Peak event analysis: a novel empirical method for the evaluation of elevated particulate events.

BACKGROUND: We report on a novel approach to the analysis of suspended particulate data in a rural setting in southern Ontario. Analyses of suspended particulate matter and associated air quality standards have conventionally focussed on 24-hour mean levels of total suspended particulates (TSP) and particulate matter <10 microns, <2.5 microns and <1 micron in diameter (PM10, PM2.5, PM1, respectively). Less emphasis has been placed on brief peaks in suspended particulate levels, which may pose a substantial nuisance, irritant, or health hazard. These events may also represent a common cause of public complaint and concern regarding air quality. METHODS: Measurements of TSP, PM10, PM2.5, and PM1 levels were taken using an automated device following local complaints of dusty conditions in rural south-central Ontario, Canada. The data consisted of 126,051 by-minute TSP, PM10, PM2.5, and PM1 measurements between May and August 2012. Two analyses were performed and compared. First, conventional descriptive statistics were computed by month for TSP, PM10, PM2.5, and PM1, including mean values and percentiles (70th, 90th, and 95th). Second, a novel graphical analysis method, using density curves and line plots, was conducted to examine peak events occurring at or above the 99th percentile of per-minute TSP readings. We refer to this method as "peak event analysis". Findings of the novel method were compared with findings from the conventional approach. RESULTS: Conventional analyses revealed that mean levels of all categories of suspended particulates and suspended particulate diameter ratios conformed to existing air quality standards. Our novel methodology revealed extreme outlier events above the 99th percentile of readings, with peak PM10 and TSP levels over 20 and 100 times higher than the respective mean values. Peak event analysis revealed and described rare and extreme peak dust events that would not have been detected using conventional descriptive statistics. CONCLUSIONS: Peak event analysis underscored extreme particulate events that may contribute to local complaints regarding intermittently dusty conditions. These outlier events may not appear through conventional analytical approaches. In comparison with conventional descriptive approaches, peak event analysis provided a more analytical and data-driven means to identify suspended particulate events with meaningful and perceptible effects on local residents.

Effect of contrast enhanced CT scans on heterogeneity corrected dose computations in the lung.

The aim of this study was to investigate and, if possible, compensate for the effect of intravenous contrast-enhanced CT scans on the treatment planning dose distributions for lung patients. The contrast and noncontrast CT scans of 3 patients were registered, and the effect of contrast on the Hounsfield units (HU) was assessed. The effect of contrast was then simulated in the CT scans of 18 patients receiving radiotherapy of the lung by modification of the CT numbers for relevant sections of noncontrast-enhanced CT scans. All treatment planning was performed on the Pinnacle3 planning system. The dose distributions computed from simulated contrast CT scans were compared to the original dose distributions by comparison of the monitor units (MUs) for each beam in the treatment plan required to deliver the prescribed dose to the isocenter as well as a comparison of the total MUs for each patient, a percentage change in required MUs being equivalent to a percentage change in the dose. A correction strategy to enable the use of contrast-enhanced CT scans in treatment planning was developed, and the feasibility of applying the strategy was investigated by calculating dose distributions for both the original and simulated contrast CT scans. A mean increase in the overall patient MUs of 1.0 +/- 0.8% was found, with a maximum increase of 3.3% when contrast was simulated on the original CT scans. The simulated contrast scans confirmed that the use of contrast-enhanced CT scans for routine treatment planning would result in a systematic change in the dose delivered to the isocenter. The devised correction strategy had no clinically relevant effect on the dose distribution for the original CT scans. The application of the correction strategy to the simulated contrast CT scans led to a reduction of the mean difference in the overall MUs to 0.1 +/- 0.2% compared to the original scan, demonstrating that the effect of contrast was eliminated with the correction strategy. This work has highlighted the problems associated with using contrast-enhanced CT scans in heterogeneity corrected dose computation. Contrast visible in the CT scan is transient and should not be accounted for in the treatment plan. A correction strategy has been developed that minimizes the effect of intravenous contrast while having no clinical effect on noncontrast CT scans. The correction strategy allows the use of contrast without detriment to the treatment plan.

Investigation of a Patient Reported Outcome tool to assess radiotherapy-related toxicity prospectively in patients with lung cancer.

BACKGROUND AND PURPOSE: There is a paucity of data regarding the feasibility and relevance of Patient Reported Outcome (PRO) tools to assess radiotherapy-related toxicity in lung cancer. MATERIAL AND METHODS: From January to June 2013, lung cancer patients undergoing thoracic radiotherapy/chemo-radiotherapy completed nine patient-adapted Common Terminology Criteria for Adverse Events (CTCAE), the European Organisation for Research and Treatment of Cancer Quality of Life (QoL) questionnaire and the Hospital Anxiety and Depression Scale (HADS) at baseline, the end of radiotherapy and at follow-up. Clinicians completed the same CTCAE items and agreement between patients' and clinicians' reporting was assessed using weighted kappa coefficients. QoL and HADS scores were correlated with the patients' and clinicians' reported toxicity. RESULTS: 70/116 patients completed the questionnaires for at least one time point excluding baseline. Agreement between patients' and clinicians' reported toxicity ranged from slight to substantial. Most discrepancies were within one grade and patients reported greater severity than clinicians for most symptoms. QoL and HADS scores were more strongly correlated with the patients' compared to clinicians' matching toxicity reports. The PRO tool was found to be statistically reliable. CONCLUSIONS: The use of a PRO tool in lung cancer radiotherapy is feasible, reliable and acceptable to patients. PROs should be integrated in future clinical trials evaluating new radiotherapy approaches to assess toxicity.

