Practice Patterns of Radiation Field Design for Sentinel Lymph Node-Positive Early-Stage Breast Cancer

Accepted Manuscript Practice Patterns of Radiation Field Design for Sentinel Lymph Node Positive Early Stage Breast Cancer Soheila Azghadi, Megan Daly, Jyoti Mayadev PII:

S1526-8209(16)30105-7

DOI:

10.1016/j.clbc.2016.05.009

Reference:

CLBC 476

To appear in:

Clinical Breast Cancer

Received Date: 8 January 2016 Revised Date:

6 April 2016

Accepted Date: 9 May 2016

Please cite this article as: Azghadi S, Daly M, Mayadev J, Practice Patterns of Radiation Field Design for Sentinel Lymph Node Positive Early Stage Breast Cancer, Clinical Breast Cancer (2016), doi: 10.1016/ j.clbc.2016.05.009. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Practice Patterns of Radiation Field Design for Sentinel Lymph Node Positive Early

Soheila Azghadi, Megan Daly, and Jyoti Mayadev

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Stage Breast Cancer

Radiation Oncology Department, University of California Davis School of Medicine

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Objective:

Recent randomized trials have led to decreased use of completion axillary lymph node

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dissection (ALND) in early stage breast cancer patients with a positive sentinel lymph node (SLN) causing controversy surrounding radiotherapy coverage of the axilla. We investigate practice variation among radiation oncologists in regional nodal coverage for

Methods:

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clinicopathologic scenarios, and evaluate axillary field design decision-making processes.

A customized, web-based questionnaire was emailed to 983 community (n=617) and

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academic (n=366) radiation oncologists with breast cancer subspecialty practicing in the United States. The survey consisted of 18 multiple-choice questions evaluating general

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clinical preferences surrounding radiation therapy( RT) field design for patients with early stage breast cancer with a positive SLN. Seven case scenarios were developed to investigate field design in the setting of specific clinical and pathologic risk factors. Nodal coverage was classified as standard tangents (T), high tangents (HT), tangents and a supraclavicular field (SCF), or tangents and full axillary coverage (AX).

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Results: 145 evaluable responses were collected, with a response rate of 15.0%. Twelve (8.3%) of respondents report using completion ALND for patients with 1-3 positive SLN without

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extracapsular extension (ECE) and 66 (45.5%) perform ALND with 1-3 positive SLN with ECE. For micrometastatic SLN, with no lymphvascular system invasion (LVSI),

115 (87.1%) used T or HT. The use of neoadjuvant chemotherapy(NAC) influenced RT

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field design for patients with a positive SLN without ECE, 64 (48.5%) using SCF or AX treatment without NAC and 94 (70.7%) using SCF and AX after NAC. With

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macrometastatic SLN involvement, most respondents preferred SCF (45.27%) and AX (45.66%), in comparison to micrometastatic involvement for which HT (43.61%) was frequently chosen. Forty (27.8%) report using online predictive nomograms to predict further axillary involvement, with no difference between academic and community

Conclusion:

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radiation oncologists (p=0.11).

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In SLNB positive early stage breast cancer with omission of completion ALND, there is increasing use of axillary RT to cover the undissected axilla. Most respondents use a

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SCF or AX for patients with low to intermediate pathologic features. Online prediction nomograms are used by a minority of practitioners to assist in clinical decision-making in this setting.

Introduction Axillary lymph node dissection has historically been the therapeutic standard

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procedure in the surgical management of breast cancer1-3. Early stage breast cancer patients with potentially low risk of axillary involvement were comprehensively treated

such as the need for radiation therapy to the low or high axilla 4.

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with an ALND to stage their axilla to base further therapeutic management decisions

However, over the last several years, high impact randomized trials have allowed for risk stratification in breast cancer axillary therapeutic management. Recently, the

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National Surgical Adjuvant Bowel and Breast Project (NSABP) trial, and the American College of Surgeons Oncology Group (ACOSOG) trial, ACOSOG Z-0011, addressed the

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utility of an ALND versus a sentinel node dissection in eligible patients. The ACOSOG trial identified no difference in axillary recurrence or overall survival (OS) at 5 years in women randomized to either sentinel lymph node biopsy alone versus sentinel lymph node biopsy followed by a standard level I and II axillary dissection 5.. Given these

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results, there continues to be strides to avoid a completion ALND in selected patients. Traditionally, radiation oncologists relied on the ALND results in order to design the radiation treatment fields with the characteristics and the number of positive sentinel

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nodes referenced to predict involvement of the level III/supraclavicular lymph nodes .With the recent results of the ACSOG-Z0011 trial available to suggest no detriment

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with the omission of ALND in early stage breast cancer patients with a limited number of involved sentinel nodes, radiation oncologists face uncertainty in their practice for coverage of the axilla 6,7. In an effort to investigate the practice patterns among radiation oncologists for radiation field design in patients with early stage breast cancer with a positive sentinel node who do not have a completion ALND, we conducted an emailbased survey to help guide clinicians.

