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6. Stress Axis in the Cancer Patient: Clinical Aspects and Management

Author

Felicetti Francesco, Nervo Alice, Gatti Filippo, Rosso Daniela, Brignardello Enrico, and Arvat Emanuela

Subjects
hypothalamus-pituitary-adrenal axis, adrenal insufficiency, adverse event, cancer survivors, chemotherapy, radiotherapy, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Hypothalamus–pituitary–adrenal (HPA) axis alterations are common in cancer patients, mainly due to the different antitumoral therapies, which lead to several acute and late endocrine side effects. This review summarizes the most recent evidence regarding HPA derangement, both in patients with active neoplasms and in cancer survivors, with particular attention to the impact of the different antitumoral treatments, focusing on the major clinical aspects. While acute hormone failure usually results from injury caused directly by tumor burden or surgical interventions, short- and long-term effects are generally due to chemotherapy, radiotherapy and, as more recently shown, to different types of targeted- and immuno-therapy. Adrenal insufficiency (AI) is mostly caused by pituitary or hypothalamic injury rather than a direct damage of the adrenal gland. Moreover, other treatments commonly employed as supportive therapy or in the context of palliative care (i.e., glucocorticoids, opioids) can lead to HPA dysfunction. Epidemiology and pathophysiology of stress axis alterations in cancer patients still require clarification. Since AI may represent a life-threatening condition, monitoring adrenal function in cancer patients is mandatory, especially in subjects who experience fatigue or during stress conditions, in order to promptly start replacement treatment when needed.

Published
2021
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14. A Prospective, Multicenter Study Examining the Relationship between Thyroid Cancer Treatment Outcomes and the Presence of Autoimmune Thyroiditis

Author

De Leo, Simone, primary, D'Elia, Silvia, additional, Grani, Giorgio, additional, Dondi, Francesco, additional, Bertagna, Francesco, additional, Puxeddu, Efisio, additional, Morelli, Silvia, additional, piovesan, alessandro, additional, Nervo, Alice, additional, Zatelli, Maria Chiara, additional, Gagliardi, Irene, additional, Samà, Maria Teresa, additional, Aimaretti, Gianluca, additional, Crocetti, Umberto, additional, Massa, Michela, additional, Deandrea, Maurilio, additional, Retta, Francesca, additional, Pagano, Loredana, additional, Rossi, Mattia, additional, Solaroli, Erica, additional, Pezzullo, Luciano, additional, Chiofalo, Maria Grazia, additional, pontecorvi, alfredo, additional, Lombardi, Celestino Pio, additional, Antonelli, Alessandro, additional, Patrizio, Armando, additional, Messuti, Ilaria, additional, Magri, Flavia, additional, Spiazzi, Giovanna, additional, Ceresini, Graziano, additional, Bruno, Rocco, additional, Sparano, Clotilde, additional, Centanni, Marco, additional, Crescenzi, Anna, additional, Tallini, Giovanni, additional, Marotta, Vincenzo, additional, Madeo, Bruno, additional, Mian, Caterina, additional, Filetti, Sebastiano, additional, Durante, Cosimo, additional, and Fugazzola, Laura, additional

Published
2023
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16. Recurrence and mortality rate in an Italian multi-center case series of parathyroid atypical adenomas and carcinomas

Author

Barale, Marco, primary, Nervo, Alice, additional, Craparo, Andrea, additional, Pusterla, Alessia, additional, Retta, Francesca, additional, Maiorino, Federica, additional, Castellano, Elena, additional, Piovesan, Alessandro, additional, Gianotti, Laura, additional, Borretta, Giorgio, additional, Procopio, Massimo, additional, and Arvat, Emanuela, additional

Published
2023
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17. A Data-Driven Approach to Refine Predictions of Differentiated Thyroid Cancer Outcomes: A Prospective Multicenter Study

