Publications by authors named "Emin Darendeliler"

34 Publications

Treatment outcomes of prostate cancer patients with Gleason score 8-10 treated with definitive radiotherapy : TROD 09-001 multi-institutional study.

Strahlenther Onkol 2019 Oct 29;195(10):882-893. Epub 2019 May 29.

Department of Radiation Oncology, Hacettepe University, Faculty of Medicine, 06100, Ankara, Turkey.

Purpose: To validate the clinical outcomes and prognostic factors in prostate cancer (PCa) patients with Gleason score (GS) 8-10 disease treated with external beam radiotherapy (EBRT) + androgen deprivation therapy (ADT) in the modern era.

Methods: Institutional databases of biopsy proven 641 patients with GS 8-10 PCa treated between 2000 and 2015 were collected from 11 institutions. In this multi-institutional Turkish Radiation Oncology Group study, a standard database sheet was sent to each institution for patient enrollment. The inclusion criteria were, T1-T3N0M0 disease according to AJCC (American Joint Committee on Cancer) 2010 Staging System, no prior diagnosis of malignancy, at least 70 Gy total irradiation dose to prostate ± seminal vesicles delivered with either three-dimensional conformal RT or intensity-modulated RT and patients receiving ADT.

Results: The median follow-up time was 5.9 years (range 0.4-18.2 years); 5‑year overall survival (OS), biochemical relapse-free survival (BRFS) and distant metastases-free survival (DMFS) rates were 88%, 78%, and 79%, respectively. Higher RT doses (≥78 Gy) and longer ADT duration (≥2 years) were significant predictors for improved DMFS, whereas advanced stage was a negative prognosticator for DMFS in patients with GS 9-10.

Conclusions: Our results validated the fact that oncologic outcomes after radical EBRT significantly differ in men with GS 8 versus those with GS 9-10 prostate cancer. We found that EBRT dose was important predictive factor regardless of ADT period. Patients receiving 'non-optimal treatment' (RT doses <78 Gy and ADT period <2 years) had the worst treatment outcomes.
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http://dx.doi.org/10.1007/s00066-019-01476-zDOI Listing
October 2019

RE: Osteosarcoma of the rib: a rare presentation.

Turk Pediatri Ars 2018 Dec 1;53(4):270. Epub 2018 Dec 1.

Istanbul University, Oncology Institute, Department of Radiation Oncology, Istanbul, Turkey.

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http://dx.doi.org/10.5152/TurkPediatriArs.2016.48048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408185PMC
December 2018

Nimotuzumab-containing regimen for pediatric diffuse intrinsic pontine gliomas: a retrospective multicenter study and review of the literature.

Childs Nerv Syst 2019 01 11;35(1):83-89. Epub 2018 Nov 11.

Oncology Institute, Istanbul University, Istanbul, Turkey.

Purpose: Nimotuzumab is an IgG1 antibody that targets epidermal growth factor receptor (EGFR). Overexpression of EGFR is detected in some pediatric brain tumors including diffuse intrinsic pontine gliomas (DIPG)s.

Methods: Since May 2010, nimotuzumab, combined with carboplatin or vinorelbine or Temozolomide (TMZ), was administered during progressive disease (PD) after the use of the institutional protocol consisting of radiotherapy (RT) + TMZ and adjuvant TMZ. After May 2012, children with newly diagnosed disease received TMZ during RT, and nimotuzumab and TMZ after RT. Nimotuzumab was given as 150 mg/m/dose once a week for 12 weeks, and then every other week with TMZ until PD. PD patients were switched to nimotuzumab + vinorelbine combination until death.

Results: Nimotuzumab was used in 24 children with DIPG (seven in the PD group, 17 in the newly diagnosed patient group). In the PD group, median survival time was 12 months (7-42 months); 1-year and 2-year overall survival (OS) rates were 42.9 ± 18% and 14.3 ± 13%, respectively. The median survival in this group, after the initiation of nimotuzumab was 6 months (3-8 months). In the newly diagnosed patient group, median survival time was 11 months (3-35 months) and median progression free survival was 4 months (1-21 months). The 1-year OS in this group was 35.3 ± 11% and 2 year OS was 11.8 ± 7%. Nimotuzumab ± chemotherapy was well tolerated with no major adverse effect.

Conclusion: Nimotuzumab-containing regimens are feasible and tolerable; it might be that some patients either with newly diagnosed DIPG or with progressive disease may benefit modestly from nimotuzumab-containing combinations.
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http://dx.doi.org/10.1007/s00381-018-4001-9DOI Listing
January 2019

Primary Rhabdomyosarcoma of the Breast: Imaging Findings and Literature Review.

Breast Care (Basel) 2018 Aug 22;13(4):293-297. Epub 2018 May 22.

Pediatric Radiology Division, Radiology Department, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.

Background: Primary breast rhabdomyosarcoma (RMS) can occur in children. There is a lack of knowledge regarding radiologic findings and added diffusion-weighted magnetic resonance imaging (MRI) features of RMS in the literature.

Case Report: A 12-year-old girl was diagnosed with primary alveolar RMS of the breast. Gray scale ultrasound revealed posterior acoustic enhancement behind a well-circumscribed, multilobulated hypoechoic mass. Doppler ultrasound revealed increased peripheral and central vascularity. Hypointense septations on T2-weighted image exhibiting more enhancement than the stroma on late gadolinium-enhanced images were striking within a hyperintense mass. A hyperintense hemorrhagic focus on T1-weighted image was present in the absence of any necrosis. Avid enhancement on early postcontrast images proceeding from the periphery to the center was depicted.

Conclusion: A rapidly enlarging mass with an echogenic peripheral rim together with posterior acoustic enhancement on gray scale ultrasound, intense vascularity on Doppler ultrasound, axillary lymphadenopathy, and satellite nodules on MRI should raise suspicion. Enhancing central and peripheral septations are suggestive of RMS. Dynamic contrast-enhanced MRI in suspected cases can provide valuable data in the differential diagnosis.
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http://dx.doi.org/10.1159/000487750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167649PMC
August 2018

Osteosarcoma of the rib: A rare presentation.

Turk Pediatri Ars 2018 Mar 1;53(1):57-60. Epub 2018 Mar 1.

Istanbul University, Oncology Institute, Department of Radiation Oncology, Istanbul, Turkey.

