Minimally invasive surgical coronary artery bypass in women.

Minimally invasive coronary artery bypass grafting (CABG) has emerged as a viable alternative to conventional sternotomy CABG in select patients requiring coronary revascularization. Specific techniques vary, but minimally invasive CABG (i.e., MIDCAB) usually involves revascularization of the left anterior descending (LAD) artery with the left internal mammary artery (LIMA). Minimally invasive CABG can be performed without cardiopulmonary bypass through a small anterior thoracotomy incision with robotic assistance. Use of minimally invasive CABG may offer specific benefits for women requiring revascularization, particularly given that female gender is an independent risk factor for inferior outcomes following CABG. Here we describe how to perform robot-assisted minimally invasive CABG, with a focus on technical modifications aimed at improving outcomes in women.

Targeting IL-6 to prevent cardiac allograft rejection.

Outcomes following heart transplantation remain suboptimal with acute and chronic rejection being major contributors to poor long-term survival. IL-6 is increasingly recognized as a critical pro-inflammatory cytokine involved in allograft injury and has been shown to play a key role in regulating the inflammatory and alloimmune responses following heart transplantation. Therapies that inhibit IL-6 signaling have emerged as promising strategies to prevent allograft rejection. Here, we review experimental and pre-clinical evidence that supports the potential use of IL-6 signaling blockade to improve outcomes in heart transplant recipients.

Use of computed tomography (CT) for preoperative planning in patients undergoing coronary artery bypass grafting (CABG).

Surgical planning for coronary artery bypass grafting (CABG) can be enhanced with the use of computed tomographic (CT) imaging to better understand the surgical field for optimal conduct of the case as well as risk assessment for outcomes. CABG via primary sternotomy, redo sternotomy, and minimally-invasive thoracotomy each pose unique surgical considerations and risks that can be better characterized with a preoperative CT scan. CT and CT angiographic (CTA) techniques with or without intravenous (IV) contrast can provide a noninvasive assessment of the vascular and bony structures and direct surgical planning techniques. Herein we discuss the role of CT/CTA imaging of the chest in preoperative planning of different strategies of CABG.

Novel approaches for long-term lung transplant survival.

Allograft failure remains a major barrier in the field of lung transplantation and results primarily from acute and chronic rejection. To date, standard-of-care immunosuppressive regimens have proven unsuccessful in achieving acceptable long-term graft and patient survival. Recent insights into the unique immunologic properties of lung allografts provide an opportunity to develop more effective immunosuppressive strategies. Here we describe advances in our understanding of the mechanisms driving lung allograft rejection and highlight recent progress in the development of novel, lung-specific strategies aimed at promoting long-term allograft survival, including tolerance.

IL-6 Directed Therapy in Transplantation.

Purpose of Review: IL-6 is a pleiotropic, pro-inflammatory cytokine that plays an integral role in the development of acute and chronic rejection after solid organ transplantation. This article reviews the experimental evidence and current clinical application of IL-6/IL-6 receptor (IL-6R) signaling inhibition for the prevention and treatment of allograft injury. Recent Findings: There exists a robust body of evidence linking IL-6 to allograft injury mediated by acute inflammation, adaptive cellular/humoral responses, innate immunity, and fibrosis. IL-6 promotes the acute phase reaction, induces B cell maturation/antibody formation, directs cytotoxic T-cell differentiation, and inhibits regulatory T-cell development. Importantly, blockade of the IL-6/IL-6R signaling pathway has been shown to mitigate its harmful effects in experimental studies, particularly in models of kidney and heart transplant rejection. Currently, available agents for IL-6 signaling inhibition include monoclonal antibodies against IL-6 or IL-6R and janus kinase inhibitors. Recent clinical trials have investigated the use of tocilizumab, an anti-IL-6R mAb, for desensitization and treatment of antibody-mediated rejection (AMR) in kidney transplant recipients, with promising initial results. Further studies are underway investigating the use of alternative agents including clazakizumab, an anti-IL-6 mAb, and application of IL-6 signaling blockade to clinical cardiac transplantation. Summary: IL-6/IL-6R signaling inhibition provides a novel therapeutic option for the prevention and treatment of allograft injury. To date, evidence from clinical trials supports the use of IL-6 blockade for desensitization and treatment of AMR in kidney transplant recipients. Ongoing and future clinical trials will further elucidate the role of IL-6 signaling inhibition in other types of solid organ transplantation.

