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1. The role of serum thymidine kinase 1 activity in neoadjuvant-treated HER2-positive breast cancer: biomarker analysis from the Swedish phase II randomized PREDIX HER2 trial

Author

Zhu, Yajing, Zerdes, Ioannis, Matikas, Alexios, Cruz, Ivette Raices, Bergqvist, Mattias, Elinder, Ellinor, Bosch, Ana, Lindman, Henrik, Einbeigi, Zakaria, Andersson, Anne, Carlsson, Lena, Dreifaldt, Ann Charlotte, Isaksson-Friman, Erika, Hellstrom, Mats, Johansson, Hemming, Wang, Kang, Bergh, Jonas C. S., Hatschek, Thomas, and Foukakis, Theodoros

Published
2024
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2. Thymidine kinase activity levels in serum can identify HR+ metastatic breast cancer patients with a low risk of early progression (SWOG S0226)

Author

Bergqvist, Mattias, Nordmark, Adrian, Williams, Amy, Paoletti, Costanza, Barlow, William, Cobain, Erin F, Mehta, Rita S, Gralow, Julie R, Hortobagyi, Gabriel N, Albain, Kathy S, Pusztai, Lajos, Sharma, Priyanka, Godwin, Andrew K, Thompson, Alastair M, Hayes, Daniel F, and Rae, James M

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Prevention, Cancer, Breast Cancer, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Female, Humans, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Breast Neoplasms, Prognosis, Progression-Free Survival, Receptor, ErbB-2, Thymidine Kinase, Thymidine kinase, biomarker, disease progression, monitoring treatment, breast cancer, endocrine therapy, Receptor, erbB-2, Environmental Biotechnology, Toxicology, Bioinformatics and computational biology, Medical biotechnology, Environmental biotechnology
Abstract

BackgroundSome patients with metastatic breast cancer (MBC) stay on endocrine therapy (ET) for years and others progress quickly. Serum thymidine kinase activity (TKa), an indicator of cell-proliferation, is a potential biomarker for monitoring ET and predicting MBC outcome. We have previously reported TKa as being prognostic in MBC in SWOG S0226. Here, new data on progression within 30/60 days post sampling, with a new, FDA approved version of DiviTum®TKa highlighting differences vs. a Research Use Only version is reported.Methods1,546 serum samples from 454 patients were assessed, collected at baseline and at 4 subsequent timepoints during treatment. A new predefined cut-off tested the ability to predict disease progression. A new measuring unit, DuA (DiviTum® unit of Activity) is adopted.ResultsA DiviTum®TKa score

Published
2023

3. Evaluating Serum Thymidine Kinase 1 in Hormone Receptor Positive Metastatic Breast Cancer Patients Receiving First Line Endocrine Therapy in the SWOG S0226 Trial

Author

Paoletti, Costanza, Barlow, William E, Cobain, Erin F, Bergqvist, Mattias, Mehta, Rita S, Gralow, Julie R, Hortobagyi, Gabriel N, Albain, Kathy S, Pusztai, Lajos, Sharma, Priyanka, Godwin, Andrew K, Thompson, Alastair M, Hayes, Daniel F, and Rae, James M

Subjects
Clinical Research, Cancer, Breast Cancer, Rehabilitation, Clinical Trials and Supportive Activities, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Hormonal, Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Clinical Trials as Topic, Female, Humans, Kaplan-Meier Estimate, Middle Aged, Prognosis, Receptor, ErbB-2, Receptors, Estrogen, Receptors, Progesterone, Retrospective Studies, Thymidine Kinase, Treatment Outcome, Receptor, erbB-2, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

PurposeSerum thymidine kinase 1 (sTK1) activity is associated with poor prognosis in metastatic breast cancer (MBC). We assessed the prognostic effect of sTK1 in patients with hormone receptor-positive MBC treated on a prospective randomized trial of anastrozole (A) versus A plus fulvestrant (A + F).Patients and methodssTK1 was assessed in 1,726 serums [baseline (BL), cycles 2, 3, 4, and 7] using the DiviTum assay. A prespecified cutoff of ≥200 Du/L was considered high. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier, log-rank tests, and Cox regression.ResultsBL sTK1 was elevated in 171 (40%) of 432 patients. Patients with high versus low BL sTK1 had significantly worse PFS [median 11.2 vs. 17.3 months, HR = 1.76; 95% confidence interval (CI; 1.43-2.16); P < 0.0001] and OS [median 30 vs. 58 months, HR = 2.38; 95% CI (1.91-2.98); P < 0.0001]. OS was significantly better for patients with high sTK1 who did not have prior adjuvant tamoxifen and who received A + F versus A alone [median 46 vs. 21 months, HR = 0.58; 95% CI (0.38-0.87); P = 0.0087]. Patients with low sTK1 had no difference in outcomes by therapy (P = 0.44). At serial timepoints, high versus low sTK1 had significantly worse subsequent PFS and OS [at cycle 2: PFS HR = 1.70, 95% CI (1.34-2.17); P < 0.0001, OS HR = 2.51, 95% CI (1.93-3.26); P < 0.0001].ConclusionsHigh sTK1 at BL and subsequent timepoints is associated with worse prognosis in patients with MBC starting first-line endocrine therapy (ET). Patients with low sTK1 at BL have comparable outcomes on single-agent or combination ET.

Published
2021

4. Use of liquid biomarker thymidine kinase activity (TKa) to predict outcome and progression in patients with metastatic breast cancer (MBC) in the GEICAM/2014-12 FLIPPER trial.

