18 results on '"Schaule, J."'
Search Results
2. PD-0064 Metastases-directed SRT combined with systemic therapy: 2y results of the TOaSTT real-world database
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Kroeze, S., primary, Schaule, J., additional, Spaas, M., additional, Kahl, K.H., additional, Verhoeff, J.J., additional, Schneiders, F.L., additional, Blanck, O., additional, Lohaus, F., additional, Rogers, S., additional, Kaul, D., additional, Benavente, S., additional, Combs, S.E., additional, Skazikis, G., additional, Baumann, K., additional, Popp, I., additional, Koppe, F., additional, Geinitz, H., additional, de Jaeger, K.E., additional, Siva, S., additional, Stera, S., additional, Wittig-Sauerwein, A., additional, Lewitzki, V., additional, Eckert, F., additional, Schymalla, M.M., additional, and Guckenberger, M., additional
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- 2023
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3. Toxicity of SRT combined with targeted agents: prospective analysis of the TOaSTT database
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Kroeze, S., Schaule, J., Spaas, M., Kahl, K. H., Verhoeff, J. J., Schneiders, F. L., Blanck, O., Lohaus, F., Rogers, S., Kaul, D., Benavente, S., Combs, S. E., Skazikis, G., Baumann, K., Popp, I., Koppe, F., Geinitz, H., de Jaeger, K. E., Siva, S., Stera, S., Wittig-Sauerwein, A., Lewitzki, V., Eckert, F., Schymalla, M. M., Guckenberger, M., Molecular cell biology and Immunology, and Radiation Oncology
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- 2021
4. Toxicity of stereotactic Radiotherapy in Combination with targeted System Therapies: prospective Analysis of the TOaSTT Database
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Kroeze, S., Fritz, C., Schaule, J., Spaas, M., Kahl, K., Verhoeff, J., Schneiders, F., Blanck, O., Lohaus, F., Rogers, S., Kaul, D., Benavente, S., Combs, S., Skazikis, G., Baumann, K., Popp, I., Koppe, F., Geinitz, H., de Jaeger, K., Siva, S., Stera, S., Wittig-Sauerwein, A., Lewitzki, V., Eckert, F., Schymalla, M., Guckenberger, M., Molecular cell biology and Immunology, and Radiation Oncology
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- 2021
5. OC-0626 Toxicity of SRT combined with targeted agents: prospective analysis of the TOaSTT database
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Kroeze, S., primary, Schaule, J., additional, Spaas, M., additional, Kahl, K.H., additional, Verhoeff, J.J., additional, Schneiders, F.L., additional, Blanck, O., additional, Lohaus, F., additional, Rogers, S., additional, Kaul, D., additional, Benavente, S., additional, Combs, S.E., additional, Skazikis, G., additional, Baumann, K., additional, Popp, I., additional, Koppe, F., additional, Geinitz, H., additional, de Jaeger, K.E., additional, Siva, S., additional, Stera, S., additional, Wittig-Sauerwein, A., additional, Lewitzki, V., additional, Eckert, F., additional, Schymalla, M.M., additional, and Guckenberger, M., additional
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- 2021
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6. Additional file 1 of Intrafractional stability of MR-guided online adaptive SBRT for prostate cancer
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Schaule, J., Chamberlain, M., Wilke, L., Baumgartl, M., Krayenbühl, J., Zamburlini, M., Mayinger, M., Andratschke, N., Tanadini-Lang, S., and Guckenberger, M.
- Abstract
Additional file 1: Table S1. Couch shifts; A lateral, B vertical, C axial shifts in cm. Each line represents one volunteer. Bold = median.
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- 2021
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7. Additional file 3 of Intrafractional stability of MR-guided online adaptive SBRT for prostate cancer
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Schaule, J., Chamberlain, M., Wilke, L., Baumgartl, M., Krayenbühl, J., Zamburlini, M., Mayinger, M., Andratschke, N., Tanadini-Lang, S., and Guckenberger, M.
