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Melanoma: HELP
Articles by Robert H. I. Andtbacka
Based on 33 articles published since 2009
(Why 33 articles?)
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Between 2009 and 2019, Robert Andtbacka wrote the following 33 articles about Melanoma.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline NCCN Guidelines Insights: Melanoma, Version 3.2016. 2016

Coit, Daniel G / Thompson, John A / Algazi, Alain / Andtbacka, Robert / Bichakjian, Christopher K / Carson, William E / Daniels, Gregory A / DiMaio, Dominick / Fields, Ryan C / Fleming, Martin D / Gastman, Brian / Gonzalez, Rene / Guild, Valerie / Johnson, Douglas / Joseph, Richard W / Lange, Julie R / Martini, Mary C / Materin, Miguel A / Olszanski, Anthony J / Ott, Patrick / Gupta, Aparna Priyanath / Ross, Merrick I / Salama, April K / Skitzki, Joseph / Swetter, Susan M / Tanabe, Kenneth K / Torres-Roca, Javier F / Trisal, Vijay / Urist, Marshall M / McMillian, Nicole / Engh, Anita. ·From Memorial Sloan Kettering Cancer Center; Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance; UCSF Helen Diller Family Comprehensive Cancer Center; Huntsman Cancer Institute at the University of Utah; University of Michigan Comprehensive Cancer Center; The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute; UC San Diego Moores Cancer Center; Fred & Pamela Buffett Cancer Center; Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine; The University of Tennessee Health Science Center; Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute; University of Colorado Cancer Center; Aim at Melanoma; Vanderbilt-Ingram Cancer Center; Mayo Clinic Cancer Center; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Robert H. Lurie Comprehensive Cancer Center of Northwestern University; Yale Cancer Center/Smilow Cancer Hospital; Fox Chase Cancer Center; Dana-Farber/Brigham and Women's Cancer Center; The University of Texas MD Anderson Cancer Center; Duke Cancer Institute; Roswell Park Cancer Institute; Stanford Cancer Institute; Massachusetts General Hospital Cancer Center; Moffitt Cancer Center; City of Hope Comprehensive Cancer Center; University of Alabama at Birmingham Comprehensive Cancer Center; and National Comprehensive Cancer Network. ·J Natl Compr Canc Netw · Pubmed #27496110.

ABSTRACT: The NCCN Guidelines for Melanoma have been significantly revised over the past few years in response to emerging data on a number of novel agents and treatment regimens. These NCCN Guidelines Insights summarize the data and rationale supporting extensive changes to the recommendations for systemic therapy in patients with metastatic or unresectable melanoma.

2 Guideline Melanoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology. 2016

Coit, Daniel G / Thompson, John A / Algazi, Alain / Andtbacka, Robert / Bichakjian, Christopher K / Carson, William E / Daniels, Gregory A / DiMaio, Dominick / Ernstoff, Marc / Fields, Ryan C / Fleming, Martin D / Gonzalez, Rene / Guild, Valerie / Halpern, Allan C / Hodi, F Stephen / Joseph, Richard W / Lange, Julie R / Martini, Mary C / Materin, Miguel A / Olszanski, Anthony J / Ross, Merrick I / Salama, April K / Skitzki, Joseph / Sosman, Jeff / Swetter, Susan M / Tanabe, Kenneth K / Torres-Roca, Javier F / Trisal, Vijay / Urist, Marshall M / McMillian, Nicole / Engh, Anita. · ·J Natl Compr Canc Netw · Pubmed #27059193.

ABSTRACT: This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Melanoma focuses on adjuvant therapy and treatment of in-transit disease, because substantial changes were made to the recommendations for the 2016 update. Depending on the stage of the disease, options for adjuvant therapy now include biochemotherapy and high-dose ipilimumab. Treatment options for in-transit disease now include intralesional injection with talimogene laherparepvec (T-VEC), a new immunotherapy. These additions prompted re-assessment of the data supporting older recommended treatment options for adjuvant therapy and in-transit disease, resulting in extensive revisions to the supporting discussion sections.

3 Guideline Melanoma, version 4.2014. 2014

Coit, Daniel G / Thompson, John A / Andtbacka, Robert / Anker, Christopher J / Bichakjian, Christopher K / Carson, William E / Daniels, Gregory A / Daud, Adil / Dimaio, Dominick / Fleming, Martin D / Gonzalez, Rene / Guild, Valerie / Halpern, Allan C / Hodi, F Stephen / Kelley, Mark C / Khushalani, Nikhil I / Kudchadkar, Ragini R / Lange, Julie R / Martini, Mary C / Olszanski, Anthony J / Ross, Merrick I / Salama, April / Swetter, Susan M / Tanabe, Kenneth K / Trisal, Vijay / Urist, Marshall M / McMillian, Nicole R / Ho, Maria / Anonymous5170793. ·From 1Memorial Sloan-Kettering Cancer Center; 2Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance; 3Huntsman Cancer Institute at the University of Utah; 4University of Michigan Comprehensive Cancer Center; 5The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute; 6UC San Diego Moores Cancer Center; 7UCSF Helen Diller Family Comprehensive Cancer Center; 8Fred & Pamela Buffett Cancer Center at The Nebraska Medical Center; 9St. Jude Children's Research Hospital/The University of Tennessee Health Science Center; 10University of Colorado Cancer Center; 11Aim at Melanoma; 12Dana-Farber/Brigham and Women's Cancer Center; 13Vanderbilt-Ingram Cancer Center; 14Roswell Park Cancer Institute; 15Moffitt Cancer Center; 16The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; 17Robert H. Lurie Comprehensive Cancer Center of Northwestern University; 18Fox Chase Cancer Center; 19The University of Texas MD Anderson Cancer Center; 20Duke Cancer Institute; 21Stanford Cancer Institute; 22Massachusetts General Hospital Cancer Center; 23City of Hope Comprehensive Cancer Center; 24University of Alabama at Birmingham Comprehensive Cancer Center; and 25National Comprehensive Cancer Network. ·J Natl Compr Canc Netw · Pubmed #24812131.

ABSTRACT: The NCCN Guidelines for Melanoma provide multidisciplinary recommendations for the management of patients with melanoma. These NCCN Guidelines Insights highlight notable recent updates. Dabrafenib and trametinib, either as monotherapy (category 1) or combination therapy, have been added as systemic options for patients with unresectable metastatic melanoma harboring BRAF V600 mutations. Controversy continues regarding the value of adjuvant radiation for patients at high risk of nodal relapse. This is reflected in the category 2B designation to consider adjuvant radiation following lymphadenectomy for stage III melanoma with clinically positive nodes or recurrent disease.

4 Guideline Melanoma, version 2.2013: featured updates to the NCCN guidelines. 2013

Coit, Daniel G / Andtbacka, Robert / Anker, Christopher J / Bichakjian, Christopher K / Carson, William E / Daud, Adil / Dimaio, Dominick / Fleming, Martin D / Guild, Valerie / Halpern, Allan C / Hodi, F Stephen / Kelley, Mark C / Khushalani, Nikhil I / Kudchadkar, Ragini R / Lange, Julie R / Lind, Anne / Martini, Mary C / Olszanski, Anthony J / Pruitt, Scott K / Ross, Merrick I / Swetter, Susan M / Tanabe, Kenneth K / Thompson, John A / Trisal, Vijay / Urist, Marshall M / McMillian, Nicole / Ho, Maria / Anonymous4310755. ·Memorial Sloan-Kettering Cancer Center. ·J Natl Compr Canc Netw · Pubmed #23584343.

