Trends in utilization of hypofractionated whole breast irradiation (HF-WBI) in triple negative breast cancer (TNBC): a national cancer database (NCDB) analysis.

PURPOSE: We sought to identify trends over time with respect to the use of hypofractionated whole breast irradiation (HF-WBI) in women with triple negative breast cancer (TNBC) in the national cancer database (NCDB). METHODS: Trends in utilization of HF-WBI in women diagnosed with T1-2N0 TNBC in the NCDB between 2008 and 2013 were analyzed. Case-matched luminal A women were used for comparison. Variables included age, race, year of diagnosis, insurance status, income quartile, receipt of neoadjuvant chemotherapy, and institution (academic vs. community). Chi square, logistic regression, and multivariate analysis was performed. RESULTS: Utilization of HF-WBI among the 53,269 TNBC women identified steadily increased from 4.7% in 2008 to 14.0% in 2013 for women with TNBC compared to luminal A cancer whose utilization increased from 7.3 to 23.3% over the same time frame (p < 0.001). On univariate analysis, HF-WBI was associated with increasing age (p < 0.001), Medicare insurance (p < 0.001), race (p = 0.041), diagnosis after 2011 (p < 0.001), higher income quartile (p < 0.001), and treatment at academic institutions (p < 0.001). On multivariate analysis, age (p < 0.001, OR 1.038 per year), income quartile (p = 0.002, OR 1.061 per increase in quartile), treatment at an academic institution (p < 0.001, OR 1.78) significantly increased use of HF-WBI. CONCLUSIONS: Treatment at an academic center and year of diagnosis were most correlated with increased HF-WBI in T1-2N0 TNBC women in the NCDB from 2008 to 2013, followed by increasing age and income. Only 14% of T1-2N0 TNBC women received HF-WBI in 2013. Focus on increased utilization is needed for non-academic centers, lower income, and younger women.

Utilization of hypofractionated whole-breast radiation therapy in patients receiving chemotherapy: a National Cancer Database analysis.

PURPOSE: Results from four major hypofractionated whole-breast radiotherapy (HF-WBRT) trials have demonstrated equivalence in select patients with early-stage breast cancer when compared with conventionally fractionated WBRT (CF-WBRT). Because relatively little data were available on patients receiving neoadjuvant or adjuvant chemotherapy, consensus guidelines published in 2011 did not endorse the use of HF-WBRT in this population. Our goal is to evaluate trends in utilization of HF-WBRT in patients receiving chemotherapy. METHODS AND MATERIALS: We retrospectively analyzed data from 2004 to 2013 in the National Cancer DataBase on breast cancer patients treated with HF-WBRT who met the clinical criteria proposed by consensus guidelines (i.e., age >0 years, T1-2N0, and breast-conserving surgery), regardless of receipt of chemotherapy. We employed logistic regression to delineate and compare clinical and demographic factors associated with utilization of HF-WBRT and CF-WBRT. RESULTS: A total of 56,836 women were treated with chemotherapy and WBRT (without regional nodal irradiation) from 2004 to 2013; 9.0% (n = 5093) were treated with HF-WBRT. Utilization of HF-WBRT increased from 4.6% in 2004 to 18.2% in 2013 (odds ratio [OR] 1.21/year; P < 0.001). Among patients receiving chemotherapy, factors most dramatically associated with increased odds of receiving HF-WBRT on multivariate analysis were academic facilities (OR 2.07; P < 0.001), age >80 (OR 2.58; P < 0.001), west region (OR 1.91; P < 0.001), and distance >50 miles from cancer reporting facility (OR 1.43; P < 0.001). Factors associated with decreased odds of receiving HF-WBRT included white race, income <$48,000, lack of private insurance, T2 versus T1, and higher grade (all P < 0.02). CONCLUSIONS: Despite the absence of consensus guideline recommendations, the use of HF-WBRT in patients receiving chemotherapy has increased fourfold (absolute = 13.6%) over the last decade. Increased utilization of HF-WBRT should result in institutional reports verifying its safety and efficacy.

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

PURPOSE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Factors Influencing Management and Outcome in Patients with Occult Breast Cancer with Axillary Lymph Node Involvement: Analysis of the National Cancer Database.

BACKGROUND: Occult breast cancer (OBC) is rare and optimal local-regional (LR) management has not been defined. Using a patient registry database, we examine factors associated with treatment and outcomes in OBC. METHODS: Female patients with cT0 N1/2 M0 BC were selected from the National Cancer Database (2004-2013) and categorized into four treatment groups: MAST = mastectomy with axillary lymph node dissection (ALND) ± radiation (RT); RT + ALND = RT with ALND, no breast surgery; ALND = ALND alone; OBS = no breast surgery, RT, or ALND. Patient characteristics and overall survival (OS) were compared between groups, and multivariable analysis was used to identify factors associated with treatment and OS. RESULTS: Among 2.03 million BC cases, 1853 females (0.09%) with cT0 N1/2 M0 disease were identified and 1231 patients were categorized into a treatment group: MAST = 592, RT + ALND = 342, ALND = 106, OBS = 191. On logistic regression, care at an academic center was associated with a higher likelihood of RT + ALND compared with MAST (odds ratio 2.03, 95% confidence interval [CI] 1.50-2.74, p < 0.001). Patients treated with RT + ALND had significantly better OS on univariate survival analysis compared with patients treated with MAST (hazard ratio [HR] 0.475, 95% CI 0.306-0.736, p = 0.001). RT + ALND was independently associated with OS on multivariable survival analysis (HR 0.509, 95% CI 0.321-0.808, p = 0.004), after adjusting for covariates. CONCLUSIONS: Patients with OBC were more likely to undergo RT + ALND if they received care at an academic center. Patients treated with RT + ALND had significantly better OS compared with patients treated with MAST, after adjusting for covariates. This supports the use of RT + ALND as LR treatment for patients with OBC.