- Abstract
Additional file 3: Fig. S1. D1ccrectum for the baseline plan on the MR of the day compared to the adapted plan. Bar = median.
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- 2021
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8. Additional file 2 of Intrafractional stability of MR-guided online adaptive SBRT for prostate cancer
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Schaule, J., Chamberlain, M., Wilke, L., Baumgartl, M., Krayenbühl, J., Zamburlini, M., Mayinger, M., Andratschke, N., Tanadini-Lang, S., and Guckenberger, M.
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Data_FILES - Abstract
Additional file 2: Table S2. Dose Constraints.
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- 2021
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9. Metastasis directed stereotactic radiotherapy in NSCLC patients progressing under targeted- or immunotherapy: efficacy and safety reporting from the 'TOaSTT' database
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Kroeze, SGC, Schaule, J, Fritz, C, Kaul, D, Blanck, O, Kahl, KH, Roeder, F, Siva, S, Verhoeff, JJC, Adebahr, S, Schymalla, MM, Glatzer, M, Szuecs, M, Geier, M, Skazikis, G, Sackerer, I, Lohaus, F, Eckert, F, Guckenberger, M, Kroeze, SGC, Schaule, J, Fritz, C, Kaul, D, Blanck, O, Kahl, KH, Roeder, F, Siva, S, Verhoeff, JJC, Adebahr, S, Schymalla, MM, Glatzer, M, Szuecs, M, Geier, M, Skazikis, G, Sackerer, I, Lohaus, F, Eckert, F, and Guckenberger, M
- Abstract
BACKGROUND: Metastasis directed treatment (MDT) is increasingly performed with the attempt to improve outcome in non-small cell lung cancer (NSCLC) patients receiving targeted- or immunotherapy (TT/IT). This study aimed to assess the safety and efficacy of metastasis directed stereotactic radiotherapy (SRT) concurrent to TT/IT in NSCLC patients. METHODS: A retrospective multicenter cohort of stage IV NSCLC patients treated with TT/IT and concurrent (≤ 30 days) MDT was established. 56% and 44% of patients were treated for oligoprogressive disease (OPD) or polyprogressive disease (PPD) under TT/IT, polyprogressive respectively. Survival was analyzed using Kaplan-Meier and log rank testing. Toxicity was scored using CTCAE v4.03 criteria. Predictive factors for overall survival (OS), progression free survival (PFS) and time to therapy switch (TTS) were analyzed with uni- and multivariate analysis. RESULTS: MDT of 192 lesions in 108 patients was performed between 07/2009 and 05/2018. Concurrent TT/IT consisted of EGFR/ALK-inhibitors (60%), immune checkpoint inhibitors (31%), VEGF-antibodies (8%) and PARP-inhibitors (1%). 2y-OS was 51% for OPD and 25% for PPD. After 1 year, 58% of OPD and 39% of PPD patients remained on the same TT/IT. Second progression after MDT was oligometastatic (≤ 5 lesions) in 59% of patients. Severe acute and late toxicity was observed in 5.5% and 1.9% of patients. In multivariate analysis, OS was influenced by the clinical metastatic status (p = 0.002, HR 2.03, 95% CI 1.30-3.17). PFS was better in patients receiving their first line of systemic treatment (p = 0.033, HR 1.7, 95% CI 1.05-2.77) and with only one metastases-affected organ (p = 0.023, HR 2.04, 95% CI 1.10-3.79). TTS was 6 months longer in patients with one metastases-affected organ (p = 0.031, HR 2.53, 95% CI 1.09-5.89). Death was never therapy-related. CONCLUSIONS: Metastases-directed SRT in NSCLC patients can be safely performed concurrent to TT/IT with a low risk of severe toxicity
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- 2021
10. Continued versus Interrupted Targeted Therapy during Metastasis-Directed Stereotactic Radiotherapy: A Retrospective Multi-Center Safety and Efficacy Analysis
