Pulmonary artery intimal sarcoma (PAIS) is a rare and aggressive malignancy originating from the intimal layer of the pulmonary artery with poor prognosis due to its aggressive nature. The management of PAIS poses both diagnostic and therapeutic challenges. It presents with nonspecific symptoms and is often misdiagnosed as pulmonary embolism. While surgical resection is the primary treatment modality, the role of adjuvant chemotherapy and radiotherapy remains uncertain. However, given the high recurrence rate, adjuvant chemotherapy and/or radiotherapy have been utilized in a limited number of case reports. We present the case of a 46-year-old woman who was diagnosed with PAIS and underwent surgical resection followed by adjuvant chemotherapy (ChT) and radiotherapy (RT), demonstrating good tolerance to this multimodal treatment approach.

10045 Background: The prognosis of children with diffuse intrinsic pontine gliomas (DIPG)/diffuse midline glioma (DMG) is dismal. Radiotherapy (RT) is considered the standard of treatment. We previously published results of our center, where patients receiving temozolomide or other chemotherapy after radiotherapy (RT) had a better survival than those receiving RT alone (1). This study aims to evaluate a larger cohort of children with DMG in a single center. Methods: We retrospectively reviewed demographic, clinical characteristics and treatment outcome of children with DMG diagnosed and treated at Istanbul University, Oncology Institute between Feb1999-Feb 2023. We compared the groups that received only radiotherapy (Group 1, only RT, n=19), the ones that received RT with concomitant and adjuvant temozolomide po (Group 2-n= 38 TMZ 75 mg/m2/day for 6 weeks concomitant (c.) with RT, followed by TMZ (200 mg/m2/day) for 5 days every 28 days until progression or for 12 cycles), and the ones that received RT with c. TMZ, followed by other systemic agents (Group 3 n= 18 RT c.TMZ, followed by nimotuzumab containing regimens; Group 4 the rest 26 received other agents such as bevacizumab, CCNU, ONC201 and other). The ones that progressed on group 2, received nimotuzumab containing or other regimens. Results: 114 children (49 female, 65 male) with a mean age of 7± 4 years (6 months-16 years) were analyzed. The most frequent clinical findings were ataxia, strabismus and motor weakness. 108 had diffuse intrinsic pontine gliomas (DIPG). In total 106 patients received RT, 54-60 Gy to the tumor site. The overall survival (OS) in all patients at 2 years, 3 years and 5 years were 25.6%,15% and 11.5% respectively. The 2 years, 3 years and 5 years OS in group1 were 0.79%, 0% ,0% respectively; in group 2 they were 38.4%, 27.9%, 16%respectively ; in group 3 they were 17.6% , 0 % ,0% respectively, in Group 4 they were 10.3%, 0.34%, 0% respectively, The OS in Group 2 or3 or 4 were significantly higher than group 1 (only RT) (P =0.002, p=0.004, p<0.001,respectively). There was no major side effect due to TMZ, nor nimotuzumab. Seven patients were re-irradiated at progression. The number of patients undergoing biopsies and molecular testing increased to 50% of the patients after 2016 versus only in two patients previously. Conclusions: In our series, the overall survival was significantly superior in patients who received RT with concurrent and adjuvant temozolomide and/or adjuvant nimotuzumab containing regimens or other adjuvant systemic treatment in comparison to patients that received RT alone, suggesting that adding systemic treatment after RT (poTMZ or iv nimotuzumab containing regimens or other) may help extend survival. Oral temozolomide may be easier to use as first line treatment after radiotherapy especially in resource limited settings, switching to nimotuzumab containing or other chemotherapy and/or re-radiotherapy at progression. 1. Kebudi R, 2013.

Purpose/Objective(s) Survival is poor in relapsed medulloblastoma. Despite salvage treatments, retaining tumor control is difficult. While the role of re-irradiation in other recurrent brain tumors is growing, strong data/proof of its effectiveness on medulloblastoma is still lacking. Materials/Methods Eighteen years old or younger medulloblastoma patients, who were diagnosed between 1990 and 2020 and underwent re-irradiation for recurrent disease, were evaluated retrospectively. Patient and tumor characteristics, treatment details, progression-free survival (PFS) and overall survival (OS) after recurrence, and acute and late effects of treatment were evaluated. The retrospective study design has been approved by the institutional review board. Results Twenty-seven recurrent medulloblastoma patients who received re-irradiation were included. Six patients were in the standard-risk group, and 21 patients were in the high-risk group at initial diagnosis. Recurrence was intracranial in seven (26%) patients, neuro-axial spread in six (22%) patients, and both intracranial and neuro-axial spread in 14 (52%) patients. Among these patients, 10 of them could be operated on for recurrence. At relapse 19 received craniospinal irradiation (CSI), and eight received focal radiotherapy (RT). One-year and two-year PFS were 57% and 33% and 1-year and 2-year OS were 67% and 44% respectively. In univariate analysis, the median survival after relapse was significantly higher in males (18 vs 78 months p:0.043), in those who had a relapse 24 months after diagnosis (16 vs 88 months p:0.007), and in those who received chemotherapy (ChT) after re-RT (66 vs 8 months p: 0.01). There was no difference in survival between focal irradiation and CSI (p:0.81). One patient has developed multiple basal-cell skin carcinomas in the radiation field. Conclusion In recurrent medulloblastoma, re-irradiation is a treatment option that can increase disease control.

