Postmastectomy Radiotherapy In Patients Research Articles

The role of postmastectomy radiation therapy in patients with immediate prosthetic breast reconstruction: A meta-analysis.

Objective:The controversy remains as to whether immediate prosthetic breast reconstruction with postmastectomy radiation therapy (PMRT) is associated with acceptable complications and aesthetic outcomes. The aim of this meta-analysis was to provide a pooled analysis of comparative clinical studies that evaluated breast cancer patients who were treated with a mastectomy and an immediate prosthetic breast reconstruction to compare the complications and satisfaction of those who underwent or did not undergo PMRT.Methods:According to the recommendations of the Cochrane Collaboration, we established a rigorous study protocol. We performed a systematic electronic search of the PubMed and Embase databases to identify articles for inclusion in our meta-analysis. Reconstruction failure, overall complications, capsular contracture, and patient satisfaction were analyzed individually.Results:Fifteen controlled trials were included, comprising 5314 patients (1069 PMRT vs 4245 non-PMRT). Primary outcomes revealed a statistically significant increase in overall complications [odds ratio (OR) 3.45; 95% confidence interval (95% CI) 2.62–4.54; P < .00001], reconstruction failure (OR: 2.59; 95% CI 1.46–4.62; P = .001), and capsular contracture (OR: 5.26, 95% CI: 2.73–10.13, P < .00001) after receiving PMRT.Conclusion:Our review found that PMRT for patients who underwent immediate implant-based breast reconstruction led to higher risks of reconstruction failure, overall complications, and capsular contracture. However, it is still the standard adjuvant therapy for mastectomy patients who have opted for immediate implant-based breast reconstruction.

The role of postmastectomy radiotherapy in patients with stage II breast cancer

The role of postmastectomy radiotherapy in patients with stage II breast cancer

The Role of Postmastectomy Radiation Therapy for Clinical Stage II-III Breast Cancer Patients With Pathological Complete Remission of Axillary Lymph Nodes After Neoadjuvant Chemotherapy

With the increasing use of neoadjuvant chemotherapy (NAC), patients with pathologically involved nodes had a great chance to be found as pathologically node negative at the time of definitive surgery. Several retrospective studies addressed that there were no survival benefits in those patient with pathologically complete remission (pCR) of axillary lymph node who treated with postmastectomy radiotherapy (PMRT) after NAC. We aim to retrospectively evaluate the role of PMRT in clinical stage II-III breast cancer patients with pathological nodes negative (ypN0) after NAC. We retrospectively identified 946 breast cancer patients with clinical stage II-III who underwent NAC in our center between 2003 and 2013. There were 290 patients achieved ypN0 after mastectomy and the clinical outcomes of the patients had been elucidated. The effects of PMRT on locoregional recurrence-free survival (LRRFS), disease-free survival (DFS) and overall survival (OS) were evaluated by Kaplan-Meier method and compared using the log-rank test. Prognostic factors associated with survival were evaluated by univariate and multivariate analysis. The median age was 50 years old (range, 25-80 years). All patients received 2-8 cycles (median, 4 cycles) of preoperative chemotherapy contained with anthracycling and paclitaxel and mastectomy. Of the 290 patients, 217 (74.8%) underwent PMRT and 73 (25.2%) did not. With a median follow-up time of 63 month, 12 patients developed LRR and 39 developed distant metastasis. The 5-year LRRFS, DFS and OS was 94.2%, 79.3% and 91.8% in no-PMRT group and 95.9%, 84.3% and 92.4% in PMRT group, respectively (p=NS). There was no significant difference between the patients with PMRT and without PMRT in terms of survival outcome, even for the subgroup of patients with clinical stage III disease or with residual disease in breast after NAC. On univariate and multivariate analysis, there were no benefits of PMRT on LRRFS (hazard ratio [HR], 0.714; 95% confidence interval [CI], 0.193-2,634; p =0.612), DFS (HR 0.908; 95%[CI], 0.477-1.734; p = 0.773) or OS (HR, 0.829; 95% [CI], 0.291-2.359; p =0.725). Age at diagnosis，ER and LVI status, adjuvant chemotherapy were independent prognostic factors for LRRFS （p＜0.01）, primary tumor response to NAC was marginally significant with poor LRRFS (hazard ratio [HR] 0.109; 95% CI, 0.011-1.098; p=0.06). Advanced Clinical T stage (T3-T4) was independently associated with decreased DFS and OS. Patients who achieved ypN0 after NAC without PMRT had similar outcomes compared with patients treated with PMRT, regardless of clinical stage and primary tumor response. PMRT might not be necessary for ypN0 patients. Prospective randomized study is needed to identify whether it is safe to omit PMRT in patients with clinical stage II-III disease and achieved ypN0 after NAC and mastectomy

Immediate Breast Reconstruction with Abdominal Free Flap and Adjuvant Radiotherapy: Evaluation of Quality of Life and Outcomes.