In children and adolescents with chest pain and dyspnea, pneumonia, pleural effusion, and empyema are the frequent causes in the differential diagnosis. Malignant tumors of the chest wall are rare and most originate from the ribs. In children, the most frequent malignant tumor of the rib is Ewing's sarcoma. Osteosarcomas of the rib are very rare. Osteosarcoma has a predilection for rapidly growing long bones including the femur, tibia and humerus in adolescents. In this paper, we present an adolescent girl who presented with chest pain and dyspnea with osteosarcoma that originated from the rib and extended to the right hemithorax.
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http://dx.doi.org/10.5152/TurkPediatriArs.2018.4689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070218PMC
March 2018

Vincristine, irinotecan, and temozolomide treatment for refractory/relapsed pediatric solid tumors: A single center experience.

J Oncol Pharm Pract 2019 Sep 6;25(6):1343-1348. Epub 2018 Aug 6.

4 Division of Pediatric Hematology-Oncology, Department of Pediatrics, Bezmialem Vakif University, Istanbul, Turkey.

Background: Although the survival of pediatric cancer has increased dramatically in the last decades, the survival of refractory, relapsed, and metastatic cases is still dismal. The combination of irinotecan and temozolomide has shown activity against refractory/relapsed pediatric solid tumors.

Method: Thirty-four children with refractory/relapsed solid tumors who had previously been heavily pretreated and who were given vincristine, irinotecan, and temozolomide as third- or further line chemotherapy during 2004-2015 were evaluated.

Results: Patients were diagnosed with Ewing sarcoma (n = 15), rhabdomyosarcoma (n = 8), neuroblastoma (n = 8), osteosarcoma (n = 2), and Wilms' tumor (n = 1). Thirty patients presented with disease progression on therapy and the other four presented with relapsing. A total of 141 cycles were administered. Radiotherapy was used in 17 patients and surgery in 4 as local therapy. Among all patients, 6 had complete response, 3 had partial response, 14 had stable disease, and 11 had progressive disease. The objective response was 26.4% (complete response + partial response) and median survival duration was six months. The first and second year overall survival rates were 22.3% and 16.8%. The objective response in Ewing sarcoma patients was 40%. Diarrhea was the most common toxicity and 14 (10%) courses were associated with grade 3-4 diarrhea.

Conclusions: In heavily pretreated patients with refractory/relapsed solid tumors, the vincristine, irinotecan, and temozolomide regimen seemed promising in Ewing sarcoma patients and was well tolerated.
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http://dx.doi.org/10.1177/1078155218790798DOI Listing
September 2019

Absolute dose verification of static intensity modulated radiation therapy (IMRT) with ion chambers of various volumes and TLD detectors.

Rep Pract Oncol Radiother 2018 Jul-Aug;23(4):242-250. Epub 2018 May 19.

Istanbul University, Institute of Oncology, Department of Medical Physics, 34390 Capa, Istanbul, Turkey.

Aim: This study aims at examining absolute dose verification of step-and-shoot intensity modulated radiation treatment (IMRT) of prostate and brain patients by use of ion chambers of two different volumes and thermoluminescent detectors (TLD).

Background: The volume of the ion chamber (IC) is very important for absolute dose verification of IMRT plans since the IC has a volume average effect. With TLD detectors absolute dose verification can be done measuring the dose of multiple points simultaneously.

Materials And Methods: Ion chambers FC65-P of volume 0.65 cc and semiflex of volume 0.125 cc as well as TLDs were used to measure the central axis absolute dose of IMRT quality assurance (QA) plans. The results were compared with doses calculated by a treatment planning system (TPS). The absolute doses of off axis points located 2 cm and 4 cm away from the isocenter were measured with TLDs.

Results: The measurements of the 0.125 cc ion chamber were found to be closer to TPS calculations compared to the 0.65 cc ion chamber, for both patient groups. For both groups the root mean square (RMS) differences between doses of the TPS and the TLD detectors are within 3.0% for the central axis and points 2 cm away from the isocenter of each axis. Larger deviations were found at the field edges, which have steep dose gradient.

Conclusions: The 0.125 cc ion chamber measures the absolute dose of the isocenter more accurately compared to the 0.65 cc chamber. TLDs have good accuracy (within 3.0%) for absolute dose measurements of in-field points.
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http://dx.doi.org/10.1016/j.rpor.2018.04.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035899PMC
May 2018

Relationships between serum PSA levels, Gleason scores and results of 68Ga-PSMAPET/CT in patients with recurrent prostate cancer.

Ann Nucl Med 2017 Nov 12;31(9):709-717. Epub 2017 Sep 12.

Department of Nuclear Medicine, Istanbul Faculty of Medicine, Istanbul University, Ic Hastalıkları Binasi, Nukleer Tip Anabilim Dali, Istanbul, Turkey.

Aim: To investigate the relationship between serum PSA level, Gleason score of PCa and the outcomes of Ga-PSMA PET/CT in patients with recurrent PCa.

Methods: A total of 109 consecutive patients (median age 71 years; range 48-89 years) who had PSA recurrence after RP and/or hormonotherapy and/or radiotherapy were included in this study. Local recurrences, lymph node metastasis (pelvic, abdominal and/or supradiaphragmatic), bone metastases (oligometastatic/multimetastatic) and other metastatic sites (lung, liver, brain, etc) were documented.

Results: In 91(83.4%) patients at least one lesion characteristic for PCa was detected byGa-PSMA PET/CT. The median serum total PSA (tPSA) was 6.5 (0.2-640) ng/ml.There was a significant difference between Ga-PSMA PET/CT positive and negative patients in terms of serum total PSA value. No statistical significance was found between positive and negative Ga-PSMA PET/CT findings in terms of Gleason score. Local recurrence was detected in 56 patients. whereas lymph node metastases were demonstrated in 46 patients. Pelvic nodal disease was the most frequent presentation followed by abdominal and supradiaphragmaticnodal involvement. Bone metastases [oligometastasis, (n = 20); multimetastasis, (n = 35)⦌ were also detected in 55 patients. In the ROC analysis for the study cohort, the optimal cut-off value of total serum PSA was determined as 0.67 ng/ml for distinguishing between positive and negative Ga-PSMA PET/CT images, with an area under curve of 0.952 (95% CI 0.911-0.993).

Conclusions: Ga-PSMA PET/CT was found to be an effective tool for the detection of recurrent PCa. Even though no relationship was detected between the GS and Ga-PSMA PET/CT findings, serum total PSA values may be used for estimating the likelihood of positive Ga-PSMA PET/CT results.
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http://dx.doi.org/10.1007/s12149-017-1207-yDOI Listing
November 2017

Silencing Sensitizes Prostate Cancer Cells to Enzalutamide-mediated Androgen Receptor Blockade.