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. 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. 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. 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.

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.

10547 Background: The aim of this study is to evaluate the demographic, clinical and therapeutic characteristics and long-term outcome in childhood nasopharyngeal carcinoma (NPC) in a single center. Methods: Data of 97 patients < 18 years with NPC, treated in the Istanbul University Oncology Institute from November 1989 to January 2018 were evaluated retrospectively. All patients received three courses of neoadjuvant chemotherapy (1989-1991; cisplatinum, 5-fluorouracil; 1992-2008: Bleomycin, epirubicin and cisplatinum- BEP; since 2008-EP) followed by radiotherapy given both to the primary tumor and to the metastatic cervical lymph nodes. Results: Sixty-nine boys and 28 girls (M:F = 2.5) with a median age of 14 yrs (6-18), presented mostly with a lump in the neck, headache, and ear and nose problems. Median follow-up was 83 months (3 months-26.6 years). Ninety percent of the biopsies of NPC were WHO type III tumors. Most patients had advanced stage tumors, 5 had distant metastatis. Chemotherapy was followed with radiotherapy 60-66 Gy to the primary tumor and involved lymph nodes, and 50-54Gy to the uninvolved cervical nodal region. The 10-year overall survival (OS) rate was 79%. There was no significant difference in OS in patients who received BEP or EP. Seventeen patients died, 2 due to accident/suicide, 3 with second primary cancer, 12 with recurrent/progressive disease. Seven second malignancies developed in six patients, six in the irradiated field at a median of 12 years (5- 25 years). Late effects included hypothyroidism, neck fibrosis, xerostomia, bony hypoplasia, skin problems and hearing loss. Conclusions: Children with advanced NPC treated with neoadjuvant chemotherapy and radiotherapy have a high locoregional control rate and much higher long-term survival (OS 79 %) than that reported in our center before 1990's when most recieved only radiotherapy (46%) or radiotherapy and adjuvant chemotherapy (58 %) (IJ Radiation Oncology Biol Phys 1996). Neoadjuvant therapy with EP chemotherapy seems to be as effective as BEP. Survivors should be followed for long-term morbidities, including second malignancies.

Radiotherapy (RT) may result in platelet activation and thrombosis development. To the best of our knowledge, the potential effect of volumetric-modulated arc therapy (VMAT), a novel radiotherapy technique, on platelet function and microRNA (miRNA/miR) expression has not been previously investigated. The present study aimed to determine the effect of VMAT on the alterations in platelet function parameters and miRNA expression levels. A total of 25 patients with prostate cancer and 25 healthy subjects were included in the present study. Blood samples were collected from the patient group on the day prior to RT (pre-RT), the day RT was completed (post-RT day 0), and 40 days following the end of therapy (post-RT day 40). Platelet count, mean platelet volume (MPV) value, platelet aggregation, plasma P-selectin, thrombospondin-1, platelet factor 4, plasma miR-223 and miR-126 expression levels were measured. A significant decrease in platelet count in the post-RT day 0 group was measured in comparison with the pre-RT and the post-RT day 40 groups. Pre-RT MPV values were higher than those of the post-RT day 0 and the post-RT day 40 groups. No significant differences were observed in the levels of platelet activation markers or miR-223 and miR-126 expression levels between the RT groups. Although RT may result in a reduction in platelet and MPV counts, the results of the present study indicate that platelet activation markers are not affected by VMAT. Therefore, it is possible that no platelet activation occurs during VMAT, owing to the conformal dose distributions, improved target volume coverage and the sparing of normal tissues from undesired radiation.