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Kroeze, SGC, Fritz, C, Schaule, J, Blanck, O, Kahl, KH, Kaul, D, Siva, S, Gerum, S, Claes, A, Sundahl, N, Adebahr, S, Stera, S, Schymalla, MM, Abbasi-Senger, N, Buergy, D, Geier, M, Szuecs, M, Lohaus, F, Henke, G, Combs, SE, Guckenberger, M, Kroeze, SGC, Fritz, C, Schaule, J, Blanck, O, Kahl, KH, Kaul, D, Siva, S, Gerum, S, Claes, A, Sundahl, N, Adebahr, S, Stera, S, Schymalla, MM, Abbasi-Senger, N, Buergy, D, Geier, M, Szuecs, M, Lohaus, F, Henke, G, Combs, SE, and Guckenberger, M
- Abstract
The increasing use of targeted therapy (TT) has resulted in prolonged disease control and survival in many metastatic cancers. In parallel, stereotactic radiotherapy (SRT) is increasingly performed in patients receiving TT to obtain a durable control of resistant metastases, and thereby to prolong the time to disseminated disease progression and switch of systemic therapy. The aims of this study were to analyze the safety and efficacy of SRT combined with TT in metastatic cancer patients and to assess the influence of continuous vs. interrupted TT during metastasis-directed SRT. The data of 454 SRTs in 158 patients from the international multicenter database (TOaSTT) on metastatic cancer patients treated with SRT and concurrent TT (within 30 days) were analyzed using Kaplan-Meier and log rank testing. Toxicity was defined by the CTCAE v4.03 criteria. The median FU was 19.9 mo (range 1-102 mo); 1y OS, PFS and LC were 59%, 24% and 84%, respectively. Median TTS was 25.5 mo (95% CI 11-40). TT was started before SRT in 77% of patients. TT was interrupted during SRT in 44% of patients, with a median interruption of 7 (range 1-42) days. There was no significant difference in OS or PFS whether TT was temporarily interrupted during SRT or not. Any-grade acute and late SRT-related toxicity occurred in 63 (40%) and 52 (33%) patients, respectively. The highest toxicity rates were observed for the combination of SRT and EGFRi or BRAF/MEKi, and any-grade toxicity was significantly increased when EGFRi (p = 0.016) or BRAF/MEKi (p = 0.009) were continued during SRT. Severe (≥grade 3) acute and late SRT-related toxicity were observed in 5 (3%) and 7 (4%) patients, respectively, most frequently in patients treated with EGFRi or BRAF/MEKi and in the intracranial cohort. There was no significant difference in severe toxicity whether TT was interrupted before and after SRT or not. In conclusion, SRT and continuous vs. interrupted TT in metastatic cancer patients did not influence OS or
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- 2021
11. Intrafractional stability of MR-guided online adaptive SBRT for prostate cancer
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Schaule, J; https://orcid.org/0000-0001-5870-0980, Chamberlain, M, Wilke, L, Baumgartl, M, Krayenbühl, J, Zamburlini, M, Mayinger, M, Andratschke, N, Tanadini-Lang, S, Guckenberger, Matthias; https://orcid.org/0000-0002-7146-9071, Schaule, J; https://orcid.org/0000-0001-5870-0980, Chamberlain, M, Wilke, L, Baumgartl, M, Krayenbühl, J, Zamburlini, M, Mayinger, M, Andratschke, N, Tanadini-Lang, S, and Guckenberger, Matthias; https://orcid.org/0000-0002-7146-9071
- Abstract