The effects of postoperative radiotherapy on free flap-based breast reconstruction are still controversial. Poor outcomes, breast distortion, and fat necrosis have been traditionally documented. The aim of this study was to evaluate whether adjuvant radiotherapy affects the quality of life, satisfaction, and cosmetic result in patients undergoing immediate breast reconstruction with autologous free flap. Between January of 2013 and December of 2016, 230 patients underwent mastectomy with immediate free flap reconstruction at the authors' institution. Patients were divided into two groups depending on whether they received postmastectomy radiotherapy. Quality of life measured with the BREAST-Q questionnaire, self-reported aesthetic outcomes, and general satisfaction were assessed and compared. Fat necrosis of the flap and its severity were also analyzed as the main surgical outcomes. Mean follow-up time after reconstruction was 23 months (range, 6 to 48 months). No significant difference in quality of life or satisfaction scores were found between patients that underwent postmastectomy radiotherapy and patients who did not receive adjuvant radiotherapy. There were no significant differences in rates of fat necrosis between the groups (11.1 percent versus 13.76 percent; p = 0.75). Postmastectomy radiotherapy in patients undergoing immediate breast reconstruction with free flaps does not seem to affect quality of life, satisfaction with the outcome, or the cosmetic result as perceived by the patients. The potential need for postoperative radiotherapy should not hinder women from the benefits of autologous immediate breast reconstruction. Therapeutic, III.

Multivariate Preoperative and Intraoperative Predictors of Postmastectomy Radiation Therapy in Patients for Whom Immediate Breast Reconstruction Is Planned.

Postmastectomy radiation therapy often impacts decision-making and outcomes of breast reconstruction. However, plastic surgeons typically have limited information regarding the likelihood of radiation therapy when decisions about immediate breast reconstruction are made. The study objective was to examine whether commonly available information can be used to predict the probability of radiation therapy. A retrospective review was performed of patients undergoing mastectomy and sentinel lymph node biopsy. Multivariate logistic regression analysis of variables available in greater than 95 percent of patients was performed in relation to predicting radiation therapy. A total of 322 patients were reviewed, of whom 55 (17.1 percent) received radiation therapy, which was indicated for patients having four or more positive axillary lymph nodes in all cases. Multivariate logistic regression identified the intraoperative sentinel lymph node frozen section results (OR, 27.3), tumor size (OR, 1.7), and age (OR, 0.96) as significant predictors. The sentinel lymph node frozen section exhibited negative and positive predictive values for radiation therapy of 95.4 percent and 54.3 percent, respectively. When sentinel lymph node frozen section was combined with tumor size greater than or equal to 2.0 cm, the positive predictive value increased to 80.5 percent. Immediate breast reconstruction patients who have negative intraoperative sentinel lymph node frozen section results have a less than 5 percent chance of radiation therapy, whereas patients with positive intraoperative sentinel lymph node frozen section results and tumor size greater than or equal to 2.0 cm have a greater than 80 percent chance of radiation therapy. Risk, III.

Abstract P1-10-08: Factors affecting the administration of post-mastectomy radiation therapy (PMRT) in Michigan