Prognostic Significance of Surgical Margin Size After Neoadjuvant FOLFOX and/or FOLFIRI for Colorectal Liver Metastases.

PURPOSE: Optimal margin size when resecting colorectal liver metastases (CRLM) remains unclear, particularly in the setting of perioperative chemotherapy. We evaluated the prognostic significance of margin size in patients who received neoadjuvant FOLFOX and/or FOLFIRI prior to resection of CRLM. METHODS: Clinicopathologic factors were collected for patients who underwent curative liver resections for CRLM between 4/2004-1/2016 and received neoadjuvant oxaliplatin and/or irinotecan and 5-FU (FOLFOX, FOLFIRI). Margins were categorized as < 1, ≥ 1-< 5, ≥ 5-< 10, or ≥ 10 mm and evaluated for association with overall survival (OS) and disease-free survival (DFS) by Cox multiple regression analysis. Margin status was classified as positive (< 1 mm) or negative (≥ 1 mm) and similarly evaluated. RESULTS: Of 227 patients, the median age was 58 years and most had synchronous (80%) lesions. The majority had colon cancers (75%). Margin sizes were 13% < 1 mm, 27% ≥ 1-< 5 mm, 23% ≥ 5-< 10 mm, 36% ≥ 10 mm. Most (63%) received chemotherapy post-liver resection. Five-year OS and DFS were 54% (95% CI 46-62%) and 22% (95% CI 16-28%), respectively. Positive margins significantly increased the risk of death without post-liver resection chemotherapy (HR = 3.32, p = 0.0077), but not with post-liver resection chemotherapy (HR = 1.00, p = 0.99). Negative margin sizes of ≥ 1-< 5, ≥ 5-< 10, and ≥ 10 mm were not significant predictors of OS (p > 0.05). CONCLUSION: Patients undergoing liver resection for CRLM should receive post-resection chemotherapy if negative margins (≥ 1 mm) cannot be achieved. For patients receiving FOLFOX and/or FOLFIRI chemotherapy, wider margins did not improve OS.

The need for preoperative baseline arm measurement to accurately quantify breast cancer-related lymphedema.

Breast cancer-related lymphedema (BCRL) is a feared outcome of breast cancer treatment, yet the push for early screening is hampered by a lack of standardized quantification. We sought to determine the necessity of preoperative baseline in accounting for temporal changes of upper extremity volume. 1028 women with unilateral breast cancer were prospectively screened for lymphedema by perometry. Thresholds were defined: relative volume change (RVC) ≥10 % for clinically significant lymphedema and ≥5 % including subclinical lymphedema. The first postoperative measurement (pseudo-baseline) simulated the case of no baseline. McNemar's test and binomial logistic regression models were used to analyze BCRL misdiagnoses. Preoperatively, 28.3 and 2.9 % of patients had arm asymmetry of ≥5 and 10 %, respectively. Without baseline, 41.6 % of patients were underdiagnosed and 40.1 % overdiagnosed at RVC ≥ 5 %, increasing to 50.0 and 54.8 % at RVC ≥ 10 %. Increased pseudo-baseline asymmetry, increased weight change between baselines, hormonal therapy, dominant use of contralateral arm, and not receiving axillary lymph node dissection (ALND) were associated with increased risk of underdiagnosis at RVC ≥ 5 %; not receiving regional lymph node radiation was significant at RVC ≥ 10 %. Increased pseudo-baseline asymmetry, not receiving ALND, and dominant use of ipsilateral arm were associated with overdiagnosis at RVC ≥ 5 %; increased pseudo-baseline asymmetry and not receiving ALND were significant at RVC ≥ 10 %. The use of a postoperative proxy even early after treatment results in poor sensitivity for identifying BCRL. Providers with access to patients before surgery should consider the consequent need for proper baseline, with specific strategy tailored by institution.

Comparison of intra-operative specimen mammography to standard specimen mammography for excision of non-palpable breast lesions: a randomized trial.

