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Cancers
Special Issues
Endocrine Toxicities of Antineoplastic Therapy
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Endocrine Toxicities of Antineoplastic Therapy

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

Deadline for manuscript submissions: closed (15 August 2022) | Viewed by 18170

Special Issue Editor

Prof. Marialuisa Luisa Appetecchia

E-Mail Website
Guest Editor
Oncological Endocrinology Unit, IRCCS Regina Elena National Cancer Institute, Roma, Italy
Interests: thyroid cancer; neuroendocrine tumors; multiple endocrine neoplasia; parathyroid diseases; pituitary diseases; adrenal tumors.

Special Issue Information

Dear Colleagues,

In recent years, new antineoplastic medical therapies have significantly improved the prognosis of patients affected by advanced or metastatic malignancies. However, these drugs are burdened with many side effects, among which endocrine toxicities are non-negligible and include life-threatening complications, such as hypophysitis or primary adrenal insufficiency.

On the other hand, classical chemotherapy can also influence the endocrine system.

However, the timely recognition and treatment of drug-induced endocrine diseases allows us not only to treat patients and improve their quality of life but also, in many cases, to give patients the opportunity to continue effective treatment.

The aims of this Special Issue are:

—to describe the most common endocrine toxicities related to both classical chemotherapy and to new biological drugs, such as immune checkpoint inhibitors and tyrosine kinase inhibitors;

—to highlight the current state of the art in diagnostic and therapeutic approaches to endocrine toxicities; and

—to underline the importance of a strong collaboration between oncologists and endocrinologists.

Prof. Marialuisa Luisa Appetecchia
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 short 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

  • endocrine toxicities
  • hypophysitis
  • immune checkpoint inhibitors
  • tyrosine kinase inhibitors
  • chemotherapy
  • thyroid dysfunction
  • insulin-deficient diabetes mellitus
  • primary adrenal insufficiency
  • cancer-treatment-induced bone loss
  • electrolyte alteration

Published Papers (7 papers)

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Editorial

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4 pages, 210 KiB  
Editorial
Endocrine Toxicities of Antineoplastic Therapy
by Giulia Puliani and Marialuisa Appetecchia
Cancers 2021, 13(2), 294; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13020294 - 14 Jan 2021
Cited by 3 | Viewed by 1406
Abstract
In recent years, the prognosis of many solid tumors has improved markedly thanks to new treatment strategies, including tyrosine kinase inhibitors (TKIs) and immunotherapy [...] Full article
(This article belongs to the Special Issue Endocrine Toxicities of Antineoplastic Therapy)

Research

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13 pages, 1193 KiB  
Article
Adrenal Insufficiency with Anticancer Tyrosine Kinase Inhibitors Targeting Vascular Endothelial Growth Factor Receptor: Analysis of the FDA Adverse Event Reporting System
by Emanuel Raschi, Michele Fusaroli, Valentina Giunchi, Andrea Repaci, Carla Pelusi, Veronica Mollica, Francesco Massari, Andrea Ardizzoni, Elisabetta Poluzzi, Uberto Pagotto and Guido Di Dalmazi
Cancers 2022, 14(19), 4610; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14194610 - 22 Sep 2022
Cited by 8 | Viewed by 1781
Abstract
Background: We described clinical features of adrenal insufficiency (AI) reported with tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor receptor (VEGFR) in the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: Reports of AI recorded in FAERS (January [...] Read more.
Background: We described clinical features of adrenal insufficiency (AI) reported with tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor receptor (VEGFR) in the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: Reports of AI recorded in FAERS (January 2004–March 2022) were identified through the high-level term “adrenal cortical hypofunctions”. Demographic and clinical features were inspected, and disproportionality signals were detected through the Reporting Odds Ratio (ROR) and Information Component (IC) with relevant 95% confidence/credibility interval (CI), using different comparators and adjusting the ROR for co-reported corticosteroids and immune checkpoint inhibitors (ICIs). Results: Out of 147,153 reports with VEGFR-TKIs, 314 cases of AI were retained, mostly of which were serious (97.1%; hospitalization recorded in 44.9%). In a combination regimen with ICIs (43% of cases), VEGFR-TKIs were discontinued in 52.2% of the cases (26% as monotherapy). The median time to onset was 72 days (IQR = 14–201; calculated for 189 cases). A robust disproportionality signal emerged, also in comparison with other anticancer drugs (ROR = 2.71, 95%CI = 2.42–3.04; IC = 0.25, 95%CI = 0.07–0.39). Cabozantinib, sunitinib and axitinib generated robust disproportionality even after ROR adjustment. Conclusions: We call pharmacologists, internists, oncologists and endocrinologists to raise awareness of serious AI with VEGFR-TKIs, and to develop dedicated guidelines, especially for combination regimens with immunotherapy. Full article
(This article belongs to the Special Issue Endocrine Toxicities of Antineoplastic Therapy)
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Graphical abstract

