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Article ; Online: ASO Author Reflections: Morbidity and Outcomes of Primary Tumor Management in Patients with Widely Metastatic Well-Differentiated Small Bowel Neuroendocrine Tumors.

Nigam, Aradhya / Untch, Brian R

2024 Volume 31, Issue 4, Page(s) 2359–2360

MeSH term(s)	Humans ; Neuroendocrine Tumors/therapy ; Neuroendocrine Tumors/secondary ; Intestinal Neoplasms/surgery ; Pancreatic Neoplasms ; Morbidity ; Stomach Neoplasms
Language	English
Publishing date	2024-01-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	1200469-8
ISSN	1534-4681 ; 1068-9265
ISSN (online)	1534-4681
ISSN	1068-9265
DOI	10.1245/s10434-023-14823-3
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Article: Cooperative Genomic Lesions in HRAS-Mutant Cancers Predict Resistance to Farnesyltransferase Inhibitors.

Nigam, Aradhya / Krishnamoorthy, Gnana / Chatila, Walid / Berman, Katherine / Saqcena, Mahesh / Walch, Henry / Ho, Alan / Schultz, Nikolaus / Fagin, James / Untch, Brian

Research square

2023

Abstract: The clinical development of farnesyltransferase inhibitors (FTI) ... ...

Abstract	The clinical development of farnesyltransferase inhibitors (FTI) for
Language	English
Publishing date	2023-07-14
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-3154719/v1
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Article ; Online: FGFR2::TACC2 fusion as a novel KIT-independent mechanism of targeted therapy failure in a multidrug-resistant gastrointestinal stromal tumor.

Dermawan, Josephine K / Vanderbilt, Chad M / Chang, Jason C / Untch, Brian R / Singer, Samuel / Chi, Ping / Tap, William D / Antonescu, Cristina R

Genes, chromosomes & cancer

2022 Volume 61, Issue 7, Page(s) 412–419

Abstract: Genetic alterations in FGF/FGFR pathway are infrequent in gastrointestinal stromal tumors (GIST), with rare cases of quadruple wildtype GISTs harboring FGFR1 gene fusions and mutations. Additionally, FGF/FGFR overexpression was shown to promote drug ... ...

Abstract	Genetic alterations in FGF/FGFR pathway are infrequent in gastrointestinal stromal tumors (GIST), with rare cases of quadruple wildtype GISTs harboring FGFR1 gene fusions and mutations. Additionally, FGF/FGFR overexpression was shown to promote drug resistance to kinase inhibitors in GISTs. However, FGFR gene fusions have not been directly implicated as a mechanism of drug resistance in GISTs. Herein, we report a patient presenting with a primary small bowel spindle cell GIST and concurrent peritoneal and liver metastases displaying an imatinib-sensitive KIT exon 11 in-frame deletion. After an initial 9-month benefit to imatinib, the patient experienced intraabdominal peritoneal recurrence owing to secondary KIT exon 13 missense mutation and FGFR4 amplification. Despite several additional rounds of tyrosine kinase inhibitors (TKI), the patient's disease progressed after 2 years and presented with multiple peritoneal and liver metastases, including one pericolonic mass harboring secondary KIT exon 18 missense mutation, and a concurrent transverse colonic mass with a FGFR2::TACC2 fusion and AKT2 amplification. All tumors, including primary and recurrent masses, harbored an MGA c.7272 T > G (p.Y2424*) nonsense mutation and CDKN2A/CDKN2B/MTAP deletions. The transcolonic mass showed elevated mitotic count (18/10 HPF), as well as significant decrease in CD117 and DOG1 expression, in contrast to all the other resistant nodules that displayed diffuse and strong CD117 and DOG1 immunostaining. The FGFR2::TACC2 fusion resulted from a 742 kb intrachromosomal inversion at the chr10q26.3 locus, leading to a fusion between exons 1-17 of FGFR2 and exons 7-17 TACC2, which preserves the extracellular and protein tyrosine kinase domains of FGFR2. We present the first report of a multidrug-resistant GIST patient who developed an FGFR2 gene fusion as a secondary genetic event to the selective pressure of various TKIs. This case also highlights the heterogeneous escape mechanisms to targeted therapy across various tumor nodules, spanning from both KIT-dependent and KIT-independent off-target activation pathways.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Carrier Proteins/genetics ; Gastrointestinal Stromal Tumors/drug therapy ; Gastrointestinal Stromal Tumors/genetics ; Gastrointestinal Stromal Tumors/pathology ; Gene Fusion ; Humans ; Imatinib Mesylate ; Liver Neoplasms/drug therapy ; Liver Neoplasms/genetics ; Mutation ; Proto-Oncogene Proteins c-kit/genetics ; Receptor, Fibroblast Growth Factor, Type 2/genetics ; Receptor, Platelet-Derived Growth Factor alpha/genetics ; Tumor Suppressor Proteins/genetics
Chemical Substances	Antineoplastic Agents ; Carrier Proteins ; TACC2 protein, human ; Tumor Suppressor Proteins ; Imatinib Mesylate (8A1O1M485B) ; FGFR2 protein, human (EC 2.7.10.1) ; Proto-Oncogene Proteins c-kit (EC 2.7.10.1) ; Receptor, Fibroblast Growth Factor, Type 2 (EC 2.7.10.1) ; Receptor, Platelet-Derived Growth Factor alpha (EC 2.7.10.1)
Language	English
Publishing date	2022-02-22
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1018988-9
ISSN	1098-2264 ; 1045-2257
ISSN (online)	1098-2264
ISSN	1045-2257
DOI	10.1002/gcc.23030
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Zs.A 2966: Show issues