Standard specimen mammography (SSM) is performed in the radiology department after wire-localized excision of non-palpable breast lesions to confirm the presence of the target and evaluate margins. Alternatively, intra-operative specimen mammography (ISM) allows surgeons to view images in the operating room (OR). We conducted a randomized study comparing ISM and SSM. Women undergoing wire-localized excision for breast malignancy or imaging abnormality were randomized to SSM or ISM. For SSM, the specimen was transported to the radiology department for imaging and interpretation. For ISM, the specimen was imaged in the OR for interpretation by the surgeon and sent for SSM. Interpretation time was from specimen leaving OR until radiologist interpretation for SSM and from placement in ISM device until surgeon interpretation for ISM. Procedure and interpretation times were compared. Concordance between ISM and SSM for target and margins was evaluated. 72 patients were randomized, 36 ISM and 36 SSM. Median procedure times were similar, 48.5 (17-138) min for ISM, and 54 (17-40) min for SSM (p = 0.72), likely since specimens in both groups traveled to radiology for SSM. Median interpretation time was significantly shorter with ISM, 1 (0.5-2.0) and 9 (4-16) min for ISM and SSM, respectively (p < 0.0001). Among specimens with ISM and SSM, concordance was 100 % (35/35) for target and 93 % (14/15) for margins. In this randomized trial, use of ISM compared with SSM significantly reduced interpretation times, while accurately identifying the target. This could result in decreased operative costs from shorter OR times with use of ISM.

Immediate Implant Reconstruction Is Associated With a Reduced Risk of Lymphedema Compared to Mastectomy Alone: A Prospective Cohort Study.

OBJECTIVE: We sought to determine the risk of lymphedema associated with immediate breast reconstruction compared to mastectomy alone. BACKGROUND: Immediate breast reconstruction is increasingly performed at the time of mastectomy. Few studies have examined whether breast reconstruction impacts development of lymphedema. METHODS: A total of 616 patients with breast cancer who underwent 891 mastectomies between 2005 and 2013 were prospectively screened for lymphedema at our institution, with 22.2 months' median follow-up. Mastectomies were categorized as immediate implant, immediate autologous, or no reconstruction. Arm measurements were performed preoperatively and during postoperative follow-up using a Perometer. Lymphedema was defined as 10% or more arm volume increase compared to preoperative. Kaplan-Meier and Cox regression analyses were performed to determine lymphedema rates and risk factors. RESULTS: Of 891 mastectomies, 65% (580/891) had immediate implant, 11% (101/891) immediate autologous, and 24% (210/891) no reconstruction. The two-year cumulative incidence of lymphedema was as follows: 4.08% [95% confidence interval (CI): 2.59-6.41%] implant, 9.89% (95% CI: 4.98-19.1%) autologous, and 26.7% (95% CI: 20.4-34.4%) no reconstruction. By multivariate analysis, immediate implant [hazards ratio (HR): 0.352, P < 0.0001] but not autologous (HR: 0.706, P = 0.2151) reconstruction was associated with a significantly reduced risk of lymphedema compared to no reconstruction. Axillary lymph node dissection (P < 0.0001), higher body mass index (P < 0.0001), and greater number of nodes dissected (P = 0.0324) were associated with increased lymphedema risk. CONCLUSIONS: This prospective study suggests that in patients for whom implant-based reconstruction is available, immediate implant reconstruction does not increase the risk of lymphedema compared to mastectomy alone.

Impact of Ipsilateral Blood Draws, Injections, Blood Pressure Measurements, and Air Travel on the Risk of Lymphedema for Patients Treated for Breast Cancer.

