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Endocrine, Metabolic & Immune Disorders - Drug Targets

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ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

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Research Article

Endocrine Adverse Events Related To Immune Checkpoint Inhibitor Treatment: Relationship Between Antibodies and Severity of Thyroid Dysfunction

Author(s): María Miguélez González*, Alba Galdón Sanz-Pastor, Roberto Áñez Gómez, Noemi Brox Torrecilla, Diego Muñoz Moreno, Laura González Fernández, Alejandra Maricel Rivas, Aurelio López Guerra, Rosa Álvarez, José Ángel Arranz, Iván Márquez Rodas, Vicente Escudero, María Sanjurjo, Javier Martín Vallejo, Miguel Martín and Olga González Albarrán

Volume 24, Issue 14, 2024

Published on: 14 February, 2024

Page: [1628 - 1639] Pages: 12

DOI: 10.2174/0118715303280679240206100137

Price: $65

Abstract

Objective: The purpose of this study was to identify predictive and risk factors for the development of immune-related endocrinopathies and to analyze the incidence and characteristics of immune-related endocrinopathies in our population

Design: A retrospective, single-centre cohort carried out at Gregorio Marañón Hospital between January 2018 -December 2019.

Methods: A total of 163 patients were enrolled. In January 2018 and December 2019, we treated patients who underwent ICI treatment in the Medical Oncology Department of General University Hospital Gregorio Marañón, a tertiary care public hospital in Madrid, as part of an observational, retrospective, single-center cohort study.

Results: Endocrinopathies were diagnosed in 19.5% of the patients (n = 32). The tumours with the highest incidence of endocrinopathies were non-small cell lung cancer (25,9%), kidney cell cancer (25%) and hepatocarcinoma (20%). Among the 32 patients who developed endocrinopathy, 18,8%, 19,13%, and 21,28% received anti-CTLA-4, anti-PD-1 and anti-PDL-1, respectively. Thyroid dysfunction was the most frequent endocrinopathy (12,8%). A higher percentage of patients with negative antiTPO and antiTG antibodies developed G1 hypothyroidism compared to patients with positive antibodies who developed a higher proportion of G2 hypothyroidism. The presence of an initial phase of thyrotoxicity was not related to greater severity. We observed longer progression-free survival in patients who developed thyroid dysfunction.

Conclusion: Pre-existing antibodies were independently associated with endocrinopathies. Moreover, our study let us conclude that the presence of thyroid autoantibodies may be related to its severity. It is important to determine anti-thyroid antibodies prior to the start of immunotherapy as a risk factor for thyroid dysfunction, which in turn is a prognostic marker.

