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Article ; Online: Revisiting C.G. Moertel's land of small tumors.

Kvols, Larry K

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2008 Volume 26, Issue 31, Page(s) 5005–5007

MeSH term(s)	Angiogenesis Inhibitors/therapeutic use ; Antineoplastic Agents, Hormonal/therapeutic use ; Carcinoid Tumor/blood supply ; Carcinoid Tumor/secondary ; Carcinoid Tumor/therapy ; Chemoembolization, Therapeutic ; Clinical Trials as Topic ; Digestive System Surgical Procedures ; Hepatic Artery ; Humans ; Interferons/therapeutic use ; Liver Neoplasms/blood supply ; Liver Neoplasms/secondary ; Liver Neoplasms/therapy ; Malignant Carcinoid Syndrome/pathology ; Malignant Carcinoid Syndrome/therapy ; Radiopharmaceuticals/therapeutic use ; Somatostatin/analogs & derivatives ; Somatostatin/therapeutic use ; Treatment Outcome
Chemical Substances	Angiogenesis Inhibitors ; Antineoplastic Agents, Hormonal ; Radiopharmaceuticals ; Somatostatin (51110-01-1) ; Interferons (9008-11-1)
Language	English
Publishing date	2008-11-01
Publishing country	United States
Document type	Comment ; Editorial ; Review
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.2008.19.2161
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Article: Radiation sensitizers: a selective review of molecules targeting DNA and non-DNA targets.

Kvols, Larry K

Journal of nuclear medicine : official publication, Society of Nuclear Medicine

2005 Volume 46 Suppl 1, Page(s) 187S–90S

Abstract: The ideal radiation sensitizer would reach the tumor in adequate concentrations and act selectively in the tumor compared with normal tissue. It would have predictable pharmacokinetics for timing with radiation treatment and could be administered with ... ...

Abstract	The ideal radiation sensitizer would reach the tumor in adequate concentrations and act selectively in the tumor compared with normal tissue. It would have predictable pharmacokinetics for timing with radiation treatment and could be administered with every radiation treatment. The ideal radiation sensitizer would have minimal toxicity itself and minimal or manageable enhancement of radiation toxicity. The ideal radiation sensitizer does not exist today. This review outlines the concept of combining 2 modalities of cancer treatment, radiation and drug therapy, to provide enhanced tumor cell kill in the treatment of human malignancies and discusses molecules that target DNA and non-DNA targets. Combining drugs that have unique mechanisms of action and absence of overlapping toxicities with systemically administered radiotherapy should be exploited in future clinical trials. This is an exciting time in clinical oncology research, because we have a plethora of new molecules to evaluate.
MeSH term(s)	Animals ; Antineoplastic Agents/therapeutic use ; Combined Modality Therapy ; DNA, Neoplasm/drug effects ; Drug Delivery Systems/methods ; Humans ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/radiotherapy ; Radiation-Sensitizing Agents/administration & dosage
Chemical Substances	Antineoplastic Agents ; DNA, Neoplasm ; Radiation-Sensitizing Agents
Language	English
Publishing date	2005-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	80272-4
ISSN	1535-5667 ; 0161-5505 ; 0097-9058 ; 0022-3123
ISSN (online)	1535-5667
ISSN	0161-5505 ; 0097-9058 ; 0022-3123
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Article ; Online: Recent progress in the understanding, diagnosis, and treatment of gastroenteropancreatic neuroendocrine tumors.

Turaga, Kiran K / Kvols, Larry K

CA: a cancer journal for clinicians

2011 Volume 61, Issue 2, Page(s) 113–132

Abstract: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are relatively rare tumors that arise from the diffuse neuroendocrine system. This heterogeneous group of tumors was often considered a single entity. This belied their biological diversity, and the ...

