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Cancers
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Management and Treatment of Endocrine Tumors
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Management and Treatment of Endocrine Tumors

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

Deadline for manuscript submissions: closed (30 August 2022) | Viewed by 20653

Special Issue Editor

Prof. Dr. Jean-Christophe Lifante

E-Mail Website
Guest Editor
1. Endocrine Surgery Department, hôpital Lyon sud, Hospices Civils de Lyon, 69310 Pierre Bénite, France
2. RESHAPE Research on Healthcare Performance, INSERM U1290 -UCBL 1, Domaine Rockefeller, 8 avenue Rockefeller, 69003 Lyon, France
Interests: thyroid surgery; thyroid carcinomas; primary hyperparathyroidism; adrenal surgery; adrenal cancers; pheochromocytoma; endocrine pancreatic tumors; health performance research

Special Issue Information

Dear Colleagues,

Endocrine surgery is currently a well-recognized specialty of general surgery. Like all medical specialties, when interest in an area increases, the knowledge that concerns it rapidly expands; meanwhile, the endocrine surgeon’s profile continues to diversify. Several years ago, endocrine surgeons generally treated thyroid, parathyroid, adrenal, intestine, and pancreatic tumors. Currently, some surgeons specialize in one field of endocrine surgery, whereas others maintain a more general practice. Nonetheless, an endocrine surgeon must be more than a good surgeon and must have excellent knowledge in radiology, nuclear medicine, endocrinology, pathology, and oncology. Recent significant progress in these fields includes the use of positrons. Remarkably, novel functional imaging radioisotopes using positron emission tomography (PET) and computed tomography (CT) tracers, including gallium-68 (68Ga)-DOTATATE, have been successfully expanded in tumor localization and visualization. Other PET/CT tracers have also become essential in the diagnosis of recurrence of numerous endocrine tumors.

The treatment of endocrine tumors has changed during the last decade. The extent of thyroid cancer surgery continues to become less invasive, while the imaging strategy aids in the success of parathyroid surgery. Moreover, research on optimal lymph node dissection in the surgical treatment of intestine endocrine tumors continually expands. Although techniques of mini-invasive surgery remain poorly established in all fields, this research area is advancing rapidly. Furthermore, the progression of genetic tumors has modified patient management and allowed prophylactic surgery in certain cases. Thus, the oncologic treatments of endocrine tumors are in constant evolution with the use of new targeted therapy.

This series of articles, original articles, and reviews is presented by an international team of experts in endocrine tumors. From these works, we try to cover all research fields concerning the management of these tumors.

Prof. Dr. Jean-Christophe Lifante
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

  • thyroid cancers
  • primary hyperparathyroididsm
  • thyroid cancer surgery
  • adrenal tumors
  • pheochromocytoma
  • pancreatic endocrine tumors
  • intestine NETs
  • nuclear medicine

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Published Papers (7 papers)