Randomised phase II trial of 4 dose levels of single agent docetaxel in performance status (PS) 2 patients with advanced non-small cell lung cancer (NSCLC): DOC PS2 trial. Manchester lung cancer group.

BACKGROUND: The role of chemotherapy for advanced NSCLC patients and ECOG PS2 remains controversial. We evaluated 4 doses of 3-weekly docetaxel to identify a less toxic, clinically effective dose. METHODS: Seventy-three patients with stage III (22%) (unsuitable for radical surgery/radiotherapy) and IV (78%) NSCLC were randomized to receive 4 doses of 3-weekly docetaxel, for 4 cycles: arm (A) 40 mg/m(2) (n=17), arm (B) 50 mg/m(2) (n=17), arm (C) 60 mg/m(2) (n=19), arm (D) 50 mg/m(2) escalated by 10 mg/m(2) to a maximum of 70 mg/m(2) (n=19). Primary endpoints: maximum tolerated dose, RR, duration of response, symptom improvement, toxicity and QoL. Secondary endpoint: overall survival (OS). Patients and disease characteristics were well balanced. Median age was 67 (range 45-81), there were 32 male and 41 female, histology subtype: squamous/adenocarcinoma/mixed/NOS=42%/49%/4%/5%. RESULTS: Seven patients did not receive any treatment because of deterioration in PS or death. 50% of patients in arm D, who received more than one cycle, received dose escalation. There was no statistical difference in the number of cycles administered (arms A, B and D: median 2 cycles and arm C: median 3 cycles) and no difference in RR: arm A=6%, arm B=6%, arm C=10%, and arm D=0%. There was no statistically significant difference in grade 3/4 neutropenia and thrombocytopenia between the four arms. No difference was observed in hospitalization rate, blood transfusions, antibiotics administration and non-haematological toxicity. QoL: no difference in total scores between baseline and cycles 1-4. There was a significant decrease in pain scores from baseline to post cycles 2 and 3 (p=0.025 and p=0.002, respectively). There was no difference in OS (p=0.992). Median survival and 6-month survival were 61, 86, 88 and 97 days and 29%, 33%, 21% and 26% for arms A, B, C, and D, respectively. CONCLUSIONS: Clinical efficacy of docetaxel was observed at all dose levels. Higher dose levels were not associated with increased toxicities, use of IV antibiotics or hospitalization rates. However, the median survival observed is shorter than historical data and do not support further evaluation of these doses of single agent docetaxel in this population.

Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and cisplatin in patients with advanced nonsmall cell lung carcinoma.

BACKGROUND: The authors compared gemcitabine and carboplatin (GC) with mitomycin, ifosfamide, and cisplatin (MIC) or mitomycin, vinblastine, and cisplatin (MVP) in patients with advanced nonsmall cell lung carcinoma (NSCLC). The primary objective was survival. Secondary objectives were time to disease progression, response rates, evaluation of toxicity, disease-related symptoms, World Health Organization performance status (PS), and quality of life (QoL). METHODS: Three hundred seventy-two chemotherapy-naïve patients with International Staging System Stage III/IV NSCLC who were ineligible for curative radiotherapy or surgery were randomized to receive either 4 cycles of gemcitabine (1000 mg/m(2) on Days 1, 8, and 15) plus carboplatin (area under the serum concentration-time curve, 5; given on Day 1) every 4 weeks (the GC arm) or MIC/MVP every 3 weeks (the MIC/MVP arm). RESULTS: There was no significant difference in median survival (248 days in the MIC/MVP arm vs. 236 days in the GC arm) or time to progression (225 days in the MIC/MVP arm vs. 218 days in the GC arm) between the 2 treatment arms. The 2-year survival rate was 11.8% in the MIC/MVP arm and 6.9% in the GC arm. The 1-year survival rate was 32.5% in the MIC/MVP arm and 33.2% in the GC arm. In the MIC/MVP arm, 33% of patients responded (4 complete responses [CRs] and 57 partial responses [PRs]) whereas in the GC arm, 30% of patients responded (3 CRs and 54 PRs). Nonhematologic toxicity was comparable for patients with Grade 3-4 symptoms, except there was more alopecia among patients in the MIC/MVP arm. GC appeared to produce more hematologic toxicity and necessitated more transfusions. There was no difference in performance status, disease-related symptoms, or QoL between patients in the two treatment arms. Fewer inpatient stays for complications were required with GC. CONCLUSIONS: The results of the current study failed to demonstrate any difference in efficacy between the newer regimen of GC and the older regimens of MIC and MVP. Cancer 2003;98:542-53.