Abstract Background: Evidence-based guidelines for locoregional therapy of invasive breast cancer treated with mastectomy include adjuvant PMRT for: ≥4 positive axillary lymph nodes (LN); T3 or above; or a positive surgical margin. We assessed PMRT uptake using data from the Michigan Breast Oncology Quality Initiative (MiBOQI), a Blue Cross Blue Shield of Michigan/Blue Care Network-sponsored collaborative quality initiative, and identified factors influencing its use in Michigan. Methods: We prospectively collected clinical data on all patients with stage I-III breast cancer in 25 health systems belonging to MiBOQI and identified patients who underwent mastectomy from 2008 to 2013. Patients with previous cancer, bilateral disease, or treated with neoadjuvant chemotherapy were excluded. Univariate and multivariate analyses were performed to identify independent factors associated with the use of PMRT in patients with 0, 1-3, and 4+ positive LNs. Covariates included age, hormone receptor status, HER2 status, surgical margin, T category, Charlson comorbidity index, and immediate reconstruction. Two-tailed p-values &amp;lt;0.05 were considered significant. Analyses were carried out using SAS software, version 9.4 (SAS Institute, Cary, NC). Results: We identified 6,596 patients with stage I-III invasive breast cancer. Of these, 4,455 had no positive axillary LNs; 1,481, 1-3 positive LNs; and 660, ≥4 positive LNs. There was wide variation in PMRT use across MiBOQI sites, from 13% to 63.% in patients with 1-3 positive LNs (overall 42%) and from 35% to 91% in patients with 4+ positive LNs (overall 69%). In multivariate analyses stratified by nodal status (0, 1-3, 4+), age ≥ 70 yrs was negatively associated with PMRT. We also noted lower PMRT use in women aged 51-69 with 0 and 1-3 positive LNs (Table 1). Table 1. Multivariate analysis: PMRT and age (+)LNs = 0(+)LNs = 1-3(+)LNs ≥ 4AgeOdds ratiop-valueOdds ratiop-valueOdds ratiop-value≤50 y (reference)1.0 1.0 1.0 51-69 y0.70 (0.49 - 0.98)0.030.69 (0.54 - 0.88)&amp;lt;0.00011.03 (0.63 - 1.65)&amp;lt;0.0001≥70 y0.60 (0.37 - 0.96) 0.26 (0.18 - 0.37) 0.31 (0.18 - 0.54) In the 0 and 1-3 positive node groups, PMRT use was strongly associated with T category and close or positive margin status (Table 2). Table 2: Surgical characteristics and PMRT uptake (+)LNs = 0(+)LNs = 1-3(+)LNs ≥4VARIABLEOdds ratiop-valueOdds ratiop-valueOdds ratiop-valueMargin status Negative (reference)1.0 1.0 1.0 Positive16.7 (10.5 - 26.7)&amp;lt;0.00012.27 (1.32 - 3.90)0.0010.69 (0.32 - 1.47)0.90Close (&amp;lt;1 mm)4.63 (3.03 - 7.10) 1.90 (1.29 - 2.80) 0.97 (0.55 - 1.69) T category T0 to T2 (reference)1.0 1.0 1.0 T3 to T426.2 (16.4 - 41.8)&amp;lt;0.00013.24 (2.19 - 4.78)&amp;lt;0.00010.86 (0.57 - 1.28)0.45 Finally, there was no association between PMRT use and hormone receptor status, HER2 status, Charlson comorbidity index, or reconstructive surgery at the time of mastectomy. Conclusions: PMRT use across Michigan was lower than the American College of Surgeons Commission on Cancer target of 90% in patients with 4 or more positive LNs. Contrary to common belief, immediate reconstructive surgery was not independently associated with decreased PMRT uptake. Understanding reasons for nonuse of PMRT may lead to interventions to increase its use by MiBOQI member institutions in patients for whom it is indicated. Citation Format: Gorski DH, Braun T, Munir K, Griggs JJ, Breslin TM, Henry NL. Factors affecting the administration of post-mastectomy radiation therapy (PMRT) in Michigan [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-10-08.

Neoadyavant chemotherapy and postoperative irradiation in breast cancer: interrelation and prospects

In 2005 the Oxford meta-analysis of individual patient data from many trials showed no benefit to postmastectomy radiotherapy in node-negative breast cancer patients but reduced 5-year local recurrence and 15-year breast cancer mortality in patients with node-positive disease who underwent axillary lymphnode dissection. Despite these data, there is still some debate over the appropriateness of postmastectomy radiotherapy in patients with 1 to 3 involved lymph nodes. Neoadjuvant chemotherapy leads to clinical and pathological response in a certain proportion of patients. So far, the universal approach was to ignore the information on response to chemotherapy and recommend postmastectomy radiotherapy based on pre-chemo clinical disease status. The main goal of this article is first to summarize the evidence for the use of postmastectomy radiotherapy in a more traditional treatment sequence, and then show new evidence that highlights how information about the response to chemotherapy can be incorporated into the decision regarding the need and benefit of postmastectomy radiotherapy in the context of neoadjuvant chemotherapy.

Postmastectomy Radiotherapy in Patients with pT1-2N1 Breast Cancer Treated with Taxane-Based Chemotherapy: A Retrospective Multicenter Analysis (KROG 1418).

PurposeThe purpose of this study was to evaluate the impact of postmastectomy radiotherapy (PMRT) on loco-regional recurrence-free survival (LRRFS), disease-free survival (DFS), and overall survival (OS) in pT1-2N1 patients treated with taxane-based chemotherapy. Materials and MethodsWe retrospectively reviewed the medical data of pathological N1 patients who were treated with modified radical mastectomy and adjuvant taxane-based chemotherapy in 12 hospitals between January 2006 and December 2010. Results We identified 714 consecutive patients. The median follow-up duration was 69 months (range, 1 to 114 months) and the 5-year LRRFS, DFS, and OS rates were 97%, 94%, and 98%, respectively, in patients who received PMRT (PMRT [+]). The corresponding figures were 96%, 90%, and 96%, respectively, in patients who did not receive PMRT (PMRT [–]). PMRT had no significant impact on survival. Upon multivariable analysis, only the histological grade (HG) was statistically significant as a prognostic factor for LRRFS and DFS. In a subgroup analysis of HG 3 patients, PMRT (+) showed better DFS (p=0.081).Conclusion PMRT had no significant impact on LRRFS, DFS, or OS in pT1-2N1 patients treated with taxane-based chemotherapy. PMRT showed a marginal benefit for DFS in HG 3 patients. Randomized studies are needed to confirm the benefit of PMRT in high risk patients, such as those with HG 3.