Development of tumor-infiltrating CD8+ T cell memory precursor effector cells and antimelanoma memory responses are the result of vaccination and TGF-ß blockade during the perioperative period of tumor resection.

A main goal of cancer immunology research is the formation of Ag-specific memory T cell immunity capable of activation upon tumor re-encounter. The requirements necessary to overcome the inhibitory signals present in the tumor microenvironment and form such memory T cell responses are unknown. In contrast to previous studies targeting tumors expressing highly immunogenic model Ags, we demonstrate that alleviating tumor-induced suppression along with vaccination against authentic Ags during the perioperative period provides long-lasting protection against a highly suppressive and poorly immunogenic melanoma. In this study, we employed DNA vaccination with an immunologically optimized mouse melanoma-shared Ag, Trp1ee/ng, combined with systemic TGF-ß blockade during the perioperative period of primary tumor resection, to confer protection against B16 melanoma, and against JBRH, an independently derived melanoma unrelated to B16. Importantly, we demonstrate that correlative to memory responses, perioperative immunotherapy increases the formation of tumor-infiltrating and tumor-reactive CD8(+) T cells expressing low levels of the transcription factor T-bet, defined as memory precursor effector cells. We show that conditions for an immunologically fertile environment are met when TGF-ß blockade and vaccination are applied during the perioperative period of primary tumor resection. These findings address limitations of current CD8(+) T cell immunotherapies against cancer by generating effective CD8(+) T cell memory recall responses.

Longevity of Outcomes Following Reduction Mammoplasty.

Background: Reduction mammoplasty has been shown to provide wide-ranging benefits for patients including improved quality of life in terms of physical function and mental health. However, most existing studies have been limited to the 1-year postoperative period. The aim of this study was to investigate long-term outcomes after reduction mammoplasty. Methods: Patients who underwent reduction mammoplasty at a single institution were identified retrospectively and grouped into 3 categories based on time since surgery: (i) 5 to 10 years, (ii) 10 to 15 years, and (iii) more than 15 years. A telephone survey was administered to measure satisfaction and symptom relief following reduction mammoplasty. Results: A total of 124 patients completed the survey and were included in the study. The majority of patients in all 3 groups reported marked symptoms relief (75% vs 82% vs 82%, P = .84). Overall satisfaction after reduction mammoplasty was high in all 3 subgroups and did not significantly decrease over time (4.16 vs 3.97 vs 3.7, P = .216) despite high proportions of patients reporting an increase in breast size since surgery (40% vs 70% vs 51%, P = .0297). Conclusions: Overall, reduction mammoplasty has long-lasting benefits for patients with macromastia. Overwhelmingly, patients report satisfaction with the procedure and marked symptom relief that is sustained for as long as 15 years after surgery.

A Case of Benign Phyllodes Tumor in a Transgender Woman Receiving Cross-Sex Hormones.

Phyllodes tumor is a relatively uncommon fibroepithelial neoplasm of the breast characterized by proliferation of both stromal and epithelial elements. Benign phyllodes tumors are distinguished from fibroadenomas by their prominent leaf-like architecture and exaggerated intracanalicular stromal growth pattern. Typically, these lesions affect older natal females; however, we present what we believe is the first reported case of benign phyllodes tumor in a hormonally treated transgender woman.

Patient-reported Adherence to Adjuvant Aromatase Inhibitor Therapy Using the Morisky Medication Adherence Scale: An Evaluation of Predictors.

OBJECTIVES: Endocrine therapy is part of standard adjuvant therapy for patients with hormone receptor-positive breast cancer and has been shown to improve recurrence-free and overall survival. However, adherence to endocrine therapy is suboptimal and is difficult to measure. In this study we evaluate the feasibility of using the Morisky Medication Adherence Scale (MMAS) to assess patient adherence to aromatase inhibitor (AI) therapy. METHODS: Patients with stage 1 to 3, hormone receptor-positive breast cancer receiving adjuvant AI therapy were prospectively enrolled on an Institutional Review Board approved protocol. The MMAS questionnaire was administered to each patient and adherence was measured. Information on duration of AI therapy, patient and tumor characteristics, and treatment was collected. A multivariable logit model approach was utilized to evaluate potential barriers to adherence. RESULTS: Between 2011 and 2014, 100 patients were enrolled. The distribution of adherence levels was 13% low, 37% medium, and 50% high. High adherence was reported more frequently in white women (58%), patients with stage 2 and 3 disease (54%), and patients who did not receive chemotherapy (62%). Multivariable analysis demonstrated that higher adherence was more likely in white women compared with African American women (estimated odds ratio=2.8). CONCLUSIONS: Using the MMAS, only 50% of women with stage 1 to 3 breast cancer reported high adherence to AI therapy, consistent with other reports showing suboptimal adherence to adjuvant endocrine therapy. The MMAS allows for the rapid assessment of adherence to oral adjuvant endocrine therapy and is valuable in a busy clinical setting.

