2010NCCN隆突性皮肤纤维肉瘤治疗指南

Continue NCCN Clinical Practice Guidelines in Oncology™ Dermatofibrosarcoma Protuberans V.1.2010 www.nccn.org Version 1.2010, 03/19/10 © 2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Guidelines Index DFSP Table of Contents Discussion, ReferencesDermatofibrosarcoma Protuberans Practice Guidelines in Oncology – v.1.2010NCCN ® NCCN Dermatofibrosarcoma Protuberans Panel Members * Stanley J. Miller, MD/Chair The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Murad Alam, MD Robert H. Lurie Comprehensive Cancer Center of Northwestern University James Andersen, MD City of Hope Comprehensive Cancer Center Daniel Berg, MD Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance Christopher K. Bichakjian, MD University of Michigan Comprehensive Cancer Center Glen Bowen, MD Huntsman Cancer Institute at the University of Utah Richard T. Cheney, MD Roswell Park Cancer Institute L. Frank Glass, MD H. Lee Moffitt Cancer Center & Research Institute � � � � � � � � � � ¶ ¶ ¶ Kishwer S. Nehal, MD Memorial Sloan-Kettering Cancer Center Kelly C. Nelson, MD Duke Comprehensive Cancer Center Paul Nghiem, MD, PhD Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance Thomas Olencki, DO Arthur G. James Cancer Hospital & Richard J. Solove Research Institute at The Ohio State University � � � � � � � ¶ ¶ ¶ ¶ ‡ Clifford S. Perlis, MD, MBe Fox Chase Cancer Center E. William Rosenberg, MD St. Jude Children’s Research Hospital/ University of Tennessee Cancer Institute Ashok R. Shaha, MD Memorial Sloan-Kettering Cancer Center Marshall M. Urist, MD University of Alabama at Birmingham Comprehensive Cancer Center Linda C. Wang, MD, JD Dana-Farber/Brigham and Women’s Cancer Center John A. Zic, MD Vanderbilt-Ingram Cancer Center � � � Dermatology ¶ Surgery/Surgical oncology Otolaryngology Pathology/Dermatopathology † Medical oncology § Radiotherapy/Radiation oncology ‡ Hematology/Hematology oncology * Writing Committee Member Continue NCCN Guidelines Panel Disclosures Roy C. Grekin, MD UCSF Helen Diller Family Comprehensive Cancer Center Dennis E. Hallahan, MD Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine Anne Kessinger, MD UNMC Eppley Cancer Center at The Nebraska Medical Center Nancy Y. Lee, MD Memorial Sloan-Kettering Cancer Center Nanette Liegeois, MD, PhD The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Daniel D. Lydiatt, DDS, MD UNMC Eppley Cancer Center at The Nebraska Medical Center Jeff Michalski, MD, MBA Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine William H. Morrison, MD The University of Texas M.D. Anderson Cancer Center � � � ¶ § † § ¶ ¶ § § Version 1.2010, 03/19/10 © 2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Guidelines Index DFSP Table of Contents Discussion, ReferencesDermatofibrosarcoma Protuberans Practice Guidelines in Oncology – v.1.2010NCCN ® Table of Contents NCCN Dermatofibrosarcoma Protuberans Panel Members Summary of Guidelines Updates Clinical Presentation, Preliminary Treatment, and Workup (DFSP-1) Treatment and Follow-up (DFSP-2) Excision (DFSP-A) Guidelines Index Print the Dermatofibrosarcoma Protuberans Guidelines Dermatofibrosarcoma Protuberans These guidelines are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult these guidelines is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient's care or treatment. The National Comprehensive Cancer Network makes no representations nor warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way. These guidelines are copyrighted by National Comprehensive Cancer Network. All rights reserved. These guidelines and the illustrations herein may not be reproduced in any form without the express written permission of NCCN. ©2010. For help using these documents, please click here Discussion References Clinical Trials: NCCN Categories of Evidence and Consensus: The believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. To find clinical trials online at NCCN member institutions, All recommendations are Category 2A unless otherwise specified. See NCCN click here: nccn.org/clinical_trials/physician.html NCCN Categories of of Evidence and Consensus Version 1.2010, 03/19/10 © 2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Guidelines Index DFSP Table of Contents Discussion, ReferencesDermatofibrosarcoma Protuberans Practice Guidelines in Oncology – v.1.2010NCCN ® Summary of the Guidelines updates Summary of changes in the 1.2010 version of the Dermatofibrosarcoma Protuberans guidelines from the 1.2009 version include: Footnote “d”; First sentence: “(180-200 cGy fractions per day)” changed to “( cGy fractions per day)”.