Anticancer Res 2017 07;37(7):3631-3637

Oncology Institute, Istanbul University, Istanbul, Turkey

Background/aim: Prostate cancer (PCa) is an androgen-dependent disease. Novel anti-androgens (i.e. enzalutamide) have recently been developed for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC). Evidence is accumulating that prostate cancer antigen 3 (PCA3) is involved in androgen receptor (AR) signaling. Here, in combination with enzalutamide-mediated AR blockade, we investigated the effect of PCA3 targeting on the viability of PCa cells.

Materials And Methods: In hormone-sensitive LNCaP cells, AR-overexpressing LNCaP-AR cells and VCaP cells (representing CRPC), PCA3 was silenced using siRNA oligonucleotides. Gene expression and cell viability was assessed in PCA3-silenced and/or AR-blocked cells.

Results: PCA3 targeting reduced the expression of AR-related genes (i.e. prostate-specific antigen (PSA) and prostate-specific transcript 1 (non-protein coding) (PCGEM1)) and potentiated the effect of enzalutamide. Proliferation of PCa cells was suppressed upon PCA3 silencing with a greater effect in LNCaP-AR cells. Furthermore, PCA3 silencing sensitized PCa cells to enzalutamide-induced loss of cell growth.

Conclusion: PCA3, as a therapeutic target in PCa, might be used to potentiate AR antagonists.
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http://dx.doi.org/10.21873/anticanres.11733DOI Listing
July 2017

Neoadjuvant sequential chemoradiotherapy versus radiotherapy alone for treatment of high-risk extremity soft tissue sarcoma: a single-institution experience.

Contemp Oncol (Pozn) 2017 22;21(1):60-65. Epub 2017 Mar 22.

Department of Radiation Oncology, Institute of Oncology, Istanbul University, Istanbul, Turkey.

Aim Of The Study: Patients with large and high-grade extremity soft-tissue sarcoma are at significant risk for distant metastasis and sarcoma-related death. There is no randomized trial comparing chemoradiotherapy to radiotherapy in the neoadjuvant setting for high risk extremity soft-tissue sarcoma. The aim of this study is to evaluate the outcomes of patients treated with two different modalities (neoadjuvant sequential chemoradiotherapy vs. radiotherapy alone) in a single center.

Material And Methods: Data of 67 patients were analyzed retrospectively. Thirty-four patients received neoadjuvant sequential chemoradiotherapy (2-3 cycles of doxorubicin (75 mg/m) and ifosfamide (6 g/m) followed by radiotherapy of 28 Grays (Gy) administered as 8 fractions of 35 Gy) and 33 patients received radiotherapy alone. R0 resection rates and 3-year survival estimates were evaluated.

Results: Median follow-up time was 37 months. The estimated 3-year overall and disease-free survival rates for the whole patient group were 79% (95% CI: 67.0-86.4) and 57.9% (95% CI: 46.3-69.0), respectively. The most common side effects were nausea and leucopenia. Three-year overall, disease-free, local recurrence-free and distant recurrence-free survival rates did not differ significantly. All patients except one underwent wide excision or compartmental resection. R0 resection rate for the whole patient group was 92.5% ( = 62). Sites of progression were similar across both treatment arms.

Conclusions: Preoperative hypofractionated radiotherapy alone or sequentially with chemotherapy result in high rates of limb salvage and acceptable toxicity. Our study results did not show a statistically significant treatment effect regarding survival and patterns of failure.
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http://dx.doi.org/10.5114/wo.2017.66658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385480PMC
March 2017

Conventionally Fractionationed Volumetric Arc Therapy versus Hypofractionated Stereotactic Body Radiotherapy: Quality of Life, Side Effects, and Prostate-Specific Antigen Kinetics in Localized Prostate Cancer.

Value Health Reg Issues 2016 09 6;10:91-99. Epub 2016 Oct 6.

Department of Radiation Oncology, Institute of Oncology, Istanbul University, Istanbul, Turkey.

Objectives: To compare conventionally fractionationed volumetric arc therapy (VMAT) and hypofractionated stereotactic body radiotherapy (SBRT) modalities in terms of prostate-specific antigen (PSA) kinetics, toxicity, and quality of life (QOL) in patients with localized prostate cancer.

Methods: Patients received radical radiotherapy as either 33.5 Gy/5 fr for SBRT or 75.6 Gy/35 fr for VMAT. International Prostate Symptom Score (IPSS) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Prostate Cancer Module (QLQ-PR25) forms were used to assess QOL.

Results: Of the 48 patients (28 in SBRT and 20 in VMAT) included in the study, 40 (20 in SBRT and 20 in VMAT) were evaluated for QOL status. PSA control rate was 100% and PSA nadir value was 0.5 ng/dl in both arms during the median follow-up period of 23 months. The magnitude of PSA bounce was higher in the SBRT arm than in the VMAT arm (P = 0.01). The PSA decline rate in the VMAT arm was higher than in the SBRT arm (P = 0.028). Three (10.7%) patients treated with SBRT who had a history of transurethral resection of the prostate (TURP) experienced grade 3 urinary toxicity. No significant difference was observed concerning sexual activity and sexual functioning scores, whereas scores at 10.5 and 13.5 months were decreased in both arms. The SBRT and VMAT arms had similar urinary incontinence, bowel symptoms, and IPSS obstruction scores. The magnitude of increase in IPSS scores at treatment completion was higher in the VMAT arm than in the SBRT arm (P = 0.046). The decrease in hormonal symptom scores at 4.5, 10.5, and 13.5 months was higher in the VMAT arm than in the SBRT arm (P = 0.007, 0.027, and 0.021, respectively).

Conclusions: Both treatment modalities had similar effectiveness and provided acceptable outcomes in terms of toxicity and QOL. Grade 3 urinary toxicities might be eliminated with careful patient selection for SBRT.
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http://dx.doi.org/10.1016/j.vhri.2016.08.001DOI Listing
September 2016

Breast Metastases in Children and Adolescents With Rhabdomyosarcoma: A Large Single-Institution Experience and Literature Review.

