The contemporary management of cancers of the sinonasal tract in adults.

Sinonasal malignancies make up <5% of all head and neck neoplasms, with an incidence of 0.5-1.0 per 100,000. The outcome of these rare malignancies has been poor, whereas significant progress has been made in the management of other cancers. The objective of the current review was to describe the incidence, causes, presentation, diagnosis, treatment, and recent developments of malignancies of the sinonasal tract. The diagnoses covered in this review included sinonasal undifferentiated carcinoma, sinonasal adenocarcinoma, sinonasal squamous cell carcinoma, and esthesioneuroblastoma, which are exclusive to the sinonasal tract. In addition, the authors covered malignances that are likely to be encountered in the sinonasal tract-primary mucosal melanoma, NUT (nuclear protein of the testis) carcinoma, and extranodal natural killer cell/T-cell lymphoma. For the purpose of keeping this review as concise and focused as possible, sarcomas and malignancies that can be classified as salivary gland neoplasms were excluded.

Real-World Evaluation of Disease Progression After CDK 4/6 Inhibitor Therapy in Patients With Hormone Receptor-Positive Metastatic Breast Cancer.

BACKGROUND: Cyclin-dependent kinase 4/6 inhibitors (CDKi) have changed the landscape for treatment of patients with hormone receptor positive, human epidermal growth factor receptor 2-negative (HR+/HER-) metastatic breast cancer (MBC). However, next-line treatment strategies after CDKi progression are not yet optimized. We report here the impact of clinical and genomic factors on post-CDKi outcomes in a single institution cohort of HR+/HER2- patients with MBC. METHODS: We retrospectively reviewed the medical records of patients with HR+/HER2- MBC that received a CDKi between April 1, 2014 and December 1, 2019 at our institution. Data were summarized using descriptive statistics, the Kaplan-Meier method, and regression models. RESULTS: We identified 140 patients with HR+/HER2- MBC that received a CDKi. Eighty percent of patients discontinued treatment due to disease progression, with a median progression-free survival (PFS) of 6.0 months (95% CI, 5.0-7.1), whereas those that discontinued CDKi for other reasons had a PFS of 11.3 months (95% CI, 4.6-19.4) (hazard ratio (HR) 2.53, 95% CI, 1.50-4.26 [P = .001]). The 6-month cumulative incidence of post-CDKi progression or death was 51% for the 112 patients who progressed on CDKi. Patients harboring PTEN mutations pre-CDKi treatment had poorer clinical outcomes compared to those with wild-type PTEN. CONCLUSION: This study highlights post-CDKi outcomes and the need for further molecular characterization and novel therapies to improve treatments for patients with HR+/HER2- MBC.

CDK 4/6 inhibitors are associated with a high incidence of thrombotic events in women with breast cancer in real-world practice.

PURPOSE: Cyclin-dependent kinase (CDK) 4/6 inhibitors are integral treatment for advanced hormone receptor positive breast cancer; however, venous thromboembolic events (VTE) occurred in 1%-5% of clinical trial patients. Thrombosis rates in the real-world setting remain unclear. We aimed to define the rate of thromboembolic events, risk factors for thrombosis on CDK 4/6 inhibitors and evaluate the Khorana VTE risk score as a predictive tool for VTE in patients on CDK 4/6 therapy. METHODS: Multicenter retrospective analysis of adult breast cancer patients prescribed palbociclib, ribociclib, or abemaciclib. The primary endpoint was thrombosis during treatment or within 30 days of CDK inhibitor discontinuation. Cox regression was used to model time-to-thrombosis, starting from a patient's initiation of CDK 4/6 therapy. The extended Kaplan-Meier method and Cox modeling were used to assess the effect of time-varying thrombosis status on overall survival. RESULTS: Two hundred and sixty-six patients were included (89% on palbociclib, 14% on abemaciclib, 7% on ribociclib). Twenty-nine thrombotic events occurred in 26 (9.8%) women. Of these events, 72% were venous and 34% were arterial. The 1-year incidence of thrombosis was 10.4% overall, 10.9% on palbociclib, 8.3% on ribociclib, and 4.8% on abemaciclib. Hemoglobin less than 10 g/dL was a statistically significant predictor of thrombosis (HR 3.53, P: .014). Khorana score ranged from 0-3, with the majority between 0 and 1 and was not predictive of VTE. Thrombosis was associated with reduced overall survival (HR 1.28, P: .128, median 7.3 months) compared to not having a CDK-associated clot (median 35.7 months). DISCUSSION: VTE in our analysis is higher than reported in clinical trials and arterial thrombosis comprised over one-third of events. The highest incidence was with palbociclib, followed by ribociclib. Khorana score did not predict VTE risk. Larger, real-world studies are needed. The role for prophylactic anticoagulation is yet to be defined in this patient population.

