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MELANOMA/SKIN CANCERS Locoregional Therapies in the Setting of Systemic Treatment Advances: What’s Next? CHAIR Sanjiv S. Agarwala, MD St. Luke’s Medical Center Easton, PA SPEAKERS Ahmad A. Tarhini, MD, PhD University of Pittsburgh Pittsburgh, PA Dirk J. Grünhagen, MD, PhD Erasmus MC Cancer Institute Rotterdam, Netherlands
GRÜNHAGEN, KROON, AND VERHOEF Perfusion and Infusion for Melanoma In-Transit Metastases in the Era of Effective Systemic Therapy Dirk J. Grünhagen, MD, PhD, Hidde M. Kroon, MD, PhD, and Cornelis Verhoef, MD, PhD OVERVIEW The management of melanoma in-transit metastases (IT-mets) is challenging. For many years, the absence of effective systemic therapy has prompted physicians to focus on regional therapies for melanoma confined to the limb. The introduction of isolated limb perfusion (ILP) and isolated limb infusion (ILI) has enabled effective delivery of cytotoxic drugs in an isolated circuit, so as to overcome systemic toxicity and maximize local response. Both techniques have evolved over years and both tumor necrosis factor (TNF)-alpha–based ILP and ILI have distinct indications. The development of new systemic treatment options for patients with melanoma in the past decade has shed a new light on melanoma therapy. The present manuscript focuses on the modern role of ILI and ILP in the treatment of patients with melanoma with in-transit metastases in the era of effective systemic therapy. The response and control rates of ILI/ILP are still superior to rates achieved with systemic agents. The extent of disease in patients with stage III disease, however, warrants effective systemic treatment to prolong survival. There is great potential in combining rapid response therapy such as ILI/ILP with systemic agents for sustainable response. Trial results are eagerly awaited. Melanoma incidence in the United States has increased during recent decades to an estimated number of 76,100 new cases in 2014, 1 comprising 4.6% of all new cancer cases. In approximately 5% to 8% of these patients, IT-mets will develop during the course of the disease. These IT-mets are a result of tumor emboli trapped within the dermal and subdermal lymphatics and can occur anywhere between the site of the primary tumor and the draining regional lymph node basin. The management of these IT-mets is challenging, as they are often numerous and can be bulky. The median time between diagnosis of the primary tumor and the development of IT-mets is between 13 months and 16 months. If a patient develops IT-mets, this is often a prelude to the appearance of systemic disease. In the current American Joint Committee on Cancer Melanoma Staging and Classifıcation, patients with IT-mets are staged N2 or N3, depending on associated lymph node metastases. The corresponding 5-year survival rates are 69% and 52%, respectively. 2 Various treatment options exist for melanoma IT-mets, as the presentation can range from very few and tiny lesions easily amenable to local excision, to more than 100 and extremely bulky lesions in previously extensively treated extremities. This wide range of clinical presentation demands a tailored approach for each patient. Whereas, in some patients, resection of limited disease is part of a curative approach, other patients may need treatment of their IT-mets even in the presence of stage IV disease for palliative reasons. The treatment of these IT-mets can therefore be challenging, especially when the interval between new lesions is short, when numerous and bulky metastases are present, or when multiple treatment modalities have already been applied and failed. It is in this context that Creech and Krementz developed the concept of ILP in 1958. 