P14.101 Glioblastoma survival outcomes related to cortical/neural stem cells regions

Abstract BACKGROUND Subventricular brain zone (SVZ) and hippocampal regions are supposed to harbor astrocyte-like neural stem cells. While some tumors may arise from transformed SVZ stem cells, other may be initiated by neo-plastic transformation of non-SVZ progenitor cells or mature glial cells. Lim′s et al classification (Neuro-Oncology 2007) of initial glioblastoma location, related to these neural stem cells regions, was predictive for invasive and multifocal tumor phenotype. The aim of this retrospective single-institutional study is to evaluate the relations of this Lim classification on survival parameters in unselected cohort of glioblastoma patients. MATERIAL AND METHODS Patients treated between 2014–2017 were grouped according to initial location of their contrast enhancing lesion as follows: Lim1 (SVZ+⋯SVZ/hippocampal involvement and Cortex+⋯cortex involvement), Lim2 (SVZ+ and Cortex-), Lim3 (SVZ- and Cortex+) and Lim4 (SVZ- and Cortex-). All patients underwent radiotherapy, some patients were indicated to full treatment according to Stupp regimen (at least 3 cycles of adjuvant chemotherapy after postsurgery chemoradiotherapy). RESULTS In total, 144 patients were analyzed (94 men, mean age 59 years). 47 patients (30.5%) were treated according to Stupp regimen. Lim1 classification was presented in 74 (48%) patients, Lim2 in 22 (14.3%), Lim3 in 50 (32.5%) and Lim4 in 8 (5.2%) patients. Cortical structures (Lim1 and Lim3) were involved in 124 (80.5%) patients. Median overall survival was significantly better in patients treated according to Stupp regimen (23.3 vs. 8.6 months, p<0.001). Median overall survival differs in respective Lim groups: 12.3, 5.6, 11.8 and 6.6 months (p=0.07). Better survival was in patients with cortical involvement (Lim1+Lim3): 12.3 vs. 6.4 months (p=0.02), especially in subgroup of patients who were not treated according to Stupp regimen (8.9 vs. 4.4 months, p=0.02) vs. those after Stupp regimen (23 vs. 23.4 months, p=0.7). CONCLUSION Initial location of enhancing glioblastoma was prognostic for overall survival, with better outcomes in patients presented by involvement of cortical structures comparing to subventricular/hippocampal zones. Molecular patterns may further clarify potential effects of neural stem cells in glioma genesis mirrored in different clinical behavior and location of initial tumor. Supported by Ministry of Health of the Czech Republic, grant No. 18-03-00469

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P14.107 Rapid early progression of glioblastoma is not related to cortical/neural stem cells regions

Neuro-Oncology ◽

10.1093/neuonc/noz126.342 ◽

2019 ◽

Vol 21 (Supplement_3) ◽

pp. iii93-iii93

Author(s):

R Jancalek ◽

T Kazda ◽

R Belanova ◽

P Pospisil ◽

P Burkon ◽

...

Keyword(s):