Author

Albanell, Joan, primary, Williams, Amy, additional, Martínez, Maria Teresa, additional, Ritzen, Hanna, additional, Paris, Lorena, additional, O'Connor, Miriam, additional, De la Cruz Merino, Luis, additional, Santaballa, Ana, additional, Martinez-Jañez, Noelia, additional, Moreno Antón, Fernando, additional, Fernández, Isaura, additional, Alarcón Company, Jesús, additional, Guerra, Juan Antonio, additional, Ruiz-Borrego, Manuel, additional, Morris, Patrick G., additional, Portela, Marta, additional, Herranz, Jesús, additional, Caballero, Rosalia, additional, Bergqvist, Mattias, additional, and Rojo Todo, Federico Gustavo, additional

Published
2024
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7. A Subset of Non-Small Cell Lung Cancer Patients Treated with Pemetrexed Show 18F-Fluorothymidine “Flare” on Positron Emission Tomography

Author

Aravind, Preetha, primary, Popat, Sanjay, additional, Barwick, Tara D., additional, Soneji, Neil, additional, Lythgoe, Mark, additional, Sreter, Katherina B., additional, Lozano-Kuehne, Jingky P., additional, Bergqvist, Mattias, additional, Patel, Neva, additional, Aboagye, Eric O., additional, and Kenny, Laura M., additional

Published
2023
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8. FIGURE 1 from Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy

Author

Sah, Vasu R., primary, Jespersen, Henrik, primary, Karlsson, Joakim, primary, Nilsson, Lisa M., primary, Bergqvist, Mattias, primary, Johansson, Iva, primary, Carneiro, Ana, primary, Helgadottir, Hildur, primary, Levin, Max, primary, Ullenhag, Gustav, primary, Ståhlberg, Anders, primary, Olofsson Bagge, Roger, primary, Nilsson, Jonas A., primary, and Ny, Lars, primary

Published
2023
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9. Supplementary Table S3 from Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy

Author

Sah, Vasu R., primary, Jespersen, Henrik, primary, Karlsson, Joakim, primary, Nilsson, Lisa M., primary, Bergqvist, Mattias, primary, Johansson, Iva, primary, Carneiro, Ana, primary, Helgadottir, Hildur, primary, Levin, Max, primary, Ullenhag, Gustav, primary, Ståhlberg, Anders, primary, Olofsson Bagge, Roger, primary, Nilsson, Jonas A., primary, and Ny, Lars, primary

Published
2023
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10. Figure S1 from Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy

Author

Sah, Vasu R., primary, Jespersen, Henrik, primary, Karlsson, Joakim, primary, Nilsson, Lisa M., primary, Bergqvist, Mattias, primary, Johansson, Iva, primary, Carneiro, Ana, primary, Helgadottir, Hildur, primary, Levin, Max, primary, Ullenhag, Gustav, primary, Ståhlberg, Anders, primary, Olofsson Bagge, Roger, primary, Nilsson, Jonas A., primary, and Ny, Lars, primary

Published
2023
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11. FIGURE 5 from Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy

Author

Sah, Vasu R., primary, Jespersen, Henrik, primary, Karlsson, Joakim, primary, Nilsson, Lisa M., primary, Bergqvist, Mattias, primary, Johansson, Iva, primary, Carneiro, Ana, primary, Helgadottir, Hildur, primary, Levin, Max, primary, Ullenhag, Gustav, primary, Ståhlberg, Anders, primary, Olofsson Bagge, Roger, primary, Nilsson, Jonas A., primary, and Ny, Lars, primary

Published
2023
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12. FIGURE 4 from Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy

Author

Sah, Vasu R., primary, Jespersen, Henrik, primary, Karlsson, Joakim, primary, Nilsson, Lisa M., primary, Bergqvist, Mattias, primary, Johansson, Iva, primary, Carneiro, Ana, primary, Helgadottir, Hildur, primary, Levin, Max, primary, Ullenhag, Gustav, primary, Ståhlberg, Anders, primary, Olofsson Bagge, Roger, primary, Nilsson, Jonas A., primary, and Ny, Lars, primary

Published
2023
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13. Data from Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy

Author

Sah, Vasu R., primary, Jespersen, Henrik, primary, Karlsson, Joakim, primary, Nilsson, Lisa M., primary, Bergqvist, Mattias, primary, Johansson, Iva, primary, Carneiro, Ana, primary, Helgadottir, Hildur, primary, Levin, Max, primary, Ullenhag, Gustav, primary, Ståhlberg, Anders, primary, Olofsson Bagge, Roger, primary, Nilsson, Jonas A., primary, and Ny, Lars, primary

Published
2023
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14. FIGURE 2 from Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy

Author

Sah, Vasu R., primary, Jespersen, Henrik, primary, Karlsson, Joakim, primary, Nilsson, Lisa M., primary, Bergqvist, Mattias, primary, Johansson, Iva, primary, Carneiro, Ana, primary, Helgadottir, Hildur, primary, Levin, Max, primary, Ullenhag, Gustav, primary, Ståhlberg, Anders, primary, Olofsson Bagge, Roger, primary, Nilsson, Jonas A., primary, and Ny, Lars, primary

Published
2023
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15. FIGURE 3 from Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy

Author

Sah, Vasu R., primary, Jespersen, Henrik, primary, Karlsson, Joakim, primary, Nilsson, Lisa M., primary, Bergqvist, Mattias, primary, Johansson, Iva, primary, Carneiro, Ana, primary, Helgadottir, Hildur, primary, Levin, Max, primary, Ullenhag, Gustav, primary, Ståhlberg, Anders, primary, Olofsson Bagge, Roger, primary, Nilsson, Jonas A., primary, and Ny, Lars, primary

Published
2023
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16. FIGURE 6 from Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy

Author

Sah, Vasu R., primary, Jespersen, Henrik, primary, Karlsson, Joakim, primary, Nilsson, Lisa M., primary, Bergqvist, Mattias, primary, Johansson, Iva, primary, Carneiro, Ana, primary, Helgadottir, Hildur, primary, Levin, Max, primary, Ullenhag, Gustav, primary, Ståhlberg, Anders, primary, Olofsson Bagge, Roger, primary, Nilsson, Jonas A., primary, and Ny, Lars, primary

Published
2023
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17. Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy

Author

Sah, Vasu R., primary, Jespersen, Henrik, additional, Karlsson, Joakim, additional, Nilsson, Lisa M., additional, Bergqvist, Mattias, additional, Johansson, Iva, additional, Carneiro, Ana, additional, Helgadottir, Hildur, additional, Levin, Max, additional, Ullenhag, Gustav, additional, Ståhlberg, Anders, additional, Olofsson Bagge, Roger, additional, Nilsson, Jonas A., additional, and Ny, Lars, additional

Published
2023
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18. Figure S3 from Chemokine analysis in patients with metastatic uveal melanoma suggests a role for CCL21 signaling in combined epigenetic therapy and checkpoint immunotherapy

Author

Sah, Vasu R, primary, Jespersen, Henrik, primary, Karlsson, Joakim, primary, Nilsson, Lisa M, primary, Bergqvist, Mattias, primary, Johansson, Iva, primary, Carneiro, Ana, primary, Helgadottir, Hildur, primary, Levin, Max, primary, Ullenhag, Gustav J., primary, Ståhlberg, Anders, primary, Olofsson Bagge, Roger, primary, Nilsson, Jonas A., primary, and Ny, Lars, primary

Published
2023
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19. Supplementary Table S1 from Chemokine analysis in patients with metastatic uveal melanoma suggests a role for CCL21 signaling in combined epigenetic therapy and checkpoint immunotherapy

Author

Sah, Vasu R, primary, Jespersen, Henrik, primary, Karlsson, Joakim, primary, Nilsson, Lisa M, primary, Bergqvist, Mattias, primary, Johansson, Iva, primary, Carneiro, Ana, primary, Helgadottir, Hildur, primary, Levin, Max, primary, Ullenhag, Gustav J., primary, Ståhlberg, Anders, primary, Olofsson Bagge, Roger, primary, Nilsson, Jonas A., primary, and Ny, Lars, primary

Published
2023
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20. Data from Chemokine analysis in patients with metastatic uveal melanoma suggests a role for CCL21 signaling in combined epigenetic therapy and checkpoint immunotherapy

Author

Sah, Vasu R, primary, Jespersen, Henrik, primary, Karlsson, Joakim, primary, Nilsson, Lisa M, primary, Bergqvist, Mattias, primary, Johansson, Iva, primary, Carneiro, Ana, primary, Helgadottir, Hildur, primary, Levin, Max, primary, Ullenhag, Gustav J., primary, Ståhlberg, Anders, primary, Olofsson Bagge, Roger, primary, Nilsson, Jonas A., primary, and Ny, Lars, primary

Published
2023
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25. Table S1 from Evaluating Serum Thymidine Kinase 1 in Patients with Hormone Receptor–Positive Metastatic Breast Cancer Receiving First-line Endocrine Therapy in the SWOG S0226 Trial

Author

Paoletti, Costanza, primary, Barlow, William E., primary, Cobain, Erin F., primary, Bergqvist, Mattias, primary, Mehta, Rita S., primary, Gralow, Julie R., primary, Hortobagyi, Gabriel N., primary, Albain, Kathy S., primary, Pusztai, Lajos, primary, Sharma, Priyanka, primary, Godwin, Andrew K., primary, Thompson, Alastair M., primary, Hayes, Daniel F., primary, and Rae, James M., primary

Published
2023
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26. Data from Evaluating Serum Thymidine Kinase 1 in Patients with Hormone Receptor–Positive Metastatic Breast Cancer Receiving First-line Endocrine Therapy in the SWOG S0226 Trial

Author

Paoletti, Costanza, primary, Barlow, William E., primary, Cobain, Erin F., primary, Bergqvist, Mattias, primary, Mehta, Rita S., primary, Gralow, Julie R., primary, Hortobagyi, Gabriel N., primary, Albain, Kathy S., primary, Pusztai, Lajos, primary, Sharma, Priyanka, primary, Godwin, Andrew K., primary, Thompson, Alastair M., primary, Hayes, Daniel F., primary, and Rae, James M., primary

Published
2023
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27. Figure S2 from Evaluating Serum Thymidine Kinase 1 in Patients with Hormone Receptor–Positive Metastatic Breast Cancer Receiving First-line Endocrine Therapy in the SWOG S0226 Trial

Author

Paoletti, Costanza, primary, Barlow, William E., primary, Cobain, Erin F., primary, Bergqvist, Mattias, primary, Mehta, Rita S., primary, Gralow, Julie R., primary, Hortobagyi, Gabriel N., primary, Albain, Kathy S., primary, Pusztai, Lajos, primary, Sharma, Priyanka, primary, Godwin, Andrew K., primary, Thompson, Alastair M., primary, Hayes, Daniel F., primary, and Rae, James M., primary

