Observational Study Evaluating The Efficacy And Effects On Quality Of Life Of Targeted Treatments Following TKIs In mRCC

Completed

Conditions: Renal Cell Carcinoma

Registration Number: NCT02315755

Lead Sponsor: Pfizer

Brief Summary: Metastatic renal cell carcinoma (mRCC) is the most common malignant tumour of the kidneys. Targeted therapies, which were recently introduced in the treatment of mRCC, have become the standard treatment in these patients. With improved survival rate and a tolerable side effect profile, Tyrosine Kinase Inhibitors (TKIs) have largely replaced conventional immunotherapies worldwide.

In Turkey, due to reimbursement conditions, cytokine (interferon alpha) treatment is the standard treatment as first-line therapy.

Therefore, the data on quality of life (QoL) from the pivotal studies with standard TKI treatment does not reflect the QoL status of patients treated with TKIs as second or third line treatment in Turkey. In this study, the clinical outcomes and the impact on quality of life of targeted treatments following TKIs will be explored. To our knowledge, since there is no similar reimbursement condition in the world placing IFN as the first line standard treatment, this will be the first study evaluating the QoL status with targeted therapies used as 3rd line treatment in mRCC patients.

Detailed Description: Background:

Metastatic renal cell carcinoma (mRCC) is the most common malignant tumour of the kidneys. Targeted therapies, which were recently introduced in the treatment of mRCC, have become the standard treatment in these patients \[1\]. With improved survival rate and a tolerable side effect profile, Tyrosine Kinase Inhibitors (TKIs) have largely replaced conventional immunotherapies worldwide. \[2-3\] In Turkey, due to reimbursement conditions defined by the authority, cytokine (interferon alpha) treatment is the standard treatment as first-line therapy \[4\].

Rationale:

TKI therapy is used after interferon alpha in Turkey due to current reimbursement status. Therefore, the data on quality of life (QoL) from the pivotal studies with standard TKI treatment does not reflect the QoL status of patients treated with TKIs as second or third line treatment in Turkey. In this study, the clinical outcomes and the impact on quality of life of targeted treatments following TKIs will be explored. To our knowledge, since there is no similar reimbursement condition in the world placing IFN as the first line standard treatment, this will be the first study evaluating the QoL status with targeted therapies used as 3rd line treatment in mRCC patients.

Research Question and Objectives

Research Question:

There is no data available in the literature explaining the effect of targeted therapies used as 3rd line treatment following IFN and TKIs in metastatic renal cell carcinoma patients. Therefore, it is essential to understand health-related quality of life and efficacy of targeted therapies used as 3rd line treatment due to current reimbursement conditions in Turkey.

Primary Objective:

* Measurement of health-related quality of life with targeted therapy used as 3rd line treatment

* Overall response rate at the end of follow up

* Median progression free survival according to RECIST version 1.1

Secondary Objectives:

* Overall survival rate

* Effect of quality of life on prognosis.

* Adverse events during 3rd line targeted treatment according to CTCAE.4.03

* Dose modifications due to adverse events

* Correlation between efficacy (overall response rate at month 12 and median PFS) and dose modifications due to adverse events

* Correlation between efficacy (overall response rate at month 12 and median PFS) and blood pressure Study Design: This is a multi-center, national, non-interventional/observational study. It has been defined according to the NUTS (Nomenclature of Territorial Units for Statistics: Nomenclature d'unites Territoriales Statistiques, French) criteria, which is a regional classification, created in order to reduce interregional disparities in socio-economic analysis of the regions, and to produce data comparable to that of the European Union (EU). Turkey has been divided into 12 NUTS regions depending on the economic, social, cultural, and geographical aspects, and the population size. In this study, patients with metastatic renal cell carcinoma from centers in 12 NUTS regions of Turkey will be included, who meet the inclusion criteria. In this study, approximately 152 patients planned to be recruited in 12 months and followed-up for 12 months. Additionally, every patient will be followed-up once for survival follow-up in order to assess the overall survival before the site close out visit. Survival follow-up will be performed via telephone visit or site visit if exist.

