Tıp Fakültesi / Faculty of Medicine

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    Prognostic Value of 18F-Fluorodeoxyglucose Uptake in Pelvic Lymph Nodes in Patients with Cervical Cancer Treated with Definitive Chemoradiotherapy
    (2015) Onal, Cem; Guler, Ozan C.; Reyhan, Mehmet; Yapar, Ali Fuat; 0000-0001-6908-3412; 0000-0003-1715-4180; 0000-0002-2742-9021; 0000-0001-8550-3368; 25641567; AAC-5654-2020; AAI-8973-2021; D-5195-2014; AAJ-5242-2021; HOC-5611-2023
    Purpose. To evaluate the prognostic significance of the maximum standardized uptake (SUVmax) value for pelvic lymph nodes in patients with cervical cancer and its impact on treatment response, disease control, and survival. Methods. Ninety-three patients with pelvic or para-aortic metastasis detected by PET/CT and treated with definitive chemoradiotherapy were evaluated. The impact of pelvic lymph node SUVmax on prognostic factors and treatment outcomes was assessed. Results. The size and SUVmax of pelvic lymph nodes were significantly correlated (r = 0.859; p < 0.001). Patients with pelvic and para-aortic lymph node metastases had significantly higher SUVmax values for both primary tumor (23.4 +/- 9.2 vs. 18.5 +/- 73; p = 0.01) and pelvic lymph nodes (11.4 +/- 4.6 vs. 7.4 +/- 3.8; p = 0.001). Patients with pelvic lymph node SUVmax >= 7.5 had significantly higher primary tumor SUVmax, larger pelvic lymph nodes, higher rates of para-aortic lymph node metastasis, and lower post-therapy complete response rates. Overall survival (OS) and disease-free survival (DFS) rates were significantly higher in patients with SUVmax < 7.5 compared to patients with SUVmax >= 7.5. In a multivariate analysis, pelvic lymph node SUVmax and post-therapy metabolic response were significant prognostic factors for both OS and DFS for all patients, but no significant prognostic factors were found in pelvic lymph node metastasis only. Conclusions. Patients with highly FDG-avid pelvic lymph nodes have a higher risk of disease recurrence with worse survival. Identification of these patients may assist in the evaluation of the clinical benefits of additional treatments. (C) 2015 Elsevier Inc. All rights reserved.
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    Treatment Outcomes of Patients with Cervical Cancer with Complete Metabolic Responses After Definitive Chemoradiotherapy
    (2014) Onal, Cem; Reyhan, Mehmet; Guler, Ozan C.; Yapar, Ali Fuat; https://orcid.org/0000-0002-2742-9021; https://orcid.org/0000-0001-8550-3368; https://orcid.org/0000-0001-6908-3412; https://orcid.org/0000-0003-1715-4180; 24562649; HOC-5611-2023; AAJ-5242-2021; AAC-5654-2020; AAI-8973-2021
    Purpose We sought to evaluate failure patterns and prognostic factors predictive of recurrences and survival in cervical cancer patients who are treated with definitive chemoradiotherapy (ChRT), who have a subsequent complete metabolic response (CMR) with (18) F-fluorodeoxyglucose positron-emission tomography (FDG-PET) after treatment. Methods The records of 152 cervical cancer patients who were treated with definitive chemoradiotherapy were evaluated. All patients underwent pre-treatment positron emission tomography (PET-CT), and post-treatment PET-CT was performed within a median of 3.9 months (range, 3.0-9.8 months) after the completion of ChRT. The prognoses of partial response/progressive disease (PR/PD) cases (30 patients, 18 %) and CMR cases (122 patients, %82) were evaluated. Univariate and multivariate analysis effecting the treatment outcome was performed in CMR cases. Results The median follow-ups for all patients and surviving patients were 28.7 (range, 3.3-78.7 months) and 33.2 months (range, 6.23-78.7 months), respectively. Four-year overall survival (OS) rate was significantly better in patients with CMR compared to patients with PR/PD (66.9 % vs. 12.4 %, p < 0.001, respectively). Patients with PR/PD had higher maximum standardized uptake value (SUVmax) of primary cervical tumor (26.4 +/- 10.1 vs. 15.9 +/- 6.3; p < 0.001) and larger tumor (6.4 cm +/- 2.3 cm vs. 5.0 cm +/- 1.4 cm; p < 0.001) compared to patients with CMR. Of the 122 patients with post-treatment CMRs, 25 (21 %) developed local, locoregional, or distant failure. In univariate analysis, tumor size a parts per thousand yen 5 cm, 'International Federation of Obstetricians and Gynecologists' (FIGO) stage a parts per thousand yenaEuro parts per thousand IIB, and pelvic and/or para-aortic lymph node metastasis were predictive of both overall survival (OS) and disease-free survival (DFS), while histology was predictive of only OS. In multivariate analysis, tumor size, stage and lymph node metastasis were predictive of OS and DFS. Conclusion Although CMR is associated with better outcomes, relapses remain problematic, especially in patients with bulky tumors (a parts per thousand yen 5 cm), extensive stage (a parts per thousand yen IIB) or pelvic and/or para-aortic lymph node metastasis. These findings could support the need for more aggressive treatment or adjuvant chemotherapy regimens.