� 200 ( )DFSP-2 Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. UPDATES Version 1.2010, 03/19/10 © 2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Guidelines Index DFSP Table of Contents Discussion, ReferencesDermatofibrosarcoma Protuberans Practice Guidelines in Oncology – v.1.2010NCCN ® Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. CLINICAL PRESENTATION CLINICAL FINDINGS Suspicious lesion H&P Complete skin exam � � Biopsy H&E Immunopanel (eg, CD34, factor XIIIa) Note and report evidence of fibrosarcoma change a � � � Inadequate biopsy Adequate biopsy Rebiopsya PRELIMINARY TREATMENT See Treatment (DFSP-2) aThis tumor is frequently misdiagnosed, even with multiple preliminary biopsies. DFSP-1 Version 1.2010, 03/19/10 © 2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Guidelines Index DFSP Table of Contents Discussion, ReferencesDermatofibrosarcoma Protuberans Practice Guidelines in Oncology – v.1.2010NCCN ® Consider radiation therapy or Imatinib mesylate d e Metastasis Consider clinical trial, imatinib mesylate , chemotherapy, RT or resection as feasible, given the specific clinical circumstances e Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. TREATMENT Excisionb Positive surgical margins Positive surgical margins Negative surgical margins Negative surgical margins Observe or Consider adjuvant RTc,d FOLLOW-UP � � Check primary site every 6-12 months Patient education about regular self-exam b c d The surgical approach to DFSP must be meticulously planned. Size and location of the tumor and cosmetic issues will dictate the most appropriate surgical procedure. Consider postoperative radiation therapy for large lesions or if there is concern about adequacy of surgical margins. 5,000-6,000 cGy for close-to-positive or positive margins (200 cGy fractions per day). Fields to extend widely beyond surgical margin (eg, 3-5 cm), when clinically feasible. Tumors lacking the t(17;22) translocation may not respond to imatinib. Molecular analysis of a tumor using cytogenetics may be useful prior to the institution of imatinib therapy. e See Excision (DFSP-A). Re-resectionb DFSP-2 Recurrence Re-resection as feasible or Consider RT if not given previously or Imatinib mesylate in cases where unacceptable functional or cosmetic outcomes will occur e Version 1.2010, 03/19/10 © 2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Guidelines Index DFSP Table of Contents Discussion, ReferencesDermatofibrosarcoma Protuberans Practice Guidelines in Oncology – v.1.2010NCCN ® Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. PRINCIPLES OF EXCISION Goal: Every effort should be made to achieve clear surgical margins. Tumor characteristics include long, irregular, subclinical extensions. Varied Approaches: Mohs technique Modified Mohs = Mohs technique with additional final margin for permanent section assessment. CCPDMA= Complete circumferential and peripheral deep-margin assessment. 2-4 cm margins to investing fascia of muscle or pericranium with clear pathologic margins, when clinically feasible. Reconstruction: Immediate reconstruction in most cases It is preferable to delay reconstruction involving extensive undermining or flaps until negative surgical margins are assessed and certified pathologically clear. If there is concern that the surgical margins are not completely clear, avoid undermining and consider split thickness skin grafting (STSG) to monitor for recurrence. � � � � � � � � 1 See the NCCN Soft Tissue Sarcoma Guideline for Principles of Sarcoma Surgery (SARC-C) DFSP-A 1Mohs technique is used primarily in DFSP to insure complete removal and clear margins, and secondarily for its tissue sparing capabilities. Version 1.2010, 03/19/10 © 2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-1 Guidelines Index DFSP Table of Contents Discussion, References Practice Guidelines in Oncology – v.1.2010 Dermatofibrosarcoma Protuberans ® NCCN Discussion NCCN Categories of Evidence and