Author

Grani, Giorgio, primary, Gentili, Michele, additional, Siciliano, Federico, additional, Albano, Domenico, additional, Zilioli, Valentina, additional, Morelli, Silvia, additional, Puxeddu, Efisio, additional, Zatelli, Maria Chiara, additional, Gagliardi, Irene, additional, Piovesan, Alessandro, additional, Nervo, Alice, additional, Crocetti, Umberto, additional, Massa, Michela, additional, Samà, Maria Teresa, additional, Mele, Chiara, additional, Deandrea, Maurilio, additional, Fugazzola, Laura, additional, Puligheddu, Barbara, additional, Antonelli, Alessandro, additional, Rossetto, Ruth, additional, D’Amore, Annamaria, additional, Ceresini, Graziano, additional, Castello, Roberto, additional, Solaroli, Erica, additional, Centanni, Marco, additional, Monti, Salvatore, additional, Magri, Flavia, additional, Bruno, Rocco, additional, Sparano, Clotilde, additional, Pezzullo, Luciano, additional, Crescenzi, Anna, additional, Mian, Caterina, additional, Tumino, Dario, additional, Repaci, Andrea, additional, Castagna, Maria Grazia, additional, Triggiani, Vincenzo, additional, Porcelli, Tommaso, additional, Meringolo, Domenico, additional, Locati, Laura, additional, Spiazzi, Giovanna, additional, Di Dalmazi, Giulia, additional, Anagnostopoulos, Aris, additional, Leonardi, Stefano, additional, Filetti, Sebastiano, additional, and Durante, Cosimo, additional

Published
2023
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18. Management of Progressive Radioiodine-Refractory Thyroid Carcinoma: Current Perspective

Author

Nervo,Alice, Retta,Francesca, Ragni,Alberto, Piovesan,Alessandro, Gallo,Marco, and Arvat,Emanuela

Subjects
Cancer Management and Research
Abstract

Alice Nervo,1 Francesca Retta,1 Alberto Ragni,2 Alessandro Piovesan,1 Marco Gallo,2 Emanuela Arvat1 1Oncological Endocrinology Unit, Department of Medical Sciences, Città Della Salute e Della Scienza Hospital, University of Turin, Turin, Italy; 2Endocrinology and Metabolic Diseases Unit, AO SS. Antonio e Biagio e Cesare Arrigo Hospital, Alessandria, ItalyCorrespondence: Alice Nervo, Oncological Endocrinology Unit, Department of Medical Sciences, Città Della Salute e Della Scienza Hospital, University of Turin, Via Genova 3, Turin, 10126, Italy, Tel +390116336611, Fax +390116334703, Email anervo@cittadellasalute.to.itAbstract: Patients with thyroid cancer (TC) usually have an excellent prognosis; however, 5– 10% of them develop an advanced disease. The prognosis of this subgroup is still favourable if the lesions respond to radioactive iodine (RAI) treatment. Nearly two-thirds of advanced TC patients become RAI-refractory (RAI-R), and their management is challenging. A multidisciplinary approach in the context of a tumour board is essential to define a personalized strategy. Systemic therapy is not always the best option. In case of slow neoplastic growth and low tumour burden, active surveillance may represent a valuable choice. Local approaches might be considered if the disease progression is limited to a single or few lesions, also in combination and during systemic therapy. Antiresorptive treatment may be started in presence of bone metastases. In case of rapid and/or symptomatic progression involving multiple lesions and/or organs, systemic therapy has to be considered, in absence of contraindications. The multi-kinase inhibitors (MKIs) lenvatinib and sorafenib are currently available as first-line treatment for advanced progressive RAI-R TC. Among second-line options, cabozantinib has been recently approved in RAI-R TC who progressed during MKIs targeting the vascular endothelial growth factor receptor (VEGFR). In the last few years, next-generation sequencing (NGS) assays have been increasingly employed, permitting identification of the genetic alterations harboured by TC, with a significant impact on patients’ management. Novel selective targeted therapies have been introduced for the treatment of RAI-R TC in selected cases: REarranged during Transfection (RET) inhibitors (selpercatinib and pralsetinib) and Tropomyosin Receptor Kinase (TRK) inhibitors (larotrectinib and entrectinib) have recently expanded the panorama of the therapeutic options. Moreover, immune checkpoint inhibitors (ICIs) have shown promising results, and they are still under investigation.Keywords: multidisciplinary tumour board, loco-regional treatment, multi-kinase inhibitor, selective RET inhibitor, selective TRK inhibitor, immunotherapy

Published
2022

29. 8th edition of the AJCC/TNM staging system of thyroid cancer: what to expect (ITCO#2)

Author

Lamartina, Livia, primary, Grani, Giorgio, additional, Arvat, Emanuela, additional, Nervo, Alice, additional, Zatelli, Maria Chiara, additional, Rossi, Roberta, additional, Puxeddu, Efisio, additional, Morelli, Silvia, additional, Torlontano, Massimo, additional, Massa, Michela, additional, Bellantone, Rocco, additional, Pontecorvi, Alfredo, additional, Montesano, Teresa, additional, Pagano, Loredana, additional, Daniele, Lorenzo, additional, Fugazzola, Laura, additional, Ceresini, Graziano, additional, Bruno, Rocco, additional, Rossetto, Ruth, additional, Tumino, Salvatore, additional, Centanni, Marco, additional, Meringolo, Domenico, additional, Castagna, Maria Grazia, additional, Salvatore, Domenico, additional, Nicolucci, Antonio, additional, Lucisano, Giuseppe, additional, Filetti, Sebastiano, additional, and Durante, Cosimo, additional