Published
2023
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28. Abstract OT3-11-01: TK IMPACT: Treatment Monitoring of Hormone Receptor Positive (HR+), HER2 Negative (HER2-) Metastatic Breast Cancer (MBC) Patients Receiving CDK 4/6 Inhibitors (CDK4/6i) with DiviTum® Thymidine Kinase 1 Activity

Author

Bagegni, Nusayba A., primary, Grigsby, Isabella, additional, Nehring, Leslie, additional, Luo, Jingqin, additional, Carson, Jennifer Powers, additional, Gibson, David W., additional, Horvath, Meghan, additional, Clifton, Katherine K., additional, Ademuyiwa, Foluso O., additional, Suresh, Rama, additional, Frith, Ashley, additional, Davis, Andrew A., additional, Peterson, Lindsay L., additional, Bose, Ron, additional, Williams, Amy, additional, Bergqvist, Mattias, additional, and Ma, Cynthia, additional

Published
2023
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29. Abstract P5-02-27: Serum thymidine kinase activity as a prognostic marker in women with metastatic breast cancer treated with two different schedules of palbociclib plus second-line endocrine therapy within the CCTG MA38 trial

Author

McCartney, Amelia, primary, Biagioni, Chiara, additional, Chen, Bingshu, additional, Shepherd, Lois, additional, Gelmon, Karen, additional, Joy, Anil A., additional, Parulekar, Wendy, additional, Bergqvist, Mattias, additional, Migliaccio, Ilenia, additional, Leo, Angela, additional, Benelli, Matteo, additional, Risi, Emanuela, additional, Moretti, Erica, additional, Livraghi, Luca, additional, Biganzoli, Laura, additional, and Malorni, Luca, additional

Published
2023
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30. Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy

Author

Sah, Vasu R., Jespersen, Henrik, Karlsson, Joakim, Nilsson, Lisa M., Bergqvist, Mattias, Johansson, Iva, Carneiro, Ana, Helgadottir, Hildur, Levin, Max, Ullenhag, Gustav, Stahlberg, Anders, Bagge, Roger Olofsson, Nilsson, Jonas A., Ny, Lars, Sah, Vasu R., Jespersen, Henrik, Karlsson, Joakim, Nilsson, Lisa M., Bergqvist, Mattias, Johansson, Iva, Carneiro, Ana, Helgadottir, Hildur, Levin, Max, Ullenhag, Gustav, Stahlberg, Anders, Bagge, Roger Olofsson, Nilsson, Jonas A., and Ny, Lars

Abstract

Purpose: Patients with metastatic uveal melanoma have limited therapeutic options and high mortality rate so new treatment options are needed.Patients and Methods: We previously reported that patients treated with the PD-1 inhibitor pembrolizumab and the histone deacetylase inhibitor entinostat in the PEMDAC trial, experienced clinical benefits if their tu-mor originated from iris or was wildtype for BAP1 tumor suppressor gene. Here we present the 2-year follow-up of the patients in the PEMDAC trial and identify additional factors that correlate with response or survival.Results: Durable responses were observed in 4 patients, with additional 8 patients exhibiting a stable disease. The median overall survival was 13.7 months. Grade 3 adverse events were reported in 62% of the patients, but they were all manageable. No fatal toxicity was observed. Activity of thymidine kinase 1 in plasma was higher in patients with stable disease or who progressed on treatment, compared with those with partial response. Chemokines and cytokines were analyzed in plasma. Three chemokines were significantly different when comparing patients with and without response. One of the factors, CCL21, was higher in the plasma of respond-ing patients before treatment initiation but decreased in the same patients upon treatment. In tumors, CCL21 was expressed in areas resembling ter -tiar y lymphoid structures (TLS). High plasma levels of CCL21 and presence of TLS-like regions in the tumor correlated with longer survival.Conclusions: This study provides insight into durable responses in the PEMDAC trial, and describes dynamic changes of chemokines and cytokines in the blood of these patients.Significance: The most significant finding from the 2-year follow-up study of the PEMDAC trial was that high CCL21 levels in blood was associated with response and survival. CCL21 was also expressed in TLS-like regions and presence of these regions was associated with longer survival. These analyses of soluble

Published
2023
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33. A Subset of Non-Small Cell Lung Cancer Patients Treated with Pemetrexed Show 18 F-Fluorothymidine "Flare" on Positron Emission Tomography.

Author

Aravind, Preetha, Popat, Sanjay, Barwick, Tara D., Soneji, Neil, Lythgoe, Mark, Sreter, Katherina B., Lozano-Kuehne, Jingky P., Bergqvist, Mattias, Patel, Neva, Aboagye, Eric O., and Kenny, Laura M.

