2010NCCN+Merkel细胞癌治疗指南

Continue NCCN Clinical Practice Guidelines in Oncology™ Merkel Cell Carcinoma 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 MCC Table of Contents Discussion, ReferencesMerkel Cell Carcinoma Practice Guidelines in Oncology – v.1.2010NCCN ® NCCN Merkel Cell Carcinoma 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 MCC Table of Contents Discussion, ReferencesMerkel Cell Carcinoma Practice Guidelines in Oncology – v.1.2010NCCN ® Table of Contents NCCN Merkel Cell Carcinoma Panel Members Guidelines Index Print the Merkel Cell Carcinoma Guidelines Summary of Guidelines Updates Clinical Presentation, Preliminary Workup, and Clinical Findings (MCC-1) Primary Treatment of Clinical N0 (MCC-2) Primary Treatment of Clinical N+ (MCC-3) Treatment of Clinical M1(MCC-4) Follow-up and Recurrence (MCC-5) Principles of Radiation Therapy (MCC-A) Principles of Excision (MCC-B) Chemotherapy Agents (MCC-C) Merkel Cell Carcinoma 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 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 MCC Table of Contents Discussion, ReferencesMerkel Cell Carcinoma Practice Guidelines in Oncology – v.1.2010NCCN ® Summary of changes in the 1.2010 version of the Merkel Cell Carcinoma guidelines from the 1.2009 version include: After “Clinical N0”: Formerly the page was separated into 3 pathways “Prior wide excision”, No prior wide excision, and “Head and Neck cases”. The pathways have been revised into two separate pathways “Prior wide excision” and No prior wide excision” for clarity. Footnote “i” that states, “Because of the high rate of false negativity, SLNB may not always be considered reliable in the head and neck region. However, it may have prognostic value” is new to the page. Footnote “f” regarding when to consider observation was revised. Footnote “j” that states, “ In selected cases in which surgical excision is not possible, surgery is refused by the patient, or would result in significant morbidity, radiation mono-therapy may be considered” is new to the page. Footnote “2” is new to the page. Footnotes “4” and “5” were revised. Principles of Excision. Footnote “2” that states, “If Mohs is used for MCC, a debulked specimen of the central portion of the tumor should be sent for permanent section microstaging,” is new to the page. Chemotherapy Agents Disseminated disease: The phrase “As clinical judgment indicates” was added. “Cisplatin plus etoposide” changed to “Cisplatin ± etoposide”. “Carboplatin plus etoposide” changed to “Carboplatin ± etoposide”. “Topetecan has been used” changed to “Topetecan”. � � � � � � � � � Clinical Presentation; Suspicious lesion; Second bullet: “Complete skin and regional lymph node examination” changed to “Complete skin and lymph node examination”. Footnote “b”: PET changed to PET-CT. (Also for ) The sentence “It may be useful in identifying distant metastases.” was added. Principles of Radiation Therapy Nodal bed; No SLNB or LN Dissection: The second and third arrows regarding dosing for clinical adenopathy for head and neck/axilla groin were combined and are now listed as “Clinically evident lymphadenopathy”. � � � � � � MCC-3 � � ( ) ( ) ( ): MCC-1 MCC-2 MCC-A ( ): ( ): MCC-B MCC-C Summary of the Guidelines updates UPDATES 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. 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 MCC Table of Contents Discussion, ReferencesMerkel Cell Carcinoma Practice Guidelines in Oncology – v.1.2010NCCN ® MCC-1 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 PRELIMINARY WORKUP CLINICAL FINDINGS Suspicious lesion H&P Complete skin and lymph node examination � � Biopsy H&E Immunopanel � � a � � Imaging studies as clinically indicated Consider multidisciplinary tumor board consultation b Clinical N+ Clinical N0 Clinical M1 Merkel cell carcinoma See Primary and Adjuvant Treatment (MCC-2) See Primary and Adjuvant Treatment (MCC-3) See Treatment (MCC-4) DIAGNOSIS ADDITIONAL WORKUP a b An appropriate immunopanel should preferably include CK-20 and thyroid transcription factor-1 (TTF-1). Imaging (CT, MR, or PET-CT) may be indicated to evaluate for the possibility of a skin metastasis from a noncutaneous primary neuroendocrine carcinoma (eg, small cell lung cancer), especially in cases where CK-20 is negative. It may be useful in identifying distant metastases. 