Real-world evaluation of effectiveness and tolerance of chemotherapy for early-stage breast cancer in older women.

PURPOSE: Older patients with early-stage breast cancer (ESBC) tend to receive less aggressive treatment, have higher mortality rates, and are underrepresented in clinical trials. Outcomes, tolerance and toxicity of chemotherapy are underreported. Thus, we assessed the outcomes of chemotherapy in the real-world in a community oncology setting. METHODS: We retrospectively chart reviewed consecutive older patients (≥ 70 years) with ESBC diagnosed between January 1, 2010, and December 31, 2016, who received chemotherapy at our institution. Study outcomes were survival estimates. Logistic regression determined associations with measures of intolerance. RESULTS: Of 1296 patients, 229 received chemotherapy. Overall, 24% had early chemotherapy cessation; 18% had dose reductions; and 27% had dose delays. Severe, life threatening and lethal toxicities occurred in 38%, 1.3%, and 2.2%, respectively; constitutional toxicity (37%) was the most common. The 1- and 3-year overall survivals were 94% and 79%; 1- and 3-year breast-specific survivals were 96% and 89%, while 1- and 3-year disease-free survivals were 95% and 82%, respectively. Anthracyclines were the most poorly tolerated regimen having associations with hospital visits (OR 10.97, 95% CI 2.10-57.23) and severe toxicities (OR 5.28, 95% CI 1.27-21.89). Anti-HER2 therapies (OR 3.03, 95% CI 1.18-7.78) and poorer performance status (PS) (OR 7.48, 95% CI 1.75-31.98) were associated with severe toxicities. Older age (> 80 years) was associated with early cessation of therapy (OR 3.64, 95% CI 1.34-9.83). CONCLUSIONS: Chemotherapy can be effectively delivered to older patients with ESBC and is reasonably well tolerated. The high rate of anthracycline intolerability, poorer PS, and advanced age should be considered when tailoring treatment regimens.

Serum Neurofilament Light, Glial Fibrillary Acidic Protein and Tau Are Possible Serum Biomarkers for Activity of Brain Metastases and Gliomas.

BACKGROUND: Primary central nervous system (CNS) tumors and brain metastases (BMs) are major causes of morbidity and mortality, accompanied by low survival rates. Efforts to early discovery of CNS malignancies are critical. However, to date, there are no biomarkers approved for detection of cancer activity in the brain. Blood levels of neurofilament light (NfL) and tau, as well as glial fibrillary acidic protein (GFAp), show promise as biomarkers for brain injury in previous studies. Therefore, we performed a cross-sectional study to investigate correlations of those biomarkers with CNS activity of gliomas and BMs. METHODS: Serum samples of 36 participants of a single centered institution were tested for NfL, GFAp and tau with Simoa immunoassay, and correlated with clinical and radiological data. RESULTS: NfL and GFAp levels were significantly associated with the state of intracranial disease (analysis of variance (ANOVA), PsNfL = 0.03; ANOVA, PGFAp = 0.03). Although statistically significant (P = 0.04), differences in concentrations were not clinically meaningful for tau levels. Serum NfL (sNfL) and GFAp concentrations were higher in the group of patients with CNS tumors with disease in progression versus CNS with stable disease (P = 0.03 and P = 0.01, respectively). In addition, sNfL were higher in patients with metastatic solid tumors with known BMs than in those with metastatic tumors with no BM (P = 0.0004). CONCLUSION: sNfL and GFAp both apparently vary closely with presence and activity of gliomas and BMs. Further studies in larger populations are needed to expand these findings.

ICU Deaths in Patients With Advanced Cancer.

