Use Of Regional Nodal Irradiation Research Articles

Clinical Experience of Axillary Radiotherapy for Node-positive Breast Cancer

AimsPatients with breast cancer who have positive lymph nodes are currently recommended axillary node clearance (ANC) or regional nodal irradiation (RNI). ANC is associated with complications such as lymphoedema, brachial plexopathy and shoulder stiffness. The AMAROS Group showed RNI to be non-inferior to ANC with regards to survival and recurrence, and with a better quality of life. We conducted a large real-world population study to show our centre's experience with the use of RNI and to contribute to the current discussion around the management of node-positive breast cancer. Materials and methodsWe evaluated patients who received RNI as opposed to ANC between 2006 and 2009 (n = 190). Patients had a range of cancer subtypes/grades. All had positive axillary disease, identified by axillary node sampling or sentinel lymph node biopsy. Systemic therapy was given as per standard protocol. Our data were compared with those of patients who had RNI (n = 681) in AMAROS. Patients were followed up retrospectively and overall survival, breast cancer-specific survival, distant metastasis-free survival, locoregional recurrence and toxicity were recorded, including lymphoedema, brachial plexopathy and shoulder stiffness. Survival analysis was performed on R via the Kaplan–Meier method. Univariate and multivariate analyses were also performed. Toxicity data were reported as percentages. Patients meeting POSNOC trial criteria (one to two positive sentinel lymph nodes, macrometastasis, receiving adjuvant chemotherapy) including if oestrogen receptor-positive (stratified POSNOC) were identified for subgroup analysis in the regression model. ResultsLocoregional recurrence was 3.16% versus AMAROS RNI of 1.82%. Overall survival was slightly lower in our population, but cancer-specific survival was higher than AMAROS. Lymphoedema rates were 5.8% versus AMAROS 11% in RNI and 23% in ANC arms, respectively. Brachial plexopathy was 1.6% and arm/shoulder stiffness 7.4%. AMAROS conducted a quality of life survey pertaining to arm/shoulder stiffness, mobility and function, which seemed to affect about 18% in the RNI arm. Univariate analysis revealed POSNOC status, especially if also oestrogen receptor-positive, to be a low risk group with hazard ratio 0.42 (0.20–0.83, P = 0.015). Extracapsular extension of lymph node metastasis was a poor prognostic factor; hazard ratio 4.39 (1.45–14.0, P = 0.009). ConclusionWe support the conclusion of the AMAROS trial with survival and recurrence following RNI being non-inferior to ANC, and with similarly favourable toxicity data. We support the continuing use of RNI as a treatment option for patients with node-positive breast cancer. Further research is required to answer the key questions regarding personalised management for node-positive breast cancer, with regards to de-escalation and also intensification for the patients exhibiting adverse tumour biology.

Patterns and Longitudinal Changes in The Practice of Breast Cancer Radiotherapy in Korea: Korean Radiation Oncology Group 22-01

To analyze contemporary practice patterns in breast cancer radiotherapy (RT) and to assess longitudinal changes therein over 5 years in Korea. A nationwide survey was conducted among board-certified radiation oncologists in Korea by the Division for Breast Cancer of the Korean Radiation Oncology Group in March 2022. The survey consisted of 44 questions related to six domains: hypofractionated (HypoFx) whole breast RT, accelerated partial breast RT (APBI), regional nodal irradiation (RNI), RT for ductal carcinoma in situ (DCIS), postmastectomy RT (PMRT), and tumor bed boost. In total, 70 radiation oncologists from 61 of 101 (60%) institutions participated in the survey. HypoFx RT was used by 62 respondents (89%), which has significantly increased from 36% in 2017. The HypoFx RT was commonly administered at 40-42.5 Gy in 15-16 fractions. APBI was used by 12 respondents (17%), which has increased from 5% in 2017. The use of RNI did not change significantly: ≥ pN2 (6%), ≥ pN1 (33%), and ≥ pN1 with pathological risk factors (61%). However, the indications for use of internal mammary lymph node (IMN) irradiation have expanded. In particular, the rates of routine treatment of IMN (11% from 6% in 2017) and treatment in cases of ≥ pN2 (27% from 14% in 2017) have doubled; however, the rate of treatment for only IMN involvement, identified on imaging, has decreased to 31% from 47% in 2017. With regard to DCIS, the use of hypoFx RT increased to 75% from 25%, and the rate of omission on of RT after breast-conserving surgery decreased to 38% from 48% in 2017. The use of hypoFx RT for PMRT also increased to 36% from 8% in 2017. The adoption of HypoFx RT after breast-conserving surgery in invasive breast cancer and DCIS has increased significantly, whereas that for PMRT has increased moderately, compared to 2017. Further studies are required to determine the optimal use of RNI.