Background: MR-guided online adaptive stereotactic body radiation therapy (SBRT) for prostate cancer aims to reduce toxicity by full compensation of interfractional uncertainties. However, the process of online adaptation currently takes approximately 45 min during which intrafractional movements remain unaccounted for. This study aims to analyze the dosimetric benefit of online adaptation and to evaluate its robustness over the duration of one treatment fraction. Methods: Baseline MR-scans at a MR-linear accelerator were acquired for ten healthy male volunteers for generation of mock-prostate SBRT plans with a dose prescription of 5 × 7.25 Gy. On a separate day, online MR-guided adaptation (ViewRay® MRIdian) was performed, and thereafter MR images were acquired every 15 min for 1 h to assess the stability of the adapted plan. Results: A dosimetric benefit of online MR-guided adaptive re-planning was observed in 90% of volunteers. The median D95CTV- and D95PTV-coverage was improved from 34.8 to 35.5 Gy and from 30.7 to 34.6 Gy, respectively. Improved target coverage was not associated with higher dose to the organs at risk, most importantly the rectum (median D1ccrectum baseline plan vs. adapted plan 33.3 Gy vs. 32.3 Gy). The benefit of online adaptation remained stable over 45 min for all volunteers. However, at 60 min, CTV-coverage was below a threshold of 32.5 Gy in 30% of volunteers (30.6 Gy, 32.0 Gy, 32.3 Gy). Conclusion: The dosimetric benefit of MR-guided online adaptation for prostate SBRT was robust over 45 min in all volunteers. However, intrafractional uncertainties became dosimetrically relevant at 60 min and we therefore recommend verification imaging before delivery of MR-guided online adapted SBRT. Keywords: MR-guided radiotherapy; Online adaptation; Plan-of-the-day; Prostate SBRT.
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- 2021
12. Stereotactic radiotherapy combined with immunotherapy or targeted therapy for metastatic renal cell carcinoma
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Kroeze, SGC, Fritz, C, Schaule, J, Siva, S, Kahl, KH, Sundahl, N, Blanck, O, Kaul, D, Adebahr, S, Verhoeff, JJC, Skazikis, G, Roeder, F, Geier, M, Eckert, F, Guckenberger, M, Kroeze, SGC, Fritz, C, Schaule, J, Siva, S, Kahl, KH, Sundahl, N, Blanck, O, Kaul, D, Adebahr, S, Verhoeff, JJC, Skazikis, G, Roeder, F, Geier, M, Eckert, F, and Guckenberger, M
- Abstract
OBJECTIVES: To evaluate the safety and efficacy of stereotactic radiotherapy (SRT) in patients with metastatic renal cell carcinoma (mRCC) concurrently receiving targeted therapy (TT) or immunotherapy. PATIENTS AND METHODS: Data on patients with mRCC were extracted from a retrospective international multicentre register study (TOaSTT), investigating SRT concurrent (≤30 days) with TT/immune checkpoint inhibitor (ICI) therapy. Overall survival (OS), progression-free survival (PFS), local metastasis control (LC) and time to systemic therapy switch were analysed using Kaplan-Meier curves and log-rank testing. Clinical and treatment factors influencing survival were analysed using multivariate Cox regression. Acute and late SRT-induced toxicity were defined according to the Common Terminology Criteria for Adverse Events v.4.03. RESULTS: Fifty-three patients who underwent 128 sessions of SRT were included, of whom 58% presented with oligometastatic disease (OMD). ICIs and TT were received by 32% and 68% of patients, respectively. Twenty patients (37%) paused TT for a median (range) of 14 (2-21) days. ICI therapy was not paused in any patient. A median (range) of 1 (1-5) metastatic tumour was treated per patient, with a median (range) SRT dose of 65 (40-129.4) Gy (biologically effective dose). The OS, LC and PFS rates at 1 year were 71%, 75% and 25%, respectively. The median OS and PFS were not significantly different among patients receiving TT vs those receiving ICIs (P = 0.329). New lesions were treated with a repeat radiotherapy course in 46% of patients. After 1 year, 62% of patients remained on the same systemic therapy as at the time of SRT; this was more frequent for ICI therapy compared to TT (83% vs 36%; P = 0.035). OMD was an independent prognostic factor for OS (P = 0.004, 95% confidence interval [CI] 0.035-0.528) and PFS (P = 0.004; 95% CI 0.165-0.717) in multivariate analysis. Eastern Cooperative Oncology Group performance status (ECOG-PS) was the other indep
