{"id":57082,"date":"2024-03-20T10:08:00","date_gmt":"2024-03-20T10:08:00","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=57082"},"modified":"2024-04-02T04:34:40","modified_gmt":"2024-04-02T04:34:40","slug":"clinical-molecular-subgroups-and-survival-rates-finding-of-childhood-medulloblastoma-a-ten-years-moroccan-experience-in-pediatric-hematology-and-oncology-center","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol17no1\/clinical-molecular-subgroups-and-survival-rates-finding-of-childhood-medulloblastoma-a-ten-years-moroccan-experience-in-pediatric-hematology-and-oncology-center\/","title":{"rendered":"Clinical, Molecular Subgroups and Survival Rates Finding of Childhood Medulloblastoma: A Ten Years Moroccan Experience in Pediatric Hematology and Oncology Center."},"content":{"rendered":"\n

Introduction<\/strong><\/p>\n\n\n\n

MB is one of the most common malignant brain tumors of childhood, representing 20% or more of all pediatric cancers\n\u00ad\u00ad\u00ad<\/sup>1\u20134<\/sup>. during the last few years, a huge improvement\nhas been made in terms of overall survival rates, the median overall survival\nof all subgroups is estimated to be 70%5,6<\/sup>. Recent studies on MB have unveiled that\nstratifying risk according to molecular subtypes is more precise, providing\nvaluable guidance for clinical treatment decisions and determining\nclinical prognosis 5,7,8<\/sup>. Four\nprimary molecular subgroups of MB patients are categorized in the 2021 World\nHealth Organization categorization of brain Tumors: WNT and SHH with wild-type\nTP53, SHH and mutant TP53, and non-WNT\/non-SHH 9<\/sup>.<\/sup><\/p>\n\n\n\n

According to Ellison\net al, the  MB may be divided into Three primary subgroups (WNT, SHH, and\nnonWNT\/nonSHH) using antibodies(beta-catenin, Gab1, and Yap1)10<\/sup>. The immunohistochemistry (IHC) is rapid way, economical,\nand feasible on Formalin-Fixed, Paraffin-Embedded (FFPE) tumor tissues and also\ngives results similar to those using DNA-methylation profiling in earlier\nstudies 11,12<\/sup>. in addition, this technique is reliable, easily\nobtained, and commonly used for analyses of MB subgroup classification by many authors 10,12\u201314<\/sup>. <\/p>\n\n\n\n

To date, no studies\nhave been conducted in Morocco to perform molecular subgroups using IHC to classify\npediatric patients with MB into the three main subgroups. Therefore, in this\ninvestigation, our purpose was to<\/strong> establish clinical and\nparaclinical profiles and use beta-catenin, GAB1, YAP1, and P53 antibodies to\ndetermine the molecular subgroups. Finally evaluating the survival rates of the\nMoroccan with MB.<\/p>\n\n\n\n

Patients and Methods<\/strong><\/p>\n\n\n\n

Retrospectively, we conducted a cross-sectional analysis of health records from patients who were diagnosed and treated at Rabat’s University Hospital Ibn Sina from January 2010 until December 2019. Only patients who were under 18 years old at the moment of diagnosis and had histological confirmation by the 2007 categorization of the World Health Organization (WHO)15<\/sup> (figure 2) were included. From the health records, Follow-up data, demographics, clinical features, and paraclinical features were gathered.The patients were divided into two risk categories, namely standard and high. Patients without metastasis disease, residual tumor \u22641.5 cm2<\/sup>, classical or desmoplasic variant, and age >3 years were assigned to standard risk whereas those with Metastasis disease, large cell or anaplastic (LCA) variant, residual tumor > 1.5 cm2<\/sup>, and age \u22643 years were assigned to high-risk. In cases with molecular subgroups assessment, the tumors were classified into three main subgroups according to World Health Organization (WHO) classifications 201616<\/sup>. We were able to identify molecular subgroups By using the IHC technique. Beta-catenin, GAB1, YAP1, and P53 antibodies were applied to 5 \u03bcm sections of (FFPE) tumor tissues, and the three primary subgroups of MBwere categorized by different IHC staining to the antibodies, companies, dilutions and antibody sources for IHC studies are indicated in table 1 and figure 2.<\/p>\n\n\n\n

