Objectives:The aim of the study was to evaluate the long-term outcome and late effects in pediatric patients with nasopharyngeal carcinoma (NPC) treated with neoadjuvant chemotherapy (NACT), followed by radiotherapy (RT).Methods: Ninety-two children (65 male, 27 female) diagnosed with NPC between 1989 and 2017 in the Istanbul University, Institute of Oncology were evaluated retrospectively. NACT consisted of three cycles of cisplatin-containing regimen every 3 weeks, followed by RT. Results:The median age was 13 years (5-18 years). Most had locoregionally advanced disease (stage III/IVA/IVB) and five had distant metastases at presentation. At a median follow-up of 108 months (3-332 months), 5-and 10-year overall survival rates and event-free survival rates were 87.5%, 79.7% and 82.1%, 78.9%, respectively. Three patients with distant metastasis are long-term survivors. Thirteen patients relapsed at a median of 8 months (2-23 months). Hypothyroidism (36%) and xerostomia (25%) were the most frequent long-term treatment-related toxicities. Nine second malignancies developed in eight patients, eight in the irradiated field at a median of 14 years (range 5-26 years), five of whom are long-term survivors after curative surgery.Conclusions: Three courses of cisplatin-containing NACT, followed by RT lead to high survival and locoregional control rate in advanced stage NPC in children. Patients with distant metastasis should also be treated with curative intent by systemic chemotherapy and locoregional radiotherapy. Patients should be followed closely for recurrences and long-term morbidities including second malignancies, which may be treated with curative surgeries if diagnosed early.
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.
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. In this study the epidemiologic, clinical characteristics and outcome of children with Hodgkin disease treated with a risk adapted treatment over a 25 year period are evaluated. MethodsThis retrospective study evaluates the clinical characteristics and outcome of 122 children treated with the same institutional risk-adapted protocol in the Istanbul University, Oncology Institute between 1991-2016. Clinical staging was done according to Ann-Arbor staging, all patients had biopsy confirmation and the WHO histopathological classification was used. Imaging (ultrasound, CT/MRI and/or PET-CT since 2004) was done in all patients. Bone marrow aspiration and biopsy was done for all with B symptoms or risk group 2 and 3. Risk group 1 (clinical group IA/B and IIA) recieved 2 courses of ABVD (adriamycin 25 mg/m2, bleomycin 10 U/m2, vinblastin 6 mg/m2 and dacarbazine 375 mg/m2 , day 1 and 15) chemotherapy, risk group 2 (stage IIB and IIIA) 4 courses of ABVD, risk group 3 patients (IIIB,IVA/B) 6 courses of COPP/ABV (cyclophosphamide 600 mg/m2, vincristine 1.4 mg/m2 on day 1, procarbazine 100 mg/m2 day1-7, prednisolone 40 mg/m2 day1-14; adriamycine 35 mg/m2, bleomycin 10 U/m2, vinblastine 6 mg/m2 day 8) chemotherapy, each course administered every 28 days. All patients recieved involved field radiotherapy 15-25 Gy adjusted to age (15 Gy for < 5, 20 Gy for 5-10, 25 Gy for >10 years old), + 5 Gy for bulky disease and/or partial response to chemotherapy. Results There were 83 males and 39 females (M/F: 2.1) with a median age of 10 (2-18) years. The most frequent histological subtypes were mixed cellularity (41%) and nodular sclerosing (41%). The most common involved site was the neck (cervical and supraclavicular lymph nodes) (%85). The median follow up period was 6 1/12 years (1-25 years). The 5 year event free survival and survival were 82% and 97% for all patients; they were 86% and 97% for risk 1 (48 patients), 80% and 96% for risk 2 (29 patients), 79% and 97% for risk 3 (45 patients) . B symptoms were present in 46%; %54 were staged as I-II; 46% as stage III-IV. When classified according to two time periods: before and after 2000, the median age increased [9 (2-17) vs 11 (3-18) years], M/F ratio decreased [2.7 (36/13) vs 1.8 (47/26)] and the most common histological subtype were mixed cellularity (51%) vs nodular sclerosing (49%) respectively. The 5 year event free survival and survival were 79% and 95% before 2000 and 83,5% and 98% after 2000 respectively. Ebstein Barr Virus-Latent membrane Protein (EBV-LMP1) was found to be positive by immunohistochemistry in all tumor samples of 21 patients analyzed, all were treated before 2000. During follow-up no clinically evident cardiotoxicity or pulmonary toxicity has been observed. Three patients developed secondary tumors (Langerhans cell histiocytosis, schwannoma, non-Hodgkin's lymphoma). ConclusionThe epidemiologic features of HL is related to socioeconomic status. In our cohort, the oberved change in epidemiologic features within 25 years, such as the increase in median age, decrease in the M/F ratio and increase in nodular sclerosing subtype, is thought to be related to the socioeconomic development. A high survival rate has been achieved with the institutional risk-adapted protocol for all risk groups. The use of risk adapted protocols providing efficient and least toxic treatment is very important in pediatric Hodgkin lymphoma. Disclosures No relevant conflicts of interest to declare.