Stem Cells ◽

Overall Survival ◽

Neural Stem Cells ◽

Post Surgery ◽

Clinical Biomarkers ◽

Increased Risk ◽

Initial Location ◽

Early Progression ◽

Multifocal Tumor ◽

Tumor Phenotype

Abstract BACKGROUND Rapid early progression (REP) of glioblastoma after surgery is quite often observed on pre-radiotherapy MR scan. Clinical and molecular biomarkers indicating increased risk of this REP may be of high clinical need. Subventricular brain zone (SVZ) and hippocampal regions are supposed to harbor astrocyte-like neural stem cells with tumors arising from these transformed SVZ stem cells dreaded to be of higher risk of REP. Lim′s et al classification of initial glioblastoma location related to these neural stem cells regions was predictive for invasive and multifocal tumor phenotype. The aim of this retrospective single-institutional study is to evaluate the relations of this Lim classification on REP in unselected cohort of glioblastoma patients. MATERIAL AND METHODS Patients treated by radiotherapy between 2014–2017 were grouped as follows: Lim1 (SVZ+⋯SVZ/hippocampal involvement and Cortex+⋯cortex involvement), Lim2 (SVZ+ and Cortex-), Lim3 (SVZ- and Cortex+) and Lim4 (SVZ- and Cortex-). Some patients were indicated to Stupp regimen. REP was defined on pre-radiotherapy MR as new distant lesion, progression of residuum, or new enhancement in postsurgery cavity. RESULTS In total, 144 patients were analyzed (94 men, mean age 59 years). 47 patients (30.5%) were treated according to Stupp regimen. Lim1 classification was presented in 74 (48%) patients, Lim2 in 22 (14.3%), Lim3 in 50 (32.5%) and Lim4 in 8 (5.2%) patients. Cortical structures (Lim1 and Lim3) were involved in 124 (80.5%) patients. Median overall survival was significantly better in patients treated according to Stupp regimen (23.3 vs. 8.6 months, p<0.001) and in those without REP (18.5 vs. 10.2 months, p=0.001). REP was presented in 52% of 95 evaluable patients who underwent both post-surgery and pre-radiotherapy MR scans and there was no significant impact of time to start of radiotherapy. No significant relation between REP and Lim classification was observed (REP in 23/47 Lim1, in 8/13 Lim2, in 16/31 Lim3 and in 2/4 Lim4 patients). CONCLUSION Initial location of enhancing glioblastoma is not predictive for REP. Patients experiencing REP have significantly worse overall survival and modification of their management represents urgent unmet clinical need. Molecular and clinical biomarkers indicating increased risk of REP are needed. Supported by Ministry of Health of the Czech Republic, grant No. 18-03-00469.

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P14.59 Rapid early progression of glioblastoma is not related to cortical/neural stem cells regions

Neuro-Oncology ◽

10.1093/neuonc/noab180.170 ◽

2021 ◽

Vol 23 (Supplement_2) ◽

pp. ii49-ii49

Author(s):

T Kazda ◽

R Lakomy ◽

I Selingerova ◽

P Pospisil ◽

L Hynkova ◽

...

Keyword(s):

Stem Cells ◽

Overall Survival ◽

Neural Stem Cells ◽

Spatial Relationship ◽

Clinical Biomarkers ◽

Increased Risk ◽

Initial Location ◽

Early Progression ◽

Multifocal Tumor ◽

Relationship Of

Abstract BACKGROUND Rapid early progression (REP) of glioblastoma after surgery observed on pre-radiotherapy MRI scan is common. Subventricular zone (SVZ) and hippocampal regions are supposed to harbor astrocyte-like neural stem cells (NSC) with tumors arising from these transformed stem cells threatening of higher risk of REP. REP is defined as a new enhancing tumor or >25% increase in enhancement before radiotherapy. Lim′s classification of initial glioblastoma location related to these NSC regions predicts invasive and multifocal tumor phenotype. Glioblastomas are classified preoperatively into four groups by the spatial relationship of the contrast-enhancing lesion with the SVZ and cortex. The aim of this retrospective single-institutional study is to evaluate the relations of this Lim classification on REP in unselected cohort of glioblastoma patients. MATERIAL AND METHODS Patients receiving radiotherapy between 2014–2017 were analyzed, 95 were evaluable. 47 patients (30.5%) were treated with the Stupp regimen. Lim1 classification (contact with cortex as well as SVZ) was presented in 74(48%) patients, Lim2 (contact with SVZ only) in 22(14.3%), Lim3 (contact with cortex only) in 50(32.5%) and Lim4 in 8(5.2%) patients. A total of 52% of patients developed REP. RESULTS Significantly better overall survival was with Stupp regimen (23.3 vs. 8.6 months, p<0.001) and without REP (18.5 vs. 10.2 months, p=0.001). There was no significant impact of time to start of radiotherapy. No significant relation between REP and Lim classification was observed. CONCLUSION The initial location is not predictive for REP. Patients experiencing REP have significantly worse overall survival and modification of their management represents an urgent unmet clinical need. Molecular and clinical biomarkers indicating an increased risk of REP are needed.Presented will also be an already published analysis of clinical factors associated with REP in glioblastoma and the effect of REP and treatment on survival outcomes. Newly, we will introduce the investigator-initiated prospective academic clinical trial (GlioMET) focused on optimization of glioblastoma radiotherapy by 11C-Methionine PET scan in patients with REP. Supported by Ministry of Health of the Czech Republic AZV, No.18-03-00469 and AZV NU20-03-00148.