Immunohistochemical analysis<\/strong><\/p>\n\n\n\n

Beta-catenin was considered\nas positive if The WNT subgroup exhibited nuclear staining in more than 5% of\ntumor cells. GAB1 was assessed as positive when cytoplasmic staining was\ndetected in more than 10% of tumor cells and these cases were classified as SHH\nsubgroup. YAP1 was assessed as positive when 10% or more of cytoplasmic\nor nuclear staining was detected, these cases were classified in the WNT or SHH\nsubgroup. For P53 staining, If more than 50% of tumor cells\nexhibited strong nuclear staining, these cases were classified as the mutant\ntype otherwise it was classified as a non-mutant (wild type). (figure 3)<\/p>\n\n\n\n

Ethical statement<\/strong><\/p>\n\n\n\n

The research was carried out in compliance with the\n2013 revision of the Declaration of Helsinki. The informed permission of all\npatients’ legal representatives was obtained, and the study was authorized by\nthe ethics committee for biomedical research (CERB) of the Faculty of Medicine\nand Pharmacy Rabat. The serial number: AF 69\/22<\/p>\n\n\n\n

Statistical analysis<\/strong><\/p>\n\n\n\n

 The quantitative variables were shown as medians with interquartile ranges or mean with standard deviations, but the qualitative factors were reported as percentages. Routine clinical and radiological exams were performed on those undergoing treatment, and statistical software was used to process the data. Statistical analysis was performed. The overall survival rates were calculated from the time of diagnosis until the final follow-up or the date of death. Using the Kaplan-Meier method, survival curves were produced, and the log-rank test was used to compare overall survival between patient subgroups.  A P value of less than 0.05 was taken to be statistically significant.<\/p>\n\n\n\n

Table 1: Antibodies pannel used for immunohistochemistry technique. <\/strong><\/p>\n\n\n\n\n\n\n\n\n\n
\n

Antibodies<\/strong><\/p>\n<\/td>\n

\n

Molecular subgroups<\/strong><\/p>\n<\/td>\n

\n

Antibody sources<\/strong><\/p>\n<\/td>\n

\n

dilution<\/strong><\/p>\n<\/td>\n

\n

Companies <\/strong><\/p>\n<\/td>\n

\n

immunoreactivity<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Beta-catenin<\/strong><\/p>\n<\/td>\n

\n

WNT pathway<\/p>\n<\/td>\n

\n

Mouse monoclonal<\/p>\n<\/td>\n

\n[1:200  –  1:500]\n<\/td>\n\n

GeneTex (GTX34339)<\/p>\n<\/td>\n

\n

Nuclear + cytoplasmic<\/p>\n<\/td>\n<\/tr>\n

\n

GAB1<\/strong><\/p>\n<\/td>\n

\n

SHH pathway<\/p>\n<\/td>\n

\n

Rabbit polyclonal<\/p>\n<\/td>\n

\n[1:50  –  1:200]\n<\/td>\n\n

ABclonal(A6248)<\/p>\n<\/td>\n

\n

cytoplasmic<\/p>\n<\/td>\n<\/tr>\n

\n

YAP1<\/strong><\/p>\n<\/td>\n

\n

SHH and WNT<\/p>\n

pathway<\/p>\n<\/td>\n

\n

 <\/p>\n

Mouse monoclonal<\/p>\n<\/td>\n

\n[1:100  – 1:1000]\n<\/td>\n\n

GeneTex(GTX633541)<\/p>\n<\/td>\n

\n

Nuclear + cytoplasmic<\/p>\n<\/td>\n<\/tr>\n

\n

P53<\/strong><\/p>\n<\/td>\n

\n

Pronostic<\/p>\n

marker<\/p>\n<\/td>\n

\n

Mouse monoclonal<\/p>\n<\/td>\n

\n[1:150]\n<\/td>\n\n

ORIGENE(OTI5E2)<\/p>\n<\/td>\n

\n

Nuclear<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n

Results<\/strong><\/p>\n\n\n\n

Clinical and paraclinical features<\/strong><\/p>\n\n\n\n

Eighty-two kids with\nMB were sent to the Ibn Sina University Hospital’s Pediatric Oncology and\nHematology Department. 33 of them were eliminated for a variety of reasons from\nthe study: Two were transferred to another hospital, six lacked medical records,\neight died while receiving therapy, seven stopped receiving it, four were lost in the investigation, and six lacked\nhistologic proof. And eight patients with tumor tissues not available. There were 41 patients with available data in all\nthat were recruited. Patients with inaccurate IHC results were excluded from\nmolecular subtype classification due to inadequate tissue for reliable\nclassification. At First the initial biopsy yielded fragments with a limited\nrepresentation of the tumor tissue furthermore the tissue sections from these\ncases exhibited features of extensive necrosis in addition the presence of\npotential artifacts may introduce bias or inaccuracies in molecular subgroups\nclassification (Figure 1).<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 1: Participant flow diagram<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n\n
\"\"<\/td>\n\n

