Publications by authors named "Yavuz Anacak"

32 Publications

Primary extranodal lymphoma of the glands. Literature review and options for best practice in 2019.

Crit Rev Oncol Hematol 2019 Mar 18;135:8-19. Epub 2019 Jan 18.

APHP, Henri Mondor University Hospital, Department of Radiation Oncology and Henri Mondor Breast Center, University of Paris - Est Créteil (UPEC), INSERM, U955 Eq07, Créteil, France.

Primary extranodal non-Hodgkin's lymphomas (EN-NHL) are a heterogeneous group of malignancies that involve numerous entities with significant difference in terms of tumor site locations, prognostic factors, biology expression, and therapeutic options. In the literature, many EN-NHL types were reported from limited series which only allowed narrow views for elucidating prognostic factors and defining the role of loco-regional therapies in the era of new systemic and biologically targeted therapies. The Rare Cancer Network (RCN), an international multidisciplinary consortium, has published a number of reports on several EN-NHL sites which included many gland locations. In this review, we will focus on the recent literature for a selected number of EN-NHL types in both exocrine and endocrine gland locations. We aim to provide renewed and clear messages for the best practice in 2019 for diagnosis, histopathology, treatments, and also their prognostic implications. We believe that better understanding of molecular and genetic characteristics of these particular diseases is crucial for an appropriate management in the era of personalized treatment developments.
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http://dx.doi.org/10.1016/j.critrevonc.2019.01.005DOI Listing
March 2019

Role of consolidative radiation therapy for patients with mediastinal diffuse large B-cell lymphoma in the rituximab era.

J Cancer Res Ther 2018 Oct-Dec;14(6):1397-1402

Department of Radiation Oncology, Ege University Medical Faculty, Izmir, Turkey.

Background: The most common subtype of aggressive non-Hodgkin Lymphomas is diffuse large B-cell lymphoma (DLBCL). Mediastinal DLBCL is a distinct entity with unique clinical, pathologic, and genetic features and accepted as a subtype of DLBCL. The aim of this study is to evaluate the patients treated with consolidative radiotherapy (RT) after rituximab-containing chemotherapy for mediastinal DLBCL regarding treatment outcomes and relapse patterns.

Material And Methods: Forty-two patients with the diagnosis of mediastinal DLBCL who were treated at the Ege University Hospital between January 2008 and December 2014 were evaluated. All patients received 2-10 cycles of rituximab-containing chemotherapy schedule (mostly CHOP). RT was delivered to a total dose of 30.6-45 Gy with 1.8 Gy daily fractions in 4-5 weeks. The irradiation fields were designed by using involved lymphatic site technique.

Results: The median age at diagnosis was 53 years (range, 18-85 years). Ann Arbor clinical stage at diagnosis was as follows: 8 patients (19%) at Stage I, 20 patients (47.6%) at Stage II, 7 patients (16.7%) at Stage III, and 7 patients (16.7%) at Stage IV. The median follow-up period was 47 months (range, 7-96 months). Complete response was obtained in 27 patients (64.3%), partial response was obtained in 14 patients (33.3%) across all stages. Estimated 5-year overall survival (OS) and progression-free survival (PFS) rates were, respectively, 84% and 77% for all patients, 100% and 92% for the patients without residual disease after chemotherapy.

Conclusion: The response to chemotherapy is the most important factor affecting both OS and PFS. The role of consolidative RT is not clear in the rituximab era due to the lack of phase III trial. However, available literature shows that consolidative RT may still have a role in mediastinal DBLCLs.
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http://dx.doi.org/10.4103/jcrt.JCRT_3_17DOI Listing
February 2019

Is there an increased risk of spinal relapse in standard-risk medulloblastoma/primitive neuroectodermal tumor patients who receive only a reduced dose of craniospinal radiotherapy?

Childs Nerv Syst 2018 09 4;34(9):1657-1662. Epub 2018 Jun 4.

Faculty of Medicine, Department of Radiation Oncology, Ege University, İzmir, Turkey.

Purpose: Medulloblastoma (MBL) is the most common pediatric brain malignancy. Postoperative radiotherapy to the entire craniospinal axis is the standard-of-care but has linked to long-term morbidity. In this study, we analyzed the implication of reduced dose craniospinal radiotherapy (RT) for survival and pattern of relapse in MBL patients.

Material And Methods: The clinical characteristics of 32 consecutively diagnosed medulloblastoma/primitive neuroectodermal tumor patients were analyzed. After surgical resection, a dose of 23.4 Gy of spinal RT with a posterior fossa boost of 30.6 Gy was prescribed to standard-risk patients, whereas high-risk patients received 36 Gy spinal RT with additional boosts to the posterior fossa up to 54 Gy. Then, both groups received the same chemotherapy protocol.

Results: Five-year OS for standard and high-risk patients was 94 and 50%, respectively. When analyzing prognostic factors, postoperative tumor size is the most important one which affects the OS. Ten patients relapsed during follow-up, and there was no isolated spinal relapse in either group.

Conclusion: The risk of isolated spinal relapse does not increase with reduced-dose craniospinal RT, since there is no isolated relapse in either the standard or high-risk groups of patients.
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http://dx.doi.org/10.1007/s00381-018-3842-6DOI Listing
September 2018

Outcome and prognostic factors in 110 consecutive patients with primary uterine leiomyosarcoma: A Rare Cancer Network study.

Chin J Cancer Res 2017 Dec;29(6):521-532

Centre Hospitalier Universitaire Vaudois (CHUV), 1011 Lausanne, Switzerland.

Objective: Primary uterine leiomyosarcomas (ULMS) are rare, and the optimal treatment is controversial. We aimed to assess the outcome and prognostic factors in a multicenter population of women treated for primary ULMS.

