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ADJUVANT/NEOADJUVANT MEDICAL THERAPY OF ADULT SOFT TISSUE SARCOMAS resected retroperitoneal soft tissue sarcoma: histology-specifıc overall survival and disease-free survival nomograms built on major sarcoma center data sets. J Clin Oncol. 2013;31:1649-1655. 6. Iasonos A, Keung EZ, Zivanovic O, et al. External validation of a prognostic nomogram for overall survival in women with uterine leiomyosarcoma. Cancer. 2013;119:1816-1822. 7. Sarcoma Meta-analysis Collaboration. Adjuvant chemotherapy for localised resectable soft-tissue sarcoma of adults: meta-analysis of individual data. Lancet. 1997;350:1647-1654. 8. Pervaiz N, Colterjohn N, Farrokhyar F, et al. A systematic meta-analysis of randomized controlled trials of adjuvant chemotherapy for localized resectable soft-tissue sarcoma. Cancer. 2008;113:573-581. 9. Woll PJ, Reichardt P, Le Cesne A, et al. Adjuvant chemotherapy with doxorubicin, ifosfamide, and lenograstim for resected soft-tissue sarcoma (EORTC 62931): a multicentre randomised controlled trial. Lancet Oncol. 2012;13:1045-1054. 10. Gronchi A, Frustaci S, Mercuri M, et al. Short, full-dose adjuvant chemotherapy in high-risk adult soft tissue sarcomas: a randomized clinical trial from the Italian Sarcoma Group and the Spanish Sarcoma Group. J Clin Oncol. 2012;30:850-856. 11. Frustaci S, Gherlinzoni F, De Paoli A, et al. Adjuvant chemotherapy for adult soft tissue sarcomas of the extremities and girdles: results of the Italian randomized cooperative trial. J Clin Oncol. 2001;19:1238- 1247. 12. Frustaci S, De Paoli A, Bidoli E, et al. Ifosfamide in the adjuvant therapy of soft tissue sarcomas. Oncology. 2003;65:80-84. 13. Bramwell V, Rouesse J, Steward W, et al. Adjuvant CYVADIC chemotherapy for adult soft tissue sarcoma-reduced local recurrence but no improvement in survival: a study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. J Clin Oncol. 1994;12:1137-1149. 14. Hensley ML, Ishill N, Soslow R, et al. Adjuvant gemcitabine plus docetaxel for completely resected stages I-IV high grade uterine leiomyosarcoma: results of a prospective study. Gynecol Oncol. 2009; 112:563-567. 15. Hensley ML, Wathen JK, Maki RG, et al. Adjuvant therapy for highgrade, uterus-limited leiomyosarcoma: results of a phase 2 trial (SARC 005). Cancer. 2013;119:1555-1561. 16. von Mehren M, Randall RL, Benjamin RS, et al. Soft tissue sarcoma, version 2.2014. J Natl Compr Canc Netw. 2014;12:473-483. 17. ESMO/European Sarcoma Network Working Group. Soft tissue and visceral sarcomas: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25 (suppl 3):iii102-iii112. 18. Judson I, Verweij J, Gelderblom H, et al. Doxorubicin alone versus intensifıed doxorubicin plus ifosfamide for fırst-line treatment of advanced or metastatic soft-tissue sarcoma: A randomised controlled phase 3 trial. Lancet Oncol. 2014;15:415-423. 19. van der Graaf WT, Blay JY, Chawla SP, et al. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebocontrolled phase 3 trial. Lancet. 2012;379:1879-1886. 20. Casali PG, Fumagalli E, Gronchi A. Adjuvant therapy of gastrointestinal stromal tumors (GIST). Curr Treat Options Oncol. 2012;13:277-284. 21. Casali PG, Bruzzi P, Bogaerts J, et al. Rare Cancers Europe (RCE) methodological recommendations for clinical studies in rare cancers: a European consensus position paper. Ann Oncol. 2015;26:300-306. asco.org/edbook | 2015 ASCO EDUCATIONAL BOOK e633
DICKIE, HAAS, AND O’SULLIVAN Adjuvant Radiation for Soft Tissue Sarcomas Colleen I. Dickie, MSc, Rick Haas, MD, PhD, and Brian O’Sullivan, MD, FRCPC OVERVIEW Over recent decades, limb-preservation surgery in combination with radiotherapy achieves local control rates exceeding 90% for extremity soft tissue sarcoma (STS). Local control is not as successful for retroperitoneal sarcoma (approximately 60%) despite aggressive surgical approaches including en bloc resection of uninvolved adjacent organs combined with intensity modulated radiotherapy (IMRT). This review will discuss the indications for adjuvant radiation therapy (RT) for primary presentation of soft tissue sarcoma: “What,” referring to the type and manner of planning and delivery of RT; “When,” referring to the timing and scheduling of RT; and “Why,” referring to the rationale for the use of RT will be addressed. From a practical stand point, this Educational Chapter on “adjuvant RT” will focus on pre- and postoperative RT in the context of gross total resection for extremity and retroperitoneal soft tissue sarcoma, the two most frequent paradigms for the use of adjuvant RT. Various types of RT can be used in the treatment of STS and require attention to the application of appropriate principles for their implementation. Especially important are issues surrounding the choice of target volumes, the treatment of normal anatomy termed “organs at risk,” and processes to ensure reliability in treatment delivery. Most experience in adjuvant RT of STS is based on external beam radiotherapy (EBRT). Nevertheless, other modalities exist including brachytherapy, intraoperative RT, and hadrons (i.e., protons and carbon ions). TYPES AND METHODS OF RADIOTHERAPY DELIVERY: THE “WHAT” COMPONENT Intensity Modulated Radiotherapy Target coverage and protection of normal tissues appear to be superior for IMRT compared with traditional techniques in extremity STS (ESTS). 