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- 2020
13. Intrafractional stability of MR-guided online adaptive SBRT for prostate cancer
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Stephanie Tanadini-Lang, L. Wilke, Michael Mayinger, N. Andratschke, M. Baumgartl, M. Zamburlini, M. Chamberlain, J. Krayenbühl, Matthias Guckenberger, Jana Schaule, University of Zurich, and Schaule, J
- Subjects
Adult ,Male ,Organs at Risk ,Stereotactic body radiation therapy ,Plan-of-the-day ,medicine.medical_treatment ,R895-920 ,610 Medicine & health ,MR-guided radiotherapy ,Radiosurgery ,Prostate cancer ,Medical physics. Medical radiology. Nuclear medicine ,Online adaptation ,Prostate ,medicine ,2741 Radiology, Nuclear Medicine and Imaging ,Humans ,Radiology, Nuclear Medicine and imaging ,RC254-282 ,business.industry ,Radiotherapy Planning, Computer-Assisted ,Research ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Prostatic Neoplasms ,Radiotherapy Dosage ,Middle Aged ,medicine.disease ,10044 Clinic for Radiation Oncology ,Magnetic Resonance Imaging ,Dose prescription ,Radiation therapy ,medicine.anatomical_structure ,Oncology ,2730 Oncology ,Prostate SBRT ,Radiotherapy, Intensity-Modulated ,Mr images ,Nuclear medicine ,business ,Mri guided ,Radiotherapy, Image-Guided - Abstract
Background MR-guided online adaptive stereotactic body radiation therapy (SBRT) for prostate cancer aims to reduce toxicity by full compensation of interfractional uncertainties. However, the process of online adaptation currently takes approximately 45 min during which intrafractional movements remain unaccounted for. This study aims to analyze the dosimetric benefit of online adaptation and to evaluate its robustness over the duration of one treatment fraction. Methods Baseline MR-scans at a MR-linear accelerator were acquired for ten healthy male volunteers for generation of mock-prostate SBRT plans with a dose prescription of 5 × 7.25 Gy. On a separate day, online MR-guided adaptation (ViewRay® MRIdian) was performed, and thereafter MR images were acquired every 15 min for 1 h to assess the stability of the adapted plan. Results A dosimetric benefit of online MR-guided adaptive re-planning was observed in 90% of volunteers. The median D95CTV- and D95PTV-coverage was improved from 34.8 to 35.5 Gy and from 30.7 to 34.6 Gy, respectively. Improved target coverage was not associated with higher dose to the organs at risk, most importantly the rectum (median D1ccrectum baseline plan vs. adapted plan 33.3 Gy vs. 32.3 Gy). The benefit of online adaptation remained stable over 45 min for all volunteers. However, at 60 min, CTV-coverage was below a threshold of 32.5 Gy in 30% of volunteers (30.6 Gy, 32.0 Gy, 32.3 Gy). Conclusion The dosimetric benefit of MR-guided online adaptation for prostate SBRT was robust over 45 min in all volunteers. However, intrafractional uncertainties became dosimetrically relevant at 60 min and we therefore recommend verification imaging before delivery of MR-guided online adapted SBRT.
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- 2021
14. Continued versus Interrupted Targeted Therapy during Metastasis-Directed Stereotactic Radiotherapy: A Retrospective Multi-Center Safety and Efficacy Analysis.