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[1]
Chang, L.S.; Barroso-Sousa, R.; Tolaney, S.M.; Hodi, F.S.; Kaiser, U.B.; Min, L. Endocrine toxicity of cancer immunotherapy targeting immune checkpoints. Endocr. Rev., 2019, 40(1), 17-65.
[http://dx.doi.org/10.1210/er.2018-00006] [PMID: 30184160]
[2]
Barroso-Sousa, R.; Barry, W.T.; Garrido-Castro, A.C.; Hodi, F.S.; Min, L.; Krop, I.E.; Tolaney, S.M. Incidence of endocrine dysfunction following the use of different immune checkpoint inhibitor regimens. JAMA Oncol., 2018, 4(2), 173-182.
[http://dx.doi.org/10.1001/jamaoncol.2017.3064] [PMID: 28973656]
[3]
de Filette, J.; Andreescu, C.; Cools, F.; Bravenboer, B.; Velkeniers, B. A systematic review and meta-analysis of endocrine-related adverse events associated with immune checkpoint inhibitors. Horm. Metab. Res., 2019, 51(3), 145-156.
[http://dx.doi.org/10.1055/a-0843-3366] [PMID: 30861560]
[4]
Shang, Y.; Zhang, Y.; Li, J.; Li, P.; Zhang, X. Risk of endocrine adverse events in cancer patients treated with PD-1 inhibitors: A systematic review and meta-analysis. Immunotherapy, 2017, 9(3), 261-272.
[http://dx.doi.org/10.2217/imt-2016-0147] [PMID: 28231723]
[5]
Corsello, S.M.; Barnabei, A.; Marchetti, P.; De Vecchis, L.; Salvatori, R.; Torino, F. Endocrine side effects induced by immune checkpoint inhibitors. J. Clin. Endocrinol. Metab., 2013, 98(4), 1361-1375.
[http://dx.doi.org/10.1210/jc.2012-4075] [PMID: 23471977]
[6]
Abdel-Rahman, O.; ElHalawani, H.; Fouad, M. Risk of endocrine complications in cancer patients treated with immune check point inhibitors: A meta-analysis. Future Oncol., 2016, 12(3), 413-425.
[http://dx.doi.org/10.2217/fon.15.222] [PMID: 26775673]
[7]
Ferrari, S.M.; Fallahi, P.; Galetta, F.; Citi, E.; Benvenga, S.; Antonelli, A. Thyroid disorders induced by checkpoint inhibitors. Rev. Endocr. Metab. Disord., 2018, 19(4), 325-333.
[http://dx.doi.org/10.1007/s11154-018-9463-2] [PMID: 30242549]
[8]
Freites-Martinez, A.; Santana, N.; Arias-Santiago, S.; Viera, A. Using the common terminology criteria for adverse events (CTCAE - version 5.0) to evaluate the severity of adverse events of anticancer therapies. Actas Dermosifiliogr., 2021, 112(1), 90-92.
[http://dx.doi.org/10.1016/j.ad.2019.05.009] [PMID: 32891586]
[9]
González-Rodríguez, E.; Rodríguez-Abreu, D. Immune checkpoint inhibitors: Review and management of endocrine adverse events. Oncologist, 2016, 21(7), 804-816.
[http://dx.doi.org/10.1634/theoncologist.2015-0509] [PMID: 27306911]
[10]
Brahmer, J.R.; Lacchetti, C.; Schneider, B.J.; Atkins, M.B.; Brassil, K.J.; Caterino, J.M.; Chau, I.; Ernstoff, M.S.; Gardner, J.M.; Ginex, P.; Hallmeyer, S.; Holter Chakrabarty, J.; Leighl, N.B.; Mammen, J.S.; McDermott, D.F.; Naing, A.; Nastoupil, L.J.; Phillips, T.; Porter, L.D.; Puzanov, I.; Reichner, C.A.; Santomasso, B.D.; Seigel, C.; Spira, A.; Suarez-Almazor, M.E.; Wang, Y.; Weber, J.S.; Wolchok, J.D.; Thompson, J.A. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American society of clinical oncology clinical practice guideline. J. Clin. Oncol., 2018, 36(17), 1714-1768.
[http://dx.doi.org/10.1200/JCO.2017.77.6385] [PMID: 29442540]
[11]