ABSTRACT: The NCCN Guidelines for Melanoma provide multidisciplinary recommendations on the clinical management of patients with melanoma. This NCCN Guidelines Insights report highlights notable recent updates. Foremost of these is the exciting addition of the novel agents ipilimumab and vemurafenib for treatment of advanced melanoma. The NCCN panel also included imatinib as a treatment for KIT-mutated tumors and pegylated interferon alfa-2b as an option for adjuvant therapy. Also important are revisions to the initial stratification of early-stage lesions based on the risk of sentinel lymph node metastases, and revised recommendations on the use of sentinel lymph node biopsy for low-risk groups. Finally, the NCCN panel reached clinical consensus on clarifying the role of imaging in the workup of patients with melanoma.

5 Guideline Melanoma. 2012

Coit, Daniel G / Andtbacka, Robert / Anker, Christopher J / Bichakjian, Christopher K / Carson, William E / Daud, Adil / Dilawari, Raza A / Dimaio, Dominick / Guild, Valerie / Halpern, Allan C / Hodi, F Stephen / Kelley, Mark C / Khushalani, Nikhil I / Kudchadkar, Ragini R / Lange, Julie R / Lind, Anne / Martini, Mary C / Olszanski, Anthony J / Pruitt, Scott K / Ross, Merrick I / Swetter, Susan M / Tanabe, Kenneth K / Thompson, John A / Trisal, Vijay / Urist, Marshall M / Anonymous590720. · ·J Natl Compr Canc Netw · Pubmed #22393197.

ABSTRACT: -- No abstract --

6 Guideline Melanoma. 2009

Coit, Daniel G / Andtbacka, Robert / Bichakjian, Christopher K / Dilawari, Raza A / Dimaio, Dominick / Guild, Valerie / Halpern, Allan C / Hodi, F Stephen / Kashani-Sabet, Mohammed / Lange, Julie R / Lind, Anne / Martin, Lainie / Martini, Mary C / Pruitt, Scott K / Ross, Merrick I / Sener, Stephen F / Swetter, Susan M / Tanabe, Kenneth K / Thompson, John A / Trisal, Vijay / Urist, Marshall M / Weber, Jeffrey / Wong, Michael K / Anonymous5080627. · ·J Natl Compr Canc Netw · Pubmed #19401060.

ABSTRACT: -- No abstract --

7 Review Role of sentinel lymph node biopsy in patients with thin melanoma. 2009

Andtbacka, Robert H I / Gershenwald, Jeffrey E. ·Department of Surgery, University of Utah, Salt Lake City, Utah, USA. ·J Natl Compr Canc Netw · Pubmed #19401063.

ABSTRACT: Sentinel lymph node (SLN) biopsy has emerged over the past 2 decades as a rational approach for staging regional lymph nodes in patients with clinically node-negative melanoma (stage I and II disease). Large multi-institutional studies have confirmed that when performed by experienced surgeons, it is an accurate, reliable technique for identifying occult regional nodal disease, and that SLN status is the most important prognostic factor in patients with stage I and II melanoma. However, the incidence of occult regional nodal metastasis in patients with thin melanoma (or= 1 mitosis/mm2). Including younger age (e.g., SLN biopsy should be discussed with all patients with newly diagnosed thin melanoma.

8 Clinical Trial Randomized, Open-Label Phase II Study Evaluating the Efficacy and Safety of Talimogene Laherparepvec in Combination With Ipilimumab Versus Ipilimumab Alone in Patients With Advanced, Unresectable Melanoma. 2018

Chesney, Jason / Puzanov, Igor / Collichio, Frances / Singh, Parminder / Milhem, Mohammed M / Glaspy, John / Hamid, Omid / Ross, Merrick / Friedlander, Philip / Garbe, Claus / Logan, Theodore F / Hauschild, Axel / Lebbé, Celeste / Chen, Lisa / Kim, Jenny J / Gansert, Jennifer / Andtbacka, Robert H I / Kaufman, Howard L. ·Jason Chesney, J. Graham Brown Cancer Center, University of Louisville, Louisville, KY · Igor Puzanov, Roswell Park Cancer Institute, Buffalo · Philip Friedlander, Mt Sinai School of Medicine, New York, NY · Frances Collichio, The University of North Carolina at Chapel Hill, Chapel Hill, NC · Parminder Singh, Mayo Clinic, Phoenix, AZ · Mohammed M. Milhem, University of Iowa Hospitals and Clinics, Iowa City, IA · John Glaspy, University of California Los Angeles School of Medicine · Omid Hamid, The Angeles Clinic and Research Institute, Los Angeles · Lisa Chen, Jenny J. Kim, and Jennifer Gansert, Amgen, Thousand Oaks, CA · Merrick Ross, MD Anderson Cancer Center, Houston, TX · Claus Garbe, University Hospital Tuebingen, Tuebingen · Axel Hauschild, University of Kiel, Kiel, Germany · Theodore F. Logan, Indiana University Simon Cancer Center, Indianapolis, IN · Celeste Lebbé, Assistance Publique-Hôpital De Paris Dermatology and CIC Hôpital Saint Louis University Paris Diderot Sorbonne, Institut National de la Santé et de la Recherche Médicale U976, Paris, France · Robert H.I. Andtbacka, University of Utah, Salt Lake City, UT · and Howard L. Kaufman, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ. ·J Clin Oncol · Pubmed #28981385.

ABSTRACT: Purpose We evaluated the combination of talimogene laherparepvec plus ipilimumab versus ipilimumab alone in patients with advanced melanoma in a phase II study. To our knowledge, this was the first randomized trial to evaluate addition of an oncolytic virus to a checkpoint inhibitor. Methods Patients with unresectable stages IIIB to IV melanoma, with no more than one prior therapy if BRAF wild-type, no more than two prior therapies if BRAF mutant, measurable/injectable disease, and without symptomatic autoimmunity or clinically significant immunosuppression were randomly assigned 1:1 to receive talimogene laherparepvec plus ipilimumab or ipilimumab alone. Talimogene laherparepvec treatment began in week 1 (first dose, ≤ 4 mL × 10

9 Clinical Trial Durable response rate as an endpoint in cancer immunotherapy: insights from oncolytic virus clinical trials. 2017

Kaufman, Howard L / Andtbacka, Robert H I / Collichio, Frances A / Wolf, Michael / Zhao, Zhongyun / Shilkrut, Mark / Puzanov, Igor / Ross, Merrick. ·Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ, 08901, USA. howard.kaufman@rutgers.edu. · Huntsman Cancer Institute, University of Utah, 1950 Circle of Hope Drive, Salt Lake City, UT, 84112, USA. · The University of North Carolina Chapel Hill, 170 Manning Drive, Box 7305, Chapel Hill, NC, 27599, USA. · Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320, USA. · Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA. · MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. ·J Immunother Cancer · Pubmed #28923101.

ABSTRACT: BACKGROUND: Traditional response criteria may be insufficient to characterize full clinical benefits of anticancer immunotherapies. Consequently, endpoints such as durable response rate (DRR; a continuous response [complete or partial objective response] beginning within 12 months of treatment and lasting ≥6 months) have been employed. There has not, however, been validation that DRR correlates with other more traditional endpoints of clinical benefit such as overall survival. METHODS: We evaluated whether DRR was associated with clinically meaningful measures of benefit (eg, overall survival [OS], quality of life [QoL], or treatment-free interval [TFI]) in a phase 3 clinical trial of an oncolytic virus for melanoma treatment. To evaluate the association between DRR and OS and to mitigate lead time bias, landmark analyses were used. QoL was evaluated using the FACT-BRM questionnaire (comprising the FACT-BRM Physical, Social/Family, Emotional, and Functional well-being domains, the Additional Concerns, Physical and Mental treatment-specific subscales, and the Trial Outcome Index [TOI]). TFI was defined as time from the last study therapy dose to first subsequent therapy dose (including any systemic anticancer therapy for melanoma after study therapy discontinuation). RESULTS: Four hundred thirty-six patients were included in the intent-to-treat population. Achieving DR was associated with a statistically significant improvement in OS in a landmark analysis at 9 months (HR = 0.07; P = 0.0003), 12 months (HR = 0.05, P < 0.0001), and 18 months (HR = 0.11; P = 0.0002) that persisted after adjusting for disease stage and line of therapy. Achieving a DR was associated with a longer median TFI (HR = 0.33; P = 0.0007) and a higher TOI improvement rate (58.1% versus 30.0%; P = 0.025). CONCLUSIONS: Achieving a DR was associated with clinical benefits such as improved OS and QoL and prolonged TFI, thus supporting the usefulness of DR as a meaningful immunotherapy clinical trial endpoint. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT00769704 ( https://clinicaltrials.gov/ct2/show/NCT00769704 ) October 7, 2008.