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 MCC Table of Contents Discussion, ReferencesMerkel Cell Carcinoma Practice Guidelines in Oncology – v.1.2010NCCN ® MCC-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. Clinical N0 Prior wide local excisionc No prior wide local excision Sentinel lymph node biopsy with appropriate immunopanel (SLN) g h Excisionj Negative margins See Follow-up (MCC-5) SLN positive SLN negative �Multidisciplinary tumor board consultation � � Node dissection and/or radiation therapy May consider adjuvant chemotherapy e,k l,m Radiation therapy or Consider observation d,e f PRIMARY AND ADJUVANT TREATMENT: CLINICAL N0 DISEASE c l After wide local excision, sentinel lymph node biopsy may be considered in selected patients, although accuracy of results may be compromised, especially in non- extremity regions. Radiation therapy to primary site, in transit lymphatics (when feasible), and/or draining nodal basins. Consider observation of the tumor bed, in cases where the primary tumor is small, widely excised with no other adverse risk factors. Because of the high rate of false negativity, SLNB may not always be considered reliable in the head and neck region. However, it may have prognostic value. d e f h i m g j The preferred treatment sequence is for the sentinel lymph node biopsy to precede the excision. In selected cases in which complete surgical excision is not possible, surgery is refused by the patient, or would result in significant morbidity, radiation mono-therapy may be considered For lymph nodes that are positive only by immunohistochemical methods but not H+E, consider RT as the sole therapy to the draining nodal basin(s). An appropriate immunopanel for SLN examination should preferably include CK-20, and pancytokeratins (AE1/AE3). Available retrospective studies do not suggest prolonged survival benefit for adjuvant chemotherapy. k See Principles of Radiation Therapy (MCC-A) See Chemotherapy Agents (MCC-C) . . See Principles of Excision (MCC-B) See Principles of Radiation Therapy [MCC-A]) . ( . Radiation therapy or Consider observation d,e f Head and neck cases Radiation therapy to primary site, nodal beds and in transit lymphatics e Trunk and extremities Consider sentinel lymph node (SLN) biopsy with appropriate immunopanel g,i h Excisionj SLN Biopsy 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 MCC Table of Contents Discussion, ReferencesMerkel Cell Carcinoma Practice Guidelines in Oncology – v.1.2010NCCN ® MCC-3 � � � Multidisciplinary tumor board consultation Node dissection and/or radiation therapy May consider adjuvant chemotherapy e l,m 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 N+ � � FNA Immunopanelh M0 M1 See Treatment of M1 disease (MCC-4) FNA Negative Open biopsy Biopsy positive Biopsy negative Follow appropriate Clinical N0 pathway (MCC-2) PRIMARY AND ADJUVANT TREATMENT: CLINICAL N+ DISEASE e h n An appropriate immunopanel for LN examination should preferably include CK-20 and pancytokeratins (AE1/AE3). Available retrospective studies do not suggest prolonged survival benefit for adjuvant chemotherapy. Imaging (CT, MR, or PET-CT) may be indicated to evaluate extent of lymph node and/or visceral organ involvement. l m See Principles of Radiation Therapy (MCC-A) See Chemotherapy Agents (MCC-C) . . See Follow-up (MCC-5) Imaging studies as clinically indicated n FNA Positive 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 MCC Table of Contents Discussion, ReferencesMerkel Cell Carcinoma Practice Guidelines in Oncology – v.1.2010NCCN ® MCC-4 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 M1 Multidisciplinary tumor board consultation TREATMENT: CLINICAL M1 DISEASE See Follow-up (MCC-5) Best supportive care Consider any of the following therapies or combinations of: Chemotherapy and � � � Surgery Radiation therapye l (See NCCN Palliative Care Guideline) e l . See Principles of Radiation Therapy (MCC-A). See Chemotherapy Agents (MCC-C) 