PURPOSE: The goal of this study was to investigate the association between blood draws, injections, blood pressure readings, trauma, cellulitis in the at-risk arm, and air travel and increases in arm volume in a cohort of patients treated for breast cancer and screened for lymphedema. PATIENTS AND METHODS: Between 2005 and 2014, patients undergoing treatment of breast cancer at our institution were screened prospectively for lymphedema. Bilateral arm volume measurements were performed preoperatively and postoperatively using a Perometer. At each measurement, patients reported the number of blood draws, injections, blood pressure measurements, trauma to the at-risk arm(s), and number of flights taken since their last measurement. Arm volume was quantified using the relative volume change and weight-adjusted change formulas. Linear random effects models were used to assess the association between relative arm volume (as a continuous variable) and nontreatment risk factors, as well as clinical characteristics. RESULTS: In 3,041 measurements, there was no significant association between relative volume change or weight-adjusted change increase and undergoing one or more blood draws (P = .62), injections (P = .77), number of flights (one or two [P = .77] and three or more [P = .91] v none), or duration of flights (1 to 12 hours [P = .43] and 12 hours or more [P = .54] v none). By multivariate analysis, factors significantly associated with increases in arm volume included body mass index ≥ 25 (P = .0236), axillary lymph node dissection (P < .001), regional lymph node irradiation (P = .0364), and cellulitis (P < .001). CONCLUSION: This study suggests that although cellulitis increases risk of lymphedema, ipsilateral blood draws, injections, blood pressure readings, and air travel may not be associated with arm volume increases. The results may help to educate clinicians and patients on posttreatment risk, prevention, and management of lymphedema.

Impact of adjuvant taxane-based chemotherapy on development of breast cancer-related lymphedema: results from a large prospective cohort.

Taxane-based chemotherapy for the treatment of breast cancer is associated with fluid retention in the extremities; however, its association with development of breast cancer-related lymphedema is unclear. We sought to determine if adjuvant taxane-based chemotherapy increased risk of lymphedema or mild swelling of the upper extremity. 1121 patients with unilateral breast cancer were prospectively screened for lymphedema with perometer measurements. Lymphedema was defined as a relative volume change (RVC) of ≥10 % from preoperative baseline. Mild swelling was defined as RVC 5- <10 %. Clinicopathologic characteristics were obtained via medical record review. Kaplan-Meier and Cox proportional hazard analyses were performed to determine lymphedema rates and risk factors. 29 % (324/1121) of patients were treated with adjuvant taxane-based chemotherapy. The 2-year cumulative incidence of lymphedema in the overall cohort was 5.27 %. By multivariate analysis, axillary lymph node dissection (ALND) (p < 0.0001), higher body mass index (p = 0.0007), and older age at surgery (p = 0.04) were significantly associated with increased risk of lymphedema; however, taxane chemotherapy was not significant when compared to no chemotherapy and non-taxane chemotherapy (HR 1.14, p = 0.62; HR 1.56, p = 0.40, respectively). Chemotherapy with docetaxel was significantly associated with mild swelling on multivariate analysis in comparison to both no chemotherapy and non-taxane chemotherapy groups (HR 1.63, p = 0.0098; HR 2.15, p = 0.02, respectively). Patients who receive taxane-based chemotherapy are not at an increased risk of lymphedema compared to patients receiving no chemotherapy or non-taxane adjuvant chemotherapy. Those treated with docetaxel may experience mild swelling, but this does not translate into subsequent lymphedema.

Increased rates of pregnancy complications in women with celiac disease.

BACKGROUND: Celiac disease is an immune-mediated small bowel disorder that develops in genetically susceptible individuals upon exposure to dietary gluten. Celiac disease could have extra-intestinal manifestations that affect women's reproductive health. The aim of this study was to investigate fertility and outcomes of pregnancy among women with celiac disease. METHODS: In a retrospective cohort study, we analyzed information collected from patients at a tertiary care celiac center and from members of 2 national celiac disease awareness organizations. Women without celiac disease were used as controls. Women completed an anonymous online survey, answering 43 questions about menstrual history, fertility, and outcomes of pregnancy (329 with small bowel biopsy-confirmed celiac disease and 641 controls). RESULTS: Of the 970 women included in the study, 733 (75.6%) reported that they had been pregnant at some point; there was no significant difference between women with celiac disease (n=245/329, 74.5%) and controls (488/641, 76.1%; P=0.57). However, fewer women with celiac disease than controls (79.6% vs. 84.8%) gave birth following 1 or more pregnancies (P=0.03). Women with celiac disease had higher percentages of spontaneous abortion than controls (50.6% vs. 40.6%; P=0.01), and of premature delivery (23.6% vs. 15.9% among controls; P=0.02). The mean age at menarche was higher in the celiac disease group (12.7 years) than controls (12.4 years; P=0.01). CONCLUSIONS: In a retrospective cohort analysis examining reproductive features of women with celiac disease, we associated celiac disease with significant increases in spontaneous abortion, premature delivery, and later age of menarche.