Palliation of hepatic tumors.

Palliation is treatment aimed at alleviating the symptomatic effects of a disease rather than at curing the disease. The four most common types of liver tumors that often require palliative treatment include hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), metastatic colorectal carcinoma (mCRC), and metastatic neuroendocrine tumors (mNET). Modalities employed in the palliative treatment of these tumors most often include resection, stenting, chemotherapy, radiation, ablation, and the general treatment of liver failure symptoms. Many of these modalities can be applied to the palliative care of all hepatic tumor types, regardless of the specific tumor histology--as incurable cancers often converge along a final common pathway. We herein provide a review of the therapeutic approaches to palliate hepatic tumors, as well as how such therapies are designed to alleviate the symptoms of patients with end-stage liver tumors.

NKG2D signaling on CD8⁺ T cells represses T-bet and rescues CD4-unhelped CD8⁺ T cell memory recall but not effector responses.

CD4-unhelped CD8(+) T cells are functionally defective T cells primed in the absence of CD4(+) T cell help. Given the co-stimulatory role of natural-killer group 2, member D protein (NKG2D) on CD8(+) T cells, we investigated its ability to rescue these immunologically impotent cells. We demonstrate that augmented co-stimulation through NKG2D during priming paradoxically rescues memory, but not effector, CD8(+) T cell responses. NKG2D-mediated rescue is characterized by reversal of elevated transcription factor T-box expressed in T cells (T-bet) expression and recovery of interleukin-2 and interferon-γ production and cytolytic responses. Rescue is abrogated in CD8(+) T cells lacking NKG2D. Augmented co-stimulation through NKG2D confers a high rate of survival to mice lacking CD4(+) T cells in a CD4-dependent influenza model and rescues HIV-specific CD8(+) T cell responses from CD4-deficient HIV-positive donors. These findings demonstrate that augmented co-stimulation through NKG2D is effective in rescuing CD4-unhelped CD8(+) T cells from their pathophysiological fate and may provide therapeutic benefits.

TNF-based isolated hepatic perfusion.

Unresectable primary and metastatic cancers confined to the liver often determine the prognosis for patients with primary hepatic cancers, colorectal cancer, ocular melanoma, and neuroendocrine tumors. Although many locoregional therapies have emerged as options for patients with unresectable liver malignancies, these treatments frequently have limited clinical benefit. Isolated hepatic perfusion (IHP) has emerged as a regional therapy effective in inducing tumor regression in isolated liver metastases from multiple histologies. Tumor necrosis factor alpha (TNF) is a biologic agent well suited to isolated therapy because of its single-dose efficacy, synergistic effect with hyperthermia, and effects on tumor neovasculature. When combined with chemotherapeutic agents in IHP, TNF may improve response rates in patients with hepatic metastases of some histologies. However, there are additional toxicities associated with the administration of TNF and further studies are needed to determine whether TNF confers a clinical advantage in IHP.

Surgical management of early-stage hepatocellular carcinoma: resection or transplantation?

BACKGROUND: The surgical management of hepatocellular carcinoma in patients with well-compensated cirrhosis is controversial. The purpose of the current study was to compare the outcome of patients with well-compensated cirrhosis and early stage hepatocellular carcinoma treated with initial hepatic resection versus transplantation. METHODS: Between 1985 and 2008, 245 patients underwent hepatic resection, and 134 patients underwent liver transplantation for early stage hepatocellular carcinoma. All patients had well-compensated cirrhosis. Prognostic factors were evaluated using univariate and multivariate analyses; survival was calculated using the Kaplan-Meier method. RESULTS: Compared with transplantation, patients undergoing resection had larger tumors and a higher incidence of microscopic vascular invasion. Transplantation was associated with better 5-year disease-free and overall survival compared with resection. Hepatitis status, presence of microscopic vascular invasion, and tumor size were predictors for recurrence, while the presence of microscopic vascular invasion and tumor size conferred an increased risk of death. The disease-free survival advantage with transplantation was more pronounced in hepatitis C patients compared with non-hepatitis and hepatitis B patients. The overall survival advantage with transplantation persisted in cases of solitary lesions < or = 3 cm, but was attenuated in patients with a MELD score < or = 8. CONCLUSION: In well-compensated cirrhotic patients with early stage hepatocellular carcinoma, transplantation was associated with longer disease-free and overall survival. Patients undergoing resection did, however, have tumors with more advanced pathologic features. Patients best suited for initial resection as the treatment of hepatocellular carcinoma were those with a MELD score