J Pediatr Hematol Oncol 2017 01;39(1):67-71

Departments of *Pediatric Hematology and Oncology, Cerrahpasa Faculty of Medicine †Pediatric Hematology and Oncology ∥Radiation Oncology, Oncology Institute ‡Pediatric Surgery, Istanbul School of Medicine, Istanbul University §Department of Surgery and Surgical Oncology, School of Medicine, Maltepe University, Istanbul, Turkey.

Introduction: Breast metastasis is rare in childhood malignancies. Soft tissue sarcomas, especially rhabdomyosarcomas (RMS), and hematologic neoplasms, such as lymphomas, are the most common tumors that metastasize to the breast, albeit rare.

Materials And Methods: All cases with breast metastasis within a cohort of 200 RMS patients followed in our institution during 1990 to 2014 were assessed retrospectively and the literature was reviewed.

Results: There were 3 adolescent female patients with breast metastasis. All had alveolar histology. The primary tumors were in the parameningeal sites, extremities, and the perineum, respectively. Two patients had breast metastasis at diagnosis, and 1 during follow-up. In 1 breast lesion, there was a complete response to chemotherapy, and in another there was no response to chemotherapy, and the patient underwent radical mastectomy. In the third patient, there was partial response, and lesions progressed. All patients died with recurrent/progressive disease, 2 with no recurrence in the breast. In the English literature, there are 70 cases including our cases. All but 1 involve female patients, all adolescents, most have alveolar histology and poor prognosis. All had chemotherapy, whereas some had surgery and/or radiotherapy for local treatment.

Conclusion: Breast metastasis should be considered in adolescent female patients with RMS. Optimal management is not clear. Besides chemotherapy, mastectomy and radiotherapy should be considered on a case basis.
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http://dx.doi.org/10.1097/MPH.0000000000000680DOI Listing
January 2017

Impact of Superoxide Dismutase-Gliadin on Radiation-induced Fibrosis: An Experimental Study.

In Vivo 2016 Jul-Aug;30(4):451-6

Department of Radiation Oncology, Medical Faculty, Istanbul University, Istanbul, Turkey.

Aim: Radiation-induced fibrosis (RIF) has since long been considered as irreversible. Further understanding of its mechanisms has led to trials investigating RIF treatment and prevention. The effect of superoxide dismutase (SOD)-gliadin, an oral form of SOD that resists gastrointestinal inactivation, on RIF treatment was evaluated in this experimental study.

Materials And Methods: A total of 36 Wistar albino mice were randomly distributed into four groups. According to group, 25 Gy radiation or sham-radiation were performed on day 0. Acute and late reactions were recorded. After 6 months, mice were treated with SOD-gliadin, 10,000 units per kg per day, or placebo. SOD-gliadin and placebo treatments were administered daily for 8 days by oral gavage. Later the mice were sacrificed, dissected and histopathologically analyzed. Accumulated hyaline and collagen at the dermis is an indicator of fibrosis. Therefore measurements of the dermal thickness were used to quantify the degree of RIF. Additionally, the morphological changes were analyzed, and the differences reported.

Results: The mean and standard deviation for dermal thickness were 0.45±0.09 mm in the sham-irradiated placebo-treated group, 0.51 mm±0.16 mm in the sham-irradiated SOD-gliadin-treated group, 0.92 mm±0.23 mm in the irradiated placebo-treated group and 0.71 mm±0.17 mm in the irradiated SOD-gliadin-treated group. The difference in mean dermal thickness between irradiated placebo-treated and irradiated SOD-gliadin-treated mice was statistically significant (p=0.002).

Conclusion: Quality of life while prolonging survival has an increasing importance in patients with cancer. RIF can be a crucial problem after all radiotherapy modalities. SOD-gliadin has advantageous effects on conditions that call for an increased expression of antioxidant enzymes. The results of our study suggest that oral SOD-gliadin may prevent or ameliorate RIF and patients can benefit from the positive effects of SOD.
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July 2017

Survival and prognostic factors in adult patients with recurrent or refractory ewing sarcoma family tumours: a 13-years retrospective study in Turkey.

In Vivo 2014 May-Jun;28(3):403-9

Division of Medical Oncology, Institute of Oncology, Istanbul University, Istanbul, Turkey.

Aim: The aim of the present study was to evaluate the results of treatment and prognostic factors in adult patients with recurrent or refractory Ewing's sarcoma family tumors (ESFT).

Patients And Methods: We retrospectively evaluated treatment outcomes of 54 consecutive patients with ESFT (aged 15 years or more) with complete medical records, who were treated with multimodal therapies after recurrence at the Istanbul University, Institute of Oncology.

Results: The commonly used chemotherapy regimens at relapse were ifosfamide and etoposide (IE), ifosfamide and etoposide plus carboplatin (ICE), and oral etoposide. The median progression-free survival and overall survival for the entire group were 6.3 (95% confidence interval, 3.08-9.60) and 8.6 (95% confidence interval CI, 4.7-12.4) months, respectively. Multivariate analysis using a Cox proportional hazards model showed that non-IE/ICE chemotherapy regimens (p=0.003, hazard ratio=2.38) and the presence extrapulmonary metastases (p=0.045, hazard ratio=2.15) were associated with worse overall survival.

Conclusion: In primary refractory or relapsed ESFT, the presence of extrapulmonary metastases and treatment with salvage regimens other than ifosfamide and etoposide and/or carboplatin correlate with a poor prognosis.
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January 2015

A modified protocol with vincristine, topotecan, and cyclophosphamide for recurrent/progressive ewing sarcoma family tumors.

Pediatr Hematol Oncol 2013 Apr;30(3):170-7

Department of Pediatric Hematology-Oncology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.

Purpose: Topotecan has recently been used in the treatment of pediatric cancer. We evaluated our experience with the modified combination of vincristine, topotecan, and cyclophosphamide (VTC) given in 3 days, in children with recurrent Ewing sarcoma.

Method: Children received vincristine (1.5 mg/m(2)/1st day), cyclophosphamide (600 mg/m(2)/day × 2 days) + mesna, and topotecan (1 mg/m(2)/day × 3 days) every 21 days.

Result: A total of 118 courses of VTC were given to 13 patients. One patient received VTC both at first and at second relapse. Thus, 14 relapse episodes in 13 patients were evaluated. After three courses of VTC chemotherapy (CT), two achieved complete response (CR), five achieved partial response, thus an objective response was attained in 7/14 (50%) episodes. Two patients had stable disease and two patients progressed. In three episodes, CR was achieved by surgery before CT. One of them had a second relapse and attained CR with VTC. Median time from diagnosis to relapse was 23 months (5-45 months). Site of relapse was local in four patients, and metastatic in 10 episodes of nine patients. Seven patients are alive, three with no evidence of disease and four alive with disease; six have died of disease. Local treatment was used in 11 episodes. The toxicity of the VTC combination was limited mainly to the hematopoietic system.