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    Prognostic Value of Metabolic Tumor Volume and Total Lesion Glycolysis in Esophageal Carcinoma Patients Treated with Definitive Chemoradiotherapy
    (2018) Yildirim, Berna A.; Torun, Nese; Guler, Ozan C.; Onal, Cem; 0000-0001-6908-3412; 0000-0001-6661-4185; 0000-0002-2742-9021; 0000-0002-5597-676X; 29668513; AAC-5654-2020; V-5717-2017; D-5195-2014; AAE-2718-2021
    PurposeThe aim of this study was to evaluate the prognostic importance metabolic tumor volume (MTV), total lesion glycolysis (TLG), and standardized uptake value (SUV) in patients with esophageal cancer treated with definitive chemoradiotherapy.Patients and methodsSeventy-two esophageal cancer patients treated with definitive chemoradiotherapy [57 (79%) patients] or definitive radiotherapy [15 (21%) patients] were retrospectively analyzed. The regions equal to or greater than SUV of 2.5 were selected to delineate MTV and TLG was calculated by multiplying the mean SUV by the MTV of the primary lesions. The overall survival (OS) and disease-free survival (DFS) were evaluated for all patients and also patients with squamous cell carcinoma.ResultsThe median survival time was 13.4 months (range: 1.8-119.3 months) for all patients. Maximum SUV, mean SUV, MTV, and TLG values were significantly higher in patients with extensive T-stage (T3-T4) compared with patients with T1-T2 disease. Patients with regional lymph node metastasis had significantly higher MTV and TLG values compared with patients with no lymph node metastasis. On multivariate analysis, MTV, TLG, presence of lymph node metastasis, and lack of concurrent chemotherapy were negative significant prognostic factors for OS and DFS for the entire cohort and for patients with squamous cell carcinoma esophageal cancer.ConclusionMetabolic volumes (MTV and TLG), regional lymph node metastasis, and concurrent chemotherapy are major prognostic factors for DFS and OS in patients with esophageal carcinoma. In addition, MTV and TLG are important in predicting nodal metastasis, and together with metabolic volumes, SUV are associated significantly with local tumor invasion.
