA stimulated MMP-1 and uPA proteolytic activity, as well as CD24 expression. Both Ral proteins were capable of Cyclin D1 upregulation, JNK1 kinase activation, and stimulation of colony growth and motility. Among three main RalB effectors (RalBP1, exocyst complex and PLD1), PLD1 was essential for RalB-dependent metastasis stimulation. Conclusions Presented results are the first data on direct comparison of RalA and RalB impact as well as of RalA/RalB simultaneous expression influence on in vivo cell metastatic activity. We showed that RalB activation significantly more than RalA stimulates SMA. This property correlates with the ability of RalB to stimulate in vitro invasion and serum directed cell movement. We also found that RalB-PLD1 interaction is necessary for the acquisition of RalB-dependent high metastatic cell phenotype. These findings contribute to the identification of molecular mechanisms of metastasis and tumor progression.

Published
2011
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