Conclusion: In conclusion, the modified VTC protocol in 3 days every 3 weeks seems to be effective and tolerable in children and adolescents with recurrent/progressive Ewing sarcoma.
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http://dx.doi.org/10.3109/08880018.2013.767868DOI Listing
April 2013

Serum M65 as a biomarker for metastatic renal cell carcinoma.

Clin Genitourin Cancer 2013 Sep 4;11(3):290-6. Epub 2013 Feb 4.

Department of Medical Oncology, Institute of Oncology, Istanbul University, Istanbul, Turkey.

Introduction/background: Effective cancer biomarkers for early detection, prognosis, or therapy response prediction are urgently need in metastatic RCC. M30 and M65 are released during apoptotic cell death and precisely reflect epithelial tumor cell death. The aim of this study was to determine the prognostic value of plasma M30 and M65 levels in predicting survival rates for patients with metastatic RCC.

Patients And Methods: Thirty-nine patients with metastatic RCC and 39 healthy control subjects were included in this study. Serum M30 and M65 levels were measured by ELISA.

Results: The median ages of the patients and control subjects were 60 and 58 years, respectively. No difference was detected in the median serum M30 level between the patients and control subjects (53.7 vs. 49.1 U/L; P = .31). The median serum M65 level was significantly higher in patients than in control subjects (334.0 vs. 179.1 U/L; P < .001). Receiver operating characteristic analysis revealed that the best cutoff value for serum M65 level for predicting progression-free survival (PFS) was 313.6 U/L. The median PFS of patients whose M65 levels were ≤ 313.6 U/L was better than that of patients whose M65 levels were > 313.6 U/L (P = .03).

Conclusion: To the best of our knowledge, this is the first study to evaluate serum M30 and M65 levels in patients with RCC. Serum M65 levels were significantly elevated in patients with metastatic RCC compared with healthy individuals. In addition, the serum M65 level could be predictive of PFS in patients with RCC.
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http://dx.doi.org/10.1016/j.clgc.2013.01.001DOI Listing
September 2013

Pediatric diffuse intrinsic pontine glioma patients from a single center.

Childs Nerv Syst 2013 Apr 8;29(4):583-8. Epub 2012 Dec 8.

Pediatric Hematology-Oncology, Cerrahpasa Medical Faculty and Oncology Institute, Istanbul University, Istanbul, Turkey.

Background: The prognosis of children with diffuse intrinsic pontine gliomas (DIPG) is dismal. This study aims to evaluate the characteristics and treatment outcome of children with DIPG in a single center.

Methods: We reviewed the outcome of children with DIPG treated at the Oncology Institute of Istanbul University from February 1999 to May 2012.

Results: Fifty children (26 female, 24 male) with the median age of 7 years were analyzed. The median duration of symptoms was 30 days. All patients received radiotherapy (RT). Before the year 2000, 12 patients received only RT. Thirty-eight had concomitant and/or adjuvant chemotherapy with RT. Between 2000 and 2004, 17 patients received cis-platinum or vincristine as sensitizers during RT and CCNU + vincristine combination after RT. Since 2004, 21 patients received temozolomide (TMZ) concomitantly during RT and as adjuvant chemotherapy after RT. The median survival time of all patients was 13 months (1-160 months). Patients receiving RT + TMZ had a significantly higher overall survival than patients with only RT (p = 0.018). Patients receiving RT + chemotherapy other than TMZ also had a significantly higher overall survival than patients receiving only RT (p = 0.013). Patients receiving RT + TMZ + and chemotherapy other than TMZ had a significantly higher survival than patients receiving only RT (p = 0.005).

Conclusion: In our series, patients receiving RT + TMZ and also patients receiving RT + chemotherapy other than TMZ had a significantly higher overall survival than patients treated with only RT. Hence, administering chemotherapy during and after RT seems to prolong survival in some DIPG patients.
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http://dx.doi.org/10.1007/s00381-012-1986-3DOI Listing
April 2013

Mucoepidermoid carcinoma of the parotid gland in childhood survivor of acute lymphoblastic leukemia with need of radiotherapy for treatment and review of the literature.

Pediatr Hematol Oncol 2012 May;29(4):380-5

Diagnosis of secondary malignancies began with the increasing survival in childhood cancer. Children treated for acute lymphoblastic leukemia (ALL) have an increased risk for developing mucoepidermoid carcinoma (MEC) of the parotid gland. The latent period ranges from 5 to 16 years. A 2 6/12-year-old girl was treated for pro-B ALL. Treatment included multidrug chemotherapy, prophylactic intrathecal methotrexate, and cranial radiotherapy. MEC of the left parotid gland was diagnosed at the age of 8 years, 3 years after completing treatment. She was treated with multiple surgery and radiotherapy. The authors aimed to emphasize the need for concern about second cancers of the parotid gland in children treated for ALL.
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http://dx.doi.org/10.3109/08880018.2012.673696DOI Listing
May 2012

Response rates and adverse effects of continuous once-daily sunitinib in patients with advanced renal cell carcinoma: a single-center study in Turkey.

Jpn J Clin Oncol 2011 Dec 19;41(12):1380-7. Epub 2011 Oct 19.

Division of Medical Oncology, Specialist in Internal Medicine, Institute of Oncology, Istanbul University, Istanbul, Turkey.

Objective: Therapy targeted against the vascular endothelial growth factor pathway is a standard of care for patients with metastatic renal cell carcinoma. This study assessed the response rates and toxicity profiles of sunitinib on a continuous once-daily dosing regimen in Turkish patients with metastatic renal cell carcinoma.

Methods: Between April 2006 and August 2010, 74 patients with metastatic renal cell carcinoma who received sunitinib on a continuous, once-daily dosing regimen were included. Sunitinib was administered daily at a dose of either 37.5 mg (94% of the patients) or 25 mg (6% of the patients), without interruption, either as a second-line treatment after interferon-α or as a first-line treatment. Response, toxicity, progression-free survival and overall survival were evaluated.

