Pretreatment neutrophil-to-lymphocyte ratio as a marker of outcomes in nivolumab-treated patients with advanced non-small-cell lung cancer.

OBJECTIVES: Efficient use of nivolumab in non-small-cell lung cancer (NSCLC) has been limited by the lack of a definitive predictive biomarker. In patients with metastatic melanoma treated with ipilimumab, a pretreatment neutrophil-to-lymphocyte ratio (NLR)<5 has been associated with improved survival. This retrospective cohort study aimed to determine whether the pretreatment NLR was associated with outcomes in NSCLC patients treated with nivolumab. METHODS: We reviewed the medical records of all patients with previously treated advanced NSCLC who received nivolumab between March 2015 and March 2016 outside of a clinical trial at the University of Pennsylvania. Patients were dichotomized according to pretreatment NLR<5 vs. ≥5. Multivariable logistic regression and Cox proportional hazards models were used to assess the impact of pretreatment NLR on overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). RESULTS: 175 patients were treated. Median age was 68 (range, 33-88); 54% were female. Twenty-five percent of patients had an Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2; 46% had received ≥2 prior systemic therapies. In multivariate analyses, pretreatment neutrophil-to-lymphocyte ratio (NLR) ≥5 was independently associated with inferior OS (median 5.5 vs. 8.4 months; HR 2.07, 95% CI 1.3-3.3; p=0.002) and inferior PFS (median 1.9 vs. 2.8 months; HR 1.43, 95% CI 1.02-2.0; p=0.04). CONCLUSIONS: In a cohort of patients with NSCLC treated with nivolumab in routine practice, pretreatment NLR≥5 was associated with inferior outcomes. It is unclear whether this marker is predictive or prognostic. Prospective studies are warranted to determine the utility of NLR in the context of other biomarkers of programmed death-1 (PD-1) therapy.

Use of Survivorship Care Plans and Analysis of Patient-Reported Outcomes in Multinational Patients With Lung Cancer.

PURPOSE: Lung cancer is the leading cause of cancer death and is a significant source of morbidity. Patient-reported outcomes (PROs) have been shown to be prognostic for survival. We have analyzed emerging patterns of longitudinal PROs collected in the development of survivorship care plans (SCPs). METHODS: OncoLife and the LIVESTRONG Care Plans are Internet-based programs designed to generate unique SCPs. We selected SCPs from patients identifying as survivors of primary lung cancer. Patient-reported demographics and treatment and toxicity data were examined. Effects were categorized by the physiologic system that they affected. RESULTS: Six hundred eighty-nine plans were created for users self-identifying as survivors of primary lung cancer. Average time from diagnosis to reporting was 1.68 years (range, 0 to 24 years). Most were white (85.9%), well educated (61.1% "some college" or higher), and lived in the United States (90.7%). Patients underwent chemotherapy (75.8%), radiotherapy (54.7%), and surgery (54.4%). Neurocognitive symptoms (eg, fatigue, cognitive changes) were the most common (48.8%), especially among those receiving chemotherapy, followed by musculoskeletal/dermatologic symptoms (14.1%) and thoracic symptoms (13.5%). Only 11.2% were initially offered an SCP. Of those offered SCPs, 54.5% were offered by their health care provider, and most often were at a non-university-based cancer center (66.2%). CONCLUSION: For patients with lung cancer worldwide, it is feasible to obtain PROs and to create SCPs through an Internet-based program. As patients with lung cancer achieve improved survival, further attention should be paid to PROs. Surprisingly, neurocognitive symptoms seem to be the most common issues and therefore the most important to address. Increased effort should be made to provide SCPs, particularly in urban and university cancer center settings.

Patient reported late effects of gynecological cancer treatment.