Higham, C.E.; Olsson-Brown, A.; Carroll, P.; Cooksley, T.; Larkin, J.; Lorigan, P.; Morganstein, D.; Trainer, P.J. Society for endocrinology endocrine emergency guidance: Acute management of the endocrine complications of checkpoint inhibitor therapy. Endocr. Connect., 2018, 7(7), G1-G7.
[http://dx.doi.org/10.1530/EC-18-0068] [PMID: 29930025]
[12]
Su, Q.; Zhang, X.; Wang, D.; Zhang, H.; Zhu, C.; Hou, Y.; Liu, J.; Gao, Z. The risk of immune-related endocrine disorders associated with anti-PD-1 inhibitors therapy for solid tumors: A systematic review and meta-analysis. Int. Immunopharmacol., 2018, 59, 328-338.
[http://dx.doi.org/10.1016/j.intimp.2018.04.021] [PMID: 29679857]
[13]
Lu, J.; Yang, J.; Liang, Y.; Meng, H.; Zhao, J.; Zhang, X. Incidence of immune checkpoint inhibitor-associated diabetes: A meta-analysis of randomized controlled studies. Front. Pharmacol., 2019, 10, 1453.
[http://dx.doi.org/10.3389/fphar.2019.01453] [PMID: 31920646]
[14]
Maher, V.E.; Fernandes, L.L.; Weinstock, C.; Tang, S.; Agarwal, S.; Brave, M.; Ning, Y.; Singh, H.; Suzman, D.; Xu, J.; Goldberg, K.B.; Sridhara, R.; Ibrahim, A.; Theoret, M.; Beaver, J.A.; Pazdur, R. Analysis of the association between adverse events and outcome in patients receiving a programmed death protein 1 or programmed death ligand 1 antibody. J. Clin. Oncol., 2019, 37(30), 2730-2737.
[http://dx.doi.org/10.1200/JCO.19.00318] [PMID: 31116675]
[15]
Attia, P.; Phan, G.Q.; Maker, A.V.; Robinson, M.R.; Quezado, M.M.; Yang, J.C.; Sherry, R.M.; Topalian, S.L.; Kammula, U.S.; Royal, R.E.; Restifo, N.P.; Haworth, L.R.; Levy, C.; Mavroukakis, S.A.; Nichol, G.; Yellin, M.J.; Rosenberg, S.A. Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4. J. Clin. Oncol., 2005, 23(25), 6043-6053.
[http://dx.doi.org/10.1200/JCO.2005.06.205] [PMID: 16087944]
[16]
Freeman-Keller, M.; Kim, Y.; Cronin, H.; Richards, A.; Gibney, G.; Weber, J.S. Nivolumab in resected and unresectable metastatic melanoma: Characteristics of immune-related adverse events and association with outcomes. Clin. Cancer Res., 2016, 22(4), 886-894.
[http://dx.doi.org/10.1158/1078-0432.CCR-15-1136] [PMID: 26446948]
[17]
Haratani, K.; Hayashi, H.; Chiba, Y.; Kudo, K.; Yonesaka, K.; Kato, R.; Kaneda, H.; Hasegawa, Y.; Tanaka, K.; Takeda, M.; Nakagawa, K. Association of immune-related adverse events with nivolumab efficacy in non–small-cell lung cancer. JAMA Oncol., 2018, 4(3), 374-378.
[http://dx.doi.org/10.1001/jamaoncol.2017.2925] [PMID: 28975219]
[18]
Ricciuti, B.; Genova, C.; De Giglio, A.; Bassanelli, M.; Dal Bello, M.G.; Metro, G.; Brambilla, M.; Baglivo, S.; Grossi, F.; Chiari, R. Impact of immune-related adverse events on survival in patients with advanced non-small cell lung cancer treated with nivolumab: Long-term outcomes from a multi-institutional analysis. J. Cancer Res. Clin. Oncol., 2019, 145(2), 479-485.
[http://dx.doi.org/10.1007/s00432-018-2805-3] [PMID: 30506406]
[19]
Eggermont, A.M.M.; Kicinski, M.; Blank, C.U.; Mandala, M.; Long, G.V.; Atkinson, V.; Dalle, S.; Haydon, A.; Khattak, A.; Carlino, M.S.; Sandhu, S.; Larkin, J.; Puig, S.; Ascierto, P.A.; Rutkowski, P.; Schadendorf, D.; Koornstra, R.; Hernandez-Aya, L.; Di Giacomo, A.M.; van den Eertwegh, A.J.M.; Grob, J.J.; Gutzmer, R.; Jamal, R.; Lorigan, P.C.; Krepler, C.; Ibrahim, N.; Marreaud, S.; van Akkooi, A.; Robert, C.; Suciu, S. Association between immune-related adverse events and recurrence-free survival among patients with stage III melanoma randomized to receive pembrolizumab or placebo. JAMA Oncol., 2020, 6(4), 519-527.