Subjects
LUNG cancer, CANCER chemotherapy, POSITRON emission tomography computed tomography, METASTASIS, TREATMENT effectiveness, CANCER patients, RADIOPHARMACEUTICALS, RESEARCH funding, DESCRIPTIVE statistics, PEMETREXED, OVERALL survival
Abstract

Simple Summary: Thymidylate synthase (TS) inhibitors have remained among the most effective chemotherapies used in the treatment of various cancer types. Imaging of tumour proliferative activity while on antifolates has been studied with 3′-deoxy-3′-[18F]fluorothymidine positron emission tomography (18F-FLT PET) imaging. The aim of this study was to use 18F-FLT PET/CT imaging to understand the basis of early drug action with the antifolate drug pemetrexed on TS inhibition. While every patient showed a global change in the plasma marker of TS inhibition after drug administration, tumour TS inhibition was selective and patients who showed a tumour change in the imaging biomarker had a greater therapy response and longer overall survival following a combination treatment including pemetrexed. The study findings implicate the potential use of 18F-FLT PET/CT to understand the basis of drug action in other studies involving TS inhibitors. Thymidylate synthase (TS) remains a major target for cancer therapy. TS inhibition elicits increases in DNA salvage pathway activity, detected as a transient compensatory "flare" in 3′-deoxy-3′-[18F]fluorothymidine positron emission tomography (18F-FLT PET). We determined the magnitude of the 18F-FLT flare in non-small cell lung cancer (NSCLC) patients treated with the antifolate pemetrexed in relation to clinical outcome. Method: Twenty-one patients with advanced/metastatic non-small cell lung cancer (NSCLC) scheduled to receive palliative pemetrexed ± platinum-based chemotherapy underwent 18F-FLT PET at baseline and 4 h after initiating single-agent pemetrexed. Plasma deoxyuridine (dUrd) levels and thymidine kinase 1 (TK1) activity were measured before each scan. Patients were then treated with the combination therapy. The 18F-FLT PET variables were compared to RECIST 1.1 and overall survival (OS). Results: Nineteen patients had evaluable PET scans at both time points. A total of 32% (6/19) of patients showed 18F-FLT flares (>20% change in SUVmax-wsum). At the lesion level, only one patient had an FLT flare in all the lesions above (test–retest borders). The remaining had varied uptake. An 18F-FLT flare occurred in all lesions in 1 patient, while another patient had an 18F-FLT reduction in all lesions; 17 patients showed varied lesion uptake. All patients showed global TS inhibition reflected in plasma dUrd levels (p < 0.001) and 18F-FLT flares of TS-responsive normal tissues including small bowel and bone marrow (p = 0.004 each). Notably, 83% (5/6) of patients who exhibited 18F-FLT flares were also RECIST responders with a median OS of 31 m, unlike patients who did not exhibit 18F-FLT flares (15 m). Baseline plasma TK1 was prognostic of survival but its activity remained unchanged following treatment. Conclusions: The better radiological response and longer survival observed in patients with an 18F-FLT flare suggest the efficacy of the tracer as an indicator of the early therapeutic response to pemetrexed in NSCLC. [ABSTRACT FROM AUTHOR]

Published
2023
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34. Serum thymidine kinase 1 and its kinetics in HER2-positive breast cancer: Results from the Swedish phase II PREDIX HER2 trial.

Author

Zhu, Yajing, primary, Wang, Kang, additional, Zerdes, Ioannis, additional, Matikas, Alexios, additional, Bergqvist, Mattias, additional, Elinder, Ellinor, additional, Bosch, Ana, additional, Lindman, Henrik, additional, Einbeigi, Zakaria, additional, Andersson, Anne, additional, Carlsson, Lena, additional, Dreifaldt, Ann Charlotte, additional, Isaksson-Friman, Erika, additional, Hellstrom, Mats, additional, Johansson, Hemming, additional, Bergh, Jonas C. S., additional, Hatschek, Thomas, additional, and Foukakis, Theodoros, additional

Published
2022
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35. [18F]Fluorothymidine(FLT)-PET imaging of thymidine kinase 1 pharmacodynamics in non-small cell lung cancer treated with pemetrexed.

Author

Aravind, Preetha, primary, Popat, Sanjay, additional, Barwick, Tara D., additional, Soneji, Neil, additional, Lythgoe, Mark, additional, Lozano-kuehne, Jingky, additional, Sreter, Katherina Bernadette, additional, Bergqvist, Mattias, additional, Patel, Neva H., additional, Aboagye, Eric O., additional, and Kenny, Laura M., additional

Published
2022
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36. Serum thymidine kinase activity in patients with hormone receptor-positive and HER2-negative metastatic breast cancer treated with palbociclib and fulvestrant.

Author

UCL - (MGD) Service d'oncologie médicale, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, Malorni, Luca, Tyekucheva, Svitlana, Hilbers, Florentine S, Ignatiadis, Michail, Neven, Patrick, Colleoni, Marco, HENRY, Stéphanie, Ballestrero, Alberto, Bonetti, Andrea, Jerusalem, Guy, Papadimitriou, Konstantinos, Bernardo, Antonio, Seles, Elena, Duhoux, Francois, MacPherson, Iain R, Thomson, Alastair, Davies, David Mark, Bergqvist, Mattias, Migliaccio, Ilenia, Gebhart, Géraldine, Zoppoli, Gabriele, Bliss, Judith M, Benelli, Matteo, McCartney, Amelia, Kammler, Roswitha, De Swert, Heidi, Ruepp, Barbara, Fumagalli, Debora, Maibach, Rudolf, Cameron, David, Loi, Sherene, Piccart, Martine, Regan, Meredith M, International Breast Cancer Study Group, Breast International Group and PYTHIA Collaborators, UCL - (MGD) Service d'oncologie médicale, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, Malorni, Luca, Tyekucheva, Svitlana, Hilbers, Florentine S, Ignatiadis, Michail, Neven, Patrick, Colleoni, Marco, HENRY, Stéphanie, Ballestrero, Alberto, Bonetti, Andrea, Jerusalem, Guy, Papadimitriou, Konstantinos, Bernardo, Antonio, Seles, Elena, Duhoux, Francois, MacPherson, Iain R, Thomson, Alastair, Davies, David Mark, Bergqvist, Mattias, Migliaccio, Ilenia, Gebhart, Géraldine, Zoppoli, Gabriele, Bliss, Judith M, Benelli, Matteo, McCartney, Amelia, Kammler, Roswitha, De Swert, Heidi, Ruepp, Barbara, Fumagalli, Debora, Maibach, Rudolf, Cameron, David, Loi, Sherene, Piccart, Martine, Regan, Meredith M, International Breast Cancer Study Group, and Breast International Group and PYTHIA Collaborators