The impact of breast cancer-related lymphedema on the ability to perform upper extremity activities of daily living.

We sought to assess the association of breast cancer-related lymphedema (BCRL) with the ability to perform upper extremity activities of daily living (ADL) in our patient population. 324 breast cancer patients who had received treatment for unilateral breast cancer at our institution between 2005 and 2014 were prospectively screened for lymphedema. Bilateral arm measurements were performed pre-operatively and during post-operative follow-up using a Perometer. Patients completed an extensive quality of life (QOL) questionnaire at the time of each study assessment. Lymphedema was defined as a relative volume change (RVC) of ≥10% from the patient's pre-operative baseline measurement. Linear regression models were used to evaluate the relationship between post-operative arm function score (as a continuous variable) and RVC, demographic, clinical, and QOL factors. By multivariate analysis, greater fear of lymphedema (p < 0.0001), more pain (p < 0.0001), body mass index >25 (p = 0.0015), mastectomy (p = 0.0001), and having an axillary node dissection (p = 0.0045) were all associated with lower functional scores. Higher emotional well-being score (p < 0.0001) and adjuvant chemotherapy (p = 0.0005) were associated with higher post-operative functional score. Neither low-level volume changes (5-10 % RVC) nor BCRL (RVC ≥10 %) were associated with ability to perform upper extremity ADL as measured by self-report (p = 0.99, p = 0.79). This prospective study demonstrates that low-level changes in arm volume (RVC 5-10 %) as well as clinically significant BCRL (RVC ≥10 %) did not impact the self-reported ability to use the affected extremity for ADL. These findings may help to inform clinicians and patients on the importance of prospective screening for lymphedema and QOL which enables early detection and intervention.

Radiation therapy risk factors for development of lymphedema in patients treated with regional lymph node irradiation for breast cancer.

PURPOSE: We previously evaluated the risk of breast cancer-related lymphedema (LE) with the addition of regional lymph node irradiation (RLNR) and found an increased risk when RLNR is used. Here we analyze the association of technical radiation therapy (RT) factors in RLNR patients with the risk of LE development. METHODS AND MATERIALS: From 2005 to 2012, we prospectively screened 1476 women for LE who underwent surgery for breast cancer. Among 1507 breasts treated, 172 received RLNR and had complete technical data for analysis. RLNR was delivered as supraclavicular (SC) irradiation (69% [118 of 172 patients]) or SC plus posterior axillary boost (PAB) (31% [54 of 172]). Bilateral arm volume measurements were performed pre- and postoperatively. Patients' RT plans were analyzed for SC field lateral border (relative to the humeral head), total dose to SC, RT fraction size, beam energy, and type of tangent (normal vs wide). Cox proportional hazards models were used to analyze associated risk factors for LE. RESULTS: Median postoperative follow-up was 29.3 months (range: 4.9-74.1 months). The 2-year cumulative incidence of LE was 22% (95% confidence interval [CI]: 15%-32%) for SC and 20% (95% CI: 11%-37%) for SC plus PAB (SC+PAB). None of the analyzed variables was significantly associated with LE risk (extent of humeral head: P=.74 for <1/3 vs >2/3, P=.41 for 1/3 to 2/3 vs >2/3; P=.40 for fraction size of 1.8 Gy vs 2.0 Gy; P=.57 for beam energy 6 MV vs 10 MV; P=.74 for tangent type wide vs regular; P=.66 for SC vs SC+PAB). Only pretreatment body mass index (hazard ratio [HR]: 1.09; 95% CI: 1.04-1.15, P=.0007) and the use of axillary lymph node dissection (HR: 7.08, 95% CI: 0.98-51.40, P=.05) were associated with risk of subsequent LE development. CONCLUSIONS: Of the RT parameters tested, none was associated with an increased risk of LE development. This study underscores the need for future work investigating alternative RLNR risk factors for LE.