15 pages, 752 KiB  
Article
Graves’ Disease during Immune Checkpoint Inhibitor Therapy (A Case Series and Literature Review)
by Mathilde Peiffert, Christine Cugnet-Anceau, Stephane Dalle, Karim Chikh, Souad Assaad, Emmanuel Disse, Gérald Raverot, Françoise Borson-Chazot and Juliette Abeillon-du Payrat
Cancers 2021, 13(8), 1944; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13081944 - 17 Apr 2021
Cited by 19 | Viewed by 3632
Abstract
Thyrotoxicosis is an adverse event associated with immune checkpoint inhibitors (ICPis) that occurs in 0.6 to 3.2% of treated patients, depending on ICPi class. Presentation usually consists of a biphasic thyroiditis with transient thyrotoxicosis and secondary hypothyroidism. ICPi-induced Graves’ disease (GD), due to [...] Read more.
Thyrotoxicosis is an adverse event associated with immune checkpoint inhibitors (ICPis) that occurs in 0.6 to 3.2% of treated patients, depending on ICPi class. Presentation usually consists of a biphasic thyroiditis with transient thyrotoxicosis and secondary hypothyroidism. ICPi-induced Graves’ disease (GD), due to the stimulating activity of TSH-receptor autoantibodies (TRAb), is extremely rare. The aim of this retrospective study was to describe the characteristics and evolution of GD during ICPi therapy. Five among 243 patients followed for ICPi-induced thyrotoxicosis showed TRAb positivity (2% of the cohort). GD occurred quickly after initiation of ICPis; its course was typical for two patients, with prolonged requirement for antithyroid drug treatment (ATD). The three other patients experienced biphasic thyroiditis with secondary hypothyroidism requiring long-term substitution. Three other patients had a diagnosis of GD before starting ICPis; they evolved toward hypothyroidism with early cessation of ATD and long-term substitution treatment during ICPi treatment. None developed significant Graves’ orbitopathy. ICPi treatment was not interrupted for thyroid dysfunction. In conclusion, GD is a rare, immune-related adverse event of ICPis with an unusual course and frequent evolution to biphasic thyroiditis. In the case of ICPi-induced thyrotoxicosis in the presence of TRAb, observing the spontaneous evolution and performing a scintigraphy are useful before starting ATD treatment. Pre-existing GD is not exacerbated by ICPis and tends to evolve towards hypothyroidism. ICPi treatment can be maintained with adequate biochemical surveillance. Full article
(This article belongs to the Special Issue Endocrine Toxicities of Antineoplastic Therapy)
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Review