Published
2018
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30. 8th edition of the AJCC/TNM staging system of thyroid cancer: What to expect (ITCO#2)

Author

Lamartina, Livia, Grani, Giorgio, Arvat, Emanuela, Nervo, Alice, Zatelli, Maria Chiara, Rossi, Roberta, Puxeddu, Efisio, Morelli, Silvia, Torlontano, Massimo, Massa, Michela, Bellantone, Rocco Domenico Alfonso, Pontecorvi, Alfredo, Montesano, Teresa, Pagano, Loredana, Daniele, Lorenzo, Fugazzola, Laura, Ceresini, Graziano, Bruno, Rocco, Rossetto, Ruth, Tumino, Salvatore, Centanni, Marco, Meringolo, Domenico, Castagna, Maria Grazia, Salvatore, Domenico, Nicolucci, Antonio, Lucisano, Giuseppe, Filetti, Sebastiano, Durante, Cosimo, Bellantone, Rocco (ORCID:0000-0002-0844-3469), Pontecorvi, Alfredo (ORCID:0000-0003-0570-6865), Lamartina, Livia, Grani, Giorgio, Arvat, Emanuela, Nervo, Alice, Zatelli, Maria Chiara, Rossi, Roberta, Puxeddu, Efisio, Morelli, Silvia, Torlontano, Massimo, Massa, Michela, Bellantone, Rocco Domenico Alfonso, Pontecorvi, Alfredo, Montesano, Teresa, Pagano, Loredana, Daniele, Lorenzo, Fugazzola, Laura, Ceresini, Graziano, Bruno, Rocco, Rossetto, Ruth, Tumino, Salvatore, Centanni, Marco, Meringolo, Domenico, Castagna, Maria Grazia, Salvatore, Domenico, Nicolucci, Antonio, Lucisano, Giuseppe, Filetti, Sebastiano, Durante, Cosimo, Bellantone, Rocco (ORCID:0000-0002-0844-3469), and Pontecorvi, Alfredo (ORCID:0000-0003-0570-6865)

Abstract

Differentiated thyroid cancer (DTC) has become one of the most frequently diagnosed malignancies, especially among women and young adults (Davies & Welch 2014). The outcomes are generally very good: disease recurrence rates are low (Durante et al. 2013), and survival rates are excellent.

Published
2018

31. Quality of Life during Treatment with Lenvatinib for Thyroid Cancer: The Patients’ Perspective beyond the Medical Evaluation

Author

Nervo, Alice, Ragni, Alberto, Piovesan, Alessandro, Marica, Valentina, Migliore, Enrica, Gallo, Marco, and Arvat, Emanuela

Abstract

Background:Lenvatinib (LEN) has shown great efficacy but important toxicity in patients with advanced radioactive iodine-refractory (RAI-R) thyroid cancer (TC); a focused evaluation of its impact on patients’ quality of life (QoL) is still lacking. Our prospective study investigated the impact of this drug on QoL in a group of RAI-R TC patients treated at our centre. Methods:All patients filled in two questionnaires before and during treatment: (1) the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events adapted questionnaire, assessing prevalence, severity, and/or interference on daily activities of the most frequent symptomatic adverse events (AEs) reported in previous clinical trials during therapy with LEN, and (2) the European Quality of Life 5 Dimensions 3 Levels (EQ-5D-3L) questionnaire, providing the EQ-5D index and the EQ visual analogue scale (EQ-VAS). Data from baseline questionnaires were compared with those obtained 3, 6, and 12 months after the start of treatment. Results:In our population (n= 20), an overall increased perception of symptomatic AEs emerged during treatment (statistically significant for abdominal pain, asthenia/fatigue, decreased appetite, and xerostomia). The median EQ-5D index and EQ-VAS scores after 3 months of treatment were lower than at baseline, almost returning to initial values after 12 months. Conclusion:RAI-R TC patients reported a general increase in prevalence and interference on daily activities of symptomatic AEs during therapy with LEN. Self-perceived QoL initially decreased during therapy. However, our data suggest that QoL could be restored after 12 months; this trend might partly reflect the impact of therapy optimisation.