Results: Of the 74 patients, 65 (88%) were diagnosed with clear cell renal cell carcinoma. The median treatment duration was 10 months (range, 2-42 months). The most common treatment-related adverse events were fatigue (75%), stomatitis (51%) and hypertension (50%). The most common Grade 3 or 4 adverse events were anemia (10%) and hand-foot syndrome (7%). Dose reductions were required in 50% of the patients, and early treatment discontinuation was necessary in 16% of the patients. Cardiovascular events were the most common adverse events that resulted in drug discontinuation. The objective response rate and the disease control rate were 30 and 78%, respectively. The median progression-free survival and overall survival were 13 and 25 months, respectively.

Conclusions: Continuous, once-daily administration of sunitinib was generally well tolerated in Turkish patients with advanced renal cell carcinoma in a daily practice setting. This study's response rates were comparable to those in previous randomized trials.
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http://dx.doi.org/10.1093/jjco/hyr151DOI Listing
December 2011

Investigation of miR-21, miR-141, and miR-221 in blood circulation of patients with prostate cancer.

Tumour Biol 2011 Jun 28;32(3):583-8. Epub 2011 Jan 28.

Department of Radiation Oncology, Istanbul University Oncology Institute, 34390 Capa, Istanbul, Turkey.

In addition to their potential as tissue-based markers for cancer classification and prognostication, the study of microRNAs (miRNAs) in blood circulation is also of interest. In the present study, we investigated the amounts of three cancer-related miRNAs, miR-21, -141, and -221 in blood plasma of prostate cancer (PCa) patients. A cohort of 51 patients with PCa was enrolled into the study, and miRNAs were measured in two subgroups, with localized/local advanced or metastatic PCa. A group of 20 healthy individuals served as the control group. miRNAs were quantified from the total RNA fraction using 200 μl plasma and the small RNA molecule RNU1A as a control for normalizing the miRNA amounts in circulation. We found similar levels of three miRNAs in healthy subjects with median values of 0.039, 0.033 and 0.04, respectively; (p = n.s.). In the patients, the miRNA levels were higher, with miR-21 being the highest (median, 1.51). The miR-221 levels were intermediate (median, 0.71) while the miR-141 displayed the lowest levels (median, 0.051). The differences between the control group and the patients were highly significant for the miR-21 (p < 0.001; area under the curve (AUC), 88%) and -221 (p < 0.001; AUC, 83%) but not for the miR-141 (p = 0.2). In patients diagnosed with metastatic PCa, levels of all three miRNAs were significantly higher than in patients with localized/local advanced disease where the difference for the miR-141 was most pronounced (p< 0.001; AUC, 75.5%). In conclusion, analysis of miR-21, -141, and -221 in blood of PCa patients reveals varying patterns of these molecules in clinical subgroups of PCa.
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http://dx.doi.org/10.1007/s13277-011-0154-9DOI Listing
June 2011

Post-treatment circulating plasma BMP6 mRNA and H3K27 methylation levels discriminate metastatic prostate cancer from localized disease.

Clin Chim Acta 2010 Oct 2;411(19-20):1452-6. Epub 2010 Jun 2.

Istanbul University Oncology Institute, Department of Basic Oncology, Istanbul, Turkey.

Background: We evaluated the utility of post-treatment plasma levels of the circulating bone-morphogenetic protein-6-specific mRNA (cBMP6 mRNA), cell-free DNA (cf-DNA), apoptotic nucleosomes and Histone H3 lysine 27 trimethylation (H3K27me3), in discriminating metastatic prostate cancer (PCa) from organ confined, locally controlled disease.

Methods: Peripheral blood was taken from the patients at the end of therapy, and quantitative PCR was performed to amplify cBMP6 mRNA or cf-DNA from plasma while apoptotic nucleosomes and H3K27me3 were determined by ELISA-based approaches. Following blinded measurements, the markers were compared between the patients with local (n=22), local advanced (n=11) or metastatic disease (n=28).

Results: Of the four markers investigated, the cBMP6 mRNA and H3K27me3 levels revealed significant differences between the three subgroups. We found higher levels of cBMP6 mRNA in the patients with metastases than in those with localized (p=0.001) or local advanced disease (p=0.05). When compared to cBMP6, H3K27me3 displayed an inverse distribution and was significantly lower in the patients with metastatic disease than in those with localized (p=0.05) or local advanced disease (p=0.024). There was no correlation between the different markers and total PSA levels or Gleason score at diagnosis.

Conclusion: Our study provides evidence that post-treatment analysis of cBMP6 mRNA and H3K27me3 may be used to distinguish metastatic PCa from organ confined, locally controlled disease.
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http://dx.doi.org/10.1016/j.cca.2010.05.040DOI Listing
October 2010

Treatment of Wilms tumor: a report from the Turkish Pediatric Oncology Group (TPOG).

Pediatr Hematol Oncol 2010 Apr;27(3):161-78

Hacettepe University Faculty of Medicine, Dept. of Pediatric Oncology, Ankara, Turkey.

Aim: To standardize diagnosis and treatment of childhood Wilms tumor (WT) in Turkey.

Methods And Patients: Between 1998 and 2006, WT patients were registered from 19 centers. Patients <16 years with unilateral WT whose treatment started in first postoperative 3 weeks were included. Treatments were stage I favorable (FH) and unfavorable histology (UH) patients, VCR + Act-D; stage IIA FH, VCR + Act-D; stage IIB FH, VCR + Act-D + radiotherapy (RT); stage III-IV FH, VCR + Act-D + adriamycin (ADR) + RT; stages II-IV UH tumors, VCR + Act-D + ADR + etoposide + RT.

Results: 165/254 registered cases were eligible (bilateral, 5.9%) [median age 3.0 years; M/F: 0.99; 50/165 cases < or =2 years]. 9.7% cases had UH tumors. Disease stages were stage I 23.6%; IIA 36.4%; IIB 5.5%; III 22.4%; IV 12.1%. Cases >2 years had significantly more advanced disease. 1/11 cases with recurrent disease died; 2/165 had progressive disease, 2/165 had secondary cancers, and all 4 died. In all cases 4-year OS and EFS were 92.8 and 86.5%, respectively. Both OS and EFS were significantly worse in stage IV.

Conclusions: Despite problems in patient management and follow-up, treatment results were encouraging in this first national experience with a multicentric study in pediatric oncology. Revisions and modifications are planned to further improve results and minimize short- and long-term side effects.
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http://dx.doi.org/10.3109/08880010903447375DOI Listing
April 2010

Multiple anterior and posterior chamber pseudocysts in a 12-year-old boy with diffuse infiltrating retinoblastoma.