Methods: We retrospectively collected data of 110 women treated in 19 institutions of the Rare Cancer Network (RCN). Inclusion criteria consisted of a pathology report confirming the diagnosis of ULMS, aged 18-80 years, complete International Federation of Gynecology and Obstetrics (FIGO) stage information, complete information on treatment, and a minimum follow-up of 6 months. Local control (LC) and locoregional control (LRC), overall survival (OS) and disease-free survival (DFS) rates were computed using the Kaplan-Meier method. Univariate analysis was implemented using the log rank test, and multivariate analysis using the Cox model.

Results: All patients underwent surgery. Seventy-five patients (68%) received adjuvant radiotherapy (RT), including brachytherapy in 18 (16%). Seventeen patients (15%) received adjuvant chemotherapy. Median follow-up was 58 (range, 6-240) months. Five-year OS and DFS rates were 50% and 34%, and LC and LRC rates were 88% and 72%, respectively. On multivariate analysis, independent favorable prognostic factors were younger age, FIGO stage I, small tumor size, previous uterine disease, and no vascular invasion for OS and DFS. FIGO stage was the only favorable factor influencing LRC. Adjuvant local or systemic treatments did not improve the outcomes. Eight patients treated with RT presented a grade 3 acute toxicity, and only one patient with grade 3 late toxicity.

Conclusions: In this large population of primary ULMS patients, we found good results in terms of LC and LRC. Nevertheless, OS remains poor, mainly due to the occurrence of distant metastases. An early diagnosis seemed to improve the prognosis of the patients. Adjuvant local or systemic treatments, or more aggressive surgical procedures such as the Wertheim procedure, did not seem to impact the outcome.
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http://dx.doi.org/10.21147/j.issn.1000-9604.2017.06.06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5775016PMC
December 2017

SIOP PODC Adapted treatment guidelines for low grade gliomas in low and middle income settings.

Pediatr Blood Cancer 2017 12;64 Suppl 5

Great North Children's Hospital, Newcastle upon Tyne, United Kingdom.

Effective treatment of children with low grade glioma (LGG) requires a functioning multi-disciplinary team with adequate neurosurgical, neuroradiological, pathological, radiotherapy and chemotherapy facilities and personnel. In addition, the treating centre should have the capacity to manage a variety of LGG and treatment-associated complications. These requirements have made it difficult for many centers in low and middle-income countries (LMIC) to offer effective treatment and follow up. This article provides management recommendations for children with LGG according to the level of facilities available.
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http://dx.doi.org/10.1002/pbc.26737DOI Listing
December 2017

Recommendations for the treatment of children with radiotherapy in low- and middle-income countries (LMIC): A position paper from the Pediatric Radiation Oncology Society (PROS-LMIC) and Pediatric Oncology in Developing Countries (PODC) working groups of the International Society of Pediatric Oncology (SIOP).

Pediatr Blood Cancer 2017 12;64 Suppl 5

Winship Cancer Institute, Emory University, Atlanta, Georgia, USA.

Pediatric radiotherapy is a critical part of pediatric oncology protocols and the quality of the radiotherapy may determine the future quality of life for long-term survivors. Multidisciplinary team decision making provides the basis for high-quality care. However, delivery of high-quality radiotherapy is dependent on resources. This article provides guidelines for delivery of good quality radiation therapy in resource-limited countries based on rational procurement and maintenance planning, protocol development, three-dimensional planning, quality assurance, and adequate staff numbers and training.
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http://dx.doi.org/10.1002/pbc.26903DOI Listing
December 2017

The role of radiotherapy in local control of nonextremity Ewing sarcomas.

Tumori 2016 Mar-Apr;102(2):162-7. Epub 2016 Feb 19.

Department of Radiation Oncology, Faculty of Medicine, Ege University, Izmir - Turkey.

Purpose: To evaluate the results of radiotherapy and the prognostic factors affecting local control in nonextremity Ewing sarcomas.

Methods: Between 1995 and 2011, 44 patients with nonextremity Ewing sarcomas were treated with radiotherapy. Tumor localizations were pelvis in 23, spine in 13, thoracic region in 5, and cranium in 3 patients. Tumor size was ≥8 cm in 56.8% of patients. Distant metastases were present in 19 of the patients at the time of diagnosis (43.1%). All patients were treated with 12 weeks of neoadjuvant chemotherapy followed by surgery and radiotherapy (45-54 Gy) or radiotherapy alone (54-64.8 Gy). Radiotherapy was applied due to microscopic residue (R1) in 5 patients after the operation and macroscopic tumor in 39 patients (macroscopic residue [R2] and nonresectable tumor).

Results: Median follow-up was 49 months (range 9-195). Local failures developed in 7 patients (15.9%) and local control at 5 years was 81.4%. Local recurrence was detected in 6 patients (6/38) who did not have residual tumor after RT. Progression was detected in 1 patient (1/6) who had residual tumor. All those patients with local failure experienced further distant metastases. Possible prognostic factors such as age (≤17 vs >17), tumor localization, tumor volume (≤8 cm vs >8 cm), and M status at diagnosis (0 vs 1) were not related to local control.

Conclusions: Radiotherapy, either alone or adjuvant to surgery, provides local control in 80% of nonextremity Ewing sarcomas and plays an important role in treatment.
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http://dx.doi.org/10.5301/tj.5000478DOI Listing
September 2016

Successful Treatment With Total Skin Electron Beam Therapy in a Child With Isolated Cutaneous Relapsed AML.

J Pediatr Hematol Oncol 2015 Aug;37(6):e372-4

*Pediatric Hematology †Radiation Oncology, Faculty of Medicine, Ege University, Bornova, Izmir, Turkey.

