Metastatic Lung Cancer and Distress: Use of the Distress Thermometer for Patient Assessment.

BACKGROUND: Patients with metastatic lung cancer experience high levels of distress related to their disease trajectory and treatment. Oncology nurses are experts in patient care and symptom management, giving them an opportunity to screen and treat patients' distress.
. OBJECTIVES: The objectives of this study were to screen patients for distress and manage their symptoms to positively affect their quality of life, treatment adherence, and clinical outcomes, and to reduce healthcare costs. 
. METHODS: This quality improvement project was conducted to pilot the Distress Thermometer (DT) into the care of patients with thoracic cancer and to evaluate the effect of a multifaceted intervention, consisting of a patient education pamphlet and a nurse coaching call, on distress levels. 
. FINDINGS: Severe distress was reported in more than half the patients. A paired-sample t test revealed a significant decrease in distress scores following the intervention.

Circulating tumor cells as a predictive biomarker in patients with small cell lung cancer undergoing chemotherapy.

BACKGROUND: There are no biomarkers for assessment of disease burden or activity of therapy in SCLC. PATIENTS AND METHODS: We conducted a prospective study enumerating serial CTCs in patients with newly diagnosed limited disease (LD) and extensive stage (ED) SCLC. CTCs demonstrating DNA damage and apoptosis based on γH2AX and M30 staining were also assessed. We correlated CTC number with disease stage, survival outcomes and tumor burden by RECIST. RESULTS: Between 03/2011-10/2013, 50 evaluable patients were enrolled (20 LD). Baseline CTC number was higher for ED (median CTC 71 vs. 1.5 for LD; p 0.0004). Patients with <5 CTC had longer PFS but not OS (11 vs. 6.7 months, p 0.0259 and 15.5 vs. 12.9 months, p 0.4357). A higher cutoff (CTC<50 or CTC≥50) was significantly correlated with both OS (20.2 vs. 11.8 months, p 0.0116) and PFS (10 vs. 4.8 months, p 0.0002). Patients with <5 CTC on day 1 of cycle 2 had longer PFS (10 vs. 3.17 months, p<0.001) and OS (18 vs. 9 months, p 0.0001). Patients with an increase in γ2HAX-positive CTCs after chemotherapy had longer OS compared to patients without an increase (25.3 vs. 9 months, p 0.15). CONCLUSIONS: This study demonstrates that CTCs at baseline and Cycle 2 of chemotherapy correlate with disease stage and survival in patients with SCLC, suggesting that CTCs may be used as a surrogate biomarker for clinical response. Confirmatory prospective clinical trials are needed before we can incorporate routine evaluation of CTCs into clinical practice.

Palliative care and advance care planning for patients with advanced malignancies.

Patients diagnosed with an advanced cancer frequently have a very limited life expectancy and need to understand their prognosis in order to make good choices about care. Advance care planning (ACP) is an important aspect of this care but can be especially difficult to address. Most patients and families prefer direct and honest communication, but they may interpret the information they are given in very different ways. In addition, oncologists strive to communicate honestly and sensitively, but often struggle with the best approach. Finally, standardization of ACP is challenging because patients have highly individualized values, traditions and social and family dynamics that guide their preferences. Palliative Care is a rapidly growing field that specializes in communication and patient-centered approaches to care. Treatment of patients with advanced or metastatic cancer should prioritize early discussions of ACP to ensure high quality end-of-life care. When available, this care should be delivered through careful integration with palliative care specialists.

Tumor-associated neutrophils stimulate T cell responses in early-stage human lung cancer.

Infiltrating inflammatory cells are highly prevalent within the tumor microenvironment and mediate many processes associated with tumor progression; however, the contribution of specific populations remains unclear. For example, the nature and function of tumor-associated neutrophils (TANs) in the cancer microenvironment is largely unknown. The goal of this study was to provide a phenotypic and functional characterization of TANs in surgically resected lung cancer patients. We found that TANs constituted 5%-25% of cells isolated from the digested human lung tumors. Compared with blood neutrophils, TANs displayed an activated phenotype (CD62L(lo)CD54(hi)) with a distinct repertoire of chemokine receptors that included CCR5, CCR7, CXCR3, and CXCR4. TANs produced substantial quantities of the proinflammatory factors MCP-1, IL-8, MIP-1α, and IL-6, as well as the antiinflammatory IL-1R antagonist. Functionally, both TANs and neutrophils isolated from distant nonmalignant lung tissue were able to stimulate T cell proliferation and IFN-γ release. Cross-talk between TANs and activated T cells led to substantial upregulation of CD54, CD86, OX40L, and 4-1BBL costimulatory molecules on the neutrophil surface, which bolstered T cell proliferation in a positive-feedback loop. Together our results demonstrate that in the earliest stages of lung cancer, TANs are not immunosuppressive, but rather stimulate T cell responses.

