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Introduction: Diagnosis of LM is limited by low sensitivity of cerebrospinal fluid (CSF) cytopathology. Detecting tumor cells in CSF (CSF-TCs) might be more sensitive. We evaluated if CNSide (CNSide), a novel assay for tumor cell detection in CSF, can detect CSF-TCs better than conventional CSF cytology., Methods: We enrolled adults with metastatic breast cancer and clinical suspicion for LM to undergo lumbar puncture (LP) for CSF cytopathology and CNSide. CNSide captured CSF-TCs using a primary 10-antibody mixture, streptavidin-coated microfluidic channel, and biotinylated secondary antibodies. CSF-TCs were assessed for estrogen receptor (ER) expression by fluorescent antibody and HER2 amplification by fluorescent in situ hybridization (FISH). CSF cell-free DNA (cfDNA) was extracted for next-generation sequencing (NGS). Leptomeningeal disease was defined as positive CSF cytology and/or unequivocal MRI findings. We calculated sensitivity and specificity of CSF cytology and CNSide for the diagnosis of LM., Results: Ten patients, median age 51 years (range, 37-64), underwent diagnostic LP with CSF evaluation by cytology and CNSide. CNSide had sensitivity of 100% (95% Confidence Interval [CI], 40%-100%) and specificity of 83% (95% CI, 36%-100%) for LM. Among these patients, concordance of ER and HER2 status between CSF-TCs and metastatic biopsy were 60% and 75%, respectively. NGS of CSF cfDNA identified somatic mutations in three patients, including one with PIK3CA p.H1047L in blood and CSF., Conclusions: CNSide may be a viable platform to detect CSF-TCs, with potential use as a diagnostic tool for LM in patients with metastatic breast cancer. Additional, larger studies are warranted., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Epidermal growth factor receptor (EGFR) is frequently overexpressed in metastatic triple-negative breast cancer (mTNBC). One strategy for overcoming resistance to EGFR inhibition is concomitant inhibition of downstream signaling. The antidiabetic drug metformin inhibits both MAPK and PI3K/mTOR pathway signaling. We evaluated the combination of erlotinib and metformin in a phase 1 study of patients with mTNBC., Patients and Methods: Patients with mTNBC who had received at least one prior line of therapy for metastatic disease were eligible. Erlotinib dose was fixed at 150 mg daily. Metformin dose escalation was planned according to a 3 + 3 design. Dose-limiting toxicities (DLT) were assessed during the first 5 weeks of therapy. The primary objective was to determine the maximum tolerated dose of metformin with fixed-dose erlotinib. Secondary endpoints were response rate, stable disease rate, and progression-free survival., Results: Eight patients were enrolled. The median number of prior therapies for metastatic disease was 2.5 (range, 1-6). No DLT events were reported during the DLT assessment period. Most adverse events were grade 1/2. Grade 3 diarrhea despite maximum supportive care required dose reduction of metformin in one patient. Grade 3 rash led to study withdrawal in one patient. No grade 4 adverse events were reported. The best observed response was stable disease in 2 patients (25%). Median progression-free survival was 60 days (range, 36-61 days)., Conclusion: Erlotinib and metformin were well tolerated in a population of pretreated mTNBC patients but did not demonstrate efficacy in this population., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Bevacizumab is used for the treatment of metastatic colon cancer in conjunction with first-line chemotherapy. In this study, we examined receipt of first-line bevacizumab and predictors of its use among older patients with stage IV colon cancer., Materials and Methods: We used data from the Surveillance, Epidemiology, and End Results-Medicare dataset to identify patients with stage IV colon cancer diagnosed from 2005 to 2013 who received FOLFOX (5-fluorouracil/leucovorin/oxaliplatin) or FOLFIRI (5-fluorouracil/leucovorin/irinotecan) as first-line therapy. We used multivariable regression analysis to determine demographic and clinical factors associated with use of concomitant bevacizumab., Results: We identified 3785 patients with stage IV colon cancer who met our eligibility criteria. Of these, 2352 (62.1%) received bevacizumab. Bevacizumab use has decreased over time from 68.2% in 2005 to 57.6% in 2013 (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.91-0.97). Patients were less likely to receive bevacizumab if they were older (compared with 65-69 years, ≥ 80 years: OR, 0.64; 95% CI, 0.52-0.80), or had multiple comorbidities (compared with