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 MCC Table of Contents Discussion, ReferencesMerkel Cell Carcinoma Practice Guidelines in Oncology – v.1.2010NCCN ® MCC-5 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. Recurrence Local Regional Disseminated Individualized treatment Individualized treatment See Clinical M1 (MCC-4) FOLLOW-UP RECURRENCE � � � Every 1-3 mo for year 1 Every 3-6 mo for year 2 Annually thereafter Physical exam including complete skin and regional lymph node exam � � Imaging studies as clinically 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. Guidelines Index MCC Table of Contents Discussion, ReferencesMerkel Cell Carcinoma 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 RADIATION THERAPY MCC-A � � � All doses at 2 Gy/day standard fractionation. Bolus is used to achieve adequate skin dose. Wide margins (5 cm) should be used, if possible, around the primary site. If electron beam is used, an energy and isodose line (eg, 90%) should be used that will deliver adequate lateral and deep margins. Extremity and torso MCC: After negative SLNB and wide local excision (WLE), in most instances, radiation therapy is given to the primary site only. SLNB dictates the need for regional irradiation. If SLNB is negative, then regional nodal basins can be observed. If SLNB is not performed, consider irradiating nodal beds for subclinical disease. Irradiation of in transit lymphatics is often not feasible unless the primary site is in close proximity to the nodal bed. Head and neck MCC: Risk of false negative sentinel node biopsy is higher, due to aberrant lymph node drainage and frequent presence of multiple sentinel node basins. The radiation field to treat the primary site is often overlying the draining lymph node beds. Treatment options for clinically node negative MCC of the head and neck include: Perform SLNB and WLE. If SLNB is negative, options are to irradiate the primary site nodal beds and in-transit lymphatics or observe. OR Perform WLE without performing SLNB and irradiate the primary tumor site, in-transit lymphatics and regional nodal sites. � � ± 1Lymph node dissection is the recommended initial therapy for clinically evident adenopathy in the axilla or groin, followed by postoperative radiation if indicated. Shrinking field technique.2 3Consider RT when there is a potential for anatomic (eg, previous history of surgery including WLE), operator, or histologic failure (eg, failure to perform appropriate immunohistochemistry on SLNs) that may lead to a false negative SLNB. Dose recommendations for radiation therapy: Primary Site: Negative resection margins 50-56 Gy Microscopic (+) resection margins 56-60 Gy Gross (+) resection margins or unresectable 60-66 Gy � � � �After SLNB without LN Dissection � � � � Negative SLN biopsy: axilla or Radiation not indicated Negative SLN biopsy: head and neck, if at risk for false negative biopsy 46-50 Gy Microscopic N+ on SLNB: 50 Gy Microscopic N+ on SLNB: head and neck 50-56 Gy 3 3 4 groin axilla or groin 4 Nodal Bed: Clinically (-) but at risk for subclinical disease 46-50 Gy Clinically evident lymphadenopathy 60-66 Gy �No SLNB or LN Dissection � � 1,2 �After LN Dissection � � Lymph node dissection: axilla or groin 50-54 Gy Lymph node dissection: head and neck 50-60 Gy 5 4 5 Microscopic N+ is defined as single node involvement that is neither palpable clinically nor abnormal by imaging criteria which microscopically consists of small metastatic foci without extracapsular extension. RT may be omitted after axillary/groin LN dissection for microscopic disease. Postoperative irradiation is indicated for multiple involved nodes or extracapsular extension. 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 MCC Table of Contents Discussion, ReferencesMerkel Cell Carcinoma Practice Guidelines in Oncology – v.1.2010NCCN ® MCC-B 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: Clear surgical margins when clinically feasible. Varied Approaches: 1-2 cm margins to investing fascia of muscle or pericranium with clear pathologic margins, when clinically feasible. Mohs technique Modified Mohs = Mohs technique with additional final margin for permanent sect