Disparities at the Intersection of Race and Ethnicity: Examining Trends and Outcomes in Hispanic Women With Breast Cancer.

PURPOSE: We sought to examine tumor subtype, stage at diagnosis, time to surgery (TTS), and overall survival (OS) among Hispanic patients of different races and among Hispanic and non-Hispanic (NH) women of the same race. METHODS: Women 18 years of age or older who had been diagnosed with stage 0-IV breast cancer and who had undergone lumpectomy or mastectomy were identified in the National Cancer Database (2004-2014). Tumor subtype and stage at diagnosis were compared by race/ethnicity. Multivariable linear regression and Cox proportional hazards modeling were used to estimate associations between race/ethnicity and adjusted TTS and OS, respectively. RESULTS: A total of 44,374 Hispanic (American Indian [AI]: 79 [0.2%]; Black: 1,011 [2.3%]; White: 41,126 [92.7%]; Other: 2,158 [4.9%]) and 858,634 NH women (AI: 2,319 [0.3%]; Black: 97,206 [11.3%]; White: 727,270 [84.7%]; Other: 31,839 [3.7%]) were included. Hispanic Black women had lower rates of triple-negative disease (16.2%) than did NH Black women (23.5%) but higher rates than did Hispanic White women (13.9%; P < .001). Hispanic White women had higher rates of node-positive disease (23.2%) versus NH White women (14.4%) but slightly lower rates than Hispanic (24.6%) and NH Black women (24.5%; P < .001). Hispanic White women had longer TTS versus NH White women regardless of treatment sequence (adjusted means: adjuvant chemotherapy, 42.71 v 38.60 days; neoadjuvant chemotherapy, 208.55 v 201.14 days; both P < .001), but there were no significant racial differences in TTS among Hispanic patients. After adjustment, Hispanic White women (hazard ratio, 0.77 [95% CI, 0.74 to 0.81]) and Black women (hazard ratio, 0.75 [95% CI, 0.58 to 0.96]) had improved OS versus NH White women (reference) and Black women (hazard ratio, 1.15 [95% CI, 1.12 to 1.18]; all P < .05). CONCLUSION: Hispanic women had improved OS versus NH women, but racial differences in tumor subtype and nodal stage among Hispanic women highlight the importance of disaggregating racial/ethnic data in breast cancer research.

Developing Expert Gaze Pattern in Laparoscopic Surgery Requires More than Behavioral Training.

Expertise in laparoscopic surgery is realized through both manual dexterity and efficient eye movement patterns, creating opportunities to use gaze information in the educational process. To better understand how expert gaze behaviors are acquired through deliberate practice of technical skills, three surgeons were assessed and five novices were trained and assessed in a 5-visit protocol on the Fundamentals of Laparoscopic Surgery peg transfer task. The task was adjusted to have a fixed action sequence to allow recordings of dwell durations based on pre-defined areas of interest (AOIs). Trained novices were shown to reach more than 98% (M = 98.62%, SD = 1.06%) of their behavioral learning plateaus, leading to equivalent behavioral performance to that of surgeons. Despite this equivalence in behavioral performance, surgeons continued to show significantly shorter dwell durations at visual targets of current actions and longer dwell durations at future steps in the action sequence than trained novices (ps ≤ .03, Cohen's ds > 2). This study demonstrates that, while novices can train to match surgeons on behavioral performance, their gaze pattern is still less efficient than that of surgeons, motivating surgical training programs to involve eye tracking technology in their design and evaluation.

Checkpoint inhibitor immunotherapy for glioblastoma: current progress, challenges and future outlook.

INTRODUCTION: Despite maximal surgical resection and chemoradiation, glioblastoma (GBM) continues to be associated with significant morbidity and mortality. Novel therapeutic strategies are urgently needed. Given success in treating multiple other forms of cancer, checkpoint inhibitor immunotherapy remains foremost amongst novel therapeutic strategies that are currently under investigation. AREAS COVERED: Through a systematic review of both published literature and the latest preliminary data available from ongoing clinical studies, we provide an up-to-date discussion on the immune system in the CNS, a detailed mechanistic evaluation of checkpoint biology in the CNS along with evidence for disruption of these pathways in GBM, and a summary of available preclinical and clinical data for checkpoint blockade in GBM. We also include a discussion of novel, emerging targets for checkpoint blockade which may play an important role in GBM immunotherapy. EXPERT OPINION: Evidence indicates that while clinical success of checkpoint blockade for the treatment of GBM has been limited to date, through improved preclinical models, optimization in the context of standard of care therapies, assay standardization and harmonization, and combinatorial approaches which may include novel targets for checkpoint blockade, checkpoint inhibitor immunotherapy may yield a safe and effective therapeutic option for the treatment of GBM.

