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Journal articles on the topic 'Breslow intermediate'

Author: Grafiati

Published: 9 August 2021

Last updated: 22 June 2022

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1

Maji, Biplab, and Herbert Mayr. "Struktur und Reaktivität O-methylierter Breslow-Intermediate." Angewandte Chemie 124, no. 41 (September 11, 2012): 10554–58. http://dx.doi.org/10.1002/ange.201204524.

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2

Bhunia, Anup, Shridhar Thorat, Rajesh G. Gonnade, and Akkattu T. Biju. "Reaction of N-heterocyclic carbenes with chalcones leading to the synthesis of deoxy-Breslow intermediates in their oxidized form." Chemical Communications 51, no. 71 (2015): 13690–93. http://dx.doi.org/10.1039/c5cc05800g.

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Presented herein is the reaction of N-heterocyclic carbenes (NHCs) with chalcones resulting in the isolation of the deoxy-Breslow intermediate in the oxidized form. In addition, the tetrahedral intermediate formed by the initial 1,4-addition of NHC to chalcones has also been isolated.

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3

Rehbein, Julia, Stephanie-M. Ruser, and Jenny Phan. "NHC-catalysed benzoin condensation – is it all down to the Breslow intermediate?" Chemical Science 6, no. 10 (2015): 6013–18. http://dx.doi.org/10.1039/c5sc02186c.

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The NHC-catalysed benzoin condensation has been studied mechanistically by a combination of experimental and computational chemistry. The presented EPR-spectroscopic and computational data provide evidence for a radical pair as a potential second key-intermediate that is derived from the Breslow-intermediate via an SET process.

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4

Pareek, Monika, Yernaidu Reddi, and Raghavan B. Sunoj. "Tale of the Breslow intermediate, a central player in N-heterocyclic carbene organocatalysis: then and now." Chemical Science 12, no. 23 (2021): 7973–92. http://dx.doi.org/10.1039/d1sc01910d.

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Molecular insights on the formation, detection, and even isolation of the Breslow intermediate, which is the most important species in N-heterocyclic carbene (NHC) catalysis, as obtained from experimental and computational studies, are presented.

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5

DiRocco, Daniel A., Kevin M. Oberg, and Tomislav Rovis. "Isolable Analogues of the Breslow Intermediate Derived from Chiral Triazolylidene Carbenes." Journal of the American Chemical Society 134, no. 14 (March 28, 2012): 6143–45. http://dx.doi.org/10.1021/ja302031v.

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6

Nandi, Ashim, Zayed Alassad, Anat Milo, and Sebastian Kozuch. "Quantum Tunneling on Carbene Organocatalysis: Breslow Intermediate Formation via Water-Bridges." ACS Catalysis 11, no. 24 (November 29, 2021): 14836–41. http://dx.doi.org/10.1021/acscatal.1c04475.

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7

Bai, Yaguang, Wei Lin Leng, Yongxin Li, and Xue-Wei Liu. "A highly efficient dual catalysis approach for C-glycosylation: addition of (o-azaaryl)carboxaldehyde to glycals." Chem. Commun. 50, no. 87 (2014): 13391–93. http://dx.doi.org/10.1039/c4cc06111j.

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Dual catalysis by concurrent activation of glycals and (O-azaaryl)-carboxaldehydes using palladium and N-heterocyclic carbene has been developed. This activation through the formation of the Breslow intermediate and a π-allyl Pd complex is a novel and efficient approach to yield C-glycosides with yields up to 85%.

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8

Sawama, Yoshinari, Yuya Miki, and Hironao Sajiki. "N-Heterocyclic Carbene Catalyzed Deuteration of Aldehydes in D2O." Synlett 31, no. 07 (March 3, 2020): 699–702. http://dx.doi.org/10.1055/s-0040-1707993.

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An N-heterocyclic carbene (NHC)-catalyzed direct deuteration of aldehydes in a mixed solvent of deuterium oxide (D2O) and cyclopentyl methyl ether was established. The present deuteration is possibly initiated by the formation of a Breslow intermediate from the aldehyde and the NHC, with subsequent trapping by D2O providing the monodeuterated aldehyde.

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9

Paul, Mathias, Panyapon Sudkaow, Alina Wessels, Nils E. Schlörer, Jörg‐M Neudörfl, and Albrecht Berkessel. "Breslow‐Intermediate aromatischer N‐heterocyclischer Carbene (Benzimidazolin‐2‐ylidene, Thiazolin‐2‐ylidene)." Angewandte Chemie 130, no. 27 (July 2, 2018): 8443–48. http://dx.doi.org/10.1002/ange.201801676.

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10

Wong, Sandra L., Mark B. Faries, Erin B. Kennedy, Sanjiv S. Agarwala, Timothy J. Akhurst, Charlotte Ariyan, Charles M. Balch, et al. "Sentinel Lymph Node Biopsy and Management of Regional Lymph Nodes in Melanoma: American Society of Clinical Oncology and Society of Surgical Oncology Clinical Practice Guideline Update." Journal of Clinical Oncology 36, no. 4 (February 1, 2018): 399–413. http://dx.doi.org/10.1200/jco.2017.75.7724.

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Purpose To update the American Society of Clinical Oncology (ASCO)-Society of Surgical Oncology (SSO) guideline for sentinel lymph node (SLN) biopsy in melanoma. Methods An ASCO-SSO panel was formed, and a systematic review of the literature was conducted regarding SLN biopsy and completion lymph node dissection (CLND) after a positive sentinel node in patients with melanoma. Results Nine new observational studies, two systematic reviews, and an updated randomized controlled trial of SLN biopsy, as well as two randomized controlled trials of CLND after positive SLN biopsy, were included. Recommendations Routine SLN biopsy is not recommended for patients with thin melanomas that are T1a (nonulcerated lesions < 0.8 mm in Breslow thickness). SLN biopsy may be considered for thin melanomas that are T1b (0.8 to 1.0 mm Breslow thickness or < 0.8 mm Breslow thickness with ulceration) after a thorough discussion with the patient of the potential benefits and risk of harms associated with the procedure. SLN biopsy is recommended for patients with intermediate-thickness melanomas (T2 or T3; Breslow thickness of > 1.0 to 4.0 mm). SLN biopsy may be recommended for patients with thick melanomas (T4; > 4.0 mm in Breslow thickness), after a discussion of the potential benefits and risks of harm. In the case of a positive SLN biopsy, CLND or careful observation are options for patients with low-risk micrometastatic disease, with due consideration of clinicopathological factors. For higher-risk patients, careful observation may be considered only after a thorough discussion with patients about the potential risks and benefits of foregoing CLND. Important qualifying statements outlining relevant clinicopathological factors and details of the reference patient populations are included within the guideline. Additional information is available at www.asco.org/melanoma-guidelines and www.asco.org/guidelineswiki .

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11

Wu, Nathan, and Ronald Kluger. "Rates of competing fluoride elimination and iodination from a thiamin-derived Breslow intermediate." Bioorganic Chemistry 120 (March 2022): 105579. http://dx.doi.org/10.1016/j.bioorg.2021.105579.

