Browsing by Author "Alkan, A"

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    Classification of EEG recordings by using fast independent component analysis and artificial neural network
    Kocyigit, Y; Alkan, A; Erol, H
    Since there is no definite decisive factor evaluated by the experts, visual analysis of EEG signals in time domain may be inadequate. Routine clinical diagnosis requests to analysis of EEG signals. Therefore, a number of automation and computer techniques have been used for this aim. In this study we aim at designing a MLPNN classifier based on the Fast ICA that accurately identifies whether the associated subject is normal or epileptic. By analyzing a data set consisting of 100 normal and 100 epileptic EEG time series, we have found that the MLPNN classifier based on the Fast ICA achieved and sensitivity rate of 98%, and specificity rate of 90.5%. The results demonstrate that the testing performance of the neural network diagnostic system is found to be satisfactory and we think that this system can be used in clinical studies. Since the time series analysis of EEG signals is unsatisfactory and requires specialist clinicians to evaluate, this application brings objectivity to the evaluation of EEG signals.
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    New moving frames for the curves lying on a surface
    Alkan, A; Kocayigit, H; Agirman Aydin, T
    In this article, three new orthogonal frames are defined for the curves lying on a surface. These moving frames, obtained based on the Darboux frame, are called Osculator Darboux Frame, Normal Darboux Frame and Rectifying Darboux Frame, respectively. Also, the Osculator Darboux Frame components and curvatures are calculated for a presented example.
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    A RARE CAUSE OF ISCHEMIC CHEST PAIN: CONGENITAL OSTIAL ATRESIA OF THE RIGHT CORONARY ARTERY
    Tavli, T; Alkan, A; Bayturan, O; Dalgic, O; Utuk, O; Kamali, B; Madak, N
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    TWO-SIDED Γ-α-DERIVATIONS IN PRIME AND SEMIPRIME Γ-NEAR-RINGS
    Kazaz, M; Alkan, A
    We introduce the notion of two-sided Gamma-alpha-derivation of a Gamma-near-ring and give some generalizations of [1, 2].
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    Osculating mate of a Frenet curve in the Euclidean 3-space
    Alkan, A; Önder, M
    A new kind of partner curves called osculating mate of a Frenet curve is introduced. Some characterizations for osculating mate are obtained and using the obtained results some special curves such as slant helix, spherical helix, C-slant helix and rectifying curve are constructed.
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    Effects of boric acid on bone formation after maxillary sinus floor augmentation in rabbits
    Ulu, M; Kütük, N; Cicik, MF; Bilge, S; Akçay, H; Saygili, S; Tuglu, MI; Alkan, A
    PurposeAugmentation of the maxillary sinus floor with bone grafting is commonly used for successful treatment of edentulous posterior maxilla with dental implants, and it is essential to maintain good bone volume and quality for long-term success of dental implants. The aim of this experimental study was to investigate the local and systemic effects of boric acid on new bone formation after maxillary sinus floor augmentation (MSFA).Materials and methodsTwenty-four male, New Zealand rabbits were randomly divided into three groups with eight rabbits each, and bilateral MSFA was performed in each animal. An autogenous bone/xenograft mixture was used to augment the maxillary sinuses in each group. Group 1 was determined as control with no additional materials, whereas 3mg/kg boric acid (BA) was added to the mixture in group 2, and 3mg/kg boric acid solution added to drinking water daily in group 3.ResultsThe animals were sacrificed and also histologic, histomorphometric, and immunnohistochemical analyses were performed at weeks 4 and 8. At week 4, bone regeneration was better in the local BA group than in the control and systemic BA groups (p<0.05). However, no significant difference was found among the groups in terms of bone regeneration at the end of week 8 (p>0.05).ConclusionSignificant higher new bone formation was revealed by BA at early healing especially with local application. BA may be a therapeutic option for improving the bone regeneration.