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Research

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12 pages, 875 KiB  
Article
177Lu-DOTATATE Efficacy and Safety in Functioning Neuroendocrine Tumors: A Joint Analysis of Phase II Prospective Clinical Trials
by Alberto Bongiovanni, Silvia Nicolini, Toni Ibrahim, Flavia Foca, Maddalena Sansovini, Arianna Di Paolo, Ilaria Grassi, Chiara Liverani, Chiara Calabrese, Nicoletta Ranallo, Federica Matteucci, Giovanni Paganelli and Stefano Severi
Cancers 2022, 14(24), 6022; https://doi.org/10.3390/cancers14246022 - 7 Dec 2022
Cited by 1 | Viewed by 2103
Abstract
Introduction: Neuroendocrine tumors (NETs) are rare malignancies with different prognoses. At least 25% of metastatic patients have functioning neuroendocrine tumors (F-NETs) that secrete bioactive peptides, causing specific debilitating and occasionally life-threatening symptoms such as diarrhea and flushing. Somatostatin analogs (SSAs) are usually effective [...] Read more.
Introduction: Neuroendocrine tumors (NETs) are rare malignancies with different prognoses. At least 25% of metastatic patients have functioning neuroendocrine tumors (F-NETs) that secrete bioactive peptides, causing specific debilitating and occasionally life-threatening symptoms such as diarrhea and flushing. Somatostatin analogs (SSAs) are usually effective but beyond them few treatment options are available. We evaluated the clinical efficacy of 177 Lu-DOTATATE in patients with progressive metastatic F-NETs and SSA-refractory syndrome. Patients and Methods: A non-pre-planned joint analysis was conducted in patients enrolled in phase II clinical trials on metastatic NETs. We extrapolated data from F-NET patients with ≥1 refractory sign/symptom to octreotide, and ≥1 measurable lesion. Syndrome response (SR), overall survival (OS), progression-free survival (PFS), tolerance and disease response were analyzed. Results: Sixty-eight patients were enrolled, the majority (88.1%) with a SR. According to RECIST criteria, 1 (1.5%) patient showed a CR, 21 (32.3%) had a PR and 40 (61.5%) SD. At a median follow-up of 28.9 months (range 2.2–63.2) median PFS was 33.0 months (95%CI: 27.1–48.2). Median OS (mOS) had not been reached at the time of the analysis; the 2-year OS was 87.8% (95%CI: 76.1–94.1). Syndromic responders showed better survival than non-responders, with a 2-year OS of 93.9% (95%CI: 92.2–98.0) vs. 40.0% (95%CI: 6.6–73.4), respectively. A total of 233 adverse events were recorded. Grade 1–2 hematological toxicity was the most frequent. Conclusion: The 177 Lu-DOTATATE improved symptoms and disease control in patients with F-NETs. Treatment was well tolerated. The syndrome had an impact on both quality of life and OS. Full article
(This article belongs to the Special Issue Management and Treatment of Endocrine Tumors)
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13 pages, 281 KiB  
Article
Impact of Lymph Node Dissection on Postoperative Complications of Total Thyroidectomy in Patients with Thyroid Carcinoma
by Gregory Baud, Arnaud Jannin, Camille Marciniak, Benjamin Chevalier, Christine Do Cao, Emmanuelle Leteurtre, Amandine Beron, Georges Lion, Samuel Boury, Sebastien Aubert, Brigitte Bouchindhomme, Marie-Christine Vantyghem, Robert Caiazzo and François Pattou
Cancers 2022, 14(21), 5462; https://doi.org/10.3390/cancers14215462 - 7 Nov 2022
Cited by 14 | Viewed by 2282
Abstract
Background: Lymph node dissection (LND) in primary treatment of differentiated thyroid carcinoma is controversial. The aim of our retrospective study was to analyse the risk factors of post-thyroidectomy complications and to assess the morbidity of lymph node dissection, especially in the central neck [...] Read more.
Background: Lymph node dissection (LND) in primary treatment of differentiated thyroid carcinoma is controversial. The aim of our retrospective study was to analyse the risk factors of post-thyroidectomy complications and to assess the morbidity of lymph node dissection, especially in the central neck compartment, since prophylactic central lymph node dissection has not been proven to bring an overall survival benefit. Methods: We performed a retrospective analysis of postoperative complications from 1547 consecutive patients with differentiated thyroid carcinoma in an academic department of endocrine surgery over a period of 10 years. Results: A total of 535 patients underwent lymph node dissection, whereas the other 1012 did not. The rate of postoperative hypoparathyroidism was higher in patients with LND (17.6% vs. 11.4%, p = 0.001). No significant difference in the rate of permanent hypoparathyroidism (2.4% vs. 1.3%, p = 0.096) was observed between these two groups. A multivariate analysis was performed. Female gender, ipsilateral and bilateral central LND (CLND), parathyroid autotransplantation, and the presence of the parathyroid gland on the resected thyroid were associated with transient hypoparathyroidism. Bilateral CLND and the presence of the parathyroid gland on specimen were associated with permanent hypoparathyroidism. The rate of transient recurrent laryngeal nerve (RLN) injury (15.3% vs. 5.4%, p < 0.001) and permanent RLN injury (6.5% vs. 0.9%, p < 0.001) were higher in the LND group. In multivariate analysis, ipsilateral and bilateral lateral LND (LLND) were the main predictive factors of transient and permanent RLN injury. Bilateral RLN injury (2.6% vs. 0.4%, p < 0.001), chyle leakage (2.4% vs. 0%, p < 0.001), other nerve injuries (2.2% vs. 0%, p < 0.001), and abscess (2.4% vs. 0.5%, p = 0.001) were higher in the patients with LND. Conclusions: The surgical technique and the extent of lymph node dissection during surgery for thyroid carcinoma increase postoperative morbidity. A wider knowledge of lymph-node-dissection-related complications associated with thyroid surgery could help surgeons to carefully evaluate the surgical and medical therapeutic options. Full article
(This article belongs to the Special Issue Management and Treatment of Endocrine Tumors)
10 pages, 720 KiB  
Article
Prognostic Impact of Microscopic Extra-Thyroidal Extension (mETE) on Disease Free Survival in Patients with Papillary Thyroid Carcinoma (PTC)
by Nadia Bouzehouane, Pascal Roy, Myriam Decaussin-Petrucci, Mireille Bertholon-Grégoire, Chantal Bully, Agnès Perrin, Helene Lasolle, Jean-Christophe Lifante, Françoise Borson-Chazot and Claire Bournaud
Cancers 2022, 14(11), 2591; https://doi.org/10.3390/cancers14112591 - 24 May 2022
Cited by 1 | Viewed by 1724
Abstract