A 9-year-old girl diagnosed with acute myeloblastic leukemia M4 developed isolated cutaneous relapse. She was given chemotherapy including idarubicin, fludarabine, and cytarabine. Although she developed very severe pancytopenia, increase in the number and size of the lesions was seen. Total skin electron beam therapy was applied to the skin lesions for a total of 18 Gy. All lesions responded to total skin electron beam therapy, some of them completely disappeared. After resolution of the skin findings, she underwent bone marrow transplantation from her matched brother. Twenty-six months after hematopoietic stem cell transplantation she is alive without any event.
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http://dx.doi.org/10.1097/MPH.0000000000000342DOI Listing
August 2015

Long-term outcome of patients with spinal myxopapillary ependymoma: treatment results from the MD Anderson Cancer Center and institutions from the Rare Cancer Network.

Neuro Oncol 2015 Apr 9;17(4):588-95. Epub 2014 Oct 9.

Center of Proton Therapy, Paul Scherrer Institute, Villigen/Würenlingen, Switzerland (D.C.W.); Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas (Y.W., J.L.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (R.M.); Department of Radiation Oncology, Catalan Institute of Oncology, Badalona, Spain (S.V.); Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland (R.Z.); Department of Radiation Oncology, Inselspital, Bern, Switzerland (A.P.); Department of Radiation Oncology, Dr Bernard Verbeeten Instituut, Tilburg, the Netherlands (P.P.); Department of Radiation Oncology, Ege University Medical School, Izmir, Turkey (Y.A.); Department of Radiation Oncology, Faculty of Medicine, Hacettepe University, Ankara, Turkey (G.O.); Department of Robert-Janker-Klinik in Germany, Bonn, Germany (B.B.); Department of Clinical Epidemiology Unit, Department of Community Medicine, Geneva University Hospital, Geneva, Switzerland (G.H.); Department of Medicine I & Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria (M.P.).

Background: Spinal myxopapillary ependymomas (MPEs) are slowly growing ependymal gliomas with preferential manifestation in young adults. The aim of this study was to assess the outcome of patients with MPE treated with surgery, radiotherapy (RT), and/or chemotherapy.

Methods: The medical records of 183 MPE patients (male: 59%) treated at the MD Anderson Cancer Center and 11 institutions from the Rare Cancer Network were retrospectively reviewed. Mean patient' age at diagnosis was 35.5 ± 15.8 years. Ninety-seven (53.0%) patients underwent surgery without RT, and 86 (47.0%) were treated with surgery and/or RT. Median RT dose was 50.4 Gy. Median follow-up was 83.9 months.

Results: Fifteen (8.2%) patients died, 7 of unrelated cause. The estimated 10-year overall survival was 92.4% (95% CI: 87.7-97.1). Treatment failure was observed in 58 (31.7%) patients. Local failure, distant spinal relapse, and brain failure were observed in 49 (26.8%), 17 (9.3%), and 11 (6.0%) patients, respectively. The estimated 10-year progression-free survival was 61.2% (95% CI: 52.8-69.6). Age (<36 vs ≥36 y), treatment modality (surgery alone vs surgery and RT), and extent of surgery were prognostic factors for local control and progression-free survival on univariate and multivariate analysis.

Conclusions: In this series, treatment failure of MPE occurred in approximately one third of patients. The observed recurrence pattern of primary spinal MPE was mainly local, but a substantial number of patients failed nonlocally. Younger patients and those not treated initially with adjuvant RT or not undergoing gross total resection were significantly more likely to present with tumor recurrence/progression.
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http://dx.doi.org/10.1093/neuonc/nou293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4483075PMC
April 2015

Prognostic significance of bcl-2, c-myc, survivin and tumor grade in synovial sarcoma.

Turk Patoloji Derg 2014 ;30(1):55-65

Department of Pathology, Manisa State Hospital, MANİSA, TURKEY.

Objective: We aimed to determine the prognostic value of bcl-2, c-myc and survivin in synovial sarcoma cases and to evaluate the relationship between the conventional morphological findings with prognosis.

Material And Method: In this study, we evaluated 81 synovial sarcoma cases referred to our tertiary tumor center during a period of 20 years. We applied bcl-2, c-myc and survivin immunohistochemically and investigated the relationship with prognosis for those 65 cases with follow-up. The relationship between the conventional morphological findings (mitosis, necrosis, grade) with prognosis was also investigated.

Results: Five-year disease free survival rate was 44% and ten-year progression free survival rate was 38%, reflecting the aggressive behavior of synovial sarcoma. Tumor grade (according to FNCLCC) was the most significant prognostic input in this study. We obtained a significant difference between grade II (40 cases) and grade III (24 cases) group regarding progression-free survival and overall survival (p < 0.001 and p < 0.001 respectively). Grade II was divided into two groups according to mitotic index and necrosis (grade IIa and IIb) and there was a significant difference between them regarding prognosis (p=0.013 for progression free survival, p=0.003 for overall survival). There was a significant relationship between bcl-2 negative plus focally weak positive cases (9 cases) and focally strong cases (21 cases) and diffuse strong cases (35 cases) (p=0.042 and p=0.016 respectively). There was a significant relation between c-myc negative cases (25 cases) and nuclear positive cases (17 cases) regarding overall survival (p=0.043) and between c-myc negative cases and cytoplasmic positive cases (23 cases) regarding progression free survival (p=0.05). The relation between survivin and prognosis was not significant.

Conclusion: Tumor grade was the most significant prognostic parameter in this study. The grade IIa group (with less than 10 mitoses in 10 HPF, without necrosis) had a better prognosis than both the grade IIb and III groups. The grade IIb group was closer to grade III regarding the prognosis. Bcl-2 and c-myc (nuclear and/or cytoplasmic) immunohistochemical positivity had prognostic value but this finding has to be confirmed by large series.
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http://dx.doi.org/10.5146/tjpath.2013.01221DOI Listing
July 2014

Radiotherapy capacity in European countries: an analysis of the Directory of Radiotherapy Centres (DIRAC) database.

