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Henning Dralle - One of the best experts on this subject based on the ideXlab platform.

  • Histology-proven recurrence in the lateral or central neck after systematic neck dissection for Medullary Thyroid Cancer
    Endocrine, 2018
    Co-Authors: Andreas Machens, Kerstin Lorenz, Henning Dralle
    Abstract:

    Purpose To delineate risk factors for, and examine temporal patterns of, histology-proven recurrent Medullary Thyroid Cancer (MTC) after compartment-oriented surgery.

  • surgical curability of Medullary Thyroid Cancer in multiple endocrine neoplasia 2b a changing perspective
    Annals of Surgery, 2014
    Co-Authors: Michael Brauckhoff, Andreas Machens, Kerstin Lorenz, Trine Bjoro, Jan Erik Varhaug, Henning Dralle
    Abstract:

    Objective:This investigation aimed at exploring the suitability of nonendocrine manifestations preceding Medullary Thyroid Cancer (MTC) for early diagnosis of multiple endocrine neoplasia type 2B (MEN 2B).Background:MEN 2B patients, running a high risk of metastatic MTC, must be diagnosed early for

  • benefit risk balance of reoperation for persistent Medullary Thyroid Cancer
    Annals of Surgery, 2013
    Co-Authors: Andreas Machens, Henning Dralle
    Abstract:

    Objective:This investigation aimed at exploring the prospects of a cure for persistent Medullary Thyroid Cancer (MTC) stratified by basal calcitonin levels before reoperation and the number of lymph node metastases previously removed at outside facilities.Background:There is no evidence-based inform

  • Parenchymal Versus Nonparenchymal Target Lesion Response in Clinical Trials for Metastatic Medullary Thyroid Cancer
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2010
    Co-Authors: Andreas Machens, Henning Dralle
    Abstract:

    TO THE EDITOR: In their clinical trial of systemic targeted therapy in metastatic Medullary Thyroid Cancer, Lam et al did not find an association between objective index target lesion response based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria and serum biomarker (calcitonin and carcinoembryonic antigen) response. Similar results have been reported for another clinical trial of systemic targeted therapy for metastastic Medullary Thyroid Cancer. Among the 21 Medullary Thyroid Cancer patients in the trial by Lam et al, 20 patients (95%) had undergone prior surgery, the nature and extent of which was not specified. Nonparenchymal metastases to lymph nodes were noted in 19 patients (90%), whereas parenchymal metastases to lung, liver, and bone were seen in seven (33%), 13 (62%), and 13 (62%) patients, respectively, among the 21 study participants. It remains unclear if any of the 19 patients with overt lymph node metastases underwent lymph node dissections and why no attempt was made to surgically remove those lymph node metastases from the neck that were sufficiently large to fulfill RECIST criteria. Conceivably, parenchymal target lesions are perfused better than nonparenchymal target lesions. As a matter of fact, pretherapeutic calcitonin and carcinoembryonic antigen serum levels correlate more closely with largest tumor diameter in the Thyroid parenchyma (r 0.83 to 0.84; explaining 69% to 71% of the variance in primary tumor size) than with lymph node metastases (r 0.47 to 0.59; explaining no more than 44% of the variance in the number of lymph node metastases). This observation raises the possibility of a differential target lesion response in parenchymal (lung, liver, or bone) compared with nonparenchymal (lymph nodes) organs in patients with Medullary Thyroid Cancer. Such a differential response was recently described for differentiated Thyroid Cancer where the most noticeable organ-specific response was observed in the lung (median change of 22%) compared with in lymph nodes (median change, 0%; P .02). If the assumption of a better tissue-specific response of parenchymal relative to nonparenchymal target lesions to systemic targeted therapy was also confirmed for metastatic Medullary Thyroid Cancer, this certainly would have major ramifications for the design and conduct of future clinical trials, prompting performance of compartment-oriented surgery to clear the neck of gross lymph node metastases followed by systemic targeted therapy for distant metastases, for which these therapies may be more effective. In experienced hands, the surgical morbidity attendant on compartment-oriented lymph node dissection compares favorably with the toxicity associated with systemic targeted therapy.

