Improving time to molecular testing results in patients with newly diagnosed, metastatic non-small cell lung cancer (NSCLC).

244 Background: Next generation sequencing (NGS) is a crucial component of evaluation of newly diagnosed patients with metastatic non-small cell lung cancer (NSCLC) to determine appropriate first line treatment. Delays in NGS can lead to psychologic distress for patients and can affect choices in first line therapy, especially for patients with underlying targetable mutations. While more data is needed to benchmark turnaround time for NGS results, guidelines and expert consensus suggest time from diagnosis to treatment should be 15 days and turnaround time for genomic testing 10-14 days. This study was aimed at reducing time to NGS results in a large integrated health care system. Methods: Through the ASCO Quality Training Program, we reviewed electronic medical records of 25 patients with newly diagnosed, untreated metastatic NSCLC from 12/2018 to 9/2020 and determined number of days from pathological diagnosis to NGS results. We reviewed process maps for oncology, pathology, the internal data management division, and a genomic testing company to determine factors leading to significant preventable delays. Since 11/2020, we created an automated weekly report using CoPath to identify new pathological diagnoses of potential metastatic NSCLC. The oncology department reviewed these cases weekly and NGS orders were placed for patients with metastatic NSCLC. Eleven additional patients with newly diagnosed metastatic NSCLC were included in the prospective cohort. Results: Demographic characteristics are noted in Table. Our intervention reduced median time from pathological diagnosis to NGS results from 24 to 19 days. Median time from biopsy results to NGS order was reduced from 7 to 1 day. Time from specimen being sent from pathology to NGS vendor was a median of 6 days in both cohorts. Total time from pathological diagnosis to appropriate treatment was reduced from a median of 33 to 25 days. Conclusions: Delays in time to NGS results can be reduced by improved communication between departments and simple, automated interventions to ensure results are efficiently released to an oncologist. Additional Plan-Do-Study-Act cycles are currently being developed to further reduce time from biopsy results to NGS results. [Table: see text]

Download Full-text

Differential influence of antibiotic therapy and other medications on oncological outcomes of patients with non-small cell lung cancer treated with first-line pembrolizumab versus cytotoxic chemotherapy

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-002421 ◽

2021 ◽

Vol 9 (4) ◽

pp. e002421

Author(s):

Alessio Cortellini ◽

Massimo Di Maio ◽

Olga Nigro ◽

Alessandro Leonetti ◽

Diego L Cortinovis ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Objective Response ◽

Multivariable Analysis ◽

Small Cell ◽

Small Cell Lung ◽

First Line ◽

Metastatic Nsclc ◽

The Impact

BackgroundSome concomitant medications including antibiotics (ATB) have been reproducibly associated with worse survival following immune checkpoint inhibitors (ICIs) in unselected patients with non-small cell lung cancer (NSCLC) (according to programmed death-ligand 1 (PD-L1) expression and treatment line). Whether such relationship is causative or associative is matter of debate.MethodsWe present the outcomes analysis according to concomitant baseline medications (prior to ICI initiation) with putative immune-modulatory effects in a large cohort of patients with metastatic NSCLC with a PD-L1 expression ≥50%, receiving first-line pembrolizumab monotherapy. We also evaluated a control cohort of patients with metastatic NSCLC treated with first-line chemotherapy. The interaction between key medications and therapeutic modality (pembrolizumab vs chemotherapy) was validated in pooled multivariable analyses.Results950 and 595 patients were included in the pembrolizumab and chemotherapy cohorts, respectively. Corticosteroid and proton pump inhibitor (PPI) therapy but not ATB therapy was associated with poorer performance status at baseline in both the cohorts. No association with clinical outcomes was found according to baseline statin, aspirin, β-blocker and metformin within the pembrolizumab cohort. On the multivariable analysis, ATB emerged as a strong predictor of worse overall survival (OS) (HR=1.42 (95% CI 1.13 to 1.79); p=0.0024), and progression free survival (PFS) (HR=1.29 (95% CI 1.04 to 1.59); p=0.0192) in the pembrolizumab but not in the chemotherapy cohort. Corticosteroids were associated with shorter PFS (HR=1.69 (95% CI 1.42 to 2.03); p<0.0001), and OS (HR=1.93 (95% CI 1.59 to 2.35); p<0.0001) following pembrolizumab, and shorter PFS (HR=1.30 (95% CI 1.08 to 1.56), p=0.0046) and OS (HR=1.58 (95% CI 1.29 to 1.94), p<0.0001), following chemotherapy. PPIs were associated with worse OS (HR=1.49 (95% CI 1.26 to 1.77); p<0.0001) with pembrolizumab and shorter OS (HR=1.12 (95% CI 1.02 to 1.24), p=0.0139), with chemotherapy. At the pooled analysis, there was a statistically significant interaction with treatment (pembrolizumab vs chemotherapy) for corticosteroids (p=0.0020) and PPIs (p=0.0460) with respect to OS, for corticosteroids (p<0.0001), ATB (p=0.0290), and PPIs (p=0.0487) with respect to PFS, and only corticosteroids (p=0.0033) with respect to objective response rate.ConclusionIn this study, we validate the significant negative impact of ATB on pembrolizumab monotherapy but not chemotherapy outcomes in NSCLC, producing further evidence about their underlying immune-modulatory effect. Even though the magnitude of the impact of corticosteroids and PPIs is significantly different across the cohorts, their effects might be driven by adverse disease features.