Study Population:

Metastatic renal cell carcinoma patients under 3rd line targeted therapy following 1st line interferon alpha and 2nd line TKI. All patients will be ≥ 18 years old and have signed the informed consent document.

Variables:

Age, gender, height, weight, and vital signs such as blood pressure Socio-demographic characteristics ECOG performance status Concomitant diseases and medication Medical history Histopathological findings Type of the surgical procedure Treatment history and current treatment information Metastatic features MSKCC risk factors Laboratory findings The quality of life questionnaire (FKSI-15, EQ5D-3L, FKSI-DRS) on each visit. Blood pressure diary Other treatment during follow-up, if any, the dose and the duration Side effects (treatment of the side effects, interruption of the treatment, dose reduction, dose-elevation) PFS, OS and ORR evaluation during 3rd, 6th, 9th and 12th months performed according to RECIST version 1.1, additionally, every patient will be followed-up once for survival follow-up in order to assess the overall survival before the site close out visit. Survival follow-up will be performed via telephone visit or site visit if exist.

ORR: The best overall response is the best response recorded from the start of the study treatment until the end of treatment taking into account any requirement for confirmation. The patient's best overall response assignment will depend on the findings of both target and non-target disease and will also take into consideration the appearance of new lesions. Furthermore, depending on the nature of the study and the protocol requirements, it may also require confirmatory measurement.

PFS: The length of time during and after the treatment of a disease, that a patient lives with the disease but it does not get worse. In a clinical trial, measuring the progression-free survival is one way to see how well a new treatment works.

OS: 1 year Overall Survival (OS), defined as the time from the start of 3rd line treatment until death or 1 year due to any cause (measured at the end of follow-up).

Data Sources: The source of the data will be the electronic or the written patient records of the participating centers. The patient's data can be accessed through a patient file. In the centers, both systems can be used in conjunction. The data can be accessed using both systems.

Sample Size: This is a multi-center, national, non-interventional/observational study. In this study, patients with metastatic renal cell carcinoma who meet the inclusion criteria will be included from centers in 12 NUTS regions of Turkey. Since this is a non-interventional observational study, there is no specific follow-up protocol. In this study, approximately 152 patients will be evaluated.

According to Turkish Statistical Institute data at the end of 2013 population of Turkey is approximately 80 million \[5\]. In the project of Turkey Association of Cancer Research Control which was named Cancer Record and Incidence shows that cancer incidence is 100-150 in 100.000 \[6\] and 2% of all new cancers are renal cell carcinoma \[7\]. There would be 1800 new RCC patients in 1 year, and according to the OS of the disease, there would be 4000 RCC patients in Turkey. 15% of these are metastatic at the time of diagnosis and 30-40% of these are metastatic after a period of a time \[8\]. Presuming that there are 1800 patients with metastatic renal carcinoma in Turkey, the minimum sample size with 7,6 confidence interval, 95% confidence level and 80% power was calculated as 152.

Data Analysis:

Statistical analyses will be primarily of explorative and descriptive nature. Patients who received at least one dose of 3rd line therapy and have sufficient information whether they had an adverse event or not will be valid for safety analysis. Patients who received at least one dose of 3rd line therapy and have any information regarding efficacy of therapy will be valid for intent-to-treat efficacy analysis.

Demographic data, baseline characteristics, diagnosis and prior treatment of RCC, concomitant diseases, and concomitant medication will be described with summary statistics such as mean, SD, minimum, 1, 5, 25, 75, 95, 99 percent quartiles, median, maximum for continuous variables, and category counts and frequencies (percentages) for categorical variables. Concomitant diseases on the case report form correspond to MedDRA terms. Concomitant medication will be coded using WHO's drug dictionary.

