Association of a novel 27-gene immuno-oncology assay with efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer.

BACKGROUND: Immune checkpoint inhibitor (ICI) therapies represent a major advance in treating a variety of advanced-stage malignancies. Nevertheless, only a subset of patients benefit, even when selected based on approved biomarkers such as PD-L1 and tumor mutational burden. New biomarkers are needed to maximize the therapeutic ratio of these therapies. METHODS: In this retrospective cohort, we assessed a 27-gene RT-qPCR immuno-oncology (IO) gene expression assay of the tumor immune microenvironment and determined its association with the efficacy of ICI therapy in 67 advanced-stage NSCLC patients. The 27-gene IO test score (IO score), programmed cell death ligand 1 immunohistochemistry tumor proportion score (PD-L1 TPS), and tumor mutational burden (TMB) were analyzed as continuous variables for response and as binary variables for one-year progression free survival. The threshold for the IO score was prospectively set based upon a previously described training cohort. Prognostic implications of the IO score were evaluated in a separate cohort of 104 advanced-stage NSCLC patients from The Cancer Genome Atlas (TCGA) who received non-ICI therapy. RESULTS: The IO score was significantly different between responders or non-responders (p = 0.007) and associated with progression-free survival (p = 0.001). Bivariate analysis established that the IO score was independent of PD-L1 TPS and TMB in identifying patients benefiting from ICI therapy. In a separate cohort of late-stage NSCLC patients from TCGA, the IO score was not prognostic of outcome from non-ICI-treated patients. CONCLUSIONS: This study is the first application of this 27-gene IO RT-qPCR assay in a clinical cohort with outcome data. IO scores were significantly associated with response to ICI therapy and prolonged progression-free survival. Together, these data suggest the IO score should be further studied to define its role in informing clinical decision-making for ICI treatment in NSCLC.

Usefulness of patient-reported outcomes to assess the effectiveness of topical hormonal therapy for gynecologic symptoms after antihormonal treatment for breast cancer.

The aim of this retrospective study was to assess the efficacy of topical hormonal therapy (THT) to relieve vaginal symptoms resulting from antihormonal therapy in women with hormone receptor-positive breast cancer. A total of 74 breast cancer patients who received THT for vaginal complaints were retrospectively identified and statistically matched with 74 control breast cancer patients with vaginal complaints with no documented use of THT. Symptom scores were recorded from the center's proprietary patient-reported outcomes database, Patient Care Monitor (ConcertoHealthAI, Boston). A baseline score was noted at the initiation of antihormonal therapy and was followed at 6 and 12 months. The median differences between baseline, 6-month, and 12-month scores were analyzed. Repeated measures analysis of variance assessed the impact of topical hormonal replacement. There was no statistically significant difference in score change between the two groups at 6 and 12 months. In the active THT group, there were no statistically significant differences in vaginal complaints or sexual problems over time: {F (2, 146) = 0.99, P = 0.369; and F (2, 146) = 1.56, P = 0.217}, respectively. In this study, the use of topical hormonal replacement was not effective in alleviating vaginal symptoms.

Unusual recurrent metastasizing benign breast papilloma: a case report.

BACKGROUND: Papillary breast lesions may be benign, atypical, and malignant lesions. Pathological and clinical differentiation of breast papillomas can be a challenge. Unlike malignant lesions, benign breast papillomas are not classically associated with lymph node and distant metastasis. We report a unique case of a recurrent, benign breast papilloma presenting as an aggressive malignant tumor. CASE PRESENTATION: Our patient was a 56-year-old postmenopausal African American woman who was followed in the breast clinic with a long history of multiple breast papillomas. She underwent multiple resections over the course of 7-9 years. After being lost to follow-up for 2 years, she once again presented with a slowly enlarging left breast mass. Subsequent imaging revealed a predominantly cystic mass in the left breast, as well as a suspicious hypermetabolic internal mammary node and a hypermetabolic nodule in the pretracheal space. Biopsy of the internal mammary node demonstrated papillary neoplasm with benign morphology and immunostains positive for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2/Neu. Due to the clinical picture concerning for malignancy, the patient was then started on endocrine therapy with palbociclib and letrozole before surgery. She then underwent simple mastectomy and sentinel lymph node dissection with negative nodes and pathology once again revealing benign papillary neoplasm. She underwent adjuvant chest wall radiation for 6 weeks and received letrozole following completion of her radiation therapy. She was without evidence of disease 30 months after surgery. CONCLUSIONS: We present an unusual case of multiple recurrent peripheral papillomas with entirely benign histologic features exhibiting malignant behavior over a protracted period of many years, with an invasion of pectoralis musculature and possibly internal mammary and mediastinal nodes. Her treatment course included multiple surgeries (ultimately mastectomy), radiation therapy, and endocrine therapy.

