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Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Stage I and II Invasive Breast Cancer: American Society of Clinical Oncology Endorsement of the Society of Surgical Oncology/American Society for Radiation Oncology Consensus Guideline Thomas A. Buchholz, Mark R. Somerfield, Jennifer J. Griggs, Souzan El-Eid, M. Elizabeth H. Hammond, Gary H. Lyman, Ginny Mason, and Lisa A. Newman Thomas A. Buchholz, University of Texas MD Anderson Cancer Center, Houston, TX; Mark R. Somerfield, American Society of Clinical Oncology, Alexandria, VA; Jennifer J. Griggs, Lisa A. Newman, University of Michigan Comprehensive Cancer Care Center, Ann Arbor, MI; Souzan El-Eid, Summerlin Breast Center; US Oncology, Las Vegas, NV; M. Elizabeth H. Hammond, University of Utah School of Medicine and Intermountain Healthcare, Salt Lake City, UT; Gary H. Lyman, Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center, Seattle, WA; Ginny Mason, Inflammatory Breast Cancer Research Foundation, West Lafayette, IN. Published online ahead of print at www.jco.org on April 7, 2014. Clinical Practice Guideline Committee approval: January 7, 2014. Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article. Corresponding author: American Society of Clinical Oncology, 2318 Mill Rd, Suite 800, Alexandria, VA 22314; e-mail: [email protected].
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Methods The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for endorsing practice guidelines developed by other organizations. ASCO staff reviewed the SSO/ASTRO guideline for developmental rigor; an ASCO ad hoc review panel of experts reviewed the guideline content. Results The ASCO ad hoc guideline review panel concurred that the recommendations are clear, thorough, and based on the most relevant scientific evidence in this content area and that they present options acceptable to patients. According to the SSO/ASTRO guideline, the use of no ink on tumor (ie, no cancer cells adjacent to any inked edge/surface of specimen) as the standard for an adequate margin in invasive cancer in the era of multidisciplinary therapy is associated with low rates of ipsilateral breast tumor recurrence and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs. Conclusion The ASCO review panel endorses the SSO/ASTRO recommendations with qualifications, as follows. The panel reinforces and amplifies the guideline authors’ call for the monitoring of outcomes of the guideline at the institutional level, as institutions transition to adopting the SSO/ASTRO recommendations; would place greater emphasis on the importance of postlumpectomy mammography for cases involving microcalcifications; and calls for flexibility in the application of the guideline in light of the generally weak evidence supporting the recommendations. J Clin Oncol 32:1502-1506. © 2014 by American Society of Clinical Oncology
INTRODUCTION
0732-183X/14/3214w-1502w/$20.00
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Purpose The Society of Surgical Oncology (SSO)/American Society for Radiation Oncology (ASTRO) guideline on surgical margins for breast-conserving surgery with whole-breast irradiation in stage I and II invasive breast cancer was considered for endorsement.
© 2014 by American Society of Clinical Oncology
DOI: 10.1200/JCO.2014.55.1572
R
The American Society of Clinical Oncology (ASCO) Clinical Practice Guidelines Committee (CPGC) identified a guideline for endorsement that addressed margins for breast-conserving surgery with whole-breast irradiation in stage I and II invasive breast cancer. The target guideline was developed in 2013 as a joint product of the Society of Surgical Oncology (SSO) and the American Society for Radiation Oncology (ASTRO).1 There is no consensus on the question of what constitutes the optimal negative margin width in breast-conservation therapy (BCT) for invasive
breast cancer.1 As a result, there is thought to be considerable variation in surgical practice,2 and approximately 25% of women treated with BCT undergo re-excision to attain more widely clear surgical margins. These additional procedures can negatively affect cosmetic outcomes of BCT, increase surgical complications and patient physical discomfort, contribute to emotional stress in both patients and their family members, and increase medical costs and use of health care resources. To address this important topic, SSO and ASTRO convened a multidisciplinary expert guideline panel to address the relationship between margin width and ipsilateral breast tumor recurrence (IBTR).