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Article ; Online: Pancreatic metastasectomy: the Memorial Sloan-Kettering experience and a review of the literature.

Untch, Brian R / Allen, Peter J

Journal of surgical oncology

2014 Volume 109, Issue 1, Page(s) 28–30

Abstract: Isolated pancreatic metastases may occur in patients with many types of cancer. Several retrospective case series have been published demonstrating the feasibility of resection in selected patients. Here we report our experience with pancreatic ... ...

Abstract	Isolated pancreatic metastases may occur in patients with many types of cancer. Several retrospective case series have been published demonstrating the feasibility of resection in selected patients. Here we report our experience with pancreatic metastasectomy in 70 patients and review the published literature. Our findings suggest that long-term survival is associated with resection in selected patients but these outcomes must be weighed against the significant morbidity that is associated with pancreatic resection.
MeSH term(s)	Carcinoma, Renal Cell/secondary ; Carcinoma, Renal Cell/surgery ; Humans ; Metastasectomy/methods ; Pancreatic Neoplasms/mortality ; Pancreatic Neoplasms/secondary ; Pancreatic Neoplasms/surgery
Language	English
Publishing date	2014-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	82063-5
ISSN	1096-9098 ; 0022-4790
ISSN (online)	1096-9098
ISSN	0022-4790
DOI	10.1002/jso.23460
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Article ; Online: Morbidity and Outcomes of Primary Tumor Management in Patients with Widely Metastatic Well-Differentiated Small Bowel Neuroendocrine Tumors.

Nigam, Aradhya / Li, Janet W Y / Fiasconaro, Megan / Lin, Sabrina / Capanu, Marinela / Kleiman, David A / Memeh, Kelvin / Raj, Nitya / Reidy-Lagunes, Diane L / Untch, Brian R

Annals of surgical oncology

2023 Volume 31, Issue 4, Page(s) 2337–2348

Abstract: Background: The benefit of primary tumor resection in distant metastatic small bowel neuroendocrine tumors (SBNETs) is controversial, with treatment-based morbidity not well-defined. We aimed to determine the impact of primary tumor resection on ... ...