Download Full-text

Fundamental Concepts in the Application of Plasma Genotyping (Liquid Biopsy) to EGFR Mutation Detection in Non–Small-Cell Lung Cancer

JCO Precision Oncology ◽

10.1200/po.17.00125 ◽

2018 ◽

pp. 1-12

Author(s):

Adrian G. Sacher

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Kinase Inhibitors ◽

Acquired Resistance ◽

Small Cell ◽

Newly Diagnosed ◽

Small Cell Lung ◽

Metastatic Nsclc ◽

Egfr Kinase

Plasma genotyping has rapidly evolved from an investigational technology into a standard-of-care tool used to direct therapy in metastatic non–small-cell lung cancer (NSCLC). Multiple testing platforms exist for plasma genotyping, each with unique test characteristics and scientific validation. The optimal use and interpretation of plasma genotyping requires understanding of cell-free DNA biology, the assay characteristics of the available testing technologies, and the application of testing in each clinical scenario. Current recommendations for plasma genotyping in metastatic NSCLC are limited to patients with newly diagnosed disease and those with acquired resistance to targeted therapy, in particular, epidermal growth factor receptor (EGFR) kinase inhibitors. In newly diagnosed metastatic NSCLC, under certain circumstances, plasma genotyping is useful for the detection of targetable genomic alterations or nontargetable driver alterations (eg, KRAS) that are mutually exclusive with targetable alterations. In patients with acquired resistance to therapy, such as EGFR T790M-mediated acquired resistance to EGFR kinase inhibitors, plasma genotyping may detect resistance mutations missed by standard tissue genotyping because of tumor heterogeneity. In both scenarios, the high specificity and positive predictive value of validated plasma genotyping assays allow for the reliable selection of therapy on the basis of a positive plasma genotyping result. However, the modest sensitivity of these assays requires that negative results be confirmed by tissue genotyping with repeat biopsy, if necessary. There is considerable potential for plasma genotyping in the detection of early-stage disease, for patients at risk for disease recurrence, and as an integrated biomarker of therapeutic response in clinical trials of novel therapies.

Download Full-text

Depression and Survival in Metastatic Non–Small-Cell Lung Cancer: Effects of Early Palliative Care

Journal of Clinical Oncology ◽

10.1200/jco.2011.38.3166 ◽

2012 ◽

Vol 30 (12) ◽

pp. 1310-1315 ◽

Cited By ~ 145

Author(s):

William F. Pirl ◽

Joseph A. Greer ◽

Lara Traeger ◽

Vicki Jackson ◽

Inga T. Lennes ◽

...