10 Clinical Trial Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy. 2017

Ribas, Antoni / Dummer, Reinhard / Puzanov, Igor / VanderWalde, Ari / Andtbacka, Robert H I / Michielin, Olivier / Olszanski, Anthony J / Malvehy, Josep / Cebon, Jonathan / Fernandez, Eugenio / Kirkwood, John M / Gajewski, Thomas F / Chen, Lisa / Gorski, Kevin S / Anderson, Abraham A / Diede, Scott J / Lassman, Michael E / Gansert, Jennifer / Hodi, F Stephen / Long, Georgina V. ·University of California at Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA. Electronic address: aribas@mednet.ucla.edu. · University Hospital of Zurich, Zurich, Switzerland. · Roswell Park Cancer Institute, Buffalo, NY, USA. · The West Clinic, Memphis, TN, USA. · University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA. · Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. · Fox Chase Cancer Center, Philadelphia, PA, USA. · Hospital Clinic i Provincial de Barcelona, Barcelona, Spain. · Olivia Newton-John Cancer Research Institute, Austin Health, School of Cancer Medicine, LaTrobe University, Heidelberg, VIC, Australia. · Hopitaux Universitaires de Genève, Geneva, Switzerland. · University of Pittsburgh Cancer Institute and Hillman UPMC Cancer Center, Pittsburgh, PA, USA. · The University of Chicago School of Medicine, Chicago, IL, USA. · Amgen Inc., Thousand Oaks, CA, USA. · Amgen Inc., South San Francisco, CA, USA. · Merck & Co., Inc., Kenilworth, NJ, USA. · Dana-Farber Cancer Institute, Boston, MA, USA. · Melanoma Institute Australia, The University of Sydney and Royal North Shore and Mater Hospitals, Sydney, NSW, Australia. ·Cell · Pubmed #28886381.

ABSTRACT: Here we report a phase 1b clinical trial testing the impact of oncolytic virotherapy with talimogene laherparepvec on cytotoxic T cell infiltration and therapeutic efficacy of the anti-PD-1 antibody pembrolizumab. Twenty-one patients with advanced melanoma were treated with talimogene laherparepvec followed by combination therapy with pembrolizumab. Therapy was generally well tolerated, with fatigue, fevers, and chills as the most common adverse events. No dose-limiting toxicities occurred. Confirmed objective response rate was 62%, with a complete response rate of 33% per immune-related response criteria. Patients who responded to combination therapy had increased CD8

11 Clinical Trial Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma. 2017

Faries, Mark B / Thompson, John F / Cochran, Alistair J / Andtbacka, Robert H / Mozzillo, Nicola / Zager, Jonathan S / Jahkola, Tiina / Bowles, Tawnya L / Testori, Alessandro / Beitsch, Peter D / Hoekstra, Harald J / Moncrieff, Marc / Ingvar, Christian / Wouters, Michel W J M / Sabel, Michael S / Levine, Edward A / Agnese, Doreen / Henderson, Michael / Dummer, Reinhard / Rossi, Carlo R / Neves, Rogerio I / Trocha, Steven D / Wright, Frances / Byrd, David R / Matter, Maurice / Hsueh, Eddy / MacKenzie-Ross, Alastair / Johnson, Douglas B / Terheyden, Patrick / Berger, Adam C / Huston, Tara L / Wayne, Jeffrey D / Smithers, B Mark / Neuman, Heather B / Schneebaum, Schlomo / Gershenwald, Jeffrey E / Ariyan, Charlotte E / Desai, Darius C / Jacobs, Lisa / McMasters, Kelly M / Gesierich, Anja / Hersey, Peter / Bines, Steven D / Kane, John M / Barth, Richard J / McKinnon, Gregory / Farma, Jeffrey M / Schultz, Erwin / Vidal-Sicart, Sergi / Hoefer, Richard A / Lewis, James M / Scheri, Randall / Kelley, Mark C / Nieweg, Omgo E / Noyes, R Dirk / Hoon, Dave S B / Wang, He-Jing / Elashoff, David A / Elashoff, Robert M. ·From the John Wayne Cancer Institute at Saint John's Health Center, Santa Monica (M.B.F., D.S.B.H.), and the Departments of Pathology (A.J.C.), Biomathematics (H.-J.W., D.A.E., R.M.E.), and Medicine (D.A.E.), University of California, Los Angeles - both in California · Melanoma Institute Australia and the University of Sydney, Sydney (J.F.T., O.E.N.), Peter MacCallum Cancer Centre, Melbourne, VIC (M.H.), Princess Alexandra Hospital, Brisbane, QLD (B.M.S.), and Newcastle Melanoma Unit, Waratah, NSW (P.H.) - all in Australia · Huntsman Cancer Institute, Salt Lake City (R.H.A., R.D.N.), and Intermountain Healthcare Cancer Services-Intermountain Medical Center, Murray (T.L.B.) - both in Utah · Istituto Nazionale dei Tumori Napoli, Naples (N.M.), Istituto Europeo di Oncologia, Milan (A.T.), and Istituto Oncologico Veneto-University of Padua, Padua (C.R.R.) - all in Italy · H. Lee Moffitt Cancer Center, Tampa, FL (J.S.Z.) · Helsinki University Hospital, Helsinki (T.J.) · Dallas Surgical Group, Dallas (P.D.B.) · Universitair Medisch Centrum Groningen, Groningen (H.J.H.), and Netherlands Cancer Institute, Amsterdam (M.W.J.M.W.) - both in the Netherlands · Norfolk and Norwich University Hospital, Norwich (M. Moncrieff), and Guy's and St. Thomas' NHS Foundation Trust, London (A.M.-R.) - both in the United Kingdom · Swedish Melanoma Study Group-University Hospital Lund, Lund, Sweden (C.I.) · University of Michigan, Ann Arbor (M.S.S.) · Wake Forest University, Winston-Salem (E.A.L.), and Duke University, Durham (R.S.) - both in North Carolina · Ohio State University, Columbus (D.A.) · University of Zurich, Zurich (R.D.), and Centre Hospitalier Universitaire Vaudois, Lausanne (M. Matter) - both in Switzerland · Penn State Hershey Cancer Institute, Hershey (R.I.N.), Thomas Jefferson University (A.C.B.) and Fox Chase Cancer Center (J.M.F.), Philadelphia, and St. Luke's University Health Network, Bethlehem (D.C.D.) - all in Pennsylvania · Greenville Health System Cancer Center, Greenville, SC (S.D.T.) · Sunnybrook Research Institute, Toronto (F.W.), and Tom Baker Cancer Centre, Calgary, AB (G.M.) - both in Canada · University of Washington, Seattle (D.R.B.) · Saint Louis University, St. Louis (E.H.) · Vanderbilt University (D.B.J., M.C.K.), Nashville, and University of Tennessee, Knoxville (J.M.L.) - both in Tennessee · University Hospital Schleswig-Holstein-Campus Lübeck, Lübeck (P.T.), University Hospital of Würzburg, Würzburg (A.G.), and City Hospital of Nürnberg, Nuremberg (E.S.) - all in Germany · SUNY at Stony Brook Hospital Medical Center, Stony Brook (T.L.H.), Memorial Sloan Kettering Cancer Center, New York (C.E.A.), and Roswell Park Cancer Institute, Buffalo (J.M.K.) - all in New York · Northwestern University Feinberg School of Medicine (J.D.W.) and Rush University Medical Center (S.D.B.), Chicago · University of Wisconsin, Madison (H.B.N.) · Tel Aviv Sourasky Medical Center, Tel Aviv, Israel (S.S.) · M.D. Anderson Medical Center, Houston (J.E.G.) · Johns Hopkins University School of Medicine, Baltimore (L.J.) · University of Louisville, Louisville, KY (K.M.M.) · Dartmouth-Hitchcock Medical Center, Lebanon, NH (R.J.B.) · Hospital Clinic Barcelona, Barcelona (S.V.-S.) · and Sentara CarePlex Hospital, Hampton, VA (R.A.H.). ·N Engl J Med · Pubmed #28591523.