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Efficacy and Safety of Gemtuzumab-Based Regimens in Patients with CD33-Positive Refractory Leukemia.

Blood ◽

10.1182/blood.v110.11.4358.4358 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4358-4358

Author(s):

Suijing Wu ◽

Xin Du ◽

Wei Lin ◽

Jianyu Weng ◽

Jianjun Zhang ◽

...

Keyword(s):

Stem Cells ◽

Overall Survival ◽

Survival Time ◽

Myeloid Leukemia ◽

Median Overall Survival ◽

Response Rate ◽

Single Agent ◽

Efficacy And Safety ◽

Blast Phase ◽

Median Overall Survival Time

Abstract Patients with relapsed or refractory leukemia have less chances of obtaining remission than patients with newly diagnosed.It is reported that more than 80% of acute myeloid leukemia(AML) patients have myeloid blast cells that express the CD33 surface antigen. This antigen also is present on the leukemic stem cells at least some patients with chronic myeloid leukemia(CML)and acute lymphoblastic leukemia(ALL). It is absent from normal hematopoietic stem cells and nonhematopoietic cells and tissues. Gemtuzumab is a humanized anti-CD33 antibody conjugated to calicheamicin, a potent anti tumor antibiotic derived from a bacterium. It is conditionally approved in the US for treatment of CD33+ AML in first relapse in patients over 60 years[Sievers et al.Journal of Clinical Oncology,2001]. Here we evaluate the efficacy and safety of Gemtuzumab -based regimens. The study population comprise 11 patients with CD33-positive refractory leukemia (determined as CD33-antigen expression in over 50% of leukemic blasts by bone marrow aspirates and immunophenotyping), including two with myeloid blast phase of CML, one with refractory ALL, two relapsed after Auto-stem cell transplantation(Auto-SCT). The median age was 47 years. Four cases who were over 60 years or after Auto-SCT treated with single agent. The other seven cases treated with mylotarg and cytotoxic agents, including mylotarg plus idarubine (MI); Gemtuzumab plus fludarabine, cytarabine, CsA(MFAC); or plus mitoxantrone, Ara-C (MMA).The overall response rate was 54% (6/11), with 36%(4/11) patients obtaining complete remission (CR) and 18% (2/11) achieving CRp.The median overall survival time after treatment was 4.8 months, and the median overall survival time after CR was 8.2 months.Two patients with myeloid blast phase of CML achieved CR with BCR/ABL(−), the survival time after CR was 5+months and 20+months respectively, but failed in second relapse. One patient received Allo-SCT after CR with refractory ALL is still alive at present (21months) with disease free. The median time to ANC recovery of 0.5×109/L was 15 days.The common adverse events was myelosuppression (100% Grade 4 neutropenia and thrombocytopenia).Significant non-hematologic toxicitics included infection(96%), infusion-related chills and fever (55%).Although hepatic dysfunction and mucositis were observed,they were generally infrequent and not severe(Grade 1–2).Six patients (55%) developed Hepatic veno-occlusive disease(VOD), four of them were either over 60 years old or received Auto-SCT before although they received only single agent mylotarg therapy, but it was transient and no one died from it. In conclusion, patients with CD33-positive refractory leukemia, Gemtuzumab -based regimens have a comparable response rate and offer a more favorable toxicity profile, expecially for the patients with myeloid blast phase of CML. It is also effective for the patient with refractory ALL. In the treatment, we should pay attention to the hepatic condition of ones who are over 60 years old or after stem cell transplantation, attemps to avoid and treat VOD are warranted. Above all, When patients with refractory leukemia got remission, allogenic-SCT should be done as soon as possible

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