1. Malignancies in patients less than 6 months at MAHAK hospital
Dr. Azim Mehrvar,
Pediatric Hematologist-Oncologist,
AJA University of Medical Sciences, Tehran, Iran
MAHAK Pediatric Cancer Treatment and Research Center

2. God Bless Her Soul

3. Introduction
Malignancy diagnosed within the first 4 weeks of postnatal life is rare
results from processes fundamentally different to most other pediatric and adult tumors
Clinically abnormal cell function results in a spectrum of behavior ranging from the highly malignant to the completely benign

4. Tumors and Neonates
The important cause of mortality and morbidity in neonates
Only 2% of all pediatric malignancies
Wide spectrum of benign and malignant tumors
Two-thirds of these tumors can diagnose during the first week of life

5. Diagnosis of neonatal malignancies
The diagnosis of malignancy itself may therefore not be straightforward
opinions may differ between even experienced observers
Risk stratification is also difficult and often complex

6. Associations
Nearly 20% of congenital malformations associated with neonatal tumors
Probable association of maternal drug intake & tumors
Development of malignancies can be assumed entirely of prenatal origins

7. Solid tumors and neonates
Are rare in neonates and infants
Nearly 10% of pediatric malignancies
Behaves differently in terms of:
Ethiopathogenesis
Response to therapy
long term outcomes

8. Incidence of neonatal solid tumors
The highest reported incidence is in Japan
The most common solid tumors in infants and neonates are:
Neuroblastoma
Wilms’ Tumors
Teratoma
Soft Tissue Sarcoma
The rare tumors are: hepatoblastoma, CNS tumors, Retinoblastoma

9. Factors responsible for outcomes of neonatal solid tumors
Sex
Socioeconomic situations
Nutritional status
Low birth weight

10. Background of Treatment
At first these age groups received the same therapy as other children, thus their survival was worse.
At the end of 80s pilot studies had been done to change the kinds of therapies.

11. Treatment Neonate cannot be treated as a small adult
Differences in body composition modify the distribution and excretion of drugs
Immature organ systems such as the kidney or immune system may increase the susceptibility of the infant to toxic side effects of treatment
The effects of treatment on growth and development must also be considered

12. Some approaches in the treatment of infantile brain tumors
Prolonged postoperative chemotherapy and delayed irradiation as designed in the POG
Postoperative chemotherapy without irradiation in the SFOP and in the GPO studies
The role of high-dose chemotherapy with autologous stem cells transplantation

13. Literature & Review

14. The British pediatric pathology society
Estimates that:
The benign congenital neoplasia = 1:12,500 live births
The malignant congenital neoplasia = 1:17,500 live births
Neonatal malignancies: 1-2% of all pediatric malignancies
At 1985 in England 0.05% of all pediatric malignancies related to infants less than 1 year old

15. Some reports of infantile solid tumors
Kako in 2005 reported infantile NB had good prognosis
Tumor free survival rates were as:
41.6% for malignant GCT
40% renal tumors
28.6% STS
16.6% hepatoblastoma

16. Infants and neonates solid tumors in India
They evaluated 59 cases ranged 1 day to 12 months (mean age 5.18 months)

17. Infants and neonates solid tumors in India

18. Neonatal tumors through 72 cases in Valencia, Spain
During 9 years of study
2.8% of all pediatric tumors on those years
The most frequent tumors were:
Hemangiomas 20.8%
Neuroblastoma 16.7%
Teratomas 12.5%
STS 9.7%
The survival rate was 73%
The median time of follow-up was 8 years

19. Neonatal tumors through 260 cases in Tenerife, Spain
During 25 years of study
Neonatal neoplasms were per million live births
Sex as: 43.8% males; 56.2% females
The mean age of DX: 5.5 days (range 1-28 days)
The most common malignancies were:
Neuroblastoma: 31.2%
GCT: 25%
STS: 18.8%
The 5-years OS: 87.5%

20. Neonatal solid tumors through 71 cases in Institute Gustave Roussy
During 17 years
1.2% of all pediatric malignancies at Gustave Roussy
The most frequent tumors were:
Neuroblastoma 59%
Mesenchymal tumors 17%
Cerebral tumors 8%
The main therapeutic complications were: hematologic toxicities and infections
The 5-years OS: 79%

21. Neonatal solid tumors in 42 African patients
The most common types of malignancies were:

22. Neonatal malignancies in 102 Canadian patients
The most common types of malignancies were:
Neuroblastoma: 11.9%
Retinoblastoma: 11.5%
Sarcoma: 1.9%
Liver tumors: 1.8%
Wilms’ tumor: 1.3%
CNS tumors: 1%
Leukemia: 0.5%
41% of patients died from malignancy.

