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Cancers
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Frailty in Pediatric and Young Adult Cancer Survivors: From Bench...
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Frailty in Pediatric and Young Adult Cancer Survivors: From Bench to Bedside

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Epidemiology and Prevention".

Deadline for manuscript submissions: closed (10 October 2022) | Viewed by 23514

Special Issue Editor

Prof. Francesca Rossi

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Guest Editor
Department of Woman, Child, General and Special Surgery, University of Campania “Luigi Vanvitelli”, 80138 Napoli, Italy
Interests: pediatrics; hematology; oncology; pharmacology; molecular and cellular biology

Special Issue Information

Dear Colleagues,

One of the greatest successes of the field of medicine is the improvement of survival among children with cancer, with the 5-year survival rate now exceeding 80%. Unfortunately, those who are successfully treated for their primary malignancy experience increased morbidity and mortality rates compared to the general population, related to chemotherapy, radiotherapy, or both. Childhood cancer survivors are at an especially increased risk for frailty. The frailty phenotype, which identifies individuals who are highly vulnerable to adverse health outcomes, often precedes the onset of chronic disease and is a predictor of early mortality. In the elderly, frailty is influenced by lifestyle and genetics, while in young adult survivors of cancer, reduction in physiologic reserve is more likely related to organ system damage following treatments. Frailty pathogenesis can be partially explained by an imbalance between pro-inflammation and anti-inflammation, which results in inflamm-aging with a low chronic pro-inflammatory status.

This Special Issue will highlight the biological mechanisms driving the development of age-related morbidities (such as osteoporosis, obesity, infertility, and cardiovascular diseases) in childhood cancer survivors, to facilitate the identification of the early frailty markers needed to prevent this process.

Prof. Francesca Rossi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cancer survivors
  • frailty
  • inflamm-aging

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Published Papers (7 papers)

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Editorial

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4 pages, 192 KiB  
Editorial
Childhood Cancer Survivors: An Overview of the Management of Late Effects
by Maura Argenziano, Alessandra Di Paola and Francesca Rossi
Cancers 2023, 15(12), 3150; https://doi.org/10.3390/cancers15123150 - 11 Jun 2023
Cited by 1 | Viewed by 1151
Abstract
The collection of papers in this Special Issue entitled “Frailty in Pediatric and Young Adult Cancer Survivors: from bench to bedside” includes six interesting articles (five reviews and one single-center retrospective longitudinal cohort study) presented by expert researchers in the fields of oncology [...] Read more.
The collection of papers in this Special Issue entitled “Frailty in Pediatric and Young Adult Cancer Survivors: from bench to bedside” includes six interesting articles (five reviews and one single-center retrospective longitudinal cohort study) presented by expert researchers in the fields of oncology and pediatrics [...] Full article
(This article belongs to the Special Issue Frailty in Pediatric and Young Adult Cancer Survivors: From Bench to Bedside)