e22009 Background: Bilateral retinoblastomas (BRBS) comprise 25 % of all RBS. Treatment decision depends on tumor burden, potential for vision, status of the contralateral eye. As the survival rate in retinoblastoma has increased, ocular salvage and late effects has become an important issue. The aim of the study is to evaluate the demographic features, treatment modalities, and late effects in BRBS. Methods: BRBS treated in Istanbul University, Oncology Institute and Opthalmology Department between 1990-2016 were retrospectively evaluated. All patients were multidisciplinarily evaluated for chemotherapy (chemoreduction /adjuvant), local opthalmologic therapies (transpupillary thermotherapy, cryotherapy, plaque), radiotherapy, enucleation. The chemotherapy (CT) protocol used had vincristine, cisplatin, etoposide, cyclophosphamide until 2009, and vincristine, etoposide, carboplatin since then. Since 2011, intraarterial, intravitreal CT was also used. Results: 114 BRBS (228 eyes) (56 male, 58 female) with a median age of 9 months (20days-42 mo.) were evaluated. Three had extraocular disease, two trilateral RBS. Seventeen had history of retinoblastoma in their families. According to ICRB classification, there were 67 eyes in group E, 43 group D, 27 group C, 45 group B, and 19 group A. Enucleation was done in 68 (30%) eyes, mostly group E. During 1990-2000, 23/26 patients underwent enucleation, whereas 45/88 underwent enucleation after 2000. Radiotherapy was used for 30 eyes, most before 2000. Bone and soft tissue deformities and cataracts were observed in irradiated patients. Five patients had a second cancer (4 sarcomas, 1 meningioma) at a median of 11 years, four in irradiated sites. The 5 yr survival was 93.5%, 9 patients died, 4 due to second cancer. Conclusions: As the survival rate in intraocular BRBS has increased, ocular salvage and late effects have gained importance. Chemoreduction (systemic, intraarterial) and local ophtalmic therapies enable preservation of vision in most group A, B, C tumors and some D tumors. Most group E tumors require enucleation. Radiotherapy is not used in most RBS in the last decade. Intra-arterial chemotherapy is promising in maintaining ocular salvage.

e22011 Background: The 20 year cumulative risk of second malignancies (SM) in childhood cancer survivors is reported as 3.2 %. The aim of this study is to assess the incidence and outcome of SM in pediatric cancer survivors in a tertiary center in 25 years. Methods: 1500 childhood cancer survivors treated in theIstanbul University, Oncology Institute during 1990-2010 and followed up for at least 5 years from diagnosis were evaluated for second malignancies. Results: 36 SM were identified in 33 survivors at a median of 7 years (1-17) from diagnosis (AML/MDS 3[1-8], solid tumors 9 [2-17] years). The primary diagnosis was sarcomas in 11 ( 5 rhabdomyosarcomas [RMS]), CNS tumor 5, retinoblastoma 4, ALL/MDS/lymphoma 8, neuroblastoma 3, nasopharngeal sarcoma 1, disgerminoma 1. The SM were 12 sarcomas (8 osteosarcomas,1 fibrosarcoma, 1 Ewing Sarcoma, 1 Kaposi sarcoma, 1 leiomyosarcoma), 8 AML/MDS, 3 thyroid cancer, 3 malignant nerve sheath tumors (MNST) , 2 renal cell carcinomas (RCC), 2 breast cancers, 2 glioblastoma multiforme (GBM), 1 non Hodgkin's lymphoma, 1 meningioma, 1 histiocytosis (LCH). Three patients developed two separate SM each. 18 patients had previously recieved radiotherapy: 11 developed solid tumors (5 sarcomas, 3MNST, 1 GBM, 1 meningioma, 1 thyroid cancer) within the radiation field, 3 (2 RMS, 1 LCH) in proximity; 4 developed AML/MDS. 3 had prior HSCT (1 MDS developed osteosarcoma, 2 relapsed lymphomas: AML, LCH). 15 survivors are alive at a median of 4 (1-18) years after SM, 13 with no evidence of disease (NED). 18 have died at a median of 1(0.1-3)year. 1/8 with MDS/AML is alive.All survivors with thyroid cancer, renal cell carcinoma , breast cancer; also 1 MNST, 1 LCH, 6 sarcomas (1 fibrosarcoma , 4 osteosarcomas ,1 Kaposi sarcoma) are with NED, all were detected early during regular surveillance. Conclusions: The risk of SM in our series has increased with longer follow-up,(incidence 2.4 vs 1 %, the number of SM has increased from 16 to 36 in the same cohort from 2011 to 2015), empasizing the need for longer follow-up and regular surveillance which leads to early detection of SM, thus improved survival. Since, the risk of SM is associated with the cumulative dose of some chemotherapeutics, the radiation dose/field; using the most efficient and least toxic protocols is important.