ABSTRACT: BACKGROUND: Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear. METHODS: In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis. RESULTS: Immediate completion lymph-node dissection was not associated with increased melanoma-specific survival among 1934 patients with data that could be evaluated in an intention-to-treat analysis or among 1755 patients in the per-protocol analysis. In the per-protocol analysis, the mean (±SE) 3-year rate of melanoma-specific survival was similar in the dissection group and the observation group (86±1.3% and 86±1.2%, respectively; P=0.42 by the log-rank test) at a median follow-up of 43 months. The rate of disease-free survival was slightly higher in the dissection group than in the observation group (68±1.7% and 63±1.7%, respectively; P=0.05 by the log-rank test) at 3 years, based on an increased rate of disease control in the regional nodes at 3 years (92±1.0% vs. 77±1.5%; P<0.001 by the log-rank test); these results must be interpreted with caution. Nonsentinel-node metastases, identified in 11.5% of the patients in the dissection group, were a strong, independent prognostic factor for recurrence (hazard ratio, 1.78; P=0.005). Lymphedema was observed in 24.1% of the patients in the dissection group and in 6.3% of those in the observation group. CONCLUSIONS: Immediate completion lymph-node dissection increased the rate of regional disease control and provided prognostic information but did not increase melanoma-specific survival among patients with melanoma and sentinel-node metastases. (Funded by the National Cancer Institute and others; MSLT-II ClinicalTrials.gov number, NCT00297895 .).

12 Clinical Trial Cutaneous head and neck melanoma in OPTiM, a randomized phase 3 trial of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor for the treatment of unresected stage IIIB/IIIC/IV melanoma. 2016

Andtbacka, Robert H I / Agarwala, Sanjiv S / Ollila, David W / Hallmeyer, Sigrun / Milhem, Mohammed / Amatruda, Thomas / Nemunaitis, John J / Harrington, Kevin J / Chen, Lisa / Shilkrut, Mark / Ross, Merrick / Kaufman, Howard L. ·University of Utah Huntsman Cancer Institute, Salt Lake City, Utah. · St. Luke's University Hospital and Temple University, Philadelphia, Pennsylvania. · University of North Carolina, Chapel Hill, North Carolina. · Advocate Lutheran General Hospital, Park Ridge, Illinois. · University of Iowa Hospitals and Clinics, Iowa City, Iowa. · Minnesota Oncology, Fridley, Minnesota. · Mary Crowley Cancer Research Center, Dallas, Texas. · The Institute of Cancer Research/The Royal Marsden Hospital, London, UK. · Amgen, Inc, Thousand Oaks, California. · The University of Texas MD Anderson Cancer Center, Houston, Texas. · Rutgers Cancer Institute of New Jersey, Rutgers, New Jersey. ·Head Neck · Pubmed #27407058.

ABSTRACT: BACKGROUND: Cutaneous head and neck melanoma has poor outcomes and limited treatment options. In OPTiM, a phase 3 study in patients with unresectable stage IIIB/IIIC/IV melanoma, intralesional administration of the oncolytic virus talimogene laherparepvec improved durable response rate (DRR; continuous response ≥6 months) compared with subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF). METHODS: Retrospective review of OPTiM identified patients with cutaneous head and neck melanoma given talimogene laherparepvec (n = 61) or GM-CSF (n = 26). Outcomes were compared between talimogene laherparepvec and GM-CSF treated patients with cutaneous head and neck melanoma. RESULTS: DRR was higher for talimogene laherparepvec-treated patients than for GM-CSF treated patients (36.1% vs 3.8%; p = .001). A total of 29.5% of patients had a complete response with talimogene laherparepvec versus 0% with GM-CSF. Among talimogene laherparepvec-treated patients with a response, the probability of still being in response after 12 months was 73%. Median overall survival (OS) was 25.2 months for GM-CSF and had not been reached with talimogene laherparepvec. CONCLUSION: Treatment with talimogene laherparepvec was associated with improved response and survival compared with GM-CSF in patients with cutaneous head and neck melanoma. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1752-1758, 2016.

13 Clinical Trial A phase I study of intratumoral ipilimumab and interleukin-2 in patients with advanced melanoma. 2016

Ray, Abhijit / Williams, Matthew A / Meek, Stephanie M / Bowen, Randy C / Grossmann, Kenneth F / Andtbacka, Robert H I / Bowles, Tawnya L / Hyngstrom, John R / Leachman, Sancy A / Grossman, Douglas / Bowen, Glen M / Holmen, Sheri L / VanBrocklin, Matthew W / Suneja, Gita / Khong, Hung T. ·Division of Oncology, Huntsman Cancer Institute-University of Utah, Salt Lake City, UT, USA. · Department of Pathology, University of Utah, Salt Lake City, UT, USA. · School of Medicine, University of Utah, Salt Lake City, UT, USA. · Section of Surgical Oncology, Division of General Surgery Huntsman Cancer Institute-University of Utah, Salt Lake City, UT, USA. · Department of General Surgery, Intermountain Medical Center, Murray, UT, USA. · Department of Dermatology, Oregon Health & Science University-Knight Cancer Institute, Portland, OR, USA. · Department of Radiation Oncology, University of Utah, Salt Lake City, UT, USA. ·Oncotarget · Pubmed #27391442.

ABSTRACT: PURPOSE: Intratumoral interleukin-2 (IL-2) is effective but does not generate systemic immunity. Intravenous ipilimumab produces durable clinical response in a minority of patients, with potentially severe toxicities. Circulating anti-tumor T cells activated by ipilimumab may differ greatly from tumor-infiltrating lymphocytes activated by intratumoral ipilimumab in phenotypes and functionality. The objective of this study was to primarily assess the safety of intratumoral ipilimumab/IL-2 combination and to obtain data on clinical efficacy. RESULTS: There was no dose limiting toxicity. While local response of injected lesions was observed in 67% patients (95% CI, 40%-93%), an abscopal response was seen in 89% (95% CI, 68%-100%). The overall response rate and clinical benefit rate by immune-related response criteria (irRC) was 40% (95% CI, 10%-70%) and 50% (95% CI, 19%-81%), respectively. Enhanced systemic immune response was observed in most patients and correlated with clinical responses. EXPERIMENTAL DESIGN: Twelve patients with unresectable stages III/IV melanoma were enrolled. A standard 3+3 design was employed to assess highest tolerable intratumoral dose of ipilimumab and IL-2 based on toxicity during the first three weeks. Escalated doses of ipilimumab was injected into only one lesion weekly for eight weeks in cohorts of three patients. A fixed dose of IL-2 was injected three times a week into the same lesion for two weeks, followed by two times a week for six weeks. CONCLUSIONS: Intratumoral injection with the combination of ipilimumab/IL-2 is well tolerated and generates responses in both injected and non-injected lesions in the majority of patients.