Radiotherapy Use and Incidence of Locoregional Recurrence in Patients With Favorable-Risk, Node-Positive Breast Cancer Enrolled in the SWOG S1007 Trial

Little is known about regional nodal irradiation (RNI) practice patterns or rates of locoregional recurrence (LRR) with and without RNI in patients with limited nodal disease and favorable biology treated with modern surgical and systemic therapy, including approaches that de-escalate those latter treatments. To investigate how often patients with low-recurrence score breast cancer with 1 to 3 nodes involved receive RNI, incidence and predictors of LRR, and associations between locoregional therapy and disease-free survival. In this secondary analysis of the SWOG S1007 trial, patients with hormone receptor-positive, ERBB2-negative breast cancer, and a Oncotype DX 21-gene Breast Recurrence Score assay result of no more than 25, were randomized to endocrine therapy alone vs chemotherapy then endocrine therapy. Prospectively collected radiotherapy information was collected from 4871 patients treated in diverse settings. Data were analyzed June 2022 to April 2023. Receipt of RNI (targeting at least the supraclavicular region). Cumulative incidence of LRR was calculated by locoregional treatment received. Analyses were assessed for associations between invasive disease-free survival (IDFS) and locoregional therapy, adjusted for menopausal status, treatment group, recurrence score, tumor size, nodes involved, and axillary surgery. Radiotherapy information was recorded in the first year after randomization, so survival analyses were landmarked as starting at 1 year among those still at risk. Of 4871 female patients (median [range] age, 57 [18-87] years) with radiotherapy forms, 3947 (81.0%) reported radiotherapy receipt. Of 3852 patients who received radiotherapy and had complete information on targets, 2274 (59.0%) received RNI. With a median follow-up of 6.1 years, the cumulative incidence of LRR by 5 years was 0.85% among patients who received breast-conserving surgery and radiotherapy with RNI; 0.55% after breast-conserving surgery with radiotherapy without RNI; 0.11% after mastectomy with postmastectomy radiotherapy; and 1.7% after mastectomy without radiotherapy. Similarly low LRR was observed within the group assigned to endocrine therapy without chemotherapy. The rate of IDFS did not differ by RNI receipt (premenopausal: hazard ratio [HR], 1.03; 95% CI, 0.74-1.43; P = .87; postmenopausal: HR, 0.85; 95% CI, 0.68-1.07; P = .16). In this secondary analysis of a clinical trial, RNI use was divided in the setting of biologically favorable N1 disease, and rates of LRR were low even in patients who did not receive RNI. Disease-free survival was not associated with RNI receipt; omission of chemotherapy among patients similar to those enrolled in the S1007 trial is not an independent indication for use of RNI.

Patterns and Longitudinal Changes in the Practice of Breast Cancer Radiotherapy in Korea: Korean Radiation Oncology Group 22-01.

We aimed to analyze contemporary practice patterns in breast cancer radiotherapy (RT) and assess longitudinal changes over five years in Korea. In 2022, a nationwide survey was conducted among board-certified radiation oncologists. The survey consisted of 44 questions related to six domains: hypofractionated (HypoFx) whole breast RT, accelerated partial breast RT (APBI), regional nodal irradiation (RNI), RT for ductal carcinoma in situ (DCIS), postmastectomy RT (PMRT), and tumor bed boost. Seventy radiation oncologists from 61 (out of 101; 60%) institutions participated in the survey. HypoFx RT was used by 62 respondents (89%), a significant increase from 36% in 2017. HypoFx RT is commonly administered at 40-42.5 Gy in 15-16 fractions. APBI was used by 12 respondents (17%), an increase from 5% in 2017. The use of RNI did not change significantly: ≥ pN2 (6%), ≥ pN1 (33%), and ≥ pN1 with pathological risk factors (61%). However, indications for internal mammary lymph node (IMN) irradiation have expanded. In particular, the rates of routine treatment of IMN (11% from 6% in 2017) and treatment in cases of ≥ pN2 (27% from 14% in 2017) have doubled; however, the rate of treatment for only IMN involvement, identified on imaging, has decreased from 47% in 2017 to 31%. For DCIS, the use of HypoFx RT increased from 25% in 2017 to 75%, and the rate of RT omissions after breast-conserving surgery (BCS) decreased from 48% in 2017 to 38%. The use of HypoFx RT for PMRT increased from 8% in 2017 to 36%. The adoption of HypoFx RT after BCS for invasive breast cancer and DCIS has increased significantly, whereas the use of HypoFx PMRT has increased moderately since 2017. However, further studies are required to determine the optimal use of RNI.