Initial clinical experience of postmastectomy intensity modulated proton therapy in patients with breast expanders with metallic ports

PurposeThe feasibility of proton postmastectomy radiation therapy in patients reconstructed with expanders has not been previously reported, limiting treatment options. We analyzed the dosimetric impact of the metallic port contained within expanders on intensity modulated proton therapy (IMPT) and report our techniques and quality control for treating patients in this setting. Methods and materialsTwelve patients with the same expander model underwent 2-field IMPT as part of a prospective registry. All planning dosimetry was checked with an in-house graphic processing unit--based Monte Carlo simulation. Proton ranges through the expander were validated using a sample implant. Dosimetric impact of setup metallic port position uncertainty was evaluated. Pre- and posttreatment photographs were obtained and acute toxicity was graded using the Common Terminology Criteria for Adverse Events, version 4.0. ResultsNine patients had bilateral skin-sparing mastectomy with bilateral tissue expander reconstruction, and 3 patients had unilateral skin-sparing mastectomy and reconstruction. The left side was treated in 10 patients and the right side in 2. Target coverage and normal tissue dose uncertainties resulting from the expander were small and clinically acceptable. The maximum physician-assessed acute radiation dermatitis was grade 3 in 1 patient, grade 2 in 5 patients, and grade 1 in 6 patients. ConclusionsPostmastectomy IMPT in breast cancer patients with expanders is feasible and associated with favorable clinical target volume coverage and normal tissue sparing, even when taking into account treatment uncertainties; therefore, these patients should be eligible to participate in clinical trials studying the potential role of proton therapy in breast cancer. We caution, however, that institutions should carry out similar analyses of the physical properties and dosimetric impact of the particular expanders used in their practice before considering IMPT.

Improvement of survival with postmastectomy radiotherapy in patients with 1-3 positive axillary lymph nodes: A systematic review and meta-analysis of the current literature

In breast cancer with >4 positive axillary lymph nodes, it is common practice to deliver radiotherapy to the affected site following mastectomy. However, less is known regarding the benefits this may confer on women with 1-3 positive lymph nodes. In this meta-analysis, we aimed to assess whether post-mastectomy radiotherapy (PMRT) was beneficial for such patients. A literature review was conducted using the PubMed and Ovid databases. Selected studies were analysed and data regarding overall survival (OS) and locoregional recurrence (LRR) rates were extracted. Statistical analysis was then conducted in order to develop a combined risk ratio (RR) for both OS and LRR in the setting of PMRT in women with breast cancer with 1-3 positive lymph nodes. PMRT in women with 1-3 positive lymph nodes significantly reduced the risk of LRR, with a RR of 0.3 [95% confidence interval (CI): 0.23-0.38] and also showed a minor benefit in terms of OS (RR=1.03, 95% CI: 1.00-1.07). Therefore, in breast cancer patients with 1-3 positive lymph nodes, PMRT significantly reduced the risk of LRR and was associated with a minor OS benefit. Until the results of ongoing randomised controlled trials are published, PMRT should be recommended in this group of patients following a careful multidisciplinary discussion.

National Evaluation of the New Commission on Cancer Quality Measure for Postmastectomy Radiation Treatment for Breast Cancer.

Current guidelines recommend postmastectomy radiotherapy (PMRT) for patients with ≥4 positive lymph nodes and suggest strong consideration of PMRT in those with 1-3 positive nodes. These recommendations were incorporated into a Commission on Cancer quality measure in 2014. However, national adherence with these recommendations is unknown. Our objectives were to describe PMRT use in the United States in patients with stage I to III invasive breast cancer and to examine possible factors associated with the omission of PMRT. From the National Cancer Data Base, 753,536 mastectomies at 1123 hospitals were identified from 1998 to 2011. PMRT use over time was examined using random effects logistic regression analyses, adjusting for patient, tumor, and hospital characteristics. Analyses were stratified by nodal status (≥4 nodes positive, 1-3 nodes positive, node negative). The proportion of patients receiving PMRT increased from 1998 to 2011 (>4 positive nodes: 56.2 to 66.6%; 1-3 positive nodes: 28.0 to 39.1%; node-negative: 8.3 to 10.0%, p<0.001 for all). In adjusted analyses, patients with ≥4 positive nodes were more likely to have PMRT omitted if they had smaller tumors. Patients with 1-3 positive nodes were more likely to have PMRT omitted if they had lower grade or smaller tumors. Irrespective of patients' nodal status, PMRT utilization rates decreased as age increased. Though PMRT rates increased over time in patients with ≥4 and 1-3 positive nodes, PMRT in patients with ≥4 positive nodes remains underutilized. Feedback to hospitals using the new Commission on Cancer PMRT measure may help to improve adherence rates.