14 Clinical Trial Patterns of Clinical Response with Talimogene Laherparepvec (T-VEC) in Patients with Melanoma Treated in the OPTiM Phase III Clinical Trial. 2016

Andtbacka, Robert H I / Ross, Merrick / Puzanov, Igor / Milhem, Mohammed / Collichio, Frances / Delman, Keith A / Amatruda, Thomas / Zager, Jonathan S / Cranmer, Lee / Hsueh, Eddy / Chen, Lisa / Shilkrut, Mark / Kaufman, Howard L. ·Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA. Robert.Andtbacka@hci.utah.edu. · University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Vanderbilt University Medical Center, Nashville, TN, USA. · University of Iowa Hospitals and Clinics, Iowa City, IA, USA. · University of North Carolina, Chapel Hill, NC, USA. · Emory University, Atlanta, GA, USA. · Minnesota Oncology, Fridley, MN, USA. · Moffitt Cancer Center, Tampa, FL, USA. · University of Washington School of Medicine, Seattle, WA, USA. · Saint Louis University Cancer Center, St Louis, MO, USA. · Amgen Inc., Thousand Oaks, CA, USA. · Rutgers Cancer Institute of New Jersey, Rutgers, NJ, USA. ·Ann Surg Oncol · Pubmed #27342831.

ABSTRACT: PURPOSE: Talimogene laherparepvec (T-VEC) is an oncolytic immunotherapy designed to induce tumor regression of injected lesions through direct lytic effects, and of uninjected lesions through induction of systemic antitumor immunity. In this study, we describe the patterns and time course of response to T-VEC from the phase III OPTiM trial of 436 patients with unresected stages IIIB-IV melanoma. METHODS: Lesion-level response analyses were performed based on the type of lesion (injected or uninjected cutaneous, subcutaneous, or nodal lesions; or visceral lesions [uninjected]), and the best percentage change from baseline of the sum of products of the longest diameters was calculated. Patients randomized to T-VEC (n = 295) who experienced a durable response (continuous partial or complete response for ≥6 months) were evaluated for progression prior to response (PPR), defined as the appearance of a new lesion or >25 % increase in total baseline tumor area. RESULTS: T-VEC resulted in a decrease in size by ≥50 % in 64 % of injected lesions (N = 2116), 34 % of uninjected non-visceral lesions (N = 981), and 15 % of visceral lesions (N = 177). Complete resolution of lesions occurred in 47 % of injected lesions, 22 % of uninjected non-visceral lesions, and 9 % of visceral lesions. Of 48 patients with durable responses, 23 (48 %) experienced PPR, including 14 who developed new lesions only. No difference in overall survival was observed, and median duration of response was not reached in patients with PPR versus those without PPR. CONCLUSIONS: Responses in uninjected lesions provide validation of T-VEC-induced systemic immunotherapeutic effects against melanoma. PPR did not negatively impact the clinical effectiveness of T-VEC.

15 Clinical Trial Talimogene Laherparepvec in Combination With Ipilimumab in Previously Untreated, Unresectable Stage IIIB-IV Melanoma. 2016

Puzanov, Igor / Milhem, Mohammed M / Minor, David / Hamid, Omid / Li, Ai / Chen, Lisa / Chastain, Michael / Gorski, Kevin S / Anderson, Abraham / Chou, Jeffrey / Kaufman, Howard L / Andtbacka, Robert H I. ·Igor Puzanov, Vanderbilt University, Nashville, TN · Mohammed M. Milhem, University of Iowa, Iowa City, IA · David Minor, California Pacific Melanoma Center, San Francisco · Omid Hamid, The Angeles Clinic and Research Institute, Los Angeles · and Ai Li, Lisa Chen, Michael Chastain, Kevin S. Gorski, Abraham Anderson, and Jeffrey Chou, Amgen, Thousand Oaks, CA · Howard L. Kaufman, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ · and Robert H.I. Andtbacka, University of Utah, Salt Lake City, UT. ·J Clin Oncol · Pubmed #27298410.

ABSTRACT: PURPOSE: Combining immunotherapeutic agents with different mechanisms of action may enhance efficacy. We describe the safety and efficacy of talimogene laherparepvec (T-VEC; an oncolytic virus) in combination with ipilimumab (a cytotoxic T-lymphocyte-associated antigen 4 checkpoint inhibitor) in patients with advanced melanoma. METHODS: In this open-label, multicenter, phase Ib trial of T-VEC in combination with ipilimumab, T-VEC was administered intratumorally in week 1 (10(6) plaque-forming units/mL), then in week 4 and every 2 weeks thereafter (10(8) plaque-forming units/mL). Ipilimumab (3 mg/kg) was administered intravenously every 3 weeks for four infusions, beginning in week 6. The primary end point was incidence of dose-limiting toxicities. Secondary end points were objective response rate by immune-related response criteria and safety. RESULTS: Median duration of treatment with T-VEC was 13.3 weeks (range, 2.0 to 95.4 weeks). Median follow-up time for survival analysis was 20.0 months (1.0 to 25.4 months). Nineteen patients were included in the safety analysis. No dose-limiting toxicities occurred, and no new safety signals were detected. Grade 3/4 treatment-related adverse events (AEs) were seen in 26.3% of patients; 15.8% had AEs attributed to T-VEC, and 21.1% had AEs attributed to ipilimumab. The objective response rate was 50%, and 44% of patients had a durable response lasting ≥ 6 months. Eighteen-month progression-free survival was 50%; 18-month overall survival was 67%. CONCLUSION: T-VEC with ipilimumab had a tolerable safety profile, and the combination appeared to have greater efficacy than either T-VEC or ipilimumab monotherapy.

16 Clinical Trial Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma. 2015

Andtbacka, Robert H I / Kaufman, Howard L / Collichio, Frances / Amatruda, Thomas / Senzer, Neil / Chesney, Jason / Delman, Keith A / Spitler, Lynn E / Puzanov, Igor / Agarwala, Sanjiv S / Milhem, Mohammed / Cranmer, Lee / Curti, Brendan / Lewis, Karl / Ross, Merrick / Guthrie, Troy / Linette, Gerald P / Daniels, Gregory A / Harrington, Kevin / Middleton, Mark R / Miller, Wilson H / Zager, Jonathan S / Ye, Yining / Yao, Bin / Li, Ai / Doleman, Susan / VanderWalde, Ari / Gansert, Jennifer / Coffin, Robert S. ·Robert H.I. Andtbacka, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT · Howard L. Kaufman, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ · Frances Collichio, University of North Carolina Medical Center, Chapel Hill, NC · Thomas Amatruda, Minnesota Oncology, Fridley, MN · Neil Senzer, Mary Crowley Cancer Research Center, Dallas · Merrick Ross, University of Texas MD Anderson Cancer Center, Houston, TX · Jason Chesney, University of Louisville, Louisville, KY · Keith A. Delman, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA · Lynn E. Spitler, Northern California Melanoma Center, San Francisco · Gregory A. Daniels, University of California San Diego Medical Center, Moores Cancer Center, La Jolla · Yining Ye, Bin Yao, Ai Li, Ari Vander Walde, and Jennifer Gansert, Amgen, Thousand Oaks, CA · Igor Puzanov, Vanderbilt University, Nashville, TN · Sanjiv S. Agarwala, St Luke's University Hospital and Health Network, Bethlehem, and Temple University School of Medicine, Philadelphia, PA · Mohammed Milhem, University of Iowa Hospitals and Clinics, Iowa City, IA · Lee Cranmer, University of Arizona, Tucson, AZ · Brendan Curti, Earle A. Chiles Research Institute, Portland, OR · Karl Lewis, University of Colorado Cancer Center, Aurora, CO · Troy Guthrie, Baptist Cancer Institute, Jacksonville · Jonathan S. Zager, Moffitt Cancer Center, Tampa, FL · Gerald P. Linette, Washington University School of Medicine, St Louis, MO · Kevin Harrington, Institute of Cancer Research, Royal Marsden Hospital, London · Mark R. Middleton, National Institute for Health Research Biomedical Research Centre, Oxford, United Kingdom · Wilson H. Miller Jr, McGill University, Montreal, Quebec, Canada · and Susan Doleman and Robert S. Coffin, Amgen, Woburn, MA. ·J Clin Oncol · Pubmed #26014293.