Abstract	Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are relatively rare tumors that arise from the diffuse neuroendocrine system. This heterogeneous group of tumors was often considered a single entity. This belied their biological diversity, and the biggest advance in understanding these tumors over the past decades has been in understanding this diversity. Diagnosis of these tumors has been aided by advances in pathological diagnosis and classification and tumor imaging with endoscopic ultrasound and somatostatin receptor fusion imaging. Genetic and molecular advances have identified molecular targets in the treatment of these tumors. Surgery remains the mainstay of treatment, amply supported by interventional radiological techniques, including embolization. Treatment of metastatic disease has improved significantly with the addition of several new agents, including tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, and yttrium-90-DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) and lutetium-177-DOTA octreotate. Despite significant advances in the understanding and management of GEP-NETs, the survival of patients remains largely unchanged and there remains a need for the development of national and international research collaborations to spearhead future efforts.
MeSH term(s)	Biomarkers, Tumor/analysis ; Digestive System Neoplasms/diagnosis ; Digestive System Neoplasms/epidemiology ; Digestive System Neoplasms/genetics ; Digestive System Neoplasms/therapy ; Humans ; Neuroendocrine Tumors/diagnosis ; Neuroendocrine Tumors/epidemiology ; Neuroendocrine Tumors/genetics ; Neuroendocrine Tumors/therapy ; United States
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2011-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	603553-x
ISSN	1542-4863 ; 0007-9235
ISSN (online)	1542-4863
ISSN	0007-9235
DOI	10.3322/caac.20097
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Article ; Online: The North American Neuroendocrine Tumor Society (NANETS) guidelines: mission, goals, and process.

Kvols, Larry K / Brendtro, Kari L

Pancreas

2010 Volume 39, Issue 6, Page(s) 705–706

MeSH term(s)	Humans ; Neuroendocrine Tumors/classification ; Neuroendocrine Tumors/diagnosis ; Neuroendocrine Tumors/therapy ; North America ; Organizational Objectives ; Practice Guidelines as Topic ; Societies, Medical/organization & administration
Language	English
Publishing date	2010-06-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	632831-3
ISSN	1536-4828 ; 0885-3177
ISSN (online)	1536-4828
ISSN	0885-3177
DOI	10.1097/MPA.0b013e3181eb7451
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Article ; Online: Octreotide LAR in carcinoid: how to dose?

Yao, James C / Kvols, Larry K

Pancreas

2008 Volume 37, Issue 3, Page(s) 337–8; author reply 338–9

MeSH term(s)	Antineoplastic Agents, Hormonal/adverse effects ; Antineoplastic Agents, Hormonal/blood ; Antineoplastic Agents, Hormonal/therapeutic use ; Carcinoid Tumor/drug therapy ; Carcinoid Tumor/metabolism ; Dose-Response Relationship, Drug ; Drug Monitoring ; Humans ; Neuroendocrine Tumors/drug therapy ; Neuroendocrine Tumors/metabolism ; Octreotide/adverse effects ; Octreotide/blood ; Octreotide/therapeutic use ; Receptors, Somatostatin/metabolism ; Research Design ; Treatment Outcome
Chemical Substances	Antineoplastic Agents, Hormonal ; Receptors, Somatostatin ; somatostatin receptor 2 (D73QL0OMU2) ; Octreotide (RWM8CCW8GP)
Language	English
Publishing date	2008-09-23
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	632831-3
ISSN	1536-4828 ; 0885-3177
ISSN (online)	1536-4828
ISSN	0885-3177
DOI	10.1097/MPA.0b013e31818adf4b
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Article ; Online: A review of the current clinical trials for gastroenteropancreatic neuroendocrine tumours.

Strosberg, Jonathan R / Kvols, Larry K

Expert opinion on investigational drugs

2007 Volume 16, Issue 2, Page(s) 219–224

Abstract: Neuroendocrine tumours of the gastroenteropancreatic axis include carcinoid tumours and islet cell tumours of the pancreas (pancreatic endocrine tumours). Standard medical therapies prescribed for these malignancies include long-acting somatostatin ... ...

