Our results show that when the TPS ≥50% is used as the end point, PD-L1 IHC performs well with cytology cell blocks. Cell blocks should be considered as a valuable resource for PD-L1 testing in advanced NSCLC. The clinical significance of higher PD-L1 IHC scores in cytology specimens needs to be evaluated prospectively.
The results presented indicate a substantial impact of lung cancer on patients' HRQOL, with stage IV disease, line of treatment, and PD, resulting in considerable deterioration of utility. The values obtained here will inform evaluations of cost-utility for NSCLC therapies.
BackgroundBiological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC) could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail.Methods and FindingsWe carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement.ConclusionsDespite IVC’s biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC’s value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type, chemotherapy regimen and IVC in which exceptional responses occur frequently enough to justify appropriately focused clinical trials.Trial RegistrationClinicalTrials.gov NCT01050621
BackgroundAccurate prediction of outcome in advanced nonsmall-cell lung cancer (nsclc) remains challenging. Even within the same stage and treatment group, survival and response to treatment vary. We set out to determine the predictive value of inflammatory markers C-reactive protein (crp) and white blood cells (wbcs) in patients with advanced nsclc.
Patients and MethodsPatients were assigned a prognostic index (pi):• 0 for crp 10 mg/L or less and wbcs 11×10 9 /L or less,• 1 if one of the two markers was elevated, and • 2 if both markers were elevated.We then used chest computed tomography (ct) imaging to evaluate response after 2 cycles of chemotherapy treatment.
ResultsOf 134 patients, 46 had a pi of 0; 60, a pi of 1; and 28, a pi of 2. Disease progressed in 41 patients. Progression was significantly more frequent among patients with a pi of 2 (p = 0.008). Median survival was 20.0 months for the pi 0 group, 10.4 months for the pi 1 group, and 7.9 months for the pi 2 group (p < 0.001). The pi was the only significant prognostic factor for survival even after adjustment for performance status, smoking, and weight loss (hazard ratio: 1.57; 95% confidence interval: 1.2 to 2.14; p = 0.004).
ConclusionsInflammatory state correlates significantly with both chemotherapy response and survival in stage iv nsclc. The pi may provide additional guidance for therapeutic decision-making.
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