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12

Berkessel, Albrecht, Veera Reddy Yatham, Silvia Elfert, and Jörg-M. Neudörfl. "Charakterisierung der Schlüsselintermediate von carbenkatalysierten Umpolungen durch Kristallstrukturanalyse/NMR-Spektroskopie: Breslow-Intermediate, Homoenolate und Azoliumenolate." Angewandte Chemie 125, no. 42 (August 28, 2013): 11364–69. http://dx.doi.org/10.1002/ange.201303107.

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13

Alwarsh, Sefat, Kolawole Ayinuola, Silvana S. Dormi, and Matthias C. McIntosh. "Intercepting the Breslow Intermediate via Claisen Rearrangement: Synthesis of Complex Tertiary Alcohols without Organometallic Reagents." Organic Letters 15, no. 1 (December 5, 2012): 3–5. http://dx.doi.org/10.1021/ol303053c.

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14

Deng, Rui, Shuquan Wu, Chengli Mou, Jianjian Liu, Pengcheng Zheng, Xinglong Zhang, and Yonggui Robin Chi. "Carbene-Catalyzed Enantioselective Sulfonylation of Enone Aryl Aldehydes: A New Mode of Breslow Intermediate Oxidation." Journal of the American Chemical Society 144, no. 12 (March 11, 2022): 5441–49. http://dx.doi.org/10.1021/jacs.1c13384.

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15

Buonomo, O., A. Felici, AV Granai, R. Piccirillo, N. De Liguori Carino, F. Guadagni, S. Mariotti, et al. "Sentinel Lymphadenectomy in Cutaneous Melanoma." Tumori Journal 88, no. 3 (May 2002): S49—S51. http://dx.doi.org/10.1177/030089160208800343.

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Aims and Background In the last ten years validation of the sentinel lymph node (SLN) concept has led to modification of the surgical approach for patients with intermediate-risk cutaneous melanoma. Methods and Study Design Forty-eight patients affected by cutaneous melanoma with a Breslow thickness between 0.65 and 4 mm were enrolled in the study. Approximately 2 mCi of radiotracer and 1 mL of vital blue dye were injected in each patient around the site of the primary lesion. Lymphoscintigraphy was performed until the lymphatic basin and the respective SLN were localized. The whole surgical procedure consisted of enlargement of the surgical margins followed by localization and excision of the SLN(s) by using both radiotracer and vital dye. Whenever the SLN proved to be histologically positive for metastasis, complete regional lymphadenectomy was performed. Results Within 15 minutes of radiotracer administration the lymphatic basin was localized in all 48 patients by lymphoscintigraphy. Vital dye and radiotracer successfully allowed SLN localization and excision in 46 of 48 patients (97%); in one case the SLN was detected by radiotracer alone. The SLN proved to be metastatic in six (13%) of 46 evaluable patients; interestingly, in three of them the presence of metastatic cells was revealed only by immunohistochemistry. All patients with tumor-positive SLNs had primary lesions with a Breslow thickness = 2 mm. Conclusions Sentinel lymphadenectomy is able to identify lymph node involvement in patients with cutaneous melanoma with a Breslow thickness >1 mm, thus avoiding the risks associated with radical regional lymphadenectomy. Lymphoscintigraphy proved to be an important tool to obtain correct preoperative localization of the drainage basin, especially for melanomas located on the face and trunk.

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16

Lee, Jonathan H., Richard Essner, Hitoe Torisu-Itakura, Leslie Wanek, Hejing Wang, and Donald L. Morton. "Factors Predictive of Tumor-Positive Nonsentinel Lymph Nodes After Tumor-Positive Sentinel Lymph Node Dissection for Melanoma." Journal of Clinical Oncology 22, no. 18 (September 15, 2004): 3677–84. http://dx.doi.org/10.1200/jco.2004.01.012.

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Purpose Approximately 20% of sentinel node (SN) positive melanoma patients have additional non-SN (NSN) metastasis. The rationale for this study was to identify the factors associated with additional nodal disease, as a method to determine which patients may most benefit from completion lymph node dissection (CLND). Patients and Methods During 1990 to 2002, 1,599 patients have undergone SN biopsy at our institute. 19.5% underwent CLND for tumor-positive SN. One hundred ninety-one of these patients had clinicopathologic information available for review. Univariate analyses used χ2 test, Wilcoxson rank sum test, and χ2 test for trend. Multivariate analyses used logistic regression and Wald test. Results Forty-six (24%) patients had tumor-positive NSN. Univariate analyses showed that primary thickness (Breslow and Clark), primary site, SN tumor size, and number of tumor-positive SNs were significantly associated with tumor-positive NSN. Multivariate analysis (167 patients), confirmed that Breslow and SN tumor size were independently predictive. Sex, histology, ulceration, mitotic index, and SN basin location were not predictive. Risk stratification by the number of prognostic factors present (Breslow ≥ 3 mm and SN tumor size ≥ 2 mm) showed that probability of finding tumor-positive NSN was 12.3% in the low-risk group (0 factors), 30.9% in the intermediate-risk group (1 factor), and 41.9% in the high-risk group (2 factors). Conclusion Thicker primary and larger SN tumor size are factors that correlate best with tumor-positive NSN. Although none of these factors are absolutely predictive of residual nodal disease, these factors must be strongly considered if the SN contains metastasis, as they provide enhanced risk assessment for NSN tumor-positivity.

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17

Delany, Eoghan G., Claire-Louise Fagan, Sivaji Gundala, Kirsten Zeitler, and Stephen J. Connon. "Aerobic oxidation of NHC-catalysed aldehyde esterifications with alcohols: benzoin, not the Breslow intermediate, undergoes oxidation." Chemical Communications 49, no. 58 (2013): 6513. http://dx.doi.org/10.1039/c3cc42597e.

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18

Paul, Mathias, Panyapon Sudkaow, Alina Wessels, Nils E. Schlörer, Jörg‐M Neudörfl, and Albrecht Berkessel. "Rücktitelbild: Breslow‐Intermediate aromatischer N‐heterocyclischer Carbene (Benzimidazolin‐2‐ylidene, Thiazolin‐2‐ylidene) (Angew. Chem. 27/2018)." Angewandte Chemie 130, no. 27 (July 2, 2018): 8464. http://dx.doi.org/10.1002/ange.201805100.

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19

Alwarsh, Sefat, Kolawole Ayinuola, Silvana S. Dormi, and Matthias C. McIntosh. "ChemInform Abstract: Intercepting the Breslow Intermediate via Claisen Rearrangement: Synthesis of Complex Tertiary Alcohols Without Organometallic Reagents." ChemInform 44, no. 21 (May 2, 2013): no. http://dx.doi.org/10.1002/chin.201321147.

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20

B. S., Anju, Rameswar Bhattacharjee, Shourya Gupta, Soniya Ahammad, Ayan Datta, and Subrata Kundu. "Deoxygenation of nitrosoarene by N-heterocyclic carbene (NHC): an elusive Breslow-type intermediate bridging carbene and nitrene." Chemical Communications 56, no. 81 (2020): 12166–69. http://dx.doi.org/10.1039/d0cc05192f.