Abstract	Neuroendocrine tumours of the gastroenteropancreatic axis include carcinoid tumours and islet cell tumours of the pancreas (pancreatic endocrine tumours). Standard medical therapies prescribed for these malignancies include long-acting somatostatin analogues (octreotide and lanreotide) for the palliation of hormonal syndromes; cytotoxic agents (streptozocin, dacarbazine, adriamycin and 5-fluorouracil), which are primarily for the management of advanced islet cell tumours; and hepatic artery embolisation or chemoembolisation for the treatment of liver metastases. Clinical research promises to expand this therapeutic armamentarium. Most of the experimental treatments that are being evaluated in human clinical trials fall into the following categories: angiogenesis inhibitors, novel somatostatin analogues, radiolabelled somatostatin analogues, mTOR inhibitors and novel cytotoxic agents. This review summarises the present scope of clinical research in this field.
MeSH term(s)	Antineoplastic Agents/therapeutic use ; Gastrointestinal Neoplasms/drug therapy ; Gastrointestinal Neoplasms/epidemiology ; Humans ; Neuroendocrine Tumors/drug therapy ; Neuroendocrine Tumors/epidemiology ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/epidemiology ; Randomized Controlled Trials as Topic/trends
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2007-01-06
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1182884-5
ISSN	1744-7658 ; 0967-8298 ; 1354-3784
ISSN (online)	1744-7658
ISSN	0967-8298 ; 1354-3784
DOI	10.1517/13543784.16.2.219
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Article ; Online: A review of systemic and liver-directed therapies for metastatic neuroendocrine tumors of the gastroenteropancreatic tract.

Strosberg, Jonathan R / Cheema, Asima / Kvols, Larry K

Cancer control : journal of the Moffitt Cancer Center

2011 Volume 18, Issue 2, Page(s) 127–137

Abstract: Background: Treatment options for metastatic gastroenteropancreatic neuroendocrine tumors (NETs) have evolved in recent years. The somatostatin analogs octreotide and lanreotide have long been used for management of symptoms such as flushing and ... ...

Abstract	Background: Treatment options for metastatic gastroenteropancreatic neuroendocrine tumors (NETs) have evolved in recent years. The somatostatin analogs octreotide and lanreotide have long been used for management of symptoms such as flushing and diarrhea associated with hormonally active NETs. New evidence demonstrates that these agents can also inhibit tumor growth. Other novel agents targeting the VEGF and mTOR pathways have recently been investigated in multicenter phase III studies. Methods: The authors review the recent literature on treatments for metastatic gastroenteropancreatic NETs and summarize new therapeutic developments. Results: Novel agents targeting somatostatin receptors and the VEGF and mTOR pathways are capable of significantly prolonging progression-free survival in certain NET subtypes. New temozolomide-based chemotherapy regimens have demonstrated considerable activity in pancreatic NETs. Liver-targeted therapies, including surgical resection, radiofrequency ablation, and hepatic artery embolization, are effective options for patients whose metastases are predominantly confined to the liver. Embolization of (90)Y-embedded spheres (radioembolization) represents a novel approach to managing liver metastases. Conclusions: Treatment options are expanding rapidly for patients with metastatic gastroenteropancreatic NETs, driven largely by randomized, collaborative clinical trials. Future clinical trials should compare the efficacy of emerging therapies and evaluate combination vs sequential approaches.
MeSH term(s)	Angiogenesis Inhibitors/therapeutic use ; Gastrointestinal Neoplasms/pathology ; Gastrointestinal Neoplasms/therapy ; Humans ; Interferon-alpha/therapeutic use ; Liver/drug effects ; Neoplasm Metastasis ; Neuroendocrine Tumors/pathology ; Neuroendocrine Tumors/therapy ; Pancreatic Neoplasms/pathology ; Pancreatic Neoplasms/therapy ; Somatostatin/analogs & derivatives
Chemical Substances	Angiogenesis Inhibitors ; Interferon-alpha ; Somatostatin (51110-01-1)
Language	English
Publishing date	2011-04
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1328503-8
ISSN	1526-2359 ; 1073-2748
ISSN (online)	1526-2359
ISSN	1073-2748
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Article: Role of somatostatin analogs in the clinical management of non-neuroendocrine solid tumors.