[http://dx.doi.org/10.1001/jamaoncol.2019.5570] [PMID: 31895407]
[20]
Oken, M.M.; Creech, R.H.; Tormey, D.C.; Horton, J.; Davis, T.E.; McFadden, E.T.; Carbone, P.P. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am. J. Clin. Oncol., 1982, 5(6), 649-656.
[http://dx.doi.org/10.1097/00000421-198212000-00014] [PMID: 7165009]
[21]
Anic, K.; Varchola, J.; Schmidt, M.W.; Schwab, R.; Linz, V.C.; Schmidt, M.; Hardt, R.; Hartmann, E.K.; Ruckes, C.; Hasenburg, A.; Battista, M.J. Influence of interdisciplinary frailty screening on perioperative complication rates in elderly ovarian cancer patients: Results of a retrospective observational study. Arch. Gynecol. Obstet., 2022, 307(6), 1929-1940.
[http://dx.doi.org/10.1007/s00404-022-06850-4] [PMID: 36434440]
[22]
Postow, M.A.; Callahan, M.K.; Wolchok, J.D. Immune checkpoint blockade in cancer therapy. J. Clin. Oncol., 2015, 33(17), 1974-1982.
[http://dx.doi.org/10.1200/JCO.2014.59.4358] [PMID: 25605845]
[23]
Buchbinder, E.I.; Desai, A. CTLA-4 and PD-1 pathways. Am. J. Clin. Oncol., 2016, 39(1), 98-106.
[http://dx.doi.org/10.1097/COC.0000000000000239] [PMID: 26558876]
[24]
Cardona, Z.; Sosman, J.A.; Chandra, S.; Huang, W. Endocrine side effects of immune checkpoint inhibitors. Front. Endocrinol. (Lausanne), 2023, 14, 1157805.
[http://dx.doi.org/10.3389/fendo.2023.1157805] [PMID: 37251665]
[25]
Kennedy, R.; Awada, H.; Vura, N.; Ciltea, D.; Morocco, M. Endocrinopathies from checkpoint inhibitors: Incidence, outcomes, and management. Cleve. Clin. J. Med., 2023, 90(5), 307-317.
[http://dx.doi.org/10.3949/ccjm.90a.22032] [PMID: 37127339]
[26]
Kurimoto, C.; Inaba, H.; Ariyasu, H.; Iwakura, H.; Ueda, Y.; Uraki, S.; Takeshima, K.; Furukawa, Y.; Morita, S.; Yamamoto, Y.; Yamashita, S.; Katsuda, M.; Hayata, A.; Akamatsu, H.; Jinnin, M.; Hara, I.; Yamaue, H.; Akamizu, T. Predictive and sensitive biomarkers for thyroid dysfunctions during treatment with immune‐checkpoint inhibitors. Cancer Sci., 2020, 111(5), 1468-1477.
[http://dx.doi.org/10.1111/cas.14363] [PMID: 32086984]
[27]
Shalit, A.; Sarantis, P.; Koustas, E.; Trifylli, E.M.; Matthaios, D.; Karamouzis, M.V. Predictive biomarkers for immune-related endocrinopathies following immune checkpoint inhibitors treatment. Cancers (Basel), 2023, 15(2), 375.
[http://dx.doi.org/10.3390/cancers15020375] [PMID: 36672324]
[28]
Muir, C.A.; Clifton-Bligh, R.J.; Long, G.V.; Scolyer, R.A.; Lo, S.N.; Carlino, M.S.; Tsang, V.H.M.; Menzies, A.M. Thyroid immune-related adverse events following immune checkpoint inhibitor treatment. J. Clin. Endocrinol. Metab., 2021, 106(9), e3704-e3713.
[http://dx.doi.org/10.1210/clinem/dgab263] [PMID: 33878162]
[29]
Toi, Y.; Sugawara, S.; Sugisaka, J.; Ono, H.; Kawashima, Y.; Aiba, T.; Kawana, S.; Saito, R.; Aso, M.; Tsurumi, K.; Suzuki, K.; Shimizu, H.; Domeki, Y.; Terayama, K.; Nakamura, A.; Yamanda, S.; Kimura, Y.; Honda, Y. Profiling preexisting antibodies in patients treated with anti–PD-1 therapy for advanced non–small cell lung cancer. JAMA Oncol., 2019, 5(3), 376-383.
[http://dx.doi.org/10.1001/jamaoncol.2018.5860] [PMID: 30589930]
[30]