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Methods and materials We conducted a questionnaire-based survey on the patterns of practice for

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radiation field design among community and academic radiation oncologists with breast cancer subspecialty practicing in the United States. The survey was approved by UC Davis institutional review board, and responses were voluntary. We used the online

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American Society for Radiation Oncology (ASTRO) directory to randomly select

community radiation oncologists (n=617). For the second cohort, we investigated the

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academic radiation oncology departments with Accreditation Council for Graduate Medical Education (ACGME) approved residency program through a web based search of radiation oncology faculty with a clinical and research focus on breast cancers ,and obtained the email addresses from the departmental or ASTRO website (n=366). The

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invitations to participation were sent via email through the Survey Monkey website between July and September 2014. Recipients included physicians practicing in all 50 United States and Puerto Rico. Three solicitations were sent out by email after one week

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from the first request for three weeks.

The survey consisted of eighteen multiple-choice questions and was tested to

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require less than 5 minutes to complete (supplement Fig.1). Specifically, the survey consisted of two portions: 1) Background questions including demographic details and general clinical preferences on radiation field design for patients with early stage breast cancer and a positive sentinel node 2) 7 case based scenarios were presented and the participant was to select a radiation field design inclusive of a standard tangents, high tangents, tangents and a supraclavicular field, or tangents and full axillary coverage.

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Participants were asked demographic data including their primary professional affiliation, years post-residency, if their job position includes sub-specialization in breast cancer treatment, number of breast cancer patients they treat annually, and within which US

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state or territory their primary clinical practice is located. They were asked if at their

institution, patients with 1-3 positive sentinel lymph nodes with or without ECE routinely undergo completion axillary lymph node dissection. They were also queried as to use of

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online risk stratification tools to determine axillary nodal risk including nomograms to

predict further axillary lymph node involvement in 1-3 positive SLN to decide on further

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management or radiation therapy, or use the Katz nomogram to predict 4 or more positive nodes with a positive sentinel node. Finally, the participants were asked how their institutions surgically manage the axilla after neoadjuvant chemotherapy in a patient with a clinically mobile positive axillary node prior to neoadjuvant chemotherapy without

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pathological confirmation of involvement.

Seven case-based clinical scenarios were then presented designed to include varying clinical and pathologic risk factors (Table 1). Respondents were asked for each

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AX.

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scenario to select a radiation field design inclusive of a T, HT, T and a SCF, or T and

Statistical Analyses

Statistical analyses were performed using StatPlus(version 5.0), and GraphPad Prism( version 6.0) software. Differences between groups were calculated using the χ2 test for categorical variables. P < .05 was used to indicate statistical significance.

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Results: Between July and September 2014, 145 out of 983 (15.0%) invited radiation oncologists agreed to participate through the e-mail survey. Among the initial 147

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responses, 134 (13.6%) surveys were completed in their entirety.

Demographics:

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Respondents included 66 (45.5%) radiation oncologists with an academic

professional affiliation, 58(40%) community practitioners, and 21(14.5%)with a hybrid

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professional affiliation (Fig 1A). All respondents practice within the United States (US): Eastern US 22.1%, Western US 29.0%, Southeast US 17.2%, and Midwest US 31.7% (Fig 1B). 79 (54.4%) have practiced ≥10 years post-residency in the field of radiation oncology and 98(68.0%) primarily treat breast cancer patients (Fig 1C, 2A). Overall,

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53.8% treat more than 50 breast cancer patients per year (Fig 2B).

Use of a completion ALND: with or without ECE

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Following SLN biopsy with 1-3 positive nodes without ECE, 48.3% of responding physicians report that their institution does not perform completion ALND, 8.4% do

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routinely perform ALND, and 43.4% perform completion dissection on a case-by-case basis. When ECE is present, 46.2% routinely use ALND, while 16.8% do not, and 37.1% would consider ALND on a case-by-case basis in this patient population (Fig 3A). For a patient with a mobile, clinically positive axillary node prior to neoadjuvant chemotherapy without pathological confirmation of involvement, 56.3% would assess the axilla with SLN biopsy, and 43.0% and would routinely use ALND in (Fig 3B).