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    Efficacy of subsequent treatments in patients with hormone-positive advanced breast cancer who had disease progression under CDK 4/6 inhibitor therapy (vol 23, 136, 2023)
    Karacin, C; Oksuzoglu, B; Demirci, A; Keskinkiliç, M; Baytemür, NK; Yilmaz, F; Selvi, O; Erdem, D; Avsar, E; Paksoy, N; Demir, N; Göksu, SS; Türker, S; Bayram, E; Çelebi, A; Yilmaz, H; Kuzu, ÖF; Kahraman, S; Gökmen, I; Sakin, A; Alkan, A; Nayir, E; Ugrakli, M; Acar, Ö; Ertürk, I; Demir, H; Aslan, F; Sönmez, Ö; Korkmaz, T; Celayir, ÖM; Karadag, I; Kayikçioglu, E; Sakalar, T; Öktem, IN; Eren, T; Erul, E; Mocan, EE; Kalkan, Z; Yildirim, N; Ergün, Y; Akagündüz, B; Karakaya, S; Kut, E; Teker, F; Demirel, BÇ; Karaboyun, K; Almuradova, E; Ünal, OÜ; Oyman, A; Isik, D; Okutur, K; Öztosun, B; Gülbagci, BB; Kalender, ME; Sahin, E; Seyyar, M; Özdemir, Ö; Selçukbiricik, F; Kanitez, M; Dede, I; Gümüs, M; Gökmen, E; Yaren, A; Menekse, S; Ebinç, S; Aksoy, S; Imamoglu, GI; Altinbas, M; Çetin, B; Uluç, BO; Er, Ö; Karadurmus, N; Erdogan, AP; Artaç, M; Tanriverdi, Ö; Çiçin, I; Sendur, MAN; Oktay, E; Bayoglu, IV; Paydas, S; Aydiner, A; Salim, DK; Geredeli, Ç; Yavuzsen, T; Dogan, M; Hacibekiroglu, I
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    Efficacy of subsequent treatments in patients with hormone-positive advanced breast cancer who had disease progression under CDK 4/6 inhibitor therapy
    Karacin, C; Oksuzoglu, B; Demirci, A; Keskinkiliç, M; Baytemür, NK; Yilmaz, F; Selvi, O; Erdem, D; Avsar, E; Paksoy, N; Demir, N; Göksu, SS; Türker, S; Bayram, E; Çelebi, A; Yilmaz, H; Kuzu, ÖF; Kahraman, S; Gökmen, I; Sakin, A; Alkan, A; Nayir, E; Ugrakli, M; Acar, Ö; Ertürk, I; Demir, H; Aslan, F; Sönmez, Ö; Korkmaz, T; Celayir, ÖM; Karadag, I; Kayikçioglu, E; Sakalar, T; Öktem, IN; Eren, T; Urul, E; Mocan, EE; Kalkan, Z; Yildirim, N; Ergün, Y; Akagündüz, B; Karakaya, S; Kut, E; Teker, F; Demirel, BÇ; Karaboyun, K; Almuradova, E; Ünal, OÜ; Oyman, A; Isik, D; Okutur, K; Öztosun, B; Gülbagci, BB; Kalender, ME; Sahin, E; Seyyar, M; Özdemir, Ö; Selçukbiricik, F; Kanitez, M; Dede, I; Gümüs, M; Gökmen, E; Yaren, A; Menekse, S; Ebinç, S; Aksoy, S; Imamoglu, GI; Altinbas, M; Çetin, B; Uluç, BO; Er, Ö; Karadurmus, N; Erdogan, AP; Artaç, M; Tanriverdi, Ö; Çiçin, I; Sendur, MAN; Oktay, E; Bayoglu, IV; Paydas, S; Aydiner, A; Salim, DK; Geredeli, Ç; Yavuzsen, T; Dogan, M; Hacibekiroglu, I
    Background There is no standard treatment recommended at category 1 level in international guidelines for subsequent therapy after cyclin-dependent kinase 4/6 inhibitor (CDK4/6) based therapy. We aimed to evaluate which subsequent treatment oncologists prefer in patients with disease progression under CDKi. In addition, we aimed to show the effectiveness of systemic treatments after CDKi and whether there is a survival difference between hormonal treatments (monotherapy vs. mTOR-based). Methods A total of 609 patients from 53 centers were included in the study. Progression-free-survivals (PFS) of subsequent treatments (chemotherapy (CT, n:434) or endocrine therapy (ET, n:175)) after CDKi were calculated. Patients were evaluated in three