3 ILP TECHNIQUE Until recently, melanoma was infamously refractory to any kind of systemic treatment. This resistance stimulated the search for techniques that could deliver high concentrations of chemotherapy or other agents to the affected limb, without the risk for systemic toxicity. In this way, drug concentrations would potentially suffıce to achieve antitumor effect. As IT-mets of extremity melanomas are, per defınition, confıned to a limb, isolation of the affected limb from the systemic circulation would offer such an opportunity. This isolation can be achieved by surgical access to the artery and vein on either iliac, femoral, popliteal, axillary, or brachial level. The artery and vein are clamped and cannulated after which the catheters can be connected to a heart-lung machine to get an oxygenated circuit. To further isolate the limb, a tourniquet is placed proximal to the site of the perfusion. Melphalan (Lphenylalanine mustard) has been the standard drug used in ILP because of its effıcacy and toxicity profıle. 4 Drug concentrations in the limb are 20-times higher than can be achieved From the Erasmus MC Cancer Institute, Rotterdam, Netherlands. Disclosures of potential conflicts of interest are found at the end of this article. Corresponding author: Dirk J. Grünhagen, MD, PhD, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA Rotterdam, Netherlands; email: d.grunhagen@erasmusmc.nl. © 2015 by American Society of Clinical Oncology. e528 2015 ASCO EDUCATIONAL BOOK | asco.org/edbook
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AMERICAN SOCIETY OF CLINICAL ONCOLO
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American Society of Clinical Oncolo
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Controversies in Neoadjuvant Therap
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Clinical Trials of Precision Medici
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Managing Ovarian Cancer in the Olde
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Updates in the Multimodality Manage
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PEDIATRIC ONCOLOGY Real-Time Molecu
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2015 ASCO Annual Meeting Disclosure
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2015 Educational Book Expert Panel
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James Marshall, PhD Roswell Park Ca
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2015 Annual Meeting Supporters* MIS
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David Yurman Corporate Allies Conqu
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GYNECOLOGIC CANCER Cervical Cancer
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GYNECOLOGIC CANCER Managing Ovarian
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DUSKA, TEW, AND MOORE KEY POINTS A
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GYNECOLOGIC CANCER Treatment of the
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CHEMOTHERAPY FOR PATIENTS WITH BMOC
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HEALTH SERVICES RESEARCH AND QUALIT
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INDUSTRY AND ONCOLOGY KEY POINTS F
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INDUSTRY AND ONCOLOGY by (covered)
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CANCER CARE QUALITY: CURRENT STATE
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MANAGING OLDER PATIENTS WITH ALL Th
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TREATMENT OF PHILADELPHIA CHROMOSOM
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CD19 CAR THERAPY FOR ALL FIGURE 1.
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CD19 CAR THERAPY FOR ALL 5. Zhou G,
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NEW TARGETED THERAPIES FOR iNHL New
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MICHAEL W. DEININGER TABLE 1. Defin
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PEMMARAJU AND MOLITERNO TABLE 1. Ac
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GERBER, PAIK, AND DOWLATI a tumor t
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LUNG CANCER Updates in the Multimod
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WOODARD AND JABLONS section, becaus
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NASSER HANNA Current Standards and
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NASSER HANNA At the 2014 ASCO Annua
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NASSER HANNA culty of this task. Va