Kvols, Larry K / Woltering, Eugene A

Anti-cancer drugs

2006 Volume 17, Issue 6, Page(s) 601–608

Abstract: The somatostatin analogs octreotide, lanreotide and RC-160 (vapreotide) are known to have direct and indirect antitumor effects. Direct effects include the arrest of tumor growth and stimulation of apoptosis, resulting in tumor shrinkage. Indirect ... ...

Abstract	The somatostatin analogs octreotide, lanreotide and RC-160 (vapreotide) are known to have direct and indirect antitumor effects. Direct effects include the arrest of tumor growth and stimulation of apoptosis, resulting in tumor shrinkage. Indirect antiproliferative effects may occur through antiangiogenesis, immunomodulatory effects and the suppression of tumor-stimulating growth factors. With a safety profile of somatostatin analogs established over 20 years of clinical use in the treatment of neuroendocrine tumors, somatostatin analogs are attractive therapeutic options for patients with non-neuroendocrine tumors. In early clinical trials of somatostatin analogs, however, some cancer patients responded well, while others showed a lack of benefit. This variability in clinical response may reflect the selective binding affinities of octreotide, lanreotide and RC-160, which bind with high affinity to just two of the five different somatostatin receptor subtypes. Treatment response may therefore depend on the specific receptor subtype(s) present in the tumor, the relative proportion of receptor(s) expressed on the tumor cell surface and the absolute quantity of each receptor subtype. Greater understanding of the role of somatostatin receptors, their binding affinities and modes of action has led to increased research into the use of somatostatin analogs, particularly octreotide, in cancer treatment as monotherapies, in combination with hormonal treatments and cytotoxic therapies, and in both adjuvant and neoadjuvant settings. A review of the literature suggests that the antitumor potential of somatostatin analogs should be investigated further and additional studies might determine how these analogs can best be used to improve the treatment of patients with non-neuroendocrine tumors.
MeSH term(s)	Humans ; Neoplasms/diagnosis ; Neoplasms/drug therapy ; Receptors, Somatostatin/metabolism ; Somatostatin/analogs & derivatives ; Somatostatin/therapeutic use
Chemical Substances	Receptors, Somatostatin ; Somatostatin (51110-01-1)
Language	English
Publishing date	2006-07
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1065301-6
ISSN	1473-5741 ; 0959-4973
ISSN (online)	1473-5741
ISSN	0959-4973
DOI	10.1097/01.cad.0000210335.95828.ed
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Article ; Online: Prognostic validity of the American Joint Committee on Cancer staging classification for midgut neuroendocrine tumors.

Strosberg, Jonathan R / Weber, Jill M / Feldman, Max / Coppola, Domenico / Meredith, Kenneth / Kvols, Larry K

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2013 Volume 31, Issue 4, Page(s) 420–425

Abstract: Purpose: The American Joint Committee on Cancer (AJCC) staging manual has introduced a TNM staging classification for jejunal-ileal (midgut) neuroendocrine tumors (NETs). This classification has not been validated in a population consisting solely of ... ...