Lancet Oncol 2013 Feb 24;14(2):e79-86. Epub 2013 Jan 24.

Applied Radiation Biology and Radiotherapy Section, International Atomic Energy Agency, Vienna A-1400, Austria.

Radiotherapy is used for cure or palliation in around half of patients with cancer. We analysed data on radiotherapy equipment in 33 European countries registered in the Directory of Radiotherapy Centres (DIRAC) database, managed by the International Atomic Energy Agency. As of July, 2012, Europe had 1286 active radiotherapy centres. The average number of teletherapy machines per radiotherapy centre ranged from 1·2 to 7·0 in different countries. Nordic countries, the UK, the Netherlands, and Slovenia all have large centres with four to ten teletherapy machines. Most western and southern European countries have several small centres with one or two machines, with few larger centres. The fragmentation in radiotherapy services that prevails in many European countries might affect the economic burden of radiotherapy and its quality. Eastern and southeastern European countries need to expand and modernise their radiotherapy equipment.
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http://dx.doi.org/10.1016/S1470-2045(12)70556-9DOI Listing
February 2013

Validation of the Turkish versions of EORTC QLQ-C30 and BR23 modules in breast cancer patients.

Asian Pac J Cancer Prev 2011 ;12(5):1283-7

Department of Radiation Oncology, Ege University Faculty of Medicine, Izmir, Turkey.

Purpose: To test the validity and reliability of The European Organization for Research and Treatment of Cancer (EORTC) core (QLQ-C30) and breast cancer module (QLQ-BR23) for Turkish breast cancer patients.

Patients And Methods: A total of 127 patients treated with radiotherapy (RT) enrolled to this prospective study. EORTC QLQ-C30 and QLQ-BR23 modules applied to patients before initiation of RT and at follow-up period. Statistical analyses were performed by SPSS 13.0.

Results: Questionnaires' were found reliable and valid for Turkish breast cancer patients. Six of the 8 multi-item scales of QLQ-C30 had a high reliability (Cronbach's ? >0.7); where physical functioning and pain scores were less reliable (Cronbach's ? of 0.66 and 0.68 respectively). In the QLQ-BR23, 3 of 5 multi-item scales were reliable; less reliable were breast and arm symptoms scale (Cronbach's ? of 0.65 and 0.61 respectively). In our analysis the most determinative subscales of QLQ-C30 on global health was emotional functioning followed by fatigue, role functioning and appetite loss (respectively p=0.002, p=0.01; p=0.03 and p=0.08). Among QLQ-BR23 scales systemic therapy SIDE effects, future perspective and upset by hair loss subscales had high impact on global health status (respectively p=0.006; p=0.01 and p=0.03).

Conclusions: The Turkish version of EORTC QLQ-C30 and QLQ-BR23 modules are reliable and valid tools to assess quality of life of Turkish breast cancer patients.
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May 2012

The essential role of radiotherapy in the treatment of Merkel cell carcinoma: a study from the Rare Cancer Network.

Int J Radiat Oncol Biol Phys 2011 Nov 19;81(4):e583-91. Epub 2011 Jul 19.

Department of Radiation Oncology, Inselspital, Bern University Hospital, and University of Bern, Switzerland.

Purpose: To evaluate the role of postoperative radiotherapy (RT) in Merkel cell carcinoma (MCC).

Methods And Materials: A retrospective multicenter study was performed in 180 patients with MCC treated between February 1988 and September 2009. Patients who had had surgery alone were compared with patients who received surgery and postoperative RT or radical RT. Local relapse-free survival (LRFS), regional relapse-free survival (RRFS), and distant metastasis-free survival (DMFS) rates were assessed together with disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) rates.

Results: Seventy-nine patients were male and 101 patients were female, and the median age was 73 years old (range, 38-93 years). The majority of patients had localized disease (n = 146), and the remaining patients had regional lymph node metastasis (n = 34). Forty-nine patients underwent surgery for the primary tumor without postoperative RT to the primary site; the other 131 patients received surgery for the primary tumor, followed by postoperative RT (n = 118) or a biopsy of the primary tumor followed by radical RT (n = 13). Median follow-up was 5 years (range, 0.2-16.5 years). Patients in the RT group had improved LRFS (93% vs. 64%; p < 0.001), RRFS (76% vs. 27%; p < 0.001), DMFS (70% vs. 42%; p = 0.01), DFS (59% vs. 4%; p < 0.001), and CSS (65% vs. 49%; p = 0.03) rates compared to patients who underwent surgery for the primary tumor alone; LRFS, RRFS, DMFS, and DFS rates remained significant with multivariable Cox regression analysis. However OS was not significantly improved by postoperative RT (56% vs. 46%; p = 0.2).

Conclusions: After multivariable analysis, postoperative RT was associated with improved outcome and seems to be an important component in the multimodality treatment of MCC.
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http://dx.doi.org/10.1016/j.ijrobp.2011.05.028DOI Listing
November 2011

Primary mucosa-associated lymphoid tissue lymphoma of the salivary glands: a multicenter Rare Cancer Network study.

Int J Radiat Oncol Biol Phys 2012 Jan 13;82(1):315-20. Epub 2010 Nov 13.

Department of Radiation Oncology, Ege University Medical School, Izmir, Turkey.

Purpose: Involvement of salivary glands with mucosa-associated lymphoid tissue (MALT) lymphoma is rare. This retrospective study was performed to assess the clinical profile, treatment outcome, and prognostic factors of MALT lymphoma of the salivary glands.