Figure 2: histological classification <\/strong>A) <\/strong>anaplastic MB  B) classic MB  C)   MB  with extensive nodularity (MBEN)  D) desmoplasic nodular MB.<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n\n
\"\"<\/td>\nFigure 3: IHC staining  E) nuclear and cytoplasmic positivity with beta-catenin antibody (in classic  MB) F) cytoplasmic positivity with beta-catenin G) nuclear positivity with P53 antibody.<\/strong>

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

There were forty-one children in the research, ages two to fifteen, with an average age of eight years. Thirty-three of the youngsters were older than three. With 22 males and 19 females in the research, the sex ratio (male\/female) was 1.15, and a small preponderance of males was reported (53.7% vs 46.3%, respectively). The vermis was the most typical site for tumors. With almost 80.5% of cases versus 17.1 % in the cerebellar hemisphere. Hydrocephalus was reported in 26  cases. Among the histological type, there were 3 cases of large cell\/anaplastic type, 10 cases of desmoplasic\/nodular type, and 28 cases of the classic type. In our cohort, the MB with extensive nodular was not detected in any cases. Thirteen patients had recurrences. There were nine incidences of metastases at the time of diagnosis. Table 2 offers a summary of further findings.<\/p>\n\n\n\n

Table 2: Clinical and paraclinical features. (The data are displayed as median [interquartile] or n (%)).<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Characteristics                                                            <\/strong><\/p>\n<\/td>\n