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14 pages, 301 KiB  
Review
Endocrine Late Effects in Childhood Cancer Survivors
by Paula Casano-Sancho and Ana Carolina Izurieta-Pacheco
Cancers 2022, 14(11), 2630; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14112630 - 26 May 2022
Cited by 3 | Viewed by 1753
Abstract
Childhood cancer management has improved considerably over the years, leading to a significant improvement in survival of up to 80%. However, childhood cancer survivors are at the highest risk of developing sequelae resulting from treatment, with endocrine complications being frequently observed among survivors. [...] Read more.
Childhood cancer management has improved considerably over the years, leading to a significant improvement in survival of up to 80%. However, childhood cancer survivors are at the highest risk of developing sequelae resulting from treatment, with endocrine complications being frequently observed among survivors. Multiple predisposing factors for endocrine sequelae have been identified, including age at diagnosis, treatment received, radiation, tumor type, and genetic polymorphisms, which could explain the individual predisposition to develop drug toxicity. Novel agents targeting tumor growth and immune checkpoint inhibitors have recently become the cornerstone for the treatment of different cancers, triggering a myriad of immune-related endocrinopathies. Endocrine sequelae of cancer therapy will have an impact on not only childhood but also on the survival and quality of life of these highly complex patients. Therefore, lifelong monitoring of childhood cancer survivors at risk of endocrine diseases is paramount. Encouraging oncologists and endocrinologists to develop new follow-up and early detection guidelines that minimize sequelae among these patients has become a priority, promoting integration between pediatric and adult units since many sequelae may manifest only after years to decades of follow-up. Full article
(This article belongs to the Special Issue Endocrine Toxicities of Antineoplastic Therapy)
13 pages, 908 KiB  
Review
Endocrine Toxicities of Antineoplastic Therapy: The Adrenal Topic
by Agnese Barnabei, Paola Senes, Alessandro Scoppola, Alfonsina Chiefari, Giovanni Maria Iannantuono, Marialuisa Appetecchia and Francesco Torino
Cancers 2022, 14(3), 593; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14030593 - 25 Jan 2022
Cited by 5 | Viewed by 2595
Abstract
Immune checkpoint inhibitors (ICIs) have improved survival in patients affected by several solid tumours at the cost of new autoimmune adverse events. Endocrine toxicity is frequently reported in patients treated with these agents, mainly as thyroid dysfunction and hypophysitis. Primary adrenal insufficiency is [...] Read more.
Immune checkpoint inhibitors (ICIs) have improved survival in patients affected by several solid tumours at the cost of new autoimmune adverse events. Endocrine toxicity is frequently reported in patients treated with these agents, mainly as thyroid dysfunction and hypophysitis. Primary adrenal insufficiency is reported in 1–2% of patients receiving a single ICI, but its rate is approximately 5% in patients treated with a combination of two ICIs. The clinical presentation of adrenal insufficiency may be insidious due to symptoms that are not specific. The same symptoms in cancer patients are frequently multifactorial, rendering the early diagnosis of adrenal insufficiency challenging in this group of patients. As adrenal insufficiency can be fatal if not rapidly diagnosed and treated, oncologists should be aware of its clinical presentations to timely involve endocrinologists to offer patients the appropriate management. In parallel, it is essential to educate patients, their caregivers, and relatives, providing them with detailed information about the risk of adrenal insufficiency and how to manage alarming symptoms at their onset. Finally, large collaborative trials are needed to develop appropriate tests to assess better the personal risk of drug-induced adrenal insufficiency and its early diagnosis and treatment, not only in cancer patients. Full article
(This article belongs to the Special Issue Endocrine Toxicities of Antineoplastic Therapy)
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16 pages, 735 KiB  
Review
Nursing Management and Adverse Events in Thyroid Cancer Treatments with Tyrosine Kinase Inhibitors. A Narrative Review
by Aurora De Leo, Emanuele Di Simone, Alessandro Spano, Giulia Puliani and Fabrizio Petrone
Cancers 2021, 13(23), 5961; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13235961 - 26 Nov 2021
Cited by 8 | Viewed by 2951
Abstract
Background: The advent of multikinase inhibitors has changed the treatment of advanced, metastatic, unresectable thyroid cancers, refractory to available treatments. These drugs cause new adverse events that should be prevented and treated for long periods, and sometimes beyond their discontinuation. The purpose of [...] Read more.
Background: The advent of multikinase inhibitors has changed the treatment of advanced, metastatic, unresectable thyroid cancers, refractory to available treatments. These drugs cause new adverse events that should be prevented and treated for long periods, and sometimes beyond their discontinuation. The purpose of this narrative review was the description, prevention, and nursing management of the most frequent adverse events of locally advanced or metastatic differentiated thyroid cancer with sorafenib and lenvatinib, and medullary Thyroid cancer with vandetanib and cabozantinib treatment. Methods: A narrative literature review. Results: Studies included in this narrative review suggest that over 90% of patients treated with tyrosine kinase inhibitors experience at least 1 adverse event of any grade affecting their quality of life. Patients treated with tyrosine kinase inhibitors experienced at least one adverse event at any grade in ≥90% of cases, with a higher incidence in the first 6–8 weeks of treatment. The most frequent adverse events that can affect a patients’ quality of life are dermatological, gastrointestinal, cardiovascular, and metabolic. Conclusions: Early assessment of risk factors and identification of adverse events can help nurses support these patients throughout their clinical-therapeutic pathway, increasing the benefits of treatment and reducing reduction/discontinuation. Full article
(This article belongs to the Special Issue Endocrine Toxicities of Antineoplastic Therapy)
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Other

16 pages, 984 KiB  
Systematic Review
Metabolic and Endocrine Toxicities of Mitotane: A Systematic Review
by Marta Bianchini, Giulia Puliani, Alfonsina Chiefari, Marilda Mormando, Rosa Lauretta and Marialuisa Appetecchia
Cancers 2021, 13(19), 5001; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13195001 - 05 Oct 2021
Cited by 12 | Viewed by 3052
Abstract
Despite the pivotal role of mitotane in adrenocortical carcinoma (ACC) management, data on the endocrine toxicities of this treatment are lacking. The aim of this systematic review is to collect the available evidence on the side effects of mitotane on the endocrine and [...] Read more.
Despite the pivotal role of mitotane in adrenocortical carcinoma (ACC) management, data on the endocrine toxicities of this treatment are lacking. The aim of this systematic review is to collect the available evidence on the side effects of mitotane on the endocrine and metabolic systems in both children and adults affected by adrenal carcinoma. Sixteen articles on 493 patients were included. Among the adrenal insufficiency, which is an expected side effect of mitotane, 24.5% of patients increased glucocorticoid replacement therapy. Mineralocorticoid insufficiency usually occurred late in treatment in 36.8% of patients. Thyroid dysfunction is characterized by a decrease in FT4, which occurs within 3–6 months of treatment in 45.4% of patients, while TSH seems to not be a reliable marker. Dyslipidemia is characterized by an increase in both LDL-c and HDL-c (54.2%). Few studies have found evidence of hypertriglyceridemia. In males, gynecomastia and hypogonadism can occur after 3–6 months of treatment (38.4% and 35.6%, respectively), while in pre-menopausal women, mitotane can cause ovarian cysts and, less frequently, menstrual disorders. Most of these side effects appear to be reversible after mitotane discontinuation. We finally suggest an algorithm that could guide metabolic and endocrine safety assessments in patients treated with mitotane for ACC. Full article
(This article belongs to the Special Issue Endocrine Toxicities of Antineoplastic Therapy)
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