Research

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16 pages, 479 KiB  
Article
A 40-Year Cohort Study of Evolving Hypothalamic Dysfunction in Infants and Young Children (<3 years) with Optic Pathway Gliomas
by Stefania Picariello, Manuela Cerbone, Felice D’Arco, Hoong-Wei Gan, Patricia O’Hare, Kristian Aquilina, Enrico Opocher, Darren Hargrave and Helen A. Spoudeas
Cancers 2022, 14(3), 747; https://doi.org/10.3390/cancers14030747 - 31 Jan 2022
Cited by 13 | Viewed by 3194
Abstract
Despite high survival, paediatric optic pathway hypothalamic gliomas are associated with significant morbidity and late mortality. Those youngest at presentation have the worst outcomes. We aimed to assess presenting disease, tumour location, and treatment factors implicated in the evolution of neuroendocrine, metabolic, and [...] Read more.
Despite high survival, paediatric optic pathway hypothalamic gliomas are associated with significant morbidity and late mortality. Those youngest at presentation have the worst outcomes. We aimed to assess presenting disease, tumour location, and treatment factors implicated in the evolution of neuroendocrine, metabolic, and neurobehavioural morbidity in 90 infants/children diagnosed before their third birthday and followed-up for 9.5 years (range 0.5–25.0). A total of 52 (57.8%) patients experienced endo-metabolic dysfunction (EMD), the large majority (46) of whom had hypothalamic involvement (H+) and lower endocrine event-free survival (EEFS) rates. EMD was greatly increased by a diencephalic syndrome presentation (85.2% vs. 46%, p = 0.001)), H+ (OR 6.1 95% CI 1.7–21.7, p 0.005), radiotherapy (OR 16.2, 95% CI 1.7–158.6, p = 0.017) and surgery (OR 4.8 95% CI 1.3–17.2, p = 0.015), all associated with anterior pituitary disorders. Obesity occurred in 25% of cases and was clustered with the endocrinopathies. Neurobehavioural deficits occurred in over half (52) of the cohort and were associated with H+ (OR 2.5 95% C.I. 1.1–5.9, p = 0.043) and radiotherapy (OR 23.1 C.I. 2.9–182, p = 0.003). Very young children with OPHG carry a high risk of endo-metabolic and neurobehavioural comorbidities which deserve better understanding and timely/parallel support from diagnosis to improve outcomes. These evolve in complex, hierarchical patterns over time whose aetiology appears predominantly determined by injury from the hypothalamic tumour location alongside adjuvant treatment strategies. Full article
(This article belongs to the Special Issue Frailty in Pediatric and Young Adult Cancer Survivors: From Bench to Bedside)
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Review

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20 pages, 843 KiB  
Review
Osteoporosis in Childhood Cancer Survivors: Physiopathology, Prevention, Therapy and Future Perspectives
by Francesca Rossi, Chiara Tortora, Marco Paoletta, Maria Maddalena Marrapodi, Maura Argenziano, Alessandra Di Paola, Elvira Pota, Daniela Di Pinto, Martina Di Martino and Giovanni Iolascon
Cancers 2022, 14(18), 4349; https://doi.org/10.3390/cancers14184349 - 6 Sep 2022
Cited by 28 | Viewed by 3311
Abstract
The improvement of chemotherapy, radiotherapy, and surgical interventions, together with hematopoietic stem cell transplantation, increased childhood cancer survival rate in the last decades, reaching 80% in Europe. Nevertheless, anti-cancer treatments are mainly responsible for the onset of long-term side effects in childhood cancer [...] Read more.
The improvement of chemotherapy, radiotherapy, and surgical interventions, together with hematopoietic stem cell transplantation, increased childhood cancer survival rate in the last decades, reaching 80% in Europe. Nevertheless, anti-cancer treatments are mainly responsible for the onset of long-term side effects in childhood cancer survivors (CCS), including alterations of the endocrine system function and activity. In particular, the most frequent dysfunction in CCS is a metabolic bone disorder characterized by low bone mineral density (BMD) with increased skeletal fragility. BMD loss is also a consequence of a sedentary lifestyle, malnutrition, and cancer itself could affect BMD, thus inducing osteopenia and osteoporosis. In this paper, we provide an overview of possible causes of bone impairment in CCS in order to propose management strategies for early identification and treatment of skeletal fragility in this population. Full article
(This article belongs to the Special Issue Frailty in Pediatric and Young Adult Cancer Survivors: From Bench to Bedside)
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Graphical abstract