BACKGROUND: A significant number of advanced cancer admissions to the intensive care unit (ICU) are inappropriate in that they do not result in prolonged survival. No clear consensus criteria for reasonable admissions of advanced cancer patients have been developed. METHOD: We established four criteria for reasonable admissions to ICU in patients who suffered from advanced, incurable cancer: post procedure complication, recent notification of cancer, ECOG performance status of 0-1, and life expectancy of more than 6 months. Based on these criteria, we reviewed the charts of all patients who died in the ICU at the University of Tennessee Health Science Center (UTHSC) affiliated Veteran's Affairs Medical Center between 10/2005 and 10/2010. We identified patients with advanced, incurable cancer and performed an in depth review of their charts. RESULTS: In the 421 charts of patients who died in our ICU between October 2005 and October 2010 we identified 52 patients admitted to the ICU with advanced, incurable cancer. 14 patients were diagnosed with cancer one month or less prior to admission. 21 patients had ECOG performance status of 0-1. 14 patients had life expectancy of more than 6 months and 8 patients were admitted for post procedure complication. 47% of patients who did not satisfy any of our reasonable admission criteria had APDs. CONCLUSIONS: Incorporating proposed admission criteria in ICU admission guidelines may prevent 37% of inappropriate, advanced cancer admissions to the ICU. A simple increase in numbers of APDs would not likely change significantly the numbers of inappropriate ICU admissions.

Outcome of Adolescents and Young Adults Compared With Pediatric Patients With Acute Myeloid and Promyelocytic Leukemia.

BACKGROUND: Studies on the outcome of adolescents and young adults (AYAs) with acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL) are limited. METHODS: We compared the outcome of AYA (19-30 years) patients with AML and PML and pediatric (0-18 years) patients with AML (pAMLs) and APL (pAPLs) utilizing the Surveillance Epidemiology and End Results-18 registry. Early mortality rate (EMR), defined as mortality within 1 month of diagnosis, was used as a surrogate for treatment-related mortality. Survival statistics were computed using the Kaplan-Meier method. Multivariate analysis was done using logistic regression and the Cox proportional hazard regression model. RESULTS: A total of 6343 patients with AML were identified; 44.7% were AYAs. pAMLs had lower EMR (6.2% vs. 9.2%; P < .01) and higher overall survival (OS) (1-year, 70.3% vs. 62.1%; 5-year, 48.2% vs. 36.4%; P < .01). Nine hundred twenty patients with APL were also identified; 59.5% were AYAs. No statistically significant difference was found between AYAs with APL and pAPLs in EMR (11.4% vs. 14.1%; P = .23) and OS (1-year, 83.8% vs. 81.2%; P = .31 and 5-year, 68.2% vs. 73.1%; P = .11]. Comparing all patients with AML and APL, AYAs with APL and pAPLs had higher EMR (11.4% and 14.1% vs. 6.2% and 9.2%; P ≤ .01) but better OS than AYAs with AML and pAMLs (5-year OS, 68.2% and 73.1% vs. 48.2% and 36.4%; P ≤ .01). CONCLUSION: Our analysis shows AYAs with AML have worse EMR and OS compared with pAMLs. AYAs with APL and pAPLs have similar outcomes. To our knowledge, this is the first study reporting outcomes of AYAs with APL and pAPLs using a large population-based registry and their comparison with same age patients with AML.

Recent Advances in Preventing Chemotherapy-Induced Nausea and Vomiting.

Chemotherapy-induced nausea and vomiting (CINV) remains an important adverse effect of cancer therapy. The goal of CINV prophylaxis is to reduce the morbidity associated with nausea and vomiting, as well as to preserve quality of life, while maintaining the desired chemotherapy regimen. The US Food and Drug Administration has recently approved new therapies for prevention of CINV, including the neurokinin-1 (NK1) receptor antagonist rolapitant and the fixed-dose combination of the second-generation 5-hydroxytryptamine type 3 receptor antagonist palonosetron with the novel NK1 receptor antagonist netupitant. Alternative agents, like the atypical antipsychotic olanzapine, have also expanded the options available for preventing delayed and refractory CINV. Consensus guidelines for prevention of CINV from several organizations are generally consistent with one another and are updated based on expert review of available clinical trial data. This article will address changes in CINV guidelines over the past 5 years and provide updates on recently approved agents and agents that are expected to be approved, based on published phase III trials. It will also explore other factors affecting optimal CINV control, including the role of patient-related risk factors and the role of physician adherence to antiemetic guidelines in reducing the residual risk of CINV.