Background: This study assessed the risk of reduced disease-free survival (DFS) and poor clinical outcome in patients with papillary thyroid carcinomas (PTC) with microscopic extra-thyroidal extension (mETE), as compared to PTC patients without mETE. Methods: Retrospective analysis of a prospective database of patients [...] Read more.
Background: This study assessed the risk of reduced disease-free survival (DFS) and poor clinical outcome in patients with papillary thyroid carcinomas (PTC) with microscopic extra-thyroidal extension (mETE), as compared to PTC patients without mETE. Methods: Retrospective analysis of a prospective database of patients treated by total thyroidectomy and radioactive iodine (RAI) with a five-year follow-up and tumors < 40 mm. In total, 303 patients were analyzed: 30.7% presented tumors with mETE, and 69.3% without. mETE was defined as extra-thyroidal invasion without skeletal muscle involvement. The primary outcome, DFS, was defined as the interval between initial treatment and any subsequent PTC-related treatment. The second outcome was the clinical status at five years. Results: In univariate analyses, the five-year DFS was significantly lower for tumors with mETE (62.4% versus 88.1%, p < 0.001). In multivariate analysis, mETE and massive lymph node involvement (LNI) were independent prognostic factors, associated respectively with a hazard ratio of 2.55 (95% CI 1.48–4.40) and 8.94 (95% CI 4.92–16.26). mETE was significantly associated with a pejorative clinical outcome at five years, i.e., biochemical/indeterminate response and structural persistence (Respectively OR 1.83 (95% CI 0.83; 4.06) and OR 4.92 (95% CI 1.87; 12.97)). Conclusion: Our results suggest that mETE is an independent poor prognosis factor of reduced DFS and predictive of poor clinical outcome. Full article
(This article belongs to the Special Issue Management and Treatment of Endocrine Tumors)
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13 pages, 2531 KiB  
Article
Diagnostic Performance of 18F-Choline Positron Emission Tomography/Contrast-Enhanced Computed Tomography in Adenoma Detection in Primary Hyperparathyroidism after Inconclusive Imaging: A Retrospective Study of 215 Patients
by Johan Benjamin, Laure Maillard, Isabelle Morelec, Philippe Got, Françoise Borson-Chazot and Jean-Christophe Lifante
Cancers 2022, 14(8), 2029; https://doi.org/10.3390/cancers14082029 - 17 Apr 2022
Cited by 5 | Viewed by 2242
Abstract
This large, retrospective, single-centre study evaluated the diagnostic performance of 18F-choline positron emission tomography/contrast-enhanced computed tomography (PET/ceCT) in preoperative parathyroid adenoma detection in primary hyperparathyroidism cases after negative/inconclusive ultrasound or other imaging findings. We included patients who underwent surgery and 18F-choline [...] Read more.
This large, retrospective, single-centre study evaluated the diagnostic performance of 18F-choline positron emission tomography/contrast-enhanced computed tomography (PET/ceCT) in preoperative parathyroid adenoma detection in primary hyperparathyroidism cases after negative/inconclusive ultrasound or other imaging findings. We included patients who underwent surgery and 18F-choline PET/ceCT for inconclusive imaging results between 2015 and 2020. We compared the 18F-choline PET/ceCT results with surgical and histopathological findings and identified the variables influencing the correlation between 18F-choline PET/ceCT and surgical findings. Of 215 enrolled patients, 269 glands (mean lesion size, 10.9 ± 8.0 mm) were analysed. There were 165 unilocular and 50 multilocular lesions; the mean preoperative calcium level was 2.18 ± 0.19 mmol/L. Among 860 estimated lesions, 219 were classified as true positive, 21 as false positive, and 28 as false negative. The per-lesion sensitivity was 88.66%; specificity, 96.57%; positive predictive value, 91.40%; and negative predictive value, 95.39%. The detection and cure rates were 82.0% and 95.0%, respectively. On univariate and multivariate analyses, the maximum standardised uptake value (SUVmax), lesion size, and unilocularity correlated with the pathologic findings of hyperfunctioning glands. 18F-choline PET/ceCT presents favourable diagnostic performance as a second-line imaging method, with SUVmax, lesion size, and unilocularity predicting a high correlation between the 18F-choline PET/ceCT and surgical findings. Full article
(This article belongs to the Special Issue Management and Treatment of Endocrine Tumors)
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12 pages, 2491 KiB  
Article
Change of Computed Tomography-Based Body Composition after Adrenalectomy in Patients with Pheochromocytoma
by Yousun Ko, Heeryoel Jeong, Seungwoo Khang, Jeongjin Lee, Kyung Won Kim and Beom-Jun Kim
Cancers 2022, 14(8), 1967; https://doi.org/10.3390/cancers14081967 - 13 Apr 2022
Cited by 3 | Viewed by 2155
Abstract
Despite the potential biological importance of the sympathetic nervous system on fat and skeletal muscle metabolism in animal and in vitro studies, its relevance in humans remains undetermined. To clarify the influence of catecholamine excess on human body composition, we performed a retrospective [...] Read more.
Despite the potential biological importance of the sympathetic nervous system on fat and skeletal muscle metabolism in animal and in vitro studies, its relevance in humans remains undetermined. To clarify the influence of catecholamine excess on human body composition, we performed a retrospective longitudinal cohort study including 313 consecutive patients with histologically confirmed pheochromocytoma who underwent repeat abdominal computed tomography (CT) scans before and after adrenalectomy. Changes in CT-determined visceral fat area (VFA), subcutaneous fat area (SFA), skeletal muscle area (SMA), and skeletal muscle index (SMI) were measured at the level of the third lumbar vertebra. The mean age of all patients was 50.6 ± 13.6 years, and 171/313 (54.6%) were women. The median follow-up duration for repeat CTs was 25.0 months. VFA and SFA were 14.5% and 15.8% higher, respectively (both p < 0.001), after adrenalectomy, whereas SMA and SMI remained unchanged. Similarly, patients with visceral obesity significantly increased from 103 (32.9%) at baseline to 138 (44.1%) following surgery (p < 0.001); however, the prevalence of sarcopenia was unchanged. This study provides important clinical evidence that sympathetic hyperactivity can contribute to lipolysis in visceral and subcutaneous adipose tissues, but its impact on human skeletal muscle is unclear. Full article
(This article belongs to the Special Issue Management and Treatment of Endocrine Tumors)
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Review