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Nomogram Use in Predicting Further Axillary Lymph Node involvement Among all responding physicians, 28.2% report use of a nomogram to predict further

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axillary lymph node involvement in patients with 1-3 positive SLN to assist with clinical decision making (Fig 4A), including 21.1% who report using the Katz nomogram to predict involvement of ≥4 following a positive SLN, with no difference between

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academic and community radiation oncologists (p=0.11) (Fig 4B).

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Clinical vignettes

The clinical scenarios were designed to examine practice patterns in axillary coverage and radiation fields used for patients without completion ALND6 8. For a patient with <1.5 cm IDC, negative LVSI, ER positive, with micrometastatic involvement

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of one SLN without ECE, A HT was recommended by 70 (53.8%) of respondents, following 43 (33.1%) selecting standard tangents; HT field was selected significantly higher by academic affiliates (P=0.01).When the same patient presented with a single

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macroscopically involved SLN, HT was selected by (58)44.6%, with most others selecting either T+SCF (24.6%) or T+AX (23.8%); HT field was selected significantly

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higher by academic affiliates (P=0.003). With these same pathologic features present (including a macroscopically

involved SLN) following delivery of NAC, T+SCF and T+AX were most frequently recommended (34.4% and 35.9%, respectively) with no difference between academic and community respondents (P=0.06). For a 2.2 cm, ER negative tumor with LVSI and 2 macroscopically involved SLN,

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almost all respondents would use either T+SCV 62(47.3%) or T+AX 62(47.3%) with no difference between academic and community respondents(P=0.15). For a similar case, but with a multifocal, ER positive tumor, 59(45.4%) selected T+AX and 54(41.5%)

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selected T+SCF with no difference between academic and community(P=0.16). For a smaller (1.5cm) grade 3 IDC, LVSI positive, with 1 microscopically involved SNL,

58(43.6%) of respondents use HT and most others would use T/SCF (24.4%) or T/AX

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(24.1%); academic affiliated radiation oncologists selected significantly higher AX field (P<0.0001).

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After a simple mastectomy for a 2.2 cm multifocal, ER positive IDC with no LVSI, with one macroscopically involved SLN without completion dissection, 51(39.5%) of respondents recommended T+AX and 39(30.2%) selected T+SCF; academic affiliates significantly selected higher T+AX field(P=0.0002).

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Table 1.A summarizes responses to all 7 clinical vignettes. Table 1.B summarizes responses to all 7 clinical vignettes stratified by academic and community affiliation.

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Discussion

Our survey results suggest that the role of a completion ALND is decreasing, and in

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response, radiation fields are becoming larger to encompass more of the undissected axilla. Of the participants, 67% treat breast cancer as a subspeciality with 50% of respondents treating more than 50 cases per year, suggesting substantial experience and expertise among our respondents. In our study the majority of respondents (48.3%) do not routinely advocate for ALND in those with a positive SLN without ECE, illustrating the clinical relevance of our study when further pathologic nodal assessment is not

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available for axillary risk decision making strategies. Furthermore, with the core participants routinely treating breast cancer, our investigation shows increasing coverage of the axilla with radiation in those who do not have a completion ALND, even in those

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at low risk for additional axillary disease. The publication of results from large

prospective trials including Z-0011, IBCSG 23-01, NSABP-32, and AMAROS has

significantly impacted on breast cancer management 5,7,9,10. These studies in aggregate

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suggest completion ALND in breast conserving surgery does not improve disease free

survival (DFS) or overall survival (OS), but in all studies, RT was given to the majority

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of those without axillary surgery, calling the role of RT to sterilize the axilla into the limelight. Therefore, there is a challenge in RT field design to help eradicate residual microscopic disease after a SNLB alone.

The main consideration for radiation oncologists is the risk of further axillary

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nodal involvement, and how radiation field design may impact axillary recurrence risk. Traditionally, an ALND has been considered both therapeutic and diagnostic, with an adequate dissection consisting of ten or more LN. Prior to the era of SLNB, the NSABP

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B-04 conducted a randomized trial which addresses the management of the axilla in patients with node positive axilla to be treated with with RT vs. surgery11In this study,

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1079 patients with a clinically negative axilla underwent a radical mastectomy, total mastectomy without ALND but had RT to the axilla, or total mastectomy (with ALND if the clinically occult lymph nodes were positive at surgery). 586 patients with a clinically positive axilla were randomized to radical mastectomy versus total mastectomy and post mastectomy radiation to cover the axilla including the SCF and internal mammary nodes. Therefore, for a more in depth discussion, we can focus on the clinically negative patients