\n

Values (N=41)<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Sexe<\/p>\n

 <\/p>\n

\u00b7        Male<\/p>\n

\u00b7        Female<\/p>\n

 <\/strong><\/p>\n

Sex-ratio(M\/F)<\/p>\n

 <\/p>\n<\/td>\n

\n

 <\/strong><\/p>\n

 <\/p>\n

22 (53.7)<\/p>\n

19 (46.3)<\/p>\n

 <\/p>\n

 <\/p>\n

1.15<\/p>\n<\/td>\n<\/tr>\n

\n

Age (years) <\/p>\n<\/td>\n

\n

8  <\/strong>[6 \u2013 10.50]\n<\/td>\n<\/tr>\n

\n

Interval age :<\/p>\n

\u00b7        \u22643 years  <\/p>\n

\u00b7        >3 years<\/p>\n

 <\/p>\n<\/td>\n

\n

 <\/p>\n

4 (9.8)<\/p>\n

37 (90.2)<\/p>\n

 <\/p>\n<\/td>\n<\/tr>\n

\n

Hydrocephalus :<\/p>\n

\u00b7        Yes<\/p>\n

\u00b7        No<\/p>\n

 <\/strong><\/p>\n<\/td>\n

\n

 <\/p>\n

26 (63.4)<\/p>\n

15 (36.6)<\/p>\n<\/td>\n<\/tr>\n

\n

Tumor location :<\/p>\n

\u00b7        Vermis<\/p>\n

\u00b7        Cerebellar hemisphere<\/p>\n

\u00b7        No data<\/p>\n

 <\/strong><\/p>\n<\/td>\n

\n

 <\/p>\n

33(80.5)<\/p>\n

7(17.1)<\/p>\n

1 (2.4)<\/p>\n<\/td>\n<\/tr>\n

\n

Metastasis disease<\/p>\n

\u00b7        M+<\/p>\n

\u00b7        M0<\/p>\n

 <\/strong><\/p>\n<\/td>\n

\n

22  (53.7)<\/p>\n

19 (46.3)<\/p>\n<\/td>\n<\/tr>\n

\n

Histological type :<\/p>\n

\u00b7        Classic<\/p>\n

\u00b7        Nodular\/desmoplasic \/MBEN <\/p>\n

\u00b7        Anaplasic\/Large cell (LCA)<\/p>\n<\/td>\n

\n

 <\/p>\n

28 (68.3)<\/p>\n

10(24.4)<\/p>\n

3(7.3)<\/p>\n<\/td>\n<\/tr>\n

\n

surgery :<\/p>\n

\u00b7        Complete resection<\/p>\n

\u00b7        Incomplete resection<\/p>\n<\/td>\n

\n

 <\/p>\n

12 (29.3)<\/p>\n

29 (70.7)<\/p>\n<\/td>\n<\/tr>\n

\n

Radiotherapy<\/p>\n

\u00b7        Yes<\/p>\n

\u00b7        no<\/p>\n<\/td>\n

\n

 <\/strong><\/p>\n

36 (87.8)<\/p>\n

5  (12.2)<\/p>\n<\/td>\n<\/tr>\n

\n

Prognosis :<\/p>\n

\u00b7        standard  risk   <\/p>\n

\u00b7        high risk<\/p>\n<\/td>\n

\n

 <\/strong><\/p>\n

17 (41.5)<\/p>\n

24 (58.5)<\/p>\n<\/td>\n<\/tr>\n

\n

Recurrence :<\/p>\n

\u00b7        Yes<\/p>\n

\u00b7        No<\/p>\n<\/td>\n

\n

 <\/strong><\/p>\n

        13 (31.7)<\/p>\n

        28 (68.3)<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n

Clinicopathological characteristics and molecular subgroups<\/strong><\/p>\n\n\n\n

According to their molecular characteristics, 6(30%) patients were in the non-WNT\/SHH, 13(65%) patients, and one patient(5%) were in the SHH group and the WNT group respectively. All cases of the SHH group were SHH wild-type (table 3). Histologically, desmoplastic\/nodular\/MBEN  variants were observed in the SHH group, All classical variants were included in the nonWNT\/nonSHH group.LCA variants were included in the SHH group Tumors, and metastasis disease were detected among 7(more than 50%) patients in  (the SHH group) and four patients in the nonWNT\/nonSHH group.Table 4 provides a summary of the outcomes.<\/p>\n\n\n\n

Table 3: Molecular subgroups features (Data are presented as n (%)) <\/strong><\/p>\n\n\n\n\n\n\n
\n

Characteristics<\/strong><\/p>\n<\/td>\n

\n

Values (N=20)<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Medulloblastoma subgroups :<\/p>\n

\u00b7         Non-WNT\/Non-SHH       <\/p>\n

\u00b7        SHH      <\/p>\n

\u00b7        WNT  <\/p>\n<\/td>\n

\n

6(30)<\/p>\n

13(65)<\/p>\n

1(5)<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n

Table 4: Association between molecular subgroups and demographic, extent resection, metastasis disease, prognosis, and histological variant.<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n
\n

