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

God Bless Her Soul

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

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

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

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

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

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

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

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.

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

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

Literature & Review

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

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

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

Infants and neonates solid tumors in India

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

Neonatal tumors through 260 cases in Tenerife, Spain During 25 years of study Neonatal neoplasms were 276.5 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%

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%

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

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.

Malignancies in patients less than 6 months at MAHAK hospital

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

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

Sex & age groups

Diagnoses Diagnosis n Retinoblastoma 73 Neuroblastoma 23 Brain tumor 20 Leukemia 18 Sarcoma 8 Wilms’ tumor 4 Other 7 Total 153

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

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

Diagnoses & sex

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

Diagnoses & age groups

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

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

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

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

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

Recurrence & Sex

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

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

Status & sex

Status & age groups

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%

PFS One year PFS

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%

OS 3-years OS 5-years OS

All of the diagnoses

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

Finally the last words…..

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

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

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

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