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21

Wong, Sandra L., Charles M. Balch, Patricia Hurley, Sanjiv S. Agarwala, Timothy J. Akhurst, Alistair Cochran, Janice N. Cormier, et al. "Sentinel Lymph Node Biopsy for Melanoma: American Society of Clinical Oncology and Society of Surgical Oncology Joint Clinical Practice Guideline." Journal of Clinical Oncology 30, no. 23 (August 10, 2012): 2912–18. http://dx.doi.org/10.1200/jco.2011.40.3519.

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Purpose The American Society of Clinical Oncology (ASCO) and Society of Surgical Oncology (SSO) sought to provide an evidence-based guideline on the use of lymphatic mapping and sentinel lymph node (SLN) biopsy in staging patients with newly diagnosed melanoma. Methods A comprehensive systematic review of the literature published from January 1990 through August 2011 was completed using MEDLINE and EMBASE. Abstracts from ASCO and SSO annual meetings were included in the evidence review. An Expert Panel was convened to review the evidence and develop guideline recommendations. Results Seventy-three studies met full eligibility criteria. The evidence review demonstrated that SLN biopsy is an acceptable method for lymph node staging of most patients with newly diagnosed melanoma. Recommendations SLN biopsy is recommended for patients with intermediate-thickness melanomas (Breslow thickness, 1 to 4 mm) of any anatomic site; use of SLN biopsy in this population provides accurate staging. Although there are few studies focusing on patients with thick melanomas (T4; Breslow thickness, > 4 mm), SLN biopsy may be recommended for staging purposes and to facilitate regional disease control. There is insufficient evidence to support routine SLN biopsy for patients with thin melanomas (T1; Breslow thickness, < 1 mm), although it may be considered in selected patients with high-risk features when staging benefits outweigh risks of the procedure. Completion lymph node dissection (CLND) is recommended for all patients with a positive SLN biopsy and achieves good regional disease control. Whether CLND after a positive SLN biopsy improves survival is the subject of the ongoing Multicenter Selective Lymphadenectomy Trial II. Copyright © 2012 American Society of Clinical Oncology and Society of Surgical Oncology. All rights reserved. No part of this document may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without written permission by the American Society of Clinical Oncology and Society of Surgical Oncology.

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22

Berkessel, Albrecht, and Silvia Elfert. "On the Involvement of a Spiroepoxide Intermediate in N-Heterocyclic Carbene (NHC)-Catalyzed Benzoin Condensations - An Approach by Oxygenation of Deoxy-Breslow Intermediates." Advanced Synthesis & Catalysis 356, no. 2-3 (February 2, 2014): 571–78. http://dx.doi.org/10.1002/adsc.201300801.

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23

Bortolini, Olga, Cinzia Chiappe, Marco Fogagnolo, Alessandro Massi, and Christian Silvio Pomelli. "Formation, Oxidation, and Fate of the Breslow Intermediate in the N-Heterocyclic Carbene-Catalyzed Aerobic Oxidation of Aldehydes." Journal of Organic Chemistry 82, no. 1 (December 22, 2016): 302–12. http://dx.doi.org/10.1021/acs.joc.6b02414.

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24

Bielecki, Michael, and Ronald Kluger. "The Need for an Alternative to Radicals as the Cause of Fragmentation of a Thiamin-Derived Breslow Intermediate." Angewandte Chemie International Edition 56, no. 22 (April 28, 2017): 6321–23. http://dx.doi.org/10.1002/anie.201702240.

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Bielecki, Michael, and Ronald Kluger. "The Need for an Alternative to Radicals as the Cause of Fragmentation of a Thiamin-Derived Breslow Intermediate." Angewandte Chemie 129, no. 22 (April 28, 2017): 6418–20. http://dx.doi.org/10.1002/ange.201702240.

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26

Delany, Eoghan G., Claire-Louise Fagan, Sivaji Gundala, Kirsten Zeitler, and Stephen J. Connon. "ChemInform Abstract: Aerobic Oxidation of NHC-Catalyzed Aldehyde Esterifications with Alcohols: Benzoin, Not the Breslow Intermediate, Undergoes Oxidation." ChemInform 44, no. 44 (October 14, 2013): no. http://dx.doi.org/10.1002/chin.201344083.

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27

Sijan, Goran, Jefta Kozarski, Nenad Stepic, Sasa Milojevic, Dara Stefanovic, Zeljka Tatomirovic, Ljiljana Jaukovic, Svetlana Vesanovic, and Milica Rajovic. "Validity of ultrasound-guided aspiration needle biopsy in the diagnosis of micrometastases in sentinel lymph nodes in patients with cutaneous melanoma." Vojnosanitetski pregled 73, no. 10 (2016): 934–40. http://dx.doi.org/10.2298/vsp150227042s.

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Background/Aim. Cutaneous melanoma is one of the most aggressive solid cancers, that develops local, regional and distant metastases. The presence of metastases in lymph nodes is in correlation with Breslow tumor thickness. According to various researches, in melanoma with more than 4 mm Breslow thickness, lymph node micrometastases can be found in 60-70% of cases. Sentinel lymph nodes biopsy is a diagnostic procedure for lymph node micrometastasis detection, which is necessary for disease staging. In recent studies, ultrasound-guided fine needle aspiration with cytology (US FNAC) of the sentinel lymph node was used as less invasive procedure, but is not accepted as the standard procedure. The goal of this work was to define sensitivity, specification and precision of the ultrasound-guided fine needle aspiration method in comparison with standard sentinel lymph node biopsy. Methods. After obtaining the Ethics Committee?s permission, from 2012 to 2014 a total of 60 patients with cutaneous melanoma were enrolled, and divided into three groups: group I with thin melanoma, group II with intermediate thickness melanoma and group III with thick melanoma. The presence of micrometastases in sentinel regional lymph nodes was analyzed by US FNAC. The results obtained were compared to sentinel lymph nodes biopsy (SLNB) results. The golden standard for calculating the specific, sensitive and precise characteristics of the method of US FNAC of sentinel lymph nodes was histopathologic lymph node examination of sentinel lymph nodes acquired through biopsy. Results. Detection rate of US FNAC was 0% in the group I, 5% in the group II and 30% in the group III. SLNB detection rates were: 10% in the group I, 15% in the group II, and 45% in the group III. In melanoma thicker than 4 mm, 15% of the patients were false negative by US FNAC. The sensitivity of US FNAC for all the patients was 50%: in the group I, 0%; in the group II, 33.3%; and in the group III, 66.6%. The method specificity for all examined patients was 100% and accuracy 88%: group I, 90%; group II, 90%; group III, 85%. The FNAC and SLNB micrometastasis detection rate was significantly higher in melanoma with Breslow thickness > 4 mm (group 3) in comparison to thin and intermediate thickness tumors. Conclusion. The method of ultrasound-guided fine needle aspiration of sentinel lymph nodes, according to its sensitivity, has a place in the diagnostics of micrometastasis in regional lymph nodes only in thick melanoma, but not in thin and intermediary thickness melanoma. The results must be confirmed in a larger number of patients. If this observation could be confirmed, it would rationalize treatment of patients with thick melanoma, decrease the number of operations and shorten the time to make the diagnosis.

