Objective: Triple negative breast cancer is an aggressive variant of breast cancer; it forms about 15% of breast cancer cases. It lacks the responsiveness to hormonal and targeted therapies. Anthracyclines remain the treatment option for these patients. Anthracyclines are cardiotoxic, so predicting sensitivity of response by biological predictors may have a role in selecting suitable candidates for these drugs. Material and methods: This study included 50 TNBC cases, from National Cancer Institute, Cairo University(NCI-CU), Egypt, who underwent surgery and received adjuvant chemotherapy. Archived blocks were obtained and immunostaining for Ki-67 LI and Fluorescent In situ Hybridization (FISH) technique to assess TOP2A gene copy number and chromosome 17CEP status were done. Analysis of association between TOP2A alterations and CEP17 polysomy as well as Ki-67 LI with other clinicopathological parameters was done. Associations between the biological markers and event free survival (EFS) and overall survival (OS), were also performed. Results: TOP2A alteration was seen in 9/50 cases (5 amplified and 4 deleted). CEP17 Polysomy was detected in 14% of cases. Most of patients (80%) showed Ki-67 LI ≥20%. There was a significant association between TOP2A gene and CEP17 status. Outcome was better with abnormal TOP2A gene status and CEP17 polysomy, radiotherapy and combined anthracyclines and taxanes in the adjuvant setting, however P-values were not significant. Conclusion: TOP2A gene alterations and CEP17 polysomy may have prognostic and predictive role in TNBC treated with adjuvant Anthracyclines.
Background: Neuroblastoma (NB) is remarkable for its wide spectrum of clinical behavior and biological characteristics in relation to outcome. The use of aggressive therapy, including autologous hematopoietic stem cell transplantation (HSCT) and the addition of isoretionin (cis-Retinoic Acid/cis-RA), has increased survival rates of patients with advanced disease. Methods: Pediatric 271 newly diagnosed high risk NB patients were prospectively enrolled into the study. Patients received neoadjuvant chemotherapy of alternating cycles: [cyclophosphamide, doxorubicin, vincristine (CAdO)] and [etoposide, carboplatin]. Intensification courses of "ICE" (ifosfamide, carboplatin, and etoposide) regimen were administered to patients with bone marrow (BM) residual infiltration. Whenever safely feasible, complete surgical resection or debulking of the primary tumor was attempted for patients achieving partial response. Eligible patients underwent HSCT, while radiation therapy to the primary and metastatic sites, as well as maintenance with cis-RA was given for 6 months. Results: The median age of our patients was 2.8 years with male to female ratio of 1.65:1. At 4 years, the overall and event free survivals were 33.7% and 23.3% for the entire group under study, with significantly higher rates (42.7% and 35.6%, respectively) for HSCT patients (n = 94; p < 0.001). The outcome was also significantly correlated with response to induction therapy, pathological subtype, as well as other variables. Conclusion: Myeloablative therapy followed by stem cell rescue is regarded as the most important goal of high risk NB treatment to improve survival till present. Each of consolidation HSCT, post induction disease status, as well as international neuroblastoma pathology classification (INPC) subtype was an independent predictive variable of survival. A collaborative effort with an emphasis on biologic characteristics of aggressive disease and tailored therapy needs to be strengthened to further our understanding of this disease.
Background:Treatment of non‐Hodgkin lymphoma (NHL) is an example of successful therapy of cancer in children with a cure rate approximating 80%. Unfortunately, relapsed NHL has a dismal outcome, and customary treatment is by highly toxic chemotherapy followed by hematopoietic stem cell transplantation (HSCT).Aims:To analyze prognostic factors, and to report treatment outcome of relapsing/refractory mature B cell NHL.Methods:A retrospective analysis including all patients less than 18 years initially diagnosed as mature B cell NHL who were primary refractory to chemotherapy or relapsed during the period between July 2012 till end of 2017 at the Children Cancer Hospital Egypt (CCHE).Results:Out of 494 patients diagnosed during the study period, 34 (7%) were included in our study. Twenty‐three (67.6%) had Burrkitt lymphoma, while 5 (14.7%) had diffuse large B cell lymphoma. The majority were males (79.4%), with a median age 6.2 years. According to Modified Murphy Staging, 6 patients (17.6%) were stage II, 24 (70.6%) stage III, and 4 (11.8%) stage IV. Bone marrow (BM) involvement at presentation was detected in 2 patient, and 3 (8.8%) had CNS infiltration. Thirty patients (88.2%) received LMB protocol, and 4 (11.8%) R‐CHOP as primary chemotherapy. One patient (2.9%) was treated as low risk, 28 (82.4%) as intermediate, and 5 (14.7%) high risk. Median delay in 1st line treatment was 22 days (range 0 to 162).Twenty two patients (64.7%) relapsed, and 12 (35.3%) had tumor progression. Relapse was early in 15 (68.2%), and late in 7 patients (31.8%). It was documented by tissue biopsy in 30 patients (88.2%), and bone marrow aspirate in 3 (8.8%). Patients relapsed other than primary site were 6/34 (17.6%). CNS relapse was detected in 8 (23.5%), BM in 8 (20.5%), while combined BM and CNS in 2 (5.9%). R‐ICE was the 2nd line of treatment in 29 patients (85.3%), and complete 2nd remission (CR) was achieved in 7 patients (20.6%). Allogeneic HSCT was done for 2 patients (5.9%), and autologous HSCT for 3 patients (8.8%). Finally, 7/34 (20.5%) patients were alive in CR, and 24/37 (70.5%) died. The 3 years Overall survival (OS) 35.3%, with no statistical difference between relapsing and progression. The 3 years OS for patient who underwent HSCT was 80% compared 20% for no HSCT (p = 0.034).Summary/Conclusion:Our relapse rate is higher than the literature probably due to delay of chemotherapy with loss of dose intensity. For patients in second remission, HSCT markedly improves the outcome.
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