Wael Makar | Cairo University (original) (raw)

Papers by Wael Makar

Journal of Clinical Oncology, May 20, 2008

Journal of Cancer Treatment and Research, 2019

As survival rates in children with medulloblastoma improve, the issue of late effects of treatmen... more As survival rates in children with medulloblastoma improve, the issue of late effects of treatment becomes more important. One possible consequence of treatment with cisplatin-based chemotherapy and radiotherapy is sensorineural hearing loss, this clinically important side effect, which can cause difficulties in speech, language, communication and learning must be considered during treatment planning. Characteristically, sensorineural hearing loss occurs 6-12 months following radiotherapy and can be irreversible3.

AIM: The aim of the study is to compare the toxicity and cost-effectiveness between metronomic an... more AIM: The aim of the study is to compare the toxicity and cost-effectiveness between metronomic and intermittent capecitabine as maintenance therapy in female patients with metastatic breast cancer. PATIENTS AND METHODS: All metastatic breast cancer patients with HER2 negative were included. The whole study population received six cycles of Docetaxel/Capecitabine then patients were randomized to either continuous (650 mg/m twice daily continuous) or intermittent Capecitabine (1000 mg/m twice daily every 21 days) as maintenance. RESULTS: The study included 51 patients, 26 in the metronomic arm and 25 in the continuous. The median number of maintenance cycles, as well as the partial response, was higher in the continuous (18 vs. 13 cycles, p: 0.031; p: 0.038). The continuous arm was tolerable with significant less Grade 3 and 4 toxicity regarding nausea, vomiting, hand and foot syndrome, neutropenia, and elevated liver enzymes. (p: 0.03, 0.045, 0.051, 0.048, 0.06, respectively). On mul...

Research in Oncology

Purpose: To compare and evaluate Thyroid gland radiation doses in intensity modulated radiotherap... more Purpose: To compare and evaluate Thyroid gland radiation doses in intensity modulated radiotherapy (IMRT) and 3D-conformal radiotherapy (3D-CRT) technique for postoperative treatment of breast cancer. Patients and methods: Twenty patients with breast cancer, IMRT and 3D-CRT plans were generated using XIO planning system to analyze and compare with respect to doses to thyroid gland using the parameters (Dmax, Dmin, Dmean, and V5Gy). results: Thyroid radiation doses were more in IMRT than in 3D-conformal technique particularly Dmax in (Breast conservative surgery) BCS cases which showed statistical significance (833.60 ± 38.14 cGy Vs 113.6 ± 12.93 cGy, P-value < 0.05). V5Gy was statistically significant in all cases (7.70 ± 1.43% Vs 0.00%, with P-value = 0.0001). conclusion: IMRT associated with excess radiation doses to thyroid gland than the 3D-conformal technique in postoperative radiotherapy of breast cancer.

Research in Oncology

Background: Breast cancer is a heterogenous group of diseases classified into the biological subt... more Background: Breast cancer is a heterogenous group of diseases classified into the biological subtypes luminal A, luminal B, HER2-enriched and triple negative. These subtypes have different treatment response patterns and survival rates. Ki-67 is the most commonly used proliferative marker in breast cancer and is used for the distinction between luminal A and B subtypes. Methods: A retrospective study that included patients with early breast cancer diagnosed between 2010 and 2016 and treated in a single cancer center. Results: The medical records of 498 patients were retrospectively reviewed. The median age of patients was 51 years (range: 21-81) and the median value of Ki-67 level among them was 20% (interquartile range: 10-30%). Ki-67 was significantly higher in younger (<35 years) and premenopausal patients (p=0.0002 and 0.0055, respectively). Higher Ki-67 level associated significantly with higher T stage, estrogen and progesterone receptors-negativity, HER2-positivity and higher grade (p=0.0256, <0.0001, <0.0001, =0.0001 and =0.0031; respectively). Univariate Cox regression analysis showed that the ≥14% and ≥20% cutoff values of Ki-67 level are associated with poorer diseasefree survival (DFS) (HR=1.989 [95%CI: 1.163-3.402, p=0.0121] and HR=1.616 [95%CI: 1.001-2.61, p=0.0496], respectively). On stratifying patients according to the Ki-67 proliferation index into three strata, <14%, ≥14%-<20% and ≥20%; DFS differed significantly between them (p=0.0394). The 5-year DFS rate for the three strata was 82.2%, 64.7% and 64.8%; respectively. Conclusion: Early breast cancer patients with lower Ki-67 levels have significantly better DFS. A Ki-67 cutoff value of ≥14% appears to correlate better with DFS than the newer cutoff value of ≥20%.