1,2 A recent retrospective review spanning noncoincident treatment time periods compared surgery combined with either IMRT (165 patients) or conventional EBRT (154 patients). Allowing for known limitations associated with studies involving treatments deployed over different eras, IMRT demonstrated signifıcantly reduced local recurrence (LR) for primary ESTS (7.6% LR for IMRT vs. 15.1% LR for conventional RT; p 0.02). 3 Two recently completed prospective phase II trials, from Princess Margaret (NCT00188175) and the Radiation Therapy Oncology Group (RTOG 0630; NCT00589121), investigated if preoperative image-guided radiotherapy (IGRT) using conformal RT/IMRT can reduce RT related morbidities. The characteristics of the Princess Margaret Hospital (PMH) and RTOG 0630 trials are not identical in several ways and are contrasted (Table 1). 4,5 The PMH trial showed less wound healing complication rates (30.5%) in lower extremity compared with the 43% risk in the previous Canadian Sarcoma Group NCIC SR2 trial that only used two-dimensional and three-dimensional RT. 6 The need for tissue transfer, RT chronic morbidities, and subsequent secondary operations for wound complications was reduced while maintaining good function and local control (93.2%). The recently published results of the RTOG- 0630 trial reported a signifıcant reduction of late toxicities compared with the NCIC-SR2 trial (10.5% vs. 37% in SR2), which is very similar to the IGRT PMH trial. Importantly, both trials defıned the clinical target volume (CTV) differently (longitudinal margin of 3 cm from the gross tumor for high-grade lesions and 2 cm for low-grade lesions vs. 4 cm longitudinal margins in the PMH trial). Potentially, the reduction in CTV margins of this degree could explain the improvement in limb function with comparable local control, although, an alternative possibility is the reduction in normal tissues receiving the target dose in all dimensions that is shared by both studies. Brachytherapy Brachytherapy has several theoretical advantages. With appropriate selection, local dose intensifıcation to target structures with surrounding normal tissue protection is feasible. The treatment time is shorter, theoretically limiting tumor From the Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada; Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada; Department of Radiotherapy, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands. Disclosures of potential conflicts of interest are found at the end of this article. Corresponding author: Brian O’Sullivan, MD, FRCPC, Princess Margaret Hospital, University of Toronto, Rm 5-624, 610 University Ave., Toronto, ON M5G 2M9, Canada; email: brian.o’sullivan@rmp.uhn.on.ca. © 2015 by American Society of Clinical Oncology. e634 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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INVITED ARTICLES This year’s invi
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WONG, CAPASSO, AND ECKHARDT 3 3 sc
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WONG, CAPASSO, AND ECKHARDT terize
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STEPHEN T. SONIS portantly, patient
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HUSSAIN AND DIPAOLA TABLE 1. U.S. F
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HUSSAIN AND DIPAOLA mizing use of p
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EDWARD S. KIM TABLE 1. Selected Umb
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INVITED ARTICLES HEAD AND NECK CANC
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GROSS AND COHEN treatments are poor
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GILBERT ET AL tional scholars, lead
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INVITED ARTICLES GASTROINTESTINAL C
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ENG ET AL colorectal cancer. Indeed
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INVITED ARTICLES BREAST CANCER I Wi
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WILLIAM M. SIKOV gational treatment
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BREAST CANCER Controversies in Neoa
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BREAST CANCER Individualizing the A
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ADDRESSING BARRIERS TO BREAST CANCE
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REFORMING THE BUY-AND-BILL CHEMOTHE
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CARE DELIVERY AND PRACTICE MANAGEME
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INTEGRATING ICD-10 IN YOUR PRACTICE
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CENTRAL NERVOUS SYSTEM TUMORS Brain
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AHLUWALIA AND WINKLER TARGETING ANG
