Diabetes mellitus (DM) is commonly found in cancer patients. The relationship between DM and cancer appears to be bidirectional: DM has been associated with an increased risk of developing several types of cancer while also cancer treatments, through the induction of metabolic derangements, can facilitate the onset of DM, or worsen glucose control. In particular, novel antineoplastic treatments such as immunotherapy and targeted therapies have been associated with both acute and long-term metabolic consequences. An adequate management of DM in cancer patients is pivotal, since DM can negatively affect the clinical outcomes of these subjects, being associated with worse survival. However, DM management in cancer patients may be challenging given the peculiarities of these conditions. Lower reliability of HbA1c, a thorough evaluation of the safety profile of antidiabetic drugs, and the need to adapt glycemic targets to patients' prognosis should be taken into consideration. Moreover, DM is commonly encountered also in the ever-growing population of cancer survivors, contributing to their increased cardiovascular risk. In conclusion, taking in consideration the lack of specific guidelines, the particular features of the condition, and the potential impact on prognosis, a multidisciplinary management of DM in cancer patients and survivors is warranted.
The spectrum of bone morbidity in childhood cancer survivors (CCS) is broad and extends beyond "low bone mineral density" to structural damage including fracture-induced vertebral deformity, and joint collapse due to osteonecrosis or slipped capital femoral epiphysis. In addition, short stature, scoliosis, leg length discrepancy, and vertebral deformity can arise from critical interference with growth plate activity. In some cases, insufficient residual growth potential or irreversible growth plate damage can lead to permanent structural deformity, leaving the patient with chronic functional limitations. In this chapter, we describe the clinical manifestations, natural history, and risk factors for cancer-related bone morbidity, approaches to monitoring and diagnosis, and the (paucity of) data available on prevention and treatment measures. In so doing, we unveil important biological principles about the potential for the pediatric skeleton to recover from bone morbidity, obviating the need for treatment, versus permanent structural damage that can negatively impact quality of life over the long-term. These observations, in turn, illuminate the unmet needs that drive future research to improve musculoskeletal strength and mobility in this setting.
Cancer therapy-induced bone loss (CTIBL), occurring especially in hormone-treated breast and prostate cancer patients, is a noteworthy long-term consequence of cancer treatments. Because of its negative impact on the quality life of cancer survivors, it deserves much attention. We here summarize the pathophysiology of CTIBL in breast and prostate cancer, its clinical presentation, management, and treatment.
Although childhood-onset craniopharyngioma is a low-grade intracranial tumor with excellent prognosis in terms of overall survival, survivors may suffer from devastating consequences caused by hypothalamic damage. Disease- or treatment-related hypothalamic damage leads to disturbed hunger-satiety and thirst feelings, decreased energy expenditure, behavioral problems, disturbances of circadian rhythm, temperature dysregulation, and pituitary dysfunction. These children are at great risk for developing the metabolic syndrome and comorbidities leading to premature mortality. In this chapter, we shall discuss hypothalamic-pituitary morbidity and outcome of childhood-onset craniopharyngioma patients and future perspectives for improvement.
With improved survival of childhood, adolescent, and young adult (CAYA) cancer, the European survivor population of 300,000-500,000 continues to expand. Most survivors will experience at least one and often multiple cancer- and treatment-related late effects throughout their lives, including endocrine toxicities. Besides affecting their physical and psychosocial health status, these might reduce life expectancy and quality of life. Prevalent endocrine complications include hypothalamic-pituitary dysfunction, central precocious puberty, primary thyroid, male or female gonadal dysfunction, metabolic syndrome, and low bone mineral density. Long-term follow-up (LTFU) care, including education, risk-based prevention, and surveillance strategies, is essential to reduce the burden of endocrine complications and to allow for timely interventions. To integrate scientific expert knowledge, evidence-based clinical practice guidelines have been developed by the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) and PanCare. These guide LTFU care by describing risk populations and preferred surveillance modalities. Moreover, consensus-based recommendations have been developed by PanCareFollowUp where evidence-based guidance is still awaited. The PanCareSurFup models of care guidelines recommend multidisciplinary team care at or under guidance of a cancer survivorship expert center, so CAYA cancer survivors receive appropriate care and support to optimize health.
Hypothalamic-pituitary (HP) dysfunctions are commonly reported complications in survivors of childhood cancer. These include growth hormone deficiency, luteinizing hormone/follicle-stimulating hormone deficiency, thyroid-stimulating hormone deficiency, adrenocorticotropic hormone deficiency, central precocious puberty, hyperprolactinemia, and central diabetes insipidus. Local tumor invasion and surgical or radiation-induced injury represent the highest risk factors. New treatment modalities, such as immunotherapy and molecular targeted therapy have the potential to cause autoimmune hypophysitis. Untreated HP dysfunctions are associated with adverse physical and psychosocial consequences and reduced quality of life. Systematic and periodic endocrine assessments optimize early diagnosis and timely treatment and may improve long-term health outcomes.
Long-term cancer survivors are at high risk of developing cardiac complications from the treatments, both systemic agents and thoracic irradiation, received to cure the primary tumor. Modern advances, particularly in the field of radiotherapy, aim to reduce the risk of cardiovascular disease. Also, new diagnostic tools increasingly improve their efficacy in early detection of the preclinical treatment-induced cardiac damage. In this review, we summarize the mechanisms of radiotherapy- and chemotherapy-induced cardiac injury, the available clinical data, the strategies to mitigate cardiac exposure with modern radiotherapy and the current diagnostic tools for an early detection and prompt management of these complications in long-term cancer survivors.
Modern advances in oncological treatments determined a significant improvement in survival rates for several malignancies. Nevertheless, survivorship and quality of life of cancer survivors may be negatively impaired by metabolic and endocrine side effects related to anticancer treatments, including alterations of pituitary-gonadal axis function. In fact, both medical (chemo- and radiotherapy) and surgical approaches may negatively impact on gonadal function, leading to transient or permanent hypogonadism and infertility. In view of these considerations, fertility preservation (FP) should be a primary concern in all oncological patients who may potentially achieve parenthood, irrespectively from their sex and pubertal status at treatment, and adequate counselling should be provided before undergoing gonadotoxic therapy or gonadectomy. Cryopreservation of gametes, when feasible, represents the mainstay for FP in postpubertal age, while procedures involving storage of tissue specimens or stem cells should still be considered as experimental. Given the complexity of both hormonal and psychological implications in this clinical setting, a multidisciplinary approach is advisable for optimal FP and for early diagnosis and treatment of hypogonadism.