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with occult positive nodes. In the patients with clinically negative nodes and who received an ALND, 40% were found to have pathologically positive lymph nodes at the time of surgery. Therefore, one can make an estimate that those clinically negative

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patients randomized to the total mastectomy had a similar percentage of occult positive axillary lymph nodes. Furthermore, the cumulative incidence of local or regional recurrence was the and was lowest in the group treated with total mastectomy and

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radiation therapy, p=0.002 for the three-way comparison. The benefit from radiation

therapy was related to a significant reduction in local recurrence, illustrating the benefit

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of RT to reduce the risk of axillary recurrences in patients with microscopic disease in the axilla11. In addition, in those patients with a clinically positive axilla, we can examine the comparison between the radical mastectomy group vs. coverage of the axilla with RT to effectively target gross disease in the axilla. At 25 years, there was no difference in

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relapse free survival, DFS, or OS between the groups 11. Based on the data from NSABP B-04, there is continued suggestion that radiation can effectively treat microcscopic

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disease in the axilla.

According to the American Society of Clinical Oncology clinical practice

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guideline update 2014, patients with T1or T2 breast cancer with one or two positive axillary SLNs are advised against a completion ALND 12. This clinical impactful statement is largely based on the American College of Surgeons Oncology Group Z0011 randomized trial. The decision to omit or not omit ALND should be individualized in patients with breast cancer with one or two positive SLN13. For example, the tumor burden in the studied population in Z0011 was low, with this low tumor burden depicted in the study population as having higher OS compared to the rate of 80% predicted. In

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addition, patients recruited to the study have low-risk breast cancer, a high proportion of patients were lost to follow-up; there was a significant amount of missing data, and there was no prospective RT quality assurance program to mitigate any bias in RT target

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volume definition13 14. Generalizability of the results of Z0011 trial which did not include estrogen receptor negative and HER2 positive subtypes might be questionable. Also, the recruitment rates were 50% of original target rate in the study design 13. Most significant

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to radiation field design is the lack of radiation quality assurance and field design on the NSABP 32 and Z-0011trials. In fact, recent data from Jagsi et al., show that several

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patients treated on Z-0011 were treated with a high tangential radiation field and therefore had “treatment” targeted at the axilla 15. Studies show that using standard tangential fields cover more than 50% of level I and 20% to 30% of level II nodes receive 95% of the prescribed dose based on patients’ anatomy and the location of the upper TF

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border 16,17. Therefore, a potential reason for the < 1% regional recurrence rate on the Z0011 study, despite 27% of patients having positive undissected nodes, might be the use of HT radiation fields that covered a substantial portion of the axillary nodal region 6,18.

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Another study that examines the use of completion ALND is the International Breast Cancer Study Group (ICBSG) 23-01. In this study, 931 patients with a breast

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primary less than 5cm and >1 micrometastatic SLNB were randomized between ALND and observation, with 98% of breast conservation patients treated with RT. The RT fields were not discussed in the publication, but 22% of the patients in the group without axillary dissection who had breast-conserving surgery received either no radiation therapy (3%) or received intraoperative partial breast irradiation alone (19%), which cannot sterilize any residual axillary disease. There was no difference in local recurrence

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(LR), DFS, or OS between the arms of the study. Therefore, it is difficult to conclude the effect of RT in this study without RT field design. One could postulate that in patients with limited axillary lymph node burden, the risk of further nodal involvement is low

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which does not require additional therapy with RT or surgery 9. In addition, the recently reported European Organization for Research and Treatment of Cancer (EORTC) “After Mapping of the Axilla: Radiotherapy or Surgery?” (AMAROS) trial showed no

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difference between ALND and AX radiation in those with a positive SLNB. The RT

fields were comprehensive with inclusion of the SCF. Five-year axillary recurrence was

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0.43% (95% CI 0.00–0.92) after axillary lymph node dissection versus 1.19% (0.31– 2.08) after axillary radiotherapy. Lymphedema in the ipsilateral arm was noted significantly more often after axillary lymph node dissection than after axillary radiotherapy at 1 year, 3 years, and 5 years 12.