Methods And Materials: Thirteen member centers of the Rare Cancer Network from 10 countries participated, providing data on 63 patients. The median age was 58 years; 47 patients were female and 16 were male. The parotid glands were involved in 49 cases, submandibular in 15, and minor glands in 3. Multiple glands were involved in 9 patients. Staging was as follows: IE in 34, IIE in 12, IIIE in 2, and IV in 15 patients.

Results: Surgery (S) alone was performed in 9, radiotherapy (RT) alone in 8, and chemotherapy (CT) alone in 4 patients. Forty-one patients received combined modality treatment (S + RT in 23, S + CT in 8, RT + CT in 4, and all three modalities in 6 patients). No active treatment was given in one case. After initial treatment there was no tumor in 57 patients and residual tumor in 5. Tumor progression was observed in 23 (36.5%) (local in 1, other salivary glands in 10, lymph nodes in 11, and elsewhere in 6). Five patients died of disease progression and the other 5 of other causes. The 5-year disease-free survival, disease-specific survival, and overall survival were 54.4%, 93.2%, and 81.7%, respectively. Factors influencing disease-free survival were use of RT, stage, and residual tumor (p < 0.01). Factors influencing disease-specific survival were stage, recurrence, and residual tumor (p < 0.01).

Conclusions: To our knowledge, this report represents the largest series of MALT lymphomas of the salivary glands published to date. This disease may involve all salivary glands either initially or subsequently in 30% of patients. Recurrences may occur in up to 35% of patients at 5 years; however, survival is not affected. Radiotherapy is the only treatment modality that improves disease-free survival.
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http://dx.doi.org/10.1016/j.ijrobp.2010.09.046DOI Listing
January 2012

Twinning partnerships through International Atomic Energy Agency (IAEA) to improve radiotherapy in common paediatric cancers in low- and mid-income countries.

Radiother Oncol 2009 Nov 10;93(2):368-71. Epub 2009 Sep 10.

Applied Radiation Biology and Radiotherapy, Division of Human Health, IAEA and Department of Radiotherapy and Oncology, University of Turku, Finland.

Purpose: The article summarises the current use of radiotherapy (RT) in childhood cancer and suggests methods to improve current practice in regions where outcomes of paediatric cancer patients are inferior to those of high-income countries.

Methods And Materials: The International Atomic Energy Agency (IAEA) is supporting low- and mid-income countries (LMICs) in upgrading cancer care where nuclear applications, particularly RT, are used. A consensus meeting of experts was invited to advise IAEA on the needs for RT in paediatric cancer patients. The current indications for RT were reviewed, together with regional differences in access, practice and outcome.

Results: Regional variations in the use of evidence-based multidisciplinary care including RT were associated with varying outcomes of paediatric cancer patients. The contribution of modern and investigational technology to these differences is uncertain and should be determined in clinical trials. Adequate resources are required to support children through the acute phase of treatment and to permit early recognition and management of late effects. An IAEA sponsored project for prospective data collection to assess the current and future status of radiation treatment in childhood cancer in LMICs has commenced.

Conclusion: RT remains an essential component of the multidisciplinary management of many paediatric cancers. Excessive variations in outcome are inappropriate and call for action on harmonising training programmes and compliance with evidence-based recommendations. Training projects targeting paediatric cancer care are being implemented and clinical studies comparing new technologies against evidence-based approaches are needed to achieve this goal. The IAEA has an important role in these activities and has commenced prospective data collection in 13 LMICs to monitor trends in treatment techniques and outcomes.
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http://dx.doi.org/10.1016/j.radonc.2009.08.018DOI Listing
November 2009

The results of surgery, with or without radiotherapy, for primary spinal myxopapillary ependymoma: a retrospective study from the rare cancer network.

Int J Radiat Oncol Biol Phys 2009 Jul 26;74(4):1114-20. Epub 2009 Feb 26.

Department of Radiation Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

Purpose: The aim of this study was to assess the outcome of patients with primary spinal myxopapillary ependymoma (MPE).

Materials And Methods: Data from a series of 85 (35 females, 50 males) patients with spinal MPE were collected in this retrospective multicenter study. Thirty-eight (45%) underwent surgery only and 47 (55%) received postoperative radiotherapy (RT). Median administered radiation dose was 50.4 Gy (range, 22.2-59.4). Median follow-up of the surviving patients was 60.0 months (range, 0.2-316.6).

Results: The 5-year progression-free survival (PFS) was 50.4% and 74.8% for surgery only and surgery with postoperative low- (<50.4 Gy) or high-dose (>or=50.4 Gy) RT, respectively. Treatment failure was observed in 24 (28%) patients. Fifteen patients presented treatment failure at the primary site only, whereas 2 and 1 patients presented with brain and distant spinal failure only. Three and 2 patients with local failure presented with concomitant spinal distant seeding and brain failure, respectively. One patient failed simultaneously in the brain and spine. Age greater than 36 years (p = 0.01), absence of neurologic symptoms at diagnosis (p = 0.01), tumor size >or=25 mm (p = 0.04), and postoperative high-dose RT (p = 0.05) were variables predictive of improved PFS on univariate analysis. In multivariate analysis, only postoperative high-dose RT was independent predictors of PFS (p = 0.04).

Conclusions: The observed pattern of failure was mainly local, but one fifth of the patients presented with a concomitant spinal or brain component. Postoperative high-dose RT appears to significantly reduce the rate of tumor progression.
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http://dx.doi.org/10.1016/j.ijrobp.2008.09.034DOI Listing
July 2009

Medulloblastoma: clinicopathologic evaluation of 42 pediatric cases.

Childs Nerv Syst 2009 Mar 13;25(3):353-6. Epub 2009 Jan 13.

Department of Pathology, Ege University Faculty of Medicine, Izmir, Turkey.

Purpose: The aim of this study was to assess the prognostic value of MIB-1 and p53 in the pediatric medulloblastoma group.