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28

Eldh, Jan, Mart Suurkula, and Hans Holmström. "Prognosis for Localized Cutaneous Melanoma Treated with Wide Excision Only, with Special Reference to Development of Regional Node Metastases." Tumori Journal 73, no. 1 (February 1987): 51–54. http://dx.doi.org/10.1177/030089168707300110.

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A consecutive series of 564 patients with localized (Stage I) melanoma treated by wide excision only were followed for at least 5 years. The median tumor thickness was 1.50 mm, and 30 % were ulcerated. The female/male ratio was 54/46. The overall survival rates were 80 % at 5 years and 73 % at 10 years. The survival rates were statistically significantly better for females, even when tumor thickness and ulceration were taken into consideration. Twenty percent developed regional node metastases after an average remission period of 13 months. The actuarial survival rates after node dissection were 32 % at 5 years and 27 % at 10 years. A subgroup with an exceptionally poor prognosis and a high rate of regional node dissemination was looked for. Only 26 % of the intermediate thickness group (1.50–3.99 mm, Breslow) developed nodal metastasis, whereas patients with thick lesions (> 4 mm) had a metastasis rate of 43 %. Patients with thick lesions may therefore benefit more from elective node dissection than patients with lesions of intermediate thickness. Patient characteristics, e.g., sex and tumor characteristics (ulceration), may prove to be of importance in a prospective trial on elective node dissection.

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29

Juhl, Martin, Myungjo Kim, Hee-Yoon Lee, Mu-Hyun Baik, and Ji-Woong Lee. "Aldehyde Carboxylation: A Concise DFT Mechanistic Study and a Hypothetical Role of CO2 in the Origin of Life." Synlett 30, no. 09 (March 19, 2019): 987–96. http://dx.doi.org/10.1055/s-0037-1611738.

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Carbon dioxide is arguably one of the most stable carbon-based molecules, yet enzymatic carbon fixation processes enabled the sustainable life cycle on Earth. Chemical reactions involving CO2-functionalization often suffer from low efficiency with highly reactive substrates. We recently reported mild carboxylation of aldehydes to furnish α-keto acids – a building block for chiral α-amino acids via reductive amination. Here, we discuss potential reaction mechanisms of aldehyde carboxylation reactions based on two promoters: NHCs and KCN in the carboxylation reaction. New DFT mechanistic studies suggested a lower reaction barrier for a CO2-functionalization step, implying a potential role of CO2 in prebiotic evolution of organic molecules in the primordial soup.1 Introduction: Aldehydes, Benzoins, Carboxylic Acids2 CO2-Activation: NHC, Cyanide, Lewis Acid and Water3 A Breslow Intermediate: Benzoin Reaction vs. Carboxylation with CO2 4 Carboxylation in the Primordial Soup5 Conclusion

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30

Roumen, R. M. H., M. S. Schuurman, M. J. Aarts, A. J. G. Maaskant-Braat, G. Vreugdenhil, and W. J. Louwman. "Survival of sentinel node biopsy versus observation in intermediate-thickness melanoma: A Dutch population-based study." PLOS ONE 16, no. 5 (May 25, 2021): e0252021. http://dx.doi.org/10.1371/journal.pone.0252021.

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Background The Multicenter Selective Lymphadenectomy Trial (MSLT-1) comparing survival after a sentinel lymph node biopsy (SLNB) versus nodal observation in melanoma patients did not show a significant benefit favoring SLNB. However, in subgroup analyses melanoma-specific survival among patients with nodal metastases seemed better. Aim To evaluate the association of performing a SLNB with overall survival in intermediate thickness melanoma patients in a Dutch population-based daily clinical setting. Methods Survival, excess mortality adjusted for age, gender, Breslow-thickness, ulceration, histological subtype, location, co-morbidity and socioeconomic status were calculated in a population of 1,989 patients diagnosed with malignant cutaneous melanoma (1.2–3.5 mm) on the trunk or limb between 2000–2016 in ten hospitals in the South East area, The Netherlands. Results A SLNB was performed in 51% of the patients (n = 1008). Ten-year overall survival after SLNB was 75% (95%CI, 71%-78%) compared to 61% (95%CI 57%-64%) following observation. After adjustment for risk factors, a lower risk on death (HR = 0.80, 95%CI 0.66–0.96) was found after SLNB compared to observation only. Conclusions SLNB in patients with intermediate-thickness melanoma on trunk or limb resulted in a 14% absolute and significant 10-year survival difference compared to those without SLNB.

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31

Olusanya, Abimbola O., Dhruvil R. Shah, Anthony D. Yang, Emanual Maverakis, Robert J. Canter, and Steve R. Martinez. "Prevalence of sentinel lymph node evaluation in patients with thick primary cutaneous melanoma." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): e19013-e19013. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e19013.

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e19013 Background: Sentinel lymph node biopsy (SLNB) was developed for intermediate thickness melanoma. Its use for thick cutaneous melanoma is controversial. We aimed to report on clinical and pathologic factors associated with the overuse of SLNB for thick primary cutaneous melanoma. Methods: The Surveillance, Epidemiology, and End Results database was queried for patients who underwent surgery for thick primary cutaneous melanoma (known Breslow thickness > 4.00 mm) from 2004 to 2008. We excluded patients with mucosal melanoma, those without a biopsy-proven diagnosis, those diagnosed at autopsy, patients whose lymph node evaluation was unknown or other than SLNB “yes” or SLNB “no”. We used multivariate logistic regression models to predict use of SLNB. Covariates examined included: age sex, race/ethnicity, Breslow depth, tumor histology, tumor location, and ulceration status. Likelihood of undergoing sentinel lymph node biopsy was reported as odds ratios (OR) with 95% confidence intervals (CI); significance was set at p ≤ 0.05. Results: Among 1,981 patients with thick cutaneous melanoma, 1,158 (58.2%) received a SLNB. On multivariate analysis, patients with primary melanomas of the arm (OR 2.07, CI 1.56-2.75; p<0.001), leg (OR 2.40, CI 1.70-3.40; p<0.001) and trunk (OR 1.82, CI 1.38-2.40; p<0.001) had an increased likelihood of receiving a SLNB, as did those with desmoplastic histology (OR 1.47, CI 1.11-1.96; p=0.008). Conclusions: A significant number of patients with thick melanomas receive a SLNB, even though this procedure was not developed for this patient population. We have identified predictors associated with the use of SLNB. These include: arm, leg and trunk primary sites and desmoplastic histology. Further research to assess whether use of SLNB in this population is detrimental or beneficial is needed.