OBJECTIVE: There are a large number of gynecological cancer survivors in the United States living with long term sequelae of their treatment. Patient reported outcomes are essential in capturing patients' experiences in order to address survivorship issues; however, patient reported toxicities are not often collected or reported. METHODS: A web-based survivorship care plan tool was used to collect patient reported toxicity data for 390 women who had undergone treatment for gynecological cancer. Demographic, diagnosis, treatment modality and toxicity data were reviewed. RESULTS: Median age of diagnosis was 49 years, and 88% (n=334) of the women were Caucasian and had attended at least some college. Only 10% (n=38) had previously been offered a survivorship care plan or survivorship information. Almost half of the patients had ovarian cancer (46%, n=180), 23% had cervical cancer (n=92) and 28% had uterine cancer (n=109). Late effects most commonly reported for all gynecological malignancy survivors using this tool were cognitive changes, sexual side effects, changes in bowel patterns, peripheral neuropathy and skin changes. CONCLUSION: Women with gynecological cancers experience a plethora of late effects; however, very few of them have access to a survivorship plan to cope with these issues. Patient reported side effects, especially sexual dysfunction, occur more commonly than previously reported. Patient-focused tools to evaluate these side effects and access to survivorship plans are needed for comprehensive care of gynecologic cancer survivors.

Risk for unplanned hospital readmission of patients with cancer: results of a retrospective medical record review.

PURPOSE/OBJECTIVES: To identify potential factors that place patients with cancer at risk for unplanned readmissions after discharge from the hospital. DESIGN: Retrospective, descriptive, medical record review. SETTING: A National Cancer Institute-designated comprehensive cancer center in an urban area of the Northeastern United States. SAMPLE: 78 patients were selected from those readmitted within seven days of discharge. For each readmission case, a nonreadmitted patient was randomly selected and matched on discharge date and reason for prior admission. The age range was 22-87 years, men and women were equally represented, and 88% were Caucasian. METHODS: The Readmission Criteria Record was developed to collect data from medical records about factors associated with readmission, including demographics, severity of illness, support at home, symptoms, and comorbidities. MAIN RESEARCH VARIABLES: Criteria associated with readmission risk. FINDINGS: Patients who had gastrointestinal cancer, nausea within 24 hours of discharge, financial and insurance concerns, or caregiver difficulty or those who lived alone were more likely to be readmitted within seven days of discharge. Patients were more likely to be readmitted on Friday than any other day. Among readmitted patients, 48% were readmitted within one to two days postdischarge. CONCLUSIONS: Knowledge of factors that may place patients with cancer at an increased risk for readmission and subsequent implementation of appropriate interventions during hospitalization may help to decrease risk of readmission. IMPLICATIONS FOR NURSING: The factors identified provide a basis for assessment, planning, interventions, and follow-up of patients to help reduce the risk of readmission and, thus, poor outcomes.

Angiogenesis in collagen I requires alpha2beta1 ligation of a GFP*GER sequence and possibly p38 MAPK activation and focal adhesion disassembly.

Angiogenesis depends on proper collagen biosynthesis and cross-linking, and type I collagen is an ideal angiogenic scaffold, although its mechanism is unknown. We examined angiogenesis using an assay wherein confluent monolayers of human umbilical vein endothelial cells were overlain with collagen in a serum-free defined medium. Small spaces formed in the cell layer by 2 h, and cells formed net-like arrays by 6-8 h and capillary-like lumens by 24 h. Blocking of alpha2beta1, but not alpha1 or alpha(v)beta3 integrin function halted morphogenesis. We found that a triple-helical, homotrimeric peptide mimetic of a putative alpha2beta1 binding site: alpha1(I)496-507 GARGERGFP*GER (where single-letter amino acid nomenclature is used, P* = hydroxyproline) inhibited tube formation, whereas a peptide carrying another putative site: alpha1(I)127-138 GLP*GERGRP*GAP* or control peptides did not. A chemical inhibitor of p38 mitogen-activated protein kinase (p38 MAPK), SB202190, blocked tube formation, and p38 MAPK activity was increased in collagen-treated cultures, whereas targeting MAPK kinase (MEK), focal adhesion kinase (FAK), or phosphatidylinositol 3-kinase (PI3K) had little effect. Collagen-treated cells had fewer focal adhesions and 3- to 5-fold less activated FAK. Thus capillary morphogenesis requires endothelial alpha2beta1 integrin engagement of a single type I collagen integrin-binding site, possibly signaling via p38 MAPK and focal adhesion disassembly/FAK inactivation.