Characteristics<\/strong><\/p>\n<\/td>\n

\n

WNT<\/strong><\/p>\n<\/td>\n

\n

SHH<\/strong><\/p>\n<\/td>\n

\n

Non-WNT\/non-SHH<\/strong><\/p>\n<\/td>\n

\n

Total<\/strong><\/p>\n

(N=20)<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Sexe<\/p>\n

\u00b7        Male<\/p>\n

\u00b7        Female<\/p>\n<\/td>\n

\n

 <\/p>\n

0<\/p>\n

2<\/p>\n<\/td>\n

\n

 <\/p>\n

8<\/p>\n

7<\/p>\n<\/td>\n

\n

 <\/p>\n

2<\/p>\n

1<\/p>\n<\/td>\n

\n

 <\/p>\n

10<\/p>\n

10<\/p>\n<\/td>\n<\/tr>\n

\n

surgery :<\/p>\n

\u00b7        incomplete resection<\/p>\n

\u00b7        complete resection<\/p>\n<\/td>\n

\n

 <\/p>\n

2<\/p>\n

0<\/p>\n<\/td>\n

\n

 <\/p>\n

9<\/p>\n

4<\/p>\n<\/td>\n

\n

 <\/p>\n

4<\/p>\n

2<\/p>\n<\/td>\n

\n

 <\/p>\n

14<\/p>\n

6<\/p>\n<\/td>\n<\/tr>\n

\n

Metastasis disease:<\/p>\n

\u00b7        M0<\/p>\n

\u00b7        M+<\/p>\n<\/td>\n

\n

 <\/p>\n

1<\/p>\n

0<\/p>\n<\/td>\n

\n

 <\/p>\n

6<\/p>\n

7<\/p>\n<\/td>\n

\n

 <\/p>\n

2<\/p>\n

4<\/p>\n<\/td>\n

\n

 <\/p>\n

9<\/p>\n

11<\/p>\n<\/td>\n<\/tr>\n

\n

Histological type :<\/p>\n

\u00b7        Classic<\/p>\n

\u00b7        Nodular\/desmoplasic\/MBEN  <\/p>\n

\u00b7        Anaplasic\/Large cell<\/p>\n<\/td>\n

\n

 <\/p>\n

1<\/p>\n

0<\/p>\n

0<\/p>\n<\/td>\n

\n

 <\/p>\n

7<\/p>\n

4<\/p>\n

2<\/p>\n<\/td>\n

\n

 <\/p>\n

5<\/p>\n

1<\/p>\n

0<\/p>\n<\/td>\n

\n

 <\/p>\n

13<\/p>\n

5<\/p>\n

2<\/p>\n<\/td>\n<\/tr>\n

\n

Prognosis :<\/p>\n

\u00b7        Standard risk<\/p>\n

\u00b7        High risk<\/p>\n<\/td>\n

\n

 <\/p>\n

0<\/p>\n

1<\/p>\n<\/td>\n

\n

 <\/p>\n

6<\/p>\n

7<\/p>\n<\/td>\n

\n

 <\/p>\n

3<\/p>\n

3<\/p>\n<\/td>\n

\n

 <\/p>\n

9<\/p>\n

11<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n

Survival analysis based on clinical and histo-molecular subgroups:<\/strong><\/p>\n\n\n\n

The follow-up period in this investigation was 44.48 months on average (range: 22 to 70 months). After three and five years, the overall survival (OS) rates were, respectively, 70% and 52% (Figure 4). Males had an OS rate of 42% after five years, but females had an OS rate of 63% (P=0.19). According to our research, patients who had radiation therapy outlived the other patients in terms of total five-year survival (50% versus 25%, P=0.035) (Figure 5). We found that there was no apparent difference in the overall survival rate in the total and the partial resection (58% and 50%, respectively, P=0.56). A statistically significant P was observed in the period from surgery to radiation If the interval was more than 120 days. It was found that patients who began radiation therapy before 120 days had the highest OS rates (65%), whereas patients who began therapy beyond 120 days had the lowest rates (28%; P=0.002) (Figure 5). According to the risk category, individuals at high risk had 5-year OS  rates of 42% as opposed to 63% for patients at normal risk (P=0.077). Furthermore, we discovered that, patients who did not have metastases had an 80% of five-year OS, while individuals with metastases had the lowest survival rates (21%)(figure 6). Based on histology, the 5-year OS for the classic, anaplastic\/large cell, and nodular\/desmoplasic types was 53%, 0%, and 50%, respectively (P=0.029). OS rates were lowest for the anaplastic type (Figure 7). Table 5 displays all of the results.<\/p>\n\n\n\n

Table 5: Survival based on sex, radiation, prognosis, metastasis, histology, and molecular subgroups. ( CI, confidence interval; RT, radiotherapy).<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Category<\/strong><\/p>\n<\/td>\n