Purpose or Objective:The fear of radiotherapy-induced urinary incontinence (URINC) often contraindicates postprostatectomy RT (POPRT), despite the lack of accurate data about its real incidence and severity.The purpose of this analysis was to analyze clinico-dosimetric factors predicting severe, self-reported URINC 1 and 2 years after POPRT. Material and Methods:In 2012 a longitudinal, observational study aimed at assessing URINC from POPRT including prophylactic whole-pelvis irradiation (WPRT) was activated at our Institute.For the evaluation of urinary toxicity, 2 validated questionnaires, IPSS and ICIQ-SF, are to be filled-in by pts at baseline, at RT mid-point and end, at 3 and 6 months after RT conclusion, and every 6 months thereafter.This analysis pertains to the first 101 pts correctly filling the questionnaires at baseline and at 12 months (60 also at 2 years).Fifty-four and 47 pts were treated with adjuvant (ADV) and salvage (SALV) intent after a median of 4 and 38 months, respectively, from radical prostatectomy (RP), with either conventional (n= 42) or moderately hypofractionated (n=59) regimens, at a median 2-Gy equivalent dose (EQD2) to the prostatic bed of 70 and 74 Gy in ADV and SALV cohort, respectively, and a median EQD2 dose of WPRT of 50 Gy. Results:The mean baseline ICIQ scores were 7.8 and 4.8 in ADV and SALV cohorts, respectively (p = 0.009).The corresponding values at 1 and 2 years were 7.4 vs 7.3 and 8.5 vs 7.9, respectively.Severe URINC (³ 13 points) was recorded in 23% and 19% at 1 year, and in 37% and 21% of pts treated with ADV and SALV intent, respectively (p ≤0.20).The 75th quartiles of ICIQ at 12 (ICIQ12) and 24 (ICIQ24) months (12 and 13 points, respectively), were set as end-points for regression logistic analysis.Several clinico-dosimetric factors, including age, diabetes, hypertension, pT and pN stage, # of removed LNs, RT intent, time from RP to RT, fractionation, EQD2, adjuvant androgen deprivation (AAD), IQIQ and IPSS baseline values were analyzed.Variables with a p-value <0.20 at univariable analysis were entered into a backward stepwise multivariable model indicating baseline ICIQ and nocturia (IPSS item #7) and AAD as predictors of ICIQ12 (AUC 94%), while baseline ICIQ and EQD2 predicted ICIQ24 (AUC 89%). Conclusion:The risk of long-term severe URINC 1 and 2 years after POPRT is strongly modulated by baseline URINC, and by AAD and higher EQD2, respectively (Figure 1).

IntroductionThe survival of children with Hodgkin lymphoma have increased significantly raising the issue of decreasing late effects by using risk adapted treatment. Hodgkin lymphoma has different epidemiologic features in developed and developing countries.

OBJECTIVES: The aim of this study is to identify demographic, clinical and survival features of childhood central nervous system (CNS) tumors admitted to Istanbul University, Oncology Institute, Pediatric Hematology-Oncology in 22 years. METHODS: Charts of patients <19 years admitted were evaluated retrospectively. (Istanbul University Cerrahpasa Medical Faculty Clinical Trials, Ethics Committee no. 83045809-3507). RESULTS: CNS tumors (n = 494) comprised 20,5 % of the 2413 children with cancer, diagnosed between 1990-2012. Male/female:1,25. Median age was 6,5 years (0.13-18yrs). 51 patients had NF1, 4 had tuberosclerosis. Distrubution according to histopathology/diagnosis was as follows: 35 % (n = 173) Medulloblastoma and other embryonal tumors, 17% (n = 84) astrocytoma other than optic gliomas, 16,5% (n = 82) ependymoma and choroid plexus tumors, 14% (n = 69) optic glioma, and 12,8% (n = 63) diffuse pontine gliomas. 5-yrs and 10-yrs overall survival (OS) in the whole group were 61% and 55,4% respectively. 29,6 % of the patients had metastasis in the CSF and/or the spinal axis and/or gross residual tumor, these had 5-yrs and 10-yrs OS of 36,5% and 27,2 %, whereas the rest had 5-yrs and 10-yrs OS are 73% and 68,9% (p < 0,001). Medulloblastoma and other embryonal tumors had 5-yrs and 10-yrs OS 58,4% and 57,5% . Ependymoma and choroid plexus carcinomas had 5-yrs and 10-yrs OS of 48,4% and 31,4%. Low grade and high grade astrocytomas had 10-yrs OS of 95 % and 40% respectively (p < 0,001). Second tumors were diagnosed in two medulloblastoma patients, one malignant nerve sheath tumor at 9 years, a case with concurrent high glade glioma and mediastinal lymphoblastic lymphoma at 3,5 years. CONCLUSIONS: The most common solid tumor in our cohort, similar to developed countries, was CNS tumors. Embryonal tumors comprised the majority of the CNS tumors treated in our institution. 5 year survival was 61 %. These children should be followed up for late effects including second tumors.

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.