  • importance of gender specific calcitonin thresholds in screening for occult sporadic Medullary Thyroid Cancer
    Endocrine-related Cancer, 2009
    Co-Authors: Andreas Machens, Florian Hoffmann, Carsten Sekulla, Henning Dralle
    Abstract:

    Men and women differ in Thyroidal C-cell mass and calcitonin secretion. This difference may have implications for the definition of calcitonin thresholds to distinguish sporadic C-cell hyperplasia from occult Medullary Thyroid Cancer. This retrospective study examined the hypothesis that gender-specific calcitonin thresholds predict occult Medullary Thyroid Cancer more accurately among patients with increased basal calcitonin levels than unisex thresholds. A total of 100 consecutive patients were evaluated with occult sporadic C-cell disease no larger than 10 mm who were referred for increased basal calcitonin levels and underwent pentagastrin stimulation preoperatively at this institution. Altogether, gender-specific calcitonin thresholds predicted Medullary Thyroid Cancer better than unisex thresholds. At lower (Medullary Thyroid Cancer four to eight times more often than men. Most discriminatory between C-cell hyperplasia and Medullary Thyroid Cancer was a basal calcitonin threshold of 15 pg/ml (corrected 20 pg/ml) for women and 80 pg/ml (corrected 100 pg/ml) for men, based on the greatest accuracy at the lowest possible calcitonin level. The respective gender-specific stimulated peak calcitonin thresholds were 80 pg/ml (corrected 100 pg/ml) and 500 pg/ml. Corresponding positive predictive values for Medullary Thyroid Cancer at these calcitonin thresholds were 89 and 90% for women, as opposed to 100% for men. To increase the positive predictive value for women to 100%, the respective calcitonin thresholds would have to be raised to 40 pg/ml (corrected 50 pg/ml) and 250 pg/ml. These findings indicate that gender-specific calcitonin thresholds predict sporadic occult Medullary Thyroid Cancer better than unisex thresholds.

Andreas Machens - One of the best experts on this subject based on the ideXlab platform.

  • Histology-proven recurrence in the lateral or central neck after systematic neck dissection for Medullary Thyroid Cancer
    Endocrine, 2018
    Co-Authors: Andreas Machens, Kerstin Lorenz, Henning Dralle
    Abstract:

    Purpose To delineate risk factors for, and examine temporal patterns of, histology-proven recurrent Medullary Thyroid Cancer (MTC) after compartment-oriented surgery.

  • surgical curability of Medullary Thyroid Cancer in multiple endocrine neoplasia 2b a changing perspective
    Annals of Surgery, 2014
    Co-Authors: Michael Brauckhoff, Andreas Machens, Kerstin Lorenz, Trine Bjoro, Jan Erik Varhaug, Henning Dralle
    Abstract:

    Objective:This investigation aimed at exploring the suitability of nonendocrine manifestations preceding Medullary Thyroid Cancer (MTC) for early diagnosis of multiple endocrine neoplasia type 2B (MEN 2B).Background:MEN 2B patients, running a high risk of metastatic MTC, must be diagnosed early for

  • benefit risk balance of reoperation for persistent Medullary Thyroid Cancer
    Annals of Surgery, 2013
    Co-Authors: Andreas Machens, Henning Dralle
    Abstract:

    Objective:This investigation aimed at exploring the prospects of a cure for persistent Medullary Thyroid Cancer (MTC) stratified by basal calcitonin levels before reoperation and the number of lymph node metastases previously removed at outside facilities.Background:There is no evidence-based inform

  • Parenchymal Versus Nonparenchymal Target Lesion Response in Clinical Trials for Metastatic Medullary Thyroid Cancer
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2010
    Co-Authors: Andreas Machens, Henning Dralle
    Abstract:

    TO THE EDITOR: In their clinical trial of systemic targeted therapy in metastatic Medullary Thyroid Cancer, Lam et al did not find an association between objective index target lesion response based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria and serum biomarker (calcitonin and carcinoembryonic antigen) response. Similar results have been reported for another clinical trial of systemic targeted therapy for metastastic Medullary Thyroid Cancer. Among the 21 Medullary Thyroid Cancer patients in the trial by Lam et al, 20 patients (95%) had undergone prior surgery, the nature and extent of which was not specified. Nonparenchymal metastases to lymph nodes were noted in 19 patients (90%), whereas parenchymal metastases to lung, liver, and bone were seen in seven (33%), 13 (62%), and 13 (62%) patients, respectively, among the 21 study participants. It remains unclear if any of the 19 patients with overt lymph node metastases underwent lymph node dissections and why no attempt was made to surgically remove those lymph node metastases from the neck that were sufficiently large to fulfill RECIST criteria. Conceivably, parenchymal target lesions are perfused better than nonparenchymal target lesions. As a matter of fact, pretherapeutic calcitonin and carcinoembryonic antigen serum levels correlate more closely with largest tumor diameter in the Thyroid parenchyma (r 0.83 to 0.84; explaining 69% to 71% of the variance in primary tumor size) than with lymph node metastases (r 0.47 to 0.59; explaining no more than 44% of the variance in the number of lymph node metastases). This observation raises the possibility of a differential target lesion response in parenchymal (lung, liver, or bone) compared with nonparenchymal (lymph nodes) organs in patients with Medullary Thyroid Cancer. Such a differential response was recently described for differentiated Thyroid Cancer where the most noticeable organ-specific response was observed in the lung (median change of 22%) compared with in lymph nodes (median change, 0%; P .02). If the assumption of a better tissue-specific response of parenchymal relative to nonparenchymal target lesions to systemic targeted therapy was also confirmed for metastatic Medullary Thyroid Cancer, this certainly would have major ramifications for the design and conduct of future clinical trials, prompting performance of compartment-oriented surgery to clear the neck of gross lymph node metastases followed by systemic targeted therapy for distant metastases, for which these therapies may be more effective. In experienced hands, the surgical morbidity attendant on compartment-oriented lymph node dissection compares favorably with the toxicity associated with systemic targeted therapy.

  • importance of gender specific calcitonin thresholds in screening for occult sporadic Medullary Thyroid Cancer
    Endocrine-related Cancer, 2009
    Co-Authors: Andreas Machens, Florian Hoffmann, Carsten Sekulla, Henning Dralle
    Abstract:

    Men and women differ in Thyroidal C-cell mass and calcitonin secretion. This difference may have implications for the definition of calcitonin thresholds to distinguish sporadic C-cell hyperplasia from occult Medullary Thyroid Cancer. This retrospective study examined the hypothesis that gender-specific calcitonin thresholds predict occult Medullary Thyroid Cancer more accurately among patients with increased basal calcitonin levels than unisex thresholds. A total of 100 consecutive patients were evaluated with occult sporadic C-cell disease no larger than 10 mm who were referred for increased basal calcitonin levels and underwent pentagastrin stimulation preoperatively at this institution. Altogether, gender-specific calcitonin thresholds predicted Medullary Thyroid Cancer better than unisex thresholds. At lower (Medullary Thyroid Cancer four to eight times more often than men. Most discriminatory between C-cell hyperplasia and Medullary Thyroid Cancer was a basal calcitonin threshold of 15 pg/ml (corrected 20 pg/ml) for women and 80 pg/ml (corrected 100 pg/ml) for men, based on the greatest accuracy at the lowest possible calcitonin level. The respective gender-specific stimulated peak calcitonin thresholds were 80 pg/ml (corrected 100 pg/ml) and 500 pg/ml. Corresponding positive predictive values for Medullary Thyroid Cancer at these calcitonin thresholds were 89 and 90% for women, as opposed to 100% for men. To increase the positive predictive value for women to 100%, the respective calcitonin thresholds would have to be raised to 40 pg/ml (corrected 50 pg/ml) and 250 pg/ml. These findings indicate that gender-specific calcitonin thresholds predict sporadic occult Medullary Thyroid Cancer better than unisex thresholds.

Rebecca S. Sippel - One of the best experts on this subject based on the ideXlab platform.