Keyword(s):

Lung Cancer ◽

Palliative Care ◽

Small Cell Lung Cancer ◽

Survival Benefit ◽

Small Cell ◽

Newly Diagnosed ◽

Small Cell Lung ◽

Early Palliative Care ◽

Metastatic Nsclc ◽

Oncology Care

Purpose In a randomized trial, early palliative care (EPC) in patients with metastatic non–small-cell lung cancer (NSCLC) was observed to improve survival. In a secondary analysis, we explored the hypothesis that the survival benefit resulted from improving depression. Patients and Methods In total, 151 patients with newly diagnosed metastatic NSCLC participated in a randomized trial of EPC integrated with standard oncology care versus standard oncology care alone. Depression was assessed at baseline and at 12 weeks with the Patient Health Questionnaire-9 (PHQ-9) and was scored diagnostically by using Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, criteria for major depression syndrome (MDS). Depression response was considered ≥ 50% reduction in PHQ-9 scores at 12 weeks. Survival differences were tested with log-rank and Cox proportional hazards models. Results At baseline, 21 patients (14%) met MDS criteria. MDS significantly predicted worse survival (hazard ratio, 1.82; P = .02). Patients assigned to EPC had greater improvements in PHQ-9 scores at 12 weeks (P < .001); among patients with MDS, those receiving EPC had greater rates of depression response at 12 weeks (P = .04). However, improvement in PHQ-9 scores was not associated with improved survival, except in a sensitivity analysis in which patients who died before 12 weeks were modeled to have worse depression. The group randomly assigned to EPC remained independently associated with survival after adding improvement in PHQ-9 scores to the survival model. Conclusion Depression predicted worse survival in patients with newly diagnosed metastatic NSCLC. Although EPC was associated with greater improvement in depression at 12 weeks, the data do not support the hypothesis that treatment of depression mediated the observed survival benefit from EPC.

Download Full-text

Hypoalbuminaemia as a Prognostic Biomarker of First-Line Treatment Resistance in Metastatic Non-small Cell Lung Cancer

Frontiers in Nutrition ◽

10.3389/fnut.2021.734735 ◽

2021 ◽

Vol 8 ◽

Author(s):

Mark Stares ◽

Amanda Swan ◽

Kirsten Cumming ◽

Tze-En Ding ◽

James Leach ◽

...

Keyword(s):

Lung Cancer ◽

Targeted Therapy ◽

Small Cell Lung Cancer ◽

Progressive Disease ◽

Treatment Resistance ◽

Small Cell ◽

Small Cell Lung ◽

First Line ◽

Metastatic Nsclc ◽

Pre Treatment

Introduction: Despite significant advances in systemic anticancer therapy (SACT) for non-small cell lung cancer (NSCLC), many patients still fail to respond to treatment or develop treatment resistance. Albumin, a biomarker of systemic inflammation and malnutrition, predicts survival in many cancers. We evaluated the prognostic significance of albumin in patients receiving first-line targeted therapy or immunotherapy-based SACT for metastatic NSCLC.Methods: All patients treated with first-line targeted therapy or immunotherapy-based SACT for metastatic NSCLC at a regional Scottish cancer centre were identified. Serum albumin at pre-treatment, after 12-weeks of treatment, and at the time of progressive disease were recorded. The relationship between albumin (≥ 35g/L v <35g/L) and overall survival (OS) was examined.Results: Data were available for 389 patients of both targeted therapy cohort (n = 159) and immunotherapy-based therapy cohort (n = 230). Pre-treatment albumin was predictive of OS in each cohort at HR1.82 (95%CI 1.23–2.7) (p =0.003) and HR2.55 (95%CI 1.78–3.65) (p < 0.001), respectively. Pre-treatment albumin <35 g/L was associated with a significantly higher relative risk of death within 12 weeks in each cohort at RR9.58 (95%CI 2.20–41.72, p = 0.003) and RR3.60 (95%CI 1.74–6.57, p < 0.001), respectively. The 12-week albumin was predictive of OS in each cohort at HR1.88 (95%CI 1.86–4.46) (p < 0.001) and HR2.67 (95%CI 1.74–4.08) (p < 0.001), respectively. 46 out of 133 (35%) evaluable patients treated with targeted therapy and 43 out of 169 (25%) treated with immunotherapy-based therapy crossed over albumin prognostic groups between pre-treatment and 12-week. The prognostic value of 12-week albumin was independent of pre-treatment albumin status. A majority of patients had albumin <35g/L at the time of progressive disease when it was also predictive of survival following progressive disease at HR2.48 (95%CI 1.61–3.82) (p < 0.001) and HR2.87 (95%CI 1.91–4.31) (p < 0.001) respectively).Conclusions: Albumin is a reliable prognostic factor in patients with metastatic NSCLC, predicting survival independent of the class of drug treatment at various time points during the patient journey. Tracking albumin concentrations during systemic therapy may indicate disease activity or treatment response over time.

Download Full-text