Childhood rhabdomyosarcoma has been fatal. Recovery rates have increased by 50 percent since 1975. In children five years of age or younger survival rates are up to 65 percent. In adolescents younger than 15 years old, the survival rate has increased up to 30 percent.

Adult survivors of childhood cancer have some physical, psychological, and social difficulties.

Premature heart disease is a major long-term complication in adult survivors of childhood cancer. Adult survivors are eight times more likely to die of heart disease than other people, and more than half of children treated for cancer develop some type of cardiac abnormality, although this may be asymptomatic or too mild to qualify for a clinical diagnosis of heart disease.

Familial and genetic factors are identified in 5-15% of childhood cancer cases. In <5-10% of cases, there are known environmental exposures and exogenous factors, such as prenatal exposure to tobacco, X-rays, or certain medications. For the remaining 75-90% of cases, however, the individual causes remain unknown. In most cases, as in carcinogenesis in general, the cancers are assumed to involve multiple risk factors and variables.

Aspects that make the risk factors of childhood cancer different from those seen in adult cancers include:

- Different, and sometimes unique, exposures to environmental hazards. Children must often rely on adults to protect them from toxic environmental agents.

- Immature physiological systems to clear or metabolize environmental substances

- The growth and development of children in phases known as "developmental windows" result in certain "critical windows of vulnerability".

Also, a longer life expectancy in children avails for a longer time to manifest cancer processes with long latency periods, increasing the risk of developing some cancer types later in life.

There are preventable causes of childhood malignancy, such as delivery overuse and misuse of ionizing radiation through computed tomography scans when the test is not indicated or when adult protocols are used.

Esthesioneuroblastoma is a slow developing but malignant tumor with high reoccurrence rates because of its anatomical position. The tumor composition, location and metastatic characteristics as well as the treatment plan determine prognosis. Common clinical classification systems for esthesioneuroblastoma include the Kadish classification and the Dulguerov classfictation. Histopathological characteristics on top of Kadish classification can further determine cancer prognosis. In severe, Kadish class C tumors, Haym's grades of pathology are important for prognosis. Patients with low grade Kadish class C tumors have a 10-year survival rate of 86 percent compared to patients with high grade class C tumors who have a survival rate of 28 percent. Surgically treated patients with high grade tumors are more likely to experience leptomeningeal metastases or involvement of the cerebral spinal fluid unlike patients with low grade tumors who usually only see local recurrence. Survival rates for treated esthesioneuroblastoma are best for surgery with radiotherapy (65%), then for radiotherapy and chemotherapy (51%), just surgery (48%), surgery, radiotherapy and chemotherapy (47) and finally just radiotherapy (37%). From the literature, radiotherapy and surgery seem to boast the best outcome for patients. However, it is important to understand that to some degree, prognosis is related to tumor severity. More progressed, higher grade tumors would result in chemotherapy or radiotherapy as the only treatment. It is no surprise that the prognosis would be worse in these cases.

Although reliable and comprehensive incidence statistics are nonexistent, LCLC-RP is a rare tumor, with only a few hundred cases described in the scientific literature to date. LCLC's made up about 10% of lung cancers in most historical series, equating to approximately 22,000 cases per year in the U.S. Of these LCLC cases, it is estimated that about 1% will eventually develop the rhabdoid phenotype during tumor evolution and progression. In one large series of 902 surgically resected lung cancers, only 3 cases (0.3%) were diagnosed as LCLC-RP. In another highly selected series of large-cell lung carcinoma cases, only 4 of 45 tumors (9%) were diagnosed as the rhabdoid phenotype using the 10% criterion, but another 10 (22%) had at least some rhabdoid cell formation. It appears likely, therefore, that LCLC-RP probably comprises between 0.1% and 1.0% of all lung malignancies.

Similar to nearly all variants of lung carcinoma, large cell lung carcinoma with rhabdoid phenotype appears to be highly related to tobacco smoking. It also appears to be significantly more common in males than in females.

Patients who have been diagnosed with ARMS often have poor outcomes. The four year survival rate without remission for local ARMS tumors is 65 percent, while the four year survival rate with metastatic ARMS is only 15 percent. Patients who have metastatic ARMS positive with PAX3-FOXO1 fusion often have a poorer outcome than patients positive with PAX7-FOXO1 fusion, with a four-year survival rate of 8 percent and 75 percent respectively. Other variables affect the four year survival rate, such as, primary tumor site, size of primary tumor, amount of local invasion, number of distal lymph nodes spread to, and whether metastasis has occurred. Prognosis for patients who have primary tumor sites within the bones often have higher survival rates and respond well to treatment options. While patients who have primary tumor sites within the nasopharynx region with metastases to the breast have very poor outcomes. Patients who are fusion protein negative with low risk clinical features should be treated with reduced therapy, while patients who are fusion protein positive with low risk clinical features should be treated as an intermediate risk and have more intensive therapy regimens.