Materials And Method: Forty-two pediatric medulloblastoma cases diagnosed in a single institution during the past 10 years were evaluated. Follow-up data were available for 35 patients.

Results: The immunoreactivity of MIB-1 ranged from 10% to 95%; p53 immunoreactivity was found in five cases. Of the 35 patients with follow-up, 34 patients received a combination of chemotherapy and radiotherapy, while one received chemotherapy alone. The follow-up period ranged from 5 to 64 months. Of the 35 patients, 21 were alive without any evidence of recurrent disease, three were alive with evidence of recurrent disease and 11 died of disease during follow-up. The mean survival for these 11 patients was 21.9+/-10.4 months. Of the 35 cases, 16 had MIB-1 value of 25% or lower and 19 had a value of 26% or more. Of the 16 cases with low MIB-1 value, six died of disease; of the 19 cases with high MIB-1 value, five died of disease. The statistical difference between MIB-1 and prognosis was not significant. Three of the 35 (8.5%) cases were found to be positive with p53 protein; no correlation was observed between p53 immunoreactivity and prognosis.

Conclusion: It appears that the MIB-1 value and p53 immunoreactivity have no relation with prognosis in pediatric medulloblastomas. However, it is convenient to support these findings with large series.
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http://dx.doi.org/10.1007/s00381-008-0784-4DOI Listing
March 2009

Multiple spinal metastases of cranial gliosarcoma: a case report and review of the literature.

J Neurooncol 2008 Jun;88(2):199-204

Department of Radiation Oncology, Ege University Faculty of Medicine, 35100 Bornova, Izmir, Turkey.

Gliosarcoma is a rare brain tumor that consists of both glial and mesenchymal components. We report the case of a 68-year-old female with cranial gliosarcoma metastatic to the spinal cord. Initially, the patient was diagnosed with cranial gliosarcoma and treated with surgical resection followed by radiotherapy. Four months after she completed treatment, she presented with a sudden onset of hemiplegia. MRI (Magnetic Resonance Imaging) scan demonstrated two masses at the thoracic spinal cord. Immediate surgery was performed and the lesions were resected. No further therapy was recommended due to the poor condition of the patient. The patient subsequently died 3 months after diagnosis of the spinal cord metastases. There are about 20 reported cases of metastatic gliosarcoma and most focus on systemic metastases of gliosarcoma. Spinal cord metastases are, however, very rare and here we report such a case. Available literature on metastatic gliosarcoma was also reviewed.
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http://dx.doi.org/10.1007/s11060-008-9550-4DOI Listing
June 2008

Association between the rates of synchronous and metachronous metastases: analysis of SEER data.

Oncology (Williston Park) 2007 Jun;21(7):828-34; discussion 834, 842, 845

Department of Radiation Oncology, Ege University Medical School, Izmir, Turkey.

Patients with cancer are usually staged based on the presence of detectable regional and/or distant disease. However, staging is inexact and cM0 patients may have microscopic metastases (cM0pM1) that later cause relapse and death. Since the clinical tools used to stage patients are fairly similar for different tumors, the ratio of the rates of metachronous to synchronous metastases should be similar for different tumors (hypothesis #1). Improvements in diagnostic tools should have caused the ratio of metachronous-to-synchronous metastases to have decreased over time (hypothesis #2). Finally, the fraction of patients with either metachronous or synchronous metastases should have declined over time due to increased screening and earlier diagnoses (hypothesis #3). To test these hypotheses, Surveillance, Epidemiology, and End Results (SEER) data from 1973-1998 were analyzed for 19 solid tumors. A linear relationship was seen between the rates of metachronous and synchronous metastases, with modestly strong correlation coefficients, consistent with hypothesis #1. Over time, changes in staging methods have not significantly altered the ratio of metachronous/synchronous metastases, contrary to hypothesis #2. Also over time, a decrease in the number of patients with metastases was found, consistent with hypothesis #3. Therefore, the rate of anticipated metachronous metastases can be estimated from the rate of clinically evident metastases at presentation. Changes in screening/staging of disease over time may have reduced the overall fraction of patients with metastases.
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June 2007

Retrospective analysis of seven patients with adult-onset langerhans cell histiocytosis syndromes: A single center experience.

Turk J Haematol 2007 Jun;24(2):75-9

Langerhans cell histiocytosis syndromes have been described as encompassing a range of disorders, such as eosinophilic granuloma, Letterer-Siwe syndrome and Hand-Schüller-Christian disease. These disorders have been mainly diagnosed at early ages of life and are relatively rare entities in adult age groups. In this study, we aimed to retrospectively evaluate the patients with Langerhans cell histiocytosis followed-up in our hospital. Seven patients were treated between 1995 and 2005. Median age of patients was 27.5 (18-40) years. Main complaints were classified as bone pain in multiple sites (100%), polydipsia (28%), lung infiltration (14%), oral mucosal infiltration (14%), and cranial nerve infiltration (14%). Two patients were diagnosed as Hand-Schüller-Christian disease, and the others were accepted as eosinophilic granuloma. There was no bone marrow or any other organ infiltration except lung infiltration in one patient. Bone infiltration was the prominent sign in all patients with a minimum of one to maximum of seven different sites. All patients were alive during the follow-up period. All patients were treated with radiotherapy except one patient treated with chemotherapy regimen started with vincristine plus dexamethasone and continued with cladribine. Three of seven patients were treated with combined modality, one patient with only chemotherapy and the others with only radiotherapy. There was no grade 3-4 hematological or systemic side effects of treatment. Relapses were detected in only two patients as new bone infiltrations which responded completely to radiotherapy. Langerhans cell histiocytosis syndromes have a relatively benign course in adult patients and can be treated with either radiotherapy or chemo-radiotherapy successfully.
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June 2007

Gastric and non-gastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue: A single-center experience.