comorbidity score of 0, score of 1: OR, 0.73; 95% CI, 0.60-0.89)., Conclusion: Over one-half of elderly patients received bevacizumab as part of their first-line therapy for stage IV colon cancer. Bevacizumab use has been slowly decreasing since 2005. Newer anti-epidermal growth factor receptor treatments have not been supplanting bevacizumab, as first-line biologic use in general has also decreased during this time period., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Shortly after the year 2000, randomized trials demonstrated that patients with metastatic colon cancer treated with infusional 5-fluorouracil (5-FU)/leucovorin with either oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) had a comparable progression-free survival benefit, superior to patients who received 5-FU/leucovorin alone. Factors associated with the initial receipt of the FOLFOX or FOLFIRI regimen are unknown. Our goal was to investigate the patterns and predictors of use for first-line FOLFOX and FOLFIRI., Patients and Methods: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data set to identify patients with newly diagnosed stage IV colon cancer between the years 2005 and 2013 who received either first-line FOLFOX or FOLFIRI. We used logistic regression to assess demographic and clinical predictors for FOLFOX versus FOLFIRI. Survival was compared by Kaplan-Meier models., Results: Overall, 3000 patients (79.3%) received FOLFOX and 785 (20.7%) FOLFIRI. FOLFOX was associated with later year of diagnosis (odds ratio [OR] = 0.66, 95% confidence interval [CI], 0.54 to 0.82 for 2011-2013 vs. 2005-2007), being female (OR = 0.82; 95% CI 0.69 to 0.98), and living in the southern region of the United States. FOLFIRI was associated with having a higher comorbidity index (OR = 1.33; 95% CI, 1.07 to 1.67 for >1 comorbidity score vs. 0). There was no survival difference observed between the two treatments., Conclusion: The majority of SEER-Medicare patients received FOLFOX and not FOLFIRI as a first-line treatment for stage IV colon cancer. Several demographic and clinical factors were associated with the use of each specific regimen. No survival difference was detected for the 2 groups., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: High-intensity care including hospitalizations, chemotherapy, and other interventions at the end of life is costly and often of little value for cancer patients. Little is known about patterns of end-of-life care and resource utilization for women with uterine cancer., Objective: We examined the costs and predictors of aggressive end-of-life care for women with uterine cancer., Study Design: In this observational cohort study the Surveillance, Epidemiology, and End Results-Medicare linked database was used to identify women age ≥65 years who died from uterine cancer from 2000 through 2011. Resource utilization in the last month of life including ≥2 hospital admissions, >1 emergency department visit, ≥1 intensive care unit admission, or use of chemotherapy in the last 14 days of life was examined. High-intensity care was defined as the occurrence of any of the above outcomes. Logistic regression models were developed to identify factors associated with high-intensity care. Total Medicare expenditures in the last month of life are reported., Results: Of the 5873 patients identified, the majority had stage IV cancer (30.2%), were white (79.9%), and had endometrioid tumors (47.6%). High-intensity care was rendered to 42.5% of women. During the last month of life, 15.0% had ≥2 hospital admissions, 9.0% had a hospitalization >14 days, 15.3% had >1 emergency department visits, 18.3% had an intensive care unit admission, and 6.6% received chemotherapy in the last 14 days of life. The percentage of women who received high-intensity care was stable over the study period. Characteristics of younger age, black race, higher number of comorbidities, stage IV disease, residence in the eastern United States, and more recent diagnosis were associated with high-intensity care. The median Medicare payment during the last month of life was $7645. Total per beneficiary Medicare payments remained stable from $9656 (interquartile range $3190-15,890) in 2000 to $9208 (interquartile range $3309-18,554) by 2011. The median health care expenditure was 4 times as high for those who received high-intensity care compared to those who did not (median $16,173 vs $4099)., Conclusion: Among women with uterine cancer, high-intensity care is common in the last month of life, associated with substantial monetary expenditures, and does not appear to be decreasing., (Copyright © 2017 Elsevier Inc. All rights reserved.)