Journal of Cancer Research and Therapeutics

Asian Pacific Journal of Cancer Prevention

Background: Breast cancer (BC) is the second most common cancer worldwide. MicroRNAs are a group ... more Background: Breast cancer (BC) is the second most common cancer worldwide. MicroRNAs are a group of non-coding, single stranded RNAs of ~ 22 nucleotides, which regulate gene expression at the post-transcriptional level. Circulating miRNAs have been found as potential blood based predictive biomarkers. Purpose: we aim to evaluate miR-34a and miR-125b to predict outcome from neoadjuvant chemotherapy in Egyptian BC patients. Methodology: Quantitative assessment of plasma miR-34a and miR-125b expression was performed by qRT-PCR. Thirty nine newly diagnosed locally advanced BC female patients with 10 age and sex matched healthy volunteers were included in the study. Results: We performed ROC curve analysis to evaluate the diagnostic value for the miR-34a with AUCs = 0.995, cutoff point of 2.57 sensitivity 97.4%, specificity 100%, PPV 100%, NPV 83.3% and accuracy 97.7%. miR-125b had AUC = 0.68 and a cutoff point of 8.69 with sensitivity 66.7%, specificity 70.0%, PPV 90.6%, NPV 41.2% and accuracy 73.5%. miR-34a expression were significantly higher in BC patients compared to controls with p value <0.001*. Also, miR-34a expression level was significantly higher in patients with progressive disease with P value =0.03*. However, miR-125b expression levels were insignificantly higher in responsive patients with p value = 0.2. Conclusion: miRNAs are crucial candidates for novel molecular targeted therapies due to their capability to regulate numerous genes in molecular pathways. Our data suggest that circulating miR-34a and miR-125b expression levels could be promising highly accurate non-invasive biomarkers in diagnosing BCs. miR-34a can predict chemotherapeutic resistance associated with higher expression levels in non-responsive patients.

Asian Pacific Journal of Cancer Care

Background: The purpose of the study is to evaluate and compare the psychological impact of vario... more Background: The purpose of the study is to evaluate and compare the psychological impact of various therapeutic modalities in pediatric cancer by comparing them to healthy children across age groups.Methods: The semi-structured and the Mini International Neuropsychiatric interview (M.I.N.I Kids Test) were administered to 80 children including 40 cancer patients and 40 healthy children. Results: CNS tumors were the most commontumor 47.5% followed by heamatological malignancies 35% and Non CNS solid tumors 17.5%. About two thirds of the sample reported social problems followed by school problems in 57.5% of cases. By analyzing the mood changes, there was significant depression, anxiety disorders, panic attacks and separation anxiety between the patients and the control (p= <0.001). The patients had also significant lack of attentionand stubbornness (p=<0.001). These problems did not show any difference between sex except for depression and social worries which were more in girls...

Research in Oncology

Background: Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is characteri... more Background: Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is characterized by being more aggressive, presentation in younger age, and higher response rate to chemotherapy. It is more likely to recur and to metastasize early. Methods: Retrospective review of the medical records of TNBC patients treated in a single Egyptian cancer center during a 4-year period. Results: Sixty-five patients were included. Forty-six percent of patients were < 50 years old and 22% had a positive family history. Ten (15%) patients were metastatic at presentation. Modified radical mastectomy was performed in 42% of patients and adjuvant chemotherapy was administered in 55% of them. Relapse occurred in 12 (22%) out of 55 patients who had no distant metastasis at presentation (M0). The overall survival rate of M0 patients at 12, 24 and 36 months was 96%, 91% and 88%; respectively. The disease-free survival rate of M0 patients at 12, 24 and 36 months was 90%, 81% and 71%; respectively. Conclusion: TNBC is an aggressive subtype of breast cancer that occurs at younger age. Frequently, it is of high grade and presents in an advanced stage.

Research in Oncology

Background: Craniospinal irradiation followed by a boost to the posterior fossa combined with cis... more Background: Craniospinal irradiation followed by a boost to the posterior fossa combined with cisplatinbased chemotherapy after maximal safe resection is the standard of care in treatment of pediatric medulloblastoma. Sensorineural hearing loss is one of the most serious positble late effect of this treatment. Material and Method: Five high-risk medulloblastoma pediatric patients were treated by craniospinal irradiation (36 Gy) combined with cisplatin weekly followed by a boost of irradiation (18 Gy) to the posterior fossa by 3D-CRT plan. Dosimetric plans by IMRT were done to the 5 cases to compare between 3D-CRT and IMRT in sparing of the different OARs as well as their coverage of the target. Results: By comparing the mean doses and DVHs for the 3D-CRT and IMRT plans, it was obvious that IMRT plans were able to spare the cochlea more than the 3D-CRT. As the cochlea received 80.5% (43.5 Gy) of the prescribed dose in the IMRT plans compared to 94.5% (51. Gy) of the prescribed dose in the 3D-CRT plans, even the target was better covered by IMRT as it has been shown when comparing the DVHs of the different plans. Conclusion: IMRT increases the conformality of dose of radiation in the target and limiting the dose to the OARs especially the cochlea thus reducing the incidence of sensory hearing loss.