groups as those who received CDKi in first-line (group A, n:202), second-line (group B, n: 153) and >= 3rd-line (group C, n: 254). PFS was compared according to the use of ET and CT. In addition, ET was compared as monotherapy versus everolimus-based combination therapy. Results The median duration of CDKi in the ET arms of Group A, B, and C was 17.0, 11.0, and 8.5 months in respectively; it was 9.0, 7.0, and 5.0 months in the CT arm. Median PFS after CDKi was 9.5 (5.0-14.0) months in the ET arm of group A, and 5.3 (3.9-6.8) months in the CT arm (p = 0.073). It was 6.7 (5.8-7.7) months in the ET arm of group B, and 5.7 (4.6-6.7) months in the CT arm (p = 0.311). It was 5.3 (2.5-8.0) months in the ET arm of group C and 4.0 (3.5-4.6) months in the CT arm (p = 0.434). Patients who received ET after CDKi were compared as those who received everolimus-based combination therapy versus those who received monotherapy ET: the median PFS in group A, B, and C was 11.0 vs. 5.9 (p = 0.047), 6.7 vs. 5.0 (p = 0.164), 6.7 vs. 3.9 (p = 0.763) months. Conclusion Physicians preferred CT rather than ET in patients with early progression under CDKi. It has been shown that subsequent ET after CDKi can be as effective as CT. It was also observed that better PFS could be achieved with the subsequent everolimus-based treatments after first-line CDKi compared to monotherapy ET.
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    Histological and Biochemical Investigation of the Effects of Low Intensity Pulsed Ultrasound on Orthodontic Tooth Movement
    Cesur, MG; Onal, T; Bilgin, MD; Sirin, FB; Inan, S; Koken, EC; Alkan, A; Cesur, G
    Objective: The goal of our study is to assess the effects of low intensity pulsed ultrasound on orthodontic tooth movement in rats. Methods: For this study, 40 adult male Wistar albino rats (12-weeks old age) were used from the Animal Laboratory at Adnan Menderes University. Rats were divided into four groups each of ten. Group 1 was the untreated as a control. In group 2, an orthodontic spring was used to move teeth. For groups 3 and 4, orthodontic treatment was combined with low intensity pulsed ultrasound at 16 J/cm2 or 48 J/cm2 for 14 days, respectively. Tooth movement was measured at the last day of treatment. Serum bone alkaline phosphatase (BALP) and C-telopeptide type I collagen (CTX-I) levels were analyzed biochemically. The number of osteoclasts, osteoblasts and inflammatory cells, capillary density and new bone formation was determined histologically. Receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin (OPG), vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-beta) were assessed using immunohistochemical staining. Results: BALP and CTX-I levels in group 4 were significantly higher compared to control (p<0.05). Tooth movement and the number of osteoclasts, inflammatory cells and capillary density in group 4 were significantly greater than group 2 (p<0.05). The intensity levels of RANKL and OPG in group 4 were significantly greater than group 2 (p<0.05). Conclusions: Ultrasound is a noninvasive application and promising therapy for accelerating bone remodelling during orthodontic tooth movement.