Esthesioneuroblastoma accounts for 2% of all intranasal tumors with an incidence of 0.4 cases per million people. Fewer than 700 cases of esthesioneuroblastoma have been seen in the US since 1988. Fewer than 400 unique cases have been reported globally. Esthesioneuroblastoma can occur at any time, with peak occurrence reported in the second and sixth decade of life.

Childhood rhabdomyosarcoma is difficult to diagnose. Factors that increase the likelihood of this cancer include Li-Fraumeni syndrome, type one Neurofibromatosis, Beckwith-Wiedemann syndrome, Costello syndrome, and Noonan syndrome. Each contribute to deformations of bones, tissue, and muscles.

Sarcoma botryoides normally is found in children under 8 years of age. Onset of symptoms occurs at age 3 years (38.3 months) on average. Cases of older women with this condition have also been reported.

Soft-tissue sarcomas are relatively uncommon cancers. They account for less than 1% of all new cancer cases each year. This may be because cells in soft tissue, in contrast to tissues that more commonly give rise to malignancies, are not continuously dividing cells.

In 2006, about 9,500 new cases were diagnosed in the United States. Soft-tissue sarcomas are more commonly found in older patients (>50 years old) although in children and adolescents under age 20, certain histologies are common (rhabdomyosarcoma, synovial sarcoma).

Around 3,300 people were diagnosed with soft tissue sarcoma in the UK 2011.

Most soft-tissue sarcomas are not associated with any known risk factors or identifiable cause. There are some exceptions:

- Studies suggest that workers who are exposed to chlorophenols in wood preservatives and phenoxy herbicides may have an increased risk of developing soft-tissue sarcomas. An unusual percentage of patients with a rare blood vessel tumor, angiosarcoma of the liver, have been exposed to vinyl chloride in their work. This substance is used in the manufacture of certain plastics, notably PVC.

- In the early 1900s, when scientists were just discovering the potential uses of radiation to treat disease, little was known about safe dosage levels and precise methods of delivery. At that time, radiation was used to treat a variety of noncancerous medical problems, including enlargement of the tonsils, adenoids, and thymus gland. Later, researchers found that high doses of radiation caused soft-tissue sarcomas in some patients. Because of this risk, radiation treatment for cancer is now planned to ensure that the maximum dosage of radiation is delivered to diseased tissue while surrounding healthy tissue is protected as much as possible.

- Kaposi's sarcoma, a rare cancer of the cells that line blood vessels in the skin and mucus membranes, is caused by Human herpesvirus 8. Kaposi's sarcoma often occurs in patients with AIDS (acquired immune deficiency syndrome). Kaposi's sarcoma, however, has different characteristics than typical soft-tissue sarcomas and is treated differently.

- In a very small fraction of cases, sarcoma may be related to a rare inherited genetic alteration of the p53 gene and is known as Li-Fraumeni syndrome. Certain other inherited diseases are associated with an increased risk of developing soft-tissue sarcomas. For example, people with neurofibromatosis type I (also called von Recklinghausen's disease, associated with alterations in the NF1 gene) are at an increased risk of developing soft-tissue sarcomas known as malignant peripheral nerve sheath tumors. Patients with inherited retinoblastoma have alterations in the RB1 gene, a tumor suppressor gene, and are likely to develop soft-tissue sarcomas as they mature into adulthood.

LCLC-RP are considered to be especially aggressive tumors with a dismal prognosis. Many published cases have shown short survival times after diagnosis. Some studies suggest that, as the proportion of rhabdoid cells in the tumor increases, the prognosis tends to worsen, although this is most pronounced when the proportion of rhabdoid cells exceeds 5%. With regard to "parent" neoplasms other than LCLC, adenocarcinomas with rhabdoid features have been reported to have worse prognoses than adenocarcinomas without rhabdoid features, although an "adenocarcinoma with rhabdoid phenotype" tumor variant has not been specifically recognized as a distinct entity under the WHO-2004 classification system.

Interestingly, there are case reports of rhabdoid carcinomas recurring after unusually long periods, which is unusual for a fast-growing, aggressive tumor type. One report described a very early stage patient whose tumor recurred 6 years after initial treatment. Although rapidly progressive, fulminant courses seem to be the rule in this entity, long-term survival has also been noted, even post-metastectomy in late stage, distant metastatic disease.

Neuroblastoma comprises 6–10% of all childhood cancers, and 15% of cancer deaths in children. The annual mortality rate is 10 per million children in the 0- to 4-year-old age group, and 4 per million in the 4- to 9-year old age group.

The highest incidence is in the first year of life, and some cases are congenital. The age range is broad, including older children and adults, but only 10% of cases occur in people older than 5 years of age. A large European study reported less than 2% of over 4000 neuroblastoma cases were over 18 years old.