23. Malignancies in patients less than 6 months at MAHAK hospital

24. Designing the study All of the children ≤ 6 months
Who referred to MAHAK hospital for diagnosis and treatment
From Apr 2007 to Sept 2017
Totally 153 children

25. Sex & Age Sex Age at diagnosis 2 days to 6 months (193 days)
Median 3 months (105 days)
86 males children
67 females children

26. Sex & age groups

27. Diagnoses Diagnosis n Retinoblastoma 73 Neuroblastoma 23 Brain tumor20
Leukemia 18
Sarcoma 8
Wilms’ tumor 4
Other 7
Total
153

28. Diagnosis’ subgroups Patients (153) RB 73 NB 23 BT 20 Leukemia 18
Astrocytoma 8
Optic glioma 4
EP 3
MB 2
AT/RT 2
PNET 1
Leukemia 18
AML 9
ALL 8
CML 1
Sarcoma 8
RMS 7
Ewing 1
Wilms’ tumor 4
Other 7
HLH 2
Teratoma 2
Hepatoblastoma 3

29. Diagnoses & sex Diagnoses Male Female Retinoblastoma 39 34
Neuroblastoma 15 8
Wilms’ tumor 2
ALL 7 1
AML 4 5
CML -
Medulloblastoma
Ependymoma
PNET
Optic glioma
Astrocytoma 3
AT/RT
Diagnoses
Male
Female
Rhabdomyosarcoma 6 1
Ewing family -
Teratoma 2
Hepatoblastoma 3
HLH

30. Diagnoses & sex

31. Diagnoses & age groups Diagnoses < 1 1-3 3-6 Retinoblastoma 6 20 47
Neuroblastoma 3 4 16
Wilms tumor - 1
ALL 2 5
AML
CML
Medulloblastoma
Ependymoma
PNET
Optic glioma
Astrocytoma
AT/RT
Diagnoses
< 1
1-3
3-6
Rhabdomyosarcoma 1 3
Ewing family -
Teratoma
Hepatoblastoma 2
HLH

32. Diagnoses & age groups

33. Background 29 patients (19%) had familial marriage
57 patients (37.2%) had family history of cancer
23 patients out of 57 (40%) had family history of retinoblastoma

34. Recurrence 42 patients (27.4%) had recurrence
11 cases out of 42 (26.2%) had second relapse
3 patients out of 11 (27.3%) had third relapse

35. The median time of first relapse
The time of first relapse was from 60 days to 5 years
The median time of first relapse was 9.5 months

36. The median time of second relapse
The time of second relapse since the first relapse was from 43 days to 3 years
The median time of second relapse was 13 months

37. The median time of third relapse
The time of third relapse since the second relapse was from 50 days to 1 year
The median time of third relapse was 4 months

38. Recurrence & Sex

39. Recurrence & age groups
Significant relation between recurrence and the age group of 3-6 months
P-Value: 0.014

40. Status of the patients
84 patients (54.9%) are at the phase of end of treatment
18 patients (11.8%) are still under treatment
11 patients (11.1%) referred to their cities for continuing their treatment
34 patients (22.2%) died

41. Status & sex

42. Status & age groups

43. PFS Progression Free Survival time was from 14 days to 5 years
The median time of PFS was 7 months
The 1-year PFS was 31.3 ± 0.05%
The 2-years PFS was 13.2 ± 0.04%

44. PFS
One year PFS

45. OS The over all survival was from 14 days to 9 years
The median time of follow-up was 15 months
The 3-years OS was 77.1 ± 0.04%
The 5-years OS was 68.5 ± 0.05%

46. OS
3-years OS
5-years OS

47. All of the diagnoses

48. Last status Diagnoses Off treatment During treatment
Referred to other cities
Death
Total
Retinoblastoma 52 10 3 8 73
Neuroblastoma 15 4 2 23
Brain tumor 12 1 20
Leukemia 11 18
Sarcoma - 6
Wilms’ tumor
Other 7

50. Finally the last words…..

51. The rarity of neonatal malignancies makes it imperative that clinicians report their experience.

52. At this single center study the most common malignancies in patients less than 6 months were retinoblastoma, neuroblastoma and brain tumors.

53. The low PFS rates mean that there are high risk factors to proceed the recurrence, and there should be multidisciplinary decisions to decrease these factors

54. The high rate of overall survival showed the good prognosis of patients