J Pediatr Ophthalmol Strabismus 2009 Sep-Oct;46(5):312-6. Epub 2009 Sep 22.

Istanbul University, Istanbul Faculty of Medicine, Department of Ophthalmology, Capa, 34390, Istanbul, Turkey.

Diffuse infiltrating retinoblastoma is a rare subtype, occurring in 1% of all patients with retinoblastoma. It usually presents with pseudoinflammatory response in the anterior chamber and the vitreous, masquerading as endophthalmitis or uveitis. This report describes a 12-year-old boy with multiple free-floating intraocular pseudocysts as a unique finding in diffuse infiltrating retinoblastoma. These pseudocysts represent necrotic seeds without epithelial lining. Invasive surgical procedures should be avoided in children presenting with atypical, chronic, unilateral intraocular inflammation of unknown cause until retinoblastoma is excluded.
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http://dx.doi.org/10.3928/01913913-20090903-11DOI Listing
November 2009

The role of surgery and radiotherapy in treatment of soft tissue sarcomas of the head and neck region: review of 30 cases.

J Craniomaxillofac Surg 2009 Jan 18;37(1):42-8. Epub 2008 Sep 18.

Kocaeli University, Faculty of Medicine, Department of Radiation Oncology, Turkey.

Background: Thirty adult patients with head and neck soft tissue sarcoma (HNSTS) treated between 1987 and 2000 were retrospectively analysed.

Patients And Methods: The most frequent histopathological subtypes were chondrosarcomas (27%) and malignant fibrous histiocytoma (20%). The surgical resection was performed in 25 of the 30 patients (83%). Twenty-three patients in the surgical resection arm received postoperative radiotherapy.

Results: Five-year local control rates for patients with negative surgical margins (n=9), microscopically positive disease (n=10), gross residual disease (n=6) and inoperable cases (n=5) were 64, 70, 20 and 0%, respectively. However, there was no significant difference in local control between patients with negative or microscopically positive disease who received postoperative radiotherapy (71 vs. 70%). The patients who received doses>or=60 Gy had significantly higher local control rates than the ones who received doses lower than 60 Gy (p=0.048). The local control rates were lower in patients with grade 2-3 tumours when compared with grade 1 tumours (44 vs. 83%). The median overall survival of whole group was 31 months. Median survivals of patients receiving both surgery and radiotherapy with negative and microscopically positive margins were significantly better than patients who were not treated with surgery (34.8 and 36 vs. 13.3 months).

Conclusion: Our results confirm that the optimal treatment of HNSTSs is complete surgical excision, and that postoperative adjuvant radiotherapy clearly improves local control.
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http://dx.doi.org/10.1016/j.jcms.2008.07.007DOI Listing
January 2009

Clinical outcome of rhabdomyosarcoma in adolescent and adult patients: single center experience from Turkey.

Tohoku J Exp Med 2007 Nov;213(3):221-9

Department of Medical Oncology, Istanbul University Institute of Oncology, Istanbul, Turkey.

Rhabdomyosarcoma (RMS) is rare disease in adults (age >or= 16 years). The data from randomized prospective trials are scarce; the clinical outcome of these patients seems poor with the currently available treatment strategies. In this study, we report a single institution's experience in the treatment of adult RMS. We reviewed the medical records of patients with RMS who were >or= 16 years and have been treated in our institution between 1988 and 2003 retrospectively. We analyzed the survival outcome of these patients and the prognostic impact of clinical/pathological factors on their survival. In total, 23 patients with RMS were identified. Median age was 26 years (range, 16-72 years). Majority of patients were male (n: 17, 73.9%), and had large tumors (>or= 5 cm, n: 13, 56.5%), localized disease (N0, M0, n: 12, 52.2%), and embryonal histology (n: 10, 43.5%). Median overall survival was 31.3 months, and the 3-year progression-free survival and overall survival rates were 19.9% and 34.94%, respectively. Patients with smaller tumors (< 5 cm) (p < 0.04), local disease (p < 0.01), and normal lactic dehydrogenase (LDH) level (p < 0.01) at the time of diagnosis were found to have better survival outcome. The tumor size, serum LDH level, and metastatic disease at the time of diagnosis are potential predictors of outcome in patients with adult RMS. Adult RMS is an aggressive disease with poor survival despite treatment. The data from prospective, randomized multicenter trials are necessary in order to improve the clinical outcome of adult RMS patients.
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http://dx.doi.org/10.1620/tjem.213.221DOI Listing
November 2007

Hypertrophic osteoarthropathy and intrathoracic Hodgkin's disease in children.

Leuk Res 2006 Jul 28;30(7):899-902. Epub 2005 Nov 28.

Istanbul University, Oncology Institute, Division of Pediatric Oncology, Turkey.

Background: Hypertrophic osteoarthropathy (HOA) is a syndrome characterized by clubbing of the fingers and toes, periosteal new bone formation of the long bones and polyarthritis.

Case Report: In this report, two children with intrathoracic Hodgkin's disease and HOA are presented.

Conclusions: Intrathoracic neoplasms are one of the major causes of HOA in adults; however HOA is rarely associated with intrathoracic malignancies in children. HOA associated with intrathoracic Hodgkin's disease is even more rare, but should be kept in mind.
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http://dx.doi.org/10.1016/j.leukres.2005.10.019DOI Listing
July 2006

Ependymal tumors in childhood.

Pediatr Blood Cancer 2005 Sep;45(3):298-303

Department of Radiation Oncology, Istanbul University-Istanbul Medical Faculty, 34390 Capa Istanbul, Turkey.

Background: Ependymal tumors are classified as ependymoma (benign or low grade) versus anaplastic ependymoma (malignant or high grade). Ependymomas represent 5-10% of intracranial neoplasm in children. In this study, demographic data and the treatment results of pediatric patients with ependymal tumors, treated in a single institute, is reported.