Abstract

Biomarkers for cyclin-dependent kinase 4/6 inhibitors, such as palbociclib, for patients with hormone receptor-positive/HER2-negative metastatic breast cancer are lacking. Thymidine kinase is a proliferation marker downstream of the cyclin-dependent kinase 4/6 pathway. We prospectively investigated the prognostic role of serum thymidine kinase activity (sTKa), in patients treated with Palbociclib + fulvestrant. PYTHIA was a phase II, single-arm, multicentre, trial that enrolled 124 post-menopausal women with endocrine-resistant hormone receptor-positive/HER2-negative metastatic breast cancer. Serum samples were collected pre-treatment (pre-trt; n = 122), at day 15 of cycle 1 (D15; n = 108), during the one week-off palbociclib before initiating cycle 2 (D28; n = 108) and at end of treatment (n = 76). sTKa was determined centrally using Divitum®, a refined ELISA-based assay with a limit of detection of 20 Divitum Units (Du)/L. The primary study endpoint was progression-free survival, assessed for its association with pre- and on-treatment sTKa. Data from 122 women were analysed. Pre-treatment sTKa was not associated with clinical characteristics and moderately correlated with tissue Ki-67. Palbociclib + fulvestrant markedly suppressed sTKa levels at D15, with 83% of patients recording levels below limit of detection. At D28, sTKa showed a rebound in 60% of patients. At each timepoint, higher sTKa was associated with shorter progression-free survival (each p < 0.001), with the strongest effect at D15. STKa is an independent prognostic biomarker in patients treated with palbociclib. High pre-treatment sTKa and its incomplete suppression during treatment may identify patients with poorer prognosis and primary resistance. This warrants validation in prospective comparative trials. CLINICALTRIALS. NCT02536742; EudraCT 2014-005387-15.

Published
2022

37. Serum thymidine kinase 1 and its kinetics in HER2-positive breast cancer : Results from the Swedish phase II PREDIX HER2 trial

Author

Zhu, Yajing, Wang, Kang, Zerdes, Ioannis, Matikas, Alexios, Bergqvist, Mattias, Elinder, Ellinor, Bosch, Ana, Lindman, Henrik, Einbeigi, Zakaria, Andersson, Anne, Carlsson, Lena, Dreifaldt, Ann Charlotte, Isaksson-Friman, Erika, Hellstrom, Mats, Johansson, Hemming, Bergh, Jonas C. S., Hatschek, Thomas, Foukakis, Theodoros, Zhu, Yajing, Wang, Kang, Zerdes, Ioannis, Matikas, Alexios, Bergqvist, Mattias, Elinder, Ellinor, Bosch, Ana, Lindman, Henrik, Einbeigi, Zakaria, Andersson, Anne, Carlsson, Lena, Dreifaldt, Ann Charlotte, Isaksson-Friman, Erika, Hellstrom, Mats, Johansson, Hemming, Bergh, Jonas C. S., Hatschek, Thomas, and Foukakis, Theodoros

Published
2022

38. Serum thymidine kinase activity in patients with hormone receptor-positive and HER2-negative metastatic breast cancer treated with palbociclib and fulvestrant

Author

Malorni, Luca, primary, Tyekucheva, Svitlana, additional, Hilbers, Florentine S., additional, Ignatiadis, Michail, additional, Neven, Patrick, additional, Colleoni, Marco, additional, Henry, Stéphanie, additional, Ballestrero, Alberto, additional, Bonetti, Andrea, additional, Jerusalem, Guy, additional, Papadimitriou, Konstantinos, additional, Bernardo, Antonio, additional, Seles, Elena, additional, Duhoux, Francois P., additional, MacPherson, Iain R., additional, Thomson, Alastair, additional, Davies, David Mark, additional, Bergqvist, Mattias, additional, Migliaccio, Ilenia, additional, Gebhart, Géraldine, additional, Zoppoli, Gabriele, additional, Bliss, Judith M., additional, Benelli, Matteo, additional, McCartney, Amelia, additional, Kammler, Roswitha, additional, De Swert, Heidi, additional, Ruepp, Barbara, additional, Fumagalli, Debora, additional, Maibach, Rudolf, additional, Cameron, David, additional, Loi, Sherene, additional, Piccart, Martine, additional, and Regan, Meredith M., additional

Published
2022
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39. Abstract P5-13-22: Serum thymidine kinase 1 activity (TKa) levels and progression-free survival (PFS) in patients (pts) with hormone receptor positive (HR+) HER2-negative metastatic breast cancer (MBC) on palbociclib (Pb) and endocrine therapy (ET)