Increasing Utilization of Regional Nodal Irradiation for Patients with Low-Risk Node-Positive Breast Cancer

<h3>Purpose/Objective(s)</h3> For patients with biologically low-risk, N1 breast cancer, the benefit of regional nodal irradiation (RNI) and post-mastectomy radiotherapy (PMRT) is unclear and is the subject of ongoing clinical trials. Population-level data of rates of RNI receipt is lacking in this cohort, and may be increasing despite its uncertain benefit. The purpose of this study was to determine if there was increasing use of RNI and PMRT for low-risk, N1 breast cancer. <h3>Materials/Methods</h3> This was a population-based study of all patients diagnosed between 2005 to 2014 in the [state/province] of [blinded], who underwent breast conserving surgery (BCS) or mastectomy for breast cancer. We based our definition of low-risk on the original inclusion criteria of MA.39/TAILOR RT trial, which is a non-inferiority clinical trial examining whether the omission of RNI is non-inferior. We included: pT1-2 pN1 (macroscopically node-positive) breast cancer. To define a biologically low-risk population, we included patients with a Luminal A subtype. This was approximated by: ER Allred 6-8/8, PR Allred 6-8/8, HER2-negative, and Grade 1-2. Patients who underwent a BCS and mastectomy were analyzed separately. The primary outcome was RNI receipt for patients who had a BCS, and PMRT receipt for those who had a mastectomy. We performed a multivariate, logistic regression to see whether year of diagnosis predicted for receipt of radiation. Other variables included in the multivariate model were defined a priori, based on factors known to influence RNI and PMRT receipt in the literature. <h3>Results</h3> There were 637 women who had BCS and 532 who had mastectomy in this cohort. For patients who had BCS, the rates of RNI receipt by years were: 2005-2008 68%, 2009-2011 79%, 2012-2014 89%. For patients who had a mastectomy, the rates of PMRT receipt by years were: 2005-2008 67%, 2009-2011 68%, 2012-2014 80%. During this time period, decreasing rates of ALND were observed: 2005-2008: 92%, 2009-2011 74%, 2012-2014 42%. On multivariate analysis of patients who had a BCS, RNI receipt was associated with number of involved macroscopic nodes (p=0.002) and date of diagnosis (p<0.001), but not age (p=0.2), presence of LVI (p=0.2), ALND (p=0.08), or chemotherapy receipt (p=0.9). For patients who had a mastectomy, PMRT receipt on multivariate analysis was associated with number of involved macroscopic nodes (p=0.02) and chemotherapy receipt (p=0.004), but not age (p=0.09), LVI (p=0.3), or diagnosis date (p=0.1). <h3>Conclusion</h3> There was an increased rate of RNI receipt, and a trend for increased receipt of PMRT for patients with low-risk, node-positive breast cancer between 2005 to 2014. This population-level data shows the large proportion of women who may be spared RNI if the MA.39 non-inferiority trial determines that omission of RNI is safe.

Abstract PD4-07: Contemporary practice patterns for the use of regional nodal irradiation during post-lumpectomy radiotherapy for patients with N0/N1 breast cancer