Research in Oncology

Background: Ependymoma is a rare disease accounting for 5-10% of brain tumors. Different prognost... more Background: Ependymoma is a rare disease accounting for 5-10% of brain tumors. Different prognostic factors including type of surgery, tumor histopathologic type, site, age, metastasis and stage, affect the survival with a wide variation ranging from 10-87%. patients and methods: This clinical study is based on 30 patients diagnosed with intra-cranial ependymoma treated at NEMROCK between1998-2004 with a median follow up period of 8.5 years. The patient's age ranged between 2 and 56 years with a median of 16.5 years (SD 16.48). Radiation therapy given was either craniospinal irradiation including; Whole brain irradiation 36 Gy in18 fractions, whole spine irradiation 24Gy in 12 fractions and boost to post fossa 18 Gy in 10 fractions or wide field irradiation with safety margin 2-3 cm of normal tissue all around the tumor to a total dose of 54 Gy in 27 fractions. Data of the patients was studied as regards different prognostic factors in correlation to progression free and overall survival as well as treatment related events. results: The 5 year overall survival and event free survival were 61.4% and 40.9%, respectively. The median event free survival was 39.047 months (95% Cl of 29.058-49.036). The OS for supratentorial site (81%) was superior to that of infratentorial site (56%) and the difference was statistically significant (p 0.0489). The OS was affected significantly by sex, grade and radiotherapy (p 0.017, 0.010, 0.027, respectively) in favor of male sex, Grade I and wide field radiotherapy. Pattern of relapse was only local recurrence. conclusion: Despite the rarity of ependymoma and low number of patients, this retrospective study may add weight to the findings of others that suggest the importance of total surgical excision as well as the use of radiation therapy in the management of this group of patients.

Journal of Clinical Oncology, May 20, 2008

Journal of Cancer Treatment and Research, 2019

As survival rates in children with medulloblastoma improve, the issue of late effects of treatmen... more As survival rates in children with medulloblastoma improve, the issue of late effects of treatment becomes more important. One possible consequence of treatment with cisplatin-based chemotherapy and radiotherapy is sensorineural hearing loss, this clinically important side effect, which can cause difficulties in speech, language, communication and learning must be considered during treatment planning. Characteristically, sensorineural hearing loss occurs 6-12 months following radiotherapy and can be irreversible3.

AIM: The aim of the study is to compare the toxicity and cost-effectiveness between metronomic an... more AIM: The aim of the study is to compare the toxicity and cost-effectiveness between metronomic and intermittent capecitabine as maintenance therapy in female patients with metastatic breast cancer. PATIENTS AND METHODS: All metastatic breast cancer patients with HER2 negative were included. The whole study population received six cycles of Docetaxel/Capecitabine then patients were randomized to either continuous (650 mg/m twice daily continuous) or intermittent Capecitabine (1000 mg/m twice daily every 21 days) as maintenance. RESULTS: The study included 51 patients, 26 in the metronomic arm and 25 in the continuous. The median number of maintenance cycles, as well as the partial response, was higher in the continuous (18 vs. 13 cycles, p: 0.031; p: 0.038). The continuous arm was tolerable with significant less Grade 3 and 4 toxicity regarding nausea, vomiting, hand and foot syndrome, neutropenia, and elevated liver enzymes. (p: 0.03, 0.045, 0.051, 0.048, 0.06, respectively). On mul...

Research in Oncology

Purpose: To compare and evaluate Thyroid gland radiation doses in intensity modulated radiotherap... more Purpose: To compare and evaluate Thyroid gland radiation doses in intensity modulated radiotherapy (IMRT) and 3D-conformal radiotherapy (3D-CRT) technique for postoperative treatment of breast cancer. Patients and methods: Twenty patients with breast cancer, IMRT and 3D-CRT plans were generated using XIO planning system to analyze and compare with respect to doses to thyroid gland using the parameters (Dmax, Dmin, Dmean, and V5Gy). results: Thyroid radiation doses were more in IMRT than in 3D-conformal technique particularly Dmax in (Breast conservative surgery) BCS cases which showed statistical significance (833.60 ± 38.14 cGy Vs 113.6 ± 12.93 cGy, P-value < 0.05). V5Gy was statistically significant in all cases (7.70 ± 1.43% Vs 0.00%, with P-value = 0.0001). conclusion: IMRT associated with excess radiation doses to thyroid gland than the 3D-conformal technique in postoperative radiotherapy of breast cancer.