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32

Scheri, R. P., L. Wanek, R. Essner, and D. Morton. "Improved long-term survival in patients with intermediate thickness primary melanoma managed by sentinel node biopsy." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 8576. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.8576.

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8576 Background: Although improved disease-free survival (DFS) with sentinel node biopsy (SNB) for clinically localized melanoma was observed at the interim analysis from the first Multicenter Selective Lymphadenectomy Trial (MSLT-I) there was not yet an improvement in overall survival (OS). We hypothesize this was due to the few observed early deaths. To investigate this we simulated the MSLT-1 protocol using our institutional database. Methods: 3,800 patients undergoing wide excision with or without SNB were matched by primary stage/ulceration/site and patient demographics. Patients with positive sentinel nodes (SN) underwent immediate completion lymphadenectomy (CLND) whereas non-SNB patients managed by nodal observation underwent delayed CLND at nodal recurrence. Survival was determined by the Kaplan-Meier method. Significance was determined using log-rank and Cox regression analysis. Results: Among matched pairs of SNB and non-SNB patients with 1.2–3.5 mm primaries, projected 10-year OS was 76% with SNB versus 63% without SNB (p=0.0008). There was no corresponding statistically significant difference between all 2001 SNB patients and 1799 non-SNB patients, or within the thin primary and thicker primary groups. By multivariate analysis, only SN status (p<0.0001), Breslow thickness (p<0.0001) and ulceration (p=0.0001) were independently predictive of OS. Conclusions: Our long-term data suggest that performing SNB will improve OS in patients with intermediate thickness melanoma but not with thicker or thinner melanomas as compared to observation and delayed CLND. No significant financial relationships to disclose. [Table: see text]

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Shah, Dhruvil R., Anthony D. Yang, Emanual Maverakis, and Steve R. Martinez. "Sentinel lymph node evaluation among elderly melanoma patients: Missed opportunities?" Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): e19001-e19001. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e19001.

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e19001 Background: Elderly patients may not receive indicated therapies offered to younger patients. We hypothesized that elderly patients with intermediate thickness cutaneous melanoma would be less likely to receive a sentinel lymph node biopsy than their younger counterparts. Methods: The Surveillance, Epidemiology, and End Results database was queried for patients who underwent surgery for intermediate thickness cutaneous melanoma (Breslow thickness 0.75 to 4.00 mm) from 2004 to 2008. We excluded patients with mucosal melanoma, those without a biopsy-proven diagnosis, and those diagnosed at autopsy. Patients were categorized according to age by decade. We used multivariate logistic regression models to predict use of sentinel lymph node biopsy. Additional covariates other than age included sex, race/ethnicity, T stage, tumor histology, tumor location, ulceration, and LDH status. Likelihood of undergoing sentinel lymph node biopsy was reported as odds ratios (OR) with 95% confidence intervals (CI); significance was set at p ≤ 0.05. Results: Among 12,283 patients with intermediate thickness cutaneous melanoma, 12,206 had complete information regarding the use of sentinel lymph node biopsy. Of these, 6,642 (54.4%) underwent sentinel node biopsy. On multivariate analysis, patients in the two oldest age categories were less likely to receive sentinel node biopsies (age 70 to 79 years OR 0.65, CI 0.55-0.76 and age 80 years or more OR 0.29, CI 0.24-0.35). Additional factors associated with a decreased likelihood of receiving a sentinel node biopsy included head and neck primary tumor site (OR 0.57, CI 0.51-0.64), high (OR 0.45, CI 0.31-0.65) or unknown (OR 0.32, CI 0.28-0.36) serum LDH, Asian (OR 0.58, CI 0.36-0.94) or unknown (OR 0.51, CI 0.36-0.72) race, and lentigo histology (OR 0.79, CI 0.66-0.95). Conclusions: Elderly patients with intermediate thickness melanoma are less likely to receive sentinel node biopsy than their younger counterparts. The elderly may benefit from sentinel node biopsy, and efforts should be made to increase performance of this procedure in this population. Further research to assess reasons why the elderly are less likely to receive sentinel node biopsy are needed.

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de la Fouchardière, Arnaud, Felix Boivin, Heather C. Etchevers, and Nicolas Macagno. "Cutaneous Melanomas Arising during Childhood: An Overview of the Main Entities." Dermatopathology 8, no. 3 (August 1, 2021): 301–14. http://dx.doi.org/10.3390/dermatopathology8030036.

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Cutaneous melanomas are exceptional in children and represent a variety of clinical situations, each with a different prognosis. In congenital nevi, the risk of transformation is correlated with the size of the nevus. The most frequent type is lateral transformation, extremely rare before puberty, reminiscent of a superficial spreading melanoma (SSM) ex-nevus. Deep nodular transformation is much rarer, can occur before puberty, and must be distinguished from benign proliferative nodules. Superficial spreading melanoma can also arise within small nevi, which were not visible at birth, usually after puberty, and can reveal a cancer predisposition syndrome (CDKN2A or CDK4 germline mutations). Prognosis is correlated with classical histoprognostic features (mainly Breslow thickness). Spitz tumors are frequent in adolescents and encompass benign (Spitz nevus), intermediate (atypical Spitz tumor), and malignant forms (malignant Spitz tumor). The whole spectrum is characterized by specific morphology with spindled and epithelioid cells, genetic features, and an overall favorable outcome even if a regional lymph node is involved. Nevoid melanomas are rare and difficult to diagnose clinically and histologically. They can arise in late adolescence. Their prognosis is currently not very well ascertained. A small group of melanomas remains unclassified after histological and molecular assessment.

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Agarwala, Sanjiv S., Sandra J. Lee, Waiki Yip, Uma N. Rao, Ahmad A. Tarhini, Gary I. Cohen, Douglas S. Reintgen, et al. "Phase III Randomized Study of 4 Weeks of High-Dose Interferon-α-2b in Stage T2bNO, T3a-bNO, T4a-bNO, and T1-4N1a-2a (microscopic) Melanoma: A Trial of the Eastern Cooperative Oncology Group–American College of Radiology Imaging Network Cancer Research Group (E1697)." Journal of Clinical Oncology 35, no. 8 (March 10, 2017): 885–92. http://dx.doi.org/10.1200/jco.2016.70.2951.

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Purpose To test the efficacy of 4 weeks of intravenous (IV) induction with high-dose interferon (IFN) as part of the Eastern Cooperative Oncology Group regimen compared with observation (OBS) in patients with surgically resected intermediate-risk melanoma. Patients and Methods In this intergroup international trial, eligible patients had surgically resected cutaneous melanoma in the following categories: (1) T2bN0, (2) T3a-bN0, (3) T4a-bN0, and (4) T1-4N1a-2a (microscopic). Patients were randomly assigned to receive IFN α-2b at 20 MU/m2/d IV for 5 days (Monday to Friday) every week for 4 weeks (IFN) or OBS. Stratification factors were pathologic lymph node status, lymph node staging procedure, Breslow depth, ulceration of the primary lesion, and disease stage. The primary end point was relapse-free survival. Secondary end points included overall survival, toxicity, and quality of life. Results A total of 1,150 patients were randomly assigned. At a median follow-up of 7 years, the 5-year relapse-free survival rate was 0.70 (95% CI, 0.66 to 0.74) for OBS and 0.70, (95% CI, 0.66 to 0.74) for IFN ( P = .964). The 5-year overall survival rate was 0.83 (95% CI, 0.79 to 0.86) for OBS and 0.83 (95% CI, 0.80 to 0.86) for IFN ( P = .558). Treatment-related grade 3 and higher toxicity was 4.6% versus 57.9% for OBS and IFN, respectively ( P < .001). Quality of life was worse for the treated group. Conclusion Four weeks of IV induction as part of the Eastern Cooperative Oncology Group high-dose IFN regimen is not better than OBS alone for patients with intermediate-risk melanoma as defined in this trial.