© 2014 by American Society of Clinical Oncology
Information downloaded from jco.ascopubs.org and provided by at UNIVERSITY CHICAGO on October 4, 2014 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 128.135.12.127
ASCO Endorsement of SSO/ASTRO Surgical Margins for Breast Cancer Guideline
OVERVIEW OF THE ASCO GUIDELINE ENDORSEMENT PROCESS
In 2006, the ASCO Board of Directors approved a policy and set of procedures for endorsing clinical practice guidelines that have been developed by other professional organizations. The goal of the endorsement policy is to increase the number of high-quality, ASCOvetted guidelines available to the ASCO membership. The guideline under endorsement consideration is reviewed and approved by the ASCO CPGC. The CPGC review includes two parts: methodologic review and content review. The content review is completed by an ASCO panel (Appendix Table A1, online only). The methodologic review is completed by a member of the CPGC Methodology Subcommittee and/or by ASCO senior guideline staff using the Rigour of Development subscale of the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. In addition to this methodologic review, ASCO staff conduct literature searches to identify relevant studies and additional systematic reviews, meta-analyses, and guidelines that have been published since the guideline under endorsement was completed. The content review is completed by an ad hoc ASCO panel. The panel members are asked to complete an eight-item Guideline Endorsement Content Review Form that assesses the perceived clarity and clinical utility of the recommendations and the degree to which the recommendations are consistent with the content reviewers’ interpretation of the available data on the topic in question. Final review and approval are competed by the ASCO CPGC after approval by the
ASCO panel. Additional details of the methods used for the development of this guideline are reported in an online Methods Supplement available at http://www.asco.org/endorsements/. Disclaimer The clinical practice guideline and other guidance published herein are provided by ASCO to assist providers in clinical decision making. The information herein should not be relied on as being complete or accurate, nor should it be considered as inclusive of all proper treatments or methods of care or as a statement of the standard of care. With the rapid development of scientific knowledge, new evidence may emerge between the time information is developed and when it is published or read. The information is not continually updated and may not reflect the most recent evidence. The information addresses only the topics specifically identified herein and is not applicable to other interventions, diseases, or stages of disease. This information does not mandate any particular course of medical care. Furthermore, the information is not intended to substitute for the independent professional judgment of the treating provider, because the information does not account for individual variation among patients. Recommendations reflect high, moderate, or low confidence that the recommendation reflects the net effect of a given course of action. The use of words like must, must not, should, and should not indicate that a course of action is recommended or not recommended for either most or many patients, but there is latitude for the treating physician to select other courses of action in individual cases. In all
THE BOTTOM LINE ASCO GUIDELINE UPDATE
What Margin Width Minimizes the Risk of Ipsilateral Breast Tumor Recurrence? Target Population ● Patients with stage I and II breast cancer. The guideline pertains to patients with invasive breast cancer who have undergone whole-breast irradiation. Target Audience ● Radiation oncologists, pathologists, surgeons, medical oncologists oncology nurses, and patients/caregivers. Recommendations ● The SSO/ASTRO guideline concluded that the use of no ink on tumor (ie, no cancer cells adjacent to any inked edge/surface of the specimen) as the standard for an adequate margin in invasive cancer in the era of multidisciplinary therapy is associated with low rates of ipsilateral breast tumor recurrence and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs. Qualifying Statements ● The ASCO panel reinforces and amplifies the guideline authors’ call for the monitoring of outcomes of the guideline at the institutional level, as institutions transition to adopting the SSO/ASTRO recommendations; would place greater emphasis on the importance of postlumpectomy mammography for cases involving microcalcifications; and calls for flexibility in the application of the guideline in light of the generally weak evidence supporting the recommendations. ASCO believes that cancer clinical trials are vital to inform medical decisions and improve cancer care and that all patients should have the opportunity to participate.
www.jco.org
© 2014 by American Society of Clinical Oncology
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cases, the selected course of action should be considered by the treating provider in the context of treating the individual patient. Use of the information is voluntary. ASCO provides this information on an as-is basis and makes no warranty, express or implied, regarding the information. ASCO specifically disclaims any warranties of merchantability or fitnessforaparticularuseorpurpose.ASCOassumesnoresponsibilityfor anyinjuryordamagetopersonsorpropertyarisingoutoforrelatedtoany use of this information or for any errors or omissions. Guideline and Conflicts of Interest The expert panel was assembled in accordance with the ASCO Conflicts of Interest Management Procedures for Clinical Practice Guidelines (Procedures; summarized at http://www .asco.org/conflictsofinterest). Members of the panel completed the ASCO disclosure form, which requires disclosure of financial and other interests that are relevant to the subject matter of the guideline, including relationships with commercial entities that are reasonably likely to experience direct regulatory or commercial impact as a result of promulgation of the guideline. Categories for disclosure include employment relationships, consulting arrangements, stock ownership, honoraria, research funding, and expert testimony. In accordance with the Procedures, the majority of the members of the panel did not disclose any such relationships.
SSO/ASTRO CONSENSUS GUIDELINE
Clinical Questions and Target Population The SSO/ASTRO guideline addressed the overarching clinical question of what margin width minimizes the risk of IBTR. The guideline panel also considered a range of clinical circumstances that might affect this relationship, such as patient age, tumor histology, technique of radiation therapy delivery, and use of systemic therapy. The complete set of clinical questions and corresponding recommendations and levels of evidence supporting the recommendations is provided in Table 1. The target population for the SSO/ASTRO guideline was patients with stage I or II breast cancer. The guideline pertains to patients with invasive breast cancer who have undergone whole-breast irradiation. The guideline scope did not encompass patients with noninvasive breast cancer, patients treated with partial-breast irradiation, and/or patients treated with systemic therapy before surgery. Summary of SSO/ASTRO Guideline Development Methodology and Key Evidence The SSO/ASTRO guideline was developed by a joint, multidisciplinary expert panel that included a patient representative and
Table 1. Summary of SSO/ASTRO Clinical Practice Guideline Recommendations Clinical Question What is the absolute increase in risk of IBTR with a positive margin? Can the use of radiation boost, systemic therapy, or favorable tumor biology mitigate this increased risk? Do margin widths wider than no ink on tumor cells reduce the risk of IBTR?