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In light of the ICBSG 23-01, Z-0011 trial and AMAROS trials, the role of radiation in sterilizing the axilla to translate into clinical recurrence risk reduction is potentially significant. To help determine the risk of further axillary nodal involvement, there are

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several prediction tools available online to help guide clinicians. For example, the Katz nomogram can be used as a potential predictor of having four or more involved nodes

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which is helpful for surgeons, and radiation oncologists to make decisions whether dissect or radiate the axilla 19. However, a limited number of survey participants used nomograms prediction tools in their decision making capacity. 21.1% use the Katz nomogram, and only 28.2% reported that they use the MD Anderson Cancer Center or Memorial Sloan Kettering nomogram to predict axillary nodal involvement. In addition, although the nomograms published are available for widespread use, they are validated

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single institution data, which may contain practices that are not widely used. For example, the Katz nomogram was validated on data from MD Anderson cancer center, where most clinically node negative patients have high resolution ultrasound as a portion

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of their staging workup. Therefore, the clinically negative SLNB patients may have a higher risk of additional nodal involvement in a clinic that does not use imaging for

axillary staging and relies on physical exam alone prior to SLNB. Interestingly, for a

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field that is dominated by computation, 78.9% of participants do not use a nomogram for

coverage alone.

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further prediction of axillary nodal involvement, and use clinical judgment for axillary

In our study, the majority of radiation oncologists use a SCF or AX field for the case scenarios presented, showing that the participants’ clinical judgment may overestimate the potential axillary involvement.

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From our survey results, we found not surprisingly, that the limited extent of surgery has increased radiation fields in early stage breast cancer. In our clinical scenario 2 with limited risk factors, 58(44.6%) would treat with high tangents, 32(24%) would add

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a superclavicular field and 31(23%) would cover the entire axilla in the radiation field design. In scenario number 5, with a 2.2cm primary tumor, ER+, and 2 involved SLN,

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no ECE, 113(87%) of the respondents would cover more of the axilla than a high tangent, involving a SCF or AX field. On the other hand, with a validated nomogram for the same scenario using a grade of 1 and routine immunohistochemical analysis on the SLNB, there is a 14% risk of further axillary lymph nodes involved. Therefore, in this era of personalized medicine, our study shows a potential disconnect between risk stratification and RT field design even in those patients with low risk of harboring disease

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in the axilla20. The risk of larger radiation fields is not without potential risk. There is a higher dose to the brachial plexus, risk of lymphedema, and pneumonitis with more extensive axillary coverage20,21.

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Our survey was a volunteer based online questionnaire with respondents who

either practice in the community or in an academic setting, and routinely manage breast cancer. Given the growing interest in regional nodal irradiation, a limitation of our

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survey is that we did not include the option for the participant to include more

comprehensive nodal coverage extending to the internal mammary nodes in our case

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based scenarios. Interestingly, we had 2 participants email free text to our authors that they may have included internal mammary nodal coverage in some of the clinical case vignettes given the recent study finding from the MA.20 trial which showed that additional regional nodal radiation (RNI), inclusive of the internal mammary nodes

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reduced the risk of locoregional and distant recurrence, and improves DFS with a trend in improved OS22. The question remains for most of the early stage breast cancer cases with positive sentinel nodes, “what is the true risk of lymph node disease that would

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potentially warrant the potential side effect profile of radiation treatment to the comprehensive regional lymphatics?” 23. The results of MA.20 have led several radiation

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oncologists to the conclusion that regional nodal RT is needed even in cases of low axillary risk, and that radiation has a systemic effect as well as local control. However, the final conclusion of this study demonstrated that the addition of regional nodal irradiation to whole-breast irradiation after breast-conserving surgery in women with node-positive or high-risk node-negative breast cancer did not improve overall survival but did reduce breast-cancer recurrence. This study emphasizes the importance of a risk

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stratified treatment decision which involves a careful discussion of the potential risks and benefits of regional nodal radiation with the patient 22. Conclusions

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There is increasing use of radiation to the axilla in patients with positive SLN when omitting a completion ALND. Despite various risk stratification scenarios, most

respondents use a SCF or full axillary coverage for most cases. Online prediction

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nomograms are used by a minority of practitioners to assist in clinical decision-making in this setting. Individualized treatment plans and risk adaptive approach should be

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considered in order to provide true benefit of axillary radiation therapy.

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Figures: Figure 1.

Demographics. 1.A) Primary Professional Affiliation. 45.5% of respondents have academic, 40% have community, and 14.5% have hybrid affiliation. 1.B) Respondents

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from all US Territories.v31.7% from Midwest US, 29.0% from Western US, 22.1% from Eastern US, and 17.2% from Southeast US.1.C) Years Post-Residency. 54.4% of respondents are in more 10 years post-residency (PR), 26.6% are 5-9 years PR,

Figure 2.