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    Prognostic Use of Pretreatment Hematologic Parameters in Patients Receiving Definitive Chemoradiotherapy for Cervical Cancer
    (2016) Onal, Cem; Guler, Ozan C.; Yildirim, Berna A.; 0000-0002-2742-9021; 0000-0001-6661-4185; 0000-0001-6908-3412; 27206286; D-5195-2014; V-5717-2017; AAC-5654-2020
    Objectives: The aim of this work was to evaluate the prognostic role of pretreatment neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in recipients of definitive chemoradiotherapy (ChRT) for cervical cancer. Methods: In 235 patients given definitive ChRT for histologically confirmed cervical cancer, clinical data and pretreatment complete blood cell counts were analyzed. Prognostic and therapeutic ramifications of NLR and PLR were assessed. Results: Median pretreatment NLR and PLR were 3.03 (range, 1.04-13.03) and 133.02 (range, 36.3-518.16), respectively. Both NLR and PLR correlated significantly with tumor size, lymph node metastasis, and treatment response. In addition to NLR and PLR, tumor stage, size, and nodal metastasis were identified by univariate analysis as significant predictors of overall survival (OS) and progression-free survival (PFS). By multivariate analysis, independent predictors of OS and PFS were NLR (OS: hazard ratio [HR], 3.322; 95% confidence interval [CI], 1.905-5.790; PFS: HR, 3.579; 95% CI, 2.106-6.082; both P < 0.001) and lymph node metastasis (OS: HR, 2.620; 95% CI, 1.706-4.023; PFS: HR, 2.989; 95% CI, 1.918-4.378; both P < 0.001), although patients' age (HR, 1.019; 95% CI, 1.003-1.035; P = 0.02) was also significantly predictive of OS. Conclusions: Pretreatment NLR and PLR were associated with larger tumors, lymph node metastasis, and poorer therapeutic responses to definitive ChRT. By multivariate analysis, pretreatment NLR and lymph node metastasis were found independently predictive of OS and PFS, whereas patients' age was significantly predictive of OS only. In patients with advanced cervical cancer, NLR is a potential biomarker, serving to guide systemic therapy and predict treatment outcomes.
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    Prognostic Value of Metabolic Response Measured by F-18-FDG-PET in Oesophageal Cancer Patients Treated with Definitive Chemoradiotherapy
    (2016) Onal, Cem; Torun, Nese; Guler, Ozan C.; Yildirim, Berna A.; 0000-0002-2742-9021; 0000-0001-6661-4185; 0000-0002-5597-676X; 0000-0001-6908-3412; 27612030; D-5195-2014; V-5717-2017; AAE-2718-2021; AAC-5654-2020
    BackgroundThis study aimed to assess the efficacy of fluorine-18 fluorodeoxyglucose (F-18-FDG)-PET for predicting overall survival (OS) and disease-free survival (DFS) in oesophageal cancer patients after definitive chemoradiotherapy (CRT) and prognostic importance of metabolic response detected by post-treatment PET at least 3 months after completing CRT.Materials and methodsData from 58 oesophageal cancer patients receiving definitive CRT were retrospectively analysed. Post-treatment F-18-FDG-PET was delivered at a median of 3.2 (range, 3.0-6.4) months after CRT. The impact of metabolic response determined by post-treatment F-18-FDG-PET, maximum post-treatment standardized uptake value (SUVmax) and percent SUV change (pretreatment to post-treatment) on survival was analysed.ResultsThe median follow-up was 19.7 (range, 4.2-91.9) months for all patients and 28.2 (range, 13.7-91.9) months for survivors. The mean pretreatment and post-treatment SUVmax and the median percent SUV decrease were 18.66.4, 6.2 +/- 4.6 and -73% (+13 to -100%). Pretreatment SUVmax was higher in patients with locoregional or distant failure than in those without (P<0.001). Pretreatment SUVmax was lower in patients with a complete response (CR) than in those without a CR (P=0.006). Two-year OS and DFS were higher in patients with CR compared with those without CR (P<0.001). CR rates detected by post-treatment F-18-FDG-PET were lower in patients with lymph node metastases or longer tumours than in those with shorter tumours or no metastases. During multivariate analysis, post-treatment SUVmax was a significant predictor for OS, and post-treatment SUVmax, percent SUV decrease and tumour length were significant prognostic factors for DFS.ConclusionMetabolic response assessed by post-treatment F-18-FDG-PET at least 3 months after CRT showed that post-treatment SUVmax and percent SUV change were important survival predictors.