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    Efficacy of everolimus plus hormonal treatment after cyclin-dependent kinase inhibitor; real-life experience, A TOG study
    Beypinar, I; Demir, H; Yaslikaya, S; Köseci, T; Demir, B; Çolak, G; Agaoglu, AB; Sahbazlar, M; Sanci, PC; Cabuk, D; Isik, U; Sahin, E; Coskun, A; Caner, B; Aykut, T; Artac, M; Duygulu, ME; Sever, N; Öksüz, S; Turan, N; Aykan, MB; Tüzün, EK; Uysal, M; Ugurlu, I; Sakin, A; Acar, C; Özaskin, D; Sakalar, T; Keskinkilic, M; Yavuzsen, T; Köse, N; Ertürk, I; Yildirim, N; Balçik, OY; Alkan, A; Selvi, O; Ercin, E; Ünal, OU; Karaçin, C
    Purpose In advanced breast cancer, endocrine therapy is preferred in the absence of visceral crisis. Cyclin-dependent kinase inhibitors (CDKi) are the gold standards. The selection of subsequent treatments after CDKi treatment is still controversial, and the efficacy of everolimus (EVE) combinations is unknown. In this study, we aimed to investigate the efficacy of EVE after CDKi administration in real-life experiences. Method The study received data from 208 patients from 26 cancer centers. Demographic and histologic features, diagnosis, progression, last visit dates, and toxicities were recorded. This study was a retrospective case series. Results One hundred and seven patients received palbociclib, while 101 patients received ribociclib as a CDKi. The overall response and disease control rates of EVE combinations were 60% and 88%, respectively. In univariate analysis, the absence of liver metastasis, age > 40 years, better type of response, and immediate treatment after CDKi were related to increased progression-free survival. Liver metastasis and response type were significantly associated with overall survival. In the multivariate analysis, response remained significant in terms of progression-free survival, while response type, liver metastatic disease, and hematologic toxicity were prognostic in terms of overall survival. Conclusion This study provides evidence of the benefits of EVE combinations after CDKi treatment. EVE combinations may be more appropriate for patients with non-liver metastasis, and the first treatment response shows the benefit of treatment. In addition, immediate treatment after CDKi treatment is more beneficial than later lines of treatment.
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    Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences
    Tural, D; Ölmez, ÖF; Sümbül, AT; Artaç, M; Özhan, N; Akar, E; Çakar, B; Köstek, O; Ekenel, M; Erman, M; Coskun, HS; Selçukbiricik, F; Keskin, Ö; Türköz, FP; Oruç, K; Bayram, S; Yglmaz, U; Bilgetekin, I; Ygldgz, B; Sendur, MAN; Paksoy, N; Dirican, A; Erdem, D; Selam, M; Tanrgverdi, Ö; Paydas, S; Urakçg, Z; Atag, E; Güncan, S; Ürün, Y; Alkan, A; Kaya, AO; Özyükseler, DT; Taskaynatan, H; Ygldgrgm, M; Sönmez, M; Basoglu, T; Gündüz, S; Kglgçkap, S
    Background: Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies in patients with locally advanced or metastatic platinum resistant urothelial carcinoma. Objective: To compare the real-life experience and data of clinical trials on ATZ treatment in metastatic urothelial carcinoma. Design, setting, and participants: Patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy from an expanded access program were retrospectively studied. Data of patients were obtained from their files and hospital records. Safety was evaluated for patients treated with at least one cycle of ATZ. Outcome measurements and statistical analysis: The primary endpoint was objective response rate (ORR). The secondary endpoints are overall survival (OS), progression-free survival (PFS), duration of response, and safety profile of patients. Kaplan-Meier methods were used to calculate median follow-up and estimate PFS and OS. Results and limitations: Data of 115 enrolled patients were analyzed. Most of the patients (92.3%, n = 106) had received chemotherapy regimen only once prior to ATZ. The median follow-up duration was 23.5 mo. The complete response rate, partial response rate, and ORR were 8.7% (n = 10), 20.0% (n = 23), and 28.7% (n = 33), respectively. The median duration of response was 20.4 mo (95% confidence interval [CI], 6.47-28.8). Of the 33 patients who responded to treatment, 60% (n = 20) had an ongoing response at the time of the analysis. PFS and OS with ATZ were 3.8 mo (95% CI, 2.25-5.49) and 9.8 mo (95% CI, 6.7-12.9), respectively. All-cause