Published
2021
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33. Sorafenib treatment of radioiodine-refractory advanced thyroid cancer in daily clinical practice: a cohort study from a single center

Author

Gallo, Marco, primary, Michelon, Federica, additional, Castiglione, Anna, additional, Felicetti, Francesco, additional, Viansone, Alessandro Adriano, additional, Nervo, Alice, additional, Zichi, Clizia, additional, Ciccone, Giovannino, additional, Piovesan, Alessandro, additional, and Arvat, Emanuela, additional

Published
2014
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34. A Data-Driven Approach to Refine Predictions of Differentiated Thyroid Cancer Outcomes: A Prospective Multicenter Study

Author

Giorgio Grani, Michele Gentili, Federico Siciliano, Domenico Albano, Valentina Zilioli, Silvia Morelli, Efisio Puxeddu, Maria Chiara Zatelli, Irene Gagliardi, Alessandro Piovesan, Alice Nervo, Umberto Crocetti, Michela Massa, Maria Teresa Samà, Chiara Mele, Maurilio Deandrea, Laura Fugazzola, Barbara Puligheddu, Alessandro Antonelli, Ruth Rossetto, Annamaria D’Amore, Graziano Ceresini, Roberto Castello, Erica Solaroli, Marco Centanni, Salvatore Monti, Flavia Magri, Rocco Bruno, Clotilde Sparano, Luciano Pezzullo, Anna Crescenzi, Caterina Mian, Dario Tumino, Andrea Repaci, Maria Grazia Castagna, Vincenzo Triggiani, Tommaso Porcelli, Domenico Meringolo, Laura Locati, Giovanna Spiazzi, Giulia Di Dalmazi, Aris Anagnostopoulos, Stefano Leonardi, Sebastiano Filetti, Cosimo Durante, Grani, Giorgio, Gentili, Michele, Siciliano, Federico, Albano, Domenico, Zilioli, Valentina, Morelli, Silvia, Puxeddu, Efisio, Chiara Zatelli, Maria, Gagliardi, Irene, Piovesan, Alessandro, Nervo, Alice, Crocetti, Umberto, Massa, Michela, Teresa Samà, Maria, Mele, Chiara, Deandrea, Maurilio, Fugazzola, Laura, Puligheddu, Barbara, Antonelli, Alessandro, Rossetto, Ruth, D’Amore, Annamaria, Ceresini, Graziano, Castello, Roberto, Solaroli, Erica, Centanni, Marco, Monti, Salvatore, Magri, Flavia, Bruno, Rocco, Sparano, Clotilde, Pezzullo, Luciano, Crescenzi, Anna, Mian, Caterina, Tumino, Dario, Repaci, Andrea, Grazia Castagna, Maria, Triggiani, Vincenzo, Porcelli, Tommaso, Meringolo, Domenico, Locati, Laura, Spiazzi, Giovanna, Di Dalmazi, Giulia, Anagnostopoulos, Ari, Leonardi, Stefano, Filetti, Sebastiano, and Durante, Cosimo

Subjects
Endocrinology, Endocrinology, Diabetes and Metabolism, Biochemistry (medical), Clinical Biochemistry, differentiated thyroid cancer, risk stratification, evidence-based guidelines, Biochemistry, clinical practice
Abstract

ContextThe risk stratification of patients with differentiated thyroid cancer (DTC) is crucial in clinical decision making. The most widely accepted method to assess risk of recurrent/persistent disease is described in the 2015 American Thyroid Association (ATA) guidelines. However, recent research has focused on the inclusion of novel features or questioned the relevance of currently included features.ObjectiveTo develop a comprehensive data-driven model to predict persistent/recurrent disease that can capture all available features and determine the weight of predictors.MethodsIn a prospective cohort study, using the Italian Thyroid Cancer Observatory (ITCO) database (NCT04031339), we selected consecutive cases with DTC and at least early follow-up data (n = 4773; median follow-up 26 months; interquartile range, 12-46 months) at 40 Italian clinical centers. A decision tree was built to assign a risk index to each patient. The model allowed us to investigate the impact of different variables in risk prediction.ResultsBy ATA risk estimation, 2492 patients (52.2%) were classified as low, 1873 (39.2%) as intermediate, and 408 as high risk. The decision tree model outperformed the ATA risk stratification system: the sensitivity of high-risk classification for structural disease increased from 37% to 49%, and the negative predictive value for low-risk patients increased by 3%. Feature importance was estimated. Several variables not included in the ATA system significantly impacted the prediction of disease persistence/recurrence: age, body mass index, tumor size, sex, family history of thyroid cancer, surgical approach, presurgical cytology, and circumstances of the diagnosis.ConclusionCurrent risk stratification systems may be complemented by the inclusion of other variables in order to improve the prediction of treatment response. A complete dataset allows for more precise patient clustering.