Descriptive summaries of Kaplan-Meier (KM) estimates (including number of failed, number censored, 25th and 75th percentiles with respective 95% confidence level and median with 95%Confidence level) and KM curves will be presented for time-to-event efficacy variables (PFS, TTP, time to treatment failure). Mean, SD, minimum, 1, 5, 25, 75, 95, 99 percent quartiles, median, maximum will be produced for duration of treatment. Category counts and frequencies (percentages) will be calculated for tumor status at different visits and general subjective rating of efficacy of 3rd line therapy from the treating physician.

Adverse events will be summarized using the CTCAE.4.03 coding system. Event rates for single adverse events will be calculated based on the total number of patients valid for safety. Adverse events will be categorized according to relation, seriousness, CTCAE grade (version 4.03), and discontinuation of therapy, action taken and outcome. Special attention will be paid to serious adverse events and unexpected or unlisted ADRs.

Category counts and frequencies (percentages) will be calculated for overall tolerability.

Since the enrollment is after the initiation of the treatment, some information will be collected and analyzed retrospectively.

The best overall response is the best response recorded from the start of the study treatment until the end of treatment taking into account any requirement for confirmation.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 102

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: OBSERVATIONAL

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Overall Objective Response	Baseline until the maximum of 33 months	Overall objective response was defined as the percentage of participants with best confirmed response (partial response \[PR\], stable disease \[SD\] or progressive disease \[PD\]) recorded from the start of the study treatment until the end of treatment as assessed by RECIST version 1.1. PR defined as a 30% or more decrease in the sum of longest dimensions of the target lesions, taking as reference the baseline sum of longest dimensions. PD defined as at least a 20% increase in the sum of longest dimensions of target lesions, reference to the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of one or more new lesions or increase of at least 5 mm in addition to the relative increase of 20%. SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference to the smallest sum diameters while on study.
Progression Free Survival (PFS)	From the start of disease treatment until disease progression or death due to any cause (up to a maximum of 33 months)	PFS was defined as the time duration (in months) during and after the treatment of disease that a participant lived with the disease but it did not get worse or progressed. Progressive disease as per response evaluation criteria in solid tumors (RECIST) version 1.1 defined as at least a 20 percent (%) increase in the sum of longest dimensions of target lesions, reference to the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of one or more new lesions or increase of at least 5 millimeter (mm) in addition to the relative increase of 20%.
Change From Baseline in EQ5D-3L Score at Month 6	Baseline (Day 1 of Month 1), Month 6	EQ-5D-3L, a health profile questionnaire was used to assess quality of life along 5 dimensions. Participants rated 5 aspects of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The summed score ranged from 1-15 with "1" corresponding to no problems and "15" corresponding to severe problems in the 5 dimensions, where higher score indicates more severe problems.
Change From Baseline in EQ5D-3L Score at Last Follow-up	Baseline (Day 1 of Month 1), last follow up visit (up to 33 months)	EQ-5D-3L, a health profile questionnaire was used to assess quality of life along 5 dimensions. Participants rated 5 aspects of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The summed score ranged from 1-15 with "1" corresponding to no problems and "15" corresponding to severe problems in the 5 dimensions, where higher score indicates more severe problems.