What are the effects of endocrine or biologically targeted or systemic chemotherapy on IBTR? Should a patient who is not receiving any systemic treatment have wider margin widths? Should unfavorable biologic subtypes (such as triple-negative breast cancers) require wider margins (than no ink on tumor)? Should margin width be taken into consideration when determining WBRT delivery techniques? Is the presence of LCIS at the margin an indication for re-excision? Do invasive lobular carcinomas require a wider margin (than no ink on tumor)? What is the significance of pleomorphic LCIS at the margin? Should increased margin widths (wider than no ink on tumor) be considered for patients of young age (⬍ 40 years)?
What is the significance of an EIC in the tumor specimen, and how does this pertain to margin width?
Recommendation
Level of Evidence
A positive margin, defined as ink on invasive cancer or DCIS, is associated with at least a two-fold increase in IBTR; this increased risk in IBTR is not nullified by delivery of a boost, delivery of systemic therapy (endocrine, chemotherapy, biologic therapy), or favorable biology Negative margins (no ink on tumor) optimize IBTR; wider margin widths do not significantly lower this risk; the routine practice to obtain wider negative margin widths than ink on tumor is not indicated Rates of IBTR are reduced with the use of systemic therapy; in the uncommon circumstance of a patient not receiving adjuvant systemic therapy, there is no evidence suggesting that margins wider than no ink on tumor are needed Margins wider than no ink on tumor are not indicated based on biologic subtype
Meta-analysis, secondary data from prospective trials and retrospective studies
Choice of WBRT delivery technique, fractionation, and boost dose should not be dependent on the margin width
Retrospective studies
Wider negative margins than no ink on tumor are not indicated for invasive lobular cancer; classic LCIS at the margin is not an indication for re-excision; significance of pleomorphic LCIS at the margin is uncertain
Retrospective studies
Young age (ⱕ 40 years) is associated with both increased IBTR after BCT as well as increased local relapse on the chest wall after mastectomy and is also more frequently associated with adverse biologic and pathologic features; there is no evidence that increased margin width nullifies the increased risk of IBTR in young patients EIC identifies cases that may have a large residual DCIS burden after lumpectomy; there is no evidence of an association between increased risk of IBTR when margins are negative
Secondary data from prospective randomized trials and retrospective studies
Meta-analysis, retrospective studies
Multiple randomized trials, meta-analysis
Multiple retrospective studies
Retrospective studies
Abbreviations: ASTRO, American Society for Radiation Oncology; BCT, breast-conserving therapy; DCIS, ductal carcinoma in situ; EIC, extensive intraductal component; IBTR, ipsilateral breast tumor recurrence; LCIS, lobular carcinoma in situ; SSO, Society of Surgical Oncology; WBRT, whole-breast radiation therapy.
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JOURNAL OF CLINICAL ONCOLOGY
Information downloaded from jco.ascopubs.org and provided by at UNIVERSITY CHICAGO on October 4, 2014 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 128.135.12.127
ASCO Endorsement of SSO/ASTRO Surgical Margins for Breast Cancer Guideline
a methodologist. The primary evidence base was a systematic review and a study-level meta-analysis of the literature on the association between tumor margins in early-stage invasive breast cancer and local recurrence.2 Designated panel members conducted supplementary literature reviews to address specific guideline questions. The systematic review comprehensive literature searches of MEDLINE and evidence-based medicine spanned from 1965 to January 2013. The searches identified 33 studies (total of 28,162 patients) for inclusion in the guideline meta-analysis of the literature. All but two of the studies considered by the panel were retrospective in design. Indeed, it is important to note that there has never been a randomized trial that specifically compared various margin widths and outcome. Details of the search strategies, the study inclusion criteria, the outcomes of interest, and the results of the quantitative synthesis are available from the meta-analysis report published by Houssami et al.2 Major Guideline Recommendations Table 1 lists the practice recommendations for the clinical questions addressed in the SSO/ASTRO guideline. The guideline authors concluded that “the use of no ink on tumor [no cancer cells adjacent to any inked edge/surface of the specimen] as the standard for an adequate margin in invasive cancer in the era of multidisciplinary therapy is associated with low rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease healthcare costs.”1 RESULTS OF THE ASCO METHODOLOGIC REVIEW
The methodologic review of the SSO/ASTRO guideline was completed independently by two ASCO guideline staff members using the Rigour of Development subscale from the AGREE II instrument. Detailed results of the scoring for this guideline are available on request to [email protected]. Overall, the SSO/ASTRO guideline scored high (77%) in terms of methodologic quality, with only minor deviations from the ideal as reflected in the AGREE II items.