e22007 Background: Retinoblastoma (RB) is the most common intraocular malignancy in children, caused by mutations in the tumor suppressor RB1 gene. Patients with bilateral/trilateral/familial RB are considered to have hereditary RB (1 germline, 1 somatic mutation); although most unilateral RB are nonhereditary (2 somatic mutations), some have germline RB1 mutation. Identification of RB1 mutations and genetic counseling is essential to assess the risk of developing RB in the patients´ relatives and to prevent the disease. The aim of this study is to assess the frequency/type of RB1 gene mutations in a large cohort of Turkish RB cases. Methods: RB1 gene mutation screening was performed in peripheral blood samples of 219 individuals (122 children with RB/14 family members with RB/83 healthy family members of 47 probands with RB1 mutations) followed in the Istanbul University, Oncology Institute. All 27 exons and close intronic regions of the RB1 gene were sequenced for small deletions and insertions using the Sanger sequencing (2013-2018) or Next Generation Sequencing (2019-2021); large deletions and duplications were investigated both by Multiplex Ligation Probe Amplification (MLPA) and copy number variation (CNV). Correlation with demographic and clinical data were evaluated. Results: After RB1 mutation screening, mutations were detected in 57 (41.9%) of 136 patients. RB1 mutations was observed in 23/84 (27.4%) patients with unilateral RB, in 30/47 (63.8%) bilateral RB, in 3/3 trilateral RB, and1/2 unilateral retinoma. Of these mutations, 45 (78.9%) were small genetic rearrangements and 12 (21.1%) large genetic rearrangements. Frameshift mutations were found in 11, nonsense in 18, splice error in 11, and missense mutation in 1, synonymous substitution in 2, upstream substitution in 2 patients. Ten novel mutations were found. Three of 83 healthy family members also had germline RB1 mutation. The disease was hereditary in 13 (22.8%); and de novo (77.2 %) in 44 of the 57 patients with mutations. Three siblings were found to have RB1 mutation, while their parents did not. Patients diagnosed as infants (RB1 mutation found in 63.2% of 70 infants vs in 36.8% of older ones, p:0.021); those with bilateral/trilateral RB (66 vs 27.4%, p:0.0001); those with light (green-blue) iris color vs dark color (71.4% vs 36.5%. p:0.003) had higher frequency of RB1 gene mutation. There was no significant correlation regarding gender or ICRB stage and RB1 mutation frequency. Conclusions: RB1 gene mutation was found in 41.9% of Turkish children with RB, in 63.8% of bilateral and 27.4% of unilateral RB. 10 novel mutations of the RB1 gene were found according to the Leiden Open Variation Database and the Human Gene Mutation Database.The mutation frequency was significantly higher in patients with bilateral/trilateral RB, in infants, in those with light iris color. In bilateral RB with no RB1 mutation, other genes/RB1 gene methylation and expression status may play a role in the pathogenesis.
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