Change From Baseline in EQ5D-3L Scores at Month 3	Baseline (Day 1 of Month 1), Month 3	EQ-5D-3L, a health profile questionnaire was used to assess quality of life along 5 dimensions. Participants rated 5 aspects of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The summed score ranged from 1-15 with "1" corresponding to no problems and "15" corresponding to severe problems in the 5 dimensions, where higher score indicates more severe problems.
Change From Baseline in FKSI-DRS Score at Month 9	Baseline (Day 1 of Month 1), Month 9	FKSI-DRS was used to assess quality of life in participants and consisted of 9 items (lack of energy, pain, losing weight, bone pain, fatigue, short of breath, coughing, bothered by fevers, and hematuria). Each of the 9 items was answered on a 5-point Likert scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI-DRS score = sum of the 9 item scores; total range: 0 - 36; 0 (no symptom) to 36 (very much); higher score indicated greater presence of symptom.
Change From Baseline in FKSI-DRS Score at Last Follow-up	Baseline (Day 1 of Month 1), last follow up visit (up to 33 months)	FKSI-DRS was used to assess quality of life in participants and consisted of 9 items (lack of energy, pain, losing weight, bone pain, fatigue, short of breath, coughing, bothered by fevers, and hematuria). Each of the 9 items was answered on a 5-point Likert scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI-DRS score = sum of the 9 item scores; total range: 0 - 36; 0 (no symptom) to 36 (very much); higher score indicated greater presence of symptom.
Functional Assessment of Cancer Therapy Kidney Symptom Index - 15 (FKSI-15) Score at Baseline	Baseline (Day 1 of Month 1)	FKSI was used to assess quality of life (QoL) of the participants and consisted of 15 items (lack of energy, side effects, pain, losing weight, bone pain, fatigue, enjoying life, short of breath, worsened condition, appetite, coughing, bothered by fevers, ability to work, hematuria and sleep). Each of the 15 items was answered on a 5-point Likert scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI score = sum of the 15 item scores; total range: 0 - 60; 0 (no symptoms) to 60 (very much); higher score indicated greater presence of symptoms/worse quality of life.
Change From Baseline in FKSI-15 Score at Month 6	Baseline (Day 1 of Month 1), Month 6	FKSI was used to assess quality of life (QoL) of the participants and consisted of 15 items (lack of energy, side effects, pain, losing weight, bone pain, fatigue, enjoying life, short of breath, worsened condition, appetite, coughing, bothered by fevers, ability to work, hematuria and sleep). Each of the 15 items was answered on a 5-point Likert scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI score = sum of the 15 item scores; total range: 0 - 60; 0 (no symptoms) to 60 (very much); higher score indicated greater presence of symptoms/worse quality of life.
Change From Baseline in FKSI-15 Score at Month 9	Baseline (Day 1 of Month 1), Month 9	FKSI was used to assess quality of life (QoL) of the participants and consisted of 15 items (lack of energy, side effects, pain, losing weight, bone pain, fatigue, enjoying life, short of breath, worsened condition, appetite, coughing, bothered by fevers, ability to work, hematuria and sleep). Each of the 15 items was answered on a 5-point Likert scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI score = sum of the 15 item scores; total range: 0 - 60; 0 (no symptoms) to 60 (very much); higher score indicated greater presence of symptoms/worse quality of life.