EP-1164: Outcomes of postmastectomy radiotherapy in patients with 1 to 3 positive nodes in single institute

EP-1164: Outcomes of postmastectomy radiotherapy in patients with 1 to 3 positive nodes in single institute

Abstract P1-14-18: Postmastectomy radiotherapy improves the outcomes of stage III breast cancer patients with negative lymph nodes after neoadjuvant chemotherapy

Abstract Purpose: The aim of this study is to evaluate the role of postmastectomy radiotherapy (PMRT) in clinical stage II and III breast cancer patients who achieved negative node status (pN0) after neoadjuvant chemotherapy (NAC). Material and methods: We retrospectively analyzed the outcomes of 143 patients with pN0 after NAC and mastectomy at Fudan University Shanghai Cancer Center. In total, 103 (72%) patients received PMRT, and 40 (28%) patients did not. Univariate and multivariate survival analyses were performed to evaluate the effect of PMRT on locoregional recurrence-free survival (LRRFS) and overall survival (OS) of the two groups. Results: There were no differences between the two groups with respect to age, nuclear grade, estrogen receptor (ER) status, HER2/neu receptor status, lymphovascular space invasion (LVSI) status or pathological tumor size. However, a significantly higher proportion of patients in the irradiated group (64%) had clinical lymph node involvement than in the nonirradiated group (45%). After a median follow-up time of 49 months, 10 locoregional recurrence events occurred. For the entire cohort of patients, use of radiation therapy improved the 5-year LRRFS rate (94.5% vs. 80.2%; P =0.032) but not the 5-year OS rate (92.2% vs. 88.7%; P =0.617). In the subset of patients who presented with clinically stage II disease, the 5-year LRRFS and 5-year OS did not differ significantly between the PMRT and no-PMRT group (96.3% vs. 91.3%; P = 0.190 and 96.2% vs. 91.3%; P = 0.199, respectively). For patients with stage III disease at diagnosis, a trend was seen toward better local regional control with PMRT (the 5-year LRRFS rate was 92.7% vs. 64.2%; P = 0.063), although the benefit from radiation with respect to OS was not significant (5-year OS rate was 88.1% vs. 85.2%; P = 0.657). On multivariate Cox regression analyses, the clinical tumor size (hazard ratio [HR], 3.27; 95% confidence interval [CI], 1.05-10.18; P = 0.041), pathologic breast tumor response (HR, 1.82; 95% CI, 1,11-3.77; P = 0.046) and delivery of radiation therapy (HR, 1.27; 95% CI, 1.08-9.25; P = 0.047) were independent predictors of locoregional recurrence. Conclusions: For patients who achieved pN0 after NAC, PMRT seemed to provide a clinical benefit for breast cancer patients with stage III disease. Omission of PMRT in patients with stage II disease did not increase the risk of locoregional recurrence and death. Citation Format: He M, Li J, Ni X-J, Chen S, Jiang Y-Z, Di G-H, Shao Z-M. Postmastectomy radiotherapy improves the outcomes of stage III breast cancer patients with negative lymph nodes after neoadjuvant chemotherapy. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-14-18.

Temporal Trends in Postmastectomy Radiation Therapy and Breast Reconstruction Associated With Changes in National Comprehensive Cancer Network Guidelines.

Evolving data on the effectiveness of postmastectomy radiation therapy (PMRT) have led to changes in National Comprehensive Cancer Network (NCCN) recommendations, counseling clinicians to "strongly consider" PMRT for patients with breast cancer with tumors 5 cm or smaller and 1 to 3 positive nodes; however, anticipation of PMRT may lead to delay or omission of reconstruction, which can have cosmetic, quality-of-life, and complication implications for patients. To determine whether revised guidelines have increased PMRT and affected receipt of breast reconstruction. We hypothesized that (1) PMRT rates would increase for women affected by the revised guidelines while remaining stable in other cohorts and (2) receipt of breast reconstruction would decrease in these women while increasing in other groups. Retrospective, population-based cohort study of Surveillance, Epidemiology, and End Results (SEER) data on women with stage I to III breast cancer undergoing mastectomy from 2000 through 2011. Our analytic sample (N = 62,442) was divided into cohorts on the basis of current NCCN radiotherapy recommendations: "radiotherapy recommended" (tumors > 5 cm or ≥ 4 positive lymph nodes), "strongly consider radiotherapy" (tumor ≤ 5 cm, 1-3 positive nodes), and "radiotherapy not recommended" (tumors ≤ 5 cm, no positive nodes). We used Joinpoint regression analysis to evaluate temporal trends in receipt of PMRT and breast reconstruction. The 3 cohorts comprised 15,999 in the "radiotherapy recommended" group, 15,006 in the "strongly consider radiotherapy" group, and 31,837 in the "radiotherapy not recommended" group. [corrected]. Rates of PMRT were unchanged in the radiotherapy recommended (29.9%) and radiotherapy not recommended (7.4%) cohorts over the study period. Receipt of PMRT for the strongly consider radiotherapy cohort was unchanged at 26.9% until 2007. At that time, a significant change in the APC was observed (P = .01) with an increase in APC from 2.1% to 9.0% (P = .02) through the end of the study period, for a final rate of 40.5%. Breast reconstruction increased across all cohorts. Despite increasing receipt of PMRT, the strongly consider radiotherapy cohort maintained a consistent increase in reconstruction (annual percentage change, 7.4%) throughout the study period. This is similar to the increase in reconstruction observed for the radiotherapy recommended (10.7%) and radiotherapy not recommended (8.4%) cohorts. Changes in NCCN guidelines have been associated with an increase in PMRT among patients with tumors 5 cm or smaller and 1 to 3 positive nodes without an associated decrease in receipt of reconstruction. This may represent increasing clinician comfort with irradiating a new breast reconstruction and may have cosmetic and quality-of-life implications for patients.