Consensus Category 1: The recommendation is based on high-level evidence (e.g. randomized controlled trials) and there is uniform NCCN consensus. Category 2A: The recommendation is based on lower-level evidence and there is uniform NCCN consensus. Category 2B: The recommendation is based on lower-level evidence and there is nonuniform NCCN consensus (but no major disagreement). Category 3: The recommendation is based on any level of evidence but reflects major disagreement. All recommendations are category 2A unless otherwise noted. Overview NCCN Non-Melanoma Skin Cancer Panel has developed these guidelines outlining the treatment of dermatofibrosarcoma protuberans (DFSP) to supplement their other guidelines (NCCN Basal Cell and Squamous Cell Skin Cancers Guidelines and NCCN Merkel Cell Carcinoma Guidelines). The NCCN Soft Tissue Sarcoma Panel provided expert input in the development of DFSP guidelines. DFSP is an uncommon, low-grade sarcoma of fibroblast origin with an incidence rate of 4.2 to 4.5 cases per million persons per year in the United States.1,2 It rarely metastasizes. However, initial misdiagnosis, prolonged time to accurate diagnosis, and large tumor size at the time of diagnosis is common. Three-dimensional reconstruction of DFSP3 has revealed tumors with highly irregular shapes and frequent finger-like extensions.4 As a result, incomplete removal and subsequent recurrence are common. The local recurrence rate for DFSP in studies ranges from 0-60%, whereas the rate of development of regional or distant metastatic disease is only 1% and 4-5%, respectively.5 Diagnosis As with all solid tumors, clinical suspicion is confirmed by biopsy. In most cases, examination of hematoxylin and eosin-stained specimens by light microscopy results in an unequivocal diagnosis. However, differentiation of DFSP from dermatofibroma can be difficult, at times. In such instances, immunostaining with CD34, factor XIIIa, metallothioneins, tenascin, and/or stromelysin-3 may be useful.5-9 Therefore, the panel recommends that appropriate and confirmatory immunostaining be performed in all cases of suspected DFSP. Finally, it is unclear whether the histologic features of a high mitotic rate or evidence of fibrosarcomatous change (typically in more than 5% of the surgical specimen) have prognostic significance in DFSP. Studies in the biomedical literature both support10,11 and refute12 this notion. Thus, the panel requested that these two features be noted in all pathology reports assessing this tumor. When the clinician’s suspicion for DFSP is high, but the initial biopsy does not support the diagnosis, re-biopsy is recommended and may reveal tumor presence. Multiple non-supportive or equivocal biopsies over time, before definitive diagnosis, are common in the clinical history for this tumor; thus, DFSP is frequently misdiagnosed. Because metastatic disease is rare, an extensive workup is not routinely indicated unless suggestive aspects in the history and physical examination (H&E) or adverse prognostic histologic features are present. Stage I is local disease, stage II is regional disease, and stage III is distant disease. Treatment Initial treatment of DFSP is surgical. Because of its proclivity for irregular and frequently deep subclinical extensions, every effort should Version 1.2010, 03/19/10 © 2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-2 Guidelines Index DFSP Table of Contents Discussion, References Practice Guidelines in Oncology – v.1.2010 Dermatofibrosarcoma Protuberans ® NCCN be made to completely remove this tumor at the time of initial therapy. The surgical approach to DFSP must be meticulously planned. Size and location of the tumor as well as cosmetic issues will dictate the most appropriate surgical procedure. As noted in the algorithm (DFSP-A), some form of complete histologic assessment of all surgical margins before reconstruction is preferred. See NCCN Soft Tissue Sarcoma Guidelines for principles of sarcoma surgery (SARC-C). Mohs or modified Mohs surgery,3,4,13-20 and traditional wide excision,21 typically with 2-4 cm margins to investing fascia that are subsequently verified to be clear by traditional pathologic examination, are all methods to achieve complete histologic assessment.14,22 In a recent