- Author
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Kroeze SGC, Fritz C, Schaule J, Blanck O, Kahl KH, Kaul D, Siva S, Gerum S, Claes A, Sundahl N, Adebahr S, Stera S, Schymalla MM, Abbasi-Senger N, Buergy D, Geier M, Szuecs M, Lohaus F, Henke G, Combs SE, and Guckenberger M
- Abstract
The increasing use of targeted therapy (TT) has resulted in prolonged disease control and survival in many metastatic cancers. In parallel, stereotactic radiotherapy (SRT) is increasingly performed in patients receiving TT to obtain a durable control of resistant metastases, and thereby to prolong the time to disseminated disease progression and switch of systemic therapy. The aims of this study were to analyze the safety and efficacy of SRT combined with TT in metastatic cancer patients and to assess the influence of continuous vs. interrupted TT during metastasis-directed SRT. The data of 454 SRTs in 158 patients from the international multicenter database (TOaSTT) on metastatic cancer patients treated with SRT and concurrent TT (within 30 days) were analyzed using Kaplan-Meier and log rank testing. Toxicity was defined by the CTCAE v4.03 criteria. The median FU was 19.9 mo (range 1-102 mo); 1y OS, PFS and LC were 59%, 24% and 84%, respectively. Median TTS was 25.5 mo (95% CI 11-40). TT was started before SRT in 77% of patients. TT was interrupted during SRT in 44% of patients, with a median interruption of 7 (range 1-42) days. There was no significant difference in OS or PFS whether TT was temporarily interrupted during SRT or not. Any-grade acute and late SRT-related toxicity occurred in 63 (40%) and 52 (33%) patients, respectively. The highest toxicity rates were observed for the combination of SRT and EGFRi or BRAF/MEKi, and any-grade toxicity was significantly increased when EGFRi ( p = 0.016) or BRAF/MEKi ( p = 0.009) were continued during SRT. Severe (≥grade 3) acute and late SRT-related toxicity were observed in 5 (3%) and 7 (4%) patients, respectively, most frequently in patients treated with EGFRi or BRAF/MEKi and in the intracranial cohort. There was no significant difference in severe toxicity whether TT was interrupted before and after SRT or not. In conclusion, SRT and continuous vs. interrupted TT in metastatic cancer patients did not influence OS or PFS. Overall, severe toxicity of combined treatment was rare; a potentially increased toxicity after SRT and continuous treatment with EGFR inhibitors or BRAF(±MEK) inhibitors requires further evaluation.
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- 2021
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15. Stereotactic radiotherapy combined with immunotherapy or targeted therapy for metastatic renal cell carcinoma.
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Kroeze SGC, Fritz C, Schaule J, Siva S, Kahl KH, Sundahl N, Blanck O, Kaul D, Adebahr S, Verhoeff JJC, Skazikis G, Roeder F, Geier M, Eckert F, and Guckenberger M
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Renal Cell secondary, Combined Modality Therapy, Female, Humans, Kidney Neoplasms pathology, Male, Middle Aged, Retrospective Studies, Carcinoma, Renal Cell therapy, Immunotherapy, Kidney Neoplasms therapy, Radiosurgery
- Abstract
Objectives: To evaluate the safety and efficacy of stereotactic radiotherapy (SRT) in patients with metastatic renal cell carcinoma (mRCC) concurrently receiving targeted therapy (TT) or immunotherapy., Patients and Methods: Data on patients with mRCC were extracted from a retrospective international multicentre register study (TOaSTT), investigating SRT concurrent (≤30 days) with TT/immune checkpoint inhibitor (ICI) therapy. Overall survival (OS), progression-free survival (PFS), local metastasis control (LC) and time to systemic therapy switch were analysed using Kaplan-Meier curves and log-rank testing. Clinical and treatment factors influencing survival were analysed using multivariate Cox regression. Acute and late SRT-induced toxicity were defined according to the Common Terminology Criteria for Adverse Events v.4.03., Results: Fifty-three patients who underwent 128 sessions of SRT were included, of whom 58% presented with oligometastatic disease (OMD). ICIs and TT were received by 32% and 68% of patients, respectively. Twenty patients (37%) paused TT for a median (range) of 14 (2-21) days. ICI therapy was not paused in any patient. A median (range) of 1 (1-5) metastatic tumour was treated per patient, with a median (range) SRT dose of 65 (40-129.4) Gy (biologically effective dose). The OS, LC and PFS rates at 1 year were 71%, 75% and 25%, respectively. The median OS and PFS were not significantly different among patients receiving TT vs those receiving ICIs (P = 