The prognosis for rhabdomyosarcoma has improved greatly in recent decades, with over 70% of patients surviving for five years after diagnosis.

An estimated 3% of pediatric brain tumors are AT/RTs, although this percentage may increase with better differentiation between PNET/medulloblastoma tumors and AT/RTs.

As with other CNS tumors, more males are affected than females (ratio 1.6:1). The ASCO study showed a 1.4:1 male to female ratio.

Rhabdomyosarcoma is the most common soft-tissue sarcoma in children as well as the third most common solid tumor in children. Recent estimates place the incidence of the disease at approximately 4.5 case per 1 million children/adolescents with approximately 250 new cases in the United States each year. With the vast majority of cases of RMS occurring in children or adolescents, two-thirds of reported cases occur in youths under the age of 10. RMS also occurs slightly more often in males than in females, with a ratio of approximately 1.3–1.5:1. In addition, slightly lower prevalence of the disease has been reported in black and Asian children relative to white children. In most cases, there are no clear predisposing risk factors for the development of RMS. It tends to occur sporadically with no obvious cause. However, RMS has been correlated with familial cancer syndromes and congenital abnormalities including neurofibromatosis type 1, Beckwith-Wiedemann syndrome, Li–Fraumeni syndrome, cardio-facio-cutaneous syndrome, and Costello syndrome. It has also been associated with parental use of cocaine and marijuana.

Between 20% and 50% of high-risk cases do not respond adequately to induction high-dose chemotherapy and are progressive or refractory. Relapse after completion of frontline therapy is also common. Further treatment is available in phase I and phase II clinical trials that test new agents and combinations of agents against neuroblastoma, but the outcome remains very poor for relapsed high-risk disease.

Most long-term survivors alive today had low or intermediate risk disease and milder courses of treatment compared to high-risk disease. The majority of survivors have long-term effects from the treatment. Survivors of intermediate and high-risk treatment often experience hearing loss. Growth reduction, thyroid function disorders, learning difficulties, and greater risk of secondary cancers affect survivors of high-risk disease. An estimated two of three survivors of childhood cancer will ultimately develop at least one chronic and sometimes life-threatening health problem within 20 to 30 years after the cancer diagnosis.

Sarcomas are quite rare with only 15,000 new cases per year in the United States. Sarcomas therefore represent about one percent of the 1.5 million new cancer diagnoses in that country each year.

Sarcomas affect people of all ages. Approximately 50% of bone sarcomas and 20% of soft tissue sarcomas are diagnosed in people under the age of 35. Some sarcomas, such as leiomyosarcoma, chondrosarcoma, and gastrointestinal stromal tumor (GIST), are more common in adults than in children. Most high-grade bone sarcomas, including Ewing's sarcoma and osteosarcoma, are much more common in children and young adults.

There are no known risk factors that have been identified specific to the disease. The tumor appears to arise from the primitive cells of childhood, and is considered a childhood cancer.

Research has indicated that there is a chimeric relationship between desmoplastic small-round-cell tumor (DSRCT) and Wilms' tumor and Ewing's sarcoma. Together with neuroblastoma and non-Hodgkin's lymphoma, they form the small cell tumors.

DSRCT is associated with a unique chromosomal translocation t(11;22)(p13:q12) resulting in an EWS/WT1 transcript that is diagnostic of this tumor. This transcript codes for a protein that acts as a transcriptional activator that fails to suppress tumor growth.

The EWS/WT1 translocation product targets ENT4. ENT4 is also known as PMAT.

The prognosis for AT/RT has been very poor, although some indications exist that an IRSIII-based therapy can produce long-term survival (60 to 72 months). Two-year survival is less than 20%, average survival postoperatively is 11 months, and doctors often recommend palliative care, especially with younger children because of the poor outcomes. Recently, a protocol used by a multicenter trial reported in the "Journal of Clinical Oncology" resulted in a 70% survival rate at 2–3 years, with most relapses occurring within months, leading to hope that a point exists beyond which patients can be considered cured.

Patients with metastasis (disseminated tumor), larger tumors, tumors that could not be fully removed, or tumor recurrence, and who were younger than 36 months had the worst outcomes (i.e., shorter survival times).

A retrospective survey from 36 AT/RT cases at St. Jude Children's Hospital from 1984 to 2003 showed that the two-year event-free survival (EFS) for children under three was 11%, and the overall survival (OS) rate was 17%. For children aged 3 years or older, the EFS was 78% and the OS 89%. A retrospective register at the Cleveland Children's hospital on 42 AT/RT patients found median survival time is 16.25 months and a survival rate around 33%. One-quarter of these cases did not show the mutation in the "INI1/hSNF5" gene.