Basak, E.A.; van der Meer, J.W.M.; Hurkmans, D.P.; Schreurs, M.W.J.; Oomen-de Hoop, E.; van der Veldt, A.A.M.; Bins, S.; Joosse, A.; Koolen, S.L.W.; Debets, R.; Peeters, R.P.; Aerts, J.G.J.V.; Mathijssen, R.H.J.; Medici, M. Overt thyroid dysfunction and anti-thyroid antibodies predict response to anti-PD-1 immunotherapy in cancer patients. Thyroid, 2020, 30(7), 966-973.
[http://dx.doi.org/10.1089/thy.2019.0726] [PMID: 32151195]
[31]
Ando, T.; Ueda, A.; Ogawa, K.; Motoo, I.; Kajiura, S.; Nakajima, T.; Hirano, K.; Okumura, T.; Tsukada, K.; Hara, T.; Suzuki, N.; Nakada, N.; Horikawa, N.; Fujii, T.; Yasuda, I. Prognosis of immune-related adverse events in patients with advanced gastric cancer treated with nivolumab or pembrolizumab: A multicenter retrospective analysis. In Vivo, 2021, 35(1), 475-482.
[http://dx.doi.org/10.21873/invivo.12281] [PMID: 33402499]
[32]
Muir, C.A.; Wood, C.C.G.; Clifton-Bligh, R.J.; Long, G.V.; Scolyer, R.A.; Carlino, M.S.; Menzies, A.M.; Tsang, V.H.M. Association of antithyroid antibodies in checkpoint inhibitor–associated thyroid immune–related adverse events. J. Clin. Endocrinol. Metab., 2022, 107(5), e1843-e1849.
[http://dx.doi.org/10.1210/clinem/dgac059] [PMID: 35104870]
[33]
Percik, R.; Criseno, S.; Adam, S.; Young, K.; Morganstein, D.L. Diagnostic criteria and proposed management of immune-related endocrinopathies following immune checkpoint inhibitor therapy for cancer. Endocr. Connect., 2023, 12(5), e220513.
[http://dx.doi.org/10.1530/EC-22-0513] [PMID: 36884258]
[34]
Iwama, S.; Kobayashi, T.; Yasuda, Y.; Arima, H. Immune checkpoint inhibitor-related thyroid dysfunction. Best Pract. Res. Clin. Endocrinol. Metab., 2022, 36(3), 101660.
[http://dx.doi.org/10.1016/j.beem.2022.101660] [PMID: 35501263]
[35]
Zou, F.; Abu-Sbeih, H.; Ma, W.; Peng, Y.; Qiao, W.; Wang, J.; Shah, A.Y.; Glitza Oliva, I.C.; Piha-Paul, S.A.; Thompson, J.A.; Zhang, H.C.; Thomas, A.S.; Wang, Y. Association of chronic immune-mediated diarrhea and colitis with favorable cancer response. J. Natl. Compr. Canc. Netw., 2021, 19(6), 700-708.
[http://dx.doi.org/10.6004/jnccn.2020.7647] [PMID: 33316767]
[36]
Suo, A.; Chan, Y.; Beaulieu, C.; Kong, S.; Cheung, W.Y.; Monzon, J.G.; Smylie, M.; Walker, J.; Morris, D.; Cheng, T. Anti-PD1-induced immune-related adverse events and survival outcomes in advanced melanoma. Oncologist, 2020, 25(5), 438-446.
[http://dx.doi.org/10.1634/theoncologist.2019-0674] [PMID: 32048768]
[37]
Bottlaender, L.; Amini-Adle, M.; Maucort-Boulch, D.; Robinson, P.; Thomas, L.; Dalle, S. Cutaneous adverse events: A predictor of tumour response under anti‐ PD ‐1 therapy for metastatic melanoma, a cohort analysis of 189 patients. J. Eur. Acad. Dermatol. Venereol., 2020, 34(9), 2096-2105.
[http://dx.doi.org/10.1111/jdv.16311] [PMID: 32078191]
[38]
Schweizer, C.; Schubert, P.; Rutzner, S.; Eckstein, M.; Haderlein, M.; Lettmaier, S.; Semrau, S.; Gostian, A.O.; Frey, B.; Gaipl, U.S.; Zhou, J.G.; Fietkau, R.; Hecht, M. Prospective evaluation of the prognostic value of immune-related adverse events in patients with non-melanoma solid tumour treated with PD-1/PD-L1 inhibitors alone and in combination with radiotherapy. Eur. J. Cancer, 2020, 140, 55-62.
[http://dx.doi.org/10.1016/j.ejca.2020.09.001] [PMID: 33045663]
[39]