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Meves, Alexander, Ekaterina Nikolova, Joel B. Heim, Edwin J. Squirewell, Mark A. Cappel, Mark R. Pittelkow, Clark C. Otley, et al. "Tumor Cell Adhesion As a Risk Factor for Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma." Journal of Clinical Oncology 33, no. 23 (August 10, 2015): 2509–15. http://dx.doi.org/10.1200/jco.2014.60.7002.

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Purpose Less than 20% of patients with melanoma who undergo sentinel lymph node (SLN) biopsy based on American Society of Clinical Oncology/Society of Surgical Oncology recommendations are SLN positive. We present a multi-institutional study to discover new molecular risk factors associated with SLN positivity in thin and intermediate-thickness melanoma. Patients and Methods Gene clusters with functional roles in melanoma metastasis were discovered by next-generation sequencing and validated by quantitative polymerase chain reaction using a discovery set of 73 benign nevi, 76 primary cutaneous melanoma, and 11 in-transit melanoma metastases. We then used polymerase chain reaction to quantify gene expression in a model development cohort of 360 consecutive thin and intermediate-thickness melanomas and a validation cohort of 146 melanomas. Outcome of interest was SLN biopsy metastasis within 90 days of melanoma diagnosis. Logic and logistic regression analyses were used to develop a model for the likelihood of SLN metastasis from molecular, clinical, and histologic variables. Results ITGB3, LAMB1, PLAT, and TP53 expression were associated with SLN metastasis. The predictive ability of a model that included these molecular variables in combination with clinicopathologic variables (patient age, Breslow depth, and tumor ulceration) was significantly greater than a model that only considered clinicopathologic variables and also performed well in the validation cohort (area under the curve, 0.93; 95% CI, 0.87 to 0.97; false-positive and false-negative rates of 22% and 0%, respectively, using a 10% cutoff for predicted SLN metastasis risk). Conclusion The addition of cell adhesion–linked gene expression variables to clinicopathologic variables improves the identification of patients with SLN metastases within 90 days of melanoma diagnosis.

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Ferlosio, Amedeo, Monia Di Prete, Piero Rossi, Elena Campione, and Augusto Orlandi. "Bednar Tumour Occurring after Malignant Melanoma Excision." Case Reports in Pathology 2018 (October 1, 2018): 1–5. http://dx.doi.org/10.1155/2018/7694272.

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We report the case of a seventy-four-year-old man with a slow-growing 2 cm mass on the back that arose near the surgical scar of previously excised melanoma, invasive to a Breslow depth of 3 mm. Preoperative clinical diagnosis was “in-transit” melanoma metastasis. After surgical excision, histopathologic examination revealed a dermal nodular proliferation of spindle cells arranged in storiform pattern, with mild pleomorphism, infiltrating around appendages and into the subcutaneous tissue. Immunohistochemical investigation documented diffuse positivity for CD34 and vimentin of spindle cells. Scattered dendritic cells, containing dark pigment in varying proportion and positive for S100, Melan-A and HMB-45, were also observed. A final diagnosis of Bednar tumour was formulated. Subsequently, the patient developed numerous metastases from the primary melanoma and died after 18 months. Bednar tumour is a rare pigmented variant of dermatofibrosarcoma protuberans of intermediate malignant potential. The presence of pigmented cells in Bednar tumour requires careful differential diagnosis with malignant or benign pigmented skin tumours. The clinical history of a Bednar tumour developing close to the scar of a previous melanoma gives the opportunity of a critical and intriguing discussion about the potential origin of pigmented cells in this rare variant of dermatofibrosarcoma protuberans.

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Bellomo, Domenico, Suzette M. Arias-Mejias, Chandru Ramana, Joel B. Heim, Enrica Quattrocchi, Sindhuja Sominidi-Damodaran, Alina G. Bridges, et al. "Model Combining Tumor Molecular and Clinicopathologic Risk Factors Predicts Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma." JCO Precision Oncology, no. 4 (September 2020): 319–34. http://dx.doi.org/10.1200/po.19.00206.

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PURPOSE More than 80% of patients who undergo sentinel lymph node (SLN) biopsy have no nodal metastasis. Here, we describe a model that combines clinicopathologic and molecular variables to identify patients with thin- and intermediate-thickness melanomas who may forgo the SLN biopsy procedure because of their low risk of nodal metastasis. PATIENTS AND METHODS Genes with functional roles in melanoma metastasis were discovered by analysis of next-generation sequencing data and case-control studies. We then used polymerase chain reaction to quantify gene expression in diagnostic biopsy tissue across a prospectively designed archival cohort of 754 consecutive thin- and intermediate-thickness primary cutaneous melanomas. Outcome of interest was SLN biopsy metastasis within 90 days of melanoma diagnosis. A penalized maximum likelihood estimation algorithm was used to train logistic regression models in a repeated cross-validation scheme to predict the presence of SLN metastasis from molecular, clinical, and histologic variables. RESULTS Expression of genes with roles in epithelial-to-mesenchymal transition (glia-derived nexin, growth differentiation factor 15, integrin-β3, interleukin 8, lysyl oxidase homolog 4, transforming growth factor-β receptor type 1, and tissue-type plasminogen activator) and melanosome function (melanoma antigen recognized by T cells 1) were associated with SLN metastasis. The predictive ability of a model that only considered clinicopathologic or gene expression variables was outperformed by a model that included molecular variables in combination with the clinicopathologic predictors Breslow thickness and patient age (area under the receiver operating characteristic curve, 0.82; 95% CI, 0.78 to 0.86; SLN biopsy reduction rate, 42%; negative predictive value, 96%). CONCLUSION A combined model that included clinicopathologic and gene expression variables improved the identification of patients with melanoma who may forgo the SLN biopsy procedure because of their low risk of nodal metastasis.

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Eriksson, Hanna, Kari Nielsen, Ismini Vassilaki, Jan Lapins, Rasmus Mikiver, Johan Lyth, and Karolin Isaksson. "Trend Shifts in Age-Specific Incidence for In Situ and Invasive Cutaneous Melanoma in Sweden." Cancers 13, no. 11 (June 7, 2021): 2838. http://dx.doi.org/10.3390/cancers13112838.