the most relevant scientific evidence in this content area and that they present options acceptable to patients. Overall, the ad hoc review panel agrees with the recommendations as stated in the guideline, with the following qualifications: First, the ASCO panel reinforces and amplifies the guideline authors’ call for the monitoring of outcomes of the guideline at the institutional level, as institutions transition to adopting the SSO/ ASTRO recommendations. Margin assessments can be influenced by institution-specific practices related to specimen handling, imaging, and processing. Outcome monitoring should include frequency of re-excision, rates of local recurrence, and the institutional or program standard for defining a minimal negative margin thickness (ie, distance between cancer cells and inked margin surface on microscopic specimen sections) as being adequate. Second, because this guideline will likely result in narrower margins and fewer patients undergoing re-excisions, the ASCO panel would place a heightened emphasis on the importance of postlumpectomy mammography for cases involving microcalcifications. If narrower margins become more common as a consequence of the SSO/ ASTRO guideline, postlumpectomy mammography for cases that involve satellite lesions or microcalcifications will be essential to insure adequate resection of the primary site of disease before proceeding to breast irradiation. Finally, the inherent weaknesses of the retrospective, observational studies on which the SSO/ASTRO recommendations are based, particularly the selection bias, call for flexibility in the application of the guideline. As noted by Jagsi et al,3 the SSO/ASTRO guideline authors appropriately avoided the “blanket prescription of behavior,”3(p535) thus allowing clinicians to make more individualized treatment decisions for women with early-stage breast cancer. For example, the SSO/ASTRO guideline authors state that it not known whether their guideline recommendations apply to patients treated with accelerated partial-breast irradiation. Jagsi et al analogously suggest that patients who may have been underrepresented in the studies included in the meta-analysis that informed the SSO/ASTRO guideline might reasonably be considered for re-excision. They cite the example of a young woman with “multiple very close margins of less than 1 mm across a broad front, an extensive intraductal component, and large breasts that would easily accommodate a re-excision.”3(p536)
METHODS AND RESULTS OF THE ASCO UPDATED LITERATURE SEARCH
ENDORSEMENT RECOMMENDATION
ASCO guideline staff updated the SSO/ASTRO literature search. Adapting the strategy described in the meta-analysis report by Houssami et al,2 MEDLINE was searched from January 2013 to November 23, 2013. The search was restricted to articles published in English and to systematic reviews, meta-analyses, and randomized controlled trials. The updated search yielded 28 records. A review of these results revealed no new evidence that would warrant substantive modification of the SSO/ASTRO practice recommendations.
The ASCO ad hoc guideline review panel has reviewed the SSO/ ASTRO guideline and endorses the adoption of the guideline, with minor qualifications.
RESULTS OF THE ASCO CONTENT REVIEW
The ASCO ad hoc panel reviewed the SSO/ASTRO guideline and concurs that the recommendations are clear, thorough, and based on www.jco.org
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
AUTHOR CONTRIBUTIONS Administrative support: Mark R. Somerfield Manuscript writing: All authors Final approval of manuscript: All authors © 2014 by American Society of Clinical Oncology
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REFERENCES 1. Moran, MS, Schnitt, SJ, Giuliano, AE, et al: Society of Surgical Oncology-American Society for Radiation Oncology consensus guideline on margins
for breast-conserving surgery with whole breast irradiation in stage I and II invasive breast cancer. Ann Surg Oncol 21:704-716, 2014 2. Houssami, N, Macaskill, P, Luke Mannovich, M, et al: The association of surgical margins and local recurrence in women with early-stage invasive breast
cancer treated with breast-conserving therapy: A meta-analysis. Ann Surg Oncol 21:717-730, 2014 3. Jagsi, R, Smith, BD, Sabel, M, et al: Individualized, patient-centered application of consensus guidelines to improve the quality of breast cancer care. Int J Radiat Oncol Biol Phys 88:535-536, 2014
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Quitting Smoking for People With Cancer ASCO offers a companion piece to the Tobacco Cessation Guide that physicians can give to their patients who smoke. This booklet reinforces the message that quitting smoking is beneficial, no matter what the diagnosis. It also offers information on the health benefits of quitting smoking, how patients can talk to the doctor about their tobacco use, various methods patients can use to quit smoking, and a list of resources, including help lines and mobile apps, that patients can use to stop smoking. The booklets can be ordered as a set of 10 provider guides/115 patient booklets or as a set of 125 patient booklets through the ASCO University Bookstore (www.cancer.net/estore). ASCO members receive a 20% discount.