Abstract	Purpose: The American Joint Committee on Cancer (AJCC) staging manual has introduced a TNM staging classification for jejunal-ileal (midgut) neuroendocrine tumors (NETs). This classification has not been validated in a population consisting solely of midgut NETs. The purpose of this study was to test the prognostic validity of the classification in such a population. Methods: Patients with jejunal and ileocecal NETs who were treated at the Moffitt Cancer Center between 2000 and 2010 were assigned stages (I through IV). Kaplan-Meier analyses for overall survival (OS) were performed on the basis of TNM stage and pathologic grade. Multivariate modeling was performed using Cox proportional hazards regression. Results: We identified 691 patients with jejunal-ileocecal NETs. The AJCC classification in aggregate was highly prognostic for OS (P < .001). Five-year OS rates for stages I through IV were 100%, 100%, 91%, and 72%, respectively. The survival difference between stages III and IV was significant (P < .001); the difference between stages I/II versus III was not statistically significant (P = .1). Among patients with stage IIIB tumors, 5-year survival rates were 95% for resectable tumors versus 78% for unresectable mesenteric tumors (P = .02). A proliferative threshold of five mitoses per 10 high-power fields (HPF) was of greater prognostic value than a threshold of two mitoses per 10 HPF for discriminating between low- and intermediate-grade tumors. Conclusion: Stage I and II midgut NETs are associated with identical survival rates. Stage IIIB tumors are heterogeneous, with significant differences in survival observed between resectable mesenteric lymph nodes versus unresectable masses in the root of the mesentery. A higher mitotic cutoff of five per 10 HPF may lead to improved prognostic differentiation between low- and intermediate-grade tumors. Revisions to the current AJCC staging and grading classification may be warranted.
MeSH term(s)	Adult ; Advisory Committees ; Aged ; Aged, 80 and over ; Female ; Humans ; Intestinal Neoplasms/complications ; Intestinal Neoplasms/mortality ; Intestinal Neoplasms/pathology ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Staging ; Neuroendocrine Tumors/complications ; Neuroendocrine Tumors/mortality ; Neuroendocrine Tumors/pathology ; Prognosis ; Reproducibility of Results ; Risk Assessment ; United States/epidemiology
Language	English
Publishing date	2013-02-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.2012.44.5924
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Zs.A 1847: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Aggressive surgical resection in the management of pancreatic neuroendocrine tumors: when is it indicated?

Hodul, Pamela J / Strosberg, Jonathan R / Kvols, Larry K

Cancer control : journal of the Moffitt Cancer Center

2008 Volume 15, Issue 4, Page(s) 314–321

Abstract: Background: Pancreatic neuroendocrine tumors (PNETs) comprise a heterogeneous group of neoplasms for which treatment is variable, depending on the clinical stage. Despite this diversity, surgery remains the gold standard in the management of PNETs. This ...

Abstract	Background: Pancreatic neuroendocrine tumors (PNETs) comprise a heterogeneous group of neoplasms for which treatment is variable, depending on the clinical stage. Despite this diversity, surgery remains the gold standard in the management of PNETs. This paper discusses whether aggressive surgical intervention is indicated for PNETs and investigates what prognostic factors may assist in predicting which patients with invasive disease will benefit most from surgical intervention. Methods: A review was conducted of large surgical series reported in the English literature over the last 10 years as they pertain to current surgical intervention in PNETs and of prognostic factors related to surgical outcome and survival. Results: Improved survival can be achieved with aggressive surgical management of PNETs. The presence of hepatic metastases is not a contraindication to surgical resection of the primary PNET. Results of series that reported prognostic factors are heterogeneous. Conclusions: Aggressive surgical resection for selected individuals with PNETs can be performed safely and may improve both symptomatic disease and overall survival. Consideration for resection of primary PNETs should be given to patients with treatable hepatic metastases. Prognostic indices such as tumor differentiation and ability to achieve R0/R1 resection have been linked to survival outcome in PNETs and should be considered when planning aggressive surgical management for this disease.
MeSH term(s)	Decision Making ; Humans ; Neoadjuvant Therapy ; Neuroendocrine Tumors/mortality ; Neuroendocrine Tumors/pathology ; Neuroendocrine Tumors/surgery ; Pancreatic Neoplasms/mortality ; Pancreatic Neoplasms/pathology ; Pancreatic Neoplasms/surgery ; Prognosis
Language	English
Publishing date	2008-10
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1328503-8
ISSN	1526-2359 ; 1073-2748
ISSN (online)	1526-2359
ISSN	1073-2748
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