ABSTRACT: PURPOSE: Talimogene laherparepvec (T-VEC) is a herpes simplex virus type 1-derived oncolytic immunotherapy designed to selectively replicate within tumors and produce granulocyte macrophage colony-stimulating factor (GM-CSF) to enhance systemic antitumor immune responses. T-VEC was compared with GM-CSF in patients with unresected stage IIIB to IV melanoma in a randomized open-label phase III trial. PATIENTS AND METHODS: Patients with injectable melanoma that was not surgically resectable were randomly assigned at a two-to-one ratio to intralesional T-VEC or subcutaneous GM-CSF. The primary end point was durable response rate (DRR; objective response lasting continuously ≥ 6 months) per independent assessment. Key secondary end points included overall survival (OS) and overall response rate. RESULTS: Among 436 patients randomly assigned, DRR was significantly higher with T-VEC (16.3%; 95% CI, 12.1% to 20.5%) than GM-CSF (2.1%; 95% CI, 0% to 4.5%]; odds ratio, 8.9; P < .001). Overall response rate was also higher in the T-VEC arm (26.4%; 95% CI, 21.4% to 31.5% v 5.7%; 95% CI, 1.9% to 9.5%). Median OS was 23.3 months (95% CI, 19.5 to 29.6 months) with T-VEC and 18.9 months (95% CI, 16.0 to 23.7 months) with GM-CSF (hazard ratio, 0.79; 95% CI, 0.62 to 1.00; P = .051). T-VEC efficacy was most pronounced in patients with stage IIIB, IIIC, or IVM1a disease and in patients with treatment-naive disease. The most common adverse events (AEs) with T-VEC were fatigue, chills, and pyrexia. The only grade 3 or 4 AE occurring in ≥ 2% of T-VEC-treated patients was cellulitis (2.1%). No fatal treatment-related AEs occurred. CONCLUSION: T-VEC is the first oncolytic immunotherapy to demonstrate therapeutic benefit against melanoma in a phase III clinical trial. T-VEC was well tolerated and resulted in a higher DRR (P < .001) and longer median OS (P = .051), particularly in untreated patients or those with stage IIIB, IIIC, or IVM1a disease. T-VEC represents a novel potential therapy for patients with metastatic melanoma.

17 Article Routine retrieval of pelvic sentinel lymph nodes for melanoma rarely adds prognostic information or alters management. 2019

Swords, Douglas S / Andtbacka, Robert H I / Bowles, Tawnya L / Hyngstrom, John R. ·Department of Surgery, University of Utah. · Intermountain Healthcare, Surgical Services, Intermountain Medical Center, Salt Lake City, Utah, USA. ·Melanoma Res · Pubmed #30161040.

ABSTRACT: Pelvic sentinel lymph nodes (SLNs) are commonly identified during inguinal SLN biopsy for melanoma, but retrieval is not uniform among surgeons/centers. Few studies have assessed rates of micrometastases in pelvic versus superficial inguinal SLNs. Previous studies suggested that presence of pelvic SLNs was predicted by aggressive pathologic features and that their presence portended a worse prognosis. The objectives of this study were to examine presurgical predictors of pelvic SLNs among patients undergoing inguinal SLN biopsy, assess rates of micrometastases in superficial inguinal versus pelvic SLNs, and determine whether presence of pelvic SLNs was associated with long-term outcomes. Multivariable regression was used to assess presurgical factors associated with presence of pelvic SLNs. Rates of micrometastases in superficial inguinal versus pelvic SLNs in patients who had a pelvic SLN were compared with McNemar's test. Groin recurrence, disease-free survival (DFS), and disease-specific survival were analyzed by Kaplan-Meier method. A multivariable Cox model for DFS was performed. Pelvic SLNs were retrieved in 100/537 (18.6%) superficial inguinal SLN biopsies and no preoperative factors predicted their presence. In patients with a pelvic SLN, micrometastases were present in 3.0% of pelvic versus 34.0% of superficial inguinal SLN biopsies (P<0.001). There were no differences in groin recurrence, DFS, and disease-specific survival for patients with/without pelvic SLNs in univariate analyses (all P>0.2) or in the multivariable Cox model for DFS (hazard ratio: 1.1, 95% confidence interval: 0.6-2.1). In conclusion, pelvic SLNs harbor micrometastases less frequently than superficial inguinal SLNs do, suggesting that omission of pelvic SLN biopsy may be reasonable.

18 Article Similar survival of patients with multiple versus single primary melanomas based on Utah Surveillance, Epidemiology, and End Results data (1973-2011). 2018

Grossman, Douglas / Farnham, James M / Hyngstrom, John / Klapperich, Marki E / Secrest, Aaron M / Empey, Sarah / Bowen, Glen M / Wada, David / Andtbacka, Robert H I / Grossmann, Kenneth / Bowles, Tawnya L / Cannon-Albright, Lisa A. ·Department of Dermatology, University of Utah Health Sciences Center, Salt Lake City, Utah; Department of Oncological Sciences, University of Utah Health Sciences Center, Salt Lake City, Utah; Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, Utah. Electronic address: doug.grossman@hci.utah.edu. · Department of Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah. · Department of Surgery, University of Utah Health Sciences Center, Salt Lake City, Utah; Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, Utah. · University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin. · Department of Dermatology, University of Utah Health Sciences Center, Salt Lake City, Utah. · Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, Utah. · Department of Dermatology, University of Utah Health Sciences Center, Salt Lake City, Utah; Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, Utah. · Department of Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah; Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, Utah. · Department of Surgery, University of Utah Health Sciences Center, Salt Lake City, Utah. · Department of Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah; Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, Utah; George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah. ·J Am Acad Dermatol · Pubmed #29499295.

ABSTRACT: BACKGROUND: Survival data are mixed comparing patients with multiple primary melanomas (MPM) to those with single primary melanomas (SPM). OBJECTIVES: We compared MPM versus SPM patient survival using a matching method that avoids potential biases associated with other analytic approaches. METHODS: Records of 14,138 individuals obtained from the Surveillance, Epidemiology, and End Results registry of all melanomas diagnosed or treated in Utah between 1973 and 2011 were reviewed. A single matched control patient was selected randomly from the SPM cohort for each MPM patient, with the restriction that they survived at least as long as the interval between the first and second diagnoses for the matched MPM patient. RESULTS: Survival curves (n = 887 for both MPM and SPM groups) without covariates showed a significant survival disadvantage for MPM patients (chi-squared 39.29, P < .001). However, a multivariate Cox proportional hazards model showed no significant survival difference (hazard ratio 1.07, P = .55). Restricting the multivariate analysis to invasive melanomas also showed no significant survival difference (hazard ratio 0.99, P = .96). LIMITATIONS: Breslow depth, ulceration status, and specific cause of death were not available for all patients. CONCLUSIONS: Patients with MPM had similar survival times as patients with SPM.

19 Article Quality of life patient-reported outcomes for locally advanced cutaneous melanoma. 2018

Weitman, Evan S / Perez, Matthew / Thompson, John F / Andtbacka, Robert H I / Dalton, Jo / Martin, Mona L / Miller, Talia / Gwaltney, Chad / Sarson, David / Wachter, Eric / Zager, Jonathan S. ·Moffitt Cancer Center, Tampa, Florida. · Melanoma Institute Australia, The University of Sydney, Sydney. · Huntsman Cancer Institute, Salt Lake City, Utah. · Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. · Health Research Associates Inc. · eResearch Technology Inc., Pittsburgh, Pennsylvania, USA. · Gwaltney Consulting. · Provectus Biopharmaceuticals Australia Pty Ltd. · Provectus Biopharmaceuticals Inc. ·Melanoma Res · Pubmed #29261570.