Factors associated with fear of lymphedema after treatment for breast cancer.

PURPOSE/OBJECTIVES: To identify demographic and treatment characteristics associated with postoperative fear of lymphedema. DESIGN: Prospective cohort study. SETTING: Outpatient breast clinic at a comprehensive cancer center in the northeastern United States. SAMPLE: 324 patients undergoing treatment for unilateral breast cancer. METHODS: Women with breast cancer were prospectively screened for lymphedema (relative volume change of 10% or greater) preoperatively and every three to eight months postoperatively via Perometer arm volume measurements. Fear was simultaneously evaluated via questionnaire. Multivariate linear mixed-effects regression models were used to identify factors associated with mean postoperative fear score and to plot the average fear score over time within axillary surgery type subgroups. MAIN RESEARCH VARIABLES: Postoperative fear of lymphedema. FINDINGS: Higher preoperative fear score (p < 0.0001), younger age at diagnosis (p = 0.0038), and axillary lymph node dissection (ALND) (p < 0.0001) were significantly associated with higher mean postoperative fear score. The average fear score changed nonlinearly over time (p < 0.0001), decreasing from preoperative to 24 months postoperative and leveling thereafter. CONCLUSIONS: Preoperative fear, younger age at diagnosis, and ALND may contribute to postoperative fear of lymphedema. IMPLICATIONS FOR NURSING: Individualized education that begins preoperatively, continues throughout treatment, and is re-emphasized 24 months postoperatively may help minimize fear of lymphedema.

Lymphedema following breast cancer treatment and impact on quality of life: a review.

Lymphedema resulting from breast cancer treatment is a chronic condition which can significantly compromise quality of life. We sought to review various aspects of breast-cancer related lymphedema including measurement techniques, definitions, risk factors, and specifically, impact on physical, psychological, and emotional well-being of women treated for breast cancer. For the purpose of this review, we performed a literature search using PubMed for articles on lymphedema secondary to breast cancer treatment published since 1997. While improvements in breast cancer therapy have contributed to a decrease in the incidence of lymphedema, the overall negative impact the condition has on patients and survivors has remained unchanged. The development of lymphedema results in physical impairments including compromised function, diminished strength, fatigue, and pain in the affected arm. Affected women may have decreased self-confidence resulting from a distorted body image. Negative emotions reported by women with lymphedema include anxiety, frustration, sadness, anger, fear, and increased self-consciousness. Lymphedema secondary to breast cancer treatment remains a significant quality of life issue, with known consequences related to a woman's physical, psychological, and emotional well-being.

Surgical excision of radial scars diagnosed by core biopsy may help predict future risk of breast cancer.

Radial scars (RS's) are benign breast lesions known to be associated with carcinomas and other high-risk lesions (HRL's). The upgrade rate to carcinoma after core biopsy revealing RS is 0-40 %. We sought to determine the outcomes of RS with and without HRL diagnosed by core biopsy. Patients who underwent core biopsy revealing RS without carcinoma at our institution between 1/1996 and 11/2012 were identified from a surgical pathology database. Retrospective chart review was utilized to classify patients as RS-no HRL or RS-HRL. HRL was defined as ADH, LCIS, and/or ALH. We determined upgrade rate to carcinoma at surgical excision, and upgrade to HRL for RS-no HRL patients. Univariate analysis was performed to identify risk factors for upgrade in RS-no HRL patients. 156 patients underwent core biopsy revealing RS, 131 RS-no HRL (84 %), and 25 RS-HRL (16 %). The overall rate of upgrade to invasive carcinoma was 0.8 % (1/124). 1.0 % (1/102) of RS-no HRL and 13.6 % (3/22) of RS-HRL patients were upgraded to DCIS (P = 0.0023). The upgrade of RS-no HRL to HRL at excision was 21.6 % (22/102). By univariate analysis, RS-no HRL with radiologic appearance of a mass/architectural distortion had a significantly higher rate of upgrade to HRL or carcinoma compared with calcifications (P = 0.03). Excision of RS to rule out associated invasive carcinoma is not warranted, given a <1 % rate of upgrade at excision. However, excision to evaluate for non-invasive cancer or HRL may be considered to help guide clinical decision-making about use of chemoprevention.