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22 pages, 1222 KiB  
Review
Bronchial Carcinoids: From Molecular Background to Treatment Approach
by Marta Araujo-Castro, Eider Pascual-Corrales, Javier Molina-Cerrillo, Nicolás Moreno Mata and Teresa Alonso-Gordoa
Cancers 2022, 14(3), 520; https://doi.org/10.3390/cancers14030520 - 20 Jan 2022
Cited by 8 | Viewed by 4962
Abstract
A better understanding of the genetic and molecular background of bronchial carcinoids (BCs) would allow a better estimation of the risk of disease progression and the personalization of treatment in cases of advanced disease. Molecular studies confirmed that lungs neuroendocrine tumors (NETs) and [...] Read more.
A better understanding of the genetic and molecular background of bronchial carcinoids (BCs) would allow a better estimation of the risk of disease progression and the personalization of treatment in cases of advanced disease. Molecular studies confirmed that lungs neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) are different entities; thus, no progression of NET to NEC is expected. In BCs, MEN1 gene mutations and deletions and decreased gene expression have been associated with a poor prognosis. ATRX mutation has also been linked to a shorter disease-specific survival. In terms of therapeutic targets, PI3K/AKT/mTOR pathway mutations have been described in 13% of typical carcinoids (TCs) and 39% of atypical carcinoids (ACs), representing a targetable mutation with kinase inhibitors. Regarding treatment, surgical resection is usually curative in localized BCs and adjuvant treatment is not routinely recommended. Multiple options for systemic therapy exist for patients with advanced BCs, although limited by a heterogeneity in the scientific evidence behind their use recommendation. These options include somatostatin analogues, everolimus, peptide receptor radionuclide therapy, chemotherapy, radiotherapy, antiangiogenic agents, and immunotherapy. In this article, we provide a comprehensive review about the molecular and genetic background of BCs, and about the treatment of local and metastatic disease, as well as the main paraneoplastic syndromes that have been associated with this tumor. Full article
(This article belongs to the Special Issue Management and Treatment of Endocrine Tumors)
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Graphical abstract