The longest-term survivals reported in the literature are:

- (a) Hilden and associates reported a child who was still free from disease at 46 months from diagnosis.

- (b) Olson and associates reported a child who was disease free at five years from diagnosis based on the IRS III protocol.

- (c) In 2003, Hirth reported a patient who had been disease-free over six years.

- (d) Zimmerman in 2005 reported 50-to-72 month survival rates on four patients using an IRS III-based protocol. Two of these long-term survivors had been treated after an AT/RT recurrence.

- (e) A NYU study (Gardner 2004) has four of 12 longer-term AT/RT survivors; the oldest was alive at 46 months after diagnosis.

- (f) Aurélie Fabre, 2004, reported a 16-year survivor of a soft-tissue rhabdoid tumor.

- (g) Medical University of Vienna, 2013, reported a 16-year survivor, among other long-term survivors

Cancer treatments in long-term survivors who are children usually cause a series of negative effects on physical well being, fertility, cognition, and learning.

Alveolar rhabdomyosarcoma (ARMS) is a sub-type of the rhabdomyosarcoma soft tissue cancer family whose lineage is from mesenchymal cells and are related to skeletal muscle cells. ARMS tumors resemble the alveoli tissue that can be found in the lungs. Tumor location varies from patient to patient, but is commonly found in the head and neck region, male and female urogenital tracts, the torso, and extremities. Two fusion proteins can be associated with ARMS, but are not necessary, PAX3-FKHR (now known as FOXO1). and PAX7-FKHR. In children and adolescents ARMS accounts for about 1 percent of all malignancies, has an incidence rate of 1 per million, and most cases occur sporadically with no genetic predisposition.

The prognosis for DSRCT remains poor. Prognosis depends upon the stage of the cancer. Because the disease can be misdiagnosed or remain undetected, tumors frequently grow large within the abdomen and metastasize or seed to other parts of the body.

There is no known organ or area of origin. DSRCT can metastasize through lymph nodes or the blood stream. Sites of metastasis include the spleen, diaphragm, liver, large and small intestine, lungs, central nervous system, bones, uterus, bladder, genitals, abdominal cavity, and the brain.

A multi-modality approach of high-dose chemotherapy, aggressive surgical resection, radiation, and stem cell rescue improves survival for some patients. Reports have indicated that patients will initially respond to first line chemotherapy and treatment but that relapse is common.

Some patients in remission or with inoperable tumor seem to benefit from long term low dose chemotherapy, turning DSRCT into a chronic disease.

Embryonal rhabdomyosarcoma (ERMS) is a rare histological form of cancer of connective tissue wherein the mesenchymally-derived malignant cells resemble the primitive developing skeletal muscle of the embryo. It is the most common soft tissue sarcoma occurring in children.

NUT carcinoma (formerly NUT midline carcinoma), is a rare genetically defined, very aggressive squamous cell epithelial cancer that usually arises in the midline of the body and is characterized by a chromosomal rearrangement in the nuclear protein in testis gene. In approximately 75% of cases, the coding sequence of "NUTM1" on chromosome 15q14 is fused to "BRD4" or "BRD3", which creates a chimeric gene that encodes the "BRD-NUT" fusion protein. The remaining cases, the fusion of NUTM1 is to an unknown partner gene, usually called "NUT"-variant.

Rhabdomyosarcoma, or RMS, is an aggressive and highly malignant form of cancer that develops from skeletal (striated) muscle cells that have failed to fully differentiate. It is generally considered to be a disease of childhood, as the vast majority of cases occur in those below the age of 18. It is commonly described as one of the "small, round, blue cell tumours of childhood" due to its appearance on an H&E stain. Despite being a relatively rare cancer, it accounts for approximately 40% of all recorded soft tissue sarcomas. RMS can occur in any site on the body, but is primarily found in the head, neck, orbit, genitourinary tract, genitals, and extremities. There are no clear risk factors for RMS, but the disease has been associated with some congenital abnormalities. Signs and symptoms vary according to tumor site, and prognosis is closely tied to the location of the primary tumor. Common site of metastasis include the lungs, bone marrow, and bones. There are many classification systems for RMS and a variety of defined histological types. Embryonal rhabdomyosarcoma is the most common type and comprises about 60% of cases. Patient outcomes vary considerably, with 5 years survival rates between 35% and 95% depending on the type of RMS involved, so clear diagnosis is critical for effective treatment and management. Unfortunately, accurate and quick diagnosis is often difficult due to the heterogeneity of RMS tumors and a lack of strong genetic markers of the disease. Treatment usually involves a combination of surgery, chemotherapy, and radiation. Sixty percent to 70% of newly diagnosed patients with nonmetastatic disease can be cured using this combined approach to therapy. Despite aggressive multimodality treatment, less than 20% of patients with metastatic RMS are able to be cured of their disease.