Akamatsu, H.; Murakami, E.; Oyanagi, J.; Shibaki, R.; Kaki, T.; Takase, E.; Tanaka, M.; Harutani, Y.; Yamagata, N.; Okuda, Y.; Furuta, K.; Sugimoto, T.; Teraoka, S.; Hayata, A.; Tokudome, N.; Ozawa, Y.; Mori, K.; Koh, Y.; Yamamoto, N. Immune-related adverse events by immune checkpoint inhibitors significantly predict durable efficacy even in responders with advanced non-small cell lung cancer. Oncologist, 2020, 25(4), e679-e683.
[http://dx.doi.org/10.1634/theoncologist.2019-0299] [PMID: 32297443]
[40]
Indini, A.; Di Guardo, L.; Cimminiello, C.; Prisciandaro, M.; Randon, G.; De Braud, F.; Del Vecchio, M. Immune-related adverse events correlate with improved survival in patients undergoing anti-PD1 immunotherapy for metastatic melanoma. J. Cancer Res. Clin. Oncol., 2019, 145(2), 511-521.
[http://dx.doi.org/10.1007/s00432-018-2819-x] [PMID: 30539281]
[41]
Shankar, B.; Zhang, J.; Naqash, A.R.; Forde, P.M.; Feliciano, J.L.; Marrone, K.A.; Ettinger, D.S.; Hann, C.L.; Brahmer, J.R.; Ricciuti, B.; Owen, D.; Toi, Y.; Walker, P.; Otterson, G.A.; Patel, S.H.; Sugawara, S.; Naidoo, J. Multisystem immune-related adverse events associated with immune checkpoint inhibitors for treatment of non–small cell lung cancer. JAMA Oncol., 2020, 6(12), 1952-1956.
[http://dx.doi.org/10.1001/jamaoncol.2020.5012] [PMID: 33119034]
[42]
Yamauchi, I.; Yasoda, A.; Matsumoto, S.; Sakamori, Y.; Kim, Y.H.; Nomura, M.; Otsuka, A.; Yamasaki, T.; Saito, R.; Kitamura, M.; Kitawaki, T.; Hishizawa, M.; Kawaguchi-Sakita, N.; Fujii, T.; Taura, D.; Sone, M.; Inagaki, N. Incidence, features, and prognosis of immune-related adverse events involving the thyroid gland induced by nivolumab. PLoS One, 2019, 14(5), e0216954.
[http://dx.doi.org/10.1371/journal.pone.0216954] [PMID: 31086392]
[43]
Kobayashi, T.; Iwama, S.; Yasuda, Y.; Okada, N.; Okuji, T.; Ito, M.; Onoue, T.; Goto, M.; Sugiyama, M.; Tsunekawa, T.; Takagi, H.; Hagiwara, D.; Ito, Y.; Suga, H.; Banno, R.; Yokota, K.; Hase, T.; Morise, M.; Hashimoto, N.; Ando, M.; Fujimoto, Y.; Hibi, H.; Sone, M.; Ando, Y.; Akiyama, M.; Hasegawa, Y.; Arima, H. Pituitary dysfunction induced by immune checkpoint inhibitors is associated with better overall survival in both malignant melanoma and non-small cell lung carcinoma: A prospective study. J. Immunother. Cancer, 2020, 8(2), e000779.
[http://dx.doi.org/10.1136/jitc-2020-000779] [PMID: 32606047]
[44]
Faje, A.T.; Lawrence, D.; Flaherty, K.; Freedman, C.; Fadden, R.; Rubin, K.; Cohen, J.; Sullivan, R.J. High‐dose glucocorticoids for the treatment of ipilimumab‐induced hypophysitis is associated with reduced survival in patients with melanoma. Cancer, 2018, 124(18), 3706-3714.
[http://dx.doi.org/10.1002/cncr.31629] [PMID: 29975414]
[45]
Del Rivero, J.; Cordes, L.M.; Klubo-Gwiezdzinska, J.; Madan, R.A.; Nieman, L.K.; Gulley, J.L. Endocrine-related adverse events related to immune checkpoint inhibitors: Proposed algorithms for management. Oncologist, 2020, 25(4), 290-300.
[http://dx.doi.org/10.1634/theoncologist.2018-0470] [PMID: 32297436]
[46]
Spagnolo, C.C.; Giuffrida, G.; Cannavò, S.; Franchina, T.; Silvestris, N.; Ruggeri, R.M.; Santarpia, M. Management of endocrine and metabolic toxicities of immune-checkpoint inhibitors: from clinical studies to a real-life scenario. Cancers (Basel), 2022, 15(1), 246.
[http://dx.doi.org/10.3390/cancers15010246] [PMID: 36612243]

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