Abstract	Background: The benefit of primary tumor resection in distant metastatic small bowel neuroendocrine tumors (SBNETs) is controversial, with treatment-based morbidity not well-defined. We aimed to determine the impact of primary tumor resection on development of disease-specific complications in patients with metastatic well-differentiated SBNETs. Patients and methods: A retrospective analysis was performed of patients diagnosed with metastatic well-differentiated jejunal/ileal SBNETs at a single tertiary care cancer center from 1980 to 2016. Outcomes were compared on the basis of treatment selected at diagnosis between patients who underwent initial medical treatment or primary tumor resection. Results: Among 180 patients, 71 underwent medical management and 109 primary tumor resection. Median follow-up was 116 months. Median event-free survival did not differ between treatment approaches (log-rank p = 0.2). In patients medically managed first, 16/71 (23%) required surgery due to obstruction, perforation, or bleeding. These same complications led to resection at presentation in 31/109 (28%) surgically treated patients. Development of an obstruction from the primary tumor was not associated with disease progression/recurrence (HR 1.14, 95% CI 0.75-1.75) with all patients recovering postoperatively. Ongoing tumor progression requiring secondary laparotomy was associated with worse mortality (HR 7.51, 95% CI 3.3-16.9; p < 0.001) and occurred in 20/109 (18%) primary tumor resection and 7/16 (44%) initially medically treated patients. Conclusions: Rates of event-free survival among patients with metastatic SBNETs do not differ on the basis of primary tumor management. The development of an obstruction from the primary tumor was not associated with worse outcomes with all patients salvaged. Regardless of initial treatment selected, patients with metastatic SBNET should be closely followed for early signs of primary tumor complications.
MeSH term(s)	Humans ; Retrospective Studies ; Neuroendocrine Tumors/surgery ; Intestinal Neoplasms/surgery ; Pancreatic Neoplasms ; Stomach Neoplasms
Language	English
Publishing date	2023-11-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	1200469-8
ISSN	1534-4681 ; 1068-9265
ISSN (online)	1534-4681
ISSN	1068-9265
DOI	10.1245/s10434-023-14637-3
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Article ; Online: RAS

Sfreddo, Hannah J / Koh, Elizabeth S / Zhao, Karena / Swartzwelder, Christina E / Untch, Brian R / Marti, Jennifer L / Roman, Benjamin R / Dublin, Jared / Wang, Ronald S / Xia, Rong / Cohen, Jean-Marc / Xu, Bin / Ghossein, Ronald / Givi, Babak / Boyle, Jay O / Tuttle, R Michael / Fagin, James A / Wong, Richard J / Morris, Luc G T

Thyroid : official journal of the American Thyroid Association

2024 Volume 34, Issue 4, Page(s) 450–459

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	Humans ; Thyroid Nodule/diagnostic imaging ; Thyroid Nodule/genetics ; Thyroid Nodule/surgery ; Thyroid Neoplasms/diagnostic imaging ; Thyroid Neoplasms/epidemiology ; Thyroid Neoplasms/genetics ; Retrospective Studies ; Prevalence ; Watchful Waiting
Language	English
Publishing date	2024-03-28
Publishing country	United States
Document type	Multicenter Study ; Journal Article
ZDB-ID	1086044-7
ISSN	1557-9077 ; 1050-7256
ISSN (online)	1557-9077
ISSN	1050-7256
DOI	10.1089/thy.2023.0544
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Zs.A 3307: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Expert Consensus Practice Recommendations of the North American Neuroendocrine Tumor Society for the management of high grade gastroenteropancreatic and gynecologic neuroendocrine neoplasms.

Eads, Jennifer R / Halfdanarson, Thorvardur R / Asmis, Tim / Bellizzi, Andrew M / Bergsland, Emily K / Dasari, Arvind / El-Haddad, Ghassan / Frumovitz, Michael / Meyer, Joshua / Mittra, Erik / Myrehaug, Sten / Nakakura, Eric / Raj, Nitya / Soares, Heloisa P / Untch, Brian / Vijayvergia, Namrata / Chan, Jennifer A

Endocrine-related cancer

2023 Volume 30, Issue 8

Abstract: High-grade neuroendocrine neoplasms are a rare disease entity and account for approximately 10% of all neuroendocrine neoplasms. Because of their rarity, there is an overall lack of prospectively collected data available to advise practitioners as to how ...