retrospective review of 48 patients, positive margins were more frequent with wide excision than with Mohs, but the local recurrence rates were statistically similar (3.6% vs 0%, respectively, P = 1.0).23 Immediate reconstruction can be performed in most cases. If there is concern that the surgical margins are not completely clear, tissue rearrangement should be avoided, and split thickness skin grafting (STSG) should be considered to monitor for recurrence. DFSP is characterized by a translocation between chromosomes 17 and 22 [t(17:22)] resulting in the over expression of platelet-derived growth factor receptor β (PDGFRB).24-26 These findings suggest that targeting PDGF receptors may lead to the development of new therapeutic options for DFSP. In recently published results, imatinib mesylate, a protein tyrosine kinase inhibitor, has shown clinical activity against localized and metastatic DFSP tumors containing t(17:22).27-30 Imatinib mesylate has recently been approved by the FDA for the treatment of unresectable, recurrent and/or metastatic DFSP in adult patients.31 Because tumors lacking the t(17;22) translocation may not respond to imatinib molecular analysis of a tumor using cytogenetics may be useful prior to the institution of imatinib therapy. Radiation has occasionally been used as a primary therapeutic modality for DFSP,32 but it is more commonly used as adjuvant therapy after surgery.33-35 Postoperative radiation therapy can also be considered for negative margins for large lesions or if there is concern about the adequacy of the surgical margins. Postoperative radiation therapy or imatinib mesylate should be considered for positive surgical margins following re-resection (DFSP-2), if further resection is not feasible (unresectable disease). Radiation therapy, if not given previously, or imatinib mesylate should be considered for patients with recurrent disease, if additional resection would lead to unacceptable functional or cosmetic outcomes (DFSP-2). Clinical trials, imatinib mesylate, chemotherapy, radiation therapy or re-resection as feasible under specific clinical circumstances should all be considered in the rare event of metastatic disease. Several clinical trials are underway for the treatment of DFSP with imatinib. To access current clinical trials, go to www.clinicaltrials.gov. Follow-up Finally, given the historically high local recurrence rates for DFSP, ongoing clinical follow-up of the primary site every 6-12 months is indicated, with re-biopsy of any suspicious regions. Although metastatic disease is rare, a guided H&E should be performed as well, with additional imaging studies as indicated. Version 1.2010, 03/19/10 © 2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. REF-1 Guidelines Index DFSP Table of Contents Discussion, References Practice Guidelines in Oncology – v.1.2010 Dermatofibrosarcoma Protuberans ® NCCN References 1. Criscione VD, Weinstock MA. Descriptive epidemiology of dermatofibrosarcoma protuberans in the United States, 1973 to 2002. J Am Acad Dermatol. 2007;56:968-973. 2. Rouhani P, Fletcher CD, Devesa SS, Toro JR. Cutaneous soft tissue sarcoma incidence patterns in the U.S. : an analysis of 12,114 cases. Cancer. 2008;113:616-627. 3. Haycox CL, Odland PB, Olbricht SM, Casey B. Dermatofibrosarcoma protuberans (DFSP): growth characteristics based on tumor modeling and a review of cases treated with Mohs micrographic surgery. Ann Plast Surg. 1997;38:246-251. 4. Ratner D, Thomas CO, Johnson TM, et al. Mohs micrographic surgery for the treatment of dermatofibrosarcoma protuberans. Results of a multiinstitutional series with an analysis of the extent of microscopic spread. J Am Acad Dermatol. 1997;37:600-613. 5. Vidimos AT, Helm TN, Papay FA. Dermatofibrosarcoma protuberans. In: Cutaneous Oncology: Pathophysiology, Diagnosis, and Management. Malden, MA: Blackwell Scientific. 1998:822-831. 6. Cribier B, Noacco G, Peltre B, Grosshans E. Stromelysin 3 expression: a useful marker for the differential diagnosis dermatofibroma versus dermatofibrosarcoma protuberans. J Am Acad Dermatol. 2002;46:408-413. 7. Kahn HJ, Fekete E, From L. Tenascin differentiates dermatofibroma from dermatofibrosarcoma protuberans: comparison with CD34 and factor XIIIa. Hum Pathol. 2001;32:50-56.