Author

O'Sullivan, Ciara C, primary, He, Jun, additional, Sinnwell, Jason, additional, Suman, Vera J, additional, Kalari, Krishna R, additional, Vedell, Peter T, additional, Moyer, Ann M, additional, Tang, Xiaojia, additional, Thompson, Kevin J, additional, Casey, Abe Eyman, additional, Moreno-Aspitia, Alvaro, additional, Northfelt, Donald W, additional, Liu, Minetta C, additional, Haddad, Tufia C, additional, Chumsri, Saranya, additional, McMenomy, Brendan, additional, Peethambaram, Prema, additional, Ruddy, Kathryn J, additional, Giridhar, Karthik V, additional, Leon-Ferre, Roberto A, additional, Bergqvist, Mattias, additional, Nordmark, Adrian, additional, Weinshilboum, Richard M, additional, Wang, Liewei, additional, and Goetz, Matthew P, additional

Published
2022
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40. Plasma Thymidine Kinase Activity as a Novel Biomarker in Metastatic Melanoma Patients Treated with Immune Checkpoint Inhibitors

Author

Costa Svedman, Fernanda, primary, Jalsenius, Marie, additional, Höiom, Veronica, additional, Grozman, Vitali, additional, Bergqvist, Mattias, additional, Söderdahl, Fabian, additional, Eriksson, Hanna, additional, Rotstein, Samuel, additional, Ny, Lars, additional, Ascierto, Paolo A., additional, Brage, Suzanne Egyhazi, additional, and Helgadottir, Hildur, additional

Published
2022
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41. Evaluating Serum Thymidine Kinase 1 in Patients with Hormone Receptor–Positive Metastatic Breast Cancer Receiving First-line Endocrine Therapy in the SWOG S0226 Trial

Author

Paoletti, Costanza, primary, Barlow, William E., additional, Cobain, Erin F., additional, Bergqvist, Mattias, additional, Mehta, Rita S., additional, Gralow, Julie R., additional, Hortobagyi, Gabriel N., additional, Albain, Kathy S., additional, Pusztai, Lajos, additional, Sharma, Priyanka, additional, Godwin, Andrew K., additional, Thompson, Alastair M., additional, Hayes, Daniel F., additional, and Rae, James M., additional

Published
2021
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43. Evaluating Serum Thymidine Kinase 1 in Patients with Hormone Receptor-Positive Metastatic Breast Cancer Receiving First-line Endocrine Therapy in the SWOG S0226 Trial.

Author

Paoletti, Costanza, Paoletti, Costanza, Barlow, William E, Cobain, Erin F, Bergqvist, Mattias, Mehta, Rita S, Gralow, Julie R, Hortobagyi, Gabriel N, Albain, Kathy S, Pusztai, Lajos, Sharma, Priyanka, Godwin, Andrew K, Thompson, Alastair M, Hayes, Daniel F, Rae, James M, Paoletti, Costanza, Paoletti, Costanza, Barlow, William E, Cobain, Erin F, Bergqvist, Mattias, Mehta, Rita S, Gralow, Julie R, Hortobagyi, Gabriel N, Albain, Kathy S, Pusztai, Lajos, Sharma, Priyanka, Godwin, Andrew K, Thompson, Alastair M, Hayes, Daniel F, and Rae, James M

Abstract

PurposeSerum thymidine kinase 1 (sTK1) activity is associated with poor prognosis in metastatic breast cancer (MBC). We assessed the prognostic effect of sTK1 in patients with hormone receptor-positive MBC treated on a prospective randomized trial of anastrozole (A) versus A plus fulvestrant (A + F).Patients and methodssTK1 was assessed in 1,726 serums [baseline (BL), cycles 2, 3, 4, and 7] using the DiviTum assay. A prespecified cutoff of ≥200 Du/L was considered high. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier, log-rank tests, and Cox regression.ResultsBL sTK1 was elevated in 171 (40%) of 432 patients. Patients with high versus low BL sTK1 had significantly worse PFS [median 11.2 vs. 17.3 months, HR = 1.76; 95% confidence interval (CI; 1.43-2.16); P < 0.0001] and OS [median 30 vs. 58 months, HR = 2.38; 95% CI (1.91-2.98); P < 0.0001]. OS was significantly better for patients with high sTK1 who did not have prior adjuvant tamoxifen and who received A + F versus A alone [median 46 vs. 21 months, HR = 0.58; 95% CI (0.38-0.87); P = 0.0087]. Patients with low sTK1 had no difference in outcomes by therapy (P = 0.44). At serial timepoints, high versus low sTK1 had significantly worse subsequent PFS and OS [at cycle 2: PFS HR = 1.70, 95% CI (1.34-2.17); P < 0.0001, OS HR = 2.51, 95% CI (1.93-3.26); P < 0.0001].ConclusionsHigh sTK1 at BL and subsequent timepoints is associated with worse prognosis in patients with MBC starting first-line endocrine therapy (ET). Patients with low sTK1 at BL have comparable outcomes on single-agent or combination ET.