\n

Os after<\/strong><\/p>\n

3 year (%)<\/strong><\/p>\n<\/td>\n

\n

Os  after<\/strong><\/p>\n

5 year (%)<\/strong><\/p>\n<\/td>\n

\n

The Mean (months 95% CI)<\/strong><\/p>\n<\/td>\n

\n

Log Rank test (Montel_cox)<\/strong><\/p>\n

           P<\/em><\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

sex<\/p>\n

\u00b7        Male          <\/p>\n

\u00b7        Female         <\/p>\n<\/td>\n

\n

60%<\/p>\n

83%<\/p>\n<\/td>\n

\n

42%<\/p>\n

63%<\/p>\n<\/td>\n

\n[45.68         83.94]\n[61.90         96.89]\n<\/td>\n\n

\n<\/p>

\n<\/p>

P=0.19<\/p>\n<\/td>\n<\/tr>\n

\n

histological type<\/p>\n

\u00b7        Classic<\/p>\n

\u00b7        Nodular\/desmoplasic  <\/p>\n

\u00b7        Anaplasic\/Large cell<\/p>\n<\/td>\n

\n

75%<\/p>\n

80%<\/p>\n

0%<\/p>\n<\/td>\n

\n

53%<\/p>\n

50%<\/p>\n

0%<\/p>\n

<\/p>\n<\/td>\n

\n[59.52           95.80]\n[47.73         115.90]\n[12.28            35.72]\n

<\/p>\n<\/td>\n

\n

\n<\/p>

\n<\/p>

\n<\/p>

P=0.029<\/p>\n<\/td>\n<\/tr>\n

\n

Metastasis disease :<\/p>\n

\u00b7        M0      <\/p>\n

\u00b7        M+ <\/p>\n<\/td>\n

\n

86%<\/p>\n

57%<\/p>\n<\/td>\n

\n

80%<\/p>\n

21%<\/p>\n<\/td>\n

\n[85.72         129.58]\n[31.94           59.03]\n<\/td>\n\n

P=0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Type of resection:<\/p>\n

\u00b7        Complete         <\/p>\n

\u00b7        Incomplete   <\/p>\n<\/td>\n

\n

75%<\/p>\n

76%<\/p>\n<\/td>\n

\n

58%<\/p>\n

50%<\/p>\n<\/td>\n

\n[58.81         112.13]\n[57.62           97.58]\n<\/td>\n\n

P=0.56<\/p>\n<\/td>\n<\/tr>\n

\n

Radiotherapy<\/p>\n

\u00b7        yes              <\/p>\n

\u00b7        No                 <\/p>\n<\/td>\n

\n

77%<\/p>\n

25%<\/p>\n<\/td>\n

\n

56%<\/p>\n

25%<\/p>\n<\/td>\n

\n[66.79         103.02]\n[5.67             51.32]\n<\/td>\n\n

\n<\/p>

P=0.035<\/p>\n<\/td>\n<\/tr>\n

\n

The duration between RT & surgery<\/p>\n

\u00b7        <120 days         n=27<\/p>\n

\u00b7        >=120 days       n=9<\/p>\n

 (patients didn\u2019t undergo RT n=5)<\/p>\n<\/td>\n

\n

84%<\/p>\n

55%<\/p>\n<\/td>\n

\n

65%<\/p>\n

28%<\/p>\n<\/td>\n

\n[81.47         121.97]\n[27.74           59.09]\n<\/td>\n\n

\n<\/p>

P=0.002<\/p>\n<\/td>\n<\/tr>\n

\n

Molecular subgroups :<\/p>\n

(Patients with accurate IHC n=20)<\/strong><\/p>\n

\u00b7        WNT                           <\/p>\n

\u00b7        SHH                             <\/p>\n

\u00b7        Non-WNT\/Non-SHH <\/p>\n<\/td>\n

\n

<\/p>\n

100%<\/p>\n

53%<\/p>\n

83%<\/p>\n<\/td>\n

\n

<\/p>\n

100%<\/p>\n

36%<\/p>\n

55%<\/p>\n<\/td>\n

\n

\n<\/p>

\n<\/p>

NO DATA<\/p>\n

NO DATA<\/p>\n

NO DATA<\/p>\n<\/td>\n

\n

<\/p>\n

P=0.38<\/p>\n

<\/p>\n<\/td>\n<\/tr>\n

\n

Prognosis (Risk group)<\/p>\n

\u00b7        High risk                    <\/p>\n

\u00b7        Standard risk     <\/p>\n<\/td>\n

\n

69%<\/p>\n

100%<\/p>\n<\/td>\n

\n

42%<\/p>\n

63%<\/p>\n<\/td>\n

\n[41.75           71.58]\n[75.84         125.42]\n<\/td>\n\n

\n<\/p>

P=0.077<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n\n
\"\"<\/td>\n\n

Figure 4: The overall survival estimation using Kaplan-Meier<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n\n
\"\"<\/td>\n\n

Figure 5: 1)<\/strong> Kaplan-Meier calculates OS based on the period between surgery and radiation. 2) Kaplan-Meier calculates overall survival based on the radiation.<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n\n
\"\"<\/td>\n\n

Figure 6: Kaplan-Meier calculates overall survival based on metastasis disease<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n\n
\"\"<\/td>\n\n

Figure 7: Kaplan-Meier calculates overall survival based on molecular subgroup and histological type<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Discussion<\/strong><\/p>\n\n\n\n