Postmastectomy Radiation Therapy and Breast Reconstruction--Marching Forward Together or Apart?

Postmastectomyradiationtherapy (PMRT)and immediate reconstruction eachplay important roles in the treatment of patientswithbreast cancer.GivingPMRT increases cure rates for subgroupswith substantial risks of local-regional recurrence.1 Many individuals wish to have immediatebreast reconstruction to reduce the psychological and social consequences of mastectomy. However, PMRT increases the risks of complications andpoor cosmetic results after breast reconstruction. Immediate reconstruction limits the technical approaches available for delivering PMRT, potentially resulting in increased heart and lung doses. Improvements in surgical and radiation techniquesover timehavedecreasedbutnot entirely eliminated these problems.2,3 The studybyFrasier and colleagues4 in this issueof JAMA Oncology showed that use of both PMRT and breast reconstruction increasedduring the recentpast in theUnitedStates, despite these deleterious interactions. The increase in PMRT rates was almost entirely confined to patients with tumors 5 cm or smaller with 1 to 3 involved axillary nodes at “intermediate” risk of local regional recurrence, for whom the 2009 guidelines of the National Comprehensive Cancer Network (NCCN) said PMRT should be “strongly considered.” (This increase seems to have begun in earnest in 2007 [see their Figure4].This likely reflects the impactofearlierguidelinesand editorials that encouragedPMRT tobeusedmoreoften in this group.)Asexpected, absolute ratesof reconstruction throughout the study period remained higher for patientswith lowor intermediate risks of local-regional recurrence than for individuals at high risk, for whom the guidelines unequivocally recommended PMRT. These findings are quite plausible and consistent with other studies, which they ably discuss. The authors also cogently point out the many limitations of using the Surveillance, Epidemiology, and End Results (SEER) database to determine patterns of care. One major problem is that SEER does not capture PMRT or reconstructive surgery performed more than 4 months after the initiation of therapy. Many patients now receive postoperative chemotherapy programs lasting 3 to 6 months before starting PMRT; and, particularly but not exclusively in community practices, consultation with a radiation oncologist is often not scheduled until near the end of or after chemotherapy, delaying the final decision well beyond this 4-month window. (One way to overcome this analytic problem is to use health insurance databases that capture care over longer periods.5) Themost critical questions regarding theuseofPMRTand breast reconstructionare, however, difficult to answer in such a study as the present one. First, did patients who would potentially benefit from PMRT not receive it because they underwent reconstruction? Second, didpatientswhowanted reconstructionnot receive itbecause theirphysiciansanticipated that they might need PMRT preoperatively? Treating physicians’ opinions are important to patients trying to decide whether they will undergo PMRT.6 That seems even more likely when guidelines do not explicitly mandate whether treatment be given. Such ambiguity (reflecting a lack of consensus in the profession) leaves room for potentially relevant but also extraneous medical and nonmedical factors to affect decision making. The authors found that tumor size (T1 vs T2) and grade (1 vs 2 or 3) affected the frequency of PMRT use in the intermediate-risk subgroup. However, other pathologic findings often used to select patients for PMRT are not included in the SEER database (eg, the presence of lymphovascular invasion and margin involvement). Patient socioeconomic status and comorbidities are not available in SEER. Hence, biases against using PMRT in patients who already underwent reconstruction could be hard to tease out even with matched-pair and propensity analysis. Still, it might be helpful to examine whether PMRT was used more or less often for the subgroups of patients who did or did not undergo reconstruction, both for the population as a whole and for the NCCNdefined subgroups. This might shed light on the disturbing fact that only two-thirds of patients aged 64 years or younger in the “recommend radiotherapy” group received it at the end of the study period. Was the increased use of reconstruction in this group partly to blame for the rate not being higher? For almost all patients, recommendations for PMRT are made after surgery, based on the pathologic findings. (The exception is patients with clinical stage III, or “locally advanced,” breast cancer.) The decision whether to perform reconstruction is made without this knowledge, as the authors note. Nonetheless, in practice the well-known though imperfect relationship between clinical and pathologic stages results inapreoperative“impression”ofwhetherPMRTwill likely be needed thatmay influence physician and patient behavior. For example, do physicians equally often recommend immediate reconstruction topatientswith4-cmpalpablemassesand severalpalpable ipsilateralaxillarynodesastopatientswithnonpalpable 1-cm cancers and nonpalpable nodes? These recommendations again are likely tohave an effect becausepatients’ concernsabout increasedrisksofcomplications fromPMRTare often decisive in their decisions whether to undergo immediate reconstruction.7Perhaps therewasamodest increase in the useof reconstruction inpatientswhohadPMRTbut a substantial increase in reconstruction in patients who did not have PMRT. Or perhaps the use of reconstruction increased by the Related article page 95 Research Original Investigation Trends in Postmastectomy Radiation Therapy and Breast Reconstruction