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14.0% are 3-5 years PR, and 5.0% are 0-2 years PR.

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Breast Cancer (BC) Sub-Specialty and Number of BC Patients(Pt.) per year. 2.A. 67.60% of respondents primarily treat BC patients. 2.B) 53.80% of Respondents treat more than 50 Pts. per year, 39.30% treat 20-50 Pts. per year, and 6.9% treat less than 20 Pts. per year. Figure 3. Addressing the Axilla in patients with 1-3 positive SLN and clinically mobile

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Axillary node. 3.A) 8.30% perform ALND in patients with 1-3 positive SLN without extracapsular extension (ECE), 46.10% perform ALND in patients with 1-3 SLN with

mobile axillary node prior to chemotherapy. Figure 4.

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ECE. 3.B) 56.30% perform SNB, and 42.90% perform ALND in surgically managing a

Nomogram. 4.A) 28.20% use nomogram to further predict axillary management in

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patient with 1-3 positive SLN. 4.B) 21.10% use Katz nomogram to predict 4 or more

AC C

EP

TE D

M AN U

positive nodes with a positive SLN.

Fig. 1

14.5%

M AN U

SC

RI PT

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22.1%

31.7%

45.5%

Academic

40%

Community

A

TE D

Hybrid

17.2%

5.0%

B

14.0%

AC C

EP

26.6%

C

>10 54.4%

5-9 Yr 3-5 Yr 0-2 Yr

Eastern US Western US 29.0%

Southeast US Midwest US

Fig.2

67.60%

M AN U

SC

RI PT

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53.80%

39.30%

No

TE D

32.40%

Yes

AC C

EP

A

6.90%

<20 Pt

20-50 Pt B

>50 Pt

Fig. 3

ALND with 1-3 Posi ve SLN(%)

Addressing the Axilla

No ECE

TE D

46.10%

8.30%

ECE

AC C

EP

A

M AN U

SC

RI PT

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56.30%

SNB

42.90%

ALND

B

Fig. 4

M AN U

SC

RI PT

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Nomogram 38.00%

28.20%

78.90%

Yes

TE D

21.10%

No

AC C

EP

A

Yes

No B

SC

RI PT

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fields.

M AN U

Table 1 summarizes the clinical vignettes and the % responses in selecting radiation

Clinical Scenario

No. of Posi ve Sen nel Nodes

Standard Tangents(%)

High Tangents(%)

Tangents and Supraclavicular Field(%)

Tangents and Full Axillary Coverage(%)

1

IDC, 1.5cm, ER posi ve, LSVI nega ve

One(micro)

33.1

53.8

7.7

5.4

2

IDC, 1.5cm,Grade 3, ER Posi ve, LSVI nega ve, ECE nega ve

One(macro)

6.9

44.6

24.6

23.8

3

IDC, 1.5cm, ER posi ve, LVSI nega ve, ECE nega ve, a er neoadjuvant chemotherapy

One(macro)

2.3

27.5

34.4

35.9

4

IDC, 2.2cm, ER nega ve, LVSI posi ve

Two(macro)

0.8

4.6

47.3

47.3

5

IDC, 2.2cm,ER posi ve, LVSI posi ve, mul focal

Two(macro)

0.8

12.3

41.5

45.4

6

IDC, 1.5cm,grade 3, LVSI posi ve

One(micro)

6.9

44.3

24.4

24.4

7

s/p mastectomy, 2.2primary, mul focal, ER posi ve, LVSI nega ve

One(macro)

0.8

16.3

30.2

39.5

AC C

EP

TE D

#

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Abbreviations: DC: ductal carcinoma; ECE, extracapsular extension; ER, estrogen

M AN U

SC

RI PT

receptor; LVSI, lymphvascular space involvement

Table 2. summarizes the clinical vignettes and the % responses in selecting radiation fields in academic and community affiliated respondents. Responses that accounted for

AC C

EP

TE D

less than 20% were excluded from the analysis.