17 pages, 3639 KiB  
Review
Short and Long-Term Toxicity in Pediatric Cancer Treatment: Central Nervous System Damage
by Iside Alessi, Anna Maria Caroleo, Luca de Palma, Angela Mastronuzzi, Stefano Pro, Giovanna Stefania Colafati, Alessandra Boni, Nicoletta Della Vecchia, Margherita Velardi, Melania Evangelisti, Alessia Carboni, Andrea Carai, Luciana Vinti, Massimiliano Valeriani, Antonino Reale, Pasquale Parisi and Umberto Raucci
Cancers 2022, 14(6), 1540; https://doi.org/10.3390/cancers14061540 - 17 Mar 2022
Cited by 20 | Viewed by 4898
Abstract
Neurotoxicity caused by traditional chemotherapy and radiotherapy is well known and widely described. New therapies, such as biologic therapy and immunotherapy, are associated with better outcomes in pediatric patients but are also associated with central and peripheral nervous system side effects. Nevertheless, central [...] Read more.
Neurotoxicity caused by traditional chemotherapy and radiotherapy is well known and widely described. New therapies, such as biologic therapy and immunotherapy, are associated with better outcomes in pediatric patients but are also associated with central and peripheral nervous system side effects. Nevertheless, central nervous system (CNS) toxicity is a significant source of morbidity in the treatment of cancer patients. Some CNS complications appear during treatment while others present months or even years later. Radiation, traditional cytotoxic chemotherapy, and novel biologic and targeted therapies have all been recognized to cause CNS side effects; additionally, the risks of neurotoxicity can increase with combination therapy. Symptoms and complications can be varied such as edema, seizures, fatigue, psychiatric disorders, and venous thromboembolism, all of which can seriously influence the quality of life. Neurologic complications were seen in 33% of children with non-CNS solid malign tumors. The effects on the CNS are disabling and often permanent with limited treatments, thus it is important that clinicians recognize the effects of cancer therapy on the CNS. Knowledge of these conditions can help the practitioner be more vigilant for signs and symptoms of potential neurological complications during the management of pediatric cancers. As early detection and more effective anticancer therapies extend the survival of cancer patients, treatment-related CNS toxicity becomes increasingly vital. This review highlights major neurotoxicities due to pediatric cancer treatments and new therapeutic strategies; CNS primary tumors, the most frequent solid tumors in childhood, are excluded because of their intrinsic neurological morbidity. Full article
(This article belongs to the Special Issue Frailty in Pediatric and Young Adult Cancer Survivors: From Bench to Bedside)
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17 pages, 331 KiB  
Review
Possible Mechanisms of Subsequent Neoplasia Development in Childhood Cancer Survivors: A Review
by Jarmila Kruseova, Ales Vicha, Barbara Feriancikova and Tomas Eckschlager
Cancers 2021, 13(20), 5064; https://doi.org/10.3390/cancers13205064 - 10 Oct 2021
Cited by 6 | Viewed by 2200
Abstract
Advances in medicine have improved outcomes in children diagnosed with cancer, with overall 5-year survival rates for these children now exceeding 80%. Two-thirds of childhood cancer survivors have at least one late effect of cancer therapy, with one-third having serious or even life-threatening [...] Read more.
Advances in medicine have improved outcomes in children diagnosed with cancer, with overall 5-year survival rates for these children now exceeding 80%. Two-thirds of childhood cancer survivors have at least one late effect of cancer therapy, with one-third having serious or even life-threatening effects. One of the most serious late effects is a development of subsequent malignant neoplasms (histologically different cancers, which appear after the treatment for primary cancer), which occur in about 3–10% of survivors and are associated with high mortality. In cancers with a very good prognosis, subsequent malignant neoplasms significantly affect long-term survival. Therefore, there is an effort to reduce particularly hazardous treatments. This review discusses the importance of individual factors (gender, genetic factors, cytostatic drugs, radiotherapy) in the development of subsequent malignant neoplasms and the possibilities of their prediction and prevention in the future. Full article
(This article belongs to the Special Issue Frailty in Pediatric and Young Adult Cancer Survivors: From Bench to Bedside)
19 pages, 1596 KiB  
Review
Biological Aspects of Inflamm-Aging in Childhood Cancer Survivors
by Francesca Rossi, Alessandra Di Paola, Elvira Pota, Maura Argenziano, Daniela Di Pinto, Maria Maddalena Marrapodi, Caterina Di Leva, Martina Di Martino and Chiara Tortora
Cancers 2021, 13(19), 4933; https://doi.org/10.3390/cancers13194933 - 30 Sep 2021
Cited by 26 | Viewed by 4469
Abstract
Anti-cancer treatments improve survival in children with cancer. A total of 80% of children treated for childhood cancer achieve 5-year survival, becoming long-term survivors. However, they undergo several chronic late effects related to treatments. In childhood cancer survivors a chronic low-grade inflammation, known [...] Read more.
Anti-cancer treatments improve survival in children with cancer. A total of 80% of children treated for childhood cancer achieve 5-year survival, becoming long-term survivors. However, they undergo several chronic late effects related to treatments. In childhood cancer survivors a chronic low-grade inflammation, known as inflamm-aging, is responsible for frailty, a condition characterized by vital organ failure and by premature aging processes. Inflamm-aging is closely related to chemotherapy and radiotherapy, which induce inflammation, accumulation of senescent cells, DNA mutations, and the production of reactive oxygen species. All these conditions are responsible for the onset of secondary diseases, such as osteoporosis, cardiovascular diseases, obesity, and infertility. Considering that the pathobiology of frailty among childhood cancer survivors is still unknown, investigations are needed to better understand frailty’s biological and molecular processes and to identify inflamm-aging key biomarkers in order to facilitate the screening of comorbidities and to clarify whether treatments, normally used to modulate inflamm-aging, may be beneficial. This review offers an overview of the possible biological mechanisms involved in the development of inflamm-aging, focusing our attention on immune system alteration, oxidative stress, cellular senescence, and therapeutic strategies. Full article
(This article belongs to the Special Issue Frailty in Pediatric and Young Adult Cancer Survivors: From Bench to Bedside)
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Other