0.329). New lesions were treated with a repeat radiotherapy course in 46% of patients. After 1 year, 62% of patients remained on the same systemic therapy as at the time of SRT; this was more frequent for ICI therapy compared to TT (83% vs 36%; P = 0.035). OMD was an independent prognostic factor for OS (P = 0.004, 95% confidence interval [CI] 0.035-0.528) and PFS (P = 0.004; 95% CI 0.165-0.717) in multivariate analysis. Eastern Cooperative Oncology Group performance status (ECOG-PS) was the other independent prognostic factor for OS (P = 0.001, 95% CI 0.001-0.351). Acute grade 3 toxicity was observed in two patients, and late grade 3 toxicity in one patient. No grade 4 or 5 toxicity was observed., Conclusion: Combined treatment with TT or immunotherapy and concurrent SRT was safe, without signals of increased severe toxicity. As we observed no signal of excess toxicity, full-dose SRT should be considered to achieve optimal metastasis control in patients receiving TT or immunotherapy. Favourable PFS and OS were observed for patients with oligometastatic RCC with a good ECOG-PS, which should form the basis for prospective testing of this treatment strategy in properly designed clinical trials., (© 2020 The Authors BJU International © 2020 BJU International Published by John Wiley & Sons Ltd.)
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- 2021
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16. Metastasis directed stereotactic radiotherapy in NSCLC patients progressing under targeted- or immunotherapy: efficacy and safety reporting from the 'TOaSTT' database.
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Kroeze SGC, Schaule J, Fritz C, Kaul D, Blanck O, Kahl KH, Roeder F, Siva S, Verhoeff JJC, Adebahr S, Schymalla MM, Glatzer M, Szuecs M, Geier M, Skazikis G, Sackerer I, Lohaus F, Eckert F, and Guckenberger M
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung mortality, Carcinoma, Non-Small-Cell Lung pathology, Combined Modality Therapy, Disease Progression, Humans, Lung Neoplasms mortality, Lung Neoplasms pathology, Middle Aged, Prospective Studies, Radiosurgery adverse effects, Carcinoma, Non-Small-Cell Lung radiotherapy, Immune Checkpoint Inhibitors therapeutic use, Lung Neoplasms radiotherapy, Molecular Targeted Therapy, Radiosurgery methods
- Abstract
Background: Metastasis directed treatment (MDT) is increasingly performed with the attempt to improve outcome in non-small cell lung cancer (NSCLC) patients receiving targeted- or immunotherapy (TT/IT). This study aimed to assess the safety and efficacy of metastasis directed stereotactic radiotherapy (SRT) concurrent to TT/IT in NSCLC patients., Methods: A retrospective multicenter cohort of stage IV NSCLC patients treated with TT/IT and concurrent (≤ 30 days) MDT was established. 56% and 44% of patients were treated for oligoprogressive disease (OPD) or polyprogressive disease (PPD) under TT/IT, polyprogressive respectively. Survival was analyzed using Kaplan-Meier and log rank testing. Toxicity was scored using CTCAE v4.03 criteria. Predictive factors for overall survival (OS), progression free survival (PFS) and time to therapy switch (TTS) were analyzed with uni- and multivariate analysis., Results: MDT of 192 lesions in 108 patients was performed between 07/2009 and 05/2018. Concurrent TT/IT consisted of EGFR/ALK-inhibitors (60%), immune checkpoint inhibitors (31%), VEGF-antibodies (8%) and PARP-inhibitors (1%). 2y-OS was 51% for OPD and 25% for PPD. After 1 year, 58% of OPD and 39% of PPD patients remained on the same TT/IT. Second progression after MDT was oligometastatic (≤ 5 lesions) in 59% of patients. Severe acute and late toxicity was observed in 5.5% and 1.9% of patients. In multivariate analysis, OS was influenced by the clinical metastatic status (p = 0.002, HR 2.03, 95% CI 1.30-3.17). PFS was better in patients receiving their first line of systemic treatment (p = 0.033, HR 1.7, 95% CI 1.05-2.77) and with only one metastases-affected organ (p = 0.023, HR 2.04, 95% CI 1.10-3.79). TTS was 6 months longer in patients with one metastases-affected organ (p = 0.031, HR 2.53, 95% CI 1.09-5.89). Death was never therapy-related., Conclusions: Metastases-directed SRT in NSCLC patients can be safely performed concurrent to TT/IT with a low risk of severe toxicity. To find the ideal sequence of the available multidisciplinary treatment options for NSCLC and determine what patients will benefit most, a further evaluated in a broader context within prospective clinical trials is needed continuation of TT/IT beyond progression combined with MDT for progressive lesions appears promising but requires prospective evaluation., Trial Registration: retrospectively registered.