Turk J Haematol 2007 Jun;24(2):57-63

Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) is a distinct lymphoma with specific clinical and pathological features that occurs in diverse anatomic locations. We conducted this retrospective study to demonstrate our experience in patients with MALT lymphomas and compare our results with the literature. We studied 23 patients with histologically confirmed diagnosis of MALT lymphomas (12 with gastric, 11 with non-gastric localization) treated during the past 13 years. The female/male ratio of patients was 15/8 with a median age at presentation of 56 years (range 27-88 years). 16 patients (70%) with stage I and II, 7 patients (30%) with stage III and IV were admitted. At presentation 93% of patients had good performance status (ECOG<2) and 5 (22%) had B-symptoms. There was no difference between gastric and non-gastric MALT lymphomas when compared with sex, age, ECOG performance status, stage of the disease. Patients were treated with different treatment modality; H. Pylori eradication only (8.6%), radiotherapy only (21.7%), surgery alone (4.%) or followed by radiotherapy (26%) or chemotherapy (21.7%). All the patients are alive with a median 33 months (range 8-153 months) of follow-up and the 5- year PFS in gastric lymphoma and non-gastric lymphoma were 86% and 84% respectively with no statistical difference (p=0.5). Because of the indolent course the prognosis of MALT lymphoma was good regardless of the treatment modalities. The treatment choice should be patient-tailored, taking into account the site, stage, age and other clinical characteristic of patient.
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June 2007

Treatment results of 165 pediatric patients with non-metastatic nasopharyngeal carcinoma: a Rare Cancer Network study.

Radiother Oncol 2006 Oct 11;81(1):39-46. Epub 2006 Sep 11.

Hacettepe University, Oncology Institute, Ankara, Turkey.

Purpose: This Rare Cancer Network (RCN) study was performed in pediatric nasopharyngeal carcinoma (PNPC) patients to evaluate the optimal dose of radiotherapy and to determine prognostic factors.

Patients And Methods: The study included 165 patients with the diagnosis of PNPC treated between 1978 and 2003. The median age was 14 years. There were 3 (1.8%) patients with stage I, 1 (0.6%) with IIA, 10 (6.1%) with IIB, 60 (36.4%) with III, 44 (26.7%) with IVA, and 47 (29%) with IVB disease. While 21 (12.7%) patients were treated with radiotherapy (RT) alone, 144 (87.3%) received chemotherapy and RT. The median follow-up time was 48 months.

Results: The actuarial 5-year overall survival (OS) was 77.4% (95% CI: 70.06-84.72), whereas the actuarial 5-year disease-free survival (DFS) rate was 68.8% (95% CI: 61.33-76.31). In multivariate analysis, unfavorable factors were age >14 years for LRC (p=0.04); male gender for DMFS (p=0.03); T3/T4 disease for LRFS (p=0.01); and N3 disease for DFS (p=0.002) and OS (p=0.002); EBRT dose of less than 66 Gy for LRFS (p=0.02) and LRRFS (p=0.0028); and patients treated with RT alone for LRFS (p=0.0001), LRRFS (p=0.007) and DFS (p=0.02).

Conclusion: Our results support the current practice of using combined radiation and chemotherapy for optimal treatment of NPC. However, research should be encouraged in an attempt to reduce the potential for long-term sequelae in pediatric patients given their relatively favorable prognosis and potential for longevity.
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http://dx.doi.org/10.1016/j.radonc.2006.08.019DOI Listing
October 2006

Daily subcutaneous amifostine administration during irradiation of pediatric head and neck cancers.

Pediatr Blood Cancer 2007 May;48(5):579-81

Department of Radiation Oncology, Ege University Medical School, Turkey.

Five pediatric patients with head and neck cancers were treated with radiotherapy. Subcutaneous injections of 200 mg flat dose amifostine were given 30 min prior to radiation fractions. A total of 129 amifostine injections were done. Grade 3 nausea occurred three times and emesis only once. Hypotension, hypocalcemia, or allergic reactions following injections were not recorded. No grade 3 or 4 mucosal or skin reactions occurred. After 16 months, all patients were alive and disease-free. There were no grade 3 or 4 side effects of radiotherapy on follow-up. Further studies with more patients are required to determine the role of amifostine in pediatric radiation oncology, but these data should contribute to the clinical spectrum of amifostine use in pediatric oncology.
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http://dx.doi.org/10.1002/pbc.20740DOI Listing
May 2007

Outcomes and patterns of failure in solitary plasmacytoma: a multicenter Rare Cancer Network study of 258 patients.

Int J Radiat Oncol Biol Phys 2006 Jan 17;64(1):210-7. Epub 2005 Oct 17.

Department of Radiation Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

Purpose: To assess the outcomes and patterns of failure in solitary plasmacytoma (SP).

Methods And Materials: The data from 258 patients with bone (n = 206) or extramedullary (n = 52) SP without evidence of multiple myeloma (MM) were collected. A histopathologic diagnosis was obtained for all patients. Most (n = 214) of the patients received radiotherapy (RT) alone; 34 received chemotherapy and RT, and 8 surgery alone. The median radiation dose was 40 Gy. The median follow-up was 56 months (range 7-245).

Results: The median time to MM development was 21 months (range 2-135), with a 5-year probability of 45%. The 5-year overall survival, disease-free survival, and local control rate was 74%, 50%, and 86%, respectively. On multivariate analyses, the favorable factors were younger age and tumor size <4 cm for survival; younger age, extramedullary localization, and RT for disease-free survival; and small tumor and RT for local control. Bone localization was the only predictor of MM development. No dose-response relationship was found for doses >30 Gy, even for larger tumors.