Abstract	High-grade neuroendocrine neoplasms are a rare disease entity and account for approximately 10% of all neuroendocrine neoplasms. Because of their rarity, there is an overall lack of prospectively collected data available to advise practitioners as to how best to manage these patients. As a result, best practices are largely based on expert opinion. Recently, a distinction was made between well-differentiated high-grade (G3) neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas, and with this, pathologic details, appropriate imaging practices and treatment have become more complex. In an effort to provide practitioners with the best guidance for the management of patients with high-grade neuroendocrine neoplasms of the gastrointestinal tract, pancreas, and gynecologic system, the North American Neuroendocrine Tumor Society convened a panel of experts to develop a set of recommendations and a treatment algorithm that may be used by practitioners for the care of these patients. Here, we provide consensus recommendations from the panel on pathology, imaging practices, management of localized disease, management of metastatic disease and surveillance and draw key distinctions as to the approach that should be utilized in patients with well-differentiated G3 neuroendocrine tumors vs poorly differentiated neuroendocrine carcinomas.
MeSH term(s)	Humans ; Female ; Neuroendocrine Tumors/diagnosis ; Neuroendocrine Tumors/therapy ; Neuroendocrine Tumors/pathology ; Consensus ; Neoplasm Grading ; Carcinoma, Neuroendocrine/diagnosis ; Carcinoma, Neuroendocrine/therapy ; Carcinoma, Neuroendocrine/pathology ; North America ; Pancreatic Neoplasms/diagnosis ; Pancreatic Neoplasms/therapy ; Pancreatic Neoplasms/pathology
Language	English
Publishing date	2023-07-11
Publishing country	England
Document type	Journal Article
ZDB-ID	1218450-0
ISSN	1479-6821 ; 1351-0088
ISSN (online)	1479-6821
ISSN	1351-0088
DOI	10.1530/ERC-22-0206
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Article ; Online: Primary Mesenchymal Tumors of the Thyroid Gland: A Modern Retrospective Cohort Including the First Case of TFE3-Translocated Malignant Perivascular Epithelioid Cell Tumor (PEComa).

Zhang, Lingxin / Lubin, Daniel / Sinard, John H / Dickson, Brendan C / Antonescu, Cristina R / Wu, Hao / Panni, Roheena Z / Dogan, Snjezana / Untch, Brian R / Ghossein, Ronald A / Xu, Bin

Head and neck pathology

2022 Volume 16, Issue 3, Page(s) 716–727

Abstract: Primary mesenchymal tumors of the thyroid gland are extremely rare, with only case reports and small case series documented in the English literature, many of which were published prior to the era of molecular pathology. In the current study, we aim to ... ...

Abstract	Primary mesenchymal tumors of the thyroid gland are extremely rare, with only case reports and small case series documented in the English literature, many of which were published prior to the era of molecular pathology. In the current study, we aim to present a contemporary multi-centric cohort of thyroid mesenchymal tumors. Nineteen primary thyroid mesenchymal tumors were collected from three tertiary centers. Their clinicopathologic features, immunoprofile, molecular alterations, and outcome were described. Eight cases were classified as benign or intermediate with solitary fibrous tumor being the most common histotype (n = 3). The remaining 11 cases were malignant, including three angiosarcomas, one epithelioid hemangioendothelioma, one adamantinoma-like Ewing sarcoma, one biphasic synovial sarcoma, one malignant melanocytic peripheral nerve sheath tumor (melanotic schwannoma), one myxofibrosarcoma, and two undifferentiated pleomorphic/spindle sarcomas (one of which was radiation-induced). Six tumors showed characteristic diagnostic translocations. We herein also described the first case of thyroid malignant perivascular epithelioid cell tumor (PEComa) with RBM10-TFE3 fusion in a 35-year-old female patient. Thyroid mesenchymal tumors, benign or malignant, are rare with a broad spectrum of possible diagnoses. A comprehensive examination to include histology, immunohistochemistry, and molecular testing is essential for the correct diagnosis and to distinguish them from anaplastic thyroid carcinoma. PEComa may occur as a primary tumor of the thyroid gland, expanding the histologic spectrum of thyroid mesenchymal tumors.
MeSH term(s)	Adult ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; Biomarkers, Tumor ; Child ; Female ; Humans ; Neuroendocrine Tumors ; Perivascular Epithelioid Cell Neoplasms ; RNA-Binding Proteins ; Retrospective Studies ; Sarcoma ; Thyroid Neoplasms
Chemical Substances	Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; Biomarkers, Tumor ; RBM10 protein, human ; RNA-Binding Proteins ; TFE3 protein, human
Language	English
Publishing date	2022-02-26
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	2407834-7
ISSN	1936-0568 ; 1936-055X
ISSN (online)	1936-0568
ISSN	1936-055X
DOI	10.1007/s12105-022-01428-7
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Article ; Online: Tumor Grade Predicts for Calcitonin Doubling Times and Disease-Specific Outcomes After Resection of Medullary Thyroid Carcinoma.