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MAWRIN, CHUNG, AND PREUSSER Biology
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MICHAEL A. POSTOW Managing Immune C
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PRECISION THERAPY FOR RECTAL CANCER
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EGIDIO DEL FABBRO tion of precachex
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EGIDIO DEL FABBRO FIGURE 3. Mechani
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GERM CELL TUMORS: LOOKING TO THE FU
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SALVAGE CHEMOTHERAPY Salvage Therap
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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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MANAGING OLDER PATIENTS WITH ALL TA
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MANAGING OLDER PATIENTS WITH ALL FI
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MANAGING OLDER PATIENTS WITH ALL ra
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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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PEMMARAJU AND MOLITERNO TABLE 1. Ac
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PEMMARAJU AND MOLITERNO drome (BCS)
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BEYOND SECOND-LINE TREATMENT FOR LU
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GERBER, PAIK, AND DOWLATI gression
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LILENBAUM, LEIGHL, AND NEUBAUER tha
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BERNARDO H.L. GOULART The Value of
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BERNARDO H.L. GOULART every 6 month
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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 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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DAVID W. SCOTT Cell-of-Origin in Di
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CHEAH, OKI, AND FANALE Novel Treatm
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CHEAH, OKI, AND FANALE eral T cell
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CHEAH, OKI, AND FANALE 77. Cairns R
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STEPHEN ANSELL associated with pati
Page 668 and 669:
STEPHEN ANSELL Disclosures of Poten
Page 670 and 671:
MATEOS AND SAN MIGUEL Smoldering Mu
Page 672 and 673:
MATEOS AND SAN MIGUEL years. This f
Page 674 and 675:
MATEOS AND SAN MIGUEL previously me
Page 676 and 677:
MATEOS AND SAN MIGUEL TABLE 2. Risk
Page 678 and 679:
MATEOS AND SAN MIGUEL 30. Rajkumar
Page 680 and 681:
BHUTANI, LANDGREN, AND USMANI of th
Page 682 and 683:
BHUTANI, LANDGREN, AND USMANI bette
Page 684 and 685:
BHUTANI, LANDGREN, AND USMANI fıne
Page 686 and 687:
BHUTANI, LANDGREN, AND USMANI FIGUR
Page 688 and 689:
BHUTANI, LANDGREN, AND USMANI 15. K
Page 690 and 691:
MOREAU AND TOUZEAU Multiple Myeloma
Page 692 and 693:
MOREAU AND TOUZEAU other effıcacy
Page 694 and 695:
MOREAU AND TOUZEAU was able to indu
Page 696 and 697:
MOREAU AND TOUZEAU Group consensus
Page 698 and 699:
LYMPHOMA AND PLASMA CELL DISORDERS
Page 700 and 701:
MANAGEMENT OF CLL Up-Front Manageme
Page 702 and 703:
MANAGEMENT OF CLL than 17p-/TP53mut
Page 704 and 705:
MANAGEMENT OF CLL could be associat
Page 706 and 707:
MANAGEMENT OF CLL tion by nonmalign
Page 708 and 709:
MANAGEMENT OF CLL fludarabine and c
Page 710 and 711:
MANAGEMENT OF CLL lymphocytic leuke
Page 712 and 713:
PROGNOSTIC FACTORS AND ADJUVANT RAD
Page 714 and 715:
Page 716 and 717:
Page 718 and 719:
MERKEL CELL CARCINOMA Merkel Cell C
Page 720 and 721:
MERKEL CELL CARCINOMA tions in PIK3
Page 722 and 723:
MERKEL CELL CARCINOMA treating MCC
Page 724 and 725:
MERKEL CELL CARCINOMA 32. Leonard J
Page 726 and 727:
MELANOMA/SKIN CANCERS Locoregional
Page 728 and 729:
PERFUSION AND INFUSION IN THE ERA O
Page 730 and 731:
Page 732 and 733:
Page 734 and 735:
NEOADJUVANT THERAPY OF MELANOMA Neo
Page 736 and 737:
NEOADJUVANT THERAPY OF MELANOMA TAB
Page 738 and 739:
NEOADJUVANT THERAPY OF MELANOMA ity
Page 740 and 741:
NEOADJUVANT THERAPY OF MELANOMA 4.
Page 742 and 743:
MELANOMA/SKIN CANCERS Targeted Mole
Page 744 and 745:
SULLIVAN ET AL FIGURE 1. Relevant S
Page 746 and 747:
SULLIVAN ET AL Resistance to BRAF i
Page 748 and 749:
SULLIVAN ET AL TABLE 1. Clinical Tr
Page 750 and 751:
SULLIVAN ET AL 17. Halait H, Demart
Page 752 and 753:
SULLIVAN ET AL NRAS-mutant melanoma
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 766 and 767:
Page 768 and 769:
Page 770 and 771:
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 836 and 837: PROFESSIONAL DEVELOPMENT The Challe
Page 838 and 839: ADVANCES IN WEBSITE INFORMATION RES
Page 846 and 847: COMMUNICATION AND TECHNOLOGY: IT’
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: ADJUVANT/NEOADJUVANT MEDICAL THERAP
Page 870 and 871: INDICATIONS FOR ADJUVANT RADIATION
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 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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