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#

Clinical Scenario

No. of Posi ve Sen nel Nodes

T(%)

HT(%) Community

Academic

T&SCF(%)

T&AX(%)

Academic Community Academic Community

IDC, 1.5cm, ER posi ve, LSVI nega ve

One(micro)

32

37

61

3

14

3

3

0.12

2

IDC, 1.5cm,Grade 3, ER Posi ve, LSVI nega ve, ECE nega ve

One(macro)

6

9

50

35

16

37

27

18

0.004

3

IDC, 1.5cm, ER posi ve, LVSI nega ve, ECE nega ve, a er neoadjuvant chemotherapy

One(macro)

1

3

34

18

30

38

4

IDC, 2.2cm, ER nega ve, LVSI posi ve

Two(macro)

0

1

3

7

44

51

5

IDC, 2.2cm,ER posi ve, LVSI posi ve, mul focal

Two(macro)

0

2

11

15

40

47

6

IDC, 1.5cm,grade 3, LVSI posi ve

One(micro)

11

7

48

35

11

39

30

18

<0.0001

7

s/p mastectomy, 2.2primary, mul focal, ER posi ve, LVSI nega ve

One(macro)

0

9

13

1

28

18

43

38

0.0002

RI PT

1

33

38

0.07

52

38

0.15

49

35

0.16

M AN U

SC

44

P Value

Academic Community

TE D

Abbreviations: DC: ductal carcinoma; ECE, extracapsular extension; ER, estrogen

AC C

EP

receptor; LVSI, lymphvascular space involvement

Supplement Figure 1.

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1. What is your primary professional affiliation? -Community

-Hybrid

2. How many years post-residency have you been in practice? -Currently in training -0-2

-3-5

-5-9

->10

RI PT

-Academic

3. Does your job position include treating breast cancer primarily?

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-Yes -No

-<20

-20-50

->50

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4. How many breast cancer patients do you treat per year?

5. In what state or US territory is your primary clinical practice? -Eastern US

-Western US

-Southeast US

-Midwest US

All questions below refer to an early stage breast cancer case after a lumpectomy.

TE D

6. Do patients with 1-3 positive sentinel lymph nodes (SLN) without extracapsular extension (ECE) routinely undergo completion axillary node dissection at your

-Yes

-No

-Sometimes

EP

institution?

7. Do patients with 1-3 positive SLN with ECE routinely undergo completion axillary

AC C

node dissection at your institution? -Yes

-No

-Sometimes

8. Do you use a nomogram (such as the MD Anderson Cancer Center or Memorial Sloan Kettering) to predict further axillary lymph node involvement in with 1-3 positive SLN to decide on further management with surgery or radiation therapy? -Yes

-No

-Sometimes

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9. Do you use the Katz nomogram to predict 4 or more positive nodes with a positive sentinel node? -Yes -No

supraclavicular field for treatment? -10-15%

-15-20%

-20-25%

->25%

RI PT

10. If your answer to question 9 is Yes, what percent would prompt the addition of a

-Not applicable

SC

11. A patient has a clinically mobile positive axillary node prior to neoadjuvant

chemotherapy without pathological confirmation of involvement. How would your

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institution surgically manage the axilla after neoadjuvant chemotherapy? -Sentinel node biopsy

-Axillary node dissection

Case Scenarios

-No further axillary surgery

12. 65 yo female is s/p lumpectomy with a 1.5cm infiltrating ductal cancer (IDC), no

TE D

lymphvascular space involvement (LVSI), ER+ has one SLN (micro) without ECE. Which radiation field do you treat? -Standard Tangents

-High Tangents

-Tangents and a supraclavicular field

EP

-Tangents and full axillary coverage

13. 51 yo female is s/p lumpectomy with a 1.5cm IDC, grade 3, no LVSI, 1.5cm primary,

AC C

ER+ has one SLN (macro) without ECE. Which radiation field do you treat? -Standard Tangents

-High Tangents -Tangents and a supraclavicular field

-Tangents and full axillary coverage 14. 60 yo female is s/p lumpectomy with a 1.5cm IDC, no LVSI, ER+ has one SLN (macro) without ECE after neoadjuvant chemotherapy. Which radiation field do you treat?

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-Standard Tangents

-High Tangents

-Tangents and a supraclavicular field

-Tangents and full axillary coverage 15. 43 yo female is s/p lumpectomy with a 2.2cm IDC, LVSI positive, ER negative has 2

-Standard Tangents -High Tangents

RI PT

SLN (macro). Which radiation field do you treat? fields do you treat?

-Tangents and a supraclavicular field

-Tangents and full axillary coverage

SC

16. 60 yo female is s/p lumpectomy with a 2.2cm IDC, LVSI positive, ER positive, multifocal, has 2 SLN (macro). Which radiation field do you treat?

-Tangents and full axillary coverage

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-Standard Tangents -High Tangents -Tangents and a supraclavicular field

17. 45 yo female is s/p lumpectomy with a 1.5cm IDC, grade 3, LVSI positive, with 1 SNL (micro). Which radiation field do you treat?