Change From Baseline in FKSI-15 Score at Last Follow-up	Baseline (Day 1 of Month 1), last follow-up visit (up to 33 months)	FKSI was used to assess quality of life (QoL) of the participants and consisted of 15 items (lack of energy, side effects, pain, losing weight, bone pain, fatigue, enjoying life, short of breath, worsened condition, appetite, coughing, bothered by fevers, ability to work, hematuria and sleep). Each of the 15 items was answered on a 5-point Likert scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI score = sum of the 15 item scores; total range: 0 - 60; 0 (no symptoms) to 60 (very much); higher score indicated greater presence of symptoms/worse quality of life.
EuroQol-5 Dimension-3 Level (EQ5D-3L) Scores at Baseline	Baseline (Day 1 of Month 1)	EQ-5D-3L, a health profile questionnaire was used to assess quality of life along 5 dimensions. Participants rated 5 aspects of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The mean of the summed score ranged from 1 to 3 with "1" corresponding to no problems and "3" corresponding to severe problems in the 5 dimensions, where higher score indicates more severe problems. Total index EQ-5D-3L summary score is weighted with a range of -0.594 (worst) to 1.0 (best).
Functional Assessment of Cancer Therapy Kidney Symptom Index-Disease-Related Symptoms (FKSI-DRS) Score at Baseline	Baseline (Day 1 of Month 1)	FKSI-DRS was used to assess quality of life in participants and consisted of 9 items (lack of energy, pain, losing weight, bone pain, fatigue, short of breath, coughing, bothered by fevers, and hematuria). Each of the 9 items was answered on a 5-point Likert scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI-DRS score = sum of the 9 item scores; total range: 0 - 36; 0 (no symptom) to 36 (very much); higher score indicated greater presence of symptom.
Change From Baseline in FKSI-DRS Score at Month 3	Baseline (Day 1 of Month 1), Month 3	FKSI-DRS was used to assess quality of life in participants and consisted of 9 items (lack of energy, pain, losing weight, bone pain, fatigue, short of breath, coughing, bothered by fevers, and hematuria). Each of the 9 items was answered on a 5-point Likert scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI-DRS score = sum of the 9 item scores; total range: 0 - 36; 0 (no symptom) to 36 (very much); higher score indicated greater presence of symptom.
Change From Baseline in FKSI-DRS Score at Month 6	Baseline (Day 1 of Month 1), Month 6	FKSI-DRS was used to assess quality of life in participants and consisted of 9 items (lack of energy, pain, losing weight, bone pain, fatigue, short of breath, coughing, bothered by fevers, and hematuria). Each of the 9 items was answered on a 5-point Likert scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI-DRS score = sum of the 9 item scores; total range: 0 - 36; 0 (no symptom) to 36 (very much); higher score indicated greater presence of symptom.
Change From Baseline in FKSI-15 Score at Month 3	Baseline (Day 1 of Month 1), Month 3	FKSI was used to assess QoL of the participants and consisted of 15 items (lack of energy, side effects, pain, losing weight, bone pain, fatigue, enjoying life, short of breath, worsened condition, appetite, coughing, bothered by fevers, ability to work, hematuria and sleep). Each of the 15 items was answered on a 5-point Likert scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI score = sum of the 15 item scores; total range: 0 - 60; 0 (no symptoms) to 60 (very much); higher score indicated greater presence of symptoms/worse quality of life.
Change From Baseline in EQ5D-3L Score at Month 9	Baseline (Day 1 of Month 1), Month 9	EQ-5D-3L, a health profile questionnaire was used to assess quality of life along 5 dimensions. Participants rated 5 aspects of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The summed score ranged from 1-15 with "1" corresponding to no problems and "15" corresponding to severe problems in the 5 dimensions, where higher score indicates more severe problems.