Abstract BACKGROUND: Current national guidelines encourage consideration for treating the at-risk regional nodes (axillary, supraclavicular, and/or internal mammary) with directed regional nodal irradiation (RNI) during post-lumpectomy radiotherapy for high risk N0 (node negative) and N1 (1-3 nodes positive) breast cancer patients. This recommendation is based on the results of several randomized trials published over the last decade. Evidence regarding translation of these trials into clinical practice in the United States has been limited to date. In this study, we sought to characterize the temporal changes in and clinical factors associated with the utilization of RNI during post-lumpectomy radiotherapy for N0-N1 breast cancer across a contemporary, statewide consortium of radiation oncology practices. METHODS: Within a statewide radiation oncology quality consortium, 12,170 breast cancer patients were consecutively enrolled between 1/1/2013 and 10/31/2019 in both academic (teaching) and community (non-teaching) facilities. Data on receptor status, adjuvant systemic therapy, age, TNM stage, extent of axillary surgery, race, body mass index (BMI), type of treating facility, and year completing radiotherapy (RT) were collected. Eligibility for the present analysis was limited to patients with N0 and N1 disease not receiving neoadjuvant systemic therapy and receiving adjuvant radiotherapy after lumpectomy for non-metastatic breast cancer. Multiple variable logistic regression models were separately fit to explain the use of directed RNI (to the axilla, supraclavicular region, and/or internal mammary region) for the N0 and N1 populations separately and described using odds ratios (OR), with significant ORs (p&amp;lt;0.05) reported. RESULTS: A total of 8,468 patients from 29 treating facilities met the inclusion criteria: 6,929 (81.8%) with N0 and 1,539 (18.2%) N1 disease. RNI was performed in addition to whole breast radiation in 95 (1.4%) and 908 (59%) patients in the N0 and N1 cohorts respectively. For the N0 cohort, significant correlates of RNI on multivariable analysis (MVA) were receipt of adjuvant chemotherapy (OR 2.7), higher T-stage (OR 1.9 for T2 vs T1 and 27.3 for T3/T4 vs T1), axillary surgery [compared to sentinel node biopsy (SLN) alone : no axillary surgery (OR 14.5), axillary lymph node dissection (ALND) with 10+ nodes removed (OR 15.1) ALND after SLN (OR 2.7)], and underweight BMI (OR 4.9 compared to overweight, which was the reference as the largest BMI category). For the N1 cohort, MVA suggested adjuvant chemotherapy (OR 1.8) and larger tumors (OR 1.6 [T2 vs T1]) were significantly associated with use of RNI. The year completing RT was also significantly associated with RNI use, with 22% and 15% increases per year from 2013 to 2019 in the N0 and N1 cohorts, respectively. Lastly, receiving treatment in an academic facility compared to a community facility was significantly associated with receipt of RNI in both the N0 (OR 1.8) and N1 (OR 2.2) cohorts. CONCLUSION: In this large cohort, selective use of RNI added to post-lumpectomy whole breast radiotherapy is estimated to have increased over time, suggesting growing implementation of recent trial data and current clinical practice guidelines. Patient, treatment, and tumor characteristics appear to factor into the decision to treat with RNI, but differences in use between academic and community practices suggest opportunities for improving the consistency of care across care delivery settings. Ongoing trials seeking to identify subgroups of N1 patients in whom RNI can safely be omitted may be especially important to inform decisions, given the almost even split (59% receiving, 41% not) in practice observed in this large American cohort. Citation Format: Derek Bergsma, Kent Griffith, Reshma Jagsi, Michael Dominello, Thomas Boike, Joshua Dilworth, Amit Bhatt, Frank Vicini, Maggie Grubb, Jean Moran, James Hayman, Lori Pierce, on behalf of MROQC, the Michigan Radiation Oncology Quality Consortium. Contemporary practice patterns for the use of regional nodal irradiation during post-lumpectomy radiotherapy for patients with N0/N1 breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD4-07.

Development and external validation of a nomogram to predict four or more positive nodes in breast cancer patients with one to three positive sentinel lymph nodes

ObjectiveTo develop a nomogram for predicting the possibility of four or more positive nodes in breast cancer patients with 1–3 positive sentinel lymph nodes (SLN). Materials and methodsRetrospective analysis of data of patients from two institutions was conducted. The inclusion criteria were: invasive breast cancer; clinically node negative; received lumpectomy or mastectomy plus SLN biopsy followed by axillary lymph node dissection (ALND); and pathologically confirmed T1-2 tumor, with 1–3 positive SLNs. Patients from one institution formed the training group and patients from the other the validation group. Univariate and multivariate analyses were performed to identify the predictors of four or more positive nodes. These predictors were used to build the nomogram. The area under the receiver operating characteristic curve (AUC) was calculated to assess the accuracy of the model. ResultsOf the 1480 patients (966 patients in the training group, 514 in the validation group), 306 (20.7%) had four or more positive nodes. Multivariate stepwise logistic regression showed number of positive (p < .001) and negative SLN (p < .001), extracapsular extension (p < .001), pT stage (p = .016), and tumor location in outer upper quadrant (p = .031) to be independent predictors of four or more positive nodes. The nomogram was built using these five factors. The AUC was 0.845 in the training group and 0.804 in the validation group. ConclusionThe proposed nomogram appears to accurately estimate the likelihood of four or more positive nodes and could help radiation oncologists to decide on use of regional nodal irradiation (RNI) for breast cancer patients with 1–3 positive nodes but no ALND.

Trends in Regional Nodal Management of Breast Cancer Patients with Low Nodal Burden.