and any-grade adverse events were observed in 113 (98%) patients. Of the patients, 64% experienced a treatment-related adverse event of any grade and 24 (21.2%) had a grade 3-4 treatment-related adverse event. Limitations of the study included its retrospective design, and determination of treat-ment response based on clinical notes and local radiographic studies. Conclusions: In these real-life data, ATZ was effective and well tolerated in patients with metastatic urothelial carcinoma who have progressed with platinum-based first-line chemotherapy. ATZ is an effective and tolerable treatment for patients with locally advanced or metastatic platinum-resistant urothelial carcinoma in our study, similar to previously reported trials. Patient summary: Atezolizumab is effective and well-tolerated in patients with meta-static urothelial cancer who progressed with first-line chemotherapy, consistent with the outcomes of the previous clinical trials in this setting. (c) 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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    The prognostic impact of Her2 status in early triple negative breast cancer: a Turkish Oncology Group (TOG) study
    Özyurt, N; Alkan, A; Gülbagci, B; Seyyar, M; Aydin, E; Sahbazlar, M; Türker, M; Kinikoglu, O; Yerlikaya, T; Dinç, G; Aytaç, A; Kalkan, Z; Ebinç, S; Gültürk, I; Keskinkiliç, M; Isleyen, ZS; Çaglayan, D; Türkel, A; Aydin, E; Sakalar, T; Sekmek, S; Yildirim, N; Koçak, S; Okutur, K; Özveren, A; Dursun, B; Kitapli, S; Eren, OÖ; Beypinar, I; Hacibekiroglu, I; Çabuk, D; Karaman, E; Acar, Ö; Paydas, S; Eryilmaz, MK; Demir, B; Oruç, Z; Yilmaz, M; Biricik, FS; Salim, DK; Tanriverdi, Ö; Dogan, M
    The studies evaluating the impact of Her2 levels in neoadjuvant setting have conflicting data. The aim of the study was to evaluate the prognostic impact of Her2 status in early triple negative breast cancer(TNBC). In the study TNBC patients who were treated with neoadjuvant chemotherapy (NAC) and surgery were analyzed retrospectively. The primary aim of the study was to analyze the impact of Her2 status(Her2-0 and Her2-low) on pathological complete response (pCR). The secondary objectives were disease free survival (DFS) and overall survival (OS). 620 female triple negative breast cancer patients were evaluated. 427 patients (68.9%) had Her2-0 and 193(31.1%) had her2-low pathology. The pCR rates were similar between Her2-0 and Her2-low patients (33.0% vs. 27.5%, p = 0.098). Although Her2-0 group has better DFS (106 vs. 50 months, p = 0.002), in multivariate analysis it had a HR of 0.74 (p = 0.06). In addition, OS was similar (131 vs. 105 months, p = 0.13) with a HR of 0.88 (p = 0.61). In multivariate analysis; presence of LVI (HR:2.2 (95% CI 1.1-3.5) p = 0.001), Clinical stage T1/T2 (HR:0.39 (95% CI 0.2-0.6) p < 0.001) and lymph node negativity (HR:0.35 (95% CI 0.1-0.9) p = 0.03) were independent factors for OS. Although there were pathological and clinical differences, the pCR, DFS and OS were similar between Her2-0 and Her2-low TNBC patients. The importance of Her2 status of TNBC in neoadjuvant setting should be further studied.
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    Efficacy of first-line CDK 4-6 inhibitors in premenopausal patients with metastatic breast cancer and the effect of dose reduction due to treatment-related neutropenia on efficacy: a Turkish Oncology Group (TOG) study
    Yildirim, HC; Kapar, C; Koksal, B; Seyyar, M; Sanci, PC; Guliyev, M; Perkin, P; Buyukkor, M; Yaslikaya, S; Majidova, N; Keskinkilic, M; Ozaskin, D; Avci, T; Gunes, TK; Arcagok, M; Topal, A; Keskin, GSY; Kavgaci, G; Yildirim, N; Celayir, OM; Avci, N; Aslan, F; Alkan, A; Erciyestepe, M; Cengiz, M; Pehlivan, M; Gulmez, A; Beypinar, I; Tuylu, TB; Kayikcioglu, E; Chalabiyev, E; Turhal, S; Guzel, HG; Ayas, E; Sahbazlar, M; Dulgar, O; Demir, H; Yavuzsen, T; Bayoglu, V; Salim, DK; Ozturk, B; Ozdemir, F; Kara, O; Oksuzoglu, B; Bal, O; Demirci, NS; Yilmaz, M; Cabuk, D; Aksoy, S