ABSTRACT: Locally advanced cutaneous melanoma has marked quality-of-life implications; however, the patient experience of symptom management and subsequent impact on quality of life has not been well described. This study aims to address the impact on patients of advanced cutaneous melanoma through qualitative interviews. Adults with stage IIIB, IIIC, or IV (M1a) cutaneous melanoma were recruited from two cancer centers in the USA and one in Australia. Telephone interviews were conducted to assess how locoregionally advanced cutaneous melanoma impacted everyday life. Interviews were recorded, transcribed, and coded for qualitative analysis. Twenty-two melanoma patients were interviewed, mean age 69.7 years (range: 52-83), 64% male. The study included stage IIIB (36%), stage IIIC (59%), and stage IV M1a (5%) patients. Emotional health/self-perception issues were the most commonly identified (41% of patient impact expressions), including worry, concern, embarrassment, self-consciousness, fear, and thoughts of death. Limitations of lifestyle and activities were also identified (28% of expressions) including leisure and social activities, physical functioning, general functioning, and personal care. Coping strategies such as modified clothing choices, increased use of pain and/or anti-inflammatory medications, and avoidance/protection from the sun represented 20% of all impact expressions. Ratings of the degree of difficulty patients experienced (using an 11-point numerical rating scale) ranged from 0.0 to 10.0 (mean 5.7, SD 2.9). Condition-related and treatment-related factors were well characterized in patients with locally advanced cutaneous melanoma. This provides a strong foundation for assessment of how cutaneous melanoma impacts quality of life.

20 Article Osseointegrated Prosthetic Ear Reconstruction in Cases of Skin Malignancy: Technique, Outcomes, and Patient Satisfaction. 2018

Agarwal, Cori A / Johns, Dana / Tanner, Paul B / Andtbacka, Robert H I. · ·Ann Plast Surg · Pubmed #28984657.

ABSTRACT: BACKGROUND: Ear reconstruction with osseointegrated prosthetic implants is a well-established method of reconstruction after resection of skin malignancies on the external ear. There is limited literature reporting technique, outcomes, and patient satisfaction. METHODS: We evaluated our outcomes over a 5-year period looking at osseointegrated prosthetic reconstruction after auriculectomy for external ear skin malignancies. We report demographics, disease characteristics, technique, and complications. The patients were surveyed looking at 6 domains: satisfaction, stability, comfort, ease of use, level of self-consciousness, and preoperative education. RESULTS: Of the 21 patients included in the study, 14 (67%) were treated for invasive melanoma (Breslow depth, >0.8mm), 4 (19%) for squamous cell carcinoma, 2 (10%) for basal cell carcinoma, and 1 (5%) for an atypical fibroxanthoma. Complications rates were low. There were no cases of infection, hematoma, or bleeding. In 2 patients (9.5%), 1 of the 3 implants failed to osseointegrate and was removed, but the prosthesis was able to be secured with the remaining 2 posts. There were 3 cases (14%) of delayed healing and 1 with excessive granulation tissue growth. Survey results showed high satisfaction in all measured domains. CONCLUSIONS: In cases of skin malignancy requiring total or subtotal auriculectomy, prosthetic ear reconstruction with osseointegrated implants is a good alternative to reconstruction with autologous tissue. Our experience demonstrates good outcomes and with low complication rates and high patient satisfaction.

21 Article SCF-KIT signaling induces endothelin-3 synthesis and secretion: Thereby activates and regulates endothelin-B-receptor for generating temporally- and spatially-precise nitric oxide to modulate SCF- and or KIT-expressing cell functions. 2017

Chen, Lei L / Zhu, Jing / Schumacher, Jonathan / Wei, Chongjuan / Ramdas, Latha / Prieto, Victor G / Jimenez, Arnie / Velasco, Marco A / Tripp, Sheryl R / Andtbacka, Robert H I / Gouw, Launce / Rodgers, George M / Zhang, Liansheng / Chan, Benjamin K / Cassidy, Pamela B / Benjamin, Robert S / Leachman, Sancy A / Frazier, Marsha L. ·Department of Sarcoma, University of Texas M D Anderson Cancer Center, Houston, Texas, United States of America. · Department of Epidemiology, University of Texas M D Anderson Cancer Center, Houston, Texas, United States of America. · ARUP Laboratories, Salt Lake City, Utah, United States of America. · Research Information Services & Technology, University of Texas M D Anderson Cancer Center, Houston, Texas, United States of America. · Pathology, University of Texas M D Anderson Cancer Center, Houston, Texas, United States of America. · Vel-Lab Research, Missouri City, Texas, United States of America. · Department of Surgery, University of Utah, Salt Lake City, Utah, United States of America. · Department of Internal Medicine, University of Utah, Salt Lake City, Utah, United States of America. · Department of Hematology & Oncology, The Second Hospital of Lanzhou University, Lanzhou, Gansu, P. R. China. · Department of Biology, University of Utah, Salt Lake City, Utah, United States of America. · Department of Dermatology, University of Utah, Salt Lake City, Utah, United States of America. · Graduate School of Biomedical Sciences, University of Texas M D Anderson Cancer Center, Houston, Texas, United States of America. ·PLoS One · Pubmed #28880927.

ABSTRACT: We demonstrate that SCF-KIT signaling induces synthesis and secretion of endothelin-3 (ET3) in human umbilical vein endothelial cells and melanoma cells in vitro, gastrointestinal stromal tumors, human sun-exposed skin, and myenteric plexus of human colon post-fasting in vivo. This is the first report of a physiological mechanism of ET3 induction. Integrating our finding with supporting data from literature leads us to discover a previously unreported pathway of nitric oxide (NO) generation derived from physiological endothelial NO synthase (eNOS) or neuronal NOS (nNOS) activation (referred to as the KIT-ET3-NO pathway). It involves: (1) SCF-expressing cells communicate with neighboring KIT-expressing cells directly or indirectly (cleaved soluble SCF). (2) SCF-KIT signaling induces timely local ET3 synthesis and secretion. (3) ET3 binds to ETBR on both sides of intercellular space. (4) ET3-binding-initiated-ETBR activation increases cytosolic Ca2+, activates cell-specific eNOS or nNOS. (5) Temporally- and spatially-precise NO generation. NO diffuses into neighboring cells, thus acts in both SCF- and KIT-expressing cells. (6) NO modulates diverse cell-specific functions by NO/cGMP pathway, controlling transcriptional factors, or other mechanisms. We demonstrate the critical physiological role of the KIT-ET3-NO pathway in fulfilling high demand (exceeding basal level) of endothelium-dependent NO generation for coping with atherosclerosis, pregnancy, and aging. The KIT-ET3-NO pathway most likely also play critical roles in other cell functions that involve dual requirement of SCF-KIT signaling and NO. New strategies (e.g. enhancing the KIT-ET3-NO pathway) to harness the benefit of endogenous eNOS and nNOS activation and precise NO generation for correcting pathophysiology and restoring functions warrant investigation.

22 Article Risk factors for development of melanoma brain metastasis and disease progression: a single-center retrospective analysis. 2017

Gardner, Laura J / Ward, Morgan / Andtbacka, Robert H I / Boucher, Kenneth M / Bowen, Glen M / Bowles, Tawnya L / Cohen, Adam L / Grossmann, Kenneth / Hitchcock, Ying J / Holmen, Sheri L / Hyngstrom, John / Khong, Hung / McMahon, Martin / Monroe, Marcus M / Ross, Carolyn B / Suneja, Gita / Wada, David / Grossman, Douglas. ·Departments of aDermatology bSurgery cMedicine dRadiation Oncology eOncological Sciences fHuntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, Utah, USA. ·Melanoma Res · Pubmed #28800031.