American College of Surgeons Oncology Group Z0011 confirms the safety of omitting axillary lymph node dissection (ALND) and regional nodal irradiation (RNI) in breast cancer patients with one to two positive sentinel lymph nodes (SLNs), without compromising disease-free survival (DFS) and overall survival (OS). In contrast, the NCIC MA20 trial showed improved DFS in node-positive patients undergoing ALND and RNI. We sought to examine how these data have influenced the management of patients with limited nodal burden. Using the National Cancer Database, patients diagnosed between 2010 and 2015 and who met the criteria for Z0011 were identified. Logistic regression was used to analyze factors associated with practice patterns. The Cox proportional hazards model was used to assess the association of ALND and RNI with OS. Omission of ALND in Z0011-eligible patients reached 89.2% in 2015. This Z0011-compliant group was more likely to undergo RNI compared with the non-compliant group (36.4% vs. 31.3%; p < 0.05), with RNI increasing to 43.8% by 2015. Factors associated with the use of RNI included later year of diagnosis [odds ratio (OR) 1.8, 95% confidence interval (CI) 1.6-2.1], hormone receptor-negative tumor (OR 1.2, 95% CI 1.1-1.4), grade 3 tumor (OR 1.2, 95% CI 1.1-1.3), treatment at a non-academic site (OR 1.2, 95% CI 1.1-1.3) and two versus one positive SLN (OR 2.0, 95% CI 1.8-2.2). With 43months median follow-up, RNI was not associated with improved OS. Since the publication of Z0011, the omission of ALND has become widespread; however nearly half of these women now receive RNI. The optimal radiation therapy approach for this low nodal burden population warrants further study.

Increasing utilization of regional nodal irradiation in elderly node-positive women and declining emphasis on demographic factors.

To evaluate the practice patterns for the use of regional nodal irradiation (RNI) in treatment of elderly women with low volume node-positive breast cancer in the setting of breast conservation surgery (BCS). Women aged 70-89 diagnosed with unilateral, pathologic T1-2N1M0 breast cancer from 2004 to 2013, who underwent BCS and received radiotherapy were identified from the National Cancer Database. In 2011, two major trials were presented that helped define indications for RNI. Patients were dichotomized into "early", i.e. diagnosed up to 2010, and "late" cohorts. Patient and treatment characteristics were compared between the cohorts and logistic regression used to determine independent factors associated with the receipt of RNI. 7228 women met inclusion criteria; 4330 (59.9%) in early and 2898 (40.1%) in late cohorts. Utilization of RNI increased from 33.9% in early to 42.5% in late cohorts (P≤0.001) and was independent of a general increase in RNI utilization. RNI in the early and late cohorts was not different between the study population and younger women (P>0.05). RNI utilization increased in both cohorts with increasing number of positive lymph nodes. In the early cohort, RNI was also associated with higher grade, white race and lower income. In the late cohort, RNI increased with the presence of multiple, predefined risk factors. There was an increase in utilization of RNI for elderly patients from 2004 to 2013. In more recent years, the primary factors associated with receipt of RNI were tumor related with declining importance of demographic factors.

Use of regional nodal irradiation and its association with survival for women with high-risk, early stage breast cancer: A National Cancer Database analysis

PurposeThe role of regional nodal irradiation (RNI) for patients with breast cancer remains controversial, particularly on the basis of nodal involvement. Using the National Cancer Database, we aimed to validate published data on whether expanding treatment fields from whole-breast irradiation (WBI) to encompass the regional nodes (WBI+RNI) affected overall survival (OS) for patients with node-positive (pN1-3) or high-risk node-negative (pN0) breast cancer treated with breast-conserving surgery and adjuvant chemotherapy. Methods and materialsWomen diagnosed with invasive breast cancer between 2004 and 2012 who met the selection criteria for the National Cancer Institute of Canada MA.20 trial were identified and stratified by receipt of RNI. Propensity score matching was used to compare 1:1 matched pairs of patients. Five-year OS was estimated using the Kaplan-Meier method. We used multivariate logistic regression to predict receipt of WBI+RNI and a multivariable Cox model to examine associations between patients' demographic, tumor, and treatment characteristics and OS using double robust estimation. ResultsOf 23,567 patients, 6,920 (29%) received WBI+RNI and 16,647 (71%) WBI. Median follow-up was 56 months. Use of WBI+RNI increased from 25.2% in 2004 to 32.2% in 2012 (P < .001). Patients receiving WBI+RNI more often had negative hormone-receptor status, ≥5 cm tumors and >1 involved node, and were not privately insured. For all patients, the 5-year OS rates were 90.8% with WBI+RNI versus 92.6% with WBI (P < .001). In the matched cohort (n = 10,922), the corresponding 5-year OS rates were 92% and 91.9% (P = .45), respectively. On multivariate analysis, WBI+RNI did not affect OS in the matched cohort (hazard ratio, 1.02; 95% confidence interval, 0.89-1.17, P = .76), regardless of pathologic nodal status. ConclusionsIn this large retrospective analysis, use of WBI+RNI did not affect 5-year OS rates for women with high-risk, early stage breast cancer undergoing breast-conserving surgery and adjuvant chemotherapy, regardless of nodal status, which confirms the findings of the MA.20 trial.