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    Predicting Tumor Recurrence in Patients with Cervical Carcinoma Treated with Definitive Chemoradiotherapy: Value Of Quantitative Histogram Analysis On Diffusion-Weighted MR Images
    (2017) Erbay, Gurcan; Onal, Cem; Karadeli, Elif; Guler, Ozan C.; Arica, Sami; Koc, Zafer; https://orcid.org/0000-0002-1706-8680; https://orcid.org/0000-0002-0352-8818; https://orcid.org/0000-0001-6908-3412; https://orcid.org/0000-0003-0987-1980; 27445314; AAK-5370-2021; HOC-5611-2023; AAK-5399-2021; AAC-5654-2020; S-8384-2016
    Background: Further research is required for evaluating the use of ADC histogram analysis in more advanced stages of cervical cancer treated with definitive chemoradiotherapy (CRT). Purpose: To investigate the utility of apparent diffusion coefficient (ADC) histogram derived from diffusion-weighted magnetic resonance images in cervical cancer patients treated with definitive CRT. Material and Methods: The clinical and radiological data of 50 patients with histologically proven cervical squamous cell carcinoma treated with definitive CRT were retrospectively analyzed. The impact of clinicopathological factors and ADC histogram parameters on prognostic factors and treatment outcomes was assessed. Results: The mean and median ADC values for the cohort were 1.043 +/- 0.135 x 10(-3) mm(2)/s and 1.018 x 10(-3) mm(2)/s (range, 0.787-1.443 x 10(-3) mm(2)/s). The mean ADC was significantly lower for patients with advanced stage (>= IIB) or lymph node metastasis compared with patients with stage < IIB or no lymph node metastasis. The mean ADC, 75th percentile ADC (ADC75), 90th percentile ADC (ADC90), and 95th percentile ADC (ADC95) were significantly lower in patients with tumor recurrence compared with patients without recurrence. In multivariate analysis, tumor size, ADC75 and ADC95 were independent prognostic factors for both overall survival and disease-free survival. Conclusion: ADC histogram parameters could be markers for disease recurrence and for predicting survival outcomes. ADC75, ADC90, and ADC95 of the primary tumor were significant predictors of disease recurrence in cervical cancer patients treated with definitive CRT.
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    Incidence and Impact of Pretreatment Tumor Cavitation on Survival Outcomes of Stage III Squamous Cell Lung Cancer Patients Treated With Radical Concurrent Chemoradiation Therapy
    (2018) Topkan, Erkan; Selek, Ugur; Ozdemir, Yurday; Yildirim, Berna A.; Guler, Ozan C.; Ciner, Fuat; Besen, A. A.; Findikcioglu, Alper; Ozyilkan, Ozgur; https://orcid.org/0000-0001-8120-7123; https://orcid.org/0000-0002-2218-2074; https://orcid.org/0000-0001-6661-4185; https://orcid.org/0000-0001-6908-3412; https://orcid.org/0000-0002-7862-0192; https://orcid.org/0000-0001-8825-4918; 29887509; AAG-2213-2021; AAG-5629-2021; V-5717-2017; AAC-5654-2020; AAD-6910-2021; AFT-2303-2022; AAD-2817-2021
    Purpose: To investigate the incidence and influence of tumor cavitation (TC) on survival outcomes of locally advanced squamous cell lung cancer (LA-SqCLC) patients treated with concurrent chemoradiation therapy (C-CRT). Methods and Materials: Records of 789 stages IIIA/B squamous cell lung cancer (SqCLC) patients treated with C-CRT who received 1 to 3 cycles of platinum-based doublet chemotherapy during 60 to 66 Gy radiation therapy (RT) were analyzed retrospectively. Primary endpoint was the association between overall survival (OS) and pretreatment TC status. Secondary endpoints included locoregional progression-free survival (LRPFS), progression-free survival (PFS), and incidence of TC and correlated factors. Results: Pretreatment TC occurred in 95 patients (12%), being significantly more common in those patients with ever-smoking history (12.6% vs 3.9%; P < .001), weight loss >5% (20.9% vs 7.1%; P < .001), and hemoptysis (27.1% vs 6.4%; P <. 001). Rates of acute and late toxicities were similar in patients who presented with and without TC (P > .05 for each). For the whole cohort, at a median follow-up of 22.9 months (range: 2.4-71.1), the respective median OS, LRPFS, and PFS estimates were 23.7, 14.7, and 10.7 months. In multivariate analysis, stage IIIB disease (P < .001; hazard ratio [HR]: 1.33; 95% CI: 1.21-1.45), weight loss > 5% (P < .001; HR: 2.10; 95% CI: 1.85-2.35), anemia (P < .001; HR: 1.82; 95% CI: 1.67-1.97), and presence of TC (P < .001; HR: 1.54; 95% CI: 1.37-1.71) appeared to be independently associated with poorer OS durations, likewise the LRPFS (P < .001 for each of these covariates), and PFS (P < .001 for each of these covariates), respectively. Conclusions: Present results showed that the TC occurred in 12% of LA-SqCLC patients, which was strongly associated with poorer PFS, LRPFS, and OS outcomes after definitive C-CRT. (C) 2018 Elsevier Inc. All rights reserved.