Patients And Methods: Between 1989 and 2001, 40 (22 M/18 F) previously untreated patients with a median age of 5.5 years (3 months-15 years), of histologically proven ependymal tumors (except ependymoblastomas) were referred to the Institute of Oncology, University of Istanbul. The localization was supratentorial in 18, infratentorial in 20, both supra and infratentorial in two patients. Histologic subgroups were 18 ependymomas (43.6%), and 22 anaplastic ependymomas (56.4%). Total tumor resection was performed in 20 patients (50%), subtotal in 18 patients (45%), and biopsy only in 2 patients (5%). Postoperative treatment consisted of regional (8 patients) or craniospinal (CSI) (9 patients) radiotherapy (RT) in patients with ependymoma; regional (7 patients) or CSI RT (14 patients) with chemotherapy (ChT) in patients with anaplastic ependymoma; ChT only (1 patient) in patients less than 3 years of age. The standard technique for posterior fossa irradiation was parallel-opposed lateral fields and total dose was 45-54 Gy. Between September 1989 and May 1991 patients received regimen A, which consisted of RT followed by eight-in-one ChT, given every 4 weeks for eight courses. Patients who were treated between June 1991 and July 1994, received regimen B, which included two courses of postoperative "VEC" (vincristine, etoposide, cisplatin) ChT, administered every 3 weeks, followed by RT applied with low dose concomitant cisplatin used as a radiosensitizer. Patients with objective response to postoperative "VEC" continued to have "VEC" after completion of RT for six more courses. From August 1994 on, patients received regimen C, consisting of RT and concomitant infusion of cisplatin followed by "VCPCU" (vincristine, cyclophosphamide, procarbazine, lomustine) administered every 4 weeks for eight courses.

Results: A total of 40 patients were included in the outcome and survival data. The 5-year overall survival (OS) rate was 64.9%, and the 5-year progression-free survival rate was 50.8% for the whole series. Median time for progression or relapse was 24.3 months and there were 19 patients (43.6%) with relapse or progression. Non-metastatic patients (P = 0.0008, 5-year OS rate was 82% vs. 29%), and totally resected patients (P = 0.01, 5-year OS rate was 80% vs. 55%), and > or =3 years of age (P = 0.04, 5-year OS rate was 75% vs. 38%) had significantly better outcome.

Conclusions: The majority of complete responders were patients who had total tumor removal. Treatment failure occurred mainly within the first 2 years, and outcome was dismal for patients who relapsed or had progressive disease. The median age at diagnosis is 6 years in our patient group; younger children (less than 3 years old) have less favorable outcome. There was no significant difference in survival or progression-free survival between the two histologic subtypes.
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http://dx.doi.org/10.1002/pbc.20212DOI Listing
September 2005

Primary uterine lymphoma: case report and literature review.

Aust N Z J Obstet Gynaecol 2005 Feb;45(1):88-9

Radiation Oncology Department, Istanbul University Institute of Oncology, Turkey.

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http://dx.doi.org/10.1111/j.1479-828X.2005.00329.xDOI Listing
February 2005

Brain metastasis in pediatric extracranial solid tumors: survey and literature review.

J Neurooncol 2005 Jan;71(1):43-8

Division of Pediatric Oncology, Oncology Institute, Istanbul University, Capa, Istanbul, Turkey.

Objectives: Brain is a rare site of metastasis in most extracranial pediatric solid tumors. The aim of this study is to investigate the incidence, treatment, prognosis of brain metastasis in extracranial pediatric malignant tumors in a single institution and to review the literature.

Methods: From September 1989 to December 2002, 1100 children
Results: Sixteen (10 female, 6 male) of 1100 patients (1.45%) with extracranial solid tumors developed brain metastases. The median age of the patients was 10.5 (1-16) years. The diagnosis was sarcomas in 12 patients: 5 osteosarcomas, 4 Ewing's sarcoma family tumors, 1 rhabdomyosarcoma, 1 clear cell sarcoma of the soft tissue, 1 alveolar soft part sarcoma. Two patients had Wilms' tumor and two had germ cell tumors. Four patients (25%) had brain metastasis at diagnosis. Twelve (75%) developed brain metastasis during therapy or relapse at a median duration of 16 (1-70) months from initial diagnosis. All patients had metastases to various sites, mostly lung, at the time the brain metastases were detected. Treatment included surgery, followed by postoperative radiotherapy (RT) and chemotherapy (CT) in 1, S and RT in 1, S in 1, RT and CT in 6, RT in 1, CT in 1 and no treatment in 5. Only one patient with alveolar soft part sarcoma is alive with disease 20 months from diagnosis of brain metastasis. All other patients died at a median time of 2 months (2 days-6 months) from the time of brain metastasis.

Conclusions: Children with metastatic cancer who develop headaches or any other neurologic symptom should be investigated for possible brain metastasis. Although, the outcome for these patients is dismal in this series and in the literature; reports of long term survival in a few cases with Wilms' tumor, osteosarcoma and alveolar soft part sarcoma who had isolated brain metastasis, suggest that a subset of patients may benefit from therapy.
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http://dx.doi.org/10.1007/s11060-004-4840-yDOI Listing
January 2005

Ewing's sarcoma of the axial system in patients older than 15 years: dismal prognosis despite intensive multiagent chemotherapy and aggressive local treatment.

Jpn J Clin Oncol 2004 Nov;34(11):667-72

Medical Oncology Department, Istanbul Medical Faculty, University of Istanbul, Istanbul, Turkey.

Background: Older age and axial location of Ewing's sarcoma have been reported as unfavorable prognostic factors.

Methods: The records of patients older than 15 years with the Ewing's family of tumors were reviewed retrospectively. After the induction chemotherapy consisting of alternating vincristine, adriablastin, cyclophosphamide (VAC) and etoposide, ifosfamide with mesna protection (IE), a local treatment modality was chosen based on tumor and patient characteristics.

Results: Twenty-five patients with a median age of 19 years were evaluated. Median follow-up was 26 months (range 4-58). Seventeen patients (68%) had died. In univariate analysis, factors predictive of shorter survival were the patients presenting with metastatic disease, with the primary tumor located at the pelvis, those who never achieved complete response to chemotherapy and those who had chemotherapy for <12 months. Only a negative link with pelvic location was observed in multivariate analysis [risk ratio 7.5; 95% confidence interval (CI) 1.52-37.06; P = 0.0134]. Median progression-free survival (PFS) and overall survival (OS) were 10 months (95% CI 6.2-13.8) and 14 months (95% CI 9.3-18.7), respectively. Cumulative 2-year PFS and OS were 19.0% (95% CI, SD +/-8.4) and 32.7% (95% CI, SD +/-9.8), respectively.

Conclusions: The prognosis of patients with axial Ewing's sarcoma is dismal despite an intensive, multimodality approach including multiagent, alternating chemotherapy, surgery and/or radiotherapy. A more aggressive approach should be considered for this group of Ewing's sarcoma patients.
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http://dx.doi.org/10.1093/jjco/hyh122DOI Listing
November 2004