The median age at the moment of diagnosistypically\nfalls between 5 and 6 years in children 17\u201319<\/sup>, which is\nconsistent with our results. In our series, the median age at the moment of\ndiagnosis is 8 years, the age range is 2 to 15 years. MB\ndemonstrates a notable male preponderance, a phenomenon extensively observed in\nvarious investigations, including the CBTRUS 2014 report, where the\nmale-to-female sex ratio often surpasses 1.7 20\u201322<\/sup> our\nstudy findings indeed corroborate this slight male predominance, with an\nincidence rate of 53.7% in male patients, resulting in a sex ratio of 1.15.<\/p>\n\n\n\n

Age is one of the clinical criteria utilized to\nclassify risk associated with MB. Infants and children diagnosed before the age\nof three appear to exhibit a less favorable prognosis, with reduced overall\nsurvival compared to younger patients23\u201325<\/sup>. Within our\ndataset, 5-year survival data indicates that the survival rate for children\nunder 3 years of age does not exceed 50%. These findings may be attributed to\nthe high malignancy of tumors, delayed diagnosis, and inadequate, or even the\nabsence of, post-surgical irradiation. Nevertheless, It is pertinent to\nemphasize that a recent meta-analysis and a retrospective study in Brazil did\nnot identify age as a significant prognostic factor 5,26<\/sup>.<\/p>\n\n\n\n

Histologically, the desmoplastic\/nodular type had the best mean survival (more than 80 months) (P=0.029), while the classic form was the most common (n=28). Our outcomes coincided with those of an international meta-analysis conducted by Rucktowski et al., the histological variant MBDN is an independent favorable prognostic factor, even in the presence of metastases27<\/sup>. Furthermore, the results published by Von Bueren et al. have shown a significantly higher  OS as well as event-free survival rate after 5 years in patients with MBDN\/MBEN treated exclusively with chemotherapy compared to other patients (respective values of p < 0.008 and p < 0.001.)17<\/sup>.<\/p>\n\n\n\n

In our series, tumor resection did not appear to be\nassociated with a better Os rate (p=0.56). There is controversy regarding the\nsurvival rate after total resection (GTR), subtotal resection (NTR) (tumor\nresidue < 1.5 cm\u00b2), or partial resection (STR) (RT>1.5 cm\u00b2). Some authors\nhave reported a correlation between total resection and a better survival rate,\nparticularly demonstrating a benefit in terms of progression-free survival\n(PFS) for patients who underwent total resection (GTR) compared to those with\npartial resection (STR) p=0.0228<\/sup>.<\/p>\n\n\n\n

In our series, radiotherapy appears to play an important role in improving survival. Indeed, the 5 years Os rate was significantly higher in patients who received chemotherapy and radiation combined compared to those who only received post-surgical chemotherapy (55.5% versus 25%) (p=0.035). These findings are consistent with previous results reported by Paulino29<\/sup>. Furthermore, the duration of radiotherapy (RT) is of paramount importance. Authors Back et al. observed a significant association between the duration of radiation and relapse-free survival (RFS) (p=0.049) 30<\/sup>.<\/p>\n\n\n\n

The period between the initial radiation treatment and surgery is an important consideration in the management of MB.  is advised that radiation begin 30 days after the surgery and not exceed 90 days 19<\/sup>. This recommendation is based on clinical evidence, including a subsequent study by Chin et al., which identified a decrease in overall survival after 5 years in patients who started radiotherapy early, within three weeks following surgery 31<\/sup>. Furthermore, Dietzsch et al. reported in a multicenter study that the time between radiation treatment and surgery is an independent prognostic factor. Patients who underwent radiotherapy with an interval exceeding 49 days had a lower rate of progression-free survival (PFS) compared to those with a shorter interval 32<\/sup>. However, authors showed a less favorable event-free survival (EFS) after 3 and 5 years for metastatic patients who started radiotherapy before 110 days compared to those with an interval exceeding 110 days (p=0.04) 33<\/sup>. In our study, we found that the interval between surgery and the initiation of radiotherapy had a statistically significant P value. Patients with an interval of less than 120 days had the Os after 5 years higher than those with an interval exceeding 120 days (p=0.002). This prolonged interval can be explained by several factors, including delays in patient management, Insufficient collaboration and communication among various healthcare professionals (surgical, radiological, and oncological), a high volume of patients scheduled for radiotherapy, insufficient patient information (irregular consultations and follow-up), challenging communication with parents (illiteracy, missed appointments), and logistical challenges related to rural settings, wide geographical distribution, and difficult access areas. The 5-year overall survival rates (21%) were impacted by the stage of metastasis, patients with metastasis disease had the lower OS after 5 years  (21% versus 80% P=0.001). Multiple series reported similar outcomes33,34<\/sup>.<\/p>\n\n\n\n