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JOURNAL OF CLINICAL ONCOLOGY
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ASCO Endorsement of SSO/ASTRO Surgical Margins for Breast Cancer Guideline
Acknowledgment We thank the Clinical Practice Guidelines Committee members for their thoughtful reviews of and insightful comments on this guideline document, especially Alexi Wright, MD, MPH, for her review of the draft guideline manuscript. We are also grateful to Nehmat Houssami, MBBS, MPH, PHD, for sharing the literature search strategy that her group used to inform its meta-analysis. Appendix
Table A1. Panel Members Member
Affiliation
Thomas A. Buchholz, MD (co-chair) Lisa A. Newman, MD, MPH (co-chair) Souzan El-Eid, MD M. Elizabeth H. Hammond, MD Jennifer J. Griggs, MD Gary H. Lyman, MD, MPH Ginny Mason, RN, BSN (patient representative)
University of Texas MD Anderson Cancer Center, Houston, TX University of Michigan Comprehensive Cancer Center, Ann Arbor, MI Summerlin Breast Center; US Oncology, Las Vegas, NV University of Utah School of Medicine and Intermountain Healthcare, Salt Lake City, UT University of Michigan Comprehensive Cancer Care Center, Ann Arbor, MI Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center, Seattle, WA Inflammatory Breast Cancer Research Foundation, West Lafayette, IN
www.jco.org
© 2014 by American Society of Clinical Oncology
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Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Stage I and II Invasive Breast Cancer: American Society of Clinical Oncology Endorsement of the Society of Surgical Oncology/American Society for Radiation Oncology Consensus Guideline Thomas A. Buchholz, Mark R. Somerfield, Jennifer J. Griggs, Souzan El-Eid, M. Elizabeth H. Hammond, Gary H. Lyman, Ginny Mason, and Lisa A. Newman Thomas A. Buchholz, University of Texas MD Anderson Cancer Center, Houston, TX; Mark R. Somerfield, American Society of Clinical Oncology, Alexandria, VA; Jennifer J. Griggs, Lisa A. Newman, University of Michigan Comprehensive Cancer Care Center, Ann Arbor, MI; Souzan El-Eid, Summerlin Breast Center; US Oncology, Las Vegas, NV; M. Elizabeth H. Hammond, University of Utah School of Medicine and Intermountain Healthcare, Salt Lake City, UT; Gary H. Lyman, Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center, Seattle, WA; Ginny Mason, Inflammatory Breast Cancer Research Foundation, West Lafayette, IN. Published online ahead of print at www.jco.org on April 7, 2014. Clinical Practice Guideline Committee approval: January 7, 2014. Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article. Corresponding author: American Society of Clinical Oncology, 2318 Mill Rd, Suite 800, Alexandria, VA 22314; e-mail: [email protected].
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Methods The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for endorsing practice guidelines developed by other organizations. ASCO staff reviewed the SSO/ASTRO guideline for developmental rigor; an ASCO ad hoc review panel of experts reviewed the guideline content. Results The ASCO ad hoc guideline review panel concurred that the recommendations are clear, thorough, and based on the most relevant scientific evidence in this content area and that they present options acceptable to patients. According to the SSO/ASTRO guideline, the use of no ink on tumor (ie, no cancer cells adjacent to any inked edge/surface of specimen) as the standard for an adequate margin in invasive cancer in the era of multidisciplinary therapy is associated with low rates of ipsilateral breast tumor recurrence and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs. Conclusion The ASCO review panel endorses the SSO/ASTRO recommendations with qualifications, as follows. The panel reinforces and amplifies the guideline authors’ call for the monitoring of outcomes of the guideline at the institutional level, as institutions transition to adopting the SSO/ASTRO recommendations; would place greater emphasis on the importance of postlumpectomy mammography for cases involving microcalcifications; and calls for flexibility in the application of the guideline in light of the generally weak evidence supporting the recommendations. J Clin Oncol 32:1502-1506. © 2014 by American Society of Clinical Oncology
INTRODUCTION
0732-183X/14/3214w-1502w/$20.00
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Purpose The Society of Surgical Oncology (SSO)/American Society for Radiation Oncology (ASTRO) guideline on surgical margins for breast-conserving surgery with whole-breast irradiation in stage I and II invasive breast cancer was considered for endorsement.
© 2014 by American Society of Clinical Oncology
DOI: 10.1200/JCO.2014.55.1572
R
The American Society of Clinical Oncology (ASCO) Clinical Practice Guidelines Committee (CPGC) identified a guideline for endorsement that addressed margins for breast-conserving surgery with whole-breast irradiation in stage I and II invasive breast cancer. The target guideline was developed in 2013 as a joint product of the Society of Surgical Oncology (SSO) and the American Society for Radiation Oncology (ASTRO).1 There is no consensus on the question of what constitutes the optimal negative margin width in breast-conservation therapy (BCT) for invasive
breast cancer.1 As a result, there is thought to be considerable variation in surgical practice,2 and approximately 25% of women treated with BCT undergo re-excision to attain more widely clear surgical margins. These additional procedures can negatively affect cosmetic outcomes of BCT, increase surgical complications and patient physical discomfort, contribute to emotional stress in both patients and their family members, and increase medical costs and use of health care resources. To address this important topic, SSO and ASTRO convened a multidisciplinary expert guideline panel to address the relationship between margin width and ipsilateral breast tumor recurrence (IBTR).