Conclusion: Progression to MM remains the main problem. Patients with extramedullary SP had the best outcomes, especially when treated with moderate-dose RT. Chemotherapy and/or novel therapies should be investigated for bone or bulky extramedullary SP.
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http://dx.doi.org/10.1016/j.ijrobp.2005.06.039DOI Listing
January 2006

Evaluation of the effects of radiotherapy to the chiasm and optic nerve by visual psychophysical and electrophysiologic tests in nasopharyngeal carcinoma.

Int J Radiat Oncol Biol Phys 2004 Mar;58(4):1141-6

Department of Radiation Oncology, Ege University Faculty of Medicine, Izmir, Turkey.

Purpose: To evaluate the effects of high-dose radiotherapy (RT) to the chiasm and optic nerves in locally advanced nasopharyngeal carcinoma patients by visual psychophysical and electrophysiologic tests.

Methods And Materials: A series of visual tests, including visual evoked potentials (VEPs), contrast sensitivity, and visual field and visual acuity tests, were administered to 27 patients with locally advanced (T4) nasopharyngeal carcinoma who had undergone RT to high doses 6 to 74 months previously. As a control group, the same tests were administered to 40 unirradiated patients who had been referred to the ophthalmology department for any reason.

Results: The median values of VEP latency, VEP amplitude, and contrast sensitivity and the rate of visual field defect were significantly worse in the RT group (p = 0.06, p <0.001, p <0.001, and p = 0.005, respectively). No dose-response relationship was found in any tests when 50 Gy was the cutoff value. However, a positive correlation between the interval after RT and VEP latency (r = 0.406, p = 0.003) and a negative correlation between the interval and contrast sensitivity (r = -0.499, p <0.001) was noted; no correlation could be established regarding VEP amplitude and the interval after RT.

Conclusion: Radiation-induced injury to the anterior visual pathways could result in an increase in VEP latency and a decrease in VEP amplitude and contrast sensitivity. This injury seems to be a continuous process developing with time.
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http://dx.doi.org/10.1016/j.ijrobp.2003.08.014DOI Listing
March 2004

Radiotherapy-induced secondary cranial neoplasms in children.

Childs Nerv Syst 2004 Jan 29;20(1):46-9. Epub 2003 Jul 29.

Department of Pediatrics, Division of Pediatric Oncology, Ege University School of Medicine, 35100, Izmir, Turkey.

Background: Secondary malignant neoplasms (SMN) in CNS tumor survivors has become problem of increasing concern over the last 20 years. These tumors usually occur in a different site from the primary brain tumor several years after treatment.

Case Report: We report secondary cranial malignant neoplasms in three patients who were treated with irradiation and chemotherapy for their primary brain tumors. The first case is a male survivor of an orbital rhabdomyosarcoma who developed a meningioma 8 years later. The other two cases are female survivors of ependymomas who were irradiated at the age of 3 and developed secondary gliomas 8 and 17 years after therapy respectively.

Conclusion: Patients carry a risk of developing SMNs many years later since irradiation is still an important part of the treatment. An SMN may have a benign course, as in meningioma, or be a dilemma for the patient, as in glioblastoma.
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http://dx.doi.org/10.1007/s00381-003-0798-xDOI Listing
January 2004

Total skin electron irradiation: evaluation of dose uniformity throughout the skin surface.

Med Dosim 2003 ;28(1):31-4

Department of Oncology, Rambam Medical Center, Haifa, Israel.

In this study, in vivo dosimetic data of 67 total skin electron irradiation (TSEI) treatments were analyzed. Thermoluminescent dosimetry (TLD) measurements were made at 10 different body points for every patient. The results demonstrated that the dose inhomogeneity throughout the skin surface is around 15%. The homogeneity was better at the trunk than at the extratrunk points, and was worse when a degrader was used. There was minimal improvement of homogeneity in subsequent days of treatment.
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http://dx.doi.org/10.1016/S0958-3947(02)00235-2DOI Listing
August 2003

Radiotherapy in maxillary sinus carcinomas: evaluation of 79 cases.

Rhinology 2003 Mar;41(1):44-8

Ege University, Faculty of Medicine, Department of Radiation Oncology, Izmir, Turkey.

Purpose: The aim of this study is to evaluate the outcome of patients with maxillary sinus carcinoma after radiotherapy regarding local control, prognostic factors and morbidity of treatment.

Materials And Methods: Between January 1983 and December 1996, 79 cases of maxillary sinus carcinoma without any evidence of distant metastases, were treated with radiotherapy.

Results: Fifty-two patients (65.8%) were male and 27 (34.2%) were female. The median age was 57. Histologically 62% were epidermoid carcinoma, 32.9% were non-epidermoid carcinoma and 5.1% were unclassified. Sixteen patients (20.5%) had T2, 25 (29.8%) had T3 and 38 (49.7%) had T4 tumour while 13 patients (16.5%) had lymph node metastases. Fifty-nine patients (74.4%) underwent surgical resection followed by postoperative radiotherapy and 20 patients (25.3%) received radiotherapy alone. The median follow-up was 71 months; 5-year overall survival and local control rates were 53% and 54% respectively. Prognostic factors influencing the overall survival were histologic type (epidermoid carcinoma, p = 0.02), advanced T stage (p = 0.04), postoperative residual tumour (p = 0.002) and lymph node involvement (p = 0.01) whereas the factors influencing local control were histologic type (p = 0.05) and postoperative residual tumour (p = 0.005). Late radiation morbidity were cataract (11.4%), loss of vision (8.9%), trismus (5.1%) and hearing loss (2.5%).

Conclusion: In maxillary sinus carcinomas high rates of local control can be achieved with surgery and radiotherapy. Postoperative radiotherapy can have a positive impact on local control and overall survival especially in patients with early stage tumour of non-epidermoid histology and without residual disease after surgery.
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March 2003