Postmastectomy radiation therapy after neoadjuvant chemotherapy: review and interpretation of available data.

Postmastectomy radiotherapy (PMRT) has been shown to decrease locoregional recurrence and improve overall survival in patients with tumors greater than 5 cm or positive nodes. Because neoadjuvant chemotherapy (NAC) can cause significant downstaging, the indications for PMRT in the setting of NAC remain controversial and thus careful consideration of clinical stage at presentation, pathologic response to NAC, and other clinical characteristics, such as grade and biomarker status is required. The current review synthesizes both prospective and retrospective data to provide evidence for recommending PMRT after NAC for patients presenting with cT3-4 disease, cN2-3 disease, and residual nodal disease, as well as rationale for omitting PMRT in patients with cT1-2N0-1 disease who achieve a pathologic complete response. Other scenarios, including nodal complete response in the presence of other risk factors, are also explored. The topics of pre-NAC clinical staging and pathologic axillary nodal staging are reviewed, and radiation portal design is briefly discussed.

Increased utilization of postmastectomy radiotherapy in the United States from 2003 to 2011 in patients with one to three tumor positive nodes.

There have been few recent studies that have examined the use of postmastectomy radiotherapy (PMRT) for patients with 1-3 positive nodes. We utilized the National Cancer Data Base to examine trends in PMRT for 346,218 patients with Stage I-III breast cancer from 2003 to 2011. Neoadjuvant therapy cases were excluded. Log linear models examined trends in PMRT and logistic regressions were used to examine factors related to PMRT. The proportion of pT1-2N1 patients receiving PMRT increased from 23.9% in 2003 to 36.4% in 2011 with an annual percent change (APC) of 6.2% (P < 0.001). There were significant increases in the use of PMRT amongst patients with one (APC = 7.7%), two (APC = 6.7%), and three (APC = 4.2%) positive nodes. In 2011, 27.8%, 43.8%, and 57.8% of patients with one, two or three positive nodes underwent PMRT, respectively. The number of positive nodes and tumor size were the strongest independent predictors of PMRT in the 1-3 node group; lymphovascular invasion, invasive lobular histology, and triple negative phenotypes were also associated with PMRT use. PMRT for patients with pT1-2N1 disease has increased with the greatest increase seen in those with one tumor positive node. Tumor factors remain strong independent predictors of PMRT.

Modified partially wide tangents technique in post-mastectomy radiotherapy for patients with left-sided breast cancer.

The role of internal mammary nodes (IMN) irradiation for breast cancer patients after mastectomy remains controversial. This study aimed to compare different techniques for radiation of the chest wall (CW) and IMN post-mastectomy for left-breast cancer patients in terms of dose homogeneity within planning target volume (PTV) and dose to critical structures. Thirty patients underwent CT simulation, while CW, IMN, left lung, heart and contralateral breast were contoured. Three three-dimensional conformal radiotherapy (3D-CRT) techniques, namely, standard tangents, partially wide tangents (PWT), and modified PWT techniques plus intensity modulated radiotherapy (IMRT) technique have been used to radiate CW and IMN. In addition to the target coverage and dose homogeneity, we also evaluated the dose to the critical structures including heart, left lung and contralateral breast. All three 3D-CRT techniques provided satisfactory coverage regarding total PTV. The PWT and the modified PWT gave better coverage of IMN PTV with V(47.5) of (96.83 ± 4.56)% and (95.19 ± 3.90)% compared to standard tangents ((88.16 ± 7.77)%), P < 0.05. The standard tangents also contributed the biggest IMN V(D105%), V(D110%), V(D115%) and V(D120%). The lowest mean dose of the heart was achieved by the modified PWT ((8.47 ± 2.30) Gy), compared with PWT ((11.97 ± 3.54) Gy) and standard tangents ((11.18 ± 2.53) Gy). The mean dose of lung and contralateral breast with the modified PWT was significantly lower than those with PWT. Comparing IMRT with the modified PWT, both techniques provided satisfactory coverage. The conformity indexes (CI) with IMRT (CI1: 0.71 ± 0.02; CI2: 0.64 ± 0.02) were better than those with the modified PWT (CI1: 0.50 ± 0.02; CI2: 0.45 ± 0.02). The mean dose, V(5), V(10) and V(5-10) of heart and left lung with the modified PWT were significantly lower than those with the IMRT. The mean dose and V(D2%) of contralateral breast with the modified PWT were not significantly different from the IMRT (P = 0.868 and P = 0.212). No single technique provides both the best CW and IMN coverage with minimum lung and heart dose. The modified PWT technique can be used as a clinical tool for the treatment of the left-sided post-mastectomy breast cancer patients to provide homogeneous target coverage while maintaining low doses to normal tissue.

