FACTIBILIDAD Y ASPECTOS ÉTICOS:

LEs of cancer vary widely, depending upon factors such as the type and dose of treatment used and the age the patient is when undergoing treatment. Survivors of TYA cancer are at greater risk of cardiovascular disease, second malignancy and pulmonary complications, as well as psychosocial difficulties, than survivors of childhood cancer105_.

Many LEs have been known about for many years and the majority are well documented. A number of longitudinal studies, such as the British Childhood Cancer Survivor Study (BCCSS)106_{, the Childhood Cancer Survivor Study}

(CCSS)107 _{and the St Jude Lifetime Cohort Study (SJLife)}108 _{in the USA and}

the Swiss Childhood Cancer Survivor Study (SCCSS)109 _{have followed up}

patients for several decades and collated data from self-reports and

questionnaires on the health problems survivors have developed. Due to their reliance on questionnaires and self-reporting, however, they are all at risk of potential bias as they will not capture data on non-responders. The Adult Life after Childhood Cancer in Scandinavia (ALiCCS) study110 _{is a retrospective}

cohort study which is aiming to gather data from hospitals and disease registries on late effects of CYP’s cancer on a population level, which should

enhance the quality of data available on late effects. This study should potentially have fewer issues with bias because data is from registries and hospitals, rather than relying on participants returning questionnaires.

Known LEs include cardiovascular disease111_{, reproductive health problems}112

and subsequent primary neoplasms (SPNs)113_{. Respiratory}104_{, renal}114_,

endocrine115 _{and neurological}116 _{complications have also been described in the}

literature. LEs vary depending on the treatment received; for example patients who received chest radiotherapy are at considerable increased risk of

developing breast cancer117_{, whilst patients treated with anthracyclines may go}

on to develop cardiomyopathy118_{. Age at diagnosis and treatment of cancer}

also plays a role in the types of LEs which may develop. 1.6.1 Cardiovascular disease

Diseases of the cardiovascular system are 4-6 times more prevalent in CYP’s cancer survivors than the general population119,120_{. This includes conditions}

such as peripheral vascular disease, valvular heart disease, cardiac failure and myocardial infarction. Stroke risk is also elevated in CYP’s cancer survivors121_,

with a small but non-negligible subset experiencing recurrent stroke122_.

Survivors of both Hodgkin’s and non-Hodgkin’s lymphoma are at particular risk of cardiovascular diseases123_{, as are patients who have received thoracic}

radiotherapy or high dose anthracyclines124_.

1.6.2 Subsequent primary neoplasms

Subsequent primary neoplasms are tumours which arise in differing locations, or are histologically distinct, from the initial cancer and are thus distinct from relapse113 _{and are a considerable source of anxiety for cancer survivors and}

their families125_{. Around 1 in 25 CYP’s cancer survivors will develop an SPN in}

the 25 years following their original diagnosis126_{. Survivors of childhood cancer}

are 3-6 times more likely to develop SPNs than older patients127_{, and survivors}

of TYA cancer are also at increased risk of SPNs compared to older adults128_.

Survivors of TYA cancer often develop an SPN relatively soon after their initial cancer treatment, and shorter intervals between cancer diagnoses are

associated with poorer prognosis129_{. SPNs have been observed following}

treatment for a variety of cancers, including Burkitt’s lymphoma130_,

1.6.3 Sexual and reproductive health

Many chemotherapeutic agents, as well as radiotherapy to the lower abdomen and pelvis, may result in sub fertility112_{. Surgery may also result in difficulties}

achieving or carrying a pregnancy, either due to direct removal of the female reproductive organs134 _{or as a result of cervical incompetence following more}

targeted surgeries135_{. Sexual health problems such as erectile dysfunction}136,137

and decreased arousal138 _{are also seen commonly, and are particularly}

prevalent in those treated for cancer in the TYA period139_{. Difficulties with}

sexual health140,141 _{and sub fertility}142,143 _{have a considerable negative impact}

on mental health and quality of life. Conversely, psychological difficulties are one potential cause of sexual dysfunction144_{. Although there are strategies}

available to try to mitigate sub fertility, there are also multiple potential complications which may occur even if a pregnancy can be successfully achieved145_.

1.6.4 Respiratory disease

Diseases of the respiratory system affect CYP’s cancer survivors at a greater rate than the general population, with one in five having at least one respiratory diagnosis by 35 years post diagnosis146_{. Chest radiotherapy is strongly}

associated with pulmonary fibrosis, with a cumulative incidence of 3.5% by 20 years after the original cancer diagnosis104_{. Cranio-spinal irradiation, which is}

likely to involve at least some radiation to the chest by virtue of the location of the spine, is also associated with increased risk of respiratory pathology147_.

Chemotherapy with bleomycin is also associated with lung fibrosis, which can be particularly problematic following exposure to high concentration oxygen and thus cause serious potential problems during future general

anaesthesia148_.

1.6.5 Renal disease

Many chemotherapeutic agents are nephrotoxic and can cause both acute and late decreases in renal function, particularly platinum compounds, alkylating agents and methotrexate114_{. Reported prevalence of renal dysfunction among}

long term CYP’s cancer survivors varies considerably, but some studies report rates of up to 84%, with nephrectomy and radiotherapy to the kidney being notable risk factors along with the aforementioned chemotherapeutic agents149_.

1.6.6 Endocrine disease

Endocrine disorders are prevalent in CYP survivors, with one study reporting that nearly half had at least one endocrine problem. The greatest risk is seen in those treated for CNS tumours, who are at risk of pituitary damage as a result of surgery or radiotherapy, and Hodgkin’s lymphoma150_{. High rates of obesity}

and metabolic syndrome amongst CYP’s cancer survivors, which are risk factors for the development of diabetes mellitus, may explain some of this pathology151_{. Patients exposed to total body irradiation, chest or abdominal}

radiotherapy, as well as high dose therapy and stem-cell transplants, are at particular risk for developing metabolic syndrome152,153_.

1.6.7 Neurological disease

Aside from stroke, which has already been described in the cardiovascular disease section, neurological disease is not a major LE for many CYP’s cancer survivors. However, for survivors of CNS tumours, it can be a major issue. Seizures, motor impairment and sensorineural hearing loss will affect 41%, 35% and 23% of survivors respectively by 30 years post tumour diagnosis116_.