Targeting PD-L1 Initiates Effective Antitumor Immunity in a Murine Model of Cushing Disease.

PURPOSE: Although pituitary adenoma is classified as benign, Cushing disease is associated with significant morbidity due to the numerous sequelae of elevated cortisol levels. Successful therapy for Cushing disease remains elusive due to high rates of treatment-refractory recurrence. The frequent emergence of lymphocytic hypophysitis following checkpoint blockade for other cancers, as well as the expression of PD-L1 on pituitary adenomas, suggest a role for immunotherapy. EXPERIMENTAL DESIGN: This study confirms PD-L1 expression on functioning pituitary adenomas and is the first to evaluate the efficacy of checkpoint blockade (anti-PD-L1) therapy in a preclinical model of Cushing disease. RESULTS: Herein, treatment with anti-PD-L1 was successful in reducing adrenocorticotropic hormone plasma levels, decreasing tumor growth, and increasing survival in our model. Furthermore, tumor-infiltrating T cells demonstrated a pattern of checkpoint expression similar to other checkpoint blockade-susceptible tumors. CONCLUSIONS: This suggests that immunotherapy, particularly blockade of the PD1/PD-L1 axis, may be a novel therapeutic option for refractory Cushing disease. Clinical investigation is encouraged.

Operative and peri-operative considerations in the management of brain metastasis.

The number of patients who develop metastatic brain lesions is increasing as the diagnosis and treatment of systemic cancers continues to improve, resulting in longer patient survival. The role of surgery in the management of brain metastasis (BM), particularly multiple and recurrent metastases, remains controversial and continues to evolve. However, with appropriate patient selection, outcomes after surgery are typically favorable. In addition, surgery is the only means to obtain a tissue diagnosis and is the only effective treatment modality to quickly relieve neurological complications or life-threatening symptoms related to significant mass effect, CSF obstruction, and peritumoral edema. As such, a thorough understanding of the role of surgery in patients with metastatic brain lesions, as well as the factors associated with surgical outcomes, is essential for the effective management of this unique and growing patient population.

DCIS with Microinvasion: Is It In Situ or Invasive Disease?

BACKGROUND: Ductal carcinoma in situ (DCIS) with microinvasion (DCISM) can be challenging in balancing the risks of overtreatment versus undertreatment. We compared DCISM, pure DCIS, and small volume (T1a) invasive ductal carcinoma (IDC) as related to histopathology, treatment patterns, and survival outcomes. METHODS: Women ages 18-90 years who underwent breast surgery for DCIS, DCISM, or T1a IDC were selected from the SEER Database (2004-2015). Multivariate logistic regression and Cox proportional hazards models were used to estimate the association of diagnosis with treatment and survival, respectively. RESULTS: A total of 134,569 women were identified: 3.2% DCISM, 70.9% DCIS, and 25.9% with T1a IDC. Compared with invasive disease, DCISM was less likely to be ER+ or PR+ and more likely to be HER2+. After adjustment, DCIS and invasive patients were less likely to undergo mastectomy than DCISM patients (DCIS: OR 0.53, 95% CI 0.49-0.56; invasive: OR 0.86, CI 0.81-0.92). For those undergoing lumpectomy, the likelihood of receiving radiation was similar for DCISM and invasive patients but lower for DCIS patients (OR 0.57, CI 0.52-0.63). After adjustment, breast-cancer-specific survival was significantly different between DCISM and the other two groups (DCIS: HR 0.59, CI 0.43-0.8; invasive: HR 1.43, CI 1.04-1.96). However, overall survival was not significantly different between DCISM and invasive disease, whereas patients with DCIS had improved OS (HR 0.83, CI 0.75-0.93). CONCLUSIONS: Although DCISM is a distinct entity, current treatment patterns and prognosis are comparable to those with small volume IDC. These findings may help providers counsel patients and determine appropriate treatment plans.

The Evolving Modern Management of Brain Metastasis.

The incidence of brain metastases is increasing as cancer therapies improve and patients live longer, providing new challenges to the multidisciplinary teams that care for these patients. Brain metastatic cancer cells possess unique characteristics that allow them to penetrate the blood-brain barrier, colonize the brain parenchyma, and persist in the intracranial environment. In addition, brain metastases subvert the innate and adaptive immune system, permitting evasion of the antitumor immune response. Better understanding of the above mechanisms will allow for development and delivery of more effective therapies for brain metastases. In this review, we outline the molecular mechanisms underlying development, survival, and immunosuppression of brain metastases. We also discuss current and emerging treatment strategies, including surgery, radiation, disease-specific and mutation-targeted systemic therapy, and immunotherapy.