© 2014 by American Society of Clinical Oncology
Information downloaded from jco.ascopubs.org and provided by at UNIVERSITY CHICAGO on October 4, 2014 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 128.135.12.127
ASCO Endorsement of SSO/ASTRO Surgical Margins for Breast Cancer Guideline
OVERVIEW OF THE ASCO GUIDELINE ENDORSEMENT PROCESS
In 2006, the ASCO Board of Directors approved a policy and set of procedures for endorsing clinical practice guidelines that have been developed by other professional organizations. The goal of the endorsement policy is to increase the number of high-quality, ASCOvetted guidelines available to the ASCO membership. The guideline under endorsement consideration is reviewed and approved by the ASCO CPGC. The CPGC review includes two parts: methodologic review and content review. The content review is completed by an ASCO panel (Appendix Table A1, online only). The methodologic review is completed by a member of the CPGC Methodology Subcommittee and/or by ASCO senior guideline staff using the Rigour of Development subscale of the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. In addition to this methodologic review, ASCO staff conduct literature searches to identify relevant studies and additional systematic reviews, meta-analyses, and guidelines that have been published since the guideline under endorsement was completed. The content review is completed by an ad hoc ASCO panel. The panel members are asked to complete an eight-item Guideline Endorsement Content Review Form that assesses the perceived clarity and clinical utility of the recommendations and the degree to which the recommendations are consistent with the content reviewers’ interpretation of the available data on the topic in question. Final review and approval are competed by the ASCO CPGC after approval by the
ASCO panel. Additional details of the methods used for the development of this guideline are reported in an online Methods Supplement available at http://www.asco.org/endorsements/. Disclaimer The clinical practice guideline and other guidance published herein are provided by ASCO to assist providers in clinical decision making. The information herein should not be relied on as being complete or accurate, nor should it be considered as inclusive of all proper treatments or methods of care or as a statement of the standard of care. With the rapid development of scientific knowledge, new evidence may emerge between the time information is developed and when it is published or read. The information is not continually updated and may not reflect the most recent evidence. The information addresses only the topics specifically identified herein and is not applicable to other interventions, diseases, or stages of disease. This information does not mandate any particular course of medical care. Furthermore, the information is not intended to substitute for the independent professional judgment of the treating provider, because the information does not account for individual variation among patients. Recommendations reflect high, moderate, or low confidence that the recommendation reflects the net effect of a given course of action. The use of words like must, must not, should, and should not indicate that a course of action is recommended or not recommended for either most or many patients, but there is latitude for the treating physician to select other courses of action in individual cases. In all
THE BOTTOM LINE ASCO GUIDELINE UPDATE
What Margin Width Minimizes the Risk of Ipsilateral Breast Tumor Recurrence? Target Population ● Patients with stage I and II breast cancer. The guideline pertains to patients with invasive breast cancer who have undergone whole-breast irradiation. Target Audience ● Radiation oncologists, pathologists, surgeons, medical oncologists oncology nurses, and patients/caregivers. Recommendations ● The SSO/ASTRO guideline concluded that the use of no ink on tumor (ie, no cancer cells adjacent to any inked edge/surface of the specimen) as the standard for an adequate margin in invasive cancer in the era of multidisciplinary therapy is associated with low rates of ipsilateral breast tumor recurrence and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs. Qualifying Statements ● The ASCO panel reinforces and amplifies the guideline authors’ call for the monitoring of outcomes of the guideline at the institutional level, as institutions transition to adopting the SSO/ASTRO recommendations; would place greater emphasis on the importance of postlumpectomy mammography for cases involving microcalcifications; and calls for flexibility in the application of the guideline in light of the generally weak evidence supporting the recommendations. ASCO believes that cancer clinical trials are vital to inform medical decisions and improve cancer care and that all patients should have the opportunity to participate.
www.jco.org
© 2014 by American Society of Clinical Oncology
Information downloaded from jco.ascopubs.org and provided by at UNIVERSITY CHICAGO on October 4, 2014 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 128.135.12.127
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cases, the selected course of action should be considered by the treating provider in the context of treating the individual patient. Use of the information is voluntary. ASCO provides this information on an as-is basis and makes no warranty, express or implied, regarding the information. ASCO specifically disclaims any warranties of merchantability or fitnessforaparticularuseorpurpose.ASCOassumesnoresponsibilityfor anyinjuryordamagetopersonsorpropertyarisingoutoforrelatedtoany use of this information or for any errors or omissions. Guideline and Conflicts of Interest The expert panel was assembled in accordance with the ASCO Conflicts of Interest Management Procedures for Clinical Practice Guidelines (Procedures; summarized at http://www .asco.org/conflictsofinterest). Members of the panel completed the ASCO disclosure form, which requires disclosure of financial and other interests that are relevant to the subject matter of the guideline, including relationships with commercial entities that are reasonably likely to experience direct regulatory or commercial impact as a result of promulgation of the guideline. Categories for disclosure include employment relationships, consulting arrangements, stock ownership, honoraria, research funding, and expert testimony. In accordance with the Procedures, the majority of the members of the panel did not disclose any such relationships.
SSO/ASTRO CONSENSUS GUIDELINE
Clinical Questions and Target Population The SSO/ASTRO guideline addressed the overarching clinical question of what margin width minimizes the risk of IBTR. The guideline panel also considered a range of clinical circumstances that might affect this relationship, such as patient age, tumor histology, technique of radiation therapy delivery, and use of systemic therapy. The complete set of clinical questions and corresponding recommendations and levels of evidence supporting the recommendations is provided in Table 1. The target population for the SSO/ASTRO guideline was patients with stage I or II breast cancer. The guideline pertains to patients with invasive breast cancer who have undergone whole-breast irradiation. The guideline scope did not encompass patients with noninvasive breast cancer, patients treated with partial-breast irradiation, and/or patients treated with systemic therapy before surgery. Summary of SSO/ASTRO Guideline Development Methodology and Key Evidence The SSO/ASTRO guideline was developed by a joint, multidisciplinary expert panel that included a patient representative and
Table 1. Summary of SSO/ASTRO Clinical Practice Guideline Recommendations Clinical Question What is the absolute increase in risk of IBTR with a positive margin? Can the use of radiation boost, systemic therapy, or favorable tumor biology mitigate this increased risk? Do margin widths wider than no ink on tumor cells reduce the risk of IBTR?