13 pages, 1302 KiB  
Systematic Review
Serum Anti-Müllerian Hormone Levels and Risk of Premature Ovarian Insufficiency in Female Childhood Cancer Survivors: Systematic Review and Network Meta-Analysis
by Marco Torella, Gaetano Riemma, Pasquale De Franciscis, Marco La Verde and Nicola Colacurci
Cancers 2021, 13(24), 6331; https://doi.org/10.3390/cancers13246331 - 16 Dec 2021
Cited by 12 | Viewed by 3044
Abstract
Background: Female childhood cancer survivors (CCS) might have impaired ovarian reserves, especially after alkylating agents or radiotherapy. The purpose of this systematic review and network meta-analysis is to evaluate the role of serum anti-Müllerian hormone (AMH) for ovarian reserve screening and the risk [...] Read more.
Background: Female childhood cancer survivors (CCS) might have impaired ovarian reserves, especially after alkylating agents or radiotherapy. The purpose of this systematic review and network meta-analysis is to evaluate the role of serum anti-Müllerian hormone (AMH) for ovarian reserve screening and the risk of premature ovarian insufficiency (POI) according to the subtype of childhood cancer. (2) Methods: PRISMA-NMA guidelines were followed. We carried out a network meta-analysis based on a random effects model for mixed multiple treatment comparisons to rank childhood cancers effects on fertility by surface under the cumulative ranking curve (SUCRA). Studies were selected only if they had an age-matched control group. Quality assessment was performed using Newcastle–Ottawa Scale. The co-primary outcomes were mean AMH levels and the incidence of POI. (3) Results: A total of 8 studies (1303 participants) were included. Women treated for a neuroblastoma during infancy were more likely to be ranked first for impaired AMH levels (SUCRA = 65.4%), followed by mixed CCS (SUCRA = 29.6%). The greatest rates of POI were found in neuroblastoma survivors (SUCRA = 42.5%), followed by acute lymphoid leukemia (SUCRA = 26.3%) or any other neoplasia (SUCR A = 20.5%). (4) Conclusions: AMH represents a trustworthy approach for ovarian reserve screening. Direct and indirect comparisons found no differences in mean AMH levels and POI risk between subtypes of CCS and healthy controls. SUCRA analysis showed that female neuroblastoma survivors were more at risk for reduced serum AMH levels and increased risk of POI. Full article
(This article belongs to the Special Issue Frailty in Pediatric and Young Adult Cancer Survivors: From Bench to Bedside)
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