Published
2023
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35. Data-Driven Thyroglobulin Cutoffs for Low- and Intermediate-Risk Thyroid Cancer Follow-Up: ITCO Real-World Analysis.

Author

Grani G, D'Elia S, Puxeddu E, Morelli S, Arvat E, Nervo A, Spiazzi G, Rolli N, Zatelli MC, Ambrosio MR, Ceresini G, Marina M, Mele C, Aimaretti G, Santaguida MG, Virili C, Crescenzi A, Palermo A, Giaccherino RR, Meomartino L, Castagna MG, Maino F, Trevisan M, De Leo S, Chiofalo MG, Pezzullo L, Sparano C, Petrone L, Dalmazi GD, Napolitano G, Tumino D, Crocetti U, Bertagna F, Deandrea M, Antonelli A, Mian C, Carbone A, Monti S, Porcelli T, Brigante G, Barbaro D, Alfò M, Ferraro Petrillo U, Filetti S, and Durante C

Abstract

Context: The utility of thyroglobulin (Tg) in the follow-up of differentiated thyroid cancer (DTC) patients has been well-documented. Although third-generation immunoassays have improved accuracy, limitations persist (interfering anti-Tg antibodies and measurement variability). Evolving treatment strategies require a reevaluation of Tg thresholds for optimal patient management., Objective: To assess the performance of serum Tg testing in two populations: patients receiving total thyroidectomy and radioiodine remnant ablation (RRA), or treated with thyroidectomy alone., Design: Prospective observational study. Setting. Centers contributing to the Italian Thyroid Cancer Observatory (ITCO) database., Patients: We included 540 patients with 5 years of follow-up and negative anti-Tg antibodies., Interventions: Serum Tg levels assessed at 1-year follow-up visit., Main Outcome Measure: Detection of structural disease within 5 years of follow-up., Results: After excluding 26 patients with structural disease detected at any time point, the median Tg did not differ between patients treated with or without radioiodine. Data-driven Tg thresholds were established based on the 97th percentile of Tg levels in disease-free individuals: 1.97 ng/mL for patients undergoing thyroidectomy alone (lower than proposed by the MSKCC protocol and ESMO Guidelines, yet demonstrating good predictive ability, with a negative predictive value (NPV) of 98%) and 0.84 ng/mL for patients receiving post-surgical RRA. High sensitivity and NPV supported the potential of these thresholds in excluding structural disease., Conclusions: This real-world study provides evidence for the continued reliability of 1-year serum Tg levels. The data-driven Tg thresholds proposed offer valuable insights for clinical decision-making in patients undergoing total thyroidectomy with or without RRA., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Published
2024
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36. Lenvatinib in Advanced Radioiodine-refractory Thyroid Cancer: A Snapshot of Real-life Clinical Practice.

Author

Nervo A, Gallo M, Samà MT, Felicetti F, Alfano M, Migliore E, Marchisio F, Berardelli R, Arvat E, and Piovesan A

Subjects
Aged, Antineoplastic Agents adverse effects, Antineoplastic Agents therapeutic use, Disease Progression, Drug Resistance, Neoplasm, Female, Gastrointestinal Diseases chemically induced, Humans, Hypertension chemically induced, Iodine Radioisotopes therapeutic use, Kaplan-Meier Estimate, Male, Middle Aged, Phenylurea Compounds adverse effects, Quinolines adverse effects, Retrospective Studies, Thyroid Neoplasms pathology, Treatment Outcome, Phenylurea Compounds therapeutic use, Quinolines therapeutic use, Thyroid Neoplasms drug therapy
Abstract

Background: We retrospectively analyzed the efficacy and safety of lenvatinib in 12 patients with advanced radioiodine-refractory thyroid cancer in the setting of daily clinical practice., Patients and Methods: The starting daily dose of lenvatinib was 24 mg, tapered in the case of adverse events. Disease status was periodically evaluated by a single radiologist and safety assessment was regularly performed., Results: After a median follow-up of 13.3 months, 6- and 12-month progression-free survival rates were 63.6% and 54.6%, respectively. Overall survival at 6 and 12 months was 83.3% and 75.0%. Partial response was observed in five patients, while two showed stable disease as their best response. Conversely, progressive disease at first radiological assessment was detected in four patients. All patients experienced at least one adverse event, including systemic and gastrointestinal toxicity, high blood pressure and hand-foot syndrome. In order to manage toxicity, transient drug interruption and dose reduction were required in 10 and 9 cases, respectively., Conclusion: Our data confirm lenvatinib efficacy in patients with advanced thyroid cancer, despite an important toxic profile., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Published
2018
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