  • trends in the presentation treatment and survival of patients with Medullary Thyroid Cancer over the past 30 years
    Surgery, 2017
    Co-Authors: Reese W Randle, Rebecca S. Sippel, Courtney J Balentine, Glen Leverson, Jeffrey A Havlena, David F Schneider, Susan C Pitt
    Abstract:

    Background The impact of recent medical advances on disease presentation, extent of operation, and disease-specific survival for patients with Medullary Thyroid Cancer is unclear. Methods We used the Surveillance, Epidemiology, and End Results registry to compare trends over 3 time periods, 1983–1992, 1993–2002, and 2003–2012. Results There were 2,940 patients diagnosed with Medullary Thyroid Cancer between 1983 and 2012. The incidence of Medullary Thyroid Cancer increased during this time period from 0.14 to 0.21 per 100,000 population, and mean age at diagnosis increased from 49.8 to 53.8 ( P P P  = .57). In addition, the proportion of patients undergoing a total Thyroidectomy and lymph node dissection increased from 58.2% to 76.5% during the study period ( P P P  = .003) and distant (40% to 51%, P  = .02) disease. Conclusion These data demonstrate that the extent of operation is increasing for patients with Medullary Thyroid Cancer. Disease-specific survival is also improving, primarily in patients with regional and distant disease.

  • Trends in the presentation, treatment, and survival of patients with Medullary Thyroid Cancer over the past 30 years
    Surgery, 2016
    Co-Authors: Reese W Randle, Rebecca S. Sippel, Courtney J Balentine, Glen Leverson, Jeffrey A Havlena, David F Schneider, Susan C Pitt
    Abstract:

    The impact of recent medical advances on disease presentation, extent of operation, and disease-specific survival for patients with Medullary Thyroid Cancer is unclear. We used the Surveillance, Epidemiology, and End Results registry to compare trends over 3 time periods, 1983-1992, 1993-2002, and 2003-2012. There were 2,940 patients diagnosed with Medullary Thyroid Cancer between 1983 and 2012. The incidence of Medullary Thyroid Cancer increased during this time period from 0.14 to 0.21 per 100,000 population, and mean age at diagnosis increased from 49.8 to 53.8 (P < .001). The proportion of tumors ≤1 cm also increased from 11.4% in 1983-1992, 19.6% in 1993-2002, to 25.1% in 2003-2012 (P < .001), but stage at diagnosis remained constant (P = .57). In addition, the proportion of patients undergoing a total Thyroidectomy and lymph node dissection increased from 58.2% to 76.5% during the study period (P < .001). In the most recent time interval, 5-year, disease-specific survival improved from 86% to 89% in all patients (P < .001) but especially for patients with regional (82% to 91%, P = .003) and distant (40% to 51%, P = .02) disease. These data demonstrate that the extent of operation is increasing for patients with Medullary Thyroid Cancer. Disease-specific survival is also improving, primarily in patients with regional and distant disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  • Current Understanding and Management of Medullary Thyroid Cancer
    The oncologist, 2013
    Co-Authors: Madhuchhanda Roy, Herbert Chen, Rebecca S. Sippel
    Abstract:

    Medullary Thyroid Cancer (MTC) typically accounts for 3%-4% of all Thyroid Cancers. Although the majority of MTCs are sporadic, 20% of cases are hereditary. Hereditary MTC can be found in multiple endocrine neoplasia 2A or 2B or as part of familial MTC based on a specific germline mutation in the RET proto-oncogene. This article discusses the current approaches available for the diagnosis, evaluation, and management of patients and their family members with suspected MTC. The disease is predominantly managed surgically and typically requires a total Thyroidectomy and lymph node dissection. A review of recent guidelines on the extent and timing of surgical excision is discussed. There are not very many effective systemic treatment options for MTC, but several emerging therapeutic targets have promise.

  • hereditary Medullary Thyroid Cancer age appropriate Thyroidectomy improves disease free survival
    Annals of Surgical Oncology, 2013
    Co-Authors: Kevin Shepet, Rebecca S. Sippel, Amal Alhefdhi, Ngan Lai, Haggi Mazeh, Herbert Chen
    Abstract:

    Background Twenty-five percent of Medullary Thyroid Cancer (MTC) cases are hereditary. The ideal age for prophylactic Thyroidectomy is based on the specific RET mutation involved. The purpose of this study was to determine whether such age-appropriate prophylactic Thyroidectomy results in improved disease-free survival.