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Background: The incidence of invasive cutaneous melanoma (CM) is increasing in Sweden. The aim was to present age- and sex-specific trends of the age-standardised incidence and the average annual percentage change (AAPC) for in situ and invasive CM. Methods: Joinpoint regression models were used to analyse data from the Swedish Cancer Register and the Swedish Melanoma Registry 1997–2018 (N = 35,350 in situ CM; 59,932 CM). Results: The AAPC of CM for women was 4.5 (4.1–5.0; p < 0.001) for the period 1997–2018. For men, the APCC was 4.2 (3.0–5.4; p < 0.001), with a significantly higher annual percentage change (APC) for the period 2000–2018 (5.0; 4.6–5.4; p < 0.001) compared to 1997–1999. An increasing annual incidence of CM ≤ 0.6 mm and 0.7 mm Breslow tumour thickness was found for men with a significant incidence shift for the period 2006–2015, respectively. Similarly for women, with a significantly higher APC for CM ≤ 0.6 mm from 2005. The incidence of intermediate thick CM (2.1–4.0 mm) has not increased since 2011. The incidence of CM > 4.0 mm has been increasing among both sexes, with a significantly lower APC among women from 2005. Conclusions: The incidence of in situ and low-risk CM ≤ 1.0 mm in tumour thickness has been rising among both sexes since the 2000s.

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N, Oliveira, Kandathi LJ, and Tchernev G. "Borderline Intermediary Thickness Cutaneous Melanoma: Standard Approach and The New Possibilities for Removal in one Surgical Session." Journal of Clinical Research in Dermatology 8, no. 2 (June 1, 2021): 1–4. http://dx.doi.org/10.15226/2378-1726/8/2/001135.

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Here we present a case of a 48-year-old female with a melanocytic lesion on the lateral aspect of the right thigh [Figure 1a-1d]. The patient observed a steady growth of the lesion over the last few years and attended our clinic for a dermatological consultation in March 2021. She was otherwise healthy and she reported anamnestic data was unremarkable. On examination of the lateral femoral region of the right thigh, the presence of a single, nodular, hyperpigmented lesion of 1.5cm was noted. The dome shaped lesion was dark brown in colour, smooth and elevated on palpation, and well demarcated from surrounding healthy tissue. Based on the clinical and dermatoscopical findings, a nodular melanoma of intermediate thickness was suspected. Further laboratory workup was conducted and showed no significant deviations from normal paraclinical values. Screening was also negative for tumour spread. All other paraclinical data was unremarkable. Diagnostic work up including CT of the thorax and abdomen detected no metastatic dissemination. The standard two step approaches based on the current AJCC guidelines was employed. The primary excision was performed with 0.5 cm safety margins in all directions [Figure 1e-f]. The elliptical defect was subsequently closed by single interrupted sutures. Histopathological verification confirmed the diagnosis of a nodular malignant melanoma, pT2b N0M0, stage 1B, Clark IV, Breslow thickness of 2mm, without ulceration, with high mitotic activity, well defined lymphocytic stromal reaction and clean resection margins.

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LJ, Kandathil, Oliveira N, Patterson JW, and Tchernev G. "Borderline Intermediate Thickness Cutaneous Melanoma Class B: Isn’t it Time for Personalised One Step Surgical Approach as Standard Clinical Behaviour?" Journal of Clinical Research in Dermatology 8, no. 2 (2021): 1–5. http://dx.doi.org/10.15226/2378-1726/8/2/001137.

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We present a 40-year-old female who visited our clinic with a solitary lesion on the posterolateral aspect of the lower left leg (Figure 1a). She noticed a progressive change in the size and shape of the lesion and decided to consult a dermatologist in March 2021. The patient had a history of Hashimoto’s thyroiditis that was well-controlled onlevothyroxine. No other comorbidities were reported and she was otherwise healthy. During the clinical examination a single pigmented patch measuring 2.5 cm in greatest diameter was identified. Morphologically the lesion was asymmetrical with irregular borders and uneven colour. At the centre, an exudative, ulcerated nodule was also noted (Figure1a-f). Clinical and dermatoscopic findings were consistent with the diagnosis of a superficial spreading cutaneous melanoma. Ultrasound diagnostics of the abdominal cavity and retroperitoneal organs showed no signs of tumor spread. Chest radiography was also within normal limits. Laboratory testing showed an elevated uric acid level of 456 μmol/l (reference range 142 - 340 μmol/l), but otherwise all other parameters were normal. Following the recommended American Joint Committee on Cancer (AJCC) guidelines, we performed a primary resection with 0.5 cm margins in all directions. The resected tissue was subsequently sent for histopathological evaluation and confirmed the diagnosis of borderline intermediate thickness malignant melanoma - class B, 4 mm Breslow thickness, Clark IV, (pT4BN0M0) (Figure2a-d). There was high mitotic activity but no spontaneous regression, insignificant lymphocytic stromal reaction and clear resection margins. Post diagnostic workup, including chest and abdominal CT, showed no signs of metastatic dissemination. One week later, the patient was sent to the National Oncology Hospital for re-excision and Sentinel Lymph Node Biopsy (SLNB). The re-excision of additional 2cm from the previous surgical scar was conducted in parallel with removal of the draining sentinel lymph node (Figures 3a & 3d). The closure of the defect after re-excision led to the unfortunate complication of wound dehiscence and failure to close successfully (Figure 3b-c). However, after several sessions of debridement, cleansing, rebandaging and administration of antibiotics, there was visible improvement with subsequent resolution(Figure 3d-f). Since that time, she has been in excellent condition, and no complications have been reported to date.

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Wheatley, K., N. Ives, A. Eggermont, J. Kirkwood, N. Cascinelli, S. N. Markovic, B. Hancock, S. Lee, and S. Suciu. "Interferon-α as adjuvant therapy for melanoma: An individual patient data meta-analysis of randomised trials." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 8526. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.8526.

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8526 Background: Many randomised trials have evaluated the role of adjuvant interferon-a (IFN) in high-risk melanoma, some suggesting benefit and others not. To assess the totality of current evidence, an individual patient data (IPD) meta-analysis of all available trials was performed. Methods: Standard IPD meta-analysis methods were used to assess event-free (EFS) and overall survival (OS), with odds ratios (OR) and 95% confidence intervals (CI) calculated. Trials were divided by dose of IFN - high (20 MU/m2), intermediate (5–10 MU), low (3 MU) and very low (1 MU). Subgroup analyses by patient age, gender and disease characteristics were also performed. Results: IPD was provided for 10 of 13 reported trials of IFN vs. no IFN (for the other 3 trials published data were used). 6067 patients (IPD available for 85%) were included in the analysis, with over 3,700 and 3,000 events for EFS and OS. There was statistically significant benefit for IFN for both EFS (OR=0.87, CI=0.81–0.93, p=0.00006) and OS (0.9, 0.84–0.97, p=0.008). There was no evidence of differences according to dose (Table 1; trend p>0.1) or duration of IFN. This proportional survival advantage translates into an absolute benefit of about 3% (CI 1%-5%) at 5 years. The effect of IFN did not differ with age, gender, tumor site, Breslow thickness, clinical nodes or disease stage. Only for ulceration was there some evidence of an interaction (p=0.03); patients with ulcerated tumors had greater benefit from IFN (EFS: OR=0.76, OS: OR=0.77) than those with no ulceration (EFS: OR=0.94, OS: OR=0.98). Conclusions: This meta-analysis provides evidence that adjuvant IFN significantly reduces the risk of relapse and improves overall survival, although the absolute survival benefit is relatively small. This analysis does not however, clarify the optimal (high, intermediate or low) dose of IFN. Given the large number of subgroup analyses performed, the apparent increased benefit in patients with ulceration requires confirmation. No significant financial relationships to disclose.