ABSTRACT: Melanoma metastasis to the brain is associated with a poor prognosis. We sought to determine patient demographics and primary tumor factors associated with the development of brain metastasis (BM) and survival. We also investigated whether the BM detection setting (routine screening vs. symptomatic presentation) affected clinical outcomes. A database of melanoma patients seen from 1999 to 2015 at our institution was reviewed to identify patients who developed BM. Patients with BM were matched by initial stage with patients who did not develop BM as a control group. Patient demographics, primary tumor characteristics, and clinical outcomes were analyzed. A total of 123 patients with BM were matched by initial presenting stage to 237 patients without BM. The characteristics of the primary melanoma tumor associated with BM development included location on the scalp (P=0.030), nodular histologic type (P=0.020), and Breslow depth more than 4 mm (P=0.048), whereas location on the leg was associated with decreased BM risk (P=0.006). In patients with BM, time to first recurrence for melanomas of the scalp was significantly shorter (10.8 vs. 24.8 months, P=0.007) than nonscalp head and neck tumors. Patient stage, tumor depth, nodular type, and ulceration were also associated with worse clinical outcomes. There were no differences in the clinical outcomes between patients whose BM were detected upon routine screening versus those detected upon symptomatic presentation. In summary, factors predictive of development of BM included primary scalp location, nodular type, and depth. In BM patients, scalp location, stage, tumor depth, nodular type, and ulceration, but not detection setting, were associated with worse clinical outcomes.

23 Article The Impact of Smoking on Sentinel Node Metastasis of Primary Cutaneous Melanoma. 2017

Jones, Maris S / Jones, Peter C / Stern, Stacey L / Elashoff, David / Hoon, Dave S B / Thompson, John / Mozzillo, Nicola / Nieweg, Omgo E / Noyes, Dirk / Hoekstra, Harald J / Zager, Jonathan S / Roses, Daniel F / Testori, Alessandro / Coventry, Brendon J / Smithers, Mark B / Andtbacka, Robert / Agnese, Doreen / Schultz, Erwin / Hsueh, Eddy C / Kelley, Mark / Schneebaum, Schlomo / Jacobs, Lisa / Bowles, Tawnya / Kashani-Sabet, Mohammed / Johnson, Douglas / Faries, Mark B. ·Division of Surgical Oncology, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USA. · Department of Molecular Oncology, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USA. · Department of Biostatistics, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USA. · UCLA Department of Biostatistics, Los Angeles, CA, USA. · Melanoma Institute Australia, Sydney, NSW, Australia. · Istituto Nazionale dei Tumori Napoli, Napoli, Italy. · IHC Cancer Services, Intermountain Medical Center, Salt Lake City, UT, USA. · Universitair Medisch Centrum Groningen, Groningen, The Netherlands. · H. Lee Moffitt Cancer Center, Tampa, USA. · NYU Langone Medical Center, New York, USA. · Istituto Europeo di Oncologia, Milano, Italy. · Royal Adelaide Hospital Discipline of Surgery, Royal Adelaide HospitalUniversity of Adelaide, Adelaide, SA, Australia. · Princess Alexandra Hospital, Woolloongabba, Queensland, Australia. · Huntsman Cancer Institute, Salt Lake City, USA. · Ohio State University, Columbus, USA. · Nuremberg General Hospital - Paracelsus Medical University, Nuremberg, Germany. · Saint Louis University, St. Louis, USA. · Vanderbilt University, Nashville, USA. · Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel. · Johns Hopkins Medical Institute, Baltimore, USA. · California Pacific Medical Center, San Francisco, USA. · Department of Melanoma Research, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USA. mark.faries@jwci.org. ·Ann Surg Oncol · Pubmed #28224364.

ABSTRACT: BACKGROUND: Although a well-established causative relationship exists between smoking and several epithelial cancers, the association of smoking with metastatic progression in melanoma is not well studied. We hypothesized that smokers would be at increased risk for melanoma metastasis as assessed by sentinel lymph node (SLN) biopsy. METHODS: Data from the first international Multicenter Selective Lymphadenectomy Trial (MSLT-I) and the screening-phase of the second trial (MSLT-II) were analyzed to determine the association of smoking with clinicopathologic variables and SLN metastasis. RESULTS: Current smoking was strongly associated with SLN metastasis (p = 0.004), even after adjusting for other predictors of metastasis. Among 4231 patients (1025 in MSLT-I and 3206 in MSLT-II), current or former smoking was also independently associated with ulceration (p < 0.001 and p < 0.001, respectively). Compared with current smoking, never smoking was independently associated with decreased Breslow thickness in multivariate analysis (p = 0.002) and with a 0.25 mm predicted decrease in thickness. CONCLUSION: The direct correlation between current smoking and SLN metastasis of primary cutaneous melanoma was independent of its correlation with tumor thickness and ulceration. Smoking cessation should be strongly encouraged among patients with or at risk for melanoma.

24 Article Benign melanocytic lymph node deposits in the setting of giant congenital melanocytic nevi: the large congenital nodal nevus. 2015

Bowen, Anneli R / Duffy, Keith L / Clayton, Frederic C / Andtbacka, Robert H I / Florell, Scott R. ·Department of Dermatology, University of Utah, Salt Lake City, UT, USA. · Department of Pathology, University of Utah, Salt Lake City, UT, USA. · Division of Surgical Oncology, Department of Surgery, University of Utah, Salt Lake City, UT, USA. ·J Cutan Pathol · Pubmed #26268779.

ABSTRACT: BACKGROUND: Benign melanocytic rests are a frequent finding in superficial lymph nodes removed during sentinel lymph node biopsies for melanoma. Whereas the histopathology of these deposits is well understood, very little is known regarding melanocytic lymph node deposits in the setting of giant congenital melanocytic nevi. METHODS: We analyzed lymph nodes removed from the drainage basin of giant congenital melanocytic nevi in three patients who had developed melanoma within their giant congenital nevi. RESULTS: Two of three patients showed widespread, capsular and parenchymal melanocytic deposits in multiple nodes (9 of 11 nodes in one patient and 6 of 8 in the other). Melanocytes were small, non-mitotically active and resembled those in the associated giant congenital melanocytic nevus. Melanocytes were arranged singly and in small nests ∼0.05 mm in diameter, with some larger sheets up to 1 mm. Nodal melanocytes stained for Melan A and S100 on immunohistochemical evaluation, but showed negative or minimal HMB-45 reactivity. CONCLUSIONS: Evaluation of lymph nodes in the setting of giant congenital melanocytic nevi is complicated by the presence of often numerous, parenchymal melanocytic nevic deposits. Bland cytology and minimal or absent HMB-45 staining may be helpful in differentiating these nodal melanocytic nevi from metastatic melanoma. We term this phenomena large congenital nodal nevus.

25 Article The role of thioredoxin reductase 1 in melanoma metabolism and metastasis. 2015

Cassidy, Pamela B / Honeggar, Matthew / Poerschke, Robyn L / White, Karen / Florell, Scott R / Andtbacka, Robert H I / Tross, Joycelyn / Anderson, Madeleine / Leachman, Sancy A / Moos, Philip J. ·Department of Dermatology, Oregon Health & Science University, Portland, OH, USA. · Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, USA. · Department of Dermatology, University of Utah, Salt Lake City, UT, USA. · Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA. ·Pigment Cell Melanoma Res · Pubmed #26184858.

ABSTRACT: Although significant progress has been made in targeted and immunologic therapeutics for melanoma, many tumors fail to respond, and most eventually progress when treated with the most efficacious targeted combination therapies thus far identified. Therefore, alternative approaches that exploit distinct melanoma phenotypes are necessary to develop new approaches for therapeutic intervention. Tissue microarrays containing human nevi and melanomas were used to evaluate levels of the antioxidant protein thioredoxin reductase 1 (TR1), which was found to increase as a function of disease progression. Melanoma cell lines revealed metabolic differences that correlated with TR1 levels. We used this new insight to design a model treatment strategy that creates a synthetic lethal interaction wherein targeting TR1 sensitizes melanoma to inhibition of glycolytic metabolism, resulting in a decrease in metastases in vivo. This approach holds the promise of a new clinical therapeutic strategy, distinct from oncoprotein inhibition.

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