  • Surgical management of Medullary Thyroid Cancer.
    Minerva endocrinologica, 2012
    Co-Authors: H Mazeh, Rebecca S. Sippel
    Abstract:

    Although Thyroid Cancer accounts for only 1.5% of all malignancies in the US it is the most rapidly increasing Cancer in incidence and it is the most common endocrine malignancy that accounts for over 95% of the endocrine malignancies. Medullary Thyroid Cancer (MTC) originates from the parafollicular C cells and it represents 6-8% of all Thyroid Cancer cases. As many as 25% of the MTCs are familial and carry a specific germline mutation as compared to only than 10% familial inheritance in non-Medullary Thyroid Cancers. While well-differentiated Thyroid malignancies carry a very good prognosis, recurrence and survival rates of patients with MTC are significantly worse. The difference in cell origin and differentiation also results in different available adjunct therapy. The aim of this study is to review in detail the surgical management of patients with MTC.

Susan C Pitt - One of the best experts on this subject based on the ideXlab platform.

  • trends in the presentation treatment and survival of patients with Medullary Thyroid Cancer over the past 30 years
    Surgery, 2017
    Co-Authors: Reese W Randle, Rebecca S. Sippel, Courtney J Balentine, Glen Leverson, Jeffrey A Havlena, David F Schneider, Susan C Pitt
    Abstract:

    Background The impact of recent medical advances on disease presentation, extent of operation, and disease-specific survival for patients with Medullary Thyroid Cancer is unclear. Methods We used the Surveillance, Epidemiology, and End Results registry to compare trends over 3 time periods, 1983–1992, 1993–2002, and 2003–2012. Results There were 2,940 patients diagnosed with Medullary Thyroid Cancer between 1983 and 2012. The incidence of Medullary Thyroid Cancer increased during this time period from 0.14 to 0.21 per 100,000 population, and mean age at diagnosis increased from 49.8 to 53.8 ( P P P  = .57). In addition, the proportion of patients undergoing a total Thyroidectomy and lymph node dissection increased from 58.2% to 76.5% during the study period ( P P P  = .003) and distant (40% to 51%, P  = .02) disease. Conclusion These data demonstrate that the extent of operation is increasing for patients with Medullary Thyroid Cancer. Disease-specific survival is also improving, primarily in patients with regional and distant disease.

  • Trends in the presentation, treatment, and survival of patients with Medullary Thyroid Cancer over the past 30 years
    Surgery, 2016
    Co-Authors: Reese W Randle, Rebecca S. Sippel, Courtney J Balentine, Glen Leverson, Jeffrey A Havlena, David F Schneider, Susan C Pitt
    Abstract:

    The impact of recent medical advances on disease presentation, extent of operation, and disease-specific survival for patients with Medullary Thyroid Cancer is unclear. We used the Surveillance, Epidemiology, and End Results registry to compare trends over 3 time periods, 1983-1992, 1993-2002, and 2003-2012. There were 2,940 patients diagnosed with Medullary Thyroid Cancer between 1983 and 2012. The incidence of Medullary Thyroid Cancer increased during this time period from 0.14 to 0.21 per 100,000 population, and mean age at diagnosis increased from 49.8 to 53.8 (P < .001). The proportion of tumors ≤1 cm also increased from 11.4% in 1983-1992, 19.6% in 1993-2002, to 25.1% in 2003-2012 (P < .001), but stage at diagnosis remained constant (P = .57). In addition, the proportion of patients undergoing a total Thyroidectomy and lymph node dissection increased from 58.2% to 76.5% during the study period (P < .001). In the most recent time interval, 5-year, disease-specific survival improved from 86% to 89% in all patients (P < .001) but especially for patients with regional (82% to 91%, P = .003) and distant (40% to 51%, P = .02) disease. These data demonstrate that the extent of operation is increasing for patients with Medullary Thyroid Cancer. Disease-specific survival is also improving, primarily in patients with regional and distant disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Martin Schlumberger - One of the best experts on this subject based on the ideXlab platform.