Published
2021

44. Abstract PS12-02: Safety and efficacy of an alternative schedule of palbociclib (PAL) in hormone receptor positive (HR+), HER2 negative (HER2-) metastatic breast cancer (MBC) and the utility of serum thymidine kinase 1 (sTK1) activity in predicting PAL response

Author

Krishnamurthy, Jairam, primary, Luo, Jingqin, additional, Suresh, Rama, additional, Ademuyiwa, Foluso, additional, Rigden, Caron, additional, Reardon, Timothy, additional, Clifton, Katherine, additional, Weilbaecher, Katherine, additional, Frith, Ashley, additional, Roshal, Anna, additional, Tandra, Pavan, additional, Cherian, Mathew, additional, Summa, Tracy, additional, Thomas, Shana, additional, Hernandez-Aya, Leonel, additional, Bergqvist, Mattias, additional, Peterson, Lindsay, additional, and Ma, Cynthia X, additional

Published
2021
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45. Abstract PS2-04: Evaluating serum thymidine kinase 1 in hormone receptor positive metastatic breast cancer patients receiving first line endocrine therapy in the SWOG S0226 trial

Author

Paoletti, Costanza, primary, Barlow, William E., additional, Bergqvist, Mattias, additional, Mehta, Rita S., additional, Gralow, Julie R., additional, Hortobagyi, Gabriel N., additional, Albain, Kathy S., additional, Pusztai, Lajos, additional, Sharma, Priyanka, additional, Godwin, Andrew K., additional, Thompson, Alastair M., additional, Hayes, Daniel F., additional, and Rae, James, additional

Published
2021
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46. Abstract PS5-05: Serum thymidine kinase activity in patients with luminal metastatic breast cancer treated with palbociclib and fulvestrant within the PYTHIA trial

Author

Malorni, Luca, primary, Tyekucheva, Svitlana, additional, Hilbers, Florentine S, additional, Ignatiadis, Michail, additional, Neven, Patrick, additional, Colleoni, Marco, additional, Henry, Stéphanie, additional, Ballestrero, Alberto, additional, Bonetti, Andrea, additional, Jerusalem, Guy, additional, Papadimitriou, Konstantinos, additional, Bernardo, Antonio, additional, Duhoux, Francois, additional, MacPherson, Iain, additional, Thomson, Alastair, additional, Davies, David Mark, additional, Bergqvist, Mattias, additional, Benelli, Matteo, additional, McCartney, Amelia, additional, De Swert, Heidi, additional, Ruepp, Barbara, additional, Rabaglio, Manuela, additional, Maibach, Rudolf, additional, Piccart, Martine, additional, and Regan, Meredith M, additional

Published
2021
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47. Abstract PS5-24: Novel genomic variants and pathways associated with baseline serum thymidine kinase 1 levels in HR-positive HER2-negative MBC patients commencing palbociclib and letrozole

Author

Sullivan, Ciara C O, primary, Kalari, Krishna R, additional, Suman, Vera J, additional, Vedell, Peter T, additional, Moyer, Ann, additional, Casey, Abraham D Eyman, additional, Sinnwell, Jason, additional, Tang, Xiaojia, additional, Thompson, Kevin, additional, Moreno-Aspitia, Alvaro, additional, Northfelt, Donald W, additional, Liu, Minetta C, additional, Haddad, Tufia C, additional, Chumsri, Saranya, additional, Peethambaram, Prema, additional, Ruddy, Kathryn J, additional, Giridhar, Karthik V, additional, Leon-Ferre, Roberto A, additional, Nordmark, Adrian, additional, Bergqvist, Mattias, additional, McMenomy, Brendan P, additional, Weinshilboum, Richard M, additional, Wang, Liewei, additional, and Goetz, Matthew P, additional

Published
2021
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48. Plasma Thymidine Kinase Activity as a Biomarker in Patients with Luminal Metastatic Breast Cancer Treated with Palbociclib within the TREnd Trial

Author

McCartney, Amelia, primary, Bonechi, Martina, additional, De Luca, Francesca, additional, Biagioni, Chiara, additional, Curigliano, Giuseppe, additional, Moretti, Erica, additional, Minisini, Alessandro Marco, additional, Bergqvist, Mattias, additional, Benelli, Matteo, additional, Migliaccio, Ilenia, additional, Galardi, Francesca, additional, Risi, Emanuela, additional, De Santo, Irene, additional, Romagnoli, Dario, additional, Biganzoli, Laura, additional, Di Leo, Angelo, additional, and Malorni, Luca, additional

Published
2020
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49. Abstract P5-06-11: Serum thymidine kinase-1 activity (TKa) as a prognostic marker in premenopausal women with hormone receptor positive (HR+) operable breast cancer (BC)

Author

Malorni, Luca, primary, Migliaccio, Ilenia, additional, Biagioni, Chiara, additional, Rossi, Lorenzo, additional, De Santo, Irene, additional, Love, Richard L, additional, McCartney, Amelia, additional, Bergqvist, Mattias, additional, Bonechi, Martina, additional, De Luca, Francesca, additional, Galardi, Francesca, additional, Benelli, Matteo, additional, Romagnoli, Dario, additional, Risi, Emanuela, additional, Biganzoli, Laura, additional, Laudico, Adriano, additional, Van Dinh, Nguyen, additional, and Leo, Angelo Di, additional

Published
2020
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50. Abstract P5-01-12: Plasma thymidine kinase 1 activity and outcome of ER+ HER2- metastatic breast cancer patients treated with palbociclib and endocrine therapy

Author

Cabel, Luc, primary, Tanguy, Marie Laure, additional, Lerebours, Florence, additional, Brain, Etienne, additional, Loirat, Delphine, additional, Bergqvist, Mattias, additional, Cottu, Paul, additional, Donnadieu, Anne, additional, Bethune, Anne, additional, Rodrigues, Manuel, additional, Pierga, Jean-Yves, additional, and Bidard, François-Clément, additional

Published
2020
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