What are the effects of endocrine or biologically targeted or systemic chemotherapy on IBTR? Should a patient who is not receiving any systemic treatment have wider margin widths? Should unfavorable biologic subtypes (such as triple-negative breast cancers) require wider margins (than no ink on tumor)? Should margin width be taken into consideration when determining WBRT delivery techniques? Is the presence of LCIS at the margin an indication for re-excision? Do invasive lobular carcinomas require a wider margin (than no ink on tumor)? What is the significance of pleomorphic LCIS at the margin? Should increased margin widths (wider than no ink on tumor) be considered for patients of young age (⬍ 40 years)?
What is the significance of an EIC in the tumor specimen, and how does this pertain to margin width?
Recommendation
Level of Evidence
A positive margin, defined as ink on invasive cancer or DCIS, is associated with at least a two-fold increase in IBTR; this increased risk in IBTR is not nullified by delivery of a boost, delivery of systemic therapy (endocrine, chemotherapy, biologic therapy), or favorable biology Negative margins (no ink on tumor) optimize IBTR; wider margin widths do not significantly lower this risk; the routine practice to obtain wider negative margin widths than ink on tumor is not indicated Rates of IBTR are reduced with the use of systemic therapy; in the uncommon circumstance of a patient not receiving adjuvant systemic therapy, there is no evidence suggesting that margins wider than no ink on tumor are needed Margins wider than no ink on tumor are not indicated based on biologic subtype
Meta-analysis, secondary data from prospective trials and retrospective studies
Choice of WBRT delivery technique, fractionation, and boost dose should not be dependent on the margin width
Retrospective studies
Wider negative margins than no ink on tumor are not indicated for invasive lobular cancer; classic LCIS at the margin is not an indication for re-excision; significance of pleomorphic LCIS at the margin is uncertain
Retrospective studies
Young age (ⱕ 40 years) is associated with both increased IBTR after BCT as well as increased local relapse on the chest wall after mastectomy and is also more frequently associated with adverse biologic and pathologic features; there is no evidence that increased margin width nullifies the increased risk of IBTR in young patients EIC identifies cases that may have a large residual DCIS burden after lumpectomy; there is no evidence of an association between increased risk of IBTR when margins are negative
Secondary data from prospective randomized trials and retrospective studies
Meta-analysis, retrospective studies
Multiple randomized trials, meta-analysis
Multiple retrospective studies
Retrospective studies
Abbreviations: ASTRO, American Society for Radiation Oncology; BCT, breast-conserving therapy; DCIS, ductal carcinoma in situ; EIC, extensive intraductal component; IBTR, ipsilateral breast tumor recurrence; LCIS, lobular carcinoma in situ; SSO, Society of Surgical Oncology; WBRT, whole-breast radiation therapy.
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ASCO Endorsement of SSO/ASTRO Surgical Margins for Breast Cancer Guideline
a methodologist. The primary evidence base was a systematic review and a study-level meta-analysis of the literature on the association between tumor margins in early-stage invasive breast cancer and local recurrence.2 Designated panel members conducted supplementary literature reviews to address specific guideline questions. The systematic review comprehensive literature searches of MEDLINE and evidence-based medicine spanned from 1965 to January 2013. The searches identified 33 studies (total of 28,162 patients) for inclusion in the guideline meta-analysis of the literature. All but two of the studies considered by the panel were retrospective in design. Indeed, it is important to note that there has never been a randomized trial that specifically compared various margin widths and outcome. Details of the search strategies, the study inclusion criteria, the outcomes of interest, and the results of the quantitative synthesis are available from the meta-analysis report published by Houssami et al.2 Major Guideline Recommendations Table 1 lists the practice recommendations for the clinical questions addressed in the SSO/ASTRO guideline. The guideline authors concluded that “the use of no ink on tumor [no cancer cells adjacent to any inked edge/surface of the specimen] as the standard for an adequate margin in invasive cancer in the era of multidisciplinary therapy is associated with low rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease healthcare costs.”1 RESULTS OF THE ASCO METHODOLOGIC REVIEW
The methodologic review of the SSO/ASTRO guideline was completed independently by two ASCO guideline staff members using the Rigour of Development subscale from the AGREE II instrument. Detailed results of the scoring for this guideline are available on request to [email protected]. Overall, the SSO/ASTRO guideline scored high (77%) in terms of methodologic quality, with only minor deviations from the ideal as reflected in the AGREE II items.