  • Chemotherapy and tyrosine-kinase inhibitors for Medullary Thyroid Cancer
    Best practice & research. Clinical endocrinology & metabolism, 2017
    Co-Authors: Julien Hadoux, Martin Schlumberger
    Abstract:

    Medullary Thyroid Cancer (MTC) represents 3% of all clinical Thyroid Cancers and arises from Thyroid C cells that produce calcitonin. Locally advanced or metastatic MTC requires a careful work-up including measurement of serum calcitonin and carcinoembryonic antigen, determination of their doubling time and comprehensive imaging to determine the extent of the disease, its aggressiveness, and the need for treatment. Cytotoxic chemotherapy can control tumor burden in some patients with response rates of around 20% in old series. For the last 10 years, systemic therapy for MTC patients with large tumor burden and documented progression of the disease has involved the use of tyrosine kinase inhibitors targeting VEGFR and ret. Progression-free survival benefits have been demonstrated for both vandetanib and cabozantinib, as compared to placebo. Although these molecules are effective, they also have specific toxicity profiles which require a thorough clinical management in specialized centers. In the present review, we describe the work-up and treatment modalities of patients with advanced or metastatic Medullary Thyroid Cancer with a focus on chemotherapy and targeted therapy results.

  • Management of advanced Medullary Thyroid Cancer
    The lancet. Diabetes & endocrinology, 2015
    Co-Authors: Julien Hadoux, Furio Pacini, R. Michael Tuttle, Martin Schlumberger
    Abstract:

    Medullary Thyroid Cancer arises from calcitonin-producing C-cells and accounts for 3-5% of all Thyroid Cancers. The discovery of a locally advanced Medullary Thyroid Cancer that is not amenable to surgery or of distant metastases needs careful work-up, including measurement of serum calcitonin and carcinoembryonic antigen (and their doubling times), in addition to comprehensive imaging to determine the extent of the disease, its aggressiveness, and the need for any treatment. In the past, cytotoxic chemotherapy was used for treatment but produced little benefit. For the past 10 years, tyrosine kinase inhibitors targeting vascular endothelial growth factor receptors and RET (rearranged during transfection) have been used when a systemic therapy is indicated for large tumour burden and documented disease progression. Vandetanib and cabozantinib have shown benefits on progression-free survival compared with placebo in this setting, but their toxic effect profiles need thorough clinical management in specialised centres. This Review describes the management and treatment of patients with advanced Medullary Thyroid Cancer with emphasis on current targeted therapies and perspectives to improve patient care. Most treatment responses are transient, emphasising that mechanisms of resistance need to be better understood and that the efficacy of treatment approaches should be improved with combination therapies or other drugs that might be more potent or target other pathways, including immunotherapy.

  • cabozantinib in progressive Medullary Thyroid Cancer
    Journal of Clinical Oncology, 2013
    Co-Authors: Rossella Elisei, Martin Schlumberger, Barbara Jarzab, S Muller, Patrick Schoffski, Marcia S Brose, Manisha H Shah, Lisa Licitra, Viktor Medvedev, Michael C Kreissl
    Abstract:

    Purpose Cabozantinib, a tyrosine kinase inhibitor (TKI) of hepatocyte growth factor receptor (MET), vascular endothelial growth factor receptor 2, and rearranged during transfection (RET), demonstrated clinical activity in patients with Medullary Thyroid Cancer (MTC) in phase I. Patients and Methods We conducted a double-blind, phase III trial comparing cabozantinib with placebo in 330 patients with documented radiographic progression of metastatic MTC. Patients were randomly assigned (2:1) to cabozantinib (140 mg per day) or placebo. The primary end point was progression-free survival (PFS). Additional outcome measures included tumor response rate, overall survival, and safety. Results The estimated median PFS was 11.2 months for cabozantinib versus 4.0 months for placebo (hazard ratio, 0.28; 95% CI, 0.19 to 0.40; P < .001). Prolonged PFS with cabozantinib was observed across all subgroups including by age, prior TKI treatment, and RET mutation status (hereditary or sporadic). Response rate was 28% for c...