P291 Influence of radiation boost on local control in patients with ductal carcinoma in situ

Goals: The aim of this study is to evaluate the role of postmastectomy radiotherapy (PMRT) in clinical stage II and III breast cancer patients who achieved negative node status (pN0) after neoadjuvant chemotherapy (NAC). Methods:We retrospectively analyzed the outcomes of 143 patients with pN0 after NAC and mastectomy at Fudan University Shanghai Cancer Center. In total, 103 (72%) patients received PMRT, and 40 (28%) patients did not. Univariate and multivariate survival analyses were performed to evaluate the effect of PMRT on locoregional recurrence-free survival (LRRFS) and overall survival (OS) of the two groups. Results: There were no differences between the two groups with respect to age, nuclear grade, estrogen receptor (ER) status, HER2/neu receptor status, lymphovascular space invasion (LVSI) status or pathological tumor size. However, a significantly higher proportion of patients in the irradiated group (64%) had clinical lymph node involvement than in the nonirradiated group (45%). After a median follow-up time of 49 months, 10 locoregional recurrence events occurred. For the entire cohort of patients, use of radiation therapy improved the 5-year LRRFS rate (94.5% vs. 80.2%; P = 0.032) but not the 5-year OS rate (92.2% vs. 88.7%; P = 0.617). In the subset of patients who presented with clinically stage II disease, the 5-year LRRFS and 5-year OS did not differ significantly between the PMRT and no-PMRT group (96.3% vs. 91.3%; P = 0.190 and 96.2% vs. 91.3%; P = 0.199, respectively). For patientswith stage III disease at diagnosis, a trend was seen toward better local regional control with PMRT (the 5-year LRRFS rate was 92.7% vs. 64.2%; P = 0.063), although the benefit from radiation with respect to OS was not significant (5-year OS rate was 88.1% vs. 85.2%; P = 0.657). On multivariate Cox regression analyses, the clinical tumor size (hazard ratio [HR], 3.27; 95% confidence interval [CI], 1.05–10.18; P = 0.041), pathologic breast tumor response (HR, 1.82; 95%CI, 1.11– 3.77; P = 0.046) and delivery of radiation therapy (HR, 1.27; 95%CI, 1.08–9.25; P = 0.047) were independent predictors of locoregional recurrence. Conclusion: For patientswho achieved pN0 after NAC, PMRT seemed to provide a clinical benefit for breast cancer patients with stage III disease. Omission of PMRT in patients with stage II disease did not increase the risk of locoregional recurrence and death. Disclosure of Interest: No significant relationships.

Development and validation of a gene profile predicting benefit of postmastectomy radiotherapy in patients with high-risk breast cancer: a study of gene expression in the DBCG82bc cohort.

To identify genes predicting benefit of radiotherapy in patients with high-risk breast cancer treated with systemic therapy and randomized to receive or not receive postmastectomy radiotherapy (PMRT). The study was based on the Danish Breast Cancer Cooperative Group (DBCG82bc) cohort. Gene-expression analysis was performed in a training set of frozen tumor tissue from 191 patients. Genes were identified through the Lasso method with the endpoint being locoregional recurrence (LRR). A weighted gene-expression index (DBCG-RT profile) was calculated and transferred to quantitative real-time PCR (qRT-PCR) in corresponding formalin-fixed, paraffin-embedded (FFPE) samples, before validation in FFPE from 112 additional patients. Seven genes were identified, and the derived DBCG-RT profile divided the 191 patients into "high LRR risk" and "low LRR risk" groups. PMRT significantly reduced risk of LRR in "high LRR risk" patients, whereas "low LRR risk" patients showed no additional reduction in LRR rate. Technical transfer of the DBCG-RT profile to FFPE/qRT-PCR was successful, and the predictive impact was successfully validated in another 112 patients. A DBCG-RT gene profile was identified and validated, identifying patients with very low risk of LRR and no benefit from PMRT. The profile may provide a method to individualize treatment with PMRT.