Can palliative home care reduce 30-day readmissions? Results of a propensity score matched cohort study.

OBJECTIVE: This study examined the impact of palliative home nursing care on rates of hospital 30-day readmissions. METHODS: The electronic health record based retrospective cohort study was performed within home care and palliative home care programs. Participants were home care patients discharged from one of three urban teaching hospitals. Outcome measures were propensity score matched rates of hospital readmissions within 30 days of hospital discharge. RESULTS: Of 406 palliative home care patients, matches were identified for 392 (96%). Of 15,709 home care patients, 890 were used at least once as a match for palliative care patients, for a total final sample of 1282. Using the matched sample we calculated the average treatment effect for treated patients. In this sample, palliative care patients had a 30-day readmission probability of 9.1% compared to a probability of 17.4% in the home care group (mean ATT: 8.3%; 95% confidence interval [CI] 8.0%-8.6%). This effect persisted after adjustment for visit frequency. CONCLUSIONS: Palliative home care may offer benefits to health systems by allowing patients to remain at home and thereby avoiding 30-day rehospitalizations.

Enhanced effector responses in activated CD8+ T cells deficient in diacylglycerol kinases.

Recent clinical trials have shown promise in the use of chimeric antigen receptor (CAR)-transduced T cells; however, augmentation of their activity may broaden their clinical use and improve their efficacy. We hypothesized that because CAR action requires proteins essential for T-cell receptor (TCR) signal transduction, deletion of negative regulators of these signaling pathways would enhance CAR signaling and effector T-cell function. We tested CAR activity and function in T cells that lacked one or both isoforms of diacylglycerol kinase (dgk) expressed highly in T cells, dgkα and dgkζ, enzymes that metabolize the second messenger diacylglycerol (DAG) and limit Ras/ERK activation. We found that primary murine T cells transduced with CARs specific for the human tumor antigen mesothelin showed greatly enhanced cytokine production and cytotoxicity when cocultured with a murine mesothelioma line that stably expresses mesothelin. In addition, we found that dgk-deficient CAR-transduced T cells were more effective in limiting the growth of implanted tumors, both concurrent with and after establishment of tumor. Consistent with our studies in mice, pharmacologic inhibition of dgks also augments function of primary human T cells transduced with CARs. These results suggest that deletion of negative regulators of TCR signaling enhances the activity and function of CAR-expressing T cells and identify dgks as potential targets for improving the clinical potential of CARs.

Immunological effects of the TGFß-blocking antibody GC1008 in malignant pleural mesothelioma patients.

We evaluated a neutralizing anti-TGFß antibody (GC1008) in cancer patients with malignant pleura mesothelioma (MPM). The goal of this study was to assess immunoregulatory effects in relation to clinical safety and clinical response. Patients with progressive MPM and 1-2 prior systemic therapies received GC1008 at 3mg/kg IV over 90 min every 21 d as part of an open-label, two-center Phase II trial. Following TGFß blockade therapy, clinical safety and patient survival were monitored along with the effects of anti-TGFß antibodies on serum biomarkers and peripheral blood mononuclear cells (PBMC). Although designed as a larger trial, only 13 patients were enrolled when the manufacturer discontinued further development of the antibody for oncology indications. All participants tolerated therapy. Although partial or complete radiographic responses were not observed, three patients showed stable disease at 3 mo. GC1008 had no effect in the expression of NK, CD4+, or CD8+ T cell activating and inhibitory markers, other than a decrease in the expression of 2B4 and DNAM-1 on NK cells. However, serum from 5 patients showed new or enhanced levels of antibodies against MPM tumor lysates as measured by immunoblotting. Patients who produced anti-tumor antibodies had increased median overall survival (OS) (15 vs 7.5 mo, p < 0.03) compared with those who did not. To our knowledge, these data represent the first immune analysis of TGFß- blockade in human cancer patients.