    The only phase 3 study on the effectiveness of CDK 4-6 inhibitors in first-line treatment in premenopausal patients with hormone receptor (HR) positive, HER2 negative metastatic breast cancer is the MONALEESA-7 study, and data on the effectiveness of palbociclib is limited. Data are also limited regarding the effectiveness of CDK 4-6 inhibitors in patients whose dose was reduced due to neutropenia, the most common side effect of CDK 4-6 inhibitors. In our study, we aimed to evaluate the effectiveness of palbociclib and ribociclib in first-line treatment in patients with premenopausal metastatic breast cancer and the effect of dose reduction due to neutropenia on progression-free survival. Our study is a multicenter, retrospective study, and factors affecting progression-free survival (PFS) were examined in patients diagnosed with metastatic premenopausal breast cancer from 29 different centers and receiving combination therapy containing palbociclib or ribociclib in the metastatic stage. 319 patients were included in the study. The mPFS for patients treated with palbociclib was 26.83 months, and for those receiving ribociclib, the mPFS was 29.86 months (p = 0.924). mPFS was 32.00 months in patients who received a reduced dose, and mPFS was 25.96 months in patients who could take the initial dose, and there was no statistical difference (p = 0.238). Liver metastasis, using a fulvestrant together with a CDK 4-6 inhibitor, ECOG PS 1 was found to be a negative prognostic factor. No new adverse events were observed. In our study, we found PFS over 27 months in patients diagnosed with premenopausal breast cancer with CDK 4-6 inhibitors used in first-line treatment, similar to post-menopausal patients. We did not detect any difference between the effectiveness of the two CDK 4-6 inhibitors, and we showed that there was no decrease in the effectiveness of the CDK 4-6 inhibitor in patients whose dose was reduced due to neutropenia.
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    Prognostic factors in patients with metastatic urothelial carcinoma who have treated with Atezolizumab
    Tural, D; Ölmez, ÖF; Sümbül, AT; Özhan, N; Çakar, B; Köstek, O; Ekenel, M; Erman, M; Coskun, HS; Selçukbiricik, F; Keskin, Ö; Türköz, FP; Oruç, K; Bayram, S; Bilgetekin, I; Yildiz, B; Sendur, MAN; Paksoy, N; Dirican, A; Erdem, D; Selam, M; Tanriverdi, Ö; Paydas, S; Urakçi, Z; Atag, E; Güncan, S; Ürün, Y; Alkan, A; Kaya, AO; Özyükseler, DT; Taskaynatan, H; Yildirim, M; Sönmez, M; Basoglu, T; Gündüz, S; Kiliçkap, S; Artaç, M
    Background Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies of patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of Atezolizumab was modest. In the current study, we evaluated the pretreatment prognostic factors for overall survival in patients with metastatic urothelial carcinoma who have progressed after first-line chemotherapy in the Expanded-Access Program of Atezolizumab. Patients and methods In this study, we present a retrospective analysis of 113 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of the patients was obtained from patient files and hospital records. Eligible patients included metastatic urothelial carcinoma patients treated with at least one course of ATZ. Univariate analysis was used to identify clinical and laboratory factors that significantly impact OS. Variables were retained for multivariate analysis if they had a statistical relationship with OS (p < 0.1), and then included a final model of p < 0.05. Results The median follow-up duration was 23.5 months. Of the patients, 98 (86.7%) were male and 13.3% were female. The median age was 65 years of age (37-86). In univariate analysis, primary tumor location in the upper tract, increasing absolute neutrophil count (ANC), increasing absolute lymphocyte count, neutrophil-to-lymphocyte ratio (NLR) > 3, liver metastases, baseline creatinine clearance less (GFR) than 60 ml/min, Eastern Cooperative Oncology Group (ECOG) performance status (1 >=), and hemoglobin levels below 10 mg/dl were all the significantly associated with OS. Three of the five adverse prognostic factors according to the Bellmunt criteria were independent of short survival: liver metastases HR 3.105; 95% CI 1.673-5.761; p < (0.001), ECOG PS (1 >=) HR 2.184; 95% CI 1.120-4.256; p = 0.022, and Hemoglobin level below 10 mg/dl HR 2.680; 95% CI 1.558-4.608; p < (0.001). In addition, NLR > 3 hazard ratio [HR] 2.092; 95% CI 1.031-4.243; p = 0.041 and GFR less than 60 ml/min HR 1.829; 95% CI 1.1-3.041; p = 0.02, maintained a significant association with OS in multivariate analysis. Conclusions This model confirms the Bellmunt model with the addition of NLR > 3 and GFR less than 60 ml/min and can be associated with clinical trials that use immunotherapy in patients with bladder cancer.