Other

Jump to: Research, Review

15 pages, 719 KiB  
Systematic Review
Management of Patients with Treatment of Pheochromocytoma: A Critical Appraisal
by Florence Bihain, Claire Nomine-Criqui, Philippe Guerci, Stephane Gasman, Marc Klein and Laurent Brunaud
Cancers 2022, 14(16), 3845; https://doi.org/10.3390/cancers14163845 - 9 Aug 2022
Cited by 8 | Viewed by 4249
Abstract
The management of pheochromocytomas has significantly evolved these last 50 years, especially with the emergence of new technologies such as laparoscopic procedures in the 1990s. A preoperative blockade using antihypertensive medications to prevent intraoperative hemodynamic instability and cardiocirculatory events is recommended by current [...] Read more.
The management of pheochromocytomas has significantly evolved these last 50 years, especially with the emergence of new technologies such as laparoscopic procedures in the 1990s. A preoperative blockade using antihypertensive medications to prevent intraoperative hemodynamic instability and cardiocirculatory events is recommended by current clinical guidelines. However, these guidelines are still based on former experiences and are subject to discussion in the scientific community. The aim of this systematic review was to assess the evolution of the management of pheochromocytomas. Laparoscopic procedure is established as the standard of care in current practices. Preoperative medical preparation should be questioned because it does not significantly improve intraoperative events or the risk of postoperative complications in current clinical practice. Current clinical recommendations should be revised and upgraded to current clinical practices. Full article
(This article belongs to the Special Issue Management and Treatment of Endocrine Tumors)
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