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- 2021
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17. Correction to: Predicting survival in melanoma patients treated with concurrent targeted- or immunotherapy and stereotactic radiotherapy : Melanoma brain metastases prognostic score.
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Schaule J, Kroeze SGC, Blanck O, Stera S, Kahl KH, Roeder F, Combs SE, Kaul D, Claes A, Schymalla MM, Adebahr S, Eckert F, Lohaus F, Abbasi-Senger N, Henke G, Szuecs M, Geier M, Sundahl N, Buergy D, Dummer R, and Guckenberger M
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- 2020
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18. Predicting survival in melanoma patients treated with concurrent targeted- or immunotherapy and stereotactic radiotherapy : Melanoma brain metastases prognostic score.
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Schaule J, Kroeze SGC, Blanck O, Stera S, Kahl KH, Roeder F, Combs SE, Kaul D, Claes A, Schymalla MM, Adebahr S, Eckert F, Lohaus F, Abbasi-Senger N, Henke G, Szuecs M, Geier M, Sundahl N, Buergy D, Dummer R, and Guckenberger M
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Immunological therapeutic use, Brain Neoplasms secondary, Female, Humans, Immunotherapy methods, Male, Melanoma secondary, Middle Aged, Molecular Targeted Therapy methods, Prognosis, Radiosurgery methods, Retrospective Studies, Brain Neoplasms mortality, Brain Neoplasms therapy, Combined Modality Therapy methods, Melanoma mortality, Melanoma therapy
- Abstract
Background: Melanoma patients frequently develop brain metastases. The most widely used score to predict survival is the molGPA based on a mixed treatment of stereotactic radiotherapy (SRT) and whole brain radiotherapy (WBRT). In addition, systemic therapy was not considered. We therefore aimed to evaluate the performance of the molGPA score in patients homogeneously treated with SRT and concurrent targeted therapy or immunotherapy (TT/IT)., Methods: This retrospective analysis is based on an international multicenter database (TOaSTT) of melanoma patients treated with TT/IT and concurrent (≤30 days) SRT for brain metastases between May 2011 and May 2018. Overall survival (OS) was studied using Kaplan-Meier survival curves and log-rank testing. Uni- and multivariate analysis was performed to analyze prognostic factors for OS., Results: One hundred ten patients were analyzed. 61, 31 and 8% were treated with IT, TT and with a simultaneous combination, respectively. A median of two brain metastases were treated per patient. After a median follow-up of 8 months, median OS was 8.4 months (0-40 months). The molGPA score was not associated with OS. Instead, cumulative brain metastases volume, timing of metastases (syn- vs. metachronous) and systemic therapy with concurrent IT vs. TT influenced OS significantly. Based on these parameters, the VTS score (volume-timing-systemic therapy) was established that stratified patients into three groups with a median OS of 5.1, 18.9 and 34.5 months, respectively (p = 0.001 and 0.03)., Conclusion: The molGPA score was not useful for this cohort of melanoma patients undergoing local therapy for brain metastases taking into account systemic TT/IT. For these patients, we propose a prognostic VTS score, which needs to be validated prospectively.
- Published
- 2020
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