Breast cancer: rational use of regional nodal irradiation needed.

Breast cancer: rational use of regional nodal irradiation needed.

Personalization of loco-regional care for primary breast cancer patients (part 2).

Kyoto Breast Cancer Consensus Conference, Kyoto, Japan, 18-20 February 2014 The loco-regional management of breast cancer is increasingly complex with application of primary systemic therapies, oncoplastic techniques and genetic testing for breast cancer susceptibility. Personalization of loco-regional treatment is integral to optimization of breast cancer care. Clinical and pathological tumor stage, biological features and host factors influence loco-regional treatment strategies and extent of surgical procedures. Key issues including axillary staging, axillary treatment, radiation therapy, primary systemic therapy (PST), preoperative hormonal therapy and genetic predisposition were identified and discussed at the Kyoto Breast Cancer Consensus Conference (KBCCC2014). In the second of a two part conference scene, consensus recommendations for radiation treatment, primary systemic therapies and management of genetic predisposition are reported and focus on the following topics: influence of both clinical response to PST and stage at presentation on recommendations for postmastectomy radiotherapy; use of regional nodal irradiation in selected node-positive patients and those with adverse pathological factors; extent of surgical resection following downstaging of tumors with PST; use of preoperative hormonal therapy in premenopausal women with larger, node-negative luminal A-like tumors and managing increasing demands for contralateral prophylactic mastectomy in patients with a unilateral sporadic breast cancer.

DEGRO practical guidelines: radiotherapy of breast cancer III—radiotherapy of the lymphatic pathways

The purpose of this work is to update the practical guidelines for adjuvant radiotherapy of the regional lymphatics of breast cancer published in 2008 by the breast cancer expert panel of the German Society of Radiation Oncology (DEGRO). A comprehensive survey of the literature concerning regional nodal irradiation (RNI) was performed using the following search terms: "breast cancer", "radiotherapy", "regional node irradiation". Recent randomized trials were analyzed for outcome as well as for differences in target definition. Field arrangements in the different studies were reproduced and superimposed on CT slices with individually contoured node areas. Moreover, data from recently published meta-analyses and guidelines of international breast cancer societies, yielding new aspects compared to 2008, provided the basis for defining recommendations according to the criteria of evidence-based medicine. In addition to the more general statements of the German interdisciplinary S3 guidelines updated in 2012, this paper addresses indications, targeting, and techniques of radiotherapy of the lymphatic pathways after surgery for breast cancer. International guidelines reveal substantial differences regarding indications for RNI. Patients with 1-3 positive nodes seem to profit from RNI compared to whole breast (WBI) or chest wall irradiation alone, both with regard to locoregional control and disease-free survival. Irradiation of the regional lymphatics including axillary, supraclavicular, and internal mammary nodes provided a small but significant survival benefit in recent randomized trials and one meta-analysis. Lymph node irradiation yields comparable tumor control in comparison to axillary lymph node dissection (ALND), while reducing the rate of lymph edema. Data concerning the impact of 1-2 macroscopically affected sentinel node (SN) or microscopic metastases on prognosis are conflicting. Recent data suggest that the current restrictive use of RNI should be scrutinized because the risk-benefit relationship appears to shift towards an improvement of outcome.

Patterns of regional node irradiation therapy following breast-conserving surgery: Report from the National Cancer Data Base 2003-2007.