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Berkessel, Albrecht, Silvia Elfert, Kerstin Etzenbach-Effers, and J. Henrique Teles. "Aldehyde Umpolung by N-Heterocyclic Carbenes: NMR Characterization of the Breslow Intermediate in its Keto Form, and a Spiro-Dioxolane as the Resting State of the Catalytic System." Angewandte Chemie International Edition 49, no. 39 (August 19, 2010): 7120–24. http://dx.doi.org/10.1002/anie.200907275.

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Moncrieff, Marc D., David Gyorki, Robyn Saw, Andrew J. Spillane, Howard Peach, Deemesh Oudit, Jenny Geh, et al. "1 Versus 2-cm Excision Margins for pT2-pT4 Primary Cutaneous Melanoma (MelMarT): A Feasibility Study." Annals of Surgical Oncology 25, no. 9 (May 30, 2018): 2541–49. http://dx.doi.org/10.1245/s10434-018-6470-1.

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Abstract Background There is a lack of consensus regarding optimal surgical excision margins for primary cutaneous melanoma > 1 mm in Breslow thickness (BT). A narrower surgical margin is expected to be associated with lower morbidity, improved quality of life (QoL), and reduced cost. We report the results of a pilot international study (MelMarT) comparing a 1 versus 2-cm surgical margin for patients with primary melanoma > 1 mm in BT. Methods This phase III, multicentre trial [NCT02385214] administered by the Australia & New Zealand Medical Trials Group (ANZMTG 03.12) randomised patients with a primary cutaneous melanoma > 1 mm in BT to a 1 versus 2-cm wide excision margin to be performed with sentinel lymph node biopsy. Surgical closure technique was at the discretion of the treating surgeon. Patients’ QoL was measured (FACT-M questionnaire) at baseline, 3, 6, and 12 months after randomisation. Results Between January 2015 and June 2016, 400 patients were randomised from 17 centres in 5 countries. A total of 377 patients were available for analysis. Primary melanomas were located on the trunk (56.9%), extremities (35.6%), and head and neck (7.4%). More patients in the 2-cm margin group required reconstruction (34.9 vs. 13.6%; p < 0.0001). There was an increased wound necrosis rate in the 2-cm arm (0.5 vs. 3.6%; p = 0.036). After 12 months’ follow-up, no differences were noted in QoL between groups. Discussion This pilot study demonstrates the feasibility of a large international RCT to provide a definitive answer to the optimal excision margin for patients with intermediate- to high-risk primary cutaneous melanoma.

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Alwarsh, Sefat, Yi Xu, Steven Y. Qian, and Matthias C. McIntosh. "Radical [1,3] Rearrangements of Breslow Intermediates." Angewandte Chemie 128, no. 1 (November 10, 2015): 363–66. http://dx.doi.org/10.1002/ange.201508368.

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Alwarsh, Sefat, Yi Xu, Steven Y. Qian, and Matthias C. McIntosh. "Radical [1,3] Rearrangements of Breslow Intermediates." Angewandte Chemie International Edition 55, no. 1 (November 10, 2015): 355–58. http://dx.doi.org/10.1002/anie.201508368.

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Paul, Mathias, Martin Breugst, Jörg-Martin Neudörfl, Raghavan B. Sunoj, and Albrecht Berkessel. "Keto–Enol Thermodynamics of Breslow Intermediates." Journal of the American Chemical Society 138, no. 15 (April 6, 2016): 5044–51. http://dx.doi.org/10.1021/jacs.5b13236.

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Castellano, Daniel E., Emilio Esteban, Luis Leon Mateos, Aranzazu Gonzalez del Alba, Maria Jose Mendez Vidal, Jose Angel Arranz Arija, Xavier Garcia del Muro, et al. "Prospective assessment of circulating endothelial cells (CECs) as pharmacodynamic marker in first line clear cell renal cell carcinoma (CCRCC): The CIRCLES study (SOGUG 2011-01)." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): e15586-e15586. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e15586.

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e15586 Background: Angiogenesis inhibitors have become a cornerstone in the management of CCRCC. Since CECs counts have been proposed as a surrogate biomarker of antiangiogenic activity they could potentially be used to assess the efficacy of such drugs. Methods: An observational prospective multicenter study was designed. Patients with confirmed CCRCC on first line treatment (any drug) who have not progressed after 3 months on therapy were considered eligible. CECs (CD146+, CD 105+,CD 45- DAPI + cells assessed by the Cell Search system), were determined every 6 weeks for 15 months or radiological tumor progression. External monitoring of clinical data was performed. Results: 75 patients (29% female, 71% male) were included between June 2011 and January 2013 from 11 Spanish institutions. Median age was 62 years (range 37-81). Distribution of patients according to MSKCC risk cathegories was: good 32%, intermediate 66% and poor 1.5%. 90% of patients have received sunitinib, 6% pazopanib, 1% temsirolimus, and was not available in 3%. With a median follow-up of 7 months (range 0-11.8) 13 patients have progressed and median progression free survival (PFS) has not been reached. At baseline median CECs count was 47 cells/4 ml (range 4-485). A trend towards worse PFS has been identified in patients with basal CEC levels below the median (p= 0.063 Breslow test). When baseline CEC counts were compared to counts at tumor progression no significant difference was found. Patient and/or tumor characteristics (sex, MSKCC prognostic cathegory, number of metastatic sites, and prior response to therapy) did not seem to influence CECs levels at baseline. Conclusions: CEC counts remain estable in CCRCC patients treated with antiangiogenic inhibitors whohad not progressed to first line therapy. Low CEC counts seem to identify a population with shorter response to therapy. Thus, CEC could be a reliable pharmacodynamic marker able to assess the antiangiogenic activity of a drug. Long-term follow-up results will be presented.

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Maji, Biplab, and Herbert Mayr. "Structures and Reactivities of O-Methylated Breslow Intermediates." Angewandte Chemie International Edition 51, no. 41 (September 11, 2012): 10408–12. http://dx.doi.org/10.1002/anie.201204524.

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Hsieh, Ming-Hsiu, and Jen-Shiang K. Yu. "Fragmentation and rearrangement of Breslow intermediates: branches to both radical and ionic pathways." Physical Chemistry Chemical Physics 23, no. 48 (2021): 27377–84. http://dx.doi.org/10.1039/d1cp03118j.

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