Racial Difference in Symptom Onset to Door Time in ST Elevation Myocardial Infarction.

BACKGROUND: There are poorer outcomes following ST elevation myocardial infarction in blacks compared to white patients despite comparable door-to-reperfusion time. We hypothesized that delays to hospital presentation may be contributory. METHODS AND RESULTS: We conducted a retrospective analysis of the 1144 patients admitted for STEMI in our institution from 2008 to 2013. The door-to-balloon time (D2BT) and symptom-onset-to-door time (SODT) were compared by race. Bivariate analysis was done comparing the median D2BT and SODT. Stratified analyses were done to evaluate the effect of race on D2BT and SODT, accounting for insurance status, age, sex and comorbidities. The mean age was 59±13 years; 56% of this population was black and 41% was white. Males accounted for 66% of this population. The median D2BT was 60 minutes (interquartile range [IQR] 42-82), and median SODT was 120 minutes (IQR 60-720). There was no significant difference in D2BT by race (P=0.86). Black patients presented to the emergency room (ER) later than whites (SODT=180 [IQR 60-1400] vs 120 [IQR 60-560] minutes, P<0.01) and were more likely to be uninsured (P<0.01). After controlling for comorbidities, insurance, and socioeconomic status, blacks were 60% more likely to present late after a STEMI (OR 1.6, P<0.01). A subset analysis excluding transferred patients showed similar results. CONCLUSIONS: Black patients present later to the ER after STEMI with no difference in D2BT compared to whites. This difference in time to presentation may be one of the factors accounting for poor outcomes in this population.

Comparative Survival of Patients With Anal Adenocarcinoma, Squamous Cell Carcinoma of the Anus, and Rectal Adenocarcinoma.

BACKGROUND: Anal adenocarcinoma (AA) represents 5% to 10% of anal cancer. Little is known about its natural history and prognosis. Using population-based data, we defined the outcomes of AA relative to other anorectal malignancies. PATIENTS AND METHODS: We analyzed the Surveillance, Epidemiology, and End Results 18 database to identify patients ≥ 18 years old with AA, squamous cell carcinoma of the anus (SCCA), and rectal adenocarcinoma (RA) diagnosed between 1990 and 2011. Median overall survival (OS), 1-year, 3-year, 5-year, and 10-year OS were computed using actuarial methods. The log rank test was used to estimate the difference between Kaplan-Meier survival curves. A Cox proportional hazard regression model was used to adjust the effects of other covariates on survival, including age, year diagnosed, sex, stage, surgery, and radiation. RESULTS: Of 57,369 cases, 0.8% (n = 462) were patients with AA, 87.8% (n = 50,382) were patients with RA, and 11.4% (n = 6525) were patients with SCCA. The median age for AA was 69 years (range, 20-96 years), 66 years (range, 18-103 years) for RA, and 66 years (range, 14-104 years) for SCCA. The median OS was significantly lower for AA (33 months), compared with SCCA (118 months) and RA (68 months) (P < .01). In multivariate analysis, AA had a worse prognosis compared with SCCA (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.59-0.75; P < .01) and RA (HR, 0.68; 95% CI, 0.61-0.77; P < .01), after adjusting for age, sex, race, stage, grade, radiation, and surgery. There was a strong trend for improved survival among patients who received radical surgery (HR, 0.71; 95% CI, 0.51-1.00; P = .05). CONCLUSION: AA confers a significantly worse prognosis than SCCA and RA.

ST Segment Elevation Myocardial Infarction in a 23-Year-Old Woman Following Plasmapheresis.

A 23 year old woman presented with acute ST Elevation Myocardial Infarction (STEMI) three hours after donating plasma. Her only risk factors were obesity and cigarette smoking. She was found to have ST elevation in the anterior and inferior leads. Coronary angiography revealed extensive left anterior descending (LAD) thrombosis. Coagulopathy workup was negative. We propose that plasmapheresis in a known cigarette smoker led to an acute thrombotic event resulting in a STEMI.