The majority of MB molecular subgroups were classified\nas SHH subtypes (13 cases), however other studies showed the nonWNT\/nonSHH as\nthe major type 8,28<\/sup>. histologically,\nall desmoplastic\/nodular\/MBEN variants were observed in the SHH group and the four\ncases of classic variants were among the nonWNT\/nonSHH group which was\nconsistent with other research10,12<\/sup>. the WNT\ngroup was observed in one patient which may be due to the small size of our\ncohort. Zhukova et al showed a significant difference in terms of five-year\noverall survival between the SHH group with and without tp53 mutations\n(81%  +\/- 5% and 41%  +\/-9%  \np<0.001 respectively)35<\/sup>. additionally, The majority\nof non-metastatic SHH patients are classified under the average\/standard risk\ncategory, exhibiting a five-year overall survival rate exceeding 80% 8,20<\/sup>. In our\ndata, the SHH group with tp53 mutation was not observed, therefore the five-year\nOS was lower by 45%, this may be due to the high frequency of metastatic\ndisease in the SHH group (>50 %). the non-WNT\/SHH subgroup displayed the most\nunfavorable outcome, primarily due to its resistance to therapy, as documented\nin previous studies36,37<\/sup>. moreover,\nit exhibited elevated rates of metastatic disease at the time of diagnosis 10<\/sup>. Wnt\ntumors contributed almost 14 % of all MB in these studies 10,38<\/sup>. The\nmajority of WNT patients are typically located in the midline (vermian)8,14<\/sup>.they\nhad long-term survival rates(>90%)10<\/sup>.\nas well Thompson et al published the results of WNT tumors with incomplete\nresection are considered as low risk 28<\/sup>.\nIn our series, only one case of 19 patients was in the WNT group.<\/p>\n\n\n\n

Limitation of the study<\/strong><\/p>\n\n\n\n

The study has a limited sample size and the results\nare from a single institution, moreover, we couldn\u2019t identify P53 mutation by\nwild spread immunostain or by sequencing and other subgroups such as group 3\nand group 4 (MYC amplification not available in the laboratory).<\/p>\n\n\n\n

Conclusion<\/strong><\/p>\n\n\n\n

The study provides epidemiological data about\nchildhood MB from a single institution in Morocco. In terms of overall survival\nrates, the results are quite promising. However, there is still a need to\nreduce the large gap between high and low-income countries and improve survival\noutcomes. To achieve this, expanding the network of the oncology centers is\nrecommended as well as implementing twinning and telemedicine initiatives.<\/p>\n\n\n\n

What is already known on this topic <\/strong><\/p>\n\n\n\n

Radiotherapy is a prognosis factor in MB management.<\/p>\n\n\n\n

The metastasis disease impacts negatively the overall survival. <\/p>\n\n\n\n

The desmoplasic\/nodular\/ MBEN variants had the best mean survival rates.<\/p>\n\n\n\n

What this study adds<\/strong><\/p>\n\n\n\n

The overall survival rates of childhood MB in Morocco.<\/p>\n\n\n\n

The duration between surgery and radiotherapy was significant.<\/p>\n\n\n\n

The study provides clinical and paraclinical features of childhood MB.<\/p>\n\n\n\n

Acknowledgements<\/strong><\/p>\n\n\n\n

All authors\ncontributed to this study by making substantial contributions :<\/p>\n\n\n\n

Conception: Mr Mohamed, Pr Hessissen, and Pr Cherradi Design: Pr ouazzani and Pr Alae. Acquisition data: Mr Mohamed Analysis and interpretation: Pr Razine and Dr El Hilali Drafting the manuscript: Mr Mohamed, Pr Hessissen, and Pr Cherradi Revising the manuscript: Pr Hessissen, Pr Cherradi, and Pr Oudghiri<\/p>\n\n\n\n

Conflict of interest<\/strong><\/p>\n\n\n\n

All authors declare that they have no\nconflicts of interest<\/p>\n\n\n\n

Funding Sources<\/strong><\/p>\n\n\n\n

there is no funding Sources<\/p>\n\n\n\n

References<\/strong><\/p>\n\n\n\n

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