Research in Oncology

Background: Breast cancer is a heterogenous group of diseases classified into the biological subt... more Background: Breast cancer is a heterogenous group of diseases classified into the biological subtypes luminal A, luminal B, HER2-enriched and triple negative. These subtypes have different treatment response patterns and survival rates. Ki-67 is the most commonly used proliferative marker in breast cancer and is used for the distinction between luminal A and B subtypes. Methods: A retrospective study that included patients with early breast cancer diagnosed between 2010 and 2016 and treated in a single cancer center. Results: The medical records of 498 patients were retrospectively reviewed. The median age of patients was 51 years (range: 21-81) and the median value of Ki-67 level among them was 20% (interquartile range: 10-30%). Ki-67 was significantly higher in younger (<35 years) and premenopausal patients (p=0.0002 and 0.0055, respectively). Higher Ki-67 level associated significantly with higher T stage, estrogen and progesterone receptors-negativity, HER2-positivity and higher grade (p=0.0256, <0.0001, <0.0001, =0.0001 and =0.0031; respectively). Univariate Cox regression analysis showed that the ≥14% and ≥20% cutoff values of Ki-67 level are associated with poorer diseasefree survival (DFS) (HR=1.989 [95%CI: 1.163-3.402, p=0.0121] and HR=1.616 [95%CI: 1.001-2.61, p=0.0496], respectively). On stratifying patients according to the Ki-67 proliferation index into three strata, <14%, ≥14%-<20% and ≥20%; DFS differed significantly between them (p=0.0394). The 5-year DFS rate for the three strata was 82.2%, 64.7% and 64.8%; respectively. Conclusion: Early breast cancer patients with lower Ki-67 levels have significantly better DFS. A Ki-67 cutoff value of ≥14% appears to correlate better with DFS than the newer cutoff value of ≥20%.

Journal of Cancer Research and Therapeutics

Asian Pacific Journal of Cancer Prevention

Background: Breast cancer (BC) is the second most common cancer worldwide. MicroRNAs are a group ... more Background: Breast cancer (BC) is the second most common cancer worldwide. MicroRNAs are a group of non-coding, single stranded RNAs of ~ 22 nucleotides, which regulate gene expression at the post-transcriptional level. Circulating miRNAs have been found as potential blood based predictive biomarkers. Purpose: we aim to evaluate miR-34a and miR-125b to predict outcome from neoadjuvant chemotherapy in Egyptian BC patients. Methodology: Quantitative assessment of plasma miR-34a and miR-125b expression was performed by qRT-PCR. Thirty nine newly diagnosed locally advanced BC female patients with 10 age and sex matched healthy volunteers were included in the study. Results: We performed ROC curve analysis to evaluate the diagnostic value for the miR-34a with AUCs = 0.995, cutoff point of 2.57 sensitivity 97.4%, specificity 100%, PPV 100%, NPV 83.3% and accuracy 97.7%. miR-125b had AUC = 0.68 and a cutoff point of 8.69 with sensitivity 66.7%, specificity 70.0%, PPV 90.6%, NPV 41.2% and accuracy 73.5%. miR-34a expression were significantly higher in BC patients compared to controls with p value <0.001*. Also, miR-34a expression level was significantly higher in patients with progressive disease with P value =0.03*. However, miR-125b expression levels were insignificantly higher in responsive patients with p value = 0.2. Conclusion: miRNAs are crucial candidates for novel molecular targeted therapies due to their capability to regulate numerous genes in molecular pathways. Our data suggest that circulating miR-34a and miR-125b expression levels could be promising highly accurate non-invasive biomarkers in diagnosing BCs. miR-34a can predict chemotherapeutic resistance associated with higher expression levels in non-responsive patients.