1101 Background: A recent randomized trial (MA.20) showed that regional nodal irradiation (RNI) in addition to breast irradiation in high risk node negative and 1-3 node positive patients undergoing breast-conserving therapy (BCT) reduced the risk of recurrence and improved disease-free survival. We investigated the trends of RNI use in the United States and related factors for the use of RNI using the National Cancer Data Base. Methods: This study includes 292,598 stage I-III breast cancer patients without neoadjuvant therapy who underwent BCT from 2003-2007. We investigated pathological, patient, and facility factors related to RNI use, by multivariable logistic regression, with odds ratio (OR) estimations. Results: The proportion of radiotherapy use after BCT slightly declined from 78.6% in 2003 to 75.6% in 2007. The use of breast irradiation plus RNI decreased from 10.8% in 2003 to 8.3% in 2007 (p&lt;0.0001). The number of tumor positive lymph nodes strongly determined the use of additional RNI: 4.4% patients with negative nodes, 22.8% patients with 1-3 nodes, and 39.7% patients with 4 or more nodes received breast irradiation plus RNI after undergoing BCT (p&lt;0.0001). The proportion of patients undergoing RNI significantly decreased over the study period from 43.3% to 37.2% in the 4+ node positive group, and from 23.6% to 22.0% in the 1-3 node positive group. At comprehensive community cancer centers, 25.5% patients with 1-3 positive nodes were treated with breast irradiation plus RNI (vs. 23.2% in community cancer centers and 21.1% in academic/research cancer centers). Among node negative patients, 11.5% of those with tumor size greater than 5 cm received additional RNI, compared to 4.3% in patients with tumors less than 5cm (p&lt;0.0001). Other significant factors related to RNI use included higher tumor grade, younger age, facility location, and facility volume. Conclusions: The use of RNI varies by number of tumor positive nodes and facility factors. Only 22.8% of patients with 1-3 positive nodes underwent RNI. Future studies are needed to determine if the use of RNI will increase after publication of the MA.20 trial especially for the 1-3 node positive group.

P3-13-05: Analysis of Heart Dose-Volume Parameters and Cardiac Events among Node Positive Breast Cancer (NPBC) Patients Treated with Three-Dimensional Conformal Radiation Therapy (3D-CRT).

Abstract Background For NPBC patients the use of regional nodal irradiation (RNI) to the supraclavicular, axillary, internal mammary lymph nodes (IMN) in addition to the chest wall and/or breast can maximize locoregional control and improve overall survival. However, comprehensive RNI for breast cancers located on the left side has been linked to late cardiac morbidity, potentially lessening the therapeutic benefit of treatment. The optimal radiation dose-volume constraints for the heart in this setting are not fully understood. We examined NPBC patients treated with RNI using 3D-CT based radiation therapy (RT) to evaluate cardiac dose and incidence of cardiac events. Methods: Between 2000 and 2007, 150 NPBC patients were treated with RNI following lumpectomy or mastectomy using 3D-CRT. In all cases, treatment target and normal tissue volumes were delineated on treatment CT scans. The heart contour included the ventricles and the left atrium. The dose-volume histogram of the cardiac doses delivered and the incidence of cardiac events is reported. Results: Median follow-up of surviving patients is 7 (1-10.6) years. Median patient age is 50 (27-91). 52.35% are premenopausal, 75.7% estrogen receptor positive, 66.3% progesterone receptor positive and 15.92% HER-2 positive. Mean positive lymph nodes is 5 (1-29). Extracapsular extension is present in 47.31%. Mean microscopic tumor size is 3.73 (0.1-21) cm. The IMN receive &amp;gt; 40 Gy in 65.5%. 94% had chemotherapy, and in 82.3% it was anthracycline-based. At the time of RT, 12.2% smoked, 9.5% had diabetes, 32.4% with hypertension, and 4.7% with a history of coronary artery disease. There was 1 (0.7%) right sided patient with cardiac events and 4 (2.7%) left sided experiencing cardiac events (p = 0.121, Fisher's Exact test). A total of 10 cardiac diagnoses were experienced among the 5 patients: coronary artery disease with myocardial infarction (3), congestive heart failure (2), cardiomyopathy (2), and arrhythmia (3). The median time interval to onset of the events is 2.5 years (0-4.3 years). The cardiac doses among 150 patients are as follows: mean V25 is 5.7, (0.0 - 20.0%), V25 is &amp;lt; 9 % in 74.4% of patients, mean V45 is 1.8% (0-13.3%), V45 is &amp;lt; 5.5% in 91.8%. The mean maximum point dose is 42.8 Gy, and the mean heart dose is 5.6 Gy (0.2−25.3 Gy). The mean V25 and V45 in those 5 patients with a cardiac event is 6.7% (0.9−11.9%) and 3.7% (0-6.6%), respectively; in the 145 remaining patients, 5.7% (0-20.0%) and 1.7% (0-13.3%), respectively. The mean heart dose in those with an event is 5.2 Gy (2.4−7.3 Gy) versus 5.6 Gy (0.2−25.3 Gy) in the remaining patients. Conclusions: The cardiac event rate among these NPBC patients treated with RNI and anthracycline-based chemotherapy is low. However, those patients with cardiac events have a higher mean V45. No other dose-volume relationships are discernible. Additional analysis using 3DCRT volumes are important to validate these findings and better define the dose-volume parameters for cardiac toxicity. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-13-05.