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    Prognostic Value of The Glasgow Prognostic Score For Glioblastoma Multiforme Patients Treated With Radiotherapy and Temozolomide
    (2018) Topkan, Erkan; Selek, Ugur; Ozdemir, Yurday; Yildirim, Berna A.; Guler, Ozan C.; Ciner, Fuat; Mertsoylu, Huseyin; Tufan, Kadir; https://orcid.org/0000-0001-8120-7123; https://orcid.org/0000-0002-2218-2074; https://orcid.org/0000-0001-6661-4185; https://orcid.org/0000-0001-6908-3412; https://orcid.org/0000-0002-1932-9784; https://orcid.org/0000-0003-1509-4575; 29696530; AAG-2213-2021; AAG-5629-2021; V-5717-2017; AAC-5654-2020; M-9530-2014; AAK-1686-2021
    To evaluate the prognostic value of the Glasgow Prognostic Score (GPS), the combination of C-reactive protein (CRP) and albumin, in glioblastoma multiforme (GBM) patients treated with radiotherapy (RT) and concurrent plus adjuvant temozolomide (GPS). Data of newly diagnosed GBM patients treated with partial brain RT and concurrent and adjuvant TMZ were retrospectively analyzed. The patients were grouped into three according to the GPS criteria: GPS-0: CRP < 10 mg/L and albumin > 35 g/L; GPS-1: CRP < 10 mg/L and albumin < 35 g/L or CRP > 10 mg/L and albumin > 35 g/L; and GPS-2: CRP > 10 mg/L and albumin < 35 g/L. Primary end-point was the association between the GPS groups and the overall survival (OS) outcomes. A total of 142 patients were analyzed (median age: 58 years, 66.2% male). There were 64 (45.1%), 40 (28.2%), and 38 (26.7%) patients in GPS-0, GPS-1, and GPS-2 groups, respectively. At median 15.7 months follow-up, the respective median and 5-year OS rates for the whole cohort were 16.2 months (95% CI 12.7-19.7) and 9.5%. In multivariate analyses GPS grouping emerged independently associated with the median OS (P < 0.001) in addition to the extent of surgery (P = 0.032), Karnofsky performance status (P = 0.009), and the Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) classification (P < 0.001). The GPS grouping and the RTOG RPA classification were found to be strongly correlated in prognostic stratification of GBM patients (correlation coefficient: 0.42; P < 0.001). The GPS appeared to be useful in prognostic stratification of GBM patients into three groups with significantly different survival durations resembling the RTOG RPA classification.