Risk of lymphedema after mastectomy: potential benefit of applying ACOSOG Z0011 protocol to mastectomy patients.

Axillary lymph node dissection (ALND) and radiation therapy (RT) are commonly recommended for mastectomy patients with positive sentinel lymph node biopsy (SLNB). Effective alternatives to ALND that reduce lymphedema risk are needed. We evaluated rates of lymphedema in mastectomy patients who received SLNB with RT, compared to ALND with or without RT. 627 breast cancer patients who underwent 664 mastectomies between 2005 and 2013 were prospectively screened for lymphedema, median 22.8 months follow-up (range 3.0-86.9). Each mastectomy was categorized as SLNB-no RT, SLNB + RT, ALND-no RT, or ALND + RT. RT included chest wall ± nodal radiation. Perometer arm volume measurements were obtained pre- and post-operatively. Lymphedema was defined as ≥10 % arm volume increase. Kaplan-Meier and Cox regression analyses were performed to determine lymphedema rates and risk factors. Of 664 mastectomies, 52 % (343/664) were SLNB-no RT, 5 % (34/664) SLNB + RT, 9 % (58/664) ALND-no RT, and 34 % (229/664) ALND + RT. The 2 year cumulative lymphedema incidence was 10.0 % (95 % CI 2.6-34.4 %) for SLNB + RT compared with 19.3 % (95 % CI 10.8-33.1 %) for ALND-no RT, and 30.1 % (95 % CI 23.7-37.8 %) for ALND + RT. The lowest cumulative incidence was 2.19 % (95 % CI 0.88-5.40 %) for SLNB-no RT. By multivariate analysis, factors significantly associated with increased lymphedema risk included RT (p = 0.0017), ALND (p = 0.0001), greater number of lymph nodes removed (p = 0.0006), no reconstruction (p = 0.0418), higher BMI (p < 0.0001) and older age (p = 0.0021). In conclusion, avoiding completion ALND and instead receiving SLNB with RT may decrease lymphedema risk in patients requiring mastectomy. Future trials should investigate the safety of applying the ACOSOG Z0011 protocol to mastectomy patients.

The impact of radiation therapy on the risk of lymphedema after treatment for breast cancer: a prospective cohort study.

PURPOSE/OBJECTIVE: Lymphedema after breast cancer treatment can be an irreversible condition with a negative impact on quality of life. The goal of this study was to identify radiation therapy-related risk factors for lymphedema. METHODS AND MATERIALS: From 2005 to 2012, we prospectively performed arm volume measurements on 1476 breast cancer patients at our institution using a Perometer. Treating each breast individually, 1099 of 1501 patients (73%) received radiation therapy. Arm measurements were performed preoperatively and postoperatively. Lymphedema was defined as ≥10% arm volume increase occurring >3 months postoperatively. Univariate and multivariate Cox proportional hazard models were used to evaluate risk factors for lymphedema. RESULTS: At a median follow-up time of 25.4 months (range, 3.4-82.6 months), the 2-year cumulative incidence of lymphedema was 6.8%. Cumulative incidence by radiation therapy type was as follows: 3.0% no radiation therapy, 3.1% breast or chest wall alone, 21.9% supraclavicular (SC), and 21.1% SC and posterior axillary boost (PAB). On multivariate analysis, the hazard ratio for regional lymph node radiation (RLNR) (SC ± PAB) was 1.7 (P=.025) compared with breast/chest wall radiation alone. There was no difference in lymphedema risk between SC and SC + PAB (P=.96). Other independent risk factors included early postoperative swelling (P<.0001), higher body mass index (P<.0001), greater number of lymph nodes dissected (P=.018), and axillary lymph node dissection (P=.0001). CONCLUSIONS: In a large cohort of breast cancer patients prospectively screened for lymphedema, RLNR significantly increased the risk of lymphedema compared with breast/chest wall radiation alone. When considering use of RLNR, clinicians should weigh the potential benefit of RLNR for control of disease against the increased risk of lymphedema.