Secondary Outcome Measures

Name	Time	Method
Overall Survival at Year 1: Percentage of Participants Who Survived at Year 1	Baseline until death due to any cause (up to 1 year)	Overall survival at Year 1 (Month 12) was defined as the time from the start of 3rd line treatment until death or 1 year due to any cause (measured at the end of 12 month follow-up/observation period). Percentage of participants who survived at the completion of 1 year (12 months) period were reported in this outcome measure.
Number of Participants With Grade 3 or Higher Severe Adverse Events (AEs) Based on NCI CTCAE Version 4.03	Baseline up to 12 months	An AE was any untoward medical occurrence in a participant who received disease treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant and jeopardized the participants or required treatment to prevent other AE outcomes for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs were graded according to the National Cancer Institute- Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 and coded using the Medical Dictionary for Regulatory Activities (MedDRA) as Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe, Grade 4: Life threatening, Grade 5: Death related to AE. AEs included both SAEs and non-SAEs.
Overall Survival	From the start of 3rd line treatment until death due to any cause (up to a maximum of 33 months)	Overall survival was defined as the time from the start of 3rd line treatment until date of death due to any cause.
Number of Participants With Dose Modifications of Third-Line Treatment Due to Adverse Events	Baseline up to Month 3, 6, 9 and 12	Number of participants that required dose modifications of third line treatment due to AEs were reported in this outcome measure. Dose modification was categorized as escalation (increase in dose), delay or interruptions (change in dose time or skipping any dose), reduction (decrease in dose).
Correlation Coefficient Between Efficacy and Dose Modifications Due to AEs	Baseline up to Month 12 follow-up visit
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Baseline up to 12 months	An AE was any untoward medical occurrence in a participant who received disease treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant and jeopardized the participants or required treatment to prevent other AE outcomes for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment emergent AEs were events which occurred between start of disease treatment and up to Month 12 follow-up visit, that were absent before treatment or that worsened relative to pre-treatment state. AEs included both non-SAE and SAEs.
Time to Treatment Failure	Baseline until disease progression or discontinuation, due to any cause (up to 33 months)	Time to treatment failure was defined as the time from the start of treatment to the date of disease progression or date of permanent discontinuation. PD as per RECIST version 1.1 was defined as at least a 20% increase in the sum of longest dimensions of target lesions, reference to the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of one or more new lesions or increase of at least 5 mm in addition to the relative increase of 20%.
Number of Participants With Treatment-Emergent Adverse Events (AEs) During Third Line Targeted Treatment	Baseline up to 12 months	An AE was any untoward medical occurrence in a participant who received disease treatment without regard to possibility of causal relationship. Treatment emergent AEs during third line targeted treatment were events which occurred between first dose of third line targeted treatment and up to Month 12 follow-up visit, that were absent before treatment or that worsened relative to pre-treatment state.
Correlation Coefficient Between Efficacy and High Blood Pressure (>150 / 90 Millimeter of Mercury )	Baseline up to Month 12 follow-up visit

Trial Locations

Locations (19): Gazi University
🇹🇷
Ankara, Besevler, Turkey
Trakya Universitesi Tip Fakultesi Ic Hastaliklari Anabilim Dali Tibbi Onkoloji Bilim Dal
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Edirne, Turkey
Abdurrahman Yurtaslan Onkoloji Hastanesi
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Ankara, Demetevler, Turkey
Ankara Numune Egitim Arastirma Hastanesi
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Ankara, Turkey
Ali Osman Sonmez Onkoloji Hastanesi
🇹🇷
Bursa, Turkey
Dr Lufti Kirdar Kartal Egitim ve Arastirma Hastanesi
🇹🇷
Kartal, Turkey
Ege Universitesi Tip Fakultesi
🇹🇷
Bornova/Izmir, Turkey
Dicle Universitesi Tip Fakultesi
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Diyarbakir, Turkey
Bezmialem Vakif Universitesi Tip Fakultesi Hastanesi
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Istanbul, Turkey
Marmara Üniversitesi Pendik Eğtim Araştırma Hastanesi
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Pendik, İ̇stanbul, Turkey
Hacettepe University School of Medicine, Department of Medical Oncology
🇹🇷
Ankara, Turkey
Istanbul Universitesi Istanbul Tip Fakultesi Onkoloji Enstitusu
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Istanbul, Turkey
Dokuz Eylul Universitesi Tip Fakultesi
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Izmir, Turkey
Karadeniz Teknik Universitesi Tip Fakultesi Tibbi Onkoloji Bilim Dali
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Trabzon, Turkey
Izmir Katip Celebi Universitesi Ataturk Egitim Arastirma Hastanesi Medikal Onkoloji Departmani
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Izmir, Turkey
Inonu Universitesi Tip Fakultesi Medikal Onkoloji Bilim Dali
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Malatya, Turkey
Erciyes Universitesi Tip Fakultesi
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Talas / Kayseri, Turkey
Konya Necmettin Erbakan Universitesi Meram Tip Fakultesi Tibbi Onkoloji Anabilim Dali
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Konya, Turkey
Gaziantep Universitesi Tip Fakultesi
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Sehitkamil/Gaziantep, Turkey