TE D

-Standard Tangents -High Tangents -Tangents and supraclavicular field -Tangents and full axillary coverage

18. 57 yo female with 2.2cm primary, ER positive, no LVSI, multifocal with 1 sentinel

EP

node involved (macro) after a simple mastectomy. Further axillary surgery is not possible. How would you treat this patient? -Standard Tangents -High Tangents

AC C

-No radiation

-Tangents and suprascapular field

-Tangents and full axillary coverage

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Supplement Figure 1. Questionnaire. 1. What is your primary professional affiliation? -Community

-Hybrid

2. How many years post-residency have you been in practice? -Currently in training -0-2

-3-5

-5-9

->10

RI PT

-Academic

SC

3. Does your job position include treating breast cancer primarily? -Yes -No

-<20

-20-50

->50

M AN U

4. How many breast cancer patients do you treat per year?

5. In what state or US territory is your primary clinical practice? -Eastern US

-Western US

-Southeast US

-Midwest US

TE D

All questions below refer to an early stage breast cancer case after a lumpectomy. 6. Do patients with 1-3 positive sentinel lymph nodes (SLN) without extracapsular

institution? -Yes

-No

EP

extension (ECE) routinely undergo completion axillary node dissection at your

-Sometimes

AC C

7. Do patients with 1-3 positive SLN with ECE routinely undergo completion axillary node dissection at your institution? -Yes

-No

-Sometimes

8. Do you use a nomogram (such as the MD Anderson Cancer Center or Memorial Sloan Kettering) to predict further axillary lymph node involvement in with 1-3 positive SLN to decide on further management with surgery or radiation therapy?

ACCEPTED MANUSCRIPT

-Yes

-No

-Sometimes

9. Do you use the Katz nomogram to predict 4 or more positive nodes with a positive

-Yes -No

RI PT

sentinel node?

10. If your answer to question 9 is Yes, what percent would prompt the addition of a

-10-15%

-15-20%

-20-25%

->25%

-Not applicabale

SC

supraclavicular field for treatment?

11. A patient has a clinically mobile positive axillary node prior to neoadjuvant

M AN U

chemotherapy without pathological confirmation of involvement. How would your institution surgically manage the axilla after neoadjuvant chemotherapy? -Sentinel node biopsy

-Axillary node dissection

Case Scenarios

-No further axillary surgery

TE D

12. 65 yo female is s/p lumpectomy with a 1.5cm infiltrating ductal cancer (IDC), no lymphvascular space involvement (LVSI), ER+ has one SLN (micro) without ECE. Which radiation field do you treat?

-High Tangents

EP

-Standard Tangents

-Tangents and a supraclavicular field

-Tangents and full axillary coverage

AC C

13. 51 yo female is s/p lumpectomy with a 1.5cm IDC, grade 3, no LVSI, 1.5cm primary, ER+ has one SLN (macro) without ECE. Which radiation field do you treat? -Standard Tangents

-High Tangents -Tangents and a supraclavicular field

-Tangents and full axillary coverage 14. 60 yo female is s/p lumpectomy with a 1.5cm IDC, no LVSI, ER+ has one SLN (macro) without ECE after neoadjuvant chemotherapy. Which radiation field do you

ACCEPTED MANUSCRIPT

treat? -Standard Tangents

-High Tangents

-Tangents and a supraclavicular field

-Tangents and full axillary coverage

RI PT

15. 43 yo female is s/p lumpectomy with a 2.2cm IDC, LVSI positive, ER negative has 2 SLN (macro). Which radiation field do you treat? fields do you treat? -Standard Tangents -High Tangents

-Tangents and a supraclavicular field

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-Tangents and full axillary coverage

16. 60 yo female is s/p lumpectomy with a 2.2cm IDC, LVSI positive, ER positive,

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multifocal, has 2 SLN (macro). Which radiation field do you treat?

-Standard Tangents -High Tangents -Tangents and a supraclavicular field -Tangents and full axillary coverage

17. 45 yo female is s/p lumpectomy with a 1.5cm IDC, grade 3, LVSI positive, with 1

TE D

SNL (micro). Which radiation field do you treat?

-Standard Tangents -High Tangents -Tangents and supraclavicular field -Tangents and full axillary coverage

EP

18. 57 yo female with 2.2cm primary, ER positive, no LVSI, multifocal with 1 sentinel node involved (macro) after a simple mastectomy. Further axillary surgery is not

AC C

possible. How would you treat this patient? -No radiation

-Standard Tangents -High Tangents

-Tangents and suprascapular field

-Tangents and full axillary coverage