A phenocopy signature of TP53 loss predicts response to chemotherapy.

In preclinical studies, p53 loss of function impacts chemotherapy response, but this has not been consistently validated clinically. We trained a TP53-loss phenocopy gene expression signature from pan-cancer clinical samples in the TCGA. In vitro, the TP53-loss phenocopy signature predicted chemotherapy response across cancer types. In a clinical dataset of 3003 breast cancer samples treated with neoadjuvant chemotherapy, the TP53-loss phenocopy samples were 56% more likely to have a pathologic complete response (pCR), with a significant association between TP53-loss phenocopy and pCR in both ER positive and ER negative tumors. In an independent clinical validation in the I-SPY2 trial (N = 987), we confirmed the association with neoadjuvant chemotherapy pCR and found higher rates of chemoimmunotherapy response in TP53-loss phenocopy tumors compared to non-TP53-loss phenocopy tumors (64% vs. 28%). The TP53-loss phenocopy signature predicts chemotherapy response across cancer types in vitro, and in a proof-of-concept clinical validation is associated with neoadjuvant chemotherapy response across multiple clinical breast cancer cohorts.

Thrombotic events in patients using cyclin dependent kinase 4/6 inhibitors, analysis of existing ambulatory risk assessment models and the potential influences of tumor specific risk factors.

Cyclin dependent kinase 4 of 6 inhibitors (CDKi) are key therapeutics in the treatment of advanced breast cancer and have recently been approved in small cell lung cancer for the prevention of myelosuppression. Thrombotic events have emerged as a significant treatment related adverse event in up to 5% of patients in clinical trials and has been reported at higher rates, up to 10%, in real world analysis. The prothrombotic mechanisms of CDKis, however, remain unknown. Cancer specific risk assessment models exist to identify who may be at highest risk of thrombosis and who could potentially benefit from prophylactic anticoagulation. However, these models may not be accurate in patients taking CDKis and may not fully capture recently identified thrombotic risk factors such as tumor specific somatic mutations. In the following manuscript, we summarize the literature on thrombotic events with CDKis in clinical trials and real-world settings, review the existing thrombosis risk assessment models for ambulatory cancer patients, and discuss the literature on tumor mutations and role in cancer associated thrombosis.

Gender and Patient Satisfaction in a Veterans Health Administration Outpatient Chemotherapy Unit.

Background: Our objective was to explore whether differences in patient satisfaction based on gender exist at the Veterans Affairs Portland Health Care System (VAPHCS) outpatient chemotherapy infusion unit. Methods: Veterans who received outpatient infusion treatments at the VAPHCS outpatient chemotherapy infusion unit from 2018 to 2020 were invited to take an anonymous survey. Response differences were analyzed using Fisher exact and Welch t tests. Male and female patient lists were first generated based on Computerized Patient Record System designation, then defined and results reported based on gender self-identification from survey responses. Results: The survey was conducted over a 2-week period during January and February of 2021. In total, 69 veterans were contacted: 21 (70%) of 30 female and 20 (51%) of 39 male veterans completed the survey. Most (62%) female patients were aged < 65 years, and 52% were treated for breast cancer. Most (90%) male patients were aged ≥ 65 years, and most commonly treated for prostate cancer (20%) or a hematologic malignancy (20%). Using our survey, patient satisfaction (SD) was 8.7 (2.2) on a 10-point scale among women, and 9.6 (0.6) among men (P = .11). History of sexual abuse or harassment was reported by 86% of women compared with 10% of men (P < .001). Women reported feeling uncomfortable around other patients in the infusion unit compared with men (29% vs 0%; P = .02) and discomfort in relaying uncomfortable feelings to a clinician (29% vs 0%; P = .02). Conclusions: Gender seems to be related to how veterans with cancer perceive their ambulatory cancer care. This may be due to the combination of a high history of sexual abuse and/or harassment among women who represent a minority of the total infusion unit population, the majority of whom receive treatment for a primarily gender-specific breast malignancy. Analysis was limited by the small sample size of women, many with advanced malignancy.