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LYMPHOMA AND PLASMA CELL DISORDERS
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NOWAKOWSKI AND CZUCZMAN sociated wi
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CHEAH, OKI, AND FANALE Novel Treatm
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Page 754 and 755: KLEPIN, RODIN, AND HURRIA Treating
Page 756 and 757: KLEPIN, RODIN, AND HURRIA plication
Page 758 and 759: KLEPIN, RODIN, AND HURRIA plan was
Page 760 and 761: KLEPIN, RODIN, AND HURRIA patient-s
Page 762 and 763: KLEPIN, RODIN, AND HURRIA 62. Blanc
Page 764 and 765: PERIPHERAL NEUROTOXICITY IN CANCER
Page 772 and 773: PARTRIDGE, JACOBSEN, AND ANDERSEN C
Page 774 and 775: PARTRIDGE, JACOBSEN, AND ANDERSEN c
Page 776 and 777:
PARTRIDGE, JACOBSEN, AND ANDERSEN w
Page 778 and 779:
PARTRIDGE, JACOBSEN, AND ANDERSEN v
Page 780 and 781:
LESLIE R. SCHOVER Sexual Healing in
Page 782 and 783:
LESLIE R. SCHOVER tinuous ADT in pr
Page 784 and 785:
LESLIE R. SCHOVER 12. Potosky AL, H
Page 786 and 787:
CATHERINE H. VAN POZNAK TABLE 1. Wo
Page 788 and 789:
CATHERINE H. VAN POZNAK (tamoxifen,
Page 790 and 791:
CATHERINE H. VAN POZNAK TABLE 3. FD
Page 792 and 793:
CATHERINE H. VAN POZNAK premenopaus
Page 794 and 795:
SHARI GOLDFARB KEY POINTS Brea
Page 796 and 797:
SHARI GOLDFARB and friction with va
Page 798 and 799:
SHARI GOLDFARB importance both duri
Page 800 and 801:
PATIENT AND SURVIVOR CARE Moving Su
Page 802 and 803:
MAYER ET AL TABLE 1. Quality Metric
Page 804 and 805:
MAYER ET AL to enhance the quality
Page 806 and 807:
MAYER ET AL FIGURE 2. (A) Infertili
Page 808 and 809:
MAYER ET AL efıcial suggests that
Page 810 and 811:
PATIENT AND SURVIVOR CARE The Chall
Page 812 and 813:
BRUERA AND PAICE Choice of Opioid a
Page 814 and 815:
BRUERA AND PAICE toxicity and proce
Page 816 and 817:
BRUERA AND PAICE effective. Basic s
Page 818 and 819:
PEDIATRIC ONCOLOGY Real-Time Molecu
Page 820 and 821:
CARROLL, RAETZ, AND MEYER KEY POINT
Page 822 and 823:
CARROLL, RAETZ, AND MEYER most are
Page 824 and 825:
CARROLL, RAETZ, AND MEYER markers a
Page 826 and 827:
PEDIATRIC ONCOLOGY Translating Surv
Page 828 and 829:
REDUCING THE BURDEN OF LATE EFFECTS
Page 830 and 831:
Page 832 and 833:
Page 834 and 835:
Page 836 and 837:
PROFESSIONAL DEVELOPMENT The Challe
Page 838 and 839:
ADVANCES IN WEBSITE INFORMATION RES
Page 840 and 841:
Page 842 and 843:
Page 844 and 845:
Page 846 and 847:
COMMUNICATION AND TECHNOLOGY: IT’
Page 848 and 849:
Page 850 and 851:
Page 852 and 853:
PATIENT-REPORTED OUTCOMES IN ONCOLO
Page 854 and 855:
PATIENT-REPORTED OUTCOMES IN ONCOLO
Page 856 and 857:
PROFESSIONAL DEVELOPMENT Trends, An
Page 858 and 859:
CLINICAL ONCOLOGY PRACTICE 2015 FIG
Page 860 and 861:
CLINICAL ONCOLOGY PRACTICE 2015 (6.
Page 862 and 863:
CLINICAL ONCOLOGY PRACTICE 2015 Pro
Page 864 and 865:
ADJUVANT/NEOADJUVANT MEDICAL THERAP
Page 866 and 867:
Page 868 and 869:
Page 870 and 871:
INDICATIONS FOR ADJUVANT RADIATION
Page 872 and 873:
Page 874 and 875:
Page 876 and 877:
Page 878 and 879:
SARCOMA Latest Advances in Systemic
Page 880 and 881:
SYSTEMIC THERAPY FOR OSTEOSARCOMA A
Page 882 and 883:
SYSTEMIC THERAPY FOR OSTEOSARCOMA A
Page 884 and 885:
RETHINKING TREATMENT FOR CHONDROSAR
Page 886 and 887:
Page 888 and 889:
Page 890 and 891:
Page 892 and 893:
BONE SARCOMAS IN ADULTS local disea
Page 894 and 895:
BONE SARCOMAS IN ADULTS structure a
Page 896 and 897:
SARCOMA Well-Differentiated and Ded
Page 898 and 899:
ABBAS MANJI ET AL ticular region. 7
Page 900 and 901:
ABBAS MANJI ET AL MYXOID (ROUND CEL
Page 902 and 903:
ABBAS MANJI ET AL versus doxorubici
Page 904 and 905:
SHLUSH AND HERSHKOVITZ Clonal Evolu
Page 906 and 907:
SHLUSH AND HERSHKOVITZ FIGURE 1. Ti
Page 908 and 909:
TUMOR BIOLOGY New Strategies to Und
Page 910 and 911:
KNAPP, DHAWAN, AND OSTRANDER in dog
Page 912 and 913:
KNAPP, DHAWAN, AND OSTRANDER TABLE
Page 914 and 915:
KNAPP, DHAWAN, AND OSTRANDER 14. Fe
Page 916 and 917:
SOURBIER, SRINIVASAN, AND LINEHAN M
Page 918 and 919:
SOURBIER, SRINIVASAN, AND LINEHAN F
Page 920 and 921:
SOURBIER, SRINIVASAN, AND LINEHAN T
Page 922:
Author Index Abbas Manji, Gulam ...
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