Nigam, Aradhya / Xu, Bin / Spanheimer, Philip M / Ganly, Ian / Tuttle, R Michael / Wong, Richard J / Shaha, Ashok R / Ghossein, Ronald A / Untch, Brian R

Thyroid : official journal of the American Thyroid Association

2022 Volume 32, Issue 10, Page(s) 1193–1200

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	Humans ; Calcitonin ; Ki-67 Antigen ; Retrospective Studies ; Carcinoma, Neuroendocrine/surgery ; Carcinoma, Neuroendocrine/pathology ; Thyroid Neoplasms/pathology ; Prognosis ; Thyroid Hormones
Chemical Substances	Calcitonin (9007-12-9) ; Ki-67 Antigen ; Thyroid Hormones
Language	English
Publishing date	2022-09-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1086044-7
ISSN	1557-9077 ; 1050-7256
ISSN (online)	1557-9077
ISSN	1050-7256
DOI	10.1089/thy.2022.0217
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Article ; Online: Prophylactic Lateral Neck Dissection for Medullary Thyroid Carcinoma is not Associated with Improved Survival.

Spanheimer, Philip M / Ganly, Ian / Chou, Joanne F / Capanu, Marinela / Nigam, Aradhya / Ghossein, Ronald A / Tuttle, R Michael / Wong, Richard J / Shaha, Ashok R / Brennan, Murray F / Untch, Brian R

Annals of surgical oncology

2021 Volume 28, Issue 11, Page(s) 6572–6579

Abstract: Background: Patients with medullary thyroid carcinoma (MTC) often receive lateral lymph node dissection with total thyroidectomy when calcitonin levels are elevated, even in the absence of structural disease, but the effect of this intervention on ... ...

Abstract	Background: Patients with medullary thyroid carcinoma (MTC) often receive lateral lymph node dissection with total thyroidectomy when calcitonin levels are elevated, even in the absence of structural disease, but the effect of this intervention on disease-specific outcomes is not known. Patients and methods: We retrospectively reviewed patients from 1986 to 2017 who underwent thyroidectomy with curative intent for MTC at our institution. The association of disease-specific survival and clinicopathologic features was examined using univariate and multivariate Cox regression. Results: We identified 316 patients who underwent curative resection for MTC. Overall and disease-specific survival were 76% and 86%, respectively, at 10 years. To investigate the effect of prophylactic ipsilateral lateral lymph node dissection, we analyzed 89 patients without known structural disease in the neck lymph nodes at the time of resection and preoperative calcitonin > 200 pg/ml, of whom 45 had an ipsilateral lateral lymph node dissection (LND) and 44 did not. There were no differences in tumor size or preoperative calcitonin levels. There was no difference at 10 years in cumulative incidence of recurrence in the neck (20.9% LND vs. 30.4% no LND, p = 0.46), cumulative incidence of distant recurrence (18.3% vs. 18.4%, p = 0.97), disease-specific survival (86% vs. 93%, p = 0.53), or overall survival (82% vs. 90%, p = 0.6). Conclusion: Lateral neck dissection in the absence of clinical or radiologic abnormal lymph nodes is not associated with improved survival in patients with MTC.
MeSH term(s)	Humans ; Lymphatic Metastasis ; Neck Dissection ; Neoplasm Recurrence, Local/surgery ; Retrospective Studies ; Thyroid Neoplasms/surgery ; Thyroidectomy
Language	English
Publishing date	2021-03-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	1200469-8
ISSN	1534-4681 ; 1068-9265
ISSN (online)	1534-4681
ISSN	1068-9265
DOI	10.1245/s10434-021-09683-8
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