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    Chemoradiotherapy-İnduced Hemoglobin Nadir Values And Survival in Patients With Stage III Non-Small Cell Lung Cancer
    (2018) Topkan, Erkan; Selek, Ugur; Ozdemir, Yurday; Yildirim, Berna A.; Guler, Ozan C.; Mertsoylu, Huseyin; Hahn, Stephen M.; https://orcid.org/0000-0001-8120-7123; https://orcid.org/0000-0002-2218-2074; https://orcid.org/0000-0001-6661-4185; https://orcid.org/0000-0001-6908-3412; https://orcid.org/0000-0002-1932-9784; 29858023; AAG-2213-2021; AAG-5629-2021; V-5717-2017; AAC-5654-2020; M-9530-2014
    Purpose: We investigated the influence of change in hemoglobin (Hgb) levels during concurrent chemoradiotherapy (C-CRT) on outcomes of non-anemic patients with stage IIIA/B non-small cell lung cancer (NSCLC). Methods: We identified 722 patients with stage IIIA/B NSCLC without anemia at baseline [hemoglobin (Hgb) < 12 g/dL for women or < 13 g/dL for men], either nonsmokers or ex-smokers, who received C-CRT between 2007 and 2012. All patients had received 1 - 3 cycles of platinum-based doublet chemotherapy during radiotherapy to 60 - 66 Gy and had documented Hgb measurements before treatment and at weekly intervals for 6 weeks during the C-CRT. Potential associations were assessed between baseline, nadir, extent of change in Hgb level, and anemia and overall survival (OS), locoregional progression-free survival (LRPFS), and PFS. Results: The median baseline Hgb level was 13.9 g/dL (range 12.0-16.8) and declined to a median 12.4 g/dL (range 7.9-16.1) during treatment. Anemia appeared in 237 patients (32.8%) and was more common among women (44.8% vs. 26.5%, P < 0.001). Neither baseline Hgb level nor change during treatment nor anemia emergence influenced any survival endpoint. Receiver operating curve analysis revealed an Hgb nadir of 11.1 g/dL to be associated with outcomes, in that a nadir Hgb < 11.1 g/dL (in 156 patients) was linked with shorter median OS time (P < 0.001), LRPFS time (P < 0.001), and PFS time (P < 0.001); retained significance for all three endpoints in multivariate analyses; and was more strongly associated with OS in squamous cell carcinoma (P < 0.001) than in adenocarcinoma (P = 0.009). Conclusion: Nadir Hgb < 11.1 g/dL levels during C-CRT were associated with significantly poorer survival times in initially non-anemic patients presenting with locally advanced NSCLC.
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    Stereotactic body radiotherapy for oligoprogressive lesions in metastatic castration-resistant prostate cancer patients during abiraterone/enzalutamide treatment
    (2021) Onal, Cem; Kose, Fatih; Ozyigit, Gokhan; Aksoy, Sercan; Oymak, Ezgi; Muallaoglu, Sadik; Guler, Ozan C.; Tilki, Burak; Hurmuz, Pervin; Akyol, Fadil; 0000-0002-2742-9021; 33905131; D-5195-2014
    Background Metastasis-directed therapy (MDT) utilizing stereotactic body radiotherapy (SBRT) for oligoprogressive lesions could provide a delay in next-line systemic treatment (NEST) change while undergoing androgen receptor-targeted agents (ARTA) treatment. We evaluated prognostic factors for prostate cancer-specific survival (PCSS) and progression-free survival (PFS) to characterize patients receiving treatment with ARTA who may benefit from MDT for oligoprogressive lesions. The impact of MDT on delaying NEST and the predictive factors for NEST-free survival (NEST-FS) were also assessed. Materials and Methods The clinical data of 54 metastatic castration-resistant prostate cancer patients with 126 oligoprogressive lesions receiving abiraterone (1 g/day) or enzalutamide (160 mg/day) before or after systemic chemotherapy were analyzed. A median of three lesions (range: 1-5) were treated with MDT. The primary endpoints were PCSS and PFS. The secondary endpoints were time to switch to NEST and NEST-FS. Results The median follow-up time was 19.1 months. Univariate analysis showed that the number of oligoprogressive lesions treated with SBRT and the time between the start of ARTA treatment and oligoprogression were significant prognostic factors for PCSS, and the timing of ARTA treatment (before or after chemotherapy) and the prostate-specific antigen (PSA) response after MDT were significant prognostic factors for PFS. Multivariate analysis showed that early MDT for oligoprogressive lesions delivered less than 6 months after the beginning of ARTA and higher PSA levels after MDT were significant predictors of worse PCSS and PFS. The median total duration of ARTA treatment was 13.8 months. The median time between the start of ARTA treatment and the start of MDT for oligoprogressive lesions was 5.2 months, and MDT extended the ARTA treatment by 8.6 months on average. Thirty-two (59.3%) patients continued ARTA treatment after MDT. ARTA treatment after chemotherapy, early oligoprogression requiring MDT, and lower radiation doses for MDT were independent predictors of NEST-FS in multivariate analysis. Conclusions MDT for oligoprogressive lesions is effective and may provide several benefits compared to switching from ARTA treatment to NEST. Patients with early progression while on ARTAs and inadequate PSA responses after MDT have a greater risk of rapid disease progression and poor survival, which necessitates intensified treatment.