Comparison of practice patterns and treatment techniques for regional nodal irradiation with breast conservation vs. postmastectomy in stage I-II breast cancer

Comparison of practice patterns and treatment techniques for regional nodal irradiation with breast conservation vs. postmastectomy in stage I-II breast cancer

Incidence and time of occurrence of regional recurrence in stage i-ii breast cancer: value of adjuvant irradiation

Purpose: The value of adjuvant radiation therapy (RT) of the axilla and supraclavicular fossa is controversial in early-stage breast cancer. This retrospective study was undertaken to identify pathological risk factors that would predict which subsets of patients would benefit from regional nodal irradiation (RNI). Methods and Materials: A total of 1309 women with Stage I/II breast cancer underwent full axillary dissection and either mastectomy ( n = 894) or breast-conserving surgery ( n = 415). Of these, 712 patients received RNI. The median axilla/supraclavicular fossa dose was 50 Gy. Results: The 10-year actuarial rate of axillary failure (AXF) was 0.5% in N0 and 2.8% in N1 patients ( p = 0.0014). The number of retrieved nodes, ≤ 5 vs. > 5, also correlated with AXF; the respective rate was 4.3% vs. 1.2% ( p = 0.0142). Neither the incidence of AXF nor the time to AXF was affected significantly by the use of RNI, but in N1 patients with retrieved nodes ≤ 5, the rate of AXF was 8.3% without RNI vs. 0% with RNI ( p = 0.2340). The 10-year actuarial rate of supraclavicular failure (SCF) was 1.2% in N0 and 6.3% in N1 patients ( p = 0.0000). SCF was also associated with the extent of nodal involvement ( p = 0.0031). The incidence of SCF was not significantly affected by the use of RNI. However, when the results of N1bii and N1biv patients were evaluated as a single group, the effect of RNI was significant ( p = 0.0358). The rates of SCF without RNI were high in patients with N1bii or N1biv stage: 10% and 37.5% and, with RNI, 3.2% and 18.2%, respectively. These findings were reinforced by the various combinations of T- and N1-stage. The mean time to SCF was 53.6 months in the irradiated and 24.9 months in the nonirradiated patients ( p = 0.0007). Conclusions: After a complete axillary dissection, only N1 patients with retrieved nodes ≤ 5 may be considered for axillary RT. Elective supraclavicular RT is suggested for patients with N1bii or N1biv stage. Supraclavicular irradiation decreases the incidence and delays the appearance of SCF.

The role of regional nodal irradiation in the management of patients with early-stage breast cancer treated with breast-conserving therapy

To determine the incidence of regional nodal failure (RNF) and indications for regional nodal irradiation (RNI) in patients with Stage I and II breast cancer treated with breast-conserving therapy (BCT). Four hundred fifty-six patients with Stage I/II breast cancer were treated with BCT at William Beaumont Hospital. All patients underwent excisional biopsy and 288 (63%) were reexcised. A Level I/II ipsilateral axillary lymph node dissection was performed on 431 patients (95%). Pathologically involved nodes were found in 106 (23%) cases (69 with one to three nodes and 37 with > or = four nodes involved). All patients received whole breast irradiation (median dose 50 Gy) and 415 (91%) were boosted to the tumor bed (median total dose 60.4 Gy). Three hundred and sixty (79%) patients received breast alone irradiation and 96 (21%) also received RNI. The median axilla/supraclavicular fossa dose was 50 Gy. With a median follow-up of 83 months, 15 patients developed a RNF for a 5- and 8-year actuarial rate of 3 and 4%, respectively. The 5- and 8-year actuarial rates of axillary failure (AF) were 0.7 and 1.0%, respectively. The incidence of RNF or AF was not affected by the use of RNI in N0 or N1 patients with one to three positive nodes. Only in patients with four or more positive nodes was there a trend towards improved regional control with RNI (p = 0.09). However, patient numbers were extremely small, and this improvement was limited to a reduction in the rate of failure in the supraclavicular fossa (SCF) (20 vs. 0%, p = 0.04). Multiple clinical, pathologic, and treatment related factors were analyzed for an association with AF. On univariate analysis, AF was associated with the number of lymph nodes excised (p < 0.0001) estrogen receptor status (p = 0.0016), and pathologic node status (p = 0.0021). Regional nodal failure as the first site of failure is uncommon in patients with early-stage breast cancer treated with BCT with < or = three positive lymph nodes and appears unaffected by RNI. For patients with four or more positive lymph nodes, a trend towards improved RNF was noted with RNI, primarily in the SCF. However, patient numbers were extremely small in all subsets analyzed. Additional studies are needed to further define the need for RNI in these patients and help determine other factors associated with RNF.