the most relevant scientific evidence in this content area and that they present options acceptable to patients. Overall, the ad hoc review panel agrees with the recommendations as stated in the guideline, with the following qualifications: First, the ASCO panel reinforces and amplifies the guideline authors’ call for the monitoring of outcomes of the guideline at the institutional level, as institutions transition to adopting the SSO/ ASTRO recommendations. Margin assessments can be influenced by institution-specific practices related to specimen handling, imaging, and processing. Outcome monitoring should include frequency of re-excision, rates of local recurrence, and the institutional or program standard for defining a minimal negative margin thickness (ie, distance between cancer cells and inked margin surface on microscopic specimen sections) as being adequate. Second, because this guideline will likely result in narrower margins and fewer patients undergoing re-excisions, the ASCO panel would place a heightened emphasis on the importance of postlumpectomy mammography for cases involving microcalcifications. If narrower margins become more common as a consequence of the SSO/ ASTRO guideline, postlumpectomy mammography for cases that involve satellite lesions or microcalcifications will be essential to insure adequate resection of the primary site of disease before proceeding to breast irradiation. Finally, the inherent weaknesses of the retrospective, observational studies on which the SSO/ASTRO recommendations are based, particularly the selection bias, call for flexibility in the application of the guideline. As noted by Jagsi et al,3 the SSO/ASTRO guideline authors appropriately avoided the “blanket prescription of behavior,”3(p535) thus allowing clinicians to make more individualized treatment decisions for women with early-stage breast cancer. For example, the SSO/ASTRO guideline authors state that it not known whether their guideline recommendations apply to patients treated with accelerated partial-breast irradiation. Jagsi et al analogously suggest that patients who may have been underrepresented in the studies included in the meta-analysis that informed the SSO/ASTRO guideline might reasonably be considered for re-excision. They cite the example of a young woman with “multiple very close margins of less than 1 mm across a broad front, an extensive intraductal component, and large breasts that would easily accommodate a re-excision.”3(p536)
METHODS AND RESULTS OF THE ASCO UPDATED LITERATURE SEARCH
ENDORSEMENT RECOMMENDATION
ASCO guideline staff updated the SSO/ASTRO literature search. Adapting the strategy described in the meta-analysis report by Houssami et al,2 MEDLINE was searched from January 2013 to November 23, 2013. The search was restricted to articles published in English and to systematic reviews, meta-analyses, and randomized controlled trials. The updated search yielded 28 records. A review of these results revealed no new evidence that would warrant substantive modification of the SSO/ASTRO practice recommendations.
The ASCO ad hoc guideline review panel has reviewed the SSO/ ASTRO guideline and endorses the adoption of the guideline, with minor qualifications.
RESULTS OF THE ASCO CONTENT REVIEW
The ASCO ad hoc panel reviewed the SSO/ASTRO guideline and concurs that the recommendations are clear, thorough, and based on www.jco.org
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
AUTHOR CONTRIBUTIONS Administrative support: Mark R. Somerfield Manuscript writing: All authors Final approval of manuscript: All authors © 2014 by American Society of Clinical Oncology
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REFERENCES 1. Moran, MS, Schnitt, SJ, Giuliano, AE, et al: Society of Surgical Oncology-American Society for Radiation Oncology consensus guideline on margins
for breast-conserving surgery with whole breast irradiation in stage I and II invasive breast cancer. Ann Surg Oncol 21:704-716, 2014 2. Houssami, N, Macaskill, P, Luke Mannovich, M, et al: The association of surgical margins and local recurrence in women with early-stage invasive breast
cancer treated with breast-conserving therapy: A meta-analysis. Ann Surg Oncol 21:717-730, 2014 3. Jagsi, R, Smith, BD, Sabel, M, et al: Individualized, patient-centered application of consensus guidelines to improve the quality of breast cancer care. Int J Radiat Oncol Biol Phys 88:535-536, 2014
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Quitting Smoking for People With Cancer ASCO offers a companion piece to the Tobacco Cessation Guide that physicians can give to their patients who smoke. This booklet reinforces the message that quitting smoking is beneficial, no matter what the diagnosis. It also offers information on the health benefits of quitting smoking, how patients can talk to the doctor about their tobacco use, various methods patients can use to quit smoking, and a list of resources, including help lines and mobile apps, that patients can use to stop smoking. The booklets can be ordered as a set of 10 provider guides/115 patient booklets or as a set of 125 patient booklets through the ASCO University Bookstore (www.cancer.net/estore). ASCO members receive a 20% discount.
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ASCO Endorsement of SSO/ASTRO Surgical Margins for Breast Cancer Guideline
Acknowledgment We thank the Clinical Practice Guidelines Committee members for their thoughtful reviews of and insightful comments on this guideline document, especially Alexi Wright, MD, MPH, for her review of the draft guideline manuscript. We are also grateful to Nehmat Houssami, MBBS, MPH, PHD, for sharing the literature search strategy that her group used to inform its meta-analysis. Appendix
Table A1. Panel Members Member
Affiliation
Thomas A. Buchholz, MD (co-chair) Lisa A. Newman, MD, MPH (co-chair) Souzan El-Eid, MD M. Elizabeth H. Hammond, MD Jennifer J. Griggs, MD Gary H. Lyman, MD, MPH Ginny Mason, RN, BSN (patient representative)
University of Texas MD Anderson Cancer Center, Houston, TX University of Michigan Comprehensive Cancer Center, Ann Arbor, MI Summerlin Breast Center; US Oncology, Las Vegas, NV University of Utah School of Medicine and Intermountain Healthcare, Salt Lake City, UT University of Michigan Comprehensive Cancer Care Center, Ann Arbor, MI Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center, Seattle, WA Inflammatory Breast Cancer Research Foundation, West Lafayette, IN
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