Asian Pacific Journal of Cancer Care

Background: The purpose of the study is to evaluate and compare the psychological impact of vario... more Background: The purpose of the study is to evaluate and compare the psychological impact of various therapeutic modalities in pediatric cancer by comparing them to healthy children across age groups.Methods: The semi-structured and the Mini International Neuropsychiatric interview (M.I.N.I Kids Test) were administered to 80 children including 40 cancer patients and 40 healthy children. Results: CNS tumors were the most commontumor 47.5% followed by heamatological malignancies 35% and Non CNS solid tumors 17.5%. About two thirds of the sample reported social problems followed by school problems in 57.5% of cases. By analyzing the mood changes, there was significant depression, anxiety disorders, panic attacks and separation anxiety between the patients and the control (p= <0.001). The patients had also significant lack of attentionand stubbornness (p=<0.001). These problems did not show any difference between sex except for depression and social worries which were more in girls...

Research in Oncology

Background: Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is characteri... more Background: Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is characterized by being more aggressive, presentation in younger age, and higher response rate to chemotherapy. It is more likely to recur and to metastasize early. Methods: Retrospective review of the medical records of TNBC patients treated in a single Egyptian cancer center during a 4-year period. Results: Sixty-five patients were included. Forty-six percent of patients were < 50 years old and 22% had a positive family history. Ten (15%) patients were metastatic at presentation. Modified radical mastectomy was performed in 42% of patients and adjuvant chemotherapy was administered in 55% of them. Relapse occurred in 12 (22%) out of 55 patients who had no distant metastasis at presentation (M0). The overall survival rate of M0 patients at 12, 24 and 36 months was 96%, 91% and 88%; respectively. The disease-free survival rate of M0 patients at 12, 24 and 36 months was 90%, 81% and 71%; respectively. Conclusion: TNBC is an aggressive subtype of breast cancer that occurs at younger age. Frequently, it is of high grade and presents in an advanced stage.

Research in Oncology

Background: Craniospinal irradiation followed by a boost to the posterior fossa combined with cis... more Background: Craniospinal irradiation followed by a boost to the posterior fossa combined with cisplatinbased chemotherapy after maximal safe resection is the standard of care in treatment of pediatric medulloblastoma. Sensorineural hearing loss is one of the most serious positble late effect of this treatment. Material and Method: Five high-risk medulloblastoma pediatric patients were treated by craniospinal irradiation (36 Gy) combined with cisplatin weekly followed by a boost of irradiation (18 Gy) to the posterior fossa by 3D-CRT plan. Dosimetric plans by IMRT were done to the 5 cases to compare between 3D-CRT and IMRT in sparing of the different OARs as well as their coverage of the target. Results: By comparing the mean doses and DVHs for the 3D-CRT and IMRT plans, it was obvious that IMRT plans were able to spare the cochlea more than the 3D-CRT. As the cochlea received 80.5% (43.5 Gy) of the prescribed dose in the IMRT plans compared to 94.5% (51. Gy) of the prescribed dose in the 3D-CRT plans, even the target was better covered by IMRT as it has been shown when comparing the DVHs of the different plans. Conclusion: IMRT increases the conformality of dose of radiation in the target and limiting the dose to the OARs especially the cochlea thus reducing the incidence of sensory hearing loss.

Research in Oncology

Background: Ependymoma is a rare disease accounting for 5-10% of brain tumors. Different prognost... more Background: Ependymoma is a rare disease accounting for 5-10% of brain tumors. Different prognostic factors including type of surgery, tumor histopathologic type, site, age, metastasis and stage, affect the survival with a wide variation ranging from 10-87%. patients and methods: This clinical study is based on 30 patients diagnosed with intra-cranial ependymoma treated at NEMROCK between1998-2004 with a median follow up period of 8.5 years. The patient's age ranged between 2 and 56 years with a median of 16.5 years (SD 16.48). Radiation therapy given was either craniospinal irradiation including; Whole brain irradiation 36 Gy in18 fractions, whole spine irradiation 24Gy in 12 fractions and boost to post fossa 18 Gy in 10 fractions or wide field irradiation with safety margin 2-3 cm of normal tissue all around the tumor to a total dose of 54 Gy in 27 fractions. Data of the patients was studied as regards different prognostic factors in correlation to progression free and overall survival as well as treatment related events. results: The 5 year overall survival and event free survival were 61.4% and 40.9%, respectively. The median event free survival was 39.047 months (95% Cl of 29.058-49.036). The OS for supratentorial site (81%) was superior to that of infratentorial site (56%) and the difference was statistically significant (p 0.0489). The OS was affected significantly by sex, grade and radiotherapy (p 0.017, 0.010, 0.027, respectively) in favor of male sex, Grade I and wide field radiotherapy. Pattern of relapse was only local recurrence. conclusion: Despite the rarity of ependymoma and low number of patients, this retrospective study may add weight to the findings of others that suggest the importance of total surgical excision as well as the use of radiation therapy in the management of this group of patients.